13.2 Hypertensive Disorders of Pregnancy & Gestational Diabetes

1. Hypertensive Disorders of Pregnancy

Hypertensive disorders complicate up to 10% of pregnancies and represent a leading cause of maternal and perinatal morbidity and mortality worldwide.

Clinical Spectrum & Diagnostic Criteria

1. Chronic Hypertension:
   • Systolic BP >= 140 mmHg and/or Diastolic BP >= 90 mmHg diagnosed prior to pregnancy or before 20 weeks of gestation, or persisting >12 weeks postpartum.
   • CHAP Trial Benchmark: In pregnant women with mild chronic hypertension, treating to a blood pressure target of <140/90 mmHg (target 110-135/85 mmHg) significantly reduces the risk of preeclampsia, preterm birth, placental abruption, and fetal/neonatal death without impairing fetal growth.
   • First-line oral agents: Labetalol (100-800 mg PO BID-TID), Extended-Release Nifedipine (30-90 mg PO daily), and Methyldopa (250-1000 mg PO BID-TID).
2. Gestational Hypertension:
   • New-onset systolic BP >= 140 mmHg and/or diastolic BP >= 90 mmHg on two occasions at least 4 hours apart developing after 20 weeks of gestation in a previously normotensive woman, without proteinuria or systemic severe features.
3. Preeclampsia:
   • New-onset hypertension (SBP >= 140 or DBP >= 90 mmHg after 20 weeks) PLUS Proteinuria:

     • = 300 mg per 24-hour urine collection, OR

     • Urine Protein-to-Creatinine Ratio (UPCR) >= 0.3 mg/mg (30 mg/mmol), OR
     • Urine dipstick protein >= 2+ (used only if quantitative methods unavailable).
   • Preeclampsia in the Absence of Proteinuria: Diagnosed when new-onset hypertension after 20 weeks is accompanied by any Severe Feature:
     • Severe Blood Pressure: SBP >= 160 mmHg or DBP >= 110 mmHg on 2 occasions >=15 minutes apart
     • Thrombocytopenia: Platelet count < 100,000 /µL
     • Impaired Liver Function: Serum transaminases (AST/ALT) > 2x upper limit of normal, or severe persistent right upper quadrant / epigastric pain unresponsive to analgesics
     • Renal Insufficiency: Serum creatinine > 1.1 mg/dL or a doubling of serum creatinine in the absence of other underlying renal disease
     • Pulmonary Edema
     • New-Onset Cerebral or Visual Disturbances: Photopsia, scotomata, cortical blindness, severe persistent throbbing headache unresponsive to acetaminophen
4. Eclampsia:
   • Development of new-onset generalized tonic-clonic seizures in a woman with preeclampsia, in the absence of other neurological conditions (epilepsy, intracranial hemorrhage, encephalitis).
5. HELLP Syndrome:
   • Severe variant of preeclampsia characterized by:
     • Hemolysis: Microangiopathic hemolytic anemia with schistocytes on peripheral smear, elevated total bilirubin >=1.2 mg/dL, and elevated LDH > 600 U/L
     • Elevated Liver enzymes: Serum AST or ALT >= 2x upper limit of normal
     • Low Platelets: Thrombocytopenia with platelet count < 100,000 /µL

Preeclampsia Prevention with Low-Dose Aspirin

• Indication: Recommended for women at high risk of preeclampsia (history of preeclampsia, multifetal gestation, chronic hypertension, pregestational type 1 or 2 diabetes, chronic kidney disease, autoimmune disease [SLE, antiphospholipid syndrome]). Also recommended if >=2 moderate risk factors (nulliparity, obesity BMI >30, maternal age >=35, black race, low socioeconomic status).
• Regimen: Low-dose Aspirin (81 to 162 mg daily) initiated between 12 and 16 weeks of gestation (and before 28 weeks) and continued daily until delivery.

Acute Management of Severe Preeclampsia & Eclampsia

+-----------------------------------------------------------------------------------+
|              ACUTE MANAGEMENT OF SEVERE PREECLAMPSIA / ECLAMPSIA                  |
+-----------------------------------------------------------------------------------+
| 1. SEIZURE PROPHYLAXIS: Intravenous Magnesium Sulfate                             |
|    - Loading Dose: 4 to 6 g IV over 15-20 minutes                                 |
|    - Maintenance Dose: 1 to 2 g/hour continuous IV infusion                       |
|    - Duration: Maintain throughout labor and for 24 hours postpartum              |
|    - Monitoring: Patellar reflexes (loss at 9-12 mg/dL), RR (>12/min),            |
|                  urine output (>=30 mL/hr; Mg is cleared 100% renally)           |
|    - Toxicity Antidote: IV Calcium Gluconate (1 g IV 10% solution over 5 min)     |
+-----------------------------------------------------------------------------------+
| 2. URGENT ANTIHYPERTENSIVE THERAPY (SBP >=160 or DBP >=110 mmHg >=15 min)          |
|    - IV Labetalol: 20 mg IV initial -> 40 mg at 10 min -> 80 mg q10m (max 300 mg) |
|    - IV Hydralazine: 5-10 mg IV initial -> 10 mg at 20 min (max 20-30 mg)         |
|    - Oral Nifedipine IR: 10-20 mg PO (repeat in 20-30 min PRN; avoid sublingual)  |
+-----------------------------------------------------------------------------------+
| 3. DEFINITIVE TREATMENT: Planned Delivery                                         |
|    - >=34 0/7 weeks with severe features: Prompt delivery after stabilization     |
|    - Maternal/fetal instability (eclampsia, HELLP, pulmonary edema, abruption,   |
|      non-reassuring fetal tracing): Immediate delivery at ANY gestational age     |
|    - Without severe features: Planned delivery at 37 0/7 weeks                    |
+-----------------------------------------------------------------------------------+

2. Gestational Diabetes Mellitus (GDM)

Pathophysiology & Screening Protocols

During normal pregnancy, placental secretion of diabetogenic hormones—predominantly Human Placental Lactogen (hPL), progesterone, cortisol, and prolactin—induces physiologic maternal peripheral insulin resistance to facilitate glucose shunting to the developing fetus. Gestational Diabetes Mellitus (GDM) develops when maternal pancreatic beta-cell insulin secretion is insufficient to overcome this pregnancy-induced insulin resistance.

