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

International Journal of Environmental Research and Public Health
Q2
Feb 2013
Citations:38
Influential Citations:3
Interventional (Human) Studies
84
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Enhanced Details

Methods
Double-blind randomized controlled trial conducted at six craniofacial clinics in Brazil. Participants were women aged 16–45 years with nonsyndromic/isolated oral clefts or who had at least one previous child with such clefts and resided in the study catchment area. A total of 2,508 women were randomized to two folic acid regimens.
Intervention
Daily oral folic acid supplementation; two regimens: 4 mg/day (high dose) and 0.4 mg/day (low dose); started before pregnancy and continued through the first trimester if pregnant, or until end of participation if not pregnant; pills identical in appearance and taken as a single daily pill.
Results
Recurrence rates were 2.9% in the 0.4 mg group and 2.5% in the 4 mg group (p=0.59). The combined recurrence rate was 2.7%; excluding a Van der Woude syndrome case reduces to 1.6%. No significant differences between groups in birth weight, gestational age, length at birth, head circumference, Apgar scores, or preeclampsia. Compliance was high (~74%), and folate biomarkers were higher in the 4 mg group. Authors conclude that high-dose folic acid did not reduce recurrence versus low-dose and did not worsen fetal growth or perinatal outcomes; results suggest low-dose folic acid may be sufficient for recurrence risk reduction, but the study was underpowered to detect smaller differences and larger trials are needed. High periconceptional folic acid appears safe.
Limitations
Small sample size with lower-than-expected enrollment; underpowered to detect modest differences in recurrence; early termination of non-pregnant recruitment; use of historic controls for some comparisons; potential confounding from folate intake from other sources; limited generalizability to Brazilian clinical settings; recruitment strategy changes during the trial.

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 s...