618 - Association of prolonged rupture of membranes with gram-negative late-onset sepsis in preterm infants

Poster Number: 618
Publication Number: 618.571

Background: In preterm infants, prolonged rupture of membrane (PROM, >18 hours from membrane rupture to birth) is associated with a higher risk of early-onset sepsis (EOS, ≤3 days after birth), primarily by gram-negative organisms such as Escherichia coli. PROM allows mother-to-infant transmission of opportunistic pathogens that colonize and cause invasive infections. Colonization when not resulting in EOS may potentially remain a risk factor for late-onset sepsis (LOS, >3 days after birth).

Objective: To determine the age-specific association of gram-negative and overall infections with PROM exposure in preterm infants.

Design/Methods: Retrospective observational cohort study of preterm infants (≤35 weeks gestational age (GA)) admitted to two perinatal centers from 2009-2020. Primary outcome was blood or CSF culture-confirmed infection with a gram-negative organism in four age categories: T1 (0-3 days), T2 (4-10 days), T3 (11-17 days), and T4 (>17 days). The secondary outcome was all culture-confirmed infection. Infection episodes were either new pathogens or the same pathogen identified after 48 hours of prior antibiotic treatment. Infants with confirmed infection during one age category were excluded from the subsequent category. We used logistic regression, adjusting for sex, GA, and birth weight, to compare age-specific risks of gram-negative and overall infections between exposure groups.

Results: Of the 7241 eligible infants, 1292 (17.9%) were born after PROM. These infants were more frequently male, vaginally born, and had lower GA and birth weight (Table 1). PROM-exposed infants had a higher incidence of EOS (1.4% vs. 0.4%, p < 0.001) and LOS (5.8% vs. 4.1%, p 0.007), and a higher incidence of gram-negative infections within these groups (Table 1). At each age category, the proportion of infants with gram-negative infections was higher among PROM-exposed infants (Figure 1). PROM-exposed infants had higher odds for Gram-negative infections in age categories T1, T2, and T4 (Table 2). After adjusting for covariates, we found that the odds for gram-negative infections remained significantly elevated in PROM-exposed infants in T1 and T4.

Conclusion(s): PROM-exposed infants have higher adjusted odds of gram-negative infections in the first 3 days and >17 days after birth. Further investigation into the higher risk for gram-negative infections in PROM-exposed infants may inform the targeted implementation of organism-specific prevention measures in neonatal sepsis. Our ongoing research is focused on understanding how antibiotic treatment modifies the association between membrane rupture and infection.