Transplacental cardiovascular effects of four popular analgesics in rats

The purpose of this study is to clarify fetal cardiovascular effects of four popular analgesics administered to a maternal animal model. Clinical doses of aspirin (14 mg/kg), acetaminophen (14 mg/kg), ibuprofen (6 mg/kg), or indomethacin (0.7 mg/kg) were administered orally to near-term rats. At 1, 4, 8, or 24 hours later fetuses were delivered by cesarean section, and were fixed immediately by the whole-body freezing technique. The ductus diameter, pericardial effusion, and volume and mass of the ventricles were studied by photographing multiple planes of the heart. Fetal ductal constriction was most remarkable with ibuprofen, with the diameter decreased 70% +/- 5% (mean +/- SEM) at 1 to 8 hours. Both ventricles were dilated 60% +/- 27%, and pericardial fluid was increased 120% +/- 20%. These changes partly disappeared at 24 hours. Milder but more persistent effects were observed with indomethacin. The fetal ductus was constricted 30% at 4 to 24 hours. Pericardial fluid was increased 140% +/- 30% at 24 hours. Aspirin and acetaminophen constricted the fetal ductus 10%. In conclusion, clinical doses of ibuprofen and indomethacin constricted the fetal rat ductus and caused cardiac failure. The effects of aspirin and acetaminophen were much milder.