PEDIA 3A: NEONATOLOGY B USE AT YOUR OWN RISK!

Sources: PowerPoint and Manual. I also included

October 2019 samplex Q&As from EJG at the end of every topic.
Please feel free to correct mistakes or message me if

you have any questions. Thank you. God bless! J

GASTROINTESTINAL DISORDERS OF THE NEWBORN UPPER GUT OBSTRUCTION

NORMAL STOOL PATTERN

NEONATAL DIGESTIVE SYSTEM DISORDERS

SIGNS OF ILLNESS
• Vomiting
• Constipation
• Diarrhea SAMPLEX REVIEW: VOMITING
• Whitish plaques on mucosa (Thrush) • Most consistent sign of intestinal obstruction in newborns
• Abdominal distention or discoloration (Bilious)
• 2 day old infant, bilious vomiting since milk feeding was
VOMITING
started: Diagnosis: Duodenal atresia
• May be normal during 1st few hours after birth
• May be due to gastric irritation by the gastric mucosa swallowed
CONSTIPATION
during delivery
• > 90% of well full-term newborns pass meconium in 24 hours (Day 1)
• A frequent symptom in neonates
• ~20% of VLBW pass meconium beyond 24 hours
• X-ray of abdomen: Air fluid levels, distended bowel loops, double
bubble sign, pneumoperitoneum • If without meconium in 24-36 hours, consider intestinal
obstruction
Upper Gi atresia (esophageal, • Consider: intestinal atresia, aganglionic megacolon, meconium ileus,
Maternal polyhydramnios meconium plug, congenital hypothyroidism
duodenal, ileal)
Persistent Intestinal obstruction and ­ ICP
Bile-stained vomitus/emesis Obstruction beyond duodenum
Vomiting with first feeding Esophageal obstruction
Bile stained, non-projectile Intestinal obstruction

DIFFERENTIAL DIAGNOSIS
Malrotation +/- midgut volvulus Day 1
Congenital Diaphragmatic
Persistent vomiting
Hernia
Pyloric stenosis Beyond 1st week of life
With common early sign of
Hirschsprung disease
vomiting with obstipation
Regurgitation from overfeeding
Failure to eructate swallowed air Hirschsprung Disease

DIAGNOSIS
MECONIUM PLUG SYNDROME
• ABDOMINAL XRAY (KUB and cross-table lateral views)
- air-fluid levels, distended bowel loops, characteristic pattern of • Mildest and most common cause of bowel obstruction among
newborns
obstruction, pneumoperitoneum contrast swallow with small
• Lower colon, anorectal or any part of the gut; anorectal plugs may
bowel follow through is indicated for bilious vomiting
cause ulceration and perforation
• 10-30% of patients will show HD
NORMAL GAS PATTERN
• Diagnosis of exclusion
Jejunum 15-60 min o Plain AXR (Left lateral decubitus or cross-table lateral)
Ileum 2-3 hours o Contrast study
Colon 3 hours
NO RECTAL GAS at 24 hours is ABNORMAL

TRANSCRIBER DIANA J of
1 21
 SAMPLEX REVIEW: MECONIUM PLUG SYNDROME • Characterized by varying degrees of mucosal or transmural
necrosis of the intestine
• Cases:
• Abdominal distention or discoloration of the abdomen
o No bowel movement since birth with abdominal
distention. Rectal exam, passes out a pearly white,
EPIDEMIOLOGY
hard substance.
• No sex or race predilection
o Breastfeeding but feeds infrequently, PE: active, pinkish,
• Incidence: 1-5% of admissions to the NICU
irritable with slightly distended abdomen. Rectal exam:
• Common among preterms (90% of cases)
strained and a pearly white substance was passed. Next
• Age of onset: varies inversely with gestation
action: Observe and continue breastfeeding
• Incidence and case fatality rate: increase with decreasing BW and
gestational age
• Rarely occur in term infants
MECONIUM ILEUS
• Multifactorial etiology
• In Cystic Fibrosis, with limited digestive properties due to absence of
pancreatic enzyme for digestion
PATHOLOGY AND PATHOGENESIS
• Clinical manifestations: abdominal distention, persistent vomiting
• Loss of intestinal integrity, coagulation necrosis. accumulation of air in
• Differential diagnoses: other causes of intestinal obstruction
the submucosa/subserosa perforation, peritonitis, sepsis, shock, death
• Diagnosis: Presumptive if
• Distal ileum, proximal colon; sometimes, gangrene from stomach to
o With similarly affected sibling
rectum is noted
o PE of doughy or cordlike masses
o X-ray picture of variable width and uneven gas pattern, bubbly • Five I’s – immaturity, ischemia, ingestion, infection, immunologic
granular appearance of air infiltrating meconium
RISK FACTORS
• Treatment: Enema or Laparotomy
IMMATURITY
ISCHEMIA
MECONIUM PERITONITIS
INTAKE • Hypertonic milk – too rapid feeding
• Intestinal perforation could have occurred in utero or shortly after birth
• Most often due to complicated meconium ileus in patients with CF • Klebsiella and Enterobacter spp. (63%)
• Naturally sealed perforation may cause no symptoms or with signs of • E. coli (21%)
meconium peritonitis INFECTION • Coagulase negative staphylococci (30%)
• Clinical manifestations: • Occasional anaerobes (6%)
o Abdominal distention • Candida isolates (10%)
o Vomiting IMMUNOLOGIC • Cytokines – tumor necrosis factor (PAF)
o No stools • Immunologic Factors
• Treatment: o Deficiency of secretory IgA
o Treat shock
o GI T lymphocytes
o Eliminate obstruction
o Limited antibody response
o Drain peritoneal cavity
o Antibiotics
• Luminal factors
o Decreased gastric H+ ion output
o Decreased proteolytic enzyme activity
DIARRHEA
PREMATURITY o Decreased motility
• Refers to change in frequency of bowel movements and character of
• Immature GI mucosal barrier
stools
o Increased mucosal permeability
THRUSH (to bacteria)
• Whitish plaques on mucosa o Microvillus properties/composition
• Can be seen in healthy neonates in the early part o Mucin blanket composition
• Transmission from maternal vaginal moniliasis to the oral mucosa o Immature regulation of circulation
• Secondary infection: antibiotic treatment contact with infected infants o Abnormal bacterial colonization
and personnel • Perinatal asphyxia?
• Diastolic steal of PDA? CHD?
• Obstruction due to umbilical catheter?
IMPAIRED
• Polycythemia
SPHLANCNIC
• Ineffective intestinal microvascular
BLOOD SUPPLY
autoregulation
• Cocaine (vasoconstrictive and
hemodynamic properties)
• Reaction to fermentation
• Reaction to hyperosmolar feedings
INTRALUMINAL
• Reaction to frequency or volume of feeding
NECROTIZING ENTEROCOLITIS INJURY
• Microbial infection
• Serious disease of the newborn of unknown etiology
• Most common GI emergency in the neonate • Bacterial toxins

PEDIA 3A: NEONATOLOGY B 2 of 21
PATHOGENESIS

TABLE 1. MODIFIED BELL’S STAGING CRITERIA FOR NEONATAL NEC

RADIOLOGIC
STAGE SYSTEMIC SIGNS INTESTINAL SIGNS TREATMENT
SIGNS
­ pre-gavage residuals
Mild abdominal distention
IA SUSPECTED NEC NPO
Emesis Normal
Antibiotics for 3 days
Temperature instability Guaiac + stools Mild ileus
pending cultures
Apnea Bright red blood from
IB SUSPECTED NEC
Bradycardia rectum
Lethargy Same as above + NPO
Ileus
IIA DEFINITE NEC: diminished or absent bowel Antibiotics for 7-10 days if
Pneumatosis
MILDLY ILL sounds examination is normal
intestinalis
+/-Abdominal tenderness in 24-48 hours
Above + definite abdominal
Above + Mild tenderness Same as IIA NPO
IIB DEFINITE NEC:
metabolic acidosis, +/- abdominal cellulitis or +/- portal vein gas Antibiotics x 14 days
MODERATELY ILL
thrombocytopenia RLQ mass +/- ascites NaHCO3 for acidosis
Absent bowel sounds
Same as above +
200 cc/kg/day fluids
Same as IIB + FFP, Inotropes
IIIA ADVANCED NEC: hypotension,
Above + signs of Same as IIB Ventilation treatment
SEVERELY ILL, bradycardia, severe
generalized, peritonitis, Definite ascites Paracentesis
BOWEL INTACT apnea, combined
marked tenderness, Surgical intervention if medical
respiratory and management fails within 24-48
distention of abdomen,
metabolic acidosis hours
abdominal wall erythema
DIC, neutropenia,
IIIB ADVANCED NEC:
anuria Same as IIB + Same as above + surgical
SEVERELY ILL,
pneumoperitoneum intervention
BOWEL PERFORATED

