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 postmenstrual age and furosemide dosing practices in very preterm infants

Journal of Perinatology volume 42, pages 461–467 (2022)Cite this article

Subjects

Abstract

Objective

Furosemide renal clearance is slow after very preterm (VP) birth and increases with postnatal maturation. We compared furosemide dose frequency and total daily dose between postmenstrual age (PMA) groups in VP infants.

Study design

Observational cohort study of VP infants exposed to a repeated-dose course of furosemide in Pediatrix neonatal intensive care units (NICU) from 1997 to 2016.

Results

We identified 6565 furosemide courses among 4638 infants. There were no statistically significant differences between PMA groups on the odds of receiving more frequent furosemide dosing. Furosemide courses initiated at <28 weeks PMA were associated with a higher total daily dose than those initiated at a later PMA.

Conclusions

Furosemide dosing practices in the NICU are similar across PMA groups, despite maturational changes in drug disposition. Research is needed to identify and test rational dosing strategies across the PMA spectrum for this commonly used but unproven pharmacotherapy.

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

Similar content being viewed by others

References

  1. Clark RH, Bloom BT, Spitzer AR, Gerstmann DR. Reported medication use in the neonatal intensive care unit: data from a large national data set. Pediatrics. 2006;117:1979–87.

    Article  Google Scholar 

  2. Hsieh EM, Hornik CP, Clark RH, Laughon MM, Benjamin DK, Smith PB, et al. Medication use in the neonatal intensive care unit. Am J Perinatol. 2014;31:811–21.

    Article  Google Scholar 

  3. Laughon MM, Chantala K, Aliaga S, Herring AH, Hornik CP, Hughes R, et al. Diuretic exposure in premature infants from 1997 to 2011. Am J Perinatol. 2015;32:49–56.

    PubMed  Google Scholar 

  4. Bamat NA, Kirpalani H, Feudtner C, Jensen EA, Laughon MM, Zhang H, et al. Medication use in infants with severe bronchopulmonary dysplasia admitted to United States children’s hospitals. J Perinatol. 2019;39:1291–9.

    Article  Google Scholar 

  5. Mirochnick MH, Miceli JJ, Kramer PA, Chapron DJ, Raye JR. Furosemide pharmacokinetics in very low birth weight infants. J Pediatr. 1988;112:653–7.

    Article  CAS  Google Scholar 

  6. Vert P, Broquaire M, Legagneur M, Morselli PL. Pharmacokinetics of furosemide in neonates. Eur J Clin Pharm. 1982;22:39–45.

    Article  CAS  Google Scholar 

  7. Peterson RG, Simmons MA, Rumack BH, Levine RL, Brooks JG. Pharmacology of furosemide in the premature newborn infant. J Pediatr. 1980;97:139–43.

    Article  CAS  Google Scholar 

  8. Furosemide Injection, USP [package insert]. American Regent Inc: Shirley, NY. 2011. https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/018579s029lbl.pdf.

  9. Brater DC. Update in diuretic therapy: clinical pharmacology. Semin Nephrol. 2011;31:483–94.

    Article  CAS  Google Scholar 

  10. Thompson EJ, Benjamin DK, Greenberg RG, Kumar KR, Zimmerman KO, Laughon M, et al. Pharmacoepidemiology of furosemide in the neonatal intensive care unit. Neonatology. 2020;117:780–4.

    Article  CAS  Google Scholar 

  11. Von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. PLoS Med. 2007;4:1623–7.

    Google Scholar 

  12. Spitzer AR, Ellsbury DL, Handler D, Clark RH. The pediatrix babysteps® data warehouse and the pediatrix qualitysteps improvement project system – tools for “meaningful use” in continuous quality improvement. Clin Perinatol. 2010;37:49–70.

    Article  Google Scholar 

  13. BabysSteps and the Clinical Data Warehouse, Pediatrix Medical Group. 2015. https://docplayer.net/5901868-Pediatrix-medical-group-babysteps-and-the-clinical-data-warehouse.html.

  14. Jensen EA, Dysart K, Gantz MG, McDonald S, Bamat NA, Keszler M, et al. The diagnosis of bronchopulmonary dysplasia in very preterm infants: an evidence-based approach. Am J Respir Crit Care Med. 2019;200:751–9.

    Article  CAS  Google Scholar 

  15. Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2001;163:1723–9.

    Article  CAS  Google Scholar 

  16. Lasix (furosemide) Tablets 20, 40, and 80 mg [package insert]. Sanofi-Aventis LLC: Bridgewater, NJ. 2010. https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/016273s061lbl.pdf.

  17. van den Anker JN. Pharmacokinetics and renal function in preterm infants. Acta Paediatr. 1996;85:1393–9.

