What are the guidelines for using Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) during pregnancy?

Guidelines for NSAID Use During Pregnancy

NSAIDs should be avoided in the third trimester of pregnancy due to significant risks of premature closure of the ductus arteriosus and should be used with caution in the first and second trimesters for short-term treatment only. 1

Safety Profile by Trimester

First Trimester

• NSAIDs appear relatively safe during early pregnancy with no significant evidence of increased risk of miscarriage or teratogenicity 1
• Most reassuring data available for ibuprofen, followed by diclofenac 2, 1
• NSAIDs can interfere with ovulation and fertility:
  • May induce luteinized unruptured follicle (LUF) syndrome 2
  • Women with difficulty conceiving should consider discontinuing NSAIDs 2

Second Trimester

• Short-term use (7-10 days) appears relatively safe 2, 3
• Preference for nonselective NSAIDs with short half-life (e.g., ibuprofen) in the lowest effective dose 2, 1
• Prolonged use in late second trimester requires monitoring as it may cause:
  • Oligohydramnios 4
  • Premature constriction of the ductus arteriosus 4

Third Trimester

• Strongly contraindicated after gestational week 28 2, 1
• Significant risks include:
  • Premature closure of the ductus arteriosus 2, 5
  • Oligohydramnios 5, 6
  • Pulmonary hypertension in the newborn 5, 6
  • Prolonged gestation and labor 5
  • Increased peripartum blood loss 5

Specific Recommendations

1. Choice of NSAID if needed:

   • Nonselective NSAIDs are conditionally recommended over COX-2 specific inhibitors due to lack of data on the latter 2, 1
   • Ibuprofen is preferred due to short half-life and most available safety data 2, 1

2. Duration of treatment:

   • Limit to short-term use (7-10 days maximum) in first and second trimesters 2, 3
   • Use lowest effective dose 2

3. Alternative options:

   • Acetaminophen is the safest analgesic option throughout pregnancy 1
   • For chronic inflammatory conditions, consider:
     • Hydroxychloroquine 2
     • Sulfasalazine 2
     • Low-dose prednisone (≤5 mg/day) 2, 1

4. Monitoring:

   • If long-term NSAID use is required in second trimester, monitor with fetal echocardiography to check for ductal constriction 1
   • Monitor for oligohydramnios if treatment continues beyond 48 hours 7

Special Considerations

• Breastfeeding: Ibuprofen, indomethacin, and naproxen are considered safe during breastfeeding, with low infant exposure via breast milk 1, 5
• Preeclampsia: Avoid NSAIDs in women with preeclampsia, especially with acute kidney injury 1
• Rheumatic diseases: For patients with rheumatic diseases requiring anti-inflammatory treatment after 32 weeks, low-dose prednisone may be used throughout pregnancy 2, 1

Common Pitfalls to Avoid

1. Using NSAIDs after gestational week 28 (end of second trimester)
2. Prolonged use of NSAIDs even in second trimester (>7-10 days)
3. Using COX-2 specific inhibitors due to limited safety data
4. Failing to consider the impact of NSAIDs on fertility when treating women trying to conceive
5. Not considering alternative safer medications like acetaminophen or pregnancy-compatible disease-modifying drugs for chronic conditions

Remember that while short-term use in the first and early second trimester appears relatively safe, the risks increase significantly as pregnancy progresses, with absolute contraindication in the third trimester.