Descriptions of Hypertensive Disorders of Pregnancy
by Classification and General Conventional Treatment Approaches
A great deal of debate and uncertainty surrounds the etiology, classification, and medical treatment of pregnancy hypertensive disorders. The following discussion provides a brief overview of the salient points of each of the pregnancy hypertensive disorders and their specific medical treatments based on current recommendations.
Preeclampsia is a disease specific to pregnancy, with “cure” occurring only upon delivery of the placenta. The etiology of preeclampsia remains unknown, although there are numerous theories. It appears that it is a complex, multifactorial condition with genetic factors, immunologic factors, altered inflammatory pathways, insulin resistance (obesity, hyperlipidemia, glucose intolerance), endothelial dysfunction, macronutrient and micronutrient deficiencies, altered placental angiogenesis, and subclinical infections possibly participating in the risk of developing this condition. Advanced maternal age, first pregnancy, poor nutrition, residence at high altitudes, and lack of adequate prenatal care have also been associated with increased risk. There is a common thread in all cases: poor placental perfusion associated with maternal vasoconstriction and subsequent maternal multiorgan failure.
Early identification of preeclampsia increases the likelihood of proper early management and reduction of poor prenatal outcome. Unfortunately, in spite of a great deal of investigation into serum markers that might help to identify women at risk of developing preeclampsia, no reliable markers have been found, nor is there a consistent standard for clinical identification of this potentially devastating condition. Similarly, no preventative measures for preeclampsia have been identified with any certainty. Current pharmacotherapy is able to reduce blood pressure and prevent the development of eclampia (preeclampsia with seizures), but it cannot stop the progression of the condition once it is established. Fetal intrauterine growth restriction is a major consequence of this disease. Initial ultrasound at 18 to 20 weeks gestation documents baseline fetal growth. When a woman is diagnosed with preeclampsia, serial ultrasounds at 28 to 32 weeks gestation and then monthly until term, are suggested for objective measurement. Fetal well-being tests such as non-stress tests (NST) and biophysical profile (BPP) are ordered in the third trimester. Fetal movement counts are helpful as a subjective measurement the woman can do at home. A variety of therapeutic strategies have been evaluated for the prevention and treatment of preeclampsia. These are discussed in the following.
Diuretics were once assumed to be a beneficial part of treatment of preeclampsia with its attendant hypertension and edema. However, women with preeclampsia are actually hypovolemic and hemoconcentrated; therefore, the use of diuretics may exacerbate the condition, and thus their use for this condition has been abandoned.
There is no evidence that salt restriction is of any benefit in the prevention or treatment of preeclampsia.
Antihypertensive therapy for women with preeclampsia does not affect the underlying disease process or improve mother-baby outcome. Further, antihypertensive medications have been associated with adverse side effects, including total placental hypoperfusion; thus, their use is reserved for the treatment of chronic and severe hypertension.
Data from randomized trials and meta-analysis have been conflicting on the prophylactic and therapeutic effects of low-dose aspirin for preeclampsia. The use of aspirin is predicated on the fact that widely disseminated endo-thelial dysfunction and platelet disturbances are associated with the etiology of this condition. Low-dose aspirin is thought to be effective because of its thromboxane synthesis inhibition, with consequent reduction in platelet aggregation, as well as its ability to inhibit free radical formation (lipid peroxides) and support of resistance to angiotensin II in pregnant women with increased susceptibility to this vasoconstriction substance. The most recent systematic review of all randomized trials to meet the reviewer’s inclusion criteria (39 trials with a total of 30,563 women) showed a positive safety profile with a moderate, but significant, reduction in the risk of preeclampsia regardless of weeks gestation at trial entry or dose of aspirin. A 15% reduction in incidence of preeclampsia was observed, with an 8% reduction in preterm birth and a 14% reduction in risk of perinatal death. In spite of disagreement of the value of aspirin for preeclampsia in earlier studies, all studies have demonstrated that aspirin use in recommended doses during pregnancy appears safe. Recent evidence suggests that the earlier in pregnancy that the aspirin is started, the greater the benefit. The recommended dosage range for optimal effects is between 80 and 150 mg per day, specifically to be taken at bedtime.
