The effects of nifedipine on pregnancy outcome and morphology of the placenta, uterus, and cervix during late pregnancy in the rat

OBJECTIVE: Although the calcium antagonist nifedipine has been reported to suppress preterm labor, little is known of the effects of long-term nifedipine use in late pregnancy. In this study the effects of nifedipine on pregnancy outcome and the morphologic features of the reproductive tract in the late-pregnant rat were investigated. STUDY DESIGN: From days 14 to 21 of gestation pregnant rats were administered three or 30 times the maximum human dose of nifedipine reported to suppress preterm labor. Analysis was performed on day 21. RESULTS: Blood vessel dilatation, increased vascularization of the uterus and placenta, and trophoblast hypertrophy were seen in both nifedipine-treated groups. Placental weight was increased in the higher-dose group, but neither dose of nifedipine resulted in any change of fetal survival or malformations. Pup weight was not different from that of controls in the lower-dose group but was significantly reduced ( p < 0.001) with the higher dose. Histologic changes in uterine musculature and cervical collagen were consistent with the inhibitory effects of nifedipine on uterine contractions. CONCLUSION: The results suggest that, in addition to tocolysis, nifedipine can cause vascular dilatation in both the uterus and the placenta. The use of nifedipine within the normal dose range does not appear to adversely affect fetal outcome and may potentially improve fetal outcome in some disorders of pregnancy.