Skip to main content

Advertisement

SpringerLink
Log in

Low technology, mild controlled hypothermia for necrotizing enterocolitis treatment: an initiative to improve healthcare to preterm neonates.

  • Original Article
  • Published:
European Journal of Pediatrics Aims and scope Submit manuscript

Abstract

Necrotizing enterocolitis (NEC) treatment remains unchanged for years. Data suggest that mild controlled hypothermia could potentially improve NEC outcomes. Our units presented unfavourable outcomes on NEC. The aim was to assess our experience with low technology, mild controlled hypothermia on NEC outcomes, and improve preterm infants’ healthcare. This was a single-center quality improvement study with retrospective cohort design at the neonatal intensive care unit in the university hospital. Forty-three preterm infants with NEC (Modified Bell’s Stage II/III) were included: 19 in the control group (2015–2018) and 24 in the hypothermia group (2018–2020). The control group received standard treatment (fasting, abdominal decompression, and broad-spectrum antibiotics). The hypothermia group underwent cooling to 35.5 °C for 48 h after NEC diagnosis, along with conventional treatment. The primary outcomes are intestinal perforation, need for surgery, duration of parenteral nutrition, death, and extensive resection of the small intestine. There was no statistical difference in the NEC score. The hypothermia group required less surgery (aRR 0.40; 95% CI 0.19–0.85), presented less bowel perforation (aRR 0.39; 95% CI 0.18; 0.83), had a shorter duration of parenteral nutrition (aHR 5.28; 95% CI 1.88–14.89), did not need extensive intestinal resection, (0 vs 15.7%), and did not experience any deaths (0 vs 31.6%).

Conclusions: In our experience, low technology, mild controlled hypothermia was feasible, not related to adverse effects, and effective treatment for NEC Modified Bell’s Stage II/III. It avoided surgery, bowel perforation, and extensive intestinal resection; reduced mortality; and shortened parenteral nutrition duration.

What is Known:

• New approaches have been proposed to avoid enterocolitis incidence; however, the treatment of enterocolitis stage 2 has been the same for decades, and unfavourable outcomes remain despite conventional management.

• Studies suggest that hypothermia can be an alternative to enterocolitis treatment.

What is New:

• Mild controlled hypothermia can be an additional practice to treat enterocolitis stage 2, is feasible, and is not related to adverse effects to preterm infants.

• It can decrease surgery needs, duration of parenteral nutrition, and death and avoids extensive intestinal resection in preterm infants.

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

Fig. 1
Fig. 2

Similar content being viewed by others

Data availability

all the data are available for inquiry or analysis.

Code availability

N/A

Abbreviations

CPAP:

Continuous positive airway pressure

NEC:

Necrotizing enterocolitis

NICU:

Neonatal intensive care unit

nSOFA:

Sequential organ failure assessment

VLBW:

very low birth weight

References

  1. Neu J, Walker WA (2011) Necrotizing enterocolitis. N Engl J Med 364(3):255–264. https://doi.org/10.1056/NEJMra1005408

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Warner BB, Deych E, Zhou Y, Hall-Moore C, Weinstock GM, Sodergren E, Shaikh N, Hoffmann JA, Linneman LA, Hamvas A, Khanna G, Rouggly-Nickless LC, Ndao IM, Shands BA, Escobedo M, Sullivan JE, Radmacher PG, Shannon WD, Tarr PI (2016) Gut bacteria dysbiosis and necrotising enterocolitis in very low birthweight infants: a prospective case-control study. Lancet. 387(10031):1928–1936. https://doi.org/10.1016/S0140-6736(16)00081-7

    Article  PubMed  PubMed Central  Google Scholar 

  3. Ganapathy V, Hay JW, Kim JH (2012) Costs of necrotizing enterocolitis and cost-effectiveness of exclusively human milk-based products in feeding extremely premature infants. Breastfeed Med 7(1):29–37. https://doi.org/10.1089/bfm.2011.0002

