title: High dosage folic acid supplementation, oral cleft recurrence and fetal growth.
abstract: OBJECTIVE
  To evaluate the effects of folic acid supplementation on isolated oral cleft recurrence and fetal growth.
  
  
  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.
authors: Department of Health Management and Policy, University of Iowa, Iowa City, IA 52242, USA. jeff-murray@uiowa.edu.
authors: George L
authors: GL
authors: Wehby
authors: Têmis Maria
authors: TM
authors: Félix
authors: Norman
authors: N
authors: Goco
authors: Antonio
authors: A
authors: Richieri-Costa
authors: Hrishikesh
authors: H
authors: Chakraborty
authors: Josiane
authors: J
authors: Souza
authors: Rui
authors: R
authors: Pereira
authors: Carla
authors: C
authors: Padovani
authors: Danilo
authors: D
authors: Moretti-Ferreira
authors: Jeffrey C
authors: JC
authors: Murray
mesh_terms: D000328:Adult; D001938:Brazil; D002971:Cleft Lip / Q000517:prevention & control*; D002972:Cleft Palate / Q000517:prevention & control*; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D005492:Folic Acid / Q000008:administration & dosage*; D006801:Humans; D011247:Pregnancy; D014803:Vitamin B Complex / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D014803:Vitamin B Complex; D005492:Folic Acid
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