OB/GYN

Management of hypertension in pregnant and postpartum women: Introduction (UpToDate)
There are four major hypertensive disorders that occur in pregnant women:
– Preeclampsia-eclampsia
– Preexisting hypertension
– Preeclampsia superimposed upon preexisting hypertension
– Gestational hypertension

The diagnosis of a hypertensive disorder in a pregnant woman depends, in part, upon the gestational age at presentation.

PREECLAMPSIA refers to the syndrome of new onset of hypertension and proteinuria after 20 weeks of gestation in a previously normotensive woman (table 1), or worsening hypertension with new onset proteinuria in a woman with preexisting hypertension (superimposed preeclampsia).

PREEXISTING HTN is defined as systolic pressure ≥140 mmHg and/or diastolic pressure ≥90 mmHg that antedates pregnancy, is present before the 20th week of pregnancy, or persists longer than 12 weeks postpartum.

GESTATIONAL HTN refers to elevated blood pressure first detected after 20 weeks of gestation in the absence of proteinuria. Over time, some patients with gestational hypertension will develop proteinuria and be considered preeclamptic, while others will be diagnosed with preexisting hypertension because of persistent blood pressure elevation postpartum.

Management of hypertension in pregnant and postpartum women: Approach summary (UpToDate)
When hypertension is diagnosed in a pregnant woman, the major issues are:
– Establishing a diagnosis
– Deciding the blood pressure at which treatment should be initiated and the target blood pressure, and
– Avoiding drugs that may adversely affect the fetus.

In contrast to nonpregnant individuals in whom blood pressure is staged as normal, prehypertension, or stage 1 or 2, blood pressure in pregnant women is either NORMAL, MILD to MODERATE hypertension (140 to 159/90 to 109 mmHg), or SEVERE hypertension (≥160/110 mmHg).

Target blood pressure:
– The rapidity with which blood pressure should be brought to safe levels is controversial. Cerebral or myocardial ischemia or infarction can be induced by aggressive antihypertensive therapy if the blood pressure falls below the range at which tissue perfusion can be maintained by autoregulation. Therefore, reducing mean arterial pressure by no more than 25 percent over two hours and achieving a target of 130 to 150 mm Hg systolic and 80 to 100 mm Hg diastolic seems reasonable.
– We acknowledge the lack of clinical trial data to support these recommendations, and the need to individualize therapy based upon maternal and fetal factors.

Management of hypertension in pregnant and postpartum women: Treatment of preeclampsia summary (UpToDate)
Definition of pre-eclampsia:
Systolic blood pressure ≥140 mmHg
OR
Diastolic blood pressure ≥90 mmHg
AND
Proteinuria ≥0.3 grams in a 24-hour urine specimen

We suggest avoiding antihypertensive therapy for mild to moderate hypertension associated with preeclampsia (Grade 2B). There are no proven benefits to mother or fetus, other than reduction in risk of severe hypertension, and we are concerned about potential adverse fetal effects.

We recommend treatment of severe hypertension (Grade 1B). The goal of treatment is to prevent maternal cerebrovascular complications. We initiate antihypertensive therapy in adult women at systolic pressures ≥150 mm Hg and diastolic blood pressures ≥100 mmHg. We initiate treatment at a lower threshold in younger women whose baseline blood pressure was low, and in those with symptoms that may be attributable to elevated blood pressure (eg, headache, visual disturbances, chest discomfort).

Other organizations, such as the American College of Obstetricians and Gynecologists, have recommended treatment of hypertension when systolic blood pressure is ≥160 mm Hg.

For acute blood pressure therapy, we recommend intravenous labetalol (Grade 2B) or hydralazine.

Our target blood pressure goal is systolic pressure of 140 to 150 mmHg and diastolic pressure of 90 to 100 mmHg.

Gestational hypertension summary (UpToDate)
– Gestational hypertension is defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg after the 20th week of pregnancy without proteinuria in a previously normotensive woman. These criteria distinguish gestational hypertension from preeclampsia (proteinuria must be present) and chronic hypertension (hypertension antedates pregnancy or develops before the 20th week of pregnancy).
– Preeclampsia develops in 15 to 25 percent of women initially diagnosed with gestational hypertension.
– Pregnancy outcomes of patients with mild gestational hypertension are generally favorable, whereas pregnancies associated with severe gestational hypertension are at increased risk for maternal and perinatal morbidity, similar to the rates reported for women with severe preeclampsia.
– The main goals in the diagnostic evaluation of women with gestational hypertension are to distinguish this disorder from preeclampsia, which has a different course and prognosis, and determine whether hypertension is mild or severe, which affects management and outcome.
– We suggest following pregnancies with mild gestational hypertension with weekly prenatal visits and fetal assessment and delivery at 40 weeks of gestation (Grade 2C). If gestational hypertension is accompanied by any of the symptoms or laboratory abnormalities associated with severe preeclampsia, we manage the patient as if she has severe preeclampsia, including antihypertensive therapy, prompt delivery, and use of magnesium sulfate for seizure prophylaxis.
– Gestational hypertension is likely to recur with subsequent pregnancies and is associated with development of hypertension later in life.
Management of hypertension in pregnant and postpartum women: Treatment of gestational hypertension summary (UpToDate)
Definition of gestational hypertension:
Systolic blood pressure ≥140 mmHg
OR
Diastolic blood pressure ≥ 90 mmHg
AND no proteinuria
Developing AFTER the 20th week of gestation in women known to be normotensive before pregnancy. Blood pressure should be elevated on at least two occasions at least six hours apart.

