synthesis is postulated to have antiandrogenic effects, leading to a slightly increased risk of congenital cryptorchism. Prostaglandins also influence renal blood flow and glomerular filtration rate. The incidence of renal dysfunction in the setting of maternal NSAID use ranges from 1.5% to 20%, with risk increasing as exposure occurs closer to delivery. Fetal effects of in utero NSAID exposure range from transient fetal oligohydramnios to lethal neonatal renal failure. Prostaglandins also play a primary role in maintaining patency of the ductus arteriosus. Nonsteroidal anti-inflammatory drugYinduced constriction of the ductus arteriosus can lead to neonatal pulmonary hypertension. Although constriction of the ductus arteriosus resolves within 24 hours of NSAID cessation, the transient premature closure is thought to cause enduring ischemic injury to the vascular muscle wall. The damaged ductus arteriosus is subsequently less responsive to increases in oxygen tension, leading to detrimental patency of the ductus arteriosus after delivery. Finally, the antiplatelet effects of aspirin have been implicated in the increased incidence of neonatal bleeding after premature delivery in women with recent exposure to high-dose aspirin (325Y600 mg). Although limited use of small doses of NSAIDs and aspirin during the second and third trimester is probably safe, continuous or excessive inhibition of prostaglandin, prostacyclin, and thromboxane synthesis may have enduring urogenital, pulmonary, and/or hematologic fetal effects.After delivery, breast-feeding offers continued infant exposure to both beneficial and, rarely, harmful maternal serum components. The fraction of maternal drug detected in the breast milk depends on the dose as well as the specific drug characteristics. Nonsteroidal anti-inflammatory drugs are acidic medications with low lipid solubility and high protein binding, features that mitigate against substantial transfer into breast milk. In addition, because NSAIDs are extensively protein-bound, gastrointestinal absorption is limited, and the infant is generally exposed to less than 1% of the initial maternal dose. As a result, nonselective NSAIDs are listed as compatible with breast-feeding by the American Academy of Pediatrics. Aspirin, on the other hand, should be used with caution or avoided, during breast-feeding. Infants have immature enzymes and metabolic pathways. Reduced clearance of aspirin by neonates could potentially lead to accumulation and toxic effects even when repeated exposures are small. Although the adverse effects of aspirin on platelet function are a theoretical risk, the World Health Organization Working Group on Human Lactation has classified aspirin as unsafe for use by nursing women. Neither NSAIDs nor aspirin is completely devoid of neonatal risk. Even if neonatal exposure is low, there is the possibility the infant may be allergic to the drug or especially sensitive to the adverse effect profile. For that reason, when a nursing mother requires a medication, the drug should be tak...
