Oral cleft prevention program (OCPP)

George L Wehby,Antonio Richieri-Costa,Tyler Hartwell,Lorette Javois,Rui Pereira,Fernanda Queiros,Jeffrey C Murray,Temis Felix,Norman Goco,Camilla Vila Nova Guimaraes,Danilo Moretti-Ferreira,Steve Litavecz,Hrishikesh Chakraborty,Carla Padovani

doi:10.1186/1471-2431-12-184

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

Highlights

Introduction to study and screeningPotential subjects will be contacted to verify the age and nonsyndromic cleft lip with/without palate (NSCL/P), present the study, and assess their interest to participate and willingness to be screened to determine final eligibility
This study provides an opportunity for huge savings in 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

Summary

Introduction

Introduction to study and screeningPotential subjects will be contacted to verify the age and NSCL/P, present the study, and assess their interest to participate and willingness to be screened to determine final eligibility. The study staff will mail letters of invitation to identified potentially eligible subjects for attendance at prescheduled recruitment meetings. These meetings will take place at public facilities (e.g. health centers, schools, churches, or other public facilities) as coordinated with local community leaders. The local network of social workers may be used to visit invited subjects and confirm their intention to attend these meetings This is especially helpful for contact with potential subjects with incorrect contact information in the HRAC database. Study objectives and significance Statement of the problem Craniofacial anomalies comprise a significant component of morbid human birth defects They require surgical, nutritional, dental, speech, medical, and behavioral interventions and impose a substantial economic burden. Birth defects will eventually supplant infectious diseases and prematurity as a single major cause of morbidity and mortality in the first month of life, as has become evident in Western developed populations

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