Effect of intramuscular sulfadoxine-pyrimethamine on pregnant Wistar rats

Sulfadoxine-pyrimethamine preparations are used commonly for the treatment and or prevention of malaria in the endemic regions of Sub-Sahara Africa. Pyrimethamine alone has been shown to be teratogenic in rats, mice and hamsters, and others animals.

Pregnant Wistar rats were divided into three groups. The first group received a therapeutic dose of sulfadoxine-pyrimethamine (0.72 mg/kg body weight) intramuscularly (1.m) on the 5th, 12th, and 19th of gestation (3 doses). The second group received a similar dose on the 10th and 17th days of gestation (2 doses); the third group received the same dose on the 15th and 22nd days of gestation (2 doses). Controls for each group received 2 ml of physiological saline through the same route on similar days instead of the drugs.

All control animals produced normal litters (average 5.6), but group 3a animals produced litters with no obvious congenital malformations (average 4.8). Animals in groups 1a and 2a produced no litters. When they were sacrificed, they showed implantation sites in their uterine horns. Histological sections of these implantation sites showed that the embryos had been resorbed.

Therapeutic dose of sulfadoxine-pyrimethamine (0.72 mg/kg body weight) administered early in gestation resulted in complete embryo resorption in Wistar rats. The use of these preparations in early pregnancy in man demands caution.