Beginning at ~20 weeks' gestation, most amniotic fluid is produced by the fetal kidneys. NSAIDs inhibit renal prostaglandins and decrease renal blood flow. Maternal NSAID use can cause fetal renal dysfunction and a decrease in amniotic fluid production, which can impair pulmonary, digestive, and muscular development and lead to malformations, growth restriction, and preterm birth.2

An FDA review found that most published oligohydramnios cases associated with NSAID use occurred during the third trimester after several days to weeks of treatment, but some appear to have occurred as early as 20 weeks' gestation and after as little as 48 hours of treatment. Oligohydramnios was usually reversible within 3-6 days after NSAID discontinuation. Among the cases identified by the review were 20 published reports of neonatal renal dysfunction following in utero NSAID exposure and 35 instances of serious oligohydramnios or neonatal renal dysfunction associated with maternal NSAID use that were reported to the FDA Adverse Event Reporting System (AERS). Neonatal death resulting from renal failure or dialysis complications occurred in 8 of the published cases.1

Except for ophthalmic formulations and low-dose aspirin (81 mg/day), NSAIDs should not be taken during pregnancy after 30 weeks' gestation, and they should be avoided if possible between 20 and 30 weeks. If an NSAID must be used after 20 weeks' gestation, it should be taken at the lowest effective dose for the shortest possible duration. Ultrasound monitoring of the amniotic fluid should be considered if NSAID use for >48 hours is necessary.