Download Pre-eclampsia

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 preeclampsia/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
4) Gestational
superimposed on Chronic
Hypertension
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…
Imbalance between vasodilator
mediators (prostaglandin, NO)
and vasoconstrictor mediators
(thromboxane) results in
endothelial dysfunction
Aspirin level of
action
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
Fetus and Placenta
• 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
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 preeclampsia, 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.
CLASP
 The 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 pregnancyrelated 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 agents
Do not use the following to prevent hypertensive disorders during
pregnancy:
• nitric oxide donors • progesterone • diuretics • low molecular
weight heparin.
Nutritional supplements
Do 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.
Diet
Do not recommend salt restriction during pregnancy solely to
prevent gestational hypertension or pre-eclampsia.
RECURRENCE
Thank you
REFERENCES
• Diagnosis, pathophysiology and management of preeclampsia: 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 20032005
• Calcium supplementation during pregnancy for preventing
hypertensive disorders and related problems.AUHofmeyr GJ, Lawrie
TA, Atallah AN, Duley LSO. Cochrane Database Syst Rev. 2010;