Hypertension during pregnancy

Preeclampsia-Eclampsia Syndrome

Students should be able to define and classify hypertensive disease in

pregnancy, including preeclampsia, eclampsia, and the HELLP syndrome;
to discuss the pathophysiology of preeclampsia and its diagnosis,
evaluation, and initial management, including labor management and
the appropriate use of magnesium sulfate; and understand and be able
to discuss the effects of preeclampsia on pregnancy (mother and fetus)
and the converse.

ypertensive disorders occur in approximately 12% to 22% of pregnancies

and cause substantial perinatal morbidity and mortality for both mother
and fetus. Hypertensive disease is directly responsible for approximately
20% of maternal deaths in the United States. The exact cause of
hypertension in pregnancy remains unknown.

CLASSIFICATION
Various classifications of hypertensive disorders in pregnancy have been
proposed. Box 16.1 presents a commonly used classification. Because
hypertensive disorders in pregnancyrepresent a spectrum of disease,
classification systems should be used as a guide only.

1- Chronic Hypertension Chronic hypertensionis defined as

hypertension present before the 20th week of pregnancy or
hypertension present before pregnancy. The categories of
hypertension in pregnancy and the blood pressure (BP) criteria
used to define each are as follows:

• Mild hypertension: Systolic pressure of ≥140–180 mm Hg or diastolic

pressure of ≥90–100 mm Hg or both

• Severe hypertension: Systolic pressure of ≥180 mm Hg or diastolic

pressure of ≥100 mm Hg A major risk with chronic hypertension is the
development of preeclampsia or eclampsia later in the pregnancy, which
is relatively common and difficult to diagnose. The acute onset of
proteinuria and worsening hypertension in women with chronic
hypertension is suggestive of superimposed preeclampsia.

2- Gestational Hypertension Hypertension that develops after

20 weeks of gestation in the absence of proteinuria and returns to
normal postpartum is termed gestational
[Link] hypertension develops in 5% to 10% of
pregnancies that proceed beyond the first trimester, with a 30%
incidence in multiple gestations, regardless of parity. Maternal
morbidity is directly related to the severity and duration of
hypertension. Approximately 25% of women with gestational
hypertension develop superimposed preeclampsia or eclampsia. It
is often difficult to distinguish between preeclampsia and
gestational hypertension when a patient is seen late in pregnancy
with an elevated blood pressure level. In such cases, it is always
wise to assume that the findings represent preeclampsia and treat
accordingly.
3- Preeclampsia Preeclampsiais the development of hypertension
with proteinuria and edema after 20 weeks of [Link]
condition can occur earlier in the presence of gestational
trophoblastic disease (see Chapter 41, Gestational Trophoblastic
Neoplasia). Risk factors for preeclampsia are in Box 16.2. The
criteria for diagnosis of preeclampsia are:
• Blood pressure of ≥140 mm Hg systolic or ≥90 mm Hg diastolic
that occurs after 20 weeks of gestation in a womanwith previously
normal blood pressure
• Proteinuria, defined as urinary excretion of 0.3 g protein or
higher in a 24-hour urine specimen Severe preeclampsia is
characterized by one or more of the following:
 • Blood pressure ≥160 mm Hg systolic or ≥110 mm Hg diastolic
on two occasions at least 6 hours apart while the patient is on
bed rest
 Marked proteinuria (generally ≥5 g per 24-hour urine
collection, or 3+ or more on two dipstick of random urine
samples collected at least 4 hours apart)
  • Oliguria <500 mL in 24 hours
 • Cerebral or visual disturbances such as headache and
scotomata (“spots” before the eyes)
 • Pulmonary edema or cyanosis
 • Epigastric or right-upper-quadrant pain (probably caused by
subcapsular hepatic hemorrhage or stretching of Glisson
capsule)
 • Evidence of hepatic dysfunction •
 Thrombocytopenia
 • Intrauterine fetal growth restriction (IUGR) These changes
illustrate the multisystem involvement associated with
preeclampsia. Severe preeclampsia is an indication for delivery,
regardless of gestational age or maturity.
4- Eclampsia Eclampsiais the additional presence of convulsions
(grand mal seizures) in a woman with preeclampsia that is not
explained

by a neurologic disorder. Eclampsia occurs in 0.5% to 4% of patients with

preeclampsia.

