{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T23:04:31Z","timestamp":1782169471151,"version":"3.54.5"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate the diagnostic accuracy of early pregnancy biomarkers for predicting gestational diabetes mellitus (GDM).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We searched PubMed, Web of Science, Embase, and Cochrane Library from inception to December 2024 (specific dates: PubMed January 1980-December 31, 2024; Web of Science January 1980-December 31, 2024; Embase January 1980-December 31, 2024; Cochrane Library 1996-December 31, 2024) for studies evaluating first or early second trimester biomarkers for GDM prediction. ClinicalTrials.gov was also searched for ongoing studies. Eligible studies included prospective cohort, case-control, or cross-sectional designs reporting diagnostic accuracy metrics. Quality assessment was performed using QUADAS-2. Meta-analyses were conducted for biomarkers evaluated in \u22653 studies using random-effects models. Sample size adequacy was assessed based on the number of GDM cases, with a minimum of 100 events considered necessary for reliable pooled estimates. Diagnostic accuracy was assessed through pooled sensitivity, specificity, diagnostic odds ratio (DOR), and area under the receiver operating characteristic curve (AUROC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Twelve studies with sample sizes ranging from 75 to 41, 786 participants were included. Only one study comprehensively evaluated inflammatory markers, reporting a first-trimester model combining TNF-\u03b1 with clinical parameters (maternal age, BMI, family history) and biochemical markers (fasting glucose, lipid profile). Pregnancy-associated plasma protein-A (PAPP-A) levels showed a trend toward lower values in women who developed GDM (SMD -0.558, 95% CI: -1.155 to 0.040). Metabolomic markers, particularly acylcarnitines C5 and C5:1, demonstrated excellent discrimination (AUROC 0.934, 95% CI: 0.873-0.995). The overall pooled sensitivity was 81.6% (95% CI: 68.7%-90.0%), specificity 93.4% (95% CI: 81.4%-97.9%), DOR 73.84 (95% CI: 5.65-964.94), and AUROC 0.881 (95% CI: 0.795-0.967). Substantial heterogeneity was observed across studies (I\u00b2=94-97%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Early pregnancy biomarkers show moderate to high diagnostic accuracy for GDM prediction. However, high heterogeneity and limited data on integrated multi-marker panels constrain clinical application. Standardization of protocols and validation in diverse populations are needed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1749694","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T05:19:15Z","timestamp":1774502355000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Early pregnancy biomarkers for gestational diabetes mellitus prediction: a systematic review and meta-analysis of routine laboratory, metabolic, and inflammatory markers"],"prefix":"10.3389","volume":"17","author":[{"given":"Wenhui","family":"Li","sequence":"first","affiliation":[{"name":"Research Center for High Altitude Medicine, Qinghai University","place":["Xining, China"]},{"name":"Qinghai Provincial Key Laboratory of Plateau Medical Application, Key Laboratory of Ministry of Education, Qinghai-Utah Joint Research Key Laboratory for High Altitude Medicine, Qinghai University","place":["Xining, China"]},{"name":"Department of Laboratory, The Fifth People\u2019s Hospital of Qinghai Province","place":["Xining, Qinghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengjuan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Laboratory, The Fifth People\u2019s Hospital of Qinghai Province","place":["Xining, Qinghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailin","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Laboratory, The Fifth People\u2019s Hospital of Qinghai Province","place":["Xining, Qinghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Tong","sequence":"additional","affiliation":[{"name":"Qinghai Provincial Key Laboratory of Traditional Chinese Medicine Research for Glucolipid Metabolic Diseases, Qinghai University","place":["Xining, Qinghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,26]]},"reference":[{"key":"B1","volume-title":"IDF Diabetes Atlas","year":"2021"},{"key":"B2","doi-asserted-by":"publisher","first-page":"107843","DOI":"10.1016\/j.diabres.2019.107843","article-title":"Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition","volume":"157","author":"Saeedi","year":"2019","journal-title":"Diabetes Res Clin Pract"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.2337\/db08-1112","article-title":"Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study: