Postpartum Preeclampsia: Clinical Overview of Hypertensive Crisis

Postpartum preeclampsia is defined as the delayed onset of preeclampsia presenting 48 hours to 6 weeks after birth.¹ Postpartum stroke occurs on average in 34.2 per 100,000 deliveries and preeclampsia or eclampsia are associated with a 4-fold increased risk of stroke.² Risk factors for pregnancy-related stroke are similar to those for postpartum preeclampsia including being Black and older than 35 years.³ Timely recognition and treatment of postpartum preeclampsia are essential to improving morbidity and mortality in postpartum patients.

Uncertainty About Incidence

The incidence of postpartum preeclampsia is 0.3% to 27.5%.⁴ The exact number of postpartum preeclampsia cases is not fully known since most patients with this condition present to the emergency department (ED) for care. Much of the research on postpartum preeclampsia is performed by studying single-center data specifically focused on obstetrics patients and does not include those who present to the ED with a symptomatic hypertensive event after a pregnancy.⁴

The pathophysiology of antepartum preeclampsia can involve both maternal and/or paternal factors. It is widely believed that abnormal development of the placenta causes early-onset preeclampsia, which is why delivery is often the definitive treatment. However, this is not the case for postpartum preeclampsia as delivery of the placenta has already occurred. The exact development of postpartum preeclampsia is not completely understood; however, during normal pregnancy, an increase of up to 45% of plasma volume occurs to meet the greater circulatory needs of the placenta and maternal organs.⁵ An increase in plasma volume means further retention of water and sodium that causes a proportional increase in blood pressure. Patients who receive large amounts of fluids between labor and the postpartum period because of anesthesia or cesarean delivery are more likely to experience a state of volume overload resulting in hypertension.

Patients who require greater amounts of analgesia because of cesarean section, lacerations, or episiotomies are also more likely to require nonsteroidal anti-inflammatory drugs (NSAIDs).² A group of obstetricians studied 6 cases of postpartum hypertensive crises in which NSAIDs contributed to significant increases in blood pressure.⁶ The NSAIDs discussed were ibuprofen and indomethacin and the time between taking the NSAID and onset of hypertensive crises ranged from 2 to 10 hours.⁶ This influence of NSAIDs on blood pressure is thought to be caused by the increase in synthesis of renal vasoconstrictors as well as retention of sodium and water.⁶

Other medications that are thought to play a role in postpartum preeclampsia include the ergot alkaloids such as ergotamine and methylergonovine for treatment of uterine atony and prevention of uterine hemorrhage.¹ These medications work through alpha adrenergic receptors that cause peripheral vasoconstriction and should not be used in people with hypertension as it can exacerbate an episode of hypertensive crises.

Who is at Risk?

A study conducted from January 2014 to June 2018 was conducted to identify risk factors associated with postpartum preeclampsia.¹ The study consisted of controls with uncomplicated pregnancies (n=26,936) and cases of patients with postpartum preeclampsia (n=121). The 121 individuals diagnosed with postpartum preeclampsia did not have a previous diagnosis of antepartum preeclampsia or a history of chronic hypertension. The study discovered that patients were more likely to suffer from postpartum preeclampsia if they were non-Hispanic Black patients, had a BMI of 30 or more, were 35 years of age or older, and had a delivery via cesarean (Table 1).¹

Table 1. Risk Factors Associated With Postpartum Preeclampsia¹

Risk Factor	Controls n=26,936	Cases n=121	P value
Race      Caucasian      Non-Hispanic Black      Asian/Pacific Islander      Other/unspecified	19,332 (71.8%) 4846 (18.0%) 1873 (7.0%) 885 (3.3%)	74 (61.2%) 38 (31.4%) 5 (4.1%) 4 (3.3%)	.003
Age (median)	30 years	31 years	.02
Prepregnancy BMI (median)	24.3	28.3	<.001
Cesarean delivery	6938 (25.8%)	49 (40.5%)	<.001

Hallmarks of Disorder

Aside from hypertension, many patients are only aware of their elevated blood pressure because of symptoms. Many of the hallmarks of the disorder are prodromal symptoms that occur before the progression to eclampsia and are similar to those in antepartum preeclampsia. When these symptoms present, the patient must receive prompt treatment to reduce blood pressure. These symptoms include¹:

