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Update in early detection and management of PE
Eduard Gratacos
www.medicinafetalbarcelona.org
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Early and late PE
Prediction of late disease
Early detection with angiogenic factors
Update in management
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www.medicinafetalbarcelona.org/
Early and late PE
Prediction of late disease
Early detection with angiogenic factors
Update in management
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Normal and abnormal placental implantation
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Endothelial diseaseMOTHER
DAMAGE
DYSFUNCTION
HYPERSTIMULATION
EARLY-ONSET PE AND IUGRRelation between placental and maternal disease
Endothelial disease (poor implantation)
PLACENTA
HTA!
proteinuria
plateletshemolysisliverHELLP
eclampsia
IUGR
DPPNI
Fetal hypoxia
PRED
ISPO
SITI
ON
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20 30 4025 35
www.fetalmedicinebarcelona.org/
EARLY-ONSET LATE-ONSET
PREECLAMPSIA
IUGR
PREECLAMPSIA + IUGR
1 %
1 %
4-8 %
4-8 %
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MATERNALPREDISPOSITION
ANOMALOUSPLACENTATION
PREECLAMPSIADisease of the vascular endothelium which requires
baseline hyperstimulation state (gestation)
+ maternal predisposition +/- additional insult (anomalous placentation)
Gestational Age
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PE
20 30 4025 35
0
5
10
%
EARLY-ONSET PE (1%) LATE-ONSET PE (4-8%)
PROBLEM: MANAGEMENT PROBLEM: DIAGNOSIS
Degree plac. insufficiency: HIGH Degree plac. insufficiency: LOW
Maternal predisposition + Maternal predisposition +++
Prediction 1 trimester Prediction 2-3 T
34
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EARLY(<34w)
LATE(>34w)
Maternal severe disease 83% 30%
Association IUGR 78% 15%
Abnormal Umbilical Artery Doppler 78% 43%
Abnormal Uterine Artery Doppler 95% 46%
Abnormal placental pathology +++ +
Sibai’06, Levine’06, Crispi’06, Egbor’06, Zhang’03, Sibai’03
PREECLAMPSIA: EARLY VERSUS LATE
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www.medicinafetalbarcelona.org/
Early and late PE
Prediction of late disease
Early detection with angiogenic factors
Update in management
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Prediction of PE
PE
Detection Rates (for FPR 10%)
11-14w
LATE PE
25-65%EARLY PE
80-90%
INTEGRATED FIRST TRIMESTER APPROACHmaternal + UtA Doppler + biomarkers
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UtA Doppler: Quan9ta9ve assessmentPulsa9lity index
0
1,0
2,0
3,0
4,0
10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42
Gómez O, Figueras F. Reference ranges for uterine artery mean pulsa9lity index at 11-‐41 weeks of gesta9on. Ultrasound Obstet Gynecol. 2008 Aug;32(2):128-‐32
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A priori risk
A priori + Biophysical
with Angiogenic
Early(n=56)
First trimester screening
Crovetto et al, FDT, in press
DR 68% ! (5% FPR) DR 76%! (10% FPR)
A priori risk
A priori + Biophysical
with Angiogenic
DR 88% ! (5% FPR) DR 91%! (10% FPR)
Late(n=246)
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Prediction of PE
PE
Detection Rates (for FPR 10%)
32-34w
LATE PE
70-75 %
Lai et al. Fetal Diagn Ther 2013(BP, UtA Doppler, sEng)
Chaiworapongsa et al. AJOG 2013(PlGF, sFlt-1, sEng)
THIRD TRIMESTER APPROACHmaternal OR UtA Doppler OR biomarkers
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Early and late PE
Prediction of late disease
Early detection (angiogenic factors)
Update in management
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Respecto a la proteinuria…
1. Solamente la proteinuria de 24 horas puede ser considerada un criterio diagnóstico
2. El ratio C/P es igual de sensible que la proteinuria de 24h3. La proteinuria cualitativa solamente tiene valor cuando es positiva
Caso clínico
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Respecto a la proteinuria…
1. Solamente la proteinuria de 24 horas puede ser considerada un criterio diagnóstico
2. El ratio C/P es igual de sensible que la proteinuria de 24h3. La proteinuria cualitativa solamente tiene valor cuando es positiva
Caso clínico
El RCP debería desplazar la proteinuria cualitativa en casos de sospecha
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pregnancy + hypertension: PE or gestational hypertension?
Ultrasounduterine artery / fetal Doppler
ClinicalBP
maternal historyBiomarkers
PlGF/sFlt-1/sEng/VCAM/othersClinical case
Pregnant women with HTA
5-10 % (750,000 / y Europe + America)
CURRENTLY:• identification at dx poor• strict follow up needed (large # exams)• misuse of resources
Integrated one-stepdiagnostic system
Clinical need: integrated one-step diagnostic system for placental disease
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PREECLAMPSIA
Levine RJ. N Engl J Med. 2004
Screening•First trimester
PREDICTION
•Third trimester
PROGNOSIS
Early iden9fica9on in suspected pateints
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PlGF<p5 in suspected PE (n=625)
Delivery due to PE <14 days
Chappell, Circulation, 2013
Sensitivity 96
0
20
40
60
80
100
<35 wn=287
35 to 36 wn=137
>37wn=201
70
57
%Screening test PE within 14d(patients<35w)
Blood pressure 0.67(0.05)
Urate 0.68 (0.06)
ALT 0.61 (0.05)
Dipstick Proteinuria 0.76 (0.04)
PlGF 0.87(0.03)
PlGF+BP+Urate+ALT 0.87 (0.03)
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Early and late PE
Prediction of late disease
Early detection (with angiogenic factors)
Update in management
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¿Como tratamos la preeclampsia leve?
•Reposo relativo y dieta normal
•Control diario Pródromos, TA (~80/130-105/155)
Peso
•Control analítica/15d y fetal/semanal
•Finalización a las 38+1 semanas(HYPITAT-I)
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¿Cuándo finalizaremos la PE grave?
§>34.0
§>32.0.o si PIERS >5%
§Cualquier EG sí:
oTA refractaria a 2 fármacos
oPródromos eclampsia persistentes
oAfectación orgánica progresiva: renal, hepática, PLT
oComplicaciones maternas: EAP, DPPNI oIndicaciones fetales (=CIR)
Sí <32 semanas y Bishop<5: CS 85%
¿Como tratamos la preeclampsia grave?
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PREECLAMPSIA
¿existen criterios de gravedad?
síno PREECLAMPSIA LEVE
TA>160/110proto >5g
GOT/GPT>70PLT<100000
LDH>700Edema pulmónCreatinina>1.5
Pródromos NRL
¿existe hemolisis y plaquetopenia y elevación GOT/GPT?
nosí
PREECLAMPSIA GRAVE
HELLP
ECLAMPSIA
¿ha convulsionado o está en coma?
nosí
H hemolisisEL elevated liver enzimsLP low platelets
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PREECLAMPSIA
¿existen criterios de gravedad?
síno PREECLAMPSIA LEVE
TA>160/110proto >5g
GOT/GPT>70PLT<100000
LDH>700Edema pulmónCreatinina>1.5
Pródromos NRL
¿existe hemolisis y plaquetopenia y elevación GOT/GPT?
nosí
PREECLAMPSIA GRAVE
HELLP
ECLAMPSIA
¿ha convulsionado o está en coma?
nosí
H hemolisisEL elevated liver enzimsLP low platelets
Edat gestacional
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Caso clínico
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Early and late PE
Prediction of late disease
Early detection (with angiogenic factors)
Update in management