associations with neonatal anthropometrics","volume":"58","year":"2009","journal-title":"Diabetes"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60731-5","article-title":"Type 2 diabetes mellitus after gestational diabetes: a systematic review and meta-analysis","volume":"373","author":"Bellamy","year":"2009","journal-title":"Lancet"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-016-3985-5","article-title":"Gestational diabetes mellitus and long-term consequences for mother and offspring: a view from Denmark","volume":"59","author":"Damm","year":"2016","journal-title":"Diabetologia"},{"key":"B6","article-title":"ACOG Practice Bulletin No. 190: Gestational diabetes mellitus","volume":"131","year":"2018","journal-title":"Obstet Gynecol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2013.206920","article-title":"Diagnosis of gestational diabetes mellitus: it is time for international consensus","volume":"60","author":"Sacks","year":"2014","journal-title":"Clin Chem"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.2337\/dc18-1646","article-title":"Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (HAPO FUS): maternal gestational diabetes mellitus and childhood glucose metabolism","volume":"42","author":"Lowe","year":"2019","journal-title":"Diabetes Care"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.2337\/dc15-2672","article-title":"Heterogeneous contribution of insulin sensitivity and secretion defects to gestational diabetes mellitus","volume":"39","author":"Powe","year":"2016","journal-title":"Diabetes Care"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9378(99)70662-9","article-title":"Longitudinal changes in glucose metabolism during pregnancy in obese women with normal glucose tolerance and gestational diabetes mellitus","volume":"180","author":"Catalano","year":"1999","journal-title":"Am J Obstet Gynecol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"3342","DOI":"10.3390\/ijms19113342","article-title":"The pathophysiology of gestational diabetes mellitus","volume":"19","author":"Plows","year":"2018","journal-title":"Int J Mol Sci"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2015.04.006","article-title":"Inflammation in maternal obesity and gestational diabetes mellitus","volume":"36","author":"Pantham","year":"2015","journal-title":"Placenta"},{"key":"B13","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1007\/s11892-016-0715-9","article-title":"Impact of systemic inflammation on the progression of gestational diabetes mellitus","volume":"16","author":"Lekva","year":"2016","journal-title":"Curr Diabetes Rep"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.49.4.603","article-title":"Decreased insulin receptor tyrosine kinase activity and plasma cell membrane glycoprotein-1 overexpression in skeletal muscle from obese women with gestational diabetes mellitus (GDM): evidence for increased serine\/threonine phosphorylation in pregnancy and GDM","volume":"49","author":"Shao","year":"2000","journal-title":"Diabetes"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1126\/science.271.5249.665","article-title":"IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity-induced insulin resistance","volume":"271","author":"Hotamisligil","year":"1996","journal-title":"Science"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1001\/jama.286.3.327","article-title":"C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus","volume":"286","author":"Pradhan","year":"2001","journal-title":"JAMA"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.51.7.2207","article-title":"TNF-alpha is a predictor of insulin resistance in human pregnancy","volume":"51","author":"Kirwan","year":"2002","journal-title":"Diabetes"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1002\/pd.2733","article-title":"First trimester pregnancy-associated plasma protein-A in pregnancies complicated by subsequent gestational diabetes","volume":"31","author":"Beneventi","year":"2011","journal-title":"Prenat Diagn"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2012.08.033","article-title":"Noninvasive prenatal testing for fetal trisomies in a routinely screened first-trimester population","volume":"207","author":"Nicolaides","year":"2012","journal-title":"Am J Obstet Gynecol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2004.06.052","article-title":"First-trimester maternal serum PAPP-A and free-beta subunit human chorionic gonadotropin concentrations and nuchal translucency are associated with obstetric complications: a population-based screening study (the FASTER Trial)","volume":"191","author":"Dugoff","year":"2004","journal-title":"Am