{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T10:03:26Z","timestamp":1784801006559,"version":"3.55.0"},"reference-count":16,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"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: Total parenteral nutrition (TPN) is essential for neonates unable to receive adequate enteral feeding, but its long-term metabolic effects remain uncertain. This study evaluated associations between neonatal TPN exposure, exposure duration, and later endocrinologic or metabolic disorders. Methods: This nationwide cohort included 2,424,716 infants born in South Korea between 2005 and 2010. TPN exposure was identified during the first 28 days of life. The primary outcome was the first occurrence of type 2 diabetes mellitus (T2DM), essential hypertension, dyslipidemia, or obesity during follow-up of up to 18 years. The primary analysis used inverse probability of treatment-weighted (IPTW) Cox models, whereas duration-based associations were evaluated using secondary exploratory multivariable Cox regression. Results: The final cohort included 2,303,567 infants, of whom 7656 received TPN. In the primary IPTW analysis, any neonatal TPN exposure was not associated with either the primary composite outcome (HR 1.01, 95% CI 0.94\u20131.09; p = 0.801) or T2DM (HR 1.12, 95% CI 0.93\u20131.35; p = 0.215). In secondary exploratory multivariable analyses, TPN exposure for \u22653 days was associated with T2DM (adjusted HR 2.14, 95% CI 1.34\u20133.41; p = 0.001), whereas exposure for 1\u20132 days was not. Conclusions: The primary IPTW analysis showed no significant association between any neonatal TPN exposure and the primary composite outcome or T2DM. The association observed for \u22653 days in secondary exploratory analyses should be regarded as hypothesis-generating.<\/jats:p>","DOI":"10.3390\/nu18152406","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T09:11:26Z","timestamp":1784797886000},"page":"2406","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neonatal Total Parenteral Nutrition and Long-Term Metabolic Outcomes: An 18-Year Nationwide Cohort Study of 2.3 Million Infants"],"prefix":"10.3390","volume":"18","author":[{"given":"Tak Kyu","family":"Oh","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea"},{"name":"Department of Anesthesiology and Pain Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In-Ae","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea"},{"name":"Department of Anesthesiology and Pain Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Chen, C.Y., Lai, M.Y., Lee, C.H., and Chiang, M.C. (2025). Nutritional Management for Preterm Infants with Common Comorbidities: A Narrative Review. Nutrients, 17.","DOI":"10.3390\/nu17121959"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2315","DOI":"10.1016\/j.clnu.2018.06.945","article-title":"ESPGHAN\/ESPEN\/ESPR\/CSPEN guidelines on pediatric parenteral nutrition: Amino acids","volume":"37","author":"Carnielli","year":"2018","journal-title":"Clin. Nutr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1136\/bmj.301.6761.1111","article-title":"The fetal and infant origins of adult disease","volume":"301","author":"Barker","year":"1990","journal-title":"BMJ"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1056\/NEJMra0708473","article-title":"Effect of in utero and early-life conditions on adult health and disease","volume":"359","author":"Gluckman","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1152\/physrev.00029.2013","article-title":"Early developmental conditioning of later health and disease: Physiology or pathophysiology?","volume":"94","author":"Hanson","year":"2014","journal-title":"Physiol. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"517","DOI":"10.3390\/nu7010517","article-title":"Nutritionally-induced catch-up growth","volume":"7","author":"Phillip","year":"2015","journal-title":"Nutrients"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1203\/PDR.0b013e3181ebb541","article-title":"Neonatal exposure to oxidants induces later in life a metabolic response associated to a phenotype of energy deficiency in an animal model of total parenteral nutrition","volume":"68","author":"Kleiber","year":"2010","journal-title":"Pediatr. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1210\/jcem-63-2-492","article-title":"Incretin effects of increasing glucose loads in man calculated from venous insulin and C-peptide responses","volume":"63","author":"Nauck","year":"1986","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3353","DOI":"10.1016\/j.tjnut.2024.08.031","article-title":"Feeding Parenteral Nutrition in the Neonatal Period Programs Dyslipidemia in Adulthood in Yucatan Miniature Pigs","volume":"154","author":"Randunu","year":"2024","journal-title":"J. Nutr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"105076","DOI":"10.1155\/2011\/105076","article-title":"Early-life origins of type 2 diabetes: Fetal programming of the beta-cell mass","volume":"2011","author":"Portha","year":"2011","journal-title":"Exp. Diabetes Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/S2352-4642(20)30104-8","article-title":"Long-term developmental effect of withholding parenteral nutrition in paediatric intensive care units: A 4-year follow-up of the PEPaNIC randomised controlled trial","volume":"4","author":"Jacobs","year":"2020","journal-title":"Lancet Child Adolesc. Health"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1203\/01.PDR.0000148284.58934.1C","article-title":"Altered adiposity after extremely preterm birth","volume":"57","author":"Uthaya","year":"2005","journal-title":"Pediatr. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1016\/S0140-6736(07)61602-X","article-title":"The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: Guidelines for reporting observational studies","volume":"370","author":"Altman","year":"2007","journal-title":"Lancet"},{"key":"ref_14","first-page":"e15","article-title":"Cohort profile: The national health insurance service\u2013national sample cohort (NHIS-NSC), South Korea","volume":"46","author":"Lee","year":"2017","journal-title":"Int. J. Epidemiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2837","DOI":"10.1002\/sim.5705","article-title":"The performance of different propensity score methods for estimating marginal hazard ratios","volume":"32","author":"Austin","year":"2013","journal-title":"Stat. Med."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Hamasaki, A., Harada, N., Muraoka, A., Yamane, S., Joo, E., Suzuki, K., and Inagaki, N. (2024). The integrated incretin effect is reduced by both glucose intolerance and obesity in Japanese subjects. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1301352"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/15\/2406\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T09:26:57Z","timestamp":1784798817000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/15\/2406"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,23]]},"references-count":16,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["nu18152406"],"URL":"https:\/\/doi.org\/10.3390\/nu18152406","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,23]]}}}