176 Obstetrics and Gynecology

BOX 16.1 Hypertensive Disorders in Pregnancy

Gestational hypertension Preeclampsia Mild Severe Eclampsia Chronic

hypertension preceding pregnancy (any cause) Chronic hypertension
(any cause) with superimposed gestational hypertension Superimposed
preeclampsia Superimposed eclampsia

BOX 16.2 Risk Factors for Preeclampsia

Nulliparity Multifetal gestation Maternal age over 35 years Preeclampsia

in a previous pregnancy Chronic hypertension Pregestational diabetes
Vascular and connective tissue disorders Nephropathy Antiphospholipid
syndrome Obesity African-American race
• Marked proteinuria (generally ≥5 g per 24-hour urine collection, or 3+
or more on two dipstick of random urine samples collected at least 4
hours apart) • Oliguria <500 mL in 24 hours • Cerebral or visual
disturbances such as headache and scotomata (“spots” before the eyes)
• Pulmonary edema or cyanosis • Epigastric or right-upper-quadrant
pain (probably caused by subcapsular hepatic hemorrhage or stretching
of Glisson capsule) • Evidence of hepatic dysfunction •
Thrombocytopenia • Intrauterine fetal growth restriction (IUGR) These
changes illustrate the multisystem involvement associated with
preeclampsia. Severe preeclampsia is an indication for delivery,
regardless of gestational age or maturity.

Eclampsia Eclampsiais the additional presence of convulsions (grand mal

seizures) in a woman with preeclampsia that is not explained

Most cases of eclampsia occur within 24 hours of delivery, but

approximately 3% of cases are diagnosed between 2 and 10 days
postpartum.

HELLP Syndrome HELLP syndrome is the presence of hemolysis,

elevated liver enzymes, andlowplatelet count.

HELLP syndrome, like severe preeclampsia, is an indication for

delivery to avoid jeopardizing the health of the woman.

This syndrome is now appreciated as a distinct clinical entity, occurring

in 4% to 12% of patients with severe preeclampsia or eclampsia. Criteria
for diagnosis are: • Microangiopathic hemolysis • Thrombocytopenia •
Hepatocellular dysfunction

PATHOPHYSIOLOGY
Hypertension in pregnancy affects the mother and newborn to varying
degrees. Given the characteristic multisystem effects, it is clear that
several pathophysiologic mechanisms are involved (Fig. 16.1). The
predominant pathophysiologicfinding in preeclampsia and gestational
hypertension ismaternal [Link] potential causes for
maternal vasospasm have been postulated:

1. Vascular changes: Instead of noting the physiologic trophoblast-

mediated vascular changes in the uterine vessels (decreased
musculature in the spiral arterioles leads to the development of a low-
resistance, lowpressure,high-flow system), inadequate maternal vascular
response is seen in cases of preeclampsia and/or intrauterine fetal
growth restriction. Endothelial damage is also noted within the vessels.
2. Hemostatic changes: Increased platelet activation with increased
consumption in the microvasculature is noted during the course of
preeclampsia. Endothelial fibronectin levels are increased and
antithrombin III and α2-antiplasmin levels are decreased, reflecting
endothelial damage. Low antithrombin III levels are permissive for
microthrombi development. Endothelial damage is then thought to
promote further vasospasm.

3. Changes in prostanoids: Prostacyclin (PGI2) and thromboxane (TXA2)

are increased during pregnancy, with the balance in favor of PGI2. In
patients who develop preeclampsia, the balance shifts to favor TXA2.
Again, PGI2 functions to promote vasodilatation and

decrease platelet aggregation, and TXA2promotes vasoconstriction and

platelet aggregation. Because of this imbalance, vessel constriction
occurs.

4. Changes in endothelium-derived factors: Nitric oxide, a potent

vasodilator, is decreased in patients with preeclampsia and may explain
the evolution of vasoconstriction in these patients.

5. Lipid peroxide, free radicals, and antioxidant release: Lipid peroxides

and free radicals have been implicated in vascular injury and are
increased in pregnancies complicated by preeclampsia. Decreased
antioxidant levels are also noted.
These five mechanisms, in any combination or permutation, are thought
to contribute to the following common pathophysiologic changes seen in
patients with preeclampsia:

1. Cardiovascular effects:Elevated blood pressure is seen as the result

of potential vasoconstriction as well as an increase in cardiac output.

2. Hematologic effects: Plasma volume contraction may develop, with

risk of rapid onset hypovolemic shock, if hemorrhage occurs. Plasma
volume contraction is reflected in increased hematocrit values.
Thrombocytopenia/disseminated intravascular coagulation may also
develop from microangiopathic hemolytic anemia. Involvement of the
liver may lead to hepatocellular dysfunction and further evolution of
coagulopathy. Third spacing of fluid may be noted, because of increased
blood pressure and decreased plasma oncotic pressure.