The indications for and choice of antihypertensive therapy in women with gestational hypertension are the same as for women with preeclampsia.

Management of hypertension in pregnant and postpartum women: Treatment of preexistent hypertension summary (UpToDate)
We suggest avoiding treatment of uncomplicated mild to moderate essential HTN (Grade 2B). There are no proven benefits to mother or fetus, other than reduction in risk of severe HTN. The concern with Rx is potential adverse effects on fetal growth.

In women with uncomplicated essential HTN already on antihypertensive therapy who have early pregnancy blood pressures less than 120/80 mmHg, we suggest tapering/discontinuing antihypertensive drugs and closely monitoring the blood pressure response (Grade 2C). Our indications for initiating or reinstituting antihypertensive therapy are persistent diastolic pressures of 95 to 99 mmHg, systolic pressures ≥150 mmHg, or signs of hypertensive end-organ damage. These thresholds, although not in the severe range, allow nonemergent intervention with oral drugs while HTN is only moderately elevated.

Subgroups of women with mild HTN appear to be at greater risk of maternal or fetal complications and may benefit from antihypertensive therapy.

Severe HTN is treated to protect the mother from serious complications (e.g., stroke, HF, renal failure).

We suggest therapy with either methyldopa or labetalol (Grade 2B). A long acting calcium channel blocker (eg, nifedipine) can be added if needed.

The blood pressure goal in women without end-organ damage is systolic pressure 140 to 150 mmHg and diastolic pressure 90 to 100 mmHg. In women with end-organ damage, the goal is <140/90 mmHg and as low as 120/80 mmHg. Nonsteroidal antiinflammatory medications may contribute to blood pressure elevation postpartum.

Management of hypertension in pregnant and postpartum women: Indications for treatment of preexistent hypertension TO AVOID MATERNAL CARDIO/CEREBROVASCULAR EVENTS (UpToDate)
Normotensive or mildly hypertensive
– Women with preexisting HTN who are normotensive or mildly hypertensive on medication may continue their therapy or have their antihypertensive agents tapered and/or stopped during pregnancy, with close monitoring of the maternal blood pressure response. Acceptable BP control (systolic less than 140 to 150 or diastolic less than 90 to 99 mmHg) in the second trimester in the absence of antihypertensive therapy may be present due to the normal decrease in blood pressure at this time. There is no consensus on the best approach.
– Our indications for initiating or reinstituting antihypertensive therapy are persistent diastolic pressures of 95 to 99 mmHg, systolic pressures ≥150 mmHg, or signs of hypertensive target-organ damage. These thresholds, although not in the severe range, allow nonemergent intervention with oral drugs while HTN is only moderately elevated.

Complicated and secondary HTN
Subgroups of women with mild HTN appear to be at greater risk of maternal or fetal complications and may benefit from antihypertensive therapy. Therapy has been suggested for women with:
– Secondary, rather than essential, HTN (eg, renal disease, collagen vascular disease, coarctation)
– Target-organ damage (eg, left ventricular hypertrophy, microalbuminuria, retinopathy)
– Dyslipidemia
– Maternal age over 40 years old
– History of stroke
– Previous perinatal loss
– Diabetes

Severe HTN
Severe hypertension (blood pressure ≥160/100 mmHg), particularly if associated with signs of early hypertensive encephalopathy, should be treated to protect the mother from serious complications, such as stroke, heart failure, or renal failure.

Management of hypertension in pregnant and postpartum women: Drug doses for oral treatment of HYPERTENSION in pregnancy graphic (UpToDate)
Same treatements for long-term treatment of preeclampsia OR preexistent hypertension:

Methyldopa: 250 mg 2-3 times daily, increase every 2 days as needed, maximum dose 3 g/day

Labetalol: 100 mg 2 times daily, increase by 100 mg twice daily every 2-3 days as needed, maximum dose 2400 mg/day

Nifedipine: 30 to 60 mg once daily as a sustained release tablet, increase at 7 to 14 day intervals, maximum dose 120 mg/day

Management of hypertension in pregnancy and postpartum women: Choice of drug and dose for ACUTE MANAGEMENT OF SEVERE HYPERTENSION in preeclampsia and gestational hypertension (UpToDate)
Labetalol
– We recommend IV labetalol. Randomized trials comparing labetalol to nicardipine or methyldopa have shown that labetalol is effective and generally safe in pregnancy, although data are limited.
– Dose: Begin with 20 mg IV over 2 minutes followed at 10-minute intervals by doses of 20 to 80 mg up to a maximum total cumulative dose of 300 mg. As an example, give 20 mg, then 40 mg, then 80 mg, then 80 mg, then 80 mg. A constant infusion of 1 to 2 mg/min can be used instead of intermittent therapy. The fall in blood pressure begins within 5 to 10 minutes and lasts from 3-6 hours.

or Hydralazine
– IV hydralazine has been used extensively in the setting of preeclampsia. Hydralazine has been widely used for many years in the setting of acute HTN in pregnancy and is an acceptable antihypertensive drug in this setting.
– Dose: begin with 5 mg IV over 1-2 minutes; if the blood pressure goal is not achieved within 20 minutes, give a 5 to 10 mg bolus depending upon the initial response. The maximum bolus dose is 20 mg. If a total dose of 30 mg does not achieve optimal BP control, another agent should be used. The fall in BP begins within 10 to 30 minutes and lasts from 2-4 hours.

