HYPERTENSIVE DISORDERS DURING PREGNANCY ppsx

379
CLASSIFICATION
The hypertensive disorders of pregnancy have been variously clas-
sified without consensus being achieved as to a lasting classifica-
tion. A practical classification may be achieved by modification of
the system proposed by the American Committee on Maternal Wel-
fare (1985).
I. Pregnancy Induced Hypertension (Preeclampsia-eclampsia,
toxemia, EPH, and gestosis)
●
Gestational hypertension
*
●
Preeclampsia
1. Mild
*
2. Severe
*
●
HELLP Syndrome
*
●
Eclampsia
*
II. Chronic hypertension
●
Primary (essential, idiopathic)
●
Secondary (to some known cause)
1. Renal: e.g., parenchymal (glomerulonephritis, chronic
pyelonephritis, interstitial nephritis, and polycystic kid-

ney disease), renovascular nephritis
2. Adrenal: cortical-Cushing’s disease, hyperaldosteronism,
medullary-pheochromocytoma
3. Other: coarctation of the aorta, thyrotoxicosis, etc.
III. Chronic hypertension with superimposed preeclampsia
IV.Transient (atypical, undiagnosed) hypertension (a nebulous group
of patients who develop hypertension in labor or immediately
postpartum)
13
HYPERTENSIVE DISORDERS
DURING PREGNANCY
CHAPTER
*
Modifications
Copyright 2001 The McGraw-Hill Companies. Click Here for Terms of Use.
BENSON & PERNOLL’S
380 HANDBOOK OF OBSTETRICS AND GYNECOLOGY
PREGNANCY-INDUCED
HYPERTENSION
DEFINITIONS, INCIDENCE, ETIOLOGY,
AND IMPORTANCE
Preeclampsia-eclampsia, a multisystem disorder of unknown etiol-
ogy peculiar to pregnant women, remains a major contributor to
maternal and perinatal morbidity and mortality both in developing
as well as industrialized nations. Currently, it is not possible to pre-
dict who will acquire the processes. There are no strategies for pre-
vention. This group of conditions are progressive, but with variable
presentations and rates of progression. Moreover, after clinical
symptoms have occurred, there are only symptomatic therapeutic
options. One or another of the hypertensive disorders will compli-

cate approximately 10% of pregnancies.
The mildest form of the process is gestational hypertension,
which consists of systolic blood pressure .140 with a rise of .30
mmHg and/or diastolic blood pressure of .90 mmHg with a rise of
.15 mmHg. Only 15%–25% of women having gestational hyper-
tension will develop preeclampsia. This progression is more likely
with earlier presentation or if the woman has had a prior sponta-
neous abortion. Women with gestational hypertension Ͼ36 weeks
have ϳ10% risk of developing preeclampsia.
Preeclampsia is characterized by hypertension (as previously de-
fined), plus generalized edema, and/or proteinuria occurring after the
20th week of pregnancy (usually in the last trimester or early puer-
perium). Any two of the three signs are diagnostic. The only excep-
tion to the 20th week for onset is when pregnancy-induced hyper-
tension (PIH) is associated with trophoblastic disease. Preeclampsia
is divided into mild and severe, based on blood pressure and labora-
tory abnormalities (see below).
Although up to 40% of patients with preeclampsia will have
some hemostatic abnormalities, for reasons yet unknown, some
preeclamptic patients will develop the HELLP syndrome. This
includes the signs of preeclampsia (as above) plus hemolysis (H),
elevated liver enzymes (EL), and low platelets (LP, see below).
These gravidas deserve even more special consideration because
of the potential for poor perinatal and maternal prognosis with-
out early diagnosis and proper therapy, including expeditious
delivery.
Eclampsia, the most fulminating degree of PIH, is character-
ized by convulsions or coma, in addition to the other signs and
symptoms of preeclampsia. Uncontrolled preeclampsia may progress
to eclampsia, with resultant permanent disability or death.

Chronic hypertension (CH) alone or with superimposed pre-
eclampsia (SIPE) must be differentiated from PIH. The risks of
chronic hypertension in pregnancy (abruptio placenta, fetal growth
restriction and prematurity) are worsened by the superimposition of
preeclampsia. Additionally, the maternal and perinatal risk increase
in relation to the severity of the preexisting chronic hypertension.
About 8% (recent reports range from 5%–10%) of all pregnant
women in the United States develop preeclampsia; however, there
is great geographic variation in incidence. Approximately 5% of
these cases progress to eclampsia, and about 5% of women with
eclampsia die of the disease or its complications. At least 95% of
cases of PIH occur after the 32nd week, and about 75% of these
patients are primigravidas. The incidence is at least doubled with
multiple pregnancy, hydatidiform mole, and polyhydramnios. Prim-
igravidas of all ages are affected. PIH is more prevalent among
blacks and Native Americans than whites.
Other factors predisposing to PIH include age Ͻ20 and Ͼ35,
vascular or renal disease, diabetes mellitus, gestational diabetes mel-
litus, obesity, chronic hypertension, pheochromocytoma, systemic
lupus erythematosus, nonimmune fetal hydrops, malnutrition, and
low socioeconomic status.
Interestingly, if a multigravida remarries, her chance of having
PIH with her next pregnancy is similar to what it would be as a nul-
lipara. Pregnancies achieved through assisted reproductive tech-
nology with a male donor to whom the gravida has not previously
been exposed have the same risk as a primigravida, even if they are
a multipara. In preliminary data, donated gametes further increase
the risk of preeclampsia (to Ͼ18%). All of these conditions con-
tribute to maternal and perinatal morbidity and mortality; however,
given the spectrum of the processes, the amount and type of risk is

