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.

  • Clinical Research Article
  • Published:

Extremely preterm infants with adverse neurological outcome present more frequently impaired right ventricular performance

Pediatric Research volume 98, pages 1403–1411 (2025)Cite this article

Abstract

Background

The relationship between cardiovascular impairment and adverse outcome is insufficiently studied in preterm populations. Our aim was to analyze and compare cardiac performance during postnatal transition in extremely low gestational age infants (ELGANs) with and without adverse short-term neurological outcome.

Methods

Prospective observational cohort study. Continuous multimodal monitoring and targeted neonatal echocardiographic studies were conducted within the first 24 h of life (TNE1) and between 24 and 72 h (TNE2). Adverse outcome was defined as the composite of death, significant interventricular hemorrhage, or white matter injury.

Results

Of the 46 patients included, 21(45.7%) presented adverse outcome. There were no differences in left ventricular performance. During TNE1, infants with adverse outcome exhibited lower tricuspid annulus plane systolic excursion (TAPSE) and right ventricular global longitudinal strain (GLS-RV), alongside longer RV isovolumic relaxation time (IVRT) and higher RV Myocardial Performance Index (MPI). RV output positively correlated with peak systolic and mean velocity of the middle cerebral artery. By TNE2, RV performance differences had disappeared.

Conclusions

Impaired RV performance during early postnatal period is more frequent in ELGANs with adverse neurological outcome. Cerebral blood flow relies more on RV output. The potential role of early RV dysfunction in brain damage deserves further research.

Impact

  • Extremely preterm infants with adverse short-term neurological outcome present more frequently right ventricular dysfunction during early postnatal period, with a positive correlation between cerebral blood flow velocities and right ventricular output.

  • RV performance may play a critical role in maintaining adequate cerebral blood flow; thus a subtle dysfunction could aggravate brain injury.

  • This is the first study pointing towards a potential association between early RV dysfunction and adverse neurological outcome during neonatal transition in extremely preterm infants.

  • Our study highlights the importance of early cardiac assessment and provides a new perspective for improving neonatal care and outcomes for this vulnerable population

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

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

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

Fig. 1

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Harrison, M. S. & Goldenberg, R. L. Global burden of prematurity. Semin. Fetal Neonatal Med. 21, 74–79 (2016).

    Article  PubMed  Google Scholar 

  2. Barthel, D., Göbel, A., Barkmann, C., Helle, N. & Bindt, C. Does Birth-Related Trauma Last? Prevalence and Risk Factors for Posttraumatic Stress in Mothers and Fathers of VLBW Preterm and Term Born Children 5 Years After Birth. Front. Psychiatry 11, 575429 (2020).

  3. Ni, Y., Beckmann, J., Hurst, J. R., Morris, J. K. & Marlow, N. Size at birth, growth trajectory in early life, and cardiovascular and metabolic risks in early adulthood: EPICure study. Arch. Dis. Child Fetal Neonatal Ed. 106, 149–155 (2021).

    Article  PubMed  Google Scholar 

  4. Smith, L. K. et al. Quantifying the burden of stillbirths before 28 weeks of completed gestational age in high-income countries: a population-based study of 19 European countries. Lancet 392, 1639–1646 (2018).

    Article  PubMed  Google Scholar 

  5. Morgan, A. S., Mendonça, M., Thiele, N. & David, A. L. Management and outcomes of extreme preterm birth. The BMJ 376, e055924 (2022).

  6. Spittle, A. J., Cameron, K., Doyle, L. W. & Cheong, J. L. Motor Impairment Trends in Extremely Preterm Children: 1991-2005. Pediatrics 141, e20173410 (2018).

  7. Rees, P. et al. Preterm Brain Injury and Neurodevelopmental Outcomes: A Meta-Analysis. Pediatrics 150, e2022057442 (2022).

  8. Noori, S., McCoy, M., Anderson, M. P., Ramji, F. & Seri, I. Changes in cardiac function and cerebral blood flow in relation to peri/intraventricular hemorrhage in extremely preterm infants. J. Pediatr. 164, 264-70.e1-3 (2014).

  9. Wu, T. W., Azhibekov, T. & Seri, I. Transitional hemodynamics in preterm neonates: Clinical relevance. Pediatr. Neonatol. 57, 7–18 (2016).

