We searched the medical literature and the FDA Adverse Event Reporting System (FAERS) for cases of oligohydramnios or neonatal renal dysfunction associated with nonsteroidal anti-inflammatory drug (NSAID) use during pregnancy.
We reviewed the medical literature, including case reports, randomized controlled studies, and observational studies.1-17 Most of the publications showed that oligohydramnios is mostly observed during the third trimester, but there are multiple reports suggesting an earlier onset, around 20 weeks of gestation. Low amniotic fluid levels were detected with use of NSAIDs for varying amounts of time, ranging from 48 hours to multiple weeks. In most cases, oligohydramnios was reversible within 72 hours to 6 days following the discontinuation of the NSAID. In many reports, oligohydramnios was reversed when the NSAID was discontinued, and the oligohydramnios reappeared after reinitiation of treatment with the same NSAID. In some reports, when a particular NSAID was discontinued and another one was started, oligohydramnios did not reoccur with the new NSAID.
We also identified case reports/case series in the medical literature describing the onset of renal failure in neonates exposed to NSAIDs in utero.18-27 The duration of exposure ranged from 2 days to 11 weeks. The case reports and case series described 20 neonates exposed to NSAIDs in utero, who experienced neonatal renal dysfunction in the first days following birth. The severity of renal dysfunction varied greatly from normalization at 3 days to persistent anuria requiring dialysis and/or exchange transfusion. Out of 11 total deaths, eight neonates were reported to have died as a direct consequence of renal failure or due to complications from dialysis.
A search of FAERS through July 21, 2017, identified 35 cases of oligohydramnios or neonatal renal dysfunction associated with NSAID use during pregnancy. There were 32 cases of oligohydramnios, including eight cases of oligohydramnios and neonatal renal dysfunction, and three cases of neonatal renal dysfunction that did not report oligohydramnios. All cases reported a serious outcome. Five cases reported neonatal death, which in all cases were associated with neonatal renal failure. All cases reported a temporal association with an NSAID and oligohydramnios or neonatal renal dysfunction, with oligohydramnios occurring as early as 20 weeks gestation. In 11 cases, a positive dechallenge was reported where the amniotic fluid volume returned to normal after the NSAID was discontinued. In all 11 cases of neonatal renal dysfunction, the neonate was born preterm before 37 weeks gestation.