variable. This information is summarized as follows.
Although many associations have been detailed (see previous
discussion), the cause of preeclampsia-eclampsia remains unknown
and speculation has been so rife that this disorder has been called
a disease of theories. Currently there are four popular hypotheses:
●
Placental ischemia. Increased trophoblast deportation, as a
consequence of ischemia, may inflict endothelial cell dys-
function. Certainly evidence for endothelial involvement in
this condition abounds.
●
Preeclampsia is the manifestation of a toxic reaction. At least
two areas are being investigated: Very low density lipopro-
tein toxicity prevention. In pregnancy, nonesterified fatty
CHAPTER 13
HYPERTENSIVE DISORDERS DURING PREGNANCY
381
BENSON & PERNOLL’S
382 HANDBOOK OF OBSTETRICS AND GYNECOLOGY
acids are mobilized to compensate for increased energy de-
mands. Albumin, which has a specific antitoxic activity, also
transports the nonesterified fatty acids from adipose tissues
to the liver. Low albumin concentrations may allow an ex-
pression of very low density lipoprotein toxicity. Impaired
antioxidant activity and the reduction of antioxidant levels,
which increase the level of lipid peroxidation products, may
cause peroxidative damage of vascular endothelium.
●
Immune maladaptation. The immune interaction between
mother and invading cytotrophoblast may be aberrant, lead-

ing to shallower endovascular cytotrophoblastic cell inva-
sion of spiral arteries. This dysfunction may lead to in-
creased decidual release of cytokines, proteolytic enzymes,
and free radial species. Preeclampsia is associated with
widespread apoptosis of placental cytotrophoblasts with the
uterine wall.
●
Genetic imprinting. Genetic imprinting for pregnancy in-
duced hypertension could be based on a single recessive gene
or a dominant gene with incomplete penetrance (depending
on fetal genotype). Preeclampsia during the pregnancy of a
mother is a risk factor for development of preeclampsia dur-
ing the pregnancy of her daughters.
PATHOLOGIC PHYSIOLOGY
VASOSPASM
Arteriolar spasm, consistently observed in the retinas, kidneys, brain,
and splanchnic region, promotes hypertension. Furthermore, the nor-
mal refractoriness to angiotensin II (A-II) is lost weeks before the
onset of preeclampsia. In contrast, normal pregnant women lose their
refractoriness to A-II after receiving prostaglandin synthetase in-
hibitors (e.g., aspirin, which implicates prostaglandin as a mediator
of vascular reactivity to A-II during pregnancy). Moreover, A-II re-
fractoriness can be restored to preeclamptic individuals by drugs that
increase levels of cyclic AMP (cAMP) (e.g., theophylline). An im-
balance between prostacyclin (PGI
2
), a vasodilator and inhibitor of
platelet aggregation, and thromboxane (TXA
2
), a vasoconstrictor and

platelet aggregator in preeclampsia, also occurs because PGI
2
pro-
duction is decreased months before the clinical onset of preeclamp-
sia. Mild preeclampsia is associated with lower systemic daytime
production of prostacycline, elevated plasma norepinephrine levels,
and blunting of the normal diurnal variations of brain natriuretic pep-
tide, atrial natriuretic peptide, norepinephrine, and aldosterone.
SODIUM AND WATER RETENTION
Sodium retention is an adjunct of growth and is normal during preg-
nancy, but sodium retention, particularly intracellular, is exagger-
ated in PIH. Nonetheless, sodium retention does not cause this dis-
order. However, an alteration at the cellular membrane level may
inhibit the usual exchange of sodium. Reduced serum levels of al-
bumin and globulin resulting from proteinuria account for the di-
minished oncotic pressure of the blood despite hemoconcentration.
Increased excretion of corticosteroids (including aldosterone) and
vasopressin in certain patients suggests increased tissue concentra-
tions of these substances. This results in enhanced sodium and wa-
ter retention.
PROTEINURIA
Degenerative changes in the glomeruli permit loss of protein via
the urine. The albumin–globulin ratio in the urine of patients with
preeclampsia-eclampsia is approximately 3:1 (vs. 6:7 in patients
with glomerulonephritis). In this case, renal tubular disease con-
tributes only slightly to the leakage of protein.
HEMATOLOGIC ALTERATIONS
The Hgb and Hct are elevated due to hemoconcentration. Preeclamp-
sia is a hypercoagulative status that may be explained by a de-
rangement of the platelet L-arginine-nitric oxide pathway. Severe

preeclampsia-eclampsia shares similarities with the disorders of
coagulation because disseminated intravascular coagulation (DIC)
of varying degrees so frequently occurs. The magnitude of the
coagulation defect does not always correlate with the severity of
preeclampsia-eclampsia. The alterations may include thrombocy-
topenia, decreased coagulation factors (especially reduced fibrino-
gen), and the presence of fibrin split products. Microfibrin emboli
may occur in the lungs, liver, or kidneys. Occasionally, hemolysis
(e.g., microangiopathic hemolytic anemia, deformed red blood
cells), elevated liver enzymes, and thrombocytopenia occur in pa-
tients with preeclampsia-eclampsia. This combination is termed the
HELLP syndrome.
BLOOD CHEMISTRY
ABNORMALITIES
Uric acid levels are generally .6 mg/dL. Serum creatinine is most
often normal but may be elevated in severe cases. Some serum
CHAPTER 13
HYPERTENSIVE DISORDERS DURING PREGNANCY
383
BENSON & PERNOLL’S
384 HANDBOOK OF OBSTETRICS AND GYNECOLOGY
albumin and globulin are lost via the urine, but blood proteins must
also be lost or destroyed in other ways, since proteinuria alone is
not sufficient to explain the abnormally low protein levels in severe
cases. Acidosis occurs after convulsions. Elevated levels of hepatic
enzymes indicate hepatic dysfunction. Placental clearance of dehy-
droepiandosterone sulfate (DHEAS), as a measure of placental per-
fusion, decreases before the onset of preeclampsia.
In summary, PIH is marked by vasospasm. Whereas normal
pregnancy is marked by sodium and water retention, together with

