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Chapter 23 - Fetal Growth Restriction: Placental Basis and Implications for Clinical Practice

from Fetal Growth and Well-being

Published online by Cambridge University Press:  21 October 2019

Mark D. Kilby
Affiliation:
University of Birmingham
Anthony Johnson
Affiliation:
University of Texas Medical School at Houston
Dick Oepkes
Affiliation:
Leids Universitair Medisch Centrum
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Summary

Advances in obstetrical ultrasound technology, combined with newer magnetic resonance imaging (MRI) methods, cell-free fetal DNA testing in maternal blood, and comprehensive molecular testing of the fetus, have greatly improved prenatal diagnostic capabilities in the context of fetal growth restriction (FGR) as shown in Chapter 24. Increased understanding and use of these resources means the likelihood of recognizing a fetal basis for FGR before birth, and managing it accordingly, will increase. The presumption of a placental basis for FGR dominates everyday clinical practice, yet paradoxically at present the application of current knowledge of what constitutes true ‘placental insufficiency’ has not translated into improved maternal care and perinatal outcomes. As an example, 33% of 650 women recruited to the landmark DIGITAT (Disproportionate Intrauterine Growth Intervention Trial at Term) trial had no postnatal evidence of FGR (defined as birth weight <10th percentile) [1]. Since obstetricians manage suspected FGR prior to delivery, they fear a risk of antepartum stillbirth and deploy frequent short-term tests of fetal well-being (biophysical profile, Doppler ultrasound, and non-stress tests), even via hospital admission, in the absence of any objective placental diagnosis. Fortunately, recent advances in the understanding of the placental basis of FGR have led to much-improved precision in both screening for the disease [2, 3] and in the prenatal diagnosis of the placental basis of FGR [4]. This chapter is designed to equip obstetricians, midwives and maternal–fetal medicine sub-specialists with key concepts in placental development and pathology that directly contribute to the care of women with suspected FGR pregnancies.

Type
Chapter
Information
Fetal Therapy
Scientific Basis and Critical Appraisal of Clinical Benefits
, pp. 248 - 263
Publisher: Cambridge University Press
Print publication year: 2020

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References

Boers, KE, Vijgen, SM, Bijlenga, D, van der Post, JA, Bekedam, DJ, Kwee, A, et al. Induction versus expectant monitoring for intrauterine growth restriction at term: randomised equivalence trial (DIGITAT). BMJ. 2010; 341: c7087.Google Scholar
Audette, MC, Kingdom, JC. Screening for fetal growth restriction and placental insufficiency. Semin Fetal Neonatal Med. 2018; 23: 119–25.CrossRefGoogle ScholarPubMed
Gaccioli, F, Aye, I, Sovio, U, Charnock-Jones, DS, Smith, GCS. Screening for fetal growth restriction using fetal biometry combined with maternal biomarkers. Am J Obstet Gynecol. 2018; 218: S725–37.Google Scholar
Kingdom, JC, Audette, MC, Hobson, SR, Windrim, RC, Morgen, E. A placenta clinic approach to the diagnosis and management of fetal growth restriction. Am J Obstet Gynecol. 2018; 218: S803–17.Google Scholar
