PREECLAMPSIA - Overview and Update -

Professor Shaun Brennecke Director

Department of Maternal Fetal Medicine Royal Women’s Hospital

Parkville, Victoria, Australia

The past, the present, the future: challenges & opportunities for

Maternal & Child Health Nurses and Midwives

Annual Conference 18 August 2018

PREECLAMPSIA

OVERVIEW

PREECLAMPSIA

DEFINITION

PREGNANCY INDUCED…..

• Hypertension

• Proteinuria

• Generalised oedema

• Multisystem dysfunctions

The Hypertensive Disorders of Pregnancy: Classification, Diagnosis and Management

International Society for the Study of Hypertension in Pregnancy

Proposed Recommendations for International Practice

Brown MA, Magee LA, Kenny LC, Karumanchi SA, McCarthy F, Saito S, Hall D, Warren C, Adoyi G, Ishaku S. on behalf of the International Society for the Study of Hypertension in Pregnancy (ISSHP).

CLINICAL FEATURES OF PREECLAMPSIA

• First pregnancy

• New onset hypertension

• New onset proteinuria

• Generalised oedema

• Unpredictable progression to ECLAMPSIA

• Widespread maternal organ failure

• Feto-placental compromise

PREECLAMPSIA

FEATURES

• Unique to human pregnancy

• Usually latter half of pregnancy

• Disease of first pregnancy

• Resolves following delivery

Preeclampsia is the most common serious medical disease of human pregnancy with an incidence of 1-5% in most parts of the world

PREECLAMPSIA

SIGNIFICANCE

WORLDWIDE …..

A mother dies every 8 minutes

from

complications of preeclampsia

PREECLAMPSIA

CURRENT AUSTRALIAN FIGURES

Mild Preeclampsia 5-10%

Severe Preeclampsia 1-2%

Maternal Mortality 15%

Perinatal Mortality 10%

Labour Inductions 20%

Caesarean Sections 15%

Preterm Deliveries 5-10%

Maternal Bed Costs $50 million pa

Neonatal Bed Costs $10 million pa

SIGNIFICANCE

PREECLAMPSIA

PROBLEMS FOR THE MOTHER

High blood pressure … If severe → weakens blood vessels → stroke

→ weakens the heart → heart failure

“Leaky” kidneys → protein in urine

“Leaky” blood vessels → swelling of face and limbs

Fits/convulsions/ “epilepsy”

“Thinning” of blood → uncontrolled bleeding

Liver failure → jaundice

“Wet” lungs

THE HELLP

SYNDROME

Haemolysis

Elevated Liver Enzymes

Low Platelet Count

PREECLAMPSIA PROBLEMS FOR THE BABY

Impaired functioning of placenta (afterbirth), so…. - baby’s supply of nutrients in womb decreased - baby’s supply of oxygen in womb decreased

- baby’s growth in womb slowed - baby’s survival in womb jeopardised

Possible need therefore for early delivery, so… -problems of prematurity…

difficulty breathing difficulty fighting infection difficulty absorbing food

and so on

SEVERE PREECLAMPSIA MANAGEMENT PRINCIPLES

Admission Stabilisation Blood pressure control Seizure prophylaxis Fluid balance Fetal welfare surveillance Multidisciplinary care DELIVERY Third stage management Postpartum observation Follow-up

SEVERE PREECLAMPSIA

KEY TREATMENT PRINCIPLE

PE IS CURED

BY DELIVERY

BUT NOT

AT DELIVERY

PATIENT ISSUES

Subjective health/objective ill-health dichotomy

Emotional distress and anxiety

Reversal of expectations/medicalisation of pregnancy

Denial

Guilt

Loss of control

Information needs

Clinical uncertainties

Clinical environment – physical, language, personnel

The baby

The father

Follow-up

www.aapec.org.au

PREECLAMPSIA

UPDATE

WHAT CAUSES

PREECLAMPSIA?

“Preeclampsia is a disease of theories”

Paul Zweifel German Obstetrician

1916

Bell E. Nature Reviews Immunology (2004)

DEFICIENT PLACENTATION IN PREECLAMPSIA

PREECLAMPSIA IS A MULTISYSTEM DISORDER

MATERNAL CIRCULATING PLGF IS ABNORMALLY LOW IN PREECLAMPSIA

Levine RJ et al (2004) NEJM 350(7): 672-683

Maynard SE et al. J Clin Invest (2003)

MATERNAL CIRCULATING sFlt-1 IS ABNORMALLY HIGH IN PREECLAMPSIA

VASCULAR DYSFUNCTION IN PREECLAMPSIA

Biochemical Society Transactions (2009) 37, 1237-1242

Asif Ahmed and Melissa J. Cudmore

Schoofs K et al. J Perinat Med (2014)

sFlt-1/PlGF RATIO AND PREGNANCY OUTCOME

sFlt-1/PlGF RATIO

A Test of Placental Dysfunction

CAN WE USE THIS TEST TO

PREDICT PREECLAMPSIA?