J Obstet Gynecol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2008.08.022","article-title":"Global placental gene expression in gestational diabetes mellitus","volume":"200","author":"Enquobahrie","year":"2009","journal-title":"Am J Obstet Gynecol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2006.06.094","article-title":"Intermediate metabolism in association with the amino acid profile during the third trimester of normal pregnancy and diet-controlled gestational diabetes","volume":"196","author":"Pappa","year":"2007","journal-title":"Am J Obstet Gynecol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.2337\/db15-1748","article-title":"Metabolic networks and metabolites underlie associations between maternal glucose during pregnancy and newborn size at birth","volume":"65","author":"Scholtens","year":"2016","journal-title":"Diabetes"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.2337\/dc16-2452","article-title":"Maternal BMI and glycemia impact the fetal metabolome","volume":"40","author":"Lowe","year":"2017","journal-title":"Diabetes Care"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.2337\/dc09-1848","article-title":"International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy","volume":"33","year":"2010","journal-title":"Diabetes Care"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.2337\/dc20-S002","article-title":"Classification and diagnosis of diabetes: standards of medical care in diabetes-2020","volume":"43","year":"2020","journal-title":"Diabetes Care"},{"key":"B27","doi-asserted-by":"publisher","first-page":"i4338","DOI":"10.1136\/bmj.i4338","article-title":"External validation of prognostic models to predict risk of gestational diabetes mellitus in one Dutch cohort: prospective multicentre cohort study","volume":"354","author":"Lamain-de Ruiter","year":"2016","journal-title":"BMJ"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpobgyn.2014.09.006","article-title":"The first trimester: prediction and prevention of the great obstetrical syndromes","volume":"29","author":"Sweeting","year":"2015","journal-title":"Best Pract Res Clin Obstet Gynaecol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"e16503","DOI":"10.2196\/16503","article-title":"Comparison of multivariable logistic regression and other machine learning algorithms for prognostic prediction studies in pregnancy care: systematic review and meta-analysis","volume":"8","author":"Sufriyana","year":"2020","journal-title":"JMIR Med Inform"},{"key":"B30","doi-asserted-by":"publisher","first-page":"66","DOI":"10.53070\/bbd.1350356","article-title":"Predicting Parkinson\u2019s disease progression: a noninvasive method leveraging voice inputs","volume":"8","author":"Hassan","year":"2023","journal-title":"Comput Sci"},{"key":"B31","article-title":"IoT-based smart wearable belt for tracking fetal kicks and movements in expectant mothers","author":"Ahmad","year":"2025","journal-title":"IEEE Sens J"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.47852\/bonviewAIA52024517","article-title":"Preterm birth prediction using an explainable machine learning approach","author":"Hassan","year":"2025","journal-title":"Artif Intell Appl"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.2337\/dc11-1643","article-title":"Screening for gestational diabetes mellitus: are the criteria proposed by the International Association of the Diabetes and Pregnancy Study Groups cost-effective","volume":"35","author":"Werner","year":"2012","journal-title":"Diabetes Care"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2012.06.048","article-title":"Gestational diabetes screening with the new IADPSG guidelines: a cost-effectiveness analysis","volume":"207","author":"Mission","year":"2012","journal-title":"Am J Obstet Gynecol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s44196-025-00760-4","article-title":"Enhanced model for gestational diabetes mellitus prediction using a fusion technique of multiple algorithms with explainability","volume":"18","author":"Hassan","year":"2025","journal-title":"Int J Comput Intell Syst"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3109\/14767058.2013.765845","article-title":"The cost-effectiveness of gestational diabetes screening including prevention: application of a new model in India and Israel","volume":"26","author":"Marseille","year":"2013","journal-title":"J Matern Fetal Neonatal Med"},{"key":"B37","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-155-8-201110180-00009","article-title":"QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies","volume":"155","author":"Whiting","year":"2011","journal-title":"Ann Intern