The diagnosis of hypertensive disorders complicating pregnancy, as outlined by the Working Group (2000), is shown in Table 23-1. There are five types of hypertensive disease that complicate pregnancy: (1) gestational hypertension (formerly pregnancy-induced hypertension or transient hypertension), (2) preeclampsia, (3) eclampsia, (4) preeclampsia superimposed on chronic hypertension, and (5) chronic hypertension. An important consideration in this classification is differentiating hypertensive disorders that precede pregnancy from preeclampsia, which is a potentially more ominous disease.
TABLE 23-1. Diagnosis of Hypertensive Disorders Complicating Pregnancy
Hypertension is diagnosed when blood pressure is 140/90 mm Hg or greater, using Korotkoff phase V to define diastolic pressure. Edema has been abandoned as a diagnostic criterion because it occurs in too many normal pregnant women to be discriminant. In the past, it had been recommended that an increment of 30 mm Hg systolic or 15 mm Hg diastolic blood pressure be used as a diagnostic criterion, even when absolute values were below 140/90 mm Hg. This criterion is no longer recommended because evidence shows that women in this group are not likely to suffer increased adverse pregnancy outcomes. That said, women who have a rise of 30 mm Hg systolic or 15 mm Hg diastolic warrant close observation.
Hypertensive disorders complicating pregnancy are common and form one part of the deadly triad, along with hemorrhage and infection, that results in much of the maternal morbidity and mortality related to pregnancy. How pregnancy incites or aggravates hypertension remains unsolved despite decades of intensive research, and hypertensive disorders remain among the most significant unsolved problems in obstetrics.
As shown in Table 23-1, the diagnosis of gestational hypertension is made in women whose blood pressure reaches 140/90 mm Hg or greater for the first time during pregnancy, but in whom proteinuria has not developed. Gestational hypertension is termed transient hypertension if preeclampsia does not develop and the blood pressure has returned to normal by 12 weeks postpartum. Importantly, women with gestational hypertension may develop other signs associated with preeclampsia—for example, headaches, epigastric pain, or thrombocytopenia—which influence management.
Preeclampsia is a pregnancy-specific syndrome of reduced organ perfusion secondary to vasospasm and endothelial activation. Proteinuria is described as 300 mg or more of urinary protein per 24 hours or persistent 30 mg/dL (1 + dipstick) in random urine samples. The degree of proteinuria may fluctuate widely over any 24-hour period, even in severe cases. Therefore, a single random sample may fail to demonstrate significant proteinuria. The combination of proteinuria plus hypertension during pregnancy markedly increases the risk of perinatal morbidity and mortality.
The incidence of preeclampsia is commonly cited to be about 5 percent, although remarkable variations are reported. The incidence is influenced by parity, with nulliparous women having a greater risk (7 to 10 percent) when compared with multiparous women. Other risk factors associated with preeclampsia include multiple pregnancy, history of chronic hypertension, maternal age over 35 years, excessive maternal weight, and African American ethnicity.
Severity of Preeclampsia
The severity of preeclampsia is assessed by the frequency and intensity of the abnormalities listed in Table 23-2. The more profound these aberrations, the more likely is the need for pregnancy termination. Importantly, the differentiation between mild and severe preeclampsia can be misleading because apparent mild disease may progress rapidly to severe disease.
TABLE 23-2. Indicators of Severity of Gestational Hypertensive Disordersa
Eclampsia is the occurrence of seizures in a woman with preeclampsia that cannot be attributed to other causes. The seizures are grand mal and may appear before, during, or after labor. Eclampsia may be encountered up to 10 days postpartum.
Preeclampsia Superimposed upon Chronic Hypertension
All chronic hypertensive disorders, regardless of their cause, predispose to development of superimposed preeclampsia or eclampsia. These disorders can create difficult problems with diagnosis and management in women who are not seen until after midpregnancy. The diagnosis of chronic underlying hypertension is suggested by (1) hypertension antecedent to pregnancy, (2) hypertension detected before 20 weeks (unless there is gestational trophoblastic disease), or (3) persistent hypertension long after delivery. Additional historical factors that help support the diagnosis are multiparity and hypertension complicating a previous pregnancy other than the first. There is also usually a strong family history of essential hypertension.
Pathological deterioration of function in a number of organs and systems, presumably as a consequence of vasospasm and ischemia, has been identified in severe preeclampsia and eclampsia.
Any satisfactory theory on the pathophysiology of preeclampsia must account for the observation that hypertensive disorders due to pregnancy are very much more likely to develop in the woman who (1) is exposed to chorionic villi for the first time; (2) is exposed to a superabundance of chorionic villi, as with twins or hydatidiform mole; (3) has preexisting vascular disease; or (4) is genetically predisposed to hypertension developing during pregnancy.
