Neonatal care

Common Problems Antenatal Neonatal

care
in Newborns resuscitation

Part 2/2 Immediate

postnatal care

Care prior to
discharge
After discharge

Satit Manopunya, MD
Division of Neonatology, Department of Pediatrics During first month
Faculty of Medicine, Chiang Mai University

Outline Terminology
preterm
1 Principle of newborn care extremely

GA
2 Perinatal asphyxia Gestational
Preterm Term Post-term
age ✓ Chronological age = actual age
✓ Postmenstrual age (PMA) = GA + post-natal age
✓ Corrected age = age after 40 weeks
3 Respiratory distress ไอออน
\< 0 ค แบก
1 year
Birth DOL 28

Age
4 Neonatal sepsis
NEONATE INFANT

Principle of neonatal care Growth assessment at birth

se ลง
4,000 g
Newborn 1,000 g 1,500 g 0
2,500 g
polyiytemih

10% Neonatal resuscitation

hypoyly
Birth hypothermia

Initial evaluation & care weight ELBW VLBW LBW Normal Macrosomia

Fenton 2013
BW BW
Review Risk Complete Routine P10 P90
of History Assessment Physical Examination Newborn care
- Antenatal care: - Maternal risk - Maturity - Skin-to-skin contact
ANC, serology, risk - Perinatal risk - Growth - Breastfeeding
SGA AGA
AGA LGA
- Perinatal care: - Neonatal risk - Vital signs - Medication: Vit.K, eyes care OFC
Delivery, resuscitation, - Anomalies - Vaccination: HBV, BCG
Apgar score - Sick ?
G ilin
Symmetrical SGA
เลิ กทําตัเล่มล่ อน
P10 Asymmetrical SGA
prot
แเอา Uteroplatental ihlUff,
High-risk Newborn Sick
Alteration of conscious
Neonates
Maternal risk Respiratory distress
Seizure Abnormal tone
• Demographic social factors: age, socioeconomic, marriage
•
o
Maternal disease: HT, DM, immune-mediated dz., genetic dz. etc. Crying Irritability
• Infection: STD, asymptomatic bacteriuria
• Illicit drug/ smoking/ alcohol

Tachycardia อาเจี ยนเชน bile

Perinatal risk Vomiting
• Inadequate antenatal care Bradycardia
• Multiple gestation Feeding
• Antepartum hemorrhage Central cyanosis intolerance
• Oligo-/ polyhydramnios
• Abnormal fetal U/S findings Hypotension Diarrhea
• Intrauterine infection ด่ แ
า บบ1ล้อ
• Delivery process & neonatal resuscitation
Shock ๆ

Neonatal risk Acidosis Fever

• Preterm, post-term
• LBW, SGA, LGA Hypoglycemia Hypothermia
• 0 birth injury
Asphyxia,
• Anomalies/ syndrome Hyperglycemia Temperature instability
• Abnormal physical examination

Principle of neonatal care Common problems in neonates

birth asphyxia failuretoexhebit
Newborn Perinatal asphyxia
เกิ ดต่ แก'intrauterine ได้ hypoxia

Respiratory distress

Neonatal sepsis
Initial evaluation & care
Neonatal hypoglycemia
Well newborn High-risk newborn Sick newborn
Neonatal anemia
Skin-to-skin contact Cause identification
Proper investigation

Breastfeeding Monitoring
Specific treatment Neonatal polycythemia

Rooming-in Supportive care

Re-evaluation
& promptly treatment Neonatal jaundice
NB screening Closed monitoring

Perinatal Asphyxia Perinatal Asphyxia

ftevmเดี ยวกัน
Birth asphyxia Failure to establish breathing at birth (by WHO) Incidence
ํารํ๊ หายใจด้วยตนเองไม่ได้ V
ตําแต่ ก่อนคลอดก็ asphyxiagt
อาจมี • 1 – 1.5 % of live births 11US ตา
Perinatal asphyxia • Overall mortality rate ~ 20% \ 3 ใน 4 ท์รอดhiก1
• Accounted for 30-35% of early neonatal mortality
• Impaired gas exchange leads to fetal hypoxemia and hypercarbia
(~ 900,000 - 1,000,000 deaths each year)
• Timing of the insults: antepartum – intrapartum – postpartum
• Neurodevelopmental sequelae in survived patients ~ 30%
• Biochemical definition:
Umbilical arterial pH < 7.0 or base excess < -12 to -16
arแหง ( risk of adverse neurological sequelae) Etiology
เด็ ก
i ณื
ญื ะ๊
Perinatal or neonatal depression • Antepartum period impaired gas exchange across placenta
• Intrapartum period secondary to respiratory abnormalities
• Clinical conditions detected on physical examination in the immediate • Postpartum period cardiovascular abnormalities
postnatal period within the first hour of life neurologic abnormalities
➢ Depressed mental status
➢ Muscle hypotonia HCOVCM ใน า ชม
Apneq
➢ Disturbances in cardiovascular or respiratory function
• Persistent symptoms > 1 hour  Neonatal encephalopathy
สมองทํางานไม่บก ตั Front Pediatr. 2019;7:489 Manual of Neonatal Care 7th edition. 2012
 Perinatal Asphyxia Perinatal Asphyxia
Infection Trauma