    Article  Google Scholar 

  18. Thayyil S, Sheik S, Kempley ST, Sinha A. A gestation- and postnatal age-based reference chart for assessing renal function in extremely premature infants. J Perinatol. 2008;28:226–9.

    Article  CAS  Google Scholar 

  19. Miall LS, Henderson MJ, Turner AJ, Brownlee KG, Brocklebank JT, Newell SJ, et al. Plasma creatinine rises dramatically in the first 48 h of life in preterm infants. Pediatrics. 1999;104:1–4.

    Article  Google Scholar 

  20. Mirochnick MH, Miceli JJ, Kramer PA, Chapron DJ, Raye JR. Renal response to furosemide in very low birth weight infants during chronic administration. Dev Pharm Ther. 1990;15:1–7.

    Article  CAS  Google Scholar 

  21. Bamat NA, Nelin TD, Eichenwald EC, Kirpalani H, Laughon MM, Jackson WM, et al. Loop diuretics in severe bronchopulmonary dysplasia: cumulative use and associations with mortality and age at discharge. J Pediatr. 2021;231:43–9.

    Article  CAS  Google Scholar 

  22. Tuck S, Morselli P, Broquaire M, Vert P. Plasma and urinary kinetics of furosemide in newborn infants. J Pediatr. 1983;103:481–5.

    Article  CAS  Google Scholar 

  23. Okazaki K, Fukuoka N, Kuboi T, Unemoto J, Kondo M, Kusaka T, et al. Furosemide clearance in very preterm neonates early in life: a pilot study using scavenged samples. Pediatr Int. 2021:1–6. https://doi.org/10.1111/ped.14735.

  24. Stewart A, Brion LP. Intravenous or enteral loop diuretics for preterm infants with (or developing) chronic lung disease. Cochrane Database Syst Rev. 2011;9:CD001817.

    Google Scholar 

  25. Greenberg RG, Gayam S, Savage D, Tong A, Gorham D, Sholomon A, et al. Furosemide exposure and prevention of bronchopulmonary dysplasia in premature Infants. J Pediatr. 2019;208:134–40.

    Article  CAS  Google Scholar 

Download references

Funding

This work was supported by Eunice Kennedy Shriver National Institute of Child Health and Human Development grant K23HD10165 to NAB and National Heart, Lung, and Blood Institute Award K24HL143283 to MML. The funding sources had no role in the study design; the collection, analysis, and interpretation of the data; the writing of the report or the decision to submit for publication. NAB wrote the first draft of the manuscript. No compensation honorarium, grant, or other forms of payment was given to produce the manuscript.

Author information

Authors and Affiliations

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

    Nicolas A. Bamat, Scott A. Lorch & Eric C. Eichenwald

  2. Center for Pediatric Clinical Effectiveness, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Nicolas A. Bamat

  3. Center for Clinical Pharmacology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Nicolas A. Bamat & Athena F. Zuppa

  4. Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA

    Elizabeth J. Thompson, Rachel G. Greenberg, P. Brian Smith, Christoph P. Hornik & Jason E. Lang

  5. Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA

    Rachel G. Greenberg, P. Brian Smith & Christoph P. Hornik

  6. Department of Anesthesiology and Critical Care Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Athena F. Zuppa

  7. Department of Neonatology, Baylor University Medical Center, Dallas, TX, USA

    Veeral N. Tolia

  8. The MEDNAX Center for Research, Education, Quality and Safety, Sunrise, FL, USA

    Veeral N. Tolia & Reese H. Clark

  9. Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Matthew M. Laughon

Authors
  1. Nicolas A. Bamat
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elizabeth J. Thompson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rachel G. Greenberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Scott A. Lorch
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Athena F. Zuppa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Eric C. Eichenwald
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Veeral N. Tolia
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Reese H. Clark
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. P. Brian Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Christoph P. Hornik
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Jason E. Lang
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Matthew M. Laughon
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Study conception: NAB, EJT, RGG, SAL, AFZ, ECE, MML. Study design: NAB, EJT, RGG, PBS, MML. Data acquisition: EJT, RGG, VNT, RHC, CPH. Data analysis: NAB, EJT, RGG, MML. Data interpretation: all authors. Drafting the work: NAB, EJT, RGG, MML. Revising it for critically important intellectual content: all authors.

Corresponding author

Correspondence to Nicolas A. Bamat.

Ethics declarations

Competing interests

The authors declare no competing interests.

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

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bamat, N.A., Thompson, E.J., Greenberg, R.G. et al. Association between postmenstrual age and furosemide dosing practices in very preterm infants. J Perinatol 42, 461–467 (2022). https://doi.org/10.1038/s41372-022-01320-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41372-022-01320-w

This article is cited by

Search

Advanced search

Quick links