Epidemiological assessment of misoprostol teratogenicity

To verify if any of the 15 congenital defects already reported in association with misoprostol can be found within an epidemiological registry of congenital defects.

Case-control study including case-sick and case-health controls.

Comparison of misoprostol exposure for each specific defect, using the exposure for the rest of defects as a reference group.

Four thousand six hundred seventy-three consecutive newborn infants with malformations of unknown aetiology, in the Latin American Collaborative Study of Congenital Malformation.

There was no difference in exposure rate between the malformed (34/4,673) and nonmalformed (23/4,980) newborns. Four of the five more frequently cited defects in the literature were found to be in excess: constriction ring, terminal transverse-limb defects, hydrocephalus, and arthrogryposis. Equinovarus feet had a normal frequency in our study. Thirteen different defects not described in the literature were seen in our misoprostol exposed cases, but only holoprosencephaly and bladder exstrophy significantly exceeded the expected number.

The confirmation from an epidemiological registry of an association for four of the five more commonly observed congenital defects among misoprostol exposed children described in the literature seems indicative of a real teratogenic effect. The defects are of vascular disruption type. However, additional attempts to achieve abortion could not be excluded as a concurrent contribution.