Calcium channel blockers
– SR nifedipine (30 mg) and IR nicardipine are options. Nicardipine can be given IV. Experience with these drugs in pregnancy is more limited than for labetalol and hydralazine; however, published experience showed that target BP was reached within 23 minutes in 70 percent of pregnant patients with severe HTN and 91 percent reached target BP within 130 minutes, with no severe maternal or fetal side effects. IR nifedipine is NOT USED due to risk of serious cardiovascular morbidity.

Management of hypertension in pregnancy and postpartum women: Choice of drug and dose for Longer-term BP control during expectant management of severe preeclampsia (UpToDate)
Occasionally, preeclamptic women with severe hypertension are stabilized and not delivered immediately. Oral antihypertensive therapy is often indicated for these patients.

Options for oral antihypertensive therapy are the same as for women with preexisting hypertension:

Methyldopa: 250 mg 2-3 times daily, increase every 2 days as needed, maximum dose 3 g/day

Labetalol: 100 mg 2 times daily, increase by 100 mg twice daily every 2-3 days as needed, maximum dose 2400 mg/day

Nifedipine: 30 to 60 mg once daily as a sustained release tablet, increase at 7 to 14 day intervals, maximum dose 120 mg/day

Management of hypertension in pregnancy and postpartum women: Antihypertensives contraindicated in pregnancy (UpToDate)
Drugs contraindicated in pregnancy:

– Nitroprusside is contraindicated in the later stages of pregnancy due to possible fetal cyanide poisoning if used for more than four hours. However, nitroprusside (0.5 to 10 mcg/kg/min) can be considered an agent of last resort for urgent control of refractory severe hypertension.

– ACE-I/ARBs and direct renin inhibitors are contraindicated at all stages of pregnancy, as they are associated with significant fetal renal abnormalities when maternal exposure has been in the latter half of pregnancy, and with fetal cardiac abnormalities after first trimester exposure.

Management of hypertension in pregnancy and postpartum women: Antihypertensives while breastfeeding (UpToDate)
Breastfeeding mothers:
– Beta-adrenergic blockers and calcium channel blockers enter breast milk; however, most appear to be safe during lactation and are considered “compatible” with breastfeeding by the AAP.
– Diuretics may reduce milk volume, but their use is compatible with breastfeeding per AAP.

Within each class of antihypertensive agents, physicians should select the medication with the lowest transfer into human milk.

Beta-blockers and alpha/beta-blockers
– Propranolol, metoprolol, and labetalol have the lowest transfer into milk, with relative infant doses of less than 2 percent. None has been associated with adverse events in infants.
– In contrast, case reports have implicated both acebutolol and atenolol in beta-blockade in nursing infants. These drugs should be avoided in breastfeeding mothers, if possible; if used, the infant should be observed for signs of beta-blockade.
– There are no human data on bisoprolol, but transfer into milk in rats is low (<2 percent). There are no human data on carvedilol, but because of its low molecular weight, it is likely to be excreted into breast milk. Calcium channel blockers - Diltiazem, nifedipine, nicardipine, and verapamil are associated with a relative infant dose < 2%. The AAP lists all three as compatible with breastfeeding. ACE-Is — These drugs are transferred into milk at very low levels. Captopril and enalapril have been reviewed by the AAP and are compatible for use in lactation. However, newborns may be more susceptible to the hemodynamic effects of these drugs, such as hypotension, and sequelae such as oliguria and seizures. No info on ARBs.

Clinical features, diagnosis, and long-term prognosis of preeclampsia summary (UpToDate)
Risk factors include past history of preeclampsia, nulliparity, pregestational diabetes, chronic hypertension, obesity, family history of preeclampsia, and multiple gestation.

The gradual development of hypertension and proteinuria in pregnancy is usually due to preeclampsia, particularly in a primigravida. These findings typically become apparent in the latter part of the third trimester and progress until delivery, but some women develop symptoms in the latter half of the second trimester or intrapartum or the early postpartum period.

The diagnosis of preeclampsia is clinical, based on the new onset of hypertension and proteinuria after 20 weeks of gestation in a previously normotensive woman.

Preeclampsia is characterized as mild or severe. Criteria for severe disease are listed in the table. Severe hypertension, coagulopathy, thrombocytopenia, liver function abnormalities, and fetal growth restriction are features of severe disease. Symptoms can include headache, visual disturbance (blurring, flashing lights, defects), epigastric pain, nausea/vomiting, or decreased fetal movement.

Differential diagnosis includes preexisting hypertension, gestational hypertension, exacerbation of underlying renal disease, acute fatty liver of pregnancy, thrombotic thrombocytopenic purpura-hemolytic uremic syndrome, exacerbation of systemic lupus erythematosus, and gestational thrombocytopenia and autoimmune thrombocytopenia.

Prognostic issues include an increased risk of recurrence in subsequent pregnancies and possible LT risks of cardiovascular disease and type 2diabetes.

