Maternal Alcohol Consumption during Pregnancy and the Risk of Orofacial Clefts in Infants: a Systematic Review and Meta-Analysis

Background The teratogenic effects of maternal alcohol consumption during pregnancy include anomalies of craniofacial structures derived from the cranial neural crest cells. The presence of specific craniofacial anomalies contributes to the diagnosis of fetal alcohol spectrum disorders. Cleft lip and palate [orofacial clefts (OFCs)], also derived from the cranial neural crest cells, are common congenital anomalies, but their relationship with prenatal alcohol consumption is unknown. Methods To evaluate the association between maternal consumption of alcohol during pregnancy and the occurrence of OFCs in infants, we conducted a systematic review and meta-analyses of published studies. We examined the associations between any alcohol consumption, binge level drinking, and heavy and moderate levels of consumption vs. no or low levels of consumption. Results After screening 737 publications, we identified 33 studies (23 case-control and 10 cohort studies). There was considerable heterogeneity in individual study design, quality measures and study results. Findings from random effects meta-analyses suggest no relationship between prenatal alcohol consumption and the occurrence of OFCs {pooled odds ratios for any alcohol intake and binge level drinking respectively: cleft lip with or without cleft palate 1.00 [95% confidence interval (CI) 0.86, 1.16] from 18349 participants in 13 studies, 1.04 [95% CI 0.87, 1.24] [8763 individuals, 4 studies]; cleft palate only 1.05 [95% CI 0.92, 1.21] [21459 individuals, 17 studies], 0.94 [95% CI 0.74, 1.21] [7730 participants, 4 studies]}. Conclusions While we found no association between alcohol consumption during pregnancy and OFCs in infants, the influence of study design, particularly in relation to alcohol exposure measurement and OFC ascertainment cannot be ignored.