PEDIA 3A: NEONATOLOGY B 3 of 21
CLINICAL MANIFESTATION
• Gradual or sudden onset and catastrophe
• Age of onset is inversely related to gestational age
• 1st sign: lethargy, temperature instability
• Nonspecific signs: gastrointestinal, systemic

DIAGNOSIS
Figure 4. Abdominal R-ray of preterm infant with Stage III
• Very high index of suspicion is essential!
NEC, showing free air within peritoneal cavity (arrows),
• Plain Abdominal X-ray indicative of intestinal perforation
o Pneumatosis intestinalis
o Portal vein gas TREATMENT
o Pneumoperitoneum
• No definitive treatment
• Serum electrolyte
• Intensive therapy is advisable for suspected as well as
• Acid-base determination diagnosed cases (Supportive)
• CBC with platelet count o Cessation of feeding (NPO)
• Blood culture o Nasogastric decompression
• Hepatic UTS o IV fluids
o Acid-base and electrolyte balance
o Systemic antibiotics
o When present, umbilical catheters should be removed
o Ventilatory support
STAGE I o Resuscitation with blood, crystalloids, and inotropes
(NEC o Check coagulation profile
SUSPECT) o Frequent PE, AXR
o Peritoneal drainage

Ileus INDICATIONS FOR SURGERY

• Failure to respond to medical management
• Single, fixed bowel loop
• Erythema of the abdominal wall
• Pneumoperitoneum
• Palpable mass
• Positive result of paracentesis
• Perforation among unstable patients
STAGE II
• IMPORTANT:
(DEFINITE
o Surgical consult should be done early in the course of
NEC)
treatment
o Frequent abdominal examination and determination of
abdominal girth and abdominal x-rays
o Isolation and grouping of infants at similar increased risk into
cohorts separate from other infants should be instituted to
contain epidemic
Pneumatosis intestinalis
(air in bowel wall)
COMPLICATIONS
• Strictures (10%)
• Short bowel syndrome: malabsorption, growth failure,
malnutrition (25%)
• Metabolic complications related to TPN
• Cholestatic jaundice

STAGE III PROGNOSIS

(SEVERE
• Medical management fails in about 20% of patients in whom there
DISEASE
is pneumatosis intestinalis at diagnosis.
• With present vigorous medical and surgical management, 75%
survive.

Portal venous gas

Pneumoperitoneum

PEDIA 3A: NEONATOLOGY B 4 of
21
PREVENTION CLINICAL MANIFESTATIONS
• Judicious feeding protocols • Seen at birth or anytime
- Slow advancement of no more than 15-20 cc/kg/day • Cephalocaudal progression
• Passive enteric immunization with breastmilk and Ig • Dermal pressure determines progression, approximates level
(Breastfeeding babies with reduced risk of NEC) (mg/dl), cannot replace serum values
- Protective advantage from milk macrophages & phagocytes, o Face – 5
IgA & IgG, immunocompetent T & B lymphocytes potentiating o Mid-abdomen – 15
effect of complements, lysozymes, lactoferrin & secretory IgA o Soles – 20
- Presence of hormones (TSH, prolactin, steroid), enzymes
(amylase, lipase) & growth factors (EGF) MAJOR RISK FACTORS FOR SEVERE HYPERBILIRUBINEMIA
- Promotion of healthy gut flora with Lactobacillus bifidus • Gestational age 35-36 weeks
• Induction of intestinal maturation with steroids • Previous sibling on phototherapy
• Probiotics, Oral antibiotics? • Cephalohematoma or significant bruising
• Exclusive BF with excessive weight loss
SAMPLEX REVIEW: NEC • Nursing not going well
• NEC Prevention • East Asian race
o Breastfeeding/breastmilk, Probiotics
• Stages and Findings: SAMPLEX REVIEW: SEVERE HYPERBILIRUBINEMIA
o Stage I: Ileus • Case
o Stage II: Pneumatosis intestinalis o Jaundice on the 12th hour of life. Dermal pressure at the
o Stage III: Portal venous gas, Pneumoperitoneum level of his soles (20 mg/dL). Do: Serum bilirubin
• Cases: determination or Maximum intensive photography
o 10 day old premature infant, episodes of apnea, increased exposure
abdominal girth, abdominal distention, tolerating enteral
feeding, less active with gastric residual of half of previous DIFFERENTIAL DIAGNOSIS
feeding, mottling x-ray – dilated bowel loops 1st 24 Erythroblastosis fetalis, concealed hemorrhage,
hours sepsis or congenital infections

JAUNDICE AND HYPERBILIRUBINEMIA 2nd - 3rd day Physiologic or familial non-hemolytic, BF jaundice
• Jaundice is the most common condition that requires
medical attention in newborns After 3rd Bacterial sepsis, UTI, other infections,
o Yellow discoloration of skin and sclerae day polycythemia
o The result of accumulation of bilirubin
BM jaundice, sepsis, congenital atresia or paucity
• Newborn icterus notable once total bilirubin >5-6 mg/dL (versus
After 1st of bile ducts, hepatitis, galactosemia,
older children/adults once >2 mg/dL)
week hypothyroidism, CF, hemolytic anemia (RBC
• Common and maybe benign problem among newborn
morphology)
• Due to deposition of unconjugated and/or conjugated bilirubin in
the skin
DIAGNOSIS
• Depending on etiology, can appear at birth or anytime
• Serum bilirubin fractions
• In 1st week of life: occurs in 60% of full term, 80% preterm infants
• Hemoglobin (CBC, APC), Reticulocyte count, Peripheral smear
• Physiologic role of bilirubin: Antioxidant
• Blood type
• Unconjugated hyperbilirubinemia is potentially neurotoxic
o Etiology: increase in bilirubin load, problem with the • Coomb’s test
transferase enzyme
BILIRUBIN METABOLISM
• Conjugated hyperbilirubinemia may mean presence of a serious
STEPS OF HEME DEGRADATION
hepatic or systemic illness
• Formation of bilirubin
• Uptake of Bilirubin by liver
ETIOLOGY
• Conjugation of bilirubin
Factors which reduce retention of bilirubin in the circulation
• Fate of Bilirubin
• Hypoproteinemia
o Secretion of bilirubin into bile
• Drugs which displace bilirubin from albumin binding sites o Formation of urobilins in the intestine
• Cheun-Lin herbal tea o Excretion in urine and stool
• Acidosis
• Increased FFA concentration
• Oxytocin
Conditions which increase neuronal susceptibility to injury
Delayed passage of meconium
Dehydration
Polycythemia

PEDIA 3A: NEONATOLOGY B 5 of
21
 PATHOPHYSIOLOGY: HYPERBILIRUBINEMIA

FATE OF BILIRUBIN

PEDIA 3A: NEONATOLOGY B 6 of
21
INDIRECT VS DIRECT HYPERBILIRUBINEMIA PREMATURITY
• INCREASE UNCONJUGATED (INDIRECT) BILIRUBIN Decreased glucoronyl transferase in liver
o Increased formation/synthesis Decreased serum albumin
o Decreased transport/uptake Hemolysis, Sepsis
o Decreased conjugation Hypoxemia, Hypothermia
o Decreased elimination Drug therapy
o Increased reabsorption INCREASED ENTEROHEPATIC CIRCULATION
- Most concerning due to risk for encephalopathy or Pyloric stenosis
kernicterus if not treated rapidly Small/Large bowel obstruction

• INCREASE CONJUGATED (DIRECT) BILIRUBIN

DIRECT HYPERBILIRUBINEMIA
o Decreased excretion of bilirubin mono/diglucuronide
• Considered elevated when:
o Level > 2.0 mg/dL (severe > 5.0 mg/dL)
SAMPLEX REVIEW: HYPERBILIRUBINEMIA o Level > 15% of total serum bilirubin
• UNCONJUGATED: breastfeeding jaundice, kernicterus, Rh • Risk factors
incompatibility, physiologic jaundice, sepsis o Low gestational age
• CONJUGATED: Biliary atresia o Early and/or prolonged exposure to TPN
• BOTH: Inspissated bile o Lack of enteral feeding
o Sepsis
INDIRECT HYPERBILIRUBINEMIA • Clinical hallmarks: icterus, acholic stools, dark urine
DIFFERENTIAL DIAGNOSES
DIFFERENTIAL DIAGNOSES

