BMJ, doi: 10.1136/bmj.39079.618287.0B, (Published 26 January 2007)

RESEARCH

Folic acid supplements and risk of facial clefts: national population based case-control study

Allen J Wilcox ^1*, Rolv Terje Lie ², Kari Solvoll ³, Jack Taylor ¹, D Robert McConnaughey ⁴, Frank Åbyholm ⁵, Hallvard Vindenes ⁶, Stein Emil Vollset ², Christian A Drevon ³

¹ Epidemiology Branch, National Institute of Environmental Health Sciences/NIH, Durham, NC 27709, USA
² Department of Public Health and Primary Health Care, Section for Epidemiology and Medical Statistics, University of Bergen, Norway
³ Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway
⁴ WESTAT, Durham, NC
⁵ Department of Plastic Surgery, Rikshospitalet, Oslo
⁶ Department of Plastic Surgery, Haukeland University Hospital, Bergen

^* Correspondence to: wilcox{at}niehs.nih.gov.

Objective To explore the role of folic acid supplements, dietary folates, and multivitamins in the prevention of facial clefts.

Design National population based case-control study.

Setting Infants born 1996-2001 in Norway.

Participants 377 infants with cleft lip with or without cleft palate; 196 infants with cleft palate alone; 763 controls.

Main outcome measures Association of facial clefts with maternal intake of folic acid supplements, multivitamins, and folates in diet.

Results Folic acid supplementation during early pregnancy (400 µg/day) was associated with a reduced risk of isolated cleft lip with or without cleft palate after adjustment for multivitamins, smoking, and other potential confounding factors (adjusted odds ratio 0.61, 95% confidence interval 0.39 to 0.96). Independent of supplements, diets rich in fruits, vegetables, and other high folate containing foods reduced the risk somewhat (adjusted odds ratio 0.75, 0.50 to 1.11). The lowest risk of cleft lip was among women with folate rich diets who also took folic acid supplements and multivitamins (0.36, 0.17 to 0.77). Folic acid provided no protection against cleft palate alone (1.07, 0.56 to 2.03).

Conclusions Folic acid supplements during early pregnancy seem to reduce the risk of isolated cleft lip (with or without cleft palate) by about a third. Other vitamins and dietary factors may provide additional benefit.

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(Accepted 18 December 2006)
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Rapid Responses:

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Data-driven post-hoc choices

Johannes C. van der Wouden, et al.
bmj.com, 22 Mar 2007 [Full text]

Lack of evidence of a protective effect of folic acid against cleft lip.

Fionnuala Cooney
bmj.com, 21 Oct 2007 [Full text]

The authors respond.

Allen J Wilcox, et al.
bmj.com, 25 Oct 2007 [Full text]