Enteral Feeding During Therapeutic Hypothermia for Hypoxic–Ischemic Encephalopathy in Neonates: A Multicentre Study from Italy and Belgium
6 affiliations
- 1Neonatal Intensive Care Unit, “Bambino Gesù” Children’s Hospital IRCCS, 00165 Rome, Italy
- 2Faculty of Medicine and Surgery, Unicamillus, Saint Camillus International University of Health and Medical Sciences, 00131 Rome, Italy
- 3Division of Neonatology, Cliniques Universitaires Saint Luc, Université Catholique de Louvain, 1200 Brussels, Belgium
- 4Faculty of Medicine, Imperial College, London SW7 2AZ, UK
- 5Division of Child Neurology, Department of Pediatrics, Cliniques Universitaires Saint-Luc, Institute of Neuroscience (IoNS), Université Catholique de Louvain, 1200 Brussels, Belgium
- 6Neonatal Sub-Intensive Care Unit and Follow-Up, “Bambino Gesù” Children’s Hospital IRCCS, 00165 Rome, Italy
Abstract
Background: Enteral feeding during therapeutic hypothermia (TH) for hypoxic–ischemic encephalopathy (HIE) remains heterogeneous across centres because of concerns regarding feeding intolerance and the risk of necrotizing enterocolitis (NEC). Evidence regarding optimal feeding initiation and advancement remains limited. Methods: We performed a secondary analysis of a multicentre retrospective cohort of infants with HIE treated with TH at two tertiary neonatal intensive care units in Italy and Belgium between 2011 and 2024. We included survivors with complete nutritional data, aware that this restriction, adopted because feeding-related endpoints cannot be assessed in non-survivors, may introduce survivor bias. Feeding practices, enteral feeding progression, feeding tolerance, and gastrointestinal outcomes were evaluated. Results: Of 302 infants in the original cohort, 276 were included. Enteral feeding during TH was administered to 166 infants (60.1%). Enteral feeding volumes remained low during the first three days of life but progressively increased thereafter. Despite inter-center differences in feeding strategies (initiation and advancement), time to full enteral feeding (median 9 days; IQR 7–12) was comparable overall (Italy: median 9 days, IQR 7–12; Belgium: median 10 days, IQR 7–14; p = 0.323). Infants receiving enteral nutrition during TH were observed to achieve full enteral feeding earlier than those not fed during cooling (median 8.0 vs. 12.0 days, p < 0.001) and to have a shorter length of hospital stay (median 11.0 vs. 15.0 days, p < 0.001). Breastfeeding at discharge was also observed more frequently among infants who received enteral nutrition during TH (79.5% vs. 54.5%, p < 0.001). Feeding intolerance occurred in 47 infants (17.0%) and temporary feeding withdrawal in 31 (11.2%). Only three infants (1.1%) developed Bell stage IIA NEC, with no progression to more advanced disease or surgery. NEC was more frequent among infants with Sarnat stage III HIE than among those with stage I–II disease (8.3% vs. 0.4%, p = 0.022). Conclusions: Enteral feeding during TH was feasible, and gastrointestinal complications were uncommon. These findings support the feasibility of cautious enteral feeding during TH. The concentration of NEC events among infants with severe HIE, although based on only three cases, is hypothesis-generating and suggests that future studies should evaluate feeding strategies according to both neurological severity and physiological stability. Whether earlier initiation or faster advancement is beneficial in clinically stable infants cannot be determined from these observational data and should be addressed in prospective studies.
