Pre-eclampsia and Eclampsia

Hypertension developing after 20 weeks gestation with one or more of the following—

• Severe preoteinuria
• Maternal organ dysfunction (including renal, hepatic, hematological, neurological complications) or
• Uteroplacental dysfunction/fetal growth dysfunction

Eclampsia is the occurrence of seizures (grand mal) in a patient with pre-eclampsia after excluding other causes.

Responsible for 14% of maternal deaths yearly (60,000—75,000)

In the developing world, the incidence is reported to be 4—18%.

Associated with high maternal and perinatal morbidity and mortality.

Cure is delivery.

Hypertension is defined as blood pressure measurement equal to or greater than DBP of 90mmHg, SBP of 140 mmHg on two or more consecutive occasions at least 4 hours apart.

It is a disease with several theories.

The cause and course is unknown.

It is more likely a disease of poor trophoblastic invasion in the myometrium resulting in the poor vasodilatation of maternal spiral arteries. This results in inadequate perfusion and ischemia in the second half of pregnancy.

An imbalance in angiogenic molecules play a major role in the pathogenesis of pre-eclampsia, raising the possibility that these molecules may be targeted for preventive measures and possible palliative therapy.

Many investigators believe that the placenta is the trigger for endothelial cell injury.

The theories

• Endothelial cell injury
• Immunologic theory
• Imbalance between prostaglandins and pro-angiogenic and anti-angiogenic factors
• Altered vascular reactivity
• Compromised placental perfusion
• DIC, etc.

According to ACOG 2013

1. PE without severe features
2. PE with severe features

Subclassification

1. Early-onset PE (with delivery at <34 + 0 weeks of gestation)
2. Preterm PE (with delivery at <37 + 0 weeks of gestation)
3. Late-onset PE (with delivery at ≥34 + 0 weeks of gestation)
4. Term PE (with delivery at ≥37 + 0 weeks of gestation)

Pre-eclampsia can also be classified as mild or severe; however, this is an old classification.

Severe when it is associated with complications such as—

• Systolic BP of 160 mmHg or diastolic BP of 110 mmHg
• Proteinuria >2g in 24h
• Oliguria < 500ml in 24h
• Cerebral or visual disturbances
• Epigastric pain
• Elevated liver enzymes
• Thrombocytopenia
• Retinal hemorrhages, exudates or papilledema
• Pulmonary edema

The classification of hypertensive diseases in pregnancy according to the NHBPEP Working Group is as follows:

Gestational hypertension

• BP of 140/90 mmHg or greater for the first time during pregnancy
• No proteinuria
• BP returns to normal less than 12 weeks post-partum
• Final diagnosis made only post-partum

Chronic hypertension

• BP of 140/90 mmHg or greater before pregnancy or diagnosed before 20 weeks gestation, not attributable to gestational trophoblastic disease
OR
• Hypertension first diagnosed after 20 weeks gestation and persistent after 12 weeks post-partum

Superimposed pre-eclampsia (on chronic hypertension)

• New onset proteinuria (≥300 mg/24h) in a woman with hypertension but no proteinuria before 20 weeks gestation.
• A sudden increase in proteinuria or blood pressure, or platelet count less than 100,000 in women with hypertension and proteinuria before 20 weeks gestation.

• First pregnancy
• Previous history and family history
• Black race
• Maternal age > 40 years
• 10 years or more since last baby.
• Low socioeconomic status
• Hydatidiform mole
• Polyhydraminos
• multiple pregnancy
• Obesity
• DM
• chronic hypertension
• Pre-existing renal disease
• Thrombophilia
• Autoimmune disease
• Low vitamin D level
• Low dietary and serum calcium
• High level of glycosylated fibronectin in first trimester
• Couple-related factors
• Limited sperm exposure
• Primiparity
• Pregnancies after donor insemination, oocyte donation, or embryo donation
• Protective effect of partner change in the case of previous pre-eclamptic pregnancy
• Maternal susceptibility genes
• Family history of pre-eclampsia
• Smoking (reduced risk)
• Hydropic degeneration of placenta

Patients are usually asymptomatic at the onset of the disease

Hypertension and proteinuria are the most common clinical signs but the absence of these signs does not exclude the diagnosis.

Maternal and fetal complications

Maternal symptoms include—

• Headache
• Double or blurred vision
• Nausea and vomiting
• Epigastric pain
• Rapidly increasing or severe edema
• Hyperreflexia

Urinalysis should be done daily to check for proteinuria and a 24h urine protein should be done to assess the progression of proteinuria, which correlates with the degree of renal damage.

Hematocrit/hemoglobin concentration to assess for anemia/hemoconcentration. Severe anemia is associated with a higher risk for pre-eclampsia. Hemconcentration can be caused by the diminished plasma volume seen in these patients.

Platelet count- platelet count can fall due to intravascular destruction and increased consumption.