    Article  PubMed  Google Scholar 

  10. Tan, C. M. J. & Lewandowski, A. J. The Transitional Heart: From Early Embryonic and Fetal Development to Neonatal Life. Fetal Diagnosis Ther. 47, 373–386 (2020).

    Article  Google Scholar 

  11. Bensley, J. G., Moore, L., De Matteo, R., Harding, R. & Black, M. J. Impact of preterm birth on the developing myocardium of the neonate. Pediatr. Res. 83, 880–888 (2018).

    Article  PubMed  Google Scholar 

  12. Stranak, Z. et al. International survey on diagnosis and management of hypotension in extremely preterm babies. Eur. J. Pediatr. 173, 793–798 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  13. Bruckner, M., Pichler, G. & Urlesberger, B. NIRS in the fetal to neonatal transition and immediate postnatal period. Semin. Fetal Neonatal Med. 25, 101079 (2020).

  14. Dempsey, E. M. & Barrington, K. J. Treating hypotension in the preterm infant: When and with what: A critical and systematic review. J. Perinatol. 27, 469–478 (2007).

  15. Deshpande, P. et al. Relationship between cerebral oxygenation, cardiac output, and blood pressure during transitional period in extremely low gestational age neonates. Front. Pediatr. 11, 1187769 (2023).

  16. El-Khuffash, A., Herbozo, C., Jain, A., Lapointe, A. & Mcnamara, P. J. Targeted neonatal echocardiography (TnECHO) service in a Canadian neonatal intensive care unit: A 4-year experience. J. Perinatol. 33, 687–690 (2013).

    Article  CAS  PubMed  Google Scholar 

  17. Tissot, C. & Singh, Y. Neonatal functional echocardiography. Curr. Opin. Pediatr. 32, 235–244 (2020).

    Article  PubMed  Google Scholar 

  18. Giesinger Regan et al. Impact of Early Hemodynamic Screening on Extremely Preterm Outcomes in a High-Performance Center. Am. J. Respir. Crit. Care Med. 209, 767–767 (2024).

    Article  Google Scholar 

  19. Deshpande, P. et al. Combined Multimodal Cerebral Monitoring and Focused Hemodynamic Assessment in the First 72 h in Extremely Low Gestational Age Infants. Neonatology 117, 504–512 (2020).

    Article  CAS  PubMed  Google Scholar 

  20. Richardson, D. K., Corcoran, J. D., Escobar, G. J. & Lee, S. K. SNAP-II and SNAPPE-II: Simplified newborn illness severity and mortality risk scores. J. Pediatrics 138, 92–100 (2001).

    Article  CAS  Google Scholar 

  21. Bell, M. J. et al. Neonatal Necrotizing Enterocolitis Therapeutic Decisions Based upon Clinical Staging. Ann. Surg. 187, 1–7 (1978).

  22. Lang, R. M. et al. Recommendations for cardiac chamber quantification by echocardiography in adults: An update from the American society of echocardiography and the European association of cardiovascular imaging. Eur. Heart J. Cardiovasc. Imaging 16, 233–271 (2015).

    Article  PubMed  Google Scholar 

  23. Rios, D. R. et al. Early Role of the Atrial-Level Communication in Premature Infants with Patent Ductus Arteriosus. J. Am. Soc. Echocardiogr. 34, 423–432.e1 (2021).

    Article  PubMed  Google Scholar 

  24. Nestaas, E., Schubert, U., de Boode, W. P. & EL-Khuffash, A. Tissue Doppler velocity imaging and event timings in neonates: a guide to image acquisition, measurement, interpretation, and reference values. Pediatr. Res. 84, 18–29 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  25. EL-Khuffash, A., Schubert, U., Levy, P. T., Nestaas, E. & de Boode, W. P. Deformation imaging and rotational mechanics in neonates: a guide to image acquisition, measurement, interpretation, and reference values. Pediatr. Res. 84, 30–45 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  26. Papile, L.-A., Burstein, J., Burstein, R. & Koffler, H. Incidence and evolution of subependymal and intraventricular hemorrhage: A study of infants with birth weights less than 1,500 gm. J. Pediatr. 92, 529–534 (1978).

    Article  CAS  PubMed  Google Scholar 

  27. Briana, D. D. & Malamitsi-Puchner, A. Low-grade intraventricular hemorrhage of preterm infants: neurodevelopmental and motor outcome. J. Matern. Fetal Neonatal Med. 34, 646–652 (2021).

