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Blood pressure values and hypotension management in extremely preterm infants: a multi-center study

Journal of Perinatology volume 42, pages 1169–1175 (2022)Cite this article

Subjects

Abstract

Objective

To describe high/low daily blood pressures (BP) and variability in BP management with vasoactive infusions (VI) and/or hydrocortisone (HC) in extremely preterm infants.

Study design

Analysis of data from 24–27 weeks’ gestation infants in the Preterm Erythropoietin Neuroprotection (PENUT) Trial. Daily high/low BPs, the use of VI and/or HC, and adverse outcomes were compared descriptively and using regression models.

Results

936 infants were included; 64% untreated, 20% VI, 3% HC, and 13% VI + HC. BP ranges are described for the 602 untreated infants. Considerable inter- and intra-center variability was demonstrated in the rate of VI and/or HC use and the lowest BP on the day of VI or HC initiation.

Conclusions

Despite published expert opinion guidance regarding BP management in extremely preterm infants, our results suggest a continued lack of consensus result in both inter- and intra-center variability in practice. Well-designed studies in the field are urgently needed.

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Fig. 1: Lowest and highest daily systolic, diastolic, and mean arterial blood pressures for infants who received no anti-hypotensive treatment within the first 14 days of life.
Fig. 2: Lowest daily mean arterial blood pressures for infants, stratified by gestational age and treatment/mortality.
Fig. 3: Variability in treatment thresholds and types of treatment by study site.
Fig. 4: Survival and time until weaning off of vasoactive infusions (VI), by treatment group.

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References

  1. Batton B, Li L, Newman NS, Das A, Watterberg KL, Yoder BA, et al. Use of antihypotensive therapies in extremely preterm infants. Pediatrics. 2013;131:e1865–73.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Dempsey EM. Challenges in treating low blood pressure in preterm infants. Child (Basel, Switz). 2015;2:272–88.

    Google Scholar 

  3. 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 Off J Calif Perinat Assoc. 1995;15:470.

    CAS  Google Scholar 

  4. Watkins AM, West CR, Cooke RW. Blood pressure and cerebral haemorrhage and ischaemia in very low birthweight infants. Early Hum Dev. 1989;19:103–10.

    Article  CAS  PubMed  Google Scholar 

  5. Versmold HT, Kitterman JA, Phibbs RH, Gregory GA, Tooley WH. Aortic blood pressure during the first 12 h of life in infants with birth weight 610 to 4,220 grams. Pediatrics. 1981;67:607–13.

    Article  CAS  PubMed  Google Scholar 

  6. Hegyi T, Carbone MT, Anwar M, Ostfeld B, Hiatt M, Koons A, et al. Blood pressure ranges in premature infants. I. The first hours of life. J Pediatr. 1994;124:627–33.

    Article  CAS  PubMed  Google Scholar 

  7. Demarini S, Dollberg S, Hoath SB, Ho M, Donovan EF. Effects of antenatal corticosteroids on blood pressure in very low birth weight infants during the first 24 h of life. J Perinatol. 1999;19:419–25.

    Article  CAS  PubMed  Google Scholar 

  8. Stark MJ, Hodyl NA, Andersen CC. Effects of antenatal magnesium sulfate treatment for neonatal neuro-protection on cerebral oxygen kinetics. Pediatr Res. 2015;78:310–4.

    Article  CAS  PubMed  Google Scholar 

  9. Moise AA, Wearden ME, Kozinetz CA, Gest AL, Welty SE, Hansen TN. Antenatal steroids are associated with less need for blood pressure support in extremely premature infants. Pediatrics 1995;95:845–50.

    Article  CAS  PubMed  Google Scholar 

  10. Batton B, Li L, Newman NS, Das A, Watterberg KL, Yoder BA, et al. Evolving blood pressure dynamics for extremely preterm infants. J perinatology: Off J Calif Perinat Assoc. 2014;34:301–5.

