Signs of Iron Deficiency Without Anemia in Pregnancy
Iron deficiency without anemia in pregnancy presents primarily with non-specific symptoms including fatigue, reduced exercise capacity, poor quality of life, pagophagia (ice craving), and restless leg syndrome, though these symptoms often overlap with normal pregnancy complaints. 1
Clinical Manifestations
Iron deficiency represents a spectrum from iron depletion to iron-deficient erythropoiesis to frank anemia, and symptoms can occur before hemoglobin drops below diagnostic thresholds. 2
Primary Symptoms
- Fatigue and reduced working capacity - This is the most common presenting symptom, though it can be difficult to distinguish from normal pregnancy-related tiredness 3, 1
- Pagophagia (ice craving) - A specific form of pica that is highly suggestive of iron deficiency even without anemia 1
- Restless leg syndrome - An uncomfortable sensation in the legs that worsens at rest 1
- Poor quality of life - General malaise and reduced functional capacity 1
Neurological and Cognitive Effects
- Impaired neurocognitive function - Iron deficiency affects brain development and function even before anemia develops 4
- Mood disturbances - Iron is essential for neurotransmitter synthesis including serotonin, norepinephrine, and dopamine 4
Diagnostic Considerations
The challenge in pregnancy is that standard hemoglobin/hematocrit screening may miss iron deficiency without anemia, as these tests only detect anemia once iron stores are severely depleted. 4
Laboratory Findings in Iron Deficiency Without Anemia
- Normal hemoglobin (≥11.0 g/dL first trimester, ≥10.5 g/dL second/third trimester) but depleted iron stores 5
- Low serum ferritin - Though this marker has limitations in pregnancy as it decreases in late pregnancy despite adequate bone marrow iron stores 4
- Serum ferritin is an acute phase reactant, which can be falsely elevated in the presence of inflammation or infection 4
Prevalence and Risk Factors
Based on NHANES data, 18.6% of pregnant women have iron deficiency, but only 16.2% of those also have anemia, meaning a substantial proportion have iron deficiency without meeting anemia criteria. 4
High-risk groups include:
- Women with diets lacking iron-rich foods (vegetarian/vegan diets) 4, 2
- Non-Hispanic Black and Mexican American women 4
- Women with gastrointestinal conditions or medications that decrease iron absorption (e.g., antacids) 4
- Women with short intervals between pregnancies 4
- Women with parity of 2 or more 4
Clinical Implications
Both iron deficiency with and without anemia are associated with adverse outcomes, including impaired neurocognitive development in children and suboptimal immune responses. 4
Maternal Risks
- Increased risk of preterm labor 1
- Higher rates of cesarean delivery 1
- Increased postpartum hemorrhage risk 1
- Greater likelihood of requiring blood transfusion at delivery 5
Fetal and Neonatal Risks
- Intrauterine growth retardation 6
- Low birth weight 4, 1
- Small for gestational age newborns 1
- Compromised memory, processing, and bonding in the newborn, with some deficits persisting into adulthood 1
- Possible association with autism spectrum disorders (though causation not established) 1
Common Pitfalls
The most significant pitfall is relying solely on hemoglobin/hematocrit screening, which misses the substantial population with iron deficiency without anemia. 4 The USPSTF notes that evidence is insufficient regarding routine screening and supplementation benefits, yet the CDC recommends universal low-dose supplementation (30 mg/day) starting at the first prenatal visit as primary prevention. 4
Another critical issue is that physiologic hemodilution during pregnancy makes determining exact prevalence rates difficult, as normal pregnancy causes hemoglobin dilution that can be mistaken for pathologic anemia or mask true iron deficiency. 4