CHEARS

 Pre-eclampsia is a condition that affects 2-5 percent of all pregnancies and is the main cause of maternal and perinatal death. Preeclampsia, one of four hypertensive diseases of pregnancy, is defined as new-onset hypertension and proteinuria occurring after 20 weeks of pregnancy. It is now known to be a complicated, progressive, multisystem condition with a wide range of symptoms.

Diagnosis:

A diagnosis of preeclampsia can be made when hypertension arises after 20 weeks gestation and is accompanied by one or more of the following signs of organ involvement:

Renal involvement:

Significant proteinuria – a spot urine protein/creatinine ratio ≥ 30mg/mmol,Serum or plasma creatinine > 90 μmol/L Oliguria: 600mIU/L,

Liver involvement :

Raised serum transaminases Severe epigastric and/or right upper quadrant pain.

Neurological involvement Convulsions (eclampsia) Hypereflexia with sustained clonus Persistent, new headache Persistent visual disturbances (photopsia, scotomata, cortical blindness, posterior reversible encephalopathy syndrome, retinal vasospasm) Stroke Pulmonary oedema Fetal growth restriction (FGR)

Haematological involvement: Thrombocytopenia 600mIU/L, decreased haptoglobin Disseminated intravascular coagulation

1ST TRIMESTER

Combined screening during 1st trimester is the most effective way to identify women at high risk for pre-eclampsia

Combined screening

The combined screening program is made up of four steps that require short training and minimal additional investment in equipment for screening programs.

1. Record medical history, weight and height.

2. Take blood sample for measuring PlGF 1-2-3TM test.

3. Measure blood pressure 2 times from both arms simultaneously.

4. If accessible, measure uterine artery Doppler pulsatility index.

2ND & 3RD TRIMESTER

In pregnancies that develop pre-eclampsia, maternal serum placental growth factor (PlGF) levels decrease significantly, while soluble fms-like tyrosine kinase 1 (sFlt-1) levels increase significantly several weeks prior to clinical symptom onset. Thus, PlGF and sFlt-1 are important biomarkers used to identify high risk women that are likely to develop preterm pre-eclampsia later in their pregnancy and to predict the onset of pre-eclampsia. Biomarker levels are also found to be correlating with severity of disease.

dye called Congo Red is found to be specifically bound to pre-eclampsia specific misfolded protein aggregates (Congophilia) which are secreting to urine during pre-eclampsia. A test based on selected binding of Congo Red dye to misfolded proteins present in the urine of women affected with pre-eclampsia provides a fast aid in diagnosis for women with suspected pre-eclampsia

During 2T and 3T sFlt1 and PlGF are both predictive and diagnostic for PE. It has been shown that increased levels of sFlt-1 and decreased levels of PlGF in maternal serum can predict the subsequent onset of pre-eclampsia. Determining serum sFlt and PlGF levels, used as ratio, improves the clinical management and decision making (risk stratification) with women showing signs and symptoms of pre-eclampsia.

PATHOPHYSIOLOGY

Preeclampsia results from impaired trophoblast differentiation and invasion in early pregnancy, which stimulates sustained oxidative stress and a systemic inflammatory response.

Abnormal placentation has been suggested as an extrinsic cause leading to early onset of preeclampsia.

Recent work has suggested that late onset preeclampsia (≥34 weeks’ gestation) may be triggered by a distinct, intrinsic pathology involving microvillus overcrowding. This is thought to occur as placental growth reaches its limits at term, with diminishing villous pore size impeding perfusion and increasing oxidative stress.

Effective management of preeclampsia may be divided into three categories; prevention of preeclampsia, early detection, and treatment.

