Abstract
Objective: We report on the risk of miscarriage with high- and low-dosage periconceptional folic acid (FA) supplementation from a double-blind randomized clinical trial for prevention of orofacial cleft recurrence in Brazil.
Methods: Women at risk of recurrence of orofacial clefts in their offspring were randomized into high (4 mg/day) and low (0.4 mg/day) doses of FA supplementation. The women received the study pills before pregnancy, and supplementation continued throughout the first trimester. Miscarriage rates were compared between the two FA groups and with the population rate.
Results: A total of 268 pregnancies completed the study protocol, with 141 in the 4.0-mg group and 127 in the 0.4-mg group. The miscarriage rate was 14.2% in the low-dose FA group (0.4 mg/day) and 11.3% for the high-dose group (4 mg/day) (P=0.4877). These miscarriage rates are not significantly different from the miscarriage rate in the Brazilian population, estimated to be around 14% (P=0.311).
Conclusions: These results indicate that high-dose FA does not increase miscarriage risk in this population and add further information to the literature on the safety of high FA supplementation for prevention of birth defect recurrence.
This study was funded by grant U01HD040561 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and grant U01DE017958-05 from the National Institute of Dental and Craniofacial Research (NIDCR). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIDCR or NICHD.
Brazilian participating sites: Obras Sociais Irmã Dulce (OSID), Salvador (BA); Hospital de Reabilitação de Anomalias Craniofaciais (HRAC)-Bauru (SP), Centro de Atendimento Integral ao Fissurado Lábio-palatal (CAIF), Curitiba (PR); Fundação para Reabilitação das Deformidades Crânio-Faciais (FUNDEF), Lajeado (RS); Hospital das Clínicas de Porto Alegre (RS); and Centro de Atenção aos Defeitos da Face do IMIP, Recife (PE).
Fernanda Queirós’ research was supported by a fellowship from CAPES/Fulbright (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil/Fulbright Program for non-US citizens, USA; 15087696-1836/07-2).
Conflict of interest statement
Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article.
Ethics approval: The study was approved by the Brazilian National Committee for Ethics in Research (Comissão Nacional de Ética em Pesquisa–CONEP) on September 20, 2001 (ref. no. 1130/2001).
Authors’ contributions: JCM and GLW developed the concept and study design. The data were gathered by CVN, FQ, TMF, LL, and CP. CVN, GLW, and FQ were responsible for the overall drafting of the article. HC and GLW conducted the analysis and contributed to the interpretation of the data along with JM, CVN, FQ, NG, EV, and CP. All authors had final approval of the article to be published.
References
[1] Berry RJ, Li Z, Erickson JD, Li S, Moore CA, Wang H, et al. Prevention of neural-tube defects with folic acid in China. China–U.S. Collaborative Project for Neural Tube Defect Prevention. N Engl J Med. 1999;341:1485–90.10.1056/NEJM199911113412001Search in Google Scholar
[2] Cecatti JG, Guerra GV, Sousa MH, Menezes GM. Abortion in Brazil: a demographic approach. Rev Bras Ginecol Obstet. 2010;32:105–11.10.1590/S0100-72032010000300002Search in Google Scholar
[3] Czeizel AE, Dudas I, Metneki J. Pregnancy outcomes in a randomised controlled trial of periconceptional multivitamin supplementation. Final report. Arch Gynecol Obstet. 1994;255:131–9.10.1007/BF02390940Search in Google Scholar
[4] De-Regil LM, Fernandez-Gaxiola AC, Dowswell T, Pena-Rosas JP. Effects and safety of periconceptional folate supplementation for preventing birth defects. Cochrane Database Syst Rev. 2010;(10):CD007950.10.1002/14651858.CD007950.pub2Search in Google Scholar
[5] Genisca AE, Frias JL, Broussard CS, Honein MA, Lammer EJ, Moore CA, et al. Orofacial clefts in the National Birth Defects Prevention Study, 1997–2004. Am J Med Genet A. 2009;149A:1149–58.10.1002/ajmg.a.32854Search in Google Scholar
[6] Gindler J, Li Z, Berry RJ, Zheng J, Correa A, Sun X, et al. Folic acid supplements during pregnancy and risk of miscarriage. Lancet. 2001;358:796–800.10.1016/S0140-6736(01)05969-4Search in Google Scholar
[7] MRC Vitamin Study Research Group. Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group. Lancet. 1991;338:131–7.10.1016/0140-6736(91)90133-ASearch in Google Scholar
[8] Rosenberg IH. Science-based micronutrient fortification: which nutrients, how much, and how to know? Am J Clin Nutr. 2005;82:279.10.1093/ajcn/82.2.279Search in Google Scholar
[9] Wehby GL, Murray JC. Folic acid and orofacial clefts: a review of the evidence. Oral Dis. 2010;16:11–9.10.1111/j.1601-0825.2009.01587.xSearch in Google Scholar PubMed PubMed Central
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