{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T21:08:04Z","timestamp":1790024884458,"version":"4.0.1"},"reference-count":47,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T00:00:00Z","timestamp":1749168000000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Gestational diabetes mellitus (GDM) constitutes a significant health concern during pregnancy, warranting a thorough investigation into potential prognostic markers. Pregnancy\u2010associated plasma protein\u2010A (PAPP\u2010A), which is present at high levels during pregnancy, exhibits altered concentrations even before the clinical diagnosis of GDM, highlighting its potential as an early biomarker for this condition. This systematic review and meta\u2010analysis aimed to review and synthesize the latest evidence comprehensively to explore the correlation between maternal PAPP\u2010A levels and the development of GDM, drawing from the most recent publications available.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>PubMed, EMBASE, and Cochrane CENTRAL were searched systematically up to June 2, 2024. Cohort and case\u2010control studies reporting PAPP\u2010A levels in GDM and non\u2010GDM women with singleton pregnancy were eligible for inclusion. The quality of studies was measured using the Newcastle\u2010Ottawa scale (NOS). Standardized mean differences (SMDs) of PAPP\u2010A levels between GDM and non\u2010GDM, and odds ratios (ORs) of the association between PAPP\u2010A and GDM were pooled, with heterogeneity assessed using the Cochran Q test and <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup> statistic. Sensitivity analysis was employed (PROSPERO ID: CRD42024580169).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Nineteen studies involving 92 200 pregnant women were included in the systematic review and meta\u2010analysis. The gestational age at sampling varied from 10 to 14 weeks. Meta\u2010analysis revealed a significantly lower PAPP\u2010A level among women with GDM compared with those without (pooled SMD = \u22120.31, 95% CI: \u22120.56 to \u22120.06). Furthermore, meta\u2010analysis revealed that women with a low PAPP\u2010A level had a significantly higher risk of developing GDM (pooled OR = 1.75, 95% CI: 1.45\u20132.11). Despite observed publication bias, sensitivity analysis affirmed the robustness of the results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This updated systematic review and meta\u2010analysis underscored the prognostic significance of maternal PAPP\u2010A levels with respect to the development of GDM. Low PAPP\u2010A level is associated with an increased risk of GDM. These findings advocate for the inclusion of PAPP\u2010A assessment in the clinical evaluation of GDM risk.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aji.70087","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T08:04:43Z","timestamp":1749197083000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Prognostic Impact of Pregnancy\u2010Associated Plasma Protein\u2010A (PAPP\u2010A) for Gestational Diabetes Mellitus (GDM): An Updated Systematic Review and Meta\u2010Analysis of More Than 90 000 Pregnancies"],"prefix":"10.1111","volume":"93","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7371-0594","authenticated-orcid":false,"given":"Ing\u2010Luen","family":"Shyu","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology Chi Mei Medical Center  Tainan Taiwan"},{"name":"Institute of Biomedical Sciences, College of Medicine National Sun Yat\u2010sen University  Kaohsiung Taiwan"},{"name":"Department of Pharmacy Chia Nan University of Pharmacy and Science  Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yung\u2010Chieh","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Chi Mei Medical Center  Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian\u2010Ni","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Chi Mei Medical Center  Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yow\u2010Ling","family":"Shiue","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences, College of Medicine National Sun Yat\u2010sen University  Kaohsiung Taiwan"},{"name":"Institute of Precision Medicine, College of Medicine National Sun Yat\u2010sen University  Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,6]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph19052583"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.112183"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1159\/000371628"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22062965"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph17249517"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdi.13595"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc18-2021"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc18-1646"},{"key":"e_1_2_10_10_1","first-page":"1665","article-title":"Gestational Diabetes Mellitus: New Thinking on Diagnostic Criteria","volume":"14","author":"Luo J.","year":"2024","journal-title":"Life (Basel)"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/01443615.2022.2109951"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/medicina59020398"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/01443615.2019.1615041"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2017-00272"},{"key":"e_1_2_10_15_1","article-title":"First Trimester Serum Tests for Down's Syndrome Screening","volume":"2015","author":"Alldred S. 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