PHYSIOLOGIC JAUNDICE • Etiology

o Infection
DISORDERS OF PRODUCTION: INCREASED RBC o Genetic
DESTRUCTION o Metabolic
Rh, ABO o Undefined abnormalities leading to mechanical
Isoimmunization
other component incompatibilities obstruction of bile flow or functional impairment of
RBC Biochemical G6PD, hepatic excretion and bile secretion
defects Pyruvate kinase deficiency - TPN-associated
Spherocytosis - Hepatitis: Idiopathic, Infectious, Toxic
RBC Structural
Elliptocytosis - Infection: Sepsis, TORCH, UTI
Abnormalities
Infantile pyknocytosis - Biliary atresia
Infection Bacterial, viral, protozoal - Inspissated bile plug
Sequestration Bruising, cephalohematomas, - Choledochal cyst
hemangiomas - Alpha-1-antityrpsin deficiency, Galactosemia
Polycythemia IDM, delayed cord clamping • Less common causes:
o Cholelithiasis
Hemoglobinopathy
o Hypothyroidism
DISORDERS OF HEPATIC UPTAKE o Dubin-Johnson Syndrome
Gilbert Syndrome o Storage Diseases (Niemann-Pick, Gaucher’s)
o Metabolic disorders (Tyrosinemia, Fructosemia)
DISORDERS OF CONJUGATION o Trisomy 21 and 18
o Drug-induced
Crigler-Najjar Syndrome Type I
o Alagille Syndrome, Rotor’s Syndrome, Zellweger Syndrome
Crigler-Najjar Syndrome Type II
o Cystic Fibrosis
Lucey-Driscoll Syndrome
o Shock
(transient familial neonatal hyperbilirubinemia)
Hypothyroidism
THE YELLOW BABY: NEONATAL PHYSIOLOGIC JAUNDICE
OTHER CAUSES PATHOPHYSIOLOGY
• Bilirubin production is elevated because of increased breakdown
Breastfeeding Jaundice Lack of volume
of fetal erythrocytes. This is the result of the shortened lifespan of
Unknown mechanism fetal erythrocytes and the higher erythrocyte mass in neonates.
Possibly unidentified • Hepatic excretory capacity is low both because of low
Breast Milk Jaundice
component in breast milk that concentrations of the binding protein ligandin in the hepatocytes
causes increased enterohepatic and because of low activity of glucuronyl transferase, the enzyme
recirculation? responsible for binding bilirubin to glucuronic acid, thus making
Infant of Diabetic bilirubin water soluble (conjugation).
Mother • Increased hepatic circulation

PEDIA 3A: NEONATOLOGY B 7 of
21
 NONPHYSIOLOGIC (Needs further evaluation)
Jaundice that is visible during the first 24 hours of life
Infants who present with jaundice after 3-4 days of life
In infants with severe jaundice or jaundice that continues
beyond the first 1-2 weeks of life

SAMPLEX REVIEW: PHYSIOLOGIC JAUNDICE

• It is a benign process, self-limited
• Can be exaggerated process
• Unconjugated hyperbilirubinemia

PATHOLOGIC JAUNDICE
CASES IN WHICH THE CAUSE OF JAUNDICE MAY BE
SOUGHT
1. Onset within 1st 24 hours of life
2. Rises >5mg/dL/24 hours
3. Bilirubin levels >12mg/dL in full-term infants and 10-14
mg/dL in preterm infants
4. Persistence after the 2nd week of life
5. Conjugated bilirubin >2mg/dl OR greater than 20% of TB
6. Presence of other signs and symptoms
DIAGNOSIS OF HYPERBILIRUBINEMIA
FAMILY HISTORY
• Careful clinical assessment and monitoring
• Thorough history: • Previous sibling with jaundice in the neonatal period,
o Pregnancy and delivery history particularly if the jaundice required treatment
o General health status and infectious risk • Other family members with jaundice or known family history of
o Feeding method and feeding progress Gilbert syndrome
o Vital signs and ins/outs (hydration status) • Anemia, splenectomy, or bile stones in family members or
o Risk factors for isoimmunization known heredity for hemolytic disorders
o Family history and ethnicity (G6PD, spherocytosis) • Liver disease
• Physical exam: HISTORY OF PREGNANCY AND DELIVERY
o Activity level, feeding ability, bruising/hematoma, plethora
• Maternal illness suggestive of viral or other infection
• Maternal drug intake (oxytocin, diazepam)
CLINICAL HISTORY:
• Delayed cord clamping
PHYSIOLOGIC VS PATHOLOGIC JAUNDICE • Birth trauma with bruising and/or fractures
• TIME OF APPEARANCE
• DURATION POSTNATAL HISTORY
• PATTERN • Loss of stool color
• ASSOCIATED RISK FACTORS • Breastfeeding / delayed feeding
• Greater than average weight loss
CLINICAL HISTORY: PHYSIOLOGIC JAUNDICE • Symptoms or signs of hypothyroidism
• Symptoms or signs of metabolic disease (galactosemia)
• Typically, presentation is on the 2nd or 3rd day of life, declines by
the 5th day of life • Exposure to total parental nutrition
• Onset (5 days) and resolution (14 days) maybe delayed in
premature infants PHYSICAL EXAMINATION
• RISK FACTORS: • Aided by pressure on the skin, since blanching reveals the
o Maternal age, Maternal diabetes underlying color
o Prematurity • Cephalocaudal progression
o Drugs, Altitude, Polycythemia • Disappears in the opposite directioN
o Race, Male sex
o Trisomy 21
o Cutaneous bruising, Blood extravasation
o Oxytocin induction
o BF, weight loss
o Delayed BM
o Similarly involved sibling
• Diagnosis of exclusion, based on history, clinical manifestations
and laboratory data

PEDIA 3A: NEONATOLOGY B 8 of
21
 The explanation for this phenomenon is not well understood, but
both changes in bilirubin-albumin binding related to pH and
differences in skin temperature and blood flow have been
proposed. This phenomenon is claimed to be clinically useful
because, independent of other factors, visible jaundice in the
lower extremities strongly suggests the need to check the
bilirubin level, either in the serum or noninvasively via
transcutaneous bilirubinometry.

• Liver function tests:

• Neurologic findings
• Abnormal blood accumulations
• Hepatosplenomegaly, petechiae, and microcephaly may be
associated with hemolytic anemia, sepsis, and congenital
infections and should trigger a diagnostic evaluation directed
towards these diagnoses
LABORATORY EXAMINATIONS
• Visual assessment vs
• Transcutaneous Bilirubinometry vs
• Total Serum Bilirubin determination
ADDITIONAL STUDIES INDICATED IN THE FOLLOWING
SITUATIONS
• Infants who present with jaundice on the first or after the third
day of life
• Infants who are anemic at birth
• Infants who otherwise appear ill
• Infants in whom serum bilirubin levels are elevated enough to
trigger treatment
• Infants in whom significant jaundice persists beyond the first 2
weeks of life
• Infants in whom family, maternal, pregnancy, or case histories
suggest the possibility of a pathologic process
• Infants in whom physical examination reveals findings not
explained by simple physiologic hyperbilirubinemia
- Aspartate aminotransferase (ASAT or SGOT) and alanine
aminotransferase (ALAT or SGPT) levels are elevated in
hepatocellular disease
- Alkaline phosphatase and γ-glutamyltransferase (GGT) levels
are often elevated in cholestatic disease. A γ-GT/ALAT ratio
of more than 1 is strongly suggestive of biliary
obstruction.
• Tests for viral and/or parasitic infection
• Reducing substance in urine
• Blood gas measurements
• Bilirubin-binding tests
• Thyroid function tests
IMAGING STUDIES
• ULTRASONOGRAPHY
- Ultrasonography of the liver and bile ducts is warranted in
infants with laboratory or clinical signs of cholestatic disease.
• RADIONUCLIDE SCANNING
- A radionuclide liver scan for uptake of hepatoiminodiacetic
acid (HIDA) is indicated if extrahepatic biliary atresia is
suspected
HEARING SCREENING
• Brainstem auditory-evoked potentials should be obtained in the
aftermath of severe neonatal jaundice to exclude sensorineural
hearing loss.
MANAGEMENT: INDIRECT HYPERBILIRUBINEMIA

• Blood type and Rh determination in mother and infant

• Direct antiglobulin test (DAT) in the infant (Coombs test)
Most widely
• Hemoglobin and hematocrit values used
• Serum albumin levels therapeutic
• Nomogram for hour-specific bilirubin values modalities
in infants
• Measurement of end-tidal carbon monoxide in breath with neonatal
• Peripheral blood film for erythrocyte morphology jaundice
• Reticulocyte count

PEDIA 3A: NEONATOLOGY B 9 of
21
PHOTOTHERAPY Indications for Phototherapy (term/Near-Term Infants)
• 3 reactions can occur when bilirubin is exposed to light
o Photooxidation: slow process
o Configurational isomerization
- a very rapid process that changes some of the
predominant 4Z,15Z bilirubin isomers to water-soluble
isomers in which one or both of the intramolecular bonds
are opened (E,Z; Z,E; or E,E)
- formation of photo isomers is significant after as little as 15
minutes of phototherapy
- not significantly influenced by the intensity of light
o Structural isomerization
- intramolecular cyclization, resulting in the formation of
lumirubin
- enhanced by increasing the intensity of light
- during phototherapy, lumirubin may constitute 2-6% of the
total serum bilirubin concentration Bhutani curves (as see in AAP recommendations and YNHH NBSCU Guidelines)

• Use total bilirubin. Do not subtract direct reacting or

conjugated bilirubin
• Risk factors: isoimmune hemolytic disease, G6PD deficiency,
asphyxia, significant lethargy, temperature instability, sepsis,
acidosis, or albumin <3.0 g/dL (if measured)
• For well infants 35-37 6/7 weeks can adjust TSB levels for
intervention around the medium risk line. It is an option to
intervene at lower TSB levels for infants closer to 35 weeks
and at higher TSB levels for those closes to 37 6/7 week.
• It is an option to provide conventional phototherapy in hospital
or at home at TSB levels 2-3 mg/dL (35-50 mmol/L) below
those shown but home phototherapy should not be used in
any infant with risk factors.

