PRE-ECLAMPSIA

Obstetrics and Anaesthetics Meeting Oct 2013

Dr Sarah Pixton

O&G Registrar

INCIDENCE WORLDWIDE

• Pre-eclampsia (PE) is a multisystem disease that occurs in 2 to 8% of pregnant women and is a leading cause of maternal and perinatal morbidity and mortality.

• Eclampsia affects 1 in 2000 pregnancies with a 2% mortality rate and a 35% rate of significant complication.

• HELLP complicates 1 in 500 pregnancies• Worldwide, PE is responsible for approximately 50,000 maternal deaths

annually. Worldwide, 10 to 15 percent of direct maternal deaths (ie, resulting from obstetric complications of pregnancy) are associated with preeclampsia/eclampsia

• In the UK- The Confidential Enquiries reveal that deaths from pre-eclampsia/eclampsia have been reduced from 11.9/million maternities in 1985–1987 to 7.0/million maternities in 2000–2002, when there were 14 deaths. Nine women died from cerebral causes, with substandard care in 50% of cases

IN AUSTRALIA…

IN AUSTRALIA…

CLASSIFICATION OF HYPERTENSION IN PREGNANCY

1) Preeclampsia ( incl. eclampsia and HELLP)

2) Chronic Hypertension

3) Preeclampsia superimposed on Chronic Hypertension

4) Gestational Hypertension

DIAGNOSIS

• 1)Pre-eclampsia is defined as new onset of hypertension(≥140/90) after 20 weeks gestation with proteinuria ( 0.3g/24hr), in a previously normotensive woman

• 2)Chronic/pre-existing hypertension is defined as BP (≥140/90) that antedates pregnancy or is present before the 20th week of pregnancy (on at least two occasions) or persists longer than 12 weeks postpartum

DIAGNOSIS

• 3)Superimposed preeclampsia is defined by the new onset of proteinuria after 20 weeks of gestation in a woman with chronic/preexisting hypertension.

• 4)Gestational hypertension refers to hypertension without proteinuria or other signs/symptoms of preeclampsia that develops after 20 weeks of gestation and resolves by 12 weeks post partum

PATHOPHYSIOLOGY

• Abnormalities of the placental vasculature (In PE, there is an improper remodeling of spiral arteries during placentation)

• Relative placental underperfusion/ischaemia

• Release of antiangiogenic factors into maternal circulation

• Systemic endothelial dysfunction

In pre-eclampsia…

Aspirin level of action

Imbalance between vasodilator mediators (prostaglandin, NO) and vasoconstrictor mediators (thromboxane) results in endothelial dysfunction

Under normal conditions, the remodeling of maternal spiral arteries is favoured by high availability of nitric oxide (NO)

In preeclampsia, there is an improper remodeling of spiral arteries during placentation causing endothelial dysfunction

CLINICAL FEATURES

Cardiopulmonary– Hypertension is generally the earliest finding– Intravascular volume and oedema (intravascular

vol is reduced likely due to vasoconstriction). Oedema (may represent overfilling) facial oedema

– Cardiac function myocardium not affected directly by PE. high afterload in preeclampsia

– Pulmonary oedema Multifactorial- causes of pulmonary edema incl capillary leak, left heart failure, and iatrogenic volume overload

CLINICAL FEATURES

Renal

• Proteinuria: It is due, in part, to impaired integrity of the glomerular barrier and altered tubular handling of filtered proteins (hypofiltration) leading to increased protein excretion

• Renal function: GFR decreases by 30-40% • Rising Creatinine and oliguria:• ie, urine output <500 mL/24 hours,

indicates severe

disease and results from

renal vasoconstriction and

sodium retention

CLINICAL FEATURES

Haematologic• most common coagulation abnormality in

preeclampsia is thrombocytopenia.• Microangiopathic endothelial injury and

activation result in formation of platelet and fibrin thrombi in the microvasculature.

• Accelerated platelet consumption leads to thrombocytopenia

• immune mechanisms may also play a role

CLINICAL FEATURES

Hepatic• Reduced hepatic blood flow can lead to

ischemia and periportal hemorrhage. • The clinical manifestations of hepatic

dysfunction include right upper quadrant or epigastric pain, elevated transaminase levels, coagulopathy, and, in the most severe cases, subcapsular hemorrhage or hepatic rupture.

• Epigastric pain is one of the cardinal symptoms of severe preeclampsia

CLINICAL FEATURES

Neurological•  CNS manifestations of PE include headache, visual symptoms,

and hyperreflexia with sustained ankle clonus• Visual symptoms are caused, at least in part, by constriction

of retinal arteries. Symptoms include blurred vision, flashing lights and scotomata

• Seizures in a preeclamptic woman signify a change in diagnosis to eclampsia

• Stroke leading to death or disability is the most serious complication of severe preeclampsia/eclampsia

• Histopathologic correlates include hemorrhage, petechiae, cerebral edema, vasculopathy, ischemic brain damage, microinfarcts, and fibrinoid necrosis

CLINICAL FEATURES

• Chronic placental hypoperfusion results in fetal growth restriction and oligohydramnios.

