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Randomized Controlled Trial
. 2025 Jul;98(1):137-143.
doi: 10.1038/s41390-025-03928-y. Epub 2025 Feb 15.

Effect of early antibiotic exposure on necrotizing enterocolitis and growth in extremely preterm infants

Katie M Strobel  1 , Thomas R Wood  2 , Gregory C Valentine  2 , Olivia C Brandon  2 , D Taylor Hendrixson  2   3 , Dennis E Mayock  2 , Krystle M Perez  2 , Mihai Puia-Dumitrescu  2 , Patrick J Heagerty  4 , Sandra E Juul  2   5
Affiliations
Randomized Controlled Trial

Effect of early antibiotic exposure on necrotizing enterocolitis and growth in extremely preterm infants

Katie M Strobel et al. Pediatr Res. 2025 Jul.

Abstract

Background: The relationship between early antibiotic exposure, necrotizing enterocolitis (NEC), and growth faltering (GF) in extremely preterm infants is unknown.

Methods: We evaluated the association between peripartum and postnatal antibiotic exposure in the first week after birth with NEC and GF in this secondary analysis of Preterm Erythropoietin Neuroprotection Trial subjects. NEC was defined as Bell's stage ≥ IIA; GF was defined as decreased weight, length, or head circumference (HC) z-score from birth to discharge of < -0.8. Multivariable analyses were adjusted with maternal and infant factors.

Results: A total of 891 infants survived the first week and were included in the NEC analyses, while 828 infants survived to discharge and were included in the growth analyses. For every 1-day increase in infant antibiotic exposure during the first week after birth, there was a significantly increased adjusted hazard of NEC (aHR/day 1.14 [1.01-1.28], p = 0.034). Antibiotics for 3-4 days and 5-7 days total in the first week were associated with increased odds of weight GF (aOR 1.90 [1.21-2.99], aOR 2.32 [1.44-3.74]), length GF (aOR 1.76 [1.22-2.59], aOR 1.88 [1.26-2.80]), and HC GF (aOR 1.75 [1.08-2.84], aOR 1.87 [1.14-3.08]).

Conclusion: Increased antibiotic exposure in the first week after birth was associated with NEC and GF risk.

Impact: In this post-hoc analysis of a large multi-site trial, we found infant antibiotic exposure in the first week after birth was associated with an increased hazard of necrotizing enterocolitis in the extremely preterm infant after adjusting for maternal and infant factors. First week antibiotic exposure in the extremely preterm infant was associated with an increased odds of weight, linear, and head circumference growth faltering after adjusting for maternal and infant factors. These findings encourage the judicious use of early antibiotics in extremely preterm infants.

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Conflict of interest statement

Competing interests: The authors declare no competing interests. Ethical approval: The PENUT Trial was approved by the institutional review board at each participating site and was registered with the Food and Drug Administration. The study was performed in accordance with the Declaration of Helsinki. Informed consent: Each participant participated with informed consent.

References

    1. Kostlin-Gille, N. et al. Early initiation of antibiotic therapy and short-term outcomes in preterm infants: a single-centre retrospective cohort analysis. Arch. Dis. Child Fetal Neonatal Ed. 108, 623–630 (2023). - PubMed - DOI
    1. Letouzey, M. et al. Early antibiotic exposure and adverse outcomes in very preterm infants at low risk of early-onset sepsis: the Epipage-2 cohort study. J. Pediatr. 243, 91–98.e94 (2022). - PubMed - DOI
    1. Dierikx, T. H. et al. Association between duration of early empiric antibiotics and necrotizing enterocolitis and late-onset sepsis in preterm infants: a multicenter cohort study. Eur. J. Pediatr. 181, 3715–3724 (2022). - PubMed - PMC - DOI
    1. Vatne, A. et al. Early empirical antibiotics and adverse clinical outcomes in infants born very preterm: a population-based cohort. J. Pediatr. 253, 107–114.e105 (2023). - PubMed - DOI
    1. Perez, K. et al. Patterns of infections among extremely preterm infants. J. Clin. Med. 12, 2703 (2023).

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