    Article  PubMed  Google Scholar 

  4. Sankaran K, Puckett B, Lee DSC, Seshia M, Boulton J, Qiu Z, Lee SK, Canadian Neonatal Network (2004) Variations in incidence of necrotizing enterocolitis in Canadian neonatal intensive care units. J Pediatr Gastroenterol Nutr 39(4):366–372. https://doi.org/10.1097/00005176-200410000-00012

    Article  PubMed  Google Scholar 

  5. Rees CM, Eaton S, Pierro A (2010) National prospective surveillance study of necrotizing enterocolitis in neonatal intensive care units. J Pediatr Surg 45(7):1391–1397. https://doi.org/10.1016/j.jpedsurg.2009.12.002

    Article  PubMed  Google Scholar 

  6. Yee WH, Soraisham AS, Shah VS, Aziz K, Yoon W, Lee SK, the Canadian Neonatal Network (2012) Incidence and timing of presentation of necrotizing enterocolitis in preterm infants. Pediatrics. 129(2):e298–e304. https://doi.org/10.1542/peds.2011-2022

    Article  PubMed  Google Scholar 

  7. Zozaya C, García González I, Avila-Alvarez A, et al. Incidence, treatment, and outcome trends of necrotizing enterocolitis in preterm infants: A multicenter cohort study. Front Pediatr. 2020;8(188). https://doi.org/10.3389/fped.2020.00188

  8. Guner YS, Friedlich P, Wee CP, Dorey F, Camerini V, Upperman JS (2009) State-based analysis of necrotizing enterocolitis outcomes. J Surg Res 157(1):21–29. https://doi.org/10.1016/j.jss.2008.11.008

    Article  PubMed  Google Scholar 

  9. Rees CM, Pierro A, Eaton S (2007) Neurodevelopmental outcomes of neonates with medically and surgically treated necrotizing enterocolitis. Arch Dis Child Fetal Neonatal Ed 92(3):F193–F198. https://doi.org/10.1136/adc.2006.099929

    Article  PubMed  Google Scholar 

  10. Adams M, Bassler D, Darlow BA, Lui K, Reichman B, Hakansson S, Norman M, Lee SK, Helenius KK, Lehtonen L, San Feliciano L, Vento M, Moroni M, Beltempo M, Yang J, Shah PS, International Network for EvaluatingOutcomes (iNeo) of Neonates (2019) Preventive strategies and factors associated with surgically treated necrotising enterocolitis in extremely preterm infants: an international unit survey linked with retrospective cohort data analysis. BMJ Open 9(10):e031086. https://doi.org/10.1136/bmjopen-2019-031086

    Article  PubMed  PubMed Central  Google Scholar 

  11. Talavera MM, Bixler G, Cozzi C, Dail J, Miller RR, McClead R, Reber K (2016) Quality improvement initiative to reduce the necrotizing enterocolitis rate in premature infants. Pediatrics. 137(5):e20151119. https://doi.org/10.1542/peds.2015-1119

    Article  PubMed  Google Scholar 

  12. Rolnitsky A, Ng E, Asztalos E, Shama Y, Karol D, Findlater C, Garsch M, Dunn M (2019) A quality improvement intervention to reduce necrotizing Enterocolitis in premature infants with probiotic supplementation. Pediatr Qual Saf 4(5):e201. https://doi.org/10.1097/pq9.0000000000000201

    Article  PubMed  PubMed Central  Google Scholar 

  13. Gephart SM, Hanson C, Wetzel CM, Fleiner M, Umberger E, Martin L, Rao S, Agrawal A, Marin T, Kirmani K, Quinn M, Quinn J, Dudding KM, Clay T, Sauberan J, Eskenazi Y, Porter C, Msowoya AL, Wyles C, Avenado-Ruiz M, Vo S, Reber KM, Duchon J (2017) NEC-zero recommendations from scoping review of evidence to prevent and foster timely recognition of necrotizing enterocolitis. Matern Heal Neonatol Perinatol 3(1):1–14. https://doi.org/10.1186/s40748-017-0062-0

    Article  Google Scholar 

  14. Hall NJ, Eaton S, Peters MJ, et al. Mild controlled hypothermia in preterm neonates with advanced necrotizing enterocolitis. Pediatrics. 2010;125(2). https://doi.org/10.1542/peds.2008-3211