• New-onset headache
• Visual abnormalities (halos, floaters, blurred vision, photophobia)
• Abdominal pain (upper, epigastric, retrosternal)
• Altered mental status
• New onset shortness of breath

Diagnosing Postpartum Preeclampsia

The diagnostic criteria for preeclampsia and postpartum preeclampsia are the same despite the difference in time of onset. Preeclampsia is defined as a systolic pressure greater than 140 mm Hg and a diastolic pressure greater than 90 mm Hg found on at least 2 separate occasions in 4 hours after 20 weeks gestation in a patient with previously normal blood pressure. Blood pressure measurements with a systolic pressure of 160 mm Hg or more and a diastolic of 110 mm Hg or more can also be used to facilitate timely treatment in the setting of severe hypertension.⁷ In terms of postpartum preeclampsia, the onset occurs 48 hours to 6 weeks following delivery of a newborn. Postpartum preeclampsia differs from postpartum hypertension in that it includes proteinuria of 300 mg or more within a 24-hour urine collection, urine dipstick reading of 2 or more, or urine protein/creatinine ratio of 0.3 or greater (Table 2).⁷

In the absence of proteinuria with new-onset hypertension, cerebral or neurologic symptoms such as headache and vision changes, impaired liver transaminases double the normal value, thrombocytopenia with a platelet count less than 100,000/µL, epigastric or right upper quadrant discomfort, pulmonary edema, and renal insufficiency with a creatinine greater than 1.1 mg/dL or doubling of serum creatinine are all indicative of preeclampsia.^7,8

Table 2. Diagnosis Criteria for Postpartum Preeclampsia^7,8

Preeclampsia is defined as: • Systolic pressure >140 mm Hg or diastolic pressure >90 mm Hg on at least 2 separate occasions within 4 hours after 20 weeks gestation in a patient without previously diagnosed hypertension OR • Systolic pressure >160 mm Hg or diastolic pressure >110 mm Hg

Proteinuria: • ≥300 mg of protein in a 24-hour urine collection • 2+ protein on urine dipstick • Protein/creatinine ratio ≥0.3

In the absence of proteinuria: • Thrombocytopenia (platelet count <100,000/µL) • Renal insufficiency ‒ Serum creatinine >1.1 mg/dL ‒ Doubling serum creatinine • Impaired liver function (doubling of liver transaminases) • Pulmonary edema • New-onset cerebral or neurologic symptoms ‒ Headache ‒ Visual changes ‒ Stroke

Treatment

Postpartum patients presenting with hypertension and alarm symptoms such as visual disturbances, headache, and shortness of breath should be started on magnesium sulfate for seizure prophylaxis. Antihypertensives should also be started to return blood pressure to less than 140/90 within 30 to 60 minutes of confirmed hypertensive crisis.⁷ American College of Obstetricians and Gynecologists (ACOG) recommends normalizing the blood pressure below 140 to 150 mm Hg/90 to 100 mm Hg.⁷ Medications used include parenteral labetalol and hydralazine and oral nifedipine.⁹ In a systematic review of several randomized controlled trials, oral nifedipine (10 mg) was found to be equally successful in the treatment of severe hypertension in both pregnancy and postpartum when compared to parenteral agents such as labetalol and hydralazine.⁹ The use of oral nifedipine and parenteral labetalol and hydralazine had similar success rates of at least 84% of patients returning to normalized blood pressure and low rates of maternal hypotension (<2%) and are, therefore, considered first-line agents.⁷ Oral nifedipine should especially be considered if IV access is not available.⁷

Many individuals following inpatient treatment of postpartum preeclampsia will require outpatient oral antihypertensives. Oral antihypertensives should include those that are safe for those who are breastfeeding (Table 3).¹⁰ The drugs that have the lowest transfer to breast milk include β-blockers such as propranolol, metoprolol, and labetalol. Calcium channel blockers include diltiazem, nifedipine, nicardipine, and verapamil. Angiotensin-converting enzyme (ACE) inhibitors include captopril and enalapril. Diuretics include hydrochlorothiazide but may be associated with decreased milk production. Methyldopa and hydralazine are also safe for the newborn. At-home monitoring of blood pressure is also useful and patients should be advised to seek medical attention if alarm symptoms reoccur.