Women considered to be at high risk of preeclampsia (such as those with chronic hypertension, coexisting renal disease, or antiphospholipid syndrome should be referred for pre-pregnancy counseling to identify modifiable risk factors). This

management may involve cessation of smoking advice, dietary advice, adjustment of medications to optimize medical conditions such as preexisting renal disease, and cessation of potentially teratogenic agents such as warfarin and angiotensin-converting enzyme (ACE) inhibitors.. Optimal pre-pregnancy health may reduce risk of developing preeclampsia. Women thought to be at high risk should be given low-dose aspirin before 12 weeks’ gestation until 36 weeks’ gestation. Calcium supplementation (≥1 g/day) is associated with a significant reduction in the risk of preeclampsia, particularly for women with low-calcium diets.

Management of pre-eclampsia

Management of pre-eclampsia depends on the severity of the disease (with or without severe features) and gestational age at diagnosis. For pre-eclampsia without severe features, delivery is recommended at term (≥37 weeks). For pre-eclampsia with severe features, delivery is recommended if gestational age is at ≥34 weeks. Before 34 weeks of gestation, the decision to deliver should be balanced between risk of maternal or foetal complications and benefit of continuing pregnancy to foetal maturity.

Patients with gestational hypertension or mild pre-eclampsia after 36 weeks who undergo induction of labour have a reduced rate of adverse maternal outcomes (especially the development of severe hypertension), lower incidence of caesarean delivery and a better quality of life than those who had expectant management. If preterm induction of labour is contemplated, steroids are administered between 24 weeks and 34 weeks of gestation to improve fetal lung maturity. Magnesium sulfate is administered during labour and the first 24 h after delivery for seizure prophylaxis

The primary goal of treating hypertension in patients with pre-eclampsia is to prevent an acute hypertensive crisis, which might lead to intracranial haemorrhage or stroke. Acute-onset, persistent (lasting ≥15 min) and severe hypertension (systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥110 mmHg) requires immediate treatment

goal of antihypertensive therapy is not to normalize blood pressure, but to maintain uteroplacental perfusion and achieve a blood pressure within the range of 140–160/90–100 mmHg, above which loss of autoregulation of cerebral vasculature occurs.

Hydralazine, labetalol and nifedipine are the three most commonly used agents

Hydralazine 5mg IV or 10 mg IM OR

labetalol 20 mg iv bolus

Sodium nitroprusside is reserved only for the rare patients in whom hypertension is refractory to other agents, because of concerns related to cyanide and thiocyanate toxicity in the mother and baby, and potential worsening of cerebral oedema in the mother.

During labor, the management goals are to prevent seizures and control hypertension. Magnesium sulfate is the medication of choice for the prevention of eclamptic seizures in women with severe preeclampsia and for the treatment of women with eclamptic seizures. One commonly used regimen is a 6-g loading dose of magnesium sulfate followed by a continuous infusion at a rate of 2 g per hour. Magnesium sulfate has been shown to be superior to phenytoin and diazepam for the treatment of eclamptic seizures. .

Prevention

There currently are no well-established measures for preventing preeclampsia. Both low-dose aspirin therapy and daily calcium supplementation have been studied as preventive measures but have not been shown to be beneficial in the general pregnant population and are not recommended for primary prevention of preeclampsia. Some evidence does support the use of low-dose aspirin therapy and daily calcium supplementation in certain high-risk women. Calcium supplementation has been shown to produce modest blood pressure reductions in pregnant women who are at above-average risk for hypertensive disorders of pregnancy and in pregnant women with low dietary calcium intake. An optimum calcium dosage for these women has not been established. Low-dose aspirin therapy (100 mg per day or less) has been shown to reduce the incidence of preeclampsia in women who were found to have an abnormal uterine artery on Doppler ultrasound examination performed in the second trimester.

The ASPRE trial results showed that the rate of developing early onset pre-eclampsia dropped by 82% and preterm pre-eclampsia by 62% among those women who received 150 mg aspirin treatment per night and were at high risk of developing the disease

Research on the use of antioxidants in the prevention of preeclampsia is promising. However, further study is needed, and antioxidant therapy currently is not recommended.