Pre-eclampsia

Defined as ‘gestational hypertension of at least 140/90mmHg on two separate occasions

>4hrs apart accompanied by significant proteinuria of at least 300mg in 24 hr urine after 20
weeks of pregnancy’ in a previously normotensive woman and resolving completely by the
6th week postpartum.

- Complicates 2-8% of pregnancies

- Causes 15% of direct maternal deaths in UK
- 5x increase in perinatal mortality with iatrogenic prematurity being the main reason
- worldwide 70,000 women die from preeclampsia each year
- 1 in 6 stillbirth occur in pregnancies complicated by hypertension.

Proteinuria

24 hr urinary excretion of >300mg

PCR >30g or 0.3mg/nmol
ACR >8mg/mmol

Risk factors
- >40
- previous history of PET
- pre pregnancy obesity
- women who become preganant with donor eggs, embryo donation or insemination
- diabetes
- pre-existing PET
- family history of PET
- women suffering medical conditions such as antiphospholipid

Complications:
- risk of seizure
- pulmonary oedema
- placental abruption 1-4%
- oligohydramnios and FGR (up to 30%)

Pre-eclampsia also carries implications in adult life with offspring of affected pregnancies
demonstrating an increased risk of hypertension and stroke

Pathophysiology

- increased peripheral vascular resistance leads to generalised vasospasm and

hypertension.
- The intravascular compartment is reduced and endothelial damage leads to
increased vascular permeability and oedema.
- This is accompanied by a reduction in CVP/pulmonary wedge pressures.
 - The entire multisystem clinical picture of pre-eclampsia can be explained in terms of
dysfunction of the vascular endothelial cells.
- Associated with a decrease in platelet number but an increase in platelet
aggregation and adhesion to vascular endothelial cells.
- Activation of the cells results in the production of both inflammatory and oxidative
mediators, which further augment vascular dysfunction.
- The levels of anti-thrombin III, protein C and protein S all fall in PET, reflecting
increased consumption of clotting factors.

Liver- vasoconstriction of hepatic beds leads to periportal fibrin deposition, haemorrhage

and hepatocellular necrosis. More rarely hepatic infarction and rupture of the liver capsule
can occur.

Kidney- in PET there is an enhanced vascular sensitivity to angiotensin II and

norepinephrine, resulting in vasoconstriction and hypertension. The preglomerular vessels
of the renal circulation become extremely sensitive to vasoconstriction actions of
angiotensin II.
Renal function deteriorates in 2 stages in PET
Stage 1 involves impairment of tubular function (reflected by reduction in uric acid
clearance)
Later, glomerular filtration becomes impaired and proteinuria of intermediate selectivity
occurs.

Cerebral- cerebral vasoconstriction leads to focal ischaemia and abnormal electrical activity
and thus triggers seizures.

Eclampsia

- 27.5 per 10 000 maternities. (0.027%)

- intense vasoconstriction leads to abnormal electrical activity and thus triggers
seizures

- 38% antenatally
- 18 % intrapartum
- 44% postpartum (usually in the first 24-48 hours)

- 1 in 50 women with eclampsia die

- Stillbirths- 22 per 1000
- Neonatal deaths 34 per 1000

- The most common cause of women dying from eclampsia is cerebral haemorrhage

Uterine artery Doppler

- Increases resistance in uterine arteries is an early feature of PET .

 - Results from defective invasion of spiral arteries and the failure of vessels to
transform unto low resistance vessels.

Prevention of pre eclampsia

- PET has seen a 40% increase in recent years

- Use of anticoagulation not recommended

NICE recommend 75-150mg Aspiring in high risk women:

- Hypertensive during previous pregnancy

- CKD
- Autoimmune disease such as SLE or antiphospholipid syndrome
- Diabetes (type 1 or 2)
- Chronic hypertension

Treatment

- BP should be measured every 15 mins until settles <160/105 (MAP<125mmHg) then

every 30mins

First choice – labetalol

- 200mg
- if no response in 30 mins a second 200mg
- if no initial response, proceed to 50mg IV bolus over at least 5 mins repeated to max
of 200mg at 10 min intervals
- following this, labetalol infusion should be commenced at 5mg/ml at 4ml/hr via
syringe pump. (20mls/hr)
- infusion rate can be doubled every 30mins to a max 32/ml/hr (160mg/hr) until BP
has dropped and stabilised
- contraindications include severe asthma. Use with caution in cardiac disease

Second agent of choice- Hydralazine

- Bolus infusion 10-20mg over 10-20mins while measuring BP every 5 mins

- May be followed by infusion of 40mg of hydralazine in 40mls normal saline at 1-
5ml/hr (1-5mg/hr)

Magnesium sulfate
Loading dose – 4g IV over 5-10mins
Maintenance dose – 4g IV over 4 hrs (1g/hr)

Clinical review every 4 hrs for:

Continuous pulse oximetry
- Hourly urine output
- Hourly resp rate
- Reflexes every 4 hrs

Stop MgSO4 if:

- Bicep reflex absent
- Respiratory rate

Adverse effects:
- Motor paralysis
- Absent reflexes
- Respiratory depression
- Cardiac arrhythmia

Antidote
- Administer 10mls 10% calcium gluconate slowly IV

97% of MgSO4 is excreted in urine. If oligouria should be reduced/withheld.

Fluid management

- Total input should be limited to 80mls/hr (approx. 1ml/kg/hr)

- If oxytocin used, it should be a high concentration and the volume of fluid included
in total input.

PlGF

- PlGF is a protein involved in placental angiogenesis.

- In PET, the levels of PlGF can be abnormally low
- In normal pregnancy, PlGF levels rise to a peak at 26-30 weeks so when PGlF levels
do not rise during pregnancy there may be placental dysfunction.
- The test is intended for use with clinical judgment and other diagnostic tests to
assess the level of risk for delivery arising from PET within 14 days of testing

<12pg/ml- test +ve highly abnormal. Increased risk of severe placental dysfuntion requiring
delivery

>/12- <100 test +ve. Suggestive of abnormal placental dysfunction at risk of delvery
>100 normal. Suggests no placental dysfunction