The PROGNOSIS Study

Key Points

Sample size n=1050

A single sFlt/PlGF ratio cut-off value of 38 is appropriate

for gestational ages 24-37 weeks

A low sFlt-1/PlGF ratio (≤ 38) rules out preeclampsia within one week (NPV of 99.3%)

and within four weeks (NPV of 94.3%)

A high sFlt-1/PlGF ratio (> 38) predicts preeclampsia within four weeks (PPV of 36.7%)

The PROGNOSIS Study

sFlt-1/PlGF

Prediction Diagnosis

Progression of

Preeclampsia

PERT

The new PreEclampsia Ratio Test

Currently in use at the RWH

CAN WE

PREVENT PREECLAMPSIA?

Low-dose Aspirin from 16 weeks

Combined Multi-Marker Screening and Randomised Patient Treatment with Aspirin for Evidence-Based Preeclampsia Prevention

IS THERE A BETTER ANTENATAL CARE SYSTEM

FOR PREDICITNG

AND PREVENTING

PREECLAMPSIA?

DECREASING PREECLAMPSIA MORTALITY

Historical Perspective

Dr John Ballantyne 1861-1923

Edinburgh Perinatologist Apostle of Antenatal Care

DECREASING PREECLAMPSIA MORTALITY

Historical Perspective

PREECLAMPSIA

Historically, the primary medical justification

for antenatal care

Cause 1935 1950 1950 as a percentage of 1935

Toxaemia 7.8 2.6 33.3

Maternal mortality rates per 10,000 births. Source: A. Macfarlane and M. Mugford, Birth Counts: Statistics of Pregnancy and Childbirth (London, 1984), ii. 276-7.

DECLINE IN PREECLAMPSIA MATERNAL MORTALITY ENGLAND AND WALES

1935-1950

DR at 5% FPR

History MAP uA-PI PAPP-A PlGF Reference

33 X Yu (2005)

Akolekar (2011)

38 X Poon (2009)

47 X X Akolekar (2011)

54 X X Akolekar (2011)

60 X X X Foidart (2010)

78 X X X Foidart (2010)

78 X X X X X Akolekar (2011)

84 X X X X Poon (2010)

89 X X X X Poon (2010)

93 X X X X X Poon (2009)

FIRST TRIMESTER MULTIPARAMETRIC MODEL DETECTION RATES FOR EARLY-ONSET PE

History: body mass index, family history of PE, previous PE, ethnicity, smoking; MAP: mean arterial blood pressure; uA-PI: uterine artery pulsatility index

Biochemical markers: PAPP-A, PlGF

Costa FS, (2011) Rev Bras Gincol Obstet 33(11) 367-375

Nicolaides KH, Prenat Diag (2011): 31: 3-6

Pyramid of prenatal care: past (left) and future (right)

A MODEL FOR A NEW PYRAMID OF PRENATAL CARE BASED ON THE 11 TO 13 WEEKS’ ASSESSMENT

CAN WE IMPROVE ON LOW DOSE ASPIRIN

FOR PREVENTING

PREECLAMPSIA?

The ESPRESSO Trial

Can esomeprazole (Nexium)

reduce the risk of preeclampsia?

A Multicentre Trial

Principal Investigator - Prof Jon Hyett

Involving Maternity Hospital in NSW, Victoria and SA

Funded by the NHMRC

The ESPRESSO Trial

500 Pregnant Women 11-13 weeks gestation

At high risk of preeclampsia

Randomisation

Control Arm Placebo tablet daily

Active Arm 40mg esomeprazole daily

Required background therapy (Both arms) 150mg aspirin daily

Primary Endpoint Blood pressure at 36 weeks gestation

DOES PREECLAMPSIA

IMPACT ON

LATER LIFE MATERNAL

HEALTH?

PREECLAMPSIA AND

LONG TERM MATERNAL MORTALITY

Irgens et al. BMJ (2001) 323, 7323: 1213-7

PREECLAMPSIA AND MATERNAL MORTALITY

"There are very few identified risk factors

for later life heart disease in women;

preeclampsia is one of the few warning signs we'll get and we should take advantage of it"

Eleni Tsigas,

Executive Director,

Pre-eclampsia Foundation

Female Sex and Cardiovascular Disease Risk Factors

LIFE LONG SURVEILLANCE OF CARDIOVASCULAR HEALTH

Weight

Exercise

Diet

Blood Lipids

Blood Pressure

Smoking

Diabetes Screening

Alcohol

Depression and Stress

THANK YOU FOR YOUR ATTENTION!

ANY QUESTIONS?