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The familial risk of infection-related hospitalization in children: A population-based sibling study
Jessica E Miller1,2, Kim W Carter3, Nicholas de Klerk3
1Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Victoria, Australia.
Insights
Children with siblings previously hospitalized for infection face a higher risk of severe infections themselves. This sibling risk increases with the number of affected siblings, highlighting family-based public health concerns.
Area of Science:
- Epidemiology
- Public Health
- Genetics
Background:
- Childhood infections pose significant health risks.
- Understanding familial transmission patterns of infection severity is crucial for public health.
- Sibling analysis offers a unique approach to studying shared environmental and genetic factors in disease risk.
Purpose of the Study:
- To investigate the association between sibling infection-related hospitalizations and a child's risk of severe infection.
- To quantify the increased risk of infection-related hospitalization in probands with infected siblings.
- To explore the dose-dependent effect of sibling infections on childhood infection risk.
Main Methods:
- Population-based cohort study utilizing genealogical linkage in Western Australia (1980-2014).
- Infection-related hospitalizations were identified using discharge diagnostic codes.
- Adjusted Cox proportional hazard models were employed to estimate infection risks, considering sibling exposure and number of siblings.
Main Results:
- Children with at least one sibling previously hospitalized for infection had a significantly increased risk of infection-related hospitalization (aHR 1.41).
- A dose-dependent relationship was observed: risk increased with 1, 2, or 3+ affected siblings (aHRs 1.41, 1.65, 1.83, respectively).
- Highest sibling risks were noted for genitourinary, gastrointestinal, and skin/soft tissue infections, with increased risk also associated with more and older siblings.
Conclusions:
- A prior sibling hospitalization for infection is a significant risk factor for infection-related hospitalization in children.
- Findings suggest a familial component to infection severity, warranting targeted public health interventions for families with a history of childhood infections.
- The study underscores the importance of considering family history in assessing and managing severe childhood infections.
Objective:
To assess the risk of severe childhood infections within families, we conducted a sibling analysis in a population-based cohort study with genealogical linkage. We investigated the sibling risk of hospitalization with common infections, a marker of severity. We hypothesized that having siblings hospitalized for infection would increase the proband's risk of admission with infection.
Study Design:
We used population data on Western Australian live-born singletons and their siblings between 1980 and 2014. Measures of infection were infection-related hospitalizations from discharge diagnostic codes. Exposure was having a sibling who had an infection-related hospitalization. Outcomes were infection-related hospitalizations in the child/proband. Probands were followed until an infection-related hospitalization admission (up to the first three), death, 18th birthday, or end of 2014, whichever occurred first. Infection risks were estimated by adjusted Cox proportional hazard models for multiple events.
Results:
Of 512,279 probands, 142,915 (27.9%) had infection-related hospitalizations; 133,322 (26.0%) had a sibling with a previous infection-related hospitalization (i.e. exposed). Median interval between sibling and proband infection-related hospitalizations was 1.4 years (inter-quartile range 0.5-3.7). Probands had a dose-dependent increase in risk if sibling/s had 1, 2, or 3+ infection-related hospitalizations (adjusted hazard ratio, aHR 1.41, 95% CI 1.39-1.43; aHR 1.65, 1.61-1.69; aHR 1.83, 1.77-1.90, respectively). Among siblings with the same clinical infection type, highest sibling risks were for genitourinary (aHR 2.06, 1.68-2.53), gastrointestinal (aHR 2.07, 1.94-2.19), and skin/soft tissue infections (aHR 2.34, 2.15-2.54). Overall risk of infection-related hospitalization was higher in children with more siblings and with older siblings.
Conclusion:
In this population-based study, we observed an increased risk of infection-related hospitalization in children whose siblings were previously hospitalized for infection. Public health interventions may be particularly relevant in families of children hospitalized with infection.
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