What is the differential diagnosis and management for fatigue in pregnancy?

Differential Diagnosis for Fatigue in Pregnancy

Fatigue in pregnancy requires systematic evaluation for physiologic pregnancy changes, anemia, thyroid dysfunction, sleep disorders, depression/anxiety, and cardiovascular complications including preeclampsia—with management focused on treating reversible causes while recognizing that first and third trimester fatigue is nearly universal and often physiologic.

Physiologic Fatigue of Pregnancy

Fatigue affects 94.2% of pregnant women and represents a normal adaptation to pregnancy in most cases 1. The pattern is characteristically:

• First trimester: Severe fatigue due to increased oxygen consumption, rapid fetal development, cardiovascular adaptations, and rising progesterone levels 2, 3
• Second trimester: Relative improvement with energy levels often normalizing 3
• Third trimester: Recurrence of fatigue related to reduced total sleep, increased metabolic demands, and mechanical factors from the enlarging uterus 1, 3

Younger maternal age and lower prepregnancy iron stores predict more severe first trimester fatigue 3. Reduced sleep quantity directly correlates with third trimester and postpartum fatigue severity 3.

Critical Pathologic Causes Requiring Urgent Evaluation

Preeclampsia and Cardiovascular Disease

Fatigue accompanied by headache, visual disturbances, right upper quadrant pain, or hyperreflexia after 20 weeks gestation mandates immediate blood pressure assessment and evaluation for preeclampsia 4. Preeclampsia complicates 5-7% of pregnancies (25% in women with pre-existing hypertension) and presents with:

• New-onset hypertension ≥140/90 mmHg after 20 weeks 4
• Proteinuria >0.3 g/24 hours 4
• Severe features: cerebral edema (headache, visual changes, occipital blindness), hepatic involvement (RUQ pain), HELLP syndrome 4

Anemia

Obtain complete blood count, ferritin, and hemoglobin levels, as low prepregnancy iron stores and anemia directly cause fatigue throughout pregnancy and postpartum 3. Treat based on etiology with iron supplementation or other appropriate interventions 5, 6.

Thyroid Dysfunction

Screen thyroid function (TSH, free T4) as hypothyroidism commonly presents with fatigue and requires thyroid hormone replacement 6.

Systematic Evaluation Approach

Initial Screening

Use a 0-10 numeric rating scale to quantify fatigue severity 5, 6:

• Mild (1-3/10): Provide education about normal pregnancy fatigue patterns and energy conservation strategies 5
• Moderate (4-6/10): Proceed to focused evaluation for contributing factors 5, 6
• Severe (7-10/10): Conduct comprehensive evaluation immediately and consider urgent specialist referral 5, 6

Focused History

Document specific details about 6:

• Onset timing (trimester), pattern, duration, and changes over time
• Associated symptoms: pain, dyspnea, fever, neurologic changes, weight loss
• Sleep quality and quantity (sleep disturbances affect 30-75% of fatigued pregnant women) 5
• Mood symptoms suggesting depression or anxiety 4

Critical pitfall: Fatigue, appetite changes, reduced concentration, and psychomotor changes overlap between normal pregnancy and depression—use validated screening tools rather than clinical impression alone 4.

Physical Examination

Perform targeted assessment for 5, 6:

• Blood pressure measurement (hypertensive disorders complicate 15% of pregnancies) 4
• Neurologic examination for focal findings, muscle weakness, abnormal reflexes, or hyperreflexia 4, 5
• Signs of thyroid disease, anemia (pallor, tachycardia), or edema

Laboratory Evaluation

Obtain 5, 6, 3:

• Complete blood count with differential
• Ferritin and hemoglobin
• Thyroid function tests (TSH, free T4)
• Urinalysis for proteinuria if hypertension present 4
• Consider comprehensive metabolic panel if moderate-to-severe fatigue persists

Management Strategy

Treat Reversible Causes First

Address all identified contributing factors before considering fatigue as purely physiologic 6:

• Anemia: Iron supplementation or treatment based on etiology 5, 6, 3
• Hypothyroidism: Thyroid hormone replacement 6
• Depression/anxiety: Selective serotonin reuptake inhibitors or appropriate psychiatric intervention 5, 6
• Sleep disorders: Formal polysomnography if obstructive or central sleep apnea suspected 5
• Preeclampsia: Antihypertensive therapy, close monitoring, delivery planning 4, 7

Nonpharmacologic Interventions for Physiologic Fatigue

Implement structured approach including 5, 8:

• Activity-rest program: Balance activity with adequate rest periods, limit daytime naps to 20-30 minutes to preserve nighttime sleep quality 4, 2
• Sleep hygiene optimization: Consistent bedtime routine, sleep-conducive environment, avoidance of sleep disruptors 5
• Energy conservation: Prioritize essential activities, postpone nonessential tasks 4
• Structured exercise program: Stretching and aerobic exercise as tolerated (with caution for bone metastases, thrombocytopenia, or active infection in cancer patients—not typically applicable to pregnancy) 4, 5

Patient Education

Counsel women that 8, 2, 3:

• First trimester fatigue is nearly universal and represents normal physiologic adaptation
• Fatigue typically improves in second trimester
• Third trimester fatigue recurrence is expected due to sleep disruption and increased metabolic demands
• Adequate rest and sleep are essential—prepare work and home environments accordingly

Follow-Up and Monitoring

• Rescreen fatigue severity at each prenatal visit 6
• Monitor for new symptoms suggesting pathologic causes 6
• Reassess after treating identified contributing factors 6
• Pursue additional investigation if fatigue remains moderate-to-severe (≥4/10) despite treatment or if new concerning symptoms develop 5, 6

Specialist Referral Indications

Urgent referral required for 5:

• Severe hypertension or preeclampsia features 4, 7
• Neurologic abnormalities (focal findings, severe tone abnormalities)
• Hematologic concerns (WBC >20,000/mm³)

Routine referral for 5:

• Persistent moderate-to-severe fatigue despite addressing treatable factors
• Sleep disorders requiring polysomnography
• Psychiatric evaluation for depression/anxiety