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Oral Cleft Prevention Trial in Brazil

Phase 3
16 Years
45 Years
Not Enrolling
Cleft Lip, Cleft Palate

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Trial Information

Oral Cleft Prevention Trial in Brazil

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.

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.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Prevention

Outcome Measure:

Recurrence of nonsyndromic cleft lip with or without cleft palate (NSCL/P) in offspring of trial mothers

Principal Investigator

Jeff Murray, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Iowa


United States: Federal Government

Study ID:

GN 04 Aim III



Start Date:

January 2004

Completion Date:

April 2007

Related Keywords:

  • Cleft Lip
  • Cleft Palate
  • Cleft palate
  • Cleft lip
  • Folic acid
  • Global Network
  • Maternal and child health
  • International
  • Women's health
  • Brazil
  • Brasil
  • Latin America
  • Congenital defects
  • Pregnancy
  • Cleft Lip
  • Cleft Palate