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Multicenter Study
. 2025 Nov 3;8(11):e2543940.
doi: 10.1001/jamanetworkopen.2025.43940.

Time to Full Enteral Feeds and Late-Onset Sepsis in Extremely Preterm Infants

Ariel A Salas  1 , Laura Elizabeth Wiener  2 , Marissa Trotta  2 , Vivian Valcarce  1 , Mar Romero-Lopez  3 , Eric B Ortigoza  4 , Ting Ting Fu  5   6 , Kera McNelis  7 , Brenda Poindexter  7 , Waldemar A Carlo  1 ; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network
Collaborators, Affiliations
Multicenter Study

Time to Full Enteral Feeds and Late-Onset Sepsis in Extremely Preterm Infants

Ariel A Salas et al. JAMA Netw Open. .

Abstract

Importance: Recent studies suggest that early achievement of full enteral feeding improves clinical outcomes among preterm infants.

Objective: To examine the association between full enteral feeding and late-onset sepsis.

Design, setting, and participants: This secondary analysis of a cohort study prospectively followed up a multicenter cohort of preterm infants with gestational ages ranging from 23 to 28 weeks born between January 1, 2012, and December 31, 2021, at 19 US academic centers. Infants without major anomalies who received enteral feedings and survived beyond postnatal day 7 were included.

Exposure: Full enteral feeding (≥120 mL/kg/d).

Main outcomes and measures: The primary outcome was the incidence of late-onset sepsis confirmed through culture-positive results occurring more than 72 hours after birth and treated with antibiotics for 5 or more days. Other clinical outcomes assessed up to 36 weeks of postmenstrual age included necrotizing enterocolitis, death, and growth faltering (weight, length, or head circumference z score decrease >1.2). Risk estimates were adjusted for clinical variables associated with acute critical illness and birth year.

Results: Demographic and clinical data from 15 102 preterm infants were analyzed (mean [SD] maternal age, 28.7 [6.1] years; mean [SD] gestational age, 26.0 [1.6] weeks; mean [SD] birth weight, 875 [242] g; 7648 male [50.6%]). Between January 1, 2012, and December 31, 2021, the median (IQR) time to achieve full enteral feeding decreased from 18 (14-28) days to 14 (10-22) days, and the incidence of late-onset sepsis decreased from 21.1% to 16.5% (P = .003). In adjusted analyses, the relative risk of late-onset sepsis per each additional 1-week delay in achieving full enteral feeding was 16% higher (adjusted relative risk [ARR], 1.16; 95% CI, 1.14-1.18; P < .001). Delays in achieving full enteral feeding were also associated with a higher risk of necrotizing enterocolitis (ARR, 1.20; 95% CI, 1.16-1.24; P < .001) and growth faltering in weight (ARR, 1.08; 95% CI, 1.07-1.09), length (ARR, 1.03; 95% CI, 1.02-1.03), and head circumference (ARR, 1.07; 95% CI, 1.06-1.08; P < .001 for all).

Conclusions and relevance: In this cohort study of preterm infants with gestational ages ranging from 23 to 28 weeks who received enteral feeds and survived beyond postnatal day 7, delays in establishing full enteral feeding were associated with a higher risk of late-onset sepsis. These results suggest that early initiation and advancement of enteral feeding have the potential to reduce the risk of late-onset sepsis, growth faltering, and necrotizing enterocolitis.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Salas reported receiving grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development during the conduct of the study and grants from Mead Johnson Nutrition, personal fees from Mead Johnson Nutrition and Abbott, and stock options from Resbiotic outside the submitted work; in addition, Dr Salas had a patent for Instrumented Feeding Bottle issued. Dr Fu reported receiving nonfinancial support from Medela outside the submitted work. No other disclosures were reported.

Figures

Figure.
Figure.. Trends in Early Full Enteral Feeding Within First 10 Days After Birth, Clinical Outcomes, and Growth Outcomes in Infants Born Extremely Preterm
See this image and copyright information in PMC

References

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