Risk Factors and Predictors of Rebound Hyperbilirubinemia in a Term and Late-Preterm Infant with Hemolysis

Abstract

Objective This study aimed to assess the incidence and predictors of rebound in term and late-preterm infants with hemolytic hyperbilirubinemia postphototherapy.

Study Design A 4-year retrospective data analysis of neonates with hemolytic indirect hyperbilirubinemia admitted to the neonatal intensive care unit (NICU) of Medina Maternity and Children's Hospital was conducted. Bilirubin rebound was defined as the return of total serum bilirubin (TSB) to phototherapy threshold within 72 hours of postphototherapy.

Results Of 386 identified neonates; 44 (11%) experienced rebound. Neonates in the rebound group demonstrated significantly higher levels of peak TSB, TSB at discontinuation of phototherapy, and lower value of relative TSB (difference between TSB at phototherapy termination and the American Academy of Pediatrics [AAP] threshold for phototherapy at concurrent age) compared with nonrebound group (p-value: <0.001, <0.001, and 0.007, respectively). Lower value of relative TSB at stoppage of phototherapy was the single independent predictor for rebound hyperbilirubinemia by mutivariate regression (p < 0.001). A cut-off value for relative TSB at stoppage of phototherapy of 190 µmol/L had 98% sensitivity and 32% specificity to predict rebound hyperbilirubinemia.

Conclusion Relative TSB at phototherapy termination is the best predictor for postphototherapy rebound hyperbilirubinemia in neonates with hemolytic etiology.

Key Points

• 11% of neonates showed postphototherapy rebound.

• The relative TSB at stoppage of phototherapy is the best predictor for rebound hyperbilirubinemia.

• The first cohort to assess rebound in neonates with hemolysis.

Keywords

jaundice - indirect hyperbilirubinemia - rebound hyperbilirubinemia - phototherapy - neonate

Authors' Contributions

N.N. and I.N. formulated the hypothesis, designed the study protocol, supervised data collection, drafted the initial manuscript, and adapted it according to other authors' reviews. I.N. designed the statistical analysis and analyzed the data. K.S. and A.A.H. helped in designing the study, supervised data collection, analyzed the results, and critically appraised the manuscript. H.A. collected the data and approved the final manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Publikationsverlauf

Eingereicht: 01. April 2020

Angenommen: 22. September 2020

Artikel online veröffentlicht:
23. November 2020

• References

• 1 Berkwitt A, Osborn R, Grossman M. The utility of inpatient rebound bilirubin levels in infants readmitted after birth hospitalization for hyperbilirubinemia. Hosp Pediatr 2015; 5 (02) 74-78
• 2 Wickremasinghe AC, Kuzniewicz MW, McCulloch CE, Newman TB. Efficacy of subthreshold newborn phototherapy during the birth hospitalization in preventing readmission for phototherapy. JAMA Pediatr 2018; 172 (04) 378-385
• 3 Maimburg RD, Olsen J, Sun Y. Neonatal hyperbilirubinemia and the risk of febrile seizures and childhood epilepsy. Epilepsy Res 2016; 124: 67-72
• 4 Newman TB, Wu YW, Kuzniewicz MW, Grimes BA, McCulloch CE. Childhood seizures after phototherapy. Pediatrics 2018; 142 (04) e20180648
• 5 Newman TB, Wickremasinghe AC, Walsh EM, Grimes BA, McCulloch CE, Kuzniewicz MW. Retrospective cohort study of phototherapy and childhood cancer in Northern California. Pediatrics 2016; 137 (06) e20151354
• 6 Lazar L, Litwin A, Merlob P. Phototherapy for neonatal nonhemolytic hyperbilirubinemia. Analysis of rebound and indications for discontinuing therapy. Clin Pediatr (Phila) 1993; 32 (05) 264-267
• 7 Al-Saedi SA. Rebound hyperbilirubinemia in term infants after phototherapy. Saudi Med J 2002; 23 (11) 1394-1397
• 8 Yetman RJ, Parks DK, Huseby V, Mistry K, Garcia J. Rebound bilirubin levels in infants receiving phototherapy. J Pediatr 1998; 133 (05) 705-707
• 9 Kaplan M, Kaplan E, Hammerman C. et al. Post-phototherapy neonatal bilirubin rebound: a potential cause of significant hyperbilirubinaemia. Arch Dis Child 2006; 91 (01) 31-34
• 10 Barak M, Berger I, Dollberg S, Mimouni FB, Mandel D. When should phototherapy be stopped? A pilot study comparing two targets of serum bilirubin concentration. Acta Paediatr 2009; 98 (02) 277-281
• 11 Bansal A, Jain S, Parmar VR, Chawla D. Bilirubin rebound after intensive phototherapy for neonatal jaundice. Indian Pediatr 2010; 47 (07) 607-609
• 12 Chang PW, Kuzniewicz MW, McCulloch CE, Newman TB. A clinical prediction rule for rebound hyperbilirubinemia following inpatient phototherapy. Pediatrics 2017; 139 (03) e20162896
• 13 Elhawary IM, Abdel Ghany EAG, Aboelhamed WA, Ibrahim SGE. Incidence and risk factors of post-phototherapy neonatal rebound hyperbilirubinemia. World J Pediatr 2018; 14 (04) 350-356
• 14 Bel Hadj I, Boukhris R, Khalsi F. et al. ABO hemolytic disease of newborn : Does newborn's blood group a risk factor?. Tunis Med 2019; 97 (03) 455-460
• 15 American Academy of Pediatrics Subcommittee on Hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 2004; 114 (01) 297-316
• 16 Matthews D, Glader B. Erythrocyte disorders in infancy. In: Gleason C, Devaskar S. eds. Avery's Diseases of the Newborn. 9th ed.. Philadelphia, PA: Saunders; 2012: 1083-1084
• 17 Jopling J, Henry E, Wiedmeier SE, Christensen RD. Reference ranges for hematocrit and blood hemoglobin concentration during the neonatal period: data from a multihospital health care system. Pediatrics 2009; 123 (02) e333-e337
• 18 National Institute for Health and Care Excellence. Jaundice in newborn babies under 28 days: Clinical guideline. Accessed January 13, 2020 Available at: https://www.nice.org.uk/guidance/cg98
• 19 Bratlid D, Nakstad B, Hansen TWR. National guidelines for treatment of jaundice in the newborn. Acta Paediatr 2011; 100 (04) 499-505
• 20 Chang PW, Newman TB. A simpler prediction rule for rebound hyperbilirubinemia. Pediatrics 2019; 144 (01) e20183712