Gestational Hypertension – Preeclampsia

Gestation hypertension – preeclampsia

1. What every clinician should know

The term gestational hypertension-preeclampsia is used to describe a wide spectrum of disorders that are characterized by hypertension in pregnancy (Figure 1). As a group, hypertensive disorders during pregnancy are clinically heterogeneous with an estimated incidence of 6-30%, depending on parity, number of fetuses, body mass index, and previous obstetric history. The clinical presentation varies from mild hypertension to severe hypertension with or without various organ dysfunctions that can include hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome.

Classical gestational hypertension (GH) is characterized by mild hypertension without the presence of maternal symptoms, normal laboratory findings, including absent proteinuria, and normal fetal growth. The major diagnostic criteria for mild GH include a systolic blood pressure (BP) of 140-159 mm Hg and/or a diastolic BP of 90-109 mm Hg at least 4 hours apart occurring after 20 weeks gestation. Hypertension can develop during the antepartum period, labor, or within 48 hours postpartum.

Classical preeclampsia (PRE) is characterized by hypertension, as defined above, plus the presence of proteinuria (≥ 300 mg/24 hour urine collection, or a protein to creatinine ratio > 0.3 on random urine sample, or ≥ 1+ on dipstick on at least two occasions at least 4 hours apart). Preeclampsia is considered to have severe features in the presence of one or more of the findings listed in Table 1.

Preeclampsia is also diagnosed in absence of proteinuria in association with any of the symptoms or laboratory findings listed in Table II.

Table 2n

HELLP syndrome (the three main features are hemolysis, elevated liver enzymes, and low platelet count) is characterized by either GH or PRE in association with all the laboratory findings listed in Table 3. The estimated incidence of HELLP syndrome is 1 in 1,000 deliveries, and in 5-20% of patients with preeclampsia.

2. Diagnosis and differential diagnosis

Classical GH

What you should be alert for in the history

Patients with GH have no prior history of chronic hypertension and typically have normal blood pressure recordings prior to 20 weeks gestation. They are usually in their first pregnancy, and have an increased body mass index (BMI). They should have no headaches, visual changes, or respiratory or gastrointestinal symptoms.Approximately 30-50% of patients with GH will progress to preeclampsia or severe gestational hypertension, and 12-15% will ultimately develop fetal growth restriction (FGR). The rate of the progression will depend on gestational age at diagnosis. Pregnancy outcome is usually good when the diagnosis is made at ≥ 37 weeks gestation.

Characteristic findings on physical examination

Blood pressure is usually between 140-150/90-100 mm Hg with no abdominal or epigastric tenderness and no evidence of petechial hemorrhage or ecchymosis on skin examination.

Expected results of diagnostic tests

Generally, serum creatinine will be < 0.9 mg/dl (normal 0.4 – 0.9 mg/dl), the platelet count will be above 150,000 (normal, 130 – 400,000/mm ³), and AST will be < 50 IU/L (normal 10-50 IU/L). Urine protein on dipstick on random urine testing is negative, and results of 24-hour urine protein collection are < 300 mg/total volume. Fetal testing by ultrasound will reveal an estimated fetal weight (EFW) above the 10 ^th percentile, an amniotic fluid index (AFI) of > 5 cm (normal, 5-20 cm), and a reactive non-stress test (NST) during fetal heart rate monitoring.

Diagnosis confirmation and differential diagnosis

The diagnosis is confirmed when there is persistent elevation of blood pressure (in the mild range), with absent proteinuria, normal blood tests, absent maternal symptoms, and normal fetal testing. This condition can overlap with undiagnosed chronic hypertension, particularly in women with no medical care prior to pregnancy and those who present for prenatal care after 20 weeks gestation.

Preeclampsia

What you should be alert for in the history?

Patients with PRE should have no history of chronic hypertension or renal disease prior to pregnancy and/or prior to 20 weeks gestation. The patient will have new onset hypertension and proteinuria after 20 weeks gestation with or without headaches, visual changes, epigastric pain, or shortness of breath. Patients with a diagnosis of GH, chronic hypertension, and previous preeclampsia are at increased risk to develop PRE. The diagnosis should be suspected in patients with symptoms and in patients with mucosal bleeding.

In some patients, other diagnoses such as renal disease, connective tissue disease (lupus), and vascular diabetes mellitus should be considered.

Characteristic findings on physical examination

Blood pressure elevations can be mild or severe (≥ 160 mm Hg systolic and/or ≥ 110 mm Hg diastolic). Heart rate could be normal or there may be tachycardia or bradycardia. Lung exam is usually normal, unless there is evidence of congestive heart failure. Skin exam can show dependent, facial, or periorbital edema. Mucosal bleeding is usually absent. An abdominal exam can detect the presence of uterine or liver tenderness. Neurologic examination is usually normal. Fundoscopic exam will often demonstrate vasospasm of the retinal vessels.