Jackson, MR, Walsh, AJ, Morrow, RJ, Mullen, JB, Lye, SJ, Ritchie, JW. Reduced placental villous tree elaboration in small-for-gestational-age pregnancies: relationship with umbilical artery Doppler waveforms. Am J Obstet Gynecol. 1995; 172: 518–25.Google Scholar
Robson, SC, Simpson, H, Ball, E, Lyall, F, Bulmer, JN. Punch biopsy of the human placental bed. Am J Obstet Gynecol. 2002; 187: 1349–55.Google Scholar
Burton, GJ. Oxygen, the Janus gas; its effects on human placental development and function. J Anat. 2009; 215: 2735.Google Scholar
Burton, GJ, Watson, AL, Hempstock, J, Skepper, JN, Jauniaux, E. Uterine glands provide histiotrophic nutrition for the human fetus during the first trimester of pregnancy. J Clin Endocrinol Metab. 2002; 87: 2954–9.Google Scholar
Burton, GJ, Jauniaux, E, Watson, AL. Maternal arterial connections to the placental intervillous space during the first trimester of human pregnancy: the Boyd collection revisited. Am J Obstet Gynecol. 1999; 181: 718–24.CrossRefGoogle Scholar
Burton, GJ, Hempstock, J, Jauniaux, E. Oxygen, early embryonic metabolism and free radical-mediated embryopathies. Reprod Biomed Online. 2003; 6: 8496.Google Scholar
Jauniaux, E, Hempstock, J, Greenwold, N, Burton, GJ. Trophoblastic oxidative stress in relation to temporal and regional differences in maternal placental blood flow in normal and abnormal early pregnancies. Am J Pathol. 2003; 162: 115–25.Google Scholar
Kaufmann, P, Black, S, Huppertz, B. Endovascular trophoblast invasion: implications for the pathogenesis of intrauterine growth retardation and preeclampsia. Biol Reprod. 2003; 69: 17.Google Scholar
Burton, GJ, Jauniaux, E, Charnock-Jones, DS. The influence of the intrauterine environment on human placental development. Int J Dev Biol. 2010; 54: 303–12.Google Scholar
Nordenvall, M, Ullberg, U, Laurin, J, Lingman, G, Sandstedt, B, Ulmsten, U. Placental morphology in relation to umbilical artery blood velocity waveforms. Eur J Obstet Gynecol Reprod Biol. 1991; 40: 179–90.Google Scholar
Proctor, LK, Toal, M, Keating, S, Chitayat, D, Okun, N, Windrim, RC, et al. Placental size and the prediction of severe early-onset intrauterine growth restriction in women with low pregnancy-associated plasma protein-A. Ultrasound Obstet Gynecol. 2009; 34: 274–82.Google Scholar
Wright, E, Audette, MC, Ye, XY, Keating, S, Hoffman, B, Lye, SJ, et al. Maternal vascular malperfusion and adverse perinatal outcomes in low-risk nulliparous women. Obstet Gynecol. 2017; 130: 1112–20.Google Scholar
Dunk, C, Smith, S, Hazan, A, Whittle, W, Jones, RL. Promotion of angiogenesis by human endometrial lymphocytes. Immunol Invest. 2008; 37: 583610.Google Scholar
Kadyrov, M, Kingdom, JC, Huppertz, B. Divergent trophoblast invasion and apoptosis in placental bed spiral arteries from pregnancies complicated by maternal anemia and early-onset preeclampsia/intrauterine growth restriction. Am J Obstet Gynecol. 2006; 194: 557–63.Google Scholar
Burton, GJ, Woods, AW, Jauniaux, E, Kingdom, JC. Rheological and physiological consequences of conversion of the maternal spiral arteries for uteroplacental blood flow during human pregnancy. Placenta. 2009; 30: 473–82.Google Scholar
