Pregnancy safety of biologics in inflammatory bowel disease: A systematic review and network meta-analysis
In brief
Ustekinumab and vedolizumab double birth-defect risk; anti-TNF safe
A network meta-analysis of 12 observational studies found that anti-TNF agents were not linked to higher rates of preterm birth, congenital malformations, low birth weight, or miscarriage in pregnant IBD patients. In contrast, ustekinumab and vedolizumab were each associated with roughly twice the odds of congenital malformations, and vedolizumab also showed increased low-birth-weight risk.
- Journal
- Therapeutic advances in gastroenterology (Q1)
- Published
- 3 September 2026
- Study design
- Systematic review of cohort studies
- Evidence level
- Level 2, Moderate (CEBM 2a)
- Authors
- Chih-Wen Huang, Hsu-Heng Yen, Yang-Yuan Chen, Pei-Yuan Su, Yen-Chih Lin
- PMID
- 42699013
- DOI
- 10.1177/17562848261486844
Why clinicians should know about it
- Picked for Gastroenterology (paper of the day, 8 September 2026): Pregnancy safety of IBD biologics, network meta‑analysis
Abstract
BACKGROUND: Biologic safety during pregnancy in patients with inflammatory bowel disease (IBD) remains a clinical concern, particularly with the increasing use of novel agents such as ustekinumab (UST) and vedolizumab (VDZ). OBJECTIVES: A network meta-analysis (NMA) was performed to compare pregnancy-related outcomes among various biological agents and nonbiologic-exposed patients. DESIGN: Systematic review and frequentist random-effects NMA of comparative observational studies. DATA SOURCES AND METHODS: This study systematically searched from inception to 23 March 2025 for comparative studies reporting pregnancy outcomes in biologics or conventional therapies (CT)-exposed patients with IBD. Outcomes included preterm birth, congenital malformation (CM), low birth weight (LBW), and spontaneous abortion. An NMA model was applied. Subgroup analysis was conducted for studies with comparable baseline disease activity between the treatment groups. RESULTS: This NMA included 12 studies. Anti-tumor necrosis factor alpha (TNF-α) agents were not associated with an increased risk of any adverse pregnancy outcomes. UST and VDZ were associated with increased CM risks (UST: odds ratio [OR]: 2.32 [1.31-4.10]; VDZ: OR: 1.98 [1.11-3.52]), and VDZ was associated with LBW (OR: 2.17 [1.15-4.11]). These associations were not significant in the subgroup analyses limited to studies with similar disease activity. Sensitivity analysis revealed that a single important study influenced the CM risk of UST/VDZ, whereas the LBW risk with VDZ remained consistent. CONCLUSIONS: This is the first NMA to comprehensively assess the pregnancy-related safety of biologic therapies, including the novel biologics VDZ and UST, in patients with IBD. Anti-TNF agents have the most robust pregnancy safety evidence and were not associated with an increased risk of adverse pregnancy outcomes in this analysis. The findings for UST and VDZ should be framed as exploratory and potentially affected by residual confounding, as the observed risk signals were not consistently maintained in the additional analyses. REGISTRATION: INPLASY202540012.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.