Is ibuprofen (Nonsteroidal Anti-Inflammatory Drug (NSAID)) safe to use during pregnancy?

Ibuprofen Safety in Pregnancy

Ibuprofen can be used during the first and second trimesters of pregnancy at the lowest effective dose for short durations (7-10 days maximum), but must be completely discontinued after gestational week 28 due to severe fetal risks including premature closure of the ductus arteriosus and oligohydramnios. 1, 2

Trimester-Specific Recommendations

First and Second Trimesters (Before Week 28)

• Ibuprofen has the most reassuring safety data among all NSAIDs and shows no evidence of increased risk of miscarriage or teratogenicity when used appropriately in early pregnancy 1, 3

• Use only when acetaminophen (the first-line agent) is insufficient for pain or fever control 1, 4

• Limit to 200-400mg every 6-8 hours for a maximum of 7-10 days at the lowest effective dose 1

• A large cohort study of 1,117 women exposed to ibuprofen in the first trimester found no increased risk of major birth defects (4.8% vs. 4.1% in controls) or spontaneous abortion 3

Third Trimester (After Week 28)

• Ibuprofen is contraindicated after gestational week 28-30 - this is the critical cutoff, not the traditional "third trimester" designation 1, 2, 5

• Fetal risks after week 28 include:

  • Premature closure of the ductus arteriosus 1, 5, 6
  • Oligohydramnios (reduced amniotic fluid) 1, 5
  • Fetal renal dysfunction and neonatal renal impairment 5
  • Pulmonary hypertension in the newborn 2

• The FDA mandates that if NSAID use extends beyond 48 hours after 20 weeks gestation, ultrasound monitoring for oligohydramnios should be considered 5

Special Populations and Circumstances

Women Trying to Conceive

• Avoid NSAIDs entirely when actively trying to conceive, as they can interfere with ovulation by inducing luteinized unruptured follicle (LUF) syndrome 1, 2

• If NSAIDs must be used, use intermittently rather than continuously to minimize interference with ovulation 2

Chronic Inflammatory Conditions

• For women requiring long-term anti-inflammatory treatment, transition to pregnancy-compatible alternatives before conception or early in pregnancy 1

• Safe alternatives include:

  • Hydroxychloroquine 2
  • Sulfasalazine (with folate supplementation) 2
  • Low-dose prednisone (≤10mg daily) 2
  • Azathioprine 2

Clinical Decision Algorithm

1. First-line: Use acetaminophen (maximum 4g daily) for pain or fever 4

2. If acetaminophen insufficient in weeks 1-28: Consider ibuprofen 200-400mg every 6-8 hours, limiting to 7-10 days maximum 1

3. After week 28: Absolutely discontinue ibuprofen; use acetaminophen only 1, 5

4. If exposure occurred after week 28: Immediately discontinue and perform fetal assessment for ductal constriction and oligohydramnios 2

Important Caveats

• The critical gestational age cutoff is week 28, not the traditional "third trimester" boundary, as fetal sensitivity to NSAID-related cardiovascular and renal risks increases significantly after this point 1, 2

• Short-term use (7-10 days) in the first and second trimesters does not appear to pose substantial fetal risks based on current evidence 1, 7

• Among NSAIDs, ibuprofen has the most reassuring safety profile, followed by diclofenac; COX-2 selective inhibitors have limited safety data and should be avoided 1, 2

Breastfeeding

• Ibuprofen is considered safe during breastfeeding as it transfers in low amounts to breast milk 1, 6