{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T20:18:30Z","timestamp":1778098710996,"version":"3.51.4"},"reference-count":36,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,3,18]],"date-time":"2023-03-18T00:00:00Z","timestamp":1679097600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005366","name":"Universitetet i Oslo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005366","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Obstet Gynecol Scand"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Transplacental fetal cell transfer results in the engraftment of fetal\u2010origin cells in the pregnant woman's body, a phenomenon termed fetal microchimerism. Increased fetal microchimerism measured decades postpartum is implicated in maternal inflammatory disease. Understanding which factors cause increased fetal microchimerism is therefore important. During pregnancy, circulating fetal microchimerism and placental dysfunction increase with increasing gestational age, particularly towards term. Placental dysfunction is reflected by changes in circulating placenta\u2010associated markers, specifically placental growth factor (PlGF), decreased by several 100\u2009pg\/mL, soluble fms\u2010like tyrosine kinase\u20101 (sFlt\u20101), increased by several 1000\u2009pg\/mL, and the sFlt\u20101\/PlGF ratio, increased by several 10 (pg\/mL)\/(pg\/mL). We investigated whether such alterations in placenta\u2010associated markers correlate with an increase in circulating fetal\u2010origin cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and methods<\/jats:title><jats:p>We included 118 normotensive, clinically uncomplicated pregnancies (gestational age 37+1 up to 42+2\u2009weeks\u2018 gestation) pre\u2010delivery. PlGF and sFlt\u20101 (pg\/mL) were measured by Elecsys\u00ae Immunoassays. We extracted DNA from maternal and fetal samples and genotyped four human leukocyte antigen loci and 17 other autosomal loci. Paternally inherited, unique fetal alleles served as polymerase chain reaction (PCR) targets for detecting fetal\u2010origin cells in maternal buffy coat. Fetal\u2010origin cell prevalence was assessed by logistic regression, and quantity by negative binomial regression. Statistical exposures included gestational age (weeks), PlGF (100 pg\/mL), sFlt\u20101 (1000\u2009pg\/mL) and the sFlt\u20101\/PlGF ratio (10 (pg\/mL)\/(pg\/mL)). Regression models were adjusted for clinical confounders and PCR\u2010related competing exposures.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Gestational age was positively correlated with fetal\u2010origin cell quantity (DRR = 2.2, <jats:italic>P<\/jats:italic> = 0.003) and PlGF was negatively correlated with fetal\u2010origin cell prevalence (odds ratio [OR]<jats:sub>100<\/jats:sub> = 0.6, <jats:italic>P<\/jats:italic> = 0.003) and quantity (DRR<jats:sub>100<\/jats:sub> = 0.7, <jats:italic>P<\/jats:italic> = 0.001). The sFlt\u20101 and the sFlt\u20101\/PlGF ratios were positively correlated with fetal\u2010origin cell prevalence (OR<jats:sub>1000<\/jats:sub> = 1.3, <jats:italic>P<\/jats:italic> = 0.014 and OR<jats:sub>10<\/jats:sub> = 1.2, <jats:italic>P<\/jats:italic> = 0.038, respectively), but not quantity (DRR<jats:sub>1000<\/jats:sub> = 1.1, <jats:italic>P<\/jats:italic> = 0.600; DRR<jats:sub>10<\/jats:sub> = 1.1, <jats:italic>P<\/jats:italic> = 0.112, respectively).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results suggest that placental dysfunction as evidenced by placenta\u2010associated marker changes, may increase fetal cell transfer. The magnitudes of change tested were based on ranges in PlGF, sFlt\u20101 and the sFlt\u20101\/PlGF ratio previously demonstrated in pregnancies near and post\u2010term, lending clinical significance to our findings. Our results were statistically significant after adjusting for confounders including gestational age, supporting our novel hypothesis that underlying placental dysfunction potentially is a driver of increased fetal microchimerism.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aogs.14547","type":"journal-article","created":{"date-parts":[[2023,3,18]],"date-time":"2023-03-18T15:43:20Z","timestamp":1679154200000},"page":"690-698","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Markers of placental function correlate with prevalence and quantity of nucleated fetal cells in maternal circulation in normotensive term pregnancies"],"prefix":"10.1111","volume":"102","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8538-3922","authenticated-orcid":false,"given":"Heidi E.","family":"Fjeldstad","sequence":"first","affiliation":[{"name":"Faculty of Medicine University of Oslo  Oslo Norway"},{"name":"Division of Obstetrics and Gynecology Oslo University Hospital  Oslo Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3229-6830","authenticated-orcid":false,"given":"Daniel P.","family":"Jacobsen","sequence":"additional","affiliation":[{"name":"Division of Obstetrics and Gynecology Oslo University Hospital  Oslo Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guro M.","family":"Johnsen","sequence":"additional","affiliation":[{"name":"Faculty of Medicine University of Oslo  Oslo Norway"},{"name":"Division of Obstetrics and Gynecology Oslo University Hospital  Oslo Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4160-3978","authenticated-orcid":false,"given":"Meryam","family":"Sugulle","sequence":"additional","affiliation":[{"name":"Faculty of Medicine University of Oslo  Oslo Norway"},{"name":"Division of Obstetrics and Gynecology Oslo University Hospital  Oslo Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9305-7510","authenticated-orcid":false,"given":"Angel","family":"Chae","sequence":"additional","affiliation":[{"name":"Clinical Research Division, Fred Hutchinson Cancer Research Center  Seattle Washington USA"},{"name":"Department of Obstetrics and Gynecology Research Division University of Washington  Washington Seattle USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4608-0953","authenticated-orcid":false,"given":"Sami B.","family":"Kanaan","sequence":"additional","affiliation":[{"name":"Clinical Research Division, Fred Hutchinson Cancer Research Center  Seattle Washington USA"},{"name":"Chimerocyte, Inc.  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