OBJECTIVES: This study aims to evaluate the risks associated with Sulfasalazine (SSZ) and 5-aminosalicylic acid (5-ASA) use during pregnancy on perinatal outcomes in women with Inflammatory Bowel Diseases (IBD). We compared these outcomes with those of healthy pregnant women and with pregnant women with IBD not on medication. DATA SOURCES: We searched Medline, Embase, CINAHL, Scopus, and PubMed databases up to December 27, 2023. We also screened reference lists of identified studies and utilized SCOPUS to find additional relevant research. STUDY ELIGIBILITY CRITERIA: We included studies that specifically examined SSZ/5-ASA usage during pregnancy. Our outcomes of interest included congenital malformations, stillbirths, neonatal outcomes, preterm delivery, live births, small for gestational age, and pregnancy loss. SYNTHESIS METHODS: Pooled odds ratios (OR) were calculated using a random-effects model to accommodate within-study and between-study variability, given the substantial heterogeneity from differences in study designs and methodologies. The risk of bias was assessed using the Newcastle-Ottawa Scale (NOS). RESULTS: Fifteen observational studies with 2,076,932 participants were included. SSZ/5-ASA use during pregnancy was linked to a significant increase in congenital malformations (OR: 1.33, 95 % CI: 1.17-1.50), stillbirths (OR: 5.12, 95 % CI: 2.74-9.57), and preterm delivery (OR: 1.94, 95 % CI: 1.49-2.52) compared to healthy controls. However, no significant risks were found when compared with pregnant women with IBD not on medication. CONCLUSIONS: The observed risks appear related to the disease rather than medication, suggesting treatment may mitigate adverse outcomes. Distinguishing between the effects of disease and medication poses ethical challenges in pregnant populations.