Future. pathophysiology of preeclampsia. ? hypoxia. Also in. marker. 1st trim. In combi w PE s.flt-1 -- seng, PlGF, VEGF, US. Manifest.



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Take-home message Basics How to predict placental syndrome? Maternal history and exam markers Uterine artery doppler 3D Power Doppler Biochemical Salwan Al-Nasiry Gynaecoloog perinatoloog MUMC Future challenge Take-home message Basics How to predict placental syndrome? Maternal history and exam markers Uterine artery doppler 3D Power Doppler Biochemical The placenta may predict the baby Harvey Kliman Future challenge Preeclampsia: a historical prespective Take-home message Basics How to predict placental syndrome? Maternal history and exam Biochemical Uterine 3D artery doppler Power Doppler Future Placental bed

Preeclampsia: defective spiral artery remodelling Take-home message Basics How to predict placental syndrome? Maternal history and exam Biochemical markers Uterine artery doppler 3D Power Doppler Future Normal pregnancy preeclampsia pathophysiology of preeclampsia defective spiral artery remodelling? hypoxia release of placental factors? trophoblast microparticles Endothelial dysfunction Clinical preeclampsia?ros/cytokines?angiogenic factors genetic immune environment marker 1st trim 2nd trim Manifest In combi w PE s.flt-1 -- seng, PlGF, VEGF, US Also in seng -- Sflt-1, PlGF, US IUGR, SGA, HELLP PlGF seng, sflt-1 SGA PP-13 US IUGR, preterm P-Selectin sflt-1, Activin-A cf-fetal DNA Inhibin-A Tris21, IUGR, preterm cf-dna -- -- ADAM12 -- -- Tris21/18, SGA PTX-3 IUGR PAPP-A Birth wt Grill et al. Reproductive Biology and Endocrinology 2009, 7:70

Cell-free fetal DNA Cell-free fetal DNA Uterine artery Dopplers Uterine A. Dopplers 10-14 wk N= 1067 unilateral notch 23% bilateral notch 10 5.5 Dugoff et al. American Journal of Obstetrics and Gynecology (2005) 193, 1208 12 Prospectieve cohort High-risk pregnancy for placental insufficiency (medical/obs Hx) N= 61, all had screening at: 11-14 wk Serum: PAPP-A Ut A doppler Placental structure 18-24 wk Serum: hcg+afp Ut A doppler Placental structure Test # Adverse # Adverse P value LR+ (95% CI) LR- (95% CI) outcomes test abnormal (total) outcomes test normal (total) Ut A Doppler PI 6 (16) 5 (41) 0.057 3.1 (1.1 8.3) 0.71(0.51 0.97) Placental morphology 5(11) 6 (47) 0.025 3.6 (1.3 8.5) 0.63 (0.36 0.93) Biochemistry 4 (9) 6 (44) 0.053 3.3 (1.1 7.9) 0.64 (0.34 0.98) 1 abnormal tests 9 (24) 2 (34) 0.005 5.9 (1.6 24) 0.68 (0.59 0.89) 2 abnormal tests 4 (8) 7 (50) 0.035 3.6 (1.3 7.7) 0.58 (0.27 0.94) All abnormal tests 2 (3) 9 (55) 0.089 4.1 (1.1 6.3) 0.40 (0.07 0.97) Costa et al. Placenta 29 (2008) 1034 1040 Costa et al. Placenta 29 (2008) 1034 1040

Systematic review, total 79 547 patients PE 74 studies IUGR 61 studies Placental 3D Power Doppler Results Dopplers in 2nd trimester performed better than 1st trimester Most Doppler indices had poor predictive characteristics, depending on: patient risk outcome severity. high PI with notching was the best predictor of: pre-eclampsia High risk LR+ 21.0 low risk LR+ 7.5 IUGR overall LR+ 9.1 severe LR+ 14.6 Cnossen et al. CMAJ 2008;178(6):701-11 Gudmundsson et al. Semin Perinatol 33:270-280, 2009 Placental 3D Power Doppler Gebb et al. Best Practice & Research Clinical Obstetrics and Gynaecology 25 (2011) 355 366 Odibo et al. Placenta 32 (2011) 230e234 Take-home message Basics How to predict placental syndrome? Maternal history and exam Biochemical Doppler Placental structure Future challenge Abnormal placental structure (placenta lakes)

Abnormal placental structure (placenta lakes) Abnormal placental structure (placenta lakes) Routine 20-wk scan N= 109 met placenta lakes (8.7% van de populatie), groepen: I = klein, verdwijnt later = 52 II = groot, verdwijnt later = 19 III = klein, persisteert = 27 IV = groot persistereert = 11 Huwang et al. European Journal of Obstetrics & Gynecology and Reproductive Biology 162 (2012) 139 143 37-42wk geplande sectio of inleiding Onderzoekers: G. Gruiskens C. Ghousein Begeleiders: K. vdvijver (patho) M. Baldewijn (patho) S. Al-Nasiry (gyn) M. Spaanderman (gyn) Huwang et al. European Journal of Obstetrics & Gynecology and Reproductive Biology 162 (2012) 139 143 2 22-37wk, prospectief cohort, placental lakes Klinische uitkomsten (moeder, kind) Onderzoekers: G. Gruiskens C. Ghousein Begeleiders: K. vdvijver (patho) M. Baldewijn (patho) S. Al-Nasiry (gyn) M. Spaanderman (gyn)

Acute atherosis Onderzoeker: D. Stevens Long term outcome (repeat preeclampsia, CV risk profile) Begeleiders: H. Bulten(patho) J. vd Vugt (gyn) S. Al-Nasiry (gyn) M. Spaanderman (gyn) Stevens et al. 2011 Stevens et al. 2011

Clinical parameters DV Controls p-values Diastolic blood 113 108 0.027 pressure a Urine protein-tocreatinine 5.3 4.4 0.368 ratio a Thrombocytes b 135 120 0.409 LDH a 803 915 0.232 ASAT a 140 243 0.151 ALAT a 132 211 0.332 Gestational age 30w6d 32w5d 0.030 Birthweight (grams) 1176 1645 0.030 Birthweight (centile) 11.5 18.4 0.273 APGAR 1 minute 5,5 6 0.428 APGAR 5 minute 6,9 7,8 0.124 Umbilical artery ph 7.18 7.25 0.012 Histological DV Controls p-values parameters Placenta Weight (gram) 229 268 0.186 Infarction degree a 1 0,9 0.546 Infarction location b 1.4 1.3 0.726 Calcificatins degree a 0,3 0,1 0.051 Hematoma degree a 0,5 0,1 0.038 Ischemia degree a 1,7 1,5 0.213 Stevens et al. Placenta 33 (2012) 630e633 Stevens et al. unpublished final thoughts The placenta may predict the baby Harvey Kliman