Prostaglandins are found in high concentration in the term uterus and have a stimulatory effect on normal labor. NSAIDs inhibit uterine motility through COX-mediated inhibition of prostaglandin synthesis. Indomethacin is sufficiently effective at slowing uterine contractions that it has been used to treat preterm labor. Although NSAIDs are not believed to be teratogenic in humans, they do cross the placenta later in pregnancy. One of the most significant effects of fetal exposure to NSAIDs is premature constriction of the ductus arteriosus, which may result in pulmonary hypertension. Other reported effects of in utero exposure to NSAIDs include oligohydramnios, renal dysfunction, necrotizing enterocolitis, and CNS hemorrhage.

NSAID-induced inhibition of platelet aggregation may place the fetus and the mother at increased risk for bleeding. Mothers who take NSAIDs during the latter part of pregnancy appear to be at risk for increased peripartum hemorrhage. The safest recommendation is to avoid NSAID use during pregnancy, especially during the third trimester.

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