3. Renal effects: Decreased glomerular filtration rate (increasing serum

creatinine) and proteinuria (urine protein levels greater than 300 mg per
24 hours) develop secondary to atherosclerotic-like changes in the renal
vessels (glomerular endotheliosis). Uric acid filtration is decreased;
therefore, elevated maternal serum uric acid levels may be an indication
of evolving disease.

4. Neurologic effects:Hyperreflexia/hypersensitivity may develop. In

severe cases, grand mal (eclamptic) seizures may develop.

5. Pulmonary effects:Pulmonary edema may occur and can be related to

decreased colloid oncotic pressure, pulmonary capillary leak, left heart
failure, iatrogenic fluid overload, or a combination of these factors.

6. Fetal effects:Decreased intermittent placental perfusion secondary to

vasospasm is thought to be responsible for the increased incidence of
intrauterine growth restriction (<10% estimated fetal weight for
gestational age), oligohydramnios, and increased perinatal mortality of
infants born to mothers with preeclampsia. An increased incidence of
placental abruption is also seen. With the stress of uterine contractions
during labor, the placenta may be unable to adequately oxygenate the
fetus. This may result in signs of intrapartum uteroplacental
insufficiency. Specifically, a nonreassuring fetal-heart-rate pattern may
necessitate cesarean delivery. Presumably because of vasospastic
changes, placental size and function are decreased. The results are
progressive fetal hypoxia and malnutrition, as well as an increase in the
incidence of intrauterine growth restriction and oligohydramnios.

MANAGEMENT
The goal of management of hypertension in pregnancy is to balance the
management of both fetus and mother and to optimize the outcome for
[Link] blood pressure should be monitored and the mother
should be observed for the sequelae of the hypertensive disease.
Intervention for maternal indications should occur when the risk of
permanent disability or death for the mother without intervention
outweighs the risks to the fetus caused by intervention. For the fetus,
there should be regular evaluation of fetal well-being and fetal growth,
with intervention becoming necessary if the intrauterine environment
provides more risks to the fetus than delivery with subsequent care in
the newborn nursery.

Chronic Hypertension
The management of patients with chronic hypertension in pregnancy
involves closely monitoring maternal blood pressure and watching for
the superimposition of preeclampsia or eclampsia, and following the
fetus for appropriate growth and fetal [Link] treatment of
essential hypertension has been disappointing, in that no significant
improvement in pregnancy outcome has been demonstrated with
treatment. Antihypertensive medication in women with chronic
hypertensionis generally not given unless the systolic blood pressure is
150 to 160 mm Hg or the diastolic blood pressure 100 to

110 mm [Link] purpose of such medications is to reduce the likelihood

of maternal stroke. Methyldopa is a commonly used antihypertensive
medication for this purpose, although a combined alpha-and-beta-
blocker (such as labetalol) and calcium-channel blockers (such as
nifedipine) are also commonly used. It was formerly taught that diuretics
were contraindicated during pregnancy, but diuretic therapy is no longer
discontinued, and indeed is usually continued, in the patient who
already has been on such therapy before becoming pregnant.

Preeclampsia
The severity of the preeclampsia and the maturity of the fetus are the
primary considerations in the management of preeclampsia. Care must
be individualized, but there are well-accepted general guidelines. The
mainstay of management for patients with mild preeclampsiais rest and
frequent monitoring of mother and fetus. Testing for suspected fetal
growth restriction or oligohydramnios and twice-weekly nonstress tests,
biophysical profiles, or both, are commonly employed and should be
repeated as indicated, according to maternal condition. Testing is
recommended twice weekly for suspected fetal growth restriction or
oligohydramnios. Ultrasound examination for fetal growth and amniotic
fluid assessment is recommended every 3 weeks. Daily fetal movement
assessment also may prove useful.

Hospitalization is often initially recommended for women with new-

onset preeclampsia. After maternal and fetal conditions are serially
assessed, subsequent management may be continued in the hospital, at
a day-care unit, or at home on the basis of the initial assessment. For the
patient with worsening preeclampsia or the patient who has severe
preeclampsia, management is often best accomplished in a tertiary-care
setting. Daily laboratory tests and fetal surveillance may be indicated.
Stabilization with magnesium sulfate, antihypertensive therapy (as
indicated), monitoring for maternal and fetal well-being, and delivery by
either induction or cesarean delivery are required. For almost a century,
magnesium sulfate has been used to prevent and to treat eclamptic
convulsions. Other anticonvulsants, such as diazepam and phenytoin,
are rarely used because they are not as efficacious as magnesium and
because they have potential adverse effects on the fetus. Magnesium
sulfate is administered by intramuscular or intravenous routes, although
the latter is far more common. In 98% of cases, convulsions will be
prevented. Therapeutic levels are 4 to 6 mg/dL with toxic concentrations
having predictable consequences (Table 16.2). Frequent evaluations of
the patient’s patellar reflex and respirations are necessary to monitor for
manifestations of rising serum magnesium concentrations. In addition,
because magnesium sulfate is excreted solely from the kidney,
maintenance of urine output of at least 25 mL/hour will help avoid
accumulation

