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TO SCREENFOR PREECLAMPSIA
ANNA SANDSTRÖM, MD, PhD, Karolinska Universitetssjukhuset, Solna, KI/Uppsala University
Study Director Research School for Clinicians in Epidemiology, KI
Anna Sandström
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FRÅGA 1
Anna Sandström
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När ska man screena för en sjukdom?
1. Viktigt hälsoproblem (känd patogenes?)
2. Sjukdomen har ett förstadium där den
kan upptäckas
3. Fungerande test med tillräcklig precision
4. Effektiv behandling
5. Förbättrat utfall utan att skada
Anna Sandström
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När ska man screena för en sjukdom?
1. Viktigt hälsoproblem (känd patogenes?)
Anna Sandström
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En av de vanligaste orsakerna till direkt maternell och perinatal mortalitet och morbiditet
Say, L et al, Lancet Global Health 2014Anna Sandström
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FRÅGA 2
Anna Sandström
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Preeklampsi
Overall
• 3-5 %
Preterm (< 37 veckor)
• 0.7 %
• Allvarligare
Term (≥ 37 veckor)
• Majoritet
• De flesta eklamptiska anfall
• 1/3 neonatala dödsfall
Anna Sandström
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Preeklampsi beror på olika saker?
Anna Sandström
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Preeklampsi beror på olika saker?
Anna Sandström
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Hypertoni
Diabetes
SLE
Hög ålder
Fetma
Skadat endotel före graviditetenBartsch E et al. Bmj. 2016Anna Sandström
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Preeklampsi beror på olika saker?
Anna Sandström
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Lägre cardiac outputHögre blodtryckHögre resistens
Anna Sandström
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Preeklampsi beror på olika saker?
Anna Sandström
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Diagnosen sätts på symptom
HypertoniProteinuriLungödem/HjärtsviktNjursviktHjärnödem/EklampsiKoagulationspåverkanHELLP
FENOTYPVS
PATOLOGI
EndotelscellsdysfuntionHjärt-kärlsystemPlacentationImmunologi
Anna Sandström
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Testpositiva
x
x
x
x
x
x
xx
xxSant positiva
Falskt negativa
Screena för sjukdom med olika orsaker?
Anna Sandström
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När ska man screena för en sjukdom?
1. Viktigt hälsoproblem (känd patogenes?)
2. Sjukdomen har ett förstadium där den
kan upptäckas
Anna Sandström
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Bartsch E et al. Bmj. 2016
Riskfaktorer
Anna Sandström
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Blodtryck i tidig graviditet
Tan et al. Ultrasound Obstet Gynecol 2018
MAP = systoliskt BT + (2 x diastoliskt BT)
3
Anna Sandström
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Poon et al. Obstetrics and Gynecology Int, 2014
Biokemiska markörer
Anna Sandström
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När ska man screenaför en sjukdom?
1. Viktigt hälsoproblem (känd patogenes?)
2. Sjukdomen har ett förstadium där den
kan upptäckas
3. Fungerande test med tillräcklig
precision
Anna Sandström
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Anna Sandström
FRÅGA 3
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Fungerande test med tillräcklig precision
Anna Sandström
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One risk factor:
• History of hypertensive disease in a previous pregnancy
• Chronic kidney disease
• Autoimmune disease (SLE, APLS)
• Diabetes Mellitus (Type I or II)
• Chronic Hypertension
At least two risk factors:
• First pregnancy ≥ 40 years old
• Interpregnancy interval of > 10 years
• BMI at first visit ≥ 35
• Family history of PE
• Multiple pregnancy Anna Sandström
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ARG-rapport, n 72, Preeklampsi, 2014Anna Sandström
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FMF:s screening modell i gv11-14
• Maternella karakteristika och medicinskanamnes
• Medelartärblodtryck (MAP)
• Ultraljudsdatering
• Ultraljud med pulsatilt index i arteria uterina
• Biomarkörer: PAPP-A och PlGF
Anna Sandström
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Wright et al. AJOG, 2015
O’ Gorman et al. UOG, 2016
Tan et al, UOG, 2018Anna Sandström
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Screening i svensk
mödrahälsovård bland förstföderskor
Anna SandströmSandström A, Snowden M J, Höijer J,
Bottai M, Wikström-A-K
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Multivariable models in nulliparous
women in a Swedish setting
Area under the
ROC curve
(95% CI)
Sensitivity
for 10%
FPR (95% CI)
Prediction of preeclampsia < 34 weeks 0.68 (0.64-0.72) 30.6 (24.5-37.2)
Prediction of preeclampsia < 37 weeks 0.68 (0.65-0.70) 29.2 (25.2-33.4)
Prediction of preeclampsia ≥ 37 weeks 0.67 (0.66-0.68) 28.2 (26.4-30.1)
NICE-guidelines risk factors in nulliparous
women in a Swedish setting
Sensitivity
for ~5.8%
FPR (95% CI)
Prediction of preeclampsia < 34 weeks 22.2% (16.8-28.4)
Prediction of preeclampsia < 37 weeks 19.5% (16.1-23.3)
Prediction of preeclampsia ≥ 37 weeks 12.2% (10.9-13.7)
Screening i svenskmödrahälsovård bland förstföderskor
Anna Sandström
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NICE-guidelines risk factors in
nulliparous women in a Swedish
setting
Sensitivity for
~5.8% FPR (95% CI)
Prediction of preeclampsia < 37 weeks 19.5% (16.1-23.3)
NICE-guidelines risk factors in
nulliparous women U.K.
