Buy Article Permissions and Reprints 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.

Publication History

Received: 03 January 2025

Accepted: 22 July 2025

Accepted Manuscript online:
23 July 2025

Article published online:
04 August 2025

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