Neonatal hyperbilirubinemia and repercussions on neurodevelopment: A systematic review

Accumulation of bilirubin above normal levels is considered a neurological risk factor for both premature and full-term newborns. This systematic review aimed to determine the effect of neonatal hyperbilirubinemia on neurodevelopment in preterm and full-term newborns.

PubMed, EMBASE, Cochrane Library, CINAHL, PsycINFO, Scopus and Lilacs databases were searched for articles published until 1 June 2022. The quality of cohort and case-control studies was assessed with the Newcastle-Ottawa Scale, and the MINCir scale was used to evaluate the methodological quality of therapy studies or the therapeutic procedures. Premature neonates without neurological conditions and those born at term with hyperbilirubinemia as the sole risk factor were included. Studies reporting one or more neurodevelopmental outcomes were included with an inter-group comparison of a hyperbilirubinemia group versus a non-hyperbilirubinemia or non-pathological hyperbilirubinemia group. The main outcomes were auditory function, visual function, cognitive function, motor function, behavior, global development and neurological risk.

The search identified 951 studies, 19 of which (n = 2210 newborns) were finally included. Fifteen of the cohort and case-control studies presented low risk of bias, and six studies showed high methodological quality. Within the preterm population, hyperbilirubinemia as the sole risk factor was not shown to affect neurodevelopment. Auditory, neurological and motor development alterations were found in the population of full-term newborns with hyperbilirubinemia, which were more evident during the first year of life.

Elevated bilirubin levels may be a trigger for the onset of neurodevelopmental disorders in full-term infants during the first year of life. More studies are warranted in the preterm population with hyperbilirubinemia to draw conclusions about its impact on their neurodevelopment.