{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T13:18:09Z","timestamp":1775481489240,"version":"3.50.1"},"reference-count":58,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T00:00:00Z","timestamp":1739923200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000325","name":"Wellbeing of Women","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000325","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011102","name":"Seventh Framework Programme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011102","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BJOG"],"published-print":{"date-parts":[[2026,2]]},"abstract":"ABSTRACT<\/jats:title>\n \n Objective<\/jats:title>\n To assess fetal circulating free fetal haemoglobin (fHbF) levels and heme defences, correlated to fetal circulatory biometry and fetal sex in severe early\u2010onset fetal growth restriction (FGR).<\/jats:p>\n <\/jats:sec>\n \n Design, Setting and Population<\/jats:title>\n \n A prospective study severe early\u2010onset fetal growth restriction pregnancies with close clinical management (estimated fetal weight (EFW) <\u20093rd centile and <\u2009600\u2009g at 20\u201326\u2009+\u20096\u2009weeks;\n N<\/jats:italic>\n \u2009=\u200920).\n <\/jats:p>\n <\/jats:sec>\n \n Method & Main Outcome Measures<\/jats:title>\n \n Temporal fetal vascular obstetric biometry was recorded. Cord blood fHbF and key heme\u2010scavenger defences were measured and compared with normal term births (\n N<\/jats:italic>\n \u2009=\u200926) and births with late\u2010onset FGR (\n N<\/jats:italic>\n \u2009=\u200912).\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n fHbF was elevated in early\u2010onset FGR compared with normal pregnancy: 0.437(0.337\/0.753) mg\/mL; and 0.098 (0.045\/0.264) mg\/mL, respectively (\n p<\/jats:italic>\n \u2009<\u20090.0001); whilst hemopexin was downregulated in early\u2010 (\n p<\/jats:italic>\n \u2009<\u20090.001) and late\u2010onset FGR (\n p<\/jats:italic>\n \u2009<\u20090.0001), compared to normal pregnancy: 36(14\/81) \u03bcg\/mL, 25(19\/40) \u03bcg\/mL, and 155(132\/219) \u03bcg\/mL, respectively; median (interquartile ranges). Early\u2010onset FGR male fetuses had higher HbF compared with the normal males: 0.710(0.433\/0.857) mg\/mL; (\n p<\/jats:italic>\n \u2009<\u20090.001); 0.099(0.043\/0.246) mg\/mL, respectively; median (interquartile ranges). In early\u2010onset FGR, ratios of mid\u2010cerebral artery and umbilical artery pulsatility indices correlated positively with heme\u2010scavenger levels (hemopexin and a heme\u2010handling composite measure:\n p<\/jats:italic>\n \u2009<\u20090.05,\n r<\/jats:italic>\n \u2009=\u20090.672; and\n p<\/jats:italic>\n \u2009<\u20090.01,\n r<\/jats:italic>\n \u2009=\u20090.620; respectively), indicating lower levels are associated with cerebral vascular redistribution. These heme handling measures also positively correlated with gestational age at delivery (\n r<\/jats:italic>\n \u2009=\u20090.713 and\n r<\/jats:italic>\n \u2009=\u20090.642, respectively,\n p<\/jats:italic>\n \u2009<\u20090.01, both) and birthweight (\n r<\/jats:italic>\n \u2009=\u20090.742,\n p<\/jats:italic>\n \u2009<\u20090.001; and\n r<\/jats:italic>\n \u2009=\u20090.523,\n p<\/jats:italic>\n \u2009<\u20090.05; respectively).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Overproduction of fHbF and an inadequate heme defence may contribute to fetal distress and poor umbilical arterial Dopplers in early onset FGR due to elevated placental vascular resistance and vascular inflammation.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/1471-0528.18104","type":"journal-article","created":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T22:55:21Z","timestamp":1740005721000},"page":"401-411","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Free Fetal Haemoglobin in Severe Early\u2010Onset Fetal Growth Restriction: A Prospective Multi\u2010Centre Study"],"prefix":"10.1111","volume":"133","author":[{"given":"Adam","family":"Brook","sequence":"first","affiliation":[{"name":"Maternal and Fetal Health Research Centre University of Manchester Manchester UK"},{"name":"Manchester Academic Health Sciences Centre Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0659-3851","authenticated-orcid":false,"given":"Georgia","family":"Baynes","sequence":"additional","affiliation":[{"name":"Maternal and Fetal Health Research Centre University of Manchester Manchester 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