The Effects of Early-Life Iron Deficiency on Brain Energy Metabolism

Bastian, Thomas W.; Rao, Raghavendra; Tran, Phu V.; Georgieff, Michael

doi:10.1177/2633105520935104

Cited by 55 publications

(38 citation statements)

References 248 publications

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“…Even though the need for iron to promote fetal and future infant development is well known ( 91 ), the effect of iron deficiency on fetal growth is somewhat controversial. An older meta-analysis on the effect of iron supplementation during pregnancy commissioned by the WHO found that iron supplementation increased birth weight by 100 g at most ( 92 ).…”

Section: Discussionmentioning

confidence: 99%

INTERGROWTH-21 Identifies High Prevalence of Low Symphysis–Fundal Height in Indigenous Pregnant Women Experiencing Multiple Infections, Nutrient Deficiencies, and Inflammation: The Maternal Infections, Nutrient Deficiencies, and Inflammation (MINDI) Cohort

Gonzalez‐Fernandez

Nemeth

Pons³

et al. 2021

Current Developments in Nutrition

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Background In absence of ultrasound, symphysis-fundal height (SFH) can assess maternal-fetal well-being as it is associated with gestational age, fetal weight and amniotic fluid volume. However, other modifiers of SFH, including maternal infections, nutrient deficiencies and inflammation (MINDI), have not been widely explored. Objectives Our objectives were two-fold: 1) to assess prevalence of low SFH in indigenous Panamanian women using both PAHO and INTERGROWTH-21 standards and 2) to explore associations of SFH with maternal health indicators: infections (oral, skin, urogenital, nematode infections), nutrient deficiencies [protein and iron indicators (ferritin, serum iron, serum transferrin receptor, hepcidin), folate, vitamins A, D, B12] and inflammation [leukocytes, C-reactive protein, cytokines]. Methods For this cross-sectional study, low-SFH-for-gestational-age was assessed using PAHO and INTERGROWTH < 10th centile in 174 women ≥16 weeks’ gestation. Bootstrapping selected MINDI variables for inclusion in multivariable fractional polynomial (MFP) logistic regressions for low-SFH. Associations of MINDI variables with hepcidin were also investigated. Results Prevalence of low-SFH was 8% using PAHO, but using INTERGROWTH, 50.6% had SFH < 10th centile, including 37.9% <3rd centile. Both PAHO-SFH < 10% and INTERGROWTH-SFH < 3rd centiles were associated with higher hepcidin (OR 1.12, p = 0.008 and OR = 3.04. p = 0.001, respectively) and with lower TNF-α (OR = 0.73, p = 0.012 and OR = 0.93, p = 0.015, respectively). Wood smoke exposure increased the odds of PAHO-SFH < 10th centile (OR = 1.19, p = 0.009) whereas higher BMI decreased the odds of INTERGROWTH-SFH < 3rd centile (OR = 0.87, p = 0.012). Lower pulse pressure (OR = 0.90, p = 0.009) and lower inflammatory responses [lower lymphocytes (OR = 0.21, p = 0.026), IL-17 (OR = 0.89, p = 0.011)] distinguished SFH < 3rd centile from SFH 3–10 using INTERGROWTH-21standards. The MFP regression for hepcidin controlling for SFH (Adj R2 = 0.40, p = 0.001) revealed associations with indicators of inflammation (CRP, p < 0.0001; IL-17, p = 0.012), acidic urinary pH (p = 0.008) and higher intake of supplements (p = 0.035). Conclusion Associations of low SFH with MINDI variables, including hepcidin, highlight its potential for early detection of multicausal in-utero growth faltering. LAY SUMMARY Symphysis-fundal height (SFH) is a measure of maternal-fetal well-being and is commonly used when sonography is not available to assess gestational age and the health of fetal-maternal unit. This simple non-invasive indicator uses a tape measure to measure the distance between the symphysis pubis and the highest point of the growing uterus. This distance was compared with two international standards: PAHO and INTERGROWTH. Using PAHO, 8% of women had low SFH (<10th centile for gestational age), but using INTERGROWTH standards, more than half of the women had low SFH with 37.5% having very low SFH (below the 3rd centile for gestational age). A SFH < 3rd centile was associated with higher hepcidin, a protein that decreases iron availability in blood as a defense against infections. In our study, low SFH was also associated with indicators of inflammation, malnutrition and a lower maternal blood pressure. This study supports the use of SFH in remote areas to identify pregnant women at risk of a poor pregnancy outcomes.