Nanaev, A, Chwalisz, K, Frank, HG, Kohnen, G, Hegele-Hartung, C, Kaufmann, P. Physiological dilation of uteroplacental arteries in the guinea pig depends on nitric oxide synthase activity of extravillous trophoblast. Cell Tissue Res. 1995; 282: 407–21.Google Scholar
Lyall, F, Barber, A, Myatt, L, Bulmer, JN, Robson, SC. Hemeoxygenase expression in human placenta and placental bed implies a role in regulation of trophoblast invasion and placental function. Faseb J. 2000; 14: 208–19.Google Scholar
Kaufmann, P, Mayhew, TM, Charnock-Jones, DS. Aspects of human fetoplacental vasculogenesis and angiogenesis. II. Changes during normal pregnancy. Placenta. 2004; 25: 114–26.Google Scholar
Simmons, DG, Natale, DR, Begay, V, Hughes, M, Leutz, A, Cross, JC. Early patterning of the chorion leads to the trilaminar trophoblast cell structure in the placental labyrinth. Development. 2008; 135: 2083–91.CrossRefGoogle Scholar
Simpson, RA, Mayhew, TM, Barnes, PR. From 13 weeks to term, the trophoblast of human placenta grows by the continuous recruitment of new proliferative units: a study of nuclear number using the disector. Placenta. 1992; 13: 501–12.Google Scholar
Baczyk, D, Drewlo, S, Proctor, L, Dunk, C, Lye, S, Kingdom, J. Glial cell missing-1 transcription factor is required for the differentiation of the human trophoblast. Cell Death Differ. 2009; 16: 719–27.Google Scholar
Liang, CY, Wang, LJ, Chen, CP, Chen, LF, Chen, YH, Chen, H. GCM1 regulation of the expression of syncytin 2 and its cognate receptor MFSD2A in human placenta. Biol Reprod. 2010; 83: 387–95.CrossRefGoogle ScholarPubMed
Baczyk, D, Kibschull, M, Mellstrom, B, Levytska, K, Rivas, M, Drewlo, S, et al. DREAM mediated regulation of GCM1 in the human placental trophoblast. PLoS ONE. 2013; 8: e51837.Google Scholar
Kingdom, JC, Drewlo, S. Is heparin a placental anticoagulant in high-risk pregnancies? Blood. 2011; 118: 4780–8.CrossRefGoogle ScholarPubMed
Tanaka, S, Kunath, T, Hadjantonakis, AK, Nagy, A, Rossant, J. Promotion of trophoblast stem cell proliferation by FGF4. Science. 1998; 282: 2072–5.Google Scholar
Baczyk, D, Dunk, C, Huppertz, B, Maxwell, C, Reister, F, Giannoulias, D, et al. Bi-potential behaviour of cytotrophoblasts in first trimester chorionic villi. Placenta. 2006; 27: 367–74.Google Scholar
Nosi, U, Lanner, F, Huang, T, Cox, B. Overexpression of trophoblast stem cell-enriched microRNAs promotes trophoblast fate in embryonic stem cells. Cell Rep. 2017; 19: 1101–9.Google Scholar
Macara, L, Kingdom, JC, Kaufmann, P, Kohnen, G, Hair, J, More, IA, et al. Structural analysis of placental terminal villi from growth-restricted pregnancies with abnormal umbilical artery Doppler waveforms. Placenta. 1996; 17: 3748.Google Scholar
Huppertz, B, Frank, HG, Kingdom, JC, Reister, F, Kaufmann, P. Villous cytotrophoblast regulation of the syncytial apoptotic cascade in the human placenta. Histochem Cell Biol. 1998; 110: 495508.CrossRefGoogle ScholarPubMed
Ellery, PM, Cindrova-Davies, T, Jauniaux, E, Ferguson-Smith, AC, Burton, GJ. Evidence for transcriptional activity in the syncytiotrophoblast of the human placenta. Placenta. 2009; 30: 329–34.CrossRefGoogle ScholarPubMed
