Hypertensive Disorders in Pregnancy: A Comprehensive Review for the Internist

Dr Neeraj Manikath , claude.ai

Abstract

Hypertensive disorders complicate 5-10% of pregnancies worldwide and remain a leading cause of maternal and perinatal morbidity and mortality. The spectrum encompasses chronic hypertension, gestational hypertension, preeclampsia-eclampsia, and chronic hypertension with superimposed preeclampsia. While obstetricians typically manage these conditions, internists increasingly encounter pregnant patients in emergency departments, outpatient clinics, and inpatient settings. This review provides a detailed framework for understanding, diagnosing, and managing hypertensive disorders in pregnancy, with emphasis on diagnostic nuances, evidence-based management, and critical decision points that distinguish competent from expert care.

Introduction

Hypertension affects approximately 10% of pregnancies globally, with rates increasing due to advancing maternal age, obesity, and delayed childbearing. The terminology can be confusing, and the management differs substantially from non-pregnant hypertension. Understanding these distinctions is crucial for internists who may be the first point of contact for pregnant patients with elevated blood pressure.

Classification: More Than Semantics

The American College of Obstetricians and Gynecologists (ACOG) classification system divides hypertensive disorders of pregnancy into four categories, and precise classification has therapeutic implications.

Chronic Hypertension is defined as blood pressure ≥140/90 mmHg present before pregnancy, diagnosed before 20 weeks' gestation, or persisting beyond 12 weeks postpartum. The 20-week threshold is critical because it predates the typical onset of preeclampsia.

Gestational Hypertension develops after 20 weeks' gestation without proteinuria or systemic features. Approximately 15-25% of women with gestational hypertension progress to preeclampsia, making close surveillance essential.

Preeclampsia represents new-onset hypertension after 20 weeks with either proteinuria (≥300 mg/24 hours or protein/creatinine ratio ≥0.3) or, in the absence of proteinuria, new onset of thrombocytopenia, renal insufficiency, liver dysfunction, pulmonary edema, or cerebral/visual symptoms.

Chronic Hypertension with Superimposed Preeclampsia occurs when women with pre-existing hypertension develop new proteinuria, sudden worsening of hypertension, or systemic features after 20 weeks. This combination carries the highest risk for adverse outcomes.

Pearl 1: The 20-Week Rule

The 20-week gestational age serves as the diagnostic watershed between chronic and pregnancy-specific hypertension. However, preeclampsia can occasionally present before 20 weeks in the setting of molar pregnancy or antiphospholipid syndrome. When hypertension develops at 18-19 weeks, consider these rare etiologies rather than reflexively diagnosing chronic hypertension.

Pathophysiology: Understanding the Cascade

Preeclampsia is fundamentally a disease of the placenta, characterized by inadequate trophoblastic invasion and spiral artery remodeling during early pregnancy. This leads to placental hypoxia and release of anti-angiogenic factors, particularly soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin, which antagonize vascular endothelial growth factor (VEGF) and transforming growth factor-β. The resulting widespread endothelial dysfunction produces the multisystem manifestations of preeclampsia: hypertension, proteinuria, thrombocytopenia, liver dysfunction, and cerebral edema.

This pathophysiologic understanding explains several clinical observations: preeclampsia improves after delivery because the placental source of anti-angiogenic factors is removed; aspirin prophylaxis works best when started early in pregnancy before placental implantation is complete; and biomarkers like sFlt-1/PlGF ratios can predict disease development and severity.

Clinical Presentation and Diagnosis

Blood Pressure Measurement: Getting It Right

Proper blood pressure measurement in pregnancy requires attention to technique. The patient should be seated with arm at heart level after five minutes of rest. The appropriate cuff size covers 80% of the arm circumference; small cuffs overestimate pressure in obese patients. Korotkoff phase V (disappearance) should be used for diastolic pressure, not phase IV (muffling). Blood pressure should be confirmed in both arms initially, as significant asymmetry may indicate coarctation, though this is rare.

Hack 1: The Outpatient Conundrum

When evaluating a pregnant patient with elevated blood pressure in the outpatient setting, remember that anxiety-related elevations are common. If blood pressure is 140-155/90-105 mmHg without symptoms, have the patient rest in a quiet room for 15-20 minutes and remeasure. If persistently elevated on two occasions four hours apart, further evaluation is warranted. However, blood pressure ≥160/110 mmHg requires immediate treatment regardless of symptoms, as this threshold carries stroke risk.

