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:

A prospective study describing splanchnic NIRS and clinical outcomes in encephalopathic neonates receiving minimal enteral nutrition during therapeutic hypothermia

Journal of Perinatology volume 45, pages 1087–1092 (2025)Cite this article

Subjects

Abstract

Objective

To compare regional splanchnic oxygenation (SrSO2) levels and clinical outcomes between infants who received minimal enteral nutrition (MEN) during Therapeutic Hypothermia (TH), and those who did not.

Study design

A prospective, interventional cohort study with a historic control group at two Regional Perinatal Centers (NCT05471336).

Results

Participant demographics and clinical illness severity were similar between MEN (n = 40) and control (n = 40) groups. There were no significant safety events. SrSO2 levels were normal in both groups throughout. Subjects that received MEN experienced fewer central line days (5.8 v 6.9, p = 0.005) and higher rates of human milk feeding (77% v 46%, p = 0.010), and achieved full oral feeds sooner (9.9 v 13.4 days, p = 0.043).

Conclusion

Splanchnic tissue oxygenation was normal in both groups, and similar between groups throughout TH. Providing MEN during TH appears safe and effective, resulting in several important clinical benefits.

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: Mean SrSO2 during Hypothermia and Rewarming.
Fig. 2: Mean SCOR during hypothermia and rewarming.

Similar content being viewed by others

Data availability

The dataset that supports the findings of this study is not currently available in a public repository, but will be made available to reviewers or readers upon reasonable request, by contacting the corresponding author via e-mail.

References

  1. Jacobs SE, Berg M, Hunt R, Tarnow-Mordi WO, Inder TE, Davis PG. Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst Rev. 2013;2013:CD003311.

    PubMed  PubMed Central  Google Scholar 

  2. Russ JB, Simmons R, Glass HC. Neonatal encephalopathy: beyond hypoxic-ischemic encephalopathy. Neoreviews. 2021;22:e148–62.

    Article  PubMed  Google Scholar 

  3. Beltempo M, Wintermark P, Mohammad K, Jabbour E, Afifi J, Shivananda S, et al. Variations in practices and outcomes of neonates with hypoxic ischemic encephalopathy treated with therapeutic hypothermia across tertiary NICUs in Canada. J Perinatol. 2022;42:898–906.

    Article  CAS  PubMed  Google Scholar 

  4. Mohammad K, McIntosh S, Lee KS, Beltempo M, Afifi J, Tremblay S, et al. Variations in care of neonates during therapeutic hypothermia: call for care practice bundle implementation. Pediatr Res. 2023;94:321–30.

    Article  PubMed  Google Scholar 

  5. Chang LL, Wynn JL, Pacella MJ, Rossignol CC, Banadera F, Alviedo N, et al. Enteral feeding as an adjunct to hypothermia in neonates with hypoxic-ischemic encephalopathy. Neonatology. 2018;113:347–52.

    Article  PubMed  Google Scholar 

  6. Alburaki W, Scringer-Wilkes M, Dawoud F, Oliver N, Lind J, Zein H, et al. Feeding during therapeutic hypothermia is safe and may improve outcomes in newborns with perinatal asphyxia. J Matern Fetal Neonatal Med. 2022;35:9440–4.

    Article  CAS  PubMed  Google Scholar 

  7. Gale C, Longford NT, Jeyakumaran D, Ougham K, Battersby C, Ojha S, et al. Feeding during neonatal therapeutic hypothermia, assessed using routinely collected National Neonatal Research Database data: a retrospective, UK population-based cohort study. Lancet Child Adolesc Health. 2021;5:408–16.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Kumar J, Anne RP, Meena J, Sundaram V, Dutta S, Kumar P. To feed or not to feed during therapeutic hypothermia in asphyxiated neonates: a systematic review and meta-analysis. Eur J Pediatr. 2023;182:2759–73.

    Article  PubMed  Google Scholar 

  9. Marin T, Moore J. Understanding near-infrared spectroscopy. Adv Neonatal Care. 2011;11:382–8.

    Article  PubMed  Google Scholar 

  10. Bailey SM, Hendricks-Munoz KD, Mally P. Cerebral, renal, and splanchnic tissue oxygen saturation values in healthy term newborns. Am J Perinatol. 2014;31:339–44.

    PubMed  Google Scholar 

  11. El-Dib M, Abend NS, Austin T, Boylan G, Chock V, Cilio MR, et al. Neuromonitoring in neonatal critical care part I: neonatal encephalopathy and neonates with possible seizures. Pediatr Res. 2023;94:64–73.

    Article  PubMed  Google Scholar 

  12. Metcalfe KHM, Stienstra R, McHoney M. NIRS as a biomarker of bowel ischaemia & surgical pathology: a meta-analysis of studies in newborns. Early Hum Dev. 2021;161:105437.

