Skip to main content

Advertisement

SpringerLink
Log in

Systemic Hypertension in Infants with Bronchopulmonary Dysplasia

  • Pediatric Hypertension (C Hanevold, Section Editor)
  • Published:
Current Hypertension Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Neonatal hypertension is increasingly recognized as improvements in neonatal intensive care have led to increased survival of premature infants. Among infants with bronchopulmonary dysplasia (BPD), the rates of hypertension are much higher than the general neonatal population. However, the etiology and pathophysiology of this increased risk of hypertension in neonates with lung disease remain unclear.

Recent Findings

Among infants with bronchopulmonary dysplasia, the rates of hypertension are much higher than the general neonatal population. New studies suggest outcomes in neonates with BPD with hypertension are usually good, with resolution of hypertension in most infants with lung disease. Several potential mechanisms of hypertension in this patient population have been recently proposed.

Summary

This review focuses on the recent epidemiologic data on prevalence of hypertension in neonates with bronchopulmonary dysplasia, reviews the typical clinical course, and discusses available strategies for management of infants with bronchopulmonary dysplasia that develop hypertension.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Adelman RD. Neonatal hypertension. Pediatr Clin N Am. 1978;25(1):99–110.

    Article  CAS  Google Scholar 

  2. Watkinson M. Hypertension in the newborn baby. Arch Dis Child: Fetal Neonatal Ed. 2002;86(2):F78-81.

    Article  CAS  Google Scholar 

  3. Snauwaert E, Walle JV, Bruyne PD. Therapeutic efficacy and safety of ACE inhibitors in the hypertensive paediatric population: a review. Arch Dis Child. 2017;102(1):63–71.

    Article  PubMed  Google Scholar 

  4. Starr MC, Flynn JT. Neonatal hypertension: cases, causes, and clinical approach. Pediatr Nephrol. 2019;34(5):787–99.

    Article  PubMed  Google Scholar 

  5. Harer MW, Kent AL. Neonatal hypertension: an educational review. Pediatric Nephrology. 2019;34(6):1009-18. Comprehensive recent review of neonatal hypertension, including epidemiology, diagnosisand medical management.

  6. Dionne JM. Neonatal and Infant Hypertension. In: Flynn JT, Ingelfinger JR, Redwine KM, editors. Pediatr Hypertens. New York: Springer Science+Business Media; 2018. p. 539–63.

    Chapter  Google Scholar 

  7. Stoll BJ, Hansen NI, Bell EF, Walsh MC, Carlo WA, Shankaran S, et al. Trends in care practices, morbidity, and mortality of extremely preterm neonates, 1993–2012. JAMA. 2015;314(10):1039–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Alvarez-Fuente M, Arruza L, Muro M, Zozaya C, Avila A, Lopez-Ortego P, et al. The economic impact of prematurity and bronchopulmonary dysplasia. Eur J Pediatr. 2017;176(12):1587–93.

    Article  PubMed  Google Scholar 

  9. 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(6):751–9.

  10. Georgieff MK, Mills MM, Gomez-Marin O, Sinaiko AR. Rate of change of blood pressure in premature and full term infants from birth to 4 months. Pediatr Nephrol. 1996;10(2):152–5.

    Article  CAS  PubMed  Google Scholar 

  11. Kent AL, Kecskes Z, Shadbolt B, Falk MC. Blood pressure in the first year of life in healthy infants born at term. Pediatr Nephrol. 2007;22(10):1743–9.

    Article  PubMed  Google Scholar 

  12. Zubrow AB, Hulman S, Kushner H, Falkner B. Determinants of blood pressure in infants admitted to neonatal intensive care units: a prospective multicenter study. Philadelphia Neonatal Blood Pressure Study Group. J Perinatol. 1995;15(6):470–9.

  13. Pejovic B, Peco-Antic A, Marinkovic-Eric J. Blood pressure in non-critically ill preterm and full-term neonates. Pediatr Nephrol. 2007;22(2):249–57.

    Article  PubMed  Google Scholar 

  14. Flynn JT, Kaelber DC, Baker-Smith CM, Blowey D, Carroll AE, Daniels SR, et al. Clinical practice guideline for screening and management of high blood pressure in children and adolescents. Pediatrics. 2017;140(3):e20171904. Most recent guidelines for blood pressure screening in pediatric patients from the American Academy of Pediatrics. This guideline includes the recommendation for evaluation of blood pressure in all infants admitted to the NICU.

