Sulfasalazine During Pregnancy: Safety for IBD

What does the evidence say about sulfasalazine during pregnancy?

1. MotherToBaby summarizes more than 950 sulfasalazine-exposed pregnancies without a higher overall rate of birth differences. A signal in one study was difficult to interpret because the underlying illnesses and other factors were not adequately controlled. 1
2. The FDA label states that sulfasalazine inhibits folic acid absorption and metabolism. It also describes observational pregnancy comparisons in inflammatory bowel disease without clear outcome differences, while noting that case reports cannot establish whether low folate contributed to reported neural tube defects. 2
3. A 2025 meta-analysis of 15 observational studies found higher adverse-outcome estimates when sulfasalazine or 5-aminosalicylates were compared with healthy controls, but no significant increase when the comparison group had inflammatory bowel disease without these medicines. This pattern highlights confounding by the underlying disease. 3
4. A review of pregnancy in Crohn's disease and ulcerative colitis identifies active inflammatory bowel disease as a major predictor of preterm birth, low birth weight, and small-for-gestational-age birth, supporting disease control before and during pregnancy. 4
5. LactMed reports low milk transfer of sulfasalazine itself but measurable sulfapyridine, with a theoretical hemolysis concern in newborns and infants with G6PD deficiency. Most reported infants had no effects, although diarrhea and one bloody-diarrhea case support infant monitoring. 5

Is sulfasalazine safe in each trimester?

• First trimester. Folate is especially important during early fetal development, and sulfasalazine can interfere with folate absorption and metabolism. Confirm the prescribed folic acid amount before conception or as soon as pregnancy is recognized. Do not stop sulfasalazine on your own because a disease flare can also affect pregnancy.
• Second trimester. The goal is stable inflammatory bowel disease with the medication plan jointly reviewed by gastroenterology and obstetrics. Observational comparisons against people with the same disease are more informative than comparisons with healthy pregnancies, because active disease itself is linked with adverse pregnancy outcomes.
• Third trimester. Continue coordinated disease and blood-count monitoring as directed. Sulfasalazine-related newborn jaundice concerns have not been supported in a reported cohort of more than 1,800 exposed newborns, but delivery and feeding teams should still know the maternal medicine list and the baby's prematurity or G6PD status.