Risk factors Diabetes

Hypertension Maternal
factors
Hypotension Diagnosis
Pulmonary diseases in utero exposure to cocaine ● Preexist maternal problems
Cardiovascular diseases ● Changing of placenta
● Fetal conditions
Abnormal placentation
Infection
Severe anemia
Risk ?
● Intrapartum event
Abruptio placenta
Cardiomyopathy Fetal &
Placental
Hydrops
neonatal
factors
Placental infarction ● Perinatal event
factors Placental fibrosis
Congenital heart disease
PPHN
● Need for resuscitation ≥ 10 minutes
Shock
Prolapsed cord Ruptured uterus
Apgar score ● Apgar ≤ 5 for ≥ 10 minutes
Uterus &
Cord compression Cord True umbilical knot
abnormalities
Abnormal umbilical vessels Cord entanglement

Pathophysiology Blood gas

● Umbilical arterial pH ≤ 7 or base deficit ≥ 16
● First blood gas within 1 hour
Impaired maternal
oxygenation
Cellular
Hypoxic-ischemia ● End-organ damage
 Blood flow dysfunction Clinical ● Multiorgan dysfunction
 Fetal O2
requirement
Manual of Neonatal Care 7th edition. 2012 Manual of Neonatal Care 7th edition. 2012

Perinatal Asphyxia Perinatal Asphyxia

Multiorgan dysfunction Clinical manifestations
Alteration of conscious Apnea
Hypoxic ischemic Respiratory
encephalopathy depression Seizure Abnormal tone Respiratory distress

(HIE) Crying Irritability Desaturation (labile)

Stress ulcer Bradycardia GI bleeding

Myocardial Necrotizing enterocolitis Hypotension Feeding intolerance

ischemia (NEC)
Shock Jaundice
Liver injury

Anuria Oliguria
Disseminated intravascular Acute kidney injury (AKI)
coagulopathy
Bleeding tendency Hematuria
(DIC) Acute tubular necrosis (ATN)

Thrombocytopenia Metabolic disturbance Hypocalcemia Hyponatremia Hypo/hypoglycemia

Manual of Neonatal Care 7th edition. 2012 Manual of Neonatal Care 7th edition. 2012

yp

Perinatal Asphyxia Perinatal Asphyxia

Investigations Hypoxic ischemic encephalopathy (HIE)

Gel
Clinical neurological syndrome associated with perinatal asphyxia
amplitude
aEEG EEG
seizure
Chest x-ray
Therapeutic hypothermia (TH)
biniuy
Brain imaging: MRI, CT, US Blood gas

Cardiac enzymes: Trop-T, CK, CK-MB

Abdominal x-ray
Echocardiogram
Liver function test
EKG
Coagulogram
• Standard of care for infants born at GA ≥ 36 wk and BW > 1800 g

ออ
with moderate to severe HIE
• Total body or head cooling: safe and effective

mฝุ
oic CBC with PBS Urinalysis
• Target core temperature to 33 - 34 ºc for 72 hour
Iaag เจาะเป็นbaleline
Coagulogram BUN Creatinine • Should be started within 6 hours of life

µmmmm
D-dimer Fibrinogen Electrolyte Calcium Sugar

typo Manual of Neonatal Care 7th edition. 2012 Manual of Neonatal Care 7th edition. 2012
 Modified Sarnat Score Neonatal Seizure

a
Stage 1 Stage 2 Stage 3 Seizure None
Common focal Uncommon
(mild) (moderate) อ (severe) or multifocal (excluding decerebrate)

Level of conscious Hyperalert or irritable Lethargy or obtunded Stupor or coma

Spontaneous activity Active Decreased activity No activity

Moving around, Distal flexion, complete Decerebrate

Posture
flexion of hips and knees extension, frog-legged with/ without stimuli
2a = mild hypotonia 3a = flaccid
Muscle tone Normal resistance
2b = hypertonia 3b = rigid
Primitive reflex
• Sucking • Vigorous sucking • Weak or bite • Absent
• Moro • Complete • Incomplete • Absent
Autonomic systems
• HR • HR > 100 /min • HR < 100 + occasional • HR not constant, varies
 to > 120 /min <100 & > 120 /min
• Respiration • Spontaneous breathing • Periodic breathing with • Apnea or requiring
desaturation ventilator
• Pupils • Normal size and RTL • Constricted and RTL • Asymmetric pupils

antiseiure tetw
Seizure None
Common focal
or multifocal
Uncommon
(excluding decerebrate) tet

