Preeclampsia (hypertension + proteinuria) is a disorder of widespread vascular endothelial

malfunction and vasospasm that occurs after 20 weeks' gestation and can present as late as 4-6
weeks post-partum. It is clinically defined by hypertension and proteinuria, with or without
pathologic edema. Eclampsia is defined as seizures that cannot be attributable to other causes
in a woman with preeclampsia.

Preeclampsia is defined as the presence of (1) a systolic blood pressure (SBP) greater than or
equal to 140 mm Hg or a diastolic blood pressure (DBP) greater than or equal to 90 mm Hg or
higher, on two occasions at least 4 hours apart in a previously normotensive patient, OR (2) an
SBP greater than or equal to 160 mm Hg or a DBP greater than or equal to 110 mm Hg or higher

In addition to the blood pressure criteria, proteinuria of greater than or equal to 0.3 grams in a
24-hour urine specimen, a protein (mg/dL)/creatinine (mg/dL) ratio of 0.3 or higher, or a urine
dipstick protein of 1+ (if a quantitative measurement is unavailable) is required to diagnose
preeclampsia.

In a patient with new-onset hypertension without proteinuria, the new onset of any of the
following is diagnostic of preeclampsia:

• Platelet count below 100,000/μL

• Serum creatinine level above 1.1 mg/dL or doubling of serum creatinine in the absence
of other renal disease
• Liver transaminase levels at least twice the normal concentrations
• Pulmonary edema
• Cerebral or visual symptoms

Preeclampsia results in end-organ injury, e.g., the liver, kidney, lung, hearts, eyes, etc.

HELLP syndrome: hemolysis, elevated liver enzyme, low platelets

Risk factors for preeclampsia include nulliparity, age older than 40 years, black race, family
history, chronic renal disease, chronic hypertension, antiphospholipid syndrome, diabetes
mellitus, high BMI, homozygosity or heterozygosity for angiotensin gene T235.

This condition needs a multidisciplinary team approach.

Pathophysiology[1][2]: Preeclampsia is a disease of abnormal placentation. The pathogenesis is

complex and incompletely understood. However, there is consensus that the primary disease is
an abnormality of placentation. The presence of the placenta, as opposed to the fetus, is
essential to the development of pre-eclampsia, which is evident by the development of the
condition in hydatidiform mole. Pre-eclampsia only occurs in pregnancy, but has been described
in pregnancies lacking a fetus (molar pregnancies) and in the absence of a uterus (abdominal
pregnancies), suggesting that it is the presence of trophoblast tissue that provides the stimulus
for the disorder

Common pathological findings in pre-eclamptic placentae include atherosis, sclerotic narrowing

of arteries and arterioles, fibrin deposition and infarcts, which are all consistent with placental
hypoperfusion and ischemia and seem to correlate with the severity of pre-eclampsia. In
addition, marked hypertrophy of the media in the decidual vessels, known as hypertrophic
decidual vasculopathy, has been reported.

Ultrasonographic evidence of this problem includes an increase in the pulsatility index (PI) of the
uterine artery or persistent diastolic ‘notch’ in its Doppler waveform. The resistance index is also
increased. Maternal uterine artery doppler can be used for prediction (screening; the condition
hasn’t developed yet); increased impedance of uterine artery velocimetry (presence of diastolic
notch) at 16-20 weeks is predictive of preeclampsia.

With normal placentation, maternal uterine spiral arteries run through the myometrium and
into the endometrium, which in pregnancy is replaced by the decidua. Trophoblasts of fetal
origin invade these spiral arteries resulting in a loss of elasticity and vascular smooth muscle
tone. Consequently, these arteries are remodeled into low resistance capacitance vessels, which
provide sufficient placental perfusion to sustain the growing fetus.

However, in preeclampsia, trophoblastic invasion is much shallower, affecting only the spiral
arteries in the decidua. The myometrial sections remain small and constricted, resulting in a
defective uteroplacental circulation with a higher resistance. This gives rise to subsequent
placental ischemia. Why this should happen to a minority of individuals is unknown, but genetic
and immunological mechanisms are thought to be important contributors.

