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J Craniofac Surg. 2018 Sep;29(6):e534-e541. doi: 10.1097/SCS.0000000000004488.

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

Author information

Dental Research Center.
School of Dentistry.
Social Determinants of Health Research Center.
Department of Pediatric Dentistry, Dental Research Center School of Dentistry.
Department of Orthodontic, Dental Material Research Center, School of Dentistry, Mashhad University of Medical Science, Mashhad, Iran.



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) RESULTS:: 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.

[Indexed for MEDLINE]

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