Anemia During Pregnancy

1. Physiologic Basis - Why Anemia is Expected in Pregnancy

Note: Women with Hb of 13-15 g/dL may actually have inadequate plasma volume expansion, which itself is associated with low birthweight and preterm birth.

2. Types of Anemia in Pregnancy

3. Iron Deficiency Anemia (IDA)

Pathophysiology

• Iron requirements increase substantially during pregnancy (fetal/placental needs + expanded maternal RBC mass)
• Women enter pregnancy with marginal iron stores: ~50% of primigravidas have minimal marrow iron in the first trimester
• Incidence of iron deficiency rises from 18% in T1 to 29% in T3 (NHANES data)
• Only 6% of iron-deficient women are also anemic - Hb alone is insufficient screening

Clinical Features

• Symptoms: fatigue, lethargy, headache, pica (craving clay, ice, starch)
• Signs: pallor, glossitis, cheilitis, koilonychia (rare)
• Lab: microcytic (low MCV), hypochromic (low MCHC), low serum iron, high TIBC, low serum ferritin (most sensitive test - cutoff of 30 ng/mL gives 92% sensitivity, 98% specificity)

Risks of Severe IDA (Hb < 6-7 g/dL)

• Increased fetal mortality
• Preterm birth and low birthweight
• Premature rupture of membranes
• Gestational hypertension
• Reduced amniotic fluid volume
• Neonatal anemia (2024 meta-analysis PMID 39425056 confirms association between maternal and neonatal anemia)

Treatment of IDA

• Ferrous sulfate 325 mg 1-3x/day (most common in US)
• WHO recommends 60 mg elemental iron/day + folic acid
• Single daily dosing is as effective as multiple doses and reduces GI side effects (nausea, constipation, GERD)
• Intermittent dosing (2-3x/week) has equivalent efficacy with fewer side effects
• Reticulocytosis expected at 7-10 days; Hb can rise ~1 g/week in severe cases
• Absorption enhanced by 500 mg ascorbic acid co-administration
• Continue for 6 months after Hb normalizes to replete stores
• Consider vitamin B6 supplementation in non-responders

• Not used in the first trimester
• Treatment of choice for all IDA in the third trimester
• Severe IDA (Hb < 9 g/dL) in the second trimester
• Indications also include malabsorption, oral iron intolerance, need for rapid repletion

• Test dose only required for low-molecular-weight iron dextran
• Dose formula: Weight (kg) x (Target Hb - Actual Hb) x 0.24 + 500 mg; target Hb = 11-12 g/dL

• ACOG, WHO, and major health authorities recommend ≥30 mg ferrous iron daily during all pregnancies

4. Folate Deficiency Anemia

• Folate requirements increase 5-10 fold in pregnancy (for rapid cell division)
• Megaloblastic (macrocytic) anemia - the second most common type
• Higher risk with: multiple gestations, short interpregnancy interval, malnutrition, hyperemesis gravidarum, malabsorption, antiepileptic drug use, alcoholism, poor diet
• Key consequence: Low folate is strongly linked to neural tube defects; also associated with placental abruption, preeclampsia, preterm birth, spontaneous abortion

• 0.4 mg/day - routine supplementation for all pregnant women
• 1.0 mg/day - known pregnancy-related folate deficiency
• 4.0 mg/day - prior neural tube defect pregnancy (starting 1 month before conception through 12 weeks GA)
• Continue throughout 2nd and 3rd trimesters per ACOG

5. Sickle Cell Disease (SCD) and Hemoglobinopathies

Sickle Cell Disease

• Pregnant women with SCD have a 6-fold increased risk of maternal death vs. controls
• Maternal complications: more frequent painful crises, preterm labor, PROM, infections, VTE (1.7-10x higher), preeclampsia, increased cesarean rate
• Fetal complications: placental infarction/insufficiency, low birthweight, small-for-gestational-age, preterm birth

• Vasoocclusive crises: treat as in nonpregnant patients
• Hydroxyurea is CONTRAINDICATED (known teratogenicity)
• NSAIDs avoided after 30 weeks gestation
• Regional anesthesia preferred for cesarean (general anesthesia increases post-op sickling)
• Iron supplementation and transfusion are controversial - risk of iron overload
• VTE prophylaxis should be considered

Thalassemias

• Alpha-thalassemia: MCV disproportionately low relative to Hb degree; normal RBC count; normal/mildly elevated RDW - key distinction from IDA (which shows proportional MCV-Hb drop, low RBC count, elevated RDW)
• Hb Bart's hydrops fetalis (all 4 alpha genes deleted) = incompatible with extrauterine life
• Beta-thalassemia: Diagnosed via Hb HPLC (elevated HbA2 > 3.5%); partner testing and genetic counseling essential

6. Laboratory Evaluation

7. Fetal Impact

Summary

• Dilutional anemia is normal in pregnancy - treat only when iron deficient or symptomatic
• IDA accounts for ~75% of all pregnancy anemias; ferritin < 30 ng/mL is the most sensitive diagnostic marker
• Oral iron is first-line; IV iron preferred in T3 or severe anemia in T2
• Folate 0.4-4 mg/day (dose-dependent on risk) prevents megaloblastic anemia and neural tube defects
• SCD requires vigilant maternal monitoring; hydroxyurea is contraindicated
• Screen all women for thalassemia if CBC shows thalassemic indices (low MCV, normal/high RBC count, normal RDW)

Anemia in Pregnancy — 15 Marks Examination Answer

Definition

Physiological Basis (Why Anemia Occurs)

• Plasma volume increases by 47%
• RBC mass increases by only 17%

The Hb nadir occurs between 26-34 weeks of gestation.

