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Cardiovascular response and sequelae after minimally invasive surfactant therapy in growth-restricted preterm infants

Journal of Perinatology volume 40, pages 1178–1184 (2020)Cite this article

Subjects

Abstract

Objective

To study cardiovascular response to minimally invasive surfactant therapy in preterm infants with and without foetal growth restriction (FGR).

Design

Poractant alfa was administered and echocardiograms were performed before and 30 min after. FGR infants were compared with those appropriate for gestational age (AGA).

Results

Ten FGR infants were compared with 20 AGA infants (gestation [weeks], 28.9 ± 2 vs. 28.6 ± 1, p = 0.55 and birthweight [g], 813 ± 157 vs. 1141 ± 257, p = 0.01, respectively). The change in echocardiographic parameters was more prominent in AGA infants ([global contractility] fractional area change [FAC, %], FGR, 24.7 ± 2.2 to 27.9 ± 0.4, p = 0.08 vs. AGA, 26.6 ± 3 to 30.5 ± 1, p < 0.01, and [longitudinal contractility] tricuspid annular plane systolic excursion [mm], FGR, 3.9 ± 0.3 to 4.6 ± 0.5, p = 0.003 vs. AGA, 4.6 ± 0.3 to 5.5 ± 0.4, p = 0.0001). Significant difference was noted for change in FAC (%), FGR 2.1 ± 1.7 vs. AGA 4.1 ± 1.2, p = 0.02.

Conclusions

Differential cardiovascular response to minimally invasive surfactant therapy amongst FGR infants may reflect an in-utero maladaptive state.

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Fig. 1: Mechanisms and mediators in utero-placental insufficiency affecting vascular structure and function.

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References

  1. Jobe AH. The new bronchopulmonary dysplasia. Curr Opin Pediatr. 2011;23:167–72.

    Article  Google Scholar 

  2. Aldana-Aguirre JC, Pinto M, Featherstone RM, Kumar M. Less invasive surfactant administration versus intubation for surfactant delivery in preterm infants with respiratory distress syndrome: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed. 2017;102:F17–23.

    Article  Google Scholar 

  3. Göpel W, Kribs A, Ziegler A, Laux R, Hoehn T, Wieg C, et al. Avoidance of mechanical ventilation by surfactant treatment of spontaneously breathing preterm infants (AMV): an open-label, randomised, controlled trial. Lancet. 2011;378:1627–34.

    Article  Google Scholar 

  4. Kanmaz HG, Erdeve O, Canpolat FE, Mutlu B, Dilmen U. Surfactant administration via thin catheter during spontaneous breathing: randomized controlled trial. Pediatrics. 2013;131:e502–9.

    Article  Google Scholar 

  5. Kribs A, Roll C, Göpel W, Wieg C, Groneck P, Laux R, et al. Non-intubated surfactant application during CPAP-assisted spontaneous breathing versus conventional therapy in extremely preterm infants—a randomised controlled trial. JAMA Pediatr. 2015;169:723–30.

    Article  Google Scholar 

  6. Clyman R, Jobe A, Heymann M, Ikegami M, Roman C, Payne B, et al. Increased shunt through the patent ductus arteriosus after surfactant replacement therapy. J Pediatr. 1982;100:101–7.

    Article  CAS  Google Scholar 

  7. Sehgal A, Mak W, Dunn M, Kelly E, Redington A, Whyte H, et al. Haemodynamic changes after delivery room surfactant administration to very low birth weight infants. Arch Dis Child Fetal Neonatal Ed. 2010;95:F345–51.

    Article  Google Scholar 

  8. Kääpä P, Seppänen M, Kero P, Saraste M. Pulmonary haemodynamics after synthetic surfactant replacement in neonatal respiratory distress syndrome. J Pediatr. 1993;123:115–9.

    Article  Google Scholar 

  9. Sehgal A, Bhatia R, Roberts CT. Cardiorespiratory physiology following minimally invasive surfactant therapy in preterm infants. Neonatology. 2019;116:278–85.

    Article  CAS  Google Scholar 

  10. Yzydorczyk C, Armengaud JB, Peyter AC, Chehade H, Cachat F, Juvet C, et al. Endothelial dysfunction in individuals born after fetal growth restriction: cardiovascular and renal consequences and preventive approaches. J Dev Orig Health Dis. 2017;8:448–64.

    Article  CAS  Google Scholar 

  11. Sehgal K, Sehgal K, Tan K, Sehgal A. Impaired in-utero growth: an important risk factor for chronic lung disease [abstract]. Pediatr Acad Soc. 2019;E-PAS2019:442.

    Google Scholar 

  12. Lal MK, Manktelow BN, Draper ES, Field DJ. Chronic lung disease of prematurity and intrauterine growth retardation: a population-based study. Pediatrics. 2003;111:483–7.

