Hypertension in Pregnancy Management

MONITOR CONDITION OF MOTHER AND FETUS

Chronic Hypertension or Gestational Hypertension

Poorly controlled hypertension warrants weekly clinic appointments; if well controlled, it may be every 2-4 weeks.

Maternal Monitoring

In each physician visit, patients should be observed closely for early signs of preeclampsia. Antihypertensive treatment should be started if severe hypertension develops before term. Regularly monitor the patient’s BP and for the presence of side effects from treatment or complications. Women with high-risk chronic hypertension are more likely to have adverse maternal and perinatal complications. Maternal risks include disseminated vascular coagulation, placental abruption, stroke, and multiple organ failure involving the kidney and the liver. Perinatal loss and neonatal complications may occur in women with renal insufficiency (serum creatinine >1.4 mg/dL), DM with vascular involvement, severe collagen vascular disease, cardiomyopathy, or coarctation of the aorta. Other potential maternal outcomes are congestive heart failure, myocardial infarction, spontaneous coronary artery dissection, acute renal failure requiring dialysis, or death.

Fetal Monitoring

Ultrasound for assessment of fetal growth and amniotic fluid volume, and umbilical artery Doppler velocimetry may be done in women with chronic hypertension at 28, 32, and 36 weeks and with gestational hypertension at diagnosis and repeated every 2-4 weeks if normal. Cardiotocography may be done only if clinically indicated.

Preeclampsia or Eclampsia

In preeclampsia, the development of severe features or HELLP syndrome is linked to higher maternal and fetal/neonatal morbidity and mortality.

Maternal Monitoring

The purpose of maternal monitoring is to observe the progression of the condition both to prevent maternal complications during delivery and to assess fetal well-being. Monitor the BP twice weekly. Order lab tests as in the diagnosis of preeclampsia done weekly: CBC, platelet count, liver enzymes, lactate dehydrogenase (LDH), uric acid, and creatinine. Assess for proteinuria weekly. Invasive hemodynamic monitoring may be required. Monitor fluid volume expansion, especially in cases of pulmonary edema, persistent oliguria unresponsive to fluid challenge, intractable severe hypertension, and in delivery with epidural anesthesia. Pregnancy-related hypertensive disorders, particularly preeclampsia, have a higher incidence of cardiovascular (CV) diseases, including coronary artery disease, stroke, and heart failure. Maternal mortality due to preeclampsia is caused by intracranial hemorrhage, acute pulmonary edema, acute renal failure, respiratory distress syndrome, and cardiomyopathy.

Fetal Monitoring







With preeclampsia, risks of fetal prematurity or preterm birth, intrauterine growth retardation, and intrauterine death are high. Intrauterine fetal death related to preeclampsia is caused by acute and chronic hypoxia, fetal growth restriction, placental abruption, and placental insufficiency. Do a non-stress test (NST) twice weekly. Determine amniotic fluid index (AFI) once or twice weekly. Biophysical profile (BPP) weekly may replace one of the twice-weekly NSTs and AFIs. An ultrasound examination of the fetus to assess fetal growth and an umbilical artery Doppler velocimetry should be done every 2-4 weeks. Cardiotocography may be done at diagnosis of preeclampsia or severe gestational hypertension but may be repeated only if clinically indicated. 

TIMELY DELIVERY

Delivery







Close maternal and fetal surveillance is required, as prompt delivery is indicated by preeclampsia with severe features unresponsive to treatment, worsening maternal-fetal condition, lab tests showing end-organ dysfunction or fetal distress, or severe comorbidities. Expedited delivery is recommended in preeclampsia with adverse features (eg hemostatic disorders). The decision to deliver in women with preeclampsia should not depend on the degree of proteinuria or change in the amount of proteinuria.