    Article  CAS  PubMed  Google Scholar 

  13. Palleri E, van der Heide M, Hulscher JBF, Bartocci M, Wester T, Kooi EMW. Clinical usefulness of splanchnic oxygenation in predicting necrotizing enterocolitis in extremely preterm infants: a cohort study. BMC Pediatr. 2023;23:336.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Martini S, Corvaglia L. Splanchnic NIRS monitoring in neonatal care: rationale, current applications and future perspectives. J Perinatol. 2018;38:431–43.

    Article  PubMed  Google Scholar 

  15. Sarnat HB, Sarnat MS. Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study. Arch Neurol. 1976;33:696–705.

    Article  CAS  PubMed  Google Scholar 

  16. Shankaran S, Barnes PD, Hintz SR, Laptook AR, Zaterka-Baxter KM, McDonald SA, et al. Brain injury following trial of hypothermia for neonatal hypoxic-ischaemic encephalopathy. Arch Dis Child Fetal Neonatal Ed. 2012;97:F398–404.

    Article  PubMed  Google Scholar 

  17. Hu Y, Chen F, Xiang X, Wang F, Hua Z, Wei H. Early versus delayed enteral nutrition for neonatal hypoxic-ischemic encephalopathy undergoing therapeutic hypothermia: a randomized controlled trial. Ital J Pediatr. 2022;48:146.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Ojha S, Dorling J, Battersby C, Longford N, Gale C. Optimising nutrition during therapeutic hypothermia. Arch Dis Child Fetal Neonatal Ed. 2019;104:F230–F1.

    Article  PubMed  Google Scholar 

  19. Hazeldine B, Thyagarajan B, Grant M, Chakkarapani E. Survey of nutritional practices during therapeutic hypothermia for hypoxic-ischaemic encephalopathy. BMJ Paediatr Open. 2017;1:e000022.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Thyagarajan B, Tillqvist E, Baral V, Hallberg B, Vollmer B, Blennow M. Minimal enteral nutrition during neonatal hypothermia treatment for perinatal hypoxic-ischaemic encephalopathy is safe and feasible. Acta Paediatr. 2015;104:146–51.

    Article  PubMed  Google Scholar 

  21. Warchol A, Kwinta P. Nutrition of newborns with hypoxic-ischaemic encephalopathy during therapeutic hypothermia - a survey of practice in polish neonatal care units. J Mother Child. 2024;28:8–13.

    PubMed  PubMed Central  Google Scholar 

  22. Sharma S, Kallesh A, Aradhya AS, Diggikar S, Veeraiah PS, Subbareddy NN, et al. Feasibility of minimal enteral nutrition during therapeutic hypothermia for perinatal asphyxia: a five-year multicenter experience from South India. Indian J Pediatr. 2023;90:513–5.

    Article  PubMed  Google Scholar 

  23. Sakhuja P, More K, Ting JY, Sheth J, Lapointe A, Jain A, et al. Gastrointestinal hemodynamic changes during therapeutic hypothermia and after rewarming in neonatal hypoxic-Ischemic encephalopathy. Pediatr Neonatol. 2019;60:669–75.

    Article  PubMed  Google Scholar 

  24. Forman E, Breatnach CR, Ryan S, Semberova J, Miletin J, Foran A, et al. Noninvasive continuous cardiac output and cerebral perfusion monitoring in term infants with neonatal encephalopathy: assessment of feasibility and reliability. Pediatr Res. 2017;82:789–95.

    Article  PubMed  Google Scholar 

  25. Bailey SM, Mally PV. Review of splanchnic oximetry in clinical medicine. J Biomed Opt. 2016;21:091306.

    Article  PubMed  Google Scholar 

  26. Bailey SM, Hendricks-Munoz KD, Mally P. Splanchnic-cerebral oxygenation ratio (SCOR) values in healthy term infants as measured by near-infrared spectroscopy (NIRS). Pediatr Surg Int. 2013;29:591–5.

    Article  PubMed  Google Scholar 

  27. Howarth CN, Leung TS, Banerjee J, Eaton S, Morris JK, Aladangady N. Regional cerebral and splanchnic tissue oxygen saturation in preterm infants - Longitudinal normative measurements. Early Hum Dev. 2022;165:105540.

    Article  CAS  PubMed  Google Scholar 

  28. Thomas RA, Ballard MR, Aladangady N, Banerjee J. Abdominal Near Infrared Spectroscopy can be reliably used to measure splanchnic oxygenation changes in preterm infants. J Perinatol. 2023;43:716–21.

    Article  CAS  PubMed  Google Scholar 

  29. van der Heide M, Dotinga BM, Stewart RE, Kalteren WS, Hulscher JBF, Reijneveld SA, et al. Regional splanchnic oxygen saturation for preterm infants in the first week after birth: reference values. Pediatr Res. 2021;90:882–7.

