Antihypertensive Therapy in Pregnancy

Antihypertensive therapy in pregnancy prevents severe maternal hypertension, stroke and organ damage in chronic hypertension, gestational hypertension and pre-eclampsia. It does not cure pre-eclampsia, which resolves only with birth of the placenta, and it must avoid foetotoxic agents and abrupt falls in placental perfusion.

Definitions. Hypertension is 140/90 mmHg or more on 2 readings. Severe hypertension is 160/110 mmHg or more. Pre-eclampsia is new hypertension after 20 weeks with proteinuria (urine protein to creatinine ratio 30 mg/mmol or more) or maternal organ or uteroplacental dysfunction.

Treatment threshold and target. Treat at 140/90 mmHg or more; target about 135/85 mmHg. Treat severe hypertension within 30 to 60 minutes.

Diastolic floor. Avoid diastolic pressure under 80 mmHg during treatment, as overtreatment may reduce placental perfusion.

Oral first line.

• Labetalol 100 mg orally twice daily, increase every 2 to 3 days to 200 to 400 mg 3 times daily; maximum 2.4 g daily in 3 to 4 doses. Avoid in asthma.
• Nifedipine modified release 20 mg orally twice daily, up to 40 mg twice daily; once-daily formulation 30 to 60 mg, up to 90 mg (120 mg in some regions).
• Methyldopa 250 mg orally 2 to 3 times daily, increase every 2 days; maximum 3 g daily. Widely available and used first line in much of East Africa.

Oral add-on. Hydralazine 25 to 50 mg orally 3 to 4 times daily (maximum 200 mg daily) or a second first-line agent; doxazosin 1 to 4 mg daily for resistant cases.

Severe hypertension, labetalol IV. 20 mg IV over 2 minutes, then 40 mg after 10 minutes, then 80 mg every 10 minutes to a cumulative 300 mg. Alternative: 50 mg IV over at least 1 minute, repeated every 5 minutes to 200 mg. Follow with infusion 20 mg/hour, doubling every 30 minutes to a maximum of 160 mg/hour.

Severe hypertension, nifedipine oral. Immediate release 10 mg orally; repeat at 20 to 30 minutes (10 to 20 mg) if still severe; maintenance 10 to 20 mg every 4 to 6 hours; maximum 120 mg daily. Swallow whole, never sublingual.

Severe hypertension, hydralazine IV. 5 mg IV over 2 to 5 minutes; repeat 5 to 10 mg every 20 minutes to a cumulative 20 mg; then infusion 5 to 10 mg/hour titrated. Give no more than 500 mL crystalloid beforehand, and only if indicated.

Magnesium sulphate. In pre-eclampsia with severe features: 4 g IV over 5 to 15 minutes, then 1 g/hour for 24 hours after birth or the last seizure.

Prevention. Aspirin 75 to 150 mg at night from 12 weeks to 36 weeks; calcium 1.5 to 2 g daily from 20 weeks where intake is low.

After birth. Enalapril 5 to 20 mg once or twice daily, amlodipine 5 to 10 mg daily, nifedipine or labetalol. Stop methyldopa within 2 days of birth. Reduce or stop treatment when pressure falls under 130/80 mmHg.

Contraindicated in pregnancy. ACE inhibitors, angiotensin receptor blockers, direct renin inhibitors and mineralocorticoid receptor antagonists (spironolactone: anti-androgenic effect on the male foetus). Atenolol (foetal growth restriction). Thiazide diuretics are not advised for new starts; stop unless a specialist directs otherwise.

Adverse effects. Labetalol: bronchospasm, scalp tingling, neonatal bradycardia and hypoglycaemia. Nifedipine: headache, flushing, oedema, reflex tachycardia. Methyldopa: sedation, depression, raised transaminases, positive Coombs test, rarely haemolytic anaemia. Hydralazine: sudden hypotension, tachycardia, foetal distress, lupus-like syndrome with long use.

Interactions. Nifedipine with magnesium sulphate: hypotension and neuromuscular weakness; use together with close monitoring. Labetalol with insulin: masked hypoglycaemia. Nifedipine with rifampicin or carbamazepine: large fall in levels.

Special groups.

• Preconception chronic hypertension: switch ACE inhibitors and angiotensin receptor blockers before conception or within 2 days of a positive test.
• Asthma: nifedipine or methyldopa, not labetalol.
• Kidney impairment: avoid potassium supplements and potassium-sparing agents; target lower pressure in chronic kidney disease after specialist review.
• Breastfeeding: enalapril, captopril, nifedipine, amlodipine, labetalol and metoprolol are compatible.
• Regional: methyldopa and nifedipine are the most available agents in many Kenyan facilities; IV labetalol may be scarce, so nifedipine oral and hydralazine IV are frequent first choices.

Monitoring. Blood pressure every 15 minutes during acute treatment until under 160/110 mmHg, then every 30 minutes. In pre-eclampsia: full blood count, creatinine, transaminases and urine protein at diagnosis and at least twice weekly. Foetal growth and Doppler every 2 weeks.

Postnatal monitoring. Blood pressure at least 4 times daily while inpatient, then every 1 to 2 days for 2 weeks. Pressure often peaks at days 3 to 6 after birth.

Stopping rules. Reduce the dose if pressure is under 110/70 mmHg or the patient is symptomatic. Stop hydralazine for maternal tachycardia over 120 a minute.

Referral and escalation. Admit for severe hypertension, any pre-eclampsia with severe features, platelets under 100 x 10^9/L, rising creatinine, transaminases over twice normal, headache with visual disturbance, epigastric pain or foetal compromise. Arrange birth when maternal or foetal condition deteriorates despite treatment, and from 37 weeks in pre-eclampsia.