Fogarty, NM, Mayhew, TM, Ferguson-Smith, AC, Burton, GJ. A quantitative analysis of transcriptionally active syncytiotrophoblast nuclei across human gestation. J Anat. 2011; 219: 601–10.Google Scholar
Rajakumar, A, Cerdeira, AS, Rana, S, Zsengeller, Z, Edmunds, L, Jeyabalan, A, et al. Transcriptionally active syncytial aggregates in the maternal circulation may contribute to circulating soluble fms-like tyrosine kinase 1 in preeclampsia. Hypertension. 2012; 59: 256–64.CrossRefGoogle ScholarPubMed
Burton, GJ, Jones, CJ. Syncytial knots, sprouts, apoptosis, and trophoblast deportation from the human placenta. Taiwan J Obstet Gynecol. 2009; 48: 2837.Google Scholar
Parham, P, Guethlein, LA. Pregnancy immunogenetics: NK cell education in the womb? J Clin Invest. 2010; 120: 3801–4.Google Scholar
Munn, DH, Zhou, M, Attwood, JT, Bondarev, I, Conway, SJ, Marshall, B, et al. Prevention of allogeneic fetal rejection by tryptophan catabolism. Science. 1998; 281: 1191–3.CrossRefGoogle ScholarPubMed
Walker, MG, Fitzgerald, B, Keating, S, Ray, JG, Windrim, R, Kingdom, JCP. Sex-specific basis of severe placental dysfunction leading to extreme preterm delivery. Placenta. 2011; 33: 568–71.Google Scholar
Saraswat, L, Bhattacharya, S, Maheshwari, A. Maternal and perinatal outcome in women with threatened miscarriage in the first trimester: a systematic review. BJOG. 2010; 117: 245–57.Google Scholar
Porat, S, Fitzgerald, B, Wright, E, Keating, S, Kingdom, JC. Placental hyperinflation and the risk of adverse perinatal outcome. Ultrasound Obstet Gynecol. 2013; 42: 315–21.CrossRefGoogle ScholarPubMed
Fitzgerald, B, Shannon, P, Kingdom, J, Keating, S. Rounded intraplacental haematomas due to decidual vasculopathy have a distinctive morphology. J Clin Pathol. 2011; 64: 729–32.Google Scholar
Korzeniewski, SJ, Romero, R, Chaiworapongsa, T, Chaemsaithong, P, Kim, CJ, Kim, YM, et al. Maternal plasma angiogenic index-1 (placental growth factor/soluble vascular endothelial growth factor receptor-1) is a biomarker for the burden of placental lesions consistent with uteroplacental underperfusion: a longitudinal case-cohort study. Am J Obstet Gynecol. 2016; 214: 629. e1–e17.Google Scholar
Walker, MG, Fitzgerald, B, Keating, S, Ray, JG, Windrim, R, Kingdom, JC. Sex-specific basis of severe placental dysfunction leading to extreme preterm delivery. Placenta. 2012; 33: 568–71.Google Scholar
Krebs, C, Macara, LM, Leiser, R, Bowman, AW, Greer, IA, Kingdom, JC. Intrauterine growth restriction with absent end-diastolic flow velocity in the umbilical artery is associated with maldevelopment of the placental terminal villous tree. Am J Obstet Gynecol. 1996; 175: 1534–42.CrossRefGoogle ScholarPubMed
Fitzgerald, B, Levytska, K, Kingdom, J, Walker, M, Baczyk, D, Keating, S. Villous trophoblast abnormalities in extremely preterm deliveries with elevated second trimester maternal serum hCG or inhibin-A. Placenta. 2011; 32: 339–45.Google Scholar
Yung, HW, Calabrese, S, Hynx, D, Hemmings, BA, Cetin, I, Charnock-Jones, DS, et al. Evidence of placental translation inhibition and endoplasmic reticulum stress in the etiology of human intrauterine growth restriction. Am J Pathol. 2008; 173: 451–62.Google Scholar
Sharp, AN, Heazell, AE, Baczyk, D, Dunk, CE, Lacey, HA, Jones, CJ, et al. Preeclampsia is associated with alterations in the p53-pathway in villous trophoblast. PLoS ONE. 2014; 9: e87621.Google Scholar
