Phase-specific mortality risk of serum lactate thresholds in very low birth weight infants with late-onset sepsis: a retrospective cohort study

Abstract

Background: Late-onset sepsis (LOS) in very low birth weight (VLBW) infants confers substantial mortality risk. While lactate monitoring is standard, validated prognostic thresholds for mortality remain unestablished in this population. Methods: This retrospective cohort study (2014–2024) analyzed 596 VLBW infants (≤32 weeks; <1,500 g) with LOS at a tertiary NICU. Multivariable regression and piecewise linear modeling identified lactate-mortality thresholds, adjusting for gestational age, respiratory failure severity, vasopressor requirement, and multiorgan dysfunction. Bootstrap validation (1,000 iterations) assessed threshold stability. Results: Mortality occurred in 21% (125/596). Nonlinear analysis revealed critical inflection points at 2.2 mmol/L (95%CI: 1.9–2.5) and 4.0 mmol/L (95%CI: 3.7–4.3) (p < 0.001). Lactate ≤ 2.2 mmol/L demonstrated no mortality association (adjusted odds ratio = 1.84, 95%CI: 0.64–5.34; p = 0.260). Within the 2.2–4.0 mmol/L transition zone, each 1 mmol/L increment conferred a 7.0-fold mortality risk (aOR = 7.0, 95%CI: 2.13–22.78; p < 0.001). Beyond 4.0 mmol/L, the relationship attenuated (aOR = 0.90, 95%CI: 0.52–1.43; p = 0.568). Subgroup analyses indicated amplified risk among epinephrine-exposed infants (aOR = 3.40 vs. 1.78; Pinteraction = 0.094) and those with moderate-to-severe respiratory failure. Conclusion: Lactate reveals phase-specific mortality associations in VLBW infants with LOS. The 7.0-fold mortality risk increase per mmol/L in the 2.2–4.0 mmol/L interval suggests potential metabolic resuscitation targets for precision monitoring in sepsis management.