    Article  Google Scholar 

  13. Rabinovitch M, Gamble W, Nadas AS, Miettinen OS, Reid L. Rat pulmonary circulation after chronic hypoxia: hemodynamic and structural features. Am J Physiol. 1979;236:H818–27.

    CAS  PubMed  Google Scholar 

  14. Ziino AJA, Ivanovska J, Belcastro R, Kantores C, Xu EZ, Lau M, et al. Effects of Rho-kinase inhibition on pulmonary hypertension, lung growth, and structure in neonatal rats chronically exposed to hypoxia. Pediatr Res. 2010;67:177–82.

    Article  CAS  Google Scholar 

  15. Abman SH, Shanley PF, Accurso FJ. Failure of postnatal adaptation of the pulmonary circulation after chronic intrauterine pulmonary hypertension in fetal lambs. J Clin Invest. 1989;83:1849–58.

    Article  CAS  Google Scholar 

  16. Goldberg SJ, Levy RA, Siassi B, Betten J. The effects of maternal hypoxia and hyperoxia upon the neonatal pulmonary vasculature. Pediatrics. 1971;48:528–33.

    CAS  PubMed  Google Scholar 

  17. Dargaville PA, Aiyappan A, Cornelius A, Williams C, De Paoli AG. Preliminary evaluation of a new technique of minimally invasive surfactant therapy. Arch Dis Child Fetal Neonatal Ed. 2011;96:F243–8.

    Article  Google Scholar 

  18. Hayabuchi Y, Ono A, Kagami S. Pulmonary annular motion velocity assessed using Doppler tissue imaging. Circ J. 2016;80:168–76.

    Article  Google Scholar 

  19. Evans NJ, Archer LN. Doppler assessment of pulmonary artery pressure and extra pulmonary shunting in the acute phase of hyaline membrane disease. Arch Dis Child. 1999;66:6–11.

    Article  Google Scholar 

  20. Howard LS, Grapsa J, Dawson D, Bellamy M, Chambers JB, Masani ND, et al. Echocardiographic assessment of pulmonary hypertension: standard operating procedure. Eur Respir Rev. 2012;21:239–48.

    Article  Google Scholar 

  21. Milnor WR, Conti CR, Lewis KB, O’Rourke MF. Pulmonary arterial pulse wave velocity and impedance in man. Circ Res. 1969;25:637–49.

    Article  CAS  Google Scholar 

  22. Fenton TR, Kim JH. A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants. BMC Pediatr. 2013;13:59. https://doi.org/10.1186/1471-2431-13-59.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Skinner JR, Boys RJ, Hunter S, Hey EN. Pulmonary and systemic arterial pressure in hyaline membrane disease. Arch Dis Child. 1992;67:366–73.

    Article  CAS  Google Scholar 

  24. Vitali F, Galletti S, Aceti A, Aquilano G, Fabi M, Balducci A, et al. Pilot observational study on haemodynamic changes after surfactant administration in preterm newborns with respiratory distress syndrome. Ital J Pediatr. 2014;40:26.

    Article  Google Scholar 

  25. Pike K, Jane Pillow J, Lucas JS. Long term respiratory consequences of intrauterine growth restriction. Semin Fetal Neonatal Med. 2012;17:92–8.

    Article  Google Scholar 

  26. Briana DD, Malamitsi-Puchner A. Small for gestational age birth weight: impact on lung structure and function. Paediatr Respir Rev. 2013;14:256–62.

    PubMed  Google Scholar 

  27. Maritz GS, Morley CJ, Harding R. Early developmental origins of impaired lung structure and function. Early Hum Dev. 2005;81:763–71.

    Article  Google Scholar 

  28. Orgeig S, Crittenden TA, Marchant C, McMillen IC, Morrison JL. Intrauterine growth restriction delays surfactant protein maturation in the sheep fetus. Am J Physiol Lung Cell Mol Physiol. 2010;298:L575–83.

    Article  CAS  Google Scholar 

  29. Leung DY, Glagov S, Mathews MB. Elastin and collagen accumulation in rabbit ascending aorta and pulmonary trunk during postnatal growth. Correlation of cellular synthetic response with medial tension. Circ Res. 1977;41:316–23.

    Article  CAS  Google Scholar 

  30. Giussani DA, Camm EJ, Niu Y, Richter HG, Blanco CE, Gottschalk R, et al. Developmental programming of cardiovascular dysfunction by prenatal hypoxia and oxidative stress. PLoS ONE. 2012;7:e31017.

    Article  CAS  Google Scholar 

  31. Gien J, Seedorf GJ, Balasubramaniam V, Markham N, Abman SH. Intrauterine pulmonary hypertension impairs angiogenesis in vitro: role of vascular endothelial growth factor nitric oxide signalling. Am J Respir Crit Care Med. 2007;176:1146–53.