Vasospasm is basic to the pathophysiology of preeclampsia–eclampsia. This concept is based upon direct observations of small blood vessels in the nail beds, ocular fundi, and bulbar conjunctivae, and it has been surmised from histological changes seen in various affected organs. Vascular constriction causes resistance to blood flow and accounts for the development of arterial hypertension. It is likely that vasospasm itself also exerts a damaging effect on vessels. Moreover, angiotensin II causes endothelial cells to contract. These changes likely lead to endothelial cell damage and interendothelial cell leaks through which blood constituents, including platelets and fibrinogen, are deposited subendothelially. These vascular changes, together with local hypoxia of the surrounding tissues, presumably lead to hemorrhage, necrosis, and other end-organ disturbances that have been observed with severe preeclampsia.
Although there are many possible maternal consequences of hypertensive disorders due to pregnancy, for simplicity these effects are considered here using specific target organ systems. The major cause of fetal compromise occurs as a consequence of reduced uteroplacental perfusion.
Severe disturbance of normal cardiovascular function is common with preeclampsia or eclampsia. These changes are basically related to increased cardiac afterload caused by hypertension, and endothelial injury with extravasation into the extracellular space, especially the lung. Aggressive fluid administration given to women with severe preeclampsia causes normal left-sided filling pressures to become substantially elevated while increasing an already normal cardiac output to supranormal levels.
Hemoconcentration is a hallmark of severe preeclampsia–eclampsia. The virtual absence of the normally expanded blood volume of pregnancy is likely the consequence of generalized vasoconstriction made worse by increased vascular permeability.
Hematological abnormalities develop in some, but certainly not all, women who develop hypertensive disorders due to pregnancy. Thrombocytopenia at times may become so severe as to be life threatening; the level of some plasma clotting factors may be decreased; and erythrocytes may be so traumatized that they display bizarre shapes and undergo rapid hemolysis.
Maternal thrombocytopenia can be induced acutely by preeclampsia–eclampsia. After delivery, the platelet count will increase progressively to reach a normal level within 3 to 5 days. Overt thrombocytopenia, defined by a platelet count less than 100,000/μL, indicates severe disease (see Table 23-2). In most cases, delivery is indicated because the platelet count continues to decrease. In general, the lower the platelet count, the greater are maternal and fetal morbidity and mortality. The addition of elevated liver enzymes to this clinical picture is even more ominous. This combination of events is referred to as the HELLP syndrome—that is, hemolysis (H), elevated liver enzymes (EL), and low platelets (LP). Neonatal thrombocytopenia does not occur as a result of preeclampsia.
A severe deficiency of any of the soluble coagulation factors is very uncommon in severe preeclampsia–eclampsia unless another event coexists that predisposes to consumptive coagulopathy, such as placental abruption or profound hemorrhage due to hepatic infarction.
During normal pregnancy, renal blood flow and glomerular filtration rate are increased appreciably. With development of preeclampsia, renal perfusion and glomerular filtration are reduced. Plasma uric acid concentration is typically elevated, especially in women with more severe disease.
In the majority of preeclamptic women, mild-to-moderately diminished glomerular filtration appears to result from a reduced plasma volume, leading to plasma creatinine values approximately twice those expected for normal pregnancy of about 0.5 mg/dL. In some cases of severe preeclampsia, however, renal involvement is profound, and plasma creatinine may be elevated several times over nonpregnant normal values or up to 2 to 3 mg/dL. After delivery, in the absence of underlying chronic renovascular disease, complete recovery of renal function usually can be anticipated.
There should be some degree of proteinuria to establish the diagnosis of preeclampsia–eclampsia (see Table 23-1).
With severe preeclampsia, at times there are alterations in tests of hepatic function and integrity. Periportal hemorrhagic necrosis in the periphery of the liver lobule is the most likely reason for increased serum liver enzymes. Bleeding from these lesions may cause hepatic rupture, or they may extend beneath the hepatic capsule and form a subcapsular hematoma.
Central nervous system manifestations of preeclampsia, especially the convulsions of eclampsia, have been long known. Visual symptoms are another manifestation of brain involvement.
Two distinct but related types of cerebral pathology include gross hemorrhages due to ruptured arteries caused by severe hypertension. These can be seen in any woman with gestational hypertension, and preeclampsia is not necessary for their development.
Other lesions, variably demonstrated with preeclampsia but likely universal with eclampsia, are more widespread and seldom fatal. The principal cerebral lesions are edema, hyperemia, focal anemia, thrombosis, and hemorrhage.
