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Am J Perinatol
DOI: 10.1055/a-2663-5723
Original Article

Association of Placental Pathology and Antibiotic Exposure after Birth with the Severity of Necrotizing Enterocolitis in Preterm Infants: A Case–Control Study

Parvesh M. Garg
1   Department of Pediatrics/Neonatology, Wake Forest School of Medicine, Winston-Salem, North Carolina
,
Robbin Riddick
2   Department of Pediatrics/Neonatology, University of Mississippi Medical Center, Jackson, Mississippi
,
Md Abu Yusuf Ansari
3   Department of Data Science, University of Mississippi Medical Center, Jackson, Mississippi
,
Aubrey Rebentisch
2   Department of Pediatrics/Neonatology, University of Mississippi Medical Center, Jackson, Mississippi
,
Avinash Shetty
4   Department of Pediatrics/Infectious Disease, Wake Forest School of Medicine, Winston-Salem, North Carolina
,
Kristin Adams
5   Department of Pathology, University of Mississippi Medical Center, Jackson, Mississippi
,
William Hillegass
3   Department of Data Science, University of Mississippi Medical Center, Jackson, Mississippi
6   Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi
,
Padma P. Garg
2   Department of Pediatrics/Neonatology, University of Mississippi Medical Center, Jackson, Mississippi
› Institutsangaben
Funding P.M.G. is partially supported by the National Institute of General Medical Sciences of the National Institutes of Health under award number 5U54GM115428. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health (U.S. Department of Health and Human Services, National Institutes of Health, National Institute of General Medical Sciences, grant no.: 5U54GM115428).
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Abstract

Objective

This study aimed to assess the relationship between placental lesions, antibiotic exposure duration, and necrotizing enterocolitis (NEC) severity in preterm infants.

Study Design

In this single-center, case–control study, 107 infants with NEC and 130 controls were grouped by antibiotic exposure after birth: ≤3 or >3 days.

Results

Of 212 infants, 103 (48.5%) received antibiotics for ≤3 days, while 109 (51.5%) received antibiotics for >3 days. Multivariate regression analysis demonstrated that prolonged antibiotic duration (>3 vs. ≤3 days) was significantly associated with increased severity of NEC, with adjusted odds ratios (aORs) of 2.65 (95% confidence interval [CI]: 1.36–5.16; p = 0.004) for medical NEC and 3.36 (95% CI: 1.56–7.23; p = 0.002) for surgical NEC. However, prolonged antibiotic duration was not significantly associated with overall mortality (aOR = 1.16, 95% CI: 0.58–2.34; p = 0.7). Among infants diagnosed with NEC (n = 97), antibiotic duration of >3 days significantly increased the odds of mortality (aOR = 7.34, 95% CI: 1.94–48.3; p = 0.011) but was not significantly associated with NEC severity (aOR = 1.20, 95% CI: 0.49–2.94; p = 0.7). Among 64 infants with acute histologic chorioamnionitis, 37 (58%) received antibiotics for >3 days. Longer antibiotic exposure was linked to higher risks of medical NEC (79 vs. 38%; p = 0.021) and surgical NEC (62 vs. 38%; p = 0.021) compared with shorter exposure. In 134 infants with maternal vascular malperfusion (MVM), prolonged antibiotics were also associated with increased risks for medical (60 vs. 36%; p = 0.007) and surgical NEC (67 vs. 36%; p = 0.007). Concordance between clinical and pathologic chorioamnionitis was moderate (first-order agreement coefficient [AC1] = 0.60), while agreement for pregnancy-induced hypertension versus MVM was minimal (AC1 = 0.07).

Conclusion

Prolonged antibiotic exposure (>3 days) in infants with chorioamnionitis or MVM is most likely associated with increased NEC severity. Limiting antibiotic duration may reduce severe NEC risk in preterm infants.

Key Points

  • Prolonged antibiotics following birth are associated with NEC severity.

  • Infants exposed to chorioamnionitis and receiving prolonged antibiotics are more likely at NEC risk.

  • Shorter duration of antibiotics following birth may reduce NEC risk.

Keywords

placenta - antibiotics - NEC - preterm infants - surgical NEC

Note

The study was presented as a Poster at the PAS 2025 Meeting in Hawaii.


Authors' Contributions

P.M.G. designed the study. P.M.G., R.R., M.A.Y.A., A.R., K.A., A.S., W.H., and P.P.G. analyzed the collected data and wrote the manuscript. All the authors contributed to and approved the manuscript.


Supplementary Material



Publikationsverlauf

Eingereicht: 03. Januar 2025

Angenommen: 22. Juli 2025

Accepted Manuscript online:
23. Juli 2025

Artikel online veröffentlicht:
04. August 2025

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