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Women with pre-eclampsia, the hypertensive disease of pregnancy, have been reported as having changes in some individual antioxidant trace elements during pregnancy, which are related to maternal and fetal mortality and morbidity. We hypothesised that examination of the three compartments of (a) maternal plasma and urine, (b) placental tissue and (c) fetal plasma in normotensive and hypertensive pregnant women would allow identification of biologically significant changes and interactions in selenium, zinc, manganese and copper. Furthermore, these would be related to changes in the angiogenic markers, placental growth factor (PlGF) and Soluble Fms-Like Tyrosine Kinase-1 (sFlt-1) concentrations. Venous plasma and urine were collected from healthy non-pregnant women (n = 30), normotensive pregnant controls (n = 60) and women with pre-eclampsia (n = 50) in the third trimester. Where possible, matched placental tissue samples and umbilical venous (fetal) plasma were also collected. Antioxidant micronutrient concentrations were measured by inductively coupled plasma mass-spectrometry. Urinary levels were normalised to creatinine concentration. Plasma active PlGF and sFlt-1 concentrations were measured by ELISA. Maternal plasma selenium, zinc and manganese were all lower in women with pre-eclampsia (p &lt; 0.05), as were fetal plasma selenium and manganese (p &lt; 0.05 for all); maternal urinary concentrations were lower for selenium and zinc (p &lt; 0.05). Conversely, maternal and fetal plasma and urinary copper concentrations were higher in women with pre-eclampsia (p &lt; 0.05). Differences in placental concentrations varied, with lower overall levels of selenium and zinc (p &lt; 0.05) in women with pre-eclampsia. Maternal and fetal PlGF were lower and sFlt-1 higher in women with pre-eclampsia; maternal plasma zinc was positively correlated with maternal plasma sFlt-1 (p &lt; 0.05). Because of perceptions that early- and late-onset pre-eclampsia have differing aetiologies, we subdivided maternal and fetal data accordingly. No major differences were observed, but fetal sample sizes were small following early-onset. Disruption in these antioxidant micronutrients may be responsible for some of the manifestations of pre-eclampsia, including contributing to an antiangiogenic state. The potential benefits of mineral supplementation, in women with deficient intakes, during pregnancy to reduce pre-eclampsia remain an important area for experimental and clinical research.<\/jats:p>","DOI":"10.3390\/ijms24043579","type":"journal-article","created":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T05:51:06Z","timestamp":1676008266000},"page":"3579","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Alterations in Antioxidant Micronutrient Concentrations in Placental Tissue, Maternal Blood and Urine and the Fetal Circulation in Pre-eclampsia"],"prefix":"10.3390","volume":"24","author":[{"given":"Lesia O.","family":"Kurlak","sequence":"first","affiliation":[{"name":"School of Medicine (Stroke Research), University of Nottingham, Nottingham NG7 2UH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula J.","family":"Scaife","sequence":"additional","affiliation":[{"name":"Clinical, Metabolic and Molecular Physiology Research Group, University of Nottingham, Derby DE22 3DT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9711-3057","authenticated-orcid":false,"given":"Louise V.","family":"Briggs","sequence":"additional","affiliation":[{"name":"School of Engineering, University of Nottingham, Nottingham NG7 2RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6209-5987","authenticated-orcid":false,"given":"Fiona","family":"Broughton Pipkin","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynaecology, University of Nottingham, Nottingham NG5 1PB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6490-2412","authenticated-orcid":false,"given":"David S.","family":"Gardner","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine and Science, University of Nottingham, Loughborough LE12 5RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2564-7348","authenticated-orcid":false,"given":"Hiten D.","family":"Mistry","sequence":"additional","affiliation":[{"name":"Department of Women and Children\u2019s Health, School of Life Course and Population Sciences, King\u2019s College London, London SE1 1UL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.preghy.2021.09.008","article-title":"The hypertensive disorders of pregnancy: The 2021 International Society for the Study of Hypertension in Pregnancy classification, diagnosis and management recommendations for international practice","volume":"27","author":"Magee","year":"2021","journal-title":"Pregnancy Hypertens."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/S0140-6736(10)60279-6","article-title":"Pre-eclampsia","volume":"376","author":"Steegers","year":"2010","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1097\/AOG.0000000000000696","article-title":"Risk of fetal death with preeclampsia","volume":"125","author":"Harmon","year":"2015","journal-title":"Obstet. 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