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:

The use of supplemental hydrocortisone in the management of persistent pulmonary hypertension of the newborn

Abstract

Objective

Characterize association between hydrocortisone receipt and hospital outcomes of infants with persistent pulmonary hypertension of the newborn (PPHN).

Study design

Cohort study of infants ā‰„34 weeks with PPHN who received inhaled nitric oxide at <7 days of age (2010ā€“2016). We generated propensity scores, and performed inverse probability-weighted regression to estimate hydrocortisone effect on outcomes: death, chronic lung disease (CLD), oxygen at discharge.

Results

Of 2743 infants, 30% received hydrocortisone, which was associated with exposure to mechanical ventilation, sedatives, paralytics, or vasopressors (pā€‰<ā€‰0.001). There was no difference in death, CLD, or oxygen at discharge. In infants with meconium aspiration syndrome, hydrocortisone was associated with decreased oxygen at discharge (odds ratio 0.56; 95% confidence interval 0.21, 0.91).

Conclusions

There was no association between hydrocortisone receipt and death, CLD, or oxygen at discharge in our cohort. Prospective studies are needed to evaluate the effectiveness of hydrocortisone in infants with PPHN.

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

Access options

Buy this article

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

Fig. 1: Percentage of infants with PPHN receiving hydrocortisone, by year.

Similar content being viewed by others

References

  1. Fuloria M, Aschner JL. Persistent pulmonary hypertension of the newborn. Semin Fetal Neonatal Med. 2017;22:220ā€“6.

    ArticleĀ  Google ScholarĀ 

  2. Walsh-Sukys MC, Tyson JE, Wright LL, Bauer CR, Korones SB, Stevenson DK, et al. Persistent pulmonary hypertension of the newborn in the era before nitric oxide: practice variation and outcomes. Pediatrics. 2000;105:14ā€“20.

    ArticleĀ  CASĀ  Google ScholarĀ 

  3. Roberts JD Jr, Fineman JR, Morin FC 3rd, Shaul PW, Rimar S, Schreiber MD, et al. Inhaled nitric oxide and persistent pulmonary hypertension of the newborn. The inhaled nitric oxide study group. N Engl J Med. 1997;336:605ā€“10.

    ArticleĀ  CASĀ  Google ScholarĀ 

  4. Clark RH, Kueser TJ, Walker MW, Southgate WM, Huckaby JL, Perez JA, et al. Low-dose nitric oxide therapy for persistent pulmonary hypertension of the newborn. Clinical inhaled nitric oxide research group. N Engl J Med. 2000;342:469ā€“74.

    ArticleĀ  CASĀ  Google ScholarĀ 

  5. Neonatal Inhaled Nitric Oxide Study G. Inhaled nitric oxide in full-term and nearly full-term infants with hypoxic respiratory failure. N Engl J Med. 1997;336:597ā€“604.

    ArticleĀ  Google ScholarĀ 

  6. Barrington KJ, Finer N, Pennaforte T, Altit G. Nitric oxide for respiratory failure in infants born at or near term. Cochrane Database Syst Rev. 2017;1:CD000399.

    PubMedĀ  Google ScholarĀ 

  7. Baquero H, Soliz A, Neira F, Venegas ME, Sola A. Oral sildenafil in infants with persistent pulmonary hypertension of the newborn: a pilot randomized blinded study. Pediatrics. 2006;117:1077ā€“83.

    ArticleĀ  Google ScholarĀ 

  8. McNamara PJ, Laique F, Muang-In S, Whyte HE. Milrinone improves oxygenation in neonates with severe persistent pulmonary hypertension of the newborn. J Crit Care. 2006;21:217ā€“22.

    ArticleĀ  CASĀ  Google ScholarĀ 

  9. Mohamed WA, Ismail M. A randomized, double-blind, placebo-controlled, prospective study of bosentan for the treatment of persistent pulmonary hypertension of the newborn. J Perinatol. 2012;32:608ā€“13.