of the drug. Reversal of the effects of excessive magnesium

concentrations is accomplished by the slow intravenous administration
of 10% calcium gluconate, along with oxygen supplementation and
cardiorespiratory support, if needed. Antihypertensive therapy is
initiated if, on repeated measurements, the systolic blood pressure is
>160 mm Hg or if diastolic blood pressure exceeds 105 to 110 mm Hg.
Hydralazine is often the initial antihypertensive medication of choice,
given in 5- to 10-mg increments intravenously until an acceptable blood
pressure response is obtained. A 10- to 15-minute response time is
usual. The goal of such therapy is to reduce the diastolic pressure to the
90to 100-mm Hg range. Further reduction of the blood pressure may
impair uterine blood flow to rates that are

dangerous to the fetus. Labetalol is another agent used to manage

severe hypertension (Table 16.3). Once anticonvulsant and
antihypertensive therapies are established in patients with severe
preeclampsia or eclampsia, attention is directed toward delivery.
Induction of labor is often attempted, although cesarean delivery may be
needed either if induction is unsuccessful or not possible, or if the
maternal or fetal status is worsening. At delivery, blood loss must be
closely monitored, because patients with preeclampsia or eclampsia
have significantly reduced blood volumes. After delivery, patients remain
in the labor and delivery area for 24 hours (longer if the clinical situation
warrants) for close observation of their clinical progress and further
administration of magnesium sulfate to prevent postpartum eclamptic
seizures. Approximately 25% of eclamptic seizures occur before labor,
50% occur during labor, and 25% occur in the first 24 hours after
delivery. Usually, the vasospastic process begins to reverse itself in the
first 24 to 48 hours after delivery, as manifested by a brisk diuresis.

Eclampsia The eclamptic seizure is life-threatening for mother and

fetus. Maternal risks include musculoskeletal injury (including biting the
tongue), hypoxia, and [Link] therapy consists of inserting a
padded tongue blade, restraining gently as needed, providing oxygen,
assuring maintenance of an adequate airway, and gaining intravenous
access. Eclamptic seizures are usually self-limited, so medical therapy
should be directed to the initiation of magnesium therapy (4 to 6 g
slowly, intravenously) to prevent further seizures. If a patient receiving
magnesium sulfate experi

ences a seizure, additional magnesium sulfate (usually 2 g slowly) can be

given, and a blood level obtained. Other anticonvulsant therapy with
diazepam or similar drugs is generally not warranted. Transient uterine
hyperactivity for up to 15 minutes is associated with fetal heart rate
changes, including bradycardia or compensatory tachycardia, decreased
variability, and late decelerations. These are self-limited and are not
dangerous to the fetus unless they continue for 20 minutes or more.
Delivery during this time imposes unnecessary risk for mother and fetus
and should be avoided. Arterial blood gases are often obtained, any
metabolic disturbance should be corrected, and a Foley catheter should
be placed to monitor urinary output. If the maternal blood pressure is
high, if maternal urinary output is low, or if there is evidence of cardiac
disturbance, consideration of a central venous catheter and, perhaps,
continuous electrocardiogram monitoring is appropriate.

HELLP Syndrome
Patients with HELLP syndrome are often multiparous and have blood
pressure recordings lower than those of many preeclamptic patients.
The liver dysfunction may be man

Ifest

ifest as right-upper-quadrant pain, and is all too commonly

misdiagnosed as gallbladder disease or indigestion. Major morbidity and
mortality with unrecognized HELLPmake accurate diagnosis imperative.
The first symptoms are often vague, including nausea and emesis and a
nonspecific virallike syndrome. Treatment of these gravely ill patients is
best done in a high-risk obstetric center and consists of cardiovascular
stabilization, correction of coagulation abnormalities, and delivery.
Platelet transfusion before or after delivery is indicated if the platelet
count is <20,000/mm3, and it may be advisable to transfuse patients
with a platelet count <50,000/mm3 before proceeding with a cesarean
birth. Management of cases of HELLP syndrome should be individualized
based on gestational age at presentation, maternal symptoms, physical
examination, laboratory findings, and fetal status.