increased blood volume, in preeclampsia, there is enhanced sodium
and water retention with a contracted plasma volume. Swan-Ganz
catheter studies in preeclampsia reveal normal wedge pressures and
normal or elevated cardiac output.
PATHOLOGY
KIDNEY
In severe preeclampsia and eclampsia, the only typical lesion is
glomerular capillary endotheliosis (i.e., swelling of the glomerular
capillary endothelium, narrowing of the capillary lumen, and suben-
dothelial fibrinoid deposition). These abnormalities are totally re-
versible and disappear by 6 weeks postpartum. In patients with
the clinical diagnosis of preeclampsia, renal biopsy reveals glomeru-
lar capillary endotheliosis in ϳ70% of primigravidas Ͻ25 years,
and ϳ25% have unsuspected renal disease. Other electron micro-
scopic abnormalities include massive subendothelial and mesan-
gial deposits of lipids and fibrillar fibrins, monocyte invasion in
the mesangium, and rupture and duplication of the glomerular cap-
illary wall.
CARDIOPULMONARY
Pulmonary edema may occur with severe preeclampsia or eclampsia
from cardiogenic or noncardiogenic causes. It is most common post-
partum and also may be related to fluid overload and decreased
plasma colloid oncotic pressure. Preeclampsia is usually character-
ized as a hyperdynamic state, with increased cardiac output, normal
wedge pressure, and normal or slightly elevated systemic vascular re-
sistance. Aspiration of gastric contents may occur as a complication
of eclamptic seizures. Death may result from particulate matter
obstructing airways or from chemical pneumonitis, leading to the
adult respiratory distress syndrome.
GASTROINTESTINAL

In the liver, chronic passive congestion and subcapsular hemor-
rhages may develop.
FETUS
As a result of the poor intervillous blood flow, intrauterine growth
retardation may be marked. Fetal death may follow hypoxia or aci-
dosis. This is further compounded by both severe hypertension and
maternal multiple organ involvement, which may necessitate early
delivery.
PLACENTA
Grossly, no specific placental lesions are typical of preeclampsia-
eclampsia, although the placenta is often smaller than normal, and
intervillous fibrin deposits (red infarcts) are common. Increased and
more severe endarteritis and periarteritis, a thinned and broken syn-
cytium, and calcium and intervillous fibrin deposition may appear
(grossly, microscopically, and sonographically) as premature aging.
There are two very serious microscopic placental alterations in pa-
tients with preeclampsia: the spiral arteries in the myometrium fail
to lose their musculoelastic structure, and acute atherosis develops
in the myometrial segment of the spiral arteries. This leads to in-
creased vascular resistance and a compromise of the vessel lumen.
Thus, the fetus receives less intervillous blood flow.
SYMPTOMS AND SIGNS
Except for an abnormal blood pressure, patients with gestational
hypertension are usually asymptomatic. Preeclampsia-eclampsia is
characterized by hypertension, generalized edema, and proteinuria
in the absence of vascular or renal disease. The manifestations de-
velop from the 20th week of pregnancy through the 6th week after
delivery.
HYPERTENSION
Hypertension is the key sign in the diagnosis of PIH. Gestational

hypertension is a rise in systolic blood pressure of Ն30 mm Hg,
a rise in diastolic pressure of Ն15 mm Hg, or a blood pressure
of Ն140/90. Some (Canadian Hypertension Society Consensus
Conference) consider only the diastolic blood pressure. Except for
CHAPTER 13
HYPERTENSIVE DISORDERS DURING PREGNANCY
385
BENSON & PERNOLL’S
386 HANDBOOK OF OBSTETRICS AND GYNECOLOGY
very high diastolic readings (.110), it is recommended that all
diastolic readings be confirmed after 4 hours. Hypertension also
exists with a mean arterial pressure rise of 20 mm Hg. The levels
described must occur at least twice, 6 h or more apart, and be based
on previously recorded blood pressures. Occasional patients with
hypertension during pregnancy must remain unclassified until stud-
ies can be evaluated after the puerperium.
EDEMA
Edema is the least precise sign of PIH because dependent edema is
normal in pregnancy and up to 40% of patients with PIH do not have
edema. However, the following criteria may facilitate the diagnosis.
●
Generalized accumulation of fluid in tissues (i.e., Ͼ2ϩ pit-
ting edema after 1 h bedrest).
●
A weight gain of Ն2 pounds/wk because of the influence of
pregnancy.
●
Nondependent edema of the hands and face present on aris-
ing in the morning.
PROTEINURIA

Gestational proteinuria is often the last sign to develop and is de-
fined as $0.3 g/liter in a 24-h specimen or .1 g/liter (1ϩ to 2ϩ by
dipstick methods) with urinalysis on random midstream or catheter
specimens. Up to 30% of patients with eclampsia will not have pro-
teinuria, but when present, proteinuria signals increased fetal risk
(more SGA infants and enhanced perinatal mortality). If only the
noted criteria for preeclampsia are present, it is classified as mild
preeclampsia. The criteria for severe preeclampsia follow.
●
Blood pressure Ͼ160 systolic or Ͼ110 diastolic (at bedrest,
on two occasions at least 6 h apart)
●
Proteinuria Ͼ5 g/24 h (3ϩ to 4ϩ on dipstick)
●
Oliguria (Յ500 mL/24 h)
●
Cerebral or visual disturbances
●
Epigastric pain
●
Pulmonary edema or cyanosis
OTHER
Severe, persistent, generalized headache, vertigo, malaise, and
nervous irritability are prominent symptoms in cases of severe
preeclampsia. Scintillating scotomas and partial or complete blind-
ness are due to edema of the retina, retinal hemorrhage, or retinal
detachment. Epigastric pain, nausea, and liver tenderness are the
result of congestion or thrombosis of the periportal system and sub-
capsular hepatic hemorrhages.
There are no consistent symptoms of the HELLP syndrome. This

nonspecificity is problematic for early diagnosis. Similarly, eclamp-
sia may occur with little or no warning.
COMPLICATIONS
Maternal complications are related directly to progression from
gestational hypertension to preeclampsia, the HELLP syndrome or
eclampsia. The fetal complications are related to acute and chronic
uteroplacental insufficiency (e.g., asymmetric or symmetric SGA
fetus, stillbirth, or intrapartum fetal compromise) and early deliv-
ery (complications of prematurity).
LABORATORY STUDIES
All patients with PIH may need the following studies (additional
studies or repetition may also be necessary): Hct, or Hgb, WBC;
urinalysis, urine culture and sensitivity; serum protein and albu-
min/globulin ratio; and serum uric acid and creatinine. Also, de-
pending on the gestational age and seriousness of the situation, it
may be useful to determine fetal physiologic maturity by amnio-
centesis and appropriate tests. A 24-h urine collection is collected
for total protein, creatinine clearance, and vanillylmandelic acid
(if BP varies greatly). Baseline coagulation studies usually include
a platelet count, total fibrinogen, prothrombin, partial thrombo-
plastin time, and split fibrin products (if DIC is suspected). A liver
function profile is usually added to rule out HEELP syndrome. This
includes bilirubin and liver enzymes (lactate dehydrogenase, as-
partate aminotransferase, alanine amniotransferase).
Recently, some have recommended that the laboratory evalua-
tion of patients suspected of preeclampsia may be abbreviated in
certain circumstances. Specifically, if there is no evidence of bleed-
ing or of a condition that could produce coagulopathy and if the
platelet count and lactate dehydrogenase level are both normal, a
PT, a PTT, or fibrinogen test is not necessary.