    Article  CAS  Google Scholar 

  11. Vesoulis ZA, El Ters NM, Wallendorf M, Mathur AM. Empirical estimation of the normative blood pressure in infants <28 weeks gestation using a massive data approach. J perinatology: Off J Calif Perinat Assoc. 2016;36:291–5.

    Article  CAS  Google Scholar 

  12. Ahn SY, Kim ES, Kim JK, Shin JH, Sung SI, Jung JM, et al. Permissive hypotension in extremely low birth weight infants (≤1000 gm). Yonsei Med J. 2012;53:765–71.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Cunningham S, Symon AG, Elton RA, Zhu C, McIntosh N. Intra-arterial blood pressure reference ranges, death and morbidity in very low birthweight infants during the first seven days of life. Early Hum Dev. 1999;56:151–65.

    Article  CAS  PubMed  Google Scholar 

  14. Lee J, Rajadurai VS, Tan KW. Blood pressure standards for very low birthweight infants during the first day of life. Arch Dis Child Fetal neonatal Ed. 1999;81:F168–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Cordero L, Timan CJ, Waters HH, Sachs LA. Mean arterial pressures during the first 24 h of life in < or = 600-gram birth weight infants. J perinatology: Off J Calif Perinat Assoc. 2002;22:348–53.

    Article  Google Scholar 

  16. LeFlore JL, Engle WD, Rosenfeld CR. Determinants of blood pressure in very low birth weight neonates: lack of effect of antenatal steroids. Early Hum Dev. 2000;59:37–50.

    Article  CAS  PubMed  Google Scholar 

  17. Batton B, Batton D, Riggs T. Blood pressure during the first 7 days in premature infants born at postmenstrual age 23 to 25 weeks. Am J Perinatol. 2007;24:107–15.

    Article  PubMed  Google Scholar 

  18. Development of audit measures and guidelines for good practice in the management of neonatal respiratory distress syndrome. Report of a Joint Working Group of the British Association of Perinatal Medicine and the Research Unit of the Royal College of Physicians. Arch Dis Child. 1992;67:1221–7.

    Article  Google Scholar 

  19. Logan JW, O’Shea TM, Allred EN, Laughon MM, Bose CL, Dammann O, et al. Early postnatal hypotension and developmental delay at 24 months of age among extremely low gestational age newborns. Arch Dis Child Fetal Neonatal Ed. 2011;96:F321–8.

    Article  PubMed  Google Scholar 

  20. Logan JW, O’Shea TM, Allred EN, Laughon MM, Bose CL, Dammann O, et al. Early postnatal hypotension is not associated with indicators of white matter damage or cerebral palsy in extremely low gestational age newborns. J Perinatol. 2011;31:524–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Alderliesten T, Lemmers PM, van Haastert IC, de Vries LS, Bonestroo HJ, Baerts W, et al. Hypotension in preterm neonates: low blood pressure alone does not affect neurodevelopmental outcome. J Pediatr. 2014;164:986–91.

    Article  PubMed  Google Scholar 

  22. Helbock HJ, Insoft RM, Conte FA. Glucocorticoid-responsive hypotension in extremely low birth weight newborns. Pediatrics 1993;92:715–7.

    Article  CAS  PubMed  Google Scholar 

  23. Seri I, Tan R, Evans J. Cardiovascular effects of hydrocortisone in preterm infants with pressor-resistant hypotension. Pediatrics 2001;107:1070–4.

    Article  CAS  PubMed  Google Scholar 

  24. Rios DR, Moffett BS, Kaiser JR. Trends in pharmacotherapy for neonatal hypotension. J Pediatr. 2014;165:697–701.

    Article  CAS  PubMed  Google Scholar 

  25. Fanaroff JM, Wilson-Costello DE, Newman NS, Montpetite MM, Fanaroff AA. Treated hypotension is associated with neonatal morbidity and hearing loss in extremely low birth weight infants. Pediatrics 2006;117:1131–5.

