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High Dosage Folic Acid Supplementation, Oral Cleft Recurrence and Fetal Growth
Journal article   Open access   Peer reviewed

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

George L Wehby, Têmis Maria Félix, Norman Goco, Antonio Richieri-Costa, Hrishikesh Chakraborty, Josiane Souza, Rui Pereira, Carla Padovani, Danilo Moretti-Ferreira and Jeffrey C Murray
International journal of environmental research and public health, Vol.10(2), pp.590-605
02/2013
DOI: 10.3390/ijerph10020590
PMCID: PMC3635165
PMID: 23380913
url
https://doi.org/10.3390/ijerph10020590View
Published (Version of record) Open Access

Abstract

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.
cleft lip nutrition vitamins pregnancy oral clefts Brazil cleft palate folic acid birth defects prevention NCT00397917

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