Early albumin use and mortality in critically III children with severe hypoalbuminemia: a target trial emulation study

Hypoalbuminemia is highly prevalent in critically ill children and is an established independent risk factor for mortality. Whether albumin supplementation is associated with improved survival remains unclear, particularly in pediatric populations where causal evidence is sparse. This retrospective cohort study used data from the Pediatric Intensive Care (PIC) database, a single-center pediatric-specific critical care database in China, and adopted a target trial emulation (TTE) framework. Children whose first albumin measurement within 24 h of ICU admission was below 30 g/L were included (N = 1,649). Time zero was defined as the first detection of albumin below 30 g/L. The exposure was receipt of at least one dose of human albumin within 24 h after time zero. Primary outcomes were 7-day and 28-day all-cause mortality, estimated using IPTW-weighted Cox proportional hazards models with doubly robust adjustment. Sensitivity to unmeasured confounding was assessed by E-value. Among 1,649 children, 374 (22.7%) received early albumin therapy. After doubly robust adjustment, early albumin therapy was associated with reduced 7-day mortality (HR, 0.42; 95% CI, 0.24–0.74; P = 0.003; E-value = 4.21). The association with 28-day mortality was not significant (HR, 0.79; 95% CI, 0.45–1.36; P = 0.393). Relaxing the hypoalbuminemia threshold to below 35 g/L attenuated the 7-day association (HR, 0.64; 95% CI, 0.39–1.05). Extending the treatment window to 48 h further attenuated the association (HR, 0.87; 95% CI, 0.40–1.91). A significant interaction was observed between vasoactive agent use and albumin therapy (P for interaction = 0.045), with the strongest association among children not receiving vasoactive agents (HR, 0.17; 95% CI, 0.04–0.70). In critically ill children with severe hypoalbuminemia, early albumin therapy was associated with reduced 7-day mortality. This association showed clear threshold- and time-dependence, suggesting that any potential benefit may concentrate within a narrow clinical window early in the disease course. Prospective confirmation is needed. Not applicable. This is a retrospective observational study using de-identified data; the study protocol was not prospectively registered in a clinical trials registry.