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Abstract . β-Lactam antibiotics are widely used because of their lack of toxicity in humans. However, during pregnancy, exposure of the fetus is likely to occur because β-lactam antibiotics cross the placenta. The potential adverse effects of two penicillins (ampicillin, amoxicillin) and of one cephalosporin (ceftriaxone) were examined in rat kidney development. Two experimental approaches were used: metanephros organ cultures to analyze the direct effect of the drug and maternal treatment to assess the consequences of  in utero  exposure. For  in vitro  experiments, metanephroi were removed from 14-d-old fetuses and grown with or without the antibiotic at a concentration ranging from 10 to 1000 μg/ml for 6 d. For  in vivo  experiments, pregnant rats were treated with penicillin at 100 mg/kg per d for 5 d, a period overlapping early renal organogenesis. Both penicillins alter renal development  in vitro  in a dose-dependent manner, from a dose of 10 μg/ml for ampicillin and 100 μg/ml for amoxicillin. In young animals exposed to penicillins  in utero , a mild oligonephronia was present and cystic tubule dilation was observed in newborn and in young animals as well. Ceftriaxone weakly impairs  in vitro  nephrogenesis except at the dose of 1000 μg/ml that blocks kidney development completely. No effect on nephron ontogeny was observed following  in utero  exposure, but an interstitial inflammation was present in the medulla of 2-wk-old rats. In conclusion, these data show that β-lactams, at therapeutic doses, are harmful to fetal rat kidneys.

In Utero and in Vitro Exposure to β-Lactams Impair Kidney Development in the Rat