    Article  PubMed  Google Scholar 

  30. Fortune PM, Wagstaff M, Petros AJ. Cerebro-splanchnic oxygenation ratio (CSOR) using near infrared spectroscopy may be able to predict splanchnic ischaemia in neonates. Intensive Care Med. 2001;27:1401–7.

    Article  CAS  PubMed  Google Scholar 

  31. Gillam-Krakauer M, Cochran CM, Slaughter JC, Polavarapu S, McElroy SJ, Hernanz-Schulman M, et al. Correlation of abdominal rSO2 with superior mesenteric artery velocities in preterm infants. J Perinatol. 2013;33:609–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. DeWitt AG, Charpie JR, Donohue JE, Yu S, Owens GE. Splanchnic near-infrared spectroscopy and risk of necrotizing enterocolitis after neonatal heart surgery. Pediatr Cardiol. 2014;35:1286–94.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Ravikumar C, Pandey R. Feeding infants with hypoxic ischemic encephalopathy during therapeutic hypothermia. J Perinatol. 2023;43:124–7.

    Article  PubMed  Google Scholar 

  34. Dave V, Brion LP, Campbell DE, Scheiner M, Raab C, Nafday SM. Splanchnic tissue oxygenation, but not brain tissue oxygenation, increases after feeds in stable preterm neonates tolerating full bolus orogastric feeding. J Perinatol. 2009;29:213–8.

    Article  CAS  PubMed  Google Scholar 

  35. Hosseini SM, Talaei-Khozani T, Sani M, Owrangi B. Differentiation of human breast-milk stem cells to neural stem cells and neurons. Neurol Res Int. 2014;2014:807896.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Kersin SG, Ozek E. Breast milk stem cells: are they magic bullets in neonatology? Turk Arch Pediatr. 2021;56:187–91.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Ninkina N, Kukharsky MS, Hewitt MV, Lysikova EA, Skuratovska LN, Deykin AV, et al. Stem cells in human breast milk. Hum Cell. 2019;32:223–30.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Damianos A, Sammour I. Barriers in translating stem cell therapies for neonatal diseases. Semin Perinatol. 2023;47:151731.

    Article  PubMed  Google Scholar 

  39. Dix LM, van Bel F, Baerts W, Lemmers PM. Comparing near-infrared spectroscopy devices and their sensors for monitoring regional cerebral oxygen saturation in the neonate. Pediatr Res. 2013;74:557–63.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to acknowledge the support of the Neonatology faculty, fellows, residents, APPs, Nursing and Ancillary staff in the Neonatal Intensive Care Units at Hassenfeld Children’s and Bellevue Hospitals.

Author information

Authors and Affiliations

  1. Division of Neonatology, Department of Pediatrics, Hassenfeld Children’s Hospital at NYU Langone, 550 1st Avenue, New York, NY, 10016, USA

    Tatiana A. Nuzum, Sean M. Bailey, Martha Caprio & Elena V. Wachtel

  2. Division of Neonatology, Department of Pediatrics, NYCH + H Bellevue Hospital Center, 462 1st Avenue, New York, NY, 10016, USA

    Tatiana A. Nuzum, Sean M. Bailey, Martha Caprio & Elena V. Wachtel

Authors
  1. Tatiana A. Nuzum
    View author publications

    Search author on:PubMed Google Scholar

  2. Sean M. Bailey
    View author publications

    Search author on:PubMed Google Scholar

  3. Martha Caprio
    View author publications

    Search author on:PubMed Google Scholar

  4. Elena V. Wachtel
    View author publications

    Search author on:PubMed Google Scholar

Contributions

TAN and EW developed the study concept and design, and were responsible for patient recruitment. TAN was responsible for data collection and analysis. TAN, EVW and SMB interpreted results. MC served as safety monitor as designated by the institutional review board. All authors contributed to manuscript preparation.

Corresponding author

Correspondence to Tatiana A. Nuzum.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

This study was performed in accordance with the Declaration of Helsinki. Informed consent was sought for each infant assigned to the interventional arm. The study protocol and informed consent form were approved by our local institutional review boards prior to the study’s conductance (NYU Langone Health Office of Science and Research Institutional Review Board—ref #i22-00861, Bellevue Hospital Institutional Review Board—ref STUDY00003666). Need for consent was waived for the control group, as they were a retrospective sample.

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

Nuzum, T.A., Bailey, S.M., Caprio, M. et al. A prospective study describing splanchnic NIRS and clinical outcomes in encephalopathic neonates receiving minimal enteral nutrition during therapeutic hypothermia. J Perinatol 45, 1087–1092 (2025). https://doi.org/10.1038/s41372-025-02270-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41372-025-02270-9

Search

Advanced search

Quick links