Intrauterine growth retardation and lack of teratogenic effects of prenatal exposure to the combination of paracetamol and caffeine in Wistar rats

The effect of the mixture of paracetamol and caffeine on prenatal development in rats was studied. Paracetamol: caffeine was prepared with a 5:1 ratio (w/w) between compounds and administered orally in Tween-80 water suspension once a day to pregnant Wistar rats on gestation days 8 through 14 (plug = day 1). The low dose was similar to the preparation available over-the-counter (OTC), 3.5 mg/kg of paracetamol and 0.7 mg/kg of caffeine. The middle dose was 35.0 and 7.0 mg/kg, and the high dose 350.0 and 70.0 mg/kg for paracetamol and caffeine, respectively. On gestation day 21, fetuses were delivered by laparotomy. Corpora lutea, fetuses, and number of implantation sites were counted. Live fetuses were examined for external, visceral, and skeletal malformations. There was a significant decrease in maternal body weight gain and liver weight in all drug-treated groups and reduced kidney weights in the middle and high dose groups. Dose-dependent effects in the middle and high dose groups on fetal body weight/growth and placental weight were found. In none of the three dose groups was there an increase in external or internal congenital malformations. (C) 2002 Elsevier Science Inc. All rights reserved.