2020 NeoPREP Syllabus Book 1 - Fri-Sat PDF

An Intensive Review and Update of
Neonatal-Perinatal Medicine
February 7-11, 2020

Renaissance Long Beach Hotel
Long Beach, CA
SYLLABUS
Book 1
Friday, February 7, 2020

Saturday, February 8, 2020

2020 NEOPREP AN INTENSIVE REVIEW AND UPDATE OF NEONATAL-PERINATAL MEDICINE
FEBRUARY 7-11, 2020
RENAISSANCE LONG BEACH HOTEL - LONG BEACH, CA
BOOK 1 OF 2
TABLE OF CONTENTS
**Registered Attendees have full access to view and download color slides on Pedialink**
Please refer to Pedialink at www.pedialink.org for attendee course information:
 General Information  Recording CME Credit

 Accreditation Information  Course Faculty and Planning Group
 Sponsor Information  Disclosures
 Acknowledgements
*Please note: These presentations are not designated for CME credit.
FRIDAY, FEBRUARY 7, 2020

Plenary Lectures/Question and Answer Sessions
Maternal and Placental Physiology – Dr. Boggess ........................................................................ 5
Rapid Review: Maternal Conditions Affecting the Fetus and Newborn – Dr. Boggess ............ 19
High Yield Antepartum Fetal Surveillance – Dr. Boggess............................................................. 27
ARS Rapid Review - MFM Potpourri – NeoPREP Planning Committee No Handout
Labor and Delivery - Case-Based ARS – Dr. Boggess .................................................................. 43
Rapid Review: Inheritance and Genetic Testing – NeoPREP Planning Committee No Handout
Approach to Evaluating an Infant with Congenital Anomalies – Dr. Northrup ........................... 55
Approach to the Infant with Congenital Anomalies-Recognize that Disorder and Order the Correct
Test – Dr. Northrup ............................................................................................................................ 75
Term Brain Injury and Pathophysiology of HIE – Dr. Wusthoff .................................................... 89
Rapid Review: Asphyxia - Cord Gas Review, Apgar /Outcomes /Brain Development
NeoPREP Planning Committee No Handout
Preterm Brain Injury – Dr. Bonifacio No Handout
Neonatal Seizures – Dr. Wusthoff .................................................................................................... 105
Rapid Review: The Neuro Exam, Neuromuscular Disease, Preterm Outcomes

Dr. Bonifacio No Handout
BONUS SESSION Strategies to Optimize Test Success* – Dr. Savich ........................................ 117

SATURDAY, FEBRUARY 8, 2020
Cardiovascular Physiology of the Fetus – Dr. Brodsky ................................................................ 145
Cardiovascular Hemodynamics in the Newborn – Dr. Brodsky ................................................... 199
Case-Based - CHD Cyanotic Lesions – Dr. Armsby ...................................................................... 213
Case-Based - CHD Non-Cyanotic Lesions – Dr. Armsby .............................................................. 237
Statistics and Research Design – Dr. Weiner ................................................................................ 247
CORE KNOWLEDGE TRACK
ARS CALCULATIONS: Cardiology Case-Based Vignettes – Dr. Armsby and Dr. Brodsky ......... 269
Test your Knowledge - Core Knowledge in Statistics and Research Design – Dr. Weiner ...... 287
BEYOND THE BOARDS PEARLS FOR CLINICAL PRACTICE TRACK
Optimizing Delivery Room Care – Dr. Savich................................................................................. 301
Post Resuscitation Care: The Dilemma of the Baby Who Responds to Resuscitation
Dr. Goldsmith ..................................................................................................................................... 323
Common Areas of Malpractice Exposure for the Practicing Neonatologist – Dr. Goldsmith.... 341
Electrocardiograms and Neonatal Arrhythmias – Dr. Armsby ......................................................... 361

Daily Wrap Up ‐ ARS Review /Q&A – NeoPREP Planning Committee No Handout
BONUS SESSION ‐Visual Diagnosis – Picture Review and High Yield Discussion
NeoPREP Planning Committee No Handout
Maternal and Placental Physiology - Dr. Boggess
February 7, 2020
8:00am-8:40am
Learning Objectives
Maternal and Placental Physiology
• Upon completion, you will be able to
– Understand physiology of maternal adaptation to pregnancy
– Know the morphologic development of the placenta and its role in
gas exchange, oxygenation and fetal energy metabolism
– Understand embryology and physiology of multiple gestations
Kim Boggess MD
Maternal Fetal Medicine
1 3
Disclosures Physiology of Pregnancy
• I have no relevant financial relationships with the • Placenta
manufacturers(s) of any commercial products(s) and/or • Biochemistry
provider of commercial services discussed in this CME activity • Cardiac
• Pulmonary
• I do not intend to discuss an unapproved/ investigative use of a • Endocrine
commercial product/device in my presentation.
2 4
5
February 7, 2020
8:00am-8:40am
Early Placenta Third Trimester Placenta
• Homogenous mass
• Villi covered by two cell layers,
the cytotrophoblast (fetal) and Intervillous
space
syncytiotrophoblast (maternal)
• Two arteries, one vein
– Vein brings oxygenated blood to Villi lined by
fetus syncytiotrophoblast
Fetal vessel
– Arteries bring deoxygenated blood
to placenta
5 7
Early Placenta Third Trimester Placenta
• Discoid
Intervillous
space – Diameter 15‐20 cm; thickness 2.5
cm
– Weight 500 gm (15% fetal weight)
• Implanted in upper fundus 99%
– 2/3rd posterior
– 1/3rd anterior
Villi lined by cyto and
syncytiotrophoblast
6 8
6
February 7, 2020
8:00am-8:40am
Placenta ‐ Fetal Surface Placenta – Maternal Surface
• Smooth and glistening • Dull red color
• Covered with amnion which reflects on to umbilical cord • Divided into 15‐20 cotyledons
insertion • Cotyledon formed of branches of one main villus stem,
• Umbilical cord insertion eccentrically inserted covered by decidua basalis
– Radiating vessels seen coursing under the amnion (veins over
arteries)
9 11
Placenta ‐ Fetal Surface Placenta ‐ Maternal Surface
10 12
7
February 7, 2020
8:00am-8:40am
Fetus Dependent on Placenta Succinturate Placenta
• Development
• Growth
• Hormone production
• Glucose production
• Placental abnormalities can lead to fetal and neonatal
abnormalities
13 15
Placental Abnormalities Circumvellate Placenta
• Size/shape/weight
– Too big/small, too thin; bilobed, succinturate, circumvellate
• Implantation
– Placenta previa
– Bleeding (abruption)
• Adhesion
– Accreta, increta, percreta
• Cord insertion
– Marginal
– Velamentous
14 16
8
February 7, 2020
8:00am-8:40am
Placenta Previa with Accreta Biochemistry
• Hormones
– hCG
– HPL
– Estrogen
– Progesterone
– Cortisol
– Prolactin
17 19
Velamentous Cord Insertion Human Chorionic Gonadotropin
• 2 subunits: similar to FSH, LH, TSH
• Produced by blastocyst, then syncytiotrophoblast
• Predictable rise, peaks ~70 days post conception, then plateau
– Stimulates estrogen/progesterone production in ovary until placenta is
formed (~10th week)
– Suppresses maternal immune function
18 20
9
February 7, 2020
8:00am-8:40am
Human Placental Lactogen Progesterone
• Structure similar to growth hormone • Produced by corpus luteum for first 10 weeks, then
• Produced by syncytiotrophoblast syncytiotrophoblast
– Increases throughout gestation • Increases throughout pregnancy
• Little reaches fetus • Functions
• Function opposite of insulin – Decidualization of endometrium
– Increases lipid utilization, makes glucose available for fetal use, milk – Smooth muscle relaxation
production – Vasodilatation
• Promotes fetal growth – Hyperventilation
– Increased thirst, appetite, fat deposition
21 23
Estrogen Pregnancy Hormones
• Myometrial and endometrial growth
• Growth of alveoli and breast ducts
• Angiogenesis
• Protein synthesis and cholesterol metabolism
• Sodium and water retention
22 24
10
February 7, 2020
8:00am-8:40am
Beyond the Placenta Maternal Cardiac/Circulatory Systems
30% Uterus/Placenta
25 27
Maternal Cardiac/Circulatory Systems Maternal Coagulation
• Increased cardiac output • Increase in red cell mass by 30%
– To promote oxygen delivery
• Fall in systemic vascular resistance
• Increase in pro‐coagulant factors
• Mid‐trimester fall in blood pressure – Factors I, II, V, VII, VIII, X, and Xll
– Designed to maximize blood flow to uterus/placenta • Decrease in anti‐coagulant factors
– Increase in protein C resistance
– Decrease in protein S
– Overall, to promote hemostasis after delivery
• Increase in vascular stasis
26 28
11
February 7, 2020
8:00am-8:40am
Maternal Impact Maternal Respiratory System
• Supine hypotension after ~20 w • Increased minute ventilation
• Physiologic anemia • No change in respiratory rate
• Hypercoaguable state – Designed to promote oxygen delivery to fetus and allow for CO2
– Increased risk for VTE removal
– Promotes hemostasis after delivery • Fall in functional residual capacity
29 31
Fetal Impact Maternal Respiratory System
• Maternal circulation and oxygenation directly effect fetus
– Blood flow to uterus predicts blood flow to placenta
– Placental blood flow predicts fetal blood flow
– Rat and sheep hypoxia models
• Acute maternal hypoxia and fetal anemia change fetal
circulation
– Hypoxia increases flow thru fetal ductus venosus
– Anemia increases cerebral blood flow measures in MCA
30 32
12
February 7, 2020
8:00am-8:40am
Maternal Impact Placental Respiration
• Physiologic hyperventilation reduced PaCO2 (~39 to 31 mm • Impact of maternal biochemical, cardiovascular, and
Hg) pulmonary adaptations
• pH increases slightly to 7.42‐7.44 – Lower maternal bicarb allows for transfer of CO2 from fetus to
mother
• HCO3‐ decreases by ~ 4 mmol/L
– Increased blood flow increases O2 delivery
– Respiratory alkalosis with metabolic compensation
– Increased oxygenation increases O2 delivery
• Pregnant women more prone to hypoxia
• Fetal adaptation to maximize O2 delivery
– Fetal hemoglobin a2g2
33 35
Fetal Impact Oxygen Dissociation Curve
• Allows placenta to act as respiratory organ
Fetus: higher affinity esp at low O2 tension
• Transfer of CO2 from fetus to mother
• Designed for maximum oxygen delivery to placenta and
thus fetus in relatively hypoxic environment
Mother: lower
• Women with severe pulmonary disease have increased affinity due to pH
maternal/fetal morbidity
– FGR in cystic fibrosis, uncontrolled asthma
34 36
13
February 7, 2020
8:00am-8:40am
Maternal Endocrine System Fetal Thyroid
• Hypothalamus, pituitary • Begins to concentrate iodine at 10‐12 wk
• Thyroid
• Hormone synthesis begins 18‐20 wk
• Parathyroids
• Pancreas • Little maternal TSH crosses placenta
• Adrenals • Some maternal T4/T3 crosses placenta
• Ovaries
37 39
Maternal Thyroid Maternal and Fetal Impact
• First trimester cross rxn w hCG • Avoid radioactive iodide after 10 weeks

• Increase in TBG ‐ 2‐3x
– Increased hepatic synthesis • Untreated thyroid disease increases maternal
– Increased sialylation (thyroid storm) and fetal (growth restriction, CNS
• Higher total T4 and T3
– Increased TBG
development) risks
• Lower FT4
• Thyroid stimulation by hCG
• Increased iodide loss in urine
38 40
14
February 7, 2020
8:00am-8:40am
Maternal Pancreas Multiple Gestations
• Adapts to deliver glucose to placenta and fetus
• Increased insulin demand
– Estrogen stimulation of ‐cells of pancreas
– Hypertrophy/plasia of ‐cells
• Glucose major energy substrate for placenta and fetus
– Transport by facilitated diffusion by hexose transporters (GLUT3, GLUT1)
– Placental glucose oxidized to lactate, also used for fetal energy
41 43
Maternal and Fetal Impact Embryology of Twinning
• Glucose intolerance of pregnancy
• Promotes fetal growth
• Delivers glucose to placenta and fetus
– Fetus cannot make its own glucose
– Passive and facilitated diffusion across the placenta
42 44
15
February 7, 2020
8:00am-8:40am
Twin Complications Twin‐Twin Transfusion Syndrome (TTTS)
• Congenital anomalies • Treatment of stage 2 or greater at < 26 weeks with laser ablation
– Monozygote twins – Overall survival ~90%
• Growth restriction – Survival of one twin ~90%
• Preterm birth: 57% < 37 weeks – Survival of both twins ~80%
• Twin‐twin transfusion syndrome (TTTS) ‐ 10‐15% of MoDi • Complications of treatment
– Twin anemia polycythemia syndrome (TAPS) – 30% PROM
– Twin Reversed Arterial Perfusion (TRAP) sequence – 50% PTB
45 47
Twin‐Twin Transfusion Syndrome (TTTS) Twin Anemia Polycythemia Syndrome (TAPS)
• 10‐15% of monochorionic diamniotic twins • Rare complication of monochorionic twins
• 80‐100% mortality if untreated • Variant of TTTS
• Large placental A‐V anastomoses result in uneven blood flow – Smaller vessel A‐V anastomoses
• Donor and recipient twin • Donor and recipient twin
– Donor with decreased blood volume, growth restricted, poor urine • Amniotic fluid volume stays normal
output (oligohydramnios); recipient is hypervolemic, polyhydramnios • Can occur after laser vessel ablation for TTTS
• Stages 1‐5
• Treatment options include serial amnioreduction; selective laser
ablation of anastomoses; selective cord occlusion
46 48
16
February 7, 2020
8:00am-8:40am
TTTS vs TAPS Summary
• Placenta functions as respiratory and excretory organ for fetus
• Maternal physiologic changes occur to support fetal development,
sometimes to maternal detriment
• Optimizing maternal health will optimize fetal and thus newborn
health
• Twin pregnancies > complications than singletons
• Monochorionic twins > complications than than dichorionic
49 51
Twin Reversed Arterial Perfusion (TRAP) Changes in Practice
• Rare complication of monochorionic monozygotic twins • Uncomplicated monochorionic twins should have US at least every
• Normally formed donor (pump) twin 2 weeks from 16 ‐ 34 weeks’ gestation to detect TTTS
• Acardiac recipient twin • Monochorionic twins complicated by selective FGR can be treated
• Treatment by cord occlusion of acardiac twin with laser ablation, cord occlusion, or early delivery
• Follow donor for congestive heart failure • MCA Doppler assessment has essentially replaced amniocentesis
to evaluate for fetal anemia
50 52
17
18
Rapid Review: Maternal Conditions Affecting the Fetus and Newborn - Dr. Boggess
8:40am-9:00am
Maternal Conditions Affecting the Learning Objectives
Fetus and Newborn
• Know the effects on the fetus/newborn of
maternal diabetes
• Know the effects on the fetus/newborn of
selected maternal acute and chronic disease
• Understand the effects of maternal
hypertension and preeclampsia
1 3
Disclosures Diabetes in Pregnancy
• I have no relevant financial relationships with the • Type I (0.2‐0.5% pregnant women)
manufacturers(s) of any commercial products(s) – Maternal risk for DKA
and/or provider of commercial services discussed – Loss of counter‐regulatory glucagon/epi responses
in this CME activity increases risk for maternal hypoglycemia
• Type II (2.7% and expected to double by 2030!)
• I do not intend to discuss an unapproved/ – Insulin resistance
investigative use of a commercial product/device – Inadequate ‐cell response
in my presentation. – Shares many characteristics with gestational diabetes
2 4
19
8:40am-9:00am
Gestational Diabetes Maternal A1c and Fetal Malformations
• 1-14% of pregnant women
• ‘ Abnormal GTT or first recognized during gestation’
• Insulin resistance
• Diminished insulin secretory response
– Usually normal fasting response
– Postprandial hyperglycemia and increased time to reach pre-prandial
glucose levels
• Increased perinatal morbidity

• Increased risk of developing diabetes for both mother and child
5 7
Maternal Diabetes‐Fetal Risks Fetal Risks of Maternal Diabetes
• Pre‐gestational
– Miscarriage
– Congenital anomalies
• 5‐fold risk for heart defects
• CNS, genitourinary
• Pre‐gestational and gestational diabetes
– Preterm birth
– Stillbirth
6 8
20
8:40am-9:00am
Maternal Diabetes‐Fetal/Neonatal Risks Maternal Hypothyroidism
• Fetal growth disturbance/Macrosomia • Hypothyroidism
– Birth trauma Caudal regression
– Operative delivery Hydrocephalus – 0.3‐0.7 %
• Transient hyperinsulinism Neural tube defects
Anencephaly – Autoimmmune thyroiditis (Hashimoto)
• Neonatal metabolic derangements Anal atresia
– Polycythemia Hyperbilirubinemia Situs inversus – Previous treatment for hyperthyroidism
– Hypocalcemia Small left colon
– Hypoglycemia Renal anomalies – Iodine‐deficient goiter
Renal vein thrombosis
• Neonatal RDS • PTB/LBW, placental abruption, preeclampsia
9 11
Maternal Hypothyroidism‐ Effects on
Treatment of Maternal Diabetes
Fetus/Newborn
• Maternal glycemic control • IUGR
– Reduces spontaneous abortions • Neonatal neurocognitive impairment
– Reduces malformations • With appropriate maternal treatment, infants are
– Reduces macrosomia unaffected
– Reduces perinatal morbidity • Goal is to maintain clinical and biochemical
• Death, shoulder dystocia, bone fracture, nerve palsy euthyroid state
– Reduces maternal end‐organ disease • Follow TSH and FT4 in mother
10 12
21
8:40am-9:00am
Maternal Grave’s Disease and Congenital
Chronic Hypertension in Pregnancy
Hyperthyroidism
• 0.2% of pregnancies and neonatal disease in 1‐5% of these pregnancies – • 2%‐6% prevalence
uncommon • Rising due to demographic shifts in maternal age and BMI
• Transplacental passage of TSH receptor‐stimulating Ab and TSH receptor‐
blocking Ab
• If TSH receptor‐stimulating Ab> blocking Ab, will have increased TSH and Complication CHTN RR
transient hyperthyroidism Preeclampsia 25.3% 3‐10
• If TSH receptor‐blocking Ab > stimulating Ab, may develop transient SGA 11.1% 2‐3
hypothyroidism
Abruption 1.5% 2‐3
• Fetus/neonate can be affected even if mother’s Grave’s disease is inactive
because will still be exposed to antibodies Preterm birth 38.0% 3‐4
• Measurement of maternal Ab levels may predict neonatal disease PTB <35 week 18.1% 4‐5
– TSH‐Stim Ab activity >300% and TSH‐Blocking Ab activity >30% predictive Perinatal death 6.2% 3‐5
13 15
Maternal Grave’s Disease and Congenital
Chronic Hypertension
Hyperthyroidism
• In utero – fetal tachycardia, IUGR, goiter, • Low dose ASA for preeclampsia prevention
craniosynostosis, premature birth
• Follow fetal growth by ultrasound
• Postnatally – goiter, tachycardia, CHF, HTN, PPHN,
irritability, FTT, exophthalmos – Dopplers if FGR detected
• Symptoms can last for 3‐12 weeks
• Fetal testing in third trimester to screen for placental
• Maternal treatment
insufficiency
– Propylthiouracil – can cause neonatal thyroid storm
– Methimazole –aplasia cutis with 1st trimester exposure
14 16
22
8:40am-9:00am
Preeclampsia Myasthenia Gravis- Maternal

• Hypertensive disease unique to pregnancy (6‐8%) • 90% with Anti‐Acetylcholine Receptor (AChR)
• 30% severe disease antibodies
• Accounts for ~30% medically indicated preterm births • Leads to post‐synaptic inhibition of
• Poor placentation, high vascular resistance, reduced
neuromuscular transmission
uteroplacental perfusion • Weakness/fatigue of skeletal muscles
• Preterm Pre‐E: impaired fetal growth (IUGR), oligo, • Variable course in pregnancy
thrombocytopenia/neutropenia (decreased production) • Exacerbation 40%, Remission 30%, no change 30%
17 19
Preeclampsia Treatment Myasthenia Gravis –Fetus/Newborn

• Low dose aspirin for prevention • Transient Neonatal MG in 10‐20% of neonates
• No treatment other than delivery born to mother’s with MG
• Role for expectant care • Transplacental passage of IgG AChR‐Abs
– Increases GA • No correlation with severity of maternal
– Increases maternal risk disease
• Mother may be asymptomatic
18 20
23
8:40am-9:00am
Myasthenia Gravis –Fetus/Newborn Maternal Lupus
• Affected neonate often presents within a few hours and • Associated with Lupus anticoagulant,

always signs by day 3 of age; good if no signs by day 6 anticardiolipin antibodies and also
• Generalized weakness, hypotonia, facial diplegia ribonucleoprotein antibodies anti-Ro (SSA)
• Bulbar weakness poor suckling/swallowing, weak cry
• Respiratory muscle weakness may lead to respiratory failure and anti-La (SSB)
• DTRs always present • Increased risk of 1st trimester loss, IUGR
• Most severe: h/o polyhydramnios, arthrogryposis multipex
• Tx: low dose ASA, +/- corticosteroids
21 23
Myasthenia Gravis –Fetus/Newborn Lupus- Affects on fetus/newborn

Diagnosis • Increased risk of congenital heart block
• Maternal history of MG – Risk is independent of severity of maternal dz
• Rapid improvement (15 minutes) after – Greater risk if anti-Ro (SSA) and anti-La (SSB)
administration of acetylcholinesterase antibodies present
inhibitor – May lead to hydrops
Management is supportive and most recover in a
few weeks after birth (average 3 weeks)
22 24
24
8:40am-9:00am
Immune Thrombocytopenic Purpura (ITP) ‐
Maternal PKU
Maternal
• Platelet‐directed Auto‐Antibodies against both • Deficiency of phenylalanine hydroxylase (PAH)
mother’s and baby’s platelets
PAH
• Maternal platelet counts often <150K, but may phenylalanine tyrosine
be normal if h/o splenectomy
• Maternal Ab crosses placenta and destroys • Deficiency of PAH results in accumulation of phenylalanine
fetal/neonatal platelets • This leads to toxic effects in fetus
25 27
ITP – Fetus/Newborn Maternal PKU – Fetal/Newborn

• >50% will have mild thrombocytopenia (100K-150K plt ct) or • Concentration of Phenylalanine in fetal blood is 1.5X that of
normal (>150K) maternal blood because of active placental transport
• 10-30% with plt ct <50K • Maternal blood phenylalanine directly correlated with fetal affects
– Microcephaly (73%)
• Fetal in utero hemorrhage rare, and risk lowered by – IUGR (40%)
interventions provided to mother (splenectomy, IVIG, steroids) – Congenital heart defects (12%)
• Nadir in neonate’s platelet count occurs 2-5 days after birth, – Global developmental delay (90%)
and thrombocytopenia may last for weeks to months – Facial dysmorphism
• Platelet transfusion and IVIG considered for plts <20K or major • If maternal Phe concentrations kept b/n 120‐360µmol/L before
bleeding; +/- corticosteroids if refractory to IVIG conception/8wks, normal or near‐normal outcome for baby
26 28
25
26
High Yield Antepartum Fetal Surveillance - Dr. Boggess
9:00am-9:40am
Antepartum Fetal Surveillance Learning Objectives
– Name antepartum tests used to assess fetal health
– Recognize ultrasound markers of fetal disease
– Identify indications for fetal surveillance
– Understand fetal physiology during labor
– Recognize intrapartum markers of fetal
intolerance to labor
1 3
Disclosures 1st/2nd Trimester Testing

• I have no relevant financial relationships with the • Aneuploidy
manufacturers(s) of any commercial products(s)
and/or provider of commercial services discussed • Structural anomalies
in this CME activity – CNS (ONTD), Abdominal wall via serum
– Other via ultrasound
• I do not intend to discuss an unapproved/
investigative use of a commercial product/device • Metabolic/genetic disorders
in my presentation. – Smith Lemli Opitz, placental sulfatase def
2 4
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9:00am-9:40am
Aneuploidy Testing Aneuploidy Testing
• Second Trimester Serum Marker Screening
• Screening vs. diagnostic testing
– Risk assessment (age, history) TRISOMY 21 TRISOMY 18 TRISOMY 13 MONOSOMY X
– Noninvasive testing (FIRST; NIPS) AFP Low No difference High Low
– Invasive testing (CVS; amnio) hCG High Very low No difference Very high
• Serum analytes Estriol Low Low No difference Low
– 1st trimester: PAPP‐A; inhibin Inhibin‐A High No difference No difference Very high
– 2nd trimester: hcg; AFP; E3; inhibin • Elevated MSAFP ‐ unexplained; ONTD, abdominal wall defects,

placental disease
• Low uE3‐ unexplained, placental sulfatase def, Smith Lemli Opitz
5 7
Aneuploidy Testing Nuchal translucency
• First Trimester Serum Marker Screening
TRISOMY 21 TRISOMY 18/13
Free Beta hCG High Low
PAPP‐A Low Low
6 8
28
9:00am-9:40am
Nuchal translucency Fetal Central Nervous System
Normal
intracranial
image at
BPD level
‐Thalmus
‐Midline
falx
‐CSP
9 11
2nd Trimester Anatomy Ultrasound Fetal Central Nervous System

• Number of fetuses
• Placental location
• Low risk versus high risk anatomy
– Age Normal
– Family history intracranial
– Obstetric history image at
– Screening tests posterior fossa
• Soft markers for aneuploidy ‐Cisterna
– Tri 21‐nasal bone, nuchal skin fold, echogenic intracardiac focus, magna
hydronephrosis, hyperechoic bowel ‐Cerebellum
– Tri 18‐chorioid plexus cysts (1% of all pregnancies, no longer a marker)
10 12
29
9:00am-9:40am
Fetal Central Nervous System Fetal Heart
Normal Normal 4
intracranial chamber
image heart view,
‐Lateral septum
ventricle intact
‐Choroid
plexus
13 15
Fetal Central Nervous System Fetal Heart
Holopros‐ VSD
encephaly
No Midline
Fused
thalamus
14 16
30
9:00am-9:40am
Fetal Abdomen Fetal Abdomen
Normal Gastroschisis
abdomen
with
stomach,
liver
17 19
Fetal Abdomen 2nd/3rd Trimester Tests of Fetal Well‐being
Normal
abdomen,
cord
insertion
18 20
31
9:00am-9:40am
Physiology of Fetal Well Being Fetal Breathing
• Movement • Begins as early as 10 weeks
• Breathing • Correlates with maternal end tidal CO2 pp
• Behavioral coupling – Presence of functional fetal chemoreceptors
• Amniotic fluid volume • Episodic, with periods of apnea
• Growth – Periods of apnea constant 30‐40 wks
• Multivessel doppler blood flow – Dependent on duration of observation
– Umbilical artery/vein, MCA, ductus venosus • Assess fetal health as part of BPP
21 23
Fetal Movement Fetal Breathing
• When does the fetus begin to move?
– Wriggling at 8‐10 weeks
– Total body jumping
– Defined kicking, delicate hand movements and
breathing by early second trimester
– Dramatic decline in kicking with onset of highly
coordinated movements ~34‐38 weeks
• A moving fetus is generally a healthy fetus
22 24
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9:00am-9:40am
Coupled Behaviors Maximum Vertical Pocket
• Heart rate accelerations with movement
– FHT acceleration inferred to prove movement
• Breathing and movement coupled near term
• Existence of fetal BEHAVIORAL STATES
– “activity‐quiescent” cycles ~60 min at term
– Up to 10 movements every 2 hours is considered
reassuring
25 27
Amniotic Fluid Volume Oligohydramnios
• Measure of urine production • Too little fluid
• Maximum vertical pocket MVP reflects amniotic – Depends on gestational age, third trimester MVP < 2 cm
fluid (AF) volume • Placental insufficiency
• AF index by adding up MVP in 4 quadrants • Fetal renal anomaly
• Ruptured membranes
• Reduced urine output a consequence of
hypoxemia, redistribution of blood flow, and • Drug exposure (NSAIDs)
renal hemodynamics • Normal variant
26 28
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9:00am-9:40am
Oligohydramnios Fetal Growth
• Fetal effects depend on gestational age and • Maternal fundal height and weight gain
etiology • Ultrasound biometry
– If severe (and early), contractures, lung hypoplasia • Typically measure every 3‐4 weeks, depending on
– Associated with fetal growth restriction, increased
indication
risk for fetal intolerance to labor, stillbirth • Growth restriction defined as EFW < 10th
percentile; can also have isolated AC < 10th
percentile with normal EFW
29 31
Polyhydramnios Testing Methods
• > 24 cm at > 20 weeks (> 35 cm – severe) • Fetal movement counting
• Screen for diabetes, alloimmunization, • Non‐stress test
– Contraction stress test
infection, structural abnormality (10% if
severe) • Biophysical profile
– Modified BPP
• Increased risk for PTB, stillbirth, perinatal
• Umbilical artery dopplers
mortality (25% if severe)
• Fetal dopplers ‐ MCA, ductus venosus, umbilical vein
30 32
34
9:00am-9:40am
Non‐Stress Test Non Reactive Non‐Stress Test
• Defined norms based on gestational age
– Baseline rate
– Periodic changes
• Accelerations
• Decelerations (early, variable, late)
– ‘Reactivity’: two accelerations of 15 beats lasting
15 seconds (10 beats for 10 seconds if < 32 weeks)
33 35
Reactive Non‐Stress Test What Does Loss of Reactivity Mean?
• High false positive rate
– Sleeping (not moving)
• Medication exposure (opiates)
• Fetal hypoxemia/acidemia
– Other signs of fetal well‐being?
34 36
35
9:00am-9:40am
Early Deceleration Variable Deceleration
37 39
What Do Early Decelerations Mean? What Do Variable Decelerations Mean?
• Vagal response • Typically umbilical cord compression
– Physiologic – Vein compressed first
– Typically due to head compression – Then artery compressed
• 50% ‘false positive’
• If persistent can result in acidemia
38 40
36
9:00am-9:40am
Late Deceleration Biophysical Profile
• Ultrasound assessment
– Breathing
– Movement
– Flexion/extension
– Amniotic fluid
– Non stress test
• 2 points for each parameter
41 43
What Do Late Decelerations Mean? Biophysical Profile
• False positive rate 50% • 8 of 10 = 10 of 10
• Fetal acidosis • Reaction to abnormal dependent on
– Maternal acidosis gestational age and indication for testing
– Poor placental perfusion – 6 or less at term = delivery
• Maternal volume status – 6 at preterm = monitor, retest
• Sick placenta – 4 or less = delivery
42 44
37
9:00am-9:40am
Multivessel Blood Flow Umbilical Artery Dopplers
• Umbilical artery
• Ductus venosus
• Middle cerebral artery
Normal wave form
45 47
Umbilical Artery Dopplers Umbilical Artery Dopplers
• Observational studies show association
between reduced end‐diastolic flow and
increased vascular resistance in feto‐placental
circulation
• Used to assess fetus with growth restriction,
complicated twins
Absent diastolic flow
46 48
38
9:00am-9:40am
Umbilical Artery Dopplers Changes in Practice
• Incorporate information from antenatal surveillance for
prenatal counseling for high risk pregnancies
Reverse diastolic flow
49 51
Indications for Testing
• Maternal indications
– Risk for uteroplacental insufficiency
– Maternal medical disease
• Fetal indications
– Fetal growth restriction
– Fetal diseases (aneuploidy; structural; other)
– Multiple gestation
• Other indications
– Past history
50
39
40
An Intensive Review and Update of Neonatal-Perinatal Medicine
ARS Rapid Review - MFM Potpourri
(No Handouts for this Session – Available Online After the Course)
NeoPREP Planning Committee
9:40am-10:00am
41
42
Labor and Delivery - Case-Based ARS - Dr. Boggess
10:15am-11:00am
Labor and Delivery Cases Learning Objectives
– Understand fetal physiology during labor
– Recognize intrapartum markers of fetal intolerance to labor
Kim Boggess MD – Understand rationale, risks, and benefits of delayed cord clamping
1 3
Disclosures Fetal Surveillance in Labor
• I have no relevant financial relationships with the • Intermittent vs. continuous heart rate
manufacturers(s) of any commercial products(s) and/or • FHR abnormalities related to CP/CNS injury
provider of commercial services discussed in this CME activity • Performed to detect fetal hypoxia
– Associated with lower perinatal mortality but increased surgical
• I do not intend to discuss an unapproved/ investigative use of a intervention
commercial product/device in my presentation. • Wide range of interpretation
• ACOG standardized interpretation in 2009
2 4
43
10:15am-11:00am
ACOG 2009 Category II Tracing ‐ Labor
• Category I: Predictive of normal fetal acid/base balance thus no
action required
– Baseline 110‐160 bpm
– Moderate variability
– No late or variable decels (early may be present or absent)
– Accelerations may be present or absent
• Cat II: Indeterminate tracing ‐ continued evaluation and possible
additional testing
• Cat III: Abnormal tracing that requires immediate attention and
possible intervention.
5 7
Category I Tracing ‐ Labor Intrapartum Monitoring
• Goal is to prevent intrapartum stillbirth and neurologic injury
• Objective is to assess fetal oxygenation
• Understanding intrapartum fetal physiology critical for
monitoring to ‘work’
6 8
44
10:15am-11:00am
Intrapartum Fetal Physiology Fetal Response to Labor
• Labor process decreases fetal oxygen delivery • Fetus normally aerobic metabolism
• Contractions impede intervillous blood flow • Anaerobic metabolism with hypoxia
• Underlying maternal/placental health dictates fetal response – Production of lactic acid
to labor
• Accumulation of lactic acid results in metabolic acidosis; use of
• Interventions in labor can have no effect, promote, or impede buffers
fetal blood flow and oxygenation
– Narcotics • Metabolic acidemia with buffer depletion
– Epidural anesthesia
– Supine position
9 11
Fetal Response to Labor Metabolic vs. Respiratory Acidemia
• Depending on frequency and duration, interruption of oxygen • Normal umbilical (fetal) arterial and venous blood gas values
transfer can cause fetal deterioration – Arterial 7.27/55/‐3
• Begins as hypoxemia (low UA PaO2) – Venous 7.35/40/‐3
– Transient vs. Recurrent/sustained • Metabolic: accumulation of lactic acid
• Progression to hypoxia (low tissue O2 content) – Hypotension, poor tissue perfusion with dysfunction
• Respiratory: accumulation of CO2
– Respiratory not associated with poor outcomes
10 12
45
10:15am-11:00am
Category III Tracing ‐ Labor Intrapartum Monitoring Goal
• Prevent intrapartum stillbirth
• Reduce risk of hypoxic brain injury
– Most CP cases are unrelated to intrapartum events and only minority
preventable with intrapartum monitoring
• January 2003 ACOG/AAP established essential criteria that
define an acute intrapartum event sufficient to cause CP
13 15
Category III Tracing ‐ Labor Criteria to Determine Relation of Labor to CP
• UA pH < 7 and base deficit < 12 mmol/L

• Early onset moderate or several encephalopathy in infant > 34
weeks
• Spastic quadraplegic or dyskinesic CP
• Exclusion of other etiologies
14 16
46
10:15am-11:00am
Complicated Labor Complicated Labor
• Normal labor
– “Friedman” curve
• Prolonged labor
– Underlying cause
– Parity
– Effect on fetus
17 19
Complicated Labor Post Term Pregnancy
• Chorioamnionitis • > 42 weeks 0 days

– Intrauterine Infection or Inflammation or both • Increasing risk for stillbirth as placenta ages
– Maternal fever, tachycardia; fetal tachycardia • Varies by maternal age
– Elevated maternal WBC, amniotic WBC; low glucose; + AF gram stain
• Surveillance with NST/AFI or BPP starting at 41 weeks; delivery
• Associated with adverse maternal and infant outcomes by 41‐42 weeks
– Broad spectrum antibiotic treatment
– Delivery (vaginal not contraindicated)
18 20
47
10:15am-11:00am
Timing of Cord Clamping Labor and Delivery Case 1
• Immediate versus delayed
– Term versus preterm
– How long to delay? At least 30—60 sec
• ACOG Committee Opinion 543 2012 (reaffirmed 2018)
– Term infants benefit from delayed clamping
• Increased hemoglobin at birth, increased early iron stores, ? Better neuro
• Small risk for jaundice requiring phototherapy
– Preterm infants significant benefit from delayed clamping
• Better transition, higher RBC volume, decreased need for transfusion, less
NEC and IVH
21 23
Labor and Delivery Case 1 Labor and Delivery Case 1
35 yo G2P0 with prior unexplained 20 week stillbirth presents at Most likely diagnosis

32 weeks c/o painful contractions and vaginal bleeding. US at 20 1. Preterm labor
weeks normal singleton, no previa. 2. Chorioamnionitis
Vitals: Temp 37.8, BP 100/60, PR 120, RR 18, Oxygen sat 98% 3. Placental abruption
Physical exam: 4. Uterine rupture
Ab: Palpable contractions 5. 1 and 3
Cervix: 4 cm, membranes intact, cephalic presentation
Monitor shows the following:
22 24
48
10:15am-11:00am
Best next step(s) in management:
1. Send labs: CBC, T&C, fibrinogen, Urine tox
2. Start MgSO4 for neuroprotection
3. Hold betamethasone, could still be chorio
4. Based on FHTs take to OR for stat cesarean section
5. All of the above
25 27
29 yo with type 1 diabetes at 36 weeks presents with nausea, Most likely diagnosis

vomiting, and contractions and in triage CBG 340, 3+ ketones. 1. Preterm labor
Vitals: Temp 38.0, BP 120/80, PR 90, RR 28, Oxygen sat 98% 2. Chorioamnionitis
Physical exam: 3. Placental abruption
Ab: Mildly tender, no contractions palpated 4. Maternal diabetic ketoacidosis
Cervix: closed, membranes intact 5. 1 and 3
Monitor shows the following:
26 28
49
10:15am-11:00am
Best next step(s) in management: Amniocentesis performed and shows glucose < 20 and increased

1. Give late preterm betamethasone, she might deliver early
WBCs. Diagnosis of chorioamnionitis is made. The next step(s) in
management is/are:
2. Based on FHTs take to OR for stat cesarean section
1. Immediate delivery by cesarean section
3. Send labs: CMP, serum acetone, urine culture
2. Induction of labor; antibiotics to treat chorio
4. Administer insulin
3. Induction of labor; antibiotics to treat chorio; betamethasone
5. All of the above
4. Induction of labor; antibiotics to treat chorio; betamethasone;
mag sulfate
5. Transfer to MICU due to maternal sepsis
29 31
32 yo G1 P0 at 28 weeks with nausea, vomiting and chills at home. Temp on Induction of labor is initiated and vaginal delivery is imminent.

admission 39C, pulse 130 and respiratory rate 32. Oxygen saturation 92% on
room air. Plan for neonate management immediate at time of birth
PE notable for markedly tender abdomen; closed cervix includes:
Ultrasound shows fetus in cephalic position with normal growth and fluid
Differential diagnosis includes
1. Immediate cord clamping
1. Chorioamnionitis 2. Delayed cord clamping for 30 seconds
2. Pulmonary embolism 3. Placement of IV access for antibiotics
3. Thyroid storm
4. Sepsis 4. Maternal‐infant skin to skin
5. All of the above 5. None of the above
30 32
50
10:15am-11:00am
Fetal indications for delivery by cesarean section include: 29 yo G1P0 at 42 weeks admitted for induction of labor. The

1. Gastroschisis fetus is normally grown, and the MVP is 2.1 cm. Fetus is cephalic.
2. Omphalocele with liver out The patient is resistant to induction because she heard that
Pitocin has been associated with autism. The obstetric provider
3. Omphalocele with liver in has consulted with neonatology to counsel the patient regarding
4. Nonimmune hydrops neonatal risks. You tell her:
5. S1/S2 open neural tube defect
6. All of the above
33 35
Counseling for management of threatened periviable delivery at 22 1. With normal growth and fluid, induction of labor is not warranted

weeks includes all but: 2. Post term infants at 42 weeks have the same birth outcomes as
1. Providing data on neonatal survival at 22, 23, 24, 25 weeks those born at 39 or 40 weeks
2. Recommendation of antenatal corticosteroids for lung maturation 3. If meconium is present at delivery she can expect the obstetrician
3. Option of expectant management/palliative care of infant to perform oropharyngeal suction on the perineum
4. Recommendation to avoid cesarean delivery as it wont improve 4. If infant is vigorous and crying and meconium is present at
survival delivery she can expect the neonatologist to intubate for suction
5. 1 and 3 5. None of the above
34 36
51
52
Rapid Review: Inheritance and Genetic Testing
11:00am-11:30am
53
54
Approach to Evaluating an Infant with Congenital Anomalies - Dr. Northrup
11:30am-12:15pm
Approach to the Infant

with Congenital Anomalies Disclosure Information
Hope Northrup, MD, FAAP, FFACMG -Consulting fees, grant funding and Speakers’ Bureau
Department of Pediatrics compensation from BioMarin Pharmaceuticals
McGovern Medical School -grant funding from National Institute of Health
The University of Texas Health -grant funding from the Tuberous Sclerosis Alliance
Science Center at Houston
1 2
Objectives Etiologies of Congenital

Anomalies
• Explain the concepts of malformation, deformation,
and disruption • Chromosomal imbalances-chromosomal microarray
• Recognize and describe common chromosomal (CMA), FISH and karyotype (chromosomes)
aneuploidies including trisomies 13, 18 and 21 as well • Single gene disorders-gene sequencing and whole exome
as sex chromosome aneupoidies sequencing (WES)
• Recognize and describe several copy number variants • Extrinsic factors-medical hx (mechanical and
(CNVs) and single genes disorders exposures)
• List the components of the hx and PE for the neonate • Multifactorial-family hx
with congenital anomalies • Unknown
3 4
55
11:30am-12:15pm
MORPHOGENESIS MALFORMATION
• Poor organ formation
• Normal
• A defect of organ differentiation
• Abnormal=Anomaly, Dysmorphism
• Associated defects
– Malformation
• Examples
– Deformation
– cleft lip & palate
– Disruption
– congenital heart defects
5 6
MALFORMATION MAJOR
MALFORMATION
• Associated defects
Medical, surgical or cosmetic significance
• Major (significant)
2-3% of all live-born infants have a
• Minor (insignificant) major malformation
7 8
56
11:30am-12:15pm
Cleft Lip & Palate
Rudolf’s Brief Atlas of the Newborn, 1998
9 10
Rudolf’s Brief Atlas of the Newborn, 1998
11 12
57
11:30am-12:15pm
MINOR Transverse Palmar Crease
MALFORMATION
• Medically, surgically or cosmetically insignificant
• 15-40% of healthy people have a minor malformation
• 50% of minor malformation are in the head and neck

region
• May act as clues to genetic disease
13 14
2-3 Cutaneous Syndactyly
cAdapted from Marden

PM, Smith DW,
McDonald MJ: J.
Pediatr 64: 357, 1964.
Figure 4.22.11 D. Diagnostic Dysmorphology; Jon M. Aase, M.D.
15 16
58
11:30am-12:15pm
SYNDROME
Patterns of Anomalies
• Group of anomalies
• Due to a single etiology
• Syndrome • Examples
• Association – chromosomal disorders
• number
• Sequence • structure
– single gene defects
– teratogens
17 18
Trisomy 13 Trisomy 13 Phenotype

• Other craniofacial anomalies
• Also known as – Microcephaly
Patau syndrome – Low set malformed ears
• Incidence of • Midline hernias
1/10,000 –
1/25,000 • Polydactyly of hands and feet
• Craniofacial • Cardiac Anomalies in ~ 80%
anomalies • Polycystic kidneys
– Cleft lip and palate • Brain anomalies
– Micropthalmia
– Bulbous nose
19 20
59
11:30am-12:15pm
Trisomy 13 Phenotype
• Severe neurological impairment, i.e. developmental

delay
• IUGR/Failure to thrive
• Most trisomy 13 conceptions are lost prenatally
• Median Survival
– ~ 2.5 days
– ~ 90% die within first year of life
Rudolph’s Brief Atlas of the Newborn, 1998
21 22
Mneumonics Trisomy 18
• 13 Puberty Patau, Polydactyly, Polycystic kidneys, Punched out
scalp lesions • Also known as Edward syndrome
• Incidence of 1/6000 – 1/7500 live births
• #13 is considered BAD LUCK – More common at conception as ~ 95% of trisomy 18
• Brain (holoprosencephaly, microcephaly, mid scalp lesions conceptions end in miscarriage
• Airs (low set ears) • Fetal Presentation variable as seen with case reports
• Digits (extra digits, polydactyly) • Severe growth impairment
– Prenatal onset
– Failure to thrive after birth
• Leukocytes (unique nuclear projections in the neutrophils)
• Uterus (Bicornate uterus and hypoplastic ovaries) • Profound neurological impairment
– Physical and mental development severely delayed
• Cleft Lip and Palate (Bilateral)
– Hypertonic
• Kidneys (cystic)
23 24
60
11:30am-12:15pm
• Characteristic craniofacial features
– Small ears
– Small mouth
• Short sternum
• Major malformations which may be seen with +18
– Cardiac defects
– Abdominal wall defects
• Inguinal hernia
• Omphalocele
– Diaphragmatic hernia
– Renal anomalies
– GI anomalies
Arthrogryposis – joint Potter’s Atlas of Fetal and Infant Pathology, 1998
– Spina bifida
contractures
Clenched fists also sign of
hypertonicity
25 26
Rocker Bottom Feet Trisomy 18
• Survival compromised
– ~ 50% die within first month
– ~ 10% survive the first year of life
– Apnea is common cause of death
• Recurrence risk < 1%

– There is a maternal age effect with all trisomies
27 28
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11:30am-12:15pm
Mneumonics Common Features of Down Syndrome

Phenotype
• 18  Election  Edwards Upslanting
• 18 year old at a rock concert with clenched fists and palpebral
rocker bottom feet fissures
• Fist clenched for days hypoplastic nails
Brushfield
• He would be drinking too much and too busy rocking back spots
and forth he wouldn’t notice his head banging against the
wall  prominent occiput and low set ears
• He would also be too busy to go to the bathroom resulting
in his kidneys getting bent out of shape  horseshoe
kidneys Single palmar
crease
29 30
Down Syndrome Phenotype

Small mouth
Protruding tongue • Small stature
Epicanthic folds • Increased risk for malformations
– Cardiac anomalies (~40%)
Flat nasal bridge
– Duodenal atresia
Low set ears – TE fistula
Short neck • Increase risk of leukemia (15 fold)
Hypotonic as infants – • Overall life expectancy is shortened as compared to normal
muscle tone improves siblings
with age – Severe heart defects have effect on survival
– Survival well into middle age is much more common now
31 32
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11:30am-12:15pm
Down Syndrome Phenotype Physical Features of DS

• Dysplasia of middle phalanx of the 5th finger (clinodactyly)
• DS patients have developmental and cognitive delay with some • Ouch! Cardiac disease (not a stretch- picture it, it works!)
degree of intellectual disability • Wide gap between the 1st and 2nd toe
• Neck has excess skin in the back
– On average, achieve intellectual development of ~ 8 year old
• Delayed Developmental Milestones • Spots (Brushfield spots in the eye)
– Sitting • Y – Use the letter Y to remind you of the protruding tongue
• Nice transverse palmar crease (can occur in the general population too)
– Walking • Duodenal Atresia (remember the association with Hirschsprung disease)
– Talking • Really extensible joints
– Toilet training • Oncology/ leukemia risk
– All milestones are reached, albeit later than children without Down • Moro reflex is incomplete
syndrome • Ears are small and box-like
33 34
Balanced Robertsonian Translocation

Free Trisomy 21 14;21
• 96% of time
47,XY,+21 • Occurs from
nondisjunction
• Maternal meiosis I
error is by far the
most common
• Associated with
advanced maternal
age >35
• NOT considered
hereditary
• Written report from

lab reads 47,XY,+21
45,XX,der(14;21)(q10;q10)
35 36
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11:30am-12:15pm
Translocation Down Syndrome Indications for Karyotype

