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.