Expected results of diagnostic studies

Generally, the diagnosis of PRE is established on the basis of hypertension and proteinuria. Approximately 10% of patients with PRE will have elevated serum creatinine (> 0.9 mg/dl), 10% will have a platelet count < 100,000/mm ³, and 15% – 20% will have elevated AST (> 50 IU/L).Chest x-ray exams are only indicated in patients with cardio-respiratory symptoms. Neuro-imaging is rarely needed except in the presence of altered mental status, blindness, or neurologic deficit on physical examination. A cerebral CT or MRI may reveal the presence of cerebral edema, infarction, bleeding, or vasospastic processes.

Diagnosis confirmation and differential diagnosis

There is considerable overlap between the PRE and renal disease, diabetic nephropathy, exacerbation of lupus nephritis, peripartum cardiomyopathy, thyrotoxicosis, and stroke. Patients with renal disease typically will have this condition prior to pregnancy, and/or they usually have hypertension and proteinuria early in pregnancy. The same is true for patients with diabetic nephropathy, who typically have a history of diabetes for several years and are taking medications.

Exacerbation of lupus can happen before labor or during the postpartum period. Women with preeclampsia will have a negative antinuclear antibody screen, antimitochondrial antibodies, and negative serum serology. If the results of these tests are abnormal, it is advisable to consult with a maternal-fetal medicine physician, rheumatologist, or nephrologist.

In patients with thyrotoxicosis, the clinical findings will reveal palpitations, tachycardia, systolic hypertension with wide pulse pressure, markedly elevated free serum T4 levels, and undetectable levels of TSH. Congestive heart failure and FGR can be present in both severe PRE and thyrotoxicosis. In this case, a consultation with maternal-fetal medicine will help with disease diagnosis and management.

Patients with peripartum cardiomyopathy will have hypertension (30-50% of cases), edema, proteinuria, and congestive heart failure. Echocadiography will reveal abnormal ejection fraction (<45%), abnormal fractional shortening (< 20%), and abnormal left ventricular dimensions during diastole. A consultation with a cardiologist will be helpful in making the diagnosis.

Similar to PRE with severe features, a patient with stroke will have cerebral symptoms, blindness, epigastric pain, nausea and vomiting and elevated blood pressure. A consultation with a neurologist and neuro-imaging will aid in making the correct diagnosis.

Preeclampsia without proteinuria

What you should be alert for in the history

Patients with preeclampsia will present with signs, symptoms, and laboratory findings that are consistent with preeclampsia at non-classical time periods (either < 21 weeks’ gestation or > 48 hours postpartum). In addition, preeclampsia should be considered in those with only GH in association with maternal symptoms, abnormal laboratory tests (elevated liver enzymes and low platelets), or suspected fetal growth restriction (FGR).

In patients with preeclampsia, other diagnoses such as renal disease, lupus nephritis, thyrotoxicosis, thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), acute fatty liver of pregnancy (AFLP), and antiphospholipid antibody syndrome should be ruled out.

In patients with atypical preeclampsia presenting more than 48 hours postpartum, it is important to consider postdural puncture headache syndrome, reversible cerebral vasoconstriction syndrome, cerebral venous thrombosis, and other causes of stroke, and peripartum cardiomyopathy.

Characteristic findings on physical examination

Blood pressure is elevated in the majority of cases except in those of gestational proteinuria only. The heart rate can be normal, high, or low depending on the etiology. Skin examination is usually normal, but in some cases there could be edema, ecchymoses, dry skin, or even jaundice in the case of acute fatty liver of pregnancy (AFLP).

Cardiovascular examination is usually normal, or there can be evidence of congestive heart failure (thyrotoxicosis, peripartum cardiomyopathy, hypertensive encephalopathy, AFLP). Neurologic examination is usually normal except in the case of cerebral edema, infarction, or bleeding.

Expected results of diagnostic studies

Urine analysis can reveal absent, mild, or severe proteinuria with hematuria. The platelet count can be normal or reduced, serum creatinine is usually elevated, and elevated liver enzymes are common. Pulse oximetry and chest x-ray findings are usually normal except in the presence of cardio-respiratory findings.

In patients with cerebral symptoms (persistent headaches, visual symptoms, seizures, and neurologic deficits), MRI will reveal the presence of cerebral edema. However, magnetic resonance angiography (MRA) and magnetic resonance venography (MRV) will be normal.

Diagnosis confirmation and differential diagnosis

There is considerable overlap between preeclampsia and several life-threatening medical complications, as previously mentioned. Therefore, laboratory, cardiovascular, and cerebral evaluation should be performed in a step-wise fashion to rule out the presence of these disorders. The evaluation should be selective and will depend on the clinical signs, symptoms, and responses to the initial therapy, including treatment of BP, use of blood patch in case of dural puncture, use of magnesium sulfate, diuretic for congestive heart failure, etc. Consultation with maternal-fetal medicine, nephrology, or hematology will help establish the diagnosis in women with lupus, TTP, HUS, and HELLP syndrome.

HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count)

What you should be alert for in the history

Patients with HELLP syndrome will complain of nausea, vomiting, epigastric or right upper quadrant pain, or flu-like symptoms. They may also have a history of severe heartburn not responding to medications, retrosternal pain or a burning sensation, and excessive weight gain. Some patients may have a history of mucosal bleeding, such as bleeding from the gums or skin bruising ( Figure 2) or hematuria. The symptoms can develop before delivery or in the postpartum period. Approximately 20% of patients with severe preeclampsia will have HELLP syndrome.

Characteristic findings on physical examination

Blood pressure is usually elevated, but it can be normal in 20% of cases. Skin examination will reveal the presence of edema or mucosal hemorrhage. Abdominal examination will reveal the presence of liver tenderness. Pulmonary and neurologic examinations are usually normal.

Expected results of diagnostic tests

The diagnosis of HELLP syndrome is established on the basis of laboratory findings listed in Table 3. Urine protein will reveal proteinuria in 95% of cases, and there may be evidence of hematuria (Figure 3).

Diagnosis confirmation and differential diagnosis

There is an overlap between HELLP syndrome and several obstetric and surgical conditions (Table 4 ). The correct diagnosis will be established according to the presence of clinical signs and symptoms as well as the laboratory findings listed in Table V. It is important to make the correct diagnosis because management and therapies vary, including continuation of pregnancy versus delivery.

Table 5n

Gall bladder disease, pancreatitis, exacerbation of lupus, TTP, and systemic herpes (hepatitis) can develop at any time during pregnancy or postpartum, whereas HELLP syndrome is extremely rare prior to 24 weeks gestation. In addition, AFLP is unusual prior to 34 weeks gestation, whereas HUS usually develops in the postpartum period.

If gall bladder disease or pancreatitis is suspected, it is important to seek consultation with a gastroenterologist or general surgeon to confirm the diagnosis. The diagnosis of systemic herpes simplex should be made in consultation with a gastroenterologist or infectious disease specialist.

For patients with suspected exacerbation of lupus, TTP, HUS, or antiphospholipid syndrome, consultation with a nephrologist and/or a hematologist may assist in diagnosis and management.

The classical form of GH is characterized by the finding of hypertension during a prenatal visit or a visit to a triage area. There is considerable overlap between GH and other forms of hypertensive disorders in pregnancy. The incidence of GH ranges from 10-30%, with higher rates in women in their first pregnancy, women with increased BMI, and in women carrying twins.

3. Management

Antepartum

Mild GH or preeclampsia

Management of these patients must always focus on the safety of the mother and fetus, and then delivery of a mature newborn who will not require intensive or prolonged neonatal care. Once the diagnosis of mild hypertension-preeclampsia is made, subsequent management will depend on the results of maternal and fetal evaluation, gestational age, presence of labor or rupture of membranes, vaginal bleeding, and wishes of the mother.

At the time of diagnosis, all women should have a complete blood count, including platelets, serum creatinine, and liver enzymes, a 24-hour urine test for protein, and be questioned about symptoms of severe preeclampsia. Fetal evaluation should include ultrasound evaluation for estimated fetal weight and amniotic fluid index, a non-stress test (NST), and biophysical profile (BPP) if the NST is non-reactive.

Hospitalization and delivery is recommended in the case of gestational age ≥ 37 weeks and suspected abruptio placentae and gestational age ≥ 34 weeks in addition to progressive labor or rupture of membranes, estimated fetal weight < 10 ^th percentile, oligohydramnios (persistent amniotic fluid index (AFI) < 5.0 cm), and a biophysical profile ≤ 6 (normal 8-10).

Women who remain undelivered can be managed in a hospital or at home with restricted activity along with serial maternal and fetal evaluation (Figure 4). Complete bed rest is not recommended since there is no evidence that it improves outcome, and it may promote thromboembolism. Patients are instructed to have a regular diet with no salt restriction and to avoid driving. I do not recommend diuretics or other antihypertensive medications because such therapy does not improve outcome and has the potential to mask the diagnosis of severe disease.

Figure 4.n

At the time of diagnosis and each subsequent visit, women are educated and instructed about reporting symptoms of severe preeclampsia. They are also advised to immediately come to the hospital or office if they develop persistent symptoms, abdominal pain, contractions, vaginal spotting, or decreased fetal movements.

During ambulatory management, the onset of decreased fetal movement or abnormal fundal height growth (< 3 cm of what is expected for gestational age) require prompt fetal testing with NST and estimation of AFI. The development of new symptoms of severe preeclampsia or severe hypertension (diastolic BP ≥ 110 on repeat measurements) or evidence of FGR require immediate hospitalization. In addition, the development of abnormal liver enzyme levels, low platelet levels, and urine protein findings of a protein to creatinine ratio of > 0.7 or a dipstick of ≥ 3+ require hospitalization.

In women with mild GH, progression to severe gestational hypertension or preeclampsia could develop within 1 to 3 weeks after diagnosis, whereas in women with mild preeclampsia, the progression to a severe case could happen within hours or days. Therefore, close monitoring is important.

