Hyperbilirubinemia is a very common and frequently benign condition in newborns but a leading cause of hospitalisation and readmission in the first week of life. When the total serum bilirubin (TSB) rises above the high-risk zone during the first week of life, it is considered hyperbilirubinemia Nearly 8% to 11% of newborns develop significant hyperbilirubinemia. Neonatal hyperbilirubinemia accounted for 13 deaths per 1000 live births globally and ranked seventh leading cause among all causes of neonatal mortality in the first week of life.[1]. In some newborns, this can cause severe complications progressing to acute bilirubin encephalopathy and kernicterus with a high risk of neonatal mortality and long-term neurodevelopmental impairments. Severe hyperbilirubinemia and its sequelae put a disproportionately high burden in low-income and middle-income countries, primarily due to delays in timely identification and providing effective treatments. [2]. Early detection and treatment of significant hyperbilirubinemia may prevent complications. According to some studies, even moderate hyperbilirubinemia is found to be associated with an increased risk of minor neurologic dysfunction in the first year of life which is often considered safe.[3].

According to the American Academy of pediatrics, healthy newborns discharged within 48 hours of age should have a follow-up visit after 48 to 72 hours for any significant hyperbilirubinemia and other problems.[4]. However, this proposition is difficult in resource-limited settings, as a large number of newborns discharges before 48 hrs residing at a farther distance from the hospital may not come for follow-up. Several non-hemolytic prenatal, natal, and postnatal clinical risk factors as, the previous child with jaundice or treatment with phototherapy, Maternal hypertension, diabetes mellitus. Maternal age >25 years, instrumental delivery, delayed feeding, Suboptimal lactation, dehydration, oxytocin induction, Birth trauma, Maternal medications that could act as triggers in infants with G6PD deficiency or impair bilirubin-albumin binding, large for gestational age and Birth weight >3.5 kg are reported in the literature for healthy full-term newborns. These studies suggest that developing countries share a huge burden on newborns with severe hyperbilirubinemia as compared to high-income countries. [1,2,5,6,7].

Bilirubin level at or above high intermediate risk zone (over 75th percentile cutoff value) at 24 and 48 hrs of age was considered a cutoff value to find out the association with significant hyperbilirubinemia at 72 hrs of age. [8].

Statistical Analysis: Data was entered on the computer using Microsoft Office Excel Software program for Windows, then transferred to the Statistical Package of Social Science Software (SPSS) program to be statistically analysed. Comparison between groups was performed using the Mann-Whitney test for quantitative variables while comparison for qualitative variables was performed using Chi-square or Fisher’s exact test. P values less than 0.05 were considered statistically significant.

200 newborns were enrolled in the study and analysed for the association of various demographic, clinical, and laboratory markers for early prediction of significant hyperbilirubinemia in the study cohort. 55.5% of the newborn were male and 45.5% were female. 185(92%) newborns included were between 37 to 40 weeks, and 7.5% were above 40 wk of gestation. 173(86%) were appropriate for gestational age, 22 newborns (11%) were Short for gestational age, and 5 newborns were Large for gestational age. [Table1] Out of 200 newborns 19 newborns (33.5%) developed hyperbilirubinemia above high intermediate zone at 48 hrs while

Neonatal hyperbilirubinemia is the most common physical abnormality in newborns, it occurs in about 60-70% of full-term and 80% of preterm newborns. It is also the most common cause of readmission to the hospital during the early neonatal period. Approximately 4% of term neonates who are readmitted during their first week of life, 85% have jaundice.[9].

Reliable prediction of at-risk neonates may allow clinicians to plan early discharge of low-risk neonates and timely follow-up of high-risk neonates. Simple, non-invasive, and cost-effective methods should be used in high-risk neonates. Recently various new strategies are being adopted to predict significant hyperbilirubinemia in these newborns to facilitated early discharge and timely follow-up. [1,8,10]. But many of these methods are costly and require repeated sampling and close assessment, which sometimes is not practical in a busy government setting handling large numbers of newborns. Several demographic and clinical factors are described in a recent meta-analysis of available studies in low resource settings to exacerbate physiological hyperbilirubinemia and make these newborns more likely to develop complications of severe hyperbilirubinemia. [2]

Olusanya BO et al [13]. did not find these risk factors to be significant in their observation. We also did not found statistical significance for social background, and maternal age, and Parity of mother as a risk factor for hyperbilirubinemia.

During the first week of life, some newborns may suffer from caloric deprivation due to low volume of feeds and delayed enteral feeding. This condition will lead to decreased gastrointestinal activity, decreased stool frequency, delayed meconium passage further increasing enterohepatic recirculation of bilirubin. Low oral intake may induce a state of fasting in these newborns. Fasting is known to increase enterohepatic circulation by suppressing gastrointestinal motility. [14,15]. Early initiation of feeding and intervals < 3 hours are related to lower bilirubin levels in a study by M. Alex et al. [16].

Dehydration or weightless >10% in the first week, Delayed feeding, and mixed feeding was significantly associated with significant Hyperbilirubinemia in few studies. [14,16,17,18]. We did not find any statistical significance of exclusive breastfeeding in developing significant hyperbilirubinemia. As inadequate breastfeeding is more likely to cause significant hyperbilirubinemia rather than breastfeeding due to resemblance to fasting state and increased enterohepatic recirculation.

On the other hand, dehydration and delayed initiation feeding were a significant risk factors in our study causing weight loss (⩾10%) after birth which can be associated with insufficient oral intake during the first week of life. Studies by M. Alex et al. [16], Bilgin et al [17]. and Tiwari et al. [18]. also supported our observations. We observed delayed enteral feeding to be significantly associated with increased risk of hyperbilirubinemia at 48 and 72 hrs. Bhutani nomogram also identified delayed initiation of feeding as a risk factor for high intermediate risk zone.[8].

Mixed feeding frequency in our study population was found as high as 31.6%. As our hospital is tertiary care has high rates of cesarian sections leading to further delay in initiation of breastfeeding and prolonged separation leads to poor lactation in mothers. However, we did not find mixed feeding to increase the risk of hyperbilirubinemia in newborns independently. Our results were supported by other studies. [17,18].

Maximum serum bilirubin concentration can be observed till 96 hrs, and newborns in the study population might have developed hyperbilirubinemia after discharge from hospital, and most of these failed to come at follow-up due to their parent rural residence. More studies with a large sample size are needed to be done on Indian full-term healthy newborns before our conclusions can be generalized. The strength of the study is that we evaluated the risk of hyperbilirubinemia using the Bhutani nomogram as a cutoff limit of high intermediate risk zone, making our results more reliable and accurate for healthy term newborns as early as 24 hrs, who are at risk of developing subsequent hyperbilirubinemia.

The present study concluded that healthy full-term newborns with birth weight <2.5 kg, higher 24 and 48-hour serum bilirubin were more likely to experience significant hyperbilirubinemia who are often discharged from hospital early. Our study also demonstrated that delayed feeding and dehydration put these newborns at high risk for hyperbilirubinemia. Efforts should be made to implement early feeding and proper counselling during the hospital stay to improve newborn feeding practices to avoid complications of hyperbilirubinemia.

Risk factors as low birth delayed feeding, dehydration, higher 24 and 48 bilirubin level>6 and >11 mg /dl are significantly associated with hyperbilirubinemia in healthy full-term newborns.

Dr Sunil Arya-Concept, study design, data analysis, Final approval of the manuscript, Dr Jyoti Prajapati-Manuscript preparation, data analysis, statistical analysis, Review of Literature, Dr Chetan Panwar-Wrote study protocol, data collection, data analysis, statistical analysis