Clinical features, diagnosis, and long-term prognosis of preeclampsia: Factors associated with an increased risk of developing preeclampsia graphic (UpToDate)
– Nulliparity
– Preeclampsia in a previous pregnancy
– Age >40 years or <18 years - Family history of preeclampsia - Chronic hypertension - Chronic renal disease - Antiphospholipid antibody syndrome or inherited thrombophilia - Vascular or connective tissue disease - Diabetes mellitus (pregestational and gestational) - Multifetal gestation - High body mass index - Black race - Male partner whose mother or previous partner had preeclampsia - Hydrops fetalis - Unexplained fetal growth restriction - Woman herself was small for gestational age - Fetal growth restriction, abruptio placentae, or fetal demise in a previous pregnancy - Prolonged interpregnancy interval - Partner related factors (new partner, limted sperm exposure [eg, previous use of barrier contraception]) - Hydatidiform mole - Susceptibility genes
Clinical features, diagnosis, and long-term prognosis of preeclampsia: Clinical manifestations (UpToDate)
Placental pathogenic changes associated with preeclampsia first occur weeks to months before clinical manifestations develop.

The clinical features of preeclampsia described below may be explained as maternal responses to generalized endothelial dysfunction:
– Hypertension
– Proteinuria and other renal findings (i.e., hyperuricemia and hypocalciuria, oliguria, glomerular endotheliosis), oliguria, glomerular endotheliosis
– Edema (may be sudden with facial component)
– Lower intravascular volume (avoid diuretics in absence of pulmonary edema)
– Hematologic changes: PLT < 100,000 = severe preeclampsia, microangiopathic hemolysis - Liver: hepatic injury including serious complications of HELLP syndrome (Hemolysis, Elevated Liver function tests, Low Platelets). Hepatic changes = severe preeclampsia) - Epigastric pain - CNS manifestations include headache, blurred vision, scotomata, and, rarely, cortical blindness; their presence upstage the diagnosis from mild to severe preeclampsia. Seizures in a preeclamptic woman signify a change in diagnosis to eclampsia. - Heart: Preeclampsia does not directly affect the myocardium. However, decrements in left ventricular performance can occur and in most women reflect a physiologically appropriate response to increased afterload. Women with severe disease are at risk of coronary events. - Pulmonary edema: Pulmonary edema upstages the diagnosis from mild to severe preeclampsia. - Fetal consequences of chronic placental hypoperfusion are fetal growth restriction and oligohydramnios. Fetal growth restriction = severe preeclampsia. Abruptio placenta is infrequent. Indicated preterm delivery is a secondary result of fetal or maternal complications.

Management of preeclampsia summary (UpToDate)
INITIAL GOAL: ddx preeclampsia vs. other disorders.
SECONDARY GOAL: assess the severity of disease.
– Laboratory eval incl HGB/HCG and PLT, renal & hepatic fn, and fetal well-being and growth.
– Timing of delivery is based upon gestational age, maternal and fetal condition and severity. Term pregnancies are delivered upon dx; however, preterm delivery not always best interests for fetus; therefore, a more conservative approach is often considered in selected women with mild disease remote from term. Maternal end organ dysfn and nonreassuring tests of fetal well-being = delivery at any gestational age.
– General management of antepartum women with mild preeclampsia consists of freq labs (PLT, liver and renal function tests), assess maternal BP and sx, and freq eval of fetal growth and well-being.
– Antenatal glucocorticoids (betamethasone) may be given to women dx with preeclampsia 24 to 34 weeks.
– We suggest delivery rather than expectant management with preeclampsia ≥37 wks (Grade 2B).
– MgSO4 is more effective than phenytoin for prevention of eclamptic seizures. We recommend use of MgSO4 to prevent eclampsia in severe preeclampsia (Grade 1A). The benefit of MgSO4 prophylaxis is less clear in mild preeclampsia; however, we suggest use of MGSO4 to prevent eclampsia in women with mild preeclampsia (Grade 2B). We do not treat nonproteinuric women with mild gestational HTN with MgSO4.
We suggest a MgSO4 regimen consisting of a loading dose of 6 g IV over 15-20 minutes followed by 2g/hour as a continuous infusion (Grade 2C). The maintenance dose (but not the loading dose) should be adjusted in the setting of renal insufficiency.
Mild preeclampsia is associated with good maternal and fetal pregnancy outcomes. The major consequences of severe preeclampsia are increased rates of maternal liver and kidney dysfunction, induced labor, cesarean delivery, preterm birth, fetal growth restriction, and neonatal difficulty breathing.
Management of preeclampsia: Magnesium toxicity (UpToDate)
Rapid infusion of magnesium sulfate causes diaphoresis, flushing, and warmth, probably related to peripheral vasodilation and a drop in blood pressure. Nausea, vomiting, headache, muscle weakness, visual disturbances, and palpitations can also occur. Dyspnea or chest pain may be symptoms of pulmonary edema, a rare side effect of magnesium sulfate administration.

Magnesium toxicity is related to serum concentration: loss of deep tendon reflexes occurs at 9.6 to 12.0 mg/dL (4.0 to 5.0 mmol/L), respiratory paralysis at 12.0 to 18.0 mg/dL (5 to 7.5 mmol/L), and cardiac arrest at 24 to 30 mg/dL (10 to 12.5 mmol/L). Calcium gluconate (1 g intravenously over 5 to 10 minutes) should be administered only to counteract life-threatening symptoms of magnesium toxicity (such as cardiorespiratory compromise).

The risk of postpartum hemorrhage, possibly related to uterine atony from mg’s tocolytic effects, was slightly increased in one trial.

