{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T18:48:39Z","timestamp":1790362119271,"version":"4.1.0"},"reference-count":36,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T00:00:00Z","timestamp":1745366400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Preterm neonates receiving parenteral nutrition (PN) are at risk of developing refeeding syndrome (RS). Risk factors and the related consequences remain largely undefined. In particular, the reason why only some preterm neonates out of a group receiving the same nutritional protocol will develop RS is yet to be fully understood. The aims of this study were to explore the clinical and nutritional factors contributing to RS and to assess the clinical consequences of this condition. Methods: A retrospective study was conducted, including all newborns with gestational age \u2264 34 weeks and\/or body birth weight \u2264 1500 g who were consecutively admitted to the neonatal intensive care unit (NICU) of \u201cUmberto I\u201d Hospital, Sapienza University of Rome, from 2015 to 2022. The population was divided into two groups comprising newborns who developed RS (cases) and infants who did not develop the condition (controls) up to the first 2 weeks of life. The enrolled newborns were compared for clinical and nutritional factors and main morbidities. Results: A total of 412 neonates were enrolled, consisting of 53 cases and 359 controls. The main prenatal risk factor for RS was found to be fetal distress (p = 0.028). The occurrence of RS was identified as statistically significantly associated (p = 0.010; p = 0.007) with the development of extrauterine growth restriction (EUGR) and retinopathy of prematurity (ROP). Conclusions: Fetal distress is the predominant perinatal risk factor associated with the development of RS in preterm neonates managed with early currently recommended PN. These findings suggest an increased risk of ROP and EUGR in preterm neonates with RS.<\/jats:p>","DOI":"10.3390\/nu17091417","type":"journal-article","created":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T08:26:43Z","timestamp":1745396803000},"page":"1417","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Fetal Distress as a Determinant for Refeeding Syndrome in Preterm Neonates"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1947-6247","authenticated-orcid":false,"given":"Maria","family":"Di Chiara","sequence":"first","affiliation":[{"name":"Department of Maternal and Child Health, Policlinico Umberto I, Sapienza University, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Spiriti","sequence":"additional","affiliation":[{"name":"Department of Maternal and Child Health, Policlinico Umberto I, Sapienza University, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia","family":"Gloria","sequence":"additional","affiliation":[{"name":"Department of Maternal and Child Health, Policlinico Umberto I, Sapienza University, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7807-2870","authenticated-orcid":false,"given":"Gianluigi","family":"Laccetta","sequence":"additional","affiliation":[{"name":"Department of Maternal and Child Health, Policlinico Umberto I, Sapienza University, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Dito","sequence":"additional","affiliation":[{"name":"Department of Maternal and Child Health, Policlinico Umberto I, Sapienza University, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4991-9689","authenticated-orcid":false,"given":"Magda","family":"Gharbiya","sequence":"additional","affiliation":[{"name":"Department of Sense Organs, Sapienza University of Rome, 155, Viale del Policlinico, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5525-4353","authenticated-orcid":false,"given":"Giuseppe","family":"Rizzo","sequence":"additional","affiliation":[{"name":"Department of Maternal and Child Health, Policlinico Umberto I, Sapienza University, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3541-2876","authenticated-orcid":false,"given":"Gianluca","family":"Terrin","sequence":"additional","affiliation":[{"name":"Department of Maternal and Child Health, Policlinico Umberto I, Sapienza University, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2059S","DOI":"10.3945\/jn.113.176966","article-title":"The Present Challenges of Parenteral Nutrition in Preterm Infants and Children","volume":"143","author":"Vlaardingerbroek","year":"2013","journal-title":"J. Nutr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2309","DOI":"10.1016\/j.clnu.2018.06.944","article-title":"ESPGHAN\/ESPEN\/ESPR\/CSPEN Guidelines on Pediatric Parenteral Nutrition: Energy","volume":"37","author":"Joosten","year":"2018","journal-title":"Clin. Nutr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2066S","DOI":"10.3945\/jn.113.177006","article-title":"Intrauterine-like Growth Rates Can Be Achieved with Premixed Parenteral Nutrition Solution in Preterm Infants","volume":"143","author":"Rigo","year":"2013","journal-title":"J. Nutr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1007\/s40124-013-0026-4","article-title":"Aggressive Nutrition of the Preterm Infant","volume":"1","author":"Hay","year":"2013","journal-title":"Curr. Pediatr. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.earlhumdev.2010.01.014","article-title":"Early nutritional support and outcomes in ELBW infants","volume":"86","author":"Ehrenkranz","year":"2010","journal-title":"Early Hum. Dev."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Di Chiara, M., Laccetta, G., Regoli, D., Dito, L., Spiriti, C., De Santis, B., Travaglia, E., Prota, R., Parisi, P., and Brunelli, R. (2023). Delayed Macronutrients\u2019 Target Achievement in Parenteral Nutrition Reduces the Risk of Hyperglycemia in Preterm Newborn: A Randomized Controlled Trial. Nutrients, 15.","DOI":"10.3390\/nu15051279"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Boscarino, G., Conti, M.G., Gasparini, C., Onest\u00e0, E., Faccioli, F., Dito, L., Regoli, D., Spalice, A., Parisi, P., and Terrin, G. (2021). Neonatal Hyperglycemia Related to Parenteral Nutrition Affects Long-Term Neurodevelopment in Preterm Newborn: A Prospective Cohort Study. Nutrients, 13.","DOI":"10.3390\/nu13061930"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Bonsante, F., Iacobelli, S., Latorre, G., Rigo, J., De Felice, C., Robillard, P.Y., and Gouyon, J.B. (2013). Initial Amino Acid Intake Influences Phosphorus and Calcium Homeostasis in Preterm Infants\u2014It Is Time to Change the Composition of the Early Parenteral Nutrition. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0072880"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1038\/jp.2015.54","article-title":"Early hypophosphatemia in preterm infants receiving aggressive parenteral nutrition","volume":"35","author":"Galletti","year":"2015","journal-title":"J. Perinatol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Asfour, S.S., Alshaikh, B., Mathew, M., Fouda, D.I., and Al-Mouqdad, M.M. (2024). Incidence and Risk Factors of Refeeding Syndrome in Preterm Infants. Nutrients, 16.","DOI":"10.3390\/nu16152557"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1111\/j.1442-200X.2012.03590.x","article-title":"Refeeding syndrome in a small-for-dates micro-preemie receiving early parenteral nutrition","volume":"54","author":"Mizumoto","year":"2012","journal-title":"Pediatr. Int."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.clnu.2012.09.004","article-title":"Enhanced Feeding in Very-Low-Birth-Weight Infants May Cause Electrolyte Disturbances and Septicemia\u2014A Randomized, Controlled Trial","volume":"32","author":"Moltu","year":"2013","journal-title":"Clin. Nutr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1515\/jpem-2011-0485","article-title":"Hypophosphatemia in Small for Gestational Age Extremely Low Birth Weight Infants Receiving Parenteral Nutrition in the First Week after Birth","volume":"25","author":"Ichikawa","year":"2012","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1002\/jpen.1934","article-title":"Neonatal Refeeding Syndrome and Clinical Outcome in Extremely Low-Birth-Weight Babies: Secondary Cohort Analysis from the ProVIDe Trial","volume":"45","author":"Cormack","year":"2021","journal-title":"JPEN J. Parenter. Enter. Nutr."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Peila, C., Spada, E., Giuliani, F., Maiocco, G., Raia, M., Cresi, F., Bertino, E., and Coscia, A. (2020). Extrauterine Growth Restriction: Definitions and Predictability of Outcomes in a Cohort of Very Low Birth Weight Infants or Preterm Neonates. Nutrients, 12.","DOI":"10.3390\/nu12051224"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1007\/s11894-008-0084-x","article-title":"A Roadmap for Understanding and Preventing Necrotizing Enterocolitis","volume":"10","author":"Neu","year":"2008","journal-title":"Curr. Gastroenterol. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s13052-021-00956-2","article-title":"Morbidity Associated with Patent Ductus Arteriosus in Preterm Newborns: A Retrospective Case-Control Study","volume":"47","author":"Terrin","year":"2021","journal-title":"Ital. J. Pediatr."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Eisenhut, M., and Choudhury, S. (2017). In Premature Newborns Intraventricular Hemorrhage Causes Cerebral Vasospasm and Associated Neurodisability via Heme-Induced Inflammasome-Mediated Interleukin-1 Production and Nitric Oxide Depletion. Front. Neurol., 8.","DOI":"10.3389\/fneur.2017.00423"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1111\/dmcn.15468","article-title":"Retinopathy of Prematurity","volume":"65","author":"Dammann","year":"2023","journal-title":"Dev. Med. Child Neurol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1164\/ajrccm.163.7.2011060","article-title":"Bronchopulmonary Dysplasia","volume":"163","author":"Jobe","year":"2001","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"9748031","DOI":"10.1155\/2017\/9748031","article-title":"Risk