CMU clinical practice guideline for TH Management for asphyxiated baby

กื😉
๊
Less than 12-hour infant born at GA ≥ 36 wk or BW ≥ 1800 g
Supportive care Asphyxia
Miu
• Temperature control: avoid hyperthermia
ไม่No
มblood
ี gai มี euntny
Umbilical arterial gas or gas within 1 hr Perinatal events:
● Variable or late deceleration
• Control seizure: bedside aEEG monitoring
● Prolapsed / tight nuchal cord 1st line AED: Phenobarbital
pH ≤ 7.0 pH 7.01-7.15 ● Antepartum hemorrhage Other AEDs: levetiracetam, midazolam phenobarbital
BE ≥ -16 mmol/L BE -10 to 15.9 mmol/L ● Abruptio placenta
● Maternal trauma/ shock
• Respiratory support Kappa
± intubation, keep normal ventilation midazolam
1บ่แกณน์ Avoid hypoxemia → PPHN
PPHN
At 10 min of life • Cardiovascular monitoring
Closed monitoring + complete PE and
evaluate the Modified Sarnat Score
● Apgar ≤ 5
● Required
0 resuscitation
May not tolerate with multiple fluid loading
Adequate intravascular fluid → inotropes
Heaut fail
• Fluid & electrolyte
Restrict fluid & balanced I/O
Seizure Moderate to severe HIE
Correct electrolyte imbalance
Avoid hypo/ hyperglycemia
N9 9 914
THERAPEUTIC HYPOTHERMIA • Nutrition
Oral immune therapy during cooling µperfusion ต้mhypotheoon
Manual of Neonatal Care 7th edition. 2012
Slowly advanced enteral feeding อย่ าง fbed Manual of Neonatal Care 7th edition. 2012

Respiratory Distress Lung development

• The most common reasons for NICU admission: 5 Alveolar
4 Saccular
15% of term & 29% of late preterm developed RS morbidity 3 Canalicular
2 Pseudoglandular
• Could be early clinical presentations of many diseases 1 Embryogenic

• Need to identify the cause & initiate management

• Risk factors: Maternal triple I
Maternal Maternal DM
Risk Factors
- TE fistula - Respiratory distress syndrome
1 - Pulmonary sequestration 4 - Bronchopulmonary dysplasia
Prematurity Meconium-stained AF - Bronchogenic cyst - TTNB
Lung anomalies Oligohydramnios 2 - Congenital diaphragmatic hernia - MAS
Airway anomalies Cesarean section - Congenital cystic adenomatoid malformation 5 - Pneumonia
Neonatal Peripartum - PPHN
Risk Factors Risk Factors - Lung hypoplasia
- Respiratory distress syndrome
3 - Bronchopulmonary dysplasia
- Alveolar capillary dysplasia
Pediatrics in Review. 2014;35:417
 Transition to extrauterine life Respiratory physiology
Fetal Circulation During delivery Post-natal circulation
Increased systemic a. Anatomy
pressure

• High airway resistance

• Obligate nose breather

Breathing patterns in newborns

10-15 sec
Regular Short pause Rapid
1
min

TSTz_jd1
pemyea Transitional period • Periodic breathing
4 - 6 hours li tation • 30 – 60 /min
Desaturation Tachypnea Mild distress • Without clinical changing of color, HR and saturation
Neoreviews. 2017;18:e685

Respiratory symptoms Respiratory distress

Tachypnea Bradypnea
• Respiratory distress
Nasal flaring Grunting Retraction

Abnormal breath soung

• Respiratory depression Apnea

C20วั
• Hypoxemia Central cyanosis Desaturation
ldeooyttb7St
• Respiratory failure Head bobbing

Tube Edwards MO, et al.Paeditr Respir Rev. 2013;14(1):29-36

Warren JB, Anderson JM. Peditr Rev. 2010;31(12);487-495

Respiratory distress Approach ? Respiratory distress Approach ?

Respiratory Distress

History Respiratory Causes Non-respiratory Causes

Physical TREATMENT Diagnosis Congenital airway anomalies Metabolic causes

examination
Developmental lung disease Cardiac causes
Investigation
Lung parenchymal disease Hematologic causes

Clinical course Mechanical abnormalities Infectious causes

Neurological causes
 Respiratory distress Approach ? Respiratory distress Approach ?
Respiratory Respiratory
Non-respiratory cause Non-respiratory causes
Distress Distress

Metabolic cause Cardiac cause

Acyanotic CHD Cyanotic CHD

Temperature Sugar Electrolyte

0
• Hypothermia • Hypoglycemia • Hypocalcemia
< 36.5 °c < 40 mg% • Hypermagnesemia
• Hyperthermia • Hyperglycemia • Acidosis

h
> 37.5 °c > 150-180 mg%

ทิ่ ฬื๊
Shock Congestive heart failure Cyanosis Murmur
• Fever
≥ 37.8 °c Mottling skin Tachycardia Central cyanosis
Hypotension Respiratory distress Differential cyanosis
Delayed capillary refill Hepatomegaly Desaturation
Multiorgan failure Cardiomegaly Low SpO2

Respiratory distress Approach ? Cyanosis Approach ?

• Peripheral cyanosis (acrocyanosis)
บกต่
Respiratory
Non-respiratory causes Normal physiologic finding
Distress
• Central cyanosis
Cardiac cause
Central cyanosis

Acyanotic CHD Cyanotic CHD

Respiratory Cardiac Hematologic
MOST COMMON • Cyanotic heart disease • Methemoglobinemia
• Cardiopulmonary failure • Polycythemia

llw < ห
• Differential cyanosis: • Coarctation of aorta
Shock Congestive heart failure Cyanosis Murmur • Interrupted aortic arch
• Reverse differential cyanosis: • TGA with PHT
•
แบน 7 ขา
Severe CoA with PHT
• Interrupted aortic arch with PHT

Cyanosis Approach ? Respiratory distress Approach ?