SAMPLEX REVIEW: PHOTOTHERAPY

• Generally, phototherapy is very safe and may have no serious
long-term effects in neonates; however, the following adverse
effects and complications have been noted:
o Insensible water loss
o Loose stools
o Retinal damage
• The combination of hyperbilirubinemia and phototherapy can
produce DNA- strand breakage and other effects on cellular
genetic material.
• Skin blood flow is increased during phototherapy, but this effect is
less pronounced in modern servocontrolled incubators. However,
redistribution of blood flow may occur in small premature infants.
An increased incidence of patent ductus arteriosus (PDA) has
been reported in these circumstances.
• Hypocalcemia appears to be more common in premature infants
under phototherapy lights. This has been suggested to be
mediated by altered melatonin metabolism. Concentrations of
certain amino acids in total parenteral nutrition solutions subjected
to phototherapy may deteriorate.
• Works irreversibly by: Structural photoisomerization
• Case:
o 14 hour old FT infant admitted due to generalized
jaundice, Initial hgb level 10 gm/dL, serum levels: total
bilirubin level of 21 mg/dL. Next action: Maximum
intensive phototherapy for 6 hours
EXCHANGE TRANSFUSION
• The second-line treatment when phototherapy failed to control
serum bilirubin levels
• However, data have shown that treatment with IVIG in infants with
Rh or ABO isoimmunization can significantly reduce the need for
exchange transfusions and has replaced exchange transfusion as
the second-line treatment in infants with isoimmune jaundice in
most institutions
• Critical level of a particular infant may be an indication for ET
during the 1st 2 days of life when further rise is expected, but not
typically on Day 4 in tern or day 7 in the preterm as hepatic
conjugation matures
• Double-volume exchange transfusion (DVET)
- 2 x blood volume = 2 x 80 cc/kg = 160 cc/kg
• Takes about 1-1.5 hours
• Exchange at rate of ~5cc/kg/3 min
• Volume withdrawn/infused based on weight

PEDIA 3A: NEONATOLOGY B 10 of
21
 • The dashed lines for the 1st 24 hours indicate uncertainty due to
a wide range of clinical circumstances and a range of responses
to phototherapy
• Immediate exchange transfusion is recommended if infant
shows signs of acute bilirubin encephalopathy (hypertonia,
arching, retrocollis, opisthotonos, fever, high pitched cry) or if
TSB is greater or equal to 5 mg/dL (85umol/L) above these lines
• Risk factors: isommune hemolytic disease, G6PD deficiency,
asphyxia, significant lethargy, temperature instability, sepsis,
acidosis
• Procedure • Measure serum albumin and calculate B/A ratio
- Transfer care to Neonatologist and NICU • Use total bilirubin. Do not subtract direct reacting or conjugated
bilirubin
• Complications • In infant is well and 35-37 6/7 week (median risk can
- Thrombocytopenia individualize TSB levels for exchange based on actual
gestational age.
- Portal vein thrombosis/perforation
- Necrotizing Enterocolitis
- Cardiac arrythmias • Partial removal of infant’s circulating antibody coated RBCs as
well as unattached antibodies and replace them with donor RBCs
- Hypoglycemia
that lack the sensitizing antigen.
- Volume overload
• Double volume exchange ~ 85% circulating RBCs are replaced
- Arrhythmias
- HYPOcalcemia, -magnesemia, -glycemia
OTHER THERAPIES (??)
- Respiratory and metabolic acidosis
• Diet: Hydration
- HIV, Hepatitis B and C infection
• Phenobarbital
- GVHD, death
- an inducer of hepatic bilirubin metabolism, may be
administered prenatally in the mother or postnatally in the
SAMPLEX REVIEW: EXCHANGE TRANSFUSION infant
• Indications: - concerns surround the long-term effects on children
o Hyperbilirubinemia, hemolytic anemia, intractable
• Metal mesoporphyrins and protoporphyrins
metabolic acidosis
- inhibition of bilirubin production through blockage of heme
• Clue: Double – jaundice; Partial – plethora/polycythemia oxygenase.
• Oral bilirubin oxidase can reduce serum bilirubin levels,
INTRAVENOUS IMMUNE GLOBULIN (IVIG) presumably by reducing enterohepatic circulation
• Dose range for IVIG of 500-1000 mg/kg x 2 hours for Rh or ABO • Agar or charcoal feeds
incompatibility when the total serum bilirubin levels approach or - act by binding bilirubin in the gut
surpass the exchange transfusions limits • Prophylactic treatment of Rh-negative women with Rh Ig
• Indicated for avoiding bilirubin neurotoxicity when other
therapeutic modalities have failed or are not sufficient. MANAGEMENT: DIRECT HYPERBILIRUBINEMIA
• In infants with erythroblastosis who present with severe anemia, • DIAGNOSE UNDERLYING CAUSE
hydrops, or both, even in the absence of high serum bilirubin - Basic work-up: LFTs, coags, CBC, cultures
levels - Infectious work-up for TORCH or hepatitis
• Cord hemoglobin <11 g/dL - Imaging studies (RUQ U/S, HIDA scan)
• Elevated cord bilirubin level (>70 μmol/L or 4.5 mg/dL), or - Serum alpha-1-antitrypsin levels
both - Urine-reducing substances (galactosemia)
• A rapid rate of increase in the serum bilirubin level (>15-20 μmol/L - TFTs
/h or 1 mg/dL/h) - Sweat test
• A more moderate rate of increase (>8-10 μmol/L/h or 0.5 mg/dL/h) - Biopsy
in the presence of moderate anemia (11-13 g/dL).
• TREAT UNDERLYING CAUSE
- TPN-associated cholestasis
- Stop TPN or at least reduce (especially lipid) and advance
feeds
- “TPN-Cholestasis protocol” (remove trace elements certain
days)
- Ursodiol (Actigall) and ADEKs
- Phenobarbital use is controversial
- Biliary atresia with Kasai procedure +/- liver transplant
- Alpha-1-antitrypsin with liver transplant
- Choledochal cyst with surgical removal
Adapted from AAP recommendations and YNHH NBSCU Guidelines - Galactosemia with dietary elimination

PEDIA 3A: NEONATOLOGY B 11 of
21
• SUPPORTIVE CARE IF NO TREATMENT POSSIBLE
PROGNOSIS
• Excellent if the patient receives treatment according to accepted
guidelines
• Brain damage due to kernicterus remains a true risk, and the
apparent increased incidence of kernicterus in recent years may
be due to the misconception that jaundice in the healthy full-term
infant is not dangerous and can be disregarded.
KERNICTERUS aka BILIRUBIIN ENCEPHALOPATHY or BIND
• Risk of occurrence inversely proportional to age
• Rarely occurs among healthy FT and when serum unconjugated
bilirubin <25 mg/dL without hemolysis
• Etiology: Due to deposition of unconjugated bilirubin in basal
ganglia and brainstem nuclei
PATHOLOGY
• Hypothesis: bilirubin interferes with oxygen utilization by cerebral
tissue leading to injury to cell membrane
• Surface of affected brain is pale yellow
• Areas preferentially affected: corpus subthalamicum,
hippocampus, olfactory area, striate bodies, thalamus, globus
pallidus, putamen, inferior clivus, cerebellar nuclei, cranial nerve
nuclei
PREVENTION
• Some recommend universal screening for hyperbilirubinemia in 1st
24-48h of life
• Hour specific bilirubin nomogram, PE and clinical risk factors
• AAP recommendations:
- Measure serum bilirubin if jaundiced w/in 24h
- follow-up within 2-3d if D/C within 48h
• Lactation promotion, education, support
• Potentially preventable causes of kernicterus (AAP)
- Early dc with no early follow-up
SAMPLEX REVIEW: KERNICTERUS
• Can be prevented by correcting metabolic acidosis
• Memorize clinical features of both acute and chronic forms,
the phases, onset & manifestations
o Jaundiced febrile, opisthotinic: Acute, phase 2
o Chronic kernicterus: Choreoathetosis
NEONATAL CHOLESTASIS
ETIOLOGY
• Infection, Genetic, Metabolic
• Undefined abnormalities leading to mechanical obstruction of bile
flow or functional impairment of hepatic excretion and bile
secretion

