{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T12:53:20Z","timestamp":1769000000911,"version":"3.49.0"},"reference-count":54,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,1,24]],"date-time":"2024-01-24T00:00:00Z","timestamp":1706054400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Alzchem GmbH"},{"name":"Danone Nutricia Research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>(1) Background: The aim of the present paper was to study fetal and infant creatine (Cr) supply to improve nutrition and neuroprotection in term and especially in preterm infants. The primary outcomes were the placental Cr flux at the end of pregnancy and the time course of human milk (HM) Cr. (2) Methods: The estimation of placental Cr flux was based on umbilical arterial and venous cord blood Cr in 10 term infants after elective caesarian section. HM Cr, creatinine (Crn), and macronutrients were measured longitudinally in 10 mothers across the first 6 months of breastfeeding. (3) Results: At the end of pregnancy, the mean fetal Cr flux was negative (\u22122.07 mmol\/min). HM Cr was highest in colostrum, decreased significantly within the first 2 weeks of breastfeeding (p &lt; 0.05), and did not change significantly thereafter. HM Cr was not correlated with HM Crn or macronutrient composition. (4) Conclusions: The present data suggest that fetal endogenous Cr synthesis covers the needs at the end of pregnancy. However, high colostrum Cr and HM Cr levels, independent of macronutrient composition, suggest that there may be a critical Cr demand immediately after birth that needs to be covered by enteral supply.<\/jats:p>","DOI":"10.3390\/nu16030345","type":"journal-article","created":{"date-parts":[[2024,1,25]],"date-time":"2024-01-25T03:59:42Z","timestamp":1706155182000},"page":"345","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The Umbilical Cord Creatine Flux and Time Course of Human Milk Creatine across Lactation"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0152-9830","authenticated-orcid":false,"given":"Walter Alexander","family":"Mihatsch","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Ulm University, 89075 Ulm, Germany"},{"name":"Department of Health Management, Neu-Ulm University of Applied Sciences, 89231 Neu-Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8898-7107","authenticated-orcid":false,"given":"Bernd","family":"Stahl","sequence":"additional","affiliation":[{"name":"Danone Nutricia Research, 3584 CT Utrecht, The Netherlands"},{"name":"Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CT Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrike","family":"Braun","sequence":"additional","affiliation":[{"name":"Alzchem Trostberg GmbH, 83308 Trostberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,24]]},"reference":[{"key":"ref_1","unstructured":"National Library of Medicine (US) (2006). Creatine, National Library of Medicine (US)."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"11881","DOI":"10.1021\/acs.jafc.8b04031","article-title":"Chemistry of Human Breast Milk-A Comprehensive Review of the Composition and Role of Milk Metabolites in Child Development","volume":"66","author":"Garwolinska","year":"2018","journal-title":"J. Agric. Food Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1152\/physrev.2000.80.3.1107","article-title":"Creatine and creatinine metabolism","volume":"80","author":"Wyss","year":"2000","journal-title":"Physiol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1002\/9780470122952.ch4","article-title":"Creatine: Biosynthesis, regulation, and function","volume":"50","author":"Walker","year":"1979","journal-title":"Adv. Enzymol. Relat. Areas Mol. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.advenzreg.2006.12.005","article-title":"New insights into creatine function and synthesis","volume":"47","author":"Brosnan","year":"2007","journal-title":"Adv. Enzym. Regul."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1016\/j.jpeds.2006.01.043","article-title":"Arginine:glycine amidinotransferase (AGAT) deficiency in a newborn: Early treatment can prevent phenotypic expression of the disease","volume":"148","author":"Battini","year":"2006","journal-title":"J. Pediatr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1007\/s00726-011-0852-z","article-title":"Creatine deficiency syndromes and the importance of creatine synthesis in the brain","volume":"40","author":"Braissant","year":"2011","journal-title":"Amino Acids"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.pediatrneurol.2009.07.015","article-title":"Creatine and creatine deficiency syndromes: Biochemical and clinical aspects","volume":"42","author":"Nasrallah","year":"2010","journal-title":"Pediatr. Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1017\/S000711451300010X","article-title":"Creatine and guanidinoacetate content of human milk and infant formulas: Implications for creatine deficiency syndromes and amino acid metabolism","volume":"110","author":"Edison","year":"2013","journal-title":"Br. J. Nutr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1007\/s00726-016-2188-1","article-title":"The role of dietary creatine","volume":"48","author":"Brosnan","year":"2016","journal-title":"Amino Acids"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1016\/S0024-3205(01)01268-1","article-title":"Changes of tissue creatine concentrations upon oral supplementation of creatine-monohydrate in various animal species","volume":"69","author":"Ipsiroglu","year":"2001","journal-title":"Life Sci."