HYPERTENSION AND PREGNANCY

ABSTRACT
Hypertensive disorders occur in about 3-10% of all pregnancies and account for significant fetal and maternal
morbidity and mortality. They fall into four major categories: chronic hypertension, Preeclampsia-eclampsia
(pregnancy induced hypertension), chronic hypertension with superimposed preeclampsia and gestational
hypertension. The pathophysiology and treatment of hypertensive disorders in pregnancy is discussed. (Heart
Views. 2000;1(8): 309-313) © 2000 Hamad Medical Corporation.

Introduction
Blood pressure drops in early gestation and by the second trimester it is usually 10mmHg below the baseline.
This is induced by reduction in the peripheral resistance due to systemic vasodilatation and creation of a low
resistance circuit in the gravid uterus. The mechanism of the vasodilatation is not clearly understood but
decreased vascular responsiveness to the pressor effects of angiotension II and norepinephrine is a major
factor.

Hypertension in pregnancy is defined as a rise in blood pressure of at least 30 mm Hg of the systolic or 15 mm

Hg of the diastolic blood pressure above pre-gestation baseline. If previous blood pressure is not known, a
reading of 140/90 or above after the 20th week of gestation is considered abnormal. The U.S. joint National
Committee for the Prevention, Detection, Evaluation and Treatment of High Blood Pressure and the
International Society for the Study of Hypertension in Pregnancy recommend using Korotokoff Phase V
(disappearance of the sound) for determining the diastolic blood pressure. In contrast, most European
physicians use phase IV (muffling of the sound).

1. Chronic Hypertension
Chronic hypertension may be present before gestation or appear in early pregnancy, before the 20th week. It
could be essential or secondary due To parenchymal and vascular renal disease and endocrinological
disorders.

Chronic hypertension in pregnancy is mild to moderate in 95% of cases with a favorable outcome for both the
mother and the fetus. Complications of essential hypertension in pregnancy are more likely to occur with the
following:

a) Severe degree of essential hypertension. The severity of chronic hypertension seems to correlate with the
risk of superimposed preeclampsia; about 10% in pregnant women with mild chronic hypertension compared
to 50% in those with severe hypertension. In addition renal and cerebrovascular complications are more
common with severe hypertension.

b) Associated cardiovascular or cerebrovascular disease. These diseases are unusual in women in the
childbearing age and tend to occur in older age groups (above 40years) in whom hypertension could have been
present for a long time.

c) Associated renal impairment. (serum creatinine above 180 or 200 (mol/L). In such cases pregnancy tends to
be complicated by severe exacerbation of the blood pressure, premature labor and further deterioration of
maternal renal function.

d) Superimposed preeclampsia. The incidence of preeclampsia is higher in women with preexisting

hypertension.

e) The presence of certain associated conditions causes secondary hypertension e.g. Pheochromocytoma,
which is an uncommon condition but has grave consequences in pregnancy. It has a tendency to be activated
in pregnancy and when undiagnosed prior to labor, has a 50% maternal mortality. Maternal risks associated
with chronic hypertension include superimposed preeclampsia or eclampsia, deterioration of renal function,
cerebrovascular accidents, congestive heart failure and hemorrhage secondary to abruptio placentae.

Effects of chronic hypertension on the fetus and neonate include increased incidence of intrauterine growth
retardation, 15%(10), prematurity, 30% (25), and perinatal mortality, 25% (7,10).

1.1 Course of Chronic Hypertension in Pregnancy

The course of chronic hypertension is variably altered by pregnancy . About 50% of pregnant women with
chronic hypertension have decreased blood pressure often to the normal range during the midtrimester with a
relatively low risk of late exacerbation (10%). The other half of hypertensive pregnant women will continue to
have hypertension a third of whom may increase their baseline blood pressure. This group is at high risk of
developing severe hypertension.