Mg freely crosses the placenta; as a result, the cord blood concentration approximates the maternal serum concentration. Maternal therapy causes a slight decrease in baseline fetal heart rate and fetal heart rate variability, which are not clinically significant. Antenatal fetal assessment test results (eg, biophysical profile score and nonstress test reactivity) are not significantly altered.

Mg therapy also results in a transient reduction of total and ionized serum Ca concentration due to rapid suppression of PTH release. Rarely, the hypocalcemia becomes symptomatic (myoclonus, delirium, ECG abnormalities). Cessation of Mg therapy will restore normal serum Ca levels. However, Ca administration may be required if symptoms are present (calcium gluconate 1 g IV over 5-10 minutes).

Management of preeclampsia: Diagnosis (UpToDate)
Diagnosis of preeclampsia:
Systolic blood pressure ≥140 mmHg
OR
Diastolic blood pressure ≥90 mmHg
AND
Proteinuria ≥0.3 grams in a 24-hour urine specimen

Preeclampsia is the leading diagnosis whenever hypertension and proteinuria are noted in a pregnant woman. Hypertension should be confirmed by at least two measurements a minimum of six hours apart; proteinuria noted on a dipstick should be confirmed by a quantitative method (eg, urine protein-to-creatinine ratio on a random sample or 24-hour total protein excretion).

The initial goal is to support the diagnosis by excluding other disorders characterized by hypertension and proteinuria.

The secondary goal is to assess the severity of disease, whether mild or severe (there are no criteria for moderate preeclampsia). Mild preeclampsia includes those women who satisfy the criteria for preeclampsia (table 1), but do not have any features of severe disease (table 2). One or more criteria for severe preeclampsia can be present in patients with only a mild elevation in blood pressure and lack of significant symptoms.

Management of preeclampsia: Tests (UpToDate)
Tests — Laboratory evaluation helps to determine disease severity by characterizing the extent of end organ involvement:
– HCT — Hemoconcentration supports the diagnosis but hemolysis, if present, can decrease HCT.
– PLT: Thrombocytopenia is a criterion of severe dz.
– Quantification of protein excretion: Excretion of >=300 mg in 24 hours is necessary for dx. This may be determined by using the protein-to-creatinine ratio on a random specimen or by 24 hour urine collection. It is suggested by at least 1+ protein on dipstick of two urine specimens collected at least four hours apart. A dipstick of 3+ or greater or 5 g or more per day is a criterion of severe disease.
– sCRT: elevated or rising level suggests severe dz.
– sALT and sAST: Elevated or rising levels suggest hepatic dysfunction indicative of severe disease.
-sLDH: Microangiopathic hemolysis is suggested by an elevated LDH level and red cell fragmentation (schistocytes or helmet cells) on peripheral blood smear. Elevation of TB may also suggest hemolysis. Microangiopathic hemolysis is present in severe disease or HELLP syndrome (Hemolysis, Elevated Liver function tests, Low Platelets). (See “HELLP syndrome”.)
– Serum uric acid concentration — Often elevated in preeclampsia, but not diagnostic.

Fetal well-being is evaluated by a nonstress test or biophysical profile. In addition, the fetus is examined by ultrasound to evaluate growth and amniotic fluid volume. Assessment of umbilical artery Doppler flow may also aid in evaluation of the fetal condition.

Coagulation function tests (eg, prothrombin time, activated partial thromboplastin time, fibrinogen concentration) are usually normal if there is no thrombocytopenia or liver dysfunction, and therefore do not need to be monitored routinely.

Management of preeclampsia: Laboratory follow-up (UpToDate)
The minimum laboratory evaluation should include platelet count, serum creatinine, and serum AST. These tests should be repeated once or twice weekly in women with mild preeclampsia to assess for disease progression, and more often if clinical signs and symptoms suggest worsening disease.

The value of other tests is less clearly defined. A rising hematocrit can be useful to look for hemoconcentration, which suggests contraction of intravascular volume and progression to more severe disease, while a falling hematocrit may be a sign of hemolysis. An elevated serum LDH concentration is also a sign of hemolysis, and a marker of severe disease or HELLP syndrome. Hemolysis can be confirmed by observation of schistocytes and helmet cells on a blood smear.

Quantification of protein excretion can be performed using a 24-hour collection or protein-to creatinine ratio on a random specimen to determine whether the threshold for severe preeclampsia (5 g/24 hours) has been reached. Since several clinical studies have shown that neither the rate of increase nor the amount of proteinuria affects maternal or perinatal outcome in the setting of preeclampsia, repeated 24-hour urinary protein estimations are not useful once the threshold of 300 mg/24 hours for the diagnosis of preeclampsia has been exceeded. Serum creatinine alone can be used to monitor renal function

Expectant management of severe preeclampsia: Definition summary (UpToDate)
The presence of one or more of the following criteria upstages preeclampsia from mild to severe

Symptoms of central nervous system dysfunction:
– Visual disturbance (photopsia, scotomata, cortical blindness, retinal vasospasm)
– Severe headache (ie, incapacitating, “the worst headache I’ve ever had”) or headache that persists and progresses despite analgesic therapy
– Altered mental status

Symptoms of liver capsule distention:
– Right upper quadrant or epigastric pain
– Nausea, vomiting