Respiratory causes Cyanotic heart diseases Respiratory
Non-respiratory causes
Distress
Abnormal prenatal U/S - +
Hematologic cause
Central cyanosis -/+ +++
Respiratory distress +++ -/+ Anemia Polycythemia
Response to O2 +++ -/+ • Hb or Hct < 2SD • Hematocrit
Abnormal lung ausculta • Hematocrit > 65%
tion -/+ - < 40-45 % • Hyperviscosity
• Severe anemia with
Heart murmur ปกติใน + +++ high output heart failure
2 daysแรก
Cardiomegaly - +++
 Respiratory distress Approach ? Respiratory distress Approach ?
Respiratory Respiratory
Non-respiratory causes Non-respiratory cause
Distress Distress

Infectious cause Neuromuscular cause

Respiratory tract infection Systemic infection Birth depression Intracranial lesion Muscular cause
• • Maternal sedation • Brain anomalies • Diaphragm paralysis
• Pneumonia EOS
• LOS • Hypermagnesemia • Bleeding • Hypotonia
• Asphyxia • Stroke
RARE:
• Neonatal MG
• Tetanus, botulinum
• SMA

Respiratory distress Approach ? Respiratory distress Approach ?

Respiratory Respiratory
Respiratory causes Respiratory causes
Distress Distress

Congenital airway anomalies

idetat iriw2ชY
Nasal air-flow
- Choanal atresia
- Laryngeal web/ cyst
Stertor: pharynx - Tracheo/laryngomalacia
Mechanical abnormalities - Vocal cord paralysis
Hoarseness:
- Pleural effusion - Tracheal stenosis
vocal cord Inspiratory stridor: supraglottis
- Air-leak syndrome
Mass Expiratory stridor: Developmental Lung disease
tracheobronchial tree Lung parenchymal disease

2_ ยํ๋991อttil
- RDS - Lung hypoplasia
Biphasic stridor: - TTNB - CPAM
vocal cord, subglottic, trachea
- Pneumonia - Pulmonary sequestration
- Aspiration syndrome - Diaphragmatic hernia

Lung parenchymal diseases 1 Respiratory distress syndrome

• RDS or Hyaline membrane disease
1 Respiratory distress syndrome • Most common cause of respiratory distress in preterm
• Incidence: - varied with GA < 28 weeks 60-80%
32-36 weeks 15-30%
< 34 weeks ~ 20%
2 Transient tachypnea of the newborn - inverse with BW
• Pathophysiology: Surfactant deficiency  alveolar
surface tension
3 Meconium aspiration syndrome
microatelectasis

4 Neonatal pneumonia low lung volume

(FRC)

d FR
1 Respiratory distress syndrome 1 Respiratory distress syndrome
แม่ 0M
• Risk factors:
C • Chest X-ray finding:
Infant of diabetic mother (IDM)

✓ Hypoaeration L8 ช่01

}<😐
✓ Fine reticulogranular infiltration4
ญ
8
Male Cesarean section
White
(ground glass opacity)
Multiple pregnancy
Preterm
Cold stress
Precipitous delivery ✓ Air bronchograms
Perinatal asphyxia

• Prevention: - Antenatal steroid ✓ White-out lungs

- Prevent premature birth (complete opacity of lungs)

• Clinical course:
✓ Presentation within the first few hours of life
✓ Marked respiratory distress and required O2 supplementation
✓ Typically improves by age 3-4 days in correlation with diuresis
✓ Self-limited by endogenous surfactant production
Severe ROS

1 Respiratory distress syndrome 2 Transient tachypnea of the newborn

• Treatment: • TTN, TTNB or retained fetal lung fluid syndrome
Respiratory failure
In utero At birth • Most common cause of respiratory distress after term C/S

๊ ื ํา
° • Incidence: 3.6 - 5.7: 1,000 term infant
ญื ห
~ 10% in GA 33-34 weeks
~ 5% in GA 35-36 weeks
1: 1,000 preterm infants ~ 1% in Term

CUCPAP
- Prevent premature births - Early CPAP
- Antenatal steroid - Intubation • Pathophysiology: Delayed lung fluid absorption
- Mechanical ventilator
Steroid ⑦ Surfactant
Other supportive care: Surfactant therapy
- +/- NPO & i.v. fluid - Specific treatment
- Aspiration precaution
- Rescue therapy:
- Respiratory support
indicated for baby who required FiO2 > 0.3
- Oxygen supplement
- Animal-derived surfactant

ENAC
- Correct & avoid metabolic disturbance
- Closed monitoring - Intratracheal administration
- IN-SUR-E, LISA, MIS, via ETT
tube→7ส lurfai→ tube
เอา นาย

2 Transient tachypnea of the newborn 2 Transient tachypnea of the newborn

• Risk factors: IDM
• Chest x-ray findings:
Maternal asthma
✓ Hyperaeration

Male C/S < 39 weeks ✓ Fluid-filled in interlobar fissure

White Multiple pregnancy
Preterm Precipitous delivery ✓ Bilateral interstitial and alveolar
SGA/ LGA Perinatal asphyxia infiltration
✓ Prominent pulmonary vasculature
• Clinical course:
✓ Early-onset: generally within the first few minutes to hours ✓ Sunburst appearance
✓ Desaturation usually relieves by minimal O2 supplementation ✓ Pleural effusion (rare)
✓ อ
Frequently a diagnosis of exclusion
✓ Self-limited condition
✓ Rarely malignant TTNB
2 Transient tachypnea of the newborn 3 Meconium aspiration syndrome
• Treatment: • MAS
Respiratory failure
In utero After birth • Meconium-stained amniotic fluid: 10-15% of birth
(term & post-term)
• Incidence: 5% of meconium-stained AF developed MAS
- Prevent premature births - Respiratory support: as needed - Intubation
- C/S > 39 weeks
- O2 support: avoid hypoxia - Mechanical
ventilator