  15. Dionne JM, Abitbol CL, Flynn JT. Hypertension in infancy: diagnosis, management and outcome. Pediatr Nephrol. 2012;27(1):17–32. This important reivew article provided normative blood pressure data using existingpublished data to derive systolic and diastolic BP percentiles based on PMA. These valueshave the advantage of being relatively easy to use clinically, and we consider them thestandard for evaluating blood pressure in neonates.

  16. Neal WA, Reynolds JW, Jarvis CW, Williams HJ. Umbilical artery catheterization: demonstration of arterial thrombosis by aortography. Pediatrics. 1972;50(1):6–13.

    Article  CAS  PubMed  Google Scholar 

  17. Jenkins RD, Aziz JK, Gievers LL, Mooers HM, Fino N, Rozansky DJ. Characteristics of hypertension in premature infants with and without chronic lung disease: a long-term multi-center study. Pediatr Nephrol. 2017;32(11):2115–24. This multicenter retrospective cohort of infants with hypertension was the first to describe BPD-assocaited HTN and found that over one third had BPD as a likely reason for their HTN. HTN was diagnosed at an average of 40 weeks PMA and resolved in all infants.

  18. Abman SH, Warady BA, Lum GM, Koops BL. Systemic hypertension in infants with bronchopulmonary dysplasia. J Pediatr. 1984;104(6):928–31.

    Article  CAS  PubMed  Google Scholar 

  19. Flynn JT. Neonatal hypertension: diagnosis and management. Pediatr Nephrol. 2000;14(4):332–41. This important reivew article reviewes the etiologies of hypertension in neonates and provides a framework for the clinical presentation and diagnostic evaluation in neonatal patients with elevated blood pressures.

  20. Abman SH. Monitoring cardiovascular function in infants with chronic lung disease of prematurity. Arch Dis Child: Fetal Neonatal Ed. 2002;87(1):F15–8.

    Article  CAS  Google Scholar 

  21. Sehgal A, Malikiwi A, Paul E, Tan K, Menahem S. Systemic arterial stiffness in infants with bronchopulmonary dysplasia: potential cause of systemic hypertension. J Perinatol. 2016;36(7):564–9.

    Article  CAS  PubMed  Google Scholar 

  22. Jenkins R, Tackitt S, Gievers L, Iragorri S, Sage K, Cornwall T, et al. Phthalate-associated hypertension in premature infants: a prospective mechanistic cohort study. Pediatr Nephrol. 2019;34:1413–24. This single-center prospective cohort study evaluated the risk of hypertension in infants with and without exposure to phthalates during their NICU hospitalization and found an increased risk of hypertension in those with phthalate exposure. They also provide mechanistic exploration and considerations.

  23. Jenkins R, Farnbach K, Iragorri S. Elimination of intravenous Di-2-ethylhexyl phthalate exposure abrogates most neonatal hypertension in premature infants with bronchopulmonary dysplasia. Toxics. 2021;9(4):75. The same group further reported that rates of hypertension have decreased with removal of phthalates from medical products in the NICU from 10.1 to 1.4% in very low birth weight infants.

  24. Starr MC, Boohaker L, Eldredge LC, Menon S, Griffin R, Mayock DE, et al. Acute kidney injury and bronchopulmonary dysplasia in premature neonates born less than 32 weeks’ gestation. Am J Perinatol. 2020;37(3):341–8.

    Article  PubMed  Google Scholar 

  25. Askenazi DJ, Heagerty PJ, Schmicker RH, Goldstein SL, Hingorani S, Consortium PT. The impact of erythropoietin on short- and long-term kidney-related outcomes in neonates of extremely low gestational age. Results of a Multicenter, Double-Blind, Placebo-Controlled Randomized Clinical Trial. J Pediatr. 2021;232:65–72. Large multicenter study of extremely low gestational age neonates found that infants with AKI were more likely to have diastolic hypertension at 2 years of age than those who did not have AKI. Overall, cohort had a high incidence of hypertension at 2 years of age.

