Association between early blood lactate trajectories and mortality in neonates: a retrospective cohort study

Lactate is a widely used prognostic biomarker in critically ill patients, but its dynamic trajectory and prognostic value in critically ill neonates remain underexplored. This study aimed to investigate the association between dynamic lactate trajectories during the first 48 h after neonatal intensive care unit (NICU) admission and 30-day all-cause mortality risk in this population.

The association between admission blood lactate levels and 30-day all-cause mortality was assessed using multivariable Cox regression and restricted cubic spline (RCS) analysis in 1,112 neonates admitted to the NICU who were included in the blood lactate trajectory classification. Blood lactate trajectories over the first 48 h were identified using a latent growth mixture model (LGMM) based on the highest blood lactate value within each 12-hour interval. A 48-hour landmark analysis was then performed, and survival follow-up was initiated at 48 h after NICU admission among neonates who were alive and eligible for trajectory classification, yielding an analysis cohort of 1,080 neonates. The association between trajectory patterns and 30-day all-cause mortality was further evaluated using multivariable Cox regression models, adjusting for potential confounders including demographics, clinical parameters, and laboratory variables. Kaplan-Meier survival curves were generated for the four trajectory groups in the landmark cohort, and differences in survival were compared using the log-rank test.

Admission lactate levels demonstrated a linear positive association with 30-day all-cause mortality risk (p for non-linearity = 0.78), with each 1 mmol/L increase associated with a 9% increase in risk after multivariable adjustment (HR 1.09, 95% CI 1.06-1.13, p < 0.01) in 1,112 neonates. Four distinct blood lactate trajectory patterns were identified during the first 48 h after NICU admission: a rapidly declining group (Class 1, 5.75%), a stably low group (Class 2, 88.22%), a persistently intermediate group (Class 3, 4.41%), and a persistently high group (Class 4, 1.62%). In the 48-hour landmark cohort (n = 1,080), compared with the stably low group, the persistently high group had the highest risk of 30-day all-cause mortality (HR 25.61, 95% CI 8.99-73.01, p < 0.01), followed by the persistently intermediate group (HR 6.84, 95% CI 3.39-13.78, p < 0.01), while the rapidly declining group also showed a significantly increased risk after full adjustment (HR 2.63, 95% CI 1.20-5.80, p = 0.02).

Elevated lactate levels are associated with increased short-term mortality in neonates. Early lactate trajectories are associated with 30-day all-cause mortality and may provide additional clinically relevant information beyond a single admission lactate measurement, potentially aiding early risk stratification. Prospective multicenter studies are warranted to validate these findings.