Ray, JE, Garcia, J, Jurisicova, A, Caniggia, I. Mtd/Bok takes a swing: proapoptotic Mtd/Bok regulates trophoblast cell proliferation during human placental development and in preeclampsia. Cell Death Differ. 2010; 17: 846–59.Google Scholar
Baczyk, D, Audette, MC, Coyaud, E, Raught, B, Kingdom, JC. Spatiotemporal distribution of small ubiquitin-like modifiers during human placental development and in response to oxidative and inflammatory stress. J Physiol. 2018; 596: 1587–600.Google Scholar
Drewlo, S, Levytska, K, Sobel, M, Baczyk, D, Lye, SJ, Kingdom, JC. Heparin promotes soluble VEGF receptor expression in human placental villi to impair endothelial VEGF signaling. J Thromb Haemost. 2011; 9: 2486–97.CrossRefGoogle ScholarPubMed
Nevo, O, Soleymanlou, N, Wu, Y, Xu, J, Kingdom, J, Many, A, et al. Increased expression of sFlt-1 in in vivo and in vitro models of human placental hypoxia is mediated by HIF-1. Am J Physiol Regul Integr Comp Physiol. 2006; 291: R1085–93.Google Scholar
Tache, V, LaCoursiere, DY, Saleemuddin, A, Parast, MM. Placental expression of vascular endothelial growth factor receptor-1/soluble vascular endothelial growth factor receptor-1 correlates with severity of clinical preeclampsia and villous hypermaturity. Hum Pathol. 2011; 42: 1283–8.Google Scholar
Buhimschi, IA, Nayeri, UA, Zhao, G, Shook, LL, Pensalfini, A, Funai, EF, et al. Protein misfolding, congophilia, oligomerization, and defective amyloid processing in preeclampsia. Sci Transl Med. 2014; 6: 245ra92.Google Scholar
Zeisler, H, Llurba, E, Chantraine, F, Vatish, M, Staff, AC, Sennstrom, M, et al. Predictive value of the sFlt-1:PlGF ratio in women with suspected preeclampsia. N Engl J Med. 2016; 374: 1322.CrossRefGoogle ScholarPubMed
Griffin, M, Seed, PT, Duckworth, S, North, R, Myers, J, Mackillop, L, et al. Predicting delivery of a small-for-gestational-age infant and adverse perinatal outcome in women with suspected pre-eclampsia. Ultrasound Obstet Gynecol. 2018; 51: 387–95.Google Scholar
Franco, C, Walker, M, Robertson, J, Fitzgerald, B, Keating, S, McLeod, A, et al. Placental infarction and thrombophilia. Obstet Gynecol. 2011; 117: 929–34.CrossRefGoogle ScholarPubMed
Viero, S, Chaddha, V, Alkazaleh, F, Simchen, MJ, Malik, A, Kelly, E, et al. Prognostic value of placental ultrasound in pregnancies complicated by absent end-diastolic flow velocity in the umbilical arteries. Placenta. 2004; 25: 735–41.Google Scholar
Proctor, LK, Whittle, WL, Keating, S, Viero, S, Kingdom, JC. Pathologic basis of echogenic cystic lesions in the human placenta: role of ultrasound-guided wire localization. Placenta. 2010; 31: 1111–15.CrossRefGoogle ScholarPubMed
Walker, M, Whittle, W, Keating, S, Kingdom, J. Sonographic diagnosis of chronic abruption. J Obstet Gynaecol Can. 2010; 32: 1056–8.CrossRefGoogle ScholarPubMed
D’Souza, R, Keating, S, Walker, M, Drewlo, S, Kingdom, J. Unfractionated heparin and placental pathology in high-risk pregnancies: secondary analysis of a pilot randomized controlled trial. Placenta. 2014; 35: 816–23.Google Scholar
Rolnik, DL, Wright, D, Poon, LC, O’Gorman, N, Syngelaki, A, de Paco Matallana, C, et al. Aspirin versus placebo in pregnancies at high risk for preterm preeclampsia. N Engl J Med. 2017; 377: 613–22.CrossRefGoogle ScholarPubMed