Detachment of the retina may cause altered vision, although it is usually one sided and seldom causes total visual loss as in some women with cortical blindness. Surgical treatment is seldom indicated; prognosis is good, and vision usually returns to normal within a week. Cerebral edema can occur in more severe cases, and obtundation and confusion are major factors with symptoms that wax and wane. In a few cases, overt coma can occur.
A variety of biochemical and biophysical markers, based primarily on rationales implicated in the pathology and pathophysiology of hypertensive disorders due to pregnancy, have been proposed for the purpose of predicting the development of preeclampsia later in pregnancy. Investigators have attempted to identify early markers of faulty placentation, reduced placental perfusion, endothelial cell dysfunction, and activation of coagulation. Virtually all these attempts have resulted in testing strategies with low sensitivity for the prediction of preeclampsia. At the present time, there are no screening tests for preeclampsia that are reliable, valid, and economical. The interested reader is referred to Chapter 34 in Williams Obstetrics, 22nd edition, for further reading on tests for prediction of preeclampsia.
A variety of strategies have been used in attempts to prevent preeclampsia. Usually these strategies involve manipulation of diet and pharmacological attempts to modify the pathophysiological mechanisms thought to play a role in the development of preeclampsia. The latter includes use of low-dose aspirin and antioxidants.
One of the earliest efforts aimed at preventing preeclampsia was salt restriction during pregnancy. This has been proven to be ineffective. Likewise, supplemental calcium has not been shown to prevent any of the hypertensive disorders due to pregnancy. Other ineffective dietary manipulations that have been tested include administration of fish oil each day. This dietary supplement was chosen in an effort to modify the prostaglandin balance implicated in the pathophysiology of preeclampsia.
By suppression of platelet thromboxane synthesis and sparing of endothelial prostacyclin production, low-dose aspirin was thought to have the potential to prevent preeclampsia. Many randomized studies have not borne this out, and this therapy is not currently recommended.
Sera of normal pregnant women contain antioxidant mechanisms that function to control lipid peroxidation, which has been implicated in the endothelial cell dysfunction associated with preeclampsia. Sera of women with preeclampsia have been reported to have markedly reduced antioxidant activity. Moreover, antioxidant therapy significantly reduces endothelial cell activation, suggesting that such therapy might be beneficial in the prevention of preeclampsia. However, large studies of dietary supplementation have not borne this out and such therapy is not currently recommended.
Basic management objectives for any pregnancy complicated by preeclampsia are (1) termination of pregnancy with the least possible trauma to mother and fetus, (2) birth of an infant who subsequently thrives, and (3) complete restoration of health to the mother. In certain cases of preeclampsia, especially in women at or near term, all three objectives are served equally well by induction of labor. Therefore, the most important information that the obstetrician has for successful management of pregnancy complicated by hypertension, is precise knowledge of the age of the fetus.
Traditionally, the timing of prenatal examinations has been scheduled at intervals of 4 weeks until 28 weeks, and then every 2 weeks until 36 weeks, and weekly thereafter. The increased prenatal visits during the third trimester are intended for early detection of preeclampsia. Women with overt hypertension (≥140/90 mm Hg) are frequently admitted to the hospital for 2 to 3 days to evaluate the severity of new-onset pregnancy hypertension. Management of women without overt hypertension, but in whom early preeclampsia is suspected during routine prenatal visits, is primarily based upon increased surveillance. The protocol used successfully for many years at Parkland Hospital in women during the third trimester and with new-onset diastolic blood pressure readings between 81 and 89 mm Hg or sudden abnormal weight gain (more than 2 lb per week) includes return visits at 3- to 4-day intervals. Such outpatient surveillance is continued unless overt hypertension, proteinuria, visual disturbances, or epigastric discomfort supervene.
Hospitalization is considered for women with persistent or worsening hypertension or development of proteinuria. A systematic evaluation is instituted to include the following:
1. Detailed examination followed by daily scrutiny for clinical findings such as headache, visual disturbances, epigastric pain, and rapid weight gain
2. Admittance weight and every day thereafter
3. Admittance analysis for proteinuria and at least every 2 days thereafter
4. Blood pressure readings in sitting position with an appropriate sized cuff every 4 hours, except between midnight and morning
5. Measurements of plasma or serum creatinine, hematocrit, platelets, and serum liver enzymes, the frequency to be determined by the severity of hypertension
6. Frequent evaluation of fetal size and amnionic fluid volume either clinically or with sonography
If these observations lead to a diagnosis of severe preeclampsia (see Table 23-2), further management is the same as described for eclampsia (see Chapter 24).