• Universal Screening at 24 to 28 Weeks Gestation:
  • Two-Step Approach (ACOG / Carpenter-Coustan Criteria):
    • Step 1: 1-hour 50g non-fasting oral Glucose Challenge Test (GCT). If plasma glucose is >= 130 to 140 mg/dL, proceed to Step 2.
    • Step 2: 3-hour 100g diagnostic oral Glucose Tolerance Test (OGTT) performed after an overnight 8-hour fast. Diagnosis is established if >= 2 values meet or exceed the following cutoffs:
      • Fasting: >= 95 mg/dL (5.3 mmol/L)
      • 1-hour: >= 180 mg/dL (10.0 mmol/L)
      • 2-hour: >= 155 mg/dL (8.6 mmol/L)
      • 3-hour: >= 140 mg/dL (7.8 mmol/L)
  • One-Step Approach (IADPSG / ADA Criteria): Fasting 2-hour 75g OGTT. Diagnosis is established if >= 1 value is abnormal: Fasting >=92 mg/dL, 1-hour >=180 mg/dL, or 2-hour >=153 mg/dL.

Glycemic Targets in Pregnancy

• Fasting blood glucose: < 95 mg/dL (5.3 mmol/L)
• 1-hour postprandial blood glucose: < 140 mg/dL (7.8 mmol/L)
• 2-hour postprandial blood glucose: < 120 mg/dL (6.7 mmol/L)
• HbA1c target: < 6.0% to 6.5%

Stepwise Management of GDM

1. First-Line Lifestyle & Medical Nutrition Therapy (MNT):
   • Individualized dietary counseling with controlled carbohydrate distribution (33-40% complex low-glycemic carbohydrates, 20% protein, 40% healthy fats) distributed across 3 meals and 2-3 snacks.
   • Moderate postprandial physical activity (e.g., 30 minutes of brisk walking daily).
   • Blood glucose monitoring 4 times daily (fasting and 1- or 2-hour postprandial after each meal).
2. Pharmacotherapy:
   • Indicated if >20% of blood glucose values exceed targets on MNT alone over 1 to 2 weeks.
   • Insulin is the Gold Standard First-Line Medication: Insulin does not cross the placenta and provides precise glycemic titration. Typical starting dose is 0.7-1.0 units/kg/day in divided basal-bolus regimens (e.g., NPH or Detemir basal plus Lispro or Aspart rapid-acting prandial insulin).
   • Oral Agents (Second-Line):
     • Metformin: Crosses the placenta freely (fetal levels equal maternal levels). Associated with lower maternal weight gain and lower neonatal hypoglycemia compared to insulin, but has higher treatment failure rates requiring supplemental insulin (~30-40%) and potential long-term childhood metabolic impact (slightly higher childhood BMI).
     • Glyburide (Sulfonylurea): Crosses the placenta and is associated with increased rates of neonatal hypoglycemia and fetal macrosomia compared to insulin.
3. Postpartum Screening & Long-Term Risks:
   • Women with GDM have a 50% to 70% lifetime risk of developing overt Type 2 Diabetes.
   • All women with GDM must undergo a 2-hour 75g oral glucose tolerance test at 4 to 12 weeks postpartum to screen for persistent diabetes or impaired glucose tolerance.
   • If postpartum OGTT is normal, repeat glycemic screening every 1 to 3 years indefinitely.

5. Peripartum Cardiomyopathy

Peripartum cardiomyopathy is explicitly enumerated in the pregnancy blueprint subsection, and it is a diagnosis internists are positioned to make because the presenting symptoms are routinely attributed to normal late pregnancy.

Definition: new systolic heart failure with a left ventricular ejection fraction below 45%, developing in the last month of pregnancy or within five months postpartum, in a woman with no previously known structural heart disease and no other identifiable cause.

Why it is missed: dyspnea, orthopnea, fatigue and lower-extremity edema are all features of normal late pregnancy and the early puerperium. The findings that should prompt echocardiography rather than reassurance are paroxysmal nocturnal dyspnea, an S3 gallop, elevated jugular venous pressure, resting tachycardia, hypoxemia, and symptoms that worsen rather than improve after delivery.

Risk factors: advanced maternal age, multiparity, multiple gestation, preeclampsia and hypertensive disorders of pregnancy, African ancestry, and prolonged tocolytic therapy.

Evaluation: echocardiography is the key test. Natriuretic peptides are elevated and, although interpretation in pregnancy requires care, a normal natriuretic peptide level makes the diagnosis unlikely. Exclude pulmonary embolism, amniotic fluid embolism, severe preeclampsia with pulmonary edema, and pre-existing cardiomyopathy unmasked by the hemodynamic load of pregnancy.

Management differs before and after delivery:

Prognosis and counseling: roughly half of women recover ventricular function, most within six months, and recovery is more likely when the initial ejection fraction is higher. Subsequent pregnancy carries a substantial risk of relapse and of death, and that risk is markedly higher in women whose ejection fraction has not normalized. Pre-conception counseling with cardiology and maternal-fetal medicine is essential, and effective contraception should be provided in the interim. Guideline-directed therapy should not be stopped as soon as the ejection fraction normalizes, since withdrawal is associated with relapse.