(Chromosomes)
Free Trisomy 21 Translocation DS
• 96%
• 4%
• Aneuploidies including Trisomy 21, Trisomy 18 and
• Can be inherited or new in the patient
• Not inherited • 14;21 balanced translocation carriers are at Trisomy 13
increased risk to have a baby with DS
• Associated with advanced
– 10-15% if carrier is female • For suspicion of lethal trisomies (Trisomies 13 and
maternal age
– 0.5-3% risk depending on age
– 1-3% if carrier is male 18), STAT FISH aneuploidy testing obtained at same
• 21;21 balanced translocation carriers have a
100% chance of having a baby with DS time as STAT chromosomes
• This risk is higher than the one associated
with AMA • For suspicion of lethal trisomies, obtain Genetics
• Translocations do run in families Consultation
– Siblings and children of the carrier are at
risk of carrying the balanced form of the
translocation
37 38
45,X (Turner Syndrome) Turner Syndrome Phenotype
• Loss of X chromosome material is

underlying cause of Turner syndrome
• Very common chromosome abnormality phenotype
– Incidence: ~ 1/4,000 live female births • May be detected at birth due to
– Occurs in 1-2 of every 100 conceptions lymphedema of hands and feet
• 99% abort spontaneously by 28 weeks • May be detected in childhood due to
• The remaining 1% survive to term and will be diagnosed short stature
with Turner syndrome • Many detected due to delayed puberty
• Only viable monosomy
39 40
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11:30am-12:15pm
Turner Syndrome Phenotype
• Broad shield shaped chest
• Webbing of neck
– Due to lymphedema in utero
– May be seen as a cystic hygroma on
ultrasound
41 42
Turner Syndrome Phenotype Turner Syndrome Phenotype

• Phenotypic females • Cardiac defects
• Short stature – adult height usually – Coarctation of aorta is common
under 5 feet – Echocardiogram
• Sexual immaturity • Renal Anomalies
– Lack of 2° sex characteristics • Intelligence usually in normal range
– Streak gonads – Learning disabilities may be present
– Non-verbal IQ lower than verbal IQ
– Primary amenorrhea
– College and professional degrees achieved
• Referral to endocrinology for HRT
– May have problems with:
warranted
• Spatial perception
• Fine motor execution
43 44
65
11:30am-12:15pm
Chromosomes of Turner Syndrome Chromosomes of Turner Syndrome

• The most common karyotype observed is loss of the
• Other mosaic karyotypes
entire X chromosome (45,X)
– 45,X/46,XY
– Observed in ~ 50% of cases
• These patients have an increased risk (up to 20%) of
• Approximately 25% of patients are mosaic for other gonadoblastoma if the gonadal tissue remains in the abdomen
cell lines • Extremely important to rule out an XY cell line
– FISH analysis of interphase cells
– 45,X/46,XX is most common
• Phenotypic variation dependent on percentage and distribution of – 45,X/47,XXX/46,XX
abnormal cells • Some patients with a Turner syndrome phenotype have two X
• May see some development of secondary sexual characteristics and chromosomes but one is structurally abnormal
puberty with secondary amenorrhea
45 46
Genomic Resolution
from 10 megabases (Mb) to 1 base pair (bp) Utility of CMA
• Infant-multiple congenital anomalies with no

recognizable syndrome
G banding [> 4 Mb] FISH [40 to 250 kb per clone] • Infant or older child-congenital heart defect with or
without other anomalies
• Remember-in most cases, a CMA will not diagnose a
single gene disorder. A CMA detects deletions and
duplications
SNPs spaced depending on region-more in genes DNA sequence [1 bp]
47 48
66
11:30am-12:15pm
Copy Number Variants (CNV)‐Deletions
• Loss of a part of a chromosome either from the end (terminal) of the arm
4p- Deletion Syndrome
or within (interstitial) the chromosome arm
• Deletions may occur anywhere on any chromosome
– Some areas of the genome more prone to breakage than others • Partial deletion of the short arm of chromosome 4 that
• Factors affecting severity of phenotype include the terminal 4p16.3 region also called Wolf-Hirschhorn
– Size of the deletion syndrome
– Gene content of the missing segment
• Deletions may be visible on a routine karyotype or may require high
resolution chromosome analysis, FISH or Chromosomal Microarray (CMA) • 87% are de novo with 13% of parents representing balanced
for detection translocation
• Occurs 1/50,000
49 50
Clinical Features of 4p- Syndrome
• Dysmorphic features including “Greek warrior helmet”

appearance of nose, high forehead, highly arched
eyebrows, strabismus, eye or optic nerve defects,
ocular hypertelorism, epicanthal folds
• Cleft lip and/or palate
• Single transverse palmar crease
• Heart defects (VSD, ASD, pulmonic stenosis)
• Severe intellectual disability
Rudolph’s Brief Atlas of the Newborn,
1998
51 52
67
11:30am-12:15pm
Chromosome 22 Deletion Syndrome Clinical Features of 22q11

• Microdeletions in the proximal long arm of chromosome 22 are Syndrome
associated with a spectrum of disorders including, but not
limited to: • Phenotype variable
– DiGeorge syndrome • Heart Defect
• Hypoplasia or aplasia of the thymus
– Velocardiofacial syndrome
– Results in T cell deficiency and increased infection
• The common deletion of ~2.5-3.0 Mb in size cannot be seen by • Parathyroid hypoplasia
cytogenetic analysis
– Neonatal hypocalcemia
• Very common deletion occurring in 1/2000 to 1/4000 live
births • Dysmorphic facial features - extremely variable
– May be detected in asymptomatic parent • Learning disabilities
– Degree varies
• Seen in up to 5% of patients with a congenital conotruncal
heart defect
53 54
Clinical Features of 22q11

Syndrome Single Gene Disorders and
Congenital Anomalies
• Cleft palate
• Learning disabilities
• Some have psychiatric problems including • The patient has findings indicating a specific single gene
schizophrenia disorder as the cause for their findings
• Some have familial chromosome translocations • Remember-in most cases, a CMA will not diagnose a
involving chromosome 22 and another chromosome single gene disorder. A CMA detects deletions and
– Important to rule out a translocation by FISH duplications
confirmation after an abnormal CMA
55 56
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11:30am-12:15pm
CHARGE Syndrome CHARGE Syndrome

• Coloboma • Mutation in CHD7 gene located on chromosome 8q12
• Heart abnormalities • Usually a de novo mutation
• Atresia of choanae • Can be inherited: AD
• Retarded growth & mental development
• Genital hypoplasia
• Genetic testing: sequence
• Ear anomalies/ deafness
analysis of CHD7 detect
• Must include 4/6 diagnostic criteria with one being coloboma mutations in 70%
or choanal atresia
57 58
Smith-Lemli-Opitz syndrome Smith-Lemli-Opitz syndrome

• Deficiency of 7-dehydrocholesterol reductase
• prenatal and postnatal growth retardation,
microcephaly, moderate to severe intellectual • Inheritance: AR
disability
• malformations include distinctive facial features • Testing: elevation serum
(narrow forehead, epicanthal folds, ptosis, short 7-dehydrocholesterol, may be
mandible, short nose, anteverted nares, and low-set normal in 10%
ears), cleft palate, cardiac defects, underdeveloped Sequence analysis of DHCR7
external genitalia in males, postaxial polydactyly, and detects approximately 96%
2-3 syndactyly of the toes
of known mutations
59 60
69
11:30am-12:15pm
ASSOCIATION VACTERL association

• Vertebral anomalies
• Anal anomalies
• Congenital heart disease
• Group of malformations • Tracheoesophageal fistula
• Frequently found together (nonrandom) • Esophageal atresia
• Examples • Radial and/or renal anomalies
– VATERR/VATER/VACTERL • Limb defects
• Usually have 5+ anomalies
61 62
VACTERL association
• Nonrandom association of anomalies
SEQUENCE
• Not genetically linked, diagnosis of exclusion
• Normal karyotype • Group of anomalies
• Arise secondary to an initial malformation
• Examples
– Potter sequence
– holoprosencephaly sequence
63 64
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11:30am-12:15pm
DEFORMATION
• Normal tissue
Figure 2. Smith’s
Recognizable
• Acted upon by mechanical forces (extrisic and
Patterns of Human
Malformation, 5th
intrinsic)
• Examples
Edition; Kenneth
Lyons Jones, M.D.
– abnormal uterus
– multiple gestation
– abnormality of prerequisite structure
65 66
DEFORMATION
• 2% of Newborns have deformations
–Club feet
–Potter Facies
–Plagiocephaly
• Most have a good prognosis
67 68
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11:30am-12:15pm
Plagiocephaly DISRUPTION
• Normal tissue
• Acted upon by a destructive force
• Examples
– amniotic bands
– teratogens
69 70
Amniotic Band Sequence Infant of Diabetic Mother

• Impaired fetal growth
• Transient tachypnea of the newborn, RDS
• Hypoglycemia
• Hyperbilirubinemia
• Cardiomyopathy with ventricular hypertrophy and outflow
tract obstruction
• CNS malformation, caudal dysplasia
• Renal agenesis, hydronephrosis
• Duodenal or anorectal atresia, small left colon syndrome
71 72
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11:30am-12:15pm
Toxoplasmosis:
Hydrocephalus Fetal Alcohol Syndrome
• PE reveals microcephaly, short palpebral fissures, short

nose, smooth philtrum with thin upper lip, growth
deficiency (prenatal and postnatal onset)
• Occurs ~1-2/1,000 livebirths in US
• Average IQ 65 with range 20-120
• Heart murmur with VSD or ASD in some
73 74
Evaluating the Neonate with

Congenital Anomalies
• History
• Physical Exam
• Diagnostic Tests
• Consultations
Human Malformations &

Atlas of Pediatric Physical Related Anomalies, 1993
Diagnosis, 1994
75 76
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11:30am-12:15pm
Pregnancy history Family history
• Prenatal care • Pedigree

• History of consanguinity.
• Maternal diseases: diabetes, epilepsy
• Occurrence of any of the following:
• Medications and other exposures
- birth defects
• Social history: smoking and alcohol - intellectual disability
• Infections, immunizations, rubella titers - early infant deaths
• Nutritional status - miscarriages
77 78
Why make the diagnosis? Causes of Birth Defects
• Answers the family’s major question: What is wrong with my

child?
• Suggests prognosis and outcome
• Suggests appropriate medical management
• Provides genetic counseling: recurrence risks estimation,

prenatal diagnosis, identifies other family members at risk,
reproductive options
79 80
74
Approach to the Infant with Congenital Anomalies-Recognize that Disorder and Order the Correct Test - Dr. Northrup
1:15pm-2:00pm
Recognize that Disorder

and Order the Correct Disclosure Information
Test
-Consulting fees, grant funding and Speakers’ Bureau
Hope Northrup, MD, FAAP, FACMG compensation from BioMarin Pharmaceuticals
Department of Pediatrics -grant funding from National Institute of Health
McGovern Medical School -grant funding from the Tuberous Sclerosis Alliance
The University of Texas Health

Science Center at Houston
1 2
Learning Objectives What Is the Question?

• Explain the different types of genetic tests • Newborn with a constellation of symptoms that are part
(chromosomes, FISH, CMA, gene panel, and WES), the of a known syndrome?
information provided by each test and which test to • Newborn with multiple congenital anomalies?
order depending on clinical presentation. • Newborn with a suspected diagnosis of a single gene
disorder? Known versus unknown?
• Know the clinical features and inheritance patterns
some of common syndromes or associations that can be • Concern specifically for metabolic disease (inborn error
recognized in the newborn period. of metabolism)?
3 4
75
1:15pm-2:00pm
Genomic Resolution
from 10 megabases (Mb) to 1 base pair (bp)
Chromosomal Microarray (CMA)
• Enables identification of DNA deletions and
duplications across the entire genome at once
• Can be performed on samples that cannot be
G banding [> 4 Mb] FISH [40 to 250 kb per clone]
utilized to perform karyotype (e.g. postmortem
tissue)
• It is essentially the performance of thousands of
FISH analyses at once
CMA [~ 20 oligos (60 mers)/FISH verified BAC clone] DNA sequence [1 bp]
5 6
Most of the Time If No Specific Diagnosis Order Karyotype

Is Under Consideration …
(Chromosomes) When…
• Order chromosomal microarray analysis • Suspicion for a aneuploidy e.g. Down
(CMA) syndrome (Trisomy 21), Trisomy 13 or
• REMEMBER: Diagnosis of a single gene Trisomy 18, Turner syndrome
disorder cannot be made by CMA because • Because you need to know how the extra
CMA only detects deletions and duplications
genetic material is arranged
7 8
76
1:15pm-2:00pm
Why Are Chromosomes Still Important? Single Gene Disorders
• Disease caused primarily by malfunction of 1

• Other testing doesn’t tell us order! gene out of the 20,000
• In Down syndrome, we need to know order i.e. • Either, having one of your two copies of the gene
free Trisomy 21 v. translocation Trisomy 21 mutated gives you the disease (autosomal
• Balanced translocations can only be detected dominant) or having both copies mutated gives you
with chromosomes the disease (autosomal recessive)
9 10
Options for Suspected Single Gene

Single Gene Disorders
Disorders
• Order testing for the specific gene that causes the
• Gene changes are much more subtle than disorder-only useful when there is only one causative
those detected by CMA gene ie cystic fibrosis
• A specific disease and associated gene must • Order a panel to test for all genes known to cause a
be considered specific disorder ie Noonan syndrome, Cornelia de
• DNA Testing is sent to check the sequence of Lange syndrome
the actual gene • Order whole exome sequencing (WES) when
differential includes multiple possibilities or you just
don’t have a clue!
11 12
77
1:15pm-2:00pm
Suspected Inborn Error of Metabolism Case #1
• Newborn who is completely unremarkable then • You are called to a delivery of a baby boy at 33
decompensates after feeding for a short time weeks gestation
• Term baby, normal size, not dysmorphic • When the baby is born, you note: rocker bottom feet,
• Crashes with hypoglycemia, hypothermia, clenched fists (trisomy salute), other apparent joint
hyperammonemia, lactic acidosis, etc contractures, grade IV/VI heart murmur, and growth
retardation resulting in SGA
• Obtain biochemical testing STAT • distinct facies including small upturned nose, low-set
• Testing to include plasma amino acid analysis (PAAs), and malformed ears and prominent occiput
urine organic acid analysis (UOAs), acylcarnitine profile
(ACP)
13 14
What Do You Order First? Rapid Aneuploidy FISH Panel
A. Rapid aneuploidy FISH panel • The FISH panel is performed on non-dividing

interphase cells from uncultured sample
B. CMA • Thus, results can be available in 24 hours
– no cell culture necessary
C. Karyotype (Chromosomes) • This panel contains probes for chromosomes
21 13
13, 18, 21, X & Y
D. Metabolic panel (PAAs, UOAs, ACP) 18
• A normal FISH result for a male fetus shown
E. Noonan syndrome gene panel at the right X
Y
• Normal female fetus has two green
signals for X and no orange Y signal
15 16
78
1:15pm-2:00pm
Rapid Aneuploidy FISH Results

for Case 1 What do you reflex to from this rapid
• The following result aneuploidy FISH?
• Two signals for chromosome 21
• Two signals for chromosome 13
• Three signals for chromosome 18 A. WES
• One signal for X and one signal for Y B. CMA
• FISH indicates the presence of trisomy 18 or at C. Karyotype (Chromosomes)
least a part of chromosome 18
• A karyotype must still be obtained to verify
D. Metabolic panel (PAAs, UOAs, ACP)
the results and determine exact nature of E. Noonan syndrome gene panel
abnormality
• Rare occasions of false positive and false
negative results by FISH
17 18
Result Case #1
What do you reflex to if aneuploidy FISH
is negative?
A. WES
B. CMA
C. Karyotype (Chromosomes)
E. Methylation studies for Prader-Willi syndrome
47,XY,+18
19 20
79
1:15pm-2:00pm
Case #2
Case 2
• You admit a baby whose mother is 40 YO

• The baby is hypotonic
• You perform the PE (shown next)
• You hear a murmur so you obtain an
echocardiogram
• The baby has an A-V canal
21 22
Case #2 Results
What Do You Order?
A. Rapid aneuploidy FISH panel

B. CMA
D. Methylation studies for Prader-Willi syndrome
E. WES
23 24
80
1:15pm-2:00pm
Case # 3 What Do You Order?

• You have a term baby girl followed by your team
A. FISH for 22q11
who has tetralogy of Fallot and seizures with
normal calcium levels B. CMA
• You are concerned about DiGeorge syndrome C. Cornelia de Lange syndrome gene panel
(22q11 deletion syndrome) D. Metabolic panel (PAAs, UOAs, ACP)
• What do you order? E. WES
25 26
Results for Case #3 Case #4

• CMA comes back revealing a diagnosis of chromosome
1q21.1 duplication syndrome • A term baby presents at 44 hours of life with
• For congenital heart disease (CHD), the cardiac arrest
recommendation is CMA NOT FISH for 22q11 deletion • Work up reveals profound hypoglycemia
syndrome
• Baby is normally grown and not dysmorphic
• Price is similar and CMA will reveal any CNV associated
with CHD • The parents are first cousins
27 28
81
1:15pm-2:00pm
What Do You Order First? Results for case #4
• Plasma amino acids-normal; amino acids should be

A. DNA methylation studies for PWS present in certain amounts to allow for cellular
B. CMA turnover; greater elevations are c/w disease
C. Karyotype (Chromosomes) • Urine organic acids-normal; should not be present;
their presence indicates disease
• Acylcarnitine profile (ACP)-abnormal with C12-C18
E. WES elevated most c/w VLCAD to CPTII; helps detect fatty
acid oxidation defects (FAOs)
29 30
What Do You Order Next? Case #5

• a term newborn in the NICU presents with
A. WES meconium ileus
B. CMA • PE is unremarkable
C. Karyotype (Chromosomes) • first child of a Caucasian couple who are in their
D. Gene testing for VLCAD and CPTII 20s
E. Noonan syndrome gene panel • Parents are of Germanic ancestry
• No one else in the family has similar findings
31 32
82
1:15pm-2:00pm
What Do You Order? Result for Case #5
A. WES • The patient is homozygous for the delta F508

B. CMA pathogenic variant in CFTR
D. Metabolic panel (PAAs, UOAs, ACP) • Remember-in most cases, a CMA will not usually
diagnose a single gene disorder; CMA detects deletions
E. Single gene testing of the CFTR gene (causative and duplications usually including multiple genes
gene for cystic fibrosis)
33 34
Case #6 What Do You Order?

• A term male baby is born with who presents with
respiratory distress syndrome requiring intubation A. WES
• Baby is microcephalic and mildly dysmorphic with low- B. CMA (correct answer)
set ears, pointed helices and flat nasal bridge
• PE reveals mild hypotonia and a murmur
D. Gene testing for VLCAD and CPTII (correct
• Cardiac echo reveals Ebstein’s anomaly answer)
• Pregnancy and family history are unremarkable
E. Noonan syndrome gene panel
• On DOL#6, baby presents with seizures that are easily
controlled with AEDs
35 36
83
1:15pm-2:00pm
Results for Case #6 Case #7

• CMA is positive for chromosome 1p36 deletion • A term baby is born with severe hydrops
syndrome
• Respiratory distress is present
• 1p36 deletion syndrome has an extremely variable
• Baby is not dysmorphic
phenotype
• Dysmorphic features can include: low set ears, • Baby also found to have duodenal atresia
microcephaly, midface hypoplasia, flat nasal bridge, • CMA is normal
asymmetric ears and pointed chin • This falls under the “There is a wide differential
• Patients can have a variety of different heart defects, diagnosis for single gene disorders and I really don’t
hypotonia, seizures and varying degrees of ID have a clue as to which one”
37 38
What do you Order? Results for Case #7
A. WES • The baby has biallelic pathogenic variants in the gene

B. Cornelia de Lange Syndrome (CdLS) gene panel for Morquio syndrome type A
D. Metabolic panel (PAAs, UOAs, ACP) • There were multiple possibilities, particularly among the
lysosomal storage diseases (ie infantile Gaucher, Slye
E. DNA methylation for PWS syndrome, Niemann pick type C, etc) so WES was a
good choice
39 40
84
1:15pm-2:00pm
Case #8
What Do You Order?
• a baby is born who is quite
dysmorphic including synophrys
(unibrow), long curly eyelashes, A. WES
upturned nose, downturned
mouth
B. CMA
• The baby has bilateral radial ray C. Karyotype (Chromosomes)
abnormalities and a heart defect D. Metabolic panel (PAAs, UOAs, ACP)
• The baby is very small on all E. Cornelia de Lange Syndrome gene panel
growth parameters
41 42
Case 9
Case #9
• A baby is born who sadly died within 30 minutes

• This is the first child of the parents and they are
heartbroken abnormal teeth
• The x-rays enable you to make a diagnosis of

lethal infantile osteogenesis imperfecta (OI)
easy bruising
43 44
85
1:15pm-2:00pm
What Do You Order? Results for Case #9
A. WES • Sequencing is positive for biallelic pathogenic

B. CMA variants in the CRTAP gene, allowing you to refine
C. Karyotype (Chromosomes) your diagnosis to OI type VII
• By determining that the baby had a recessively
D. Metabolic panel (PAAs, UOAs, ACP) inherited form of OI, the parents now know their
E. Osteogenesis imperfecta (OI) gene panel recurrence risk is 25% with each pregnancy
• The parents now have prenatal or preimplantation
genetics (PGD) options to avoid this tragedy
recurring
45 46
Case #10 What Do You Order?

A. WES
• A baby is born at an outside hospital is transferred to B. CMA
your NICU intubated
• The baby is term and normally grown but profoundly
hypotonic D. Metabolic panel (PAAs, UOAs, ACP)
• Other than the neurologic exam, PE is unremarkable E. DNA methylation for PWS
• Specifically, the baby is not dysmorphic
• Once the baby is extubated, the baby has difficulty
feeding
47 48
86
1:15pm-2:00pm
You decide to add another test on the

Case #10 baby?
• While the DNA methylation studies for PWS are A. WES
pending, you meet the parents
B. CMA
• The mother has a history of infertility
• The mother had polyhydramnios during the pregnancy C. Karyotype (Chromosomes)
• The maternal family history includes: several D. Metabolic panel (PAAs, UOAs, ACP)
individuals with cataracts, several female members in E. Triplet repeat expansion testing of the DMPK
addition to the mother who had infertility gene for myotonic dystrophy type 1
• you notice that the mother has an expressionless face,
ptosis and has difficulty letting go when you shake her
hand
49 50
Results for Case #10
• PWS methylation studies are normal

• The triplet repeat expansion testing reveals 2,000
CTG repeats in the baby
• you can now inform the family that the mother is also
affected, explaining her findings of infertility and
muscle weakness
• The couple has a 50% recurrence risk in future
pregnancies.
51
87
88
Term Brain Injury and Pathophysiology of HIE - Dr. Wusthoff
Friday, February 7, 2020 - 2:00pm-2:50pm
Learning Objectives
Upon completion of this session, the learner should be able to:

Neonatal Brain Injury 1. Provide a differential diagnosis for neonatal encephalopathy
2. Describe the clinical and neuroimaging features of hypoxic-ischemic
Courtney Wusthoff, MD MS
brain injury
Associate Professor
Neurology & Neurological Sciences and by courtesy,
3. Describe current standards for treatment of hypoxic ischemic
Pediatrics- Neonatal and Developmental Medicine
encephalopathy (HIE)
Stanford University 4. List common presenting signs of perinatal stroke
Disclosures Acknowledgements
I have the following financial relationships with the manufacturer(s) of Miriam Martinez-Biarge
any commercial product(s) and/or provider(s) of commercial services: Frances Cowan
Sonia Bonifacio
• Consultant for: Ceribell, Persyst
• I do not plan to discuss unapproved (off-label) use of devices or

medications in my presentation
89
Outline Neonatal Brain Injury Includes a Variety of Conditions
• Acquired brain injury

• Neonatal Encephalopathy • Hypoxic ischemic encephalopathy (HIE)
• Hypoxic Ischemic Encephalopathy • Most common cause of CP in term neonates
• 1-2 per 1000 term births
• Stroke • Intraventricular hemorrhage
• Most common neurologic complication of prematurity
• 25-35% of VLBW (<1500g) infants; about half are grade 3-4
• Ischemic Stroke
• Subdural hemorrhage
• Kernicterus, infection, hypoglycemia, PVL
• National Neonatal Research Database
• Overall rates of brain injuries- 4.53-5.19 per 1000 live births
• Preterms- 25.88 per 1000
• Terms- 3.47 per 1000
15. Neurology/C.Encephalopathy Gale C et al. ADC Fetal Neo 2018
Outline Neonatal Encephalopathy Describes a Clinical Picture
• Neonatal Encephalopathy • Neonatal Encephalopathy

describes a clinical picture
• Hypoxic Ischemic Encephalopathy
• Encephalopathy =
• Stroke abnormal brain function
• Typically floppy
• May have poor/absent suck
• Poorly responsive
• Hypotonia often goes with
encephalopathy, but is not
the same thing
15. Neurology/C.Encephalopathy
90
The Modified Sarnat Scale is Used to Diagnose Neonatal Encephalopathy Outline
• Neonatal Encephalopathy
• Hypoxic Ischemic Encephalopathy
• Stroke
Shankaran et al,
NEJM, Oct 2005
15. Neurology/C.Encephalopathy/1.Know the causes, clinical features, evaluation, and management of

hypoxic- ischemic encephalopathy
Neonatal Encephalopathy Includes Several Specific Etiologies Not All Neonatal Encephalopathy is Hypoxic Ischemic Encephalopathy (HIE)
NEONATAL • Not all neonatal encephalopathy is HIE

ENCEPHALOPATHY
• Hypoxic-Ischemic Encephalopathy (HIE) is
Stroke brain injury due to lack of blood/oxygen
flow to brain
Genetic
Brain
malformation • Leading cause of disability in resource limited
Metabolic
settings
HIE • 15-20% affected die in newborn period
• >25% of survivors with neurodisability
• Therapeutic hypothermia has become
Infection/Sepsis standard of care for HIE

15. Neurology/C.Encephalopathy hypoxic- ischemic encephalopathy
91
HIE Usually has Multifactorial Etiologies Case 1
• HIE occurs in the setting of maternal factors, Conception Antepartum Intrapartum Neonatal • 39 y/o G5 P2, uncomplicated pregnancy
intrapartum events, and/or postnatal IVF/ART Infection Cord prolapse Respiratory • Baby born at 37 +5 weeks, emergency c/s for FHR decelerations
complications. arrest
• Infant found free floating in abdomen with ruptured uterus
Toxins Toxins/drugs Uterine Infection
• Not all injury is preventable “birth asphyxia” rupture • Cyanotic, floppy, apneic
• only 4% of infants with neonatal encephalopathy Maternal age Glucose/GDM Shoulder Hypoglycemia • Apgars 0, 3, 3, 3, 6
had intrapartum hypoxia alone. dystocia
Primips Pre-eclampsia Feto maternal CV instability
• Cord gas 6.9, First VBG: 7.03/54/14/-17.4
• Nonetheless, MRI studies suggest the majority hemorrhage • Intubated at 3 minutes
of infants sustain brain injury at or near the Mechanical Severe
time of birth. injury placental
• Responded to PPV but remained limp for 15-20 minutes
abruption
Anemia Amniotic fluid
embolus
• Does this baby have neonatal encephalopathy?
Hankins GD. Obstet Gynecol 2003.
Cowan F et al. Lancet 2003. Fetal size Maternal code • HIE?
Wu YW et al. Pediatrics 2004
15. Neurology/C.Encephalopathy/1.Know the causes, clinical features, evaluation, and management of 15. Neurology/C.Encephalopathy/1.Know the causes, clinical features, evaluation, and management of
hypoxic- ischemic encephalopathy hypoxic- ischemic encephalopathy
ACOG & AAP Define HIE by Multiple Criteria, Emphasize Multiple Pathways Case 2
• Apgar <5 at 5 and 10 minutes • Term baby born to 26 y/o G1P0, late prenatal care
• Fetal umbilical artery acidemia • Preterm labor at 33 weeks, treated with Mg
• pH <7.0 or BD >12 • Spontaneous labor at term, vacuum delivery
• MRI or MRS evidence of acute • Tight nuchal cord, meconium
HI brain injury • Baby born floppy, pale, apneic
• MRI at 24-96hrs most sensitive
for timing
• MRI at 10 days (b/w 7-21 days) • Does this baby have neonatal encephalopathy?
best shows full extent of injury
• Does this baby have HIE?
• Presence of multi-organ injury
2014 Task Force on Neonatal Encephalopathy
92
Therapeutic Hypothermia (TH) is the Standard of Care for HIE Careful Examination Identifies TH Candidates
• TH initiated within 6 hours of delivery proven to Normal Mild
Encephalopathy
Moderate
Encephalopathy
Severe
Encephalopathy
reduce risk of death or disability after moderate or Ferreiro, NEJM 2004 Level of
consciousness
When awake, alert, fixes Irritable, hyperalert, poor Lethargic
on visual stimuli feeding, excess crying (see example)
Stupor or coma
severe HIE (see example) alternating with sleeping
Spontaneous Frequent spontaneous Increased, jittery Decreased activity No activity

• NNT is ~ 6 to prevent neurodisability activity movements
(see example)
(see example) (see example)
Posture Extremities flexed in Slight flexion, slight Distal flexion, complete Decerebrate
• Late Hypothermia: 76% probability of reducing risk toward the trunk
(see example)
extension
(see example)
extension
(see example)
of death/disability, but effect may be modest Tone Normal
(see example)
Normal or slightly
increased
Hypotonia (focal
or general)
Flaccid
(see example)
(see example) (see example)
• Optimizing Cooling trial stopped early because of Primitive reflexes Strong coordinated suck Uncoordinated Weak or unsustained Absent
(see example) (see example) (see example)
worse outcomes with longer and/or deeper cooling Suck
Complete moro Exaggerated Incomplete Absent
Primitive reflexes
(see example)
• Preemie Hypothermia trial is ongoing Moro
Autonomic system Reactive Dilated Constricted Deviated, dilated, or
nonreactive to light
• No RCT for hypothermia in mild HIE yet Pupils
Autonomic system Normal Tachycardia Bradycardia Variable (heart rate is not
constant and varies
Laptook et al. JAMA 2017;318(16):1550-1560 Heart rate widely)
Shankaran et al. JAMA 2017;318(1):57-67. Autonomic system Normal Regular Periodic breathing Apnea
Respiration
https://people.stanford.edu/wusthoff/
Earlier Therapeutic Hypothermia (TH) is More Effective

hypoxic- ischemic encephalopathy
93
Evaluation of Suspected HIE Clarifies Diagnosis and Identifies

Neuroimaging is Useful for Diagnosis and Prognosis in HIE
Comorbidities
Differential Diagnosis Evaluations • Cranial Ultrasound

+ Readily available, non-invasive
Sepsis/Infection CBC, Cx, CRP, etc. ± User-dependent
Metabolic Encephalopathy Glucose, Metabolic Panel, lactate, ammonia, +/- • Doppler measurements of cerebral blood flow
aid accuracy
IEM screen
• CT
Genetic Etiologies Exam, History, CGH/WES – Radiation
Neuromuscular Disease Exam, CK • MRI
+ Highest quality images
HIE Lactate, blood gas, CK, LFTs, BUN/Cr, Imaging – Sedation sometimes required
– Specialized interpretation
Seizures EEG/aEEG
15. Neurology/C.Encephalopathy/1.Know the causes, clinical features, evaluation, and management of 15. Neurology/C.Encephalopathy/1. Hypoxic-Ischemic/3. Know the neuroimaging features of hypoxic-
hypoxic- ischemic encephalopathy ischemic injury in term infants
EEG/aEEG Assesses Encephalopathy and Identifies Seizures Cranial Ultrasound Findings Evolve in a Typical Pattern in HIE
•~40% of babies cooled for HIE have • Serial CUS over first 4 days most
seizures in the first 72 hours after birth helpful
• 80-90% of neonatal seizures have
• Edema often peaks at 24 hours
no clinical correlate
• Seizure medications cause • Single CUS in the first week is
“uncoupling” in 50% reported normal in 50% of neonatal
•Monitoring for seizures is recommended HIE
by the AAP, ACNS • Doppler ultrasound for resistive index
•cEEG is the gold standard for seizure
(or pulsatility index) increases
detection
sensitivity and specificity
•aEEG is a useful adjunct or alternative
where cEEG is limited
Stark & Seibert, J Ultrasound Med 1994
Babcock & Ball, Radiology 1983
Lara M. Leijser, Linda S. de Vries, Frances M. Cowan. Early Human Development, Volume 82, Issue 12, 2006, 827–835
15. Neurology/C.Encephalopathy/1.Know the causes, clinical features, evaluation, and management of 15. Neurology/C.Encephalopathy/1. Hypoxic-Ischemic/3. Know the neuroimaging features of hypoxic-
hypoxic- ischemic encephalopathy ischemic injury in term infants
94
MRI is Essential for Evaluation of Suspected HIE Certain MRI Patterns are Highly Predictive of Outcome
•Reasons to MRI
•Clarify timing/etiology
• Severity of BGT injury is most predictive of
severity of motor impairment.
•Confirm diagnosis
• Mild = 11% risk of CP, usually mild
•Aide in prognostication
• Moderate = 69% risk of CP
•Early MRI • Severe = 98% with CP, usually severe
•Ideally day 5-21 after injury in term babies
•Diffusion changes present 7-10 days, then
• Injury to the PLIC most predictive of
“pseudonormalise”
walking at age 2.
•Day 8-30 MRI has higher sensitivity for poor outcome,
• Normal = all walk by 2 years
but lower specificity than day 1-7
• Equivocal = 67% walk, but after 18 mos
•Lactate/NAA on MR Spectroscopy is 91-94% sensitive • Abnormal = 12% walk
and specific
Rutherford et al, Lancet Neurology 2010, Wintermark et al, ADC Fetal Neonat 2010.
•MRI useful even if baby is cooled Thayyil et al, Pediatrics 2010. Martinez-Biarge et al, Early Human Development 2010, Neurology 2011.
15. Neurology/C.Encephalopathy/1. Hypoxic-Ischemic/3. Know the neuroimaging features of hypoxic- 15. Neurology/C.Encephalopathy/1. Hypoxic-Ischemic/2. Know the outcome of infants with hypoxic-
ischemic injury in term infants ischemic encephalopathy & 3. Know the neuroimaging features of hypoxic-ischemic injury in term infants
HIE Causes Typical Patterns of Injury on MRI
• Basal Ganglia and Thalami (BGT)

• Particularly susceptible to injury in acute,
profound HIE
• Serve as a “relay station” for the brain
• Posterior Limb of the Interior Capsule (PLIC)
• Dense motor pathway running through the BGT
• Extremely age-dependent
• Brainstem
• Involved more often in preterms or severe injury
• Cortex and White Matter
• May be solely affected in milder HIE
• “Watershed” pattern in partial/prolonged HIE
& - !*- Ѷ /'ѵ $/-$.сппчѶ*)$!$* Ѷ /'ѵ .спррѶ-/$) 5$-" -'4 0( 1спрп
15. Neurology/C.Encephalopathy/1. Hypoxic-Ischemic/3. Know the neuroimaging features of hypoxic- c/o Frances Cowan
ischemic injury in term infants
95
Two newborns with HIE Certain MRI Patterns are Highly Predictive of Outcome
Moderate BGT Injury:10-15%

mild to mod CP
Equivocal PLIC: Abnormal PLIC:

CP 60% (Mild in ¾) CP 75% (Mod. or severe)
2/3 walk 1/5 walk
Speech/
Feeding: 40% Vision:
Lang: DQ:
feeding 20-55%
25% severe >70 in 35%
problems impairment
problems
Martinez-Biarge et al, Early Human Development 2010, Neurology 2011.

15. Neurology/C.Encephalopathy/1. Hypoxic-Ischemic/2. Know the outcome of infants with hypoxic-
ischemic encephalopathy & 3. Know the neuroimaging features of hypoxic-ischemic injury in term infants
Certain MRI Patterns are Highly Predictive of Outcome Certain MRI Patterns are Highly Predictive of Outcome
Mild BGT Injury:10-15%

mild to mod CP Severe BGT Injury:
98% CP (almost all severe)
Normal PLIC: Equivocal PLIC:

walking by 2 years 2/3 walking by 2 years
Speech/
Feeding: 90% Vision: DQ:
Speech/ Lang:
Feeding: DQ:
with feeding 50-75% with Difficult to
Lang: Vision: 95% affected,
10% mild >84 in 80%
problems impairment assess
25% rare most severe
feeding and
speech impairment
problems >70 in 90%
problems
Martinez-Biarge et al, Early Human Development 2010, Neurology 2011. Martinez-Biarge et al, Early Human Development 2010, Neurology 2011.
15. Neurology/C.Encephalopathy/1. Hypoxic-Ischemic/2. Know the outcome of infants with hypoxic- 15. Neurology/C.Encephalopathy/1. Hypoxic-Ischemic/2. Know the outcome of infants with hypoxic-
ischemic encephalopathy & 3. Know the neuroimaging features of hypoxic-ischemic injury in term infants ischemic encephalopathy & 3. Know the neuroimaging features of hypoxic-ischemic injury in term infants
96
Outline Perinatal AIS is Fundamentally Different than Adult Stroke

• 1:3000 term births
• Neonatal Encephalopathy • Nonspecific Presentation
• Hypoxic Ischemic Encephalopathy • Seizures most common presenting sign (>75%)
• ~20% of neonates with seizure have stroke
• Stroke/Bleeds • Lethargy
• Vital sign fluctuation
• Poor feeding
• NOT hemiplegia
• Multiple risk factors in setting of transient
hypercoagulability
• Outcomes better than for adults
15. Neurology/D. Intracranial hemorrhage and vascular injury/4.Perinatal cerebral/cerebellar infarction/
a. Know the pathogenesis, clinical and imaging features, diagnosis, management, and outcome associated
with perinatal cerebral and cerebellar infarction
“Stroke” May Describe Various Types of Brain Injury Imaging is Needed to Time AIS
• “Stroke” is used loosely to describe • Antenatal (before birth)

a group of disorders • Perinatal (28w-7d)
• Arterial Ischemic Stroke (AIS) (80%) • Neonatal (7d-28d)
• Sinovenous Thrombosis (SVT) • “Presumed Perinatal”
• Hemorrhages • Imaging Key for Timing and Diagnosis
• Subgaleal
• Subdural
• Subarachnoid
• Intraparenchymal
• AV Malformations

a. Know the pathogenesis, clinical and imaging features, diagnosis, management, and outcome associated
15. Neurology/D. Intracranial hemorrhage and vascular injury with perinatal cerebral and cerebellar infarction
97
AIS Rarely Has a Single Identifiable Cause Motor Deficits are Common Following Perinatal AIS
• Thrombophilia • Motor deficits

• Inflammation (infection) • Depends on location
• Genetic syndromes
• Imaging can be very helpful
• Polycythemia
• Embolism • Learning/behavior
• From placenta • 0-55%
• Cardiac • May not appear until later
• Multiple risk factors
increase risk • Epilepsy
• 1 RF = OR 4.2 • ~25%, but often not until later in
• 4 RF = OR 24.1 childhood
Lee et al JAMA February 2005;293
15. Neurology/D. Intracranial hemorrhage and vascular injury/4.Perinatal cerebral/cerebellar infarction/ 15. Neurology/D. Intracranial hemorrhage and vascular injury/4.Perinatal cerebral/cerebellar infarction/
a. Know the pathogenesis, clinical and imaging features, diagnosis, management, and outcome associated a. Know the pathogenesis, clinical and imaging features, diagnosis, management, and outcome associated
with perinatal cerebral and cerebellar infarction with perinatal cerebral and cerebellar infarction
Thrombophilia Evaluation is of Uncertain Value for Perinatal AIS Venous Infarctions Have a Different Mechanism than AIS
• Protein C & C activity
• Protein S free & function
• Antithrombin III
• Usually Multi-
• Factor VIII
factorial
• VWF • Dehydration
• Plasminogen PLA1
• Lupus anticoagulant (APL and
• Infection
ACL Abs)
• Meningo-
• Homocysteine
• B2 glycoprotein
encephalitis
• Factor V Leiden
• MTHFR
• Prothrombin gene
Lee S et al. Pediatric Neurology. 2017
15. Neurology/D. Intracranial hemorrhage and vascular injury/4.Perinatal cerebral/cerebellar infarction/ 15. Neurology/D. Intracranial hemorrhage and vascular injury/4.Perinatal cerebral/cerebellar infarction/
a. Know the pathogenesis, clinical and imaging features, diagnosis, management, and outcome associated a. Know the pathogenesis, clinical and imaging features, diagnosis, management, and outcome associated
with perinatal cerebral and cerebellar infarction with perinatal cerebral and cerebellar infarction
98
Venous Infarctions- Treatment is Controversial, Outcomes Vary Hemorrhage Location is Key in Understanding Bleeds
Type Location Risk factors Clinical management

• Management Subgaleal Between the galeal Vacuum or forceps assisted delivery - Early identification
• Normothermia aponeurosis and the - Monitor for signs of hypovolemia and shock
periosteum (just outside the Coagulopathy - May require emergent volume repletion or transfusion
• Normoglycemia skull)
• Maintain perfusion Subdural Between the dura mater and Vacuum or forceps assisted delivery - Monitor for clinical evidence of expansion
the arachnoid mater (within - In severe cases, secondary seizures or encephalopathy may
• Anticoagulation? the skull, outside the brain) Coagulopathy be present and require management
- Neurosurgical drainage rarely indicated
• Complete thrombus recanalization by 3 months
in 90% Subarachnoid Below the arachnoid mater
(on the surface of the brain)
Vacuum or forceps assisted delivery - Supportive management
- Monitor for development of secondary hydrocephalus
Coagulopathy
• 6% early death
Intraventricular Originates in the germinal Prematurity - Monitor for anemia and hypovolemia
• 17% thrombus propagation matrix (adjacent to the Chorioamnionitis - In severe cases, monitor for post-hemorrhagic hydrocephalus
ventricles) Hypotension
• 61% with abnormalities at follow up Acidosis
Respiratory distress
Moharir M et al. J Child Neuro 2011 Bicarbonate therapy
Coagulopathy
a. Know the pathogenesis, clinical and imaging features, diagnosis, management, and outcome associated 15. Neurology/D. Intracranial hemorrhage and vascular injury & E. Cranial and neurologic trauma/1.
with perinatal cerebral and cerebellar infarction Extracranial Hemorrhage
Hemorrhage Location is Key in Understanding Bleeds Changes You May Wish to Make in Practice
• Avoid the term HIE unless you are confident a neonate’s encephalopathy is due to
hypoxia-ischemic. Consider the terms “suspected” or “possible” HIE when
•Subgaleal uncertain.
•Subdural • Keep easily available a resource to guide a screening exam for encephalopathy for
•Subarachnoid quick use when deciding whether a newborn is eligible for therapeutic
hypothermia.
•Intraparenchymal • Order labs and imaging to gather data to support or refute the diagnosis of HIE in
•AV Malformations neonates.
• Use head ultrasound for immediate imaging, and MRI for definitive imaging in
suspected brain injury.
• Consider stroke as a possible diagnosis in term newborns with unexplained
lethargy, apnea, or seizures.
15. Neurology/D. Intracranial hemorrhage and vascular injury & E. Cranial and neurologic trauma/1.
Extracranial Hemorrhage
99
Resources
Executive summary: Neonatal encephalopathy and neurologic outcome, second edition. Report of the
American College of Obstetricians and Gynecologists' Task Force on Neonatal Encephalopathy. Obstet
Gynecol. 2014 Apr;123(4):896-901.
Ferriero DM, Fullerton HJ, Bernard TJ, et al; American Heart Association Stroke Council and Council on
Cardiovascular and Stroke Nursing. Management of Stroke in Neonates and Children: A Scientific
Statement From the American Heart Association/American Stroke Association. Stroke. 2019
Mar;50(3):e51-e96.
Neonatal Encephalopathy exam: https://people.stanford.edu/wusthoff/neurologic-exam-neonates-
suspected-encephalopathy-0
CPQCC ToolKit for HIE: https://www.cpqcc.org/content/early-screening-and-identification-candidates-
neonatal-therapeutic-hypothermia-toolkit
Questions?
100
Rapid Review: Asphyxia - Cord Gas Review,

Apgar /Outcomes /Brain Development
2:50pm-3:20pm
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102
Preterm Brain Injury

