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Folic Acid Use and Nonsyndromic Orofacial Clefts in China: A Prospective Cohort Study

Li, Songa; Chao, Annb; Li, Zhuc; Moore, Cynthia A.b; Liu, Yinghuic; Zhu, Jianghuic; Erickson, J. Davidb; Hao, Lingc; Berry, Robert J.b

doi: 10.1097/EDE.0b013e31824d0349
Pregnancy

Background: Questions remain about the effectiveness, dose, and timing of folic acid in preventing orofacial clefts. Case-control studies report conflicting results. There have been no cohort studies of orofacial clefts and the use of folic acid without other vitamins.

Methods: In a prospective cohort of 240,244 women enrolled between 1993 and 1995 in 1 northern and 2 southern provinces in China, we examined the risk of nonsyndromic cleft lip with or without cleft palate (CL/P) and cleft palate alone (CP) in relation to maternal use of 400 μg of folic acid without other vitamins.

Results: Daily use of 400 μg of folic acid without other vitamins, started before the last menstrual period (LMP), was associated with reduced risk of CL/P with adjusted rate ratio (aRR) of 0.69 (95% confidence interval = 0.55–0.87). The greatest reduction in risk was observed in the north among daily users who began taking folic acid pills before LMP (aRR = 0.21 [0.10–0.44]); in the south there was marginal reduction in risk (aRR = 0.81 [0.63–1.05]). No evidence of reduced CL/P risk was observed among women who started folic acid pills on or after their LMP. No persuasive evidence for reduction in CP risk was seen with folic acid pill use at any time.

Conclusion: Daily maternal consumption of 400 μg of folic acid without other vitamins, started before mother's LMP, was associated with a reduced risk of CL/P in babies born in a high-prevalence region of China.

From the aDepartment of Pediatrics, Peking University Third Hospital, Beijing, People's Republic of China; bDivision of Birth Defects and Developmental Disabilities, National Center for Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA; and cDepartment of Health Care Epidemiology, National Center for Maternal and Infant Health, Peking University Health Science Center, Beijing, People's Republic of China.

Submitted 7 January 2011; accepted 9 December 2011; posted online 13 March 2012.

Supported by Cooperative Agreement award U11/CCU015586-02 between the U.S. Centers for Disease Control and Prevention and Peking University, to provide surveillance, research, and health services evaluation directed toward the prevention of birth defects. The authors reported no other financial interests related to this research.

Supplemental digital content is available through direct URL citations in the HTML and PDF versions of this article (www.epidem.com). This content is not peer-reviewed or copy-edited; it is the sole responsibility of the author.

Correspondence: Robert J. Berry, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Atlanta, GA 30333. E-mail: RJBerry@cdc.gov.

© 2012 Lippincott Williams & Wilkins, Inc.