INTRAHEPATIC DISEASE
Metabolic, viral,
HEPATOCYTE INJURY
“idiopathic neonatal hepatitis”

BILE DUCT INJURY Bile duct hypoplasia or paucity

EXTRAHEPATIC DISEASE Extrahepatic biliary atresia

• Neuroimaging (MRI) and neuropathology. EVALUATION OF NEONATAL CHOLESTASIS

• Coronal section at level of basal ganglia showing selective • Serum bilirubin fraction
vulnerability and regional affection of globus pallidus • Assess stool color
• Serum albumin/coagulation profile
CLINICAL FEATURES • Metabolic, genetic causes – T4/TSH, sweat chloride
ACUTE FORM • Ultrasonography
• Hepatobiliary scintigraphy
poor suck, stupor, • Liver biopsy
PHASE 1 1st 1-2 days
hypotonia, seizure
BREASTFEEDING JAUNDICE
hypertonia of extensor
st • Increased bilirubin during the first week of life in breastfed infants
PHASE 2 Mid of 1 week muscles, opisthotonos,
due to both caloric and fluid deprivation
fever
• Resolves with increased breastfeeding frequency and amount of
PHASE 3 After 1st week hypertonia milk intake
CHRONIC FORM
st
SAMPLEX REVIEW: BREASTFEEDING JAUNDICE
Later in 1 opisthotonos, muscle rigidity, irregular
• Mechanism:
year movements, convulsions
o reduce caloric intake
movement disorders, muscle rigidity, o decreased milk intake with dehydration
2nd year
sensory neural hearing loss (SNHL)

complete syndrome appears:

3rd year bilateral choreoathetosis, upward gaze,
dysarthric speech

PEDIA 3A: NEONATOLOGY B 12 of
21
CASE 1 SAMPLEX REVIEW: BREASTMILK JAUNDICE
• FT baby girl born at 40 weeks to G1P0 mother • Cases:
• BW: 3200 g, APGARs: 9,9 o Generalized jaundice, exclusively breastfed infants, gained
• Pregnancy and delivery without complications weight, PE normal except for jaundice, unconjugated
• Currently DOL #2 (48h of life) fraction elevated/unconjugated hyperbilirubinemia beyong
• Nurses noted that she looks like this and call you to the Well-Baby 1st week of life
Nursery to evaluate her:
CASE 2
What else would you want to know? • Late pre-term baby boy born at 35 weeks
- How is she feeding? How is it going? • BW: 2500g, APGARs: 8,9
- Is she stooling and voiding? How often? • Pregnancy and delivery without complications
- What is her current weight? • Currently DOL #1 (12 h of life)
- How is she doing otherwise? • Nurses noted that he looks like this and called you into Room 1 to
- Does she have any risk factors? evaluate him:
- Has she had her TcB checked?
- Has she had blood bilirubin levels checked? What else would you want to know?
- How is she feeding? How is it going?
• Her mother is breastfeeding her. She thinks it is going well but this - Is she stooling and voiding? How often?
is her first baby and she is not sure if her milk is in yet. She is - What is her current weight?
feeding for 20 minutes every 4 hours. - How is she doing otherwise?
• Voided once and stooled several times since birth. - Does she have any risk factors?
• Current weight is 2850 g (about 11% less than BW). - Has she had her TcB checked?
• She seems less active and is sleeping more today. - Has she had blood bilirubin levels checked?
• No known risk factors. Mother and baby are both B positive.
• Total/direct bilirubin is 18/1 mg/dL. • He is taking Neosure formula 2 ounces q 2-3 hours.
• Voided twice and stooled several times since birth.
What is your working diagnosis? • Current weight is 2500 g (same as BW)
o BREASTFEEDING JAUNDICE • He is less active and sleeping more today.
What would you do next? • Mother is O positive and baby is A positive.
o Initiate phototherapy • Total/direct bilirubin is 18/1 mg/dL. Coombs positive.
o Monitor serial bilirubin levels
o Encourage increased frequency of feedings (q 2-3h ATC) and What is your working diagnosis?
consider supplementation prn o ABO INCOMPATIBILITY
o Request lactation consult
What would you do next?
BREASTMILK JAUNDICE o Exchange transfusion
• Jaundice among breastfed infants probably secondary to enzyme
glucuronidase facilitating intestinal reabsorption of bilirubin CASE 3
reabsorption of bilirubin • Pre-term baby boy born at 28 weeks
• Recent studies indicated that breastmilk contains high • Currently DOL 21
concentrations of nonesterified long-chain fatty acids, which • BW: 900 g, APGARs: 5,8
acts as inhibitors of hepatic UGT, causing retention of • Noted to have scleral icterus
unconjugated bilirubin
• Bilirubin levels 7.2/3.4 mg/dL
BEASTFEEDING BREASTMILK
What else would you want to know?
JAUNDICE JAUNDICE
- Does he have any risk factors?
Onset Within 1st week Beyond 1st week - How has he been acting clinically?
Low caloric intake ?B-glucoronidase in - Has he been receiving TPN? Any enteral feeds?
Etiology
Infrequent feedings some BM - Has he had any signs of infection?
- Does he have any syndromic features?
­ reabsorption of bilirubin in enterohepatic
Mechanism - What were his newborn screen results?
circulation

­ frequency of BF May temporarily hold BF • No known risk factors.

Management Phototherapy PRN
Early evaluation of BF
Phototherapy • He has been acting well without infectious symptoms.
DVET PRN • He had NEC on DOL #4 and has an ostomy and mucous fistula.
He has been on TPN since then.
• No features concerning for syndromes. Newborn screening results
were normal

PEDIA 3A: NEONATOLOGY B 13 of
21
What is your working diagnosis? SAMPLEX REVIEW: ANEMIA OF PREMATURITY
o TPN-ASSOCIATED CHOLESTASIS
• Indication for pRBC transfusion in a 1 month old former
preterm infant: Failure to gain weight
What would you do next?
• Cases:
o Try to advance enteral feeds and reduce TPN as soon as
o Formerly sick premature infant, pallor, PE: active, alert,
clinically possible
pale, RR-33, CR-130, liver palpable 2cm below right costal
o Start “cholestasis protocol”
margin. Hgb is 7 g/dL, hct 24%, his blood type is O+,
o Monitor bilirubin levels with LFTs every 2 weeks
Mom’s is A+
o Consider further work-up if bilirubin levels do not improve over
o 45 days old former premature infant, pallor, gained 700 g
time once off TPN
(birthweight 1500 gm), CBC showed anemia. Best course
of action: Start ferrous sulfate
BLOOD DISORDERS
• Most common cause of anemia in the first week of life:
ANEMIA
Hemolysis
• Hemoglobin increases with advancing gestational age
• Clinically significant anemia: feeding problems
• Anemia: Hgb values less than normal range for weight and
postnatal age
• VLBW have values 1-2 g/dl less than term infants HEMOLYTIC DISEASE OF THE NEWBORN
ERYTHROBLASTOSIS FETALIS
Physiologic • 8-12 weeks in term
• Caused by transplacental passage of maternal passage of
anemia • 6 weeks in preterm
maternal antibody active against paternal RBC antigens in the
• Pallor, heart failure and shock infant ?
Anemia at birth • Acute or chronic fetal blood loss, hemolysis • Common: Rh and ABO Incompatibility
or underproduction of erythrocytes • Leads to anemia and jaundice