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BibTeX
@article{rose2026enteral,
title = {{Enteral Feeding During Therapeutic Hypothermia for Hypoxic–Ischemic Encephalopathy in Neonates: A Multicentre Study from Italy and Belgium}},
author = {Domenico Umberto De Rose and Iliana Bersani and Guglielmo Salvatori and Francesca Campi and Ludovica Martini and Chiara Maddaloni and Sara Ronci and Alessandra Santisi and Immacolata Savarese and Cinzia Auriti and Elena Camacho Santamaria and Anaïs De Groote and Katherine Carkeek and Giulia Iacona and Maria Roberta Cilio and Maria Paola Ronchetti and Annabella Braguglia and Olivier Danhaive and Andrea Dotta and Fiammetta Piersigilli},
journal = {Nutrients},
year = {2026},
month = oct,
doi = {10.3390/nu18193240},
url = {https://europepmc.org/article/PMC/PMC13666962},
note = {CC BY},
}
RIS
TY - JOUR
TI - Enteral Feeding During Therapeutic Hypothermia for Hypoxic–Ischemic Encephalopathy in Neonates: A Multicentre Study from Italy and Belgium
AU - Domenico Umberto De Rose
AU - Iliana Bersani
AU - Guglielmo Salvatori
AU - Francesca Campi
AU - Ludovica Martini
AU - Chiara Maddaloni
AU - Sara Ronci
AU - Alessandra Santisi
AU - Immacolata Savarese
AU - Cinzia Auriti
AU - Elena Camacho Santamaria
AU - Anaïs De Groote
AU - Katherine Carkeek
AU - Giulia Iacona
AU - Maria Roberta Cilio
AU - Maria Paola Ronchetti
AU - Annabella Braguglia
AU - Olivier Danhaive
AU - Andrea Dotta
AU - Fiammetta Piersigilli
PY - 2026
DA - 2026/10/01
JO - Nutrients
DO - 10.3390/nu18193240
UR - https://europepmc.org/article/PMC/PMC13666962
AB - Background: Enteral feeding during therapeutic hypothermia (TH) for hypoxic–ischemic encephalopathy (HIE) remains heterogeneous across centres because of concerns regarding feeding intolerance and the risk of necrotizing enterocolitis (NEC). Evidence regarding optimal feeding initiation and advancement remains limited. Methods: We performed a secondary analysis of a multicentre retrospective cohort of infants with HIE treated with TH at two tertiary neonatal intensive care units in Italy and Belgium between 2011 and 2024. We included survivors with complete nutritional data, aware that this restriction, adopted because feeding-related endpoints cannot be assessed in non-survivors, may introduce survivor bias. Feeding practices, enteral feeding progression, feeding tolerance, and gastrointestinal outcomes were evaluated. Results: Of 302 infants in the original cohort, 276 were included. Enteral feeding during TH was administered to 166 infants (60.1%). Enteral feeding volumes remained low during the first three days of life but progressively increased thereafter. Despite inter-center differences in feeding strategies (initiation and advancement), time to full enteral feeding (median 9 days; IQR 7–12) was comparable overall (Italy: median 9 days, IQR 7–12; Belgium: median 10 days, IQR 7–14; p = 0.323). Infants receiving enteral nutrition during TH were observed to achieve full enteral feeding earlier than those not fed during cooling (median 8.0 vs. 12.0 days, p < 0.001) and to have a shorter length of hospital stay (median 11.0 vs. 15.0 days, p < 0.001). Breastfeeding at discharge was also observed more frequently among infants who received enteral nutrition during TH (79.5% vs. 54.5%, p < 0.001). Feeding intolerance occurred in 47 infants (17.0%) and temporary feeding withdrawal in 31 (11.2%). Only three infants (1.1%) developed Bell stage IIA NEC, with no progression to more advanced disease or surgery. NEC was more frequent among infants with Sarnat stage III HIE than among those with stage I–II disease (8.3% vs. 0.4%, p = 0.022). Conclusions: Enteral feeding during TH was feasible, and gastrointestinal complications were uncommon. These findings support the feasibility of cautious enteral feeding during TH. The concentration of NEC events among infants with severe HIE, although based on only three cases, is hypothesis-generating and suggests that future studies should evaluate feeding strategies according to both neurological severity and physiological stability. Whether earlier initiation or faster advancement is beneficial in clinically stable infants cannot be determined from these observational data and should be addressed in prospective studies.
SN - 2072-6643
ER -