IMAGING
Sonography is useful in detailing the fetal size and position and in
estimation of well-being. Additionally, Doppler evaluation of the
uterine artery velocimetry may be useful in predicting adverse preg-
nancy outcomes from compromised fetuses.
CHAPTER 13
HYPERTENSIVE DISORDERS DURING PREGNANCY
387
BENSON & PERNOLL’S
388 HANDBOOK OF OBSTETRICS AND GYNECOLOGY
MANAGEMENT
The objectives of treatment of all hypertensive states complicating
pregnancy are to prevent or control convulsions, ensure survival of
the mother without (or with minimal) morbidity, and deliver a sur-
viving infant without serious sequelae.
GENERAL MEASURES
If the patient is stable and not severely preeclamptic or eclamptic,
general diet without sodium restriction may be appropriate, as is
unrestricted fluid intake (but with recorded intake and output). The
lateral recumbent position increases renal blood flow, which assists
in resolving edema. Therefore, the patient is encouraged to assume
right or left lateral recumbency as much as possible. High-risk ob-
stetric care and treatment of complications is required to optimize
outcomes. The keys to treatment are bedrest and delivery at a time
of fetal maturity.
Those who have gestational hypertension may be followed un-
der close supervision as outpatients. Such supervision usually in-
volves bedrest (lateral recumbent position as much as possible),
blood pressure evaluation (while awake) every 4 h, a daily urine
dipstick evaluation for proteinuria, a minimum of twice weekly

physician visits, weekly nonstress testing (or other evaluation of fe-
tal well-being), and maternal fetal motion counting.
Careful patient education is necessary concerning signs that
would require immediate hospitalization: proteinuria, increasing
blood pressure, severe headache, and epigastric pain.
In some circumstances, for gestational hypertension and in all
preeclamptic women, maternal hospitalization may help prevent
premature delivery and thus be less expensive (compared to pre-
mature neonatal care). An example of hospital care includes bedrest
(again, in the lateral recumbent position), daily weights, blood pres-
sures every 4 h (because the highest pressures of the day occur at
3–5 AM, it is worthwhile to screen these occasionally); daily urine
dipstick for proteinuria, and 24-h urine once or twice weekly (for
creatinine clearance and total protein). On admission and weekly
thereafter, the following laboratory studies may be employed:
hemogram, liver function studies, uric acid and creatinine, elec-
trolytes, serum albumin, and a coagulation profile.
Sonography for gestational age is usually obtained on admis-
sion and every 2 weeks thereafter. Weekly testing for fetal well-being
may be performed by serial BPPs, or NSTs. Should an abnormal-
ity arise, a CST may be necessary. Glucose tolerance testing is
indicated after 20 weeks gestation if the patient has hyperglycemia
or multiple pregnancy. A vanillylmandelic acid study is effective in
ruling out pheochromocytoma if wide blood pressure fluctuations
occur.
Criteria to allow nonhospital care for the patient commonly in-
clude an environment where bedrest is possible, BP reduction to
Յ120/80, proteinuria Յ150 mg/24 h and normal renal function,
and no evidence of CNS irritability. Any relapse or complications
require readmission to the hospital. If possible, delivery is delayed

until physiologic maturity (Ͼ36 weeks amniocentesis and testing)
occurs. If early delivery is required, induction is attemped. When
the cervix is not favorable (Bishop score Ͻ6–7), a prostaglandin
ripening agent may be useful. If induction is not a good option, if
labor is delayed, or if fetal compromise develops, cesarean section
may be a better option.
INDICATIONS FOR DELIVERY
While there are few absolutes, given the large number of variables
in fetal states, fetal maturity, intercurrent diseases, maternal status,
and so forth, some of the criteria commonly employed for delivery
follow.
Hypertension is the issue that mandates delivery in the vast ma-
jority of patients. Blood pressure elevations forcing this delivery
are consistently Ͼ100 diastolic for 24 h, and a single BP diastolic
Ͼ110 despite bedrest. Laboratory abnormalities signaling sufficient
risk to warrant delivery consideration include: proteinuria Ͼ1 g/24 h,
increasing serum creatinine, abnormal liver function studies, and
thrombocytopenia. Maternal complications signaling the consider-
ation for delivery comprise the HELLP syndrome, eclampsia, severe
preeclampsia (including signs such as epigastric pain and cerebral
symptoms), pulmonary edema, cardiac decompensation, coagu-
lopathies, and renal failure. Fetal abnormalities indicative of risk
sufficient to warrant delivery include: fetal compromise by elec-
tronic monitoring criteria; abnormal NST, CST, or BPP; and an SGA
fetus with growth failure on sonography.
SEVERE PREECLAMPSIA
Severe preeclamptics and their offspring are best cared for in ter-
tiary centers. The goals of management are prevention of convul-
sions, control of maternal blood pressure, and delivery.
For gestations of ,27 weeks, conservative management (delay-

