Intra-uterine growth retardation and limb deformities produced by neuromuscular blocking agents in the rat fetus.

Intra-uterine growth retardation and limb deformities, resembling clubfoot, were produced by tubocuararine chloride, and by toxiferine, when administered to the rat fetus between the 16th and 19th day of gestation. These effects were associated in some fetuses, but were not sex-linked. Fetuses in the middle part of the uterine horn were observed to be more vulnerable. Placentae of the affected fetuses were smaller in size and weight at birth. Direct toxic effects of the drug on the fetus and/or on the placenta, along with immobilization of the fetus in utero due to the neuromuscular blocking action of the drugs, seem responsible for these effects. These finding warrant proper caution and care in administering such drugs to women, even as late as the third trimester of pregnancy.