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

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

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

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.

Full enteral feeding (≥120 mL/kg/d).

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.

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).

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.