Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Antibiotic exposure and infection epidemiology among newborns with congenital diaphragmatic hernia

Journal of Perinatology volume 45, pages 1255–1261 (2025)Cite this article

Subjects

Abstract

Objective

To describe infection epidemiology and measure antibiotic utilization among a large cohort of newborns with congenital diaphragmatic hernia (CDH).

Study design

Retrospective observational study including inborn newborns with CDH at a level IV referral center (free-standing children’s hospital with special delivery unit) and two associated level III birth centers who underwent active care and survived to NICU admission, born 1/2013-11/2022 with available disposition.

Results

Of 381 newborns with CDH who were admitted to the NICU, 370 (97.1%) received antibiotics. There were 137 (36.1%) newborns with a positive bacterial culture from any source; 78/381 (20.4%) had a positive culture from blood, urine, or spinal fluid.

Conclusion

Nearly all newborns with CDH at our center received antibiotics during their hospitalization, but the majority did not have a positive bacterial culture result, indicating opportunities exist for antibiotic stewardship among this population.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

Data availability

The datasets generated and analyzed during the current study are not publicly available due to institutional data use restrictions, but are available from the corresponding author on reasonable request. All relevant summary data supporting the conclusions of this article are presented within the manuscript and its supplementary materials. There are no restrictions on material availability beyond those described.

References

  1. Keijzer R, Puri P. Congenital diaphragmatic hernia. Semin Pediatr Surg. 2010;19:180–5.

    Article  PubMed  Google Scholar 

  2. Keene S, Murthy K, Pallotto E, Brozanski B, Gien J, Zaniletti I, et al. Acquired infection and antimicrobial utilization during Initial NICU hospitalization in infants with congenital diaphragmatic hernia. Pediatr Infect Dis J. 2018;37:469–74.

    Article  PubMed  Google Scholar 

  3. Cox LM, Yamanishi S, Sohn J, Alekseyenko AV, Leung JM, Cho I, et al. Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences. Cell. 2014;158:705–21.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Flannery DD, Chiotos K, Gerber JS, Puopolo KM. Neonatal multidrug-resistant gram-negative infection: epidemiology, mechanisms of resistance, and management. Pediatr Res. 2022;91:380–91. Nature Publishing Group

    Article  PubMed  Google Scholar 

  5. Flannery DD, Horbar JD. Metrics of neonatal antibiotic use. Semin Perinatol. 2020;44:151329.

  6. Flannery DD, Puopolo KM. Neonatal antibiotic use: what are we doing and where shall we go? Neoreviews. 2018;19:e516–25.

    Article  Google Scholar 

  7. Puopolo KM, Benitz WE, Zaoutis TE. Management of neonates born at ≥35 0/7 weeks’ gestation with suspected or proven early-onset bacterial sepsis. Pediatrics. 2018;142:20182894.

    Article  Google Scholar 

  8. Puopolo KM, Benitz WE, Zaoutis TE. Management of neonates born at ≤34 6/7 weeks’ gestation with suspected or proven early-onset bacterial sepsis. Pediatrics. 2018;142:e20182896.

  9. Puopolo KM, Mukhopadhyay S, Hansen NI, Michael Cotten C, Stoll BJ, Sanchez PJ, et al. Identification of Extremely Premature Infants at Low Risk for Early-Onset Sepsis. Pediatrics. 2017;140:e20170925.

    Article  PubMed  Google Scholar 

  10. Reynolds TA, Goldshore MA, Flohr S, Land S, Mathew L, Gebb JS, et al. A clinical outcomes data archive for a comprehensive fetal diagnosis and treatment center. Fetal Diagn Ther. 2025;52:139–47.

  11. DeKoninck P, Gratacos E, Van Mieghem T, Richter J, Lewi P, Ancel AM, et al. Results of fetal endoscopic tracheal occlusion for congenital diaphragmatic hernia and the set up of the randomized controlled TOTAL trial. Early Hum Dev. 2011;87:619–24.