  15. Garrett-Cox RG, Pierro A, Spitz L, Eaton S (2003) Body temperature and heat production in suckling rat endotoxaemia: beneficial effects of glutamine. J Pediatr Surg 38:37–44. https://doi.org/10.1053/jpsu.2003.50006

    Article  PubMed  Google Scholar 

  16. Vinardi BS, Pierro A, Parkinson EJ et al (2003) Attenuates lung neutrophil infiltration. J Pediatr Surg 38:88–91. https://doi.org/10.1053/jpsu.2003.50017

    Article  PubMed  Google Scholar 

  17. Kimura Y, Pierro A, Eaton S (2009) Glutathione synthesis in intestinal ischaemia-reperfusion injury: effects of moderate hypothermia. J Pediatr Surg 44:353–357. https://doi.org/10.1016/j.jpedsurg.2008.10.091

    Article  PubMed  Google Scholar 

  18. Stefanutti G, Pierro A, Vinardi S, Spitz L, Eaton S (2005) Moderate hypothermia protects against systemic oxidative stress in a rat model of intestinal ischemia and reperfusion injury. Shock. 24(2):159–164. https://doi.org/10.1097/01.shk.0000168871.60531.6f

    Article  CAS  PubMed  Google Scholar 

  19. Stefanutti G, Pierro A, Parkinson EJ, Smith VV, Eaton S (2008) Moderate hypothermia as a rescue therapy against intestinal ischemia and reperfusion injury in the rat. Crit Care Med 36(5):1564–1572. https://doi.org/10.1097/CCM.0b013e3181709e9f

    Article  PubMed  Google Scholar 

  20. Couto LDCA; Souza TR; Ferreira CHF; Calixto C; Carnevale-Silva A; Aragon DC; Maiolini BL; Silva ACB; Souza GA; Martins-Filho PF; Toffolo RO; Fukamichi SL; Gonçalves-Ferri W. Unfavorable evolution of enterocolitis: the mystery continues.In: 3rd Congress of Joint European Neonatal Societies (jENS) 2019, Maastrich, The Netherlands

  21. Bell MJ, Ternberg JL, Feigin RD et al (1978) Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann Surg 187(1):1–7. https://doi.org/10.1097/00000658-197801000-00001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Ogrinc G, Davies L, Goodman D, Batalden P, Davidoff F, Stevens D (2015 Nov) SQUIRE 2.0 (standards for QUality improvement reporting excellence): revised publication guidelines from a detailed consensus process. J Contin Educ Nurs 46(11):501–507. https://doi.org/10.3928/00220124-20151020-02

    Article  PubMed  Google Scholar 

  23. Volpe JJ. Neurology of the Newborn. (Saunders, ed.). Philadelphia; 1995. https://doi.org/10.1002/mus.880180822

  24. Singh Y, Tissot C, Fraga M et al (2020) International evidence-based guidelines on point of care ultrasound (POCUS) for critically ill neonates and children issued by the POCUS working Group of the European Society of Paediatric and neonatal intensive care (ESPNIC). Crit Care 24(1):65. https://doi.org/10.1186/s13054-020-2787-9

    Article  PubMed  PubMed Central  Google Scholar 

  25. Wynn JL, Polin RA (2019) A neonatal sequential organ failure assessment score predicts mortality to late-onset sepsis in preterm very low birth weight infants. Pediatr Res 88(1):85–90. https://doi.org/10.1038/s41390-019-0517-2

    Article  PubMed  PubMed Central  Google Scholar 

  26. Gephart SM, Spitzer AR, Effken JA, Dodd E, Halpern M, McGrath JM (2014) Discrimination of GutCheck NEC: a clinical risk index for necrotizing enterocolitis. J Perinatol 34(6):468–475. https://doi.org/10.1038/jp.2014.37

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Villar J, Papageorghiou AT, Pang R, Ohuma EO, Cheikh Ismail L, Barros FC, Lambert A, Carvalho M, Jaffer YA, Bertino E, Gravett MG, Altman DG, Purwar M, Frederick IO, Noble JA, Victora CG, Bhutta ZA, Kennedy SH, International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st) (2014) The likeness of fetal growth and newborn size across non-isolated populations in the INTERGROWTH-21st project: the fetal growth longitudinal study and newborn cross-sectional study. Lancet Diabetes Endocrinol 2(10):781–792. https://doi.org/10.1016/S2213-8587(14)70121-4

