NSAIDs During Pregnancy: Safety Considerations

Safety by Trimester

The American College of Rheumatology recommends that NSAIDs should be restricted to the first and second trimesters of pregnancy, used at the lowest effective dose for short durations (7-10 days), and must be discontinued after gestational week 28 due to significant fetal risks 1, 2, 3
Early pregnancy exposure to NSAIDs shows no evidence of increased risk of miscarriage or teratogenicity 1, 2, 3
Most reassuring data are available for ibuprofen, followed by diclofenac, whereas data for COX-2 inhibitors are limited 2, 3
NSAIDs can interfere with ovulation and may reduce fertility in women trying to conceive due to luteinized unruptured follicle (LUF) syndrome 3, 4

Ibuprofen has the most reassuring safety data for use during pregnancy (first and second trimesters) 2, 3, 5
Diclofenac is considered the second safest option based on available evidence 2, 3
Nonselective NSAIDs are preferred over COX-2 inhibitors due to limited safety data for the latter 4, 6

Women actively trying to conceive should consider avoiding NSAIDs 5
If used while trying to conceive, use intermittently rather than continuously to avoid interference with ovulation 3, 4
Most NSAIDs are considered safe during breastfeeding as they transfer in low amounts to breast milk 5

Significant fetal risks of NSAID use in the third trimester include premature closure of the ductus arteriosus 3, 6, 7
Oligohydramnios (reduced amniotic fluid) is a significant fetal risk of NSAID use in the third trimester 3, 7
Pulmonary hypertension in the newborn is a potential fetal risk of NSAID use in the third trimester 5

Meloxicam is contraindicated during pregnancy, especially in the third trimester, due to significant fetal risks including premature closure of the ductus arteriosus and oligohydramnios 8
The American College of Rheumatology strongly recommends against use of NSAIDs in the third trimester 9
If an NSAID is absolutely necessary during the first or second trimester, ibuprofen has the most reassuring safety data 8
Use the lowest effective dose for the shortest duration possible (7-10 days) 8
NSAIDs can interfere with ovulation and may reduce fertility in women trying to conceive due to luteinized unruptured follicle syndrome 9

For women with inflammatory conditions requiring long-term treatment, pregnancy-compatible alternatives include hydroxychloroquine 8, 9
Sulfasalazine (with folate supplementation) is a pregnancy-compatible alternative 8, 9
Low-dose glucocorticoids (≤10 mg daily of prednisone) are a pregnancy-compatible alternative 9
Azathioprine is a pregnancy-compatible alternative 8, 9
Colchicine is a pregnancy-compatible alternative 8, 9

For inflammatory conditions requiring treatment during pregnancy, consult with rheumatology and maternal-fetal medicine to transition to pregnancy-compatible medications 8, 9
If meloxicam exposure has already occurred in the third trimester, immediate discontinuation and fetal assessment for ductal constriction and oligohydramnios is necessary 8