Association of first-trimester angiogenic factors with placental histological findings in late-onset preeclampsia |
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| Affiliation: | 1. BCNatal – Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), IDIBAPS, University of Barcelona, Centre for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain;2. Ca'' Granda, Ospedale Maggiore Policlinico, Dipartimento Ostetricia e Ginecologia, Università degli Studi di Milano, Milan, Italy;3. Biochemistry and Molecular Biology Research Centre for Nanomedicine, Hospital Univeritari Vall d''Hebron, Centre for Biomedical Research on Rare Disease (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain;4. Department of Pathology, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain;1. Bulent Ecevit University, Faculty of Medicine, Department of Biochemistry, Zonguldak, Turkey;2. Bulent Ecevit University, Faculty of Medicine, Department of Pathology, Zonguldak, Turkey;3. Bulent Ecevit University, Faculty of Medicine, Department of Gynaecology and Obstetrics, Zonguldak, Turkey;1. Department of Obstetrics & Gynecology, The Edith Wolfson Medical Center, Holon, Israel affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel;2. Department of Pathology, The Edith Wolfson Medical Center, Holon, Israel affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel;1. HCA Research, Hans Christian Andersen Children’s Hospital, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense, Denmark;2. Institute for Clinical Research, University of Southern Denmark, Campusvej 55, 5230 Odense, Denmark;3. Department of Obstetrics and Gynecology, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense, Denmark;4. Odense Patient data Explorative Network (OPEN), Odense University Hospital, Sdr. Boulevard 29, 5000 Odense, Denmark;5. Odense Child Cohort, Hans Christian Andersen Children’s Hospital, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense, Denmark;6. Department of Endocrinology, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense, Denmark;7. Experimental and Clinical Research Center, Max-Delbrueck Center and Charité Berlin and HELIOS Clinic Berlin-Buch, Lindenberger Weg 80, 13125 Berlin, Germany;1. Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy;2. Department of Obstetrics and Gynecology, Sant’Antonio Abate Hospital, Trapani, Italy;3. Gynecology and Obstetrics Department, I.R.C.C.S. San Raffaele Hospital, University Vita-Salute, Milan, Italy;4. Department of Medicine and Surgery, Division of Obstetrics and Prenatal Medicine, IRCCS Sant''Orsola-Malpighi, University of Bologna, 40138, Bologna, Italy;5. Department of Surgical Sciences, Sant’Anna Hospital, University of Turin, Turin, Italy;6. Obstetrics and Gynecology Unit, Department of Medical and Surgical Sciences for Mother, Child and Adult, University of Modena and Reggio Emilia, Modena, Italy;7. Department of Health Sciences, Division of Pathological Anatomy, San Paolo Hospital, University of Milan, Milan, Italy;8. Department of Woman, Child and Neonate, IRCCS Ca'' Granda Maggiore Hospital, University of Milan, Milan, Italy |
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| Abstract: | ObjectiveTo explore in women with late-onset preeclampsia (PE) the association between maternal levels of angiogenic/antiangiogenic factors in the first trimester of pregnancy and histological findings attributable to placental underperfusion (PUP).MethodsA nested case-control cohort study was conducted in 73 women with pregnancies complicated by late-onset PE (>34 weeks at delivery) matched with controls. First trimester uterine artery Doppler (UtA); maternal levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were retrieved. Placentas were histologically evaluated using a hierarchical and standardized classification system. One-way ANOVA with linear polynomial contrast or linear-by-linear association test was performed to test the hypothesis of a linear association across study groups (controls, PE without PUP and PE with PUP).ResultsIn 54 (74%) placentas, 89 placental histological findings qualifying for PUP were found. Across study groups, significant values were observed in maternal levels of decreased PlGF (MoM values: 1.53, 1.41 and 1.37; p < 0.001), increased sFlt-1 (MoM values: 3.11, 3.11 and 3.22; p = 0.002), increased sFlt-1/PlGF ratio (MoM values: 2.3, 2.3 and 2.44; p < 0.001), abnormal UtA Doppler (MoM values: 1, 1.26 and 1.32; p < 0.001), and worse perinatal outcomes in terms of gestational age at delivery, cesarean section for not reassuring fetal status, birth weight and neonatal acidosis.DiscussionIn late-onset PE an imbalance of circulating angiogenic and anti-angiogenic factors already present at 8–10 weeks of pregnancy was associated with histological findings reflecting placental insufficiency. An early first trimester screening by angiogenic factors might help to identify patients with placental involvement among late-onset PE cases.ConclusionIn late-onset preeclampsia, first-trimester uterine Doppler and circulating levels of angiogenic/antiangiogenic factors are associated with placental underperfusion. |
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| Keywords: | Preeclampsia First trimester screening Placental growth factor Soluble fms-like tyrosine kinase-1 Histological findings Placental underperfusion PE" },{" #name" :" keyword" ," $" :{" id" :" kwrd0045" }," $$" :[{" #name" :" text" ," _" :" preeclampsia FGR" },{" #name" :" keyword" ," $" :{" id" :" kwrd0055" }," $$" :[{" #name" :" text" ," _" :" fetal growth restriction GA" },{" #name" :" keyword" ," $" :{" id" :" kwrd0065" }," $$" :[{" #name" :" text" ," _" :" gestational age PlGF" },{" #name" :" keyword" ," $" :{" id" :" kwrd0075" }," $$" :[{" #name" :" text" ," _" :" placental growth factor sFlt-1" },{" #name" :" keyword" ," $" :{" id" :" kwrd0085" }," $$" :[{" #name" :" text" ," _" :" soluble fms-like tyrosine kinase-1 MoM" },{" #name" :" keyword" ," $" :{" id" :" kwrd0095" }," $$" :[{" #name" :" text" ," _" :" multiples of normal median EFW" },{" #name" :" keyword" ," $" :{" id" :" kwrd0105" }," $$" :[{" #name" :" text" ," _" :" estimated fetal weight UtA" },{" #name" :" keyword" ," $" :{" id" :" kwrd0115" }," $$" :[{" #name" :" text" ," _" :" uterine artery UA" },{" #name" :" keyword" ," $" :{" id" :" kwrd0125" }," $$" :[{" #name" :" text" ," _" :" umbilical artery MCA" },{" #name" :" keyword" ," $" :{" id" :" kwrd0135" }," $$" :[{" #name" :" text" ," _" :" middle cerebral artery CPR" },{" #name" :" keyword" ," $" :{" id" :" kwrd0145" }," $$" :[{" #name" :" text" ," _" :" cerebroplacental ratio PI" },{" #name" :" keyword" ," $" :{" id" :" kwrd0155" }," $$" :[{" #name" :" text" ," _" :" Doppler pulsatility index BW" },{" #name" :" keyword" ," $" :{" id" :" kwrd0165" }," $$" :[{" #name" :" text" ," _" :" birth weight PUP" },{" #name" :" keyword" ," $" :{" id" :" kwrd0175" }," $$" :[{" #name" :" text" ," _" :" placental underperfusion |
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