Laboratory Evaluation: What to Order and Why

When evaluating suspected preeclampsia, the essential laboratory panel includes:

• Complete blood count with platelet count (thrombocytopenia suggests microangiopathy)
• Comprehensive metabolic panel (creatinine elevation, transaminase elevation)
• Uric acid (elevations often precede other manifestations; levels >5.5 mg/dL are concerning)
• Lactate dehydrogenase (hemolysis marker)
• Peripheral blood smear if hemolysis suspected
• Urine protein/creatinine ratio or 24-hour urine protein

Pearl 2: The Uric Acid Insight

While uric acid elevation is not part of diagnostic criteria, it offers prognostic value. Uric acid >6.0 mg/dL at presentation predicts higher likelihood of adverse outcomes and may help guide timing of delivery. However, uric acid should not be used alone to make management decisions.

Oyster 1: Proteinuria Is Not Required

A common misconception is that preeclampsia requires proteinuria. The 2013 ACOG criteria revision recognized that preeclampsia can occur without proteinuria if other severe features are present. HELLP syndrome (Hemolysis, Elevated Liver enzymes, Low Platelets), eclampsia, and severe hypertension with thrombocytopenia all represent preeclampsia even without proteinuria. Don't be falsely reassured by absent proteinuria.

Severe Features: Recognizing the Red Flags

Preeclampsia with severe features requires heightened vigilance and often mandates delivery. Severe features include:

• Blood pressure ≥160/110 mmHg on two occasions at least four hours apart (or appropriate for immediate treatment)
• Thrombocytopenia (platelets <100,000/μL)
• Liver transaminases >2x upper limit of normal or persistent right upper quadrant pain
• Renal insufficiency (creatinine >1.1 mg/dL or doubling of baseline)
• Pulmonary edema
• New-onset cerebral or visual symptoms (persistent headache, blurred vision, scotomata)

Hack 2: The Right Upper Quadrant Pain Signal

Right upper quadrant or epigastric pain in a pregnant woman with hypertension should trigger immediate evaluation for HELLP syndrome or hepatic involvement. This pain results from hepatic capsular distension and carries risk of subcapsular hematoma or rupture—a catastrophic complication with 25% maternal mortality. Don't dismiss this as "indigestion" or "heartburn." Immediate liver function tests and close monitoring are essential.

Management Principles: Split-Hair Decision Making

When to Treat Chronic Hypertension in Pregnancy

The CHAP trial (2022) demonstrated that treating chronic hypertension to targets <140/90 mmHg improved outcomes compared with treating only severe hypertension ≥160/105 mmHg. This marked a paradigm shift from previous recommendations to withhold treatment for mild-moderate hypertension. Treatment reduced the composite outcome of preeclampsia with severe features, medically indicated preterm birth <35 weeks, placental abruption, and fetal/neonatal death.

First-line agents include labetalol (100-400 mg three times daily), nifedipine extended-release (30-90 mg daily), and methyldopa (250-500 mg three times daily). ACE inhibitors, ARBs, atenolol, and chlorothiazide are contraindicated in pregnancy.

Pearl 3: The Labetalol Limitation

While labetalol is first-line, it's contraindicated in women with asthma due to β-blocker effects. Additionally, some women develop drug-induced lupus with chronic labetalol use, presenting with arthralgias and positive ANA. If a patient develops these symptoms on labetalol, switch to nifedipine.

Acute Severe Hypertension: The 30-Minute Rule

Blood pressure ≥160/110 mmHg represents a hypertensive emergency in pregnancy due to stroke risk. Treatment should begin within 30-60 minutes of confirmation. First-line agents include:

• Labetalol 20 mg IV initially, then 40 mg, then 80 mg every 10 minutes (maximum 220 mg)
• Hydralazine 5-10 mg IV every 20 minutes
• Immediate-release nifedipine 10-20 mg orally, repeat in 20 minutes if needed

Hack 3: The Nifedipine-Magnesium Myth

A persistent myth suggests that combining nifedipine with magnesium sulfate causes dangerous hypotension or neuromuscular blockade. Multiple studies have refuted this. The two agents can be used together safely, and immediate-release oral nifedipine is often the most practical option for acute severe hypertension, particularly in settings without immediate IV access.

Magnesium Sulfate: Neuroprotection and Seizure Prophylaxis

Magnesium sulfate prevents and treats eclamptic seizures with greater efficacy than phenytoin or benzodiazepines. It's indicated for preeclampsia with severe features and should be continued for 24 hours postpartum. The loading dose is 4-6 g IV over 15-20 minutes, followed by 2 g/hour infusion.

Monitor deep tendon reflexes, respiratory rate, and urine output hourly. Hold infusion if respiratory rate <12/minute, absent reflexes, or urine output <25 mL/hour. Therapeutic levels are 4-7 mEq/L. Calcium gluconate (1 g IV) reverses magnesium toxicity.

