What are the prenatal considerations for pregnant women taking sulfasalazine?

Sulfasalazine Use During Pregnancy: Prenatal Considerations

Sulfasalazine can be safely continued throughout pregnancy with appropriate supplementation of folic acid (2 mg daily) to prevent neural tube defects. 1

Safety Profile

Sulfasalazine has a well-established safety record during pregnancy based on multiple clinical guidelines and studies:

• Meta-analyses including 2,200 women with inflammatory bowel disease (IBD) found that sulfasalazine use was not associated with significant increases in:

  • Congenital abnormalities (OR 1.16; 95% CI 0.76-1.77)
  • Stillbirth (OR 2.38; 95% CI 0.65-8.72)
  • Spontaneous abortion (OR 1.14; 95% CI 0.65-2.01)
  • Preterm delivery (OR 1.35; 95% CI 0.85-2.13) 1

• The 2020 American College of Rheumatology guidelines explicitly list sulfasalazine as compatible with pregnancy, giving it their highest recommendation level (++) for use during preconception, pregnancy, and breastfeeding 1

Important Considerations

Folic Acid Supplementation

• Sulfasalazine inhibits absorption and metabolism of folic acid
• Higher dose folic acid supplementation (2 mg daily) is required throughout pregnancy 1, 2
• This is particularly important during the first trimester to prevent neural tube defects

Disease Activity Management

• Discontinuing sulfasalazine during pregnancy significantly increases the risk of disease flares
• Among patients with ulcerative colitis, those who continued 5-ASA/sulfasalazine treatment had a 26.5% flare rate compared to 56.3% in those who decreased or discontinued therapy (OR 3.6; 95% CI 1.0-12.4) 1
• Active disease during pregnancy is associated with worse maternal and fetal outcomes than medication risks 1

Placental Transfer and Breastfeeding

• Sulfasalazine and its metabolite sulfapyridine do cross the placenta 2
• Both are present in breast milk, though sulfasalazine levels are insignificant while sulfapyridine reaches 30-60% of maternal serum levels 2
• The risk of kernicterus (bilirubin displacement) is low as sulfapyridine has poor bilirubin-displacing capacity 2
• Monitoring newborns for jaundice is recommended, particularly in premature infants or those with hemolytic disease 3

Monitoring Recommendations

1. Preconception:

   • Begin folic acid 2 mg daily at least 3 months before conception 1
   • Ensure disease is well-controlled before conception

2. During Pregnancy:

   • Continue sulfasalazine at pre-pregnancy dose
   • Maintain folic acid supplementation throughout pregnancy
   • Monitor disease activity each trimester (fecal calprotectin levels can be used for IBD) 1
   • Regular obstetric care with attention to fetal growth

3. Postpartum/Breastfeeding:

   • Sulfasalazine is compatible with breastfeeding 1
   • Consider complete blood count monitoring in newborns if concerns arise 1
   • Monitor breastfed infants for diarrhea or bloody stools, though causal relationship is not established 2

Special Situations

• For patients with severe disease requiring multiple medications, sulfasalazine is one of the safest options and can be continued
• For male partners taking sulfasalazine who are planning conception, a semen analysis may be considered if there is delayed conception, as oligospermia has been reported 1, 2

Conclusion

The benefits of continuing sulfasalazine during pregnancy to maintain disease remission outweigh the potential risks. The most important intervention is ensuring adequate folic acid supplementation (2 mg daily) to counteract the drug's interference with folate metabolism.