No Mainly supportive care:

specific treatment
- +/- NPO & i.v. fluid
- Aspiration precaution
- Temperature control
- Correct & avoid metabolic disturbance
- Closed monitoring

Meerkov M, et al. Neoreviews. 2016;17;e471

3 Meconium aspiration syndrome 3 Meconium aspiration syndrome

• Pathophysiology: • Risk factors: meconium-stained AF
- In utero Antepartum & intrapartum factors Postpartum factors
Meconium aspiration - During delivery
- GA > 40 wk - Moderate to thick MSAF - Low Apgar score < 4 at 1min
- Fetal tachycardia - Fetal bradycardia < 7 at 5 min
- Maternal smoking - Emergency C/S - Positive ventilation
Obstruction Surfactant inactivation Inflammation - SGA - LGA - Low cord pH

• Prevention: Direct tracheal suction with meconium aspirator

Air-leak
Atelectasis Air tapping syndrome
Chemical pneumonitis indicate for complete obstruction only !

Mediators → • Clinical course:

V/Q mismatch vasoconstriction ✓ Hx of meconium-stained AF
✓ Respiratory distress at birth/ shortly after birth or later
✓ Auscultation reveals rales and rhonchi
PPHN ✓ Other features associated with perinatal asphyxia,
Hypercarbia Hypoxia
pulmonary air-leak syndrome
PPHN

3 Meconium aspiration syndrome 3 Meconium aspiration syndrome

• Chest x-ray findings: • Treatment
MAS
In utero At birth
✓ Inhomogeneous lesion
- Diffuse
- Asymmetrical patchy
- Prevent fetal distress - Direct tracheal suction:
✓ Patchy or steaky infiltration - Prevent post-term delivery as indicated
Respiratory support
✓ Areas of consolidation, atelectasis
O2 supplementation
& hyperinflation
No Empirical antibiotics i.v.
✓ +/- pulmonary air-leak syndrome specific treatment
Treat the complications
- Avoid disturb & minimal intervention - Pulmonary air-leak syndrome
- Avoid hypoxia - PPHN
Other options for severe case
- ECMO
- Surfactant replacement
4 Neonatal pneumonia 4 Congenital pneumonia
• Neonatal pneumonia: • Pathophysiology:
1. Congenital pneumonia: transplacental infection
Congenital Maternal triple I Bacterial
2. Perinatal pneumonia: most common, acquired at birth infection colonization
3. Acquired pneumonia: community- or hospital-acquired Hematogenous
spreading

• Incidence: 0.28 – 1.9% Transplacental

Infected
AF
• Pathogens: virus, bacteria, fungus and protozoa infection
Ingestion
or aspiration
• Clinical manifestations:
✓ Various onset & severity
✓ Respiratory distress with clinical sepsis: Congenital Perinatal Acquired
- Temperature instability pneumonia pneumonia pneumonia
- Non-specific S&S
✓ Congenital infection (TORCHS) → congenital pneumonia
✓ Infants at risk of EOS → Perinatal pneumonia
✓ Acquired pneumonia → community- or hospital-acquired
Onset: 3 – 7 days

4 Congenital pneumonia 4 Congenital pneumonia

• Chest X-ray findings: • Treatment:
Pneumonia
In utero At birth
ยื่

ษ์
- IAP for GBS - EOS risk evaluation
- Monitor S&S - Septic W/U

0
Empirical ATBs
- Specific treatment
- Duration 7-10 days
Congenital pneumonia Perinatal pneumonia ๐
กญื้
✓ Diffuse alveolar infiltration ✓ Patchy infiltration Other supportive care:
- +/- NPO & i.v. fluid
✓ Air bronchogram ✓ Lobar consolidation - Aspiration precaution
- Temperature control
✓ Ground glass appearance - Correct & avoid metabolic disturbance
- Closed monitoring

Principle of management Neonatal sepsis

in newborn with respiratory distress • Clinical syndrome of systemic infection
• Usually bacterial infection:
more invasive and serious
Non-pulmonary
• Various clinical presentation:
Respiratory Identify cause asymptomatic, multiple and nonspecific
distress
pulmonary
• Classification:
Treatment Specific Treatment Early-onset Late-onset
Neonatal sepsis Neonatal sepsis
Respiratory support O2 supplement General care

Supportive - Non-invasive: Target for term: - Temp. control

- (+/-) NPO & i.v.
Care CPAP, HHHFNC SpO2 > 95 %
- Correct other Birth
Etiology 72 hours Prognosis
- Intubation & For preterm: metabolic problems Pathogen Clinical courses
mechanical ventilator SpO2 90-94% - Monitoring
Clinical manifestation
 Early-onset neonatal sepsis Early-onset neonatal sepsis
• Definition: bacteremia in neonate within 72 hours of age • Pathogenesis: Vertical transmission
In utero

During labor/ delivery

• Incidence: 0.5 -0.8 : 1,000 live births

Gestational age Incidence • Pathogens:
22 -24 weeks 32 : 1,000 live births microorganisms in
GU & lower GI tract
< 29 weeks 20 : 1,000 live births

< 34 weeks 6 : 1,000 live births Streptococcus agalectiae (GBS)

34 – 36 weeks 1 : 1,000 live births E. coli Enterobacter spp.

