Open Access Highly Accessed Study protocol

Oral cleft prevention program (OCPP)

George L Wehby1, Norman Goco7, Danilo Moretti-Ferreira2, Temis Felix4, Antonio Richieri-Costa3, Carla Padovani5, Fernanda Queiros5, Camilla Vila Nova Guimaraes5, Rui Pereira6, Steve Litavecz7, Tyler Hartwell7, Hrishikesh Chakraborty7, Lorette Javois8 and Jeffrey C Murray1*

Author affiliations

1 University of Iowa, Iowa City, IA, USA

2 Genetic Counseling Service – Bioscience Institute, São Paulo State University, Botucatu, Sao Paulo, Brazil

3 Hospital de Reabilitação de Anomalias Craniofaciais, Bauru, Sao Paulo, Brazil

4 Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil

5 Hospital Santo Antônio- Centrinho: Obras Sociais Irmã Dulce, Salvador, Bahia, Brazil

6 Instituto Materno Infantil Prof. Fernando Figueira, Recife, Pernambuco, Brazil

7 RTI International, Durham, NC, USA

8 Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA

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Citation and License

BMC Pediatrics 2012, 12:184  doi:10.1186/1471-2431-12-184

Published: 26 November 2012

Abstract

Background

Oral 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/design

This 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.

Discussion

The 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 Identifier

NCT00397917

Keywords:
Oral clefts; Cleft lip; Cleft palate; Craniofacial anomalies; Congenital anomalies; Birth defects; Folic acid; Vitamins; Prevention