• Hemolytic disease of the newborn, SAMPLEX REVIEW: HDN/ERYTHROBLASTOSIS FETALIS

hemorrhagic disease of the newborn, • Erythroblastosis fetalis with severe anemia may manifest with:
Anemia a few
intracranial hemorrhage, subcapsular pallor, ascites, pleural effusion
days after birth
hemorrhage, bleeding from the cord,
cephalohematoma
Rh INCOMPATIBILITY
• Hemolytic disease, bleeding from • Pathogenesis
hemangiomas, Meckel’s diverticulum,
- Mother is RH negative sensitized by the D antigen causing
Later anemia Vitamin K in large doses, Congenital
the formation of antibody formation against the D antigen
hemolytic diseases, repeated blood
- Rarely occurs in the first pregnancy
sampling
- Severity of Rh illness worsens with the successive
• LBW 1-3 months after birth < 7-10 g/dl pregnancies
• Presents with pallor, apnea, decreased
activity, poor weight gain, tachycardia, • Clinical manifestations
tachypnea, feeding problems - Wide spectrum
Anemia of
• Secondary to: repeated phlebotomy, - Mild hemolysis (15%) to severe anemia
prematurity
shortened red cell survival, rapid growth, - Severe anemia with compensatory hyperplasia of
physiologic effects of the transition from erythropoietic tissue
fetal to neonatal life - Pallor, cardiac decompensation, anasarca/hydrops fetalis,
• Treatment: pRBC transfusion circulatory collapse
- Jaundice may be absent at birth but severe cases may stain
• Bleeding from the fetal into the maternal
vernix, amniotic fluid and cord
circulation
Transplacental • Kleihauer Betke test demonstrates
• Laboratory
hemorrhage significant amount of fetal hemoglobin and
- Coomb’s test
red cells in the maternal blood on the day
of delivery - CBC
- Blood smear: polychromasia with increased nucleated RBC
• Severe distress at birth with normal - Cord bilirubin: 3-5 mg/dl
hemoglobin levels initially,
Acute blood loss
• no hepatosplenomegaly and early onset • Diagnosis
shock - Definitive: blood group incompatibility and corresponding
• Marked pallor, less distress, low antibody bound to the infant’s RBC
Chronic blood - Antenatal: previous history of sensitization (transfusion,
hemoglobin, microcytic indices, and heart
loss abortion, pregnancy)
failure
- IgG titer to antibodies to D antigen
- Assessment of the fetus

PEDIA 3A: NEONATOLOGY B 14 of
21
 - Ultrasound: skin or scalp edema, pleural or pericardial SAMPLEX REVIEW: ABO INCOMPATIBILITY
effusion, ascites • Case:
- Postnatal: blood type, hemoglobin, hematocrit, Coomb’s, o 2 day old full term infant admitted due to generalized
serum bilirubin jaundice secondary to ABO incompatibility. After 6 hours
on continuous phototherapy, serum bilirubin rose by 5
Umbilical cord hemoglobin of 10 g/dL or less and bilirubin mg/dL. Next course of action: Prepare for exchange
levels 5 mg/dL or more suggest SEVERE HEMOLYSIS. transfusion
• Due to: presence of antibody against fetal antigen
• Treatment
• Common etiology of physiologic jaundice during the first
1. Prevent intra and extrauterine death from severe anemia
week of life
2. Avoid neurotoxicity from hyperbilirubinemia
• Diagnosed by: positive direct Coomb’s test
UNBORN INFANT LIVEBORN INFANT • Most common etiology of unconjugated hyperbilirubinemia
Immediate resuscitation at during the first week of life
Serial monitoring
birth
Give fresh, low titer, POLYCYTHEMIA or PLETHORA IN THE NEWBORN
Intravascular transfusion of group O, leuko-reduced,
• Definition: Central hematocrit >65%
pRBC in the umbilical artery irradiated Rh(-) blood cross
• Maybe asymptomatic
matched against maternal
• Hyperviscosity may account for symptoms
serum
• Etiology: Increased RBC production due to chronic fetal
Complications: PROM, preterm Exchange transfusion hypoxia
delivery, infection, fetal distress, Phototherapy for jaundice • Clinical manifestations: irritability, lethargy, tachypnea, respiratory
perinatal death distress, feeding problems, hyperbilirubinemia, hypoglycemia,
thrombocytopenia, stroke, NEC, seizures
• Prevention of Rh Sensitization • Peripheral values are higher than central values
o IM injection, 300 ug anti-D globulin within 72h of delivery will • Incidence is high in:
eliminate ~ 10 ml of fetal cells from maternal circulation o High altitude
o RhoGAM at 28-32 weeks and at birth is more effective o Postmature vs term infants
o SGA vs LGA vs AGA
o IDM
SAMPLEX REVIEW: Rh INCOMPATIBILITY
o Delayed clamping,
• Characteristic of RH Incompatibility
o Recipient twin
o Can occur together with ABO incompatibility
o Trisomy 13,18 and 21
o Hydrops fetalis is a product of affected pregnancy
o Neonatal hypothyroidism and Grave’s disease
o IUGR
ABO INCOMPATIBILITY o Infants of hypertensive mothers
• Most common cause of hemolytic disease in the newborn o Adrenogenital syndrome
• 15% are at risk but only 0.3-2.2% manifest the disease o Beckwith-Wiedemann
• ABO factors have low antigenicity in the fetus and newborn
• Treatment
• Natural IgM antibodies against A and B factors present in utero do
o If asymptomatic: Hydration (enteral/IVF)
not cross the placenta
o If symptomatic or >70% hematocrit
• IgG antibodies to A antigen cross the placenta
- Partial exchange transfusion (NSS)
• Clinical manifestation: JAUNDICE
o Phototherapy
• Diagnosis
o Exchange transfusion: Type O blood, same Rh type as
o Presence of ABO incompatibility
infant
o Coomb’s test Positive
o Hyperbilirubinemia
o Anemia
o Reticulocytosis

• Treatment
o Phototherapy COMPLICATIONS
o Exchange transfusion • Seizures
• Pulmonary hypertension
• Renal vein thrombosis
• Stroke
• NEC
• Acute kidney injury

PEDIA 3A: NEONATOLOGY B 15 of
21
 SAMPLEX REVIEW: POLYCYTHEMIA/ PLETHORA LABORATORY
• Case: • PT, PTT: prolonged with decreased levels of factors II, VII, IX and
o In respiratory distress, ruddy appearance, PE: awake, X
pinkish, slightly irritable, respiratory rate of 60 bpm, liver • Normal bleeding time, fibrinogen, Factor V and VIII, platelets,
palpable 2 cm below right costal margin. CBC showed a capillary fragility, clot retraction
hgb of 210, hct 69%, WBC 22,000, neutrophilic
predominance DIFFERENTIAL DIAGNOSES
o 6 hour old post mature SGA infant, tachypnea and • Congenital coagulation defects
hypoglycemia, complete blood count showed a hematocrit • DIC
of 70%. Next course of action: Partial volume exchange • Swallowed blood syndrome
transfusion (PVET)
o Post mature, SGA with plethora TREATMENT AND PREVENTION
o Growth retarded baby with plethoric look • 1-5 mg Vitamin K, slow IV infusion
• FFP or Whole blood transfusion 10ml/kg if without
HEMORRHAGIC DISEASE OF THE NEWBORN or improvement
VITAMIN K DEFICIENCY DISORDER
• Moderate decrease of factors II, VII, IX, X normally occurs in all PREVENTION
newborns by 48-72 hours after birth with a gradual return to • Vitamin K 1mg at birth
birth levels by 7-10 days of age - May not prevent HDN in preterm
• More common among exclusively breastfed and premature
infants SAMPLEX REVIEW: VITAMIN K DEFICIENCY or
• Low vitamin K stores at birth HEMORRHAGIC DISEASE OF THE NEWBORN
• Poor placental transfer of vitamin K • DDX in umbilical cord bleeding in a 3 day old late preterm
• Low levels of vitamin K in breast milk infant
• Sterility of the gut • How much Vitamin K1 should be given at birth to a 1800 gm
baby: 1 mg
• Rarely occurs o Vitamin K 1mg administered IM in the anterolateral aspect
• Almost always associated with of the mid-thigh for preterm LGA babies
maternal medications that interfere • Parenteral Vitamin K at birth is given for the following reason/s
with vitamin K, such as o Decrease in factor II, VII, IX and X
anticonvulsants, anticoagulants, o Maternal intake of anticonvulsant drugs
and antibiotics o Prevention of hemorrhagic disease of newborn
EARLY <24 hours
• Postnatal administration of vitamin • Cases:
ONSET after birth
K has no effect in preventing early- o Bloody stools in a well 4-day old infant with deranged
onset disease. PT/PTT
• Maternal vitamin K o 14 day old full term, incessant crying, 3 hrs PTC was
supplementation that is home delivered, attended by a registered midwife, not
administered prenatally may given routine care at birth and exclusively breastfed.
prevent this form of HDN PE: pallor, bulging anterior fontanel. Diagnosis: Late
onset hemorrhagic disease of the newborn
2-7 days • Incidence: 2%
after birth in • GI, ear, nose throat mucosa,
CLASSIC
breastfed circumcision, intracranial, injection NEONATAL SEPSIS
infants sites

• Risk factors include breastfeeding,

diarrhea, hepatitis, cystic fibrosis
(CF), celiac disease, and alpha1-
antitrypin deficiency or absence of
2 weeks of
LATE prophylaxis in otherwise healthy
life until 6
ONSET infants
months
• Late-onset tends to be more
severe than early-onset or classic
disease and has a high frequency
of ICH

