Maternal smoking during pregnancy and risk of childhood-onset type 1 diabetes in offspring: A systematic review and meta-analysis

Childhood-onset type 1 diabetes (T1D) is a chronic autoimmune disease characterized by a steadily increasing global incidence and significant public health implications. The relationship between maternal smoking during pregnancy and T1D risk remains uncertain. To clarify this association, we conducted a meta-analysis of prospective cohort studies to enhance methodological reliability. We systematically searched PubMed, Embase, and Web of Science from their inception to May 2025 for prospective cohort studies examining the link between maternal smoking during pregnancy and the incidence of T1D in offspring. Risk ratios (RRs) and 95% confidence intervals (CIs) were pooled using a random-effects model, accounting for heterogeneity. Twelve prospective cohort datasets from ten studies, encompassing over 5.9 million children, were included. Maternal smoking during pregnancy was significantly associated with a reduced risk of childhood-onset T1D (RR: 0.74, 95% CI: 0.72-0.76, p < 0.001), with no evidence of statistical heterogeneity (I² = 0%, p = 0.48). This association remained robust across sensitivity analyses that excluded one dataset at a time. Subgroup analyses demonstrated consistent results across various categories, including cohort size, prevalence of maternal smoking, method of T1D diagnosis, and adjustments for maternal age, diabetes, and delivery mode. Notably, the inverse association was significantly weaker in studies that did not adjust for maternal diabetes (RR: 0.79 vs. 0.72, p for subgroup difference = 0.01). We found no substantial evidence of publication bias (Egger's test, p = 0.55). In conclusion, this meta-analysis identified an inverse association between maternal smoking during pregnancy and the incidence of childhood-onset T1D. However, this finding should be interpreted cautiously, as residual confounding cannot be ruled out, and maternal smoking is associated with numerous serious adverse health consequences.