Maternal Folic Acid Supplementation and the Risk of Oral Clefts in Offspring

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There is controversial evidence from the literature regarding the protective effect of folic acid supplementation during pregnancy against orofacial clefts. The authors undertook this meta-analysis to assess whether folate supplementation during pregnancy can reduce the risk of nonsyndromic cleft lip with or without cleft palate (CL/P) and cleft palate only (CPO) in infants.


Eligible articles were identified by searching databases, including PubMed, Medline, Scopus, ISI (Web of Knowledge) to September 2017. A meta-analysis was performed to evaluate the effects of maternal supplementation on oral clefts. Odds ratios (ORs) and 95% confidence intervals (CIs) were pooled using Stata software. Publication bias was assessed by the Begg and Egger test. (Registration ID: CRD42018083922)


Out of the 1630 articles found in the authors’ initial literature searches, 6 cohort studies, and 31 case-control studies were included in the authors’ final meta-analysis. The results of the main analysis revealed that maternal folate supplementation was associated with a modest but statically significant decreased risk of all cleft subtypes (OR = 0.69, 95% CI: 0.60, 0.78). Folic acid intake alone was inversely associated with CL/P (OR = 0.73, 95% CI: 0.62–0.85,) but to a lesser extent than CPO (OR = 0.75, 95% CI = 053–1.04). Multivitamin intake had a significant protective effect for CL/P (OR = 0.65 95% CI = 0.55–0.80) as well as CPO (OR = 0.69, 95% CI = 0.53–0.90).


Our results indicate that maternal supplementation in early pregnancy reduces the risk of nonsyndromic CL/P and CPO in infants. These data can serve to reassure women planning a pregnancy to consume multivitamins during the periconception period to protect against oral clefts.

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