    Article  PubMed  Google Scholar 

  28. Meyer MP, Chow SSW, Alsweiler J, Bourchier D, Broadbent R, Knight D, Lynn AM, Patel H (2020) Probiotics for prevention of severe necrotizing enterocolitis: experience of New Zealand neonatal intensive care units. Front Pediatr 8(April):1–9. https://doi.org/10.3389/fped.2020.00119

    Article  Google Scholar 

  29. Wang ZL, Liu L, Hu XY, Guo L, Li QY, An Y, Jiang YJ, Chen S, Wang XQ, He Y, Li LQ (2019) Probiotics may not prevent the deterioration of necrotizing enterocolitis from stage I to II/III. BMC Pediatr 19(1):1–7. https://doi.org/10.1186/s12887-019-1524-5

    Article  Google Scholar 

  30. Drucker NA, McCulloh CJ, Li B, Pierro A, Besner GE, Markel TA (2018) Stem cell therapy in necrotizing enterocolitis: current state and future directions. Semin Pediatr Surg 27(1):57–64. https://doi.org/10.1053/j.sempedsurg.2017.11.011

    Article  PubMed  Google Scholar 

  31. McCulloh CJ, Olson JK, Wang Y et al (2018) Treatment of experimental necrotizing enterocolitis with stem cell-derived exosomes. J Pediatr Surg 53:1215–1220. https://doi.org/10.1016/j.jpedsurg.2018.02.086

    Article  PubMed  PubMed Central  Google Scholar 

  32. Sim N Therapeutic controlled hypothermia in the treatment of neonates with severe necrotizing enterocolitis (CoolNEC). Bethesda (MD): ClinicalTrials.gov; 2011. doi:NCT01330576

  33. De Almeida MFB, Guinsburg R, Sancho GA et al (2014) Hypothermia and early neonatal mortality in preterm infants. J Pediatr 164(2):271–276. https://doi.org/10.1016/j.jpeds.2013.09.049

    Article  PubMed  Google Scholar 

  34. Lyu Y, Shah PS, Ye XY, Warre R, Piedboeuf B, Deshpandey A, Dunn M, Lee SK, Canadian Neonatal Network (2015) Association between admission temperature and mortality and major morbidity in preterm infants born at fewer than 33 weeks’ gestation. JAMA Pediatr 169(4):4–11. https://doi.org/10.1001/jamapediatrics.2015.0277

    Article  Google Scholar 

  35. de Siqueira Caldas JP, Ferri WAG, Marba STM, Aragon DC, Guinsburg R, de Almeida MFB, Diniz EMA, Silveira RCS, Alves Junior JMS, Pavanelli MB, Bentlin MR, Ferreira DMLM, Vale MS, Fiori HH, Duarte JLMB, Meneses JA, Cwajg S, Carvalho WB, Ferrari LSL, Silva NMM, da Silva RPGVC, Anchieta LM, Santos JPF, Kawakami MD (2019) Admission hypothermia, neonatal morbidity, and mortality: evaluation of a multicenter cohort of very low birth weight preterm infants according to relative performance of the center. Eur J Pediatr 178(7):1023–1032. https://doi.org/10.1007/s00431-019-03386-9

    Article  PubMed  Google Scholar 

  36. Chaudhary R, Farrer K, Broster S, Mcritchie L, Austin T (2013) Active versus passive cooling during neonatal transport. Pediatrics. 132(5):841–846. https://doi.org/10.1542/peds.2013-1686

    Article  PubMed  Google Scholar 

  37. Lin L, Xia X, Liu W, Wang Y, Hua Z (2019) Clinical characteristics of neonatal fulminant necrotizing enterocolitis in a tertiary Children’s hospital in the last 10 years. PLoS One 14(11):3–11. https://doi.org/10.1371/journal.pone.0224880