The timing of delivery should be individualized based on maternal and fetal condition and decided together by the physician and patient after informed discussion. Delivery within 24 hours is indicated in patients with uncontrolled severe hypertension showing signs of maternal and fetal deterioration, regardless of gestational age or fetal lung maturity. For women with preeclampsia before 34 weeks AOG at risk for delivery within 7 days, IV Magnesium sulfate and a course of corticosteroids should be administered to accelerate fetal lung maturity. Induction of labor at ≥37 weeks is recommended over expectant management in women with mild gestational hypertension or preeclampsia without severe features to reduce maternal complications without increasing cesarean or adverse neonatal outcomes. Routine planned early delivery at 34-37 weeks is not advised in women with non-severe hypertension (BP of <160/110 mmHg); expectant management with close monitoring is considered until clinical situation deteriorates or other medical indications warrant early delivery. Offer initiation of delivery at 38-39 weeks but advise it from 40 weeks in women with chronic hypertension or gestational hypertension. In women with well-controlled hypertension, delivery should be planned at around 39 weeks of gestation.

The mode of delivery should be guided by gestational age, comprehensive fetal assessment, and maternal preference. In any type of hypertensive disorder of pregnancy, vaginal delivery should be considered unless cesarean delivery is required for the usual obstetric indications. Severe hypertension is not, in itself, an indication for cesarean delivery. For patients with HELLP syndrome, cesarean delivery may increase the risk of bleeding due to thrombocytopenia and difficulty in BP control due to diminished intravascular volume. Continuous fetal monitoring is required if labor induction is to be considered. In severe preeclampsia, neuraxial anesthesia reduces the hypertensive response to pain; epidural analgesia ensures adequate anesthesia if cesarean delivery becomes necessary.

Indications for Delivery

Maternal factors for delivery are AOG ≥37 weeks, platelet of <100,000 cells/mm³ or disseminated intravascular coagulation, transfusion of any blood product, uncontrolled hypertension, eclampsia, pulmonary edema, progressive deterioration of liver or renal function, suspected abruptio placentae, persistent severe headache or other cerebral or visual disturbances, and persistent epigastric pain, or nausea and vomiting.

Fetal factors for delivery are severe growth restriction, non-reassuring fetal testing results, oligohydramnios, and fetal death. 

The goals of treatment are to prevent severe hypertension and preeclampsia (suggested BP goal <140/90¹) and to optimize maternal and fetal/neonatal clinical outcomes, ie possibly prolong gestation, giving the fetus more time to mature prior to being delivered. The 2021 International Society for the Study of Hypertension in Pregnancy recommends a target DBP of 85 mmHg regardless of SBP.

Drug treatment is indicated when BP is persistently ≥140/90 mmHg regardless of the hypertensive disorder of pregnancy. Urgent treatment is required in a monitored setting for patients with severe hypertension (≥160/110 mmHg). Acute onset of severe hypertension persisting for >15 minutes is considered a hypertensive emergency in pregnancy. The objective of treatment is to lower SBP to <160 mmHg and DBP to <110 mmHg within 30-60 minutes.

The choice of antihypertensive drug and route of administration should be guided by the initial diagnosis, anticipated time of delivery, presence or absence of preeclampsia, and the attending physician’s preference and experience. The choice of antihypertensive agents should depend on the patient’s current antihypertensive treatment, contraindications, risks, side effect profiles, cost, availability, and patient preferences. For non-urgent control of hypertension, if the target BP level is not achieved with mid-range dose monotherapy after starting with a low dose, consider the addition of another low-dose antihypertensive drug instead of increasing the dose of the same drug (maximum of three drugs). If the patient’s SBP is ≥160 mmHg, consider increasing the dose of the current antihypertensive drug or initiating a new medication.

Consider IV antihypertensive therapy if the BP is not controlled with combination oral antihypertensive regimens. IV Urapidil may be used for acute BP reduction in severe hypertension; availability may be limited in some countries. Switch to oral antihypertensive therapy once severe hypertension is resolved.

¹Recommendations for BP target goals may vary between countries. Please refer to available guidelines from local health authorities.

Centrally Acting Agents

Centrally acting agents act centrally to reduce sympathetic tone, causing a decrease in BP. These lower BP effectively.

