Why are Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) contraindicated in pregnancy?

NSAIDs Contraindications in Pregnancy

NSAIDs should be avoided in the third trimester of pregnancy (after gestational week 28) due to significant risks of premature closure of the ductus arteriosus, oligohydramnios, pulmonary hypertension, and impaired renal function in the fetus. 1, 2

Timing-Related Risks of NSAIDs in Pregnancy

• Early pregnancy (first trimester): Generally no evidence of increased risk of miscarriage or teratogenicity, with most reassuring data available for ibuprofen, followed by diclofenac 1, 2
• Second trimester: Short-term use (7-10 days) appears relatively safe, but long-term use requires careful consideration 1, 3
• Third trimester (after week 28): Contraindicated due to significant fetal risks 1, 2
• Periconception period: NSAIDs can interfere with ovulation and may reduce fertility in women trying to conceive due to luteinized unruptured follicle (LUF) syndrome 1, 2

Specific Fetal Risks in Late Pregnancy

Cardiovascular Effects

• Premature closure of the ductus arteriosus, which can lead to pulmonary hypertension in the newborn 1, 4
• The risk increases with advancing gestational age, particularly after week 28 1, 2
• This effect is due to prostaglandin inhibition, which is essential for maintaining ductal patency 5

Renal Effects

• Reduced fetal urine output leading to oligohydramnios (reduced amniotic fluid) 1, 6
• Impaired renal function in the neonate 4, 5
• These effects have been demonstrated with multiple NSAIDs including indomethacin, naproxen, ketoprofen, and ibuprofen 1

Other Fetal/Neonatal Risks

• Increased cutaneous and intracranial bleeding risk 1
• Prolonged gestation and labor due to inhibition of prostaglandin synthesis 1, 5
• Increased peripartum blood loss and maternal anemia 1

Maternal Considerations

• Potential increased risk of miscarriage with NSAID use during early pregnancy (though evidence is mixed) 5
• NSAIDs can interfere with blastocyst implantation based on animal models 1
• Women actively trying to conceive should avoid NSAIDs or use them intermittently rather than continuously 1, 2

Recommendations for NSAID Use in Pregnancy

• First trimester: Limited short-term use appears relatively safe, with ibuprofen having the most reassuring safety profile 1, 2
• Second trimester: Short-term use (7-10 days) at lowest effective dose appears to have minimal risk 1, 3
• Third trimester: All NSAIDs should be discontinued after gestational week 28 1, 2
• When analgesic/antipyretic treatment is needed during the third trimester, acetaminophen (paracetamol) is the preferred alternative 1

Pharmacological Mechanism of Harm

• NSAIDs inhibit cyclooxygenase (COX) enzymes, reducing prostaglandin synthesis 5
• Prostaglandins are essential for maintaining ductal patency and proper renal function in the fetus 5
• The risk increases with higher doses, longer duration of treatment, and advancing gestational age 1, 5

Common Clinical Pitfalls

• Many women are unaware of the risks of NSAID use in late pregnancy, with studies showing approximately 3% usage rate close to delivery despite contraindications 7
• Over-the-counter availability of many NSAIDs may contribute to inadvertent use during pregnancy 7
• The effects of NSAIDs on the fetus depend on the specific agent, dose, duration of therapy, gestational age, and time between administration and delivery 5
• Low-dose aspirin (used for preeclampsia prevention) appears to have a different risk profile than therapeutic doses of other NSAIDs 1