Abstract Background Inflammatory bowel disease (IBD) frequently affects women of reproductive age. Infertility, miscarriage, preterm birth, and low birth weight are known complications of active disease during conception and pregnancy(1-3). Biologic therapies are now widely used in the management of IBD. This systematic review and meta-analysis provides an update of pregnancy outcomes associated with biologics, incorporating recent evidence on emerging therapies. Methods We conducted a systematic review and meta-analysis according to PRISMA guidelines. MEDLINE, Embase, Cochrane, and Web of Science were searched through March 2025. Eligible studies included pregnancies in women with IBD exposed to tumour necrosis factor (TNF) inhibitors, vedolizumab (VDZ), ustekinumab (UST), Janus kinase (JAK) inhibitors or sphingosine-1-phosphate (S1P) receptor modulators, and reporting at least one adverse pregnancy outcome. The primary outcomes were early pregnancy loss (EPL), ectopic pregnancy, stillbirth, pre-eclampsia, preterm birth, low birth weight (LBW), small for gestational age (SGA), intrauterine growth restriction (IUGR), and congenital abnormalities. Pooled prevalence estimates were calculated using a random-effects model, and a network meta-analysis (NMA) was performed for biologic class comparisons. PROSPERO Protocol #CRD420251025445. Results Fifty-five studies comprising 13,888 pregnancies met inclusion criteria. Advanced therapy in IBD pregnancies was associated with a pooled prevalence rates were: EPL 9% (95% CI, 9–10%, I2 = 43.4-64.5%), ectopic pregnancy 3% (95% CI 2.6–3.3%; I2 = 0-26.2%), stillbirth 0.7% (95% CI, 0.5–0.9%; I2 = 0-13.3%), pre-eclampsia 1.8% (95% CI 1.6–2.0%; I2 = 35.9-58.3%), preterm birth 8% (95% CI, 8–9%; I2 = 0-47.5%), LBW 3% (95% CI, 3–4%; I2 = 0-55.6%), SGA 5% (95% CI, 5–6%; I2 = 0-62.4%), IUGR 1.8% (95% CI, 1.5–2.0%; I2 = 2.3-22%), and congenital abnormalities 3% (95% CI, 2–3%; I2 = 0-54%). Compared to anti-TNF, meta-analysis showed possible signals for preterm births with vedolizumab (OR 1.45, 95% CI 1.02–2.06) and congenital abnormalities with ustekinumab (OR 1.89, 95% CI 1.10–3.23). Beyond this no overall increased risk of adverse outcomes were associated with biologic exposure. Across outcomes, NMA rankings suggested that anti-TNF agents demonstrated the most consistent and favourable safety profile in pregnancy. Conclusion Anti-TNF agents remain the most extensively studied and appear safe throughout pregnancy. Vedolizumab and ustekinumab warrant continued surveillance, particularly in relation to preterm birth and congenital abnormality outcomes. This aligns with the Global Consensus Statement on Pregnancy in IBD, which supports continuation of anti-TNF during pregnancy and emphasises pharmacovigilance for newer biologics(4). References: 1. De Lima-Karagiannis A, Zelinkova-Detkova Z, van der Woude CJ. The Effects of Active IBD During Pregnancy in the Era of Novel IBD Therapies. Am J Gastroenterol. 2016;111(9):1305-12. 2. Kammerlander H, Nielsen J, Kjeldsen J, Knudsen T, Friedman S, Nørgård B. The Effect of Disease Activity on Birth Outcomes in a Nationwide Cohort of Women with Moderate to Severe Inflammatory Bowel Disease. Inflamm Bowel Dis. 2017;23(6):1011-8. 3. Molnár T, Farkas K, Nagy F, Lakatos PL, Miheller P, Nyári T, et al. Pregnancy outcome in patients with inflammatory bowel disease according to the activity of the disease and the medical treatment: a case-control study. Scand J Gastroenterol. 2010;45(11):1302-6. 4. Mahadevan U, Seow CH, Barnes EL, Chaparro M, Flanagan E, Friedman S, et al. Global Consensus Statement on the Management of Pregnancy in Inflammatory Bowel Disease. Clinical Gastroenterology and Hepatology. 2025;23(11):S1-S60. Conflict of interest: Dr. Prada, Caterina: No conflict of interest Subhaharan, Deloshaan: Nil Jones, Mark: No conflict of interest Mohsen, Waled: No conflict of interest Kakkadasam Ramaswamy, Pradeep: None
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