Congenital Abnormalities in Brazilian Children in the First Trimester of Pregnancy

ABSTRACT & COMMENTARY

Synopsis: Misoprostol use in early pregnancy is associated with congenital anomalies.

Source: Gonzalez CH, et al. Lancet 1998;351: 1624-1627.

Several previous articles have associated misoprostol use in early pregnancy with various abnormalities in newborns. While the drug is contraindicated for use in pregnant women in the United States, it is commonly used to induce illegal abortion in many other countries.

Gonzalez and colleagues used a series of 42 consecutive infants with birth defects who were known to be exposed to misoprostol in early pregnancy as the material for this paper. Each infant was examined by several different clinicians in an attempt to ascertain all major congenital anomalies.

Equinovarus with cranial-nerve deficiencies was the most common phenotype observed (17 cases). Ten other infants had equinovarus and significant arthrogryposis. Five children had only significant, lower extremity arthrogryposis and no cranial-nerve defects. The cranial-nerves most commonly involved (when they were) were V, VI, and VII.

It was possible to determine the amount of misoprostol used in 39 of the 42 cases. The most common dose was 800 mcg, but dosages ranged from 200 mcg to 16,000 mcg. Oral, oral and vaginal, and intravenous injections were all used as routes of administration. In all cases, the drug was taken during the first trimester of pregnancy.

Gonzalez et al proposed several mechanisms for the etiology of these congenital anomalies. In general, they seemed to be due to disruption of the vascular supply to the limbs in the cases of arthrogryposis. Brain stem ischemia and/or hemorrhage into the brain stem is proposed as the etiology for the cranial nerve defects. The abnormalities seen in these infants are consistent with those produced in research animals.

COMMENT BY KENNETH NOLLER, MD

Misoprostol is contraindicated for use in pregnancy in the United States. Nonetheless, it is being used with increasing frequency in association with methotrexate for inducing early abortion. While the fact that congenital anomalies are associated with the use of methotrexate in early pregnancy is widely known, many clinicians recognize that misoprostol is also a teratogenic agent. Although it rarely occurs, an occasional patient will change her mind concerning an elective termination as the process starts. Should any patient receive misoprostol and then carry the pregnancy to term, counseling regarding the risk of congenital anomalies should be completed.

Unfortunately, this article cannot give us an idea concerning the magnitude of the risk of misoprostol-induced congenital anomalies. That is, though they examined 42 cases of misoprostol-associated anomalies, we have no idea how many women received misoprostol and delivered an infant that was unaffected. It is unlikely that we will ever have good data regarding the risk. One study estimated the risk of cranial-nerve deficit to be elevated more than 25-fold.