Abstract / Summary
Importance Sepsis occurring in the first 72 hours of life is associated with high mortality and complications such as intraventricular hemorrhage (IVH), particularly in preterm infants. Although blood culture is the diagnostic standard, its low detection rate may underestimate the clinical burden of infection. Objective To determine whether molecular detection of bacterial DNA in umbilical cord tissue improves identification of preterm infants at risk of sepsis-related death or grade IV IVH. Design, Setting, and Participants Samples were collected from infants with a birth weight less than 1500 g between January 2009 and December 2021 in a research network of level 3 neonatal intensive care units (67 sites) and were analyzed by using multiplex quantitative polymerase chain reaction (qPCR) for Enterobacteriaceae and Group B Streptococcus between January 2025 and January 2026. Data analysis occurred from February to March 2026. Exposures Positive blood culture results within the first 3 days of life were compared with positive qPCR. Main Outcome and Measures Primary outcomes were sepsis-related death within the first 7 days of life and grade IV IVH. Sensitivities were compared and endpoints were assessed by calculating risk ratios and odds ratios (ORs). Results Of 30 458 eligible infants, 15 290 were included for analysis (7865 male [51.4%] and 7425 female [48.6%]). Median (IQR) birth weight was 980 (744-1240) g, and median (IQR) gestational age was 28 (26-30) weeks. Blood culture was positive in 90 infants (0.6%), whereas qPCR was positive in 546 infants (3.6%). Within the first week of life, 34 infants (0.2%) died from sepsis and 548 infants (3.6%) developed grade IV IVH. For sepsis-related mortality, umbilical cord qPCR showed a sensitivity of 41.2% (95% CI, 25.6%-59.3%; 14 of 34 infants) compared with 23.5% (95% CI, 10.7%-41.2%; 8 of 34 infants) for blood culture. For grade IV IVH, sensitivity was 8.2% (95% CI, 6.1%-10.9%; 45 of 548 infants) for qPCR and 1.6% (95% CI, 0.8%-3.1%; 9 of 548 infants) for blood culture. The association of positive umbilical cord qPCR with adverse outcome was confirmed after adjustment for known clinical risk factors of sepsis-related mortality (OR, 14.90; 95% CI, 7.26-30.65) and grade IV IVH (OR, 1.89; 95% CI, 1.36-2.64). Conclusions and Relevance In this prognostic study of 15 290 preterm infants, umbilical cord vessel qPCR identified twice as many infants who died from sepsis and 5 times as many who developed grade IV IVH compared with blood culture, suggesting that blood culture underestimates the clinical burden of neonatal sepsis.