Sonia Bonifacio, MD
3:30pm-4:15pm
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104
Neonatal Seizures - Dr. Wusthoff
4:15pm-4:45pm
Disclosures
I have the following financial relationships with the manufacturer(s) of
Neonatal Seizures any commercial product(s) and/or provider(s) of commercial services:
Courtney Wusthoff, MD MS
• Consultant for: Ceribell, Persyst
Associate Professor
Neurology & Neurological Sciences and by courtesy,
Pediatrics‐ Neonatal and Developmental Medicine • I will discuss an unapproved (off‐label) use of medications to treat
Stanford University neonatal seizures in my presentation
1 2
Learning Objectives Outline
1. Describe the spectrum of seizures in the newborn infant • Diagnosis of Neonatal Seizures
2. Describe the differential diagnosis and evaluation of neonatal • Investigations for Neonatal Seizures
seizures. • Treatment of Neonatal Seizures
3. Describe the management of neonatal seizures, including the role of • Prognosis
neurophysiologic monitoring.
3 4
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4:15pm-4:45pm
Outline Neonatal seizures are not reliably diagnosed by clinical observation alone
• Diagnosis of Neonatal Seizures • 1‐5 per 1000 in term newborns
• Investigations for Neonatal Seizures • Unclear prevalence in preterm neonates
• Clinically: 1 in 2001
• Treatment of Neonatal Seizures
• By aEEG: Up to 48%2‐4
• Prognosis • By continuous video EEG: 5%5
• Up to 85% of neonatal seizures have no clinical signs
• 1/3 of neonates with seizures have only subclinical seizures
• Up to 75% of suspected clinical seizures are not epileptic
seizures.
• Electroclinical “uncoupling” is common
1. Davis AS. J Pediatr 2010
• ~50% after phenytoin or phenobarbital 2. Shah DK Pediatr Res 2010
3. Wikstrom S Acta Pediatr 2012
4. Vesoulis ZA Pediatr Res 2013
5. Lloyd RO. J Pediatr 2017
Jonathan Green, NatGeo
Neurology: Seizures: Classification/Understand the spectrum of seizures in the newborn, Diagnosis and
management/Understand the clinical manifestations of neonatal seizures
5 6
Detailed classification of neonatal seizure syndromes is not usually
Most neonatal seizures are subclinical or focal clonic in appearance
necessary
Descriptor Clinical Appearance
“Generalized Tonic‐Clonic Seizure” • Rhythmic movements of muscle groups
Generalized Seizures Focal Seizures Clonic • Fast and slow components to movement
Tonic‐clonic Focal sensory • Frequency typically 1‐3 jerks per second
Clonic Focal motor
Typical absence Elementary clonic motor
Tonic • Sustained flexion or extension of axial and/or appendicular muscle groups
Atypical absence Asymmetric tonic motor
Myoclonic absence Temporal lobe automatisms
Tonic Hyperkinetic automatisms Myoclonic • Single or multiple rapid jerks of extremities
Spasms Inhibitor motor seizures
Myoclonic seizures Gelastic Focal • Ocular – tonic eye deviation, sustained opening, fixation, or flutter
Eyelid myoclonia (with or without Hemiclonic • Oral‐facial‐lingual movements – chewing, tongue thrusting, lip smacking
absences) (including
Myoclonic atonic Secondarily generalized • Limb movements – cycling, paddling
Negative myoclonus Reflex seizures in focal epilepsy • Autonomic phenomena – tachycardia, bradycardia, apnea
Atonic
“Subtle”)
Reflex seizures in generalized epilepsy
Subclinical • No outward clinical signs; diagnose only with EEG
Neurology: Seizures: Classification/Understand the spectrum of seizures in the newborn, Diagnosis and Neurology: Seizures: Classification/Understand the spectrum of seizures in the newborn, Diagnosis and
management/Understand the clinical manifestations of neonatal seizures management/Understand the clinical manifestations of neonatal seizures
7 8
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4:15pm-4:45pm
Tonic clonic seizures are the most common clinically apparent seizure type Subtle neonatal seizures are common
Neurology: Seizures: Classification/Understand the spectrum of seizures in the newborn Neurology: Seizures: Classification/Understand the spectrum of seizures in the newborn
9 10
Clonus can mimic seizure Some clinical movements are unclear
Neurology: Seizures: Classification/Understand the spectrum of seizures in the newborn Neurology: Seizures: Classification/Understand the spectrum of seizures in the newborn
11 12
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4:15pm-4:45pm
Clinical signs can distinguish neonatal seizures from mimics Myoclonus and jitteriness are common seizure mimics
Seizures Seizure Mimics Clonic seizure Myoclonus Jitteriness
• Triggered by touch (clonus) Can be benign variant, seizure, or
Provoking • No clear provoking cause Seizures? Yes No
• Happen only in sleep (benign sleep release phenomenon
factors • Awake or asleep
myoclonus) Very rapid, monophasic, no Repetitive; movement
Repetitive, rapid phase
Duration • Seconds to a few minutes • Prolonged without stopping Semiology return phase; isolated or &return rapid; low amplitude,
followed by slow return phase
• Appears different each time an repetitive high frequency
Quality • Stereotyped: similar each time
event occurs
Focal; can spread to other Multifocal or in unrestrained
Eye • Eyes typically open Location Focal, multifocal, or generalized
areas over course of seizure limbs
• Eyes remain closed
involvement • Eyes sometimes deviated
Rhythmic? Yes No Yes
• Alert with typical behavior during Benign myoclonus suppressible; Yes, especially with flexion of
Alertness • Unresponsive during event Suppressible? No
episode sz not joint
Stimulus induced No Sometimes Yes
• Can stop by waking baby (benign
Ability to • Cannot stop by picking baby up or Clinical picture is highly Benign sleep‐ clinical
sleep myoclonus) Diagnosis Clinical
suppress suppressing limbs suggestive, EEG confirms seizure‐ by EEG
• Can suppress by holding limb
Neurology: Seizures: Diagnosis and management/Understand the differential diagnosis and evaluation of Neurology: Seizures: Diagnosis and management/Understand the differential diagnosis and evaluation of
neonatal seizures neonatal seizures
13 14
Benign neonatal myoclonus is a common seizure mimic Outline
• Diagnosis of Neonatal Seizures
• Investigations for Neonatal Seizures
• Treatment of Neonatal Seizures
• Prognosis
Marx et al,
Epileptic Disorders
Neurology: Seizures: Diagnosis and management/Understand the differential diagnosis and evaluation of
neonatal seizures
15 16
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4:15pm-4:45pm
Amplitude‐integrated EEG (aEEG) is a useful alternative if cEEG is
Continuous EEG (cEEG) is the gold standard for neonatal seizure diagnosis
unavailable
• American Clinical Neurophysiology Society guidelines recommend 24 hours cEEG for suspected
neonatal seizures • Dual channel aEEG with raw EEG can identify 40‐90% of
• World Health Organization (WHO) recommends EEG confirmation of all clinical seizures where patients with seizures
this technology is available • aEEG identifies 12‐80% of individual seizures
• Traditional 60 minute EEG is limited for capturing • Highly dependent on user experience
seizures • Dependent on availability of raw EEG for confirmation
• Many high risk neonates have no seizures in the first • Shorter seizures more likely missed
hour of monitoring, but will have seizures later • aEEG alone may overdiagnose seizures 50‐100%
• In HIE, up to 50% of seizures start after the first 24 hours • Artifact can interfere with interpretation
• In cooling, ~5% will have seizures only during rewarming • Significant artifact present in 12‐60% of records
• Seizure medicines cause “uncoupling”‐ the outward • Especially if artifact outside 2‐15 Hz range
signs go away, but the seizure continues • Typically, raw EEG is available if options set to display
• Uncoupling observed in 50‐60% of neonates Shellhaas et al. The American Clinical Neurophysiology Society's Guideline on Continuous EEG Monitoring
in Neonates. J Clin Neurophysiol. 2011 Dec;28(6):611-7. Glass H C, Wusthoff CJ, Shellhaas RA. J Child Neurol 2013
Guidelines on Neonatal Seizures. Geneva: World Health Organization; 2011.
Neurology: Seizures: Diagnosis and management/Understand the differential diagnosis and evaluation of neonatal Neurology: Seizures: Diagnosis and management/Understand the differential diagnosis and evaluation of neonatal
seizures/Understand the management of neonatal seizures, including the role of neurophysiologic monitoring seizures/Understand the management of neonatal seizures, including the role of neurophysiologic monitoring
17 18
Most neonatal seizures are symptomatic of acute brain illness Always evaluate for the cause of neonatal seizures‐ MRI is high yield
• ~80% of neonatal seizures are symptomatic of acute • Acutely:
brain injury • head ultrasound
• Common causes: • bedside glucose
• Cerebral hypoxia‐ischemia (~50% in US)
• Stroke/hemorrhage (15‐30%)
• basic labs
• Infection • EEG
• Malformations
• Electrolytes/hypoglycemia
• As soon as possible: MRI
• ~20% due to early‐onset epilepsy • ~90% will have diagnosis apparent on
• KCNQ2 mutations most common MRI
• Brain malformations • acute brain injury
• Other syndromes Jonathan Green, NatGeo
• structural abnormality
Glass HC, Shellhaas RA, Wusthoff CJ, et al; Neonatal Seizure Registry Study Group. Contemporary Profile of Seizures in Neonates: A Prospective
Cohort Study. J Pediatr. 2016 Jul;174:98-103 Weeke LC et al. DMCN 2014
Neurology: Seizures: Diagnosis and management/Understand the differential diagnosis and evaluation of neonatal Neurology: Seizures: Diagnosis and management/Understand the differential diagnosis and evaluation of neonatal
seizures/Understand the management of neonatal seizures, including the role of neurophysiologic monitoring seizures
19 20
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4:15pm-4:45pm
Always evaluate for the cause of neonatal seizures, even if MRI is normal Outline
• Is there a benign or malignant EEG • Diagnosis of Neonatal Seizures
pattern?
• Investigations for Neonatal Seizures
• Burst suppression may suggest a
metabolic or genetic epilepsy • Treatment of Neonatal Seizures
• Early Infantile Epileptic Encephalopathy • Prognosis
• Early Myoclonic Encephalopathy
• Any clinical signs to indicate a
particular diagnosis?
• Genetic testing identifies a cause in
>60% when MRI is normal
• KCNQ2 gene mutations most common
Non‐ketotic hyperglycinemia (Glycine Encephalopathy)
Neurology: Seizures: Diagnosis and management/Understand the differential diagnosis and evaluation of neonatal
seizures/Understand the prognostic significance of electroencephalographic patterns, such as burst suppression
21 22
Have a consistent approach to treating neonatal seizures Phenobarbital remains the mainstay of neonatal seizure treatment
• Confirm “seizures” are seizures.
• 20 mg/kg load x1‐2 (to level of 40*)
• Look for a cause as you treat • 4‐6 mg/kg/d maintenance
Phenobarbital
• Treat early and consistently.
• Status Epilepticus is a neurological emergency
• Untreated seizures may contribute to worsened • 15‐20 mg/kg load x1 (to level 15‐20*)
outcomes. • 5‐10 mg/kg/d maintenance
Phenytoin
• Overtreatment is not benign.
• Be explicit about goals of treatment.
• Complete resolution of seizures on EEG? • Lorazepam: 0.1mg/kg
• Reduction of seizure burden? Benzodiazepine • Midazolam infusion
• Reduction of clinical seizure burden?
~15‐20 minutes between steps
*Post‐load levels 1‐2 hours after
Neurology: Seizures: Diagnosis and management/Understand the management of neonatal seizures Neurology: Seizures: Diagnosis and management/Understand the management of neonatal seizures
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Phenobarbital has the most experience, but many drawbacks GABA has a unique effect in the neonatal period
• Overall, seizure‐reduction efficacy of 43%1
• In combination with PHT, 60% •Normally, GABA gated
• Inconsistent practices re: loading vs maintenance chloride channels open to
• Continue through acute period allow Cl- to enter the neuron
• 23% surveyed “always” continue maintenance2
• Considerations in hypothermia
• Neuroprotective in animal models of cooling3 Cl- •This hyperpolarizes the cell,
• No clear neuroprotective benefit in humans 4,5 creating an inhibitory effect
• Pharmacokinetics6‐8
• After initial 20mg/kg load, 69% still have a level <20
• T½ increased
• Volume of Distribution increased 1.
2.
Painter MJ. NEJM 1999.
Guillet R. Pediatrics 2008.
• Pros: familiar, has some evidence basis, long half‐life 3.
4.
Barks JD. Ped Research 2010.
Meyn DF. J Pediatr 2010.
5. Sarkar S. J Perinatol 2012.
• Cons: respiratory depression, sedation, long half‐life 6.
7.
Van den Broek MP. Clin Pharmacokinet 2012
Filippi L. Epilepsia 2011.
8. Thoresen M. Pediatr Res 2003
Neurology: Seizures: Diagnosis and management/Understand the management of neonatal seizures & Development of
the Nervous System‐ Neurotransmitters: Know the major drugs that interact directly with and their effect on
Neurology: Seizures: Diagnosis and management/Understand the management of neonatal seizures neurotransmittor receptors in the developing brain
25 26
GABA can be paradoxically excitatory in the neonatal period Phenytoin can be rational polypharmacy for neonatal seizures
• Potassium/Chloride • Inhibits sodium channels at the glutamatergic synapse
transporters have not yet • Overall, seizure‐reduction efficacy of 45%1
matured • In combination with PB, 60%
• Excess Cl- inside immature • Loading vs maintenance dosing
neurons • Loading dose 15‐20 mg/kg
Cl- • When GABA-activated Cl- • Maintenance dosing difficult due to pharmacokinetics, drug interactions.
open, cell is depolarized • Fosphenytoin
• GABA has a paradoxical • Much more expensive (20x)
excitatory effect in immature • Fewer infusion‐related complications
neurons, especially in preterm • Pros: Na+ channel blocker (different than PB), quick infusion
neonates • Cons: hypotension, bradycardia, narrow therapeutic range, can’t mix in
advance/can’t store long periods 1. Painter MJ. NEJM 1999.
Neurology: Seizures: Diagnosis and management/Understand the management of neonatal seizures & Development of Neurology: Seizures: Diagnosis and management/Understand the management of neonatal seizures & Development of
the Nervous System‐ Neurotransmitters: Know the major drugs that interact directly with and their effect on the Nervous System‐ Neurotransmitters: Know the major drugs that interact directly with and their effect on
neurotransmittor receptors in the developing brain neurotransmittor receptors in the developing brain
27 28
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4:15pm-4:45pm
Levetiracetam is popular, but unproven for neonatal seizures NEOLEV2 showed levetiracetam much less effective than phenobarbital

Neonates with
• Case series showed safety & tolerability among neonates at 10‐50
Suspected
HIE Seizures LEV 40-60 PHB 20-40 Odds Ratio p-
mg/kg/day1,2,3 280 Subjects
mg/kg mg/kg (95%CI) value
• Retrospective series suggest efficacy consented,
continuous EEG
Primary Outcome:
started 24-hour seizure 15/53 (28%) 24/30 (80%) 9.8 <0.001

• Pros: much less sedating, renal metabolism If + seizures on EEG, cessation (3.13,35.54)
106 randomized, randomized to (n=83)
• Cons: limited data on efficacy, larger volume and slower infusion rate started study study Secondary Outcomes:
48-hour seizure 8/47 (17%) 18/28 (64%) 8.46 <0.001
drug
• Until recently, no high quality data on efficacy N=60
IV LEV 40 mg/kg
N=40 cessation (n=75)
1-hour seizure
(2.64,30.07)
26/53 (49%) 28/30 (93%) 14.13 <0.001
IV PB 20 mg/kg
30 cessation (3.05,134.62)
+IV LEV 20 Mins (n=83)
mg/kg
IV PB +20 mg/kg Sub-analysis of subjects with HIE treated with hypothermia
60 24-hour seizure 6/17 (35%) 9/10 (90%) 14.75 0.014
Mins cessation (1.46,783)
IV PB 20 mg/kg IV LEV 40 mg/kg
1. Furwentsches A. Seizure 2010. (n= 27)
2. Ledet DS. Euro J Paed Neurol 2010. 90
3. Ramantani G. Euro J Paed Neurol 2011. Mins
IV LEV +20
IV PB +20 mg/kg
mg/kg 120 Sharpe CM. PAS 2019 meeting
Mins c/o Richard Haas
Neurology: Seizures: Diagnosis and management/Understand the management of neonatal seizures Neurology: Seizures: Diagnosis and management/Understand the management of neonatal seizures
29 30
Benzodiazepines may be useful to treat neonatal seizures Phenobarbital remains the mainstay of neonatal seizure treatment
• At some centers, preferred second‐line drug. 1 • 20 mg/kg load x2 (to level >40*)
• Some evidence of efficacy in seizures refractory to PB + PHT2 Phenobarbital • 4‐6 mg/kg/d maintenance
• Loading vs maintenance dosing
• Midazolam
• 15‐60 micgrogram/kg load Phenytoin • 20 mg/kg load x1 (to level 15‐20*)
• Infusion 150 up to 300 micgrogram/kg/hour • 5‐10 mg/kg/d maintenance div TID
(or lidocaine?)
• Tighter titrations 118 micgrograms/kg/min also used
• Paradoxical myoclonus has been reported
• Pros: easy to titrate, familiar agents • 40‐60 mg/kg load x1‐2
• Cons: sedation, still acting on GABA‐R Levetiracetam • 40‐60 mg/kg/day maintenance div TID
1. Vento M. Acta Paediatrica 2010.
2. Castro Conde JR. Neurology 2005.
~15‐20 minutes between steps
Neurology: Seizures: Diagnosis and management/Understand the management of neonatal seizures & Development of *Post‐load levels 1‐2 hours after
the Nervous System‐ Neurotransmitters: Know the major drugs that interact directly with and their effect on
neurotransmittor receptors in the developing brain Neurology: Seizures: Diagnosis and management/Understand the management of neonatal seizures
31 32
112
4:15pm-4:45pm
Duration of treatment remains controversial Outline
• At least 24 hours to confirm seizures have stopped • Diagnosis of Neonatal Seizures
• Overall post‐neonatal epilepsy rates are ~20% • Investigations for Neonatal Seizures
• In stroke, varies depending on size of stroke and location • Treatment of Neonatal Seizures
• In HIE, associated with severity of HIE
• Prognosis
• Overall, >1 AED as a neonate increases risk of ongoing seizures
• Stop phenytoin before discharge
• Consider reducing or stopping AEDs before discharge for acute
symptomatic seizures
Neurology: Seizures: Diagnosis and management/Understand the management of neonatal seizures
33 34
Burst suppression and Early Infantile Epileptic Encephalopathies have
Prognosis following neonatal seizures is highly dependent on etiology
especially poor prognosis
•Persistent burst
•Etiology is the single suppression at 72 hours
most important in HIE carries a very
prognostic factor poor prognosis
•Higher seizure •Neonatal onset

burden is associated epilepsies with burst
with increased risk of suppression are
poor outcome typically ominous
•EIEE
•Ohtahara syndrome
Outcomes following electrographic seizures and electrographic status epilepticus in the pediatric and neonatal
ICUs. Pinchefsky, Elana; Hahn, Cecil. Current Opinion in Neurology. 30(2):156‐164, April 2017.
Neurology: Seizures: Diagnosis and management/Understand the clinical manifestations of neonatal seizures, and
Neurology: Seizures: Diagnosis and management/Understand the clinical manifestations of neonatal seizures, and their their prognosis/Understand the prognostic significance of electroencephalographic patterns, such as burst
prognosis suppression
35 36
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4:15pm-4:45pm
Summary Changes You May Wish to Make in Practice
• Neonatal seizures are most often subtle or subclinical
• Focal clonic seizures are the most common clinical seizure type • Use EEG or aEEG to confirm all suspected neonatal seizures
• Neonatal seizures cannot be reliably diagnosed by clinical observation
• 80‐90% are subclinical • Use EEG or aEEG to screen for seizures in high risk neonates
• Can be confused with jitteriness, clonus, abnormal movements
• cEEG monitoring is the gold standard for dx • For new seizures, look for reversible causes
• Babies with brain injury are at high risk for seizures
• Most neonatal seizures are symptomatic of acute injury‐ look for the cause • For neonatal seizures, use MRI to evaluate for etiology
• There is evidence to suggest neonatal seizures can be harmful, though
more research is needed • Plan neurology and neurodevelopmental follow up for all
• Current drugs are imperfect for neonatal seizures; trials of new agents
are ongoing babies with seizures
37 38
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Rapid Review: The Neuro Exam, Neuromuscular Disease, Preterm Outcomes
Sonia Bonifacio, MD
4:45pm-5:25pm
115
116
BONUS SESSION Strategies to Optimize Test Success - Dr. Savich
Friday, February 7. 2020 - 5:30pm-6:15pm
Caveats
NeoPREP
Test Taking Strategies I am not giving this talk because I enjoy

standardized tests!
by Renate D. Savich, MD I took my Recertification and I passed,
University of Mississippi
confirming that God does exist.
The Boards are hard………But you will do
fine if you study smartly and know how
to take tests.
Financial Disclosure and NeoPREP NeoPREP
Other Things Caveats

I have no financial disclosures and no conflicts of
interest.
YOU WILL PASS THE BOARDS!!!
117
NeoPREP
Test Taking Mastery: 3 Steps NeoPREP
Objectives
Identify the different classifications of test
questions
3. Master the questions
Recognize the key components of a question
Identify the most important elements of a
Build skills in identifying question and answer question and thereby increase the odds of
distracters and qualifiers
selecting the correct answer
Develop approaches to:
answering a multiple choice question
taking the test
Improve preparation in advance of the test
Test Taking Mastery: 3 Steps NeoPREP NeoPREP
NeoPREP
1. Master your material
Use the Course this week to learn material, but to
Organize study resources
also identify areas that you may need to study
Develop a study strategy more in the next few weeks before the Board Exam
2. Master test-taking Review this course after you leave here (either by
reading the syllabus or viewing the taped lectures)
Approach the exam strategically to solidify what you have learned
118
NeoPREP NeoPREP
What Do Exams Test? Question Types

Recall
Knowledge, facts
Problem Solving: Identify…
Interpretive underlying cause and/or diagnosis
Review information and reach conclusion
(e.g., diagnosis) pathophysiologic mechanism
cause of drug or treatment response
Problem-Solving
appropriate drug or treatment to administer
Action based on clinical vignette, data or
images (e.g., the most appropriate
management is …)
Question Types NeoPREP NeoPREP
Question Formats
Single answer multiple choice
Recall: Guess my...
drug True / False
toxic exposure
Matching
Interpretive: Predict…
K-type
physical findings
key results of lab investigation (A=1,2,3 B=1,3 C=2,4 D=4 only E=all)
119
What Format are the NeoPREP
What Format are the NeoPREP
Neonatal Boards? Neonatal Boards?

Part of the question review process is to
ensure that the designated answer is clearly
Exam questions are written in a single-best- correct, uncontroversial, evidence-based,
answer multiple-choice format. This is the and a better choice than any of the other
most widely used format in the testing options.
industry as it allows for greatest coverage of
content within a specified amount of time. The other options ("distracters") are designed
to reflect plausible responses likely to be
selected by less knowledgeable candidates.
What Format are the

NeoPREP NeoPREP
Neonatal Boards?
Question Format
Most exam questions are preceded by a clinical Graphical illustrations, such as x-ray studies,
stem that provides information about a patient
graphs and photographs, are used in
(including laboratory and diagnostic findings).
approximately 5 to 10% of questions; some
specialty exams use graphics more
frequently.
Each question is typically followed by 5 answer
options, 1 of which is the correct (BEST) answer.
120
NeoPREP Content Area
Respiratory
Initial MOC
12 12
NPM Exam
Selection Process Cardiovascular 9 8 Content
Percentages
Nutrition 8 8
Neurology 7 7
Each exam is based on a specific blueprint,

Genetics / Dysmorphology 7 6
2018 Outline
Infectious Disease 6 7
Latest version
also known as a content outline. The outline Maternal-Fetal Medicine 6 6
d 3% each:
defines the percentage of questions from Core Knowledge in Scholarly
Activities
5 2 Neurodevelopmental Outcomes
Immunology
each content category that will appear on Endocrine / Metabolic / Thermal 5 5 Bilirubin
Skin Disorders
the exam. Water / Salt / Renal 5 5 EENT
Hematology - Oncology 5 5 Pharmacology
Health Services/Ethics/Family
Resuscitation / Asphyxia 4 6 Counseling
Gastroenterology 4 4
NeoPREP
Selection Process
The exam selection process incorporates new The Question
questions as well as questions that have
performed well on prior exams.
Special attention is also provided to ensure

that multiple forms of an exam are balanced
with regard to difficulty and content.
121
NeoPREP
Question NeoPREP
Anatomy of a Question STEM

The stem A 15 day old infant is noted to have a soft, granular, pink tissue
Clinical vignette at the base of the umbilicus with some seropurulent discharge.
Single, clearly formulated problem There is slight erythema at the edge of the umbilicus but no
tenderness or induration. The infant is afebrile and otherwise well
Lead-in appearing.
Pose a clear question
䇾Cover-the-options䇿 rule LEAD IN The MOST appropriate management is to:
CHOICES
Choices (foils) 1. Cauterize with silver nitrate
Single correct answer (key) 2. Hospitalization and intravenous antibiotics
Incorrect answers (distracters) 3. Hospitalize and observe the infant
4. Obtain a CBC and blood culture
5. Perform a leading edge culture
NeoPREP Stem & Lead-In NeoPREP
Question
Stem: clinical vignette
A 15 day old infant is noted to have a soft, granular, pink May have photos, diagnostic images (CXR, CT, MRI)
tissue at the base of the umbilicus with some seropurulent diagrams, graphs, laboratory values, clinical readouts
discharge. There is slight erythema at the edge of the (ECG, FHR tracing)…
umbilicus but no tenderness or induration. The infant is
afebrile and otherwise well appearing. Lead-ins
Which of the following is ABnormal?
The MOST appropriate management is to: Which should be administered by IV?
1. Cauterize with silver nitrate
2. Hospitalization and intravenous antibiotics
The following is the MOST likely cause of …
3. Hospitalize and observe the infant Which is LEAST likely to produce these signs?
4. Obtain a CBC and blood culture What is the most important FIRST step?
5. Perform a leading edge culture All of the following are true EXCEPT…
122
NeoPREP NeoPREP
Examine the Question Focus on the Question

What is being asked?
What would you do first? (intubate airway vs. OR)
Then (before looking at choices)…..
GUESS THE ANSWER
Terminology-BE CAREFUL! 䇾Active䇿 thinking
Beta HCG vs. Human Chorionic Gonadotropin Not distracted by wrong answers
Strep pyogenes vs. Group A Strep
Confusing, similar
Concentrations and Routes-BE CAREFUL!

IV, ET, IM Then…read ALL the choices
cc䇻s vs. mg䇻s
Approaching the Question

NeoPREP NeoPREP
Pick the Best Answer

Guess answer is one of the choices
The answer is there....somewhere
Be careful! Distracters often…
Either: are similar to correct answer
You know it right away aim for common error in thinking
Guess answer is not a choice
You recognize it….. Re-read question
After looking at the choices
No guess
Make each potential answer a true / false
You eliminate the other answers
123
NeoPREP NeoPREP
What Separates Good from Bad
Look at Question FIRST?? “Test Takers”
HIGH performers
Ruled out alternatives MORE frequently
Sometimes in a very long clinical vignette, it Admitted knowledge deficits (Although scored HIGHER)
may be helpful to read the question first, or DID NOT reach closure before reviewing ALL alternatives
DID NOT demonstrate premature closure
reread the vignette right after reading the
question (Lead in) to figure out the LOW Performers
important information. LEAST LIKELY to rule out alternatives
Did NOT admit knowledge deficits
Demonstrated premature closure
MORE Faulty knowledge
Heist, Journal of Graduate Medical Education, December 2014
NeoPREP NeoPREP
ANSWER EVERY QUESTION Testwiseness
Answer ALL questions-leave enough time for this at The results of MC tests can be influenced by testwiseness.
the end. Testwiseness is defined as the use of metacognitive answer
strategies by test takers during examinations.
Answer even if you haven’t had time to read the
question at the very end Regardless of the knowledge domain to be assessed, test
takers are often able to identify the correct answer option or
to eliminate one or more of the distractors in an MC item solely
There is NO penalty for wrong answers-so omitting on the basis of surface characteristics or by using content-
an answer puts you at a disadvantage. independent reasoning processes.
Willing Adv in Health Sci Educ (2015) 20:247–263
124
Modifiers NeoPREP
Limiters
Clues Within Questions Often used in 䇺trick䇻 questions: a small detail inserted to
make an appealing statement false
Superlatives
Less likely to be assoc䇻d w/correct answer
all, none, never, best, always, only…
Qualifiers
More likely to be assoc䇻d w/correct answer
Usually, often, might, unlikely, sometimes, seldom,
most, probably, apt to…
Q: Asthma is….
NeoPREP
Question Flaws – Answer Strategies NeoPREP
Question Flaws & nTestmanship|

1. More common
Similar components repeated among choices
Grammatical clues among urban than
Distracters don䇻t follow the stem Q: Ifsuburban
you wantchildren
grammatically to eat a Length of each choice
fruit2.that
More common
supplements Longer, more inclusive usually contain qualifiers; often
Logical clues among suburban
potassium intake, correct-Longest Alternative Cue
Some options exhaust all possibilities thanchoose
always urban children
a:
3. Equally Answers address different management
Word or phrase repeats 1. Apple
common among e.g., 4 are tests and one is a drug dose
Vignette and one of the choices2. Banana
urban and 䇺standout䇻 slightly more likely to be the right answer
3. Cantaloupe
suburban children
Echo options 4. Mango
4. …… Numeric answers
Opposites among choices 5. Orange
5. …… Consider middle range options
125
Myths & Fallacies NeoPREP NeoPREP
Changing Answers
Donbt ever change your answer. 70
REALLY?
60
50
40
Brain knows truth before consciousness? 30
20
Does the answer completely address the 10
question? 0
Wrong to Right Right to Wrong Wrong to Wrong
Myths & Fallacies NeoPREP

Does this knowledge about
NeoPREP
Your first guess/choice is often correct but if you changing your answer
later think it䇻s wrong…change it
help?
The evidence (research studies): Students when told it helps to change an answer
gained 1.8 points
changing wrong to right (about 50-65%)
Student not informed that changing an answer
helps gained 0.9 points
right to wrong (about 10-20%)
wrong to wrong (20-30%)
Pagni J Dental Educ 2016, 81:110-115 Bauer BMC Medical Education 2007, 7:28
Bauer BMC Medical Education 2007, 7:28
126
NeoPREP
Myths & Fallacies

Preparing For & Taking
Choice nb| or nc| are more likely
Not if test is computerized and randomized
the Exam
But true for NeoReviews Plus
NeoPREP NeoPREP
All The Above BE PREPARED

None Of The Above Go to the American Board of Pediatrics website
(www.abp.org)
All of the above: find one false statement

Click on the webpages
None of the above: find one true statement
No longer used READ THE CONTENT OUTLINE
127
Maintenance of Certification-NEW
MOCA-PEDS For Neonatology
NeoPREP NeoPREP
CHOICES
1. Maintenance of Certification Exams are easier Resources
than the initial certifying exam (but they are still While you can't talk about questions or answers with anyone at any time, you can use
hard) resources (internet, books, etc.) to help you answer questions should you need to.
Choice
2. MOCA Peds If you prefer to sit for the proctored exam at a secure testing center, or if you aren't
Up to 20 timed, multiple-choice questions are delivered passing MOCA-Peds by the end of Year 4 of your 5-year MOC cycle, you can choose
quarterly. Answer them wherever you like using a computer, to sit for the proctored exam instead. MOCA-Peds will be included in the cost of your
MOC enrollment; there will be an additional seat fee to take the proctored exam.
tablet or smartphone before the end of a quarter. Answer
them one at a time or all at once. Also, your four lowest- Feedback
scored quarters will be dropped in each 5-year MOC cycle Once you submit your answer, you’re told whether you got it right or wrong, the
and won't count against you. rationale behind the correct answer and references to support it. You’ll also have
access to previously-answered questions.
To START in 2020
MOCA-PEDS For Neonatology

NeoPREP NeoPREP
2020 MOCA Peds dates

Exam Content for 2020
Most questions will be based on 45 learning
objectives drawn from the content outline that
reflects the breadth of knowledge required for
practice.
128
NeoPREP NeoPREP
MOCA-Peds for Neonatologists BE PREPARED

What to expect the day of
Featured Readings for 2020
the exam-what you can
Each year, select peer-reviewed journal articles or guidelines are bring to the room and what
featured. These readings were selected by a group of practicing is not allowed
pediatricians serving on a subboard or question-writing committee as Maintenance of
being important for every pediatrician certified in the given discipline to Certification Exams are
read. Questions on these readings will be featured within the MOCA-Peds
easier than the initial
platform. Those engaged in MOCA-Peds will have access to these
articles, at no additional charge, during the year they are featured. Up to certifying exam (but they
two questions for each featured reading will appear within MOCA-Peds, are still hard)
however, other questions may list the featured readings as references. READ THE CONTENT OUTLINE
MOCA PEDS-Neonatology NeoPREP NeoPREP
Learning Objectives
45 of them:
Read this!
1. Analyze the potential causes and treatment options for neonatal anemia in preterm and term neonates.
2. Compare the indications for and limitations of various neuroimaging studies; recognize normal and abnormal
findings that occur during development and after brain injury.
3. Demonstrate an understanding of inheritance patterns and recurrence risks for autosomal dominant disorders.
4. Describe an evaluation and management plan for an infant with suspected choanal stenosis/atresia.
5. Describe best practices for management of a newborn with persistent pulmonary hypertension (PPHN).
6. Describe indications for use, clinical effects, side effects, and toxicity for classes of drugs commonly used in the
neonate (eg, antibiotics, analgesics, anticonvulsants).
7. Describe the indications for and proper administration of supplemental oxygen immediately after birth.
8. Describe the prognosis and long-term complications of bronchopulmonary dysplasia.
9. Develop a management plan for a preterm or term infant exposed to a communicable disease such as varicella
(using knowledge of placental immunoglobulin transfer).
10. Develop a management plan for an infant born to a mother with active genital herpes or with a history of genital
herpes.
Readings
2 articles
129
NeoPREP NeoPREP
NeoPREP NeoPREP
Preparing for the Exam

STUDY
…Less
…Smarter
䇺If you䇻re not learning, stop studying䇻
Study to understand
Memorize only what you have to
130
Study to Understand NeoPREP NeoPREP
Merritt S. Mastering Multiple Choice Should I memorize

Focus on understanding, not memorizing pathways?
For example-memorize this list:
Open
YES
Sit
Insert
Turn
Press
Turn
Study to Understand NeoPREP NeoPREP
Merritt SS. Mastering

M g Multiple
M ltiple
p Choice
Focus on understanding, not memorizing
Openp n the car door
Sitt in the driver
er䇻
err䇻s seat
Just kidding!

Insert rt the keyy

Turn n the key y
Presss the g gas p pedal
Turn n the steering g wheel
Use visual images,
ima graphs, diagrams, outlines
to help you
131
NeoPREP NeoPREP
Urea Cycle Pathway Incidence vs Prevalence

Incidence
rate of occurrence of new cases
Prevalence
which is the proportion of cases in the population at a given time
Incidence conveys information about the risk of contracting

the disease, whereas prevalence indicates how widespread
the disease is.
Know key points! 1/10/2020
Rates and Proportions

NeoPREP
Odds Ratios and Relative Risk

Proportion
Part / Whole Tom Brady successfully passed to a receiver 16
29% of births by Cesarean Sx times out of 20 attempts.
Must have range 0-1 (0-100%) ODDS of Successful Pass/ODDS of Unsuccessful Pass
16/4 = 4.0
Rate
Events/Group/Time PROBABILITY (Relative Risk) of Successful Pass
IMR= 7 per 1,000 live-births per year 16/20 = 0.8
132
Preparing for the Exam – NeoPREP Preparing for the Exam – NeoPREP
Study Study
ORGANIZE YOUR TIME!
STUDY in an organized way-by yourself or with friends
STUDY
Use successive condensing-Less on paper…more in your head
If you䇻re tested with questions Use flash cards if helpful
Use active studying-don’t just read chapter after chapter
…study with questions
NeoReviewsPlus and Martin and Brodsky Neonatal Review Weight your study schedule based on:
Questions Book closest thing available your existing knowledge
core knowledge with dbang for buckb in mind
Write/underline/highlight while you learn Use this NeoPrep course to identify areas you might feel weak on and
study those areas for the next 8 weeks a little more
But be careful while studying NeoPREP Preparing for the Exam – NeoPREP
using MC tests! Study

Consequences of taking a multiple-choice test on a later general
knowledge test in which students were warned not to guess.
Make sure you review:
Pictures of syndromes
A large positive testing effect was obtained:
Prior testing of facts aided final cued-recall performance.
Graphs
Formulas-(even if you don’t need these for the Boards
However, prior testing also had negative consequences. you will sound wicked smart on rounds)
Prior reading of a greater number of multiple-choice lures decreased the positive
testing effect and increased production of multiple-choice lures as incorrect answers Genetic inheritance
on the final test.
X-rays
Multiple choice testing may inadvertently lead to the creation of false Common pathways of things (IEM, etc)
knowledge.
Roediger J Experimental Psychology: Learning, Memory, and Cognition 2005,
31:1155–1159
133
NeoPREP NeoPREP
Taking The Exam The American Board of

Cycle through the first few questions to scan
Pediatrics Pass Rates
for: Neonatal-Perinatal Medicine
What they are asking
Easy
Intermediate
Difficult 2014 2015 2016 2015 2018
N % Pass N % Pass N % Pass N % Pass N % Pass
Keep track of time Initial 429 78% 467 86% 478 85%
Take short breaks MOC-First 247 95% 459 98% 276 95% 212 97% 15 87%
Time
Expect the unexpected
Over-Thinking
NeoPREP
Donbt drain your brain on one question Question Examples

Too time consuming
Throws off rhythm
Builds frustration
Don䇻t know it….hold it & move on
Brain gains focus as progress through exam

Knowledge gained from other questions
134
Question 1 NeoPREP NeoPREP
A 15 day old infant is noted to have a soft, granular, pink Type of Question?
tissue at the base of the umbilicus with some
seropurulent discharge. There is slight erythema at the
edge of the umbilicus but no tenderness or induration. You needed to find the important
The infant is afebrile and otherwise well appearing. features, make a diagnosis and know
The
e MOST appropriate managem
management is: the management plan.
1. Cauterize with silver nitrate
2. Hospitalization and IV antibiotics
3. Hospitalize and observe the infant
4. Obtain a CBC and blood culture
Question 1 NeoPREP Question 2 NeoPREP
A 15 day old infant is noted to have a soft, granular, pink You are asked to evaluate an IUGR term infant who has subtle dysmorphic
tissue at the base of the umbilicus with some features. BW is in the 4th percentile; HC is 2nd percentile for GA. The baby
seropurulent discharge. There is slight erythema at the has downward slanting palpebral fissures, epicanthal folds and
hyperteleorism. During your examination, you notice that infant has an
edge of the umbilicus but no tenderness or induration. unusual, high-pitched cry that resembles the mewing of a cat.
The infant is afebrile and otherwise well appearing.
Of the following, the MOST likely abnormality of chromosome structure
The
Th e MOST appropriate managem
management is: causing this infantbs clinical findings is a(n):
1. Cauterize with silver nitrate 1. deletion
2. Hospitalization and IV antibiotics 2. insertion
3. Hospitalize and observe the infant 3. inversion
4. Obtain a CBC and blood culture 4. reciprocal translocation
5. Robertsonian translocation
135
NeoPREP NeoPREP
Questions
You needed to find the one important

feature, make the diagnosis, and know
the genetics of this disease.
Question 3 NeoPREP NeoPREP
A full-term female infant is born via normal spontaneous

vaginal delivery 4 hours after rupture of membranes to a
40-year-old woman. The mother’s blood type is O+; she Of the following, the MOST likely cause of this infant’s leukocytosis
has a negativeantibody screening result; she is negative is:
for group B streptococcus, hepatitis B, gonorrhea, A. bacterial sepsis
chlamydia, and human immunodeficiency virus; and she
is immune to rubella. The infant appears clinically well, B. congenital cytomegaloviral infection
but is noted to have hypotonia, macroglossia, upslanting C. congenital leukemia
palpebral fissures, epicanthal folds, and a flat mid-facies,
as well as hepatosplenomegaly. A complete blood D. leukemoid reaction
count reveals a white blood cell count of 80,000/μL E. transient myeloproliferative disorder
(80Å~109/L), with 20% circulating blasts (Figure). The
platelet count is 103 K/μL and the hematocrit is 35%.
136
A 33 week gestation infant is 4 days old with a serum bilirubin

A full-term female infant is born via normal spontaneous vaginal concentration of 13 mg/dL (222 Pmol/L). It was 7 mg/dl
delivery 4 hours after rupture of membranes to a 40-year-old yestrerday. You decide to start phototherapy. The parents, Dr.
woman. The mother’s blood type is O+; she has a and Mrs. Fanaroff, ask you how phototherapy works.
negativeantibody screening result; she is negative for group B
streptococcus, hepatitis B, gonorrhea, chlamydia, and human Of the following, the MOST important process contributing to
immunodeficiency virus; and she is immune to rubella. The infant the removal of bilirubin from the body by phototherapy is:
appears clinically well, but is noted to have hypotonia, 1. Non-configurational isomerism
macroglossia, upslanting palpebral fissures, epicanthal folds, and
a flat mid-facies, as well as hepatosplenomegaly. A complete 2. Enhanced glucuronidation
blood count reveals a white blood cell count of 80,000, with 20% 3. Lactam-lactim tautomerism
circulating blasts (Figure). The platelet count is 103 K/μL and the 4. Photo-oxidation
hematocrit is 35%.
5. Structural isomerism
NeoPREP NeoPREP
Question Question
Have to know this is Trisomy 21, that this is It didn’t matter what the clinical information
associated with TMD, and that this is what was, you just needed some idea of the
the slide shows because sepsis in a baby bilirubin pathway and how phototherapy
with Trisomy 21 is still more common than works. Even if you couldn’t remember, you
TMD. could improve the probability of a correct
answer.
137
A term male infant is born by vaginal route to a 28 yo G2

caucasian woman whose previous child is a 6 yo girl in
good health. The pregnancy was complicated by
For DR resuscitation of an infant with profound polyhydramnios and decreased fetal movement. The
bradycardia that does not improve despite effective infant is floppy from birth and requiring assisted
ventilation, the first dose of epinephrine should be: ventilation.
PE is notable for AGA growth, long slender face w/ptosis,
A. 0.01-0.03 mL/kg of 1:1,000 via ETT long tapered fingers and toes and undescended testes.
B. 0.1-0.3 mL/kg of 1:1,000 via UVC Neuro exam reveals poor arousal, paucity of spontaneous
C. 0.1-0.3 mL/kg of 1:10,000 via UVC movements, poor tone (both proximal and distal), facial
D. 0.1-0.3 mL/kg of 1:10,000 via ETT weakness, and absent DTRs. The motherbs PE is normal.
E. 0.5-1.0 mL/kg of 1:10,000 via ETT
NeoPREP Question 6 NeoPREP
Question
Lab data show decreased amplitude of motor unit
potentials on EMG, normal nerve conduction, and
If you go too quickly on this, you will miss the centrally placed nuclei in muscle fibers on muscle
correct answer and note that they asked biopsy. Brain imaging, CSF and serum CPK are
what you SHOULD DO, not what you COULD normal. At 4 weeks of age, the infant is still requiring
do! mechanical ventilation. He has no suck or swallow
and is supported on G-tube feedings.
138
A term male infant is born by vaginal route to a 28 yo G2 NeoPREP NeoPREP
caucasian woman whose previous child is a 6 yo girl in good Congenital Myotonic Dystrophy
health. The pregnancy was complicated by polyhydramnios - EMG: myotonic discharges that, acoustically, have 䇺dive
and decreased fetal movement. The infant is floppy from bomber䇻 characteristic
birth and requiring assisted ventilation .PE is notable for AGA - AD; nCTG repeats MPK gene on chr 19
growth, long slender face w/ptosis, long tapered fingers and - Characteristic maternal facies and handshake
toes and undescended testes. Neuro exam reveals poor
arousal, paucity of spontaneous movements, poor tone (both Neonatal Myasthenia Gravis
proximal and distal), facial weakness, and absent DTRs. The - EMG: fatiguability with repeat muscle stimulation
motherbs PE is normal. Lab data show decreased - AI or AR w/mutation on chr 17; abn䇻l Ach receptors
amplitude of motor unit potentials on EMG, normal nerve
conduction, and centrally placed nuclei in muscle fibers Myotubular Myopathy
on muscle biopsy. Brain imaging, CSF and serum CPK - EMG: 䇺myopathic䇻 w/ discharges of low amplitude and
are normal. At 4 weeks of age, the infant is still requiring duration
mechanical ventilation. He has no suck or swallow and is - Muscle Bx: centrally placed nuclei (rather than normal sub-
supported on G-tube feedings. sarcolemmal position)
- X-linked recessive; abn䇻l MTM gene
NeoPREP
Question
Advice From Your
Lots of extra junk in here-find what is important MOTHER
So for this, you have to have read the different
causes of a hypotonic infant, you have to have
made a chart comparing and contrasting the
laboratory findings, and you need to
understand the inheritance pattern of each.
Just do it!
139
NeoPREP NeoPREP
The Obvious Test Anxiety

The most frequently mentioned strategies
Of course, taking care of your health - such as getting address the following areas:
enough sleep, exercise, and healthy food before a test - Relaxation
can help keep your mind working at its best.
Knowledge of testing conditions
Students who get a full eight hours sleep the night before Adequate preparation through improvement of test-
a test are more likely to figure out the problems than taking and study skills
those who stay awake the entire night before studying. Effective health habits, exercise, and good nutrition
Monitoring of thinking patterns and positive self-talk
Tips to Use When you Are NeoPREP NeoPREP
TAKING the Test Test Anxiety
Do an info dump. As soon as you get your Students who experience test anxiety tend to be the
type of people who put a lot of pressure on themselves
test, quickly jot down any main formulas or to perform well. They often have unusually high
key phrases in the margin or on your dry expectations for themselves and, many times, have
erase board that you have learned that you been very good students in the past.
feel you might forget as the test progresses.
Who in this room does not fit this description?
140
Dealing with Test Anxiety – NeoPREP Dealing with Test Anxiety – NeoPREP
The Dos and Don'ts

The Dos and Don'ts DON'T
…dwell on your mistakes. Go back and correct if you
DON'T can.
....get bogged down and worry about ...cram for an exam. The amount you learn won't be
worth the stress.
questions you don’t know; move on to the
...think of yourself or the test in a negative sense.
next question. The answer may come to you
...stay up late studying the night before. You need the
or you may get clues from other exam sleep. Begin studying a several weeks in advance if
questions. possible.
Dealing with Test Anxiety – NeoPREP Dealing with Test Anxiety - NeoPREP
The Dos and Don'ts The Dos and Don'ts

DON'T
DO
...rush through the test, but work at a ...use statements such as "this is only one test," "I
comfortable pace and don’t worry about am familiar with this material," "I have the ability to
how far along others are on the test do this,” etc.
...change body position now and then.
...work on the easiest portions of the test first.
141
NeoPREP Port-wine stains, also known as nevus flammeus, are capillary malformations present at birth. 85% are NeoPREP
Question…. unilateral and most are present on the head and neck. Port-wine stains are observed in patients with
Sturge-Weber syndrome, usually located on the unilateral face in the first or second division of the
trigeminal nerve distribution.
Pat
Patients with Sturge-Weber syndrome often have the following findings:
Mental deficiency
M
Too long? Too vexing? Too S

Seizures
Hemiparesis contralateral to the facial lesion
H
Ipsilateral “tramline” intracortical calcifications
frustrating?! Affected individuals may also have ipsilateral eye abnormalities such as glaucoma, optic atrophy or
buphthalmos.
Klippel-Trenaunay-Weber syndrome also is associated with port-wine stains with superficial vascular
abnormalities that are present at birth with underlying hypertrophy of bones or soft tissues.
Beckwith-Weidemann syndrome is associated with capillary nevus flammeus and also with a large tongue,
linear earlobe fissures, exophthalmos, macrosomia, organ hyperplasia, risk of intraabdominal malignancies,
and hypoglycemia.
Cobb Syndrome is a rare congenital disorder also known as
cutaneomeningospinalangiomatosis and is associated with port-wine stains with underlying spinal
Leave it Behind! angiomas.

