1. Neonatal Hypoglycemia, Respiratory distress and Jaundice
Anchalee Yu.MD
Department of Pediatrics
Maharaj Hospital Nakhon Si Thammarat

2. 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 ?

3. Neonatal Hypoglycemia :Definition
Plasma glucose < 40 mg/dl

4. ภาวะ HYPOGLYCEMIA
1.Transient hypoglycemia 2. Persistent hypoglycemia

5. ปกติหลังคลอดทารกจะมีน้ำตาลต่ำสุดเมื่ออายุ 1-2 ชั่วโมง
ร่างกายมีกลไกทาง metabolic ดังนี้
Hepatic glycogenolysis
Hepatic gluconeogenesis
Adipose tissue lipolysis
Muscle proteolysis
Hepatic ketogenesis

6. Hepatic glycogenolysis
Hepatic gluconeogenesis
Muscle proteolysis
Adipose tissue lipolysis
glycerol
ketone
Hepatic ketogenesis

7. Transient hypoglycemia
Inadequate substrate or enzyme function
Prematurity, SGA, smaller twin
Infant with severe RD, infant of toxemic mother
Increased peripheral utilization
Abnormal temp. birth asphyxia, polycythemia
Associated with hyperinsulinism
IDM, erythroblastosis fetalis

8. Persistent hypoglycemia
Hyperinsulinemic state
Nesidioblastosis, beta cell hyperplasia, beta cell adenoma, beckwith wiedemann syndrome
Hormonal deficiency
Panhypopituitarism, ACTH deficiency
Substrate limited
Ketotic hypoglycemia, GSD, galactosemia

10. Panhypopituitarism

11. Galactosemia

12. 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,

13. อาการและอาการแสดง ภาวะ hypoglycemia เกิดได้ตั้งแต่ 1-2 ชั่วโมงหลังคลอด
ส่วนใหญ่ไม่มีอาการ
อาการ-ไม่มีลักษณะจำเพาะ

14. อาการของ hypoglycemia
Common
- jitteriness, tremors, convulsion
- episode of cyanosis
- apnea, irregular breathing
- apathy, weak, high pitched cry
- limbness or lethargy
- poor feeding
- eye rolling

15. การคำนวณ Glucose production rate (GPR)
GPR = % dextrose x rate fluid ml/hr 6 x body weight (kg)

16. มีอาการผิดปกติ และ หรือ
DTX< 40 mg/dl
Confirm ด้วย serum blood sugar
มีอาการผิดปกติ และ หรือ
DTX < 30 mg/dl*
ไม่มีอาการผิดปกติ หรือข้อห้ามการให้นม
Early feeding
ให้นม 65 cc/kg/day X 8 feed
10 % D/W 2 cc/kg/dose IV bolus
DTX ทุก ½ hr X 2 ครั้ง
Start IV glucose GPR 6-8 mg/kg/min*
DTX >40 mg/dl
DTX ทุก 1hr x 2 ครั้ง**
ทุก 2 hr x 2 ครั้ง
ทุก 4 hr
DTX ทุก 1hr x 2 ครั้ง
ทุก 2 hr x 2 ครั้ง
ทุก 4 hr

17. Management
* GPR เพิ่มได้ครั้งละ 2-3 mg/kg/minโดย เพิ่ม rate IV (ใน preterm ไม่ควรเกิน
requirement fluid per day ) หรือ strength IV
  * การให้ glucose :
Peripheral vein : ไม่เกิน 12.5 %
Umbilical artery : ไม่เกิน 15 %
Umbilical vein : ไม่จำกัด
  * ในกรณีที่ glucose production rate > mg/kg/min
ให้พิจารณา เจาะ serum cortisol, ketone ,insulin level ,growth
hormone ก่อน
ต่อมาให้ hydrocortisone 10 mg/kg/day แบ่ง ทุก 12 hr

18. Neonatal Jaundice

19. 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?