Figueras, F, Caradeux, J, Crispi, F, Eixarch, E, Peguero, A, Gratacos, E. Diagnosis and surveillance of late-onset fetal growth restriction. Am J Obstet Gynecol. 2018; 218: S790–802. e1.Google Scholar
Ting, JY, Kingdom, JC, Shah, PS. Antenatal glucocorticoids, magnesium sulfate, and mode of birth in preterm fetal small for gestational age. Am J Obstet Gynecol. 2018; 218: S818–28.Google Scholar
Nicolaides, KH. Screening for fetal aneuploidies at 11 to 13 weeks. Prenat Diagn. 2011; 31: 715.Google Scholar
Dugoff, L. First- and second-trimester maternal serum markers for aneuploidy and adverse obstetric outcomes. Obstet Gynecol. 2010; 115: 1052–61.Google Scholar
Smith, GC, Crossley, JA, Aitken, DA, Pell, JP, Cameron, AD, Connor, JM, et al. First-trimester placentation and the risk of antepartum stillbirth. JAMA. 2004; 292: 2249–54.Google Scholar
Smith, GC, Shah, I, Crossley, JA, Aitken, DA, Pell, JP, Nelson, SM, et al. Pregnancy-associated plasma protein A and alpha-fetoprotein and prediction of adverse perinatal outcome. Obstet Gynecol. 2006; 107: 161–6.CrossRefGoogle ScholarPubMed
Crovetto, F, Triunfo, S, Crispi, F, Rodriguez-Sureda, V, Roma, E, Dominguez, C, et al. First-trimester screening with specific algorithms for early- and late-onset fetal growth restriction. Ultrasound Obstet Gynecol. 2016; 48: 340–8.Google Scholar
Rizzo, G, Capponi, A, Pietrolucci, ME, Capece, A, Arduini, D. First-trimester placental volume and vascularization measured by 3-dimensional power Doppler sonography in pregnancies with low serum pregnancy-associated plasma protein a levels. J Ultrasound Med. 2009; 28: 1615–22.Google Scholar
Yigiter, AB, Kavak, ZN, Durukan, B, Isci, H, Uzuner, A, Uyar, E, et al. Placental volume and vascularization flow indices by 3D power Doppler US using VOCAL technique and correlation with IGF-1, free beta-hCG, PAPP-A, and uterine artery Doppler at 11-14 weeks of pregnancy. J Perinat Med. 2011; 39: 137–41.Google Scholar
Alanjari, A, Wright, E, Keating, S, Ryan, G, Kingdom, J. Prenatal diagnosis, clinical outcomes, and associated pathology in pregnancies complicated by massive subchorionic thrombohematoma (Breus’ mole). Prenat Diagn. 2013; 33: 973–8.Google Scholar
Saleemuddin, A, Tantbirojn, P, Sirois, K, Crum, CP, Boyd, TK, Tworoger, S, et al. Obstetric and perinatal complications in placentas with fetal thrombotic vasculopathy. Pediatr Dev Pathol. 2010; 13: 459–64.Google Scholar
Salafia, CM, Pezzullo, JC, Minior, VK, Divon, MY. Placental pathology of absent and reversed end-diastolic flow in growth-restricted fetuses. Obstet Gynecol. 1997; 90: 830–6.Google Scholar
Redline, RW. Placental pathology: a systematic approach with clinical correlations. Placenta. 2008; 29 (Suppl. A): S86–91.CrossRefGoogle Scholar
Cox, P, Marton, T. Pathological assessment of intrauterine growth restriction. Best Pract Res Clin Obstet Gynaecol. 2009; 23: 751–64.Google Scholar
Klaritsch, P, Haeusler, M, Karpf, E, Schlembach, D, Lang, U. Spontaneous intrauterine umbilical artery thrombosis leading to severe fetal growth restriction. Placenta. 2008; 29: 374–7.Google Scholar
