The Medicines and Healthcare products Regulatory Agency (MHRA) has advised healthcare professionals to avoid prescribing non-steroidal anti-inflammatory drugs (NSAIDs) to women after 20 weeks of pregnancy, owing to evidence suggesting a link with fetal renal dysfunction.
The advice comes after the regulator reviewed a study published in August 2022, which found that the use of NSAIDs in the second trimester of pregnancy “may cause oligohydramnios and ductus arteriosus constriction”.
Oligohydramnios is the reduction in volume of amniotic fluid surrounding the baby, resulting from fetal renal dysfunction, while the ductus arteriosus is a blood vessel in the baby’s heart.
Researchers based at a hospital in Berlin, Germany, conducted an observational cohort study, comparing cases of oligohydramnios and ductus arteriosus constriction in women with NSAID and/or metamizole exposure in the second and/or third trimester (n=1,092) to those who had been exposed to NSAIDs and/or metamizole in the first trimester only (n=1,154).
The study results showed that NSAID exposure in the second or third trimester led to 5 diagnoses of ductus arteriosus constriction and 41 diagnoses of oligohydramnios. Meanwhile, exposure in the first trimester led to no cases of ductus arteriosus constriction and 29 cases of oligohydramnios.
The MHRA therefore advised healthcare professionals, in guidance published on 27 June 2023, to “avoid prescribing systemic NSAIDs from week 20 of pregnancy unless clinically required and prescribe the lowest dose for the shortest time in these circumstances”.
“Please advise patients who are pregnant to avoid use of NSAIDs available without prescription from week 20 of pregnancy onwards unless advised by their healthcare professional,” it added.
“It is recognised that some patients may need short-term pain relief during pregnancy, such as for headache, toothache, muscle or joint pain. Before using any pain relief medicine available without prescription during pregnancy, patients should be advised to read the Patient Information Leaflet and only use the medication for the shortest possible time at the lowest possible dose and lowest possible frequency.”
The MHRA also reminded clinicians that NSAIDs are contraindicated during the last trimester of pregnancy (after 28 weeks).
Christina Nurmahi, lead pharmacist for the women and newborn care group at University Hospital Southampton NHS Foundation Trust, told The Pharmaceutical Journal that she “would totally agree with the MHRA recommendation to avoid NSAIDs from 20 weeks”.
“We have tended to avoid NSAIDs throughout pregnancy. Avoidance in third trimester has long been recommended and strictly adhered to, but we have been aware of concerns following an FDA publication, back in 2020, regarding avoidance from 20 weeks,” she said.
“Additionally, because of uncertainty around association with miscarriage and potential congenital anomalies, such as cardiovascular defects and orofacial clefts, we tend to avoid use in first trimester as well, where possible, recognising that there is limited, and possibly confounded data, for first trimester. So, in our organisation, we tend to err on the side of caution and avoid in all three trimesters whenever possible.”