Hepatocellular injury:
– Serum transaminase concentration ≥ twice normal

Severe blood pressure elevation:
– Systolic blood pressure ≥160 mm Hg or diastolic blood pressure ≥110 mm Hg on two occasions at least six hours apart

Thrombocytopenia:
<100,000 platelets/microL Proteinuria: ≥5 grams in 24 hours Oliguria <500 mL in 24 hours Fetal growth restriction Pulmonary edema or cyanosis

Expectant management of severe preeclampsia: Gestational age based approach to management (UpToDate)
Based on the outcome data presented above, if a woman develops severe preeclampsia before 24 weeks of gestation, we often recommend termination of pregnancy to reduce the mother’s risk of developing life-threatening morbidity (eg, cerebrovascular hemorrhage) and to prevent the birth of an infant at the limit of viability, and thus at high risk of death or severe permanent disability. Factors critical in making this decision are the estimated fetal weight, presence or absence of growth restriction, and the neonatologist’s judgment of the neonatal prognosis. If the fetus is deemed nonviable, we recommend delivery.

At 24 to 25 weeks of gestation, the decision making process is exceptionally complex; the clinician and patient should carefully weigh the risks and benefits of expectant management, taking into account individual clinical factors such as the estimated fetal weight and whether a full course of corticosteroids can be/has been administered.

Between 25 and 34 weeks of gestation, we offer expectant management to appropriately selected women, as described below.

We suggest delivery for all women with severe preeclampsia who have reached a favorable gestational age (34 or more weeks of gestation), as prolonging the pregnancy at this gestational age subjects the mother and fetus to significant risks with relatively small potential benefits.

Expectant management of severe preeclampsia: Candidates for expectant management (UpToDate)
In this environment, we offer expectant inpt mgmt in consult with MFM for pts with severe preeclampsia presenting between 24 and 34 weeks of gestation if:

Transient laboratory abnormalities:
– Asymptomatic women with severe preeclampsia by laboratory criteria alone (ALT or AST 2xULN, PLT < 100,000 cells/microL) may be managed expectantly if the abnormalities resolve within 24 to 48 hours of hospitalization. In otherwise asymptomatic or mildly hypertensive women with stable labs, it is reasonable to delay delivery, administer antenatal glucocorticoids, and repeat labs (AST, ALT, platelet count) q6-12 hours to see if they improve. Severe preeclampsia based solely on proteinuria: - In the absence of other features of severe preeclampsia, proteinuria greater than 5 g/24 hours alone is not an indication for delivery. We do not obtain repeated 24-hour urinary protein estimations. Severe preeclampsia based solely on fetal growth restriction - We offer expectant management to women whose only criterion for severe preeclampsia is the presence of fetal growth restriction (FGR) if they meet the following criteria: if mild FGR (i.e., ≥5th and <10th percentile), gestational age < 32 weeks, reassuring fetal testing. - Admission-to-delivery interval in such pregnancies averages only three days, and >85 percent will require delivery within one week of presentation.

Severe preeclampsia based solely on blood pressure criteria — Two studies have established a precedent for expectant management of patients with severe preeclampsia by blood pressure criteria alone in pregnancies 28 to 34 weeks with reassuring fetal testing. Antihypertensive agents are given to control severe hypertension.

Expectant management of severe preeclampsia: Contraindications to expectant management (UpToDate)
In some clinical situations, where risks outweigh any potential benefits, we intervene regardless of gestational age and even if 2nd corticosteroid dose not given or max therapeutic effect not achieved.

Strong consideration to abandoning expectant management and proceeding with prompt delivery if:
– Maternal hemodynamic instability (shock)
– Nonreassuring fetal testing (nonreassuring NST or BPP score, estimated fetal weight less than the fifth percentile for gestational age, oligohydramnios with AFI <5.0 cm or maximal vertical pocket <2.0 cm, and/or persistent absent or reversed diastolic flow on umbilical artery Doppler velocimetry) - Persistent severe HTN unresponsive to medical Rx - Severe H/A (ie, incapacitating, "the worst H/A of my life") or persistent progressive headache (despite analgesia), visual aberrations, or epigastric/RUQ pain - Eclampsia (See "Eclampsia".) - Pulmonary edema - Renal failure with a marked rise in sCRT (eg, rise by ≥1 mg/dL over baseline) and/or urine output < 0.5 mL/kg/hour for 2 hours unresponsive to hydration with two IV boluses of 500 mL fluid - Abruptio placentae - Laboratory abnormalities, such as: Aminotransferases increasing over 6 to 12 hours and reaching levels twice the upper limit of normal; Progressive decrease in platelet count to less than 100,000 cells/microL; and, Coagulopathy in the absence of an alternative explanation - Preterm labor - Preterm premature rupture of membranes - Maternal request for immediate delivery - HELLP syndrome — Although some studies have reported that serious maternal complications in the setting of expectant management of HELLP syndrome (Hemolysis, Elevated Liver enzymes, Low Platelets) are uncommon with careful maternal monitoring, the benefit of expectant management in this setting has not been demonstrated.

Expectant management of severe preeclampsia: Initial management of severe preeclampsia (UpToDate)
Women with suspected preeclampsia should be admitted to the hospital to confirm the diagnosis, assess severity, monitor maternal and fetal status, and initiate supportive therapy or perform delivery.