Individuals with Chédiak-Higashi have diffuse hypopigmentation but do not have port-wine stains. Affected
patients have abnormal neutrophil degranulation leading to partial oculocutaneous albinism, peripheral
neuropathy, and recurrent infections.
NeoPREP NeoPREP
A full-term female infant is born with a large sharply
demarcated flat nevus flammeus skin lesion on her neck
consistent with a port-wine stain. The family inquires if any A term female infant develops bilious vomiting at 48 hours of
other anomalies or syndromes are associated with this age. She has not passed meconium and her abdomen is
vascular skin lesion. extremely distended. Physical examination shows a normal-
appearing perineum. Abdominal radiograph shows dilated
Which of the following disorders is NOT associated with small and large bowel with absence of rectal air. No other
port-wine stains? anomalies are apparent.
A. Beckwith-Weidemann syndrome Of the following, the MOST likely diagnosis in this infant is:
B. Chédiak-Higashi syndrome A. Annular pancreas
B. Duodenal atresia
C. Cobb syndrome C. Hirschsprung disease
D. Klippel-Trenaunay-Weber syndrome D. Ileal atresia
E. Pyloric stenosis
E. Sturge-Weber syndrome
142
NeoPREP NeoPREP
A full-term infant born to parents from Saudi Arabia is noted to have

ambiguous genitalia and elevated blood pressure. The rest of the physical
examination is unremarkable. Laboratory evaluation reveals normal serum
electrolytes with elevated serum androgens and deoxycorticosterone.
Of the following, which enzymatic defect is responsible for this infant’s

congenital adrenal hyperplasia?
A. Aromatase
B. 5 alpha-reductase
C. 11 beta-hydroxylase
D. 17 alpha-hydroxylase
E. 21-hydroxylase
NeoPREP NeoPREP
11 beta-hydroxylase deficiency is the second most common

The features of the infant in the vignette are consistent with a distal cause of congenital adrenal hyperplasia, occurring particularly
intestinal obstruction, such as Hirschsprung disease. The typical neonatal in individuals of Middle Eastern descent. It results from an
presentation of Hirschsprung disease includes: delay or failure to pass inability to convert deoxycorticosterone to aldosterone and 11-
meconium, bilious emesis, and abdominal distension. The disease is deoxycortisol to cortisol. There is a resulting excess of 17 hydroxy-
characterized by congenital absence of the intramural ganglia in the
affected bowel segment. Radiographic findings demonstrate distention progesterone, which leads to increased serum androgen
of small and large bowel with lack of rectal air. production. There is no salt-wasting because
deoxycorticosterone acts as a mineralocorticoid. Male infants
An annular pancreas may lead to a duodenal atresia with finding of a have normal external genitalia at birth while females may have
double-bubble appearance radiographically and limited distal air. An ambiguous genitalia of variable severity because of increased
ileal atresia may show a triple bubble or multiple dilated bowel loops with androgen exposure. Diagnosis is confirmed with increased
air-fluid levels. Infants with a pyloric stenosis will not have bilious emesis
but rather, present with projectile non-bilious vomiting. deoxycorticosterone and deoxycortisol concentrations. Therapy
includes glucocorticoid replacement and genital
reconstruction.
143
NeoPREP
144
Cardiovascular Physiology of the Fetus - Dr. Brodsky
8:00am-8:35am
Overview
Cardiovascular Physiology of I. Review normal cardiac development
the Fetus
http://pie.med.utoronto.ca/htbg/HTBG_content/HTBG_heartEmbryologyApp.html
Dara Brodsky, MD
Beth Israel Deaconess Medical Center, Boston
Email: dbrodsky@bidmc.harvard.edu
1 3
Disclosure Overview
• Neither I nor any member of my immediate family II. Describe key features of fetal
has a financial relationship or interest with any
cardiac physiology
proprietary entity producing health care goods or
services related to the content of this activity. Fetal circulation
• My content will not include discussion/ Oxygenation
reference of commercial products or services.
Regulation of
• I do not intend to discuss an unapproved/ cardiac output
investigative use of commercial products/devices.
2 4
145
8:00am-8:35am
Overview
III. Explain cardiovascular changes that
occur during the transition to extrauterine
life
I. Cardiac Development
5 7
Overview Normal Development of the Heart

IV. What if something goes wrong?
• Heart arises from ________
How does structural heart disease impact the fetus?
How does worsening hypoxemia impact the • Cardiovascular system is the _____ (? #)
cardiovascular system? system to function in utero
• Heart formation is complete by
___________ weeks’ gestation
6 8
146
8:00am-8:35am
Lateral view Septation Anterior views

Tube Formation
RV
Anterior view
Endocardial
cushion
LV
D 15 D 17 D 20 D 21 D 34 D 38 D 46
2 flat sheets of The upper sheet Tube An atrial septum A group of cells located at the
mesodermal expands and forms a straightens out grows from within inferior part of the single ventricle
cells tube that encircles the and becomes the atrium and grows upwards to form the
other sheet linear forms 2 separate ventricular septum
septum (green
Once this tube is primum and orange
formed, beating occurs secundum)
Pie.med.utoronto.ca Pie.med.utoronto.ca
9 11
Anterior view
Looping Normal Development of the Heart
Outflow tract
Rt Lt
LV
RV
D 21 D 22 D 28 Tube formation Looping Septation

The linear tube begins to bend As looping
towards the right side continues and the
Animations for all stages:
RV becomes larger, • http://www.indiana.edu/~anat550/embryo_main/ind
= right-sided or Dextro-looping the ventricles are ex.html (also GI/limb/urinary embryology)
Distinct chambers appear now side by side
• http://pie.med.utoronto.ca/htbg/HTBG_content/HTB
G_heartEmbryologyApp.html
Pie.med.utoronto.ca
10 12
147
8:00am-8:35am
II. Fetal Cardiac Physiology Fetal Circulation

Exercise
Draw a diagram of the fetal circulation
Fetal circulation starting with blood leaving the placental
Ventricular output circulation and then ending with blood that
returns to the placenta
Oxygenation
Intracardiac pressures ?
Regulation of cardiac output
13 15
Placenta
Fetal Circulation
www.impaedcard.com
William Harvey 1628

Cunningham FG, et al (eds): In Williams Obstetrics, 21st ed, McGraw-Hill, 2001, p 102
14 16
148
8:00am-8:35am
Fetal Circulation
Role of Fetal Circulation
Umbilical vein,
ductus venosus
The fetal circulation diverts blood away
(4)
from the fetal lungs via 2 right-to-left
Foramen ovale (2) shunts:
Patent ductus – Most of DV blood is diverted directly into
arteriosus (1) the LA via the FO
Umbilical arteries – Majority of the RV output is shunted via
(5) the PDA into the aorta
only a small amount of blood goes to lungs
17 19
Fetal Circulation
Fetal Circulation
Majority of well- • Ventricles work in
oxygenated blood parallel (vs series
from UV is diverted in adult)
directly into the LA • RV  lower body
(high velocity, and placenta
direction of vessel)
• LV  heart,
Majority of IVC blood brain, and upper
diverted into RA body
Aortic isthmus narrow
(dec flow), vulnerable
Kiserud. Sem5 Fet Neon Med. 2005, p 496
to ischemia
Freed MD. In Nadas’ Pediatric Cardiology, Flyer
DC (ed), Hanley & Belfus, 1992, p. 58
18 20
149
8:00am-8:35am
Intrauterine Ventricular Output

Fetal Cardiovascular Physiology
# = % of total blood volume
Fetal circulation
• __supplies most of CO
Ventricular Output in utero (hypertrophied)
Oxygenation • RV-___% vs LV-___%
Intracardiac Pressures of total blood volume
Regulation of Cardiac Output • ___% of total blood

volume goes to fetal
lungs in the 2nd
trimester
21 23
Intrauterine Ventricular Output: Exercise

Which ventricle provides Fetal Oxygenation
most of the cardiac Exercise
output in utero?
What percentage of total Which side of the intrauterine heart (right or

blood volume is left) has higher oxygen saturations?
supplied by each
ventricle?
Why?
What percentage of total
blood volume in utero
goes to the lungs?
22 24
150
8:00am-8:35am
Fetal Oxygenation Fetal Oxygenation: Exercise

# = oxygen saturation
Highest saturations
• Slightly higher O2 (70%) are low 
saturations on __ side relatively hypoxemia
of the heart because: environment
- higher oxygenated blood
from UV via DV shunted
across PFO to LA How does the fetus
cope in this relatively
- lower RA O2 sat hypoxemic
because SVC/IVC blood environment?
returning to RA has low
Freed MD. In Nadas’ Pediatric Cardiology, Flyer DC (ed),
Hanley & Belfus, 1992, p. 58 O2 sat (40-45%) Freed MD. In Nadas’ Pediatric Cardiology, Flyer DC (ed),
Hanley & Belfus, 1992, p. 58
25 27
Fetal Oxygenation
Fetal Compensation for Hypoxemic
Environment
Benefit - blood to brain 1) fetal ___  ___ Hct  ___ O2 carrying

and coronary arteries capacity
has higher oxygen
saturation

26 28
151
8:00am-8:35am

Environment Fetal Regulation of Cardiac Output
Exercise
2) Fetal hemoglobin
- ___ward shift in
oxyhemoglobin curve How does the fetal heart increase
- ____affinity for O2 cardiac output?
- allows for increased
O2 uptake even in
relatively low oxygenated
environments, such as
placenta
29 31

3) __creased O2 consumption
Fetal heart has a _____ ability to alter
- Maternal thermoregulation cardiac output
- Minimal respiratory effort
- Minimal GI digestion and absorption
- Decreased renal tubular reabsorption
30 32
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Fetal Regulation of Cardiac Output Cardiovascular Transition

What needs to happen in order for
CO = ?? x ?? the fetus to transition effectively?
________ in pulmonary blood flow

________between systemic and
pulmonary circulations
________in ventricular roles
________from umbilical and placental
circulations
33 35
Increase in Pulmonary Blood Flow

Fetal Regulation of Cardiac Output When infant breathes RA 
vasodilator effect of
oxygen on the
CO = ?? x ?? pulmonary arterioles 
PVR decreases
Adjustment in fetal HR is the primary SVR increases
mechanism of changing CO in utero: because no longer have
low resistance placenta
fetal tachycardia  increases CO
With SVR > PVR, shunting
fetal bradycardia  decreases CO across PDA becomes left-
to-right (Ao to PA),
increasing PBF further
34 36
153
8:00am-8:35am
Closure of the Foramen Ovale Timed Cord Clamping

LA pressures higher
Effects
– because increased PBF
leads to greater amount – Maintains venous return from UV/DV and
of blood return to the LA continued LV preload until ventilation
– also due to increased established
SVR distally
RA pressures lower
– due to clamping of
umbilical vein and
decreased systemic
venous return
37 39
Closure of the PDA

1. Higher O2 concentration
within ductal tissue breathing
RA
2. Lower amount of E-type
IV. What if something goes
prostaglandins (important for
PDA patency)
wrong?
-with increased PBF,
there is increased
metabolization in lungs
-loss of placental supply

of prostaglandins
3. Bradykinin from lungs at birth 

constricts further
38 40
154
8:00am-8:35am
Abnormal Cardiac Development Right-sided Obstructive Lesion

• e.g., pulmonary atresia
• Most structural cardiac abnormalities develop by
8 weeks’ gestation • Systemic cardiac output ___
• Some progress during pregnancy because of ________because:
decreased forward flow - more blood shunted across
PFO with compensatory
Hypoplastic LV Hypoplastic preductal aorta growth of LV to provide CO
- typically with VSD, which
Less volume Lower volume ejected into increases R  L shunting
able to fill LV preductal aorta
• In most severe form,
• Cardiac surgery early in gestation  avoids oxygenation to tissues
secondary effects of decreased forward flow ___________ bec of
intracardiac mixing (no
differential), ?impact
41 43
Left-sided Obstructive Lesion

• e.g., severe aortic stenosis
Impact of Congenital Heart Disease on Fetus
• Shift of blood volume from left-
to-right at FO
• How does structural heart disease • Left-sided hypoplasia with
compensatory growth of RV
impact the fetus? because RV now provides
• Oxygenation _______ CO
• Often with VSD to increase L to
• Systemic cardiac output Rt shunting further
• Systemic preductal output
dependent on retrograde ductal
flow, ? Decreased
• Intracardiac mixing, slightly
______O2 to brain/coronary
42 44
155
8:00am-8:35am
Causes of Hypoxemia
Placental issue:
• Suggestion of diminished fetal growth O2 delivery to placenta: -impaired O2 Umbilical
-maternal hypoxemia diffusion within cord issue:
• Neurodevelopmental impact (unclear if -decreased uterine placenta -decreased
related to cerebral blood flow or degree of blood flow -inadequate umbilical
cerebral oxygenation) placental surface blood flow
• Hydrops fetalis secondary to severe:
• Chamber dilation
• AV valve regurgitation, and/or Fetal hypoxemia= reduction in
• Cardiomegaly oxygen in the fetal circulation =
decreased O2 delivery
Examples: AV canal, Ebstein’s, AS/PA without VSD
45 47
Hypoxemia Fetal Compensation

• How does a fetus with a structurally normal
Blood flow preferentially to
heart respond to worsening hypoxemia? Fetal hypoxemia
heart, brain, adrenal glands
• Definitions:
Effect of decreased
• Hypoxemia -decreased amount of O2 in the
uterine blood flow in
blood (if persists, eventually leads to hypoxia)
fetal sheep
• Hypoxia -decreased amount of O2 to tissues Jensen, et al. J Dev Physiol. 1991;15
46 48
156
8:00am-8:35am
Impact of Worsening Hypoxemia on Fetal

Fetal Compensation
Cardiovascular System
• Suppressed respiration
Obstetrics: • Bradycardia
Increased diastolic blood velocity of middle • Decrease in CO
cerebral artery
 Hibernation mode
Marker of compensatory redistribution of blood
to the brain during hypoxemia/severe anemia
49 51
Fetal Compensation Fetal Compensation

Hypoxemia • Fetal O2 delivery can be
Fetal hypoxemia
reduced by ~50%
without significant effect
Dilation of DV on O2 uptake
O2 uptake
• Despite initial fetal
• Increased UV  DV hypoxemia, still
(better oxygenated blood to adequate amt O2 to
heart)
tissues (no fetal hypoxia)
• Decreased UV
shunting to portal lactic
circulation (decreased acidemia
liver growth, decreased develops O2 delivery
abdominal circumference)
50 52
157
8:00am-8:35am
Fetal vs Neonatal Response to Hypoxemia

Fetus Neonate Summary
• Suppressed respiration • Increased respiration
• Bradycardia • Modest tachycardia Reviewed
• Decrease in CO • Slight increase in CO • Cardiac development
O2 uptake does not change O2 uptake decreases even • Fetal cardiovascular physiology
significantly = hibernation with mild hypoxemia
• Effect of structural heart disease on fetus
• Fetal response to hypoxemia
O2 uptake
O2 delivery or pO2
53 55
Impact of Severe Hypoxemia on Fetal Cardiovascular

System
Fetal Unable to compensate Cardiac Hemodynamics in the
hypoxemia
Long period Newborn
Multiple episodes
Severe Myocardial dysfunction
CHF or cardiogenic shock

Fetal hypoxia (inadequate
O2 to tissues) CO
(TV very sensitive  TR)
Metabolic acidosis
54 56
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8:00am-8:35am
Neonatal Cardiac Circulation Overview

• PFO is closed II. Review the Frank-Starling Principle
• PDA usually is closed
• Ventricles work in series

Explanation
with entire blood volume Relevance
entering and exiting
each ventricle
• LV provides all of the
systemic CO Otto Frank Ernest Starling
• RV provides all of its
output to the lungs
57 59
Overview Overview
I. Discuss determinants of cardiac output III. Explain changes in the ventricular
function curve
How does the
A
neonate
increase
cardiac output? ? X
B
Nileherb.blogspot.com
?
58 60
159
8:00am-8:35am
Determinants of Cardiac Output

Overview Exercise
IV. Describe the ventricular pressure-
volume loop CO = ?
LV
pressure
?
LV volume
61 63
Overview Determinants of Cardiac Output

V. Qp/Qs ratio
CO = SV x HR
What is the formula for calculating the Qp/Qs?
Systemic blood pressure
How is the formula derived? CO =
Total peripheral vascular resistance
Poiseuille’s law for

laminar flow:
Flow = P/R
62 64
160
8:00am-8:35am
Determinants of Cardiac Output Stroke Volume

Exercise
CO = SV x HR CO = SV x HR
In contrast to fetus, neonate not only List the 3 determinants of stroke volume
depends on HR to change CO, but also
relies on changes in SV i.e., What determines the amount of blood
Usually referring to systemic cardiac volume ejected from the LV during
output and thus, focus is on LV systole?
65 67
Stroke Volume Stroke Volume

CO = SV x HR
CO = SV x HR
Stroke Volume (SV) = volume of blood
ejected from the ventricle per beat 1. _________
2. _________
Note: this is in contrast to CO, which is 3. _________
the volume of blood ejected from the
ventricle per minute
66 68
161
8:00am-8:35am
Stroke Volume Afterload

• Most view afterload as related to SVR, and that’s
Exercise true but afterload is also impacted by changes in
size and thickness of ventricle
How would you define the following?
• = Tension/stress developed in the ventricular wall
Preload during ejection
Ventricular Ventricular P x Ventricular radius
Afterload =
wall stress Wall thickness
Contractility -If distal vascular resistance increases  increase
in proximal intraventricular P  greater systolic
wall stress (i.e., increased afterload)
69 71
Preload Afterload
• = Degree of ________________at the end Ventricular P x Ventricular radius
Ventricular
of diastole =
• = Volume in the ventricle at the ___of filling
= end-diastolic volume (EDV) -If the ventricle is dilated  increased
ventricular wall stress with greater total load
• Preload increases with: (tension) on the myocytes (i.e., higher
– __creased circulating blood volume afterload)
– __creased venous tone
-If the ventricle is hypertrophied with a
– __creased ventricular compliance thickened wall  distributed across many cells
– __creased atrial contractility  decrease in wall stress and decrease in
– __creased intrathoracic pressure afterload
70 72
162
8:00am-8:35am
Stroke Volume
Afterload (dept on preload, afterload, contractility)
• Afterload corresponds directly with end-systolic SV = End-diastolic volume - End-systolic volume

volume (ESV = residual ventricular volume)
– With increased afterload, there is more blood left = Volume in LV at end of filling
after ejection and an increased ESV
= Volume in LV at end of ejection
SV: Increase EDV and/or Decrease ESV

Preload Contractility
Ventricular compliance Afterload
(how easy it is for
heart to stretch)
73 75
Contractility Determinants of Cardiac Output
• = force and velocity of a contraction CO = SV x HR

HR
SV
Preload Afterload Contractility
Peripheral vascular
resistance
74 76
163
8:00am-8:35am
Frank-Starling Mechanism
Frank-Starling Principle
Baseline Preload (more stretch)
Increased LV diastolic filling Actin, thin

Myosin, thick
Cardiac muscle stretches

At baseline, With an increase in preload
cardiac muscle is and increased stretch, there is
Greater force of contraction not in optimal more optimal overlap between
position to create thin and thick muscle filaments
greatest force of of sarcomeres  greater force
Increased stroke volume contraction of contraction
77 79
Frank-Starling Principle Frank-Starling Principle

Heart
Pumping
SVC/IVC Aorta Ability of
Heart
Preload
78 80
164
8:00am-8:35am
Ventricular Function Curve:

Frank-Starling Principle Change in Afterload
Pumping Stroke volume
Ability of Cardiac output
Heart LV sys pressure Y Normal
Stroke work Stroke X At a given preload
volume (point X, Y), and
then increase
LV end-diastolic volume afterload:
Diastolic cardiac muscle length
LV end-diastolic pressure SVR, SV
With a dec in SV 
Preload inc in LVEDV
LV end-diastolic volume
81 83

Frank-Starling Principle: Preload Change in Afterload
Decreased afterload
(curve moves up and to left)
Stroke Y Y Normal
volume Stroke X
X volume
Increased afterload
(curve moves down
and to right)
82 84
165
8:00am-8:35am
Ventricular Function Curve: Contractility

Exercise
Ventricular Pressure-Volume Loop
What would happen to this curve if you: • Ventricular pressure-volume loops can be
• Administered epinephrine (assume effect mostly on
contractility?
used as a tool for visualizing changes in
• Infant with CHF? ventricular function as preload, afterload,
and contractility are altered
Stroke
volume
LV
pressure = 1 cardiac cycle
LV volume
85 87
Ventricular Function Curve: Ventricular Pressure-Volume Loop

Change in Contractility Exercise
__________ contractility
A
Stroke Normal LV
X pressure
volume
_______ contractility
?
B
LV end-diastolic volume LV volume
86 88
166
8:00am-8:35am
Ventricular Pressure-Volume Loop Ventricular Pressure-Volume Loop

I. Filling/Diastole
II. Isovolumic Contraction
LV LV
pressure pressure III III. Ejection/Systole
IV. Isovolumic Relaxation
IV II
I
SV
ESV EDV
LV volume LV volume
89 91
Increase in Preload
Ventricular Pressure-Volume Loop (afterload and contractility kept constant)
Exercise
A. Volume at end
D of contraction
LV MV opens LV
C
pressure pressure
B. MV closes, EDV, SV
LV contraction
A B C. Aortic valve opens
D. Aortic valve closes

B BB
ESV EDV
LV volume LV volume
90 92
167
8:00am-8:35am
Increase in Preload Qp/Qs

(afterload altered) • = Ratio of pulmonary to systemic blood flow
Exercise
• Well neonate Qp=Qs  Qp/Qs ratio ~1
Inc Preload  (note: slightly more than 1 because bronchial arteries
D. Aortic valve closes inc SV  inc return to pulmonary vein instead of systemic)
LV intra-aortic P
pressure greater than • Left-to-right intracardiac shunt (e.g., VSD)
SV
intraventricular – Greater pulmonary blood flow
P earlier  Ao – Qp/Qs >1
valve closes – If Qp/Qs > 2, suggests a large shunt
B BB earlier • Right-to-left intracardiac shunt (e.g., Tricuspid atresia)

ESV slightly – Lower amount of pulmonary blood flow
ESV
LV volume higher – Qp/Qs < 1
– If Qp/Qs < 0.7, suggests a large shunt
93 95
Qp/Qs
Exercise
Write the formula to calculate the Qp/Qs

Derivation of Formula for
Calculating the Qp/Qs Ratio
94 96
168
8:00am-8:35am
To Derive Qp/Qs  Fick Equation Deriving Qp/Qs ratio

O2 consumption = flow x 1.36 (Hb)(10)(art O2 sat – venous O2 sat)
O2 consumption is the difference between the amount of
O2 delivered by the heart and O2 returning to the heart Solving for flow…
flow = O2 consumption (mL/min)
O2 consumption = O2 delivered - O2 returning
1.36 (Hb)(10)(art O2 sat – venous O2 sat)
blood flow x O2 content blood flow x O2 content
in venous As an aside, this is the equation for cardiac index
in arterial blood
blood CI = O2 consumption (mL/min/m2)
O2 content = O2 bound to Hb + O2 dissolved in blood 1.36 (Hb)(10)(Ao O2 sat – mixed venous O2 sat)
O2 content = 1.36 (Hb)(O2 sat) + (.003 x paO2)
(1.36 mL O2 bound per gram Hb, varies 1.34-1.39) Because CI = CO/body surface area, m2 added to
numerator
O2 cons= flow x 1.36 (Hb)(10)(art O2 sat – venous O2 sat)
(O2 sat in decimal form—.99 or divide % oxygen sat by 100)
97 99
Deriving Qp/Qs ratio

Factor of 10
O2 consumption = flow x 1.36 (Hb)(art O2 sat – venous O2 sat)
Solving for flow…
mL L x 1.36 mL x Hb g
min = min g dL flow = O2 consumption
min = min g dL Deriving Qp/Qs….
Qp = O2 consumption
mL L x 1.36 mL x Hb x 10 dL 1.36 (Hb)(10)(PV O2 sat – PA O2 sat)
min = min dL L
Qs = O2 consumption
1.36 (Hb)(10)(Ao O2 sat – mixed venous O2 sat)
98 100
169
8:00am-8:35am
Deriving Qp/Qs Ratio Qp/Qs Ratio

Deriving Qp/Qs…. Qp 1 Ao O2 sat – MV O2 sat
= =
Qp = O2 consumption Qs 1 PV O2 sat – PA O2 sat
1.36 (Hb)(10)(PV O2 sat – PA O2 sat)
Qs = O2 consumption Assumptions:
1.36 (Hb)(10)(Ao O2 sat – MV O2 sat)
Ao O2 sat = pulse ox
1 No lung disease:
Qp PV O2 sat – PA O2 sat PV O2 sat = 100%
=
Qs 1
Ao O2 sat – MV O2 sat
101 103

= =
1 Qs 1 PV O2 sat – PA O2 sat
Qp PV O2 sat – PA O2 sat
=
Qs 1 Thus, if Ao = PV O2 sat and
Ao O2 sat – MV O2 sat MV = PA O2 sat  no
intracardiac shunting and
Qp/Qs = 1
Qp Ao O2 sat – MV O2 sat
=
Qs PV O2 sat – PA O2 sat
O2 sat in either decimal form or %
102 104
170
8:00am-8:35am
Summary Overview
• Reviewed effect of preload, afterload I. Review normal cardiac development
and contractility on the ventricular
function curve
• Described the ventricular pressure-
volume loop
http://pie.med.utoronto.ca/htbg/HTBG_content/HTBG_heartEmbryologyApp.html
• Discussed determinants of cardiac
output
• Derived the formula for Qp/Qs
105 107
Overview
Cardiovascular Physiology of II. Describe key features of fetal
the Fetus cardiac physiology
ANSWERS Fetal circulation
Oxygenation
Regulation of
Dara Brodsky, MD cardiac output
Beth Israel Deaconess Medical Center, Boston
Email: dbrodsky@bidmc.harvard.edu
106 108
171
8:00am-8:35am
Overview
III. Explain cardiovascular changes that
occur during the transition to extrauterine
life
I. Cardiac Development
109 111
Overview Normal Development of the Heart

IV. What if something goes wrong?
• Heart arises from mesoderm
How does structural heart disease impact the fetus?
How does perinatal depression impact the • Cardiovascular system is the first system
cardiovascular system? to function in utero
• Heart formation is complete by 8 weeks’
gestation
110 112
172
8:00am-8:35am
Lateral view Septation Anterior views

Tube Formation
RV
Anterior view
Endocardial
cushion
LV
D 15 D 17 D 20 D 21 D 34 D 38 D 46
2 flat sheets of The upper sheet Tube An atrial septum A group of cells located at the
mesodermal expands and forms a straightens out grows from within inferior part of the single ventricle
cells tube that encircles the and becomes the atrium and grows upwards to form the
other sheet linear forms 2 separate ventricular septum
septum (green
Once this tube is primum and orange
formed, beating occurs secundum)
Pie.med.utoronto.ca Pie.med.utoronto.ca
113 115
Anterior view
Looping Normal Development of the Heart
Outflow tract
Rt Lt
LV
RV
D 21 D 22 D 28 Tube formation Looping Septation

The linear tube begins to bend As looping
towards the right side continues and the
Animations for all stages:
RV becomes larger, • http://www.indiana.edu/~anat550/embryo_main/ind
= right-sided or Dextro-looping the ventricles are ex.html (also GI/limb/urinary embryology)
Distinct chambers appear now side by side
• http://pie.med.utoronto.ca/htbg/HTBG_content/HTB
G_heartEmbryologyApp.html
Pie.med.utoronto.ca
114 116
173
8:00am-8:35am
II. Fetal Cardiac Physiology Fetal Circulation

Exercise
Draw a diagram of the fetal circulation
Fetal circulation starting with blood leaving the placental
Ventricular output circulation and then ending with blood that
returns to the placenta
Oxygenation
Intacardiac pressures ?
Regulation of cardiac output
117 119
Placenta
Fetal Circulation
www.impaedcard.com
William Harvey 1628

Cunningham FG, et al (eds): In Williams Obstetrics, 21st ed, McGraw-Hill, 2001, p 102
118 120
174
8:00am-8:35am
Fetal Circulation
Role of Fetal Circulation
Umbilical vein,
ductus venosus
The fetal circulation diverts blood away
(4)
from the fetal lungs via 2 right-to-left
Foramen ovale (2) shunts:
Patent ductus – Most of DV blood is diverted directly into
arteriosus (1) the LA via the FO
Umbilical arteries – Majority of the RV output is shunted via
(5) the PDA into the aorta
only a small amount of blood goes to lungs
121 123
Fetal Circulation Fetal Circulation

Majority of well- • Ventricles work in
oxygenated blood parallel (vs series in
from UV/DV is adult)
diverted directly into
the LA (high velocity, • RV  lower body
direction of vessel) and placenta
• LV  heart, brain,
and upper body
Majority of IVC blood
diverted into RA Aortic isthmus narrow
(dec flow), vulnerable
to ischemia
Kiserud. Sem5 Fet Neon Med. 2005, p 496 Freed MD. In Nadas’ Pediatric Cardiology, Flyer
DC (ed), Hanley & Belfus, 1992
122 124
175
8:00am-8:35am
Intrauterine Ventricular Output

Fetal Cardiovascular Physiology # = % of total blood volume
• RV supplies most of CO in
Fetal circulation utero (hypertrophied)
Ventricular Output • RV-66% vs LV-34% of total

blood volume
Oxygenation
• Fetal pulmonary blood flow
Intracardiac Pressures - 7-15% 2nd trimester
- ~35% 3rd trimester (pulm
Regulation of Cardiac Output growth)
- decrease to 20% 38 weeks
(pulm vessels sensitive to
Freed MD. In Nadas’ Pediatric Cardiology, Flyer low O2, constrict)
125 127
Intrauterine Ventricular Output: Exercise

Which ventricle provides Fetal Oxygenation
most of the cardiac Exercise
output in utero?
What percentage of total Which side of the intrauterine heart (right or

blood volume is left) has higher oxygen saturations?
supplied by each
ventricle?
Why?
What percentage of total
blood volume in utero
goes to the lungs?
DC (ed), Hanley & Belfus, 1992
126 128
176
8:00am-8:35am
Fetal Oxygenation Fetal Oxygenation: Exercise

Highest saturations
• Slightly higher O2 (70%) are low 
saturations on left side relatively hypoxemia
of the heart because: environment
- higher oxygenated blood
from UV via DV shunted
across PFO to LA How does the fetus
cope in this relatively
- lower RA O2 sat hypoxemic
because SVC/IVC blood environment?
returning to RA has low
Hanley & Belfus, 1992, p. 58 O2 sat (40-45%) Freed MD. In Nadas’ Pediatric Cardiology, Flyer DC (ed),
129 131
Fetal Oxygenation
Environment
Benefit - blood to brain 1) fetal epo  Hct  O2 carrying

and coronary arteries capacity
has higher oxygen
saturation

130 132
177
8:00am-8:35am

Exercise
2) Fetal hemoglobin
- leftward shift in
oxyhemoglobin curve How does the fetal heart increase
- high affinity for O2 cardiac output?
- allows for increased
O2 uptake even in
relatively low oxygenated
environments, such as
placenta
133 135

3) Decreased O2 consumption
Fetal heart has a limited ability to alter
- Maternal thermoregulation cardiac output
- Minimal respiratory effort
- Minimal GI digestion and absorption
- Decreased renal tubular reabsorption
134 136
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8:00am-8:35am
Fetal Regulation of Cardiac Output Cardiovascular Transition

What needs to happen in order for
CO = SV x HR the fetus to transition effectively?
Increase in pulmonary blood flow
Distinction between systemic and
pulmonary circulations
Change in ventricular roles
Separation from umbilical and placental
circulations
137 139
Increase in Pulmonary Blood Flow

Fetal Regulation of Cardiac Output When infant breathes RA 
vasodilator effect of
oxygen on the
CO = SV x HR pulmonary arterioles 
PVR decreases
Adjustment in fetal HR is the primary SVR increases
mechanism of changing CO in utero: because no longer have
low resistance placenta
fetal tachycardia  increases CO
With SVR > PVR, shunting
fetal bradycardia  decreases CO across PDA becomes left-
to-right (Ao to PA),
increasing PBF further
138 140
179
8:00am-8:35am
Closure of the Foramen Ovale Timed Cord Clamping

LA pressures higher
Effects
– because increased PBF
leads to greater amount – Maintains venous return from UV/DV and
of blood return to the LA continued LV preload until ventilation
– also due to increased established
SVR distally
RA pressures lower
– due to clamping of
umbilical vein and
decreased systemic
venous return
141 143
Closure of the PDA

1. Higher O2 concentration
within ductal tissue breathing
RA
2. Lower amount of E-type
IV. What if something goes
prostaglandins (important for
PDA patency)
wrong?
-with increased PBF,
there is increased
metabolization in lungs
-loss of placental supply

of prostaglandins
3. Bradykinin from lungs at birth 

constricts further
142 144
180
8:00am-8:35am
Abnormal Cardiac Development Right-sided Obstructive Lesion

• Most structural cardiac abnormalities develop by • e.g., pulmonary atresia
8 weeks’ gestation
• Systemic cardiac output not
• Some progress during pregnancy because of impacted because:
decreased forward flow (CONCEPT—size of a
vessel or chamber dependent on flow through that - more blood shunted across
vessel or chamber) PFO with compensatory
Hypoplastic LV Hypoplastic preductal aorta growth of LV to provide CO
- typically with VSD, which
increases R  L shunting
Less volume Lower volume ejected into
able to fill LV preductal aorta • In most severe form,
• Cardiac surgery early in gestation  avoids oxygenation to tissues slightly
secondary effects of decreased forward flow decreased bec of intracardiac
mixing (no differential), ?impact
145 147
Left-sided Obstructive Lesion

Impact of Congenital Heart Disease on Fetus • e.g., severe aortic stenosis
• Shift of blood volume from
left-to-right at FO
• How does structural heart disease • Left-sided hypoplasia with
impact the fetus? compensatory growth of RV
because RV now provides
• Oxygenation even more CO
• Systemic cardiac output • Often with VSD to increase L

to Rt shunting further
• Systemic preductal output
dependent on retrograde
ductal flow, ? Decreased
• Intracardiac mixing, slightly
lower O2 to brain/coronary
146 148
181
8:00am-8:35am
Causes of Hypoxemia
Placental issue:
• Suggestion of diminished fetal growth O2 delivery to placenta: -impaired O2 Umbilical
-maternal hypoxemia diffusion within cord issue:
• Neurodevelopmental impact (unclear if -decreased uterine placenta -decreased
related to cerebral blood flow or degree of blood flow -inadequate umbilical
cerebral oxygenation) placental surface blood flow
• Hydrops fetalis secondary to severe:
• Chamber dilation
• AV valve regurgitation, and/or Fetal hypoxemia= reduction in
• Cardiomegaly oxygen in the fetal circulation =
decreased O2 delivery
Examples: AV canal, Ebstein’s, AS/PA without VSD
149 151
Hypoxemia Fetal Compensation

• How does a fetus with a structurally normal
Blood flow preferentially to
heart respond to worsening hypoxemia? Fetal hypoxemia
heart, brain, adrenal glands
• Definitions:
Effect of decreased
• Hypoxemia -decreased amount of O2 in the
uterine blood flow in
blood (if persists, eventually leads to hypoxia)
fetal sheep
• Hypoxia -decreased amount of O2 to tissues Jensen, et al. J Dev Physiol. 1991;15
150 152
182
8:00am-8:35am
Impact of Perinatal Depression on Fetal

Fetal Compensation
Cardiovascular System
• Suppressed respiration
Obstetrics: • Bradycardia
Increased diastolic blood velocity of middle • Decrease in CO
cerebral artery
 Hibernation mode
Marker of compensatory redistribution of blood
to the brain during hypoxemia/severe anemia
153 155
Fetal Compensation Fetal Compensation

Hypoxemia • Fetal O2 delivery can be
Fetal hypoxemia
reduced by ~50%
without significant effect
Dilation of DV on O2 uptake
O2 uptake
• Despite initial fetal
• Increased UV  DV hypoxemia, still
(better oxygenated blood to adequate amt O2 to
heart)
tissues (no fetal hypoxia)
• Decreased UV
shunting to portal lactic
circulation (decreased acidemia
liver growth, decreased develops O2 delivery
abdominal circumference)
154 156
183
8:00am-8:35am
Fetal vs Neonatal Response to Hypoxemia

Fetus Neonate Summary
• Suppressed respiration • Increased respiration
• Bradycardia • Modest tachycardia Reviewed
• Decrease in CO • Slight increase in CO • Cardiac development
O2 uptake does not change O2 uptake decreases even • Fetal cardiovascular physiology
significantly = hibernation with mild hypoxemia
• Effect of structural heart disease on fetus
• Fetal response to hypoxemia
O2 uptake
O2 delivery or pO2
157 159
Impact of Perinatal Depression on Fetal Cardiovascular

System
Fetal Unable to compensate Cardiac Hemodynamics in the
hypoxemia
Long period Newborn
Multiple episodes
Severe Myocardial dysfunction
CHF or cardiogenic shock

Fetal hypoxia (inadequate
O2 to tissues) CO
(TV very sensitive  TR)
Metabolic acidosis
158 160
184
8:00am-8:35am
Neonatal Cardiac Circulation Overview

• PFO is closed II. Review the Frank-Starling Principle
• PDA usually is closed
• Ventricles work in series

Explanation
with entire blood volume Relevance
entering and exiting
each ventricle
• LV provides all of the
systemic CO Otto Frank Ernest Starling
• RV provides all of its
output to the lungs
161 163
Overview Overview
I. Discuss determinants of cardiac output III. Explain changes in the ventricular
function curve
How does the
A
neonate
increase
cardiac output? ? X
B
?
162 164
185
8:00am-8:35am

Overview Exercise
IV. Describe the ventricular pressure-
volume loop CO = ?
LV
pressure
?
LV volume
165 167
Overview Determinants of Cardiac Output

V. Qp/Qs ratio
CO = SV x HR
Systemic blood pressure
How is the formula derived? CO =
Poiseuille’s law for

laminar flow:
Flow = P/R
166 168
186
8:00am-8:35am

Exercise
CO = SV x HR CO = SV x HR
In contrast to fetus, neonate not only List the 3 determinants of stroke volume
depends on HR to change CO, but also
relies on changes in SV i.e., What determines the amount of blood
Usually referring to systemic cardiac volume ejected from the LV during
output and thus, focus is on LV systole?
169 171

CO = SV x HR
CO = SV x HR
Stroke Volume (SV) = volume of blood
ejected from the ventricle per beat Preload
Afterload
Note: this is in contrast to CO, which is Contractility
the volume of blood ejected from the
ventricle per minute
170 172
187
8:00am-8:35am
Stroke Volume Afterload

• Most view afterload as related to SVR, and that’s
Exercise true but afterload is also impacted by changes in
size and thickness of ventricle
How would you define each of these?
• = Tension/stress developed in the ventricular wall
Preload during ejection
Ventricular Ventricular P x Ventricular radius

Afterload =
Contractility
-If distal vascular resistance increases  increase
in proximal intraventricular P  greater systolic
wall stress (i.e., increased afterload)
173 175
Preload Afterload
• = Degree of cardiomyocyte stretching at the Ventricular P x Ventricular radius
Ventricular
end of diastole =
• = Volume in the ventricle at the end of filling
= end-diastolic volume (EDV) -If the ventricle is dilated  increased
• Preload increases with: ventricular wall stress with greater total load
(tension) on the myocytes (i.e., higher
– Increased circulating blood volume
afterload)
– Increased venous tone
– Increased ventricular compliance -If the ventricle is hypertrophied with a
– Increased atrial contractility thickened wall  distributed across many cells
 decrease in wall stress and decrease in
– Decreased intrathoracic pressure
afterload
174 176
188
8:00am-8:35am
Stroke Volume
Afterload (dept on preload, afterload, contractility)
• Afterload corresponds directly with end-systolic SV = End-diastolic volume - End-systolic volume

volume (ESV, = residual ventricular volume)
– With increased afterload, there is more blood left = Volume in LV at end of filling
after ejection and an increased ESV
= Volume in LV at end of ejection

(how easy it is for
heart to stretch)
177 179
Contractility Determinants of Cardiac Output
• = force and velocity of a contraction CO = SV x HR

HR
SV
Peripheral vascular
resistance
178 180
189
8:00am-8:35am
Increased LV diastolic filling Actin, thin

Myosin, thick
Cardiac muscle stretches

At baseline, With an increase in preload
cardiac muscle is and increased stretch, there is
Greater force of contraction not in optimal more optimal overlap between
position to create thin and thick muscle filaments
greatest force of of sarcomeres  greater force
Increased stroke volume contraction of contraction
181 183
Frank-Starling Principle Frank-Starling Principle

Heart
Pumping
SVC/IVC Aorta Ability of
Heart
Preload
182 184
190
8:00am-8:35am

Frank-Starling Principle Change in Afterload
Pumping Stroke volume
Ability of Cardiac output
Heart LV sys pressure Y Normal
Stroke work Stroke X At a given preload
volume (point X, Y), and
then increase
LV end-diastolic volume afterload:
Diastolic cardiac muscle length
LV end-diastolic pressure SVR, SV
Preload inc in LVEDV
185 187

Frank-Starling Principle: Preload Change in Afterload
Decreased afterload
(curve moves up and to left)
Stroke Y Y Normal
volume Stroke X
X volume
Increased afterload
(curve moves down
and to right)
186 188
191
8:00am-8:35am
Ventricular Function Curve: Contractility Ventricular Pressure-Volume Loop

Exercise
What would happen to this curve if you: • Ventricular pressure-volume loops can be
contractility?
used as a tool for visualizing changes in
• Infant with CHF? ventricular function as preload, afterload,
and contractility are altered
Stroke
volume
LV
LV volume
189 191
Ventricular Function Curve: Ventricular Pressure-Volume Loop

Change in Contractility Exercise
Increased contractility
(e.g. epi)
A
Stroke Normal LV
X pressure
volume
Decreased contractility
(e.g., CHF) ?
B
LV end-diastolic volume LV volume
190 192
192
8:00am-8:35am

I. Filling/Diastole
II. Isovolumic Contraction
LV LV
pressure pressure III III. Ejection/Systole
IV. Isovolumic Relaxation
IV II
I
SV
ESV EDV
LV volume LV volume
193 195
Increase in Preload
Ventricular Pressure-Volume Loop (afterload and contractility kept constant)
Exercise
A. Volume at end
D of contraction
LV MV opens LV
C
pressure pressure
B. MV closes, EDV, SV
LV contraction

B BB
ESV EDV
LV volume LV volume
194 196
193
8:00am-8:35am
Increase in Preload Qp/Qs

(afterload altered) • = Ratio of pulmonary to systemic blood flow
Exercise
• Well neonate Qp=Qs  Qp/Qs ratio ~1
Inc Preload  (note: slightly more than 1 because bronchial arteries
D. Aortic valve closes inc SV  inc return to pulmonary vein instead of systemic)
LV intra-aortic P
pressure greater than • Left-to-right intracardiac shunt (e.g., VSD)
SV
intraventricular – Greater pulmonary blood flow
P earlier  Ao – Qp/Qs >1
valve closes – If Qp/Qs > 2, suggests a large shunt
B BB earlier • Right-to-left intracardiac shunt (e.g., Tricuspid atresia)

ESV slightly – Lower amount of pulmonary blood flow
ESV
LV volume higher – Qp/Qs < 1
197 199
Qp/Qs
Exercise
Write the formula to calculate the Qp/Qs

Derivation of Formula for
Calculating the Qp/Qs Ratio
198 200
194
8:00am-8:35am
To Derive Qp/Qs  Fick Equation Deriving Qp/Qs ratio

O2 consumption is the difference between the amount of
O2 delivered by the heart and O2 returning to the heart Solving for flow…
blood flow x O2 content blood flow x O2 content
in venous As an aside, this is the equation for cardiac index
in arterial blood
blood CI = O2 consumption (mL/min/m2)
O2 content = O2 bound to Hb + O2 dissolved in blood 1.36 (Hb)(10)(Ao O2 sat – mixed venous O2 sat)
O2 content = 1.36 (Hb)(O2 sat) + (.003 x paO2)
(1.36 mL O2 bound per gram Hb, varies 1.34-1.39) Because CI = CO/body surface area, m2 added to
numerator
201 203
Deriving Qp/Qs ratio

Factor of 10
O2 consumption = flow x 1.36 (Hb)(art O2 sat – venous O2 sat)
Solving for flow…
min = min g dL flow = O2 consumption
min = min g dL Deriving Qp/Qs….
Qp = O2 consumption
mL L x 1.36 mL x Hb x 10 dL 1.36 (Hb)(10)(PV O2 sat – PA O2 sat)
min = min dL L
Qs = O2 consumption
202 204
195
8:00am-8:35am

= =
Qp = O2 consumption Qs 1 PV O2 sat – PA O2 sat
1.36 (Hb)(10)(PV O2 sat – PA O2 sat)
Qs = O2 consumption Assumptions:
1.36 (Hb)(10)(Ao O2 sat – MV O2 sat)
Ao O2 sat = pulse ox
1 No lung disease:
Qp PV O2 sat – PA O2 sat PV O2 sat = 100%
=
Qs 1
205 207

= =
1 Qs 1 PV O2 sat – PA O2 sat
=
Qs 1 Thus, if Ao = PV O2 sat and
Ao O2 sat – MV O2 sat MV = PA O2 sat  no
intracardiac shunting and
Qp/Qs = 1
=
Qs PV O2 sat – PA O2 sat
206 208
196
8:00am-8:35am
Summary
output:
– Heart rate, stroke volume
preload, afterload, contractility
• Reviewed the Frank-Starling principle

– The more the heart is filled, the more that
is ejected (up to a certain point)
209
Summary
• Reviewed effect of preload, afterload
and contractility on the ventricular
function curve
• Described the ventricular pressure-
volume loop
output
• Derived the formula for Qp/Qs
210
197
198
Cardiovascular Hemodynamics in the Newborn - Dr. Brodsky
8:35am-9:15am
Neonatal Cardiac Circulation

• PFO is closed
Cardiac Hemodynamics in the Newborn • PDA usually is closed
• Ventricles work in series with

entire blood volume entering and
exiting each ventricle
• LV provides all of the systemic
CO
• RV provides all of its output to the
lungs
1 3
Disclosure Overview
• Neither I nor any member of my immediate family has a financial I. Discuss determinants of cardiac output
relationship or interest with any proprietary entity producing health
care goods or services related to the content of this activity.
How does the
• My content will not include discussion/
reference of commercial products or services. neonate increase
cardiac output?
• I do not intend to discuss an unapproved/
2 4
199
8:35am-9:15am
Overview Overview
II. Review the Frank-Starling Principle IV. Describe the ventricular pressure-volume loop
Explanation
Relevance
LV pressure
?
Otto Frank Ernest Starling
LV volume
5 7
Overview Overview
III. Explain changes in the ventricular function curve V. Qp/Qs ratio

A
How is the formula derived?
? X
?
6 8
200
8:35am-9:15am

Exercise
CO = ? CO = SV x HR
In contrast to fetus, neonate not only depends on HR to
change CO, but also relies on changes in SV
Usually referring to systemic cardiac output and thus,

focus is on LV
9 11

CO = SV x HR
CO = SV x HR
Stroke Volume (SV) = volume of blood ejected from
Systemic blood pressure the ventricle per beat
CO =
Note: this is in contrast to CO, which is the volume of
Poiseuille’s law for laminar
flow: blood ejected from the ventricle per minute
Flow = P/R
10 12
201
8:35am-9:15am

Exercise
CO = SV x HR How would you define each of these?
List the 3 determinants of stroke volume Preload
Afterload
i.e., What determines the amount of blood volume ejected
from the LV during systole? Contractility
13 15
Stroke Volume Preload

• = Degree of cardiomyocyte stretching at the end of diastole
• = Volume in the ventricle at the end of filling = end-diastolic
CO = SV x HR volume (EDV)
• Preload increases with:
Preload
– Increased circulating blood volume
Afterload
– Increased venous tone
Contractility – Increased ventricular compliance
– Increased atrial contractility
– Decreased intrathoracic pressure
14 16
202
8:35am-9:15am
Afterload
• Most view afterload as related to SVR, and that’s true but afterload is Afterload
also impacted by changes in size and thickness of ventricle
• Afterload corresponds directly with end-systolic volume (ESV =
• = Tension/stress developed in the ventricular wall during ejection residual ventricular volume)
– With increased afterload, there is more blood left after ejection and an
increase in ESV
Ventricular wall Ventricular P x Ventricular radius
=
stress Wall thickness
-If distal vascular resistance increases  increase in proximal

intraventricular P  greater systolic wall stress (i.e., increased
afterload)
17 19
Afterload
Contractility
Ventricular wall Ventricular P x Ventricular radius
=
stress Wall thickness • = force and velocity of a contraction
-If the ventricle is dilated  increased ventricular wall stress
with greater total load (tension) on the myocytes (i.e., higher
afterload)
-If the ventricle is hypertrophied with a thickened wall 
distributed across many cells  decrease in wall stress and
decrease in afterload
18 20
203
8:35am-9:15am
Stroke Volume (dept on preload,

afterload, contractility) Frank-Starling Principle
SV = End-diastolic volume - End-systolic volume
Increased LV diastolic filling
= Volume in LV at end of filling
= Volume in LV at end of ejection Cardiac muscle stretches
Greater force of contraction
(how easy it is for
heart to stretch) Increased stroke volume
21 23
Determinants of Cardiac Output Frank-Starling Principle

CO = SV x HR Heart
HR SVC/IVC Aorta
SV
Peripheral vascular
resistance
22 24
204
8:35am-9:15am
Actin, thin Myosin, Pumping Stroke volume
thick Ability of Cardiac output
Heart LV sys pressure
Stroke work
At baseline, cardiac With an increase in preload and increased

muscle is not in optimal stretch, there is more optimal overlap LV end-diastolic volume
position to create greatest between thin and thick muscle filaments of Diastolic cardiac muscle length
force of contraction sarcomeres  greater force of contraction LV end-diastolic pressure
Preload
25 27
Frank-Starling Principle Frank-Starling Principle: Preload
Pumping
Ability of Stroke Y
Heart volume
X
Preload
26 28
205
8:35am-9:15am
Ventricular Function Curve: Change in

Ventricular Function Curve: Contractility
Afterload Exercise
What would happen to this curve if you:
Y Normal contractility?)
Stroke X At a given preload (point
• Infant with CHF?
volume X, Y), and then increase
afterload:
Stroke
SVR, SV volume
inc in LVEDV
29 31
Ventricular Function Curve: Change in Ventricular Function Curve: Change in

Afterload Contractility
Decreased afterload Increased contractility
(curve moves up and to left) (e.g. epi)
A
Stroke Normal
Y Normal
Stroke X
X volume
volume Decreased contractility
Increased afterload (curve (e.g., CHF)
moves down and to right)
B
LV end-diastolic volume LV end-diastolic volume
30 32
206
8:35am-9:15am

• Ventricular pressure-volume loops can be used as a tool
for visualizing changes in ventricular function as preload,
LV pressure
afterload, and contractility are altered
LV
LV volume
LV volume
33 35
Ventricular Pressure-Volume Loop