Preeclampsia with severe features

Patients with severe preeclampsia require prompt hospitalization in the labor and delivery area for initial evaluation and management, including the administration of intravenous magnesium sulfate (MgSO₄) for seizure prophylaxis and antihypertensive drugs to treat severe levels of BP (systolic BP ≥ 180 mm Hg and/or diastolic BP ≥ 110 mm Hg).

During the initial observation period, maternal and fetal conditions are assessed and a decision is made regarding the need for delivery, based on a gestational age ≥ 34 or < 23 weeks, abruptio placentae, pulmonary edema, eclampsia, renal failure, disseminated intravascular coagulopathy (DIC), or non-reassuring fetal testing.

Patients with gestational age at 33 ^0/7 to 36^6/7 weeks gestation are given corticosteroids and then delivered after 48 hours.

Patients with HELLP syndrome at < 34 weeks are given corticosteroids for fetal lung maturity, and then delivered after 48 hours provided there are stable maternal laboratory values. If platelet count < 50,000/mm ³ or there is substantial increase in liver enzymes with epigastric pain, then the patient is delivered prior to the completion of corticosteroids. These women should be continued on MgSO₄ with continuous monitoring in the labor and delivery area.

Patients at 23 ^0/7 to 32 ^6/7 weeks gestation with stable maternal and fetal conditions are given steroids and then receive individualized management, as described in Figure 5.

Figure 5.n

For patients with gestational age of 23-32 weeks who remain undelivered and who have stable maternal and fetal conditions, expectant management can only be performed in a tertiary care center. In these cases, IV magnesium sulfate is discontinued. Following the initial control of severe hypertension, BP should be measured at least every 6-8 hours.

Oral medications can be utilized as expectant management is continued to keep maternal BP in the desired target. My policy is to begin an initial regimen of labetalol at 200 mg orally every 12 hours, and increase the dose up to 800 mg orally every 8 12 hours as needed (maximum total 2400 mg/d). The target range should be systolic BP of 140 155 mm Hg and a diastolic BP of 90-105 mm Hg. If the maximum dose of labetalol is inadequate to achieve the desired BP goal, then short-acting oral nifedipine can be added at an initial dose of 10 mg orally every 6 hours and increased as needed up to 20 mg every 4 hours (maximum total 120 mg/d).

An alternative regimen is a long-acting preparation of nifedipine, 30-60 mg every 12 hours as needed (maximum 240 mg/d). If there is recurrent persistent severe hypertension despite maximum doses of labetalol and nifedipine, then the patient should be transferred to labor and delivery for maternal stabilization and delivery.

During expectant management, there should be frequent monitoring of maternal and fetal conditions as described below.

Maternal assessment

• Vital signs and intake-output (at least each shift)

• Daily Weight

• Symptoms of severe preeclampsia (headaches, visual changes, retrosternal pain or pressure, shortness of breath, nausea/vomiting, epigastric pain) at least each shift.

• Presence of contractions, rupture of membranes, abdominal pain or bleeding (at least each shift).

• Daily laboratory testing (complete blood count, platelets, liver enzymes, and serum creatinine). These tests can then be done every other day if levels remain stable.

Fetal assessment

• Daily kick count and non-stress test with uterine contractions monitoring.

• Biophysical profile completed twice weekly.

• Serial fetal growth every 2 weeks, with umbilical artery Doppler studies if there is suspected FGR.

Indication for delivery during expectant management

Maternal

• Recurrent severe hypertension.

• Recurrent symptoms of severe preeclampsia.

• Significant renal dysfunction (serum creatinine ≥ 1.5 mg/dl).

• Persistent thrombocytopenia or HELLP syndrome.

• Pulmonary edema or eclampsia.

• Suspected abruptio placentae.

• Progressive labor or rupture of membranes.

Fetal

• Gestational age of 34 weeks.

• Fetal death.

• Severe FGR (estimated fetal weight < 5 ^th percentile).

• Persistent oligohydramnios (maximum vertical pocket < 2 cm or AFL 5 cm).

• BPP of ≤ 4 on at least 2 occasions 6 hours apart.

• Reverse end diastolic flow on umbilical artery Doppler.

• Recurrent variable or late decelerations during NST.

Intrapartum

The goals of management in the intrapartum period are early detection of fetal heart abnormalities and progression to severe disease, and prevention of maternal complications.

All women should receive continuous monitoring of fetal heart rate and uterine activity with special attention to hyperstimulation, presence of non-reassuring tracing (absent variability, repetitive variable or late deceleration, or bradycardia), and development of vaginal bleeding. The presence of uterine irritability or tachysystole and/or recurrent decelerations or vaginal bleeding may be the first sign of abruptio placentae.

Some women will progress to severe disease as a result of changes in cardiac output or stress hormones. Therefore, BP recordings should be performed every hour, intake and output should be assessed at least every 4 hours, and patients questioned about new onset of symptoms suggestive of severe disease. Those who develop severe hypertension and/or symptoms should be treated as having severe preeclampsia.