    Article  PubMed  Google Scholar 

  12. Mukhopadhyay S, Puopolo KM. Neonatal early-onset sepsis: epidemiology and risk assessment. Neoreviews. 2015;16:e221–30.

    Article  Google Scholar 

  13. Flannery DD, Puopolo KM. Neonatal early-onset sepsis. Neoreviews. 2022;23:756–70.

    Article  PubMed  Google Scholar 

  14. Stoll BJ, Puopolo KM, Hansen NI, Sánchez PJ, Bell EF, Carlo WA, et al. Early-onset neonatal sepsis 2015 to 2017, the rise of escherichia coli, and the need for novel prevention strategies. JAMA Pediatr. 2020;174:1–12.

    Article  Google Scholar 

  15. Flannery DD, Akinboyo IC, Mukhopadhyay S, Tribble AC, Song L, Chen F, et al. Antibiotic Susceptibility of Escherichia coli among Infants Admitted to Neonatal Intensive Care Units across the US from 2009 to 2017. JAMA Pediatrics. 2021;175:168–75. American Medical Association

    Article  PubMed  Google Scholar 

  16. Flannery DD, Puopolo KM, Hansen NI, Gerber JS, Sánchez PJ, Stoll BJ. Antimicrobial susceptibility profiles among neonatal early-onset sepsis pathogens. Pediatr Infect Dis J. 2022;41:263–71.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Flannery DD, Mukhopadhyay S, Morales KH, Dhudasia MB, Passarella M, Gerber JS, et al. Delivery characteristics and the risk of early-onset neonatal sepsis. Pediatrics. 2022;149:e2021052900.

  18. Claassen CC, Keenan WJ. Challenging the “Culture” of the tracheal aspirate. Neoreviews. 2019;20:e145–51.

    Article  PubMed  Google Scholar 

  19. Coggins SA, Glaser K. Updates in late-onset sepsis: risk assessment, therapy, and outcomes. Neoreviews. 2022;23:738–55.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Arattu Thodika FMS, Dassios T, Deep A, Greenough A. Acute kidney injury in infants with congenital diaphragmatic hernia. J Perinatol. 2022;42:925–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Jean-Baptiste N, Benjamin DK, Cohen-Wolkowiez M, Fowler VG, Laughon M, Clark RH, et al. Coagulase-negative staphylococcal infections in the neonatal intensive care unit. Infect Control Hosp Epidemiol. 2011;32:679–86.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Ericson JE, Thaden J, Cross HR, Clark RH, Fowler VG, Benjamin DK, et al. No survival benefit with empirical vancomycin therapy for coagulase-negative staphylococcal bloodstream infections in infants. Pediatr Infect Dis J. 2015;34:371–5.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Cantey JB, Anderson KR, Kalagiri RR, Mallett LH. Morbidity and mortality of coagulase-negative staphylococcal sepsis in very-low-birth-weight infants. World J Pediatr. 2018;14:269–73.

    Article  PubMed  Google Scholar 

  24. Magers J, Prusakov P, Speaks S, Conroy S, Sánchez PJ. Safety and efficacy of nafcillin for empiric therapy of late-onset sepsis in the NICU. Pediatrics. 2022;149:e2021052360.

  25. Lawrence SL, Roth V, Slinger R, Toye B, Gaboury I, Lemyre B Cloxacillin versus vancomycin for presumed late-onset sepsis in the Neonatal Intensive Care Unit and the impact upon outcome of coagulase negative staphylococcal bacteremia: a retrospective cohort study. BMC Pediatr. 2005;5:49.

  26. Hamdy RF, Bhattarai S, Basu SK, Hahn A, Stone B, Sadler ED, et al. Reducing vancomycin use in a level IV NICU. Pediatrics. 2020;146:e20192963.

    Article  PubMed  Google Scholar 

  27. Chiu CH, Michelow IC, Cronin J, Ringer SA, Ferris TG, Puopolo KM. Effectiveness of a guideline to reduce vancomycin use in the neonatal intensive care unit. Pediatr Infect Dis J. 2011;30:273–8.

