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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
Associations between multiple perinatal exposures and risk of childhood hospitalisation with infection: a
Isobel M F Todd1,2, Lars Henning Pedersen3,4, Maria C Magnus5
1Department of Paediatrics, Royal Children's Hospital, The University of Melbourne, 50 Flemington Rd, Parkville, VIC, 3052, Australia. itodd@student.unimelb.edu.au.
Insights
Multiple perinatal exposures significantly increase childhood hospitalization risk for infections. The risk escalates with the number of co-occurring exposures, especially for preterm infants, informing targeted prevention strategies.
Area of Science:
- Perinatal epidemiology
- Pediatric infectious diseases
- Public health
Background:
- Perinatal exposures are known risk factors for childhood infections.
- Previous research often examined exposures individually, neglecting combined effects.
Purpose of the Study:
- To investigate the risk of hospitalised childhood infections associated with combinations of multiple perinatal exposures.
- To evaluate the cumulative and interactive effects of various perinatal risk factors.
Main Methods:
- Nationally linked registry data from Denmark and Norway (over 1.5 million births).
- Evaluated seven perinatal exposures: maternal antibiotic use, smoking, diabetes, hypertensive disorders, C-section, small for gestational age (SGA), and preterm birth.
- Used Cox regression and meta-analysis to estimate hazard ratios (HR) for hospitalised infections before age 5.
Main Results:
- Each individual exposure increased infection risk (e.g., HR 1.45 for preterm birth).
- Cumulative risk increased with the number of exposures (HR 1.88 for 5+ exposures).
- Preterm infants with additional exposures showed particularly elevated risk.
Conclusions:
- Combined perinatal exposures pose a significant cumulative risk for hospitalised childhood infections.
- Findings support targeted interventions for high-risk infants and families.
- A straightforward method for assessing co-occurring exposure risks is presented.
Abstract:
Several perinatal exposures impact severe infection risk in offspring. However, most studies consider exposures in isolation rather than the impact of multiple co-occurring perinatal exposures. Here, we investigated the risk of hospitalised childhood infections associated with combinations of multiple perinatal exposures. We studied liveborn, singleton births in Denmark between 1997 and 2019 (n = 1,113,708) and Norway between 2008 and 2018 (n = 470,270) through national registry linkage. Seven perinatal exposures were evaluated including maternal antibiotic use during pregnancy, maternal smoking, maternal diabetes, hypertensive disorders of pregnancy, caesarean section birth, offspring being small for gestational age (SGA), and preterm birth. The outcome was hospitalised infections before 5 years age. Using Cox regression, we estimated hazard ratios (HR) of hospitalised infections for: (1) each exposure individually; (2) the cumulative number of exposures; (3) each unique combination of the seven exposures; (4) pairwise interactions between exposures. Results were combined through meta-analysis. Each exposure was individually associated with greater hospitalised infection risk with pooled HR estimates ranging from 1.08 (95% CI 1.08-1.09) for SGA to 1.45 (95% CI 1.43-1.46) for preterm birth. Cumulative risk was observed for increasing number of exposures from a pooled HR of 1.17 (95% CI 1.17-1.18) for one exposure to 1.88 (95% CI 1.78-1.99) for five or more exposures. Analyses of unique combinations of the exposures showed a particularly increased risk among preterm children with one or more additional exposures. Our findings can inform targeted strategies for the prevention and management of childhood infections. We highlight a simple, intuitive method for measuring risk associated with co-occurring exposures.
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