Bilirubin Nomogram for Prediction of Significant Hyperbilirubinemia in North Indian Neonates.

ABSTRACT

Objectives: (i) To construct hour-specific serum total bilirubin (STB) nomogram in neonates born at ≥35 weeks of gestation; (ii)To evaluate efficacy of pre-discharge bilirubin measurement in predicting hyperbilirubinemia needing treatment. Design: Diagnostic test performance in a prospective cohort study. Setting: Teaching hospital in Northern India. Subjects: Healthy neonates with gestation ≥35 weeks or birth weight ≥2000 g. Intervention Serum total bilirubin was measured in all enrolled neonates at 24±6, 72-96 and 96-144 h of postnatal age and when indicated clinically. Neonates were followed up during hospital stay and after discharge till completion of 7th postnatal day. Outcome: Key outcome was significant hyperbilirubinemia (SHB) defined as need of phototherapy based on modified American Academy of Pediatrics (AAP) guidelines. In neonates born at 38 or more weeks of gestation middle line and in neonates born at 37 or less completed weeks of gestation, lower line of phototherapy thresholds were used to initiate phototherapy. For construction of nomogram, STB values were clubbed in six-hour epochs (age ± 3 hours) for postnatal age up to 48 h and twelvehour epochs (age ± 6 hours) for age beyond 48 h. Predictive ability of the nomogram was assessed by calculating sensitivity, specificity, positive predictive value, negative predictive value and likelihood ratio, by plotting receiver-operating characteristics (ROC) curve and calculating c-statistic. Results: 997 neonates (birth weight 2627 ± 536 g, gestation 37.8±1.5 weeks) were enrolled, of which 931 completed followup. Among enrolled neonates 344 (34.5%) were low birth weight. Rate of exclusive breastfeeding during hospital stay was more than 80%. Bilirubin nomogram was constructed using 40th, 75th and 95th percentile values of hour-specific bilirubin. Pre-discharge STB of ≥95th percentile was assigned to be in high-risk zone, between 75th and 94th centile in upper-intermediate risk zone, between 40th and 74th centile in lower-intermediate risk zone and below 40th percentile in low-risk zone. Among 49 neonates with pre-discharge STB in high risk zone. 34 developed SHB (positive predictive value 69.4%, sensitivity 17.1%, positive likelihood ratio 8.26). Among 342 neonates with pre-discharge STB in low risk zone, 32 developed PHB (negative predictive value 90.6% and specificity 42.5%, positive likelihood ratio 0.37). Area under curve for this risk assessment strategy was 0.73. Conclusion: Hour-specific bilirubin nomogram and STB measurement can be used for predicting subsequent need of phototherapy. Further studies are needed to validate performance of risk demarcation zones defined in this hour-specific bilirubin nomogram.