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      The haemodynamics of the human placenta in utero

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          Abstract

          We have used magnetic resonance imaging (MRI) to provide important new insights into the function of the human placenta in utero. We have measured slow net flow and high net oxygenation in the placenta in vivo, which are consistent with efficient delivery of oxygen from mother to fetus. Our experimental evidence substantiates previous hypotheses on the effects of spiral artery remodelling in utero and also indicates rapid venous drainage from the placenta, which is important because this outflow has been largely neglected in the past. Furthermore, beyond Braxton Hicks contractions, which involve the entire uterus, we have identified a new physiological phenomenon, the ‘utero-placental pump’, by which the placenta and underlying uterine wall contract independently of the rest of the uterus, expelling maternal blood from the intervillous space.

          Abstract

          MRI provides important new insights into the function of the human placenta, revealing slow net flow and high, uniform oxygenation in healthy pregnancies, detecting changes that will lead to compromised oxygen delivery to the fetus in preeclampsia, and identifying a new physiological phenomenon, the ‘utero-placental pump’.

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          Most cited references63

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          Rheological and Physiological Consequences of Conversion of the Maternal Spiral Arteries for Uteroplacental Blood Flow during Human Pregnancy

          Physiological conversion of the maternal spiral arteries is key to a successful human pregnancy. It involves loss of smooth muscle and the elastic lamina from the vessel wall as far as the inner third of the myometrium, and is associated with a 5–10-fold dilation at the vessel mouth. Failure of conversion accompanies common complications of pregnancy, such as early-onset preeclampsia and fetal growth restriction. Here, we model the effects of terminal dilation on inflow of blood into the placental intervillous space at term, using dimensions in the literature derived from three-dimensional reconstructions. We observe that dilation slows the rate of flow from 2 to 3 m/s in the non-dilated part of an artery of 0.4–0.5 mm diameter to approximately 10 cm/s at the 2.5 mm diameter mouth, depending on the exact radius and viscosity. This rate predicts a transit time through the intervillous space of approximately 25 s, which matches observed times closely. The model shows that in the absence of conversion blood will enter the intervillous space as a turbulent jet at rates of 1–2 m/s. We speculate that the high momentum will damage villous architecture, rupturing anchoring villi and creating echogenic cystic lesions as evidenced by ultrasound. The retention of smooth muscle will also increase the risk of spontaneous vasoconstriction and ischaemia–reperfusion injury, generating oxidative stress. Dilation has a surprisingly modest impact on total blood flow, and so we suggest the placental pathology associated with deficient conversion is dominated by rheological consequences rather than chronic hypoxia.
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            Quantitative imaging of intrinsic magnetic tissue properties using MRI signal phase: an approach to in vivo brain iron metabolism?

            Quantitative susceptibility mapping (QSM) based on gradient echo (GRE) magnetic resonance phase data is a novel technique for non-invasive assessment of magnetic tissue susceptibility differences. The method is expected to be an important means to determine iron distributions in vivo and may, thus, be instrumental for elucidating the physiological role of iron and disease-related iron concentration changes associated with various neurological and psychiatric disorders. This study introduces a framework for QSM and demonstrates calculation of reproducible and orientation-independent susceptibility maps from GRE data acquired at 3T. The potential of these susceptibility maps to perform anatomical imaging is investigated, as well as the ability to measure the venous blood oxygen saturation level in large vessels, and to assess the local tissue iron concentration. In order to take into account diamagnetic susceptibility contributions induced by myelin, a correction scheme for susceptibility based iron estimation is demonstrated. The findings suggest that susceptibility contrast, and therewith also phase contrast, are not only linked to the storage iron concentration but are also significantly influenced by other sources such as myelin. After myelin correction the linear dependence between magnetic susceptibilities and previously published iron concentrations from post mortem studies was significantly improved. Finally, a comparison between susceptibility maps and processed phase images indicated that caution should be exercised when drawing conclusions about iron concentrations when directly assessing processed phase information. Copyright © 2010 Elsevier Inc. All rights reserved.
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              The likeness of fetal growth and newborn size across non-isolated populations in the INTERGROWTH-21st Project: the Fetal Growth Longitudinal Study and Newborn Cross-Sectional Study.

