Association between interpregnancy interval and risk of autism spectrum disorder: a systematic review and Bayesian network meta-analysis

Although the risk of autism spectrum disorder (ASD) has been reported to be associated with interpregnancy intervals (IPIs), their association remains debatable due to inconsistent findings in existing studies. Therefore, the present study aimed to explore their association. PubMed, Embase, Web of Science, and the Cochrane Library were systematically retrieved up to May 25, 2022. An updated search was performed on May 25, 2023, to encompass recent studies. The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS). Our primary outcome measures were expressed as adjusted odds ratios (ORs). Given various control measures for IPI and diverse IPI thresholds in the included studies, a Bayesian network meta-analysis was performed. Eight studies were included, involving 24,865 children with ASD and 2,890,289 children without ASD. Compared to an IPI of 24 to 35 months, various IPIs were significantly associated with a higher risk of ASD (IPIs < 6 months: OR = 1.63, 95% CI 1.53-1.74, n = 5; IPIs of 6-11 months: OR = 1.50, 95% CI 1.42-1.59, n = 4; IPIs of 12-23 months: OR = 1.19, 95% CI 1.12-1.23, n = 10; IPIs of 36-59 months: OR = 0.96, 95% CI 0.94-0.99, n = 2; IPIs of 60-119 months: OR = 1.15, 95% CI 1.10-1.20, n = 4; IPIs > 120 months: OR = 1.57, 95% CI 1.43-1.72, n = 4). After adjusting confounding variables, our analysis delineated a U-shaped restricted cubic spline curve, underscoring that both substantially short (< 24 months) and excessively long IPIs (> 72 months) are significantly correlated with an increased risk of ASD. Conclusion: Our analysis indicates that both shorter and longer IPIs might predispose children to a higher risk of ASD. Optimal childbearing health and neurodevelopmental outcomes appear to be associated with a moderate IPI, specifically between 36 and 60 months.