NSAID Use in Second Trimester of Pregnancy
NSAIDs can be used during the second trimester at the lowest effective dose for short durations (7-10 days maximum), but must be discontinued by gestational week 28 due to increasing fetal risks. 1
Key Recommendations
Timing and Duration
- NSAIDs are restricted to the first and second trimesters only, with mandatory discontinuation after gestational week 28 (end of second trimester), not the traditional "third trimester" designation. 1
- Short-term use of 7-10 days does not appear to pose substantial fetal risks during the second trimester. 1
- Long-term or continuous use in the late second trimester (approaching week 28) requires careful monitoring as fetal sensitivity to NSAID-related risks increases. 1, 2
Drug Selection
- Ibuprofen has the most reassuring safety data, followed by diclofenac. 1, 3
- Nonselective NSAIDs with short half-lives (like ibuprofen) are preferred over COX-2 selective inhibitors, which have limited safety data. 1, 3
- Use the lowest effective dose for the shortest possible duration. 1
Safety Profile in Second Trimester
- Early pregnancy and second trimester exposure to NSAIDs shows no evidence of increased risk of miscarriage or teratogenicity when used appropriately. 1, 3
- The critical evidence comes from the 2025 EULAR guidelines, which state that current evidence shows short-term use (7-10 days) does not appear to pose substantial risks for the fetus. 1
Specific Fetal Risks to Monitor
Second Trimester Concerns
- Oligohydramnios (reduced amniotic fluid) can occur, particularly with prolonged use in the late second trimester. 1, 2
- Premature ductus arteriosus constriction has been reported, especially after long-term exposure approaching week 28. 1, 2
- One case series documented ductus arteriosus constriction and oligohydramnios in the late second trimester after several weeks of NSAID exposure. 2
Third Trimester Risks (Why Week 28 Cutoff Matters)
- Premature closure of the ductus arteriosus with potential for persistent pulmonary hypertension in the newborn. 1, 4
- Oligohydramnios and fetal renal injury. 1, 4
- Necrotizing enterocolitis and intracranial hemorrhage. 4
Clinical Decision Algorithm
For Acute Pain Management (Second Trimester)
- First-line: Consider acetaminophen at the lowest effective dose for the shortest duration. 5
- Second-line: If acetaminophen insufficient, use ibuprofen 200-400mg every 6-8 hours, limiting duration to 7-10 days maximum. 3, 5
- Discontinue by week 28: Mark this as a hard stop in the patient's chart. 1
For Chronic Inflammatory Conditions
- Transition to pregnancy-compatible alternatives before or early in pregnancy, including:
Monitoring Requirements for Extended Use
- If NSAIDs must be used beyond 7-10 days in the late second trimester (weeks 24-28), monitor for:
Important Caveats
Fertility Considerations
- Women actively trying to conceive should avoid NSAIDs as they can interfere with ovulation by inducing luteinized unruptured follicle (LUF) syndrome. 1, 3
- Continuous periovulatory exposure can prevent ovulation and reduce fecundability. 1
Common Pitfalls to Avoid
- Do not extend NSAID use into the third trimester based on traditional trimester definitions; the cutoff is gestational week 28, not week 27 or later. 1
- Do not assume all NSAIDs are equivalent; ibuprofen and diclofenac have the most safety data, while COX-2 inhibitors should be avoided due to limited evidence. 1
- Do not prescribe NSAIDs for chronic use without transitioning to pregnancy-compatible alternatives. 1
Strength of Evidence
The 2025 EULAR guidelines represent the most recent and highest quality evidence, based on comprehensive review of available data. 1 The American College of Rheumatology 2020 guidelines provide concordant recommendations. 1 Recent research from 2022 and 2024 supports that short-term second trimester use does not pose substantial risk, but emphasizes caution with prolonged exposure. 6, 2