Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Biostatistics, School of Public Health, Key Laboratory of Public Health Safety, Fudan University, Shanghai, China.
Am J Gastroenterol. 2023 Mar 1;118(3):491-500. doi: 10.14309/ajg.0000000000002179. Epub 2023 Jan 9.
Maternal inflammatory bowel disease (IBD) during pregnancy may be associated with increased susceptibility to infection in offspring. We aimed to assess this association, taking into consideration the mediating role of anti-tumor necrosis factor α (anti-TNFα) agents and adverse birth outcomes.
This population-based cohort study included all live-born singletons born in Denmark during 1995-2016 (n = 1,343,960). The exposure was maternal IBD. Main outcome of interest was offspring infection younger than 5 years, defined by either infection-related hospitalization or systemic antibiotic prescription, whose corresponding risk estimates were hazard ratios (HRs) and incidence rate ratios (IRRs), respectively. We applied an inverse probability-weighted marginal structural model for mediation analysis.
Offspring born to mothers with Crohn's disease (CD) had an 18% increased risk of infection-related hospitalization (HR 1.18, 95% confidence interval 1.10-1.26) and a 16% increased frequency of prescribed antibiotics (IRR 1.16, 95% confidence interval 1.11-1.21). Anti-TNFα agents could explain 10% and 3% of the 2 estimated total associations, respectively, while a composite of preterm birth, low birth weight, and small for gestational age could explain 4% and 0%, respectively. The association between prenatal anti-TNFα and frequency of antibiotics attenuated after additional adjustment for maternal CD (IRR from 1.23 [0.98-1.55] to 1.10 [0.87-1.40]). Maternal ulcerative colitis, however, was not associated with offspring infection.
Maternal CD, but not ulcerative colitis, was associated with an increased risk of infection in offspring younger than 5 years, of which adverse birth outcomes and anti-TNFα had a minor role. The association between anti-TNFα agents and pediatric infection could be partially explained by maternal CD.
母亲在怀孕期间患炎症性肠病（IBD）可能会使后代更容易感染。我们旨在评估这种关联，同时考虑到抗肿瘤坏死因子α（anti-TNFα）药物和不良出生结局的中介作用。
这项基于人群的队列研究纳入了 1995 年至 2016 年期间在丹麦出生的所有活产单胎（n=1,343,960）。暴露因素为母亲的 IBD。主要观察结果为 5 岁以下儿童的感染，其定义为感染相关住院或全身抗生素处方，相应的风险估计为风险比（HR）和发病率比（IRR）。我们应用逆概率加权边缘结构模型进行中介分析。
患有克罗恩病（CD）的母亲所生的子女感染相关住院的风险增加了 18%（HR 1.18，95%置信区间 1.10-1.26），抗生素处方的频率增加了 16%（IRR 1.16，95%置信区间 1.11-1.21）。抗 TNFα 药物可以分别解释这 2 个估计总关联的 10%和 3%，而早产、低出生体重和小于胎龄儿的综合指标可以分别解释 4%和 0%。产前抗 TNFα 与抗生素使用频率之间的关联在进一步调整母亲 CD 后减弱（IRR 从 1.23 [0.98-1.55]降至 1.10 [0.87-1.40]）。然而，母亲溃疡性结肠炎与子女感染无关。
母亲 CD 而不是溃疡性结肠炎与 5 岁以下子女感染的风险增加有关，其中不良出生结局和抗 TNFα 药物的作用较小。抗 TNFα 药物与儿科感染之间的关联可能部分可以通过母亲 CD 来解释。
