High Dosage Folic Acid Supplementation, Oral Cleft Recurrence and Fetal Growth

International Journal of Environmental Research and Public Health

George L. Wehby⁷  Têmis Maria Félix¹  Norman Goco²  Antonio Richieri-Costa⁸  Hrishikesh Chakraborty⁶  Josiane Souza⁴  Rui Pereira³  Carla Padovani⁹  Danilo Moretti-Ferreira⁵ 

[1] Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul 90035-903, Brazil; E-Mail:;RTI International, Research Triangle Park, NC 27709, USA; E-Mail:;Instituto Materno Infantil Prof. Fernando Figueira-CADEFI/IMIP, Recife, Pernambuco 50070-550, Brazil; E-Mail:;Centro de Atendimento Integral ao Fissurado Lábio Palatal, Curitiba, Paraná 81.050-000, Brazil; E-Mail:;Genetic Counseling Service, São Paulo State University, Botucatu, Sao Paulo 18618-000, Brazil; E-Mail:;Department of Epidemiology and Biostatistics, University of South Carolina, Columbia, SC 29208, USA; E-Mail:;Department of Health Management and Policy, University of Iowa, Iowa City, IA 52242, USA; E-Mail:;Hospital de Reabilitação de Anomalias Craniofaciais, Bauru, Sao Paulo 17.043-900, Brazil; E-Mail:;Hospital Santo Antônio: Obras Sociais Irmã Dulce, Salvador, Bahia 40.415-000, Brazil; E-Mail:

关键词: oral clefts;    cleft lip;    cleft palate;    birth defects;    folic acid;    vitamins;    prevention;    pregnancy;    nutrition;    Brazil;   

DOI  :  10.3390/ijerph10020590

来源: mdpi

【 摘 要 】

Objectives: To evaluate the effects of folic acid supplementation on isolated oral cleft recurrence and fetal growth. Patients and Methods: The study included 2,508 women who were at-risk for oral cleft recurrence and randomized into two folic acid supplementation groups: 0.4 and 4 mg per day before pregnancy and throughout the first trimester. The infant outcome data were based on 234 live births. In addition to oral cleft recurrence, several secondary outcomes were compared between the two folic acid groups. Cleft recurrence rates were also compared to historic recurrence rates. Results: The oral cleft recurrence rates were 2.9% and 2.5% in the 0.4 and 4 mg groups, respectively. The recurrence rates in the two folic acid groups both separately and combined were significantly different from the 6.3% historic recurrence rate post the folic acid fortification program for this population (p = 0.0009 when combining the two folic acid groups). The rate of cleft lip with palate recurrence was 2.9% in the 0.4 mg group and 0.8% in the 4 mg group. There were no elevated fetal growth complications in the 4 mg group compared to the 0.4 mg group. Conclusions: The study is the first double-blinded randomized clinical trial (RCT) to study the effect of high dosage folic acid supplementation on isolated oral cleft recurrence. The recurrence rates were similar between the two folic acid groups. However, the results are suggestive of a decrease in oral cleft recurrence compared to the historic recurrence rate. A RCT is still needed to identify the effect of folic acid on oral cleft recurrence given these suggestive results and the supportive results from previous interventional and observational studies, and the study offers suggestions for such future studies. The results also suggest that high dosage folic acid does not compromise fetal growth.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.