Folic acid-containing supplement consumption during pregnancy and risk for oral clefts: a meta-analysis.
BACKGROUND
There is equivocal evidence in the published literature that folic acid supplementation during pregnancy may protect against the common congenital anomalies cleft lip with or without cleft palate (CLP) and cleft palate alone (CP). We undertook this meta-analysis to test the hypothesis that nonsyndromic oral cleft birth prevalences are different for those whose mothers took folic acid-containing supplements and for those whose mothers did not.


METHODS
Human studies published in English were identified through MEDLINE, bibliography reviews, and contacting experts in the field. Within strata of prospective and case-control studies, CLP, CP, and all clefts, respectively, were analyzed using either a fixed or random effects model, as appropriate. We assessed for publication bias using Begg and Mazumdar's rank correlation and Egger's regression-based tests.


RESULTS
Five prospective studies were analyzed, yielding combined relative risks of 0.51 (95% CI: 0.32, 0.95) for CLP, 1.19 (95% CI: 0.43, 3.28) for CP, and 0.55 (95% CI: 0.32, 0.95) for all clefts. Twelve case-control studies were assessed, which resulted in combined relative risks of 0.77 (95% CI: 0.65, 0.90) for CLP, 0.80 (95% CI: 0.69, 0.93) for CP, and 0.78 (95% CI: 0.71, 0.85) for all clefts.


CONCLUSIONS
In aggregate, our results support the hypothesis of a protective effect of folic acid-containing supplement intake during pregnancy on the risk for oral clefts, although this conclusion is tempered by the potential for bias and uncontrolled confounding.
Badovinac
Rachel L
RL
Department of Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts 02115, USA. rachel_badovinac@hsdm.harvard.edu
Werler
Martha M
MM
Williams
Paige L
PL
Kelsey
Karl T
KT
Hayes
Catherine
C
D002971:Cleft Lip / Q000453:epidemiology / Q000517:prevention & control*; D002972:Cleft Palate / Q000453:epidemiology / Q000517:prevention & control*; D019587:Dietary Supplements; D005260:Female; D005492:Folic Acid / Q000627:therapeutic use*; D006801:Humans; D007231:Infant, Newborn; D011247:Pregnancy; D012307:Risk Factors
D005492:Folic Acid