Iron deficiency in pregnancy

Abstract

Iron is essential for the function of all cells through its roles in oxygen delivery, electron transport, and enzymatic activity. Cells with high metabolic rates require more iron and are at greater risk for dysfunction during iron deficiency. Iron requirements during pregnancy increase dramatically, as the mother's blood volume expands and the fetus grows and develops. Thus, pregnancy is a condition of impending or existing iron deficiency, which may be difficult to diagnose because of limitations to commonly used biomarkers such as hemoglobin and ferritin concentrations. Iron deficiency is associated with adverse pregnancy outcomes, including increased maternal illness, low birthweight, prematurity, and intrauterine growth restriction. The rapidly developing fetal brain is at particular risk of iron deficiency, which can occur because of maternal iron deficiency, hypertension, smoking, or glucose intolerance. Low maternal gestational iron intake is associated with autism, schizophrenia, and abnormal brain structure in the offspring. Newborns with iron deficiency have compromised recognition memory, slower speed of processing, and poorer bonding that persist despite postnatal iron repletion. Preclinical models of fetal iron deficiency confirm that expected iron-dependent processes such as monoamine neurotransmission, neuronal growth and differentiation, myelination, and gene expression are all compromised acutely and long term into adulthood. This review outlines strategies to diagnose and prevent iron deficiency in pregnancy. It describes the neurocognitive and mental health consequences of fetal iron deficiency. It emphasizes that fetal iron is a key nutrient that influences brain development and function across the lifespan.

Keywords: anemia; biomarkers; brain; brain development; epigenetics; ferritin; fetal growth restriction; fetus; gestational diabetes; hemoglobin; hepcidin; hippocampus; iron; iron deficiency; mental health; metabolism; nutrition neurodevelopmental disorder; placenta; pregnancy; prematurity; preterm birth.

Figure 1:. Iron prioritization during iron deficiency in fetal and neonatal sheep^,, and monkeys.

The relative distributional flow of iron is indicated by the thickness of the blue arrows. The red blood cells receive the primary allocation followed sequentially by the brain, the heart and skeletal muscle.^– As negative iron balance progresses over time (red arrow), iron-dependent metabolic dysregulation of the skeletal muscle and heart is first noted by alterations in the serum metabolome. Progressive worsening of iron deficiency subsequently negatively affects brain metabolism at approximately the same time that serum iron panels (eg, ferritin, %TSAT) become abnormal. Iron deficiency results in anemia only in the final stage of the process.^–

Figure 2:

Gene networks involved in neurologic and mental health diseases in the adult mouse affected by gestational iron deficiency (left panel) and recovered by prenatal choline supplementation (right panel).