I do not recommend parenteral MgSO ₄ for women with mild GH or mild preeclampsia because the benefit to risk ratio for preventing seizures does not favor its routine use. However, MgSO ₄ is recommended if the patient develops symptoms of severe hypertension. My regimen includes a 6-g loading dose given IV over 20-30 minutes, followed by a maintenance dose of 2 g/hr as continuous infusion, provided that urine output is at least 100 ml in a 4-hour period, patellar reflexes are present, and respiratory rate is > 12/minute. There is no need to measure serum magnesium levels unless there is inadequate urine output, absent reflexes, or abnormal respiratory rate. Serum magnesium levels are required when there is evidence of renal dysfunction (creatinine ≥ 1.2 mg/dl).

In women with severe hypertension plus headaches and/or tachycardia (maternal heart rate > 100 bpm), I recommend bolus doses of IV labetalol starting at 20 mg with repeat doses of 40 mg, and 80 mg, and 80 mg every 15 min to achieve the desired BP target of systolic BP between 140-155 mm Hg and/or diastolic BP between 90-105 mm Hg. On the other hand, labetalol should not be used in women with moderate to severe asthma, in those with bradycardia (heart rate < 60 bpm), or in those with congestive heart failure.

In women without headaches, a heart rate < 100 bpm, or asthma, I recommend IV bolus doses of hydralazine starting at 5 mg with a repeat of 10 mg every 20 minutes to achieve the target blood pressure goal or until a maximum of 25 mg is reached. Alternately, in these women it is appropriate to use short-acting oral nifedipine at an initial dose of 10-20 mg every 20 minutes for a maximum of 60 mg.

During the administration of either of the above medications, BP should be monitored every 10 minutes until the desired BP target is desired. If the desired target is not achieved with the maximum dose of either drug, I recommend using a continuous IV infusion of labetalol at a dose of 1-2 mg/minute.

Analgesia – anesthesia for labor and delivery

Maternal pain relief during labor and delivery can be provided by either systemic opioids or segmental epidural anesthesia in all women with GH and preeclampsia. Either epidural, spinal, or combined techniques of regional anesthesia are the method of choice during cesarean section, except for women with HELLP syndrome, thrombocytopenia, DIC, or those receiving low molecular weight heparin. For the latter group of patients, most anesthesiologists prefer general anesthesia.

General anesthesia increases the risk of aspiration and failed intubation due to airway edema and is associated with marked increases in systemic and cerebral vascular pressures during intubation and extubation. Women with airway or laryngeal edema may require awake intubation under fiber optic observation with the availability of immediate tracheostomy. Changes in systemic or cerebral pressures may be attenuated by pretreatment with either labetalol or nitroglycerin injections. It is important to emphasize that anesthetic management of women with severe preeclampsia and HELLP syndrome requires the availability of personnel with special expertise in obstetric anesthesia.

Mode of delivery

The optimal method of delivery should be based on fetal gestational age, fetal presentation or lie, fetal condition, presence of labor, and cervical Bishop score. A plan for vaginal delivery should be attempted for all women with mild disease, for the majority of women with severe disease, particularly those beyond 31 weeks gestation, and for all those with established labor.

With labor induction, the likelihood of cesarean delivery increases with decreasing gestational age in the presence of severe preeclampsia (range, 93% to 97% at < 28 weeks, 53% to 65% at 28-32 weeks, and 31% to 38% at 32-34 weeks gestation). I recommend elective cesarean delivery for all women with severe preeclampsia, plus fetal growth restriction or oligohydramnios, in the presence of unfavorable cervical Bishop score if the gestational age is < 32 weeks. I recommend it for all women with severe preeclampsia below 30 weeks gestation who are not in labor and whose Bishop score is below 5. I recommend elective cesarean delivery for all women with HELLP syndrome below 32 weeks gestation who are not in labor and whose Bishop score is below 5.

Cesarean section in women with coagulopathy

There are specific factors to consider in patients with either thrombocytopenia, HELLP syndrome, or DIC with abruptio placenta requiring cesarean section. In general, these women will require general anesthesia. These women should have adequate control of BP prior to intubation and extubation, and special attention to airway patency.

For patients with DIC, it is important to correct their coagulation abnormalities with blood and blood products as needed prior to surgery or during surgery. For patients with thrombocytopenia or HELLP syndrome, my policy is to administer 6 units of platelets prior to intubation in patients with platelet count < 40,000/mm ³.

Because of the risk of oozing from DIC or thrombocytopenia after surgery, my policy is to insert a Jackson-Pratt drain in either the peritoneal or subfascial area, and to leave the wound open, as seen in Figure 6. In women with HELLP syndrome and/or DIC, the nadir in platelet count will develop 24-48 hours postpartum. The drain is usually removed 48 hours after surgery, and the wound is closed with staples under local infiltration anesthesia.

Postpartum management

During the immediate postpartum period, women with gestational hypertension-preeclampsia should receive close monitoring of vital signs, symptoms consistent with severe disease, and measurements of fluid intake and urinary output.

