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Medical Disorders During Pregnancy

Chapter 491 | Consultative Medicine, Hypertension, Cardiac Disease, Endocrine, Hematologic, Neurologic, Gastrointestinal, Infectious Disorders · Parts 19-20 – Consultative & Emerging Topics · Chapter 491

Key Clinical Points

  1. Preeclampsia is defined by new-onset hypertension (BP ≥140/90 mmHg) and proteinuria after 20 weeks gestation.
  2. Severe features of preeclampsia include BP ≥160/110 mmHg, end-organ damage (thrombocytopenia, liver impairment), or severe symptoms (headache, visual changes, epigastric pain).
  3. Gestational hypertension is new-onset hypertension after 20 weeks without proteinuria or preexisting chronic hypertension.
  4. Chronic hypertension is present before pregnancy or before 20 weeks gestation.
  5. GDM diagnosis uses a 2-step strategy: 50-g challenge followed by a 100-g GTT if the first step is positive (>130 mg/dL).
  6. Cardiac disease is the leading cause of maternal mortality; specific conditions like severe pulmonary hypertension or EF <30% are contraindications to pregnancy.
  7. Anticoagulation: LMWH must be stopped 12h before neuraxial analgesia; unfractionated heparin requires 24h.
  8. Thyroid management: PTU is preferred in the first trimester due to methimazole's risk of fetal aplasia cutis.
  9. Neurologic drugs: Lamotrigine and levetiracetam are first-line for epilepsy; valproate is avoided due to malformations.
  10. Hyperemesis Gravidarum (HG) may involve GDF15 and requires thiamine/folate to prevent refeeding syndrome.

DEFINITION & CLASSIFICATION

• Preeclampsia:

Definition (Harrison's 22e): new-onset hypertension (blood pressure ≥140/90 mmHg) and proteinuria (either a 24-h urinary protein >300 mg/24 h or a protein-creatinine ratio ≥0.3) after 20 weeks of gestation. ◦ Can be diagnosed without proteinuria if symptoms or lab abnormalities indicate end-organ damage. • Gestational Hypertension: New-onset hypertension after 20 weeks without proteinuria or preexisting chronic hypertension. • Chronic Hypertension: Hypertension present before pregnancy or before 20 weeks gestation. • Superimposed Preeclampsia: Occurs in women with pre-existing chronic hypertension. • Hyperemesis Gravidarum (HG): Severe form of nausea and vomiting preventing adequate fluid/nutritional intake; potentially involves GDF15.

Consultative Medicine

• Curbside Consults: Often incomplete/flawed; should be avoided as a general rule. • Telemedicine/EHR: Can improve access and reduce cost. • Second Opinions: Encouraged for reassurance or dissatisfaction. • Transfer of Care: Only if requested by the patient.

EPIDEMIOLOGY

• Hypertensive Disorders in Pregnancy (HDP): ◦ Prevalence is rising; ~16% of deliveries in 2019 were complicated by HDP. ◦ Approximately 5–7% of all pregnant women develop preeclampsia. • Diabetes Mellitus: ◦ Pre-gestational DM (pgDM) prevalence: 2.2% in obese patients vs. 0.5% in normal weight. ◦ Gestational Diabetes (GDM): Occurs in ~8% of pregnancies. • Obesity Impact: Increases risk for GDM, preeclampsia, cesarean delivery, congenital malformations, stillbirth, and neonatal death.

ETIOLOGY & PATHOPHYSIOLOGY

• Preeclampsia Pathophysiology: ◦ Potential causes: Chronic uteroplacental ischemia, exaggerated maternal inflammatory response, or imbalance of angiogenic factors. ◦ Mechanism: Excess production of sFlt-1 (antiangiogenesis) and decreased PlGF (angiogenic factor). ◦ Risk Marker: Ratio of circulating sFlt-1/PlGF ≥40 is associated with increased risk of severe features within 2 weeks. • Renal Adaptations: ◦ Normal pregnancy: 40% increase in GFR and creatinine clearance due to increased renal plasma flow. ◦ Risk: Patients with underlying renal disease may experience worsening hypertension or preeclampsia. • Metabolic Changes: ◦ Purpose: Shunt glucose/amino acids to fetus; mother uses ketones/triglycerides. ◦ Maternal State: Accelerated ketosis during fasting (lower glucose, higher hydroxybutyrate/acetoacetate). ◦ Insulin Resistance: Increased during pregnancy due to placental steroids, growth hormone variant, and placental lactogen.