• Preterm delivery is a secondary result of fetal or maternal complications

• Abruption is infrequent (less than 1 percent) in women with mild preeclampsia, but has been reported in 3 percent of those with severe disease

• Increased resistance in the placental vasculature is also reflected by rising Doppler indices of the umbilical artery

Fetus and Placenta

CLINICAL FEATURES OF SEVERE PE

symptoms of :• severe headache• visual disturbance• epigastric pain and/or vomiting• dyspnoea./ retrosternal chest pain• confusion

signs of :• Hypertension > 160/110• Clonus (>3 beats)• papilloedema• Liver tenderness • Severe proteinuria >5grams/24hr• HELLP syndrome• platelet count falling to below 100• abnormal liver enzymes (ALT or AST rising to above 70 iu/l)• Elevated creatinine• Fetal compromise- IUGR, Oligohydramnios, Abnormal flows

ANTENATAL MANAGEMENT

PREVENTION

• In the clinical practice, there is currently no reliable screening method in the first trimester of pregnancy with sufficient accuracy to identify women at high risk of developing pre-eclampsia, and only two interventions are strongly recommended by the World Health Organization for prevention of pre-eclampsia: high dose calcium supplementation in all women at risk or with low dietary calcium intake and low-dose aspirin.

Delivery is the only known cure.

CLASPThe Collaborative Low·dose Aspirin Study in Pregnancy (CLASP)

was performed from 1988-1993 as a randomized, double-blind, placebo-controlled trial of low-dose aspirin for the prevention or treatment of pre-eclampsia and /or fetal growth retardation.

Women between 12 and 32 weeks of pregnancy received a daily dose of 60 mg of aspirin or matching placebo until delivery if they were thought to be at higher than average risk of developing severe preeclampsia.

A total of 9364 women from 213 centers in 16 countries were randomized.

The impact of low-dose aspirin on the prevention of preeclampsia and its sequelae was smaller in CLASP than in the earlier reports possibly due to the inclusion of relatively low-risk patients in the CLASP- trial.

CLASP Results

• The prophylactic use of aspirin was associated with a decrease of 12% in the incidence of proteinuric preeclampsia, but the reduction was not statistically significant.

• No significant effect on birth weight or stillborn rate was detected. • Aspirin did, however, significantly reduce the likelihood of preterm

delivery (19.7% aspirin vs 22.2% control) There was a significant trend (p = 0.004) towards progressively greater reductions in proteinuric pre-eclampsia the more preterm the delivery.

• There was no evidence of a therapeutic effect of low-dose aspirin. • Finally, CLASP provided support with regard to the safety of

aspirin for the pregnant woman and her baby

From the NICE Guidelines..

CALCIUM SUPPLEMENTATION

• Calcium supplements (1.5-2g per day) has been evaluated for prevention of hypertensive disorders of pregnancy.

• In a systematic review of 13 randomized trials (including >15,000 women), the effects of calcium supplementation on development of pregnancy-related hypertensive disorders was assessed.– It appeared to approx halve the risk of PE (RR 0.45, 95% CI

0.31-0.65), to reduce the risk of preterm birth (RR 0.76, CI 95% 0.60-0.97), and to reduce the outcome of “ maternal death or serious morbidity” ( RR 0.80, 95% CI 0.65-0.97)

– There were no harms identified

CURRENTLY NOT RECOMMENDED..

Other pharmaceutical agentsDo not use the following to prevent hypertensive disorders during pregnancy:• nitric oxide donors • progesterone • diuretics • low molecular weight heparin.Nutritional supplementsDo not recommend the following supplements solely with the aim of preventing hypertensive disorders during pregnancy:• magnesium • folic acid • antioxidants (vitamins C and E) • fish oils or algal oils • garlic.DietDo not recommend salt restriction during pregnancy solely to prevent gestational hypertension or pre-eclampsia.

RECURRENCE

Thank you

REFERENCES

• Diagnosis, pathophysiology and management of pre-eclampsia: a review. Susana Machado, Marta Neves, Luís Freitas, Mário Campos.

Port J Nephrol Hypert 2013; 27(3): 000-000• Pre-eclampsia Sibai, Baha;Dekker, Gus;Kupferminc, Michael The

Lancet; Feb 26-Mar 4, 2005; 365, 9461; ProQuest pg. 785• NICE Guidelines: Hypertension in pregnancy :the management of

hypertensive disorders during pregnancy. Revised Jan 2011• Up to Date: Preeclampsia Clinical features and Diagnosis• www.somanz.org/guidelines -Guidelines for the Management of

Hypertensive Disorders of Pregnancy 2008• www.aihw.gov.au - Statistics Maternal deaths in Australia 2003-2005• Calcium supplementation during pregnancy for preventing hypertensive

disorders and related problems.AUHofmeyr GJ, Lawrie TA, Atallah AN, Duley LSO. Cochrane Database Syst Rev. 2010;