Our initial management of these pregnancies involves:
– Admission to the Labor and Delivery Unit. The patient may need to be monitored in this intensive setting for as long as 48 hours. She can be transferred to less intensive care when her blood pressure is stable without labile elevations into the severe range, her laboratory tests are stable or improving, and fetal testing is reassuring.
– Administration of a course of antenatal corticosteroids — Reasonable efforts should be made to delay delivery for 48 hours to complete a full course of steroids. However, intervention will be necessary if there is deterioration in maternal or fetal status.
– Seizure prophylaxis with magnesium sulfate.
– Blood pressure monitoring at least every one to two hours. Severe hypertension should be treated to reduce the risk of maternal cardiovascular complications.
– Accurate recording of fluid intake and urine output.
– Laboratory studies — We obtain a complete blood count (including platelet count and smear), electrolytes, creatinine, alanine and aspartate aminotransferase (ALT, AST), and lactic acid dehydrogenase (LDH) [32]. Albumin can be useful to help guide nutritional replacement in cases of severe proteinuria. A coagulopathy profile (PT, PTT, fibrinogen) is sent if the ALT and AST are more than twice normal, if the platelet count is less than 100,000 cells/microL, or if placental abruption is suspected.
– Assessment of fetal well-being, including a nonstress test, amniotic fluid volume determination, and estimation of fetal growth. We obtain umbilical artery Doppler velocimetry if fetal growth restriction or oligohydramnios is present.

Expectant management of severe preeclampsia: Components of expectant management (UpToDate)
If there are no contraindications to expectant management, we suggest the following regimen to minimize the risk of maternal and fetal complications:
– Hospitalize until delivery. Findings from frequent maternal and fetal assessment are reviewed throughout the day and the ongoing risks of conservative management versus the benefit of further fetal maturation are reevaluated frequently.
– Monitor blood pressure every four hours. We do not awaken patients at night to check blood pressure if they are asymptomatic and blood pressure has been well-controlled during the day. Antihypertensive therapy is given to women with chronic hypertension and those being managed according to standard protocols for severe preeclampsia by blood pressure criteria only remote from term.
– Frequently assess maternal symptoms (eg, headache, vision changes, epigastric or abdominal pain, decreased fetal activity, vaginal bleeding)
– Accurately record fluid intake and urine output to identify oliguria.
– Obtain a complete blood count, serum creatinine, and liver function tests at least twice weekly. Delivery should be considered if laboratory abnormalities worsen after an initial improvement.
– Finish the course of antenatal corticosteroids.
– Regularly assess fetal well-being. There is no standardized protocol for fetal assessment in this setting. We obtain fetal kick counts and nonstress tests at least daily, ultrasound assessment of amniotic fluid volume once or twice per week, weekly Doppler velocimetry of the umbilical artery if growth is abnormal, and ultrasound estimation of fetal growth every 7 to 14 days.
– Continue magnesium sulfate seizure prophylaxis until completion of the course of antenatal corticosteroids. If the patient remains a candidate for expectant management at that time, the magnesium sulfate can be discontinued until her status changes and preterm delivery becomes indicated.
– Consultation with neonatology and anesthesiology.
Expectant management of severe preeclampsia: NOT components of expectant management (UpToDate)
Several management strategies with no proven benefit in the setting of severe preeclampsia are commonly recommended, but are best avoided because of potential morbidity, cost, and/or patient inconvenience.

These include:
– routine use of continuous fetal heart rate monitoring,
– routine initiation of antihypertensive therapy,
– antepartum administration of magnesium sulfate seizure prophylaxis for over 48 hours,
– serial 24-hour urine collections for protein quantitation, and
– routine assessment of fetal lung maturity. However, the latter may be useful in delivery decisions between 30 and 34 weeks when there is contradictory or equivocal evidence of maternal or fetal deterioration.

Expectant management of severe preeclampsia: Delivery (UpToDate)
Indications
– Maternal indications (see contraindications to expectant management).
– In our opinion, fetal indications include nonreassuring fetal heart rate or biophysical testing, estimated fetal weight less than the fifth percentile for gestational age, oligohydramnios (defined as AFI <5.0 cm or maximal vertical pocket <2.0 cm), and/or persistent absent or reversed diastolic flow on umbilical artery Doppler velocimetry. - Obstetrical indications include preterm labor, preterm premature rupture of membranes, abruptio placentae, and fetal demise. - In the absence of any of these maternal or fetal indications for earlier intervention, we deliver women hospitalized for expectant management of severe preeclampsia at 34 weeks of gestation. We do not assess fetal lung maturity prior to delivery. Route — Cesarean delivery is reserved for standard obstetrical indications. A decision to expedite delivery in the setting of severe preeclampsia does not mandate immediate cesarean birth. Cervical ripening agents may be used if the cervix is not favorable prior to induction; however, a prolonged induction is best avoided. At ≥32 weeks of gestation, the rate of vaginal delivery after labor induction exceeds 60 percent, but at ≤28 weeks, it falls to 0 to 32 percent because of the high frequency of nonreassuring fetal heart rate tracings and failure of the cervix to dilate. For this reason, some experts recommend scheduled cesarean delivery for women with severe preeclampsia who are under 28 to 30 weeks of gestation, especially if they have a low Bishop score. We generally agree, but take parity and prior labor course into consideration, as well. Anesthesia — We suggest neuraxial anesthesia for women with adequate platelet counts.
HELLP syndrome summary (UpToDate)
HELLP syndrome (hemolysis with a microangiopathic blood smear, elevated liver enzymes, and a low platelet count) develops in approximately 1 of 1000 pregnancies overall and 10 to 20 percent of pregnancies with severe preeclampsia/eclampsia. The majority of cases are diagnosed between 28 and 36 weeks of gestation.