  26. Lurbe E, Garcia-Vicent C, Torro I, Fayos JL, Aguilar F, Llano JMd, et al. First-year blood pressure increase steepest in low birthweight newborns. J Hypertens. 2007;25(1):81–6.

  27. Dagle JM, Fisher TJ, Haynes SE, Berends SK, Brophy PD Jr. FHM, et al. Cytochrome P450 (CYP2D6) genotype is associated with elevated systolic blood pressure in preterm infants after discharge from the neonatal intensive care unit. J Pediatr. 2011;159(1):104–9.

  28. Kent AL, Chaudhari T. Determinants of neonatal blood pressure. Curr Hypertens Rep. 2013;15(5):426–32.

    Article  PubMed  Google Scholar 

  29. Sadoh WE, Ibhanesehbor SE, Monguno AM, Gubler DJ. Predictors of newborn systolic blood pressure. West Afr J Med. 2010;29(2):86–90.

    CAS  PubMed  Google Scholar 

  30. Seibert JJ, Taylor BJ, WIlliamson SJ, Williams BJ, Szabo JS, Corbitt SL. Sonographic detection of neonatal umbilical-artery thrombosis: clinical correlation. Am J Roentgenol. 1987;148(5):965–8.

  31. Boo NY, Wong NC, Zulkifli SS, Lye MS. Risk factors associated with umbilical vascular catheter-associated thrombosis in newborn infants. J Paediatr Child Health. 1999;35(5):460–5.

    Article  CAS  PubMed  Google Scholar 

  32. Barrington KJ. Umbilical artery catheters in the newborn: effects of position of the catheter tip. Cochrane Database Syst Rev. 2000;1999(2):CD000505.

  33. Tullus K, Brennan E, Hamilton G, Lord R, McLaren CA, Marks SD, et al. Renovascular hypertension in children. Lancet. 2008;371(9622):1453–63.

    Article  CAS  PubMed  Google Scholar 

  34. Lau KK, Stoffman JM, WIlliams S, McCusker P, Brandao L, Patel S, et al. Neonatal renal vein thrombosis: review of the English-language literature between 1992 and 2006. Pediatrics. 2007;120(5):e1278–84.

  35. Guay-Woodford LM, Desmond RA. Autosomal recessive polycystic kidney disease: the clinical experience in North America. Pediatrics. 2003;111(5):1072–80.

    Article  PubMed  Google Scholar 

  36. Moralioglu S, Celayir AC, Bosnali O, Pektas OZ, Bulut IK. Single center experience in patients with unilateral multicystic dysplastic kidney. J Pediatr Urol. 2014;10(4):763–8.

    Article  PubMed  Google Scholar 

  37. Selewski DT, Charlton JR, Jetton JG, Guillet R, Mhanna MJ, Askenazi DJ, et al. Neonatal Acute Kidney Injury. Pediatrics. 2015;136(2):e463–73.

    Article  PubMed  Google Scholar 

  38. Durand M, Sangha B, Cabal LA, Hoppenbrouwers T, Hodgman JE. Cardiopulmonary and intracranial pressure changes related to endotracheal suctioning in preterm infants. Crit Care Med. 1989;17(6):506–10.

    Article  CAS  PubMed  Google Scholar 

  39. Marinelli KA, Burke GS, Herson VC. Effects of dexamethasone on blood pressure in premature infants with bronchopulmonary dysplasia. J Pediatr. 1997;130(4):594–602.

    Article  CAS  PubMed  Google Scholar 

  40. Merritt JC, Kraybill EN. Effect of mydriatics on blood pressure in premature infants. J Pediatr Ophthalmol Strabismus. 1981;18(5):42–6.

    Article  CAS  PubMed  Google Scholar 

  41. Seliem WA, Falk MC, Shadbolt B, Kent AL. Antenatal and postnatal risk factors for neonatal hypertension and infant follow-up. Pediatr Nephrol. 2007;22(12):2081–7.

    Article  PubMed  Google Scholar 

  42. Sahu R, Pannu H, Yu R, Shte S, Bricker JT, Gupta-Malhotra M. Systemic hypertension requiring treatment in the neonatal intensive care unit. J Pediatr. 2013;163(1):84–8.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Blowey DJ, Duda PJ, Stokes P, Hall M. Incidence and treatment of hypertension in the neonatal intensive care unit. J Am Soc Hypertens. 2011;5(6):478–83.