    ArticleĀ  CASĀ  Google ScholarĀ 

  10. Farrow KN, Steinhorn RH. Phosphodiesterases: Emerging Therapeutic Targets for Neonatal Pulmonary Hypertension. In: Francis S, Conti M, Houslay M, editors. Phosphodiesterases as Drug Targets. Handbook of Experimental Pharmacology, vol. 204. Heidelberg, Berlin: Springer; 2011.

  11. Lakshminrusimha S, Russell JA, Steinhorn RH, Ryan RM, Gugino SF, Morin FC 3rd, et al. Pulmonary arterial contractility in neonatal lambs increases with 100% oxygen resuscitation. Pediatr Res. 2006;59:137ā€“41.

    ArticleĀ  Google ScholarĀ 

  12. Lakshminrusimha S, Steinhorn RH, Wedgwood S, Savorgnan F, Nair J, Mathew B, et al. Pulmonary hemodynamics and vascular reactivity in asphyxiated term lambs resuscitated with 21 and 100% oxygen. J Appl Physiol. 2011;111:1441ā€“7.

    ArticleĀ  Google ScholarĀ 

  13. Perez M, Lakshminrusimha S, Wedgwood S, Czech L, Gugino SF, Russell JA, et al. Hydrocortisone normalizes oxygenation and cGMP regulation in lambs with persistent pulmonary hypertension of the newborn. Am J Physiol Lung Cell Mol Physiol. 2012;302:L595ā€“603.

    ArticleĀ  CASĀ  Google ScholarĀ 

  14. Perez M, Wedgwood S, Lakshminrusimha S, Farrow KN, Steinhorn RH. Hydrocortisone normalizes phosphodiesterase-5 activity in pulmonary artery smooth muscle cells from lambs with persistent pulmonary hypertension of the newborn. Pulm Circ. 2014;4:71ā€“81.

    ArticleĀ  Google ScholarĀ 

  15. Byers HM, Dagle JM, Klein JM, Ryckman KK, McDonald EL, Murray JC, et al. Variations in CRHR1 are associated with persistent pulmonary hypertension of the newborn. Pediatr Res. 2012;71:162ā€“7.

    ArticleĀ  CASĀ  Google ScholarĀ 

  16. Spitzer AR, Ellsbury DL, Handler D, Clark RH. The Pediatrix BabySteps Data Warehouse and the Pediatrix QualitySteps improvement project system-tools for ā€œmeaningful useā€ in continuous quality improvement. Clin Perinatol. 2010;37:49ā€“70.

    ArticleĀ  Google ScholarĀ 

  17. Trembath A, Hornik CP, Clark R, Smith PB, Daniels J, Laughon M, et al. Comparative effectiveness of surfactant preparations in premature infants. J Pediatr. 2013;163:955ā€“60.e1.

    ArticleĀ  CASĀ  Google ScholarĀ 

  18. Olsen IE, Groveman SA, Lawson ML, Clark RH, Zemel BS. New intrauterine growth curves based on United States data. Pediatrics. 2010;125:e214ā€“24.

    ArticleĀ  Google ScholarĀ 

  19. Imai K, Ratkovic M. Covariate balancing propensity score. J R Stat Soc Ser B. 2014;76:243ā€“63.

    ArticleĀ  Google ScholarĀ 

  20. Pierro M, Thebaud B. Understanding and treating pulmonary hypertension in congenital diaphragmatic hernia. Semin Fetal Neonatal Med. 2014;19:357ā€“63.

    ArticleĀ  CASĀ  Google ScholarĀ 

  21. Nair J, Lakshminrusimha S. Update on PPHN: mechanisms and treatment. Semin Perinatol. 2014;38:78ā€“91.

    ArticleĀ  Google ScholarĀ 

  22. Lakshminrusimha S, Mathew B, Leach CL. Pharmacologic strategies in neonatal pulmonary hypertension other than nitric oxide. Semin Perinatol. 2016;40:160ā€“73.

