What are the optimal strategies for managing hypertension in a female patient planning to become pregnant?

From the Guidelines

For a woman planning pregnancy with hypertension, the preferred treatment approach is to transition to methyldopa, nifedipine, and/or labetalol to minimize fetal risks. This recommendation is based on the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults 1. The guideline suggests that women with hypertension who become pregnant or are planning to become pregnant should be transitioned to these medications during pregnancy.

Key Considerations

• ACE inhibitors, ARBs, and direct renin inhibitors should be avoided due to fetal risks 1.
• Preferred medications include:
  • Labetalol (starting at 100-200 mg twice daily)
  • Methyldopa (250-500 mg twice daily)
  • Nifedipine (30-60 mg extended-release daily)
• Beta-blockers like metoprolol (25-100 mg twice daily) are acceptable but may be associated with fetal growth restriction with long-term use.
• Blood pressure targets should be 120-150/80-100 mmHg to maintain adequate placental perfusion while preventing maternal complications.

Management Approach

• Pre-conception counseling is essential, and medication adjustments should be made before pregnancy when possible.
• Once pregnant, regular monitoring of blood pressure, renal function, and fetal growth is necessary.
• Lifestyle modifications including reduced sodium intake, regular physical activity, and stress management should complement pharmacological treatment.
• Aspirin 81 mg daily starting at 12-16 weeks may be recommended to reduce preeclampsia risk, as supported by the guideline 1. This approach balances maternal safety with optimal fetal outcomes, as uncontrolled hypertension increases risks of preeclampsia, placental abruption, and fetal growth restriction.

From the FDA Drug Label

Pregnancy Teratogenic Effects. Reproduction studies performed with methyldopa at oral doses up to 1000 mg/kg in mice, 200 mg/kg in rabbits and 100 mg/kg in rats revealed no evidence of harm to the fetus. There are, however, no adequate and well-controlled studies in pregnant women in the first trimester of pregnancy. Because animal reproduction studies are not always predictive of human response, methyldopa should be used during pregnancy only if clearly needed Published reports of the use of methyldopa during all trimesters indicate that if this drug is used during pregnancy the possibility of fetal harm appears remote.

Methyldopa can be used to treat hypertension in females who want to become pregnant, but it should be used with caution and only if clearly needed.

• The drug label does not provide direct evidence of harm to the fetus, but there are no adequate and well-controlled studies in pregnant women in the first trimester of pregnancy.
• Animal reproduction studies have shown no evidence of harm to the fetus.
• The possibility of fetal harm appears remote, but methyldopa should be used during pregnancy only if clearly needed 2.

Pregnancy:Teratogenic Effects: Pregnancy Category C: Teratogenic studies were performed with labetalol in rats and rabbits at oral doses up to approximately six and four times the maximum recommended human dose (MRHD), respectively. No reproducible evidence of fetal malformations was observed. Increased fetal resorptions were seen in both species at doses approximating the MRHD.

Labetalol can be used to treat hypertension in females who want to become pregnant, but it should be used with caution and only if the potential benefit justifies the potential risk to the fetus.

• The drug label does not provide direct evidence of fetal malformations, but increased fetal resorptions were seen in both species at doses approximating the MRHD.
• There are no adequate and well-controlled studies in pregnant women 3.

Pregnancy Pregnancy Category C In rodents, rabbits and monkeys, nifedipine has been shown to have a variety of embryotoxic, placentotoxic, teratogenic and fetotoxic effects

Nifedipine should be used with caution to treat hypertension in females who want to become pregnant.

• The drug label provides evidence of embryotoxic, placentotoxic, teratogenic and fetotoxic effects in rodents, rabbits, and monkeys.
• There are no adequate and well-controlled studies in pregnant women 4.

From the Research

Treatment Options for Hypertension in Women Planning for Pregnancy

• Methyldopa and labetalol are considered the first choice for treating hypertension in women planning for pregnancy 5
• Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) should be withdrawn if a hypertensive woman wishes to become pregnant 5
• A less restricted blood-pressure goal could be set for hypertensive women planning for pregnancy 5
• A healthy body weight before pregnancy could lower the risk of pregnancy-related hypertensive disorders 5

Oral Antihypertensive Regimens for Severe Hypertension in Pregnancy

• Labetalol, nifedipine retard, and methyldopa are viable initial options for treating severe hypertension in pregnancy 6
• Nifedipine retard resulted in a greater frequency of primary outcome attainment than labetalol or methyldopa 6
• All three oral drugs reduced blood pressure to the reference range in most women 6

Pharmacokinetics of Antihypertensive Drugs Throughout Pregnancy

• Methyldopa, labetalol, and nifedipine have been perceived as safe to use during pregnancy and are recommended in international guidelines for treatment of hypertension 7
• No fetal accumulation is found for any of the antihypertensive drugs studied 7
• Further studies on the relationship of both pharmacokinetics and pharmacodynamics during pregnancy and pregnancy-related pathology are urgently needed 7

Antihypertensive Medications for Severe Hypertension in Pregnancy

• Nifedipine was estimated to have a low risk in persistent hypertension compared to hydralazine and labetalol 8
• Several drugs can be used to treat severe hypertension in pregnancy, including oral/sublingual nifedipine, IV/oral labetalol, oral methyldopa, IV hydralazine, IV dihydralazine, IV ketanserin, IV nicardipine, IV urapidil, and IV diazoxide 8
• Nifedipine may be preferred as the first-line agent 8

Oral Antihypertensive Therapy for Severe Hypertension in Pregnancy and Postpartum

• Oral nifedipine, and possibly labetalol and methyldopa, are suitable options for treatment of severe hypertension in pregnancy/postpartum 9
• Nifedipine achieved treatment success in most women, similar to hydralazine or labetalol 9
• Less than 2% of women treated with nifedipine experienced hypotension 9