In women with mild GH, the BP becomes normal usually during the first week postpartum. In women with mild preeclampsia, both hypertension and proteinuria will usually resolve within 2 weeks after delivery. In these women, there is a decrease in BP within the first 48 hours, but BP increases again between 3 and 6 days postpartum. My policy is not to give antihypertensive drugs unless the systolic BP is at least 150 mm Hg and/or the diastolic BP is at least 100 mm Hg. In addition, magnesium sulfate is not used in such women unless they develop new onset symptoms. Then, I will give IV magnesium sulfate for 24 hours.

In women with severe GH or severe preeclampsia, particularly those having symptoms, IV magnesium sulfate is continued for at least 24 hours after delivery. In these women, hypertension and/or proteinuria may take longer to resolve, up to 6-12 weeks postpartum.

Antihypertensive drugs are also used when the BP exceeds 150 mm Hg systolic and/or 100 mm Hg diastolic. My drug of choice to treat hypertension is oral short-acting nifedipine (10 mg every 6 hours) or long-acting nifedipine (30-60 mg twice daily). If the BP is well-controlled and there are no maternal symptoms, the woman is then discharged home with instructions for daily BP measurements by a home visiting nurse for the first week postpartum, or longer if needed. In addition, she should be educated about the signs and symptoms of severe hypertension or preeclampsia, with instructions regarding when to report BP and symptoms to medical providers. Antihypertensive drugs are then discontinued if the BP remains below target levels.

4. Complications

Pregnancies complicated by hypertensive disorders are associated with increased risk of maternal mortality (0.1%) and increased rate of life-threatening maternal morbidities. Almost all of these complications are seen in women with severe disease.

Eclampsia

The rate of eclampsia in women with severe disease in approximately 1%-2%. This risk can be reduced by timely delivery, attention to symptoms, and by the use of prophylactic doses of magnesium sulfate during labor and immediately postpartum. In women receiving magnesium sulfate, the rate of eclampsia is reduced by 50%.

Magnesium toxicity

Inappropriate use of MgSO ₄ and/or inadequate monitoring of women receiving MgSO4 can lead to the potential of cardiorespiratory arrest. These risks can be reduced or eliminated by the development of standardized protocols for administration and monitoring of patients receiving this therapy.

It is important not to give MgSO ₄ as bolus injections. The loading dose of 4-6 g should be given in a bag that is premixed with the proper dose as continuous infusion over 20-30 minutes. The maintenance dose of 2 g/hr should be given as a continuous infusion. Vital signs, urine output, and reflexes should be monitored hourly. Early signs of magnesium toxicity include absent patellar or ankle tendon reflexes, reduced respiratory rate (< 12/minute), reduced urine output (< 100 ml/hr), nausea, vomiting, feeling warm, flushing, difficulty breathing, muscle weakness, and double vision.

If magnesium toxicity is suspected, then MgSO ₄ infusion should be discontinued and a magnesium level obtained. If the patient is having respiratory difficulty, then I recommend giving 1 g of calcium chloride IV over 5 minutes. If the patient is not breathing, then she should be promptly intubated and ventilated. In most women magnesium toxicity will resolve as magnesium is excreted by the kidneys. If the patient has acute renal failure and oliguria, then magnesium can be removed from the blood by dialysis.

Pulmonary edema

Women with severe preeclampsia, particularly those with abnormal renal function, capillary leak (HELLP syndrome, massive edema, proteinuria, and excessive weight gain), and those with early onset preeclampsia receiving expectant management are at increased risk for pulmonary edema.

In addition, these women usually receive large amounts of IV fluids during labor, as a result of pre-hydration before the administration of regional analgesia-anesthesia and IV fluids given during the administration of oxytocin and MgSO ₄ during labor and postpartum. Also, during the postpartum period, there is mobilization of extracellular fluid and auto-transfusion from the placenta, leading to increased intravascular volume. Moreover, there is reduction in serum albumin, leading to reduced oncotic pressure. As a result, these women are at increased risk for pulmonary edema, particularly during the postpartum period.

These women should have their fluid levels, oral intake, blood products, urine output, respiratory symptoms, auscultation of lung fields, and pulse oximetry monitored. Early signs of heart failure include shortness of breath when lying flat, chest tightness, the need to sit up in bed or at the edge of the bed, tachycardia, tachypnea, and abnormal pulse oximetry (oxygen saturation ≤ 92%, normal 96%-100%). If pulmonary edema is suspected, the patient should be given oxygen by face mask, and a chest x-ray should be obtained.

Treatment of pulmonary edema includes administration of oxygen, reducing the amount of fluid infusion, and administration of an IV bolus of 20 mg of furosemide. Most patients will respond to this initial therapy. If there is no response, another 40 mg bolus of IV furosemide is given. If the patient continues to deteriorate and/or if pulse oximetry levels remain below 90%, then the patient should be intubated for assisted ventilation with 100% oxygen, given morphine sulfate, and managed in an intensive care unit.

