STUDY OF POSTNATAL PHENOBARBITONE PROPHYLAXIS FOR NEONATAL JAUNDICE IN BABIES WITH BIRTH WEIGHT 1000-1499 GRAMS

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STUDY OF POSTNATAL PHENOBARBITONE PROPHYLAXIS FOR
NEONATAL JAUNDICE IN BABIES WITH BIRTH WEIGHT
1000-1499 GRAMS

• Rajesh Kumar, Anil Narang, Gurjeevan Garewal

Post Graduate Institute of Medical Education
and Research, Chandigarh
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Introduction

• TSB gt15 mg/dl 5
  (NNPD 1995)

• 1000-1499 grams PT-78, ET-38
  (Narang et al, Indian J Pediatrics)

• Death or permanent sequelae due to ET
• Healthy newborns 1
• Sick newborns - 12
  (Jackson et al, Pediatrics 1997)

• Need for prophylactic therapy - Justified

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Prophylactic Therapies

• Phototherapy
• Effective
• ?PDA, ?IWL
• Maintenance difficult costly

• Metalloporphyrins
• ? Efficacy among VLBW
• ? Safety

• Phenobarbitone
• Cheap Effective
• Available studies among VLBW Limited
• Multiple isoforms of UDPGT

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Prophylactic Phenobarbitone

• Dose dependent effect of prophylactic
  phenobarbitone

• 5 mg/kg/day x 7 days
• Plasma drug accumulation over 7 days
• Peak plasma concentration after the peak of
  TSB
• Need for loading dose
• (Willson et al, Pediatrics 1969)

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Objectives

• To evaluate the role of prophylactic postnatal
  phenobarbitone in decreasing the need of ET for
  neonatal jaundice in babies with birth weight
  1000-1499 grams

• To compare the effects of two different dosage
  schedule of prophylactic phenobarbitone

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Material and Methods

• Prospective randomized interventional study

• Study period Dec 1998 to Oct 1999

• Eligibility criteria
• Birth weight- 1000-1499 gram

• Exclusion criteria
• Antenatal phenobarbitone (within 2 weeks of
  birth)
• Chorioamnionitis
• Rh hemolytic disease
• Major CMF

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Material and Methods

• Sample size
• ? error 5, ? error 20, OR 0.25
• Incidence of ET in control group 38.2
• n 49 in each group

• Block randomization

• Group I
• Loading dose Inj. Phenobarbitone 10mg/kg
• Maintenance dose 5mg/kg (day 2 to day 5)

• Group II
• No Loading dose
• Inj. Phenobarbitone 5mg/kg (day 1 to day 5)

• Group III
• No phenobarbitone

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Methods

• Investigations
• TSB 12 hourly by direct spectrophotometry X 7
  days
• Blood groups, DCT, G6PD, Retic, PBF

• Monitoring
• Feeding, Stool frequency, Weight record
• Drowsiness, apnea
• USG head Day 1, Day 3, Day 7 SOS

• Treatment
• PT TSB (mg/dl) gt0.5 of the birth weight in
  gram
• ET TSB (mg/dl) gt1 of the birth weight in gram
• e.g. BW 1200 gms, PT- gt6 mg/dl, ET- gt12
  mg/d

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Methods

• Cleared by institute ethics committee

• Informed consent taken

• Statistical analysis
• Categorical variables Chi-square test,
  Fischer exact test
• Continuous variable ANOVA

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General characteristics
Group I (n50) Group II (n50) Group III (n50)
BW (Gms) meansd) 1257142 1268157 1257146
GA (Wks) meansd) 31.42.8 31.82.4 31.22.4
MF 2.571 0.871 1.081
Oxytocin 76 72 78
Birth Asphyxia 42 42 32
All p value gt0.05 except for MF Group I vs.
Group II or III
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Neonatal morbidity
Group I (n50) Group II (n50) Group III (n50)
HMD 32 44 34
Ventilation 44 54 56
PDA 18 16 10
IVH 16 16 26
Sepsis 20 36 28
All p value gt0.05
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Incidence causes of neonatal jaundice


Idiopathic 58 52 58
Group I (n50) Group II (n50) Group III (n50)
Significant neonatal Jaundice 70 64 86

p value Group II vs. Group III 0.011, All
other p value gt0.05
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Need of exchange transfusion
No. of babies requiring ET
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No. of total ETs
32
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5
8
GROUP I
GROUP III
GROUP II
Group I vs. Group III OR 0.18 (0.05 - 0.65),
NNT 4.2 Group II vs. Group III OR 0.35 (0.11
- 1.03) Group I vs. Group II OR 0.52 (0.12 -
2.24)
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Duration of Phototherapy
p value Group I vs. Group III 0.017
Group I vs. Group II 0.019
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Trend of TSB over 7 days
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Enteral feeding, Wt loss and stool frequency
Group I (n50) Group II (n50) Group III (n50)
Day of starting enteral feeding 2.71.5 3.5 2.18 2.9 1.8
Fluid intake(ml/kg/day) 120.4 18 122.5 16 118.9 13







Wt loss in (day1-4) 7.3 3.8 6.6 2.5 7.6 2.6
Wt loss in (day5-7) 9.8 3.4 9.9 3.4 11.2 2.6






Wt loss in (day5-7) 9.8 3.4 9.9 3.4 11.2 2.6
Stool frequency(day1-4) 3.1 1.8 3.1 1.9 3.4 1.9
Stool frequency(day 5-7) 5.4 1.4 5 1.6 5.2 1.8
All p value gt0.05
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Limitations

• Not a blinded study

• Drug level could not be monitored

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Conclusions

• Phenobarbitone (Loading maintenance) vs.
  Control
• ? need for ET
• ? duration of PT

• Phenobarbitone (Loading maintenance) vs.
  Phenobarbitone (maintenance)
• ? duration of PT

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Summary

• Problem ? incidence of ET for NNJ in babies with
  birth weight 1000-1499 grams.

• Objective To study the role of prophylactic
  phenobarbitone to ? the need for ET for NNJ.

• Finding Prophylactic phenobarbitone does ? the
  need for ET and PT for NNJ in babies with birth
  weight 1000-1499 grams.

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Recommendation

• Phenobarbitone prophylaxis is effective and
  should be used in the babies with BW 1000-1499
  grams in the dose of 10 mg/kg within 6 hours
  followed by 5mg/kg/day till day 5 of life.

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Thank You