Methyldopa







Methyldopa is considered in the initial management of severe hypertension in pregnancy. This is safe to use in pregnancy, without reports of maternal or fetal adverse effects. Long-term pediatric follow-up has confirmed the safety record. Reports show that Methyldopa continues stable uteroplacental blood flow and hemodynamics. A combination of Methyldopa and Nifedipine may be given if the BP is not controlled with a single regimen of antihypertensive agent.

Beta-Blockers 







Beta-blockers are used as initial therapy for hypertension in pregnancy, as they are non-teratogenic. Comparative trials of beta-blockers and Methyldopa have shown that beta-blockers may be more effective in BP reduction than Methyldopa, but no significant difference in maternal or perinatal outcomes has been demonstrated. These may induce fetal bradycardia, intrauterine growth retardation, and neonatal hypoglycemia.

Labetalol

Oral Labetalol is the preferred beta-blocking agent. IV Labetalol is considered the first-line agent in the treatment of severe hypertension in pregnancy, including acute hypertension in preeclampsia or eclampsia, and is advised when severe hypertension persists or recurs despite oral therapy; it rapidly controls severe resistant hypertension. Non-cardioselective beta-blocker with selective alpha₁ blocking properties that decrease peripheral vascular resistance, causing vasodilatation and decreasing BP more rapidly than other beta-blockers. Cumulative dose should be <800 mg/day to avoid fetal bradycardia.

Acebutolol, Bisoprolol, Metoprolol, Pindolol and Propranolol

Acebutolol, Bisoprolol, Metoprolol, Pindolol and Propranolol have not been associated with any adverse effects when administered in late pregnancy. There are competitive antagonists of the effects of catecholamines at beta-adrenergic receptor sites. Beta₁ receptors are found mainly in the heart, while beta₂ receptors are usually found in non-cardiac tissues, including bronchial, peripheral blood vessels, uterus, and pancreas. Blockade of beta₁ receptors reduces heart rate (HR), myocardial contractility, and the rate of conduction of impulses through the conducting system, along with adrenergic-induced renin release and lipolysis. Beta₂ blockade can increase bronchial resistance and inhibition of catecholamine-induced glucose metabolism. These agents lower BP effectively. Beta-blockers have different affinities for beta₁ or beta₂ blockade, but as doses are increased, activity of beta₂ receptors can become apparent in beta₁ selective inhibitors. Atenolol, when given in pregnancy, has been linked to fetal growth restriction or low weight for gestational age and should be avoided.

Calcium Antagonists

Experience with oral calcium antagonists in pregnancy is limited, with most uses reported in late pregnancy. No increase in major teratogenicity with exposure to calcium antagonists has been shown. Calcium antagonists inhibit the cellular influx of calcium, which is responsible for the maintenance of the plateau phase of the action potential. The cells they affect are typically the vascular smooth muscle, myocardial cells, and cells within the sinoatrial (SA) and atrioventricular (AV) nodes. They dilate coronary and peripheral arteries with little or no effect on venous tone, have a negative inotropic action, reduce heart rate, and slow AV conduction. Calcium antagonists lower the BP effectively. These may cause myocardial depression when combined with Magnesium.

Nifedipine







Nifedipine is used as a second-line antihypertensive in pregnancy. Immediate-release oral Nifedipine may also be considered as a first-line agent when IV access is unavailable. Immediate-release formulation should be reserved for control of severe, acutely elevated BP in hospitalized patients; avoid in tachycardia. A stat dose of oral Nifedipine 10 mg may be used for rapid BP control in acute hypertensive crisis. The preparations of Nifedipine appropriate for use in pregnancy are capsule and prolonged action (PA) tablet. A study has shown the safety and efficacy of long-acting Nifedipine taken orally in pregnant women with severe hypertension in pregnancy. A distinction should be made between short-acting Nifedipine for treatment of severe hypertension and both intermediate-acting prolonged action and slow-release Nifedipine for non-severe hypertension. Avoid sublingual formulation.

Nicardipine

Nicardipine is considered as a second-line alternative when IV bolus Labetalol, Hydralazine or oral Nifedipine did not relieve acute severe hypertension in pregnant women.

