What are the effects of maternal anemia on the fetus in pregnant women?

Effects of Maternal Anemia on the Fetus

Maternal anemia during pregnancy significantly increases the risk of preterm birth, low birth weight, fetal growth restriction, placental abruption, and in severe cases, fetal malformation and stillbirth, with effects becoming progressively worse as anemia severity increases. 1, 2

Critical Distinction: Maternal vs. Fetal Anemia

It is essential to understand that maternal anemia and fetal anemia are distinct conditions with different etiologies. 1 The most common causes of fetal anemia in the United States are maternal alloimmunization and parvovirus infection, not maternal iron deficiency anemia. 1 However, maternal iron deficiency anemia (IDA) does affect fetal outcomes through different mechanisms related to placental function and oxygen delivery. 1

Adverse Fetal Outcomes by Severity of Maternal Anemia

Mild Anemia (Hemoglobin 10.0-10.9 g/dL)

• Increased risk of placental abruption (36% increased risk compared to non-anemic women). 2
• Increased risk of preterm birth (8% increased risk). 2
• Increased risk of severe postpartum hemorrhage (45% increased risk), which can compromise maternal ability to care for the newborn. 2
• Increased risk of fetal malformation (15% increased risk). 2
• Paradoxically, mild anemia shows decreased risks of fetal growth restriction and stillbirth in large cohort studies, possibly reflecting appropriate plasma volume expansion. 2

Moderate Anemia (Hemoglobin 7.0-9.9 g/dL)

• Nearly doubled risk of placental abruption (98% increased risk). 2
• Increased risk of preterm birth (18% increased risk). 2
• Dramatically increased risk of severe postpartum hemorrhage (253% increased risk). 2
• Increased risk of maternal shock (50% increased risk). 2
• Increased risk of fetal malformation (19% increased risk). 2
• Increased risk of stillbirth when anemia is detected early in pregnancy. 2

Severe Anemia (Hemoglobin <7.0 g/dL)

• More than tripled risk of placental abruption (235% increased risk). 2
• Increased risk of preterm birth (36% increased risk). 2
• Massively increased risk of severe postpartum hemorrhage (1,465% increased risk). 2
• Dramatically increased risk of maternal shock (1,398% increased risk). 2
• Nearly tripled risk of maternal ICU admission (188% increased risk). 2
• Increased risk of fetal malformation (62% increased risk). 2
• Increased risk of stillbirth (86% increased risk). 2

Timing-Dependent Effects

Early Pregnancy (First and Second Trimester)

Iron deficiency anemia detected early in pregnancy carries more than a 2-fold increased risk of preterm delivery. 3 This is the critical window where maternal anemia has the most profound impact on pregnancy duration. 3, 4 Early maternal anemia is also associated with increased risk of low birth weight. 3, 4

Third Trimester

Maternal anemia diagnosed in the third trimester is usually not associated with increased risk of adverse pregnancy outcomes and may actually indicate appropriate maternal plasma volume expansion, which is physiologically normal. 3 This explains why mild anemia in late pregnancy may not be pathological. 3

Mechanisms of Fetal Harm

Impaired Placental Iron Transfer

• The fetus requires approximately 270 mg of iron transferred across the placenta during pregnancy, with 80% accruing in the third trimester. 1
• Maternal iron deficiency anemia reduces fetal iron stores, potentially extending well into the first year of life. 4
• This creates a cascade effect where the infant is at increased risk of developing iron deficiency anemia with documented adverse consequences on infant neurodevelopment. 4

Hypoxia-Induced Stress Pathway

• Maternal anemia causes fetal hypoxia, which induces both maternal and fetal stress responses. 5
• This stress stimulates synthesis of corticotropin-releasing hormone (CRH), a major risk factor for preterm labor, pregnancy-induced hypertension, eclampsia, and premature rupture of membranes. 5
• Elevated CRH increases fetal cortisol production, which may inhibit longitudinal growth of the fetus, contributing to intrauterine growth restriction. 5

Oxidative Stress and Infection Risk

• Iron deficiency increases oxidative damage to erythrocytes and the fetoplacental unit. 5
• Maternal iron deficiency increases the risk of maternal infections, which can stimulate CRH production and are a major risk factor for preterm delivery. 5

Neurocognitive Effects

Maternal iron deficiency anemia during pregnancy has been associated with neurocognitive abnormalities in offspring. 1 This occurs because fetal brain development accelerates in the second half of gestation (20-40 weeks), with rapid myelination beginning at 32 weeks and extending into the first 2 years of postnatal life. 1 Inadequate iron transfer during this critical period compromises brain development. 1

Important Clinical Caveats

High Hemoglobin is Also Harmful

High levels of hemoglobin, hematocrit, and ferritin are associated with increased risk of fetal growth restriction, preterm delivery, and preeclampsia. 3 This U-shaped relationship means that both anemia and failure to achieve appropriate hemodilution carry risks. 3

Anemia vs. Iron Deficiency

Not all maternal anemia is iron deficiency anemia, even among low-income minority women. 3 Other causes must be investigated, including hemoglobinopathies, chronic disease, and acute blood loss. 6, 7

Fetal Anemia Assessment

When maternal severe anemia is present, the fetus should be evaluated for anemia using middle cerebral artery peak systolic velocity (MCA-PSV) Doppler, as maternal severe anemia may indicate an underlying condition affecting the fetus. 6 If MCA-PSV exceeds 1.5 multiples of the median or if hydrops is present, referral to a center with expertise in intrauterine transfusion is recommended. 6

Evidence for Iron Supplementation Benefits

Iron supplementation in iron-deficient pregnant women significantly increases birth weight, but this benefit is not seen in iron-replete women. 1 A randomized controlled trial showed that antenatal iron supplementation significantly increased birth weight in women who were iron-deficient before supplementation (ferritin <15 μg/L), but not in iron-replete women. 1 Intravenous iron therapy in pregnant women with IDA was associated with higher birth weight compared to oral iron. 1

Prophylactic iron supplementation in non-deficient women may actually increase risk through mechanisms including gestational diabetes and increased oxidative stress during pregnancy. 3 This underscores the importance of screening maternal iron status early in pregnancy with hemoglobin and ferritin measurements to identify women who would truly benefit from supplementation. 1