ing delivery) may be warranted, but maternal complications (abrup-
CHAPTER 13
HYPERTENSIVE DISORDERS DURING PREGNANCY
389
BENSON & PERNOLL’S
390 HANDBOOK OF OBSTETRICS AND GYNECOLOGY
tio placenta, eclampsia, coagulopathy, renal failure, hypertensive
encephalopathy, and hepatic rupture) are directly related to the
length of time delivery is delayed. In some pregnancies distant from
term, however, attempting to lengthen gestation is the most ration-
ale choice to avoid the morbidity and mortality of early preterm de-
livery. Patient and family participation is necessary.
Severe preeclampsia is a high-risk situation that may end in ma-
ternal complications or poor perinatal outcomes despite maximal
medical efforts. For those Ն28 weeks with a tertiary care nursery
available, delivery after short-term maternal stabilization is the
treatment of choice. Laboratory assessment should be similar to the
mild preeclamptic, but it may be necessary in extreme cases to add
electrocardiography and hemodynamic monitoring. Determination
of fetal pulmonary maturity is necessary to properly time delivery.
This may be repeated at weekly intervals to accomplish delivery as
soon as survival is likely. Corticosteroid therapy for gestations of
26–34 weeks is indicated to enhance fetal lung maturity.
The severe preeclamptic may be started on magnesium sulfate
to help in preventing seizures (see dosage under “Eclampsia”). Mag-
nesium sulfate prevents seizures by direct central nervous system
action; however, magnesium sulfate decreases acetylcholine release
at the neuromuscular junction and causes paralysis at a serum level
of ϳ15 mg/dL. Magnesium sulfate potentiates both depolarizing
and nondepolarizing muscle relaxants. In patients requiring hyper-

tensive control, hydralazine and labetalol have traditionally been
the safest agents. Blood pressures of 170/110 are an emergency and
treatment with hydralazine, labetalol, or nifedipine should be initi-
ated immediately. Although the benefits and risks of antihyperten-
sive treatment should be considered in all cases of hypertension in
pregnancy, it is particularly important to treat those with sustained
systolic BP . 160 mm Hg or sustained diastolic BP . 100. With
lesser hypertensions, the decision to utilize antihypertensive therapy
may be much more individualized. In milder cases (e.g., gestational
hypertension), methyldopa is the treatment of choice. Labetalol,
pindolol, oxprenolol, and nifedipine are second-line drugs.
Those patients with nausea, vomiting, and epigastric pain are
at particular risk. Additionally, these patients may have laboratory
findings that indicate a greater maternal risk: lactate dehydroge-
nase level Ͼ1400 IU/L, aspartate aminotransferase Ͼ150 IU/L, ala-
nine aminotransferase Ͼ100 IU/L, uric acid level Ͼ7.8 mg/dL,
serum creatinine Ͼ1.0 mg/dL, and 4ϩ urinary protein by dipstick.
These factors are independent of the rising maternal risk associate
with the decreased platelet count found in full expression of the
HELLP syndrome. Prompt delivery must be considered for the in-
dications noted previously.
PREVENTION
Since there are no known specific causes of preeclampsia-eclampsia,
prevention can be achieved only in a general way by providing
the highest-quality prenatal care. The diet during pregnancy should
be high in protein and contain adequate vitamins and minerals. The
patient should be permitted to gain about 12 kg (25 pounds) more
than her ideal nonpregnant weight. A moderate salt intake is rea-
sonable. Diuretics should not be used. Alert diagnosis and effective
management of prodromal symptoms prevent clinical preeclampsia

in the third trimester. Low dose aspirin has been extensively stud-
ied and has not prevented the onset of pregnancy induced hyper-
tension. Another compound under investigation is prenatal calcium
supplements of 600 mg to 1.5 g/day. Those receiving calcium have
reduced vascular sensitivity to angiotensin II and, preliminarily, a
reduction in the rate of preeclampsia.
HELLP SYNDROME
There are no specific symptoms of the HELLP syndrome. The signs,
which are all abnormal laboratory values, should be screened for in
all preeclamptic patients. The platelet count is the most reliable in-
dicator of the HELLP syndrome. The earlier in the course of the
HELLP syndrome that the diagnosis is made, the better it is for both
maternal and perinatal prognosis.
Usually treatment is directed to: seizure prophylaxis, blood pres-
sure control, correction of the several hematological defects (transfu-
sion of blood products), and expeditious delivery. However, recent
reports indicate that nonmineralocorticosteroid therapy (high dose
dexamethasone, betamethasone 12 mg twice 12 h apart) may assist in
amelioration of the hematological abnormalities to the point that preg-
nancy may be prolonged in those distant from a time for delivery of
reasonable perinatal safety. Patients with refractory HELLP syndrome
may benefit from plasmapheresis. The maternal morbidity and mor-
tality rates associated with HELLP syndrome approaches 25%.
ECLAMPSIA
DEFINITION, INCIDENCE, ASSOCIATIONS
A patient with signs of preeclampsia who has at least one convul-
sion or episode of coma between the 20th week of pregnancy and
CHAPTER 13
HYPERTENSIVE DISORDERS DURING PREGNANCY
391

BENSON & PERNOLL’S
392 HANDBOOK OF OBSTETRICS AND GYNECOLOGY
the end of the 6th week after delivery must be presumed to have
eclampsia if other causes can be excluded. Eclampsia occurs in
0.2%–0.5% of all deliveries. The occurrence is influenced by the
same factors noted for preeclampsia. Eclampsia is classified ac-
cording to the time of occurrence of the first convulsion with
respect to the time of delivery. Prepartum eclampsia (ϳ75% of to-
tal) denotes convulsions before delivery. About 50% of postpartum
eclamptic convulsions occur within 48 h of delivery. In most series,
eclampsia will be associated with Ͼ20% of total maternal mortal-
ity. Those women dying with eclampsia tend to be relatively older,
multiparous, have underlying chronic hypertension, an early onset
of preeclampsia-eclampsia, and have multisystemic manifestations
(primarily hematological, hepatic and neurological).
SYMPTOMS AND SIGNS
Patients usually have no aura and may have one to several seizures
with a variable interval of unconsciousness. The seizures are of the
tonic-clonic type and are marked by apnea. Hyperventilation (to
compensate for the respiratory and lactic acidosis) is common af-
ter the seizure. Fever is a poor prognostic sign. Tongue biting is
common, and other complications include aspiration, head trauma,
broken bones, and retinal detachment.
LABORATORY AND IMAGING FINDINGS
A chest x-ray to rule out aspiration is necessary for the patient who
has had a seizure. If the patient has not been evaluated previously,
the studies noted above (see p. 387) should be obtained. Eclamp-
sia is associated with proteinuria of 3ϩ to 4ϩ, hemoconcentration,
a greatly reduced blood CO
2