≥ 37 weeks 0.5 : 1,000 live births Listeria monocytogenase

Non-typable H. influenzae
• Mortality rate: 3%
Klebsiella pneumoniae
Pediatrics. 2011;127:817-26.
Pediatr Infect Dis J. 2011;30:934-41. N Engl J Med 2000;352:1500-7.
Fanaroff and Martin’s Neonatal-Perinatal Medicine disease of the fetus and infant. 10th Ed. 2015:734-7.

Early-onset neonatal sepsis Early-onset neonatal sepsis

• Approach to EOS • Risk factors:
Ethnicity
Bacteriuria
4 Maternal STDs
Promptly Maternal
3 GBS colonization
Treatment Risk Factors
2 Proper
Investigation
1 Clinical • ATBs
Assessment • Supportive care
Risk • H/C: gold standard • Closed monitoring
Identification Preterm labor
• Sepsis screening:
• Asymptomatic CBC, PBS, CRP, ESR Inadequate IAP

I น รอเราเรา lnb
Male
• Sick baby Prolonged ROM > 18 hr
|ศ ผล Prematurity
• Triple I
Neonatal Peripartum Maternal infection
รักแอบรัก
Low birth weight
• Prolonged PROM ≥ 18 hr Risk Factors Risk Factors
Maternal triple I
• Intrapartum ATBs prophylaxis Co-morbidity
• Spontaneous preterm labor Perianal asphyxia

4 ข้อ

Early-onset neonatal sepsis Early-onset neonatal sepsis

• Risk factors: • Intrapartum antibiotics prophylaxis (IAP)
้
Conditions Incidence of proven sepsis
PROM > 18 hours 1%
Maternal GBS+ (pre-prophylaxis era) 0.5% - 1%
Maternal GBS+ (in prophylaxis era) 0.2% - 0.4%
Maternal GBS+ and PROM, fever or preterm 4% - 7%
Chorioamnionitis 3% - 8%
IAP GBS+ and chorioamnionitis Triple I 6% - 20%
PROM and preterm 4% - 6%
PROM and low Apgar score 3% - 4% • Risk-based approach and culture-base screening approach
Pediatr Clin N Am 2004;51:939-59. • Universal culture-based screening of GBS at GA 35-37 weeks
• IAP given for high-risk cases

MMWR Recomm Rep. 2010;59(RR-10):1-36.

 Early-onset neonatal sepsis Early-onset neonatal sepsis
• Intrapartum antibiotics prophylaxis (IAP) • Intrapartum antibiotics prophylaxis (IAP)
Indication for GBS prophylaxis Incidence of invasive GBS disease 1990-2008
Previous infant with invasive GBS disease ควรi
ก่ อน
GBS bacteriuria during current pregnancy* ระหว่ าง
กห9 ห ช่ อคส
Positive GBS vaginal-rectal screening at GA 35-37 wk during current pregnancy* thแก้r
Unknown GBS status at onset of labour and any of the following:
- Delivery at GA < 37 wk
- ROM ≥ 18 hr
- Intrapartum temperature ≥ 38 °c
- Intrapartum NAAT positive for GBS
* Except C/S is performed before onset of labor on a women with intact of membrane

Adequate IAP Appropriate ATBs Duration

Ampicillin ≥ 4 hours
Penicillin G
Cefozolin
MMWR Recomm Rep. 2010;59(RR-10):1-36. MMWR Recomm Rep. 2010;59(RR-10):1-36.

Early-onset neonatal sepsis Early-onset neonatal sepsis

• Chrorioamnionitis 120เรา • Triple I
• Revised terminology and diagnostic criteria in 2015
by the NICHD, ACOG, SMFM and AAP in 2015 Isolated Suspected Confirmed
• Intrauterine inflammation, infection or both (triple I) maternal Triple I Triple I
recommend to observe rather than treat fever

Documented fever Documented fever with… Suspected Triple I with…

BT ≥ 39° c
BT 38-38.9 ° c ≥ ½ hr Fetal tachycardia Bacteria in AF
FHR > 160 /min
Rule out other conditions Leukocytosis Low sugar AF
Isolated Suspected Confirmed epidural block WBC > 15000/cu.mm
maternal fever Triple I Triple I prostaglandin Pus per cervical os Histopathologic finding
dehydration
ambient environment

Obstet Gynecol. 2016;127(3):426-36. Obstet Gynecol. 2016;127(3):426-36.