    Article  CAS  Google Scholar 

  38. Robinson JR, Rellinger EJ, Hatch LD, Weitkamp JH, Speck KE, Danko M, Blakely ML (2017) Surgical necrotizing enterocolitis. Semin Perinatol 41(1):70–79. https://doi.org/10.1053/j.semperi.2016.09.020

    Article  PubMed  Google Scholar 

  39. Niemarkt HJ, De Meij TG, Van Ganzewinkel CJ et al (2019) Necrotizing enterocolitis, gut microbiota, and brain development: role of the brain-gut axis. Neonatology. 115(4):423–431. https://doi.org/10.1159/000497420

    Article  PubMed  Google Scholar 

  40. Biouss G, Antounians L, Li B, O’Connell JS, Seo S, Catania VD, Guadagno J, Rahman A, Zani-Ruttenstock E, Svergun N, Pierro A, Zani A (2019) Experimental necrotizing enterocolitis induces neuroinflammation in the neonatal brain. J Neuroinflammation 16(1):1–14. https://doi.org/10.1186/s12974-019-1481-9

    Article  Google Scholar 

  41. Liu X, Wen S, Zhao S et al (2018) Mild therapeutic hypothermia protects the brain from ischemia/reperfusion injury through upregulation of iASPP. Aging Dis 9(3):401–411. https://doi.org/10.14336/AD.2017.0703

    Article  PubMed  PubMed Central  Google Scholar 

  42. Cuna AC, Lee JC, Robinson AL, Allen NH, Foley JE, Chan SS (2018) Bowel ultrasound for the diagnosis of necrotizing enterocolitis: a meta-analysis. Ultrasound Q 34(3):113–118. https://doi.org/10.1097/RUQ.0000000000000342

    Article  PubMed  Google Scholar 

  43. Garami A, Steiner AA, Romanovsky AA (2018) “Fever and hypothermia in systemic inflammation.” In handbook of clinical neurology, 157:565–97. Elsevier B.V. https://doi.org/10.1016/B978-0-444-64074-1.00034-3

  44. Neu J, Pammi M (2018) Necrotizing enterocolitis: the intestinal microbiome, metabolome and inflammatory mediators. Semin Fetal Neonatal Med 23(6):400–405. https://doi.org/10.1016/j.siny.2018.08.001

    Article  PubMed  Google Scholar 

  45. Ding W, Shen Y, Li Q, Jiang S, Shen H (2018) Therapeutic mild hypothermia improves early outcomes in rats subjected to severe sepsis. Life Sci 199(February):1–9. https://doi.org/10.1016/j.lfs.2018.03.002

    Article  CAS  PubMed  Google Scholar 

  46. Watkins C, Murphy K, Yen S, Carafa I, Dempsey EM, O’Shea CA, Vercoe EA, Ross RP, Stanton C, Ryan CA (2017) Effects of therapeutic hypothermia on the gut microbiota and metabolome of infants suffering hypoxic-ischemic encephalopathy at birth. Int J Biochem Cell Biol 93(April):110–118. https://doi.org/10.1016/j.biocel.2017.08.017

    Article  CAS  PubMed  Google Scholar 

  47. Prashantha YN, Suman Rao PN, Nesargi S et al. (2018) Therapeutic hypothermia for moderate and severe hypoxic ischaemic encephalopathy in newborns using low-cost devices – ice packs and phase changing material. Paediatr Int Child Health, 1–6. https://doi.org/10.1080/20469047.2018.1500805

  48. Daetwyler K, Brotschi B, Berger TM, Wagner BP (2013) Feasibility and safety of passive cooling in a cohort of asphyxiated newborn infants. Swiss Med Wkly 143(March):1–6. https://doi.org/10.4414/smw.2013.13767

    Article  Google Scholar 

  49. Jacobs SE, Berg M, Hunt R, Tarnow-Mordi WO, Inder TE, Davis PG, Cochrane Neonatal Group (2013) Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst Rev 2013(1):CD003311. https://doi.org/10.1002/14651858.CD003311.pub3

