What are the recommended Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) for pain and fever management in pregnancy?

NSAID Use in Pregnancy: Timing-Based Recommendations

Acetaminophen is the first-line analgesic throughout pregnancy, while NSAIDs can be used cautiously during the first and second trimesters only (up to gestational week 28), with ibuprofen being the preferred NSAID if needed, but all NSAIDs must be discontinued by week 28 due to serious fetal risks. 1, 2

First-Line Treatment: Acetaminophen

• Acetaminophen remains the safest and recommended first-line medication for pain and fever management throughout all trimesters of pregnancy 3
• Use at the lowest effective dose for the shortest possible duration 3, 4
• Maximum daily dose should not exceed 4g, though consider limiting chronic use to 3g or less per day 3
• Despite emerging concerns about neurodevelopmental effects with prolonged use (>28 days), acetaminophen maintains the most favorable safety profile compared to alternatives 3, 4

NSAID Use: Strict Gestational Age Restrictions

First and Second Trimesters (Up to Week 28)

• NSAIDs may be used during the first and second trimesters if acetaminophen is insufficient, but only for short durations (7-10 days maximum) at the lowest effective dose 1, 2
• Ibuprofen is the preferred NSAID with the most reassuring safety data, followed by diclofenac 1, 2
• Early pregnancy NSAID exposure shows no evidence of increased miscarriage risk or teratogenicity when used appropriately 1, 2
• Typical dosing: ibuprofen 200-400mg every 6-8 hours, limited to 7-10 days 2

Critical Cutoff: Gestational Week 28

• All NSAIDs must be discontinued by gestational week 28 (not the traditional "third trimester" designation) 1, 2
• This timing is critical because fetal sensitivity to NSAID-related complications increases significantly after this point 2

Third Trimester (After Week 28): Absolute Contraindication

• NSAIDs are absolutely contraindicated after gestational week 28-30 1, 2, 5
• Serious fetal risks include:
  • Premature closure of ductus arteriosus 1, 5
  • Oligohydramnios (reduced amniotic fluid) 1, 2
  • Pulmonary hypertension 1
  • Impaired renal function and reduced urine output 1
  • Increased cutaneous and intracranial bleeding 1
• Maternal risks include prolonged gestation/labor, increased peripartum bleeding, and anemia 1

Specific NSAID Considerations

Ibuprofen (Preferred)

• Most reassuring safety data among NSAIDs 1, 2
• Safe during breastfeeding with low breast milk transfer 1, 2
• Must discontinue by week 28 1, 2

Naproxen

• Can be used in first/second trimester but has longer half-life than ibuprofen 1
• FDA labeling specifically warns against use in late pregnancy due to premature ductus arteriosus closure 5
• American Academy of Pediatrics considers it safe during breastfeeding 1

Indomethacin

• Associated with documented fetal complications (ductus arteriosus closure, oligohydramnios) 1
• Should be avoided unless specifically indicated for tocolysis under specialist supervision
• Safe during breastfeeding per American Academy of Pediatrics 1

COX-2 Inhibitors

• Limited safety data in pregnancy 1
• Prefer nonselective NSAIDs with short half-lives like ibuprofen over COX-2 selective agents 2

Special Populations and Situations

Women Trying to Conceive

• Avoid all NSAIDs when actively attempting conception 2
• NSAIDs can interfere with ovulation by inducing luteinized unruptured follicle (LUF) syndrome, potentially reducing fertility 2
• Continuous periovulatory NSAID exposure can prevent ovulation 2

Chronic Inflammatory Conditions

• Transition to pregnancy-compatible alternatives before conception or early in pregnancy 2
• Safe alternatives include: hydroxychloroquine, sulfasalazine (with folic acid supplementation), low-dose prednisone, azathioprine, cyclosporine, or tacrolimus 1

Breastfeeding

• Ibuprofen, indomethacin, and naproxen are considered safe during breastfeeding with trace amounts in breast milk 1
• Contraindicated when breastfeeding a neonate with jaundice due to bilirubin displacement 1

Critical Clinical Pitfalls to Avoid

1. Do not confuse "third trimester" with the critical week 28 cutoff - the restriction begins at week 28, not week 27-28 as traditionally defined for trimesters 1, 2

2. Avoid combination cold medications - many contain NSAIDs or acetaminophen; oral decongestants combined with acetaminophen should be avoided in first trimester due to increased risk of gastroschisis 3

3. Do not prescribe NSAIDs for chronic use during pregnancy - limit to 7-10 days maximum 1, 2

4. Monitor for signs of premature ductus arteriosus closure if NSAIDs were inadvertently used after week 28 - this can cause life-threatening cardiac failure in the newborn 6

5. Educate patients about over-the-counter NSAIDs - many women don't realize ibuprofen and naproxen are NSAIDs and may self-medicate inappropriately 5

Practical Algorithm for Pain Management in Pregnancy

Step 1: Attempt non-pharmacological approaches first (rest, physical therapy, heat/cold therapy) 3

Step 2: If medication needed, start with acetaminophen at lowest effective dose for shortest duration 3

Step 3: If acetaminophen insufficient AND gestational age <28 weeks, consider ibuprofen 200-400mg every 6-8 hours for maximum 7-10 days 1, 2

Step 4: If gestational age ≥28 weeks and acetaminophen insufficient, consider opioids only for severe pain at lowest effective dose for shortest time, or consult pain specialist 3

Step 5: For chronic inflammatory conditions requiring ongoing treatment, use pregnancy-compatible disease-modifying agents rather than NSAIDs 1, 2