What is the differential diagnosis and workup for a 27-year-old female in her 3rd trimester of pregnancy presenting with fever, sweats, and chills for 3 days?

Differential Diagnosis and Workup for Third Trimester Fever

For a 27-year-old woman in her third trimester presenting with 3 days of fever, sweats, and chills, the most critical immediate step is obtaining a detailed exposure history including livestock contact, sick contacts, travel, and occupational exposures to guide empiric treatment, while simultaneously ruling out pregnancy-specific liver diseases and common infections like pyelonephritis and influenza. 1

Key Differential Diagnoses

Pregnancy-Specific Conditions (Third Trimester)

• Intrahepatic cholestasis of pregnancy: Presents with pruritus and elevated bile acids >10 µmol/L, though fever is not typical 2
• Acute fatty liver of pregnancy (AFLP): Occurs week 29 and beyond, can present with fever and liver dysfunction 2
• HELLP syndrome: Typically presents between weeks 27-37 with hemolysis, elevated liver enzymes, and low platelets 2
• Preeclampsia: Occurs after 20 weeks gestation, though fever is not a primary feature 2
• Chorioamnionitis: Presents with fever, maternal tachycardia, fetal tachycardia, uterine tenderness, and purulent/foul-smelling amniotic fluid 3

Infectious Etiologies (Most Common)

• Common viral infections: Account for 37% of fever cases in pregnancy 4
• Influenza: Represents 21% of fever cases and can mimic chorioamnionitis with fever, chills, and uterine contractions 4, 5
• Pyelonephritis: Accounts for 11% of fever cases; presents with fever >38°C, chills, flank pain, costovertebral angle tenderness 4, 2
• Q fever: Critical to consider with any livestock exposure; causes fever with high risk for miscarriage, premature delivery, and intrauterine growth retardation in pregnancy 1
• Viral gastroenteritis: Represents 6% of cases 4
• Listeriosis: Must be considered though rare; associated with fever and can cause severe fetal complications 4

Essential Initial Workup

Immediate History and Physical Examination

• Exposure history: Specifically ask about livestock contact (Q fever risk), sick contacts, recent travel, occupational exposures 1
• Respiratory symptoms: Perform chest radiography if present to evaluate for pneumonia including Q fever pneumonia (>96% show radiographic abnormalities) 1
• Urinary symptoms: Assess for dysuria, frequency, urgency, flank pain suggesting pyelonephritis 2
• Obstetric symptoms: Evaluate for uterine tenderness, contractions, fetal tachycardia, purulent/foul-smelling discharge suggesting chorioamnionitis 3
• Pruritus: Ask about itching which may indicate intrahepatic cholestasis of pregnancy 2

Laboratory Evaluation

• Complete blood count: Essential baseline; most acute infections show normal white blood cell counts, though leukocytosis may suggest bacterial infection 1
• Liver function tests: Elevated transaminases occur in up to 85% of Q fever cases and help identify pregnancy-specific liver diseases 1, 2
• Serum bile acids: If pruritus present, levels >10 µmol/L diagnose intrahepatic cholestasis of pregnancy 2
• Urinalysis and urine culture: Mandatory to rule out pyelonephritis; assess white/red blood cells and nitrite 2
• Blood cultures: If fever >38.7°C (101.6°F) or patient appears septic 6
• Q fever serology: Phase I and Phase II IgG and IgM antibodies if any livestock exposure or unexplained fever 1
• Influenza testing: Given 21% prevalence in pregnant women with fever 4

Imaging Studies

• Renal ultrasound: First-line imaging for suspected pyelonephritis to rule out obstruction or stones; no radiation risk 2
• Abdominal ultrasound: Preferred imaging modality in pregnancy; can detect free peritoneal fluid and intestinal wall edema in various conditions 2
• Chest radiography: If respiratory symptoms present, safe in pregnancy with appropriate shielding 1
• MRI without gadolinium: If ultrasound inadequate and further imaging needed; preferred over CT to avoid radiation 2

Critical Management Considerations

When to Treat Empirically

• Q fever with livestock exposure: Start trimethoprim-sulfamethoxazole 160mg/800mg twice daily immediately if any livestock exposure and fever; reduces adverse fetal outcomes from 81% to 40% 1
• Pyelonephritis: Prompt empiric treatment with fluoroquinolones or cephalosporins (oral cephalosporins achieve lower concentrations than IV route) 2
• Suspected chorioamnionitis: Initiate antibiotics with anaerobic coverage if clinical criteria met (fever plus ≥2 of: maternal tachycardia, fetal tachycardia, uterine tenderness, purulent fluid, leukocytosis) 6, 3

Antipyretic Management

• Acetaminophen: First-line and only safe antipyretic during pregnancy; may provide protective effects against fever-related fetal harm 1
• Avoid NSAIDs: Not recommended in third trimester due to risk of premature ductus arteriosus closure

Antibiotics to Avoid in Pregnancy

• Doxycycline: Contraindicated due to effects on fetal bone and teeth development 1, 2
• Fluoroquinolones: Generally avoided in pregnancy though may be used for pyelonephritis when benefits outweigh risks 2

Common Pitfalls to Avoid

• Delaying Q fever treatment: Do not wait for serologic confirmation if livestock exposure present; empiric treatment dramatically improves outcomes 1
• Assuming viral without workup: 15% of fever cases in pregnancy have unknown etiology; 11% are pyelonephritis requiring antibiotics 4
• Over-prescribing antibiotics for presumed Listeria: In one study, 59% of patients received empiric amoxicillin for presumed Listeria; none had confirmed listeriosis 4
• Missing pregnancy-specific liver diseases: Any elevation in aminotransferases, bilirubin, or bile acids is abnormal in pregnancy and requires investigation 2
• Ignoring influenza: Can mimic chorioamnionitis with fever, chills, uterine tenderness, and contractions; transplacental infection is documented 5

Follow-up and Monitoring

• Reassess if symptoms persist >10 days: Watch for high fever >39°C with purulent nasal discharge or facial pain ≥3 consecutive days suggesting bacterial sinusitis 1
• Q fever monitoring: If diagnosed, continue trimethoprim-sulfamethoxazole with folic acid supplementation throughout pregnancy; perform serologic monitoring at 3,6,12,18, and 24 months postpartum to detect chronic disease progression 1
• Fetal monitoring: Increased surveillance for patients with confirmed infections, particularly Q fever which carries high risk for intrauterine growth retardation and premature delivery 1