Oral Cleft Prevention Trial in Brazil

Study Overview
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Brief Summary
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Cleft lip and palate are a significant component of morbid human birth defects in the developing world. By supplementing a high-risk group of women with folic acid (4.0 mg versus 0.4 mg) from preconception and continuing throughout the first 3 months of pregnancy in the state of Sao Paulo, Brazil, this study aims to reduce the recurrence of cleft lip and palate.

Detailed Description
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Craniofacial anomalies and cleft lip with or without cleft palate (CL/P) are a model for the impact of birth defects on fetal and neonatal health directly and maternal health indirectly. Craniofacial anomalies comprise a significant component of morbid human birth defects. The primary hypothesis is that folic acid supplementation of 4mg/day at preconception and during the first three months of pregnancy will decrease the recurrence of nonsyndromic cleft lip with or without clef palate (NSCL/P) in a high-risk group of women when compared to women taking 0.4 mg per day of folic acid. The total sample will include 2,000 women (that either have NSCL/P or that have at least one child with NSCL/P) randomly assigned to the 4 mg versus 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 primary outcome assessed is the rate of recurrences of NSCL/P in offspring of the trial mothers in each of the two study groups. Secondary outcomes include recurrence of NSCL/P compared to a historical control group; serum and red cell folate levels; severity of NSCL/P in offspring of trial mothers; twinning rate; miscarriage rate; preeclampsia; rates of other birth defects; birth weight; and gestational age. The sample size was based on historic tables of birth rates and the rates of cleft occurrences. The study hypothesizes that a total of 2000 subjects will be enrolled during a 2.5 year period; a dropout rate of 10%; birth rate for group A (women with NSCL/P) of 10% and a rate of 12% for group B (women with at least one child with NSCL/P); risk of cleft for group A is 7% and for group B is 4%; one-sided test with continuity correction.

Official Title
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Oral Cleft Prevention Trial in Brazil

Conditions
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Cleft Lip, Cleft Palate

Intervention / Treatment
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* Drug: Folic acid (0.4mg vs. 4.0mg)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All women must reside in the state where the clinic is located. Women with NSCL/P who attend the craniofacial clinics, who are 16 to 45 years of age (after age 45 fecundity decreases substantially)who attend the craniofacial clinic for their care. Women (ages 16 to 45 years of age) who have at least one natural child of any age with NSCL/P who receives care at the participating craniofacial clinics. Exclusion Criteria: Cases resulting from consanguineous couples (first, second, and third degree, i.e., first cousins or closer). Couples where at least one of the two is definitely sterilized. Women on anti-epileptic drugs. Women who are pregnant. Women who are planning to move outside of the state where the clinic is located within the next year. Women who are planning to move outside of Sao Paulo state within the next year. Women who have B12 deficiency (B12 level is below 174 pg/ml or 134.328 pmol/L). Women who have an allergy 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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Accepts Healthy Volunteers

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: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Folic acid (0.4mg vs. 4.0mg)|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence of nonsyndromic cleft lip with or without cleft palate (NSCL/P) in offspring of trial mothers |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence of NSCL/P compared to a historical control group; Overall and high versus low dose |  |  | 
| Serum and red cell folate levels |  |  | 
| Severity of NSCL/P in offspring of trial mothers |  |  | 
| Twinning rate |  |  | 
| Miscarriage rate |  |  | 
| Preeclampsia |  |  | 
| Rates of other birth defects |  |  | 
| Birth weight |  |  | 
| Gestational age |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cleft palate, Cleft lip, Folic acid, Global Network, Maternal and child health, International, Women's health, Brazil, Brasil, Latin America, ECLAMC, Congenital defects, Pregnancy