Classification / Types

1. Iron Deficiency Anemia (IDA)

Etiology

• Increased iron demand: fetal growth, placenta, expanded maternal RBC mass
• Poor prepregnancy iron stores (50% of primigravidas have minimal marrow iron)
• Inadequate dietary intake

Clinical Features

• Symptoms: Fatigue, lethargy, headache, pica (craving clay, ice, starch - classic)
• Signs: Pallor, glossitis, cheilitis, koilonychia (rare), angular stomatitis

Diagnosis

• Microcytic, hypochromic picture on peripheral smear
• Low MCV, low MCHC, low serum iron, high TIBC
• Serum ferritin - most sensitive test (cutoff < 30 ng/mL: sensitivity 92%, specificity 98%)
• Low transferrin saturation (< 16%)
• Bone marrow: absent stainable iron (gold standard, rarely done)

Maternal and Fetal Complications

• Preterm birth, low birthweight
• Premature rupture of membranes (PROM)
• Gestational hypertension
• Reduced amniotic fluid
• Increased maternal mortality
• Neonatal anemia (directly correlated to maternal iron status)

Treatment

• Ferrous sulfate 325 mg once to three times daily
• Single daily dose as effective as multiple doses; reduces GI side effects
• Reticulocytosis expected at 7-10 days; Hb rises ~1 g/week
• Add 500 mg ascorbic acid to enhance absorption
• Continue 6 months after normalization to replete stores
• Intermittent dosing (2-3x/week) acceptable - fewer side effects

• Third trimester (all IDA)
• Severe IDA (Hb < 9 g/dL) in the second trimester
• Oral iron intolerance / malabsorption
• Not used in first trimester
• Agents: Iron sucrose (most common), ferric carboxymaltose, ferric gluconate
• Dose formula: Weight × (Target Hb - Actual Hb) × 0.24 + 500 mg; target Hb = 11-12 g/dL

• ACOG and WHO: ≥ 30-60 mg elemental iron daily throughout pregnancy

2. Folate Deficiency Anemia

Etiology

• Folate requirements increase 5-10 fold in pregnancy
• Risk factors: multiple gestation, hyperemesis gravidarum, antiepileptic drugs (phenytoin, phenobarbitone), alcoholism, malnutrition, malabsorption

Clinical Features

• Megaloblastic (macrocytic) anemia
• Glossitis, angular stomatitis

Complications

• Neural tube defects (most important - spina bifida, anencephaly)
• Placental abruption, preeclampsia, preterm birth, spontaneous abortion

Diagnosis

• Macrocytic anemia with hypersegmented neutrophils on smear
• Low serum folate, low RBC folate (RBC folate is more reliable for chronic deficiency)

Treatment / Prevention

3. Sickle Cell Disease (SCD) in Pregnancy

Complications

• Maternal: 6-fold increased maternal death risk, frequent painful crises, VTE (1.7-10x more common), preeclampsia, PROM, infections, increased cesarean rate
• Fetal: Placental infarction, low birthweight, small-for-gestational-age, preterm birth

Management

• Treat pain crises as in nonpregnant patients
• Hydroxyurea - CONTRAINDICATED (teratogenic)
• NSAIDs - avoid after 30 weeks
• Regional anesthesia preferred for cesarean (general anesthesia increases sickling)
• Iron supplementation controversial (risk of iron overload)
• VTE prophylaxis

4. Thalassemia in Pregnancy

• Alpha-thalassemia trait: Mild microcytic anemia; MCV disproportionately low relative to Hb; RBC count normal or high; RDW normal - distinguishes it from IDA
• Beta-thalassemia trait: HbA2 > 3.5% on Hb electrophoresis; requires partner testing and genetic counseling
• Hb Bart's hydrops fetalis (4 alpha-gene deletion): Incompatible with life - universal stillbirth

Key Laboratory Values (Pregnancy-Adjusted)

Differential Diagnosis of Anemia Types by CBC Pattern

Summary Points (Quick Recall)

1. Most common cause of anemia in pregnancy = Iron deficiency (75%)
2. Most sensitive test for IDA = Serum ferritin (< 30 ng/mL)
3. IV iron preferred in T3 and severe IDA; not in T1
4. Folate 4 mg/day required for prior NTD pregnancy
5. Hydroxyurea contraindicated in SCD during pregnancy
6. Physiologic anemia: MCV and MCHC remain normal - reassure, no treatment needed
7. Hb nadir at 26-34 weeks due to plasma volume expansion