combining power, and increased serum
uric acid, blood nonprotein nitrogen, and blood urea nitrogen lev-
els. An ophthalmoscopic examination may reveal papilledema, reti-
nal edema as manifest by increased sheen, retinal detachment, vas-
cular spasm, arteriovenous nicking, and hemorrhages. Repeated
examination is helpful in determining improvement or failure of
treatment in preeclampsia-eclampsia. Deep tendon reflexes are ex-
aggerated and there may be pathological reflexes.
DIFFERENTIAL DIAGNOSIS
Although convulsions may be due to hypertensive encephalopathy,
epilepsy, thromboembolism, drug intoxication or withdrawal, trauma,
hypoglycemia, hypocalcemia (of parathyroid or renal origin), he-
molytic crisis of sickle cell anemia, or the tetany of alkalosis, during
pregnancy, eclampsia is the first consideration. A brief coma usually
follows the convulsions of eclampsia, but coma may also occur with-
out convulsions. Other causes of coma (in descending order of prob-
ability) are epilepsy, syncope, alcohol or other drug intoxication, aci-
dosis or hypoglycemia (diabetes), stroke, and azotemia.
MANAGEMENT
EMERGENCY MANAGEMENT
Immediate management aims to assure maternal well-being. The
first step is to obtain an unobstructed airway and to prevent mater-
nal oral injuries. This may be accomplished by insertion of an oral
airway or padded tongue depressors. Both of these methods mini-
mize tongue biting or tooth fracture, which may occur with seizures.
Suctioning of the oropharynx may be initiated as soon as it can be
ascertained that the patient will not bite the suction catheter. Ad-
ministration of oxygen by nasal prongs or mask will increase oxy-
gen saturation during this precarious interval. The next step in im-
mediate management is to control seizures. This is generally

achieved by administration of magnesium sulfate in a 4–6 g IV load-
ing dose followed by IV infusion of 1.5–2 g/h, attempting to reach
a therapeutic level of 4.8–8.4 mg/dL. When magnesium sulfate is
being administered, a urinary catheter is usually desirable to as-
certain that adequate urinary output is occurring. Magnesium sul-
fate is largely excreted by the kidneys, and the drug may reach
dangerous levels if urinary output is impaired. If seizures recur
Ͼ20 min after the loading dose and therapeutic levels are con-
firmed, consider diazepam 5–10 mg IV or up to 250 mg amobar-
bital (be aware of their effect on the fetus and neonate). Addition-
ally, it is often necessary to control hypertension (usually initiated
for sustained systolic BP Ͼ160 mm Hg or sustained diastolic Ͼ100
and with a goal to bring the diastolic to 90–100). Labetalol may be
given every 10 min: 20 mg first dose, 40 mg second dose, 80 mg
subsequent doses (to a maximum 300 mg or until blood pressure is
controlled). The second-line drug is hydralazine, although diazox-
ide, sodium nitroprusside, trimethaphan, and nitroglycerin also have
been used acutely to lower blood pressure. Each of the drugs has
side effects that must be weighed carefully to individualize therapy.
It may be necessary to gently restrain the patient to prevent bony
or soft tissue injury.
CHAPTER 13
HYPERTENSIVE DISORDERS DURING PREGNANCY
393
BENSON & PERNOLL’S
394 HANDBOOK OF OBSTETRICS AND GYNECOLOGY
GENERAL MEASURES
Hospitalization is mandatory. The patient is placed in a darkened,
quiet place at absolute bedrest, with bedrails in place for protec-
tion during convulsions. Continuous intensive nursing is required

and every effort is made to reduce stimuli, including absolute min-
imization of visitors. The patient is also not disturbed for unneces-
sary procedures (e.g., tub baths, leave the blood pressure cuff on
her arm). The patient is maintained on her sides to prevent inferior
vena cava syndrome or aspiration of vomitus. A padded tongue
blade is kept at hand to be placed between the patient’s teeth dur-
ing convulsions. As well, a bulb syringe and catheter or suction ap-
paratus is maintained at the bed side to aspirate mucus or vomitus
from the mouth, glottis, or trachea, and an oxygen mask or tent
(masks and nasal catheters produce excessive stimulation).
Typed and crossmatched whole blood (or blood products) are
kept available for immediate administration because patients with
eclampsia often develop premature separation of the placenta with
the associated-hemorrhage. Their hemodynamics are such that they
are also susceptible to shock.
LABORATORY TESTS
A retention catheter is necessary to accurately measure urinary out-
put (50–100 mL/h is desirable). Quantitative protein content of each
24-h urine specimen is obtained until the 4–5 postpartum day. Also,
creatinine clearance tests are obtained as a measure of renal func-
tion. Elevated levels of hepatic enzymes may presage liver failure.
Coagulation studies may suggest DIC.
PHYSICAL EXAMINATION
The blood pressure is obtained at least hourly during the acute phase
and every 2–4 h thereafter. Similarly, fetal heart tones are moni-
tored continuously or, at the minimum, every time the mother’s
blood pressure is obtained. An ophthalmoscopic examination may
be useful on a daily basis. Additionally, examination of the face,
extremities, and especially the sacrum (which becomes dependent
when the patient is in bed) is helpful in detection of edema. A pa-