CLINICAL FEATURES

• Hypertensive Disorders: ◦ Severe features include: → BP ≥160/110 mmHg → New-onset symptoms: headache (non-responsive to meds), visual changes, or unremitting severe epigastric pain. → Pulmonary edema. → Lab abnormalities: Thrombocytopenia (platelets <100 imes 10^9/L) or liver impairment (transaminases ≥2x normal). ◦ Eclampsia: Defined by generalized seizures in a patient with preeclampsia. ◦ HELLP Syndrome: Subtype of preeclampsia with severe features (hemolysis, elevated liver enzymes, low platelets). • Cardiac Disease: ◦ Leading cause of maternal mortality in the US. ◦ High-risk conditions (Contraindicated): Pulmonary hypertension, severe ventricular dysfunction (EF <30%), severe mitral/aortic stenosis, severe aortic dilation, or Fontan circulation with complications. • Neurologic Disorders: ◦ Common: Headaches, neuropathies. ◦ Life-threatening: Cerebrovascular accidents (CVA) → require MRI without gadolinium or head CT. ◦ Peripheral: Bell's palsy, carpal tunnel, meralgia paresthetica. ◦ Restless Leg Syndrome (RLS): Most common peripheral nerve/movement disorder; affects up to 20% of patients. • Gastrointestinal and Liver Disease: ◦ Nausea/vomiting: Up to 90% in first trimester. ◦ Hyperemesis Gravidarum: Requires hospitalization for dehydration/malnutrition.

DIFFERENTIAL DIAGNOSIS

• Hypertensive Disorders: → Chronic Hypertension vs. Superimposed Preeclampsia: Distinguished by prepregnancy evaluation to identify remediable causes. → Gestational Hypertension vs. Preeclampsia: Distinguished by absence of proteinuria or preexisting chronic hypertension. • Thrombocytopenia: → Benign gestational thrombocytopenia: Unlikely if platelet count <100,000/μL. → Other causes to rule out: Immune thrombocytopenia, preeclampsia, and thrombotic thrombocytopenic purpura. • Headache: → Must exclude preeclampsia for any patient with headache after 20 weeks gestation.

DIAGNOSTIC APPROACH

  1. Preeclampsia Diagnosis: Step 1: Confirm BP ≥140/90 mmHg on two measurements 4 h apart after 20 weeks. Step 2: Assess for proteinuria (24-h urine >300 mg/24 h OR protein-creatinine ratio ≥0.3). Step 3: If no proteinuria, check for end-organ damage signs (severe HTN ≥160/110, thrombocytopenia <100 imes 10^9/L, transaminases ≥2x normal, or symptoms like visual changes).
  2. Gestational Diabetes (GDM) Diagnosis: Step 1: 50-g oral glucose challenge at 24–28 weeks. Step 2: If result >130 mg/dL → perform 100-g GTT. Step 3: Evaluate 100-g GTT results (Fasting <95, 1h <180, 2h <155, 3h <140). Step 4: Two elevated values → positive diagnosis of GDM.
  3. Thyroid Function: Step 1: Measure free T4, free T3, and TSH using trimester-specific ranges.
  4. Infectious Disease Screening: Step 1: Screen for Syphilis, Gonorrhea, Chlamydia. Step 2: Screen for Hep B, Hep C, HIV. Step 3: Assess immunity to Rubella and Varicella (Varicella check via history first; antibody test only if no history).
  5. Anemia/Hemoglobinopathy: Step 1: First trimester and 24–28 weeks screening. Step 2: Measure ferritin to detect iron deficiency before anemia develops. Step 3: Hemoglobinopathy screen (MCV, MCH, ferritin, hemoglobin analysis).

