What are the effects of Diclofenac (Nonsteroidal Anti-Inflammatory Drug (NSAID)) on pregnancy?

Diclofenac Effects on Pregnancy

Diclofenac should be avoided in the third trimester of pregnancy due to significant risks of premature closure of the ductus arteriosus and oligohydramnios, and should be used with caution in the first and second trimesters only for short-term treatment at the lowest effective dose. 1, 2, 3

Safety Profile by Trimester

First Trimester

• Relatively safe for short-term use with no significant evidence of increased risk of teratogenicity 2, 4
• A prospective observational cohort study found no increased risk of major birth defects (1.8% vs 3.1%) or spontaneous abortion after first trimester exposure 4
• May be used cautiously for short periods (7-10 days) at the lowest effective dose 3

Second Trimester

• Conditionally recommended for short-term use (7-10 days) at the lowest effective dose 2, 3
• Long-term use or high doses (≥150mg/day) may cause early-onset oligohydramnios even before gestational week 28 5
• Nonselective NSAIDs like diclofenac are preferred over COX-2 inhibitors due to more available safety data 2, 3

Third Trimester

• Strongly contraindicated after gestational week 28 2, 3, 1
• Associated with 15-fold higher risk of premature closure of the ductus arteriosus 6
• Can cause significant fetal complications including:
  • Premature closure of the ductus arteriosus
  • Oligohydramnios
  • Neonatal renal impairment
  • Pulmonary hypertension in the newborn
  • Necrotizing enterocolitis
  • Intracranial hemorrhage 1, 7, 8

Effects on Fertility

• May interfere with ovulation and fertility by inducing luteinized unruptured follicle (LUF) syndrome 2, 3
• Women with difficulty conceiving should consider discontinuing diclofenac 2, 3
• The FDA label indicates diclofenac may delay or prevent rupture of ovarian follicles, associated with reversible infertility 1

Monitoring and Management

For Women Planning Pregnancy

• Consider discontinuing diclofenac if trying to conceive 2, 3, 1
• Switch to safer alternatives like acetaminophen for pain management 3

For Women Already Pregnant

• If diclofenac is necessary between weeks 20-28:
  • Use lowest effective dose for shortest duration possible (≤7-10 days)
  • Consider monitoring with ultrasound for oligohydramnios if treatment extends beyond 48 hours 1
  • Discontinue immediately if oligohydramnios is detected 5
• After week 28: Avoid completely 2, 3, 1

Alternative Options

• Acetaminophen is the safest analgesic option throughout pregnancy 3
• For chronic inflammatory conditions, consider:
  • Hydroxychloroquine
  • Sulfasalazine (with folic acid supplementation)
  • Low-dose prednisone (≤5-10 mg/day) 2, 3

Special Considerations

• Reversibility: Oligohydramnios caused by diclofenac exposure may be reversible after discontinuation 5
• Preeclampsia: Avoid diclofenac in women with preeclampsia, especially with acute kidney injury 3
• Breastfeeding: Diclofenac results in low infant exposure via breast milk and is generally considered safe during lactation 7

Clinical Decision Algorithm

1. First assess gestational age:

   • After 28 weeks: Do not prescribe diclofenac under any circumstances
   • Before 28 weeks: Proceed to next step

2. Evaluate treatment necessity:

   • Is acetaminophen sufficient for pain control? If yes, use acetaminophen
   • If no, proceed to next step

3. For weeks 20-28:

   • Use diclofenac only for short duration (≤7-10 days)
   • Use lowest effective dose
   • Monitor with ultrasound if treatment exceeds 48 hours
   • Discontinue immediately if oligohydramnios detected

4. For weeks 0-20:

   • Short-term use acceptable at lowest effective dose
   • Avoid prolonged use or high doses (≥150mg/day)

5. For women trying to conceive:

   • Avoid diclofenac if possible due to potential fertility effects