Electrolytes, creatinine, uric acid— serum uric acid falls in normal pregnancy but tends to be raised in pre-eclampsia as a result of reduced renal excretion and a rise correlates with poor outcome for both mother and baby. Urea and creatinine may also be raised and can indicate renal compromise.

Elevated liver enzymes— alkaline phosphatase, alanine and aspartate transaminases, lactose dehydrogenase.

Ultrasound for fetal dating and well-being.

Delivery is the cure for the disease

If the diagnosis is made, the definitive treatment is delivery to prevent development of maternal or fetal complications from disease progression: Delivery results in resolution of the disease.

Most of the complications are llife-threatening and can develop suddenly.

The optimal management of a woman with pre-eclampsia depends on and

• Gestational age
• Severity of the disease.
• Maternal and fetal condition

In asymptomatic patients— ambulatory care can be instituted

In mild disease— bed rest and delivery

At preterm gestational ages, the risks of serious sequelae from disease progression need to be balanced with the risks of preterm birth.

When mother and fetus are stable and without findings of serious end-organ dysfunction, a conservative approach with close monitoring for evidence of progression to the severe end of the disease spectrum is reasonable to achieve further fetal growth and maturity. However, at any gestational age, evidence of severe hypertension, serious maternal end-organ dysfunction, or nonreassuring tests of fetal well-being are generally an indication for prompt delivery

Do daily urinalysis and BP monitoring

Look out for dangers suggesting complications

Do baseline investigations

Use of sedatives

Use of antihypertensives if DBP is constantly >100mmHg— labetalol, nifedipine, methyldopa

A pregnancy complicated by mild pre-eclampsia at or beyond 37 weeks should be delivered.

Biophysical profile is indicated in mild disease before term, twice per week.

Where there is complication associated with mild disease after 34 weeks, delivery is recommended.

In severe pre-eclampsia

• Prevent convulsions
• Control maternal blood pressure
• Initiate delivery- deliver at 37 weeks GA
• At 32-34 weeks, deliver in severe disease after ensuring lung maturity
• Use of corticosteroids, prophylactic MgSO4
• Vaginal vs cesarean delivery; consider obstetric indications
• Make sure there are no contraindications to attempting induction of labor such as fetal malpresentation, non-reassuring fetal heart tracing, etc.

Treat as emergency and resuscitate

Control seizures using MgSO4, diazepam

Control HTN—

• Hydralazine- most commonly used; 5-10 mg IV slowly, repeated every 30 minutes.
• Labetalol
• Nifedipine- 20-30 mg 12 hrly

Delivery— state of the cervix and patient

Proper fluid management

Ensure patent airway and prevent aspiration

Ensure oxygenation and suctioning of the airway

Give loading and maintenance doses of MgSO4

Monitor closely to avoid Mg toxicity. MgSO4 seizure prophylaxis is continued for 24 hours post-partum.

Deliver once mother is stable.

Monitoring drug toxicity using clinical parameters

The parameters that need to be monitored are

• The knee jerk (should be present)
• Respiratory rate (should be more than 16/minute)
• Urine output (should be more than 25 ml/hr)

The first warning of toxicity is the loss of the knee jerk which occurs at serum magnesium level of 3.5—5 mmol/l.

Respiratory paralysis occurs at 5—6.5 mmol/l

Cardiac conduction is altered at more than 7.5 mmol/l

While cardiac arrest occurs when serum magnesium exceeds 12.5 mmol/l

Should toxicity be detected, the antidote is 1g of 10% calcium gluconate given intravenously, slowly over 10 minutes.

Complications

Maternal

1. HELLP syndrome
2. Pulmonary edema
3. Hepatic rupture
4. Renal failure
5. Seizure
6. Cerebral hemorrhage

Fetal

1. Prematurity
2. Fetal distress
3. IUGR
4. Oligohydraminios
5. Placenta abruption
6. Stillbirth

Prevention

Aspirin between 11—16 weeks GA

Vitamins C and E

Calcium— in patient with low calcium

Fish oil

Magnesium

Universal screening

The best combined test includes—

Maternal risk factors

Mean arterial pressure (MAP)

Serum placental growth factor (PLGF) and uterine artery pulsatility index (UTPI)

Serum pregnancy-associated plasma protein (PAPP-A)

Prognosis

Hypertension and other signs or symptoms of organ dysfunction associated with pre-eclampsia will have remitted by 6 weeks post-partum examination.

If abnormalities persist, the patient should be examined 6 weeks later, when any persisting pathologic conditions will probably be chronic.

Recurrence rates are higher among multiparous women with pre-eclampsia than among nulliparous women with pre-eclampsia.

Risk is also increased among multiparous women who conceive with a new father, even when the first pregnancy was normotensive.

Pre-eclampsia-eclampsia by itself is not a cause of chronic hypertension.

Women with normotensive births have a reduced risk for remote hypertension.