Neonatal Hypoglycemia,
Respiratory distress and Jaundice
Anchalee Yu.MD
Department of Pediatrics
Maharaj Hospital Nakhon Si Thammarat
Case 1
Male infant GA 36 wk ,C/S due to CPD ,
 Apgar 8,10 at 1 and 5 min
 Mild retractions and grunting
 PE : T 36.4C ,RR 80/min, lung mild
secretion sound, subcostal and intercostal
retraction
 Otherwise normal
 DTX at LR : 20 mg %
 Management ?

Neonatal Hypoglycemia :Definition

Plasma glucose < 40 mg/dl
ภาวะ HYPOGLYCEMIA
1.Transient hypoglycemia
2. Persistent hypoglycemia
ปกติหลังคลอดทารกจะมีนา้ ตาลตา่ สุ ดเมื่ออายุ 1-2 ชั่วโมมง
ร่ างกายมีกลไกทาง metabolic ดังนี้
1. Hepatic glycogenolysis
2. Hepatic gluconeogenesis
3. Adipose tissue lipolysis
4. Muscle proteolysis
5. Hepatic ketogenesis
Hepatic
glycogenolysis
Hepatic
gluconeogenesis
Muscle proteolysis
Adipose tissue lipolysis
ketone
glycerol
Hepatic ketogenesis
Transient hypoglycemia
Inadequate substrate or enzyme
function
1.
◦
◦
Prematurity, SGA, smaller twin
Infant with severe RD, infant of toxemic
mother
Increased peripheral utilization
2.
Abnormal temp. birth asphyxia,
polycythemia
3.
◦
Associated with hyperinsulinism
IDM, erythroblastosis fetalis
Persistent hypoglycemia
Hyperinsulinemic state
1.
◦
Nesidioblastosis, beta cell hyperplasia, beta
cell adenoma, beckwith wiedemann
syndrome
Hormonal deficiency
2.
◦
Panhypopituitarism, ACTH deficiency
Substrate limited
3.
◦
Ketotic hypoglycemia, GSD, galactosemia
Panhypopituitarism
Galactosemia
Persistent hypoglycemia



If GPR > 10 mg/kg/hr and or lasting more than 2
weeks
Usually symptomatic
May be associated with midline defect,micropenis

Work up: insulin, cortisol, growth hormone,
ketone, fatty acid

Treatment: hydrocortisone, glucagon, diazoxide,
อาการและอาการแสดง
ภาวะ hypoglycemia เกิดได้ ตงั ้ แต่
ชั่วโมงหลังคลอด
ส่ วนใหญ่ ไม่ มีอาการ
อาการ-ไม่ มีลักษณะจาเพาะ
1-2
อาการของ hypoglycemia
 Common
- jitteriness, tremors, convulsion
- episode of cyanosis
- apnea, irregular breathing
- apathy, weak, high pitched cry
- limbness or lethargy
- poor feeding
- eye rolling
การคานวณ Glucose production rate (GPR)
GPR = % dextrose x rate fluid ml/hr
6 x body weight (kg)
DTX< 40 mg/dl
Confirm ด้ วย serum blood sugar
ไม่ มีอาการผิดปกติ หรื อข้ อห้ ามการให้ นม
มีอาการผิดปกติ และ หรื อ
DTX < 30 mg/dl*
Early feeding
ให้ นม 65 cc/kg/day X 8 feed
10 % D/W 2 cc/kg/dose IV bolus
DTX ทุก ½ hr X 2 ครั ง้
Start IV glucose GPR 6-8 mg/kg/min*
DTX >40 mg/dl
DTX ทุก 1hr x 2 ครั ง้ **
DTX ทุก 1hr x 2 ครั ง้
ทุก 2 hr x 2 ครั ง้
ทุก 4 hr
ทุก 2 hr x 2 ครั ง้
ทุก 4 hr
Management
* GPR เพิ่มได้ ครัง้ ละ 2-3 mg/kg/minโดย เพิ่ม rate IV (ใน preterm ไม่ควรเกิน
requirement fluid per day ) หรื อ strength IV
* การให้ glucose :
Peripheral vein : ไม่เกิน 12.5 %
Umbilical artery : ไม่เกิน 15 %
Umbilical vein : ไม่จากัด
* ในกรณีที่ glucose production rate > 12-15 mg/kg/min
ให้ พิจารณา เจาะ serum cortisol, ketone ,insulin level ,growth
hormone ก่อน
ต่อมาให้ hydrocortisone 10 mg/kg/day แบ่ง ทุก 12 hr
Neonatal Jaundice
Case 2






