Association Between Maternal Smoking During Pregnancy and Risk of Autism Spectrum Disorder in Offspring: A Systematic Review

Abstract

Autism Spectrum Disorder (ASD) is a developmental condition that affects how individuals communicate, interact socially, and behave. One of the factor that is gaining attention is maternal smoking during pregnancy. Nicotine and other substances in tobacco smoke can cross the placenta and may interfere with fetal brain development. Despite these concerns, research findings on whether smoking during pregnancy increases the risk of ASD have been mixed. This review examines current evidence on the relationship between maternal smoking during pregnancy and the risk of ASD in offspring. It aims to assess the consistency and strength of reported associations, identify key confounding variables and evaluate the methodological quality of included studies. A structured search was carried out using PRISMA guidelines to identify observational studies published between January 1st 2013 and April 30th 2025. The review focused on studies with cohort, case-control, or cross-sectional designs. Study quality were assessed using tools from the Joanna Briggs Institute (JBI). From an initial pool of 6,915 records, 11 studies met the inclusion criteria. Most were conducted in high-income settings, with sample sizes ranging from fewer than 200 to over two million participants. Five studies reported statistically significant links between maternal smoking and ASD or its subtypes, though the observed effects were small. The remaining six studies, including the only one that used serum cotinine to verify smoking status, did not find a significant association. Differences in results appeared to relate to how smoking exposure and ASD were defined and measured, as well as differences between study populations. There is no clear or consistent evidence that maternal smoking during pregnancy is an independent risk factor for ASD. While some research points to a possible connection, results vary and are often limited by how smoking and ASD were assessed. Further research using more objective exposure data, larger and more diverse populations, and detailed subgroup analyses is needed to clarify whether any meaningful association exists.