Table 3. Oral Antihypertensives That Are Safe During Breastfeeding¹⁰

β-Blockers	Calcium Channel Blockers	ACE Inhibitors	Diuretics
Propranolol Initial: 80 mg/d Titrate at 1-week intervals Usual dosage range 80-160 mg/d	Diltiazem 12-hour formulations Initial: 60-120 mg twice daily Titrate after 7-14 days Usual dosage range 240-360 mg/d divided into 2 doses   24-hour formulations Initial: 120-240 mg/d Titrate after 7-14 days Usual dosage range 120-360 mg/d	Captopril Initial: 12.5-25 mg 2 or 3 times daily Titrate dose at 1- to 2-week intervals Up to 50 mg 3 times daily	Hydrochlorothiazide Initial: 12.5-25 mg/d Titrate dose as needed Up to 50 mg/d   *Thiazide diuretics can decrease milk production11
Metoprolol succinate Initial: 25 to 100 mg/d Titrate at 1-week intervals Usual dosage range 50-200 mg/d	Nifedipine Extended Release Initial: 30 or 60 mg/d Titrate dose every 1-2 weeks Usual dosage range 30-90 mg/d Maximum dose: 120 mg/d	Enalapril Initial: 5 mg/d or twice daily Double dose every 4-6 weeks as needed Up to 40 mg/d in 1 or 2 divided doses	Methyldopa Initial: 250 mg 2 or 3 times daily Titrate daily dose every 2 days Usual dose range 250-1000 mg/d in 2 divided doses Maximum dose: 3000 mg/d
Labetalol Initial: 100 mg twice daily Titrate every 2-3 days by 100 mg twice daily Usual dosage range 200-800 mg/d in 2 divided doses Maximum dose: 2400 mg/d	Nicardipine Initial: 20 mg 3 times daily Titrate every 3 days as needed Usual dosage range 20-40 mg 3 times daily		Hydralazine May be combined with methyldopa or labetalol Initial: 10 mg 4 times daily Titrate dose by 10-25 mg every 2-5 d Usual dose range 50 to 100 mg in 2-4 divided doses Maximum dose: 200 mg/d
	Verapamil Extended Release Initial: 120 or 180 mg once daily Titrate dose at weekly intervals Usual dosage range 120-360 mg/d or twice daily

Patient Outcomes

While most cases of postpartum preeclampsia will resolve by 8 weeks, there is a concern for long-term sequelae. A Danish study evaluated the long-term effects of preeclampsia. The study included more than 700,000 individuals who experienced gestational hypertension, mild preeclampsia, or severe preeclampsia. Researchers discovered preeclampsia increases an individual’s lifetime risk for chronic hypertension, ischemic heart disease, type 2 diabetes, congestive heart failure, thromboembolic events, and stroke.¹²

Patients with postpartum preeclampsia are 4 times more likely to suffer from stroke than the average postpartum person.² Studies have found that those with delayed-onset postpartum preeclampsia are 45% more likely to develop stage 1 or stage 2 hypertension within 1 year after delivery.¹ These statistics are similar to the rates of patients with antepartum preeclampsia who develop chronic hypertension. Those with antepartum preeclampsia were 11.8% more likely to develop chronic hypertension at 6 months and 26.8% more likely at 5 years (P <.01).¹³ It is thought the risk for development of chronic hypertension is dependent on the severity of preeclampsia.¹⁴

The American Heart Association recommends lifestyle modifications for individuals with prior preeclampsia to decrease cardiovascular risk.¹⁵ These lifestyle modifications included smoking cessation, DASH (Dietary Approaches to Stop Hypertension) diet, weight reduction, and physical activity.¹⁵

Grace Long, MPA, PA-C, has been practicing in gynecology since 2021, and is a graduate of the Augusta University PA Program in Augusta, Georgia. Elizabeth Prince-Coleman, MPA, PA-C, has been in practice for almost 9 years with Augusta University Health. She also serves as the program director for the Augusta University PA Program.

References

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