Which Non-Steroidal Anti-Inflammatory Drug (NSAID) can be used during pregnancy?

NSAIDs in Pregnancy: Safety and Recommendations

Acetaminophen (paracetamol) is the only analgesic that can be safely used throughout pregnancy, while NSAIDs should be avoided in the third trimester due to significant risks of premature closure of the ductus arteriosus and other fetal complications.

Safety of NSAIDs During Different Pregnancy Stages

First and Second Trimesters

• NSAIDs are generally considered safe in early pregnancy (first trimester) and most of the second trimester 1
• Low doses and intermittent use are preferred over chronic administration 1
• Nonselective NSAIDs (like ibuprofen) are conditionally recommended over COX-2 specific inhibitors due to lack of data on the latter 1
• If a woman is having difficulty conceiving, NSAIDs should be discontinued pre-conception due to possible NSAID-induced unruptured follicle syndrome 1

Third Trimester

• All NSAIDs must be discontinued 6-8 weeks before term (around 32 weeks gestation) 1, 2
• Strong recommendation against use of NSAIDs in the third trimester due to significant risks 1, 2

Potential Risks of NSAIDs in Late Pregnancy

NSAIDs used close to term can cause several serious complications:

1. Fetal risks:

   • Premature closure of the ductus arteriosus (15-fold higher risk) 3
   • Pulmonary hypertension 1, 4
   • Increased cutaneous and intracranial bleeding 1
   • Impaired renal function and reduced urine output 1, 4
   • Reduced amniotic fluid volume (oligohydramnios) 4, 5

2. Maternal risks:

   • Prolonged gestation and labor 1
   • Increased peripartum blood loss 1
   • Increased anemia 1

Safe Alternatives During Pregnancy

When analgesic or anti-inflammatory treatment is needed during pregnancy:

1. Throughout pregnancy:

   • Acetaminophen (paracetamol) is the safest first-line option 1, 2
   • Low-dose prednisone (≤10 mg daily) may be used if clinically indicated 1, 2

2. Third trimester specifically:

   • Acetaminophen only 1, 2
   • If stronger anti-inflammatory effects are needed, low-dose prednisone is preferred over NSAIDs 2

Special Considerations

• If NSAIDs must be used in the second trimester, short-term use (a few days) appears to have minimal risk 5, 6
• Prolonged NSAID use even in the second trimester may cause oligohydramnios and ductal constriction similar to third-trimester effects 5
• If indomethacin must be used before 32 weeks, fetal echocardiography should be performed within 48 hours to monitor for ductal constriction 2

Breastfeeding Considerations

• Ibuprofen, indomethacin, and naproxen are considered safe during breastfeeding 1
• These NSAIDs result in low infant exposure via breast milk 7
• NSAIDs should be avoided when breastfeeding a neonate with jaundice due to bilirubin displacement 1

Algorithm for NSAID Use in Pregnancy

1. First choice analgesic throughout pregnancy: Acetaminophen
2. If acetaminophen insufficient:
   • First/Second trimester: Short-term, intermittent use of nonselective NSAIDs (ibuprofen preferred)
   • Third trimester: Avoid all NSAIDs; use acetaminophen or low-dose prednisone if necessary
3. If chronic anti-inflammatory treatment needed: Consider pregnancy-compatible disease-modifying drugs like hydroxychloroquine, sulfasalazine, or low-dose prednisone 1

Remember that even short-term use (as little as 16 hours) of NSAIDs in the third trimester can cause significant ductal constriction and pulmonary hypertension 2.