Exercise Ventricular Pressure-Volume Loop
A. Volume at end of
D contraction
LV pressure LV pressure MV opens
C
B. MV closes, EDV, LV
? contraction
ESV EDV
LV volume LV volume
34 36
207
8:35am-9:15am
Increase in Preload
Ventricular Pressure-Volume Loop (afterload altered)
Exercise
I. Filling/Diastole
Inc Preload  inc SV
 inc intra-aortic P
II. Isovolumic Contraction DD
LV pressure LV pressure D
greater than
III III. Ejection/Systole intraventricular P
SV
IV
IV. Isovolumic Relaxation earlier Ao valve
II
closes earlier (DD)
I
ESV slightly higher
SV B BB
ESV EDV ESV
LV volume LV volume
37 39
Increase in Preload
(afterload and contractility kept constant)
Exercise
Derivation of Formula for Calculating the

LV pressure
Qp/Qs Ratio
SV
B BB
LV volume
38 40
208
8:35am-9:15am
Qp/Qs To Derive Qp/Qs  Fick Equation

• = Ratio of pulmonary to systemic blood flow
O2 consumption is the difference between the amount of O2 delivered by the
• Well neonate Qp=Qs  Qp/Qs ratio ~1 (note: slightly more than heart and O2 returning to the heart
1 because bronchial arteries return to pulmonary vein instead of systemic)
• Left-to-right intracardiac shunt (e.g., VSD)
– Greater pulmonary blood flow blood flow x O2 content blood flow x O2 content
in arterial blood in venous
– Qp/Qs >1
blood
– If Qp/Qs > 2, suggests a large shunt
O2 content = O2 bound to Hb + O2 dissolved in blood
• Right-to-left intracardiac shunt (e.g., Tricuspid atresia)
– Lower amount of pulmonary blood flow O2 content = 1.36 (Hb)(O2 sat) + (.003 x paO2)
(1.36 mL O2 bound per gram Hb, varies 1.34-1.39)
– Qp/Qs < 1
41 43
Qp/Qs
Exercise
Factor of 10
Write the formula to calculate the Qp/Qs mL L x 1.36 mL x Hb g
min = min g dL
min = min g dL
mL L x 1.36 mL x Hb x 10 dL
min = min dL L
42 44
209
8:35am-9:15am
Deriving Qp/Qs ratio Deriving Qp/Qs Ratio

Deriving Qp/Qs….
Solving for flow… Qp = O2 consumption
1.36 (Hb)(10)(PV O2 sat – PA O2 sat)
Qs = O2 consumption
As an aside, this is the equation for cardiac index 1.36 (Hb)(10)(Ao O2 sat – MV O2 sat)
CI = O2 consumption (mL/min/m2)
1
=
Because CI = CO/body surface area, m2 added to numerator Qs 1
45 47
Deriving Qp/Qs ratio Deriving Qp/Qs Ratio

O2 consumption = flow x 1.36 (Hb)(art O2 sat – venous O2 sat) Deriving Qp/Qs….
Solving for flow… 1
flow = O2 consumption =
Qs 1
Deriving Qp/Qs….
Qp = O2 consumption
1.36 (Hb)(10)(PV O2 sat – PA O2 sat) Qp Ao O2 sat – MV O2 sat
=
Qs = O2 consumption Qs PV O2 sat – PA O2 sat
O2 sat in either decimal form or %
46 48
210
8:35am-9:15am
Qp/Qs Ratio Qp/Qs Ratio

Qp 1 Ao O2 sat – MV O2 sat Qp 1 Ao O2 sat – MV O2 sat
= = = =
Qs 1 PV O2 sat – PA O2 sat Qs 1 PV O2 sat – PA O2 sat
However, if have large right to left

Assumptions: shunt (TA)
Ao O2 sat = pulse ox •lower Ao O2 sat
•lower difference between Ao and MV
No lung disease: O2 sat
PV O2 sat = 100% •small Qp/Qs ratio (less PBF)
49 51
Qp/Qs Ratio
Qp 1 Ao O2 sat – MV O2 sat Summary
= =
Qs 1 PV O2 sat – PA O2 sat • Discussed determinants of cardiac output:
– Heart rate, stroke volume
Thus, if Ao = PV O2 sat and MV = PA preload, afterload, contractility
O2 sat  no intracardiac shunting and
Qp/Qs = 1
• Reviewed the Frank-Starling principle
– The more the heart is filled, the more that is ejected (up to a
certain point)
50 52
211
8:35am-9:15am
Summary Summary
• Reviewed effect of preload, afterload and contractility • Derived the formula for Qp/Qs
on the ventricular function curve:
Stroke =
volume Qs PV O2 sat – PA O2 sat
53 55
Summary
• Described the ventricular pressure-volume loop:
LV pressure
dbrodsky@bidmc.harvard.edu
LV volume
54 56
212
Case-Based - CHD Cyanotic Lesions - Dr. Armsby
9:15am-10:15am
Congenital Heart Disease ‐ Disclosure
Cyanotic Lesions • I nor any member of my immediate family has a
financial relationship or interest with any proprietary
entity producing health care goods or services related
NeoPREP Review and Update of
to the content of this activity.
Neonatal‐Perinatal Medicine
Long Beach, CA
February 8, 2020 • The content of this presentation will not include
discussion/reference of commercial products or
services.
Laurie Armsby, MD, FSCAI, FAAP
Division of Pediatric Cardiology • I do not intend to discuss an unapproved or
Oregon Health Sciences University investigative use of commercial products/devices.
1 2
Learning Objectives Pulmonary and Systemic Flow (Q)
I. Understand the cardiovascular pathophysiology
underlying the cardiac defects that present in
the neonatal period
Qp = Flow thru the right
heart to the lungs
II. Recognize the signs and symptoms of congenital
heart disease presenting in the neonatal period
Qs = Flow thru the left
heart to the body
III. Direct therapy aimed at supporting sufficient
pulmonary and/or systemic blood flow in
patients with congenital heart disease
3 4
213
9:15am-10:15am
Pulmonary and Systemic Flow (Q) Pulmonary and Systemic Flow (Q)
L‐to‐R Shunt = Oxygenated
blood within the Left Heart or
systemic circulation returns to
Qp = Flow thru the right Qp = Qs the lungs
heart to the lungs
and Flow to lungs > Flow to body
Qs = Flow thru the left
Qp > 1
heart to the body Qp = 1
Qs
Qs
5 6
L‐to‐R Shunt = Oxygenated L‐to‐R Shunt = Oxygenated
blood within the Left Heart or blood within the Left Heart or
Qp = 4 L/min systemic circulation returns to Qp = 4 L/min systemic circulation returns to
Qs = 2 L/min the lungs Qs = 2 L/min the lungs
Qp = 4 = 2.0 Flow to lungs > Flow to body Qp = 4 = 2.0 Flow to lungs > Flow to body

Qs 2 Qs 2
Qp > 1 Qp > 1
Qs Qs
Tachypnea, Failure to Thrive
Congestive Heart Failure
7 8
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R‐to‐L Shunt = R‐to‐L Shunt =
Blue blood bypasses the lungs and Blue blood bypasses the lungs and
joins the systemic circulation Qp = 2 L/min joins the systemic circulation
Qs = 4 L/min
Qp = 2 = 0.5
Flow to body
Flow to lungs <
Qs 4
Flow to body
Flow to lungs <
Qp < 1 Qp < 1
Qs Qs
9 10
Pulmonary and Systemic Flow (Q) Pulmonary and Systemic Vascular Resistance
R‐to‐L Shunt =
Blue blood bypasses the lungs and Ohm’s Law:
Qp = 2 L/min joins the systemic circulation
Qs = 4 L/min Resistance = in Pressure across a circulation
Flow across that circulation
Qp = 2 = 0.5
Qs 4
Flow to body
Flow to lungs <
Qp < 1
Qs
Cyanosis
Acidosis, Tachypnea
11 12
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Pulmonary and Systemic Vascular Resistance Pulmonary and Systemic Vascular Resistance
Pulmonary Vascular Resistance (PVR) Pulmonary Vascular Resistance Systemic Vascular Resistance

(PVR) (SVR)
• Resistance to flow as it passes
through the lungs • Resistance to flow as it passes • Resistance to flow as it passes
through the lungs through the body
PVR = PAp – LAp PVR = PAp – LAp SVR = Aop – RAp

Qp Qp Qs
13 14
ABP Content Guidelines Congenital Heart Disease
Cyanotic Lesions Non‐Cyanotic Lesions
For each Class of Congenital Heart Lesions: • Tetralogy of Fallot • Atrial Septal Defect
• Pulmonary Atresia • Ventricular Septal Defect
i. Anatomy, Pathophysiology and Genetics
• Tricuspid Atresia • Atrioventricular Canal
ii. Clinical Features • Ebsteins Anomaly • Patent Ductus Arteriosus
iii. Diagnostic Features • D‐Transposition of the Great Arteries • Pulmonary Stenosis
(d‐TGA) • Aortic Stenosis
iv. Evaluation and Medical/Surgical Management • Total Anomalous Pulmonary Venous • Coarctation
v. Differential Diagnosis Return (TAPVR)
• Truncus Arteriosus
• Hypoplastic Left Heart Syndrome (HLHS)
• Other single ventricle lesions
15 16
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9:15am-10:15am
Congenital Heart Disease Congenital Heart Disease
Non‐Cyanotic Lesions Cyanotic Lesions
Obstruction to pulmonary
• Atrial Septal Defect • Tetralogy of Fallot blood flow and right‐to‐left
Connection btw left and
• Pulmonary Atresia shunting (insufficient pulm
right heart allowing left‐ • Ventricular Septal Defect
to‐right shunting • Tricuspid Atresia bld flow)
• Atrioventricular Canal
(excessive pulm bld flow) • Ebsteins Anomaly
• Patent Ductus Arteriosus • D‐Transposition of the Great Arteries Routing of blood into
• Pulmonary Stenosis (d‐TGA)
parallel circulations
Obstruction to flow across • Total Anomalous Pulmonary Venous
valves or great arteries • Aortic Stenosis Return (TAPVR)
• Coarctation • Truncus Arteriosus Complete mixing of
• Hypoplastic Left Heart Syndrome (HLHS) pulmonary and systemic
• Other single ventricle lesions venous return
17 18
Parallel Circulations Parallel Circulations
LA
RA
LV LV LV
RV RV RV
d‐Transposition of the in utero post‐natal

Great Arteries d‐Transposition of the d‐Transposition of the
Great Arteries Great Arteries
19 20
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9:15am-10:15am
Principles:
• Adequate 02 delivery to the tissues requires a
means of getting pulmonary venous return to the
aorta (ASD, VSD and/or PDA)
LA LA LA LV
RV
RA RA RA
LV LV LV
RV RV RV
d‐TGA + ASD d‐Transposition of the d‐TGA + VSD ± ASD

Great Arteries
LV
RV
21 22
Parallel Circulations ~70%
Parallel Circulations <70%
Principles: Principles:
• Adequate 02 delivery to the tissues requires a >90% • Adequate 02 delivery to the tissues requires a <70%
means of getting pulmonary venous return to the means of getting pulmonary venous return to the
aorta (ASD, VSD and/or PDA) aorta (ASD, VSD and/or PDA)
• Without intracardiac mixing: The pre‐ductal sat is LV • Without intracardiac mixing: The pre‐ductal sat is LV
RV RV
low. low.
• Right‐to‐left flow across PDA leads to higher post‐ Reverse differential cyanosis • Right‐to‐left flow across PDA leads to higher post‐
ductal saturations. **May miss on POxS if only LE is checked ductal saturations.
• Loss of PDA or drop in PVR decreases R‐to‐L flow
across PDA leading to drop in all sats
23 24
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9:15am-10:15am
Parallel Circulations ~80% Parallel Circulations ~60%
Signs of a stable physiology: Signs of a stable physiology:
~80% ~70%
adequate mixing: adequate mixing:
• Equal pre‐ and post‐ductal sats • Equal pre‐ and post‐ductal sats
• Sats 70‐85% LV • Sats 70‐85% LV
RV RV
• Normal pH, lactate • Normal pH, lactate
~60%
Signs of an unstable physiology:
inadequate mixing:
~60%
• pre‐ductal sats lower than post‐ductal sats
• As PVR drops, post‐ductal sats drop
• Acidosis, tachypnea, cardiovascular collapse LV
RV
25 26
Principles of Treatment: Principles of Treatment:
• Maintain ductal patency (PGE) pending echo • Maintain ductal patency (PGE) pending echo
and possibly thereafter and possibly thereafter
• Determine intracardiac mixing ability (echo) LV
• Determine intracardiac mixing ability (echo)
• If ASD is present and pre‐ductal sat is low: give 02 RV • If ASD is present and pre‐ductal sat is low: give 02
(this will increase Qp, increase L‐to‐R shunt across (this will increase Qp, increase L‐to‐R shunt across LV
RV
ASD) ASD)
• If there is only a PFO, or no ASD at all, 02 will Increasing the pulmonary blood flow
potentially worsen the hypoxemia without an ASD:
‐ increase LAp  closure of the PFO
‐ Pulmonary overcirculation without an
increase in sats, tachypnea, tachycardia
LV
RV
27 28
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9:15am-10:15am
• Maintain ductal patency (PGE) pending echo • Maintain ductal patency (PGE) pending echo
and possibly thereafter and possibly thereafter
• Determine intracardiac mixing ability (echo) • Determine intracardiac mixing ability (echo) LV
• If ASD is present and pre‐ductal sat is low: give 02 • If no ASD: Balloon atrial septostomy RV
(this will increase Qp, increase L‐to‐R shunt across LV
• pre‐ductal saturations < ~70%
RV
ASD) • inadequate intracardiac mixing
• If there is only a PFO, or no ASD at all, 02 will VSD without a good sized ASD: • small ASD and surgeon prefers infant off PGE
potentially worsen the hypoxemia ‐ Streaming: flow does not cross the • small ASD and anticipate delay in surgery
septum
• A VSD alone may or may not be sufficient to create ‐ As the PVR drops (and if you give 02):
adequate mixing Pulmonary overcirculation without an
increase in sats, tachypnea, tachycardia
LV
RV
29 30
Parallel Circulations
Principles of Treatment:
• Establish correct orientation between ventricles and great arteries
Typically 3‐7 days
of age
LV
LV RV
RV
d‐TGA s/p
d‐TGA
Arterial Switch Operation
31 32
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Congenital Heart Disease Right‐sided Obstructive Lesions
Cyanotic Lesions
• Tetralogy of Fallot Obstruction to pulmonary • Obstruction of flow to the • Physiology ⍺ severity of
• Pulmonary Atresia blood flow and pulmonary circulation obstruction
• Tricuspid Atresia right‐to‐left shunting
• Ebsteins Anomaly
• D‐Transposition of the Great Arteries Routing of blood into
(d‐TGA)
• Total Anomalous Pulmonary Venous
Return (TAPVR)
• Truncus Arteriosus Complete mixing of
33 34
Right‐sided Obstructive Lesions Right‐sided Obstructive Lesions
Tricuspid and Pulmonary Atresia
• Obstruction of flow to the • Physiology ⍺ severity of Severe

obstruction to
pulmonary circulation obstruction pulm flow and
PDA dependence
Stenosis = narrowing
Hypoplastic = small in size (ie stenotic)
Atresia = complete occlusion
No obstruction to
pulm flow and no
PDA dependence
Tricuspid Atresia w/ VSD
35 36
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9:15am-10:15am
Pulm Atresia w/ Intact
Ventricular Septum Physiologic Principles:
• The right heart pumps to the pulmonary
circulation
Pulm Atresia
Critical Pulmonary
Stenosis
w/ VSD
• The degree of obstruction determines the
level of cyanosis and ductal dependence
Pulmonary Atresia with

Intact Ventricular Septum
Tetralogy of Fallot w/
Pulmonary Stenosis
Long segment Pulm Atresia
w/ MAPCAS
37 38
Mild obstruction Severe obstruction Mild obstruction Severe obstruction
Tetralogy of Fallot with mild Pulmonary Atresia with Intact Tetralogy of Fallot with mild Pulmonary Atresia with Intact
pulmonary stenosis (“Pink Tet”) Ventricular Septum pulmonary stenosis (“Pink Tet”) Ventricular Septum
• Because of the Rt‐sided obstruction, flow
shunts Right‐to‐Left across the ASD &/or VSD
 Hypoxemia, Cyanosis
• These pts should fail the pulse ox screen with
hypoxemic pre‐ and post‐ductal sats
39 40
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9:15am-10:15am
Mild obstruction Severe obstruction Mild obstruction Severe obstruction
Tetralogy of Fallot with mild Pulmonary Atresia with Intact Tetralogy of Fallot with mild Pulmonary Atresia with Intact
pulmonary stenosis (“Pink Tet”) Ventricular Septum pulmonary stenosis (“Pink Tet”) Ventricular Septum
• With severe obstruction to pulm blood flow: • With mild obstruction to pulm blood flow: • With severe obstruction to pulm blood flow:

flow across the PDA is Left‐to‐Right there may be no/little R‐to‐L shunting flow across the PDA is Left‐to‐Right
 equal, low pre/post ductal sats  minimal hypoxemia, cyanosis  equal, low pre/post ductal sats
 ductal dependent  risk of pulmonary overcirculation, CHF  ductal dependent
41 42
Mild obstruction Severe obstruction
• The degree of obstruction determines the level of cyanosis and
ductal dependence
02 and PGE2 may not be
necessary, but are safe
pending the echo diagnosis. Except:
Goal 02sat 80% These infants may have
enough pulmonary blood
flow without the ductus;
Tetralogy of Fallot with mild Pulmonary Atresia with Intact usually need a cath to
pulmonary stenosis (“Pink Tet”) Ventricular Septum determine sources of
pulmonary blood flow
• With mild obstruction to pulm blood flow: • With severe obstruction to pulm blood flow:
there may be no/little R‐to‐L shunting flow across the PDA is Left‐to‐Right
 minimal hypoxemia, cyanosis  equal, low pre/post ductal sats
 risk of pulmonary overcirculation, CHF  ductal dependent long‐segment Pulmonary Atresia w/
MAPCAS
43 44
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9:15am-10:15am
Signs of a stable physiology: Signs of a stable physiology:
80% 96%
• 02sat 75‐85% (pre‐ and post‐ductal), • 02sat 75‐85% (pre‐ and post‐ductal),
comfortable breathing and a normal lactate comfortable breathing and a normal lactate
indicates a good balance of Qp and Qs indicates a good balance of Qp and Qs
80% 96%
Signs of an unstable physiology:
• 02sat > 90% ⍺ significant Qp
• Excessive pulm blood flow as PVR drops
• 02sat < 70%, rising lactate ⍺ insufficient Qp
Pulmonary Atresia with • Possibly reflects a closing PDA Pulmonary Atresia with
Intact Ventricular Septum Intact Ventricular Septum
45 46
Diagnostic Features: Principles of Treatment:
< 95%
• Maintain ductal patency
• Pulse ox Screening: provide a stable source of pulmonary blood flow
• Sats will be low (⍺ degree of obstruction)
• Pre‐ and post‐ductal sats will be equal
• Should be identified by POxS (abnl ≤ 95%) < 95%
• CXR: Dark lung fields, normal heart size
• ECG: ± Decreased rt‐sided voltages (left axis
deviation)
Pulmonary Atresia with Pulmonary Atresia with
47 48
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9:15am-10:15am
• Maintain ductal patency • Maintain ductal patency
provide a stable source of pulmonary blood flow provide a stable source of pulmonary blood flow
• Balance Pulmonary and Systemic Blood Flow • Balance Pulmonary and Systemic Blood Flow
(judicious use of 02) (judicious use of 02)
*Qp << Qs = cyanosis, acidosis *Qp << Qs = cyanosis, acidosis
*Qp >> Qs = congestive heart failure, acidosis *Qp >> Qs = congestive heart failure, acidosis
• If can’t increase Qp, decrease 02 demand
• mechanical ventilation
• sedation/paralysis
Pulmonary Atresia with Pulmonary Atresia with
49 50
Typically 1‐3 days
of age
Following initial supportive measures: Following initial supportive measures:
• Provide a long‐term source of pulmonary blood flow Critical Pulmonary • Provide a long‐term source of pulmonary blood flow
Stenosis
‐ relieve the obstruction (valve dilation/stent, TOF repair) ‐ relieve the obstruction (valve dilation/stent, TOF repair) Pulmonary Atresia/IVS Tricuspid Atresia
or
‐ provide an alternative to the ductus (ductal stent,
Blalock‐Taussig shunt, RV‐PA conduit)
Typically 2‐4 mo
of age
Pulmonary Atresia/VSD
Repair of Tetralogy of
Fallot
Helen Taussig Alfred Blalock Vivien Thomas
51 52
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9:15am-10:15am
Blalock‐Taussig Shunt Congenital Heart Disease

Cyanotic Lesions
• Tetralogy of Fallot Obstruction to pulmonary
• Pulmonary Atresia blood flow and
• Tricuspid Atresia right‐to‐left shunting
(d‐TGA)
• Total Anomalous Pulmonary Venous
Return (TAPVR)
• Truncus Arteriosus Complete mixing of
53 54
Complete Mixing Lesions Complete Mixing Lesions
• Pulmonary and Systemic venous return • Pulmonary and Systemic venous return
… mix together and are ejected into … mix together and are ejected into <90%
the systemic circulation the systemic circulation
• Obligate mixing of oxygenated and • Obligate mixing of oxygenated and
deoxygenated blood which is then deoxygenated blood which is then
delivered to the tissues delivered to the tissues
• These pts should fail the pulse ox
screen with hypoxemic pre‐ and post‐
ductal sats
Truncus Arteriosus Truncus Arteriosus
55 56
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9:15am-10:15am
• Pulmonary and Systemic venous return • Pulmonary and Systemic venous return
… mix together and are ejected into <90% … mix together and are ejected into
the systemic circulation the systemic circulation
• Obligate mixing of oxygenated and • Obligate mixing of oxygenated and
Left dominant Right dominant
deoxygenated blood which is then deoxygenated blood which is then Unbalanced AVC Unbalanced AVC
delivered to the tissues delivered to the tissues
• These pts should fail the pulse ox • These pts should fail the pulse ox
screen with hypoxemic pre‐ and post‐ screen with hypoxemic pre‐ and post‐
ductal sats ductal sats
Total Anomalous Pulmonary Venous Return Double Inlet LV

(TAPVR)
57 58
SVR = 12 w.u.
• Flow thru and out of the heart follows • Flow thru and out of the heart follows
the path of least resistance the path of least resistance
PVR = 2 w.u.
Resistance = in pressure • In the absence of a structural obstruction to
Flow outflow…
Truncus Arteriosus TAPVR …these lesions are not ductal dependent
…the drop in PVR over time leads to
pulmonary overcirculation and congestive
heart failure
 Tachypnea
 Poor growth Truncus Arteriosus
 Rising lactate
Right dominant Unbalanced AVC
59 60
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9:15am-10:15am
As the PVR drops over time and/or with 02:
85%
• Signs of a stable circulation: • As the increase in Qp draws flow away
• 02sat 75‐80%, comfortable breathing from the systemic circulation, the heart
and normal lactate ⍺ a good balance must increase its output to maintain
of Qp and Qs adequate Qs (oxygen delivery to the
systemic circulation)
100% • Tachycardia
• Poor growth
70%
Truncus Arteriosus Truncus Arteriosus
61 62
• In the presence of a structural obstruction
to outflow…
92%
Signs of an unstable circulation: …these lesions may be ductal dependent
• 02sat > 90%, tachycardia, tachypnea, poor (⍺ severity of obstruction)
feeding…. ⍺ Qp >> Qs ….loss of the ductus leads to collapse of
 The volume of blue blood returning from the circulation (cyanosis, shock)
the body is less than the volume of
oxygenated blood returning from the
…the drop in PVR over time leads to
100% pulmonary overcirculation and
lungs
congestive heart failure
70%
 Tachypnea
 Poor growth
Truncus Arteriosus  Rising lactate
Hypoplastic Left Heart Syndrome (HLHS)
63 64
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9:15am-10:15am
Clinical Features: Diagnostic Features:
• Cyanosis (variable 02 desaturation)
• CXR:
• Pulse ox screening should identify these • Truncus: ”Egg on a string” (no MPA)
lesions • Obstructed TAPVR: Pulmonary congestion
Truncus Arteriosus TAPVR • Once PVR drops: CM, pulm congestion Truncus Arteriosus TAPVR
• +/‐ Murmur; Single S2 (Truncus, HLHS)
• As PVR drops: • Echo:
• Rise in 02 saturation
• Assess for outflow obstruction which will
• Tachypnea indicate ductal dependence
• Tachycardia
• Poor weight gain/poor feeding • Obstructed TAPVR is often hard to see by echo
Unbalanced AVC HLHS Unbalanced AVC HLHS
65 66
Complete Mixing Lesions Medically managing PVR
Factors which Increase PVR
• Separate the two circulations
• Pre‐op: Balance the circulations and support • Pulmonary Vascoconstriction
the physiology of CHF • Hypoxia
• Acidosis (↑ pC02)
Truncus Arteriosus TAPVR
• Increased interstitial pressure
• Atelectasis
• Pulmonary edema
• Pneumothorax /Pleural effusion
• Mechanical ventilation
• Excess PEEP
• Lung hypoplasia
Unbalanced AVC HLHS • Polycythemia
67 68
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9:15am-10:15am
Medically managing PVR Complete Mixing Lesions
Factors which Increase PVR Factors which Decrease PVR
• Separate the two circulations
• Pulmonary Vascoconstriction • Pulmonary Vasodilation
• Hypoxia • Pre‐op: Balance the circulations and support the physiology of CHF
• Alveolar expansion
• Acidosis (↑ pC02)
• Alkalosis (↓ pC02)
• Increased interstitial pressure • Oxygen
• Atelectasis
• Pulmonary edema • Nitric Oxide
• Pneumothorax /Pleural effusion • Sildenafil, Bosentan, etc
• Mechanical ventilation
• Excess PEEP
• Lung hypoplasia
• Polycythemia Repair of Truncus Arteriosus
69 70
• Separate the two circulations • Separate the two circulations
• Pre‐op: Balance the circulations and support the physiology of CHF • Pre‐op: Balance the circulations and support the physiology of CHF
Stage I Norwood with
Damus‐Kaye‐Stansel (“DKS”)
and Blalock‐Taussig Shunt
If there is a single ventricle without obstruction to outflow, balance the circulations until they can be separated If there is a single ventricle with obstruction to outflow, replace the ductus and balance the circulations
until they can be separated
71 72
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9:15am-10:15am
Question 1: A newborn at 24 hours of age has a pre‐ductal
saturation of 78% and a post‐ductal saturation of 77%. His
Ductal
Dependent?
Congenital Heart Disease
pulses are easy to palpate and he is breathing comfortably. Do Cyanotic Lesions
Obstruction to pulmonary
you have enough information to know whether this patient is ± • Tetralogy of Fallot blood flow and right‐to‐left
ductal dependent? ± • Pulmonary Atresia shunting (insufficient pulm
±
• Tricuspid Atresia bld flow)
a. No but PGE should be started unless echo can be done immediately ± • Ebsteins Anomaly
± • D‐Transposition of the Great Arteries Routing of blood into
b. Yes and PGE should be started (d‐TGA)
c. Yes and PGE should not be started N • Total Anomalous Pulmonary Venous
Return (TAPVR)
N • Truncus Arteriosus Complete mixing of
Y • Hypoplastic Left Heart Syndrome (HLHS) pulmonary and systemic
± • Other single ventricle lesions venous return
73 74
Question 2: Which of the cyanotic lesions below has a higher Question 3: Which two of the cyanotic lesions below share the
potential for pulmonary hypertension which may limit the degree of physiology of pulmonary congestion, worsening hypoxemia and
pulmonary overcirculation and secondary congestive heart failure? require urgent intervention?
a. Hypoplastic Left Heart Syndrome a. Hypoplastic Left Heart Syndrome with Intact Atrial Septum
b. Truncus Arteriosus b. Truncus Arteriosus
c. Unobstructed Total Anomalous Pulmonary Venous Return c. Obstructed Total Anomalous Pulmonary Venous Return
d. Unbalanced AV canal with normal aortic and pulmonary valves d. Unbalanced AV canal with normal aortic and pulmonary valves
75 76
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9:15am-10:15am
TAPVR HLHS
• In utero there is very little flow to the
• TAPVR can be associated with pulmonary lungs, and very little flow returning to
vein obstruction, resulting in: the LA via the pulmonary veins
 pulmonary congestion
• Following birth the increase in pulmonary
 pulmonary hypertension blood flow all comes back to the
 poor gas exchange hypoplastic LA
• There is no medical treatment that • In the absence of an ASD the LAp will rise:
will stabilize this condition • Pulmonary venous congestion HLHS
• Poor gas exchange
• Emergent surgical or transcatheter
relief of the obstruction is required infra-diaphragmatic supra-cardiac • There is no medical treatment that will
TAPVR TAPVR stabilize this condition, emergent ECMO or
cath is required HLHS with
IAS
77 78
Question 4: Which cyanotic mixing Congenital Heart Disease
lesion might have a higher pre‐ductal
saturation? Cyanotic Lesions
• Tetralogy of Fallot Obstruction to pulmonary
• Pulmonary Atresia blood flow and
a. Truncus arteriosus • Tricuspid Atresia right‐to‐left shunting
b. TAPVR Truncus Arteriosus TAPVR
c. Unbalanced AV canal (d‐TGA)
d. HLHS with Mitral Stenosis and Aortic Stenosis • Total Anomalous Pulmonary Venous
Return (TAPVR)
e. HLHS with Mitral Stenosis and Aortic Atresia • Truncus Arteriosus Complete mixing of
Unbalanced AVC HLHS
79 80
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9:15am-10:15am
Study Guides
Thank you
Armsbyl@ohsu.edu
81 82
Genetic Associations Require Neonatal Intervention

Prominent forehead, butterfly hemivertebrae, anterior
Alagille JAG1 mutations Branch PA stenosis, PS, TOF Critical Pulmonary Single Ventricles with LV
chamber abnormalities of the eye d-TGA Interrupted Aortic Arch
Stenosis Outflow Obstruction
VSD, Truncus, Tetralogy of Fallot,
DiGeorge 22q11 deletions Hypoplasia of thymus and parathyroid, cleft palate
IAA
Holt Oram TBX 5 mutations Upper limb anomalies ASD, VSD
Marfans FBN 1 mutations Long limbs, scoliosis, pectus Aortic root dilation, valve prolapse
Widely spaced eyes, ptosis, low set ears, webbed neck,

Noonans PTPN mutations PV stenosis, Tetralogy of Fallot
pectus, cryptorchidism
Bilateral epicanthal folds, tongue protrusion, low nasal
Downs Trisomy 21 ASD, VSD, CAVC
bridge, hypotonia, brushfield spots
Microcephaly, cleft lip/palate, holoprosencephaly,
Patau Trisomy 13 ASD, VSD, PDA, Dextrocardia
ophthalmic issues
Microcephaly, small mouth, micrognathia, joint
Edwards Trisomy 18 VSD, PDA, Valve issues, HLHS
contractures, cleft lip/palate, scoliosis
Turners XO Webbed neck, lymphedema Bicuspid AoV, AS, CoA, IAA
Elfin facies, stellate pattern of iris, short anteverted nose, Supravalvar AS, Branch PA
Williams 7q11 deletion
long philtrum, prominent lips stenosis
Coarctation Single Ventricles with RV

TAPVR Critical Aortic Stenosis
Outflow Obstruction
83 84
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9:15am-10:15am
May Require Urgent Intervention Transposition of the Great Arteries is not all
the same….
d-TGA without ASD or VSD Obstructed TAPVR HLHS w/ Intact Atrial Septum
RA
RA
LV RV
RV
LV
Balloon Atrial Septostomy Surgical Correction Interatrial Stent or
Stage I Norwood w/ Atrial Septectomy D‐TGA L‐TGA or
congenitally corrected‐TGA
85 86
A newborn with a pre‐natal diagnosis of a A newborn with a pre‐natal diagnosis of a
VSD has 02 sats of 85% shortly after birth VSD has 02 sats of 85% shortly after birth
and is placed on 2L NC02 which bring his and is placed on 2L NC02 which bring his
02 sats to 95%. 02 sats to 95%.
4 days later his sats remain > 95% on 2L NC 4 days later his sats remain > 95% on 2L NC

02 however he has developed tachypnea 02 however he has developed tachypnea
and increased work of breathing. What is and increased work of breathing. What is
the cause of the respiratory distress? the cause of the respiratory distress?
a. Increasing right‐to‐left shunt a. Increasing right‐to‐left shunt
b. Increasing left‐to‐right shunt b. Increasing left‐to‐right shunt
c. Closure of the ductus arteriosus c. Closure of the ductus arteriosus
d. Pulmonary Hypertension d. Pulmonary Hypertension
87 88
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9:15am-10:15am
Which Right‐Sided Obstructive Lesions are Which Right‐Sided Obstructive Lesions are
Ductal Dependent? Ductal Dependent?
• Any right‐sided obstructive lesion in which there isn’t sufficient • Any right‐sided obstructive lesion in which there isn’t sufficient
pulmonary blood flow without the ductus pulmonary blood flow without the ductus
• Lesions with severe (critical) pulmonary stenosis
Critical pulmonary stenosis Tetralogy of Fallot w/

Pulmonary Stenosis
89 90
Which Right‐Sided Obstructive Lesions are
Ductal Dependent?
• Any right‐sided obstructive lesion in which there isn’t sufficient
pulmonary blood flow without the ductus
• Lesions with severe (critical) pulmonary stenosis
• Lesions with pulmonary atresia (except with multiple aorto‐
pulmonary collateral arteries (MAPCAS)
Critical pulmonary stenosis Tetralogy of Fallot w/ long‐segment PA w/

Pulmonary Stenosis MAPCAS
91
235
236
Case-Based - CHD Non Cyanotic Lesions - Dr. Armsby
10:30am-11:05am
Learning Objectives
Congenital Heart Disease –
Non‐Cyanotic Lesions I. Understand the cardiovascular pathophysiology
underlying the cardiac defects that present in
the neonatal period
Neonatal‐Perinatal Medicine II. Recognize the signs and symptoms of congenital
Long Beach, CA
February 8, 2020 heart disease presenting in the neonatal period
Laurie Armsby, MD, FSCAI, FAAP III. Direct therapy aimed at supporting sufficient

Division of Pediatric Cardiology pulmonary and/or systemic blood flow in
Oregon Health Sciences University patients with congenital heart disease
1 3
Disclosure Congenital Heart Disease
Non‐Cyanotic Lesions
• I nor any member of my immediate family has a • Atrial Septal Defect
financial relationship or interest with any proprietary Connection btw left and
right heart allowing left‐ • Ventricular Septal Defect
entity producing health care goods or services related
to‐right shunting • Atrioventricular Canal
to the content of this activity.
(excessive pulm bld flow)
• Patent Ductus Arteriosus
• The content of this presentation will not include
• Pulmonary Stenosis
discussion/reference of commercial products or Obstruction to flow across
services. valves or great arteries • Aortic Stenosis
• Coarctation
• I do not intend to discuss an unapproved or
2 4
237
10:30am-11:05am
Left‐to‐Right Shunt Lesions Left‐to‐Right Shunt Lesions
Physiologic Principles:
Physiologic Principles: • Flow thru and out of the heart follows a path
of least resistance
• Connection(s) between the left and
right heart
• No additional lesion:
• No PHTN
• No obstruction to pulmonary or
systemic flow
VSD
5 7
Left‐to‐Right Shunt Lesions Left‐to‐Right Shunt Lesions
SVR = 12 w.u.
• As PVR drops, flow thru the defect is L‐to‐R,
leading to: PVR = 2 w.u.
• pulmonary overcirculation
• congestive heart failure
• As the L‐to‐R shunt draws flow away from the
ASD VSD PDA systemic circulation, the heart must increase
its output to maintain adequate oxygen
delivery through the systemic circulation
VSD
Partial Anomalous Pulmonary
Complete Atrioventricular Canal
Venous Return
6 8
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10:30am-11:05am
Pulmonary Overcirculation ⍺ Cardiac Work Pulmonary Overcirculation ⍺ Cardiac Work
Shortly after birth Shortly after birth As PVR falls and Qp rises In CHF
Qs 3 L/min Qs 3 L/min Qs 3 L/min Qs 3 L/min
Qp 3 L/min Qp 3 L/min Qp 6 L/min Qp 12 L/min
Qp = Qs Qp = Qs Qp > Qs Qp >> Qs
Qp:Qs 1:1 Qp:Qs 1:1 Qp:Qs 2:1 Qp:Qs 4:1
9 11
Pulmonary Overcirculation ⍺ Cardiac Work L‐to‐R Shunt Lesions

Signs of a stable physiology:
• Saturations >95% (pre‐ and post‐ductal)
Shortly after birth As PVR falls and Qp rises
• Breathing comfortably
Qs 3 L/min Qs 3 L/min
• Feeding well
• Normal heart rate
Qp 3 L/min Qp 6 L/min • ± Murmur (increasing as PVR drops)
Qp = Qs Qp > Qs
Qp:Qs 1:1 Qp:Qs 2:1
10 12
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10:30am-11:05am
L‐to‐R Shunt Lesions L‐to‐R Shunt Lesions >96%
Signs of a stable physiology:
• Saturations >95% (pre‐ and post‐ductal) Diagnostic Features: >96%
• Breathing comfortably
• Pulse ox Screening:
• Feeding well • normal pre‐and post‐ductal saturation
• Normal heart rate • POxS will typically miss these lesions
• ± Murmur (increasing as PVR drops)
• CXR: ± Pulmonary congestion,
Signs of an unstable physiology: cardiomegaly
• Saturations >95% (pre‐ and post‐ductal)
• Tachypnea
• Poor feeding, poor weight gain
• Tachycardia Congestive Heart Failure
• ± Murmur (increasing as PVR drops)
13 15
L‐to‐R Shunt Lesions L‐to‐R Shunt Lesions
Diagnostic Features:
After Closure of the PDA: • Echo:
• Velocity across defect ⍺ pressure gradient
• ± Improvement in signs/symptoms in Pressure = 4v2
(if ductus was adding to the overall
Left‐to‐Right shunt)
High velocity across the ASD/VSD/PDA
= large pressure gradient
• No change in pre‐ or post‐ductal sats
Low velocity across the ASD/VSD/PDA
= small pressure gradient
14 16
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L‐to‐R Shunt Lesions
L‐to‐R Shunt Lesions
Diagnostic Features:
• Echo: Supporting the physiology:
• Velocity across defect ⍺ pressure gradient • Anticipate increasing pulmonary blood flow
• Degree of chamber enlargement ⍺ volume over time
of shunt • Decrease work of breathing
ASD VSD
• ASD  RA, RV enlargement • diuretics
• VSD  LA, LV enlargement • Provide adequate calories

• PDA  LA, LV enlargement • Support cardiac function
• ± digoxin
• Avoid oxygen
Complete AV Canal PAPVR PDA
17 19
Complications of Interventional Treatment:
L‐to‐R Shunt Lesions L‐to‐R Shunt Lesions
• Support physiology while allowing time for Atrial arrhythmias Atrial arrhythmias
Ventricular arrhythmias
defect to close or decrease in size
• If significant L‐to‐R shunt remains perform
ASD VSD
intervention to close the defect
ASD VSD
Pulm vein obstruction Recurrent laryngeal nv (s)

Atrial arrhythmia Arch obstruction (s/c)
LPA obstruction (s/c)
Femoral obstruction (c)
Complete AV Canal PAPVR PDA
PAPVR PDA
18 20
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PDA in the Preterm Infant PDA in the Preterm Infant
Pulmonary hypertension:
• Pulmonary vessels dilate to accommodate
• Pulmonary overcirculation the extra volume of flow SVR ~12 w.u.
• Pulmonary hypertension
• Once the dilation potential is maximized
• Diastolic run‐off (wide PP) the pressure within the pulmonary arteries PVR ~4 w.u.
increases
• Increased cardiac work
21 23
Pulmonary overcirculation: Pulmonary hypertension:
• Excessive pulmonary flow • Increase in PA pressure as Qp Increases is
greater in:
• Enlarged MPA, LA/LV SVR ~12 w.u.
• decreased total cross‐sectional vascular space:
SVR ~12 w.u.
• Steal from systemic circulation • prematurity
PVR ~4 w.u. • diaphragmatic hernia PVR ~4 w.u.
• Poor 02/C02 exchange • atelectasis/pneumothorax
• Tachypnea, retractions
• conditions which promote vasoconstriction:
• Poor feeding/weight gain
• acidosis/elevated pC02
• hypoxemia
Congestive Heart Failure
22 24
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10:30am-11:05am
Signs/Symptoms:
Diastolic run‐off (wide pulse pressure) • Tachypneic, Tachycardic
• PVR < SVR in systole and diastole • Increased work of breathing SVR ~12 w.u.
SVR ~12 w.u.
• steal from systemic circulation • Poor growth, poor feeding
• risk of NEC • Bounding pulses
PVR ~4 w.u. PVR ~4 w.u.
• impaired coronary perfusion • Continuous murmur
• ?myocardial fibrosis?
• bounding pulses CXR:
• continuous murmur • Incr’d vascular markings
• enlarged MPA
• cardiomegaly
25 27
PDA in the Preterm Infant Congenital Heart Disease
Non‐Cyanotic Lesions
Increased Cardiac Work Connection btw left and • Atrial Septal Defect
• Steal from systemic circulation Qp:Qs 3:1 right heart allowing left‐ • Ventricular Septal Defect
• Compensation to maintain CO: to‐right shunting • Atrioventricular Canal
• Increased HR (excessive pulm bld flow)
Qp 9 L/min • Patent Ductus Arteriosus
Which leads to: Qs 3 L/min • Pulmonary Stenosis
Obstruction to flow across
• Increased myocardial 02 demand • Aortic Stenosis
valves or great arteries
• Increased caloric needs • Coarctation
• Poor feeding/weight gain
26 28
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Valve and Arch obstructions Valve and Arch obstructions
• Physiology ⍺ severity of • Physiology ⍺ severity of Interrupted Aortic Arch

obstruction Critical PV stenosis: obstruction (IAA), Coarctation of the
‐ R‐to‐L across PFO Aorta
‐ Diminished PBF
‐ May be ductal dependent
(pre=post‐ductal sats) IAA or significant CoA:
‐ Cyanosis/Hypoxemia ‐ Ductal dependent
(covered in cyanotic CHD) ‐ R‐to‐L across ductus leads to
differential cyanosis (pre‐
Pulmonary
Otherwise is not ductal dependent. ductal sat > post‐ductal sat)
Stenosis
29 31
• Physiology ⍺ severity of Severe neonatal AV stenosis: Signs of a stable physiology:

‐ LV fxn may be very poor
obstruction ‐ L‐to‐R across PFO • Pre‐ductal 02sats >90%, normal BP and HR,
‐ Diminished SBF normal lactate
‐ May be ductal dependent
‐ Pre‐ductal > post‐ductal sat
(differential cyanosis)
‐ Drop in PVR may decrease Severe aortic stenosis
systemic flow
Aortic Stenosis
‐ Normal Sats until CO drops
‐ Severe AS: pre=post ductal sats
Otherwise is not ductal dependent. Interrupted Aortic
Arch
30 32
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10:30am-11:05am
Signs of a stable physiology: Principles of Treatment:
• Pre‐ductal 02sats >90%, normal BP and HR, • If can’t provide sufficient cardiac output,
normal lactate decrease oxygen demand
• mechanical ventilation
• sedation/paralysis
Signs of an unstable physiology: Severe aortic stenosis • Judicious use of oxygen
• Poor pulses, hypotension, tachycardia, rising
lactate
• If post‐ductal sat << pre‐ductal, likely ductal
dependent
Interrupted Aortic
Arch Interrupted Aortic Arch
33 35
• Maintain ductal patency until it is clear Following initial supportive measures:
whether the ductus is necessary
• Provide a stable source of systemic blood flow
• Balance Pulmonary and Systemic Blood Flow ‐ relieve the obstruction
*Qp << Qs = cyanosis, acidosis or
*Qp >> Qs = CHF, acidosis, shock
‐ provide an alternative to the ductus (stent the ductus,
Blalock‐Taussig shunt, Stage I Norwood, Hybrid Procedure)
• Support cardiac function
• correct acidosis
• inotropic support
• volume resuscitation Interrupted Aortic Arch
34 36
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10:30am-11:05am
Valve and Arch obstructions
Pulmonary valve stenosis Aortic Valve Stenosis
Treatment:
• Determine ductal dependence
• ± PGE
• Support cardiac output
• Mechanical ventilation/NaHC03
• Cath lab for balloon valvuloplasty
37
Thank you
Armsbyl@ohsu.edu
38
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Statistics and Research Design - Dr. Weiner
11:05am-12:05pm
Disclosures
• I have no relevant financial relationships with the
manufacturers(s) of any commercial products(s) and/or
statistics and research design provider of commercial services discussed in this CME
activity
• I do not intend to discuss an unapproved/ investigative
use of a commercial product/device in my presentation
Gary M. Weiner, MD, FAAP • I’m not a statistician, just a math‐phobic neonatologist
gweiner@umich.edu • All examples (unless otherwise stated) use simulated
data
1 2
ABP Content Specifications
Learning Objectives Core Knowledge in Scholarly Activities
• Types of variable • Assessment of study design,
• Explain how the type of variable affects the • Distribution of data performance and analysis
choice of statistical test • Hypothesis testing • Assessment of generalizability
• Statistical tests • Bias and confounding
• Describe the appropriate use of standard • Measurement of association • Causation
deviation and standard error and effect • Incidence and prevalence
• Regression • Screening
• Identify factors that strengthen causal • Diagnostic tests • Cost benefit, cost
• Systematic review and meta‐ effectiveness and outcomes
inference in observational studies analysis • Measurement
3 4
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11:05am-12:05pm
Describe blood glucose at 3 hours of
age among healthy breast feeding
if your result needs a statistician, then babies at your hospital
you should design a better experiment
Ernest Rutherford 54
Nobel Prize in Chemistry 1908
5 6
What’s a Typical Value?
“NOIR” AKA:“Central Tendency”
• Nominal‐Gender, political party • Mean • Mode
– Existential, no inherent order or superiority – Average – Most common
• Ordinal‐Apgar, ROP stage, school grades – Ratio & interval data – Nominal data
– Ordered, but not “equal” intervals
• Interval‐IQ scores, Celsius temperature • Median
– Equal intervals, but no “meaningful zero” – Middle
• Ratio‐Glucose, Weight, Kelvin Temperature – Ordinal data
– Named, ordered, equal intervals, and a meaningful zero
7 8
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11:05am-12:05pm
Effect of Extremes How Much Variation?
Measure the • If you can’t swim, should you cross a stream with an
+
mean, median, “average” depth of 3 feet?
and modal
income in this • If one hand is in an oven (450º) and one hand is in
room. Bill Gates
liquid nitrogen (‐321º), are you comfortable because
 Mean changes a lot your “average” temperature is 65º?
 Median hardly changes at all • The “average” human has one breast and one
 Mode doesn’t change testicle.
9 10
Describe Variation Standard Deviation
• Range • Interquartile Range • Deviation =
– (Max – Min) – (75th %tile ‐ 25th %tile) (Data point ‐ mean)
– Emphasizes – Middle 50% • “Average Deviation”
outliers – On average, how far
are the data points
from the mean?
– Why can’t you just
average the
deviations?
11 12
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11:05am-12:05pm
Standard Deviation Histogram
• Plot frequency of each
1. Subtract the average from glucose N = 20 babies in each sample
each data point
– Glucose on X‐axis
• Deviations
2. Square the deviations – How often it occurs on Y‐axis
• Gets rid of negatives • If I repeat the experiment,
3. Add it all and divide by “n” or each sample is slightly N = 500 babies in each sample
“n‐1” different
• Variance – Larger sample, a pattern
4. Take the square root emerges
• Return to original units – But…it doesn’t get any
• Standard Deviation “narrower”, variation still exists
13 14
The ‘Normal Distribution’ DaVinci’s Code?
– Mean, median, and
mode all the same
– Empirical rule
• 68% of data within
~ 1 SD of the mean
• 95% of data within
~ 2 SD of the mean
– “Parameters” of Leonardo da Vinci 1490 (Study of Human Proportion in the
parametric tests Manner of Vitruvius).
15 16
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11:05am-12:05pm
“Right Skewed” Precision = Reliability
• If you measured it
Mode Median Mean repeatedly, would it be the
same? 54
– Random error  decreases
# of MLB Players talk about precision
Players “median” salary and – Intra‐observer reliability
team owners talk about • If another observer 22
“mean” salary measured it, would they
agree?
– Inter‐observer reliability
Player’s Salaries
17 18
Accuracy = Validity Making Inferences
• Are you really • Predicting population “parameters” from
measuring what you 62 sample “statistics”
say you are?
– Bias or systematic error
• What is the average glucose of ALL healthy
 poor accuracy 63 breast feeding babies in the USA?
Baby’s TRUE glucose = 20 mg/dL
19 20
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11:05am-12:05pm
Thought Experiment Plot the Sample MEANS
• Travel the country • Always normally
• Take an infinite number of random samples from distributed*
the population and measure their glucose • Large samples 
narrow curves
• Plot the mean glucose for each sample
• Mean of the sample
– Each one is likely to be a little different, right? means is the true
– Caution: We are plotting the means of the population mean
samples…not the individual glucoses – Central limit theorem Infinite Number of Samples
* Always..based on some assumptions explained later
21 22
Standard Error of the Mean Save Your Travel Budget
• The ‘standard • You don’t have to take an infinite number of
deviation’ of the samples and plot them
sample means = • Use the empirical rule to estimate the
SEM
• SEM = SD / √n population mean from a single sample mean!
– SEM gets smaller as
sample size gets
larger
23 24
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11:05am-12:05pm
Save Your Travel Budget 95% Confidence Interval of The
Mean
• Means are normally • The neighborhood where you can be 95%
distributed, so just think
backwards… confident that the true population parameter
• If you’re standing at any lives
sample mean and walk +/‐
2 SEM in either direction • The neighborhood’s boundaries are defined
you’ll step on the mathematically
population mean 95/100
times 95% CI = Sample mean  (2 x SEM)
A sample
mean It’s really (1.96 x SEM), but (2 x SEM) is
pretty darn close and easier to remember
25 26
For our question What Does “Confident” Really
Mean?
• Measure glucose in 100 healthy babies at 3hrs. µ
• Assume 54 really is the
• Sample mean = 54 mg/dL (s.d. 18 mg/dL) population mean (µ)
• SEM = 18 mg/dL / √100 = 1.8 mg/dL • Repeat the experiment
• 2 x SEM = 3.6 mg/dL • No 2 means and 95% CI’s are
• Estimated population mean glucose of all likely to be exactly the same
healthy babies in USA at 3hrs. (95% CI) • But, 95/100 CI’s will include µ 54
• Sample mean  (2 x SEM) – Never know when you hit one of
5 Different Samples
= 54 mmHg (50.4, 57.6) the 5
(n=100)
Data adapted from Diwakar KK. ADC‐FN 2002
27 28
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Assumptions 2 Critical “Standards”
• Random sample of the population • Standard Deviation describes the variation in a
sample or population.
– At least representative – Doesn’t get smaller with larger sample
• Normally distributed – “D for deviation and D for description.”
– Or large sample
(n > 30)
? • Standard Error estimates how close a sample mean
is to the true population mean.
– The SD of the distribution of sample means
– Decreases as sample size increases
1936 – “E for Error and E for Estimate”
29 30
Can You Prevent HIV Transmission?
Interventions • Does ante‐partum AZT prevent vertical
transmission of HIV?
• What study design?
“Are These 2 Groups Different?”
• Why randomize?
– Evenly distribute known and unknown
confounders
31 32
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11:05am-12:05pm
Knowns and Unknowns Can You Prevent HIV Transmission?
“Reports that say that something hasn’t happened • Why blind?
are always interesting to me, because as we know, – Prevent bias
there are known knowns; there are things we know
we know. We also know there are known • What’s intention‐to‐treat analysis?
unknowns; that is to say we know there are some – Gallbladder example
things we do not know. But there are also unknown
unknowns, the ones we don’t know we don’t
know.” Donald H. Rumsfeld
Secretary of Defense 1975‐
1977, 2001‐2006
33 34
NEJM November 3, 1994 Are You Persuaded?
• 7.2% of AZT treated babies became HIV infected The proportion infected in the 2 samples were
• 21.8% of controls became infected different. Two possible conclusions:
• Relative risk of infection (RR) = – The populations they represent really have
(risk treated/risk control) = 0.072/0.218 = 0.33 different transmission risks
• “AZT treated subjects had 33% of the risk of HIV – The difference isn’t real (random chance).
If I repeat the experiment the difference will go
vertical transmission compared to controls.”
away
35 36
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11:05am-12:05pm
Was it Chance?
2 Methods 95% Confidence Interval
• Confidence Interval
– “What’s the plausible range for the true difference • RR = 0.33 (0.18, 0.60)
between the two populations?” – Calculated using Standard
Error
– Calculate a range
– “95% confident that the
• P‐Value (AKA ‐ Hypothesis testing) range 0.18‐0.60 includes
– “If the two populations really have the same risk, what’s the true RR”
1
the chance of observing such a large difference between 2 • If 95% CI crosses or RR < 1 RR > 1
random samples?” includes 1 then “no
– Calculate a probability statistical significance”
37 38
P‐Value Approach Why p‐values are so confusing
• Assume the 2 population risks are the same (null) • Question typical statistical tests answer:
• Perform a “test” – Given that there is no difference between the
– Compare measured difference to a probability distribution populations, what’s the chance that your sample would
• ACTG reports P < 0.01 look like this?
– “If the 2 populations really have the same risk, you could find a – Frequentist analysis
difference at least this large in an experiment this size by chance
alone <1 in 100 times.” • Question you were hoping they answered:
• Reject the null hypothesis – Given that your sample looks like this, what’s the chance
– If p  0.05 say, “Cannot reject the null hypothesis” that there’s no difference between the populations?
Never say “Accept the null hypothesis” – Need Bayesian analysis to answer for this question
39 40
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11:05am-12:05pm
The Tests The Tests
Interval, Ratio or Ordinal Variables Nominal Variables
• 2 Means (parametric) • Comparing proportions?
– Student’s T‐test – Chi‐square (2 )test for independence
• Before/after; twins use “Paired” T‐test
– Fisher’s exact test (small numbers)
• More than 2 Means use ANOVA
• 2 Medians (non‐parametric) • Comparing proportions with paired data
– Mann‐Whitney U test
(before/after, twins)
• Before/after, twins use Wilcoxon Signed Rank test – McNemar’s test
• More than 2 Medians use Kruskal‐Wallis test
41 42
False Alarms Missed Detections
Conclude a treatment is effective when it’s no Conclude an effective treatment is no different
different than placebo than placebo
– Type I error or  error – Type II error or  error
– “A difference, to be a difference, must make a – “Absence of proof is not proof of absence!”
difference!”
• Large studies doom you to finding clinically
insignificant differences
43 44
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11:05am-12:05pm
When studies don’t find something… Could They Have Missed It?
• Send my kids to the basement to find a tool • How long did they spend looking?
• Come back and say, “It isn’t there.” – Sample size
– Is it there or not?
• How big is the tool?
– No way to be sure.
– Effect size
• If the tool really is there, what’s the chance they would have
found it? • How messy is the basement?
– SD
Analogy from John Hartung, SUNY HSC Brooklyn Analogy from John Hartung, SUNY HSC Brooklyn
45 46
Power
• What’s the chance that you’re not going to make a
Harm and Etiology Questions
type II (missed detection) error?
– Power = 1 ‐ 
• Power increases with
– Sample size (time searching)
– Effect size (size of the tool)
– Less sampling error (messiness)
– Increasing alpha (willingness to accept the wrong tool)
47 48
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11:05am-12:05pm
Etiology Descriptive & Observational Studies
Does IUGR cause adult obesity? • “You can observe a lot just by lookin’.”
Can’t randomize to IUGR • Descriptive
– Case reports
Ethics committee wouldn’t like it – Cross‐sectional studies
Stuck with looking at the world • Observational
Yogi Bera
– Cohort studies
IUGR Baby ? Obese Man – Case‐Control studies
1925‐2015
49 50
Descriptive Cohort Study
• Good for hypotheses “What will happen?”
• Cross‐sectional survey Obese Man
– Snapshot in time. Measure outcome and exposure at IUGR Baby
Follow over
the same time. time
– Stand on the street EXPOSURE OUTCOME ?
– Measure people’s BMI and ask if they were growth‐ Calculate disease
restricted incidence
– Big risk for bias (selection, interviewer, recall) AGA Baby
Fit Man
51 52
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11:05am-12:05pm
Cohort Study Case‐Control Study
• Expensive “What happened?” ?
• May require long follow‐up CASE
Obese Man IUGR Baby
• Bad for rare diseases and those with long latency Look Backward in
Time
• Good for rare exposures
• Can establish temporal associations
• Can measure prevalence of a disease Fit Man AGA Baby
CONTROL
53 54
Case‐Control Study Relationships Between Variables
• Less expensive • Independent or predictor
variable
• Good for rare diseases and those with long latency
– Risk factor
• Bad for rare exposures (or treatment)
• Relies on people’s recall to determine exposure (bias) • Dependent or outcome
• Can’t measure prevalence of the disease variable
– The investigator selected the prevalence by determining – Variable whose
behavior/outcome you’re
how many cases/controls to enroll trying to effect or predict My Dependent Variables
55 56
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11:05am-12:05pm
Clinical Question Linear Regression
• Can maternal HgbA1c predict the baby’s • Predict a numerical
weight at 1 year? outcome (Y) from a
another numerical BW
– Independent variable: Maternal HgbA1c (ratio) variable (X)
– Predict BW from HbgA1c
– Dependent variable:
• Calculate the best fitting
Child’s weight (ratio) line HbgA1c
– Minimize (distance)2 from
each point  line
Simulated data *Simulated data
57 58
Interpreting Linear Regression Logistic Regression
• Y = β (X) + a • Predict a dichotomous
• β = Regression coefficient outcome from one or more
variables
– “Slope” term in the linear regression formula – Does birth weight predict
survival?
– Strength of the relationship between the predictor and – Does GA predict IVH?
outcome variable – Do GPA, MCAT, gender, age,
predict medical school
• Weight (kg) = 0.3 (HgbA1C) + 2 admission?
– Can add more independent variables and coefficients • Y can’t be more than 1.0 or
less than 0.
(multiple regression)
*Simulated data
59 60
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Association  Causation Evidence Favoring Causality

• Bifocal use highly associated with grey hair • Smoking cigarettes causes
lung cancer
• Bifocals do not cause grey hair – Temporal relationship
– Dose‐response
• Age is a confounder – Cessation decreases risk
• Confounder= 3rd thing that links both and is – Strength of association (OR)
– Consistent in studies of
the actual cause various designs A B
– Biologic plausibility
61 62
Take Home Messages This Afternoon (2:45pm‐4:00pm)
1. The type of outcome variable (NOIR) determines
the way you describe central tendency, • Dive a little
distribution and the “test” you choose deeper
2. Standard Deviation Describes your data
• Diagnostic tests
3. Standard Error Estimates a population parameter
from your sample • Sample problems
4. Association ≠ Causation. Watch out for • Wahooo!
confounders.
63 64
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11:05am-12:05pm
Empirical Rule
In a random sample of 100 newborns, blood glucose is normally
distributed with a mean=90 mg/dl and standard deviation=10 mg/dl.
Sample Problems We’ll Tackle This Considering the sampled newborns, which of the following is true?
Afternoon A. 5% have glucose > 110 mg/dl
B. 34% have glucose > 100 mg/dl
C. 50% have glucose > 90 mg/dl
D. Based on this sample, the standard error of the mean is 9 mg/dl
65 66
Measures of Association Statistical Tests
An RCT studies Confusemol to prevent IVH; 15 of 100 treated RCT…each subject randomized to receive one of 4 drugs…want to
compare the mean SBP between the subjects in each group. Which
babies get an IVH and 30 of 100 control babies get an IVH. statistical test to compare the 4 sample means?
A. The relative risk (RR) associated with Confusemol treatment is
0.15 A. Paired Student’s‐t test comparing each drug combination
B. ANOVA
B. The odds ratio (OR) associated with Confusemol treatment is 2.0 C. Mann‐Whitney U Test
C. Confusemol treatment resulted in a 0.50 difference in IVH rate D. Linear regression
E. Chi‐square
D. You need to treat 7 babies with Confusemol to prevent 1
additional baby from developing IVH
67 68
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11:05am-12:05pm
Diagnostic Tests Linear Regression
Auscultate 100 preemies using echo as the reference Multiple linear regression… Variable 
standard. Murmur (+) in 27 of 30 preemies with hsPDA and 14 predict Cr (mg/dL) from birth Coefficient
of 70 preemies without hsPDA. For diagnosing hsPDA… weight and presence of PDA (constant) 0.15
A. The sensitivity of auscultation is 0.80 The predicted Cr for a baby BW (kg) 0.3
B. The specificity of auscultation is 0.90 with BW 1.5 kg and no PDA. PDA (1=Y, 0=N) 1.58
C. In this sample, if a baby has a murmur, there’s a 66% A. 0.45 mg/dL
chance of having a hsPDA B. 0.60 mg/dL R2 0.7, p < 0.01
D. In this sample, if a baby does not have a murmur, there’s C. 0.80 mg/dL
an 80% chance of not having a hsPDA
D. 2.18 mg/dL
69 70
Review Review
• Sensitivity: • PPV
– Given ________, what’s the chance of a _______ – Given a patient with __ ____ ____, what’s the
______. chance of _____?
• NPV
• Specificity:
– Given a patient with __ ____ ____, what’s the
– Given ________, what’s the chance of a _______
chance of _____?
______.
71 72
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11:05am-12:05pm
Outcome Test
Means Only 2 = T‐test
(interval/ratio, parametric) Before/after, twins = Paired T‐test
More than 2 = ANOVA
Medians Only 2 = Mann‐Whitney U‐Test (AKA Wilcoxon rank sum)
(ordinal or skewed) Before/after, twins = Wilcoxon signed rank
Proportions
More than 2 = Kruskal‐Wallis
Chi‐square
Additional Slides
Small groups = Fisher’s Exact
Before/after = McNemar’s
Time to event (compare 2) Kaplan‐Meier (Log Rank) For Those Wanting a Little Extra
Time to event (make predictions) Kaplan‐Meier (Cox proportional hazards regression)
Linear relationship continuous Pearson correlation (r)
Linear relationship ordinal Spearman’s rho
Predict a number Linear regression
Predict a Yes/No Logistic regression
73 74
Bigger Sample  Narrower Confidence The Tests

Interval Time to an Event
• Survival analysis
• Increasing the sample
– Time to PICC line clotting
size x 4 cuts the width
– Kaplan‐Meier survival
of the confidence curves
interval in half
– Compare 2 curves with
‐2 SEM +2 SEM
the Log Rank test
Sample Mean
75 76
265
11:05am-12:05pm
Correlation Coefficient Pearson Product Moment
Correlation Coefficient (r)
Measures how much of a linear association • Range ‐1 to +1 r = 0.7
there is between two continuous variables – Close to ‐1 or +1
BW
– Not all meaningful relationships are linear = good linear association

– Can’t be used when one variable is used to +r = both increase together Hgb A1C
calculate the other (mid‐term and final grade) ‐r = both decrease together
r = ‐ 0.7
– Close to zero BW
= poor linear association
Hgb A1C
*Simulated data
77 78
Coefficient of Determination Rate and Proportions
• Proportion
• r2 = amount of – Part/Whole
variance shared by the r = 0.7
– 29% of births by Cesarean Section
variables
– Must range 0‐1
– 49% of variance in (0‐100%)
baby’s weight at 1 year
can be explained by • Rate
variance in the r2 = (0.7)2 = 0.49 – Events/Group/Time
mother’s HgbA1C – IMR= 7 per 1,000 live‐births per year
*Simulated data
79 80
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11:05am-12:05pm
Epidemiologist’s Sink
Recovery
• Flow of water in is the incidence Incidence
– New cases over a particular time
– Rate
• Water in the sink is the prevalence Prevalence
– Number of people affected at a moment in time
– Proportion
• Incidence x Duration of Illness = Prevalence
Mortality
81 82
267
268
ARS CALCULATIONS: Cardiology Case-Based Vignettes - Drs. Armsby and Brodsky
1:30pm-2:45pm
Disclosure
ARS Calculations: Cardiology • Neither of us nor any member of our immediate
family has a financial relationship or interest with
Case-Based Vignettes any proprietary entity producing health care goods
or services related to the content of this activity.
NeoPREP Intensive Review and Update of • Our content will not include discussion/
Neonatal-Perinatal Medicine reference of commercial products or services.
February 8, 2020 • We do intend to discuss off-label drugs (e.g.,
epinephrine) during the presentation.
Laurie Armsby, MD
Dara Brodsky, MD
1 2
Approach Fetal Oxygenation
• We’ll first provide question • Place following vessels in order from

highest to lowest oxygen saturation:
• Feel free to work in groups
Umbilical artery
• Look up when you are finished and we’ll then
Umbilical vein
discuss the answer
Uterine artery
• A copy of our slides with detailed answers are
Uterine vein
included after the question slides. Try not to
peek! • Estimate the O2 sat in each vessel
3 4
269
1:30pm-2:45pm
Fetal Oxygenation
On the 12th DOL an infant develops tachypnea, increased work of
HIGH Vessel
Vessel O2 sat breathing and a grade 2/6 systolic murmur is appreciated. An echo
demonstrates a large VSD.
O2 sat Uterine artery
The primary pathophysiology affecting this infant is:
Uterine vein
a. Ductal dependence for systemic circulation
Umbilical vein b. Ductal dependence for pulmonary circulation
LOW c. Insufficient pulmonary blood flow (cyanotic heart
O2 sat Umbilical artery disease)
d. Excessive pulmonary blood flow (congestive heart
failure)
5 6
On the 12th DOL an infant develops tachypnea, increased work of On the 12th DOL an infant develops tachypnea, increased work of
breathing and a grade 2/6 systolic murmur is appreciated. An echo breathing and a grade 2/6 systolic murmur is appreciated. An echo
demonstrates a large VSD. demonstrates a large VSD.
The timing of his symptoms is related to: The timing of his symptoms is related to:
a. Closure of the ductus arteriosus a. Closure of the ductus arteriosus 80/2

b. The normal drop in pulmonary artery pressure b. The normal drop in pulmonary artery pressure 0
over time over time
c. The normal drop in pulmonary vascular c. The normal drop in pulmonary vascular
80/6
resistance over time resistance over time
d. Development of pulmonary artery hypertension d. Development of pulmonary artery hypertension 80/6
7 8
270
1:30pm-2:45pm
Qp:Qs Worksheet
On the 12th DOL an infant develops tachypnea, increased work
of breathing and a grade 2/6 systolic murmur is appreciated. An Qp sat – sat
echo demonstrates a large VSD. =
Qs sat – sat
O2 sat 99%, MV sat 59%, PA sat 79%, PV sat 99%.
What is his Qp:Qs? O2 sat 99%, MV sat 59%, PA sat 79%, PV sat 99%
a. 1:1
b. 1:2 Qp
= =
c. 1:3 Qs
d. 2:1
e. 3:1
9 10
Cardiac Index Worksheet

A newborn infant is diagnosed with severe aortic stenosis with
severely diminished ventricular function. He is started on a PGE V02
infusion and brought to the cath lab for aortic valvuloplasty.
Qs = CI =
(Hgb)(1.36)(10) (Ao – SVC sat)
V02 150 ml/min/m2. Post-ductal aortic saturation 92%. SVC 100
saturation 33%. Hgb 12 g/dL
What is the cardiac index? V02 150 ml/min/m2. Post-ductal aortic saturation 92%.
SVC saturation 33%. Hgb 12 g/dL
a. 0.016 L/min/m2
b. 1.6 L/min/m2
c. 16 L/min/m2
d. 30.6 L/min/m2 Qs = CI =
11 12
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1:30pm-2:45pm
PVR Worksheet
in mean Pressure across a

A full term infant is diagnosed with congenital diaphragmatic hernia, pulmonary Resistance = circulation
hypertension and a bidirectional shunt across a moderate PDA. Known
pressures: Pulm artery 61/22/43, Aorta 64/30/48, Right Atrium 6, Left Atrium 7 Flow thru that circulation
mm Hg. The Qp and Qs = 3 L/min/m2.
Calculate the pulmonary vascular resistance:
Pulm artery 61/22/43, Aorta 64/30/48, Right Atrium 6, Left Atrium 7 mm
a.14 woods units m2 Hg. The Qp and Qs = 3 L/min/m2.
b.12 woods units m2
c.18 woods units m2
d.19 woods units m2
PVR = =
13 14
Lesions and pO2

Right Umbilical Umbilical Lesion/Condition
A 2 week old with a large PDA undergoes a radial arterial venous
catheterization. Which of the data sets below is consistent paO2 line paO2 line pO2
with the largest left-to-right shunt across the ductus? postductal (high line)
a. MAP 40, mean PAp 40, LAp 10, Qp 3, Qs 3 75 50 - A. ??
b. MAP 40, mean PAp 40, LAp 10, Qp 9, Qs 3 Echo: PHTN, PDA, no right-
sided obstructive lesion
c. MAP 40, mean PAp 15, LAp 6, Qp 3, Qs 3
50 50 - B. This baby is cyanotic
d. MAP 40, mean PAp 15, LAp 6, Qp 3, Qs 9 because of PHTN but there is no
differential in pre/post ductal
PaO2. How is that possible?
50 75 - C. ??
- 60 100 D. ??
15 16
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1:30pm-2:45pm
_______Cyanosis _______Cyanosis
1. ______with _______ shunting across PDA
Right Umbilical Umbilical Lesion
radial arterial venous RA LA
paO2 line paO2 line pO2
postductal (high line)
RV LV
75 50 - A. ??
Right radial pO2 = 75

PDA
PVR SVR
PA Ao
Umbilical arterial pO2 = 50
17 18
_______Cyanosis
2. if _____, PDA with ______ shunting
Right radial Umbilical
Umbilical
RA LA paO2 arterial line venous line Lesion
paO2 pO2 (high line)
(preductal)
(postductal)
Echo: PHTN, PDA, no right-
RV LV sided obstructive lesion
B. This baby is cyanotic
50 50 - because of PHTN but there is
no differential in pre/post
ductal PaO2. How is that
Right radial pO2 = 75 possible?
PDA
PVR SVR
• right arm O2 content (preductal sat) = postductal O2
PA Ao
if____________________________________)
19 20
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1:30pm-2:45pm
___________________ _______________________
____ and ____________
radial arterial venous
RA LA paO2 line paO2 line pO2
RV LV 50 75 - C. ??
• right arm O2 content (or preductal O2 content) is
now lower than postductal O2 content
PDA • =
PVR SVR
PA Ao
21 22
________________ _____________________
Right Umbilical Umbilical Lesion e.g., ______________
radial arterial venous RA LA
postductal
50 75 - C. ?? RV LV
1. ___________
2. ___________ PDA
SVR PVR
3. ___________ Ao PA
23 24
274
1:30pm-2:45pm
_____________ SVC (low pO2)

RA LA
radial arterial venous
RV LV
- 60 100 D. ?? Umbilical
venous
pO2 = 100
• Consistent with __________________
Umbilical
Diaphragm
PA Ao arterial pO2
= 60
PV
25 26
SVC
PV
RA LA A neonate fails the newborn screen. Upon transfer to the NICU

an echo shows pulmonary atresia with an intact ventricular
septum. The pre and post-ductal saturations are 78%. The most
appropriate immediate next step in treatment is:
RV LV
Umbilical a. Administer oxygen

venous Umbilical arterial b. Intubate and hypoventilate
pO2 = 60 pO2=80 (slightly c. Transport to cath lab for septostomy
higher than UV d. Start prostaglandin infusion
PA Ao
bec of mixing at
Diaphragm PFO)
27 28
275
1:30pm-2:45pm
In this infant with HLHS and aortic atresia, the aortic

An infant has a prenatal diagnosis of HLHS with aortic atresia. saturation measures 83%, the SVC saturation measures
After delivery, the infant appears mildly cyanotic with oxygen 53%.
saturation 78%. Assuming normal cardiac function and normal
lungs, the appropriate management strategy includes: Assuming normal lungs (PV sat 98%) what is the Qp:Qs?
a.0.5
a. start PGE, increase 02 sat by decreasing PVR b.2.0
b. start PGE, increase 02 sat by increasing PVR
c. start PGE, maintain current 02 saturation
d. start PGE, allow 02 sat to decrease to 65%
29 30
In this infant with HLHS and aortic atresia, the aortic The infant is administered 100% oxygen during the echo.
saturation measures 83%, the SVC saturation measures The aortic saturations increase to 92%. The SVC saturation
53%. rises to 68%.
Assuming normal lungs (PV sat 98%) what is the Qp:Qs? Again assuming normal lungs (PV sat 98%) what is the
Qp:Qs during the administration of oxygen?
a.0.5
b.2.0 MV sat 53% a.0.25
53 83 PV sat 98%
83
Ao sat: 83% b.4.0
PA sat = Ao sat
98
31 32
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1:30pm-2:45pm
The infant is administered 100% oxygen during the echo. Which subcategory of HLHS is most commonly associated with
coronary artery sinusoids?
The aortic saturations increase to 92%. The SVC saturation
rises to 68%. a.HLHS with mitral stenosis and aortic stenosis
b.HLHS with mitral atresia and aortic atresia
Again assuming normal lungs (PV sat 98%) what is the
c.HLHS with mitral stenosis and aortic atresia
Qp:Qs during the administration of oxygen? d.HLHS with mitral atresia and aortic stenosis
a.0.25 68
92
b.4.0 92 MV sat 68%
PV sat 98%
98 Ao sat: 92%
PA sat = Ao sat
33 34
Cyanotic Neonate Cyanotic Neonate

• A 3-hour old FT infant is transferred into your NICU with a
diagnosis of possible cyanotic heart disease. CXR: Normal
ABG PO2 55. pre-
cardiac size, clear lungs. She is intubated and receiving ductal sat 84%,
100% oxygen. post-83%
• ABG PO2 55. pre-ductal O2sat 84%, post-ductal O2sat 83% What is the most
likely diagnosis?
A.Ebstein’s anomaly
B.Hypoplastic left
www.msdlatinamerica.com
heart syndrome
C.Pulmonary atresia
D.Tricuspid atresia
35 36
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1:30pm-2:45pm
Diagnosis: ___________ Diagnosis: ___________
RA LA • Clue: ________QRS axis • Clue: ________ QRS axis

and cyanotic and cyanotic
• Management:
• Management:
– Don’t need PGE1
RV LV – PGE1
– Monitor acid-base balance
– Monitor acid-base balance
– Titrate O2 to maintain sats ~
– Titrate O2 to maintain sats ~ 80% 80%
– Surgical repair at 2-7d – Consider diuretic
85% – Surgical repair at 4-6m
PDA
85%
PA Ao
37 38
QRS Axis Pathognomonic Findings

Cyanotic infant + CXR: Infant of a diabetic
-90° Left Superior: mother + EKG:
1. Tricuspid atresia (LVH with
decreased RV forces)
Normal
2. AVC
+/- 0 Baby:
180°1. Normal axis °after ~1 mo
1. Normal axis
until ~1 mo What is the most likely What is the most likely
2. PA with intact VS (LVH
2. TOF (RVH) with decreased RV forces) diagnosis? cause of EKG
findings?
+
90°
39 40
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1:30pm-2:45pm
Intrauterine Cardiac Pathophysiology _________________________

• Which cardiac structural abnormality will lead to Fetal systemic cardiac output
the LOWEST intrauterine oxygen saturations is minimally impacted
provided to the brain, coronary vessels, and because RV continues to
upper body? provide most of CO
However, oxygen saturation is
• What would determine whether an infant is born lower in pre-ductal vessels
with a large or small PDA? (brain, upper body, coronary
arteries); unclear impact
• Which is more likely to have a large PDA: Uncertain long-term cognitive

left-sided obstructive lesions or right-sided outcome
obstructive lesions?
41 42
Intrauterine Cardiac Pathophysiology Intrauterine Cardiac Pathophysiology
• What would determine whether an infant is • High flow across the

born with a large or small PDA? PDA  ______ PDA
Size of intrauterine vessels is determined by flow e.g. ___-sided obstructive
across that vessel lesions
- mitral atresia/stenosis
- aortic atresia/stenosis
- coarctation of the aorta
- interrupted aortic arch
- hypoplastic left heart
syndrome
(fetal ductus provides

systemic flow)
43 44
279
1:30pm-2:45pm
Intrauterine Cardiac Pathophysiology

A 3 week old former 32wk gestational age infant has tetralogy of
• Minimal flow across Fallot. His ductus has closed over the prior few days. His
PDA  ____PDA baseline oxygen saturation is 80-85%. He intermittently develops
extreme cyanosis and agitation which is treated with 02, morphine,
e.g. ____-sided obstructive an IV fluid bolus and knee to chest manipulation. These
lesions treatments accomplish the following:
- tricuspid atresia
- Ebstein’s anomaly
- pulmonary stenosis a. Increase PVR, Decrease SVR
- pulmonary atresia
b. Decrease PVR, Increase SVR
c. Increase PVR, Increase SVR
(fetal ductus provides
pulmonary flow) d. Decrease PVR, Decrease SVR
45 46
A 5 week old infant has recurrent episodes of pallor and

inconsolability. On examination there is tachycardia and a high- The myocardial ischemia seen with this lesion is a direct
frequency systolic murmur at the apex radiating to the left axilla.
The ECG shows ST changes. The most likely diagnosis is:
result of:
a. Decrease in systemic vascular
a. Anomalous origin of the left main resistance (SVR)
coronary artery from the right main
coronary artery b. Increase in pulmonary vascular
resistance (PVR)
b. Anomalous origin of the left main
coronary artery from the pulmonary c. Decrease in pulmonary vascular
artery resistance (PVR)
c. Pericarditis d. Increase in systemic vascular

resistance (SVR)
d. Ebstein’s anomaly
47 48
280
1:30pm-2:45pm
A full term boy is found to have a pre-ductal saturation of

45% and post-ductal saturation of 75% at 15 minutes of age. A full term boy is found to have a pre-ductal saturation of 45% and post-
Which of the following is included in your differential ductal saturation of 75% at 15 minutes of age. Which of the following is
diagnosis? included in your differential diagnosis?
95 95 75
a.D-Transposition of the Great Arteries

b.L-Transposition of the Great Arteries (Corrected TGA) 75 75
75
c.Coarctation of the Aorta with PDA

d.Primary Pulmonary Hypertension with PDA
e.Total Anomalous Pulmonary Venous Return
CoA, PDA PPHTN, PDA TAPVR
49 50
45
A full term boy is found to have a pre-ductal saturation of 45% and post- An echo confirms the diagnosis of d-TGA. The decision to
ductal saturation of 75% at 15 minutes of age. Which of the following is perform a balloon atrial septostomy is primarily based upon
included in your differential diagnosis? which of the following factors? 75
95 45 a.the size of the PDA

b.the post-ductal saturation
95 75 D-TGA
c.the presence of a septal defect (ASD or VSD)
L-TGA D-TGA
51 52
281
1:30pm-2:45pm
The echo shows d-TGA with a small ASD. While

awaiting a decision about the BAS you provide 45
Additional Questions ???
Fi02 to the infant. This might increase his pre-
ductal saturation by… 75
Contact us!
a. Increasing the 02 content
returning from the lungs
D-TGA
armsbyl@ohsu.edu
b. Increasing the right-to-left shunt
across the ductus (PA to Ao) dbrodsky@bidmc.harvard.edu
c. Decrease the PVR, increase Qp,
increase LAp and increase left-
to-right flow across the ASD
53 54
Match the Genetic Disease with

the Cardiac Finding
Additional Questions for
DiGeorge syndrome Aortic aneursym
Self-Study Turner syndrome Dysplastic pulmonary
valve
Marfan syndrome
Hypertrophic
Noonan syndrome
cardiomyopathy
Pompe disease
Coarctation
Truncus arteriosus
55 56
282
1:30pm-2:45pm
Which statement is correct?

Match the Genetic Disease with
1. Tube formation  septation
the Cardiac Finding  looping
Aortic aneursym 2. Heart formation is complete

DiGeorge syndrome by 6 weeks’ gestation
Dysplastic pulmonary 3. The 2 ventricles work in
Turner syndrome valve series in utero
Marfan syndrome Hypertrophic 4. The RV provides more of the
Noonan syndrome cardiomyopathy CO than the LV in utero
Pompe disease Coarctation 5. Only 30% of the total CO
passes through the fetal
Truncus arteriosus lungs
57 58
Which statement is correct? Intrauterine Cardiac Pathophysiology

1. The fetus functions in a relatively
hypoxemic environment
• Which cardiac structural abnormality
2. The right side of the fetal heart has provides a lower oxygen saturation to the
higher O2 saturations than the left side
brain, coronary vessels, and upper body
3. The fetus adjusts CO mostly by in utero?
changing SV
4. Greater O2 exposure with first breath
leads to pulmonary vasoconstriction
59 60
283
1:30pm-2:45pm
The appropriate relationship between lung volume versus Defects that may produce a significant L-to-R shunt, producing
pulmonary vascular resistance is depicted by which curve? congestive heart failure include:
a. A
b. B C B A. a connection between the pulmonary and systemic circulations, with
obstruction to flow to the pulmonary circulation
c. C
B. a connection between the pulmonary and systemic circulations, with no
d. D D obstruction to flow to the pulmonary circulation
resistance
C. a connection between the pulmonary and systemic circulations, with
severe elevation of pulmonary vascular resistance
A
lung volume
61 62
Tetralogy of
Fallot with PS
All of the following lesions are expected to require an

Defects that may produce a significant
L-to-R shunt, producing congestive heart urgent, immediate post-natal surgical or transcatheter
failure include: interventions EXCEPT?
A. a connection between the pulmonary and systemic

circulations, with obstruction to flow to the a. d-Transposition of the Great Arteries
pulmonary circulation
b. Truncus Arteriosus with truncal regurgitation
B. a connection between the pulmonary and systemic
circulations, with no obstruction to flow to the Large VSD c. Hypoplastic Left Heart Syndrome with intact atrial septum
pulmonary circulation
d. Obstructed Total Anomalous Pulmonary Venous
C. a connection between the pulmonary and systemic Connection
circulations, with severe elevation of pulmonary
vascular resistance
Truncus Arteriosus w/
PHTN
63 64
284
1:30pm-2:45pm
A 6 day old infant presents with cyanosis, tachypnea and

A newborn, cyanotic infant is found on examination to
severe respiratory distress. There is a to-and-fro murmur
have a single S2 + bounding arterial pulses. Which is the
at the left sternal border. Based on the echo findings you
least likely lesion based on these findings:
place the baby in a prone position and his respiratory
distress is alleviated. The cardiac diagnosis is: a. Truncus arteriosus
A. d-Transposition of the Great Arteries b. Tricuspid atresia
B. Truncus Arteriosus c. Pulmonary atresia
C. Tricuspid Atresia
d. Hypoplastic left heart syndrome
D. Tetralogy of Fallot with Absent Pulmonary Valve
e. Tetralogy of Fallot with absent pulmonary valve
65 66
285
286
Test your Knowledge - Core Knowledge in Statistics and Research Design - Dr. Weiner
2:45pm-4:00pm
Disclosures
test your knowledge: • I have no relevant financial relationships with the
statistics and research design manufacturers(s) of any commercial products(s) and/or
provider of commercial services discussed in this CME
activity
• I do not intend to discuss an unapproved/ investigative
Gary M. Weiner, MD, FAAP use of a commercial product/device in my presentation
gweiner@umich.edu • I’m not a statistician, just a math‐phobic neonatologist
• All examples use simulated data
1 2
ABP Content Specifications
Learning Objectives Core Knowledge in Scholarly Activities
1. Interpret a standard deviation • Types of variable • Assessment of study design,
• Distribution of data performance and analysis
2. Calculate and interpret a relative risk, absolute risk, • Hypothesis testing • Assessment of generalizability
and number needed to treat • Statistical tests • Bias and confounding
• Measurement of association • Causation
3. Calculate and interpret diagnostic test and effect • Incidence and prevalence
characteristics (sensitivity, specificity, PPV, NPV, LR) • Regression • Screening
• Diagnostic tests • Cost benefit, cost
• Systematic review and meta‐ effectiveness and outcomes
analysis • Measurement
3 4
287
2:45pm-4:00pm
Mathematics, rightly viewed, possesses not only truth, Empirical Rule
but supreme beauty — a beauty cold and austere, like
that of sculpture, without appeal to any part of our In a random sample of 100 newborns, blood glucose is normally
weaker nature, without the gorgeous trappings of distributed with a mean=90 mg/dl and standard deviation=10 mg/dl.
painting or music, yet sublimely pure, and capable of a Considering the sampled newborns, which of the following is true?
stern perfection such as only the greatest art can show. A. 5% have glucose > 110 mg/dl
The true spirit of delight, the exaltation, the sense of B. 34% have glucose > 100 mg/dl
being more than Man, which is the touchstone of the
highest excellence, is to be found in mathematics as C. 50% have glucose > 90 mg/dl
surely as poetry. D. Based on this sample, the standard error of the mean is 9 mg/dl
Bertrand Russell
5 6
5% > 110 mg/dL?
Draw the normal curve and label it
No. 2.5% > 110 mg/dL
90
Mean = 90 mg/dl
SD = 10 mg/dl
80 100
+/‐ 1SD = 80‐100
70 110
+/‐ 2SD = 70‐110
70 110 2.5%
2.5%
7 8
288
2:45pm-4:00pm
34% > 100 mg/dL? 50% > 90 mg/dL?
½ of 68% = 34%
No. 16% > 100 mg/dL YES! 50% above the median.
50% ‐ 34% = 16% 90
80 100
16%
34%
50%
50%
9 10
SEM is 9 mg/dl?
Measures of Association
NO. SEM = 1
• Standard error of the mean (SEM) An RCT studies Confusemol to prevent IVH; 15 of 100 treated
babies get and IVH and 30 of 100 control babies get an IVH.
– AKA the SD of the sampling distribution of means
• SEM = SD / n 0.15
• The question gives us the SD and n B. The odds ratio (OR) associated with Confusemol treatment is 2.0
– SEM = 10 / 100 C. Confusemol treatment resulted in a 0.50 difference in IVH rate

– SEM = 10 / 10 = 1
11 12
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2:45pm-4:00pm
Draw a Blank 2 x 2 Table Fill it in
Outcome across the top
IVH No IVH total
IVH No IVH total
(Bad) Treatment 15 85 100
Treatment
Control 30 70 100
Control
200
N
13 14
Calculate Risk by Group Risk Ratio or Relative Risk (RR)
IVH NO IVH total
• Treated Risk IVH No IVH • Tx risk (15/100) = 0.15
TX 15 85 100
= 15/100 Totals
• Placebo risk (30/100) = 0.30
= 0.15 TX 15 85 100 • RR = Treated/control Control 30 70 100
• Control Risk
= 30/100 Control 30 70 100
= 0.15 / 0.30 = 0.50
= 0.30
“15% of treated babies got IVH compared
200 “Treated subjects had 50% of the risk
with 30% of controls” of IVH relative to controls”
15 16
290
2:45pm-4:00pm
Relative vs. Absolute Risk Sick Neighbor vs. Healthy Neighbor
• Relative risk depends on your point of 20
20
reference RR = 2.0 for both
15
• Huge differences in absolute risk may be % 10
10
masked by relative risk 0.02 0.01
5
• “Sir, you have twice the risk of dying today as 0
10% risk difference 0.01% risk difference
your next door neighbor (RR = 2).” Sick Neighbor
Me
Healthy
Neighbor
Neighbor
17 18
Absolute Risk Reduction (ARR) AKA
Number Needed to Treat
Risk Difference (RD)
RD = (Placebo risk – Treatment Risk) NNT = 1 / ARR
= 0.30 – 0.15 = 1 / (0.15)
= 6.7
= 0.15
“Confusemol resulted in a 0.15 difference “You need to treat 7 babies with Confusemol to

in IVH rates” prevent 1 additional baby from getting an IVH”
19 20
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2:45pm-4:00pm
Probability vs. Odds Odds and Odds Ratio (OR)
IVH No IVH
• Tx odds (15/85) Totals
= 0.18 Tx 15 85 100
• The probability of a yellow box is 1/4 or 0.25
• Control odds (30/70)
• The odds of a yellow box are 1:3 or 0.33 = 0.43 Control 30 70 100
Odds = Probability
(1‐ Probability)
• Odds Ratio (0.18/0.43) 45 155 200
= 0.42
Probability = Odds Calculate odds “within” the box
(1 + Odds)
21 22
Measures of Association Statistical Tests
An RCT studies Confusemol to prevent IVH; 15 of 100 treated RCT…each subject randomized to receive one of 4 drugs…want to
compare the mean SBP between the subjects in each group. Which
babies get and IVH and 30 of 100 control babies get an IVH. statistical test to compare the 4 sample means?
0.15 A. Paired Student’s‐t test comparing each drug combination
B. ANOVA
B. The odds ratio (OR) associated with Confusemol treatment is 2.0 C. Mann‐Whitney U Test
C. Confusemol treatment resulted in a 0.50 difference in IVH rate D. Linear regression
E. Chi‐square
23 24
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2:45pm-4:00pm
Outcome Test Outcome Test
Means Only 2 = T‐test Means Only 2 = T‐test

(interval/ratio, parametric) Before/after, twins = Paired T‐test (interval/ratio, parametric) Before/after, twins = Paired T‐test
More than 2 = ANOVA More than 2 = ANOVA
Medians Only 2 = Mann‐Whitney U‐Test (AKA Wilcoxon rank sum) Medians Only 2 = Mann‐Whitney U‐Test (AKA Wilcoxon rank sum)
(ordinal or skewed) Before/after, twins = Wilcoxon signed rank (ordinal or skewed) Before/after, twins = Wilcoxon signed rank
More than 2 = Kruskal‐Wallis More than 2 = Kruskal‐Wallis
Proportions Chi‐square Proportions Chi‐square
Small groups = Fisher’s Exact Small groups = Fisher’s Exact
Before/after = McNemar’s Before/after = McNemar’s
Time to event (compare 2) Kaplan‐Meier (Log Rank) Time to event (compare 2) Kaplan‐Meier (Log Rank)
Time to event (make predictions) Kaplan‐Meier (Cox proportional hazards regression) Time to event (make predictions) Kaplan‐Meier (Cox proportional hazards regression)
Linear relationship continuous Pearson correlation (r) Linear relationship continuous Pearson correlation (r)
Linear relationship ordinal Spearman’s rho Linear relationship ordinal Spearman’s rho
Predict a number Linear regression Predict a number Linear regression
Predict a Yes/No Logistic regression Predict a Yes/No Logistic regression
25 26
Diagnostic Tests Sensitivity and Specificity
Auscultate 100 preemies using echo as the reference • Sensitivity
standard. Murmur (+) in 27 of 30 preemies with hsPDA and 14 – Given a patient with disease, what’s the chance that
of 70 preemies without hsPDA. For diagnosing hsPDA…
the test will be positive?
A. The sensitivity of auscultation is 0.80
– The Positive in Disease (PID) rate
B. The specificity of auscultation is 0.90
C. In this sample, if a baby has a murmur, there’s a 66% • Specificity
chance of having a hsPDA – Given a healthy patient, what’s the chance that the
D. In this sample, if a baby does not have a murmur, there’s test will be negative?
an 80% chance of not having a hsPDA – The Negative in Health (NIH) rate
27 28
293
2:45pm-4:00pm
How Does This Help Us? PPV and NPV
• Your patient has a POSITIVE test • Positive predictive value
• Sensitivity and Specificity start with knowledge of – Given a (+) test, what’s the chance of disease?
disease state
• Helpful only at extremes – This is what you really want to know
o SnNout
• 100% Sensitive test negative, rules out disease • Negative predictive value
• Good screening tests – Given a (‐) test, what’s the chance of health?
o SpPin
• 100% Specific test positive, rules in disease
• Good follow‐up tests
29 30
Caution! Draw a Blank Table
Truth Comes
• Both PPV and NPV are heavily affected by PDA No PDA
From Heaven
disease prevalence
(+)
– Sleep deprived Murmur
– Familial Mediterranean Fever
(‐)
• If your patient’s “pre‐test” probability of
disease isn’t the same as the study group,
N
can’t use their PPV or NPV
31 32
294
2:45pm-4:00pm
Fill in the table w/ data from question. Fill in the table w/ data from question.
Add or subtract to get the rest
PDA No PDA PDA No PDA
(+) 27 14 (+) 27 14 41
Murmur Murmur True + False + All test +
(‐) (‐) 3 56 59
False ‐ True ‐ All test ‐
30 70 100 30 70 100
All diseased All healthy Total n
33 34
Review Sensitivity = Positive in Disease (PID)
• Sensitivity: PDA No PDA
(+) 27
______. Murmur Sensitivity = PID
True + False + All test +
(‐)
= 27/30
3
• Specificity: False ‐ True ‐= 0.90
All test ‐
______. 30
35 36
295
2:45pm-4:00pm
Specificity = Negative in Health (NIH) Review
PDA No PDA • PPV
(+) – Given a patient with __ ____ ____, what’s the
27 14 41
Specificity = NIH
True + False + All test + chance of _____?
= 56/70
Murmur (‐) 3 56 59 • NPV
= 0.80 False ‐ True ‐ All test ‐
– Given a patient with __ ____ ____, what’s the
30 70 100 chance of _____?
37 38
Chance of disease with (+) test is asking about Chance of no disease with (‐) test is asking about
PPV. NPV.
PDA No PDA PDA No PDA
True NEG / All with (‐) Test
(+) (+) NPV = 56 / 59
27 14 41 27 14 41
Murmur True + False + All test + Murmur True + NPV = 0.95 = 95%
False + All test +
(‐) 3True POS / All with (+) Test
56 59 (‐) 3 56 59
False ‐ True ‐ All test ‐ False ‐ True ‐ All test ‐
Calculate ACROSS
30 PPV = 27/41
70 100 30 70 100
All diseased PPV = 0.66 = 66%
All healthy Total n All diseased All healthy Total n
39 40
296
2:45pm-4:00pm
Board test trick Test Hint‐Assume 100 patients
• Test writer could just give you the prevalence DZ + DZ ‐
of disease and the sensitivity and specificity of
(+) 18 112 169
Sensitivity = PID
the test. Test 0.9 x 20 = 18
– They tell you prevalence is 20%, sensitivity is 90%, (‐) 2
specificity 60%
• You can fill in the table with just that info 20 100
41 42
Test Hint Ideal World
DZ + DZ ‐ Test Negative Test Positive
(+) 18 32
Specificity = NIH
Test
.60 x 80 = 48
(‐) 2 48
Healthy Sick
20 80 100
Test with continuous
outcome
43 44
297
2:45pm-4:00pm
More Sensitive: Lots of False
Real World
Positives
Test Negative Test Positive Test Negative Test Positive
Healthy Sick Healthy Sick

