{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T20:38:01Z","timestamp":1764794281286,"version":"build-2065373602"},"reference-count":19,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T00:00:00Z","timestamp":1644364800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["#1065854","#116071","#20000732","#1159261","#1146128","#1136418","#1176922"],"award-info":[{"award-number":["#1065854","#116071","#20000732","#1159261","#1146128","#1136418","#1176922"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Fetal growth restriction (FGR), when undetected antenatally, is the biggest risk factor for preventable stillbirth. Maternal circulating SPINT1 is reduced in pregnancies, which ultimately deliver small for gestational age (SGA) infants at term (birthweight &lt; 10th centile), compared to appropriate for gestational age (AGA) infants (birthweight \u2265 10th centile). SPINT1 is also reduced in FGR diagnosed before 34 weeks\u2019 gestation. We hypothesised that circulating SPINT1 would be decreased in co-existing preterm preeclampsia and FGR. Plasma SPINT1 was measured in samples obtained from two double-blind, randomised therapeutic trials. In the Preeclampsia Intervention with Esomeprazole trial, circulating SPINT1 was decreased in women with preeclampsia who delivered SGA infants (n = 75, median = 18,857 pg\/mL, IQR 10,782\u201329,890 pg\/mL, p &lt; 0.0001), relative to those delivering AGA (n = 22, median = 40,168 pg\/mL, IQR 22,342\u201375,172 pg\/mL). This was confirmed in the Preeclampsia Intervention 2 with metformin trial where levels of SPINT1 in maternal circulation were reduced in SGA pregnancies (n = 95, median = 57,764 pg\/mL, IQR 42,212\u201391,356 pg\/mL, p &lt; 0.0001) compared to AGA controls (n = 40, median = 107,062 pg\/mL, IQR 70,183\u2013176,532 pg\/mL). Placental Growth Factor (PlGF) and sFlt-1 were also measured. PlGF was significantly reduced in the SGA pregnancies, while ratios of sFlt-1\/SPINT1 and sFlt1\/PlGF were significantly increased. This is the first study to demonstrate significantly reduced SPINT1 in co-existing FGR and preeclamptic pregnancies.<\/jats:p>","DOI":"10.3390\/jcm11040901","type":"journal-article","created":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T21:22:15Z","timestamp":1644441735000},"page":"901","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Circulating SPINT1 Is Reduced in a Preeclamptic Cohort with Co-Existing Fetal Growth Restriction"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6996-7250","authenticated-orcid":false,"given":"Ciara N.","family":"Murphy","sequence":"first","affiliation":[{"name":"Department of Obstetrics & Gynaecology, Mercy Hospital for Women, The University of Melbourne, Heidelberg, VIC 3084, Australia"},{"name":"Mercy Perinatal, Mercy Hospital for Women, Heidelberg, VIC 3084, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0406-8964","authenticated-orcid":false,"given":"Catherine A.","family":"Cluver","sequence":"additional","affiliation":[{"name":"Mercy Perinatal, Mercy Hospital for Women, Heidelberg, VIC 3084, Australia"},{"name":"Department of Obstetrics & Gynaecology, Stellenbosch University and Tygerberg Hospital, Cape Town 7505, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan P.","family":"Walker","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynaecology, Mercy Hospital for Women, The University of Melbourne, Heidelberg, VIC 3084, Australia"},{"name":"Mercy Perinatal, Mercy Hospital for Women, Heidelberg, VIC 3084, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1966-2293","authenticated-orcid":false,"given":"Emerson","family":"Keenan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynaecology, Mercy Hospital for Women, The University of Melbourne, Heidelberg, VIC 3084, Australia"},{"name":"Mercy Perinatal, Mercy Hospital for Women, Heidelberg, VIC 3084, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roxanne","family":"Hastie","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynaecology, Mercy Hospital for Women, The University of Melbourne, Heidelberg, VIC 3084, Australia"},{"name":"Mercy Perinatal, Mercy Hospital for Women, Heidelberg, VIC 3084, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9099-7745","authenticated-orcid":false,"given":"Teresa M.","family":"MacDonald","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynaecology, Mercy Hospital for Women, The University of Melbourne, Heidelberg, VIC 3084, Australia"},{"name":"Mercy Perinatal, Mercy Hospital for Women, Heidelberg, VIC 3084, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalie J.","family":"Hannan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynaecology, Mercy Hospital for Women, The University of Melbourne, Heidelberg, VIC 3084, Australia"},{"name":"Mercy Perinatal, Mercy Hospital for Women, Heidelberg, VIC 3084, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fiona C.","family":"Brownfoot","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynaecology, Mercy Hospital for Women, The University of Melbourne, Heidelberg, VIC 3084, Australia"},{"name":"Mercy Perinatal, Mercy Hospital for Women, Heidelberg, VIC 3084, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Cannon","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynaecology, Mercy Hospital for Women, The University of Melbourne, Heidelberg, VIC 3084, Australia"},{"name":"Mercy Perinatal, Mercy Hospital for Women, Heidelberg, VIC 3084, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynaecology, Mercy Hospital for Women, The University of Melbourne, Heidelberg, VIC 3084, Australia"},{"name":"Mercy Perinatal, Mercy Hospital for Women, Heidelberg, VIC 3084, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tu\u2019uhevaha J.","family":"Kaitu\u2019u-Lino","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynaecology, Mercy Hospital for Women, The University of Melbourne, Heidelberg, VIC 3084, Australia"},{"name":"Mercy Perinatal, Mercy Hospital for Women, Heidelberg, VIC 3084, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"f108","DOI":"10.1136\/bmj.f108","article-title":"Maternal and fetal risk factors for stillbirth: Population based study","volume":"346","author":"Gardosi","year":"2013","journal-title":"BMJ"},{"key":"ref_2","first-page":"Cd008136","article-title":"Symphysial fundal height (SFH) measurement in pregnancy for detecting abnormal fetal growth","volume":"2015","author":"Peter","year":"2015","journal-title":"Cochrane Database Syst. 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