    ArticleĀ  Google ScholarĀ 

  23. Mathew B, Lakshminrusimha S. Persistent pulmonary hypertension in the newborn. Children. 2017;4:63.

    ArticleĀ  Google ScholarĀ 

  24. Fernandez E, Schrader R, Watterberg K. Prevalence of low cortisol values in term and near-term infants with vasopressor-resistant hypotension. J Perinatol. 2005;25:114ā€“8.

    ArticleĀ  CASĀ  Google ScholarĀ 

  25. Baker CF, Barks JD, Engmann C, Vazquez DM, Neal CR Jr, Schumacher RE, et al. Hydrocortisone administration for the treatment of refractory hypotension in critically ill newborns. J Perinatol. 2008;28:412ā€“9.

    ArticleĀ  CASĀ  Google ScholarĀ 

  26. Alsaleem M, Malik A, Lakshminrusimha S, Kumar VH. Hydrocortisone improves oxygenation index and systolic blood pressure in term infants with persistent pulmonary hypertension. Clin Med Insights Pediatr. 2019;13:1179556519888918.

    ArticleĀ  Google ScholarĀ 

  27. Tripathi S, Saili A. The effect of steroids on the clinical course and outcome of neonates with meconium aspiration syndrome. J Trop Pediatr. 2007;53:8ā€“12.

    ArticleĀ  Google ScholarĀ 

  28. Basu S, Kumar A, Bhatia BD, Satya K, Singh TB. Role of steroids on the clinical course and outcome of meconium aspiration syndrome-a randomized controlled trial. J Trop Pediatr. 2007;53:331ā€“7.

    ArticleĀ  Google ScholarĀ 

  29. Mokra D, Mokry J. Glucocorticoids in the treatment of neonatal meconium aspiration syndrome. Eur J Pediatr. 2011;170:1495ā€“505.

    ArticleĀ  CASĀ  Google ScholarĀ 

  30. Soukka H, Halkola L, Aho H, Rautanen M, Kero P, Kaapa P. Methylprednisolone attenuates the pulmonary hypertensive response in porcine meconium aspiration. Pediatr Res. 1997;42:145ā€“50.

    ArticleĀ  CASĀ  Google ScholarĀ 

Download references

Funding

This work was supported by Duke Clinical Research Instituteā€™s R25 Summer Training in Academic Research (STAR) Program (grant #5R25HD076475-07). This work was partially funded under the National Institute of Child Health and Human Development (NICHD) contract (HHSN275201000003I) for the Pediatric Trials Network (PI Danny Benjamin). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Author information

Authors and Affiliations

Authors

Contributions

SA is the guarantor who accepts full responsibility for the work and conduct of the study, and had access to the data. SA conceptualized and designed the study, and contributed to the data interpretation, the drafting of the initial paper, and reviewing and revising the paper. CR contributed to the data interpretation and the paper drafting. BM contributed to the data interpretation and the paper drafting. SE contributed to the data interpretation and the paper drafting. CA contributed to the data interpretation and the paper drafting. NP contributed to the data interpretation and the paper drafting. DKB contributed to the study design, data analyses, and the critical revision of the paper for important intellectual content. VNT contributed to the data interpretation and the critical revision of the paper for important intellectual content. KOZ contributed to the data interpretation and the critical revision of the paper for important intellectual content. RNG contributed to the data interpretation and the critical revision of the paper for important intellectual content. RGG contributed to the conception and design of the study, supervised the drafting of the paper, interpreted the data analyses, and reviewed and revised the paper. RGG had full access to all the data and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Corresponding author

Correspondence to Rachel G. Greenberg.

Ethics declarations

Conflict of interest

RGG has received support from industry for research services (https://dcri.org/about-us/conflict-of-interest/). The other authors have no competing interests relevant to this article to disclose.

Additional information

Publisherā€™s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Aleem, S., Robbins, C., Murphy, B. et al. The use of supplemental hydrocortisone in the management of persistent pulmonary hypertension of the newborn. J Perinatol 41, 794ā€“800 (2021). https://doi.org/10.1038/s41372-021-00943-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41372-021-00943-9

Search

Quick links