    Article  CAS  Google Scholar 

  32. Grover TR, Parker TA, Markham NE, Abman SH. rhVEGF treatment preserves pulmonary vascular reactivity and structure in an experimental model of pulmonary hypertension in fetal sheep. Am J Physiol Lung Cell Mol Physiol. 2005;289:L315–21.

    Article  CAS  Google Scholar 

  33. Rozance PJ, Seedorf GJ, Brown A, Roe G, O’Meara MC, Gien J, et al. Intrauterine growth restriction decreases pulmonary alveolar and vessel growth and causes pulmonary artery endothelial cell dysfunction in vitro in fetal sheep. Am J Physiol Lung Cell Mol Physiol. 2011;301:L860–71.

    Article  CAS  Google Scholar 

  34. Braems GA, Yao LJ, Inchley K, Brickenden A, Han VK, Grolla A, et al. Ovine surfactant protein cDNAs: use in studies on fetal lung growth and maturation after prolonged hypoxemia. Am J Physiol Lung Cell Mol Physiol. 2000;278:L754–64.

    Article  CAS  Google Scholar 

  35. Weinberg CE, Hertzberg JR, Ivy DD, Kirby KS, Chan KC, Valdes-Cruz L, et al. Extraction of pulmonary vascular compliance, pulmonary vascular resistance, and right ventricular work from single-pressure and Doppler flow measurements in children with pulmonary hypertension: a new method for evaluating reactivity—in vitro and clinical studies. Circulation. 2004;110:2609–17.

    Article  Google Scholar 

  36. Sehgal A, Gwini SM, Menahem S, Allison BJ, Miller S, Polglase GR. Preterm growth restriction and bronchopulmonary dysplasia: the vascular hypothesis and related physiology. J Physiol. 2019;597:1209–20.

    Article  CAS  Google Scholar 

  37. Hung MW, Yeung HM, Lau CF, Poon AMS, Tipoe GL, Fung ML. Melatonin attenuates pulmonary hypertension in chronically hypoxic rats. Int J Mol Sci. 2017;18:1125. https://doi.org/10.3390/ijms18061125.

    Article  PubMed Central  Google Scholar 

  38. Garcia JJ, López-Pingarrón L, Almeida-Souza P, Tres A, Escudero P, García-Gil FA, et al. Protective effects of melatonin in reducing oxidative stress and in preserving the fluidity of biological membranes: a review. J Pineal Res. 2014;56:225–37.

    Article  CAS  Google Scholar 

  39. Mauriz JL, Collado PS, Veneroso C, Reiter RJ, González-Gallego J. A review of the molecular aspects of melatonin’s anti-inflammatory actions: recent insights and new perspectives. J Pineal Res. 2013;54:1–14.

    Article  CAS  Google Scholar 

  40. Girouard H, Chulak C, Lejossec M, Lamontagne D, de Champlain J. Vasorelaxant effects of the chronic treatment with melatonin on mesenteric artery and aorta of spontaneously hypertensive rats. J Hypertens. 2001;19:1369–77.

    Article  CAS  Google Scholar 

  41. Anwar MM, Meki AR, Rahma HH. Inhibitory effects of melatonin on vascular reactivity: possible role of vasoactive mediators. Comp Biochem Physiol C Toxicol Pharm. 2001;130:357–67.

    Article  CAS  Google Scholar 

  42. Torres F, González-Candia A, Montt C, Ebensperger G, Chubretovic M, Serón-Ferré M, et al. Melatonin reduces oxidative stress and improves vascular function in pulmonary hypertensive newborn sheep. J Pineal Res. 2015;58:362–73.

    Article  CAS  Google Scholar 

  43. Sehgal A, Krishnamurthy MB, Clark M, Menahem S. ACE inhibition for severe bronchopulmonary dysplasia—an approach based on physiology. Physiol Rep. 2018;6:e13821. https://doi.org/10.14814/phy2.13821.

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Monash Newborn, Monash Children’s Hospital, Melbourne, Vic, Australia

    Arvind Sehgal, Risha Bhatia & Calum T. Roberts

  2. Department of Paediatrics, Monash University, Melbourne, Vic, Australia

    Arvind Sehgal, Risha Bhatia & Calum T. Roberts

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  1. Arvind Sehgal
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Contributions

AS—conception of the study, data acquisition, analysis and interpretation. Wrote the first draft and revised critically. RB—conception of the study and the protocol for MIST. Data analysis and interpretation. Revised draft for important intellectual content. CTR—conception of the study and the protocol for MIST. Data analysis and interpretation. Revised draft for important intellectual content.

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Correspondence to Arvind Sehgal.

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Sehgal, A., Bhatia, R. & Roberts, C.T. Cardiovascular response and sequelae after minimally invasive surfactant therapy in growth-restricted preterm infants. J Perinatol 40, 1178–1184 (2020). https://doi.org/10.1038/s41372-020-0682-5

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