Is it safe to use Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) during pregnancy?

NSAIDs During Pregnancy: Safety Considerations

NSAIDs should be restricted to the first and second trimesters of pregnancy, used at the lowest effective dose for short durations (7-10 days), and must be discontinued after gestational week 28 due to significant fetal risks. 1

Safety by Trimester

First Trimester

• Early pregnancy exposure to NSAIDs shows no evidence of increased risk of miscarriage or teratogenicity 1
• Most reassuring data are available for ibuprofen, followed by diclofenac, whereas data for COX-2 inhibitors are limited 1
• NSAIDs can interfere with ovulation and may reduce fertility in women trying to conceive due to luteinized unruptured follicle (LUF) syndrome 1

Second Trimester

• Short-term use (7-10 days) in the second trimester does not appear to pose substantial risks for the fetus 1, 2
• Safety depends on exposure time, treatment duration, dosage, and intensity of prostaglandin inhibition 1
• Nonselective NSAIDs with a short half-life (e.g., ibuprofen) are preferred 1

Third Trimester

• Strongly recommended against use of NSAIDs in the third trimester (after gestational week 28) 1
• Significant fetal risks include:
  • Premature closure of the ductus arteriosus 1
  • Oligohydramnios (reduced amniotic fluid) 1, 3
  • Pulmonary hypertension in the newborn 1, 4
  • Renal dysfunction in the fetus 1, 4, 3
  • Increased risk of intracranial hemorrhage 4

Specific Recommendations for NSAID Use

Preferred Agents

• Ibuprofen has the most reassuring safety data for use during pregnancy (first and second trimesters) 1
• Diclofenac is considered the second safest option based on available evidence 1
• Nonselective NSAIDs are preferred over COX-2 inhibitors due to limited safety data for the latter 1

Dosing Considerations

• Use the lowest effective dose for the shortest duration possible 1, 5
• Short-term use (7-10 days) is preferred over prolonged therapy 1, 2
• For women having difficulty conceiving, consider discontinuing NSAIDs 1

Special Circumstances

Preconception Period

• NSAIDs can block blastocyst implantation in animal models 1
• Women actively trying to conceive should consider avoiding NSAIDs 1
• If used while trying to conceive, use intermittently rather than continuously to avoid interference with ovulation 1

Breastfeeding

• Most NSAIDs are considered safe during breastfeeding as they transfer in low amounts to breast milk 1, 4
• Avoid in breastfeeding neonates with jaundice as NSAIDs can displace bilirubin 1

Common Pitfalls and Caveats

• Self-medication with over-the-counter NSAIDs is common during pregnancy but should be avoided without medical supervision 3, 6
• Maternal effects when NSAIDs are used close to term include prolonged gestation and labor 1, 3
• Patients should be clearly informed about the risks of third-trimester use, as many may not realize over-the-counter medications can pose significant risks 5, 6
• Long-term use even in the late second trimester should be monitored carefully for fetal effects 2
• Always balance the maternal benefits against potential fetal risks when considering NSAID use during pregnancy 3