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Neonatal jaundice and autism spectrum disorder: a systematic review and meta-analysis

Abstract

Background

Two meta-analyses concluded that jaundice was associated with an increased risk of autism. We hypothesize that these findings were due to methodological limitations of the studies included. Neonatal jaundice affects many infants and risks of later morbidity may prompt physicians towards more aggressive treatment.

Methods

To conduct a systematic literature review and a meta-analysis of the association between neonatal jaundice and autism with particular attention given to low risk of bias studies. Pubmed, Scopus, Embase, Cochrane, and Google Scholar were searched for publications until February 2019. Data was extracted by use of pre-piloted structured sheets. Low risk of bias studies were identified through predefined criteria.

Results

A total of 32 studies met the inclusion criteria. The meta-analysis of six low risk of bias studies showed no association between neonatal jaundice and autism; cohort studies risk ratio 1.09, 95% CI, 0.99–1.20, case-control studies odds ratio 1.29 95% CI 0.95, 1.76. Funnel plot of all studies suggested a high risk of publication bias.

Conclusions

We found a high risk of publication bias, selection bias, and potential confounding in all studies. Based on the low risk of bias studies there was no convincing evidence to support an association between neonatal jaundice and autism.

Impact

  • Meta-analysis of data from six low risk of bias studies indicated no association between neonatal jaundice and autism spectrum disorder.

  • Previous studies show inconsistent results, which may be explained by unadjusted confounding and selection bias.

  • Funnel plot suggested high risk of publication bias when including all studies.

  • There is no evidence to suggest jaundice should be treated more aggressively to prevent autism.

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Fig. 1
Fig. 2: PRISMA flow chart.
Fig. 3: Forest plot of the association between neonatal jaundice and ASD, low risk of bias studies.
Fig. 4: Forest plot of the association between neonatal jaundice and ASD, all studies.
Fig. 5: Forest plot of the association between neonatal jaundice and ASD, preterm infants.
Fig. 6

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Each author has met the Pediatric Research authorship requirements listed below: Substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; Drafting the article or revising it critically for important intellectual content; and final approval of the version to be published. M.L.K., J.P.P., and T.B.H. contributed substantially to conception and design, M.L.K. and M.V.P. contributed substantially to the acquisition of data. All authors contributed substantially to the analysis and interpretation of data; M.L.K. drafted the article; the remaining authors contributed in revising it critically for important intellectual content. All authors have approved the final version to be published.

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Correspondence to Monica L. Kujabi.

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Kujabi, M.L., Petersen, J.P., Pedersen, M.V. et al. Neonatal jaundice and autism spectrum disorder: a systematic review and meta-analysis. Pediatr Res 90, 934–949 (2021). https://doi.org/10.1038/s41390-020-01272-x

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