Associations Between Neonatal Jaundice and Autism Spectrum Disorder: A Systematic Review and Meta-analysis of Observational Studies

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects social function. Multiple factors are involved in ASD development.  Objectives: This study aimed to review and meta-analyze observational studies examining the association between neonatal jaundice (NNJ) and ASD.  Methods: This is a systematic review and meta-analysis based on the PECO framework. Articles published up to ۸ December ۲۰۲۴ were searched in national databases, including Danesh Gostar Barakat, Scientific Information Database (SID), MagIran, IranDoc, and international databases, including PubMed, Scopus, WOS, Cochrane, and Embase, as well as the Google Scholar search engine. Only observational studies were included. The quality of studies was assessed using the Newcastle-Ottawa scale (NOS). Data were analyzed using odds ratio (OR), relative risk (RR), and hazard ratio (HR) indices. The heterogeneity between the studies was evaluated using the I۲ indicator. Publication bias was examined using Begg’s funnel plot. Data were analyzed in STATA software, version ۱۴. Results: Of ۴۱۸ records, ۲۶ observational studies were finally included (۱۲ case-control studies, ۱۰ cohort studies, and ۴ cross-sectional studies). Overall, NNJ was associated with the risk of ASD with an OR of ۱.۶۵ (۹۵% CI, ۱.۴۴%, ۱.۸۹%). Also, the OR of the NNJ association with increased risk of ASD in newborns undergoing phototherapy was ۱.۱۹ (۹۵% CI, ۱.۱۱%, ۱.۲۷%). The OR was ۱.۲۵ in cohort studies (۹۵% CI, ۱.۱۵%, ۱.۳۶%); ۳.۲۱ in case-control studies (۹۵% CI, ۱.۸۹%, ۵.۴۵%); and ۱.۷۸ in cross-sectional studies (۹۵% CI, ۱.۱%, ۲.۸۹%). The risk of ASD due to NNJ was higher in boys (OR: ۱.۹۵, ۹۵% CI, ۱.۱۸%, ۳.۲۳%) than in girls (OR: ۱.۲۶, ۹۵% CI, ۱.۰۷%, ۱.۴۹%). Furthermore, the OR of association between NNJ and ASD was significantly higher in Taiwan, the USA, India, Brazil, Canada, Vietnam, Nepal, Qatar, Egypt, and China. NNJ and ASD were not significantly correlated in Sweden, Turkey, and Denmark. The presence of publication bias was significant (P<۰.۰۵). In other words, studies that did not report a significant association between NNJ and the risk of ASD were less likely to be published.  Conclusions: NNJ is associated with an elevated risk of ASD. Boys with jaundice are more exposed to the risk of ASD than girls. Thus, NNJ is an important issue, particularly in boys, which can lead to numerous long-term complications.

کلیدواژه ها:

Autism spectrum disorder (ASD) ، Jaundice ، Neonatal ، Severe jaundice in newborn ، Physiological neonatal jaundice (NNJ)