    Article  PubMed  Google Scholar 

  28. Deshpande, P. et al. Trends in cyclicity and amplitudes on amplitude-integrated electroencephalography during transition in extremely low gestational age infants. Acta Paediatr. Int. J. Paediatr. 112, 1213–1219 (2023).

    Article  Google Scholar 

  29. Landis, J. R. & Koch, G. G. The measurement of observer agreement for categorical data. Biometrics 33, 159–174 (1977).

    Article  CAS  PubMed  Google Scholar 

  30. Giesinger, R. E. et al. Impaired right ventricular performance is associated with adverse outcome after hypoxic ischemic encephalopathy. Am. J. Respir. Crit. Care Med. 200, 1294–1305 (2019).

    Article  CAS  PubMed  Google Scholar 

  31. Giesinger, R. E. et al. Neurodevelopmental outcome following hypoxic ischaemic encephalopathy and therapeutic hypothermia is related to right ventricular performance at 24-hour postnatal age. Arch. Dis. Child Fetal Neonatal Ed. 107, F70–F75 (2022).

    Article  Google Scholar 

  32. Moenkemeyer, F. & Patel, N. Right ventricular diastolic function measured by tissue doppler imaging predicts early outcome in congenital diaphragmatic hernia. Pediatr. Crit. Care Med. 15, 49–55 (2014).

    Article  PubMed  Google Scholar 

  33. Lamia, B., Teboul, J. L., Monnet, X., Richard, C. & Chemla, D. Relationship between the tricuspid annular plane systolic excursion and right and left ventricular function in critically ill patients. Intensive Care Med. 33, 2143–2149 (2007).

    Article  PubMed  Google Scholar 

  34. Nestaas, E., Stylen, A., Brunvand, L. & Fugelseth, D. Longitudinal strain and strain rate by tissue Doppler are more sensitive indices than fractional shortening for assessing the reduced myocardial function in asphyxiated neonates. Cardiol. Young. 21, 1–7 (2011).

    Article  PubMed  Google Scholar 

  35. Blanca, A. J. et al. Right ventricular function in infants with bronchopulmonary dysplasia and pulmonary hypertension: a pilot study. Pulm. Circ. 9, 2045894018816063 (2019).

  36. Murase, M. Assessing ventricular function in preterm infants using tissue Doppler imaging. Expert Rev. Med. Devices 13, 325–338 (2016).

    Article  CAS  PubMed  Google Scholar 

  37. Cui, W., Roberson, D. A., Chen, Z., Madronero, L. F. & Cuneo, B. F. Systolic and Diastolic Time Intervals Measured from Doppler Tissue Imaging: Normal Values and Z-score Tables, and Effects of Age, Heart Rate, and Body Surface Area. J. Am. Soc. Echocardiogr. 21, 361–370 (2008).

    Article  PubMed  Google Scholar 

  38. Sirc, J., Dempsey, E. M. & Miletin, J. Diastolic ventricular function improves during the first 48-hours-of-life in infants weighting <1250 g. Acta Paediatr. Int. J. Paediatr. 104, e1–e6 (2015).

    Article  CAS  Google Scholar 

  39. Le Duc, K. et al. Diastolic ventricular function in persistent pulmonary hypertension of the newborn. Front. Pediatr. 11, 1175178 (2023).

  40. Bussmann, N. et al. Early diastolic dysfunction and respiratory morbidity in premature infants: an observational study. J. Perinatol. 38, 1205–1211 (2018).

    Article  PubMed  Google Scholar 

  41. Jain, A. et al. A comprehensive echocardiographic protocol for assessing neonatal right ventricular dimensions and function in the transitional period: Normative data and z scores. J. Am. Soc. Echocardiogr. 27, 1293–1304 (2014).

    Article  PubMed  Google Scholar 

  42. Noori, S., Stavroudis, T. A. & Seri, I. Systemic and Cerebral Hemodynamics During the Transitional Period After Premature Birth. Clin. Perinatol. 36, 723–736 (2009).

  43. Levy, P. T., El Khuffash, A., Woo, K. V. & Singh, G. K. Right Ventricular–Pulmonary Vascular Interactions: An Emerging Role for Pulmonary Artery Acceleration Time by Echocardiography in Adults and Children. J. Am. Soc. Echocardiogr. 31, 962–964 (2018).