    Article  PubMed  Google Scholar 

  26. Limperopoulos C, Bassan H, Kalish LA, Ringer SA, Eichenwald EC, Walter G, et al. Current definitions of hypotension do not predict abnormal cranial ultrasound findings in preterm infants. Pediatrics 2007;120:966–77.

    Article  PubMed  Google Scholar 

  27. Halliday HL, Ehrenkranz RA, Doyle LW. Early (<8 days) postnatal corticosteroids for preventing chronic lung disease in preterm infants. Cochrane Database Syst Rev. 2010;1:CD001146.

    Google Scholar 

  28. Zhang R, Bo T, Shen L, Luo S, Li J. Effect of dexamethasone on intelligence and hearing in preterm infants: a meta-analysis. Neural Regen Res. 2014;9:637–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Ramanathan R, Siassi B, deLemos RA. Severe retinopathy of prematurity in extremely low birth weight infants after short-term dexamethasone therapy. J perinatology: Off J Calif Perinat Assoc. 1995;15:178–82. quiz 83-4

    CAS  Google Scholar 

  30. Juul SE, Mayock DE, Comstock BA, Heagerty PJ. Neuroprotective potential of erythropoietin in neonates; design of a randomized trial. Matern health, Neonatol Perinatol. 2015;1:27.

    Article  Google Scholar 

  31. Liang K-Y, Zeger SL. Longitudinal data analysis using generalized linear models. Biometrika 1986;73:13–22.

    Article  Google Scholar 

  32. Stuart EA, King G, Imai K, Ho D MatchIt: nonparametric preprocessing for parametric causal inference. Journal of statistical software. 2011.

  33. Seri I Hemodynamics and Cardiology: Neonatology Questions and Controversies: Elsevier Health Sciences; 2018.

  34. Munro MJ, Walker AM, Barfield CP. Hypotensive extremely low birth weight infants have reduced cerebral blood flow. Pediatrics 2004;114:1591–6.

    Article  PubMed  Google Scholar 

  35. Miall-Allen VM, de Vries LS, Whitelaw AG. Mean arterial blood pressure and neonatal cerebral lesions. Arch Dis Child. 1987;62:1068–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Laughon M, Bose C, Allred E, O’Shea TM, Van Marter LJ, Bednarek F, et al. Factors associated with treatment for hypotension in extremely low gestational age newborns during the first postnatal week. Pediatrics 2007;119:273–80.

    Article  PubMed  Google Scholar 

  37. Batton B. Neonatal Blood Pressure Standards: What Is “Normal”? Clin Perinatol. 2020;47:469–85.

    Article  PubMed  Google Scholar 

  38. Kluckow M, Evans N. Low superior vena cava flow and intraventricular haemorrhage in preterm infants. Arch Dis Child Fetal neonatal Ed. 2000;82:F188–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Batton B, Li L, Newman NS, Das A, Watterberg KL, Yoder BA, et al. Early blood pressure, antihypotensive therapy and outcomes at 18-22 months’ corrected age in extremely preterm infants. Arch Dis Child Fetal Neonatal Ed. 2016;101:F201–6.

    Article  PubMed  Google Scholar 

  40. Durrmeyer X, Marchand-Martin L, Porcher R, Gascoin G, Roze J-C, Storme L, et al. Abstention or intervention for isolated hypotension in the first 3 days of life in extremely preterm infants: association with short-term outcomes in the EPIPAGE 2 cohort study. Arch Dis Child - Fetal Neonatal Ed. 2017;102:490–6.

    Article  PubMed  Google Scholar 

  41. Dempsey EM, Barrington KJ, Marlow N, O’Donnell CPF, Miletin J, Naulaers G, et al. Hypotension in Preterm Infants (HIP) randomised trial. Arch Dis Child-Fetal Neonatal Ed. 2021;106:398–403.