tient undergoing stabilization for delivery should remain NPO.
Fluid intake and output for each 24-h period is measured and
recorded. If the urine output exceeds 700 mL/day, the output plus
insensible fluid loss (approximately 500 mL/day) is usually replaced
with salt-free fluids (including parenteral fluids). This may include
200–300 mL of 20% dextrose in water 2–3 times daily during the
acute phase to protect the liver, to replace fluids, and to aid in nu-
trition. Do not give 50% glucose, since it scleroses the veins. The
use of sodium-containing fluids (e.g., physiologic saline, Ringer’s
solution) must be monitored carefully.
Delivery is mandatory once the gravida has been stabilized and
is accomplished by the safest, most expeditious method, individu-
alized to each patient. Cesarean section is preferred for primi-
gravidas, but induction by rupture of the membranes and vaginal
delivery may be appropriate for some multiparas. Note if meconium
is present in amniotic fluid. Indications for cesarean section have
been liberalized, but cesarean section may be lethal for a patient
with continuing convulsions or coma. Seizures and insensibility
should be absent for a period of ϳ4 h before cesarean section is
performed on a maternal indication.
For cesarean section, general anesthesia or well-controlled
epidural or caudal anesthesia is generally employed. Spinal anes-
thesia is less commonly used because it may cause sudden, severe
hypotension. If an anesthetist is not available, procaine, 0.5% or 1%
(or its equivalent), can be used for local infiltration of the abdom-
inal wall. For vaginal delivery, pudendal block or local anesthesia
is preferred, but increasingly, epidural anesthesia is proving useful.
Postpartum magnesium sulfate is continued for at least 24–48 h.
Phenobarbital (120 mg/day) may be used in patients with persistent
hypertension and no spontaneous postpartum diuresis. If the diastolic

blood pressure is consistently Ͼ100, the administration of a diuretic
and methyldopa or other antihypertensives may be considered.
COMPLICATIONS
EARLY
Convulsions increase the maternal mortality rate 10-fold and the
fetal mortality rate 40-fold. The causes of maternal death due to
eclampsia are (in descending order of frequency) circulatory col-
lapse (cardiac arrest, pulmonary edema, and shock), cerebral hem-
orrhage, and renal failure. The fetus usually dies of hypoxia, aci-
dosis, or placental abruption. Blindness or paralysis (due to retinal
detachment or intracranial hemorrhage) may persist in patients who
survive eclampsia.
About 30% of patients who develop premature separation of the
placenta have one of the hypertensive disorders. Approximately half
of such patients will be found to have hypertensive disease and
about one quarter will have preeclampsia-eclampsia.
CHAPTER 13
HYPERTENSIVE DISORDERS DURING PREGNANCY
395
BENSON & PERNOLL’S
396 HANDBOOK OF OBSTETRICS AND GYNECOLOGY
Postpartum hemorrhage is common in patients with hyperten-
sive syndromes during pregnancy. Toxic delirium in patients with
eclampsia, either before or after delivery, poses serious medical and
nursing problems. Injuries incurred during convulsions include lac-
erations of lips or tongue and fractures of the vertebrae. Aspiration
pneumonia may also occur. Renal or hepatic failure and DIC are
rare maternal complications.
Preterm delivery with all attendant neonatal morbidity and mor-
tality is a marked risk with preeclampsia-eclampsia.

LATE
Fifteen to thirty-three percent of patients with severe preeclampsia
or eclampsia (without known preexisting hypertensive or renal dis-
ease) suffer a recurrence of preeclampsia-eclampsia with subsequent
pregnancies. If, however, their problem was not preeclampsia but
undiagnosed chronic hypertensive cardiovascular disease, the rate of
recurrence is nearly 100%. Permanent hypertension, the result of
vascular damage, may occur as a result of severe preeclampsia-
eclampsia in 30%–50%.
PROGNOSIS
FOR THE MOTHER
Maternal morbidity (defined by severe hypertension or multisystem
involvement) and potential mortality is enhanced even with gesta-
tional hypertension. Approximately 16% of nulligravidas with ges-
tational hypertension but no proteinuria eventually develop severe
hypertension or multisystem involvement. With gestational hyper-
tension and even one plus proteinuria, severe maternal complica-
tions eventually occurs in ϳ42% of all nulligravidas (of total, se-
vere hypertension 80%, multisystem disease 20%). The outlook for
patients with preeclampsia is materially worse, with nearly two
thirds of nulligravidas developing severe hypertension (33%) or
multisystem disease (67%). Death from preeclampsia is Ͻ0.1%. If
eclamptic seizures develop, 5%–7% of these patients will die. The
causes of death include intracranial hemorrhage, shock, renal fail-
ure, premature separation of the placenta, and aspiration pneumo-
nia. Moreover, chronic hypertension may be a sequel of eclampsia.
Although platelet counts are significantly increased postpartum af-
ter normotensive pregnancy, there is a further 2- to 3-fold rise in
preeclamptic patients. Peak values occur 6–14 d after delivery. Most
authorities recommend a complete evaluation 6 weeks to 6 months

postpartum for the women who have had eclampsia or severe
preeclampsia.
FOR THE INFANT
Preterm birth and small for gestational age infants occur more fre-
quently (Odds Ratio, OR 1.7) in gestational hypertension compared
to normotensive nulligravidas. Preeclampsia further increases both
preterm birth and small for gestational age infants (OR 14.6). Peri-
natal mortality may be as high as 20%. With early diagnosis, ante-
natal therapy, and intensive neonatal care, however, this loss can be
reduced to Ͻ10%.
CHRONIC HYPERTENSION
DEFINITION AND INCIDENCE
It is often difficult to distinguish chronic hypertension from
preeclampsia, especially when the patient registers late in pregnancy
(Table 13-1). Chronic hypertension may be present before concep-
tion or Ͻ20 weeks gestation, or hypertension may persist for Ͼ6
weeks postpartum. Superimposed preeclampsia on chronic hyper-
tension is defined by $30 systolic or $15 diastolic increase from
previous levels with either nondependent edema or proteinuria. The
correct diagnosis can be made by renal biopsy, but this carries a
considerable risk during pregnancy. Moreover, the exact diagnosis
may be academic, for (as noted previously) ϳ25% of patients with
preeclampsia have underlying renal disease and ϳ20% of patients
with the clinical diagnosis of chronic hypertension and superim-
posed preeclampsia have renal disease. Chronic hypertension oc-
curs in 0.5%–4% of pregnancies (averaging 1.5%). Approximately
80% of chronic hypertension is idiopathic, and 20% is due to renal
disease. Common associations include Ͼ30 years of age, obesity,
multiparous, diabetes mellitus, nonwhite, and family history of
hypertension. There is a .50% chance of maternal or perinatal mor-