Reduced physical activity throughout much of the day is beneficial. Absolute bed rest is not necessary, and sedatives and tranquilizers are not prescribed. Ample, but not excessive, protein and calories should be included in the diet. Sodium and fluid intakes should not be limited or forced. Further management depends upon (1) severity of preeclampsia, determined by presence or absence of conditions cited; (2) duration of gestation; and (3) condition of the cervix. Fortunately, many cases prove to be sufficiently mild and near enough to term that they can be managed conservatively until labor commences spontaneously or until the cervix becomes favorable for labor induction. Complete abatement of all signs and symptoms, however, is uncommon until after delivery. Almost certainly, the underlying disease persists until after delivery.
Delayed Delivery with Severe Preeclampsia
Women with severe preeclampsia are usually delivered without delay. In recent years, several investigators worldwide have advocated a different approach in the treatment of women with severe preeclampsia remote from term. This approach advocates conservative or “expectant” management in a selected group of women with the aim of improving infant outcome without compromising the safety of the mother. Aspects of such conservative management always include careful daily, and more frequent, monitoring of the pregnancy in the hospital with or without use of antihypertensive drugs to control hypertension. We are reluctant to advise clinicians that it is safe to expectantly manage women with persistent severe hypertension or significant hematological, cerebral, or liver abnormalities due to preeclampsia. Such women are not managed expectantly at Parkland Hospital.
In attempts to enhance fetal lung maturation, glucocorticoids have been administered to severely hypertensive pregnant women remote from term. Treatment does not seem to worsen maternal hypertension, and a decrease in the incidence of respiratory distress and improved fetal survival has been cited. Use of glucocorticoids specifically administered as a therapy for the hematological abnormalities due to severe preeclampsia will not significantly delay the need for delivery. It is not advisable to administer glucocorticoids to significantly delay delivery in women with severe laboratory abnormalities.
Home Health Care
Many clinicians feel that further hospitalization is not warranted if hypertension abates within a few days. Women with mild-to-moderate hypertension and without proteinuria are sometimes managed at home. Such management may continue as long as the disease does not worsen and if fetal jeopardy is not suspected. Sedentary activity throughout the greater part of the day is recommended. These women should be instructed in detail about reporting symptoms. Home blood pressure and urine protein monitoring or frequent evaluations by a visiting nurse may be necessary.
Termination of Pregnancy
Delivery is the cure for preeclampsia. Headache, visual disturbances, or epigastric pain are indicative that convulsions are imminent, and oliguria is another ominous sign. Severe preeclampsia demands anticonvulsant and usually antihypertensive therapy followed by delivery. Treatment is identical to that described subsequently for eclampsia. The prime objectives are to forestall convulsions, prevent intracranial hemorrhage and serious damage to other vital organs, and deliver a healthy infant.
When the fetus is known or suspected to be preterm, however, the tendency is to temporize in the hope that a few more weeks in utero will reduce the risk of neonatal death or serious morbidity. As discussed, such a policy certainly is justified in milder cases. Assessments of fetal well-being and placental function (see Chapter 17) have been attempted, especially when there is hesitation to deliver the fetus because of prematurity. Measurement of the lecithin–sphingomyelin ratio in amnionic fluid may provide evidence of lung maturity.
With moderate or severe preeclampsia that does not improve after hospitalization, delivery is usually advisable for the welfare of both mother and fetus. Labor should be induced by intravenous oxytocin. Many clinicians favor preinduction cervical ripening with a prostaglandin or osmotic dilator. Whenever it appears that labor induction almost certainly will not succeed, or attempts at induction of labor have failed, cesarean delivery is indicated for more severe cases.
For a woman near term, with a soft, partially effaced cervix, even milder degrees of preeclampsia probably carry more risk to the mother and her fetus–infant than does induction of labor by carefully monitored oxytocin induction. This is not likely to be the case, however, if the preeclampsia is mild but the cervix is firm and closed, indicating that abdominal delivery might be necessary if pregnancy is to be terminated. The hazard of cesarean delivery may be greater than that of allowing the pregnancy to continue under close observation until the cervix is more suitable for induction.
Elective Cesarean Delivery
Once severe preeclampsia is diagnosed, the obstetrical propensity is for prompt delivery. Induced labor to effect vaginal delivery has traditionally been considered to be in the best interest of the mother. Several concerns, including an unfavorable cervix precluding successful induction of labor, a perceived sense of urgency because of the severity of preeclampsia, and the need to coordinate neonatal intensive care have led some to advocate cesarean delivery.
For further reading in Williams Obstetrics, 23rd ed.,
see Chapter 34, “Hypertensive Disorders in Pregnancy.”