    Article  PubMed  Google Scholar 

  42. Vesoulis ZA, Ters NE, Foster A, Trivedi SB, Liao SM, Mathur AM. Response to dopamine in prematurity: a biomarker for brain injury? J perinatology: Off J Calif Perinat Assoc. 2016;36:453–8.

    Article  CAS  Google Scholar 

  43. Abdul Aziz AN, Thomas S, Murthy P, Rabi Y, Soraisham A, Stritzke A, et al. Early inotropes use is associated with higher risk of death and/or severe brain injury in extremely premature infants. J Matern-Fetal Neonatal Med. 2020;33:2751–8.

    Article  PubMed  Google Scholar 

  44. Solanki NS, Hoffman SB. Association between dopamine and cerebral autoregulation in preterm neonates. Pediatr Res. 2020;88:618–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Eriksen VR, Hahn GH, Greisen G. Dopamine therapy is associated with impaired cerebral autoregulation in preterm infants. Acta Paediatrica. 2014;103:1221–6.

    Article  CAS  PubMed  Google Scholar 

  46. Mizoguchi MB, Chu TG, Murphy FM, Willits N, Morse LS. Dopamine use is an indicator for the development of threshold retinopathy of prematurity. Br J Ophthalmol. 1999;83:425–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Baud O, Maury L, Lebail F, Ramful D, El Moussawi F, Nicaise C, et al. Effect of early low-dose hydrocortisone on survival without bronchopulmonary dysplasia in extremely preterm infants (PREMILOC): a double-blind, placebo-controlled, multicentre, randomised trial. Lancet. 2016;387:1827–36.

    Article  CAS  PubMed  Google Scholar 

  48. Watterberg KL, Gerdes JS, Cole CH, Aucott SW, Thilo EH, Mammel MC, et al. Prophylaxis of early adrenal insufficiency to prevent bronchopulmonary dysplasia: a multicenter trial. Pediatrics 2004;114:1649–57.

    Article  PubMed  Google Scholar 

  49. Peeples ES. An evaluation of hydrocortisone dosing for neonatal refractory hypotension. J Perinatol. 2017;37:943–6.

    Article  CAS  PubMed  Google Scholar 

  50. Vesoulis ZA, Flower AA, Zanelli S, Rambhia A, Abubakar M, Whitehead HV, et al. Blood pressure extremes and severe IVH in preterm infants. Pediatr Res. 2020;87:69.

    Article  CAS  PubMed  Google Scholar 

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Funding

This project was supported by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under award numbers U01NS077953 and U01NS077955.

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Author notes

  1. Lists of members and their affiliations appears in the Supplementary Information.

Authors and Affiliations

  1. Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE, USA

    Eric S. Peeples

  2. Child Health Research Institute, Omaha, NE, USA

    Eric S. Peeples

  3. Department of Biostatistics, University of Washington, Seattle, WA, USA

    Bryan A. Comstock & Patrick J. Heagerty

  4. Department of Pediatrics, University of Washington, Seattle, WA, USA

    Sandra E. Juul

  5. Department of Biostatistics, University of Washington, Seattle, WA, USA

    Bryan A. Comstock & Patrick J. Heagerty

  6. Department of Pediatrics, University of Washington, Seattle, WA, USA

    Sandra E. Juul

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Consortia

Preterm Erythropoietin Neuroprotection (PENUT) Trial Investigators

  • Bryan A. Comstock
  • , Patrick J. Heagerty
  •  & Sandra E. Juul

Contributions

ESP and BAC contributed to the design, analysis, and interpretation of the data, drafted the initial manuscript, and reviewed and critically revised the manuscript. PJH and SEJ contributed to the design, analysis, collection, and interpretation of the data, and reviewed and critically revised the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

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Correspondence to Eric S. Peeples.

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Peeples, E.S., Comstock, B.A., Heagerty, P.J. et al. Blood pressure values and hypotension management in extremely preterm infants: a multi-center study. J Perinatol 42, 1169–1175 (2022). https://doi.org/10.1038/s41372-022-01425-2

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