Abstract
BACKGROUND: There is limited research on the association between maternal depression and autism spectrum disorder, and existing studies face significant limitations, including inadequate control for confounders, reliance on self-reported data, small sample sizes and lack of investigation into mediating factors. This study addresses these gaps by examining the direct relationship and the potential mediating effects of preterm birth, low birth weight and low Apgar scores. METHODS: We analysed linked administrative health data involving 223,068 mother-offspring pairs in New South Wales, Australia. Maternal perinatal depressive disorders and offspring autism spectrum disorder were assessed using the International Classification of Diseases, Tenth Revision, Australian Modification (ICD-10 AM). A generalised linear model was employed to examine the association. The mediation effects of preterm birth, low birth weight and low Apgar scores were assessed through mediation analysis. RESULTS: After adjusting for a range of potential confounders, offspring of mothers with antenatal, postnatal and overall perinatal depressive disorders had a 61% (risk ratio = 1.61, 95% confidence interval = [1.12, 2.32]), 85% (risk ratio = 1.85, 95% confidence interval = [1.20, 2.86]) and 80% (risk ratio = 1.80, 95% confidence interval = [1.33, 2.43]) higher risk of autism spectrum disorder, respectively. Only about 1.29% and 1.31% of the effect of maternal antenatal depressive disorders on offspring autism spectrum disorder was mediated by preterm birth and low Apgar scores, respectively. Low birth weight had no significant mediating effect on the association. CONCLUSION: Maternal perinatal depressive disorders are associated with an increased risk of autism spectrum disorder in offspring. Preterm birth and low Apgar scores were weak mediators of this association. Early intervention strategies that aim to enhance maternal mental health and mitigate the risk of exposed offspring are needed.