Periconceptional maternal sleep disturbances and risk of congenital defects: A meta-analysis

Objectives: Sleep is vital for maternal-fetal health, yet periconceptional sleep disturbances (PSDs) remain overlooked as potential contributors to congenital defects (CDs). While prior meta-analysis examined PSDs and adverse birth outcomes, none have specifically assessed their association with CDs in offspring. Methods: A meta-analysis of observational studies was conducted using PubMed and Medline databases. Eligible studies assessed maternal PSDs, including poor sleep quality, insomnia, obstructive sleep apnea, and sleep-disordered breathing. Pooled relative effect estimates (expressed as odds ratios (ORs) with 95% confidence intervals [CIs]) were estimated using a random-effects model, followed by sensitivity and subgroup analysis. Heterogeneity and publication bias were evaluated using I 2 statistics, Egger’s test, and Begg’s funnel plots. Results: Of 553 articles screened, five studies (two case-controls and three cohorts), comprising 6,201 cases and over 9 million controls, met the inclusion criteria. Meta-analysis revealed a significant association between maternal PSDs and increased odds of CDs (pooled OR = 2.16, 95% CI: 1.57–2.98; p = 0.003), with moderate heterogeneity ( I 2 = 50%; p = 0.09). Subgroup analysis showed a significant association in cohort studies (OR = 1.88, 95% CI: 1.36–2.60; p = 0.014) with low heterogeneity ( I 2 = 17.5%; p = 0.29). However, this association was not observed in case–control studies ( p = 0.13). Sensitivity analyses confirmed the robustness of findings, and no evidence of publication bias was detected. Conclusion: This is the first meta-analysis to demonstrate a significant association between maternal PSDs and CDs and underscores the urgent need for targeted interventions and future research to explore causal mechanisms.