REDUCED RECURRENCE OF OROFACIAL CLEFTS AFTER PERICONCEPTIONAL SUPPLEMENTATION WITH HIGH-DOSE FOLIC-ACID AND MULTIVITAMINS

To assess effects of periconceptional multivitamin and folic-acid supplementation on recurrence of cleft lip with or without cleft palate (CL+/-P), we prospectively evaluated 221 pregnancies in women at risk of a child with CL+/-P. The 10-step protocol included multivitamin supplementation with SPOFAVIT (A, B1, B2, B6, C, D3, E, nicotinamide, calcium pantothenicum) and folic acid (10 mg/day), beginning greater than or equal to 2 months before planned conception and continuing for greater than or equal to 3 months thereafter. A comparison group comprised 1,901 women at risk of a child with CL+/-P who received no supplementation and gave birth within the same period as the study group. In the supplemented group, 3 of 214 informative pregnancies ended with infants with CL+/-P, a 65.4% decrease (observed versus expected value -5.67; P = 0.031, Fisher's exact test); the expected value of 8.7 was calculated based on the incidence of cleft among first-degree relatives among the comparison group. Subset analysis by proband's sex, severity of CL+/-P, and both variables showed highest supplementation efficacy in probands with unilateral cleft (82.6% decrease, P = 0.024, Fisher's exact test). No efficacy was observed for female probands with bilateral CL+/-P. Generally, efficacy was greater for subgroups with unilateral than with bilateral cleft and for male than female probands. These findings confirm the need for a randomized, double-blind, controlled multicenter trial to establish whether periconceptional vitamin supplementation prevents CL+/-P and, if it does, whether the effective agent is folic acid or multivitamins, or both combined. (C) 1995 Wiley-Liss, Inc.