The most common clinical presentation is abdominal pain and tenderness in the midepigastrium, right upper quadrant, or below the sternum. Many patients also have nausea, vomiting, and malaise, which may be mistaken for a nonspecific viral illness or viral hepatitis. Hypertension and proteinuria are present in approximately 85 percent of cases, but may be absent in women with otherwise severe HELLP syndrome.

The diagnosis is based upon the presence of all of the following 4 characteristic laboratory findings in patients of appropriate gestational age:
1. Microangiopathic hemolytic anemia with characteristic schistocytes on blood smear (picture 1). Other signs suggestive of hemolysis include an elevated indirect bilirubin and a low serum haptoglobin concentration (≤25 mg/dL).
2. Platelet count <100,000 cells/microL. 3. Serum lactate dehydrogenase >600 IU/L or total bilirubin >1.2 mg/dL.
4. Serum aspartate aminotransferase (AST) >70 IU/L.

The outcome for mothers with HELLP syndrome is generally good, but serious complications such as abruptio placentae, acute renal failure, subcapsular liver hematoma, and retinal detachment may occur. The risk of recurrence in future pregnancies appears to be increased.

HELLP syndrome: Management recommendations summary (UpToDate)
Severe maternal disease (eg, multiorgan dysfunction, disseminated intravascular coagulation, liver infarction or hemorrhage, renal failure, abruptio placenta) or nonreassuring fetal status is an indication for prompt delivery regardless of gestational age.

For pregnancies ≥34 weeks of gestation, we recommend delivery rather than expectant management (Grade 1C). In this population, the potential risks of preterm birth are outweighed by the risks associated with HELLP syndrome.

For pregnancies less than 34 weeks of gestation in which maternal and fetal status is reassuring, we suggest delivery after a course of glucocorticoids to accelerate fetal pulmonary maturity rather than expectant management or prompt delivery (Grade 2C). Although the laboratory abnormalities of HELLP syndrome will reverse in a subgroup of patients managed expectantly and serious maternal complications are uncommon with careful maternal monitoring, there is no high quality evidence showing that overall perinatal outcome is improved with expectant management.

For gestations less than 30 to 32 weeks with an unfavorable cervix, we suggest cesarean delivery to avoid a potentially long induction (Grade 2C).

We recommend not giving dexamethasone for treatment of HELLP syndrome (Grade 1B). Dexamethasone does not accelerate resolution of laboratory abnormalities or reduce the risk of maternal complications.

Eclampsia summary (UpToDate)
Eclampsia refers to the occurrence of one or more generalized convulsions and/or coma in the setting of preeclampsia and in the absence of other neurologic conditions.

An eclamptic seizure occurs in 0.5 percent of mildly preeclamptic women and 2 percent of severely preeclamptic women. The incidence of eclampsia is 4 to 5 cases per 10,000 live births in developed countries.

Just over one-third of cases occur at term, developing intrapartum or within 48 hours of delivery.

An eclamptic seizure is typically tonic-clonic and lasts 60 to 75 seconds. Symptoms that may occur before the seizure include persistent frontal or occipital headache, blurred vision, photophobia, right upper quadrant or epigastric pain, and altered mental status. In up to one-third of cases, there is no proteinuria or blood pressure is less than 140/90 mmHg prior to the seizure.

The goals of management are to stabilize the mother, prevent recurrent convulsions, treat severe hypertension to prevent cerebral hemorrhage, and initiate delivery of the fetus.

The risk of recurrent eclampsia in a future pregnancy is 2 percent.

Eclampsia: Recommendations summary (UpToDate)
For women with eclampsia, we recommend treatment with magnesium sulfate rather than other anticonvulsants (Grade 1A). Compared to phenytoin and diazepam, magnesium sulfate reduces the rate of recurrent seizures by one-half to two-thirds and reduces the rate of maternal death by one-third.

Given that intravascular administration has a faster therapeutic effect and is less painful than intramuscular administration, we suggest using an intravascular regimen (Grade 2C). We give a loading dose of magnesium sulfate 6 g intravenously over 15 minutes, followed by 2 to 3 g/hour administered as a continuous intravenous infusion. The loading dose may be given safely in the presence of renal insufficiency, but the maintenance dose should be omitted or reduced in this setting. The maintenance phase is given only if a patellar reflex is present (loss of deep tendon reflexes is the first manifestation of symptomatic hypermagnesemia), respirations are greater than 12 per minute, and urine output is over 100 mL in four hours.

In women with severe hypertension, we administer hydralazine or labetalol to achieve a systolic pressure of 140 to 155 mmHg and diastolic pressure of 90 to 105 mmHg.

Delivery is the only curative treatment, but this does not necessarily preclude induction of labor. Cesarean delivery is a reasonable option for women less than 32 weeks of gestation who have an unfavorable cervix. After a seizure, we suggest waiting 15 to 20 minutes and until the mother and fetus show signs of recovery (control of convulsions; mother oriented to name, time, and place; fetal heart rate reassuring) before proceeding to surgery, if possible.