Oral Cleft Prevention Program

Study Overview
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Brief Summary
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The purpose of this study is to asses if taking 4 mg of folic acid per day at preconception and during the first three months of pregnancy decreases the risk of having a child with cleft lip and palate compared to 0.4 mg folic acid for women who have an oral cleft or have had previously child with an oral cleft.

Detailed Description
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Cleft lip and palate is a common and burdensome birth defect that has large health ramifications and requires surgical, speech, behavioral, dental, and medical interventions. There is some evidence suggesting that taking folic acid particularly at large doses during preconception and first trimester of pregnancy may decrease the risk of oral cleft recurrence, which is the risk of having a child with an oral cleft for women who have an oral cleft or who have had a child with a cleft. However this evidence is based on study designs that are incapable of contributing the preventive effects to folic acid with adequate confidence, and the real effect of folic acid on cleft recurrence prevention remains to be identified. Taking 4 mg of folic acid per day at preconception and first trimester of pregnancy has also been shown to prevent the recurrence of neural tube defects by up to 70%, providing further support to evaluate this intervention for oral cleft recurrence. This study evaluates the effects of supplementation with 4 versus 0.4 mg of folic acid per day at preconception and during the first three months of pregnancy on recurrence of cleft lip and palate. Up to 6000 women will be randomly assigned to 4 versus 0.4 mg groups. The primary aim is to compare the recurrence rates in the offspring of trial mothers in the two groups. Secondary aims are to compare the two groups on several outcomes including miscarriage, twinning, pre-eclampsia, serum and red cell folate levels, severity of oral clefts and occurrence of other birth defects in the offspring of trial mothers, and birth weight and gestational age of trial babies, and to compare the recurrence in the two groups to that in historic controls.

Official Title
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Oral Cleft Prevention Program

Conditions
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Cleft Lip, Cleft Palate

Intervention / Treatment
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* Drug: Folic acid: 4 mg versus 0.4 mg per day


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women with cleft lip with/out palate (CLP), 16 to 45 years of age registered at the study clinics in Brazil or Women (16 to 45 years of age) with at least one natural child of any age with CLP registered at the study clinics. Women must reside in the catchment area of the study, which includes the states where the study clinics are located and surrounding states. Exclusion Criteria: Consanguineous couples (up to third degree, i.e. first cousins or closer). Pregnany at the time of recruitment. Women will be recontacted later at an appropriate time for participation in the study. Couples either one of which have been sterilized. Taking any form of seizure medication. Planning to move outside of the study catchment area within the next year. B12 deficiency (<174 pg/mL or 129.15 pmol/L). Being allergic to folic acid.

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 400 micrograms of folic acid<br>Blinded study with two arms one of 400ug in arm 1 | Drug: Folic acid: 4 mg versus 0.4 mg per day<br>* Folic acid<br>|
| Active Comparator: 4mg of folic acid<br>Second arm is 4mg of folic acid in arm 2 | Drug: Folic acid: 4 mg versus 0.4 mg per day<br>* Folic acid<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence of cleft lip and palate |  | 3 months |