Med"},{"key":"B39","doi-asserted-by":"publisher","first-page":"d549","DOI":"10.1136\/bmj.d549","article-title":"Interpretation of random effects meta-analyses","volume":"342","author":"Riley","year":"2011","journal-title":"BMJ"},{"key":"B40","unstructured":"Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy. Version 2.0\n          \n          2025"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2005.02.022","article-title":"Bivariate analysis of sensitivity and specificity produces informative summary measures in diagnostic reviews","volume":"58","author":"Reitsma","year":"2005","journal-title":"J Clin Epidemiol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2013.04.002","article-title":"Gestational diabetes mellitus: including serum pregnancy-associated plasma protein-A testing in the clinical management of primiparous women? A case-control study","volume":"100","author":"Lovati","year":"2013","journal-title":"Diabetes Res Clin Pract"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1186","DOI":"10.3390\/ijms20051186","article-title":"Urinary metabolites altered during the third trimester in pregnancies complicated by gestational diabetes mellitus: relationship with potential upcoming metabolic disorders","volume":"20","author":"L\u00f3pez-Hern\u00e1ndez","year":"2019","journal-title":"Int J Mol Sci"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1007\/s11596-014-1289-x","article-title":"Relationship between tyrosine phosphorylation and protein expression of insulin receptor and insulin resistance in gestational diabetes mellitus","volume":"34","author":"Chu","year":"2014","journal-title":"J Huazhong Univ Sci Technol Med Sci"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2006-0980","article-title":"Modulation of adipokines and cytokines in gestational diabetes and macrosomia","volume":"91","author":"At\u00e8gbo","year":"2006","journal-title":"J Clin Endocrinol Metab"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.dsx.2018.12.023","article-title":"Augmentation of IL-6 production contributes to development of gestational diabetes mellitus: an Indian study","volume":"13","author":"Siddiqui","year":"2019","journal-title":"Diabetes Metab Syndr Clin Res Rev"},{"key":"B47","doi-asserted-by":"publisher","first-page":"4168340","DOI":"10.1155\/2020\/4168340","article-title":"Comparison of machine learning methods and conventional logistic regressions for predicting gestational diabetes using routine clinical data: a retrospective cohort study","volume":"2020","author":"Ye","year":"2020","journal-title":"J Diabetes Res"},{"key":"B48","doi-asserted-by":"publisher","first-page":"287","DOI":"10.3390\/medicina59020287","article-title":"The role of lifestyle interventions in the prevention and treatment of gestational diabetes mellitus","volume":"59","author":"Zakaria","year":"2023","journal-title":"Med (Kaunas)"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2018.03.058","article-title":"Risk of gestational diabetes mellitus in relation to plasma concentrations of amino acids and acylcarnitines: a nested case-control study","volume":"140","author":"Roy","year":"2018","journal-title":"Diabetes Res Clin Pract"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1900\/RDS.2016.13.236","article-title":"First-trimester maternal serum amino acids and acylcarnitines are significant predictors of gestational diabetes","volume":"13","author":"Nevalainen","year":"2016","journal-title":"Rev Diabetes Stud"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.2337\/db17-1150","article-title":"Elevated medium-chain acylcarnitines are associated with gestational diabetes mellitus and early progression to type 2 diabetes and induce pancreatic beta-cell dysfunction","volume":"67","author":"Batchuluun","year":"2018","journal-title":"Diabetes"},{"key":"B52","doi-asserted-by":"publisher","first-page":"7038","DOI":"10.3390\/jcm12227038","article-title":"Effectiveness of lifestyle interventions during pregnancy on preventing gestational diabetes mellitus in high-risk women: a systematic review and meta-analyses of published RCTs","volume":"12","author":"Tsironikos","year":"2023","journal-title":"J Clin Med"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1749694\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T05:19:19Z","timestamp":1774502359000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1749694\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,26]]},"references-count":52,"alternative-id":["10.3389\/fendo.2026.1749694"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2026.1749694","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,26]]},"article-number":"1749694"}}