Test with continuous Test with continuous
outcome outcome
45 46
More Specific: Miss Some Sick ROC Curve
Shows trade‐off between Sens/Spec at different cutoffs
Patients
Test Negative Test Positive
Healthy Sick
Test with continuous
outcome
47 48
298
2:45pm-4:00pm
The ROC Curve Linear Regression
Shows trade‐off between Sens/Spec at different cutoffs
Best test Multiple linear regression… Variable 
predict Cr (mg/dL) from birth Coefficient
weight and presence of PDA (constant) 0.15
The predicted Cr for a baby BW (kg) 0.3
with BW 1.5 kg and no PDA. PDA (1=Y, 0=N) 1.58
Useless test A. 0.45 mg/dL
B. 0.60 mg/dL R2 0.7, p < 0.01
C. 0.80 mg/dL
D. 2.18 mg/dL
49 50
Linear Regression Take Home Messages
• BW = 1.5 kg, No PDA Variable  • When asked a SD question, draw and label the
Coefficient curve first
• Y = β1 (X1) + β2 (X2) + a (constant) 0.15 • When drawing a 2x2 table put “TRUTH” at the
• Y = 0.3 (1.5) + 1.58 (0) + 0.15 BW (kg) 0.3 top.
• Y = 0.45 + 0.15 = 0.60 PDA (1=Y, 0=N) 1.58 – Therapy question, bad outcome on the left
– Diagnostic test, having disease on the left
R2 0.7, p < 0.01 • Sensitivity and specificity START with knowledge
of disease state.
51 52
299
2:45pm-4:00pm
Thanks!
• Do a little
practice
• Read the
questions
carefully
53
300
Optimizing Delivery Room Care - Dr. Savich
1:30pm-2:20pm
Conflicts of Interest
Optimizing Delivery
Room Care • We have no conflicts of interest related to
this presentation.
NeoPREP 2020
• We will not present information on non-
approved drugs-but not everything we do in
Renate Savich, MD the DR is fully studied-and it changes all the
University of Mississippi Medical Center time!
1 2
Neonatal Resuscitation 2015 Publications for Neonatal Resuscitation

Current Updates and Controversies ILCOR NRP
NRP
1. Preparation for Resuscitation FLOW
2. Delayed Cord Clamping and Umbilical Cord
Milking
3. Management of Meconium Stained Infant
4. Temperature Management in the DR
5. Non-Invasive Ventilation Strategies in the DR
1. Tidal Volume
2. Sustained Inflation
6. Use of Oxygen in the DR
7. Monitoring Heart Rate in the DR
8. Cardiac Compressions
3 4
301
1:30pm-2:20pm
NRP-2015 How Many Babies Will Need to be Resuscitated?
Part 13: Neonatal Resuscitation

• Approximately 10% of newborns require some assistance to
2015 American Heart Association Guidelines Update for
Cardiopulmonary Resuscitation and Emergency
begin breathing at birth.
Cardiovascular Care (Reprint) • Less than 1% require extensive resuscitation measures, such
as cardiac compressions and medications.
Wyckoff PEDIATRICS 136, 2015
• Although most newly born infants successfully transition
from intrauterine to extrauterine life without special help,
because of the large total number of births, a significant
number will require some degree of resuscitation.
Perlman, Circulation. 2015;132(suppl 1): S204–S241.
5 6
Neonatal Resuscitation These Should Be Performed in Sequence
A. Initial steps in stabilization (warm and maintain

normal temperature, position, clear secretions
only if copious and/or obstructing the airway, dry,
• Neonatal cardiac arrest is stimulate) -Assess HR and Breathing
predominantly asphyxial, so
B. Ventilate and oxygenate-Assess HR
initiation of ventilation
C. Initiate chest compressions-Assess HR
remains the focus of initial
resuscitation. D. Administer epinephrine and/or volume-Assess HR
The most sensitive indicator of a successful

response to each step is an increase in
heart rate.
7 8
302
1:30pm-2:20pm
Huddle-VIDEO How Do you Prepare for a Delivery
• Resuscitate in Delivery Room or

Separate Room?
• Roles?
• Checklists?
9 10
1. Preparation for Resuscitation Resuscitation Team Position
• Anticipation of resuscitation at birth

• Perinatal risk factors
• Communication between obstetric and newborn teams
• Key questions to ask
• Preparation for resuscitation
• Personnel
• Equipment
• Team briefing
Sawyer, Seminars in Fetal and Neonatal Medicine 23 (2018) 312–320
11 12
303
1:30pm-2:20pm
Checklists-By Role or Task 2. Delayed Cord Clamping (DCC)
A. B. Neonatal Resuscitation 2015 American Heart Association

Guidelines
• Delayed cord clamping for longer than 30 seconds is reasonable for
both term and preterm infants who do not require resuscitation at birth
• Insufficient evidence to recommend an approach to cord clamping for
infants who require resuscitation at birth
• Contraindicated in placental abruption, cord
avulsion
• Studies investigating resuscitation while cord
still attached
13 14
Studies of DCC-Cochrane-Preterm Infants Preterm Death: DCC vs ECC

(With Immediate Neonatal Care After Cord Clamping)
• Delayed, rather than early, cord clamping may reduce the risk of death before
discharge for babies born preterm.
2019 Cochrane Review
• TOTAL: aRR: 0.73, 95% confidence interval (CI) 0.54 to 0.98, 20 studies, 2680 babies
• Forty-eight studies (5721 infants) were
eligible for inclusion.
• Participants were between 24 and 36 6/7
weeks’ gestation at birth.
• Evaluated delay of 30-60 seconds in most
studies.
• The maximum delay in cord clamping was
180 seconds.
Rabe, Cochrane Database of Systematic Reviews 2019
15 16
304
1:30pm-2:20pm
Preterm: IVH DCC-vs ECC Preterm: Other Benefits of Delayed Cord Clamping
• DCC Slightly reduces the number of babies with any grade IVH (aRR • Less need for transfusion after birth
0.83, 95% CI 0.70 to 0.99, 15 studies, 2333 babies) • 0.66 [0.5,0.86]
• Decrease in inotropes for low blood pressure

• 0.37 [0.17,0.81]
• Higher blood pressure

• Mean increase 2.9 mmHg
• Little or no difference for severe (IVH grades 3 and 4) (aRR 0.94,
95% CI 0.63 to 1.39, 10 studies, 2058 babies)
• NO difference in necrotizing enterocolitis
17 18
Preterm DCC vs ECC DCC and Bedside Resuscitation-Intact Cord

(With Immediate Neonatal Care After Cord Clamping)
• DCC has little or no effect on:

• Respiratory Distress Syndrome: aRR 1.09 [0.86,1.38]
• Chronic lung disease: aRR 1.04, [0.94 to 1.14]
• Home oxygen
• PDA
• ROP
Ongoing trials……
19 20
305
1:30pm-2:20pm
Preterm DCC and Ventilation with intact

cord vs ECC
Resuscitation while cord is intact:
• There is insufficient evidence to show what duration
Death or neurodevelopmental impairment at age two to three years. of delay is best, one or several minutes, and therefore the
aRR: 0.61 [0.39, 0.96
optimum time to clamp the umbilical cord remains
unclear.
• Immediate neonatal care with the cord intact requires
further study, and there are insufficient data on UCM.
Favors DCC with
Intact Cord
No difference seen in IVH, respiratory , NEC, blood transfusion or BP
CORD Pilot 2018, Rabe, Cochrane Database of Systematic Reviews 2019
21 22
Term Well Infants Benefits of Delayed vs Early Cord

Current Guidelines- Preterm Infant
Clamping
• Delayed cord clamping is suggested for
30-60 seconds for most preterm
newborns showing some signs of vigor 15 trials involving a total of 3911 women and infant pairs
(some respiratory effort, some
• Primary outcome of neonatal mortality
tone/movement)
• No significant differences between early and late clamping
• Place skin to skin with mom or OB
securely hold in a warm, dry towel or • Hemoglobin concentration in infants at 24 to 48 hours
blanket • Significantly lower in the early cord clamping group (MD -1.49 g/dL, 95%
• Very preterm newborns may be CI -1.78 to -1.21; 884 infants)
wrapped in a warm blanket or
polyethylene plastic
MacDonald, Cochrane Database of Systematic Reviews 2013
23 24
306
1:30pm-2:20pm
Term Infants: Benefits of Delayed vs Early Cord Clamping Delayed Cord Clamping in Term Asphyxia?
• When lung aeration and increased PBF have not been

established, the left ventricle output is still largely
• Iron deficient at three to six months dependent on the venous return from umbilical venous
flow, which flows via the foramen ovale directly into the
• Infants in the early cord clamping over twice as likely to
left atrium.
be iron deficient compared with infants whose cord
clamping was delayed (RR 2.65, 95% CI 1.04 to 6.73) • When the umbilical cord is clamped before lung aeration,
the loss of umbilical venous return leads to a sudden
• Phototherapy for jaundice decrease in preload for the left ventricle.
• Fewer infants in the early cord clamping group required • The lung must be aerated with resultant increased PBF in
phototherapy than in the late cord clamping group (RR order to restore cardiac output.
0.62, 95% CI 0.41 to 0.96) • DCC allows placental blood to get to lungs and then LV
with delays in spontaneous respiration.
MacDonald, Cochrane Database of Systematic Reviews 2013

• Trials of DCC with assisted ventilation?
25 26
Cord MILKING vs DELAYED Cord Clamping Cord Milking
• Some studies have suggested that cord “milking”

might accomplish goals similar to DCC, but there
is insufficient evidence of either its safety or utility
to suggest its routine use in the newly born,
particularly in extremely preterm infants
• Cord milking is rapid compression of umbilical
cord from direction of placenta to the baby, 4
times in succession
27 28
307
1:30pm-2:20pm
Current ILCOR Recs Regarding CORD MILKING 2019 Cochrane Review of Cord Milking
• Currently, ILCOR suggests against the routine use of • Delayed cord clamping (DCC)with immediate neonatal
cord milking for infants born at less than 29 weeks of care after cord clamping versus umbilical cord milking
gestation but cord milking may considered a (UCM)(three studies, 322 babies and their mothers) and UCM versus
reasonable alternative to immediate cord clamping to early cord clamping (ECC) (11 studies, 1183 babies and their mothers).
improve initial mean blood pressure, hematological
indices and ICH. • There are insufficient data for reliable conclusions about
the comparative effects of UCM compared with delayed
• However, there is no evidence for improvement or
safety in long term outcomes. or early clamping (mostly low or very low certainty).
Perlman, Circulation. 2015;132(suppl 1): S204–S241.
29 30
Premature Infants Umbilical Cord Milking UCM Results Stopped Early-WHY?
• NO Difference
in Primary
Katheria JAMA. 2019;322(19):1877-1886 Outcome-
OBJECTIVE: To determine whether the rates of death or severe intraventricular hemorrhage differ Worse for
among preterm infants receiving placental transfusion with umbilical cord milking vs delayed Vaginal
umbilical cord clamping
Delivery
INTERVENTIONS: Participants were randomized to umbilical cord milking (n = 236) or delayed
umbilical cord clamping (n = 238). Mean GA 28 weeks (23 0/7 – 31 6/7 weeks.
• No Difference
MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of death or severe
intraventricular hemorrhage to determine noninferiority of umbilical cord milking with a 1%
in Death Rate
noninferiority margin.
Katheria JAMA. 2019;322(19):1877-1886
31 32
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1:30pm-2:20pm
UCM-Very Concerning for Severe IVH!!! 2. Suctioning for Meconium
In tiniest babies-UCM had MORE Severe IVH • What is the current management No more
of babies with meconium stained questions about
amniotic fluid? meconium!!
• Vigorous?
• Non Vigorous?
• About 15% of babies have

meconium stained amniotic fluid
and it was routine to intubate
every one of these infants to
prevent Meconium Aspiration
Syndrome
• Was this correct?

Katheria JAMA. 2019;322(19):1877-1886
33 34
Video Question?
1. Would you suction this baby immediately after delivery?

2. Would you intubate and suction this baby immediately
after delivery?
3. Would you start PPV immediately after delivery?
4. Would you intubate and start PPV immediately after
delivery?
What is the latest evidence?
35 36
309
1:30pm-2:20pm
Suctioning or Intubation for Meconium in Utero Gasping

and Aspiration-Are We Too Late?
VIGOROUS NEWBORNS with Meconium
STRESS IN UTERO IN UTERO BIRTH or IN UTERO Intubation and Suctioning of Meconium In Vigorous Newborns-

Is it Beneficial?
Respiration Wiswell study
• Prospective RCT, enrolled patients from 1995 - 1997
–International collaboration, 12 centers involved
• Randomized 2,094 vigorous meconium-stained newborns
• Randomized to either intubation and suction vs. expectant
management
• Inclusion criteria: 37+ weeks, MSAF (any consistency), vigor
immediately after birth
Wiswell et al. Pediatrics 2000;105: 1-7
37 38
Delivery Room Management of the Apparently

Vigorous Meconium-stained Neonate
Occurrence
of MAS (n=62) Intubated Expectant Significance
• What about the NON-VIGOROUS Infant with

Overall 34/1051 (3.2%) 28/1043 (2.7%) NS
Meconium?
2/453 (0.4%) NS
Thin MSAF 5/447 (1.1%)
• https://www.youtube.com/watch?v=bSg48AQT
Moderately thick 6/307 (2.0%) NS
MSAF
7/301 (2.3%) RsA
Thick MSAF 22/303 (7.3%) 20/283 (7.1%) NS
More complications in those intubated: bradycardia, stridor,

laryngospasm Wiswell et al. Pediatrics 2000;105:1-7
39 40
310
1:30pm-2:20pm
ILCOR-2019 ILCOR 2019-PUBLIC COMMENT STAGE

Critical outcomes of:
Review of 3 • Survival to discharge
Chettri, J Pediatr 2015; 166:1208-13
recent • Cognitive neurodevelopmental impairment
randomized • Motor neurodevelopmental impairment
controlled trials • Hypoxic ischemic encephalopathy
for • Meconium aspiration syndrome (MAS)
NONVIGOROUS • Use of mechanical ventilation
infants with
meconium Nangia et al. Resuscitation 2016;105:79-84
• No benefit for the use of immediate laryngoscopy
stained amniotic with or without tracheal suctioning when
fluid compared to immediate resuscitation without
N=499 patients laryngoscopy
Clinical Epidemiology and Global Health 7 (2019) 165–170
41 42
Suctioning for Meconium- Why Not Routine Intubation and Suctioning for Meconium?
Current Recommendation
Suctioning Nonvigorous Infants Experts placed greater value on harm

Through Meconium-Stained avoidance:
Amniotic Fluid • delays in providing bag mask ventilation
• potential harm of the procedure
• If an infant is born through meconium-stained amniotic
fluid and presents with poor muscle tone and inadequate
breathing efforts, the infant should be placed under a over the unknown benefit of the
radiant warmer and PPV should be initiated if needed per
intervention of routine tracheal intubation
routine ILCOR guidelines:
• If the infant is not breathing or the heart rate is less than 100/min after the and suctioning
initial steps are completed.
43 44
311
1:30pm-2:20pm
Suctioning/Intubation for Meconium 3. Temperature
• Routine intubation for tracheal suctioning is no

ILCOR algorithm
longer recommended. Appropriate intervention to
stresses importance of
support ventilation and oxygenation should be
maintaining
initiated as indicated for each individual infant.
temperature during
• IF NOT BREATHING, FOLLOW ROUTINE ALGORITHM! resuscitation
• This may include intubation and suction if the airway
is obstructed or baby not breathing.
45 46
Admission Temperature of Low Birth Weight

Video Infants: Predictors and Associated Morbidities
• Preemie with Temp management • NRN, 5277 study infants; the mean birth weight and gestational
age were 1036 g and 28 weeks, respectively
• For every 1°C decrease in admission temperature:
• The odds of dying were increased by 28% (OR: 1.28; CI: 1.16–
1.41)
• The odds of late-onset sepsis were increased by 11% (OR: 1.11;
CI: 1.02–1.20)
Laptook, Pediatrics 2007;119;e643
47 48
312
1:30pm-2:20pm
Temperature Strategies at Delivery and

Temperature Resuscitation
• A variety of strategies should be used:
• Temperature should be recorded as a predictor

of outcomes and as a quality indicator. • Radiant warmers
• Temperature of newly born non-asphyxiated • Plastic wrap
• Cap
infants (preterm and term) should be
• Thermal mattress
maintained between 36.5°C and 37.5°C after • Warmed humidified gases
birth through admission and stabilization. • Increased room temperature
49 50
Hyperthermia in Asphyxia 4. Ventilation-Golden Minute
• Hyperthermia (temperature greater than Establish ventilation by 60 seconds

38°C) should be avoided because it • Golden Minute (60-second) mark for
completing the initial steps, reevaluating,
introduces potential associated risks. and beginning ventilation (if required)
• Adverse outcomes in asphyxiated term babies • Emphasize the importance of avoiding
worse with hyperthermia unnecessary delay in initiation of ventilation,
the most important step for successful
• The odds of death or disability were increased resuscitation of the newly born who has not
3.6–4 fold for each 1°C increase in the highest responded to the initial steps
quartile of skin or esophageal temperatures in

control infants from NRN study.
Laptook, Pediatrics 2008;122:491–499
51 52
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1:30pm-2:20pm
Phases of Initial Ventilation MR SOPA
Phase 1
1. Lung is fluid filled, focus on clearing liquid
2. Require higher pressure to overcome high resistance
3. Need to have sudden increase in pulmonary blood flow
VENTILATION!!!!!
Phase 2
1. Lung is air filled, premature lungs have tendency to collapse
2. Pulmonary gas exchange is possible
Initiate corrective steps if
3. Provide PEEP/CPAP to prevent collapse of alveoli Heart Rate remains
below 100 bpm after
initiation of PPV
Phase 3
1. Infant has passed the immediate transition, the lungs are
aerated,
2. Ventilation is now more focused on gas exchange and
metabolic homeostasis
53 54
Impact of Delivered Tidal Volume on the

MR SOPA if ventilation not successful Occurrence of Intraventricular Hemorrhage
• Mask is tightly applied to the face Preterm Infants During Positive Pressure Ventilation in the
Delivery Room
• Re-position the head into the “sniffing” orientation
• Infants were divided into two groups: VT<6
• Suction the nose and then the mouth quickly
mL/kg or VT>6 mL/ kg (normal and high VT,
• Open the mouth respectively)
• 165 preterm infants : 124 (75%) high VT and
• Pressure of PPV can be increased to a max of 40 cm H2O-BE 41 (25%) normal VT.
CAREFUL!
• Mean gestational age: 26 weeks and birth
• Alternate airway, i.e. ET or LMA, should be considered and planned
weight 858 (251) g and 915 (250) g
for
• Laryngeal mask airway use • Brain injury (eg, intraventricular
• Suggest LMA use as alternative to intubation during resuscitation of term and late hemorrhage (IVH)) by HUS within the first
preterm if face-mask unsuccessful days after birth.
Mian Q, et al. Arch Dis Child Fetal Neonatal Ed 2018;0:F1–F6
55 56
314
1:30pm-2:20pm
Tidal Volume: Higher vs Lower Sustained Inflation-Video

Per Cent IVH
• IVH in infants receiving VT>6 mL/kg during
PPV was diagnosed in 63 (51%) infants
compared with 5 (13%) infants receiving
VT<6 mL/kg (P=0.008).
• Severe IVH (grade III or IV) developed in

33/124 (27%) infants in the VT>6 mL/kg
group and 2/41 (6%) in the VT<6 mL/kg
group (P=0.01).
High TV Low TV
Mian Q, et al. Arch Dis Child Fetal Neonatal Ed 2018;0:F1–F6
57 58
Sustained Inflation in DR Sustained Inflation-Why?

• IMPORTANCE Preterm infants must establish regular respirations at delivery. Sustained
inflations may establish lung volume faster than short inflations.
• Some infants are judged to have inadequate
• OBJECTIVE To determine whether a ventilation strategy including sustained inflations,
breathing at birth and are resuscitated with compared with standard intermittent positive pressure ventilation, reduces
positive pressure ventilation (PPV). bronchopulmonary dysplasia (BPD) or death at 36 weeks’ postmenstrual age without
harm in extremely preterm infants.
• Giving prolonged (sustained) inflations at the start • DESIGN, SETTING, AND PARTICIPANTS Unmasked, randomized clinical trial conducted
of PPV may help clear lung fluid and establish gas in 18 neonatal intensive care units in 9 countries. Preterm infants 23 to 26 weeks’
gestational age requiring resuscitation with inadequate respiratory effort or
volume within the lungs. bradycardia were enrolled.
• INTERVENTIONS The experimental intervention was up to 2 sustained inflations at

maximal peak pressure of 25 cm H2O for 15 seconds using a T-piece and mask (n =
215); standard resuscitation was intermittent positive pressure ventilation (n = 211).
Kirpalani JAMA: 321; 2019
59 60
315
1:30pm-2:20pm
SAIL Study-Trial Stopped Early-WHY? 5. Oxygen Pulse Oximetry
It is recommended that oximetry

be used when:
• Resuscitation can be anticipated
• PPV is administered
• Central cyanosis persists beyond
the first 5 to 10 minutes of life
• Supplemental oxygen is
administered
Kirpalani JAMA: 321; 2019
61 62
Oxygen Saturations-What is Normal? Oxygen Saturation in First 10 Minutes of Life
Slightly lower for:

> 37 weeks
• Preterm babies
• Lower at 5 min
• Babies born via
Cesaerean
section < 32 weeks
All Infants
Dawson, PEDIATRICS 2010; 125: e1341

Dawson, Pediatrics 2010;125:e1340–e1347
63 64
316
1:30pm-2:20pm
Oxygen-Good or Bad? Oxidative Stress
• BEST OXYGEN STRATEGY: Hyperoxia

• One that avoids hypoxemia and hyperoxemia Antioxidant capacity in preterm and term
infants is low
• One that results in normal oxygen delivery to
tissues
• Too much oxygen in delivery room results in oxidative
stress and tissue injury Generation of
Free Radials
• Too little oxygen in the delivery room for a prolonged
period of time, especially coupled with poor cardiac
output may result in oxidative stress and tissue injury as BPD, ROP , IVH, PVL and NEC
well all associated with increased
oxidative stress
65 66
Can We Tell When Babies are Pink? Oxygen Use for Term and Preterm Infants
Recently, ILCOR has moved from a 5-year review

20 videos-asked when baby is PINK cycle to a continuous evaluation process, and this
• One infant (5%) was perceived to be pink by
all provided an opportunity to perform an updated
• Number of clinicians who thought each of the analysis on this topic by using rigorous
remaining 19 infants were never pink varied
from 1 (4%) to 22 (81%). methodology including GRADE
• The 10 infants with a maximum SpO2 >95%
were observed to be never pink on 17%
(46/270) of occasions
• SpO2 at which individual infants were
perceived to turn pink varied from 10% to 100% Welsford Pediatrics. 2019;143:e20181825
• WE JUST CANNOT AGREE/TELL WHEN A BABY IS Welsford Pediatrics. 2019;143:e20181828
“PINK”
O’Donnell et al. Arch. Dis. Child. Fetal Neonatal Ed 2007;92:F465-F4
67 68
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1:30pm-2:20pm
Oxygen-Where to Start in TERM Infants? Oxygen-Where to Start in TERM Infants?
• ILCOR Meta-analysis of five randomized controlled trials

(RCTs) and 5 quasi RCTs included 2164 patients.
• Room air (FiO2 0.21) was associated with a statistically significant benefit • No significant differences were
in short-term mortality compared with 100% oxygen (FiO2 1.0) (7 RCTs;
n = 1469; risk ratio [RR] = 0.73; 95% confidence interval [CI]: 0.57 to 0.94). observed in:
• Neurodevelopmental impairment
• (2 RCTs; n = 360; RR = 1.41; 95% CI: 0.77 to 2.60)
• Hypoxic-ischemic encephalopathy
• (5 RCTs; n = 1315; RR = 0.89; 95% CI: 0.68 to
1.18)
Welsford. Pediatrics. 2019;143:e20181825 Welsford. Pediatrics. 2019;143:e20181825

Welsford. Pediatrics. 2019;143:e20181825
69 70
Oxygen-Where to Start in TERM Infants? Oxygen-Start in TERM Infants
Confirms 2015 ILCOR rec:

“We confirm a statistically significant reduction in
short-term mortality (without statistically significant It is reasonable to initiate resuscitation with air
differences in short- and long-term neurologic (21% oxygen at sea level). Supplementary
outcomes) by using initial room air compared with oxygen may be administered and titrated to
Fio2 1.0 (100% oxygen) for term and late preterm achieve a preductal oxygen saturation
newborns (≥35 weeks’ gestation) receiving approximating the interquartile range measured
respiratory support at birth.” in healthy term infants after vaginal birth at sea
level.
Welsford. Pediatrics. 2019;143:e20181825 ILCOR, Circulation. 2015;132 [suppl 1]:S204–S241.
71 72
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1:30pm-2:20pm
Resuscitation of PRETERM Neonates With Limited Versus Resuscitation of PRETERM Neonates With Limited Versus High
High Oxygen Strategy
Oxygen
Preterm Infants-88 babies

Cochrane-10 studies, 914 infants
100% vs 21% to start
FIO2 adjusted by 10% every 30 sec
Meta-analyses of high (>40%) vs low initial oxygen
for preterm infants when titrated to oxygen sat
targets reveal no differences in
Low Oxygen Group • Mortality
• Less oxygen exposure • Intubation
• Lower oxidative stress • NDI
• Fewer ventilator days • or other outcomes
• Less BPD
Kapedia, Pediatrics 2013;132:e1488–e1496

Lui. Cochrane Database of Systematic Reviews 2018, Issue 5.
73 74
Resuscitation of PRETERM Neonates With Limited Versus

High Oxygen Strategy-Meta-Analyis Results Preterm Infant-High vs Low Oxygen
NEW ILCOR REVIEW
Ten randomized controlled studies and 4 cohort studies
included 5697 patients.
There are no statistically significant benefits of or harms from

starting with lower (21%-50%) compared with higher (60%-100%)
FiO2 in:
• Short-term mortality (n = 968; risk ratio = 0.83 [95% confidence interval 0.50 to
1.37]) Conclusion: The ideal initial Fio2 for preterm newborns is still
• Long-term mortality unknown, although the majority of newborns ≤ 32
• Neurodevelopmental impairment weeks’ gestation will require oxygen supplementation.
• or other key preterm morbidities.
Welsford Pediatrics. 2019;143:e20181828

Welsford Pediatrics. 2019;143:e20181828
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1:30pm-2:20pm
Use of Oxygen in Preterm Infants-Where to Start? Video-Hydrops
• Assessment of Heart Rate

• Resuscitation of preterm newborns
of less than 35 weeks of gestation
should be initiated with low oxygen
(21% to 30%) and the oxygen
titrated to achieve preductal
oxygen saturation approximating
the range achieved in healthy term
infants
ILCOR, Circulation. 2015;132 [suppl 1]:S204–S241.
77 78
6. Using Heart Rate to Determine
Methods to Determine Heart Rate
Next Steps
Times when HR is assessed:
1. Palpation of the Umbilical Cord
1. Before PPV started (30 2. Palpation of femoral or brachial pulses
Sec) 3. Ausculation of the Heart
2. After PPV started (30 Sec) 4. Pulse Oximeter
3. After ensuring adequate 5. ECG Monitoring
ventilation (30 Sec)
4. After initiating chest
compressions (45-60 sec) Future
A. Doppler US
5. After IV epi
B. PPG (photoplethysmography)
79 80
320
1:30pm-2:20pm
ECG Monitoring Pulse Oximetry Measures a Lower Heart Rate at Birth

Compared with Electrocardiography
HR changes (SEM) in the first

• Clinical assessment of heart rate in the delivery room has 10 minutes after birth
been found to be both unreliable and inaccurate. measured by PO (blue) and
Underestimation of the heart rate may lead to unnecessary ECG (green)
resuscitation.
• ECG has been found to display an accurate heart rate faster Pulse Ox HR consistently
than pulse oximetry. lower-unnecessary
interventions?
• Pulse oximetry more often displayed a lower rate in the first 2
minutes of life, often at levels that suggest the need for
intervention.
van Vonderen, J Pediatr 2015;166:49-53
81 82
Use of ECG Monitoring 7. Cardiac Compressions
• Assessment of heart rate remains Unchanged: Recommendations

critical during the first minute of about-
resuscitation and the use of a 3-lead • Chest compression technique
ECG may be reasonable, because • 2 thumb–encircling hands
providers may not assess heart rate • Lower 1/3 of sternum
accurately by auscultation or
palpation, and pulse oximetry may • Compression-to ventilation ratio
underestimate heart rate. • 3:1 with 90 compressions and 30
breaths per minute
• Use of the ECG does not replace the
need for pulse oximetry to evaluate • Administer 100% oxygen when
the newborn’s oxygenation. starting chest compressions.
83 84
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1:30pm-2:20pm
Two Thumb Technique for Cardiac Compressions Thank you‐Any Questions?
1/3 of way down to the back, lower 1/3 of sternum
1. Less tiring
2. More consistent placement
Coordinate with Ventilation!
3. Higher BP
4. Less damage to infant
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Post Resuscitation Care: The Dilemma of the Baby Who Responds to Resuscitation - Dr. Goldsmith
2:20pm-3:10pm
Disclosures
Post Resuscitation Care:
The Dilemma of the Baby who Responds
I have no financial
to Resuscitation investments, conflicts of
interest or other
disclosures.
Jay P. Goldsmith, MD
Tulane University I am not an obstetrician or
New Orleans, LA neurologist…
goldsmith.jay@gmail.com
1 2
Objectives
Case Presentation
• Discuss the problems with evaluating a baby for
hypothermia who has responded to DR • 40 5/7 week gestation male born by emergency C/S for non‐reassuring
fetal status
resuscitation
• Discuss the appropriate evaluation of cord blood • SROM 4 hours PTD with MSAF
gases when evaluating a baby post‐resuscitation • Baby limp with HR 60 at birth
• Discuss the use of other labs (e.g. lactate) for the • Intubated; no meconium below cords; PPV given
evaluation of babies who might benefit from • Chest compression x 30 seconds
cooling • Regular respiration by 6 minutes of age; extubated
• Discuss cooling criteria and the value of serial • O2 sats >90% by 8 min and oxygen d/c’d
physical examination in the post‐resuscitation • Apgars 1,5 and 7 (10 minutes)
baby in order to determine if the baby meets the
clinical criteria.
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2:20pm-3:10pm
At this time you would: ACOG recommendations for cord blood gases
1. Allow baby to go S‐T‐S with mother? • Low 5 minute Apgar score
• Severe IUGR
2. Request cord blood gases from OB? • Maternal thyroid disease
• Non‐reassuring EFM
3. Obtain arterial blood gas on baby? • Fever
• Multiple gestations
• C‐sections for fetal distress
• ACOG Committee Opinion #348
• Creasy and Resnik, 2014
5 6
Usefulness of cord blood gases
• Window into fetal state before delivery
• Optimal to get arterial and venous samples
• Some results may be misleading
– Technical error in running sample (i.e. air bubble)
– Mislabeled (i.e. venous gas labeled as arterial)
– Obstructed flow of cord just prior to delivery
Pomerance J: Interpreting Umbilical Cord
Blood Gases, 2nd Ed, 2012
7 8
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2:20pm-3:10pm
Cord blood gas values At this time you:
• pH: 7.14 1. Are reassured by the cord gas and allow baby to breastfeed?
• pCO2: 54 2. Request the OB team or respiratory therapist to repeat
• pO2:36 sampling, obtaining both arterial and venous samples?
• Base excess: ‐11 3. Obtain an arterial blood gas on the baby?
9 10
Umbilical Cord Gas Analysis

Placenta
Cord blood gas rules
Umbilical Vein (UV)
(from Placenta to Fetus) • UA pH should be at least .02 less than UV
• UA pCO2 should be > 4 mmHg than UV
• UV easier to obtain and may be mislabeled as UA
Umbilical Artery (UA)
• UA should have pO2 of <32 mmHg
(from Fetus to Placenta) • UV may help predict UA (Cantu, 2014)
• UA pH .02 - 0.08 Units < UV • Air bubble will ↑pH and pO2, ↓pCO2
• UA cannot have pO2 > 32-34 mmHg
• “No flow” phenomenon
• Cord gases from a doubly clamped cord are reliable for up to
• Clamped cord pHa  .02 Units/20 mins. 60 minutes
• Unclamped cord pH may fall 0.2 units/60 min
Interpreting Umbilical Cord Blood Gases, Pomerance 2nd edition, 2012
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2:20pm-3:10pm
Case: next steps Predicting Fetal Acidemia Using Umbilical
Venous Cord Gas Parameters
Jessica Cantu, MD, Jeff M. Szychowski, PhD, Xuelin Li, Joseph Biggio, MD, Rodney K.
• You correctly interpret the cord gas as venous (high pO2) and Edwards, MD, William Andrews, MD, PhD, and Alan T. N. Tita, MD, PhD
request cord arterial gas
• Result: pH: 7.07, pCO2 62, BE ‐15 • Retrospective cohort study
• At this time you are: • Evaluated 11,455 paired blood gases
1. Reassured by the gases and continue standard newborn care? (arterial and venous) from singleton
2. Concerned about significant acidosis and plan further evaluation? pregnancies
• Compared venous and arterial values
Am J OB‐Gyn, November 2014
https://www.ncbi.nlm.nih.gov/pubmed/25437720
13 14
Chart of predicted probability of arterial pH from Causes of significant fetal acidemia
venous pH
• Sudden decrease in fetal or placental blood flow
– Cord compression
– Abruption
• Fetal anemia
• Placental insufficiency (during labor)
FOR SYLLABUS only : REMOVE TABLE for copyright AND INSERT –
TABLE 2 FROM Cantu et al, Am J OB‐GYN, Nov 2014 • Maternal hypoxemia, hypotension, hypoventilation
The venous cord pH cutoff for predicted probability of acidemia by logistic regression
Venous cord pH of ≤7.06 has ≥50% probability of predicting arterial pH<7.0
• Chronic maternal conditions (e.g. pre‐eclampsia)
Venous cord pH of ≤7.10 has ≥ 50% probability of predicting arterial pH<7.05
From Cantu et al, Am J OB‐Gyn, November 2014
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2:20pm-3:10pm
Cord compression blood gases Despite the reassuring venous cord gas, you are
concerned about the significant arterial cord acidosis
• Severe compression: all 3 vessels compressed and plan further evaluation. What other evaluations
– Uncommon would consider?
– Values may be normal representing condition of fetus prior to
compression 1. Obtain neonatal blood gas?
• Moderate compression
– Thin walled vein more likely to collapse 2. Obtain cord or neonatal lactate level?
– Large A‐V difference; venous gas may be reassuring
– Fetus may also suffer hypovolemia/anemia 3. Perform a neurologic exam?
17 18
First hour neonatal blood gas Lactate from cord or baby
• Helpful to evaluate depressed neonate, especially if cord gas • Elevated cord lactates associated with HIE
not available or suspect – Lactate removed more slowly from fetal circulation than gases
• Reperfusion acidosis – Have been used to predict CNS outcome
• A criteria for therapeutic hypothermia (pH<7.0 or base deficit ≥ – No consensus on level
16) • Neonatal lactate
• Capillary blood gas may be misleading (poor perfusion in first – Shah (2004): Plasma lactate of >7.5 mmol/l in first hour predicted
hour may depress pH) mod‐severe HIE (sensitivity 94%; specificity 67%)
19 20
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2:20pm-3:10pm
Careful CNS exam using modified Sarnat criteria Whole Body Cooling Criteria

Papile and COFN: 2014
Sarnat Stage Stage 2 Stage 3

Level of conciousness Lethargic or obtunded Stuporous • Gest age ≥ 36 weeks and ≤ 6 hours of age
Spontaneous activity Decreased activity No activity and
Posture Strong distal flexion Decerebrate
Tone Hypotonia Flaccid
• pH ≤ 7.00 or base deficit ≥ 16 in cord blood
Primitive reflexes gas or neonatal sample in first hour of life
• Suck Weak Absent
• Moro Incomplete Absent and
Autonomic Function
• Pupils Constricted Dilated/non‐reactive
• Moderate or severe encephalopathy (i.e Stage
• Heart Bradycardia Variable HR 2 or 3 Sarnat)
• Respirations Periodic breathing Apnea
(Presence of 3 of 6 indicators qualifies for TH)
21 22
Whole Body Cooling Criteria Case continues
Papile and COFN: 2014
• Newborn’s arterial blood gas at 55 minutes:
• If blood gas not available or pH between 7.01 – pH 7.22, pCO2 49, pO2 74, BD 10
and 7.15 , or BD between 10 and 15.9 (either • CNS exam: pulse 180, weak cry, slowly withdraws legs with
cord or first hour neonatal gas), 2 additional stimulation, arms and legs extended, hands clenched, weak
criteria needed: suck and incomplete Moro
– History of acute perinatal event
– Need of assisted ventilation for >10 minutes or
Apgar score ≤ 5 at 10 minutes after birth
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2:20pm-3:10pm
Case continues Neuroprotection ‐ Hypothermia

Remove picture
• At this point you should: for printed
syllabus only
1. Start or refer patient for therapeutic hypothermia?
2. Observe and re‐examine baby in 2 hours?
3. Order US of brain?
Gunn A: J Perinatal Med, 2005
25 26
Hypothermia – Efficacy Hypothermia – Efficacy

• 13 randomized clinical trials
Shah Seminars in Fetal & Neonatal Med 2010
Jacobs SE et al: Cooling for newborns with H.I.E.
Jacobs SE et al: Cooling for newborns with H.I.E. Cochrane Database of Sys Rev 2013, No. CD003311
Cochrane Database of Sys Rev 2013, No. CD003311
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Fetus and Newborn Committee Recommendations
Benefits of Hypothermia in HIE Papile L and COFN, 2014
• International RCTs with entry at <6 hours in term infants with 1. Any center undertaking hypothermia should
have access to all specialized neurological
moderate‐severe encephalopathy and acidemia/acute insult services including EEG, MRI, neurological
consultation and follow up.
2. “Infants offered TH SHOULD meet inclusion
• 25% reduction in death or disability (severe: MDI or PDI <70: criteria outlined in published clinical trials.”
cerebral palsy: sensorineural loss) 3. Protocols should be in place with education of in
house and referring providers
4. Cooling infants who do not reach meet these
• NNT 5 to prevent one death or disabled child criteria (i.e <35 weeks, mild encephalopathy,
etc.) should be ONLY BE PERFORMED in a RCT
with informed parental consent.
29 30
What if baby doesn’t meet criteria? Neonatal Encephalopathy: Definition
• Is blood gas reliable?
• Is CNS exam reliable? Repeat q 2hours “A clinically defined syndrome of disturbed
neurologic function in the earliest days of life in
• Suppose baby has mild (Stage 1) encephalopathy an infant born at or beyond 35 weeks gestation
• Risks and benefits of TH in questionable clinical situations manifested by a subnormal level of
• What about cooling after 6 hours? Under 36 weeks? consciousness or seizures, and often
accompanied by difficulty in initiating and
maintaining respiration and depression of tone
and reflexes.”
Neonatal Encephalopathy and Neurologic Outcome, 2014
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2:20pm-3:10pm
Terminology
“NE” vs. “HIE” – two points of view
Terminology
“NE” vs. “HIE” – two points of view
Is use of term “HIE” appropriate in some cases? Use of term “HIE” discouraged because:

• Dx requires cerebral O2 and blood flow measures
• “NE” is vague term (“neither sufficient nor specific”).
• Usually cannot determine when HIE is the cause of NE
• Use term that “best characterizes” disorder.
• Etiologic labels unnecessary when descriptions suffice
• MRI delineated topography of lesions highly correlated with human and
• Obstacles for research (implies pathogenesis known)
animal neuropathology of perinatal HI.
• Used as evidence against providers months/years later:
• “HIE” describes NE meeting clinical features consistent with
“for not having done the c‐section 20 min earlier”
perinatal HI insult coupled with specific patterns of injury on MR.
Dammann O, Ferriero D and Gressens P. Neonatal encephalopathy or Hypoxic‐Ischemic Encephalopathy?
Appropriate Terminology Matters; Peds Res 2011; 70(1).
Volpe JJ. Neonatal encephalopathy: an inadequate term for HIE; Ann Neurol 2012 (72)
33 34
Neonatal Encephalopathy
• 2‐6/1000 live term births
• 10‐20% of infants die and 25% of survivors
have significant disability
Published • Serial clinical examination necessary to
April 2014
identify and characterize evolution
• Hypoxic‐ischemic injury accounts for 60‐75%
of etiologies
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Hypoxic Ischemic Encephalopathy (HIE) NE Staging predict outcomes
• Initial insult, and delayed energy failure
• Severity of insult clinically categorized by
– Level of consciousness
– Activity
– Tone and posture
– Autonomic function
– Reflexes Allan WA: The clinical spectrum of HIE NeoReviews, June 2002, 3 (6) 3108‐115
• Defined as: Mild, Moderate, or Severe • Presence of mod to severe NE best predictor death/severe handicap

– Note: process is a dynamic injury and exam at 2.5 years (sensitivity=96%) Levene MI, et al, Lancet 1986
• Severity of NE and the presence of seizures can predict 30‐mos
Therapeutic hypothermia (TH) is only proven treatment neurodevelop outcome, as early as DOL#1. Miller SP, et al, AJOG 2004
37 38
Modified Sarnat Exam for Neonatal Encephalopathy (NE)
Category Mild Moderate Severe
Level of consciousness Hyperalert Lethargic Stupor/coma • NE may be progressive
Spontaneous activity Present Decreased Absent – Serial exams necessary
Posture Mild distal Strong distal Decerebrate – Document accurate timing of exam
flexion flexion
Tone Normal Hypotonia Flaccid • Experience helps
Segmental myoclonus Present Present absent – Signs can be subtle.
Suck Weak Weak Absent
• Observation over time
Moro strong Incomplete Absent
Secretions Sparse Profuse Variable – Document what is observed and when
Pupils Mydriasis Constricted Variable – “non‐focal” or “normal” inadequate
Heart rate Tachycardia Bradycardia Variable
• Staging system (modified Sarnat)
Respirations Normal Periodic Apnea
Duration 1‐3 days 2‐14 days Hours to weeks – Important in deciding course of management.
– Can provide “pre‐test probability” of outcomes.
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2:20pm-3:10pm
Do patients with mild HIE (Sarnat 1) benefit from
TH?
• Population of infants with mild HIE (n=34), Pediatrics, 2016
followed to 9 years
Outcome was available in
– Lower mean IQ in those with mild HIE v controls; 53 infants with HIE and
98.6 v 109 (p=0.21)1 30 controls at 5 years.
Infants with mild HIE
– Increased thought problems with mild HIE v (n=22) had lower full
controls (p=0.001)2 scale IQ, verbal IQ and
performance IQ.
– Worse motor assessment and manual dexterity
(p=0.002)3 Infants with mild HIE did
not differ from those
1.Van Handel M, et al. Dev Neuropsychol, 2012 with moderate HIE.
2.Van Handel M, et al. J Ped Psychology, 2010
3.Van Kooij BJM, et al. Ped Research, 2008
41 42
Imaging outcomes for mild HIE
• Rate of Mod/Severe MRI injury among
• 89 patients did not meet TH criteria per neuro exam
Mild HIE (30%)
No encephalopathy Mil(d encephalopathy Study
Study Mild HIE ‐ (n) Abnormal Outcome ‐ %
(n=29) (n=60) Murray 2009 24 12.5%
Abnormal 1 7 Zhou 2010 39 33%

discharge exam Jacob 2011 40 30%
Seizures 0 5
Lally 2014 24 30%
Abnormal MRI 0 6
Death 0 1
Murray DM: Pediatrics, 2009
• In this cohort, 19 of 60 (31.6%) babies with perinatal Zhou W, et al. J Pediatr, 2010
Jacob SE, et al. Arch Pediatr Adolesc Med, 2011
acidemia had abnormal short term outcomes Lally PJ, et al. PlosOne, 2014
43 44
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2:20pm-3:10pm
TH use beyond standard criteria Risk‐Benefit ratio of therapy
UK Survey: 54 of 68 (79%) centers responding
– Separation of infant from mother
• 36 centers (75%) offered cooling for mild – Approximately 30% of infants are ventilated, does require UVC, TPN
encephalopathy and morphine
• 7 centers (19%) considered initiating cooling after 6 – 10‐20% of mild NE received some blood product – mainly FFP
hours of age – Occasional subcutaneous fat necrosis
• 13 centers (36%) discontinued cooling prior to 72
hours
• MRI was offered to all cooled babies in 29 centers
(80%)
Oliveira, V: Arch Dis Child Fetal Neonatal Ed.