Diuretics¹

The use of diuretics in pregnancy is controversial due to the theoretical risk of decreasing intravascular volume and uteroplacental perfusion, causing or exacerbating preeclampsia. However, they appear to be safe and efficacious in practice and may be administered if required, particularly in the treatment of acute pulmonary edema. Some authorities recommend the use of diuretics only in combination with other agents, especially when vasodilators exacerbate fluid retention. Diuretics lower the BP effectively and potentiate the response to other antihypertensive agents. Discuss alternative antihypertensive treatments with the patient if pregnancy is planned.

¹Please refer to Hypertension disease management chart for dosage guidelines of diuretics.

Angiotensin-Converting Enzyme (ACE) Inhibitors/Angiotensin II Antagonists/Direct Renin Inhibitors 







These agents are contraindicated in pregnancy. These may cause fetal growth restriction, oligohydramnios, neonatal renal failure, and neonatal death. Stop ACE inhibitors or angiotensin II antagonists prior to attempts at conception or when pregnancy is confirmed. Replace with Methyldopa or beta-blockers that are considered safe during pregnancy.

Vasodilators 







Hydralazine

Hydralazine IV can be used to control severe preeclampsia when other antihypertensive treatment regimens have failed. This is a second-line option, used only if other drugs are unavailable. This acts directly on the arterioles, causing vasodilatation, causing a decrease in peripheral resistance and BP. Oral Hydralazine, when used for chronic hypertension, has been found to be inferior to other agents. IV Hydralazine is effective in the treatment of high BP associated with preeclampsia; however, it has been associated with more perinatal side effects such as maternal hypotension, placental abruption, oliguria, neonatal thrombocytopenia, and lower APGAR scores.

Nitroglycerin (Glyceryl trinitrate)

Nitroglycerin given as an IV infusion in preeclampsia or eclampsia associated with pulmonary edema. This reduces cardiac oxygen demand by decreasing preload and may modestly reduce afterload, dilate coronary arteries, and improve collateral flow to ischemic regions.

Sodium Nitroprusside

Sodium nitroprusside is the last-line agent for acute hypertension in preeclampsia and should only be used when other agents fail to reduce the BP. This acts directly on arterioles and veins, causing peripheral vasodilatation that results in a decrease in peripheral resistance and BP. This is a short-acting hypotensive agent and lowers BP effectively for 1-10 minutes. This reduces BP rapidly, causing excessive hypotension. Sodium nitroprusside converts rapidly into cyanide and thiocyanate, causing cyanide accumulation and thiocyanate toxicity, thereby increasing the risk of fetal cyanide poisoning, and thus should only be used for extreme emergencies and for the shortest possible time.

Anticonvulsant

Magnesium sulfate

Magnesium sulfate decreases acetylcholine in motor nerves and acts on myocardium by slowing the rate of SA node impulse formation and prolonging conduction time. This is used for seizure prevention in gestational hypertension with severe features and preeclampsia with severe features or for treatment of eclampsia. This is also used to prevent recurrent convulsions in eclampsia. Magnesium sulfate reduces the frequency of eclampsia in pregnancy-induced hypertension or severe preeclampsia and decreases the incidence of placental abruption. This may be administered via IV route with a syringe pump or slow infusion to stabilize blood magnesium levels, or via intramuscular route. Monitor magnesium serum level in patients needing longer duration and higher doses of Magnesium sulfate. Incidence of magnesium intoxication is low in patients with preeclampsia with severe features treated with Magnesium sulfate. If magnesium toxicity is suspected, discontinue the Magnesium sulfate infusion and administer 30 mL of IV Calcium gluconate. This may cause hypotension when given concomitantly with Nifedipine.

Aspirin

Meta-analyses showed that Aspirin significantly reduces the risk of preeclampsia and adverse perinatal outcomes. This may be given at a low dose at bedtime from 12 weeks of gestation until delivery (preferably before 16 weeks until 36-37 weeks) in women with one high or ≥2 moderate risk factors for preeclampsia.

