Pregnancy and medications for inflammatory bowel disease: An updated narrative review

Table 2 Summary of systematic review and meta-analyses regarding the safety profiles of biologics and small molecules for pregnant women with inflammatory bowel disease

Biologics/small molecules	ECCO’s guideline[25]	Summaries of recent systematic review and meta-analysis
TNF inhibitors (monotherapy)	Low risk	There was an increased risk of preterm births, LBW, and cesarian section in patients with IBD treated with TNF inhibitors[27]. This study was limited in its understanding of whether anti-TNF monotherapy or its combination with thiopurines is associated with these risks
TNF inhibitors with thiopurines	Thiopurine discontinuation may be considered on an individualized basis	Meta-analyses including recent prospective studies that assess the risk of combination therapy for pregnant women with IBD are lacking
Vedolizumab	Low risk, limited data	Women treated with vedolizumab had an increased risk of preterm births and early pregnancy loss compared with those unexposed to vedolizumab during pregnancy. No differences were observed in the number of live births or congenital abnormalities[26,30]. The systematic review and meta-analyses’ results may be biased by disease activity
Ustekinumab	Low risk, limited data	A meta-analysis including two case studies showed that women treated with ustekinumab had an increased risk of early pregnancy loss compared with those treated with TNF inhibitors[26]. The prevalence of adverse pregnancy events was likely to be overestimated due to the small number of studies in this meta-analysis
JAK inhibitors	Contraindicated (no mention of upadacitinib)	N/A
Ozanimod	Contraindicated	N/A
Calcineurin inhibitors	Low risk, limited data	A meta-analysis including 4450 CNI-treated patients (4372 solid organ transplant recipients and 78 patients with IMIDs including IBD) showed that the rates of preterm delivery, LBW, and preeclampsia were 3–4 times greater than the rates in the general population. The risk of neonatal prematurity was higher in solid organ transplant recipients than in patients with IMIDs due to the higher risk of preeclampsia in solid organ transplant recipients. CNIs may be safer for pregnant women with immune-mediated diseases than for solid organ transplant recipients[38]

CNI: Calcineurin inhibitor; ECCO: European Crohn’s and Colitis Organization; IBD: Inflammatory bowel disease; IMIDs: Immune-mediated inflammatory diseases; JAK: Janus kinase; LBW: Low birth weight; TNF: Tumor necrosis factor; UC: Ulcerative colitis; N/A: Not applicable.