{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T06:34:56Z","timestamp":1791527696588,"version":"4.3.4"},"reference-count":89,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T00:00:00Z","timestamp":1740700800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T00:00:00Z","timestamp":1740700800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Growth Differentiation Factor 15 (GDF15), a nonspecific inflammatory marker and member of the TGF\u2010\u03b2 superfamily, has a well\u2010established role in both inflammation and metabolic modulation, but lacks a comprehensive paediatric literature review. In several adult disease states, including cancer cachexia and pregnancy, circulation and expression of GDF15 has been of clinical and scientific interest, but little published paediatric data exists. As such, we aim to summarize existing paediatric studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This review follows the PRISMA\u2010ScR guidelines for reporting and aims to summarize existing paediatric studies including GDF15, describe disease entities in which GDF15 has been investigated including existing reference ranges, and identify literature gaps to present future clinical and research direction. Our search strategy queried Ovid MEDLINE, Ovid Embase, Cochrane Library and Scopus databases to find original scientific articles measuring GDF15 from birth through children up to age 18. Data relating to study participant demographic and disease pathology, GDF15 measurement methods and clinical outcomes of interest were extracted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Sixty\u2010two studies were included, classified as cardiac, endocrine, mitochondrial, hematologic, neonatal, oncologic, infectious, rheumatologic, renal, neurologic or healthy. While several entities demonstrated elevated GDF15, the highest median GDF15 levels were observed in cardiac arrest 7089\u2009pg\/mL (interquartile range 3805\u201313\u2009306) and mitochondrial diseases 4640\u2009pg\/mL (1896\u201314\u2009064). In certain conditions, including cardiac stress, polycystic ovarian syndrome (PCOS), Kawasaki Disease (KD) and certain mitochondrial myopathies GDF15 can normalize with disease treatment or resolution. Of healthy children studied, GDF15 levels were highest in healthy neonates and followed a predictable pattern, decreasing over time. Mean and standard deviation values of GDF15 in healthy children were 343.8\u2009\u00b1\u2009221.0\u2009pg\/mL, with a range of 90\u20131134\u2009pg\/mL for study averages.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Circulating GDF15 has been studied in a variety of paediatric diseases. However, variable evaluated outcome measures and GDF15 measurement methodologies prevent generalizability and direct comparison of these published studies. Validating normal GDF15 levels in children with standardized and reproducible methodology will help clarify GDF15's utility as a diagnostic marker of disease, a necessary step to elucidate clinical implications of GDF15 over expression and its potential as a therapeutic target.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.13712","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T01:28:39Z","timestamp":1741742919000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Circulating Growth Differentiation Factor 15 (GDF15) in Paediatric Disease: A Systematic Review"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3191-2227","authenticated-orcid":false,"given":"David\u00a0W.","family":"Kronenberger","sequence":"first","affiliation":[{"name":"Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa\u00a0A.","family":"Zimmers","sequence":"additional","affiliation":[{"name":"Department of Cell, Developmental, and Cancer Biology, Knight Cancer Institute Oregon Health &amp; Science University  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rick\u00a0K.","family":"Ralston","sequence":"additional","affiliation":[{"name":"Ruth Lilly Medical Library Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1018-9914","authenticated-orcid":false,"given":"Daniel\u00a0V.","family":"Runco","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Pediatrics, Seattle Children's Hospital University of Washington  Seattle Washington USA"},{"name":"Ben Towne Center for Childhood Cancer Research Seattle Children's Research Institute  Seattle Washington USA"},{"name":"Fred Hutchinson Cancer Research Center  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,28]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-4781(97)00122-X"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.21.11514"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.10.3742-3751.2000"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.07.018"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac888"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2021.11.002"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-020-02459-1"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1260419"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPH.0000000000000491"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00951"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2022.12.011"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.3c00667"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.13219"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/jalm\/jfac055"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jrsm.1429"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1177\/0962280216669183"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2288-14-135"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1177\/09622802231172043"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.13105\/wjma.v3.i5.215"},{"key":"e_1_2_10_21_1","first-page":"8096","article-title":"Diagnostic Value of Growth Differentiation Factor\u201015 and \u03b22\u2010Microglobulin in Children With Congenital Heart Disease Combined With Chronic Heart Failure and Its Relationship With Cardiac Function","volume":"22","author":"Zhou X. 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