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Kaviani, M., Shaw, K., and Chilibeck, P.D. (2020). Benefits of Creatine Supplementation for Vegetarians Compared to Omnivorous Athletes: A Systematic Review. Int. J. Environ. Res. Public Health, 17.","DOI":"10.3390\/ijerph17093041"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"268","DOI":"10.2165\/00007256-199418040-00005","article-title":"Creatine in humans with special reference to creatine supplementation","volume":"18","author":"Balsom","year":"1994","journal-title":"Sport. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1002\/mrm.21068","article-title":"Intake of 13C-4 creatine enables simultaneous assessment of creatine and phosphocreatine pools in human skeletal muscle by 13C MR spectroscopy","volume":"56","author":"Kan","year":"2006","journal-title":"Magn. Reason. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1203\/00006450-199409000-00023","article-title":"Creatine deficiency in the brain: A new, treatable inborn error of metabolism","volume":"36","author":"Stockler","year":"1994","journal-title":"Pediatr. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1086\/320595","article-title":"X-linked creatine-transporter gene (SLC6A8) defect: A new creatine-deficiency syndrome","volume":"68","author":"Salomons","year":"2001","journal-title":"Am. J. Hum. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1006\/mgme.2001.3257","article-title":"Improving treatment of guanidinoacetate methyltransferase deficiency: Reduction of guanidinoacetic acid in body fluids by arginine restriction and ornithine supplementation","volume":"74","author":"Schulze","year":"2001","journal-title":"Mol. Genet. Metab."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1080\/026404102317200855","article-title":"Absorption of creatine supplied as a drink, in meat or in solid form","volume":"20","author":"Harris","year":"2002","journal-title":"J. Sport. Sci."},{"key":"ref_19","first-page":"292","article-title":"Administration of creatine and creatinine with breast milk and infant milk preparations","volume":"199","author":"Hulsemann","year":"1987","journal-title":"Klin. Padiatr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1698","DOI":"10.3945\/jn.115.210252","article-title":"Infant Maturity at Birth Reveals Minor Differences in the Maternal Milk Metabolome in the First Month of Lactation","volume":"145","author":"Spevacek","year":"2015","journal-title":"J. Nutr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1016\/j.bbrc.2015.11.114","article-title":"NMR-based metabolite profiling of human milk: A pilot study of methods for investigating compositional changes during lactation","volume":"469","author":"Wu","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_22","unstructured":"(2023, May 05). Creatine Disorders Panel CRDPP. Available online: https:\/\/www.mayocliniclabs.com\/api\/sitecore\/TestCatalog\/DownloadTestCatalog?testId=606130."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.3945\/jn.110.125476","article-title":"Suckling rat pups accumulate creatine primarily via de novo synthesis rather than from dam milk","volume":"140","author":"Lamarre","year":"2010","journal-title":"J. Nutr."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Ireland, Z., Russell, A.P., Wallimann, T., Walker, D.W., and Snow, R. (2009). Developmental changes in the expression of creatine synthesizing enzymes and creatine transporter in a precocial rodent, the spiny mouse. BMC Dev. Biol., 9.","DOI":"10.1186\/1471-213X-9-39"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1515\/jpem-2012-0293","article-title":"Arginine-guanidinoacetate-creatine pathway in preterm newborns: Creatine biosynthesis in newborns","volume":"26","author":"Lage","year":"2013","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Muccini, A.M., Tran, N.T., de Guingand, D.L., Philip, M., Della Gatta, P.A., Galinsky, R., Sherman, L.S., Kelleher, M.A., Palmer, K.R., and Berry, M.J. (2021). Creatine Metabolism in Female Reproduction, Pregnancy and Newborn Health. Nutrients, 13.","DOI":"10.3390\/nu13020490"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Tran, N.T., Kelly, S.B., Snow, R.J., Walker, D.W., Ellery, S.J., and Galinsky, R. (2021). Assessing Creatine Supplementation for Neuroprotection against Perinatal Hypoxic-Ischaemic Encephalopathy: A Systematic Review of Perinatal and Adult Pre-Clinical Studies. Cells, 10.","DOI":"10.3390\/cells10112902"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3193","DOI":"10.1113\/JP282840","article-title":"Creatine supplementation reduces the cerebral oxidative and metabolic stress responses to acute in utero hypoxia in the late-gestation fetal sheep","volume":"600","author":"Tran","year":"2022","journal-title":"J. Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3013","DOI":"10.1113\/JP283330","article-title":"Back to the beginning: Can we stop brain injury before it starts?","volume":"600","author":"Davidson","year":"2022","journal-title":"J. Physiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"992120","DOI":"10.3389\/fnut.2022.992120","article-title":"The role of nutrients in human neurodevelopment and their potential to prevent neurodevelopmental adversity","volume":"9","author":"Heland","year":"2022","journal-title":"Front. Nutr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/S0009-8981(01)00480-6","article-title":"Analysis of guanidinoacetate and creatine by isotope dilution electrospray tandem mass spectrometry","volume":"308","author":"Bodamer","year":"2001","journal-title":"Clin. Chim. Acta"},{"key":"ref_32","first-page":"505ff","article-title":"Creatine","volume":"Volume II","author":"Bergmeyer","year":"1985","journal-title":"Methoden der Enzymatischen Analysen"},{"key":"ref_33","first-page":"391","article-title":"Ueber den Niederschlag, welchen Pikrinsaeure in normalem Harn erzeugt und \u00fcber eine neue Reaction des Kreatinins","volume":"10","author":"Jaffe","year":"1886","journal-title":"Z. F\u00fcr Physiol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1002\/uog.2832","article-title":"Fetal cardiac output, distribution to the placenta and impact of placental compromise","volume":"28","author":"Kiserud","year":"2006","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1111\/j.1651-2227.2008.01042.x","article-title":"Bedside analysis of human milk for adjustable nutrition strategy","volume":"98","author":"Menjo","year":"2009","journal-title":"Acta Paediatr."