Oyster 2: Postpartum Preeclampsia

Preeclampsia can develop de novo or worsen postpartum, typically within the first 48-72 hours but occasionally up to 6 weeks. Postpartum patients with headache, visual changes, or elevated blood pressures require the same evaluation as antepartum patients. NSAID use for postpartum pain can exacerbate hypertension and should be limited in these patients.

Delivery Timing: The Ultimate Treatment

Delivery is the only definitive treatment for preeclampsia, but timing requires balancing maternal risk against fetal prematurity. General guidelines:

• Preeclampsia with severe features at ≥34 weeks: deliver
• Preeclampsia without severe features at ≥37 weeks: deliver
• Eclampsia, HELLP syndrome, or maternal instability: deliver regardless of gestational age
• Between 23-34 weeks with severe features: individualized decision with maternal-fetal medicine consultation

Corticosteroids for fetal lung maturity should be administered if delivery is anticipated before 37 weeks and there is time for at least partial course (betamethasone 12 mg IM two doses 24 hours apart).

Pearl 4: The 48-Hour Window

When severe preeclampsia develops at 23-34 weeks, the goal is stabilization for 48 hours to allow corticosteroid administration for fetal lung maturity, not prolonged expectant management. If maternal condition deteriorates despite treatment (worsening laboratory values, uncontrolled hypertension, symptoms), proceed to delivery even if 48 hours haven't elapsed.

Special Scenarios

Aspirin Prophylaxis

Low-dose aspirin (81-162 mg daily) initiated before 16 weeks' gestation reduces preeclampsia risk by 10-15% in high-risk women. High-risk factors include history of preeclampsia, multifetal gestation, chronic hypertension, diabetes, renal disease, and autoimmune disease. The US Preventive Services Task Force recommends aspirin for women with one or more high-risk factors.

Postpartum Management

Blood pressure often worsens 3-6 days postpartum before improving. Antihypertensive medication may need adjustment. All agents used during pregnancy are safe, but ACE inhibitors and ARBs become options postpartum and are compatible with breastfeeding. Methyldopa should be discontinued postpartum due to depression risk.

Follow-up blood pressure should be checked within 72 hours of discharge and again at 7-10 days. Persistent hypertension beyond 12 weeks postpartum represents chronic hypertension.

Hack 4: The Bromocriptine Contraindication

Bromocriptine for lactation suppression is absolutely contraindicated in women with hypertensive disorders due to risk of stroke and myocardial infarction. If lactation suppression is needed, use conservative measures (ice packs, tight bra, avoiding nipple stimulation).

Future Pregnancy Counseling

Women with preeclampsia have 15-25% recurrence risk in subsequent pregnancies and elevated long-term cardiovascular risk. Preeclampsia before 34 weeks carries 40% recurrence. Recommend:

• Cardiology or primary care follow-up for cardiovascular risk assessment
• Aspirin prophylaxis in future pregnancies
• Preconception counseling with maternal-fetal medicine
• Address modifiable risk factors (obesity, metabolic syndrome)
• Consider sFlt-1/PlGF testing in future pregnancies at high-risk centers

Conclusion

Hypertensive disorders of pregnancy represent a spectrum from mild chronic hypertension to life-threatening preeclampsia with severe features. Internists must recognize that pregnancy-related hypertension differs fundamentally from essential hypertension in pathophysiology, prognosis, and management. The key principles are proper classification using gestational age thresholds, recognizing severe features that mandate intervention, treating acute severe hypertension promptly, using magnesium sulfate appropriately, and understanding that delivery is definitive treatment. By mastering these nuances—the hair-splitting distinctions between categories, the subtle signs of deterioration, and the evidence-based interventions—internists can significantly impact maternal and fetal outcomes.

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Key References

1. American College of Obstetricians and Gynecologists. Gestational Hypertension and Preeclampsia: ACOG Practice Bulletin No. 222. Obstet Gynecol. 2020;135(6):e237-e260.

2. Tita ATN, Szychowski JM, Boggess K, et al. Treatment for Mild Chronic Hypertension during Pregnancy. N Engl J Med. 2022;386(19):1781-1792.

3. Magee LA, Pels A, Helewa M, et al. Diagnosis, evaluation, and management of the hypertensive disorders of pregnancy. Pregnancy Hypertens. 2014;4(2):105-145.

4. Rolnik DL, Wright D, Poon LC, et al. Aspirin versus Placebo in Pregnancies at High Risk for Preterm Preeclampsia. N Engl J Med. 2017;377(7):613-622.

5. Sibai BM. Diagnosis, controversies, and management of the syndrome of hemolysis, elevated liver enzymes, and low platelet count. Obstet Gynecol. 2004;103(5 Pt 1):981-991.