Sensitivity for
11.5% FPR (95% CI)
Prediction of preeclampsia < 37 weeks 29% (24.9-33.4)
FMF-model with only maternal risk-
factors in nulliparous women U.K.
Sensitivity for
11.5% FPR (95% CI)
Prediction of preeclampsia < 37 weeks 36% (31.5-40.5)
Wright et al. AJOG, 2015
Screening bland förstföderskorUK/Sverige
Anna Sandström
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ISSHP- International Society for the Study of Hypertension in Pregnancy
ISSHP supports first trimester screening for pre-eclampsia
when this can be integrated into the local health system,
although the cost effectiveness of this approach remains to be
established.
Brown et al. Pregnancy Hypertens, 2018Anna Sandström
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Testpositiva
x
x
x
xx
xxSant positiva
Falskt negativa
Screena för sjukdom med olika orsaker?
xx x
Anna Sandström
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När ska man screena för en sjukdom?
1. Viktigt hälsoproblem (känd patogenes?)
2. Sjukdomen har ett förstadium där den
kan upptäckas
3. Fungerande test med tillräcklig
precision
4. Effektiv behandling
Anna Sandström
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Identifiera preeklampsi i ett tidigt stadium minskar risken för
maternell morbiditet och mortalitet
Möjligt att individanpassa uppföljning under graviditet
Profylaktisk behandling?
Mol, Lancet, 2016
WHO recommendations for Prevention and treatment of pre-eclampsia and eclampsia, 2011
American College of Obstetricians and Gynecologists, Obstetrics and gynecology, 2013
Souza, Lancet, 2013
Effektiv behandling
Anna Sandström
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Anna Sandström
FRÅGA 4
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Anna Sandström
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Studiedesign
• ASA 150 mg till natten
• Start: 11-13 veckor
• Slut: 36 veckor
• Utfall: Preterm preeklampsi (<37 veckor)
Detection rate(%)
Screen positive rate (%)10%
75%
Anna Sandström
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• 26 941 kvinnor screenades• Blodtryck• PLGF, PAPP-A• A. uterina• Riskfaktorer
• 2971 högrisk (11%)
• 332 uppfyllde inte studiekriterier (majoritet använde redan ASA)
• 865 (33% tackade nej – ej separat analyserade)
• 1776 randomiserades
• 80% tog >85% av tabletterna
Studiedesign
Anna Sandström
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Resultat
• OR för preterm preeklampsi: 0.38 (0.20-0.74)
Sekundära utfall:
• OR för preeklampsi <34 veckor: 0.18 (0.03-1.03)
• OR för PE ≥ 37 veckor: 0.95 (0.57-1.57)
Anna Sandström
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Effektiv behandling
• ASA 150 mg till natten sänker risk för preterm PE med 62%
• Inga fler ”serious adverse advents” i ASA-grupp jmf med placebo-grupp. Inte heller om man tar hänsyn till BMI
Anna Sandström
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Ge ASA till alla gravida?• Compliance
• Endast 23% medicinerades trots högrisk enligt NICE guidelinesTan et al, 2018
• Risker?• Meta-analys (dos 70-325 mg) ingen ökad risk för för fatal GI
blödningElwood et al, PLOS 2016
• Oklart under graviditet
Effektiv behandling
Anna Sandström
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Non-responders 30% vid 81mg, 10% vid 121mg, 5% vid 160mg Caron et al,J Obstet Gynaecol Can 2009
Meta-analys ≥100 mg minskar risken för preeklampsi med förlossning <37 gv. Om startad ≤ 16 gv och även möjligen minskad risk för ablatio.
Roberge et al, AJOG 2017 samt Roberge et al AJOG 2018
Risker med högre doser?
Effektiv behandling –
dosering av ASA omtvistad
Anna Sandström
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När ska man screena för en sjukdom?
1. Viktigt hälsoproblem (känd patogenes?)
2. Sjukdomen har ett förstadium där den
kan upptäckas
3. Fungerande test med tillräcklig precision
4. Effektiv behandling, hälsoekonomisk
5. Förbättrat utfall utan att skada
Anna Sandström
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Förbättrat utfall utan att skada
Kan vi detta idag?
Validera i nya populationer
Anna Sandström
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Sammanfattning screening
• Preeklampsi är ett viktigt hälsoproblem
• Preeklampsi är multifaktoriellt och det finns kända
associerade faktorer inklusive maternella karakteristika,
medicinsk historia, obstetrisk anamnes samt biokemiska och
biofysiska markörer
• Dagens test har låg sensitivitet
• ASA är en effektiv förebyggande behandling, dock oklart
vilken dosering
Anna Sandström