In the first stage, trophoblast invasion is patchy and the spiral arteries retain their muscular
walls. This is thought to prevent the development of a high-flow, low-impedance uteroplacental
circulation and leads to uteroplacental ischemia. The reason why trophoblasts invade less
effectively in these pregnancies is not known but may reflect an abnormal adaptation of the
maternal immune system.

In the second stage, uteroplacental ischemia results in oxidative and inflammatory stress, with
the involvement of secondary mediators leading to endothelial dysfunction, vasospasm and
activation of the coagulation system. As the target cell of the disease process, the vascular
endothelial cell, is so ubiquitous, pre-eclampsia is a truly multisystem disorder, affecting
multiple organ systems, often concurrently.
Maternal systemic endothelial dysfunction leads to hypertension, proteinuria, edema, renal
failure, seizures, and HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) at the
severe end of the spectrum.

Cardiovascular system: Normal pregnancy is characterized by marked peripheral vasodilatation

resulting in a fall in total peripheral resistance despite an increase in plasma volume and cardiac
rate. Pre-eclampsia is characterized by marked peripheral vasoconstriction, resulting in
hypertension. The intravascular high pressure and loss of endothelial cell integrity results in
greater vascular permeability and contributes to the formation of generalized oedema.

Renal system: In the kidney, a highly characteristic lesion called glomeruloendotheliosis is seen.
This is relatively specific for pre-eclampsia (it is not seen with other hypertensive disorders) and
is associated with impaired glomerular filtration and selective loss of intermediate weight
proteins, such as albumin and transferrin, leading to proteinuria. This is turn causes a reduction
in plasma oncotic pressure and exacerbates the development of oedema

Hematological system: In the event of endothelial damage, platelets adhere to the damaged
area. Furthermore, diffuse vascular damage is associated with the laying down of fibrin. Pre-
eclampsia is association with increased fibrin deposition and a reduction in the platelet count
may accompany and occasionally predate the onset of disease.

The liver: In the liver, subendothelial fibrin deposition is associated with elevation of liver
enzymes. This can be associated with haemolysis and a low platelet count due to platelet
consumption (and subsequent widespread activation of the coagulation system). The presence
of these finding is called HELLP syndrome (haemolysis, elevation of liver enzymes and low
platelets). HELLP syndrome is a particularly severe form of pre-eclampsia, occurring in just 2–4%
of women with the disease. It is associated with a high fetal loss rate (of up to 60%).
Neurological system: The development of convulsions in a woman with pre-eclampsia is defined
as eclampsia. Vasospasm and cerebral oedema have both been implicated in the pathogenesis
of eclampsia. Retinal hemorrhages, exudates and papilledema are characteristic of hypertensive
encephalopathy and are rare in pre-eclampsia, suggesting that hypertension alone is not
responsible for the cerebral pathology.

Presentation:

Because the clinical manifestations of preeclampsia can be heterogeneous, diagnosing

preeclampsia may not be straightforward. Preeclampsia without severe features may be
asymptomatic. Many cases are detected through routine prenatal screening.

• Headache (not very serious feature by itself, as they are many possible causes)
• Dyspnea
• Epigastric or right upper quadrant abdominal pain
• Blurred vision
• Generalized edema
• Nystagmus
• Slurred speech
• Numbness

Those who developed at risk preeclampsia in a previous pregnancy are at risk of recurrence.
Aspirin prophylaxis is indicated in these patients.

Warning signs for eclampsia: epigastric pain and right upper quadrant tenderness, headache,
uncontrolled hypertension, agitation, hyperreflexia and clonus, facial (especially periorbital)
oedema, poor urine output, papilledema.

