The US Food and Drug Administration (FDA) is warning that use of nonsteroidal anti-inflammatory drugs (NSAIDs) around 20 weeks or later in pregnancy may cause fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment.
Although this safety concern is well known among certain medical specialties, the FDA wanted to communicate our recommendations more widely to educate other health care professionals and pregnant women. This issue affects all NSAIDs that are available by prescription and those that can be bought over-the-counter (OTC) without a prescription.
These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation. Oligohydramnios is often, but not always, reversible with treatment discontinuation.
Complications of prolonged oligohydramnios may include limb contractures and delayed lung maturation. In some post-marketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis were required.
If NSAID treatment is deemed necessary between 20 to 30 weeks of pregnancy, healthcare professionals should limit use to the lowest effective dose and shortest duration possible. As currently described in the NSAID labels, avoid prescribing NSAIDs at 30 weeks and later in pregnancy because of the additional risk of premature closure of the fetal ductus arteriosus.
The above recommendations do not apply to low-dose (81 mg) aspirin prescribed for certain conditions in pregnancy.
Healthcare professionals should consider ultrasound monitoring of amniotic fluid if NSAID treatment extends beyond 48 hours. Discontinue the NSAID if oligohydramnios occurs and follow up according to clinical practice.
The FDA analysed 35 cases of low amniotic fluid levels or kidney problems that were reported through the FDA’s MedWatch Program through 2017. All cases were serious. This number includes only cases submitted to FDA, so there may be additional cases. Two newborns who died had kidney failure and confirmed low amniotic fluid when mothers took NSAIDs while pregnant; 3 other newborns who died had kidney failure without confirmed low amniotic fluid when mothers took NSAIDs while pregnant. The low amniotic fluid levels started as early as 20 weeks of pregnancy. In 11 cases where low amniotic fluid levels were detected during pregnancy, the fluid volume returned to normal after the NSAID was stopped. The information from the cases was similar to what was found in the medical literature. In these publications, 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, the condition was reversible within 3 to 6 days after stopping the NSAID. In many reports, the condition was reversed when the NSAID was stopped, and it reappeared when the same NSAID was started again.
For prescription NSAIDS, the FDA is requiring changes to the prescribing information to describe the risk of kidney problems in unborn babies that result in low amniotic fluid. The FDA is recommending avoiding NSAIDs in pregnant women at 20 weeks or later in pregnancy rather than the 30 weeks currently described in NSAID prescribing information. The changes to the prescribing information also indicate that healthcare professionals should consider ultrasound monitoring of amniotic fluid if NSAID treatment extends beyond 48 hours.
The Drug Facts labels of OTC NSAIDs will also be updated. These labels already warn to avoid using NSAIDs during the last 3 months of pregnancy because the medicines may cause problems in the unborn child or complications during delivery. The Drug Facts labels already advise pregnant and breastfeeding women to ask a healthcare professional before using these medicines.