20. Bilirubin Metabolism:
* Unconjugated bilirubin is bound to albumin in plasma (hydrophobic)

21. 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

22. Hyperbilirubinemia & Clinical Outcomes:
Deposits in skin and mucous membranes
Unconjugated bilirubin deposits in the brain
Permanent neuronal damage
JAUNDICE
ACUTE BILIRUBIN ENCEPHALOPATHY
KERNICTERUS

23. 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

24. Jaundice/Icterus:

25. 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

26. Kernicterus:
* Bilirubin deposits typically in basal ganglia, hippocampus, substantia nigra, etc.

27. Kernicterus
ภาวะที่ indirect หรือ unconjugated bilirubin) เข้าสมองไปย้อมติดเซลล์สมอง อาจเรียกว่า bilirubin encephalopathy มักเกิดขึ้นที่บริเวณก้านสมอง cerebellum, basal ganglion และ hippocampus

28. 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

29. 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

30. Differential Dx of Indirect Hyperbilirubinemia:
Physiologic Jaundice
Disorders of Production
Disorders of Hepatic Uptake
Disorders of Conjugation
Other Causes

31. Differential Dx of Indirect Hyperbilirubinemia:
Physiologic Jaundice:
Progressive rise in total bilirubin between 48 and 120 hours of life (peaks at 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

32. 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

33. Differential Dx of Indirect Hyperbilirubinemia:
Disorders of Hepatic Uptake:
Gilbert Syndrome

34. Differential Dx of Indirect Hyperbilirubinemia:
Disorders of Conjugation:
Crigler-Najjar Syndrome Type I
Crigler-Najjar Syndrome Type II
Lucey-Driscoll Syndrome (transient familial neonatal hyperbilirubinemia)
Hypothyroidism

35. 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

36. Causes of Jaundice appearing after on week
Breastmilk jaundice
Galactosemia
Congenital hypothyroidism
Congenital hemolytic anemia
Cholestatic jaundice

37. Diagnosis of Hyperbilirubinemia:
Transcutaneous measurement:
Use can reduce need for blood level monitoring (Mishra et al, 2009)
Blood level measurement
- microbilirubin
- total bilirubin

38. 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)

39. Neonatal Hyperbilirubinemia:
Physiologic vs. Pathologic
Jaundice < 24 hr is always pathologic!
Indirect vs. Direct (Unconjugated vs. Conjugated)

40. 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

41. 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)

42. Predischarge TSB or TcB level in the high-risk zone
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

43. Predischarge TSB or TcB level in the high intermediate-risk zone
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

44. Management of Indirect Hyperbilirubinemia:
Indications for Phototherapy (Term/Near-Term Infants):
* Bhutani curves (as seen in AAP recommendations and YNHH NBSCU Guidelines)

45. Management in preterm baby
If TSB > Body weight in gram / 200 on phototherapy
More vulnerable for encephalopathy than term babies

46. Treatment of Indirect Hyperbilirubinemia:
Phototherapy:
* Important factors: Spectrum, irradiance, distance, surface area

47. Management of Indirect Hyperbilirubinemia:
Indications for Exchange Transfusion (Term/Near-Term Infants):
* Adapted from AAP recommendations and YNHH NBSCU Guidelines

48. Treatment of Indirect Hyperbilirubinemia:
Exchange Transfusion:
Double-volume exchange
2 x blood volume = 2 x 80 cc/kg = 160 cc/kg
Takes about hours
Exchange at rate of ~5cc/kg/3 min
Volume withdrawn/infused based on weight

49. 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

50. Improving effectiveness of phototherapy
Blue light nm gives deeper penetration
Naked baby for larger skin irradiation
Distance to baby cm
Cover with reflecting material
Long exposure as possible
Eye covering necessary

51. Complications of phototherapy
Loose watery ,brown stool
Retinal damage
Photosensitivity – burn
Dehydration
In preterm: PDA, hypocalcemia
In cholestatic Jaundice: bronze baby syndrome

52. Respiratory distress in the Neonate

53. 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 ?