The patient may develop pulmonary edema (hypoxia) and cerebral edema (convulsions)

In severe pre-eclampsia in the third trimester, there may be an increase in hemoglobin

concentration. This occurs due to hemoconcentration as a result of protein loss (proteinuria),
leading to decreased oncotic pressure and subsequent extravasation of intravascular fluid
(edema), resulting in intravascular dehydration. (Dr. Rose)

Women with new onset of mild hypertension but no other criteria for preeclampsia or an
underlying disease associated with hypertension are given the diagnosis of gestational
hypertension. These women should be followed closely since 15 to 25 percent will subsequently
develop the full diagnostic criteria for preeclampsia.

Examination:

• Vital signs
• Neurological examination (consultation needed)
• Epigastric/right upper quadrant tenderness (a worrying sign and suggests liver
involvement)
• Jaundice
o Liver injury, HELLP syndrome
 • Anemia
• Pitting edema, features of DVT
o Dependent oedema of the feet is very common in healthy pregnant women.
However, rapidly progressive oedema of the face and hands may suggest pre-
eclampsia.
• Cyanosis
• Ecchymosis (HELLP syndrome)
• Obstetric examination
o Fundal height: small for gestational age

Note: A pediatrician is needed as this condition can result in iatrogenic prematurity

(Preeclampsia is the number one indication for iatrogenic preterm delivery). Complications of
preeclampsia relating to the fetus include Fetal growth restriction and intrauterine fetal demise,
due to placental insufficiency. There is also increased risk of placental abruption.

Screening can be done for preeclampsia at 20 weeks by doppler examination of the uterine
artery, which shows a diastolic notch. This increases the risk of developing preeclampsia (Dr.
Rose) (increased impedance of uterine artery velocimetry [presence of diastolic notch] at 16-20
weeks is predictive of preeclampsia)

Management:

• Regardless of the hypertensive disorder of pregnancy, BP requires urgent treatment in a

monitored setting when severe (>160/110 mm Hg); acceptable agents for this include
oral nifedipine or intravenous labetalol or hydralazine. Oral labetalol may be used if
these treatments are unavailable.
• Regardless of the hypertensive disorder of pregnancy, BPs consistently at or >140/90
mm Hg in clinic or office (or ≥135/85 mm Hg at home) should be treated, aiming for a
target diastolic BP of 85 mm Hg in the office (and systolic BP of 110–140 mm Hg) to
reduce the likelihood of developing severe maternal hypertension and other
complications, such as low platelets and elevated liver enzymes with symptoms.
Antihypertensive drugs should be reduced or ceased if diastolic BP falls <80 mm Hg.
Acceptable agents include oral methyldopa, labetalol, oxprenolol, and nifedipine, and
second or third line agents include hydralazine and prazosin.
• Women with preeclampsia who have proteinuria and severe hypertension, or
hypertension with neurological signs or symptoms, should receive magnesium sulfate
(MgSO4) for convulsion prophylaxis.
• Because delivery is the only cure for preeclampsia, clinicians must try to minimize
maternal risk while maximizing fetal maturity. The primary objective is the safety of the
mother and then the delivery of a healthy newborn. Patients with preeclampsia without
severe features are often induced after 37 weeks' gestation. Before this, the immature
fetus is treated with expectant management with corticosteroids to accelerate lung
maturity in preparation for early delivery.
• Low-dose aspirin (81 mg/d) prophylaxis is recommended in women at high risk of
preeclampsia and should be initiated between 12 weeks and 28 weeks of gestation
 (optimally before 16 weeks) and continued daily until delivery. Aspirin blocks platelet
aggregation and vasospasm in preeclampsia.

Miscellaneous notes:

• The past obstetric history is important for previous complications, due to the risk of
recurrence.
• An Indirect Coombs test can be used to test for Rh sensitization in the mother. This can
be used to determine if the cause of hydrops fetalis is due to Rh incompatibility.
• An intrauterine transfusion provides blood to an Rh-positive fetus when fetal red blood
cells are being destroyed by Rh antibodies. A blood transfusion is given to replace fetal
red blood cells that are being destroyed by the Rh-sensitized mother's immune system.