2018, July.
45 46
Involved System n Event Incidence Relative Risk

[%(event/population)] (95% CI)
Adverse Event HT NT
Cardiovascular
Sinus Bradycardia 1292 9.5 (62/647) 0.5 (3/645) 11.59 (4.94‐27.7)
Major Arrhythmia 1292 0.3 (2/647) 0.6 (4/645) 0.55 (0.12‐2.56)

Hypotension 1221 61 (369/608) 60 (373/618) 1 (0.92‐1.09)
Hypotension requiring 768 53 (201/380) 49 (190/388) 1.09 (0.96‐1.24)
inotropes
Involved System n Event Incidence Relative Risk
[%(event/population)] (95% CI) Pulmonary HTN 616 17 (53/305) 13 (40/309) 1.36 (0.94‐1.97)
Adverse Event HT NT
Miscellaneous Hematological
Renal Impairment 667 38.5 (126/327) 45 (153/340) 0.87 (0.74‐1.02) Anemia Requiring RCC 749 13.5 (50/370) 13.4 (51/379) 1.01 (0.71‐1.43)
Oliguria 865 23 (100/435) 23 (101/430) 0.95 (0.76‐1.19) Leukopenia 547 4 (11/266) 1.4 (4/271) 2.4 (0.85‐6.79)
Hepatic Dysfunction 975 30 (147/485) 34 (169/490) 0.88 (0.74‐1.05) Thrombocytopenia 1392 34.5 (241/698) 28 (197/694) 1.21 (1.05‐1.4)
Sepsis 1221 7.5 (46/609) 8.6 (53/613) 0.87 (0.6‐1.26) Coagulopathy 1188 31 (184/589) 28 (170/599) 1.1 (0.93‐1.29)
Jacob SE, et al. Cochrane Database Syst Rev 2013 Jacob SE, et al. Cochrane Database Syst Rev 2013
47 48
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2:20pm-3:10pm
Less Frequent Adverse Events Early Discontinuation of Cooling
Lally PJ et al: Arch Dis Child Fetal Neo Ed,
• Subcutaneous Fat Necrosis 2018 July; 103 (4): F383‐0F387
• Prospective cohort of 10 babies
– Incidence 1‐3.4%1, 2
– Mild encephalopathy
– TOBY reported incidence of 1% (n=12)2 – Early cessation of cooling therapy (median 9 hours)
• Median age of appearance 6 days (4‐42 days) • MRI at 2 weeks and ND assessment at 2 years
• Hypercalcemia in 8 of 10 measured
– 5/10 had injury on MRI
• Median Ca 11.92 mg/dL (6‐20.4 mg/dL)
– 2/10 had abnormal ND at 2 years
1. Chevallier M, et al. PLOS One, 2013
2. Storhm B, et al. Pediatrics, 2011
49 50
How much NE due to antenatal vs. Neurologic exam checklists and tools
intrapartum factors? Neuro Exam basic checklist tool
• Tools and checklists
can help ensure
• Diagnosis of HIE difficult without knowledge of: completeness and
– Cerebral blood flow and oxygen content consistency in neuro
– Timing (single, multiple, variable duration/intervals) exams among
providers.
• Population studies: antenatal >> intrapartum causes Olsen SL, et al, Optimizing
– 4% of NE linked to HIE alone. therapeutic hypothermia for
West CR, Aust NZ J ObGyn 2005 , Badawi N, et al. BMJ 1998 neonatal encephalopathy,,
Pediatrics 2013
• MRI studies: intrapartum HI common in NE.
– As much as 80% of NE cases related to intrapartum asphyxia.
Cowan F, et al., Lancet 2003, Martinez‐Biarge M, et. Al. Pediatrics 2013
51 52
335
2:20pm-3:10pm
Treatments can alter clinical exam
• Cooling and treatment drugs can impact exam
• Persistent mod encephalopathy can occur in cooling
– Good outcomes despite mod NE after day 4 and re‐warming NRP 7th Edition (2016):
– 69% favorable outcome (vs 36% in non‐HT treated) Resuscitation algorithm
Gunn AJ, et al (Cool Cap Study Group) , J Pediatr 2008
• Sedating drugs may accumulate?
Morphine – slowed clearance with cooling
Róka et al., Pediatrics 2008
Phenobarbital ‐ no effect of cooling on t1/2
Shellhaas et al., Child Neurol. Soc. 2009
53 54
Problems in Post‐Resuscitation Care:
Levels of Post Delivery Care (Physician placed “on notice”)
• Post resuscitation care • Admission to wrong level of care, failure to
– Babies requiring positive pressure ventilation transfer to higher level facility
or more extensive resuscitation
• Failure to monitor glucose
– At high risk for developing subsequent
complications of an abnormal transition • Failure to monitor BP
– Manage in an environment with ongoing • Arrest/seizure (usually after 6‐12 hours) in
evaluation and monitoring well baby nursery
• The legal concept of “notice” • Failure to anticipate multi‐system organ
involvement
55 56
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2:20pm-3:10pm
Detecting neonatal seizures by exam Neonatal seizures are common
• Neonatal Seizures are common
• Neonatal seizures often subtle or subclinical and often suggest underlying
• Only 21% of neo seizures on EEG had clinical signs brain injury or dysfunction.
– Electrographic only events are common • ~50‐60% of patients in RCT’s
– More in babies with frequent sz, esp after Rx • Birth is most common time of
• Average accuracy of seizure detection was 50% life to have seizures
– 0.95/1000 term births in California
– Doctors no better than bedside nurses (OSWHPD database) Glass HC, et al. Journal of Pediatrics, 2008
Clancy et al, Epilepsia 1988
– Other estimates
Scher et al, Pediatr Neurol 2003 • 0.7 to 2.7 per 1000 live births at term
Biagioni et al, Eur J Paediatr Neurol 1998 • 57.5‐132 per 1000 live births in preterm
Malone, et al, Epilepsia, 2009
Slide courtesy of Dr. Hannah Glass
57 58
Neonatal seizures are important Assessment tools:
Brain Monitoring
• NE defined by seizures which are indicative of Sarnat
Stage 3 • Amplitude Integrated
EEG (aEEG)
• May indicate other brain injury or dysfunction, only
some of which may be amenable to cooling.
• Conventional EEG
• Associated with death or cerebral palsy
– 16% death
– 39% impaired (mental retardation, cerebral palsy) • Near Infrared
– Epilepsy Spectroscopy
Ronen, et al. Neurology, 2007
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2:20pm-3:10pm
Seizures as a Cause of Brain Injury
Neuroimaging:
Inder T: Volpe’s Neurology of the Newborn, 6th ed, 2018 Head Ultrasound
• “…the potential adverse effects of seizures on
ventilatory function, circulation, cerebral • Used widely in preterm assessments of IVH and vent size.
metabolism and subsequent brain development” • No radiation, widely available, performed at bedside.
• “…the balance of information indicates that • Not ideal for assessing acute brain injury in term infants.
repeated seizures should be stopped because
they may induce secondary brain injury and less • Low resolution.
favorable neurobehavioral outcomes.” • Large bleeds, gross malformations and cystic changes visible
• “The World Health Organization guideline on • Non-hemorrhagic lesions difficult to see.
neonatal seizures recommends treatment of all
• Echogenicity develops gradually over days.
clinical and electrographic seizures. .”
• Cerebral edema (slit like ventricles, effaced sulci) only seen 24-48
hours after injury. May help in timing.
61 62
Timing of MRI
MRI patterns of injury First/Early MRI (1‐4 days) – more helpful for timing of injury (can place
within a window of days)
‐ Diffusion abnormalities appear ~24 hours –>if present very early,
implies earlier injury.
‐ MRS: LA/NAA peaks develop
‐ Cerebral abnormalities most evident 7 days after a cerebral
injury.
• MRI/MRS most useful tools to assess neo brain injury ‐ May see unexpected findings, e.g, SVT, epid hemorrhage.
(Wintermark, Arch Dis Child Fet 2011)
• MRI patterns of injury correlate well with animal and
human neuropathology. Later MRI (7‐10 days/beyond 10d) – shows full extent and nature of
cerebral injury
• Limitation: Neonatal neuroimaging is highly specialized ‐ but subacute diffusion abnormalities disappear
and interpretation takes experience. ‐ Cooling slows resolution of diffusion abnormalities
Volpe JJ. Ann Neurol 2012
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Global HI Brain Injury: Summary Cooling AFTER 6 hours

• Patterns of injury • Question
Does initiation of hypothermia at 6 to 24 hours after birth reduce the risk of
death or disability at 18 months among term newborns with hypoxic‐ischemic
• Timing of MRI encephalopathy?
Early  appreciate acute and subacute changes
Late see full extent of injury • Findings
In this Bayesian analysis of a randomized clinical trial of 168 newborns with
hypoxic‐ischemic encephalopathy, treatment with hypothermia initiated at 6
• MR Spectroscopy to 24 hours after birth compared with noncooling resulted in a 76%
NAA/Lactate ratio in BG strong predictor of outcome probability of any reduced death or disability, and a 64% probability of at
least 2% less death or disability at 18 to 22 months.
• Hypothermia reduced gray matter injury • Meaning

– Delayed evolution of diffusion changes Hypothermia treatment initiated at 6 to 24 hours for newborns with hypoxic‐
ischemic encephalopathy may reduce death or disability but there is
uncertainty in its effectiveness.
• Ongoing trials:
– optimizing HT/ “HT plus”/ other neuroprotective agents Laptook AR et al, JAMA Pediatrics 2017
65 66
Brain imaging and NE/HIE Summary and Conclusions
• Population vs. MRI study data differ on antepartum vs. intrapartum
factors in NE • Carefully evaluate babies after successful
• Typical HI‐related injury pattern on MRI: resuscitation for TH (chemical and clinical)
– deep nuclear gray matter • Know the pitfalls of using cord blood gases to
– watershed cortical injury. meet the chemical criteria for TH
• Patterns of CP associated with HI:
– Spastic Quadriplegia
• Place baby in “post resuscitation care” and do
– Dyskinetic Cerebral Palsy) careful serial CNS evaluations of the depressed
• Early MRI (24 hours and 96 hours of life) newly born infant to determine eligibility for TH
– most sensitive for delineation of timing of perinatal cerebral injury. (best to use a standardized form)
• Late MRI (DOL 7‐21) • At the present time, use of TH should be confined
– best delineate the full extent of cerebral injury.
to patients meeting the eligibility criteria unless
• Timely attainment and accurate interpretation of MR is critical.
in an IRB approved RCT
‐ Wider availability and training of qualified neonatal neuroradiologists.
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Summary and Conclusions
• Intrapartum events cause an unknown percentage of NE and
TH is the only therapy
• NE and HIE are often used interchangeably and erroneously
• Neonatal seizures are important, difficult to diagnose clinically
and often missed; the use of aEEG and standard EEG will
greatly increase the diagnostic accuracy
• The criteria for TH will be reviewed in the next year by COFN
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Common Areas of Malpractice Exposure for the Practicing Neonatologist - Drs. Goldsmith and Savich
3:10pm-4:00pm
Common Areas of Malpractice Exposure COI Disclosures
for Neonatologists
• We have no conflicts of interest
to disclose
Jay P. Goldsmith, MD • We will not be discussing off
Tulane University label uses of any drugs or devices
Renate Savich, MD • JPG is a paid consultant to the Florida NICA
University of Mississippi Board for hypoxic brain injury to term infants
Medical Center
1 2
Objectives “Human beings, who are almost

unique in having the ability to learn
• Provide an overview of medical from the experience of others, are also
malpractice remarkable for their apparent
• Discuss specific malpractice risks for disinclination to do so.”
neonatologists
• Demonstrate ways to minimize liability
risk and better prevent malpractice
lawsuits
Douglas Adams (1952-2001)– writer, humorist, and
dramatist. Author of A Hitchhikers Guide to the Galaxy
3 4
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Civil Law Purpose of Tort Law
• Tort Law
– “Do not do unto others that which you • Compensate those injured by medical
would not have done to you” negligence
– Monetary damages (bad damages=large • Penalize wrongdoers
awards plaintiff interest) • Deter future wrongdoing
– Benchmark: more likely than not: 50.1%
criteria (not scientific, no ORs or “p”
values)
– Judge versus jury trial (State vs. Federal
Court)
5 6
However the tort system Civil Law
• Fails those who are negligently injured • Elements of a malpractice case (the 4 “D’s”)

– Duty to care (Duty)
Expensive
– Care beneath the standard (Dereliction of duty)
Slow – Injury (Damages)
Only receive 40% of payouts – Relationship between the injury and care
beneath the standard (“proximate” or Direct
• Does not effectively deter negligent behavior cause)
• Impedes efforts to improve patient safety • Plaintiff must prove ALL FOUR
– Jury sympathy for injured plaintiff (e.g. child with
CP) may undermine this concept
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Damages (the third “D”) for neonates Why are neonatal claims so expensive?
• Cerebral Palsy • Damages are assessed over the life of the claimant
• Retinopathy of prematurity • Much longer period for children than adults
• Hearing loss • Some evidence that juries tend to be sympathetic to children
plaintiffs
• Mental retardation/DD/ADHD
• Prolonged statute of limitations (up to 21 years) delays filing
• Loss of limb/skin slough
and increases cost
• Short bowel s/p NEC, gastroschisis
• Death
9 10
Donn et al. AAP News , Vol 32 #4, April 2011 “Megaverdicts”
Amount Year State Type of Case
• $60.9 million 2010 New York Negligence at birth
• $670 million 2010 California Nursing home staffing
• $58.6 million 2011 Connecticut Negligence at birth
• $144 million 2011 Michigan Negligence at birth
• $120 million 2012 New York Failure to diagnose
• $74 million 2012 California Negligence at birth
• $168 million 2012 Florida Brain damage s/p surgery
• $78.5 million 2012 Pennsylvania Negligence at birth
• $229 million 2019 Maryland Severe prematurity;
failure to counsel
11
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GREAT EXPECTATIONS
Series Episodes # Short term FOR PRINT SYLLABUS

CPRs Survival (%) REPLACE PICTURE WITH
TEXT:
Chicago 22 11 7 (64)
FOR PRINT SYLLABUS
Hope NEJM ARTICLE
REPLACE PICTURES IN SYLLABUS WITH
TEXT BOX ER 25 31 21 (68) DEMONSTRATES THAT TV
Rescue 50 18 18 (100) EPISODES HAVE INFLATED
PICTURES OF BABY AMILIA TAYLOR BORN
911 SHORT TERM SURVIVAL
IN MIAMI 10/2006 AT 283 G AT 21 6/7 AFTER CPR WITH RANGE
WEEKS WITH A LOT FOF PUBLICITY Total 97 60 46 (77) OF 60‐100%
Diem S et al. N Engl J Med 1996;334:1578-1582
13 14
Objectives What is different about Babies?
• Provide an overview of medical malpractice 1) Cannot obtain a history from babies
• Discuss specific malpractice risks in neonatology 2) Most frequent errors in diagnosis lead to severe and
• Demonstrate ways to minimize liability risk and better permanent injuries
prevent malpractice lawsuits A. Meningitis
B. Brain‐damaged infants
3) Lifetime costs of care can be staggering
4) Enormous sympathy by juries
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What is different about Babies? Documentation
• Document all care
5) No prior provider‐patient relationship
6) Families must place trust in someone unknown to – “If it wasn’t documented, it wasn’t done”
them • Document conversations with others
– Actually multiple people
7) Long stays – Include response, instructions, orders
8) Multiple medications (packaged for adults) • Never use the chart as a battleground
9) Dosages are individualized (10 fold error) and • Document use of the chain of command
change as weight changes
10) Long Statute of Limitations • Be careful of cut and paste on note templates
• User audit entry
17 18
Neonatal Litigation Hot Spots
Aap.org/nrp
2019
• Neonatal Resuscitation
• Neonatal Jaundice
• Cooling for HIE
• The Late Preterm Infant
• The VLBW Infant
• Neonatal Safety
• Sudden Unexpected Perinatal Collapse
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Case Example – Case Example –
Improper Intubation Improper Intubation
• Uncomplicated term pregnancy • Born blue and floppy
• After two hours of labor signs of fetal distress on FHR monitor • Residents gave PPV but did not intubate for
six minutes
• Thick meconium upon ROM
• First intubation was esophageal
• Respiratory therapist present for the delivery – Not detected for several minutes
• Quadriplegic cerebral palsy
• Neo arrives at 11 minutes of age
• $7.5 million settlement three days before
trial
21 22
Resuscitation Exposures Resuscitation as part of HIE case:
Claimed breaches
• Notification
• Abilities of providers doing resuscitation (Does • Failure to have appropriate or competent people at delivery
“NRP trained” mean competence?) • Failure to properly or timely intubate baby
• Failure to administer epinephrine in right dose or by IV route
• Was tube placed in trachea?
• Failure to recognize hypovolemia and administer blood or
– Signs of correct placement volume in a timely manner
– CO2 detector • Failure to administer NaHCO3
• Failure to place in appropriate nursery after resuscitation
• Reperfusion acidosis
• Failure to recognize and treat seizures
• Delays in giving meds • Failure to resuscitate baby at limits of viability or resuscitate
against parental wishes
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Attendance at Deliveries The lost art of intubation
Guidelines for Perinatal Care, 8th Edition, 2017
Downes KJ et al. J Perinatol, 2012
• 3 year review of all neonatal intubations in university based
• “At every delivery, there should be at least birthing hospital
one person whose primary responsibility is
the neonate and who is capable of initiating • 785 attempts during 362 intubations
resuscitation. Either that person or someone • Residents given first attempt in 137 intubations and were
else who is immediately available should have successful 21% of the time!!!!
the skills required to perform a complete • More successful in NICU (vs. DR), in non‐emergency situations and
resuscitation, including ventilation with bag on older and larger infants
and mask, endotracheal intubation, chest
compressions, and the use of medications.”
25 26
CO2 Detectors
ILCOR Treatment Recommendation (2015) Attendance at Deliveries: Communication
JCAHO Sentinel Event Alert, 2004
• Tracheal tube placement must be confirmed after
intubation especially in infants with a low heart rate • Organizational culture a barrier to effective
that is not rising. communication
• Exhaled CO2 detection is recommended to confirm
tracheal tube placement. • “30 minute rule”
• CO2 detector not perfect: may give false negative • “H.A.N.D.S.”
results in cardiac arrest, micropremies – H = Hemorrhage
• CO2 detector may be used with BVM ventilation to rule – A = Amniotic Fluid (? Mec stained)
out airway obstruction
– N = Number of fetuses
– D = Dates (gestational age)
– S = Strip (category I, II, III)
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Proactive Preparations Can Reduce the Time to Neonatal Litigation Hot Spots

Administration of Intravenous Epinephrine
2019
Passive Proactive p value
guidelines
(N=47)
Guidelines
(N=35)
First dose of Epinephrine given IV 3 (6%) 14 (40%) <0.001
• Cooling for HIE
Time to 1st dose of epinephrine (min) 5  3 5  2 NS
Time to 1st IV epinephrine dose (min) 9  4 5  3 <0.001
• The Preterm Infant
• Neonatal Safety
Data courtesy of M Wyckoff • Sudden Unexpected Perinatal Collapse
29 30
Jaundice Case Jaundice Case
• Kara Smalls born 0921 June 4, 2014 • June 4 – 2 hours of life – bili 5.5
• 38 5/7 weeks • June 5 nursing note “slightly jaundice”
• 8 pounds 14.8 ounces • Later June 5 “slightly jaundice”
• Breastfeeding • June 6 nursing note “mild jaundice”
• Mom O+ • Sent home June 6, 2014 10:44–49 hrs
• Kara A+ • Follow up appt. June 16, 2014
• Prior baby required phototherapy • No education on jaundice
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3:10pm-4:00pm
Jaundice Case Jaundice Case
• June 9 – three days after discharge – mom and dad noticed • June 11 – Kara had a shrill cry and seemed in pain, back was
Kara was very lethargic, could not latch, had a shrill cry and arching. Mom called the clinic and left a message. That evening
was increasingly yellow a nurse called back, heard the history, and advised Mom to call
• Called the clinic who said they would see Kara on Friday June the clinic the next morning
13, 2014
33 34
Jaundice Case
• June 12 – Mom calls the clinic several times and is seen late
that morning.
• Kara is severely jaundiced
• Blood is drawn at 11:58 and Kara is sent home ❌
• At 12:28 the bilirubin result is 33.4
• After 1:00 pm the physician calls and tells mom to bring Kara to
the hospital
Bili 5.5 at 2 hours of life
Bili 33.4 at 194 ½ hours of life Bhutani V et al. Pediatrics, 1999.
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Causes of hemolysis in neonates with extreme Lessons Learned From the Kernicterus Registry:

hyperbilirubinemia Preventive Strategies
Johnson, LH et al., J Pediatr, 2002
Christensen RD, et al; 2015
• TSB >25 mg/dl → special evalua on (EMA flow • Limited reliability of visual assessment of jaundice
cytometry, next generation gene sequencing • Interpret TSB in terms of postnatal age in hours
for hyperbilirubinemia genes)
• 12 neonates identified: • Early F/U of neonatal discharges essential
– 5: hereditary spherocytosis • “Idiopathic” hyperbilirubinemia important risk
– 2: pyruvate kinase deficiency factor for KI
– 1: severe G6PD • G6PD deficiency an important risk factor for KI
– 4: ABO hemolytic disease
37 38
Neonatal Litigation Hot Spots “If your baby was treated with whole body

cooling or a Cool‐Cap immediately after
2019 birth, he or she must have experienced birth
• Neonatal Resuscitation asphyxia. It is possible that birth asphyxia
was caused by medical
• Neonatal Jaundice malpractice. Likewise, if your child suffered
• Cooling for HIE loss of oxygen or blood during labor and
• The Late Preterm Infant delivery and was not timely treated with
hypothermia therapy, you may be eligible
• The Preterm Infant for medical negligence lawsuit. Contact our
• Neonatal Safety attorneys at…”
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HIE Exposures Therapeutic Hypothermia Criteria
• Failure to do appropriate resuscitation • ≥36 weeks and ≤6 hours of age AND
• Failure to recognize HIE and transfer within 6 hours for cooling • pH ≤ 7.00 or BD ≥16 OR
• Failure to recognize HIE and allow baby to be with mother or • Apgar ≤ 5 at 10 minutes OR
placed in term nursery until seizures noted • Continued need for resuscitation at 10 minutes AND
• Is cooling a res ipse situation that intrapartum asphyxia has • Moderate or severe encephalopathy on clinical exam
occurred?
41 42
Umbilical Cord Gas Analysis

Confusing Blood Gases Placenta
Umbilical Vein (UV)
• Cord gases: Arterial vs. venous; technical problems; poor (from Placenta to Fetus)
correlation with clinical condition
• Neonatal: reperfusion acidosis
•  pCO2 levels: Recent cord obstruction or fetal cardiac arrest
Umbilical Artery (UA)
• Capillary blood gases in the neonate: are they valid in the first (from Fetus to Placenta)
4 hours of life? • UA pH .02 - 0.08 Units < UV
• UA cannot have pO2 > 32-34 mmHg
• “No flow” phenomenon
• Clamped cord pHa  .02 Units/20 mins.
• Unclamped cord pH may fall 0.2 units/60 min
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Passive Cooling on Transport COFN Statement on Hospitals Performing
Hypothermia
• Turn off radiant warmer or add ice? Papile et al: Pediatrics, 2014
• No good data on whether it works • Capable of MRI, seizure detection, CNS
• Potential to overcool consultation, follow‐up
• Not addressed in COFN statement (Hypothermia and Neonatal • Meet inclusion criteria
Encephalopathy, Pediatrics, 2014) • Written protocol for assessment and safety
• Outreach education to other hospitals
• >6 hours, <36 weeks, longer than 72 hours in
research settings only
45 46
Neonatal Litigation Hot Spots The Great Imposter

2019
• Cooling for HIE
• The VLBW Infant
• Neonatal Safety
47 48
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3:10pm-4:00pm
Risk Differences Between Late
Preterm and Full Term infants Late Preterm Exposures
(n = 95 LPT and 90 FT)
• Temperature instability: 10% vs. 0% • Baby treated as term and complications occur
• Hypoglycemia: 15.6% vs. 5/3% in well‐baby nursery
• Need for IV: 26% vs. 5% • Baby discharged and complications occur at
home (hypothermia, hypoglycemia,
• Respiratory distress: 28.9% vs. 4.2%
dehydration, sepsis, RSV, KI).
• Apnea & bradycardia: 4.4% vs. 0%
• Baby thought to be term and develops RDS
• R/O sepsis: 37.7% vs. 12.6% with complications
• Clinical jaundice: 54.4% vs. 37.9%
Wang et al, 2004
49 50
What Should We Do ?
• The late preterm infant should not be

considered “near term”.
• Education and protocols should be
designed to ensure they are monitored
appropriately while in the nursery
• A well designed discharge process is
recommended before discharge
Usher R, et al: Judgement of Fetal Age II. Ped Clin of N. Amer , 1966.
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Neonatal Litigation Hot Spots Jones v. MetroHealth

2019 Case Facts
• Neonatal Resuscitation • 36 yo pregnant with her 2nd child in 2003
• Neonatal Jaundice • 1st child born via emergent CS at 32 weeks
• Cooling for HIE • 22-23 wks admitted to hospital three times
for preterm labor (4 days, 1 day, 6 days)
• The Late Preterm Infant • Each time labor is stopped with medication
• The VLBW Infant and bed rest – last discharge April 4
• April 10 12:30pm– PPROM at “just over 24
• Neonatal Safety weeks”  readmitted
53 54
Jones v. MetroHealth Jones v. MetroHealth

Case Facts Verdict
• Mom requests a C-Section • 10 day jury trial

– Nurse/residents on call  CS not indicated • 6/25/14 JURY FINDS FOR THE PLAINTIFF
– Attending OB sees mom at 5:30 pm  monitors
show ‘healthy baby’ • OB and medical center jointly liable
• Fetal Distress  Emergency CS at 9:00 pm • $14.5 million in damages
• Baby has massive IVH – $8 million for the child’s future medical care
• Mom & Baby file suit against OB/Hospital – $5 million for pain and suffering
– Original suit filed 2004  Dismissed 2006 – $1 million for mother’s past medical care
– Refiled 2011 – $500,000 past economic losses
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Prematurity:
The New Litigation Focus
IF COPYRIGHT PROBLEM
• Sugar for hypoglycemia
THEN DELETE FROM • Volume / pressors for hypotension
SYLLABUS. REPLACE WITH
TEXT: • Blood for anemia
COVER PICTURE FROM
• Surgery consult/NPO/Antibiotics for NEC
PEOPLE MAGAZINE • Responding to hypocarbia for PVL
SHOWING PICTURES OF
PARENTS AND PREMIES • Removing the PICC line for infection
• Failure to adequately treat apnea
The [nurse/NNP/neonatologist] was negligent for

delaying ____thus allowing the baby to go into distress
57 58
Apnea of prematurity
• Apnea and intermittent hypoxia almost universal in extremely
preterm infants
• Variable time course to resolution
• ?Emerging evidence of harm
• Medical legal implications:
– Is harm association or cause?
– Is risk modifiable through treatment?
Shankaran S, et al. Cumulative index of Exposure to Hypocarbia and
Hyperoxia as Risk Factors for PVL in VLBW infants, Pediatrics, 2006
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Neonatal Litigation Hot Spots

2019
• Cooling for HIE
• The Preterm Infant
• Neonatal Safety
61 62
Medication Errors
IF COPYRIGHT THEN JUST
REMOVE PICTURE FROM
SYLLABUS PRINT COPY
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Neonatal Litigation Hot Spots Minimizing the Chance You Will Be Sued

2019
• Documentation
• Keep up to Date
• Neonatal Jaundice • Respect Privacy / Confidentiality
• Cooling for HIE • Informed Consent
• The Late Preterm Infant • Communication
• Neonatal Safety • Apology / Disclosure of Errors
65 66
Keep Up to Date Informed Consent
• Keep informed about recent developments in the
field – literature, conferences • Much more than a signature on a form
• Incorporate current methods of diagnosis and • Nature & Purpose of Treatment
treatment into your practice • Risks
• Benefits
IF COPYRIGHT THEN JUST • Alternatives
REMOVE PICTURE FROM
SYLLABUS PRINT COPY • Informed Refusal
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IF COPYRIGHT PROBLEM IF COPYRIGHT PROBLEM
THEN REMOVE FROM THEN REMOVE FROM
SYLLABUS SYLLABUS
Readback‐Feedback
Policy
69 70
What Should We Do ? Apology / Disclosure of Errors

• Patients want to be informed when an error occurs
• Ethical obligation
• Legal obligation
• Sorry Works program
• U of Michigan program (rapid & fair compensation) halved
legal expenses
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Conclusions/Take Home Messages
• Understand areas of high ML risk
• Resuscitation training and review (video) for all NICU providers
• Review STS and rooming in protocols at hospital IF COPYRIGHT PROBLEM
THEN REMOVE FROM
• Medication error reduction SYLLABUS
– Near misses
– Communication improvement programs
• Limit catheter/device use (especially UV)
• QA program in areas of high risk, poorest outcomes
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Electrocardiograms and Neonatal Arrhythmias - Dr. Armsby
4:15pm-4:55pm
Objectives
EKG and Neonatal Arrhythmias
• Differentiate normal from abnormal EKG patterns and rhythms in the
newborn
Neonatal‐Perinatal Medicine
Long Beach, CA • Identify classic associations between abnormal ECGs and structural heart
February 8, 2020 defects in newborns
• Understand the appropriate management of common dysrhythmias in the
Laurie Armsby, MD, FSCAI, FAAP fetus and newborn
Professor of Pediatrics
Division of Pediatric Cardiology
Oregon Health Sciences University
1 3
Sinus Rhythm
Disclosure
• Impulse begins in sinus node
• I do not have a financial relationship or interest with any
proprietary entity producing health care goods or services
related to the content of this activity.
• The content of this talk will not include discussion or
reference of commercial products or services.
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Sinus Rhythm Sinus Rhythm
• Conducts across both atria (P wave) • Pauses in AV node (PR interval)
5 7
Sinus Rhythm Sinus Rhythm
• Conducts across both atria (P wave) • Passes through Purkinje fibers and
into myocardial cells (QRS complex)
• Does not conduct across AV valve
tissue
6 8
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Sinus Rhythm QRS Axis
• Electrical impulse re‐sets along • Reflects the direction of ventricular depolarization
the same pathway:
• Axis is determined using the limb leads
Repolarization (T wave)
9 11
Rhythm QRS Axis
Sinus Rhythm:
• Each limb lead has a positive pole
• P wave precedes every QRS
• QRS follows every P wave
• All P waves look the same (follow the same path thru the atria)
• P waves are upright in leads I and aVF aVR aVL
+
+
QRS after every P ‐150o ‐30o
0o +I
+120o +60o
+90o
+ +
III + II
P wave before every QRS aVF
10 12
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QRS Axis QRS Axis
• An upward deflection of the QRS in a given lead represents a • Locate an axis quadrant using leads I and aVF
force toward the positive pole of that lead
‐90o
+
+
+ ±1800 00 +
+ I
+ I
+
+ +90o
+
aVF
13 15
QRS Axis QRS Axis
• A downward deflection of the QRS in a given lead represents a
force away from the positive pole of that lead “Northwest” / LAD Left Axis Deviation
190o ‐ ‐100o ‐100o – 0o
‐AV Canal
I
‐Primum ASD
‐Tricuspid atresia
‐
‐ Rt Axis Deviation / Normal Axis
‐
+ Normal newborn Axis 0 – 100o
‐ I 100o – 190o
‐
‐ ‐RV hypertrophy
‐Tetralogy of Fallot
‐Coarctation
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Question #1 Question #2
A term baby born in a rural hospital. Hemodynamically 28wk GA infant in the NICU. Clinically stable, normal BP
stable but cyanotic at two hours of age. Pre‐ and post‐ductal and perfusion. What is the rhythm below?
saturations 80%. An ECG is faxed to you. The ECG suggests
which cardiac defect?
II
a. D‐Transposition of great arteries
b. Hypoplastic left heart syndrome
c. Tetralogy of Fallot
d. Truncus arteriosus a. Sinus arrhythmia
e. Tricuspid atresia b. Atrial flutter
c. Ectopic atrial rhythm
d. Complete heart block
17 19
Ectopic Atrial Rhythm
• an atrial myocyte remote
from the sinus node initiates
the beat
Sinus
node
II
Left Axis Deviation
‐ AV Canal
‐ Tricuspid atresia
‐ Primum ASD
18 20
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Ectopic Atrial Rhythm Question #3
Term infant in the NICU for treatment of meconium
aspiration. The rhythm disturbance below is frequently
• an atrial myocyte remote seen on telemetry. Clinically stable, normal BP and
from the sinus node initiates perfusion. What is the likely diagnosis?
the beat
• the P wave is inverted as the
conduction across the atria
travels in the opposite Sinus
direction from normal node
II
a. Sinus arrhythmia
b. Atrial flutter
c. Complete heart block
d. Premature atrial contraction
21 23
Ectopic Atrial Rhythm Premature Atrial Contractions
Etiologies:
• Sinus bradycardia (increased vagal • An atrial myocyte initiates a
tone) beat between impulses coming
• Stimulant (caffeine, epi, dopa, etc) from the sinus node
• Immature myocardium
• Sinus rhythm with dextrocardia or Sinus
lead misplacement node
II
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Types of Premature Atrial Contractions Premature Atrial Contractions
Seen in:
Early P wave • Up to 50% of newborns
Normally reaches the AV
conducted PAC node when it is Causes:
ready • Increased vagal tone
 PACs disappear when the sinus node speeds up
• Central line within the atrium
Early P wave • Electrolyte abnormalities (hypoglycemia)
Aberrant PAC reaches the AV
node too early • Hypoxemia
• Hyperthyroidism/Hypothyroidism
• Drugs ‐ Digoxin, caffeine, α, β‐agonists, etc
Early P wave
reaches the AV Treatment:
Blocked PAC node so early
• Remove the stimulant if appropriate
that it is blocked
• Usually self resolve
25 27
Identifying a Premature Atrial Contraction: the T wave
immediately before an unusual complex or a pause appears altered Premature Ventricular Contractions
Normally
conducted PAC
Aberrant PAC
• Early beat with wide QRS, without a preceding P wave
• T wave axis is directly opposite QRS
• Followed by compensatory pause

Blocked PAC
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Premature Ventricular Contractions Identifying Complete Heart Block
Seen in:
• Up to 20% of newborns
Causes:
• Immature myocardium
• Cardiomyopathy
• Electrolyte disturbance
• Metabolic disease
• Intracardiac tumors
• Long QTc Independent P and QRS
Evaluation and Treatment:
• Usually disappear in the first 4‐8 weeks of life • a P wave that should conduct (is not early or too fast) doesn’t
• Evaluate for long QTc to assess risk of ventricular tachycardia (a PVC
occurring in the setting of long QTc may lead to Torsades)
• Ventricular rate remains regular
• If PVCs are persistent (>60 PVCs/hour) perform an echo (r/o • Atrial rate (P) is faster than Ventricular rate (QRS)
myocarditis, cardiomyopathy, cardiac tumors)
29 31
Question #4 Question #5
Term infant with minimal pre‐natal care. What is the With regard to the fetal diagnosis of Complete Heart Block,
rhythm? which of the following is true?
a. 90% of mothers with SLE are symptomatic when the fetus is
a. Prolonged QT syndrome diagnosed with CHB
b. Atrial flutter b. the peak onset of bradycardia is 30‐36 wks GA
c. Complete heart block c. non‐cardiac manifestations of SLE resolve postnatally as the
autoantibodies are cleared
d. Blocked premature atrial contractions
d. the conduction defect caused by SLE is reversible
30 32
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Congenital Complete AV block Question #6
Which two structural cardiac defects are most
• CHB occurs in 1/15,000‐20,000 live births commonly associated with this rhythm?
• Hypothyroid
• Congenital heart disease
• Infiltrative/infectious processes (Lyme, etc)
• Autoimmune: 1/60 SLE mothers
• 50% of women w/ autoimmune diseases are asymptomatic
when their fetus is diagnosed with CHB
• Auto‐immune congenital heart block ⍺ ~15% mortality; a. Tricuspid Atresia and Double Inlet Left Ventricle

~10% risk of dilated cardiomyopathy b. Congenitally corrected transposition of the great arteries (L‐TGA)
and Complete AV Canal
c. d‐Transposition of the Great Arteries and Total Anomalous
Pulmonary Venous Return (TAPVR)
d. Ebsteins anomaly and Hypoplastic Left Heart Syndrome
33 35
Congenital Complete AV block Transposition of the Great Arteries
• Maternal collagen vascular disease (SLE, RA, Sjogren’s)
- passively acquired autoimmune disease Normal L‐TGA D‐TGA
- maternal autoantibodies to Ro (SS‐A) and La (SS‐B) cross
the placenta and injure the fetal heart
- peak onset of bradycardia is at 18‐24wks GA
- non‐cardiac manifestations of neonatal SLE resolve as
maternal Abs are cleared from the circulation at several
months of age, but the conduction defect is irreversible RA RA RA
LV RV LV
RV LV RV
Tricuspid valve Mitral valve Tricuspid valve
34 36
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4:15pm-4:55pm
Complete AV block – Emergent
Complete AV block ‐ Prognosis Management
Identify and treat underlying cause
• Oxygen, airway/breathing support prn
• Monitor rhythm, BP, Sats
• IO/IV access
• 12L ECG
NO
Increased mortality with: Cardiopulmonary compromise continues?
YES
• fetal diagnosis Support ABCs
Give 02 CPR if HR < 60/min with
• presence of structural cardiac disease Observe poor perfusion despite
Consider expert oxygenation and
• presence of hydrops fetalis or ventricular dysfunction consultation ventilation
• ventricular rate < 55 bpm NO Bradycardia persists?
YES
• Epinephrine
• Atropine for increased vagal tone/AV block
• Consider transthoracic/transvenous pacing
37 39
Complete AV block ‐ Question #7
Management During normal newborn exam at 1do a term infant is noted to
• Is the heart rate sufficient to maintain a good cardiac have a HR of 220/min. As you begin to determine what type of
output? SVT this is, you first consider: What is the most likely type of
tachyarrhythmia at this age?
• require emergent pacing: Neonates presenting with
congestive heart failure (anasarca, hepatomegaly, metabolic
acidosis)
• require pacemaker:
• Advanced 2nd or 3rd degree AV block assoc with symptoms
• CHB with V escape rate < 55 bpm
• CHB + CHD with V escape rate < 70 bpm
• CHB with wide QRS escape, complex V‐ectopy or V‐
dysfunction
a. Junctional tachycardia
• may require pacemaker: Asymptomatic neonates with b. Wolfe‐Parkinson‐White
ventricular rate 55‐70 bpm c. AV node re‐entrant tachycardia
d. Atrial Flutter
38 40
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4:15pm-4:55pm
Question #8 Wolfe‐Parkinson‐White (WPW)
An ECG was performed before the SVT started. What finding •Remember, the atrio‐ventricular valves
makes the diagnosis of WPW very likely? do not conduct the atrial impulse
•When the atrial impulse enters the
ventricles via the AV node 
Normal appearing PR interval
a. Tall, peaked P waves
b. Torsades de Pointes
c. Delta wave
d. Prolonged QTc
41 43
Wolfe‐Parkinson‐White (WPW) Wolfe‐Parkinson‐White (WPW)
•Remember, the atrio‐ventricular valves •An accessory pathway is a muscle
do not conduct the atrial impulse bridge permitting conduction across
the atrioventricular valves
42 44
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4:15pm-4:55pm
•When the atrial impulse enters the • How does an accessory pathway predispose to SVT?
ventricles via an accessory pathway 
Short, sloped PR interval (Delta wave)
This is
diagnostic
of an This is SVT,
accessory due to WPW
pathway
(ie WPW)
45 47
• How does an accessory pathway predispose to SVT? • An impulse can travel down the
AV node and back up the
Accessory pathway to create a
circuit
46 48
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4:15pm-4:55pm
Wolfe‐Parkinson‐White (WPW) Question #9:
• An impulse can travel down the Which structural defect is most commonly
AV node and back up the
Accessory pathway to create a associated with an accessory pathway?
circuit
• Or down the Accessory Pathway
and back up the AV node
a. Truncus arteriosus
b. Complete AV canal
c. Ebstein’s anomaly
d. Tricuspid Atresia
49 51
Wolfe‐Parkinson‐White (WPW) Ebstein’s Anomaly

• Either way, WPW can lead to a form P waves
of supraventricular tachycardia in
which:
• The impulse begins in the atria
• A circuit develops which involves
the AV node and an accessory Very tall P waves
pathway RA enlargement
Right BBB
50 52
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4:15pm-4:55pm
Diagnosis of WPW
Preventative Treatment of WPW‐type
SVT
Consider WPW if:
• Abrupt initiation and termination of
tachycardia
For recurrent neonatal WPW type SVT:
• Minimal rate variation during
tachycardia • Propranolol or Digoxin
• Procainamide
• Always 1:1 conduction
• Flecainide, Sotalol
• Goal of therapy: Decrease recurrence,
slow rate of conduction if it recurs
53 55
Treatment of WPW‐type SVT Treatment of WPW‐type SVT
• There is a “circuit” to break and it
involves the AV node
• Vagal maneuvers or Adenosine will
Question: Why doesn’t
transiently block the AV node and Adenosine always work for SVT?
break the circuit
• Cardioversion or Rapid Atrial Pacing
Answer: While WPW is the most
will also break the circuit
common type of SVT in neonates,
• Goal of therapy: break the A‐V circuit there are other causes of SVT
(Rx: Vagal maneuvers or Adenosine)
54 56
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4:15pm-4:55pm
Supraventricular Tachycardia (SVT) Supraventricular Tachycardia (SVT)
Different types of SVT with subtle Different types of SVT with subtle
differences on ECG: differences on ECG:
• Re‐entrant tachycardias between the • Re‐entrant tachycardias between the
atria and ventricles: WPW atria and ventricles: WPW
• Re‐entrant tachycardias within the • Re‐entrant tachycardias within the
atria: Atrial Flutter atria: A‐flutter
• Automatic tachycardias
57 59
Supraventricular Tachycardia (SVT) Features of Atrial Flutter
• Atrium:
Different types of SVT with subtle • Rapid atrial rate
differences on ECG: • Regular P wave rhythm (sawtooth)
• Re‐entrant tachycardias between the
atria and ventricles: WPW
• Re‐entrant tachycardias within the
atria: A‐flutter
Atrial rate >300 beats/min
58 60
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4:15pm-4:55pm
Features of Atrial Flutter Treatment of Atrial Flutter
• Atrium: • There is a “circuit” to break but it does
• Rapid atrial rate not involve the AV node
• Regular P wave rhythm (sawtooth)
• Ventricle:
• Regular or irregular (depending on conduction across AV node)
Ventricular rate ~70 beats/min
61 63
Diagnosis of Atrial Flutter Treatment of Atrial Flutter

• There is a “circuit” to break but it does
not involve the AV node
• Adenosine (transient AV node
blockade) will only briefly inhibit
conduction to the ventricle (but not
stop the atrial discharge)
• Difficult to differentiate from other narrow complex SVTs (like WPW)
when conducting 1:1 (although typically faster)
Before Adenosine Immediately after Adenosine
• A‐flutter + WPW  wide complex tachycardia (resembles VT)
• 2:1 or 3:1 conduction resembles complete heart block (but the atrial rate is
normal in CHB and very fast in Flutter)
• Giving Adenosine is diagnostic (but not therapeutic)
62 64
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4:15pm-4:55pm
Treatment of Atrial Flutter Supraventricular Tachycardia (SVT)
• There is a “circuit” to break but it does
not involve the AV node
Different types of SVT with subtle
differences on ECG:
• Adenosine (transient AV node • Re‐entrant tachycardias between the
blockade) will only briefly inhibit atria and ventricles: WPW
stop the atrial discharge) • Re‐entrant tachycardias within the
atria: A‐flutter
• Electrical cardioversion or Rapid
Atrial Pacing will “break” the circuit • Automatic tachycardias:
sinus tachycardia, ectopic atrial
tachycardia (EAT), multifocal atrial
tachycardia (MAT), junctional
ectopic tachycardia (JET)
65 67
Treatment of Atrial Flutter Diagnosis of Automatic SVT
• There is a “circuit” to break but it does Automatic tachycardias: sinus tachycardia,
not involve the AV node ectopic atrial tachycardia (EAT), multifocal
atrial tachycardia (MAT), junctional ectopic
• Adenosine (transient AV node tachycardia (JET)
blockade) will only briefly inhibit
stop the atrial discharge) Consider an automatic tachycardia if:
• Electrical cardioversion or Rapid • The heart rate increases and decreases
Atrial Pacing will “break” the circuit gradually
• The heart rate varies during the
• For recurrent A‐flutter: digoxin, propranolol tachycardia
• Goal of therapy: break or slow the atrial circuit, or decrease • The rhythm doesn’t break with
ratio of conduction across AV node (1:1  3:1) adenosine or cardioversion
Rx: Cardioversion/Rapid Atrial Pacing or beta blockers
66 68
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4:15pm-4:55pm
Treatment of Automatic SVT Conduction Intervals : Electrolyte abnormalities
• No “circuit” to break
• Vagal maneuvers or adenosine (AV node
blockade) only briefly inhibit conduction
to the ventricle
• Electrical cardioversion will “stun” but
not “stop” tachycardia Calcium
• Goal of therapy:
 slow the atrial activity or
 decrease ratio of conduction across
AV node (1:1  3:1) to at least slow
the ventricular rate
(Rx: flecainide, amiodarone, sotalol, etc…)
69 71
Question #10: Question #11:
A 1 day old FT has the ECG below. Pregnancy was c/b You establish the baby has hypocalcemia and DiGeorge
maternal DM, delivery c/b perinatal asphyxia. At birth is SGA, syndrome. Which of the following structural lesions is
has dysmorphic features and a murmur. These features not commonly associated with 22q11 deletion?
suggest an increased likelihood of:
a. Truncus arteriosus
b. Interrupted Aortic Arch
c. Tetralogy of Fallot
a. Ectopic atrial rhythm
d. Hypoplastic Left Heart
b. Hypercalcemia Syndrome
c. Hypocalcemia
d. Hyperkalemia
DiGeorge (22q11 deletion) Syndrome
70 72
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4:15pm-4:55pm
QRS
Neonatal presentation
QT interval
• During the neonatal
Prolonged QTc
period, congenital LQTS is
usually diagnosed with QT
prolongation combined
• Represents duration of ventricular with sinus bradycardia or
depolarization and repolarization
2:1 AV block (because P
• Altered by Calcium, medications waves arrive during P waves
repolarization and are blocked
• Marker for potential ventricular ‐> bradycardia) • The conduction is 2:1 AV‐block
tachyarrhythmias (Torsades)
• The non‐conducted P‐wave is
coming during the T‐wave
• Calculate QTc in lead II
• QTc up to 0.49 may be normal < 6mo
73 75
QRS
Causes of prolonged QTc Neonatal presentation
• Hypocalcemia • During the neonatal
• Hypo‐K/Hypo‐Mg period, congenital LQTS is
usually diagnosed with QT
• CNS abnormalities prolongation combined
• Myocarditis, diffuse myocardial with sinus bradycardia or
disease 2:1 AV block
P waves
• Channelopathy
• ~75% of LQTS are caused by Potassium
mutations in 3 genes: KCNQ1 Treatment: • The conduction is 2:1 AV‐block
(LQT1), KCNH2 (LQT2) and • The non‐conducted P‐wave is
SCN5A (LQT3) • Propranolol (β‐blocker) coming during the T‐wave
• ≥600 mutations have been
identified in 14 LQTS‐susceptibility
genes
Calcium
74 76
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4:15pm-4:55pm
Long QT syndrome
• Risk of ventricular arrhythmias (Torsades de Pointes)
– polymorphic VT with oscillating pattern of the QRS axis
‐ Treatment: IV Magnesium Sulfate
77
Thank You and Good Luck!
Armsbyl@ohsu.edu
78
380
Daily Wrap Up - ARS Review / Q&A
4:55pm-5:25pm
381
382
BONUS SESSION -Visual Diagnosis –

Picture Review and High Yield Discussion
5:25pm-6:30pm
383

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An Intensive Review and Update of

February 7-11, 2020

Friday, February 7, 2020

Please refer to Pedialink at www.pedialink.org for attendee course information:

 General Information  Recording CME Credit

FRIDAY, FEBRUARY 7, 2020

Maternal and Placental Physiology – Dr. Boggess ........................................................................ 5

High Yield Antepartum Fetal Surveillance – Dr. Boggess............................................................. 27

ARS Rapid Review - MFM Potpourri – NeoPREP Planning Committee No Handout

Labor and Delivery - Case-Based ARS – Dr. Boggess .................................................................. 43

Approach to Evaluating an Infant with Congenital Anomalies – Dr. Northrup ........................... 55

Term Brain Injury and Pathophysiology of HIE – Dr. Wusthoff .................................................... 89

Preterm Brain Injury – Dr. Bonifacio No Handout

Neonatal Seizures – Dr. Wusthoff .................................................................................................... 105

Rapid Review: The Neuro Exam, Neuromuscular Disease, Preterm Outcomes

Cardiovascular Physiology of the Fetus – Dr. Brodsky ................................................................ 145

Cardiovascular Hemodynamics in the Newborn – Dr. Brodsky ................................................... 199

Case-Based - CHD Cyanotic Lesions – Dr. Armsby ...................................................................... 213

Case-Based - CHD Non-Cyanotic Lesions – Dr. Armsby .............................................................. 237

Statistics and Research Design – Dr. Weiner ................................................................................ 247

CORE KNOWLEDGE TRACK

BEYOND THE BOARDS PEARLS FOR CLINICAL PRACTICE TRACK

Optimizing Delivery Room Care – Dr. Savich................................................................................. 301

Plenary Lectures/Question and Answer Sessions

Electrocardiograms and Neonatal Arrhythmias – Dr. Armsby ......................................................... 361

Placenta ‐ Fetal Surface Placenta – Maternal Surface

Placenta ‐ Fetal Surface Placenta ‐ Maternal Surface

Fetus Dependent on Placenta Succinturate Placenta

Placental Abnormalities Circumvellate Placenta

• First trimester cross rxn w hCG • Avoid radioactive iodide after 10 weeks

• Increased perinatal morbidity

Preeclampsia Myasthenia Gravis- Maternal

Preeclampsia Treatment Myasthenia Gravis –Fetus/Newborn

Myasthenia Gravis –Fetus/Newborn Maternal Lupus

• Affected neonate often presents within a few hours and • Associated with Lupus anticoagulant,

Myasthenia Gravis –Fetus/Newborn Lupus- Affects on fetus/newborn

ITP – Fetus/Newborn Maternal PKU – Fetal/Newborn

Disclosures 1st/2nd Trimester Testing

• Serum analytes Estriol Low Low No difference Low

– 1st trimester: PAPP‐A; inhibin Inhibin‐A High No difference No difference Very high

– 2nd trimester: hcg; AFP; E3; inhibin • Elevated MSAFP ‐ unexplained; ONTD, abdominal wall defects,

Free Beta hCG High Low

PAPP‐A Low Low

2nd Trimester Anatomy Ultrasound Fetal Central Nervous System

Fetal Abdomen 2nd/3rd Trimester Tests of Fetal Well‐being

ARS Rapid Review - MFM Potpourri

NeoPREP Planning Committee

Friday, February 7, 2020

ACOG 2009 Category II Tracing ‐ Labor

Category I Tracing ‐ Labor Intrapartum Monitoring

Category III Tracing ‐ Labor Intrapartum Monitoring Goal

Category III Tracing ‐ Labor Criteria to Determine Relation of Labor to CP

• UA pH < 7 and base deficit < 12 mmol/L

• Chorioamnionitis • > 42 weeks 0 days

35 yo G2P0 with prior unexplained 20 week stillbirth presents at Most likely diagnosis

29 yo with type 1 diabetes at 36 weeks presents with nausea, Most likely diagnosis

Best next step(s) in management: Amniocentesis performed and shows glucose < 20 and increased

32 yo G1 P0 at 28 weeks with nausea, vomiting and chills at home. Temp on Induction of labor is initiated and vaginal delivery is imminent.

Fetal indications for delivery by cesarean section include: 29 yo G1P0 at 42 weeks admitted for induction of labor. The

Counseling for management of threatened periviable delivery at 22 1. With normal growth and fluid, induction of labor is not warranted

Rapid Review: Inheritance and Genetic Testing

NeoPREP Planning Committee

Friday, February 7, 2020