Folic acid-containing supplement consumption during pregnancy and risk for oral clefts: A meta-analysis

Rachel L. Badovinac, Martha M. Werler, Paige L. Williams, Karl T. Kelsey, Catherine Hayes

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)8-15
Number of pages8
JournalBirth Defects Research Part A - Clinical and Molecular Teratology
Volume79
Issue number1
DOIs
StatePublished - Jan 2007

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Cleft Palate
Folic Acid
Meta-Analysis
Pregnancy
Case-Control Studies
Publication Bias
Cleft Lip
Bibliography
MEDLINE
Parturition
Prospective Studies

Keywords

  • Cleft lip
  • Cleft palate
  • Folic acid
  • Meta-analysis

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Folic acid-containing supplement consumption during pregnancy and risk for oral clefts : A meta-analysis. / Badovinac, Rachel L.; Werler, Martha M.; Williams, Paige L.; Kelsey, Karl T.; Hayes, Catherine.

In: Birth Defects Research Part A - Clinical and Molecular Teratology, Vol. 79, No. 1, 01.2007, p. 8-15.

Research output: Contribution to journalArticle

Badovinac, Rachel L. ; Werler, Martha M. ; Williams, Paige L. ; Kelsey, Karl T. ; Hayes, Catherine. / Folic acid-containing supplement consumption during pregnancy and risk for oral clefts : A meta-analysis. In: Birth Defects Research Part A - Clinical and Molecular Teratology. 2007 ; Vol. 79, No. 1. pp. 8-15.
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abstract = "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.",
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N2 - 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.

AB - 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.

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