    Article  PubMed  Google Scholar 

  44. Friedman AL, Hustead VA. Hypertension in babies following discharge from a neonatal intensive care unit. A 3-year follow-up. Pediatr Nephrol. 1987;1(1):30–4.

  45. Shah AB, Hashmi SS, Sahulee R, Pannu H, Gupta-Malhotra M. Characteristics of Systemic Hypertension in Preterm Children. J Clin Hypertens. 2015;17(5):364–70.

    Article  Google Scholar 

  46. Flynn JT, Kaelber DC, Baker-Smith CM, Blowey D, Carroll AE, Daniels SR, et al. Clinical practice guideline for screening and management of high blood pressure in children and adolescents. Pediatrics. 2017;140(3).

  47. Emery EF, Greenough A. Neonatal blood pressure levels of preterm infants who did and did not develop chronic lung disease. Early Hum Dev. 1992;31(2):149–56.

    Article  CAS  PubMed  Google Scholar 

  48. Alagappan A, Malloy MH. Systemic hypertension in very low-birth weight infants with bronchopulmonary dysplasia: incidence and risk factors. Am J Perinatol. 1998;15(1):3–8.

    Article  CAS  PubMed  Google Scholar 

  49. Farnbach K, Iragorri S, Al-Uzri A, Rozansky D, Forbush R, Jenkins R. The changing spectrum of hypertension in premature infants. J Perinatol. 2019;39(11):1528–34.

    Article  CAS  PubMed  Google Scholar 

  50. Xiao N, Tandon A, Goldstein S, Lorts A. Cardiogenic shock as the initial presentation of neonatal systemic hypertension. J Neonatal Perinatal Med. 2013;6(3):267–72.

    Article  CAS  PubMed  Google Scholar 

  51. Butt WW, Whyte H. Blood pressure monitoring in neonates: comparison of umbilical and peripheral artery catheter measurements. J Pediatr. 1984;105(4):630–2.

    Article  CAS  PubMed  Google Scholar 

  52. O’Shea J, Dempsey EM. A comparison of blood pressure measurements in newborns. Am J Perinatol. 2009;26(2):113–6.

    Article  PubMed  Google Scholar 

  53. Crossland DS, Furness JC, Abu-Harb M, Sadagopan SN, Wren C. Variability of four limb blood pressure in normal neonates. Arch Dis Child: Fetal Neonatal Ed. 2004;89(4):F325–7.

    Article  CAS  Google Scholar 

  54. Richer C, Hornych H, Amiel-Tison C, Relier JP, Giudicelli JF. Plasma renin activity and its postnatal development in preterm infants. Preliminary report Biol Neonate. 1977;31(5–6):301–4.

    Article  CAS  PubMed  Google Scholar 

  55. Flynn JT, Warnick SJ. Isradipine treatment of hypertension in children: a single-center experience. Pediatr Nephrol. 2002;17(9):748–53.

    Article  PubMed  Google Scholar 

  56. Kao LC, Durand DJ, McCrea RC, Birch M, Powers RJ, Nickerson BG. Randomized trial of long-term diuretic therapy for infants with oxygen-dependent bronchopulmonary dysplasia. J Pediatr. 1994;124(5):772–81. This study highlights the role of chronic diuretic use in treatment of hypertension in infants with oxygen-dependent (severe) bronchopulmonary dysplasia, specificially focusing on the mechanism, role, and dosing of spironolactone.

  57. Mohamed TH, Klamer B, Mahan JD, Spencer JD, Slaughter JL. Diuretic therapy and acute kidney injury in preterm neonates and infants. Pediatr Nephrol. 2021.

  58. Stewart A, Brion LP, Ambrioso-Perez I. Diuretics acting on the distal renal tubule for preterm infants with (or developing) chronic lung disease. Cochrane Database Syst Rev. 2011;2011(9):CD001817.

  59. O’Dea RF, Mirkin BL, Alward CT, Sinaiko AR. Treatment of neonatal hypertension with captopril. J Pediatr. 1988;113(2):403–6.