PEDIA 3A: NEONATOLOGY B 16 of
21
CLASSIFICATION • Neutropenia or neutrophilia
• Early onset sepsis: <72 hours of birth Blood count • Increased ratio of immature (bands): total
o Definition range from 24 hours to 6 days, but most present neutrophils
within 72 hours of birth • Thrombocytopenia
o Results from vertical exposure to high bacterial load during
• Raised in infection; also following
birth and few protective antibodies
C-reactive meconium aspiration, asphyxia, post-
• Late onset sepsis: >72 hours after birth
protein surgery
o Organisms usually acquired by nosocomial transmission from
• Takes several hours to rise – may be
person to person
normal initially

RISK FACTORS • >30 WBCs/mm3, but >20/mm3 suspicious

EARLY ONSET LATE ONSET • Protein: term infants >200mg/dl (>2g/L
• Preterm • Preterm CSF (Meningitis) • Glucose: <30% of blood glucose
• PROM (>18 hours) • Indwelling venous or arterial • May be able to observe GBS on GS
• Maternal fever in labor (>38C) catheters or tracheal tube without any white cells present
• Chorioamnionitis • Prolonged antibiotics
• Previous infected infant • Damage to skin from tape, TREATMENT
skin probes etc. • Early onset: cover gram positive and negative organisms
o Cover gram-positive and –negative organisms
CLINICAL PRESENTATION o Penicillin/amoxicillin + aminoglycoside (gentamicin/tobramycin)
• Usually non-specific deterioration • Late onset: need to also cover CONS and enterococcus
• Apnea and bradycardia o Methicillin/flucloxacillin + gentamicin/cephalosporin/gentamicin
• Respiratory distress / increased ventilatory requirements + vancomycin
• Slow feeding / vomiting / abdominal distention o If central venous catheter in place, remove if unresponsive to
• Fever / hypothermia / temperature instability antibiotics, persistent positive culture, gram-negative
• Tachycardia / collapse / shock /DIC organisms or seriously ill
• Irritability / lethargy / seizures
• Jaundice SAMPLEX REVIEW: NEONATAL SEPSIS
• Rash • Weak cry, poor suck
• Reduced limb movement in bone or joint • The most important measure in preventing neonatal sepsis:
• In meningitis (late signs) Proper hand washing
o Tense or bulging fontanelle • Considering giving appropriate antibiotics in a term
o Head retraction (opisthotonos) neonate with sepsis, one has to consider the following:
• On monitoring o Setting and timing of the disease
o Hypo/hyperglycemia o Penetration of specific antibiotics
o Neutropenia, neutrophilia, thrombocytopenia o Site of suspected infection
o Susceptibility profile
INVESTIGATIONS • Most important information needed to arrive at a
• CBC, differential, platelets diagnosis:
• CRP o Maternal history of vaginal discharge
• Blood culture o Place of birth
• Urine: microscopy and culture o Attendant of birth
• CSF, CXR (if indicated) • Management:
• Sites of infection: consider needle aspirate or biopsy for gram o Blood culture and sensitivity
stain and direct microscopy o Urinalysis and urine culture and sensitivity
• Tracheal aspirate if ventilated o CSF analysis and culture and sensitivity
• Consider • Measures needed in sick neonate with septicemia
o Maternal vaginal culture needing antibiotics
o Placental tissue (L. monocytogenes) o Coverage for gram positive and gram negative organisms
o Rapid antigen screen o Choice of antibiotics depends on its penetration across the
o Blood gases BBB
o Coagulation screen o Know how the antibiotics is metabolized and excreted
• Delivered at home assisted traditional birth attendant with
poor perinatal check-up was noted to have poor suck and
INTERPRETATION OF LABORATORY
weak cry at 14 days of life. The possible circulatory factor/s
• Gold standard but may be negative if to the development of the clinical symptomatology:
insufficient volume of blood o Absence of maternal tetanus immunization
Blood cultures
• If central line suspected, also take blood o Improper immediate neonatal care
sample from it o Possible poor cord dressings

PEDIA 3A: NEONATOLOGY B 17 of
21
 INFANT OF DIABETIC MOTHER CLINICAL PROBLEMS
• Women with diabetes in pregnancy (Type 1, 2 and Gestational) • Fetal effects
are at increased risk for adverse pregnancy outcome o Embryopathy (1st trimester)
• Risks: o Fetopathy (2nd/3rd trimesters)
o Polyhydramnios • Neonatal effects
o Pyelonephritis o Congenital Anomalies
o Chronic hypertension o Growth (Macrosomia vs. IUGR)
o Pre-eclampsia o Respiratory Distress Syndrome
o Preterm labor o Metabolic Complications
• Fetal mortality is greater than that of nondiabetic mothers o Hematologic Complications
especially after 32 weeks gestation • Long-term outcomes
• Fetal loss during pregnancy is associated with poorly
controlled maternal diabetes (ketoacidosis) and congenital
anomalies Women with 1st trimester HbA1C >12% had ­ risk of major
congenital abnormalities and spontaneous abortions
Better glycemic control = ¯ risk
PATHOPHYSIOLOGY: PEDERSEN’S HYPOTHESIS

MORBIDITIES OF IDM
• Macrosomia
• Hypocalcemia
• Polycythemia
• Hyperbilirubinemia
• Heart failure
• Small left colon syndrome
• Unexplained uterine demise
• Hypoglycemia
• Respiratory distress syndrome
• Renal vein thrombosis
• Congenital anomalies
• Septal hypertrophy
• Visceromegaly

MACROSOMIA (40%)
• Excessive weight for gestational age
• Hallmark of the diabetic pregnancy
o Despite advances in normalizing glucose in women who have
pregestational and gestational diabetes, fetal overgrowth
continues to occur at rates considerably greater than normal in
pregnancy
• Results from increased adiposity (hyperplasia and
hypertrophy) and increased liver and skeletal mass as a result
of insulin-stimulated fetal growth
• Brain and head growth are normal, which results in
disproportionality between head and shoulder size
• Due to greater size of the viscera and greater body fat

BACKGROUND AND PATHOPHYSIOLOGY

• With insulin-dependent diabetes mellitus
o Maternal hyperglycemia, hypoglycemia and ketosis can
occur during fetal organogenesis, and there is increased
incidence of fetal anomalies