    Article  PubMed Central  Google Scholar 

  50. Alsaied A, Islam N, Thalib L (2020) Global incidence of necrotizing Enterocolitis: a systematic review and meta-analysis. BMC Pediatr 20(1):344. https://doi.org/10.1186/s12887-020-02231-5

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

We acknowledge the preterm infants and his families who accepted contributed to this study and neonatology staff from Ribeirão Preto Medical School-University of São Paulo, who works with these patients.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Ribeirão Preto Medical School, University of São Paulo, Bandeirantes Avenue 3900, Ribeirão Preto, São Paulo state, Brazil

    Walusa Assad Gonçalves-Ferri, Cristina Helena Faleiros Ferreira, Thaissa Rodrigues Souza, Thayane de Castro Peres, Fabio Carmona, Davi Casale Aragon, Gerson Crott, Marisa M. Mussi-Pinhata, Jose Simon Camelo Junior & Anelise Roosch

  2. Department of Surgery. Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil

    Laryssa de Carli de Almeida Couto & Lourenço Sbragia Neto

Authors
  1. Walusa Assad Gonçalves-Ferri
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cristina Helena Faleiros Ferreira
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Laryssa de Carli de Almeida Couto
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Thaissa Rodrigues Souza
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Thayane de Castro Peres
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Fabio Carmona
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Davi Casale Aragon
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Gerson Crott
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Marisa M. Mussi-Pinhata
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jose Simon Camelo Junior
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Anelise Roosch
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Lourenço Sbragia Neto
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Walusa Assad Gonçalves–Ferri: Conception and design of the study. Statistical analysis. Contribution to analysis. Interpretation of data. Drafting of the study.

Cristina Helena Faleiros Ferreira. Acquisition of the data. Contribution to analysis Interpretation of data. Drafting of the study. Revising it critically for important intellectual content.

Laryssa de Carli: Acquisition of the data. Contribution to analysis Interpretation of data. Revising it critically for important intellectual content.

Thaissa Rodrigues Souza. Acquisition of the data. Contribution to analysis Interpretation of data. Revising it critically for important intellectual content.

Thayane de Castro Peres. Acquisition of the data. Contribution to analysis Interpretation of data. Revising it critically for important intellectual content.

Fabio Carmona. Conception and design. Acquisition of the data. Contribution to analysis Interpretation of data. Revising it critically for important intellectual content.

Davi Casale Aragon. Conception and design. Statistical analysis. Contribution to analysis Interpretation of data. Drafting of the study. Revising it critically for important intellectual content.

Gerson Crott. Acquisition of the data. Contribution to analysis Interpretation of data. Drafting of the study. Revising it critically for important intellectual content.

Marisa Mussi. Conception and design. Contribution to analysis Interpretation of data. Revising it critically for important intellectual content.

Jose Simon Camelo Junior. Contribution to analysis Interpretation of data. Drafting of the study. Revising it critically for important intellectual content.

Anelise Roosch. Contribution to analysis interpretation of data. Drafting of the study. Revising it critically for important intellectual content.

Lourenço Sbragia Neto: Contribution to analysis. Interpretation of data. Drafting of the study. Revising it critically for important intellectual content.

All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the study.

Corresponding author

Correspondence to Walusa Assad Gonçalves-Ferri.

Ethics declarations

Conflict of interest

All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript.

Ethics approval

This study was approved by the Institutional Review Board of Ribeirão Preto Medical School, University of São Paulo (FMRP-USP, CAAE number 29879620.5.0000.5440, approval number 3.920.223). The procedures used in this study adhere to the tenets of the Declaration of Helsinki.

Consent to participate

N/A

Consent for publication

N/A

Additional information

Communicated by Daniele De Luca

Publisher’s note

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

Supplementary Information

ESM 1

(PDF 33 kb)

ESM 2

(PDF 358 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gonçalves-Ferri, W.A., Ferreira, C.H.F., Couto, L.d. et al. Low technology, mild controlled hypothermia for necrotizing enterocolitis treatment: an initiative to improve healthcare to preterm neonates.. Eur J Pediatr 180, 3161–3170 (2021). https://doi.org/10.1007/s00431-021-04014-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00431-021-04014-1

Keywords

Search

Navigation