  44. El-Khuffash, A. & McNamara, P. J. Hemodynamic Assessment and Monitoring of Premature Infants. Clin. Perinatol. 44, 377–393 (2017).

  45. Hansen, M. et al. Cerebral Oximetry Monitoring in Extremely Preterm Infants. N. Engl. J. Med. 388, 1501–1511 (2023).

    Article  CAS  PubMed  Google Scholar 

  46. Alderliesten, T. et al. Cerebral oxygenation, extraction, and autoregulation in very preterm infants who develop peri-intraventricular hemorrhage. J. Pediatrics 162, 698–704.e2 (2013).

  47. Altit, G. et al. Cardiac Dysfunction in Neonatal HIE Is Associated with Increased Mortality and Brain Injury by MRI. Am. J. Perinatol. 40, 1336–1344 (2023).

    Article  PubMed  Google Scholar 

  48. Rodriguez, M. J., Martinez-Orgado, J., Corredera, A., Serrano, I. & Arruza, L. Diastolic Dysfunction in Neonates With Hypoxic-Ischemic Encephalopathy During Therapeutic Hypothermia: A Tissue Doppler Study. Front. Pediatr. 10, 880786 (2022).

  49. Rodriguez, M. J., Corredera, A., Martinez-Orgado, J. & Arruza, L. Cerebral blood flow velocity and oxygenation correlate predominantly with right ventricular function in cooled neonates with moderate-severe hypoxic-ischemic encephalopathy. Eur. J. Pediatr. 179, 1609–1618 (2020).

    Article  CAS  PubMed  Google Scholar 

  50. Wolfsberger, C. H. et al. Cerebral oxygenation immediately after birth and long-term outcome in preterm neonates—a retrospective analysis. BMC Pediatr. 23, 145 (2023).

Download references

Funding

Instituto de Salud Carlos III (ISCIII), “ PI22/01016”, co-funded by the European Union.

Author information

Authors and Affiliations

  1. Department of Neonatology. Hospital Clínico San Carlos, Madrid, Spain

    Niki Oikonomopoulou, Maria Jose Rodriguez-Castaño, Araceli Corredera, Cristina Cortés-Ledesma, Eva Vierge, Jose Martinez-Orgado & Luis Arruza

  2. Instituto de Investigación Sanitaria San Carlos (IdISSC), Madrid, Spain

    Niki Oikonomopoulou, Maria Jose Rodriguez-Castaño, Araceli Corredera, Cristina Cortés-Ledesma, Eva Vierge, Jose Martinez-Orgado & Luis Arruza

Authors
  1. Niki Oikonomopoulou
    View author publications

    Search author on:PubMed Google Scholar

  2. Maria Jose Rodriguez-Castaño
    View author publications

    Search author on:PubMed Google Scholar

  3. Araceli Corredera
    View author publications

    Search author on:PubMed Google Scholar

  4. Cristina Cortés-Ledesma
    View author publications

    Search author on:PubMed Google Scholar

  5. Eva Vierge
    View author publications

    Search author on:PubMed Google Scholar

  6. Jose Martinez-Orgado
    View author publications

    Search author on:PubMed Google Scholar

  7. Luis Arruza
    View author publications

    Search author on:PubMed Google Scholar

Contributions

Substantial contributions to conception and design– N.O., M.J.R., J.M.O., L.A. Acquisition of data- N.O., M.J.R., A.C, E.V.H., C.C.L., L.A. Analysis and interpretation of data– N.O., M.J.R., J.M.O., L.A. Drafting the article – N.O. Revising the article critically for important intellectual content– M.J.R., J.M.O, L.A. Final approval of the version to be published– N.O., M.J.R., A.C., E.V.H., C.C.L., J.M.O., L.A.

Corresponding author

Correspondence to Luis Arruza.

Ethics declarations

Competing interests

The authors declare no competing interests.

Informed consent

Informed consent was signed by the parents for all participants.

Additional information

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

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Oikonomopoulou, N., Rodriguez-Castaño, M.J., Corredera, A. et al. Extremely preterm infants with adverse neurological outcome present more frequently impaired right ventricular performance. Pediatr Res 98, 1403–1411 (2025). https://doi.org/10.1038/s41390-025-03959-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41390-025-03959-5

This article is cited by

Search

Advanced search

Quick links