{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T05:06:33Z","timestamp":1780635993479,"version":"3.54.1"},"reference-count":58,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CUHK HOPE BWCH Collaborative Medical Research Fund","award":["CF2025002"],"award-info":[{"award-number":["CF2025002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Fetal growth restriction (FGR) is a leading cause of perinatal morbidity and mortality, yet reliable first-trimester biomarkers for early prediction remain lacking. Growing evidence suggests that placental dysfunction is a central pathological driver of FGR. Therefore, placenta-derived proteins in maternal circulation may serve as mechanistically informative biomarkers for early detection. Here, we aimed to evaluate several placenta-relevant molecules as biomarkers for predicting isolated FGR and its subtypes. In this prospective nested case\u2013control study, we included singleton pregnancies that underwent Down screening in the first trimester and were subsequently diagnosed with FGR (n = 50, including early-onset FGR [EFGR] and late-onset FGR [LFGR]) and healthy pregnancies (n = 100). Pregnancies with maternal comorbidities or fetal anomalies were excluded. Maternal serum protein concentrations were measured using ELISA kits. There were no significant differences in placenta-specific protein 1 (PLAC1) or netrin-1 between the two groups. By contrast, maternal soluble programmed death-ligand 1 (sPD-L1) levels were significantly lower in overall FGR (p &lt; 0.001) and FGR subtypes (p = 0.002) than in controls. Circulating sPD-L1 levels were positively correlated with gestational age at delivery and birth weight Z score. Each one-unit increase in sPD-L1 was associated with lower odds of overall FGR (Odd ratio, OR 0.33), EFGR (OR 0.17), LFGR (OR 0.43), birth weight Z score 3\u201310% (OR 0.30), and neonatal intensive care unit (NICU) admission (OR 0.38). Moreover, first-trimester sPD-L1 predicted overall FGR (area under the receiver operating characteristic curve, AUC 0.75), EFGR (AUC 0.84), LFGR (AUC 0.70), birth weight Z score 3\u201310% (AUC 0.75), and NICU admission (AUC 0.67). Collectively, decreased maternal circulating sPD-L1 in early pregnancy may serve as a potential biomarker for isolated FGR, warranting validation in larger multicenter mechanistic studies.<\/jats:p>","DOI":"10.3390\/ijms27115037","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T14:38:42Z","timestamp":1780411122000},"page":"5037","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Serum sPD-L1 Levels in Early Pregnancy Predict Fetal Growth Restriction and Its Subtypes: A Prospective Nested Case\u2013Control Study"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0010-2819","authenticated-orcid":false,"given":"Yao","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China"},{"name":"Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruqun","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyi","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maran Bo Wah","family":"Leung","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7963-4708","authenticated-orcid":false,"given":"Lai Kwan","family":"Lam","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3928-7278","authenticated-orcid":false,"given":"Chi Chiu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China"},{"name":"Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9153-0343","authenticated-orcid":false,"given":"Tak Yeung","family":"Leung","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China"},{"name":"Hub of Obstetrics and Paediatric Excellence (HOPE), The Chinese University of Hong Kong, Hong Kong SAR, China"},{"name":"The Chinese University of Hong Kong-Baylor College of Medicine Joint Centre for Medical Genetics, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1007\/s00404-017-4341-9","article-title":"Fetal growth restriction: Current knowledge","volume":"295","author":"Nardozza","year":"2017","journal-title":"Arch. 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