Male infant 4 days old presenting with marked
jaundice for 2 days. Birth weight = 3200 gm. Apgar
score 9,10 . No complications ,on exclusive
breastfeeding , serology and screening thalassemia
mom normal
PE : marked icteric sclera, no pallor, no
hepatosplenomegaly ,BW 2900 gm,V/S normal
MB 18, Hct 45 %
Further questions or examination?
Differential diagnosis?
Management?
Bilirubin Metabolism:
* Unconjugated bilirubin is bound to albumin in plasma (hydrophobic)
Hyperbilirubinemia:
Imbalance of bilirubin production and
elimination
 In order to clear from body must be:

◦ Conjugated in liver
◦ Excreted in bile
◦ Eliminated via urine and stool
Hyperbilirubinemia & Clinical
Outcomes:
Deposits in
skin and
mucous
membranes
Unconjugated
bilirubin
deposits in the
brain
Permanent
neuronal
damage
JAUNDICE
ACUTE
BILIRUBIN
ENCEPHALO
PATHY
KERNICTERUS
Clinical Symptoms:

Jaundice/Icterus:
◦ Newborn icterus notable once total bilirubin > 5-6
mg/dL (versus older children/adults once > 2 mg/dL)
◦ Progresses cranially to caudally
◦ CAUTION: Visual assessment is subjective,
inaccurate, and dependent on observer experience!
 Keren et al Visual assessment of jaundice in term and late-preterm infants (2009)
 Nurses at HUP used 5 point-scale to rate cephalocaudal extent of jaundice
 Showed weak correlation between predicted and actual levels
Jaundice/Icterus:
Clinical Symptoms:

Acute Bilirubin Encephalopathy/Kernicterus:
◦
◦
◦
◦
◦
◦
Irritability, jitteriness, increased high-pitched crying
Lethargy and poor feeding
Back arching
Apnea
Seizures
Long-term: Choreoathetoid CP, upward gaze palsy,
SN hearing loss, dental dysplasia
Kernicterus:
* Bilirubin deposits typically in basal ganglia,
hippocampus, substantia nigra, etc.
Kernicterus
ภาวะที่ indirect
หรื อ unconjugated
bilirubin) เข้ าสมองไป
ย้ อมติดเซลล์ สมอง อาจ
เรี ยกว่ า bilirubin
encephalopathy
มักเกิดขึน้ ที่บริเวณก้ าน
สมอง cerebellum,
basal ganglion
และ hippocampus
Diagnosis of Hyperbilirubinemia:
Careful clinical assessment and monitoring
 Thorough history:

◦
◦
◦
◦
◦
◦

Pregnancy and delivery history
General health status and infectious risk
Feeding method and feeding progress
Vital signs and ins/outs (hydration status)
Risk factors for isoimmunization
Family history and ethnicity (ie. G6PD, spherocytosis, etc.)
Physical exam:
◦ Activity level, feeding ability, bruising/hematoma, plethora
Indirect Hyperbilirubinemia:
Elevated levels of bilirubin due to imbalance in
production, transport, uptake, conjugation,
excretion, and reabsorption
 Most concerning due to risk for
encephalopathy/kernicterus if not treated
rapidly

Differential Dx of Indirect Hyperbilirubinemia:
Physiologic Jaundice
 Disorders of Production
 Disorders of Hepatic Uptake
 Disorders of Conjugation
 Other Causes

Differential Dx of Indirect Hyperbilirubinemia:

Physiologic Jaundice:
◦ Progressive rise in total bilirubin between 48 and 120
hours of life (peaks at 72-96 hours)
◦ Due to higher postnatal load of bilirubin and lower
amount of liver conjugating enzyme (UGT) activity
◦ Occurs in virtually every newborn to some degree
Differential Dx of Indirect Hyperbilirubinemia:

Disorders of Production: Increased RBC destruction
◦ Isoimmunization:
 Rh, ABO, other component incompatibilities
◦ RBC Biochemical defects:
 G6PD, pyruvate kinase deficiency
◦ RBC Structural Abnormalities:
 Spherocytosis, elliptocytosis, infantile pyknocytosis
◦ Infection:
 Bacterial, viral, protozoal
◦ Sequestration:
 Bruising, cephalohematomas, hemangiomas
◦ Polycythemia:
 IDM, delayed cord clamping
◦ Hemoglobinopathy
Differential Dx of Indirect Hyperbilirubinemia:

Disorders of Hepatic Uptake:
◦ Gilbert Syndrome
Differential Dx of Indirect Hyperbilirubinemia:

Disorders of Conjugation:
◦ Crigler-Najjar Syndrome Type I
◦ Crigler-Najjar Syndrome Type II
◦ Lucey-Driscoll Syndrome (transient familial neonata
hyperbilirubinemia)
◦ Hypothyroidism
Differential Dx of Indirect Hyperbilirubinemia:

