Can ibuprofen (nonsteroidal anti-inflammatory drug (NSAID)) be prescribed during pregnancy?

Ibuprofen Use During Pregnancy

Ibuprofen can be prescribed during the first and second trimesters of pregnancy at the lowest effective dose for short durations (7-10 days), but must be discontinued after gestational week 28 due to significant fetal risks including premature closure of the ductus arteriosus and oligohydramnios. 1

Safety by Trimester

First Trimester (Weeks 0-13)

• Early pregnancy exposure to ibuprofen shows no evidence of increased risk of miscarriage or teratogenicity when used appropriately 1
• Ibuprofen has the most reassuring safety data among NSAIDs, followed by diclofenac 1
• A large cohort study of 1,117 women exposed to ibuprofen in the first trimester found no significantly increased risk of major birth defects (4.8% vs. 4.1% in controls) or distinct pattern of malformations 2
• However, women actively trying to conceive should avoid NSAIDs as they can interfere with ovulation by inducing luteinized unruptured follicle (LUF) syndrome, potentially reducing fertility 1

Second Trimester (Weeks 14-28)

• Short-term use (7-10 days) at the lowest effective dose does not appear to pose substantial fetal risks 1
• Ibuprofen may be considered during this period when needed to control disease activity in conditions like pericarditis or inflammatory arthritis 1
• The FDA label specifies that if NSAID treatment extends beyond 48 hours after 20 weeks gestation, ultrasound monitoring for oligohydramnios should be considered 3
• All NSAIDs must be discontinued by gestational week 28 (end of second trimester) 1

Third Trimester (Week 29 onwards)

• Ibuprofen is contraindicated after gestational week 28-30 due to severe fetal risks 1, 3
• Specific fetal complications include:
  • Premature closure of the ductus arteriosus with potential for persistent pulmonary hypertension 3, 4
  • Oligohydramnios (reduced amniotic fluid) from fetal renal dysfunction 3, 4
  • Neonatal renal impairment 3
  • Necrotizing enterocolitis 4
  • Intracranial hemorrhage 4

Clinical Decision-Making Algorithm

When pain management is needed during pregnancy:

1. First-line: Use acetaminophen at the lowest effective dose for the shortest duration 5

2. If acetaminophen is insufficient in first/second trimester:

   • Consider ibuprofen 200-400mg every 6-8 hours
   • Limit duration to 7-10 days maximum 1
   • Use lowest effective dose 1
   • Discontinue by gestational week 28 1

3. For chronic inflammatory conditions requiring ongoing treatment:

   • Transition to pregnancy-compatible alternatives before conception or early in pregnancy:
     • Hydroxychloroquine 1
     • Sulfasalazine (with folic acid supplementation) 1
     • Low-dose prednisone (≤5 mg/day) 1
     • Azathioprine 1

4. After gestational week 28:

   • Absolutely avoid all NSAIDs 1, 3
   • Use acetaminophen or low-dose prednisone if needed 5

Important Caveats and Pitfalls

Timing Considerations

• The critical cutoff is gestational week 28, not the traditional "third trimester" designation, as fetal sensitivity to NSAID-related risks increases significantly after this point 1
• The ESC guidelines suggest an even more conservative approach, recommending discontinuation by gestational week 20 for most NSAIDs (except low-dose aspirin ≤100mg/day) and mandatory discontinuation by week 32 1

Fertility Concerns

• Women with difficulty conceiving should discontinue NSAIDs entirely, as continuous periovulatory exposure can prevent ovulation 1
• If NSAIDs are necessary, use intermittently rather than continuously around the time of ovulation 1

Drug Selection

• Prefer nonselective NSAIDs with short half-lives (like ibuprofen) over COX-2 selective inhibitors, which have limited safety data 1
• Avoid indomethacin despite its historical use as a tocolytic, as it has greater risks than ibuprofen 1

Monitoring Requirements

• If ibuprofen use extends beyond 48 hours after 20 weeks gestation, consider ultrasound monitoring for oligohydramnios 3
• If inadvertent third-trimester exposure occurs, immediate discontinuation and fetal assessment for ductal constriction and oligohydramnios is necessary 6

Breastfeeding

• Ibuprofen is considered safe during breastfeeding as it transfers in low amounts to breast milk 1, 4
• Ibuprofen, indomethacin, and naproxen may all be considered in breastfeeding women 1