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Assessing the Heterogeneous Treatment Effects of Glucocorticoids in Infants and Toddlers with Severe Pneumonia

Year: 2025

Type: article

Abstract: Background: Community-acquired pneumonia (CAP) is a leading cause of pediatric hospitalizations and a risk factor for chronic respiratory conditions. Glucocorticoids (GCs) are used as adjunctive therapy to reduce inflammation, but their efficacy in infants and toddlers remains unclear. Method: A retrospective study of 1116 infants and toddlers with severe CAP was conducted, using causal forest to estimate individual treatment effects (ITEs), with the duration of intensive care unit (ICU) stay as the outcome. Patients were stratified based on ITEs to investigate the heterogeneous treatment effect (HTE) and identify responders. Generalized linear models validated the HTE across subclasses, followed by comparative analyses to characterize responders. Variable importance was assessed using the causal model, and Shapley additive explanations (SHAP) quantified each variable’s contribution to the ITE. Analysis was also performed in mechanically ventilated patients (MV group). Results: GCs demonstrated significant HTE. Older patients and those with elevated inflammation markers showed better responses, whereas no such benefit was observed in respiratory syncytial virus-infected patients. These subgroups experienced shorter ICU stays both in the whole cohort (β = −0.16, p < 0.001) and MV group (β = −0.34, p < 0.001), and shorter ventilation duration was observed in the MV group (β = −0.35, p < 0.001). Age and the anion gap were key predictors of ITEs. SHAP analysis revealed a positive correlation between age and GC effectiveness. Conclusions: Significant heterogeneity in GC treatment effects exists among infants and toddlers with severe CAP, highlighting the need for optimization of GC use in this population.

Source: Biomedicines

DOI: 10.3390/biomedicines13102333