Intrauterine inflammation exposure may increase the risk of late-onset sepsis in premature infants: a retrospective cohort study.

Abstract

Background: Preterm birth associated with intrauterine inflammation (IUI) has been linked to alterations in postnatal immunity and severe inflammatory complications during infancy. However, the impact of IUI on late-onset sepsis (LOS), a leading cause of mortality and morbidity in preterm infants, remains unclear. This study aims to elucidate the effect of IUI on the incidence of LOS in preterm infants by analyzing cytokine levels and white blood cell differential counts in cord blood within 24 h after birth.

Methods: This retrospective cohort study was conducted at a single tertiary neonatal center. Infants born before 37 weeks of gestation between July 2020 and June 2022 were included. Late-onset sepsis (LOS) was defined as sepsis occurring after 72 h of life during the birth hospitalization. Levels of 12 cytokines, including interleukin-1β (IL-1β), IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17, tumor necrosis factor-α (TNF-α), interferon-α (IFN-α), and IFN-γ, were measured in cord blood using multiplex bead-based flow immunoassays. Clinical data were extracted from hospital databases. Peripheral white blood cell counts within 24 h after birth were routinely recorded for preterm infants. Logistic regression analysis was used to assess the impact of cytokines and white blood cell counts on the incidence of LOS.

Results: A total of 628 preterm infants were included in this study. The mean gestational age was 33.17 ± 2.25 weeks, and the mean birth weight was 1929.50 ± 516.77 g. Of these, 42 infants (6.7%) developed late-onset sepsis (LOS). Compared to the non-LOS group, cord blood levels of IL-6 [127.81 (399.86) vs. 31.02 (127.48), p = 0.004] and IL-8 [130.37 (202.53) vs. 52.91 (101.43), p = 0.001] were significantly higher in the LOS group. No significant differences were observed in the levels of other cytokines between the groups. Peripheral neutrophil and monocyte counts were significantly lower in the LOS group [5.08 ± 3.46 vs. 8.14 ± 4.90, p < 0.001; 0.98 ± 0.56 vs. 1.37 ± 0.72, p = 0.001, respectively]. Multivariable logistic regression analysis revealed that elevated cord blood IL-6 levels and reduced peripheral neutrophil counts were associated with an increased risk of LOS, after adjusting for gestational age, gestational hypertension, and antenatal steroid use (aOR = 3.113, 95% CI: 1.239-7.819, p = 0.016; aOR = 0.340, 95% CI: 0.818-0.994, p = 0.038, respectively).

Conclusions: Elevated cord blood IL-6 levels and low peripheral neutrophil counts on the first day after birth are associated with an increased risk of LOS in preterm infants. These findings highlight the potential of these non-invasive biomarkers in clinical practice to improve the prediction of LOS risk. Early identification using these markers may facilitate targeted management strategies, thereby reducing complications and mortality rates. Moreover, the association suggests that intrauterine inflammation may have a lasting impact on immune system responses, potentially influencing susceptibility to infections later in life.