Abruptio placentae with DIC

Women with severe preeclampsia are at risk for abruptio placentae (2%-3%) prior to delivery or during labor. Warning signs and symptoms for abruptio placentae include sudden onset of abdominal pain that is constant in nature (in women with posterior placentae the pain could be in the back), the presence of uterine irritability (high-frequency, low-amplitude contractions with no relaxation between contractions), vaginal bleeding (usually absent in case of occult retroplacental bleeding), and changes in fetal heart rate tracing (tachycardia, recurrent variable or late decelerations, and ultimately bradycardia).

The presence of suspected abruptio in association with changes in fetal heart rate requires immediate delivery by cesarean section, unless delivery is imminent (within 20 minutes). Patients with abruptio placentae, particularly those with fetal demise, occult retroplacental hemorrhage, or more than 50% involvement of the placenta, and those with profuse hemorrhage are at high-risk for DIC. Management of such patients includes prompt transfusion of at least 4 units of packed red blood cells, 4 units of fresh frozen plasma, and 6 units of platelets. In addition, they should receive frequent monitoring of coagulation factors, hematocrit, vital signs, and urine output. The need for subsequent transfusions will depend on the results of blood tests. In general, DIC from abruptio will resolve within 24 hours after delivery of the placenta.

My policy is to attempt vaginal delivery in women with abruptio placentae and fetal demise irrespective of the presence of coagulopathy. It is important to attempt artificial rupture of the membranes as soon as possible. Rupture of the membranes is confirmed when there is a gush of fluid (clear or bloody). The presence of bloody leakage is not evident of rupture of membranes. In general, most women will deliver within 2-4 hours after true rupture of the membranes. During this time period, it is important to continue to monitor vital signs, blood loss, and coagulation factors with aggressive resuscitation with fluids, blood, and blood products. Cesarean section may be needed if it is impossible to rupture the membranes and there is no change in cervical dilation or if maternal vital signs become unstable despite the resuscitative measures.

Liver hemorrhage and/or subcapsular liver hematoma

Patients with HELLP syndrome are at increased risk for development of subcapsular liver hematoma and rupture. Signs and symptoms include severe persistent and constant pain in the area of the liver, marked tenderness on palpation of the liver, nausea, vomiting, shoulder pain, and pain on inspiration. Laboratory findings will reveal severe thrombocytopenia (platelet count < 20,000), low hematocrit (< 30%), and hemoglobin (< 8 g/dl). Liver enzymes can be mildly or markedly elevated, and there may be evidence of DIC.

If suspected, the patient should receive detailed ultrasound of the liver and computerized scan of the liver, if needed. If the imaging reveals intact subcapsular hematoma and maternal vital signs are stable, management should include expectant monitoring of vital signs and transfusion of blood and blood products as necessary. In addition, the patient should receive serial ultrasound examination for evaluation of the size of the hematoma and the presence of intra-peritoneal blood. If there is no change in the size of the hematoma, no evidence of bleeding, and vital signs remain stable, then management will include close observation. The patient can be discharged and followed with serial ultrasound examination. Resolution of hematoma can take up to 1 year.

In patients with ruptured subcapsular hematoma and/or in those with severe intra-abdominal hemorrhage or unstable maternal hemodynamics, management requires immediate laparotomy in consultation with a trauma surgeon and massive transfusion of blood and blood products. Surgical management will depend on the degree of the involvement of the liver hemorrhage and ability to stop the bleeding. This may include drainage and packing of the area, application of a mesh around the liver, embolization, or partial hepatectomy. Postoperative management includes transfusion, correction of DIC, and supportive care of renal and pulmonary complications.

Hypertensive encephalopathy or hemorrhage

Patients with severe hypertension or severe preeclampsia are at increased risk for the development of cerebral edema (vasogenic and cytogenic) as well as cerebral hemorrhage. The risk is particularly increased in those with persistent severe levels of hypertension over several hours, those with a vascular capillary leak, and those with severe thrombocytopenia or DIC. Presenting symptoms include sudden onset of severe headache, visual changes or loss of vision, agitation, confusion, seizures, neurologic deficit, or coma. The diagnosis is usually made by neuro-imaging (CT or MRI). Management should be made in consultation with a neurologist or neurosurgeon, as necessary. It is important to emphasize that this risk can be minimized by prompt and adequate control of persistent elevations of blood pressure.

5. Prognosis and outcome

Perinatal outcome in GH and preeclampsia will depend on one or more of the following: gestational age at diagnosis as well as at time of delivery, presence of preexisting medical conditions, and severity of the disease. In women with mild GH and preeclampsia developing at ≥ 36 weeks gestation, the rates of FGR, abruptio placentae, and perinatal death are similar to those of normotensive pregnancies. In contrast, the rates of the above complications are substantially increased in those who develop severe disease at < 32 weeks, with the highest rates in those with onset prior to 28 weeks gestation.