MANAGEMENT & TREATMENT

  1. Hypertension Management: Step 1: Target BP <140/90 mmHg. Step 2: Prophylaxis → Low-dose aspirin between 12–14 weeks for high-risk patients. Step 3: Pharmacotherapy → Labetalol or extended-release nifedipine (avoid ACE inhibitors and ARBs). Step 4: Preeclampsia without severe features → manage expectantly until 37 weeks. Step 5: Preeclampsia with severe features → delivery recommended unless <34 weeks in a tertiary center. Step 6: Delivery before 34 weeks if: unremitting symptoms, lab abnormalities, or severe BP refractory to meds.
  2. Diabetes Management: Step 1: GDM → start with nutritional therapy and weight management. Step 2: If targets not met → Insulin (preferred due to safety). Step 3: Alternatives for those declining insulin → Metformin or Glyburide. Step 4: Adjust insulin based on trimester (1st: 0.7–0.8 u/kg; 2nd: 0.8–1.0 u/kg; 3rd: 0.9–1.2 u/kg).
  3. Thyroid Management: Step 1: Hyperthyroidism → PTU (preferred in 1st trimester) or Methimazole. Step 2: Hypothyroidism → Thyroxine (increase dose by 30% upon diagnosis of pregnancy). Step 3: Contraindication → No radioiodine during pregnancy.
  4. VTE Management: Step 1: Use LMWH or unfractionated heparin. Step 2: Prophylactic LMWH → stop 12 h before epidural. Step 3: Therapeutic LMWH → stop 24 h before epidural.
  5. Neurologic Management: Step 1: Epilepsy → Lamotrigine or levetiracetam (avoid Valproate).

Hypertension Medication Table

Table 3 Summary: • Labetalol: Variable dose, BID/TID; Side effect: Bradycardia. • Nifedipine (ER): Variable dose, Daily; Side effect: Edema. • ACE/ARBs: Contraindicated due to fetal anomalies.

Insulin Dosing Table

Table 4 Summary: • 1st Trimester: 0.7–0.8 units/kg • 2nd Trimester: 0.8–1.0 units/kg • 3rd Trimester: 0.9–1.2 units/kg

Thyroid Medication Table

Table 5 Summary: • Hyperthyroidism (PTU): Preferred in 1st trimester; risk of liver failure. • Hyperthyroidism (Methimazole): Risk of fetal aplasia cutis. • Hypothyroidism (Thyroxine): Dose must increase during pregnancy.

COMPLICATIONS & PROGNOSIS

• Long-term Cardiovascular Risk: Pregnancy can have implications for long-term health; preeclampsia and hypertension are linked to cardiovascular risk. • Diabetes Long-term Risk: Metformin may lead to higher adiposity in children compared to insulin/glyburide, but insulin is preferred due to unknown long-term effects of other agents.

SPECIAL POPULATIONS

• Contraindications to Pregnancy: Pregnancy is contraindicated in: → Pulmonary hypertension → Severe ventricular dysfunction (EF <30% or NYHA class III–IV) → Severe mitral or aortic stenosis → Severe aortic dilation → Fontan circulation with severe complications. • Weight Gain Guidelines: Obesity increases risk for GDM, preeclampsia, and adverse neonatal outcomes.

KEY PEARLS & HIGH-YIELD POINTS

• Consultative Medicine: Avoid 'curbside' consults as they are often incomplete; use telemedicine or formal consultations. • Aortic Pathology: High risk of mortality in severe aortic dilation or stenosis; requires multidisciplinary heart team planning. • Neurologic Pearls: Differentiate benign symptoms (RLS, carpal tunnel) from life-threatening ones (CVA). → If CVA suspected: Use MRI without gadolinium or head CT.