Factors for the Development of Refeeding Syndrome-Like Hypophosphatemia in Very Low Birth Weight Infants","volume":"2017","author":"Igarashi","year":"2017","journal-title":"Dis. Markers"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"S1222","DOI":"10.1016\/j.ajog.2022.07.001","article-title":"Umbilical Cord pH, Blood Gases, and Lactate at Birth: Normal Values, Interpretation, and Clinical Utility","volume":"228","author":"Olofsson","year":"2023","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"S99","DOI":"10.1016\/S0301-2115(03)00179-9","article-title":"Placental Insufficiency and Its Consequences","volume":"110","author":"Gagnon","year":"2003","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1111\/apa.13093","article-title":"Extremely Preterm Infants Who Are Small for Gestational Age Have a High Risk of Early Hypophosphatemia and Hypokalemia","volume":"104","author":"Boubred","year":"2015","journal-title":"Acta Paediatr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"841","DOI":"10.17219\/acem\/70081","article-title":"Early hypophosphatemia in very low birth weight preterm infants","volume":"27","year":"2018","journal-title":"Adv. Clin. Exp. Med."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Sung, S.I., Chang, Y.S., Choi, J.H., Ho, Y., Kim, J., Ahn, S.Y., and Park, W.S. (2019). Increased Risk of Refeeding Syndrome-like Hypophosphatemia with High Initial Amino Acid Intake in Small-for-Gestational-Age, Extremely-Low-Birthweight Infants. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0221042"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Boscarino, G., Di Chiara, M., Cellitti, R., De Nardo, M.C., Conti, M.G., Parisi, P., Spalice, A., Di Mario, C., Ronchi, B., and Russo, A. (2021). Effects of Early Energy Intake on Neonatal Cerebral Growth of Preterm Newborn: An Observational Study. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-98088-4"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1038\/ejcn.2011.79","article-title":"The effect of parenteral nitrogen and energy intake on electrolyte balance in the preterm infant","volume":"65","author":"Bonsante","year":"2011","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"jpen.2739","DOI":"10.1002\/jpen.2739","article-title":"Association between Early Phosphate Intake and Refeeding Syndrome in Extremely Low-birth-weight Infants: A Retrospective Cohort Study","volume":"2025","author":"Wright","year":"2025","journal-title":"J. Parenter. Enter. Nutr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1177\/0004563214523739","article-title":"Predicting Refeeding Hypophosphataemia: Insulin Growth Factor 1 (IGF-1) as a Diagnostic Biochemical Marker for Clinical Practice","volume":"52","author":"Goyale","year":"2015","journal-title":"Ann. Clin. Biochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e140363","DOI":"10.1172\/jci.insight.140363","article-title":"IGF1, Serum Glucose, and Retinopathy of Prematurity in Extremely Preterm Infants","volume":"5","author":"Cakir","year":"2020","journal-title":"JCI Insight"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1038\/s41390-024-03208-1","article-title":"Nutritional Interventions to Prevent Retinopathy of Prematurity","volume":"96","author":"Johnson","year":"2024","journal-title":"Pediatr. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1016\/j.survophthal.2023.06.010","article-title":"Insulin-like Growth Factor-1 and Retinopathy of Prematurity: A Systemic Review and Meta-Analysis","volume":"68","author":"Fu","year":"2023","journal-title":"Surv. Ophthalmol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"135287","DOI":"10.1155\/2014\/135287","article-title":"Disturbance of Inorganic Phosphate Metabolism in Diabetes Mellitus: Its Relevance to the Pathogenesis of Diabetic Retinopathy","volume":"2014","author":"Vorum","year":"2014","journal-title":"J. Ophthalmol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S0092-8674(05)80085-6","article-title":"Role of Insulin-like Growth Factors in Embryonic and Postnatal Growth","volume":"75","author":"Baker","year":"1993","journal-title":"Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1111\/jpc.13307","article-title":"Relationship between Insulin-like Growth Factor 1, Leptin and Ghrelin Levels and Catch-up Growth in Small for Gestational Age Infants of 27\u201331 Weeks during Neonatal Intensive Care Unit Admission","volume":"53","author":"Ohkawa","year":"2017","journal-title":"J. Paediatr. Child Health"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/9\/1417\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:20:02Z","timestamp":1760030402000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/9\/1417"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,23]]},"references-count":36,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["nu17091417"],"URL":"https:\/\/doi.org\/10.3390\/nu17091417","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,23]]}}}