Is naproxen (Nonsteroidal Anti-Inflammatory Drug) safe to use in a pregnant woman?

Naproxen Use in Pregnancy

Naproxen should be avoided during pregnancy, particularly after gestational week 28, and better-studied NSAIDs like ibuprofen should be preferred if an NSAID is absolutely necessary during the first or second trimester. 1, 2

Safety by Trimester

First and Second Trimesters (Before Week 28)

• Naproxen can be used cautiously in the first and second trimesters only if absolutely necessary, but ibuprofen has significantly more reassuring safety data and should be the preferred NSAID choice 1, 2
• The American College of Rheumatology recommends that if NSAIDs must be used, they should be restricted to the first and second trimesters at the lowest effective dose for short durations (7-10 days maximum) 1
• Limited data from a German case series of 121 first-trimester naproxen exposures showed 2 major birth defects among 95 live births, but the small cohort size prevents definitive conclusions about teratogenic risk 3
• Early pregnancy exposure to NSAIDs generally shows no strong evidence of increased miscarriage risk or teratogenicity when used appropriately, though ibuprofen has the most reassuring data 1, 2
• The FDA classifies naproxen as Pregnancy Category C, meaning animal studies show potential harm but human data are insufficient, and the drug should only be used if potential benefits justify potential risks 4

Third Trimester (After Week 28)

• All NSAIDs including naproxen are contraindicated after gestational week 28-30 due to severe fetal risks 1, 2, 4
• The FDA label explicitly warns that "in late pregnancy, as with other NSAIDs, naproxen should be avoided because it may cause premature closure of the ductus arteriosus" 4
• Significant third-trimester fetal risks include:
  • Premature closure of the ductus arteriosus with potential for persistent pulmonary hypertension in the newborn 1, 5, 6
  • Oligohydramnios (reduced amniotic fluid) 1, 5, 6
  • Fetal renal injury and dysfunction 5, 6
  • Necrotizing enterocolitis 5, 6
  • Intracranial hemorrhage 5, 6

Fertility Considerations

• Women actively trying to conceive should avoid naproxen and all NSAIDs, as they can interfere with ovulation by inducing luteinized unruptured follicle (LUF) syndrome, potentially reducing fertility 1, 2
• If NSAIDs must be used while trying to conceive, use intermittently rather than continuously to minimize interference with ovulation 1

Clinical Decision-Making Algorithm

Step 1: Determine gestational age

• If ≥28 weeks: Absolutely contraindicated - discontinue immediately and consider acetaminophen or pregnancy-compatible alternatives 1, 2, 4
• If <28 weeks: Proceed to Step 2

Step 2: Assess necessity and alternatives

• First-line: Use acetaminophen at the lowest effective dose for the shortest duration 2
• If acetaminophen insufficient and NSAID required: Choose ibuprofen over naproxen (200-400mg every 6-8 hours, maximum 7-10 days) 1, 2
• For chronic inflammatory conditions requiring ongoing treatment: Transition to pregnancy-compatible alternatives such as hydroxychloroquine, sulfasalazine with folate, low-dose prednisone (≤10mg daily), azathioprine, or colchicine 1, 2

Step 3: If naproxen exposure has already occurred

• First/second trimester exposure: Reassure patient that limited data suggest low teratogenic risk, but discontinue and switch to safer alternatives 3
• Third trimester exposure: Immediate discontinuation and fetal assessment for ductal constriction and oligohydramnios is necessary 1

Breastfeeding Safety

• Naproxen is found in breast milk at approximately 1% of maximum maternal plasma concentration 4
• The FDA label states "use in nursing mothers should be avoided" due to possible adverse effects of prostaglandin-inhibiting drugs on neonates 4
• Ibuprofen is the preferred NSAID during breastfeeding with the most reassuring safety data, followed by diclofenac 7
• If naproxen must be used during breastfeeding, it should be at the lowest effective dose for the shortest duration, though safer alternatives are strongly preferred 7

Critical Pitfalls to Avoid

• Do not rely on the traditional "third trimester" designation - the critical cutoff is gestational week 28, not week 27 (traditional third trimester start), as fetal sensitivity to NSAID-related risks increases significantly after this point 1, 2
• Many women are unaware that over-the-counter NSAIDs are contraindicated in late pregnancy, with studies showing a 3% usage rate near labor despite contraindication 8
• The hemodynamic changes of pregnancy may mask early signs of NSAID-related complications 6
• Never assume short-term use in the third trimester is safe - even brief exposure can cause ductus arteriosus constriction 5, 6