1.2 Treatment

Although there is increased risk of perinatal morbidity and mortality when the mother has chronic
hypertension, most pregnancies in these women result in healthy, full term infants. A number of studies have
shown that chronic hypertension per se (without superimposed preeclampsia), has the same perinatal outcome
as normotensive pregnancy. Other studies reported higher perinatal loss in uncomplicated pregnancies with
chronic hypertension, especially with high levels of blood pressure. However, most of the increase in perinatal
morbidity and mortality is attributed to superimposed preeclampsia, which is more common in pregnant
women with chronic hypertension.

The U.S. National Institutes of Health Working Group has recently recommended initiating drug therapy in
uncomplicated chronic hypertension in pregnancy when phase V diastolic pressure levels are 100 mm Hg. This
recommendation is accepted by most authors. Excessive reduction of blood pressure is to be avoided.

Safe, oral antihypertensive drugs in pregnancy, which have stood the test of time are methydopa and
hydralazine. B-blockers are generally considered to be safe in late pregnancy, but they may impair fetal growth
when used in the first trimester. Diuretics are generally avoided because they may produce volume depletion
although this is unlikely to occur with chronic therapy with thiazides because fluid loss occurs in early
treatment. Thiazides may cause neonatal thrombocytopenia when used in the 3rd trimester. The role of calcium
channel blockers is uncertain but nifedipine has been used without major problems. ACE inhibitors are avoided
because they may adversely affect fetal and neonatal blood pressure control and renal function. Teratogenicity
has also been reported in animal studies. The newer class of angiotensin II receptor antagonists has the same
adverse effect as the ACE inhibitors.
In severe hypertension, especially in preeclampsia, intravenous hydralazime is the drug of choice. Labetolol is
also effective and safe.

2. Preeclampsia

The incidence of preeclampsia ranges between 10 and 5.7%, with 15% occurring in primigravidas and 7.3% in
multigravidas. It is further increased in multiple pregnancies and with previous preeclampsia. It usually
presents with gradual development of hypertension, proteinuria and edema in the third trimester and
progresses until delivery. Occasionally, the onset starts in the second trimester or may be delayed until
delivery or early post-partum period.

2.1 Pathogenesis

The pathogenesis of preeclampsia is incompletely understood. An important factor is inadequate maternal

vascular response to placentation. The branches of the uterine artery known as the maternal spiral arteries,
which supply blood to the placenta, are transformed in normal pregnancy from muscular arterioles to flaccid
sac-like vessels. It is hypothesized that this process is achieved by invasion of the arterial wall by trophoblast
(placental fetal tissue). This process is deficient in preeclampsia leading to reduction of more than half the
spiral artery diameter resulting in insufficient distension of the arterial wall and placental ischemia. The
decreased trophoblastic invasion of the maternal spiral arteries is due to failure of the normal differentiation by
the cytotrophoblast in which some growth factors like epidermal growth factor and insulin-like growth factor 1
play a major role.

Placental ischemia possibly leads to release of blood products, which alter vascular endothelial cell function
effecting the characteristic changes of eclampsia, mainly: a) abnormal prostaglandin metabolism, b)
intravascular coagulation, and c) increased vascular responsiveness to pressor substances, which may be
related to endothelin and nitric oxide. The circulating level of nitric oxide, a potent vasodilator, is decreased in
patients with this disorder possibly due to decreased synthesis and contributes to the pathophysiologic
changes. Placental ischemia may also be induced by other factors such as increased placental size (due to
multiple gestations) and underlying vascular disease i.e., hypertension and diabetes mellitus.

2.2 Clinical and Pathological features

Hypertension is usually the first manifestation of preeclampsia, and may preceed the onset of other clinical
features by many weeks. Occasionally, preeclampsia may have a rapid onset with all manifestations appearing
almost simultaneously. Urinary calcium excretion, which is typically increased to more than 5 mmol/day in the
third trimester in normotensive gravidas is reduced to below 2.5 mmol/L in preeclampsia. The exact mechanism
is unknown but could be due to decreased active vitamin D production. The proteinuria is usually gross and
may exceed the nephrotic range of 3.5gm/day, but the rest of the urinalysis is normal and the sediment is
typically benign. Renal function remains normal except when the hypertension is severe and uncontrolled or
when there are additional factors like disseminated intravascular coagulation. The characteristic renal
pathology is glomerular endothelial cell swelling (glomerular endotheliosis) and subendothelial deposition of
hyaline and fibrin-like material. Nephrosclerosis produced by hypertension is also seen.