bidity occurring in women who enter pregnancy with severe chronic
hypertension in association with other renocardiovascular compli-
cation.
Chronic hypertension complicating pregnancy carries signifi-
cant perinatal risk: abruptio placenta, fetal growth restriction, and
prematurity. These complications are encountered more frequently
in cases of severe hypertension, preexisting cardiovascular diseases,
preexisting renal diseases, as well as target organ damage from
CHAPTER 13
HYPERTENSIVE DISORDERS DURING PREGNANCY
397
From RR de Alvarez. In R.C. Benson, ed., Current Obstetric & Gynecologic Diagnosis & Treatment, 4th ed. Lange, 1982.
TABLE 13-1
DIFFERENTIAL DIAGNOSIS OF CHRONIC HYPERTENSIVE CARDIOVASCULAR DISEASE AND PREECLAMPSIA
Features Hypertensive Disease Preeclampsia
After 20th week of pregnancy
(exception: trophoblastic tumors)
Hypertension usually absent at 6 weeks
postpartum; always by 3 months
postpartum
Usually negative; may be positive
Psychosexual problems common
Generally teenage, early 20s
Usually primigravida
Usually eumorphic
Vascular spasm, retinal edema; rarely,
protein extravasations
Usually present (see definition); absent
at 6 weeks postpartum
Onset of hypertension

Duration of hypertension
Family history
Past history
Age
Parity
Habitus
Retinal findings
Proteinuria
Before pregnancy; during first 20 weeks of
pregnancy
Permanent; hypertension persists beyond 3
months postpartum
Often positive
Recurrent toxemia
Usually older
Usually multigravida
May be thin or brachymorphic
Often arteriovenous nicking, tortuous
arterioles, cotton wool exudates,
hemorrhages
Often none
398
hypertension. The use of antihypertensive therapy during pregnancy
in all of preceding high-risk chronic hypertensive patients has been
demonstrated to improve both maternal and perinatal outcomes.
However, in lower risk chronic hypertensive states, the data for an-
tihypertensive therapy to improve maternal or perinatal outcomes
is less convincing.
DIAGNOSIS
SIGNS

The designation of chronic hypertension in pregnancy is based on
documented hypertension before conception or hypertension ,20
weeks gestation or .6 weeks postpartum.
LABORATORY EVALUATION
Hypertensive patients should be evaluated as soon as feasible in
pregnancy. The following baseline laboratory studies (in addi-
tion to the customary prenatal laboratory tests and those for
preeclampsia) are recommended. SMA-6 or SMA-12, serum uric
acid (Ͼ5.5 mg/dL identifies women with increased likelihood of
superimposed preeclampsia), urine culture and sensitivity, 24-h
urine collection for creatinine clearance (decreased in 5%–10%
of patients, who will also have elevated serum creatinine and
proteinuria) and total protein, chest x-ray films (rule out car-
diomegaly because those with increased heart size are at greater
risk of superimposed preeclampsia, pulmonary edema, and
arrhythmias), and electrocardiogram (expect left ventricular
hypertrophy in 5%–10% of patients).
MANAGEMENT
Obstetric patients with chronic hypertensive cardiovascular or re-
nal disease should be managed similarly to those with preeclamp-
sia. Many of the former will have superimposed preeclampsia, and
it may not be possible to decide what the basic problem actually
was until at least 3–4 months after delivery, when appropriate tests
and studies should be ordered.
If the diastolic BP exceeds 100 mm Hg, antihypertensive drug
therapy is initiated to prevent maternal stroke or cardiac failure.
The aim should be maintenance of BP at 80–90 mm Hg. Whether
CHAPTER 13
HYPERTENSIVE DISORDERS DURING PREGNANCY
399

BENSON & PERNOLL’S
400 HANDBOOK OF OBSTETRICS AND GYNECOLOGY
or not uterine blood flow is autoregulated is still undecided. If it is,
antihypertensive therapy is not likely to decrease blood flow. On
the other hand, if uterine blood vessels are always fully dilated and
the flow is not autoregulated, lowering of the maternal BP should
decrease uterine blood flow—possibly harmful to the fetus. Hence,
antihypertensive drugs must be used cautiously because they carry
an uncertain risk–benefit ratio.
Methyldopa, a popular antihypertensive drug, has been used
extensively during pregnancy and is considered by some to be the
first agent of choice. However, the drug is responsible for con-
traction of the blood volume in chronic hypertension-preeclamp-
sia after recent diuretic therapy. Therefore, it may not be the drug
of choice in many preeclamptic patients. Another effective therapy
is Labetalol. Beta-blockers may cause hypoglycemia and respira-
tory depression. Moreover, these drugs blockade the tachycardiac
response of neonates of mothers on beta-blocker therapy. Alterna-
tive drugs probably are safer and are at least as effective in late
pregnancy.
FETAL ASSESSMENT
Fetal activity determinations and nonstress and stress tests are im-
portant assessment parameters because they may indirectly indicate
reduced uterine blood flow and placental function, which may be-
come critical factors in preeclampsia-eclampsia. Fetal maturity (LS
ratio or rapid surfactant test) should be determined and the fetal sta-
tus monitored closely to properly plan delivery.
CHRONIC HYPERTENSION WITH
SUPERIMPOSED PREECLAMPSIA
Patients with chronic hypertension with superimposed preeclamp-

sia (about one third of all chronic hypertensives in pregnancy) on
hospitalization may seem to stabilize but then deteriorate rapidly.
One of the complications is premature separation of the placenta,
noted in Ͼ10% of patients with chronic hypertension (Ͼ10 times
the incidence in normal pregnancy). Other problems include throm-
bocytopenia, oliguria, and retinal detachment. Even if chronic
hypertensive patients have apparently normal renal function, the
incidence of superimposed preeclampsia is 15%–30%. If there is
renal insufficiency, almost all these patients will develop
preeclampsia-eclampsia. Intrauterine growth retardation is a ma-
jor fetal hazard if preeclampsia is superimposed on chronic
hypertension. Prematurity is often another problem because
preterm delivery may occur spontaneously or by necessity.
The seriousness of the preeclampsia-eclampsia is directly re-
lated to the severity of the underlying cardiovascular disorder. The
perinatal mortality rate is much higher than that in normal preg-
nancies or in preeclampsia-eclampsia not associated with chronic
hypertensive cardiovascular disease.
CHAPTER 13
HYPERTENSIVE DISORDERS DURING PREGNANCY
401
This page intentionally left blank.