Early-onset neonatal sepsis htt

Early-onset neonatal sepsis
• Triple I Maternal Fever
• Clinical manifestations:
1 Vary asymptomatic mild severe dead

Isolated Suspected Confirmed 2 Non-specific

Maternal Fever Triple I Triple I
GA
▪

0°
Avoid ATBs treatment ≥ 34 wk
▪ Closed monitor mother for Ampicillin
additional sign & symptom
< 34 wk +
Gentamicin

ไม่ nir Add-on

If C/S

Clindamycin or Metronidazole

3 Multiorgan involvement
Obstet Gynecol. 2016;127(3):426-36.
 Early-onset neonatal sepsis Early-onset neonatal sepsis
• Clinical manifestations: • Investigation to confirm neonatal sepsis:
1 Vary asymptomatic mild severe dead 1 Hemoculture

• Gold standard 2
Specimen การวContaminoi

2 Non-specific Clinical Signs and symptoms (%) • Specialized pediatric culture bottles:
Asymptomatic 76 enriched culture media with antimicrobial neutralization
Respiratory distress 12 • Continuous-read detection systems
Poor feeding 9 • Minimum 1 ml of blood volume:
Drowsiness, hypotonia 1 reliable detection of bacteremia at a level of 1 -10 CFU
Hypoglycemia 1 • 2 separate bottles:
Temperature instability 1 confirm the true infection
Other:
jaundice, hepatomegaly, vomiting, diarrhea,
abdominal distension
Pediatrics. 2017;140(1)

3 Multiorgan involvement

Early-onset neonatal sepsis Early-onset neonatal sepsis

• Investigation to support neonatal sepsis: • Investigation to support neonatal sepsis:
2 Complete blood count 2 Complete blood count

• Common parameter: • Platelet count: non-specific, insensitivity and late indicator

✓ WBC count might be affected by GA, sex, delivery mode • Peripheral blood smear
✓ I:T ratio better sensitivity & specificity, independent of age in hr
✓ออกimmutmitotai
ANC neutremil DIC (MAHA)
Normal values of absolute neutrophil count (ANC) Vacuolization
Toxic granule
GA < 28 wk GA 28-36 wk GA > 36 wk

Early-onset neonatal sepsis Early-onset neonatal sepsis

• Investigation to support neonatal sepsis: • Investigation to support neonatal sepsis:
3 Inflammatory markers Soluble IL-2 receptor, IL-6, IL-8, TNF-alpha, CD-64 3 Inflammatory markers

C-reactive protein (CRP) Micro-ESR or ESR

• Increase within 6-8 hr and peak at 24 hr • Bedside investigation

• Consistently normal CRPs over 1st 48 hours = absent EOS • Required 0.2 ml of blood volume
negative predictive values = 99.7% • Low sensitivity 30-69%, high specificity 77-97%

Procalcitonin
PCT Other markers: Soluble IL-2 receptor
• Increase naturally over the first 24 -36 hr after birth
• Better sensitivity but non-specific compared with CRP IL-6 IL-8
Both markers may increase in response to other inflammatory process:
TNF-α
asphyxia, pneumothorax, MAS
Pediatrics. 2018;142; DOI: 10.1542/peds.2018-2894 CD-64 Pediatrics. 2018;142; DOI: 10.1542/peds.2018-2894
Pediatrics. 2018;142; DOI: 10.1542/peds.2018-2896 Pediatrics. 2018;142; DOI: 10.1542/peds.2018-2896
 Early-onset neonatal sepsis Early-onset neonatal sepsis
• Investigation to support neonatal sepsis: • Further investigation
4 Cerebrospinal fluid analysis

Combination of multiple parameters is better ! Indication: • Culture-proven sepsis

• Clinical highly suspected CNS infection
• Not response to usual empirical ATBs treatment
For meningitis diagnosis
CSF cell differential & count

CSF protein CSF sugar / blood sugar

CSF C/S CSF G/S Latex agglutination test

Int J Pediatr Res. 2016;3(7):533-9.

Risk of early-onset sepsis

Infant at risk of EOS • Uneventful preterm
Early-onset neonatal sepsis •
•
Prolonged PROM > 18 hr
Triple I
• Inadequate IAP
Approach to EOS 2023

Symptomatic infant Asymptomatic infant

• Approach to EOS
Closed
Maternal triple I GA < 34 wk GA > 34 wk monitor

2010 H/C before start empirical ATBs YES Develop clinical sepsis

NO
Sepsis screening: CBC, CRP, micro-ERS at age of 12-24 hours

2012
Negative H/C & Negative H/C &
Positive H/C
abnormal screening results normal screening results

2018 Proven sepsis Presumed sepsis less likely sepsis

Continue ATBs & Continue ATBs Discontinue ATBs

CSF analysis for 5-7 days after negative H/C > 48 hr

Early-onset neonatal sepsis Early-onset neonatal sepsis

• Antibiotic treatment • Antibiotic treatment
INDICATION

Clinically response? LAB result ? CNS infection ?

