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A Murine Model of Fetal Exposure to Maternal Inflammation to Study the Effects of Acute Chorioamnionitis on Newborn Intestinal Development
Published on: June 24, 2020
Fetal and Early-Life Antibiotics and Risk of Pediatric Inflammatory Bowel Disease: A Population-Based Nationwide
Svend Andersen1,2, Sigrid Valen Hestetun2,3, Tomm Bernklev2,4
1Department of Pediatrics, Vestfold Hospital Trust, Tønsberg, Norway.
Insights
Antibiotic exposure in children before age two increases the risk of pediatric inflammatory bowel disease (PIBD). Prenatal antibiotic exposure showed a non-significant association with PIBD development.
Area of Science:
- Pediatric gastroenterology
- Epidemiology
- Pharmacology
Background:
- Pediatric inflammatory bowel disease (PIBD) is a growing concern.
- Previous studies on antibiotic exposure and PIBD risk have yielded inconsistent results.
- The role of prenatal antibiotic exposure remains underexplored.
Purpose of the Study:
- To investigate the association between prenatal and early-life antibiotic exposure (before 2 years) and the risk of developing PIBD.
- To clarify risk estimations and include prenatal exposure in the analysis.
Main Methods:
- A register-based cohort study in Norway (2004-2020) included 536,819 children.
- Antibiotic exposure was defined by dispensed medications to mothers during pregnancy and to children before age two.
- Pediatric inflammatory bowel disease (PIBD) was identified using ICD-Tenth Revision codes.
Main Results:
- A significant association was found between antibiotic exposure before age two and increased PIBD risk (aOR 1.33).
- Maternal smoking during pregnancy amplified this association (aOR 1.42).
- A dose-response relationship was observed, with greater risk for broad-spectrum antibiotics (aOR 2.57). Prenatal exposure was not significantly associated with PIBD (aOR 1.15).
Conclusions:
- Early-life antibiotic exposure (before age two) is linked to a higher likelihood of developing pediatric inflammatory bowel disease.
- Prenatal antibiotic exposure did not show a statistically significant association with subsequent PIBD.
Objective:
To assess whether antibiotic exposure prenatally and before 2 years of age is associated with subsequent pediatric inflammatory bowel disease (PIBD), as earlier studies diverge substantially in risk estimations or do not include prenatal exposure.
Methods:
We performed a register-based cohort study including all children in Norway born 2004-2012 until study's end on December 31, 2020. Exposures were defined as dispensed antibiotics to mothers during pregnancy and to children before 2 years of age. Main outcome was International Classification of Diseases, Tenth Revision, code registrations consistent with PIBD.
Results:
Among 536 819 children, 797 PIBD cases were identified. The aOR for developing PIBD if exposed to antibiotics before 2 years of age compared with no exposure was 1.33 (95% CI 1.15-1.53), adjusted for sex and prenatal antibiotic exposure. An adjustment for maternal smoking during pregnancy increased the aOR to 1.42 (1.22-1.66), but with minimal changes after further adjustments for potential confounders related to pregnancy, birth, or socioeconomic status. A dose-response association was observed in those receiving more than 2 antibiotic courses (aOR 1.47, 1.25-1.73), and with greater effect estimates for broad-spectrum antibiotics (aOR 2.57, 1.82-3.63). Antibiotic exposure during pregnancy was numerically but not significantly associated with offspring PIBD (aOR 1.15, 0.99-1.34).
Conclusions:
Children exposed to antibiotics before 2 years of age were more likely to develop pediatric IBD than controls. Exposure prenatally to maternal antibiotics was numerically but not statistically significant associated to subsequent PIBD.
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