This study was conducted to determine the incidence and magnitude of post-phototherapy bilirubin rebound in neonates. Subjects included inborn neonates needing phototherapy for hyperbilirubinemia. Standard guidelines were used to start and stop phototherapy. Rebound bilirubin was measured 24±6 h after stopping phototherapy. Significant bilirubin rebound (SBR) was defined as post-phototherapy bilirubin level needing reinstitution of phototherapy. Among 245 neonates with hyperbilirubinemia, post-phototherapy bilirubin estimation was done in 232 neonates. A total of 17 (7.3%) neonates developed SBR. In neonates with SBR, bilirubin increased by 2.3 mg/dL (95% CI 1.6-3.0) after stopping phototherapy. Risk factors for SBR included birth at <35 weeks of gestation (RR 4.3, 95% CI 1.5-12.0), birthweight <2000 g (RR 3.2, 95% CI 1.0-10.3) and onset of jaundice at <60 h of age (RR 3.3, 95% CI 1.2-9.0). Post-phototherapy discharge and follow-up planning should take into account these risk factors.

Key words: Bilirubin, Jaundice, Neonate, Phototherapy.

This study was conducted in the neonatal unit of a teaching referral hospital. Relevant information about inborn neonates needing phototherapy for hyperbilirubinemia during birth hospitalization or readmission from January 2008 to August 2008 was retrieved from case records. For neonates born at 35 or more completed weeks of gestation, the decision to start phototherapy was made on the basis of the age of the baby in hours and serum total bilirubin (STB) levels, as per American Academy of Pediatrics guidelines(7). In hemolytic jaundice, phototherapy was stopped when two consecutive STB levels were less than 14 mg/dL. In non-hemolytic jaundice, phototherapy was stopped when a single value of STB was less than 14 mg/dL. For neonates born at less than 35 completed weeks of gestation or with birthweight less than 2500 g, phototherapy was initiated according to following level of STB: >5mg/dL in first 24 h of postnatal age, >10mg/dL or 0.8% of birthweight (whichever was lower) at 24-48 h and >15mg/dL or 0.8% of birthweight (whichever was lower) at >48 h of age. Phototherapy was stopped when STB fell 2 mg/dL below level at which phototherapy would be indicated for that age. As per unit policy, rebound bilirubin was measured 24±6 h after stopping phototherapy. Significant bilirubin rebound (SBR) was defined as post-phototherapy bilirubin level needing reinstitution of phototherapy.

Data entry and analysis were done using Epi-Info (CDC, Atlanta). Continuous data with normal distribution was analyzed by student t-test and non-normally distributed data by Mann-Whitney U test. Categorical data was analyzed by chi-square or Fisher exact test. P value of <0.05 was considered significant.

Post-phototherapy bilirubin estimation was done in 232 neonates. A total of 17 (7.3%, 95% CI 4.4-11.6) neonates developed significant bilirubin rebound. In neonates with SBR, bilirubin increased by 2.3 mg/dL (95% CI 1.6-3.0) after stopping phototherapy. Parity or age of mother, mode of delivery, positive direct Coombs test, G6PD deficiency and peak serum bilirubin were compar-able in neonates with and without SBR. Risk factors for SBR included birth at <35 weeks of gestation (15.6% vs 4.2%, RR 4.3, 95% CI 1.5-12.0), birth weight<2000 g (10.8% vs 3.6%, RR 3.2, 95% CI 1.0-10.3) and onset of jaundice at <60 h of age (14.1% vs 4.8%, RR 3.3, 95% CI 1.2-9.0). Among neonates with absence of all these three risk factors, incidence of SBR was only 2.3% (2/86). Among neonates with presence of any one and all of the three risk factors, incidence of SBR was 10.3% (15/146) and 23.1% (6/26), respectively.

In the present study, we have reported the incidence of significant bilirubin rebound after stopping intensive phototherapy. Despite hyperbilirubinemia being a common morbidity among neonates, data about the phenomenon of bilirubin rebound is lacking. To the best of our knowledges this is the first report from India about incidence of SBR.

Previous reports in international literature have indicated that SBR is rare and therefore it is unnecessary to keep an infant in the hospital after phototherapy has been discontinued to check for SBR(2-5,8). Factors reported to influence incidence of SBR include proportion of premature neonates and hemolytic jaundice, severity and onset of hyperbilirubinemia, mode of feeding and presence of other risk factors like G6PD deficiency(6,9).

In our study group, risk factors of SBR included gestation at birth<35 weeks, birth weight<2000 gm and onset of jaundice at <60 h of postnatal age. Incidence of G6PD deficiency in our study group (8.4%) was comparable with that of Kaplan, et al. who have also reported high incidence of SBR (8.7%). Rate of G6PD deficiency in neonates with SBR was higher than in those without SBR, although it did not reach statistical significance (13.3% vs 8%, P=0.36). Use of stricter criteria for stopping phototherapy may explain the lack of higher SBR in neonates with G6PD deficiency or positive direct Coombs test result.

Natural history of bilirubin levels after stopping phototherapy is still unclear. Management of hyperbilirubinemia in neonates is based on the principle of avoiding potentially ‘neurotoxic’ levels of bilirubin(10). Neurotoxic level of bilirubin may vary with postnatal age, maturity of blood-brain barrier, rate of rise of serum bilirubin, serum albumin concentration, presence of hemolysis and co-morbidities(10). The neurotoxic levels of bilirubin in late neonatal period, and whether untreated rebound bilirubin may reach those levels, are issues for further investigation.

We recommend that a rebound bilirubin level must be obtained in high-risk neonates (born at less than 35 weeks gestation or birthweight <2000 gm or onset of phototherapy within 60 h of age) 18-24 h after stopping phototherapy. Discharge may be delayed for this purpose if follow-up is not ensured.

Contributors: DC and VP designed the study. AB collected the data with help of SJ and DC. DC analyzed data and wrote the manuscript with inputs from AB, SJ and VP. All authors approved the final manuscript.

Funding: None.

Competing interests: None stated.

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