Ernest-Suarez Kenneth, Murguía-Favela Luis E, Constantinescu Cora, Fitzpatrick Tiffany, Top Karina A, Hu Jia, Jadavji Taj, Leung Yvette, Chan Melissa, Panaccione Remo, Seow Cynthia H
Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
Section of Hematology/Immunology, Department of Pediatrics, University of Calgary, Calgary, Alberta, Canada.
Clin Gastroenterol Hepatol. 2025 Apr;23(5):835-845. doi: 10.1016/j.cgh.2024.07.007. Epub 2024 Jul 31.
BACKGROUND & AIMS: Biologic therapies in the context of inflammatory bowel disease and pregnancy lead to improved maternal and fetal outcomes. Placental transfer results in detectable drug concentrations in infants. Rotavirus infection results in diarrheal related hospitalizations; however, the live oral vaccine is not currently recommended in biologic exposed infants. The aim of this study was to assess the effect of maternal biologic therapies on the infant immune system and safety of live rotavirus vaccination in biologic-exposed infants.
Biologic-exposed infants underwent standardized clinical assessments, drug concentration, and immune function testing (complete blood count, differential, immunoglobulin levels, extended B-cell and T-cell subset enumeration, Recent Thymic Emigrants, regulatory T-cell numbers, mitogen stimulation assays, and review of T-cell Receptor Excision Circles in the newborn screen). Rotavirus vaccine-specific adverse effects following immunizations up to 42 days post the last dose of the vaccine series were recorded.
There were 57 infants born to 52 mothers with inflammatory bowel disease exposed to infliximab (n = 21), adalimumab (n = 19), vedolizumab (n = 10), and ustekinumab (n = 7) in the third trimester for a median of 39 weeks (interquartile range, 38-39 weeks) at delivery. Immunologic assessments validated for age were normal in all infants despite median infliximab concentrations of 6.1 ug/mL (range, 0.4-28.8 ug/mL), adalimumab concentrations of 1.7 ug/mL (range, 0.7-7.9 ug/mL), ustekinumab concentrations of 0.6 ug/mL (range, 0-1.1), and undetectable for vedolizumab at 10.7 weeks (interquartile range, 9.4-12.4) of age. The live oral rotavirus vaccine series was provided to 50 infants with the first dose given at a median of 13 weeks of age. No adverse effects following immunization were reported.
Immune function testing was normal, and administration of live rotavirus vaccination appeared low-risk in biologic-exposed infants irrespective of circulating drug levels.
炎症性肠病患者孕期使用生物疗法可改善母婴结局。胎盘转运导致婴儿体内可检测到药物浓度。轮状病毒感染会导致因腹泻相关的住院治疗;然而,目前不建议在暴露于生物制剂的婴儿中使用口服活疫苗。本研究的目的是评估母亲生物疗法对婴儿免疫系统的影响以及在暴露于生物制剂的婴儿中接种轮状病毒活疫苗的安全性。
对暴露于生物制剂的婴儿进行标准化临床评估、药物浓度检测和免疫功能测试(全血细胞计数、分类计数、免疫球蛋白水平、扩展的B细胞和T细胞亚群计数、近期胸腺迁出细胞、调节性T细胞数量、丝裂原刺激试验以及新生儿筛查中的T细胞受体切除环检查)。记录在最后一剂疫苗接种后长达42天内接种轮状病毒疫苗后的特异性不良反应。
52名患有炎症性肠病的母亲所生的57名婴儿在孕晚期暴露于英夫利昔单抗(n = 21)、阿达木单抗(n = 19)、维得利珠单抗(n = 10)和乌司奴单抗(n = 7),分娩时孕周中位数为39周(四分位间距,38 - 39周)。尽管英夫利昔单抗浓度中位数为6.1μg/mL(范围,0.4 - 28.8μg/mL)、阿达木单抗浓度为1.7μg/mL(范围,0.7 - 7.9μg/mL)、乌司奴单抗浓度为0.6μg/mL(范围,0 - 1.1),且在10.7周龄(四分位间距,9.4 - 12.4)时未检测到维得利珠单抗,但所有婴儿经年龄校正的免疫评估均正常。50名婴儿接种了口服轮状病毒活疫苗系列,首剂接种时年龄中位数为13周。未报告接种疫苗后的不良反应。
免疫功能测试正常,且无论循环药物水平如何,在暴露于生物制剂的婴儿中接种轮状病毒活疫苗似乎风险较低。