    Article  PubMed  Google Scholar 

  28. Petel DS, Isabel S, Lee K-S, Ting JY, Kaufman DA, Sanchez PJ, et al. Empiric antibiotic prescribing practices for gram-positive coverage of late-onset sepsis in neonatal intensive care units in North America. Infect Control Hosp Epidemiol. 2024;46:1–3.

  29. Berriós-Torres SI, Umscheid CA, Bratzler DW, Leas B, Stone EC, Kelz RR, et al. Centers for disease control and prevention guideline for the prevention of surgical site infection, 2017. JAMA Surg. 2017;152:784–91.

    Article  PubMed  Google Scholar 

  30. Gottschalk A, Coggins S, Dhudasia MB, Flannery DD, Healy T, Puopolo KM, et al. Utility of anaerobic blood cultures in neonatal sepsis evaluation. J Pediatr Infect Dis Soc. 2024;13:406–12.

    Article  CAS  Google Scholar 

Download references

Funding

This study was not funded. DDF reports receiving K08 funding from the Agency for Healthcare Research and Quality, unrelated to the current study.

Author information

Authors and Affiliations

  1. Center for Fetal Diagnosis and Treatment, Children’s Hospital of Philadelphia, Pennsylvania, PA, USA

    Sabrina J. Flohr, Leny Mathew, Holly L. Hedrick & Natalie E. Rintoul

  2. Division of Pediatric General, Thoracic, and Fetal Surgery, Children’s Hospital of Philadelphia, Pennsylvania, PA, USA

    Holly L. Hedrick

  3. Division of Neonatology, Children’s Hospital of Philadelphia, Pennsylvania, PA, USA

    Natalie E. Rintoul, Alexandra K. Medoro & Dustin D. Flannery

  4. Antimicrobial Stewardship Program, Children’s Hospital of Philadelphia, Pennsylvania, PA, USA

    Talene A. Metjian

  5. Division of Infectious Diseases, Children’s Hospital of Philadelphia, Pennsylvania, PA, USA

    Sanjeev K. Swami, Jeffrey S. Gerber & Alexandra K. Medoro

Authors
  1. Sabrina J. Flohr
    View author publications

    Search author on:PubMed Google Scholar

  2. Leny Mathew
    View author publications

    Search author on:PubMed Google Scholar

  3. Holly L. Hedrick
    View author publications

    Search author on:PubMed Google Scholar

  4. Natalie E. Rintoul
    View author publications

    Search author on:PubMed Google Scholar

  5. Talene A. Metjian
    View author publications

    Search author on:PubMed Google Scholar

  6. Sanjeev K. Swami
    View author publications

    Search author on:PubMed Google Scholar

  7. Jeffrey S. Gerber
    View author publications

    Search author on:PubMed Google Scholar

  8. Alexandra K. Medoro
    View author publications

    Search author on:PubMed Google Scholar

  9. Dustin D. Flannery
    View author publications

    Search author on:PubMed Google Scholar

Contributions

SJF and DDF conceptualized and designed the study. SJF and DDF conducted the data analysis with support from LM and TAM. HLH and NER provided clinical expertise in the surgical and neonatal care of infants with CDH. SKS, JSG, and AKM contributed to interpreting infectious disease and stewardship-related findings. SJF and DDF drafted the initial manuscript, and all authors provided critical revisions. All authors reviewed and approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Dustin D. Flannery.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics approval

This study was approved and deemed an exempt review type by the Institutional Review Board at the Children’s Hospital of Philadelphia (IRB 21-018553). Informed consent was not obtained due to the study being deemed minimal risk and the Institutional Review Board granting a waiver of HIPAA authorization for accessing identifiable information from the medical record. All methods of this study were performed according to the Declaration of Helsinki.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Flohr, S.J., Mathew, L., Hedrick, H.L. et al. Antibiotic exposure and infection epidemiology among newborns with congenital diaphragmatic hernia. J Perinatol 45, 1255–1261 (2025). https://doi.org/10.1038/s41372-025-02389-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41372-025-02389-9

Search

Advanced search

Quick links