Oral cleft prevention program (OCPP)

Abstract

BackgroundOral clefts are one of the most common birth defects with significant medical, psychosocial, and economic ramifications. Oral clefts have a complex etiology with genetic and environmental risk factors. There are suggestive results for decreased risks of cleft occurrence and recurrence with folic acid supplements taken at preconception and during pregnancy with a stronger evidence for higher than lower doses in preventing recurrence. Yet previous studies have suffered from considerable design limitations particularly non-randomization into treatment. There is also well-documented effectiveness for folic acid in preventing neural tube defect occurrence at 0.4 mg and recurrence with 4 mg. Given the substantial burden of clefting on the individual and the family and the supportive data for the effectiveness of folic acid supplementation as well as its low cost, a randomized clinical trial of the effectiveness of high versus low dose folic acid for prevention of cleft recurrence is warranted.Methods/designThis study will assess the effect of 4 mg and 0.4 mg doses of folic acid, taken on a daily basis during preconception and up to 3 months of pregnancy by women who are at risk of having a child with nonsyndromic cleft lip with/without palate (NSCL/P), on the recurrence of NSCL/P. The total sample will include about 6,000 women (that either have NSCL/P or that have at least one child with NSCL/P) randomly assigned to the 4 mg and the 0.4 mg folic acid study groups. The study will also compare the recurrence rates of NSCL/P in the total sample of subjects, as well as the two study groups (4mg, 0.4 mg) to that of a historical control group.The study has been approved by IRBs (ethics committees) of all involved sites. Results will be disseminated through publications and presentations at scientific meetings.DiscussionThe costs related to oral clefts are high, including long term psychological and socio-economic effects. This study provides an opportunity for huge savings in not only money but the overall quality of life. This may help establish more specific clinical guidelines for oral cleft prevention so that the intervention can be better tailored for at-risk women.ClinicalTrials.gov IdentifierNCT00397917

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

“…This study aimed at testing the effect of 4 mg folic acid taken daily before pregnancy throughout the first trimester by women who were themselves born with a cleft or had had a prior child with a cleft on recurrence of clefting in a subsequent child compared to taking the currently recommended 0.4 mg dose [14]. A placebo control group was not used, as a low dose of folic acid had already been recommended as a standard vitamin therapy for women during preconception and pregnancy period for prevention of NTDs.…”

“…The study had a double-blinded randomized design, where both investigators and participants were blinded to the study group assignment [14]. Participants were randomly assigned before pregnancy to the two study groups of taking 4 mg or 0.4 mg pills of folic acid that were identical in appearance.…”

“…Participants who had a delay in menstruation of 14 days or more at baseline underwent a pregnancy test before randomization; only those with a negative test were randomized [14]. After randomization, all participants were asked to take a single pill of 4 mg or 0.4 mg of folic acid daily throughout the first trimester of pregnancy if they became pregnant or until end of participation in the study if they did not become pregnant.…”

“…Participants confirmed to be pregnant were advised by the study staff to stop taking the study pills at the end of the first trimester of pregnancy [14]. There were no restrictions on participants taking other supplements and vitamins before or during pregnancy as recommended by their physicians.…”

“…The Oral Cleft Prevention Program (OCPP) was as a double blinded RCT to assess the effect of high-dose versus low-dose folic acid supplementation on oral cleft recurrence among children of Brazilian women [14]. We describe the OCPP’s design and report the findings as of December 2009 after the trial was halted due to lower than expected enrollment and pregnancy rates among study participants.…”