• With gestational diabetes, because glucose intolerance does not

occur during organogenesis, the risk of anomalies is not
increased

PEDIA 3A: NEONATOLOGY B 18 of
21
 SAMPLEX REVIEW: MACROSOMIA in IDM
• At 7 days of life this term neonate was noted to have
persistence of irritability, hypotonia with 30 mg/dL blood
sugar. Consider
o Beta cells hyperplasia
o Neurohypoglycemia
o Infant of diabetic mother
• o Severity of maternal diabetes
HYPOGLYCEMIA (20-40%)
• The carryover of the fetal hyperinsulinemic state into the
immediate neonatal period places the IDM at risk of developing
hypoglycemia
• Occurs shortly after delivery because the abrupt cessation of
maternally derived glucose with cord clamping does not
immediately result in a decrease of insulin secretion in the
neonate
• Possible causes:
o Hyperinsulinism in response to fetal hyperglycemia
o Perpetuation of hypoglycemia as a result from decreased
hepatic glucose production and release which is exacerbated
by decreased catecholamine and glucagon response to
hypoglycemia
• High incidence of preterm birth, perinatal distress and disorders of
fetal growth
The strategy for treatment is to administer glucose in sufficient
quantities to attain normoglycemia while avoiding glucose
stimulation of the hypertrophied neonatal pancreas to secrete
more insulin
SAMPLEX REVIEW: HYPOGLYCEMIA in IDM
• Neonatal infants of diabetic mothers are at high risk for
hypoglycemia because:
o Hyperinsulinism
o Impaired gluconeogenesis in response to hypoglycemia
o Increased metabolic needs disproportionate to substrate
stores and calories supplied
• 35 weeks 2500g with maternal blood sugar of 230 mg/dL
developed jitteriness with incessant crying at 6 hrs of life.
The possible cause of this manifestation:
o Perpetuation of hypoglycemia as a result from
decreased hepatic glucose production and release
• Jittery and fussy. The condition could be due to:
o Hyperinsulinemia as a result of hyperglycemia
o Perpetuation of the symptoms as a result of poor
catecholamine response
o Release of glucagon
• At 6 hrs of life this 35 week neonate was noted to have
profound jitteriness, lip smacking and incessant crying.
Immediately give: Dextrose 10% bolus
• A term newborn would need the following in order to sustain
life and prevent jitteriness and incessant crying:
o Epinephrine
o Subcutaneous fats
o Decreased insulin production
PEDIA 3A: NEONATOLOGY B
HYPOCALCEMIA (50%)
• A delay in the surge of normally expected parathyroid hormone
possibly after birth
• Maternal diabetes causes increased urinary loss of magnesium,
which blunts parathyroid hormone secretion, causing neonatal
hypocalcemia
• Incidence is related to the following:
o Presence of perinatal distress
o Presence of prematurity
• Causes:
o Decreased production of PTH
o Delayed or no increase in serum PTH in the presence of
hypocalcemia
o Deficiency of PTH production rather than insensitivity to PTH
• Hypoparathyroidism is related to the hypomagnesemia that
frequently accompanies hypocalcemia in IDM
• Neonatal hypomagnesemia impairs PTH secretion and blunts end
organ response
SAMPLEX REVIEW: HYPOCALCEMIA in IDM
• 48th hour of life, neonate developed twitching with jerky
movements of all extremities.
• Persistent jitteriness followed by seizure. Possible cause
of seizure:
o Indirectly decrease calcium influx from bone to
extracellular fluid
o Lowering ionized calcium concentration
o Hypocalcemia due to increase binding of calcium to
albumin
• Hypocalcemia in asphyxiated term neonate
o Serum calcitonin concentration is higher in cord blood
than maternal blood
o Calcitonin level is high
• Jittery, tachycardic, ionized calcium was low. Condition
considered:
o Functional hypoparathyroidism
o Elevated calcitonin
o Decreased intestinal uptake of calcium due to low vit
D levels
o Increased endogenous phosphorus load
HYPOMAGNESEMIA
• May be secondary to maternal hypomagnesemia due to maternal
urinary losses
SAMPLEX REVIEW: HYPOMAGNESEMIA in IDM
• Neonate will be watched for jitteriness, irritability with
incessant crying after a double volume exchange
transfusion because of: Hypomagnesemia
RESPIRATORY DISTRESS SYNDROME (RDS)
• IDM have higher incidence of RDS
• The fetal hyperinsulinemic state restricts substrate availability for
surfactant biosynthesis and impedes fibroblast-pneumocyte factor,
which stimulates type II alveolar cells to produce surfactant.
• Previously inaccurate assessment of gestational age because of
fetal macrosomia caused inadvertent preterm delivery with
associated RDS
19 of
21
• Reasons:
o Increase incidence of preterm births
o Delayed pulmonary surfactant maturation
o Delivery by cesarean section
o Insulin is antagonist to the cortisol-induced increase in fetal
lung lecithin synthesis that normally occurs after 34 weeks
gestation
SAMPLEX REVIEW: RDS in IDM
• 1,200g 35 weeks neonate delivered spontaneously to a G1P0
mother with elevated fasting blood sugar before delivery,
developed tachypnea, cyanosis with grunting. Possible
cause/s of his present condition is/are:
o Insulin antagonizes cortisol-induced fetal lung lecithin
o Delayed pulmonary surfactant maturation
o Premature birth
• CXR: Radiolucency over the perihilar area
• Severe hyaline membrane disease
• Due to: Prematurity, decreased L/S ration,
hyperinsulinemia
POLYCYTHEMIA or HYPERVISCOSITY SYNDROME
• Animal studies suggest that fetal hyperinsulinemia and fluctuation
in fetal glucose concentrations may affect fetal oxygen availability,
thereby possibly increasing erythropoiesis
• Results from placental insufficiency causing hypoxia and increase
EPO production as a result of reduced oxygen delivery secondary
to chronic hyperglycemia and hyperinsulinism
• In vitro studies of late erythroid progenitor colonies from IDMs
indicate that they are particularly sensitive to insulin, suggesting
that the fetal hyperinsulinemic state may increase the risk of
polycythemia.
• May cause renal vein thrombosis, stroke, and other organ damage
SAMPLEX REVIEW: POLYCYTHEMIA in IDM
• 1 day old 3500g 36 weeks neonate born to a G2P2 insulin
dependent mother was noted to be plethoric. This
manifestation is due to: Chronic hypoxia
• 35 week AOG 3000 gm neonate delivered by forceps
extraction to an insulin dependent mother, plethoric with
some areas of hematoma especially on the scalp. Possible
neonatal outcomes:
o Hyperbilirubinemia, birth asphyxia, hypoglycemia
• At birth, 4200 gram 36 AOG neonate delivered by an IDM
was noted to be plethoric. This is due to:
o Evident chronic placental insufficiency, chronic
maternal hyperglycemia
PEDIA 3A: NEONATOLOGY B
HYPERBILIRUBINEMIA
• High red cell mass
• Hematomas at birth due to difficult delivery
• Factors implicated:
o Prematurity
o Traumatic delivery
o Impaired hepatic bilirubin conjugation secondary to
hypoglycemia
o Delayed oral feedings
o Polycythemia
SAMPLEX REVIEW: HYPERBILIRUBINEMIA in IDM
• Appropriate measures necessary in the treatment of infant of
insulin dependent mother who was noted to have
tachypnea, cyanosis, tachycardia and generalized
jaundice
o Double volume exchange transfusion,
o Phototherapy,
o Hematocrit determination
• Problem/s expected in a 33 weeks 2500 g born to a G2P3
insulin dependent mother include/s: Unconjugated
bilirubin value of 20 mg/dL
•
UNEXPECTED FETAL DEATH
• In the past, the risk for unexpected fetal death in late gestation
was substantial
• Improved maternal metabolic control and frequent assessment of
fetal status has greatly reduced the risk of this complication.
• The causes of unexpected fetal death are not completely
understood.
CARDIOMYOPATHY or CONGENITAL HEART DISEASE
• Thickening of the interventricular septum and left or right
ventricular wall
• Most are asymptomatic, although aortic outflow obstruction may
be sufficiently severe to cause left ventricular failure in a small
fraction of IDMs
• Generally regress during the first postnatal year
• Hypertrophic cardiomyopathy, primary hypertrophy of the IV
septum occurs 10-20% of IDM’s associated with neonatal
hypoglycemia
• Cause of septal defect involves fetal hyperinsulinism with
increased protein, glycogen and fat synthesis resulting in
hyperplasia and hypertrophy of myocardial cells
• Signs of CHF occurs within the 1st week of life
The hypertrophy is a result of fetal insulin secretion stimulating
cardiac muscle growth; septal hypertrophy occurs not only in
IDMs but in newborns who have nesidioblastosis.
20 of
21
 o Childhood obesity
- At 5 years of age there is accelerated weight gain
- At age 8 years, half has body weight of >90%
- Correlates with maternal pre-pregnant weight and amniotic
fluid insulin concentrations

SAMPLEX REVIEW:
• Infant of diabetic mother, the following has to be considered
upon discharge:
o Monitor growth pattern
SAMPLEX REVIEW: CONGENITAL HEART DISEASE
o Assess developmental mile stone
• Baby with tachypnea and cardiac murmur

TREATMENT
CONGENITAL ANOMALIES or MALFORMATIONS • Prophylactic treatment of infants of diabetic mothers should be
• IDM have 4-11% risk of major congenital malformations initiated before birth
• Incidence 6-9%, and these account for 50% of mortality • Preconception and frequent prenatal evaluation of all women with
• Most are nonspecific and non-chromosomic diabetes and pregnant women with gestational diabetes
• CNS and CHD accounts for 2/3 of malformations • Evaluation of fetal maturity, biophysical profile, Doppler
velocimetry
• No single anomaly is pathognomonic, but several are much more • Planning of the delivery in hospital where expert in obstetric and
frequent including: pediatric care is continuously available
o Cardiovascular: VSD, transposition of great vessels
o Skeletal: Caudal regression syndrome or sacral agenesis
o CNS: Meningomyelocele, anencephaly, holoprosencephaly
o Other: Renal, gastrointestinal
• Strategies to reduce the risk of congenital anomalies have focused
on normalizing the intrauterine metabolic environment before
conception

GASTROINTESTINAL
• Neonatal small left colon syndrome (microcolon, or lazy
colon syndrome) is a transient anomaly unique to IDMs
• Mechanism: hormone imbalance affecting the autonomic nervous
system increased concentrations of amylin peptide, an inhibitor of
gastric motility that is co-secreted with insulin.
• This might also explain the poor feeding that many IDMs
demonstrate during the immediate neonatal period.

LONG-TERM DEVELOPMENT
• NEUROCOGNITIVE
o Achieving optimal metabolic control during pregnancy reduces
but may not absolutely prevent the risk of poor
neurodevelopment outcome in the offspring.
o Even with improved maternal care, higher maternal fasting
beta-hydroxybutyrate concentrations in the second and third
trimesters are associated with some limitations in intelligence
and psychomotor development independent of perinatal
complications in offspring.
o Mothers whose diabetes were controlled during the later
pregnancy had significant language developmental problems

• METABOLISM
o The altered maternal metabolism also has a long-term impact
on the future health of the offspring. The risks of obesity,
impaired glucose tolerance, blunted insulin secretion, and REFERENCES:
hypertension developing during late childhood or • Powerpoint 2019
adolescence and persisting into adult life are increased in • Pediatrics Manual
offspring of diabetic mothers. • EJG Compilation

PEDIA 3A: NEONATOLOGY B 21 of
21