Hypertensive Disorders of Pregnancy
Veena Choubey
Frank R. Witter
DEFINITIONS OF HYPERTENSIVE DISORDERS
Hypertensive disorders affect 5% to 10% of all pregnancies.
Hypertension is defined as systolic blood pressure (BP) ≥140 mm Hg or diastolic BP ≥90 mm Hg on two separate occasions at least 6 hours but not more than 7 days apart.
Chronic hypertension is high BP diagnosed before pregnancy or before 20 weeks’ gestation or first recognized during pregnancy but persisting longer than 12 weeks postpartum.
Gestational hypertension, formerly known as pregnancy-induced or transient hypertension, is defined as BP ≥ 140/90 mm Hg during pregnancy or within the first 24 hours postpartum without a history of chronic hypertension and without the signs and symptoms of preeclampsia. If the BP is ≥160/110 for more than 6 hours, the diagnosis is severe gestational hypertension.
Preeclampsia is diagnosed by elevated BP and proteinuria after 20 weeks’ gestation in a patient known to be previously normotensive. Trophoblastic disease or multiple gestation can present with preeclampsia before 20 weeks’ gestation.
Mild preeclampsia is defined by the following criteria:
BP ≥ 140/90 mm Hg confirmed on two measures at least 6 hours but not more than 7 days apart, and
Proteinuria ≥300 mg on a 24-hour urine collection or two random urine dipstick results of at least 30 mg/dL (“1+”). Spot urine protein: Creatinine ratios are used by some investigators instead of 24-hour urine collection and show good predictive value in the lower and higher ranges.
Preeclamptic patients often have wide variation in urine protein values over time, possibly from renal vasospasm. Discrepancies between the random urine dipstick and 24-hour urine collection measurements have been well described. The 24-hour urine collection, therefore, remains the preferred measure for diagnosing preeclampsia.
Severe preeclampsia is classified by the following criteria:
BP during bed rest of ≥ 160 mm Hg systolic or ≥110 mm Hg diastolic; or
Proteinuria ≥5 g on a 24-hour urine collection even if BP is in the mild range. Persistent urine dipstick ≥3+ also qualifies; or
Signs, symptoms, or lab values of severe preeclampsia with any elevated BP.
Symptoms of preeclampsia may include the following: cerebral or visual disturbances (e.g., persistent headache, blurred vision, scotomata, and blindness from retinal detachment); epigastric, right upper quadrant, or constant low abdominal pain from liver dysfunction or from abruptio placentae; nausea and vomiting; dyspnea from pulmonary edema; decreased urine output, hematuria, or rapid weight gain >5 pounds in 1 week; and absent or decreased fetal movement.
Physical findings of preeclampsia may include the following:
Elevated BP measured in the sitting or semireclined position with the arm positioned roughly at heart level
Nondependent or generalized edema
Pulmonary edema, with rales or crackles on lung examination
Epigastric or right upper quadrant tenderness without a known cause, likely secondary to hepatic edema
Uterine tenderness or tetany secondary to placental abruption
Oliguria with 24-hour urine output <500 mL
Laboratory findings of preeclampsia may include the following:
Diagnostic proteinuria (described earlier)
Decreased hematocrit secondary to severe hemolysis in HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome
Microangiopathic hemolytic anemia with abnormal findings on peripheral smear, increased serum bilirubin, elevated serum lactate dehydrogenase (LDH), or decreased serum haptoglobin
Elevated hematocrit resulting from decreased intravascular volume secondary to third spacing of fluid
Elevated serum uric acid level of 5 mg/dL or greater
Elevated serum creatinine of 1.2 mg/dL or greater. Creatinine normally decreases in pregnancy, thus even slight increases warrant further investigation.
Elevated serum transaminases (aspartate aminotransferase >70 IU/L)
Thrombocytopenia with platelet count of 100,000/L or less
Prolonged prothrombin and partial thromboplastin times that may be due to primary coagulopathy, hepatic synthesis dysfunction, or abruptio placentae leading to disseminated intravascular coagulation
Decreased fibrinogen, increased fibrin degradation products, or both, as a result of coagulopathy or abruptio placentae
Fetal findings of preeclampsia may include intrauterine growth restriction (IUGR), oligohydramnios, and other signs of uteroplacental insufficiency.
Preeclampsia superimposed on chronic hypertension occurs in patients with preexisting high BP. Differentiating chronic hypertension with superimposed preeclampsia from a gestational exacerbation of chronic hypertension can be difficult, especially if there is baseline proteinuria. In general, diagnosis requires a significant change from baseline proteinuria and worsening hypertension or the development of symptoms.