Other Causes:
◦ Breastfeeding Jaundice
 Lack of volume and increased
enterohepatirecirculation
◦ Breast Milk Jaundice
 Unknown mechanism
 Possibly increased level of epidermal growth factor
in breast milk that causes increased enterohepatic
recirculation?
◦ Infant of Diabetic Mother
Causes of Jaundice appearing after
on week
Breastmilk jaundice
 Galactosemia
 Congenital hypothyroidism
 Congenital hemolytic anemia
 Cholestatic jaundice

Diagnosis of Hyperbilirubinemia:

Transcutaneous measurement:
◦ Use can reduce need for blood level
monitoring (Mishra et al, 2009)

Blood level measurement
- microbilirubin
- total bilirubin
Diagnosis of Hyperbilirubinemia:

Frequent additional studies to obtain:
◦ Blood type and Rh screening of mother and
infant
◦ DAT/Coombs testing in infant
◦ CBC (consider reticulocyte count, blood smear)

Occasional additional studies to obtain:
◦
◦
◦
◦
Albumin levels
LFTs
TFTs
Imaging: Liver/GB ultrasound, HIDA scan (r/o
biliary atresia)
Neonatal Hyperbilirubinemia:

Physiologic vs. Pathologic
◦ Jaundice < 24 hr is always pathologic!

Indirect vs. Direct (Unconjugated vs. Conjugated)
Pre-term vs. Full-term
Hyperbilirubinemia:
Pre-term infants at higher risk due to further
reduced activity of liver conjugating enzymes
 Pre-term infants can develop encephalopathy or
kernicterus at lower total bilirubin levels

Management of Indirect Hyperbilirubinemia:

Careful assessment and monitoring
◦ Visual assessment
◦ Blood level monitoring in high
risk patients
◦ Interpretation of risk levels and
need for treatment




Phototherapy
IVIg (reduces need for exchange when isoimmunization)
Exchange Transfusions
Phenobarbital (increases hepatic glucuronosyltransferase
activity; used in severe and prolonged cases only)
Risk Factors for Development of Severe Hyperbilirubinemia in Infants of
35 or More Weeks’ Gestation (in Approximate Order of Importance)
Major risk factors
•
Predischarge TSB or TcB level in the high-risk zone
•
Jaundice observed in the first 24 h
•
Blood group incompatibility with positive direct antiglobulin
•
test, other known hemolytic disease (eg, G6PD deficiency),
elevated ETCOc
•
Gestational age 35–36 wk
•
Previous sibling received phototherapy
•
Cephalohematoma or significant bruising
•
Exclusive breastfeeding, particularly if nursing is not going
well and weight loss is excessive
•
East Asian race
Risk Factors for Development of Severe Hyperbilirubinemia in Infants of
35 or More Weeks’ Gestation (in Approximate Order of Importance)
Minor risk factors
Predischarge TSB or TcB level in the high intermediate-risk zone
Gestational age 37–38 wk
Jaundice observed before discharge
Previous sibling with jaundice
Macrosomic infant of a diabetic mother
Maternal age ≥25 y
Male gender
Decreased risk (these factors are associated with decreased risk of
significant jaundice, listed in order of decreasing importance)
TSB or TcB level in the low-risk zone
Gestational age ≥41 wk
Exclusive bottle feeding
Black race
Discharge from hospital after 72 h
Management of Indirect Hyperbilirubinemia:
Indications for Phototherapy (Term/Near-Term
Infants):
* Bhutani curves (as seen in AAP recommendations and YNHH NBSCU Guidelines)
Management in preterm baby
If TSB > Body weight in gram / 200 on
phototherapy
 More vulnerable for encephalopathy than
term babies

Treatment of Indirect
Hyperbilirubinemia:

Phototherapy:
* Important factors: Spectrum, irradiance,
distance, surface area
Management of Indirect Hyperbilirubinemia:
Indications for Exchange Transfusion (Term/Near-Term Infants):
* Adapted from AAP recommendations and YNHH NBSCU Guidelines
Treatment of Indirect
Hyperbilirubinemia:

Exchange Transfusion:
◦ Double-volume exchange
 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
Discontinuation of phototherapy

Decrease of at least 0.5 to 1 mg/dL per
hour can be expected in the first 4 to 8
hours

For infants readmitted after birth may be
discontinued when the serum bilirubin
level falls below 13 to 14 mg/dL
Improving effectiveness of
phototherapy
Blue light 460-490 nm gives deeper
penetration
 Naked baby for larger skin irradiation
 Distance to baby 10-50 cm
 Cover with reflecting material
 Long exposure as possible
 Eye covering necessary

Complications of phototherapy
Loose watery ,brown stool
 Retinal damage
 Photosensitivity – burn
 Dehydration
 In preterm: PDA, hypocalcemia
 In cholestatic Jaundice: bronze baby
syndrome

Respiratory distress in the
Neonate
Case 3
Female newborn , born C/S at GA 36 wk,
apgar 8,9 at 1and 5 min respectively.
 2 hr after birth she developed mild cyanosis
and intercostal and subcostal retractions
with audible grunting
 O2 sat room air 92 %
 PE : T 36.8 C, RR 80/min, PR 150/min, lung
no secretion sound,heart normal S1S2 ,no
murmur
 Most likely diagnosis? DDx?
 Management ?

