Hypertension%20in%20pregnancy Treatment

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
  • The decision to deliver in women with preeclampsia should not depend on the degree of proteinuria or change in the amount of proteinuria
  • In any type of hypertensive disorders 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 hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome, cesarean delivery may increase the risk of bleeding due to thrombocytopenia and difficulty in BP control due to diminished intravascular volume
• 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 age of gestation (AOG) at risk for delivery within 7 days, IV Magnesium sulfate and a course of corticosteroids should be administered to accelerate fetal lung maturity
• Delivery at ≥37 weeks is advised in women with preeclampsia 
  • Planned early delivery at <37 weeks is not advised in women with a BP of <160/110 mmHg unless other medical indications warrant it 
  • Offer initiation of delivery at 38-39 weeks but advise it from 40 weeks in women with chronic hypertension or gestational hypertension

Indications for Delivery 

• Maternal
  
  • AOG ≥37 weeks
  • Platelet <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
  • Persistent epigastric pain, nausea and vomiting

• Fetal
  
  • Severe growth restriction
  • Non-reassuring fetal testing results
  • Oligohydramnios
  • Fetal death

• Goals of treatment are to prevent severe hypertension (suggested BP goal <140/90) and to 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
  • Recommendations for BP target goals may vary between countries. Please refer to available guidelines from local health authorities
• 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) 
• Choice of antihypertensive agents should depend on patient’s current antihypertensive treatment, contraindications, risks, side effect profiles, cost, availability and patient’s preferences
• For non-urgent control of hypertension, if 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 3 drugs)   
  • If 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 BP is not controlled with combination oral antihypertensive regimens 
• Switch to oral antihypertensive therapy once severe hypertension has resolved 

Centrally Acting Agents

• Act centrally to reduce sympathetic tone causing a decrease in BP
• Lower BP effectively

Methyldopa

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

Beta-Blockers 

• Used as initial therapy for hypertension in pregnancy as they are nonteratogenic
• 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 have been demonstrated
• May induce fetal bradycardia, intrauterine growth retardation and neonatal hypoglycemia

Labetalol

• Oral Labetalol is the preferred beta-blocking agent
• IV Labetalol is considered the 1st-line agent in the treatment of acute hypertension in preeclampsia, rapidly controls severe resistant hypertension
• Noncardioselective beta-blocker with selective alpha₁ blocking properties that decrease peripheral vascular resistance causing vasodilatation and decreases BP more rapidly than other beta-blockers
• Cumulative dose should be <800 mg/day to avoid fetal bradycardia 

Acebutolol, Metoprolol, Pindolol and Propranolol 

• These agents have not been associated with any adverse effects when administered in late pregnancy
• 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
• 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 low weight for gestational age

Calcium (Ca) Antagonists 

• Experience with oral Ca antagonists in pregnancy is limited with most uses reported in late pregnancy
• No increase in major teratogenicity with exposure to Ca antagonists has been shown
• Inhibit the cellular influx of Ca which is responsible for 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 and atrioventricular (AV) nodes
  • They dilate coronary and peripheral arteries with little or no effect on venous tone, have a negative inotropic action, reduce HR and slow AV conduction
• Lower BP effectively
• May cause myocardial depression when combined with Magnesium

Nifedipine 

• Used as 2nd-line antihypertensive in pregnancy
  • Immediate-release oral Nifedipine may also be considered as a 1st-line agent when IV access is unavailable 
• The preparations of Nifedipine appropriate for use in pregnancy are capsule and prolonged action tablet
  • A study has shown 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
•  Stat dose of oral Nifedipine 10 mg may be used for rapid BP control in acute hypertensive crisis

Nicardipine 

• Considered as a 2nd-line alternative when IV bolus Labetalol, Hydralazine or oral Nifedipine did not relieve acute severe hypertension in pregnant women

Diuretics 

• Use of diuretics in pregnancy is controversial due to theoretical risk of decreasing plasma volume, 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
  • Lower BP effectively and potentiate the response to other antihypertensive agents
• Discuss alternative antihypertensive treatments with patient if pregnancy is planned
• Please refer to Hypertension disease management chart for dosage guidelines of diuretics

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

• Contraindicated in pregnancy
• 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
• 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 score