Studies on the efficacy of calcium supplementation for prophylaxis and treatment of preeclampsia have been equivocal. A recent, large, multicenter, randomized prospective trial of 2 g of elemental calcium vs. placebo given to healthy, nulliparous pregnant women beginning in their second trimester showed no differences in the incidence or severity of hypertensive disorders. However, a more recent trial demonstrated benefit for women who were at very high risk for developing preeclampsia. A proposed mechanism is via prevention of a compensatory rise in parathyroid hormone associated with low serum calcium, and consequently, smooth muscle contraction; however, this remains theoretical.
Vitamins C and E
Oxidative stress has been proposed as a mechanism associated with the development of preeclampsia. Further, studies have demonstrated decreased levels of antioxidant levels in women with preeclampsia. This has prompted evaluation into the use of vitamin C and E supplements as possibly prophylaxis and therapy. The risk of developing preeclampsia was seen to be lower in high-risk women begun on supplementation at 16 to 20 weeks gestation compared with placebo. At this point, the role of anti-oxidants in this condition remains unclear. For women wishing to supplement vitamin C during pregnancy, it is recommended not to exceed 2000 mg per day to avoid the risk of sensitivity or neonatal rebound scurvy.
Chronic hypertension is defined as hypertension that predated pregnancy, or hypertension beginning prior to 20 weeks gestation. This diagnosis is not easy to establish in women who have not had care prior to pregnancy and because hypertension prior to 20 weeks gestation can also be indicative of preeclampsia that can occur early in pregnancy in a limited number of conditions. Blood pressure levels are less suggestive of poor maternal or fetal outcomes, including fetal growth retardation, prematurity, preeclampsia, placental abruption, and maternal or perinatal morbidity and mortality than are the onset of proteinuria and symptoms of preeclampsia. The health care professional may order electrocardiography, echocardiogram, ophthalmologic exam, and renal ultrasound. Women with mild hypertension (140 to 159 mm Hg systolic or 90 to 105 mm Hg diastolic) generally do well in pregnancy and, overall, do not need antihypertensive medication. In fact, women already taking antihypertensive medications may need to decrease the dose as some studies have shown decreased uteroplacental blood flow and fetal growth with medication. Tapering or stopping antihypertensive medications is done under close observation. Antihypertensive therapies are given to reduce the risk of maternal stroke and cardiovascular complication in women with a diastolic BP of >105 mm Hg. Recommendation of antihypertensive treatment is done when blood pressure levels reach or exceed 160 mm Hg systolic or 100 to 106 mm Hg diastolic, when abnormal laboratory values are found, and certainly with a combination of both abnormal factors.
Oral antihypertensive medication with methyldopa or labetalol is typically recommended. Methyldopa does not appear to have negative effects on uteroplacental blood flow. Some women, however, do not tolerate it well because of drowsiness. Labetalol, a combined alpha-and beta-blocker, is another choice and can also be prescribed postpartum when breastfeeding. Ideally, women with chronic hypertension need to be evaluated before pregnancy for severity of the hypertension, modification of lifestyle habits and target organ damage (heart, kidney). Women with significant renal impairment (serum creatinine 71.4 mg / dL) may have further deterioration in pregnancy. Women with cardiac abnormalities may have underlying diseases in addition to chronic hypertension. Most women with mild chronic hypertension (140 / 90 mm Hg) have no end-organ involvement and can have uncomplicated pregnancies.
Gestational (Transient) Hypertension
Elevated blood pressure appearing after 20 weeks without proteinuria and with normal laboratory values in a previously normotensive woman generally results in a good outcome. However, gestational hypertension is considered a provisional term. Although most women will not develop subsequent problems, up to 25% will go on to develop symptoms of preeclampsia. Women with gestational hypertension appear to be at significantly increased risk of maternal and perinatal morbidity, with elevated rates of preterm delivery, small for gestational age infants, and abruptio placenta compared significantly higher than in the general obstetrical population, and similar to rates reported for women with severe preeclampsia. Thus, women with a diagnosis of gestational hypertension should be monitored closely, with weekly prenatal visits optimal. Ultrasound and fetal well-being tests are appropriate in the third trimester. If symptoms of preeclampsia develop, women are treated as is appropriate for that condition. If elevated blood pressure readings persist 12 weeks postpartum, a diagnosis of chronic hypertension is made retrospectively.