Reister, F, Frank, HG, Kingdom, JC, Heyl, W, Kaufmann, P, Rath, W, et al. Macrophage-induced apoptosis limits endovascular trophoblast invasion in the uterine wall of preeclamptic women. Lab Invest. 2001; 81: 1143–52.CrossRefGoogle ScholarPubMed
Contro, E, deSouza, R, Bhide, A. Chronic intervillositis of the placenta: a systematic review. Placenta. 2010; 31: 1106–10.CrossRefGoogle ScholarPubMed
Uxa, R, Baczyk, D, Kingdom, JC, Viero, S, Casper, R, Keating, S. Genetic polymorphisms in the fibrinolytic system of placentas with massive perivillous fibrin deposition. Placenta. 2010; 31: 499505.Google Scholar
Fitzgerald, B, Baczyk, D, J. K, Keating, S. Villous Cytotrophoblast Phenotype Switching in Massive Perivillous Fibrinoid Deposition. Submitted for publication. 2011.Google Scholar
Boog, G. Chronic villitis of unknown etiology. Eur J Obstet Gynecol Reprod Biol. 2008; 136: 915.Google Scholar
Katzman, PJ, Murphy, SP, Oble, DA. Immunohistochemical analysis reveals an influx of regulatory T cells and focal trophoblastic STAT-1 phosphorylation in chronic villitis of unknown etiology. Pediatr Dev Pathol. 2011; 14: 284–93.CrossRefGoogle ScholarPubMed
Tang, Z, Abrahams, VM, Mor, G, Guller, S. Placental Hofbauer cells and complications of pregnancy. Ann N Y Acad Sci. 2011; 1221: 103–8.Google Scholar
Derricott, H, Jones, RL, Greenwood, SL, Batra, G, Evans, MJ, Heazell, AE. Characterizing villitis of unknown etiology and inflammation in stillbirth. Am J Pathol. 2016; 186: 952–61.Google Scholar
Levytska, K, Higgins, M, Keating, S, Melamed, N, Walker, M, Sebire, NJ, et al. Placental pathology in relation to uterine artery doppler findings in pregnancies with severe intrauterine growth restriction and abnormal umbilical artery doppler changes. Am J Perinatol. 2017; 34: 451–7.Google ScholarPubMed
Walker, MG, Hindmarsh, PC, Geary, M, Kingdom, JC. Sonographic maturation of the placenta at 30 to 34 weeks is not associated with second trimester markers of placental insufficiency in low-risk pregnancies. J Obstet Gynaecol Can. 2010; 32: 1134–9.CrossRefGoogle Scholar
Cooley, SM, Donnelly, JC, Walsh, T, McMahon, C, Gillan, J, Geary, MP. The impact of ultrasonographic placental architecture on antenatal course, labor and delivery in a low-risk primigravid population. J Matern Fetal Neonatal Med. 2011; 24: 493–7.Google Scholar
Laskin, CA, Bombardier, C, Hannah, ME, Mandel, FP, Ritchie, JW, Farewell, V, et al. Prednisone and aspirin in women with autoantibodies and unexplained recurrent fetal loss. N Engl J Med. 1997; 337: 148–53.CrossRefGoogle ScholarPubMed
Rodger, MA, Gris, JC, de Vries, JIP, Martinelli, I, Rey, E, Schleussner, E, et al. Low-molecular-weight heparin and recurrent placenta-mediated pregnancy complications: a meta-analysis of individual patient data from randomised controlled trials. Lancet. 2016; 388: 2629–41.Google Scholar
Wat, JM, Audette, M, Kingdom, JC. Molecular actions of heparin and their implications in preventing preeclampsia. J Thromb Haemost. 2018; 16 [Epub ahead of print]Google Scholar
Bewley, S, Cooper, D, Campbell, S. Doppler investigation of uteroplacental blood flow resistance in the second trimester: a screening study for pre-eclampsia and intrauterine growth retardation. BJOG. 1991; 98: 871–9.Google Scholar