Women with preeclampsia and severe features at < 28 weeks who undergo expectant management should receive extensive counseling regarding the risks of FGR, preterm birth, neonatal death, and long-term infant morbidity. Such counseling should be performed in consultation with a neonatologist.

There are minimal maternal risks when GH or preeclampsia is mild and diagnosed at ≥ 36 weeks gestation. In contrast, maternal risks are increased in patients with severe disease, particularly in those who develop at < 34 weeks gestation, who receive expectant management, with HELLP syndrome, or with preexisting medical conditions.

Women with preeclampsia and gestational hypertension are at an increased risk for recurrence in subsequent pregnancies. The likelihood for recurrence increases with decreasing gestational age in the previous pregnancy (range, 40%-60% at < 28 weeks gestation, 25%-35% at 29-36 weeks gestation, and 10%-15% at > 36 weeks gestation).

Women with preeclampsia are at increased risk for several cardiovascular and metabolic complications later in life. Therefore, they should be aware that they are at increased risk for chronic hypertension, type 2 diabetes mellitus, coronary artery disease, metabolic syndrome, end-stage renal disease, and stroke. The magnitude of this risk will depend on gestational age at onset, if there was recurrent preeclampsia, preexisting medical conditions, and whether serious complications occurred in the index pregnancy.

6. What is the evidence for specific management and treatment recommendations

Sibai, BM, Stella, CL. “Diagnosis and management of atypical preeclampsia-eclampsia”. Am J Obstet Gynecol. vol. 200. 2009. pp. 481.e1-7. (The authors review the diagnostic criteria for gestational hypertension, preeclampsia, and atypical preeclampsia. They describe the presenting signs, symptoms, and laboratory findings in women with atypical preeclampsia. They also include the differential diagnosis, and a step-wise approach for the evaluation and management of women with possible atypical preeclampsia.)

“Publications Committee, Society for Maternal-Fetal Medicine, with the assistance of Baha M. Sibai Evaluation and management of severe preeclampsia before 34 weeks’ gestation”. Am J Obstet Gynecol. vol. 205. 2011. pp. 191-8. (The authors, all authorities in the field of preeclampsia, conducted an extensive review of all published articles in the English language from 1980 through December 2010, to evaluate the risks and benefits of expectant management of severe preeclampsia remote from term. This comprehensive review provides recommendations for expectant management, including patient selection, maternal and fetal evaluation, treatment, and indications for delivery, patient counseling, and expected complications.)

Sibai, BM. “Diagnosis, controversies, and management of the syndrome of hemolysis, elevated liver enzymes, and low platelet count”. Obstet Gynecol. vol. 103. 2004. pp. 981-91. (This review by an authority on the subject describes the diagnostic criteria, evaluation, and management of patients with HELLP syndrome. In addition, the author provides data on imitators of HELLP syndrome as well as guidelines regarding counseling for subsequent pregnancies.)

“Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy”. Am J Obstet Gynecol. vol. 183. 2000. pp. S1-S22. (The authors, all experts in the field of hypertension in pregnancy, met to refine the classification and diagnostic criteria for various hypertensive disorders in pregnancy. The article reviews pathophysiology, prevention, and management, as well as long-term prognosis.)

Sibai, BM. “Etiology and management of postpartum hypertension-preeclampsia”. Am J Obstet Gynecol. vol. 206. 2012. pp. 470-5. (This review describes a stepwise approach toward the diagnosis and management of women with persistent and/or new onset hypertension or preeclampsia in the postpartum period. It also provides data on etiology and differential diagnosis with emphasis on signs, symptoms, and laboratory findings.)

Williams, D. “Long-term complications of preeclampsia”. Semin Nephrol. vol. 31. 2011. pp. 111-22. (This report by an authority in the field describes how certain pre-pregnancy risk factors predispose women to develop preeclampsia, and how the development of preeclampsia identifies some women as being at high-risk for cardiovascular and cerebrovascular complications later in life.)

Steegers, EA, Von Dadelszen, P, Duvekot, JJ, Pijnenborg, R. “Pre-eclampsia”. Lancet. vol. 376. 2010. pp. 631-44. (This is a good review of the incidence, pathogenesis, definitions, management, and prevention of preeclampsia. It also provides information on prediction and clinical presentation of women with preeclampsia.)

Duley, L, Henderson-Smart, DJ, Meher, S. “Drugs for treatment of very high blood pressure during pregnancy”. Cochrane Database Syst Rev. vol. 3. 2006. pp. CD001449(The authors of this meta-analysis evaluated the efficacy and safety of various antihypertensive drugs to treat acute, severe hypertension during pregnancy and postpartum. They concluded that the choice of antihypertensive drug (labetalol, hydralazine, or nifedipine) should depend on the clinician’s experience and familiarity with a particular drug because there is insufficient data proving superiority of one drug.)

“American College of Obstetricians and Gynecologists; Task Force on Hypertension in Pregnancy. Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy”. Obstet Gynecol. vol. 122. 2013 Nov. pp. 1122-3.

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