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:

Association between early antibiotic exposure and bronchopulmonary dysplasia or death

Journal of Perinatology volume 38, pages 1227–1234 (2018)Cite this article

Subjects

Abstract

Objective

To characterize the independent association between antibiotic exposure in the first week of life and the risk of bronchopulmonary dysplasia (BPD) or death among very preterm infants without culture-confirmed sepsis.

Methods

Retrospective cohort study using the Optum Neonatal Database. Infants without culture-confirmed sepsis born less than 1500 g and less than 32 weeks gestation between 1/2010 and 11/2016 were included. The independent association between antibiotic therapy during the first week of life and BPD or death prior to 36 weeks postmenstrual age (PMA) was assessed by multivariable logistic regression.

Results

Of 4950 infants, 3946 (79.7%) received antibiotics during the first week of life. Rates of BPD or death (41.5% vs. 31.1%, p < 0.001) and the two individual outcomes were significantly higher among antibiotic treated infants. After adjusting for potential confounding variables, antibiotic use in the first week of life was not associated with increased risk of BPD or death (OR 0.96, 95% CI [0.76,1.21]) or BPD among survivors (OR 0.86, 95% CI [0.67,1.09]). Antibiotic use was associated with increased risk of death prior to 36 weeks PMA (OR 3.01, 95% CI [1.59,5.71]), however, secondary analyses suggested this association may be confounded by unmeasured illness severity.

Conclusions

Antibiotic exposure in the first week of life among preterm infants without culture-confirmed sepsis was not independently associated with increased risk of BPD or death.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Stoll BJ, Hansen N, Fanaroff AA, Wright LL, Carlo WA, Ehrenkranz RA, et al. Changes in pathogens causing early-onset sepsis in very-low-birth-weight infants. N Engl J Med. 2002;347:240–7.

    Article  PubMed  Google Scholar 

  2. Stoll BJ, Hansen NI, Higgins RD, Fanaroff AA, Duara S, Goldberg R, et al. Very low birth weight preterm infants with early onset neonatal sepsis: the predominance of gram-negative infections continues in the National Institute of Child Health and Human Development Neonatal Research Network, 2002-2003. Pediatr Infect Dis J. 2005;24:635–9.

    Article  PubMed  Google Scholar 

  3. Stoll BJ, Hansen NI, Sanchez PJ, Faix RG, Poindexter BB, Van Meurs KP, et al. Early onset neonatal sepsis: the burden of group B Streptococcal and E. coli disease continues. Pediatrics. 2011;127:817–26.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Ting JY, Synnes A, Roberts A, Deshpandey A, Dow K, Yoon EW, et al. Association between antibiotic use and neonatal mortality and morbidities in very low-birth-weight infants without culture-proven sepsis or necrotizing enterocolitis. JAMA Pediatr. 2016;170:1181–7.

    Article  PubMed  Google Scholar 

  5. Cantey JB, Huffman LW, Subramanian A, Marshall AS, Ballard AR, Lefevre C, et al. Antibiotic exposure and risk for death or bronchopulmonary dysplasia in very low birth weight infants. J Pediatr. 2017;181:289–93.e1.

    Article  PubMed  Google Scholar 

  6. Tolia VN, Desai S, Qin H, Rayburn PD, Poon G, Murthy K, et al. Implementation of an automatic stop order and initial antibiotic exposure in very low birth weight infants. Am J Perinatol. 2017;34:105–10.

    PubMed  Google Scholar 

  7. Cotten CM, Taylor S, Stoll B, Goldberg RN, Hansen NI, Sanchez PJ, et al. Prolonged duration of initial empirical antibiotic treatment is associated with increased rates of necrotizing enterocolitis and death for extremely low birth weight infants. Pediatrics. 2009;123:58–66.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Kuppala VS, Meinzen-Derr J, Morrow AL, Schibler KR. Prolonged initial empirical antibiotic treatment is associated with adverse outcomes in premature infants. J Pediatr. 2011;159:720–5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Cotten CM, McDonald S, Stoll B, Goldberg RN, Poole K, Benjamin DK Jr. The association of third-generation cephalosporin use and invasive candidiasis in extremely low birth-weight infants. Pediatrics. 2006;118:717–22.

    Article  PubMed  Google Scholar 

  10. Benjamin DK Jr., Stoll BJ, Gantz MG, Walsh MC, Sanchez PJ, Das A, et al. Neonatal candidiasis: epidemiology, risk factors, and clinical judgment. Pediatrics. 2010;126:e865–73.

    Article  PubMed  PubMed Central  Google Scholar 

  11. de Man P, Verhoeven BA, Verbrugh HA, Vos MC, van den Anker JN. An antibiotic policy to prevent emergence of resistant bacilli. Lancet. 2000;355:973–8.

