Prenatal tolerability of acetaminophen and other over-the-counter non-selective cyclooxygenase inhibitors

Over-the-counter cyclooxygenase inhibitors are used to relief fever and various types of acute pain like headache, toothache, earache, sore throat, as well as postoperative and menstrual ones. They are also major ingredients in numerous cold and flu mixtures. Unlike well-known organ toxicological profile, their prenatal toxicity was not fully established. For a long time, acetaminophen was considered as a relatively safe antipyretic and analgesic drug during pregnancy. However, a new data indicate that it may increase the risk of cryptorchidism and asthma during childhood as well as preeclampsia, preterm birth, maternal phlebothrombosis and pulmonary embolism. Contrary to acetaminophen, non-selective cyclooxygenase inhibitors (non-steroidal anti-inflammatory drugs – NSAID; i.e., diclofenac, ibuprofen, naproxen) may also induce intrauterine growth retardation, ductus arteriosus constriction with secondary persistent pulmonary hypertension, reduced fetal renal perfusion that led to oligohydramion, prolonged pregnancy as well as increase prevalence of intracranial bleeding in newborns. Furthermore, a higher risk of miscarriage, stillbirth and some congenital malformations (cardiac and diaphragmatic defects, celosomy – gastroschisis and umbilical hernia) was reported for non-selective inhibitors, in particular high doses of acetylsalicylic acid (aspirin).