การวินิจฉัย
ประวัติ







GA
การเจ็บป่ วยของมารดา
fetal distress
วิธีการคลอด
meconium stained amniotic fluid
perinatal asphyxia
resuscitation
การตรวจร่างกาย

อาการ respiratory distress: cyanosis, tachypnea
,retraction, grunting, flaring, moaning

temperature

blood pressure

skin perfusion
Clues to Diagnosis of types of
Respiratory distress
INFORMATION FROM MATERNAL HISTORY
• Prematurity
MOST
LIKELY CONDITION INFANT
• RDS
•RDS
• Diabetes
• Hemorrhage in the days before • RDS
premature delivery
• Pneumonia
• Infection
• Premature rupture of membrane • Pneumonia
• Prolonged labor
• Pneumonia
INFORMATION FROM MATERNAL HISTORY
• Meconium - Stained amniotic fluid
• Polyhydramnios
• Excessive medications
• Traumatic or breech delivery
• Fetal tachycardia or Bradycardia
• Prolapsed cord
• Postmaturity
MOST LIKELY CONDITION
• Meconium aspiration
• Tracheoesophageal fistula
• Central nervous system
depression
• Central nervous system
• Asphyxia
• Asphyxia
• Asphyxia
Clues to Diagnosis of types of Respiratory
distress (cont.)
SIGNS IN THE BABY
ASSOCIATED CONDITION
MOST LIKELY
• Single umbilical artery
• Scaphoid abdomen
• Congenital anomalies
• Diaphragmatic hernia
• Erb / s palsy
• Phrenic nerve palsy
• Cannot breathe with mouth closed • Choanal atresia Stuffy nose
• Overdistention of lungs
• Aspiration , lobar
emphysema or Pneumothorax
• Choking after feedings
• Tracheoesophageal fistula or
pharyngeal incoordination
Investigations
•
Hct, CBC
•
dextrostix,blood sugar
•
blood gas
•
chest X-ray
•
hemoculture
•
LP
•
ultrasound,CT scan
Pulmonary disorder
 Common
RDS
TTNB
MAS
pneumonia
pneumothorax
 Less common
pulmonary hypoplasia
upper airway
obstruction
rib-cage anomaly
pulmonary
hemorrhage
diaphragmatic hernia
Extrapulmonary disorders
 Cardiac disorder
PPHN
CHD
 Metabolic
acidosis
hypoglycemia
hypothermia
 Infectious
sepsis
Extrapulmonary disorders
 Neuromuscular
CNS damage
medication
 hematologic
hypovolemia
anemia
polycythemia
management
1. Supportive care
2. respiratory care
3. maintain adequate circulation
4. correct metabolic acidosis
5.specific treatment
Supportive care
 Neutral thermal environment
keep body temperature 36.5-37.5 0C
 Nutrition –NPO?
minimal enteral feeding
parenteral nutrition
 position
respiratory care
 Oxygen therapy
aim : arterial blood gas/ capillary blood gas
pH 7.35-7.45
pH > 7.25
PaO2 50-80 mmHg
----PaCO2 35-45 mmHg pCO2 45-60
 Respiratory support
Respiratory support
1.
Oxygen canula low flow < 2 LPM
2.
Oxygen box
3.
High flow nasal canula > 2 LPM
4.
Nasal CPAP – NIPPV (nasal intermittent pos pres
ventilation)
5.
ET tube with ventilator
6.
High frequency oscillator
Respiratory support
Try non invasive respiratory support first
maintain airway positive pressure by NCPAP or NIPVV
in expiratory phase
indication
1. PaO2 < 50-60 mmHg ขณะได้ FiO2≥0.6
2. recurrent apnea
3. respiratory acidosis
Indication on ET with Ventilator
clinical criteria
1. Retraction
2. RR>70 /min
3. Cyanosis
4. Recurrent apnea
Blood gas criteria
1. pH < 7.25
2. PaO2 <50 mmHg
เมื่อให้ FiO2 100%
3. PaCO2 >60 mmHg
Choanal atresia
Macroglossia
Micrognathia
Esophageal Atresia
Diaphragmatic hernia
Diaphragmatic hernia
RDS
Pneumothorax
Cardiomegaly -CHF
Chronic lung disease
TTNB
Meconium Aspiration Syndrome