Cumulative evidence for the association between maternal hypertension and cleft lip and palate in offspring: a systematic review and meta-analysis

Objective Maternal hypertension has serious maternal and neonatal consequences. Evidence regarding the relationship between maternal hypertension and cleft lip and palate in offspring is limited and inconsistent. Therefore, we conducted a meta-analysis to evaluate the relationship between maternal hypertension and the risk of cleft lip and palate in offspring. Methods We systematically searched the following English electronic databases to identify relevant observational studies for our analysis: PubMed, Cochrane Library, Embase and Web of Science, supplemented by a manual reference researches. Study screening, data extraction, and risk-of-bias assessments were conducted independently by two researchers. A meta-analysis was performed using Stata 18.0 and Revman 5.3. Heterogeneity (I 2 statistics) and sensitivity analyses were carried out to ensure analytical rigor and robustness. Results The meta-analysis ultimately included 12 eligible studies, comprising 4,407,254 participants. Under the random-effects model, the analysis indicated an association between maternal hypertension and cleft lip and palate in offspring [OR = 1.44, 95% CI = 1.26, 1.64, p = 0.01]. Both maternal gestational hypertension and preeclampsia were associated with an increased risk of cleft lip and palate in offspring (gestational hypertension: OR = 1.36, 95% CI = 1.06, 1.74, p = 0.01, preeclampsia: OR = 2.10, 95% CI = 1.11, 3.96, p = 0.02). Sensitivity analyses supported the robustness of our results. Conclusion With our meta-analysis, we provide evidence for an association between maternal hypertension (particularly gestational hypertension and preeclampsia) and CLP in children. Given that residual confounding cannot be entirely excluded, caution is warranted in interpreting the conclusions of this study. More high-quality studies are needed to establish whether the association with maternal hypertension is causal. Systematic Review Registration PROSPERO CRD420251152806.