It is important to differentiate essential hypertension from preeclampsia.

Hypertension starting in the first trimester is usually essential. Young (less than 20 years) primigravidas are
more prone to preeclampsia. Proteinuria of more than one gram per day, which progressively increases is more
likely due to preeclampsia than essential hypertension. An elevated serum uric acid (above 330 mol/L) is
commonly seen in preeclampsia, the mechanism being increased sodium and secondary urate reabsorption by
the proximal tubule induced by renal ischemia.

2.3 Course and Treatment

Hypertension in preeclampsia tends to resolve within two to six weeks post-partum. The renal lesions also
resolve: the fibrin-like deposits disappear in a similar duration of time but glomerular endotheliosis may persist
longer.

The full management of preeclampsia is outside the scope of this article but the definitive treatment of
preeclampsia is delivery of the fetus. Preeclampsia carries a high risk to both the fetus (intrauterine growth
retardation, stillbirth and neonatal death) and the mother (seizures, severe hypertension and HELLP
Syndrome). In patients who have mild eclampsia, termination of pregnancy is not immediately indicated.
Hypotensive therapy is withheld in asymptomatic patients with a diastolic BP of less than 105 mmHg. Treating
less severe hypertension may decrease placental perfusion and does not improve maternal or fetal outcome.

2.4 Prognosis

The prognosis depends on the severity of the acute attack and the obstetric status. In primigravidas, the
condition is usually self-limiting with complete resolution of the hypertension. The possibility of developing
hypertension later on is similar to the general population. The rate of recurrence of preeclampsia in subsequent
pregnancies is low. When there is eclampsia or severe preeclampsia and when it occurs early in pregnancy
(2nd trimester), there is high rate of recurrence in subsequent pregnancies (about 65%) and later development
of hypertension. In multigravidas, late hypertension is more common than primigravidas with mild
preeclampsia.

3. Chronic Hypertension with Superimposed Preeclampsia

The incidence of chronic hypertension with superimposed preeclampsia ranges widely in different studies:
from 4.7-52%. This is related to many factors including the criteria used for the diagnosis of superimposed
preeclampsia and the population studied. An additional important factor is the severity of hypertension at the
time of pregnancy. The reported incidence of superimposed preeclampsia in patients with severe hypertension
in early pregnancy is 28-35% and was unaffected by hypotensive therapy, compared to an incidence of 4.7% for
those patients with mild hypertension.

4. Gestational Hypertension

This is also known as transient or late hypertension and is defined as elevated blood pressure occurring
antepartum, during labour or in the first 24 hours postpartum with no other signs of preeclampsia or
preexisting hypertension and resolves within ten days of delivery. It may be associated with edema, but this is
mild and infrequent. It has little adverse effect on the mother or foetus.

The exact etiology of gestational hypertension is unknown. Its incidence is higher in nulliparous women and in
those with multiparity and previous history of preeclampsia. It might be the tip of the iceberg for a mixed group
of disorders manifesting as hypertension.
Gestational hypertension may recur in subsequent pregnancies. Comparing the postpartum course of
gestational hypertension with preeclampsia, the former was associated with a shorter mean time to
normalization of blood pressure: six weeks versus 16 days. The slower rate of recovery in preeclampsia may
reflect the time required for the resolution of the endothelial damage. A five-year follow up of women with either
preeclampsia or gestational hypertension was reported by Reiter et al. Essential hypertension was found in 5%
and 16% of patients with gestational hypertension and preeclampsia respectively.

Conclusion
Although the incidence of hypertensive disorders in pregnancy is low, they account for significant fetal and
neonatal intrauterine growth retardation, prematurity, perinatal mortality and maternal cerebrovascular
accidents, deterioration of renal function, and congestive heart failure complications. The importance of early
diagnosis and management to avoid these complications cannot be over emphasized.
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