HELLP syndrome is a variant of preeclampsia defined by the following criteria:
Hemolysis identified by burr cells and schistocytes on an abnormal peripheral smear, an elevated serum bilirubin (>1.2 mg/dL) or LDH level (>600 IU/L), or a low serum haptoglobin
Thrombocytopenia with platelets ≤100,000/µL is the most consistent finding in HELLP syndrome.
Elevated liver function tests (i.e., transaminases) greater than two times the upper limit of normal
Note that hypertension may be absent (12% to 18% of cases), mild (15% to 50%), or severe (50%). Proteinuria may be absent as well (13%).
Eclampsia is seizure or unexplained coma in a patient with preeclampsia. Eclampsia can present without hypertension (16%) or proteinuria (14%).
CHRONIC HYPERTENSION
Chronic hypertension carries increased risk for superimposed preeclampsia, preterm delivery, abruptio placentae, and IUGR. See Chapter 1 for general classification and treatment of hypertension.
The differential diagnosis of chronic hypertension in pregnancy includes the following:
Essential hypertension, which accounts for 90% of hypertension outside of pregnancy
Kidney disease, adrenal disorders (e.g., primary aldosteronism, congenital adrenal hyperplasia, Cushing syndrome, pheochromocytoma), hyperthyroidism, newonset collagen vascular disease, systemic lupus erythematosus, aortic coarctation, chronic obstructive sleep apnea, and cocaine use
Worsening chronic hypertension is difficult to distinguish from superimposed preeclampsia. If seizures, thrombocytopenia, pulmonary edema, unexplained hemolysis, or elevation in liver enzyme levels develop, superimposed preeclampsia should be diagnosed. Monitoring trends in BP and urine protein may also be helpful.
A 24-hour urine calcium measurement may be useful. Urine calcium with preeclampsia is lower than in patients with hypertension alone.
A value <195 mg total urine calcium in 24 hours predicts preeclampsia with a sensitivity of 86% and specificity of 84%.
Obtain baseline information early in pregnancy for chronic hypertension, including:
History of first diagnosis, etiology, duration, and current and prior treatments
Complete medical history including cardiovascular risk factors (e.g., smoking, increased plasma lipid levels, obesity, and diabetes mellitus) and complicating medical factors (e.g., headaches, history of chest pain, myocardial infarction, stroke, renal disease)
Complete medication list including vasoactive over-the-counter drugs (e.g., sympathomimetic amines, nasal decongestants, diet pills)
Baseline complete blood count (CBC) and serum creatinine, urea nitrogen, uric acid, and calcium levels
Baseline electrocardiogram (ECG) if not documented within the prior 6 months. Echocardiogram may be indicated if evidence of left ventricular hypertrophy is present.
Baseline 24-hour urine protein
Treatment is tailored to the severity of illness and presence of comorbidities.
Mild hypertension often responds to conservative management.
Sodium restriction of ≤2.4 g/day. Dietary modifications with increased fruits and vegetables and decreased total and saturated fats can be encouraged.
Smoking and alcohol cessation
Mild activity restrictions, due to concern for decreased uteroplacental blood flow increasing risk of preeclampsia
Serial fetal growth ultrasounds every 4 to 6 weeks starting after the anatomy scan at 18 to 20 weeks’ gestation. More severe or worsening hypertension may require drug therapy and requires closer monitoring of fetal well-being. Patients receiving antihypertensive agents should undergo antepartum fetal surveillance with nonstress test (NST) or biophysical profile (BPP) and a BP check one or two times per week starting at 28 weeks’ gestation (earlier if severe hypertension or suspected IUGR).
Treatment for chronic hypertension or persistently elevated BPs can include the following during pregnancy:
Labetalol—an α1 and nonselective β-adrenergic antagonist that can be used as monotherapy or combined with hydralazine or a diuretic. The initial dose is 100 mg twice daily and may be increased in increments of 100 mg twice daily every 2 to 3 days to a maximum of 2,400 mg daily. It is contraindicated in patients with greater than first-degree heart block. Chronic beta-blocker use in pregnancy has a mild association with IUGR.
Nifedipine—a calcium channel blocker used commonly in pregnancy that allows convenient daily dosing with the sustained release formulation. A multicenter prospective study of first-trimester drug exposure to calcium antagonists found no increased teratogenicity. The initial dose of nifedipine is 30 mg daily. The dose can be increased to 60 mg daily if adequate response is not seen in 7 days. The maximum daily dose is 90 mg. There is a theoretical risk of neuromuscular blockade when magnesium and nifedipine are administered together, although this was not supported in retrospective studies.
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