Yu, CK, Smith, GC, Papageorghiou, AT, Cacho, AM, Nicolaides, KH. An integrated model for the prediction of preeclampsia using maternal factors and uterine artery Doppler velocimetry in unselected low-risk women. Am J Obstet Gynecol. 2005; 193: 429–36.Google Scholar
Pardi, G, Cetin, I, Marconi, AM, Bozzetti, P, Buscaglia, M, Makowski, EL, et al. Venous drainage of the human uterus: respiratory gas studies in normal and fetal growth-retarded pregnancies. Am J Obstet Gynecol. 1992; 166: 699706.CrossRefGoogle ScholarPubMed
Alkazaleh, F, Chaddha, V, Viero, S, Malik, A, Anastasiades, C, Sroka, H, et al. Second-trimester prediction of severe placental complications in women with combined elevations in alpha-fetoprotein and human chorionic gonadotrophin. Am J Obstet Gynecol. 2006; 194: 821–7.Google Scholar
Huang, T, Hoffman, B, Meschino, W, Kingdom, J, Okun, N. Prediction of adverse pregnancy outcomes by combinations of first and second trimester biochemistry markers used in the routine prenatal screening of Down syndrome. Prenat Diagn. 2010; 30: 471–7.Google Scholar
Schwartz, N, Coletta, J, Pessel, C, Feng, R, Timor-Tritsch, IE, Parry, S, et al. Novel 3-dimensional placental measurements in early pregnancy as predictors of adverse pregnancy outcomes. J Ultrasound Med. 2010; 29: 1203–12.Google Scholar
Kingdom, JC, Walker, M, Proctor, LK, Keating, S, Shah, PS, McLeod, A, et al. Unfractionated heparin for second trimester placental insufficiency: a pilot randomized trial. J Thromb Haemost. 2011; 9: 1483–92.CrossRefGoogle ScholarPubMed
McLaughlin, K, Baczyk, D, Potts, A, Hladunewich, M, Parker, JD, Kingdom, JC. Low molecular weight heparin improves endothelial function in pregnant women at high risk of preeclampsia. Hypertension. 2017; 69: 180–8.Google Scholar
Myers, JE, Kenny, LC, McCowan, LM, Chan, EH, Dekker, GA, Poston, L, et al. Angiogenic factors combined with clinical risk factors to predict preterm pre-eclampsia in nulliparous women: a predictive test accuracy study. BJOG. 2013; 120: 1215–23.CrossRefGoogle ScholarPubMed
McLaughlin, K, Scholten, RR, Parker, JD, Ferrazzi, E, Kingdom, JCP. Low molecular weight heparin for the prevention of severe preeclampsia: where next? Br J Clin Pharmacol. 2018; 84: 673–8.Google Scholar
Preston, FE, Rosendaal, FR, Walker, ID, Briet, E, Berntorp, E, Conard, J, et al. Increased fetal loss in women with heritable thrombophilia. Lancet. 1996; 348: 913–16.Google Scholar
Mousa, HA, Alfirevic, Z. Do placental lesions reflect thrombophilia state in women with adverse pregnancy outcome? Hum Reprod. 2000; 15: 1830–3.Google Scholar
Farine, D, Ryan, G, Kelly, EN, Morrow, RJ, Laskin, C, Ritchie, JW. Absent end-diastolic flow velocity waveforms in the umbilical artery—the subsequent pregnancy. Am J Obstet Gynecol. 1993; 168: 637–40.Google Scholar
Toal, M, Chan, C, Fallah, S, Alkazaleh, F, Chaddha, V, Windrim, RC, et al. Usefulness of a placental profile in high-risk pregnancies. Am J Obstet Gynecol. 2007; 196: 363. e1–7.Google Scholar
Staff, AC, Dechend, R, Pijnenborg, R. Learning from the placenta: acute atherosis and vascular remodeling in preeclampsia – novel aspects for atherosclerosis and future cardiovascular health. Hypertension. 2010; 56: 1026–34.Google Scholar

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