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Maternal Inflammatory Bowel Disease During Pregnancy and Infectious Disease in Offspring Younger Than 5 Years: A
Tai Ren1, Yongfu Yu2,3, Hui Wang1
1Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Insights
Maternal Crohn's disease during pregnancy increases offspring infection risk. Anti-TNFα agents and adverse birth outcomes play minor roles in this association, with maternal Crohn's disease partially explaining the link to pediatric infections.
Area of Science:
- Perinatal Medicine
- Pediatric Infectious Diseases
- Gastroenterology
Background:
- Maternal inflammatory bowel disease (IBD) during pregnancy may impact offspring infection susceptibility.
- Understanding the role of treatments like anti-tumor necrosis factor α (anti-TNFα) agents and birth outcomes is crucial.
Purpose of the Study:
- To assess the association between maternal IBD during pregnancy and offspring infection risk.
- To investigate the mediating roles of anti-TNFα agents and adverse birth outcomes.
Main Methods:
- Population-based cohort study of 1,343,960 live-born singletons in Denmark (1995-2016).
- Exposure: maternal IBD; Outcome: offspring infection (<5 years) via hospitalization or antibiotic prescription.
- Inverse probability-weighted marginal structural models used for mediation analysis.
Main Results:
- Maternal Crohn's disease (CD) associated with 18% increased hospitalization risk and 16% increased antibiotic frequency in offspring.
- Anti-TNFα agents explained 10% (hospitalization) and 3% (antibiotics) of the association.
- Adverse birth outcomes had a minimal role; maternal ulcerative colitis was not associated with offspring infection.
Conclusions:
- Maternal CD, not ulcerative colitis, increases offspring infection risk.
- Anti-TNFα agents and adverse birth outcomes play a minor mediating role.
- Maternal CD partially explains the link between anti-TNFα agents and pediatric infections.
Introduction:
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.
Methods:
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.
Results:
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.
Discussion:
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.
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