    Article  PubMed  Google Scholar 

  12. Alexander VN, Northrup V, Bizzarro MJ. Antibiotic exposure in the newborn intensive care unit and the risk of necrotizing enterocolitis. J Pediatr. 2011;159:392–7.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Patel SJ, Saiman L. Antibiotic resistance in neonatal intensive care unit pathogens: mechanisms, clinical impact, and prevention including antibiotic stewardship. Clin Perinatol. 2010;37:547–63.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Novitsky A, Tuttle D, Locke RG, Saiman L, Mackley A, Paul DA. Prolonged early antibiotic use and bronchopulmonary dysplasia in very low birth weight infants. Am J Perinatol. 2015;32:43–8.

    Article  PubMed  Google Scholar 

  15. Neu J, Douglas-Escobar M, Lopez M. Microbes and the developing gastrointestinal tract. Nutr Clin Pract. 2007;22:174–82.

    Article  PubMed  Google Scholar 

  16. Hadland SE, Wharam JF, Schuster MA, Zhang F, Samet JH, Larochelle MR. Trends in receipt of buprenorphine and naltrexone for opioid use disorder among adolescents and young adults, 2001-2014. JAMA Pediatr. 2017;171:747–55.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Jeffery MM, Hooten WM, Hess EP, Meara ER, Ross JS, Henk HJ, et al. Opioid prescribing for opioid-naive patients in emergency departments and other settings: characteristics of prescriptions and association with long-term use. Ann Emerg Med. 2017;71:326–36.e19.

    Article  PubMed  Google Scholar 

  18. Patel RM, Kandefer S, Walsh MC, Bell EF, Carlo WA, Laptook AR, et al. Causes and timing of death in extremely premature infants from 2000 through 2011. N Engl J Med. 2015;372:331–40.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Kliegman RM, Walsh MC. Neonatal necrotizing enterocolitis: pathogenesis, classification, and spectrum of illness. Curr Probl Pediatr. 1987;17:213–88.

    PubMed  CAS  Google Scholar 

  20. Olsen IE, Groveman SA, Lawson ML, Clark RH, Zemel BS. New intrauterine growth curves based on United States data. Pediatrics. 2010;125:e214–24.

    Article  PubMed  Google Scholar 

  21. Williams RL. A note on robust variance estimation for cluster-correlated data. Biometrics. 2000;56:645–6.

    Article  PubMed  CAS  Google Scholar 

  22. Cordero L, Ayers LW. Duration of empiric antibiotics for suspected early-onset sepsis in extremely low birth weight infants. Infect Control Hosp Epidemiol. 2003;24:662–6.

    Article  PubMed  Google Scholar 

  23. Esaiassen E, Fjalstad JW, Juvet LK, van den Anker JN, Klingenberg C. Antibiotic exposure in neonates and early adverse outcomes: a systematic review and meta-analysis. J Antimicrob Chemother. 2017;72:1858–70.

    Article  PubMed  Google Scholar 

  24. Abdel Ghany EA, Ali AA. Empirical antibiotic treatment and the risk of necrotizing enterocolitis and death in very low birth weight neonates. Ann Saudi Med. 2012;32:521–6.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Alm B, Erdes L, Mollborg P, Pettersson R, Norvenius SG, Aberg N, et al. Neonatal antibiotic treatment is a risk factor for early wheezing. Pediatrics. 2008;121:697–702.

    Article  PubMed  Google Scholar 

  26. Mbakwa CA, Scheres L, Penders J, Mommers M, Thijs C, Arts IC. Early life antibiotic exposure and weight development in children. J Pediatr. 2016;176:105–13.e2.

    Article  PubMed  CAS  Google Scholar 

  27. Greenwood C, Morrow AL, Lagomarcino AJ, Altaye M, Taft DH, Yu Z, et al. Early empiric antibiotic use in preterm infants is associated with lower bacterial diversity and higher relative abundance of Enterobacter. J Pediatr. 2014;165:23–9.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

DDF was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (T32HD060550). EAJ was supported by a grant from the National Health, Lung, and Blood Institute (K23HL136843).

Author information

Authors and Affiliations

  1. Division of Neonatology, Department of Pediatrics, The Children’s Hospital of Philadelphia, The University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA

    Dustin D. Flannery, Kevin Dysart & Erik A. Jensen

  2. Optum, Eden Prairie, MN, USA

    Alison Cook

  3. Division of Neonatology, Department of Pediatrics, Thomas Jefferson University Hospital/Nemours, Philadelphia, PA, USA

    Jay Greenspan & Zubair H. Aghai

Authors
  1. Dustin D. Flannery
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kevin Dysart
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alison Cook
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jay Greenspan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zubair H. Aghai
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Erik A. Jensen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dustin D. Flannery.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Flannery, D.D., Dysart, K., Cook, A. et al. Association between early antibiotic exposure and bronchopulmonary dysplasia or death. J Perinatol 38, 1227–1234 (2018). https://doi.org/10.1038/s41372-018-0146-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41372-018-0146-3

This article is cited by

Search

Advanced search

Quick links