อ
Symptomatic infant Presumed sepsis Culture-proven sepsis Culture-proven Presumed Less likely sepsis
Risk of EOS Risk of EOS Risk of EOS
Duration

Cover pathogen in Ampicillin Clinical sepsis Clinical sepsis Sepsis screening

1st Ampicillin + Gentamycin +
maternal GU & GI tract
Antibiotics

Cefotaxime
Sepsis screening Sepsis screening H/C

Empirical ATBs H/C Narrative ATBs H/C H/C

Presumed sepsis No ATBs
Meningitis Discontinue ATBs
• Aminoglycoside: nephrotoxicity, ototoxicity
• Cefotaxime: no nephrotoxicity, cross blood-brain barrier
Continued ATBs
 Early-onset neonatal sepsis Early-onset neonatal sepsis
• Antibiotic treatment • Stepwise approach to EOS
4
Clinically response? LAB result ? CNS infection ? Promptly
3 Treatment
Duration of ATBs Treatment in newborn 2 Proper
Culture-proven Investigation
• ATBs
7-10 days
1 Clinical
Gram positive bacteremia
Assessment • Supportive care
Risk of EOS Risk • Closed monitoring
Duration

• H/C: gold standard

Gram positive meningitis 14 days
Identification • Sepsis screening:
Clinical sepsis Gram negative bacteremia 14 days • Asymptomatic CBC, PBS, CRP, ESR
• Sick baby
Sepsis screening 21 days
Gram negative meningitis or 14 days • Triple I
after negative culture meningitis • Prolonged PROM ≥ 18 hr
H/C
Other focal infection due to GBS • Intrapartum ATBs prophylaxis
(e.g. cerebritis, osteomyelitis, • Spontaneous preterm labor
Meningitis 4-6 weeks
endocarditis)

Continued ATBs Pediatrics. 2014;133(6):1122-13

• Uneventful preterm
1 Infant at risk of EOS • Prolonged PROM > 18 hr
•
•
Triple I
Inadequate IAP Late-onset neonatal sepsis
2
• Definition:
Approach to EOS 2023

Symptomatic infant Asymptomatic infant

bacteremia in neonate at age of > 72 hours
4
Maternal triple I GA < 34 wk GA > 34 wk
Closed
monitor
• Incidence: 0.2 – 14 %

• Pathophysiology: Vertical transmission Acquired infection

4 H/C before start empirical ATBs YES Develop clinical sepsis
Community-acquired
NO Hospital-acquired
3 Sepsis screening: CBC, CRP, microERS at age of 12-24 hours

• Risk factors Low birth weight

Negative H/C & Negative H/C & Prematurity

Positive H/C
abnormal screening results normal screening results

H2 blocker Hospitalization
Proven sepsis Presumed sepsis less likely sepsis Parenteral nutrition Immunocompromised host
Mechanical ventilator
Comorbidities: BPD, NEC, PDA
Prolonged ATBs usage
Continue ATBs & Continue ATBs Discontinue ATBs
4 CSF analysis 4 for 5-7 days 4 after negative H/C > 48 hr Invasive procedures & catheter
Neoreviews. 2012;13:e94

Late-onset neonatal sepsis Late-onset neonatal sepsis

• Pathogen: • Clinical manifestation: Non-specific S&S
Catheter-related infection

60
55%
50
Clinical impression:
43% • Not well
40
• Temperature instability
30 29% • Poor perfusion
23% • Jaundice
20
Hospital-acquired infection
10

0
Apnea Feeding Respiratory Lethargy/
Broad-spectrum ATBs usage problems distress hypotonia

Boghossian NS, et al. J Pediatr 2013;162:1120-4. Neoreviews. 2012;13:e94

 Late-onset neonatal sepsis Late-onset neonatal sepsis
• Approach to LOS:
3
4
• Common localized infection in neonates:
Omphalitis Pneumonia UTI
นู่ ะ
Meningitis
Treatment
Proper
Investigation
• Empirical ATBs ๐
• Supportive care
• CSF analysis
• UA, U/C, G/S
2 • Sepsis screening:
CBC, PBS, CRP, ESR
1 Clinical
Assessment SYSTEMIC S&S
Clinical Normal physical exam
Impression
• Complete PE Further
LOCALIZED INFECTION Investigation
• Not well Required
Depend on site of infection
• Fever
• Empirical ATBs
further investigation
เอนneeding
malnutrition • Supportive care

Infant with clinical suspected LOS Late-onset neonatal sepsis

Approach to LOS 2020

Systemic symptoms
• Antibiotic treatment
Evidence of localized infection
without localized infection
INDICATION

Septic work up: H/C, CBC, CRP, micro-ERS Septic work up: H/C, CBC, CRP, micro-ERS

Localized infection Suspected LOS

Further W/U depends on CSF analysis & Urinalysis &

source of infection CSF C/S urine C/S Omphalitis Cloxacillin + gentamicin Ampicillin + gentamycin
ANTIBIOTICS

Pneumonia Ampicillin
Cefotaxime + amikacin
Meningitis Cefotaxime
Start empirical ATBs depends on
Start empirical ATBs depends on: Cetazidime + amikacin
- community or hospital acquired infection UTI Gentamicin/ cefotaxime
primary source of infection
- risk of catheter-related infection

Empirical ATBs C/S Narrative ATBs

Late-onset neonatal sepsis Common problems in newborns

• Antibiotic treatment L,พ่ ม UA, กับ CSF

Clinically response? LAB result ? CNS infection ?

Q&A
Culture-proven Duration of ATBs Treatment in newborn
Duration

Gram positive bacteremia 7-10 days

Clinical sepsis
Gram positive meningitis 14 days
Abnormal LAB
ะ
😐
Gram negative bacteremia 14 days
H/C
21 days
Gram negative meningitis or 14 days
Meningitis after negative culture meningitis

Other focal infection due to GBS

(e.g. cerebritis, osteomyelitis,
Continued ATBs endocarditis)
4-6 weeks

Pediatrics. 2014;133(6):1122-13