    Article  CAS  PubMed  Google Scholar 

  60. Ku LC, Zimmerman K, Benjamin DK, Clark RH, Hornik CP, Smith PB. Safety of enalapril in infants admitted to the neonatal intensive care unit. Pediatr Cardiol. 2017;38(1):155–61.

    Article  PubMed  Google Scholar 

  61. Pandey R, Koshy RG, Dako J. Angiotensin converting enzyme inhibitors induced acute kidney injury in newborn. J Matern Fetal Neonatal Med. 2017;30(6):748–50.

    Article  CAS  PubMed  Google Scholar 

  62. Tufro-McReddie A, Romano LM, Harris JM, Ferder L, Gomez RA. Angiotensin II regulates nephrogenesis and renal vascular development. Am J Physiol. 1995;269(1):F110–5.

    Article  CAS  PubMed  Google Scholar 

  63. Frolich S, Slattery P, Thomas D, Goren I, Ferreiros N, Jensen BL, et al. Angiotensin II-AT1-receptor signaling is necessary for cyclooxygenase-2-dependent postnatal nephron generation. Kidney Int. 2017;91(4):818–29.

    Article  PubMed  CAS  Google Scholar 

  64. Starr MC, Hingorani SR. Prematurity and future kidney health: the growing risk of chronic kidney disease. Curr Opin Pediatr. 2018;30(2):228–35.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Khalsa DD, Beydoun HA, Carmody JB. Prevalence of chronic kidney disease risk factors among low birth weight adolescents. Pediatr Nephrol. 2016;31(9):1509–16.

    Article  PubMed  Google Scholar 

  66. Group LBWaNNW. The impact of kidney development on the life course: a consensus document for action. Nephron. 2017;136(1):3–49.

  67. Keller G, Zimmer G, Mall G, Ritz E, Amann K. Nephron number in patients with primary hypertension. N Engl J Med. 2003;348(2):101–8.

    Article  PubMed  Google Scholar 

  68. Luyckx VA, Brenner BM. Clinical consequences of developmental programming of low nephron number. Anat Rec (Hoboken). 2020;303(10):2613–31.

    Article  Google Scholar 

  69. Gupta-Malhotra M, Banker A, Shete S, Hashmi SS, Tyson JE, Barratt MS, et al. Essential hypertension vs. secondary hypertension among children. Am J Hypertens. 2015;28(1):73–80.

  70. Anderson AH, Warady BA, Daily DK, Johnson JA, Thomas MK. Systemic hypertension in infants with severe bronchopulmonary dysplasia: associated clinical factors. Am J Perinatol. 1993;10(3):190–3.

    Article  CAS  PubMed  Google Scholar 

  71. Greenough A, Emery EF. Effect of chronic lung disease on blood pressure levels at follow up. Eur J Pediatr. 1993;152(6):516–8.

    Article  CAS  PubMed  Google Scholar 

  72. Gievers LL, Jenkins RD, Laird A, Macedo MC, Schilling D, McEvoy CT. Pulmonary function and systolic blood pressure in very low birth weight infants at 34–36 weeks of corrected age. Res Rep Neonatol. 2019;9:21–30.

    PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Riley Hospital for Children, 410 W 10th Street, Suite 2000A, Indianapolis, IN, 46202, USA

    Michelle C. Starr & Amy C. Wilson

  2. Indiana University School of Medicine, Health Information & Translational Sciences, 410 W 10th Street, Suite 2000A, Indianapolis, IN, 46202, USA

    Michelle C. Starr & Amy C. Wilson

  3. Center for Pediatric and Adolescent Comparative Effectiveness Research, Indiana University, Indianapolis, IN, USA

    Michelle C. Starr

Authors
  1. Michelle C. Starr
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Amy C. Wilson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michelle C. Starr.

Ethics declarations

Conflict of Interest

The authors declare no competing interests.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher's Note

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

This article is part of Topical Collection on Pediatric Hypertension

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Starr, M.C., Wilson, A.C. Systemic Hypertension in Infants with Bronchopulmonary Dysplasia. Curr Hypertens Rep 24, 193–203 (2022). https://doi.org/10.1007/s11906-022-01179-4

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11906-022-01179-4

Keywords

Search

Navigation