Sodium (Na) Nitroprusside 

• Last-line agent for acute hypertension in preeclampsia, should only be used when other agents fail to reduce BP
• Acts directly on arterioles and veins causing peripheral vasodilatation that results in a decrease in peripheral resistance and BP
• Short-acting hypotensive, lowers BP effectively for 1-10 minutes
  • Reduces BP rapidly causing excessive hypotension
• 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

Nitroglycerin 

• Given as an IV infusion in preeclampsia associated with pulmonary edema  
• Reduces cardiac oxygen demand by decreasing preload and may modestly reduce afterload, dilates coronary arteries and improves collateral flow to ischemic regions 

Anticonvulsant

Magnesium sulfate 

• Decreases acetylcholine in motor nerves and acts on myocardium by slowing rate of SA node impulse formation and prolonging conduction time 
• Used for seizure prevention in gestational hypertension with severe features and preeclampsia with severe features or for treatment of eclampsia
  • Used also to prevent recurrent convulsions in eclampsia
• Reduces frequency of eclampsia in pregnancy-induced hypertension or severe preeclampsia and decreases the incidence of placental abruption
• Incidence of magnesium intoxication is low in patients with preeclampsia with severe features treated with Magnesium sulfate 
• May be administered via IV route with 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

Aspirin

• Meta-analyses showed Aspirin may reduce the risk of preeclampsia and adverse perinatal outcomes
• May be given at a low dose at bedtime from 12 weeks of gestation until delivery (preferably before 16 weeks until 36 weeks) in women with high or ≥1 moderate risk factors for preeclampsia

• Consider non-drug therapy
• May taper and stop any existing antihypertensive therapy
• Prior to conception, stop ACE inhibitors or angiotensin II antagonists

Considerations 

• Monitor BP after delivery as it peaks around days 3-7 postpartum; conduct an early postpartum follow-up visit within 7-14 days of delivery 
  • BP monitoring and control should continue for up to 6 weeks postpartum
• Resolution of high BP is usually more rapid in patients with gestational hypertension
• Delayed resolution may occur in patients who suffered preeclampsia and especially in those who had longer duration of preeclampsia and greater renal impairment
  • Greatest risk of occurrence of postpartum eclampsia is within the first 48 hours

Potential Complications

• Women with hypertension that persists postpartum may develop complications eg encephalopathy, heart failure, pulmonary edema and renal failure postpartum

Treatment 

• Magnesium sulfate may be continued 12-24 hours after delivery or longer to prevent postpartum eclampsia
• Continue oral antihypertensive treatment given antepartum in severe postpartum hypertension to keep BP below 160/110 mmHg and in non-severe postpartum hypertension if with comorbidities
• Antihypertensive treatment may be reduced if BP falls <130/80 mmHg 
• For untreated women with gestational hypertension or preeclampsia, antihypertensive therapy may be started postpartum if BP is ≥150/100 mmHg

Treatment of Hypertension During Lactation

• Breastfeeding is encouraged as the amounts of antihypertensive agents taken in by the infants are very small and unlikely to cause any clinical effect 
  • Patients should monitor their infants for poor feeding, pallor, drowsiness, lethargy or cold peripheries 

Mild Hypertension 

• For mothers who want to breastfeed for a few months
  • May withhold medications with close monitoring of BP and reinstate treatment after discontinuation of lactation

Severe Hypertension  

• May consider reducing dose of antihypertensive with close observance of mother and infant or using antihypertensive agents with once-daily dosing
• If a beta-blocker is indicated, Labetalol is preferred; may also prefer long-acting Ca antagonists 
• Enalapril may also be considered with monitoring of maternal renal function and serum potassium 
• If combination therapy is indicated, may consider Amlodipine with Enalapril; consider either adding or switching one of the agents for Labetalol if this combination is ineffective or not tolerated
• Agents to avoid:
  • Angiotensin receptor blockers  
  • Atenolol, Metoprolol, Nadolol, Propranolol and Nifedipine concentrate in breast milk
  • Diuretics decrease milk volume and suppress lactation
  • Though Methyldopa may be used during breastfeeding, it is recommended to avoid it in the postnatal period due to risk of postpartum depression

• If pre-pregnancy BP was normal or unknown, stop antihypertensives 3-4 weeks postpartum
• Monitor BP at 1- to 2-week interval followed by 3- to 6-month interval for 1 year
• Start treatment if hypertension recurs postpartum