PRETERM PREECLAMPSIA

Low-risk women (<1 in 100) may continue with routine prenatal care. High-risk women (≥1 in 100) should be given Aspirin 150 mg nightly from 11-14 weeks of gestation to 36 weeks of gestation, when delivery occurs or when preeclampsia is diagnosed. Oral calcium supplementation of 0.5-2.5 g/day in early pregnancy decreases the incidence of early- and late-onset preeclampsia and hypertension among all women and also reduces severe preeclamptic complications in pregnant women with low daily calcium intake (<600 mg/day). Evidence is insufficient to recommend Vitamins C, E, and D, Omega-3 fatty acids, Magnesium, Folic acid, Heparin, Metformin and statins for reducing the risk of preeclampsia. 

Lifestyle Modification

Pregnant women without contraindications should exercise (low to moderate intensity) to prevent preeclampsia. For patients with well-controlled chronic hypertension who are used to exercising, moderate exercise during pregnancy is recommended. Avoid smoking, as it increases the risk of placental abruption in addition to fetal growth restriction. Avoid alcohol because excessive consumption may cause or exacerbate maternal hypertension and lead to congenital anomalies. Weight reduction is not recommended for the management of chronic hypertension in pregnancy. It is advised that women with BMI ≥30 kg/m² should not gain weight of >6.8 kg from preconception. BMI should be kept within the normal range prior to the next pregnancy in women with previous preeclampsia. For a healthy diet, salt restriction is not recommended for the prevention of hypertensive disorders in pregnancy; however, women with pre-existing hypertension may reasonably continue a low-sodium diet. Calcium supplementation is recommended to prevent preeclampsia in women with low dietary calcium intake (<600 mg/day).

Consider Non-Drug Therapy

Women with Low-Risk Hypertension

Consider non-drug therapy in women with low-risk hypertension. One may taper and stop any existing antihypertensive therapy. Prior to conception, stop ACE inhibitors or angiotensin II antagonists.

Patient Education 







Patient should be advised on the following effects of hypertension in pregnancy and vice versa to plan potential lifestyle and treatment changes before and during pregnancy: Women with pre-existing hypertension and TOD should be made aware that pregnancy may exacerbate the condition; chronic hypertension with early proteinuria may increase risk of adverse neonatal outcomes, whether or not preeclampsia occurs; there is an increased risk of fetal loss and deterioration of maternal renal disease if serum creatinine >1.4 mg/dL; a tenfold increase in risk of fetal loss in uncontrolled hypertension with impaired renal function during conception as compared to pregnancy with controlled hypertension or without hypertension; and the risk of developing subsequent hypertension, CV disease (eg hypertension, ischemic heart disease, heart failure, stroke), metabolic syndrome, and chronic or end-stage renal disease in the future is increased in women with hypertensive disorders of pregnancy or puerperium.

Patients should be informed about the risk of recurrence of hypertension or preeclampsia in the next pregnancy and that preeclampsia is more common in women with chronic hypertension. The risk of hypertension recurrence in the next pregnancy is higher with early-onset hypertension in the first pregnancy. Counsel the patient on the long-term perinatal and neonatal complications associated with preeclampsia: Cerebral palsy, low intelligence, visual and hearing disturbances, metabolic problems (eg insulin resistance and diabetes), neonatal hypertension and coronary artery disease. After a hypertensive pregnancy, the patient should be counseled regarding a healthy diet and lifestyle, CV disease risk assessment, and control of risk factors for long-term cardiovascular and metabolic diseases for herself and her child.

Encourage home BP monitoring for hypertensive women. Self-measured BP identifies non-sustained elevations in the BP, including masked and white coat hypertension. Counsel individuals with hypertension who are planning a pregnancy or who become pregnant that: Labetalol and extended-release Nifedipine are the preferred agents to treat hypertension and minimize fetal risk; low-dose Aspirin may reduce the risk of preeclampsia and its sequelae; the following drugs should not be used to avoid fetal harm: Angiotensin-converting enzyme (ACE) inhibitors, angiotensin II antagonists, direct renin inhibitors, and Nitroprusside or mineralocorticoid receptor antagonists (MRAs). Advise effective contraception to pregnancy-capable individuals with chronic hypertension on teratogenic therapy.