Association of high-dose bifonazole administration during early pregnancy and severe limb reduction defects in the newborn.

Neonatal limb reduction defects may be caused by exposure to an external agent. The azole derivatives are used in the treatment of systemic and dermal mycoses. Their relative teratogenic risk is still controversial. We describe two newborns with severe limb defects who were exposed to high doses of oral (an unacceptable route) and/or intravaginal bifonazole during the entire first trimester of pregnancy. Although only two cases are insufficient to establish a relationship, our data suggest that maternal intake of bifonazole in early pregnancy poses a risk of morphogenic malformations. The literature suggests several possible mechanisms.