An epidemic of hypertensive disorders of pregnancy

^{ILLUSTRATION BY KIMBERLY MARTENS FOR OBG MANAGEMENT}

Hypertension in pregnancy is a major challenge in current obstetric practice. Based on an analysis of the National Inpatient Sample, the Centers for Disease Control and Prevention (CDC) recently reported that from 2017 to 2019 the prevalence of hypertensive disorders in pregnancy increased from 13.3% to 15.9% of hospital deliveries.¹ During that same time period, the prevalence of pregnancy-associated hypertension, which includes preeclampsia, eclampsia, and gestational hypertension, increased from 10.8% to 13.0%.¹ The prevalence of chronic hypertension increased from 2.0% to 2.3%.¹ In 2017 and 2019, unspecified maternal hypertension was diagnosed in 0.5% and 0.6% of the sample, respectively.¹

Bruno and colleagues reported a 3-fold increase in the prevalence of HDPs from 1989 to 2020, with an acceleration in the rate of increase from 2010 to 2020.² The increase in prevalence of HDPs may be caused by an increase in the prevalence of advanced maternal age, obesity, and diabetes. Black patients are disproportionately impacted by both pregnancy-associated hypertension and chronic hypertension.¹ In 2019, the prevalence of pregnancy-associated hypertension was greater among Black patients (15.6%), than White (12.1%), Hispanic (10.6%), or Asian or Pacific Islander patients (7.7%).¹ Similarly, the prevalence of chronic hypertension was greater among Black patients (4.3%) than among White (2.0%), Hispanic (1.5%), or Asian or Pacific Islander patients (1.2%).¹ Racial/ethnic differences in HDPs may be influenced by poverty; structural racism; or lack of access to care, diet, and obesity.^3,4

HDPs are major contributors to maternal morbidity and mortality. The CDC reported that among maternal deaths occurring during the delivery hospitalization, 32% of the decedents had documented hypertension.¹ HDPs are associated with an approximately 2.5-fold increased risk of a severe morbidity, a composite measure that includes blood transfusion, acute kidney injury, disseminated intravascular coagulation, sepsis, shock, and pulmonary edema.⁵ A history of HDPs is associated with an approximately 67% increase in the lifetime risk of cardiovascular disease, including coronary artery disease, stroke, peripheral vascular disease, and heart failure.^6,7

What are the best antihypertensive medications for pregnancy?

All clinicians know that the use of angiotensin-converting-enzyme inhibitors (ACE-Is) and angiotensin-receptor-blockers (ARBs) are contraindicated in pregnancy because they cause major congenital anomalies, with an odds ratio of 1.8 (95% confidence interval [CI], 1.42-2.34), compared with no exposure.⁸ In addition, ACE-Is and ARBs increase the risk of stillbirth, with an odds ratio of 1.75 (95% CI, 1.21-2.53).⁸ No increase in congenital anomalies were detected for patients exposed to other antihypertensive medications.⁸ Prior to attempting conception, patients with chronic hypertension should discontinue ACE-Is and ARBs and initiate an alternative medication.

The most commonly used antihypertensive medications in pregnancy are labetalol, nifedipine, and methyldopa.⁹ Labetalol blocks the beta-1, beta-2, and alpha-1 adrenergic receptors.¹⁰ Nifedipine blocks calcium entry into cells through the L-type calcium channel.¹¹ Methyldopa is a central nervous system alpha-2 adrenergic agonist.¹² The dose range for these commonly used medications are labetalol 400 mg to 2,400 mg daily in divided doses every 8 to 12 hours, nifedipine extended-release 30 mg to 120 mg daily, and methyldopa 500 mg to 2 g daily in 2 to 4 divided doses. Some clinicians recommend prescribing divided doses of nifedipine extended release at doses ≥ 60 mg for patients who have bothersome adverse effects, hypotension following a single daily dose, or hypertension between single daily doses. The nifedipine extended release tablets should not be divided. If monotherapy with the maximal daily dose of labetalol does not achieve the blood pressure (BP) target, adding nifedipine as a second agent is an option.⁹ Similarly, if monotherapy with the maximal daily dose of nifedipine extended release does not achieve the BP target, adding labetalol as a second agent is an option.⁹

In a network meta-analysis of antihypertensive medications used in pregnancy, that included 61 trials and 6,923 participants, all the medications studied reduced the risk of developing severe hypertension by 30% to 70%.¹³ Sufficient data was available to also report that labetalol used to treat hypertension in pregnancy reduced the risk of developing proteinuria.¹³ Given similar efficacy among antihypertensive medications, patient comorbidities may influence the medication choice. For example, labetalol may not be the optimal medication for a patient with poorly controlled asthma due to its ability to cause bronchospasm.^14,15 Methyldopa may not be the optimal medication for a patient with depression.¹⁶ Based on the available data, labetalol, nifedipine, and methyldopa are the best antihypertensive medications for pregnant patients.

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