{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T07:58:21Z","timestamp":1767772701407,"version":"build-2238731810"},"reference-count":52,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2018,5,3]],"date-time":"2018-05-03T00:00:00Z","timestamp":1525305600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["PG\/11\/11\/28725"],"award-info":[{"award-number":["PG\/11\/11\/28725"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Cell free hemoglobin impairs vascular function and blood flow in adult cardiovascular disease. In this study, we investigated the hypothesis that free fetal hemoglobin (fHbF) compromises vascular integrity and function in the fetoplacental circulation, contributing to the increased vascular resistance associated with fetal growth restriction (FGR). Women with normal and FGR pregnancies were recruited and their placentas collected freshly postpartum. FGR fetal capillaries showed evidence of erythrocyte vascular pac\u03baing and extravasation. Fetal cord blood fHbF levels were higher in FGR than in normal pregnancies (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.05) and the elevation of fHbF in relation to heme oxygenase\u20101 suggests a failure of expected catabolic compensation, which occurs in adults. During\n                    <jats:italic>ex vivo<\/jats:italic>\n                    placental perfusion, pathophysiological fHbF concentrations significantly increased fetal\u2010side microcirculatory resistance (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.05). fHbF sequestered NO in acute and chronic exposure models (\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.001), and fHbF\u2010primed placental endothelial cells developed a proinflammatory phenotype, demonstrated by activation of NF\u2010\u03baB pathway, generation of IL\u20101\u00e4 and TNF\u2010\u00e4 (both\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.05), uncontrolled angiogenesis, and disruption of endothelial cell flow alignment. Elevated fHbF contributes to increased fetoplacental vascular resistance and impaired endothelial protection. This unrecognized mechanism for fetal compromise offers a novel insight into FGR as well as a potential explanation for associated poor fetal outcomes such as fetal demise and stillbirth.\u2014Broo\u03ba, A., Hoa\u03basey, A., Gurung, R., Yoong, E. E. C., Sneyd, R., Baynes, G. C., Bischof, H., Jones, S., Higgins, L. E., Jones, C., Greenwood, S. L., Jones, R. L., Gram, M., Lang, I., Desoye, G., Myers, J., Schneider, H., Hansson, S. R., Croc\u03baer, I. P., Brownbill, P. Cell free hemoglobin in the fetoplacental circulation: a novel cause of fetal growth restriction?\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    32, 5436\u20135446 (2018).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"htp:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201800264r","type":"journal-article","created":{"date-parts":[[2018,5,3]],"date-time":"2018-05-03T15:59:01Z","timestamp":1525363141000},"page":"5436-5446","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Cell free hemoglobin in the fetoplacental circulation: a novel cause of fetal growth restriction?"],"prefix":"10.1096","volume":"32","author":[{"given":"Adam","family":"Brook","sequence":"first","affiliation":[{"name":"Maternal and Fetal Health Research Centre Division of Developmental Biology and Medicine School of Medical Sciences, Faculty of Biology, Medicine, and Health, University of Manchester Manchester United Kingdom"},{"name":"St. Mary's Hospital, Manchester University National Health Service (NHS) Foundation Trust Manchester Academic Health Science Centre Manchester United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annie","family":"Hoaksey","sequence":"additional","affiliation":[{"name":"Maternal and Fetal Health Research Centre Division of Developmental Biology and Medicine School of Medical Sciences, Faculty of Biology, Medicine, and Health, University of Manchester Manchester United Kingdom"},{"name":"St. Mary's Hospital, Manchester University National Health Service (NHS) Foundation Trust Manchester Academic Health Science Centre Manchester United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rekha","family":"Gurung","sequence":"additional","affiliation":[{"name":"Maternal and Fetal Health Research Centre Division of Developmental Biology and Medicine School of Medical Sciences, Faculty of Biology, Medicine, and Health, University of Manchester Manchester United Kingdom"},{"name":"St. Mary's Hospital, Manchester University National Health Service (NHS) Foundation Trust Manchester Academic Health Science Centre Manchester United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward E. 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