Is ibuprofen (Nonsteroidal Anti-Inflammatory Drug (NSAID)) safe to use during the 2nd trimester of pregnancy?

Ibuprofen Use in the Second Trimester of Pregnancy

Ibuprofen can be used cautiously during the second trimester of pregnancy, but only at the lowest effective dose for short durations (7-10 days maximum), and must be discontinued by gestational week 28. 1, 2, 3

Safety Profile by Gestational Age

Early to Mid-Second Trimester (Weeks 14-20)

• Ibuprofen has the most reassuring safety data among all NSAIDs for use during this period, followed by diclofenac 1, 2
• Early pregnancy exposure shows no evidence of increased risk of miscarriage or teratogenicity when used appropriately 1, 4
• Short-term use (7-10 days) does not appear to pose substantial fetal risks 1, 2, 5

Late Second Trimester (Weeks 20-28)

• After gestational week 20, fetal renal sensitivity increases, creating risk for oligohydramnios (reduced amniotic fluid) 3
• The FDA label specifically warns that NSAID use at 20 weeks or later has been associated with fetal renal dysfunction leading to oligohydramnios 3
• Research confirms oligohydramnios occurred in 0.9% of second trimester exposures versus 0.2% in first trimester only exposures (5-fold increased risk), particularly with prolonged use 6
• One case documented ductus arteriosus constriction and oligohydramnios in late second trimester after long-term NSAID exposure 6

Critical Cutoff: Gestational Week 28

All ibuprofen use must be discontinued by gestational week 28 (not the traditional "third trimester" designation at 27 weeks) 1, 2, 3

Rationale for Week 28 Cutoff:

• After week 30, NSAIDs cause premature closure of the fetal ductus arteriosus, a life-threatening cardiovascular complication 3
• Risk of oligohydramnios and neonatal renal impairment increases substantially 3
• Potential for pulmonary hypertension in the newborn 7

Practical Prescribing Algorithm

Step 1: Confirm Gestational Age

• If before week 20: Ibuprofen is relatively safe for short-term use
• If weeks 20-28: Use with increased caution; monitor more closely
• If week 28 or beyond: Absolutely contraindicated 2, 3

Step 2: Dosing Parameters

• Dose: 200-400mg every 6-8 hours 2
• Duration: Maximum 7-10 days 1, 2, 5
• Principle: Lowest effective dose for shortest duration 3

Step 3: Monitoring Requirements

• If treatment extends beyond 48 hours after week 20, consider ultrasound monitoring for oligohydramnios 3
• If oligohydramnios is detected, discontinue immediately and follow up according to clinical practice 3

Important Clinical Caveats

Fertility Considerations

• Women actively trying to conceive should avoid NSAIDs entirely, as they can interfere with ovulation by inducing luteinized unruptured follicle (LUF) syndrome 2, 7
• Continuous periovulatory exposure can prevent ovulation 2

First-Line Alternative

• Acetaminophen should always be the first-line analgesic during pregnancy at the lowest effective dose for the shortest duration 1, 2
• Only consider ibuprofen when acetaminophen is insufficient 2

Long-Term Treatment Needs

• For chronic inflammatory conditions requiring ongoing treatment, transition to pregnancy-compatible alternatives before conception or early in pregnancy 2, 7:
  • Hydroxychloroquine 1, 7
  • Sulfasalazine (with folate supplementation) 1, 7
  • Low-dose prednisone (≤10 mg daily) 7
  • Azathioprine 1, 7
  • Colchicine 1, 7

Evidence Quality Considerations

The 2025 EULAR guidelines from the Annals of the Rheumatic Diseases provide the most current and authoritative recommendations 1, which align closely with FDA labeling 3. The key distinction in recent evidence is the emphasis on gestational week 28 as the hard cutoff rather than the traditional third trimester boundary, and the recognition that even late second trimester use (after week 20) carries some risk that increases with duration of exposure 6, 5.

Research data consistently shows that short-term use (under 7 days) in the second trimester appears safe, but prolonged use in the late second trimester can cause the same adverse effects seen in third trimester exposure 6, 5.