54. การวินิจฉัย ประวัติ GA การเจ็บป่วยของมารดา fetal distress วิธีการคลอด
meconium stained amniotic fluid
perinatal asphyxia
resuscitation

55. การตรวจร่างกาย
อาการ respiratory distress: cyanosis, tachypnea
,retraction, grunting, flaring, moaning
temperature
blood pressure
skin perfusion

56. Clues to Diagnosis of types of Respiratory distress
INFORMATION FROM MATERNAL HISTORY MOST LIKELY CONDITION INFANT
Prematurity
RDS
Diabetes
RDS
Hemorrhage in the days before
RDS
premature delivery
Pneumonia
Infection
Premature rupture of membrane
Pneumonia
Prolonged labor
Pneumonia

57. Meconium - Stained amniotic fluid Meconium aspiration Polyhydramnios
INFORMATION FROM MATERNAL HISTORY MOST LIKELY CONDITION
Meconium - Stained amniotic fluid
Meconium aspiration
Polyhydramnios
Tracheoesophageal fistula
Excessive medications
Central nervous system
depression
Traumatic or breech delivery
Central nervous system
Fetal tachycardia or Bradycardia
Asphyxia
Prolapsed cord
Asphyxia
Postmaturity
Asphyxia

58. Clues to Diagnosis of types of Respiratory distress (cont.)
SIGNS IN THE BABY MOST LIKELY ASSOCIATED CONDITION
Single umbilical artery
Congenital anomalies
Scaphoid abdomen
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

59. Investigations Hct, CBC dextrostix,blood sugar blood gas chest X-ray
hemoculture LP
ultrasound,CT scan

60. Pulmonary disorder Common RDS TTNB MAS pneumonia pneumothorax
Less common
pulmonary hypoplasia
upper airway obstruction
rib-cage anomaly
pulmonary hemorrhage
diaphragmatic hernia

61. Extrapulmonary disorders
Cardiac disorder
PPHN
CHD
Metabolic
acidosis
hypoglycemia
hypothermia
Infectious
sepsis

62. Extrapulmonary disorders
Neuromuscular
CNS damage
medication
hematologic
hypovolemia
anemia
polycythemia

63. management 1. Supportive care 2. respiratory care
3. maintain adequate circulation
4. correct metabolic acidosis
5.specific treatment

64. Supportive care Neutral thermal environment
keep body temperature C
Nutrition –NPO?
minimal enteral feeding
parenteral nutrition
position

65. respiratory care Oxygen therapy
aim : arterial blood gas/ capillary blood gas
pH pH > 7.25
PaO mmHg
PaCO mmHg pCO
Respiratory support

66. Respiratory support
Oxygen canula low flow < 2 LPM
Oxygen box
High flow nasal canula > 2 LPM
Nasal CPAP – NIPPV (nasal intermittent pos pres ventilation)
ET tube with ventilator
High frequency oscillator

67. Respiratory support
Try non invasive respiratory support first maintain airway positive pressure by NCPAP or NIPVV in expiratory phase indication 1. PaO2 < mmHg ขณะได้ FiO2≥ recurrent apnea 3. respiratory acidosis

68. Indication on ET with Ventilator
clinical criteria
Retraction
RR>70 /min
Cyanosis
Recurrent apnea
Blood gas criteria
1. pH < 7.25
2. PaO2 <50 mmHg
เมื่อให้ FiO2 100%
3. PaCO2 >60 mmHg

69. Choanal atresia

70. Macroglossia

71. Micrognathia

72. Esophageal Atresia

73. Diaphragmatic hernia

74. Diaphragmatic hernia

75. RDS

76. Pneumothorax

77. Cardiomegaly -CHF

78. Chronic lung disease

79. TTNB

80. Meconium Aspiration Syndrome