What medications and doses are recommended for managing hypertension in pregnancy and when is a second medication added?

Management of Hypertension in Pregnancy

First-Line Medications and Dosing

For non-severe hypertension in pregnancy (BP 140-159/90-109 mmHg), initiate treatment with oral methyldopa, labetalol, or long-acting nifedipine as first-line agents, with methyldopa traditionally preferred but all three equally acceptable. 1

Methyldopa Dosing

• Starting dose: 250 mg orally 2-3 times daily 2
• Titration: Increase at intervals of at least 2 days, preferably starting evening doses to minimize sedation 2
• Maintenance range: 500 mg to 2 g daily in 2-4 divided doses 2
• Maximum dose: 3 g daily (or 65 mg/kg in pediatric patients, whichever is less) 2
• Caution: Use with caution in women at risk for postpartum depression 1

Labetalol Dosing

• Starting dose: 100-200 mg orally twice daily for chronic management 3
• Target range: Titrate to maintain BP 110-140/85-90 mmHg 3
• Monitoring: Check BP at least twice weekly initially, then weekly once stable 3
• Contraindications: Avoid in second or third-degree AV block, maternal systolic heart failure, or severe asthma 3

Nifedipine (Long-Acting) Dosing

• Starting dose: 10-20 mg orally (extended-release formulation) 1, 4
• Titration: Adjust based on BP response 1
• Evidence: A 2019 randomized trial demonstrated nifedipine retard achieved BP control in 84% of women versus 77% with labetalol and 76% with methyldopa 4

Treatment Thresholds

When to Initiate Treatment

• Definite indication: BP ≥150/95 mmHg in any pregnant woman 1, 5
• Lower threshold (≥140/90 mmHg): Initiate in women with:
  • Gestational hypertension with or without proteinuria 1
  • Pre-existing hypertension with superimposed gestational hypertension 1
  • Hypertension with subclinical organ damage or symptoms 1
  • Chronic hypertension in pregnancy (based on CHIPS trial showing benefit of targeting diastolic BP 85 mmHg) 1

Target Blood Pressure

• Optimal range: Systolic BP 110-140 mmHg and diastolic BP 85-90 mmHg 1, 3
• Critical lower limit: Never reduce diastolic BP below 80 mmHg, as this impairs uteroplacental perfusion and compromises fetal development 3
• Action if too low: If diastolic BP falls below 80 mmHg, reduce or cease antihypertensive medication 3

When to Add a Second Medication

Add a second antihypertensive agent when BP remains ≥140/90 mmHg despite adequate dosing of the first-line medication, or when BP control cannot be maintained on 2 g of methyldopa daily. 1, 2

Second-Line Options

• If on methyldopa: Add labetalol or long-acting nifedipine 1
• If on labetalol: Add long-acting nifedipine or methyldopa 1, 3
• If on nifedipine: Add labetalol or methyldopa 1
• Thiazide diuretics: May be added at any time and are recommended if effective control cannot be achieved with other agents, though not recommended for initiation during pregnancy 1, 2
• Alternative agents: Hydralazine and prazosin may be used as second or third-line agents 6

Tolerance Considerations

• Timing: Tolerance may occur between the second and third month of therapy 2
• Management: Adding a diuretic or increasing the dose of the primary agent frequently restores effective BP control 2

Management of Severe Hypertension (≥160/110 mmHg)

Severe hypertension (BP ≥160/110 mmHg or ≥170/110 mmHg) is a hypertensive emergency requiring immediate hospitalization and urgent treatment in a monitored setting. 1, 3, 6

Acute Management Options

• IV labetalol: First-line for acute severe hypertension; give 20 mg IV bolus, then 40-80 mg every 10 minutes (maximum 300 mg total) 1
• Oral nifedipine: 10 mg orally, may repeat hourly with dose escalation if needed 1, 4
• IV hydralazine: Alternative option, though no longer preferred due to more perinatal adverse effects compared to other agents 1
• Sodium nitroprusside: Reserved for hypertensive crises, but prolonged use carries risk of fetal cyanide poisoning 1
• Nitroglycerin: Drug of choice for pre-eclampsia with pulmonary edema 1

When Three Medications Are Needed

• Indication: If BP remains ≥160/110 mmHg despite two antihypertensive agents at adequate doses 3
• Delivery consideration: Repeated severe hypertension despite three antihypertensive classes warrants consideration for delivery 3

Medications to Avoid

Absolutely Contraindicated

• ACE inhibitors, ARBs, direct renin inhibitors, MRAs, neprilysin inhibitors: Cause fetal damage and are contraindicated throughout pregnancy 1
• Women of childbearing potential: Should switch from these agents to pregnancy-safe alternatives before conception 1

Use with Caution

• Atenolol: Associated with fetal growth retardation related to duration of treatment; give with caution and avoid in early pregnancy 1, 7, 8
• Diuretics: Not recommended for BP management in pregnancy but may be used during late-stage pregnancy if needed for volume management 1

Special Monitoring and Delivery Planning

Maternal Monitoring

• Frequency: BP checks at least twice weekly initially, then weekly once stable 3
• Proteinuria assessment: Check at each visit 3
• Laboratory monitoring: If abnormal before delivery, repeat blood tests twice in the week after birth 1

Fetal Monitoring

• Initial assessment: Ultrasound to confirm fetal well-being 3
• Ongoing surveillance: Serial fundal height checks, particularly in resource-limited settings 1

Delivery Timing

• Stable hypertension: Plan delivery at 37 weeks and 0 days 3, 6
• Pre-eclampsia: Deliver at 37 weeks and 0 days 6
• Severe pre-eclampsia: Deliver promptly regardless of gestational age 1
• Earlier delivery indications: Repeated severe hypertension despite three antihypertensive classes, visual disturbances, coagulation abnormalities, or fetal distress 3, 6

Postpartum Management

• BP monitoring: Record BP shortly after birth and again within 6 hours; defer discharge for at least 24 hours or until vital signs are normal 1
• High-risk follow-up: Women with gestational hypertension or pre-eclampsia should have BP observed for 72 hours in hospital and 7-10 days postpartum 1
• Long-term surveillance: Check BP and urine at 6 weeks postpartum; refer to specialist if hypertension or proteinuria persists 1
• Breastfeeding-compatible medications: Methyldopa, labetalol, nifedipine, captopril, enalapril are compatible with breastfeeding 1
• Cardiovascular risk: Women with hypertensive disorders in pregnancy have increased lifetime cardiovascular risk and require annual medical review 6, 5