              Large differences exist in size at birth and in rates of impaired fetal growth worldwide. The relative effects of nutrition, disease, the environment, and genetics on these differences are often debated. In clinical practice, various references are often used to assess fetal growth and newborn size across populations and ethnic origins, whereas international standards for assessing growth in infants and children have been established. In the INTERGROWTH-21(st) Project, our aim was to assess fetal growth and newborn size in eight geographically defined urban populations in which the health and nutrition needs of mothers were met and adequate antenatal care was provided. For this study, fetal growth and newborn size were measured in two INTERGROWTH-21(st) component studies using prespecified markers and the same methods, equipment, and selection criteria. In the Fetal Growth Longitudinal Study (FGLS), we studied educated, affluent, healthy women, with adequate nutritional status who were at low risk of intrauterine growth restriction. The primary markers of fetal growth were ultrasound measurements of fetal crown-rump length at less than 14 weeks and 0 days of gestation and fetal head circumference from 14 weeks and 0 days to 40 weeks and 0 days of gestation, and birthlength for newborn size. In the concomitant, population-based Newborn Cross-Sectional Study (NCSS), we measured birthlength in all newborn babies from the eight geographically defined urban populations with the same methods, instruments, and staff as in FGLS. From this large NCSS cohort, we selected an FGLS-like subpopulation to match FGLS with the same eligibility criteria. Between May 14, 2009, and Aug 2, 2013, we enrolled 4607 women in FGLS and 59 137 women in NCSS. From NCSS, 20 486 (34·6%) women met the FGLS eligibility criteria, and constituted the FGLS-like subpopulation. With variance component analysis, only between 1·9% and 3·5% of the total variability in crown-rump length, fetal head circumference, and newborn birthlength could be attributed to between-site differences. With standardised site effect analysis in 16 gestational age windows from 9 weeks and 0 days of gestation to birth for the three measures (128 comparisons), only one was marginally higher than 0·5 SD of the standardised site difference range. Sensitivity analyses, excluding individual populations in turn from the pooling of all-site centiles across gestational ages, showed no noticeable effect on the 3rd, 50th, and 97th centiles derived from the remaining populations. Our populations were consistent at birth with those in the WHO Multicentre Growth Reference Study (MGRS). The mean birthlength for term newborn babies in that study was 49·5 cm (SD 1·9), which was very similar to that in the FGLS cohort (49·4 cm [1·9]) and the NCSS derived FGLS-like subpopulation (49·3 cm [1·8]). Fetal growth and newborn length are similar across diverse geographical settings when mothers' nutritional and health needs are met, and environmental constraints on growth are low. The findings for birthlength are in strong agreement with those of the WHO MGRS. These results provide the conceptual frame to create international standards for growth from conception to newborn baby, which will extend the present infant to childhood WHO MGRS standards. Bill & Melinda Gates Foundation. Copyright © 2014 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                Role: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: MethodologyRole: SoftwareRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: MethodologyRole: SoftwareRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: InvestigationRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysisRole: Writing – review & editing
                Role: Funding acquisitionRole: MethodologyRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: SoftwareRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: Academic Editor
                Journal
                PLoS Biol
                PLoS Biol
                plos
                plosbiol
                PLoS Biology
                Public Library of Science (San Francisco, CA USA )
                1544-9173
                1545-7885
                28 May 2020
                May 2020
                28 May 2020
                : 18
                : 5
                : e3000676
                Affiliations
                [1 ] Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, United Kingdom
                [2 ] National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham, United Kingdom
                [3 ] Department of Child Health, Obstetrics and Gynaecology, School of Medicine, University of Nottingham, Nottingham, United Kingdom
                [4 ] School of Life Sciences, University of Nottingham, Nottingham, United Kingdom
                [5 ] Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, United Kingdom
                Osaka University, JAPAN
                Author notes

                The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0001-5483-1684
                http://orcid.org/0000-0002-8069-9821
                http://orcid.org/0000-0003-0793-0967
                http://orcid.org/0000-0002-9266-6808
                Article
                PBIOLOGY-D-20-00235
                10.1371/journal.pbio.3000676
                7255609
                32463837
                ba81f3dc-ee9a-4e0b-b95b-20709cb1cff6
                © 2020 Dellschaft et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 30 January 2020
                : 27 April 2020
                Page count
                Figures: 5, Tables: 0, Pages: 21
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100000071, National Institute of Child Health and Human Development;
                Award ID: 1U01HD087202-01
                Award Recipient :
                This work was funded by the Human Placenta Project NIH grant 1U01HD087202-01 (PAG, NWJ, and RB) and by the Medical Research Council [grant number MC_PC_13072] (PAG and RB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Developmental Biology
                Embryology
                Placenta
                Biology and Life Sciences
                Anatomy
                Reproductive System
                Placenta
                Medicine and Health Sciences
                Anatomy
                Reproductive System
                Placenta
                Biology and Life Sciences
                Anatomy
                Body Fluids
                Blood
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                Anatomy
                Body Fluids
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                Biology and Life Sciences
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                Body Fluids
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                Physiology
                Body Fluids
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                Women's Health
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                Pregnancy
                Medicine and Health Sciences
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                Diagnostic Medicine
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                Magnetic Resonance Imaging
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                Physical Sciences
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                Biology and Life Sciences
                Neuroscience
                Brain Mapping
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                Diffusion Weighted Imaging
                Medicine and Health Sciences
                Diagnostic Medicine
                Diagnostic Radiology
                Magnetic Resonance Imaging
                Brain Morphometry
                Diffusion Weighted Imaging
                Research and Analysis Methods
                Imaging Techniques
                Diagnostic Radiology
                Magnetic Resonance Imaging
                Brain Morphometry
                Diffusion Weighted Imaging
                Medicine and Health Sciences
                Radiology and Imaging
                Diagnostic Radiology
                Magnetic Resonance Imaging
                Brain Morphometry
                Diffusion Weighted Imaging
                Research and Analysis Methods
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                Neuroimaging
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                Custom metadata
                Data are available from the Sir Peter Mansfield Data Access Committee for researchers who meet the criteria for access to confidential data.

                Life sciences
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