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.clp.2016.11.001","article-title":"\u201cBed Side\u201d Human Milk Analysis in the Neonatal Intensive Care Unit: A Systematic Review","volume":"44","author":"Fusch","year":"2017","journal-title":"Clin. Perinatol."},{"key":"ref_37","unstructured":"Bakdash, J., and Marusich, L. (2023, May 05). Available online: https:\/\/CRAN.R-project.org\/package=rmcorr."},{"key":"ref_38","unstructured":"Lentner, C. (1992). Geigy Scientific Tables, Medical Education Division, Ciba-Geigy Corp.. [8th ed.]."},{"key":"ref_39","first-page":"193","article-title":"Serum creatinine concentrations in healthy newborns: Reference ranges during the first five days of life","volume":"36","author":"Andresen","year":"1988","journal-title":"Henry Ford. Hosp. Med. J."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Gidrewicz, D.A., and Fenton, T.R. (2014). A systematic review and meta-analysis of the nutrient content of preterm and term breast milk. BMC Pediatr., 14.","DOI":"10.1186\/1471-2431-14-216"},{"key":"ref_41","first-page":"121","article-title":"Transport of Nutrients in the Early Human Placenta: Amino Acid, Creatine, Vitamin B12","volume":"Volume 1","author":"Miller","year":"1984","journal-title":"Fetal Nutrition, Metabolism, and Immunology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.placenta.2017.02.020","article-title":"Creatine biosynthesis and transport by the term human placenta","volume":"52","author":"Ellery","year":"2017","journal-title":"Placenta"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/0024-3205(75)90205-2","article-title":"Mechanisms of transport across the placenta: An in vitro approach","volume":"16","author":"Miller","year":"1975","journal-title":"Life Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"E75","DOI":"10.1152\/ajpendo.00450.2016","article-title":"Does maternal-fetal transfer of creatine occur in pregnant sheep?","volume":"313","author":"Baharom","year":"2017","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1159\/000241050","article-title":"Materno-fetal transport of creatine in the rat","volume":"33","author":"Davis","year":"1978","journal-title":"Biol. Neonate"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1093\/molehr\/gaz039","article-title":"Placental creatine metabolism in cases of placental insufficiency and reduced fetal growth","volume":"25","author":"Ellery","year":"2019","journal-title":"Mol. Hum. Reprod."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Braissant, O., Henry, H., Villard, A.M., Speer, O., Wallimann, T., and Bachmann, C. (2005). Creatine synthesis and transport during rat embryogenesis: Spatiotemporal expression of AGAT, GAMT and CT1. BMC Dev. Biol., 5.","DOI":"10.1186\/1471-213X-5-9"},{"key":"ref_48","first-page":"9","article-title":"The Biology and Husbandry of the African Spiny Mouse (Acomys cahirinus) and the Research Uses of a Laboratory Colony","volume":"55","author":"Haughton","year":"2016","journal-title":"J. Am. Assoc. Lab. Anim. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1093\/ajcn\/40.3.635","article-title":"Studies on human lactation. I. Within-feed and between-breast variation in selected components of human milk","volume":"40","author":"Neville","year":"1984","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1159\/000014189","article-title":"Changes in body composition during the initial hours of life in breast-fed healthy term newborns","volume":"77","author":"Rodriguez","year":"2000","journal-title":"Biol. Neonate"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1159\/000239767","article-title":"Neonatal period: Body composition changes in breast-fed full-term newborns","volume":"97","author":"Roggero","year":"2010","journal-title":"Neonatology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e13382","DOI":"10.14814\/phy2.13382","article-title":"Hypoxia decreases creatine uptake in cardiomyocytes, while creatine supplementation enhances HIF activation","volume":"5","author":"Santacruz","year":"2017","journal-title":"Physiol. Rep."},{"key":"ref_53","first-page":"409","article-title":"No cry at birth: Global estimates of intrapartum stillbirths and intrapartum-related neonatal deaths","volume":"83","author":"Lawn","year":"2005","journal-title":"Bull. World Health Organ."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"142","DOI":"10.3389\/fphys.2019.00142","article-title":"UNICORN Babies: Understanding Circulating and Cerebral Creatine Levels of the Preterm Infant. An Observational Study Protocol","volume":"10","author":"Berry","year":"2019","journal-title":"Front. Physiol."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/3\/345\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:48:49Z","timestamp":1760104129000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/3\/345"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,24]]},"references-count":54,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,2]]}},"alternative-id":["nu16030345"],"URL":"https:\/\/doi.org\/10.3390\/nu16030345","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,24]]}}}