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Section: Discussionmentioning

confidence: 99%

INTERGROWTH-21 Identifies High Prevalence of Low Symphysis–Fundal Height in Indigenous Pregnant Women Experiencing Multiple Infections, Nutrient Deficiencies, and Inflammation: The Maternal Infections, Nutrient Deficiencies, and Inflammation (MINDI) Cohort

Gonzalez‐Fernandez

Nemeth

Pons³

et al. 2021

Current Developments in Nutrition

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“…Indeed, the severity of adverse effects on brain development will depend primarily on how timely, dose and duration any nutrient deficiency exists, and will depend on the coincidence of two factors: the time of accelerated growth, development and development in a nutrient-dependent area and the probability of nutrient deficiency in this age. [30][31] Since it is an essential method, nutrients are required for optimal brain maturation, and brain development is especially susceptible to metabolic homeostasis disruption. 31 In the first year of development, the brain is undergoing an incredible transformation into a complex organ.…”

Section: The Importance Of Iron In Brain Developmentmentioning

confidence: 99%

The Importance of Iron To Support Optimum Cognitive Development

Sekartini

2021

World Nutr J

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The fetal brain anatomy development starts during the last trimester of pregnancy and continue in early months of life. This critical process makes it vulnerable to insufficient nutrition, while brain growth continues into adulthood, micronutrient status can affect functioning beyond childhood. Iron is an important nutrient for the production and growth of cells in the immune and neural systems. Iron deficiency (ID) is the most common nutrient deficiency in the world, affecting about half of all pregnant women and their offspring. Iron deficiency anemia has long been believed to have an effect on the central nervous system. Iron deficiency in late trimester and in newborn leads to abnormal cognitive function and emotional control that may continue in adulthood. In summary, despite some evidence that iron supplementation enhances cognitive performance. Evidence of the role of iron in brain development and the effect of iron deficiency or iron supplementation on early development is uncertain.

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“…Perinatal-life iron deficiency (ID) impairs energy metabolism in a brain region- and age-dependent manner, in particular in hippocampal neurons [ 84 ]. Iron-containing proteins involved in brain energy metabolism are aconitase (TCA), succinate dehydrogenase iron-sulfur, and cytochrome b subunits (complex II) (TCA, ETC), NADH dehydrogenase iron-sulfur proteins 1–8 (complex I) (ETC), ubiquinol:cytochrome c oxidoreductase (complex III) (ETC), cytochrome c (ETC), and cytochrome c oxidase (complex IV) (ETC) [ 84 ].…”

Section: Metabolite Supply For Liver Function and Energy Supply Fomentioning

confidence: 99%

Mitochondria at Work: New Insights into Regulation and Dysregulation of Cellular Energy Supply and Metabolism

Schirrmacher¹

2020

Biomedicines

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Mitochondria are of great relevance to health, and their dysregulation is associated with major chronic diseases. Research on mitochondria—156 brand new publications from 2019 and 2020—have contributed to this review. Mitochondria have been fundamental for the evolution of complex organisms. As important and semi-autonomous organelles in cells, they can adapt their function to the needs of the respective organ. They can program their function to energy supply (e.g., to keep heart muscle cells going, life-long) or to metabolism (e.g., to support hepatocytes and liver function). The capacity of mitochondria to re-program between different options is important for all cell types that are capable of changing between a resting state and cell proliferation, such as stem cells and immune cells. Major chronic diseases are characterized by mitochondrial dysregulation. This will be exemplified by cardiovascular diseases, metabolic syndrome, neurodegenerative diseases, immune system disorders, and cancer. New strategies for intervention in chronic diseases will be presented. The tumor microenvironment can be considered a battlefield between cancer and immune defense, competing for energy supply and metabolism. Cancer cachexia is considered as a final stage of cancer progression. Nevertheless, the review will present an example of complete remission of cachexia via immune cell transfer. These findings should encourage studies along the lines of mitochondria, energy supply, and metabolism.

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The Effects of Early-Life Iron Deficiency on Brain Energy Metabolism

Cited by 55 publications

References 248 publications

INTERGROWTH-21 Identifies High Prevalence of Low Symphysis–Fundal Height in Indigenous Pregnant Women Experiencing Multiple Infections, Nutrient Deficiencies, and Inflammation: The Maternal Infections, Nutrient Deficiencies, and Inflammation (MINDI) Cohort

INTERGROWTH-21 Identifies High Prevalence of Low Symphysis–Fundal Height in Indigenous Pregnant Women Experiencing Multiple Infections, Nutrient Deficiencies, and Inflammation: The Maternal Infections, Nutrient Deficiencies, and Inflammation (MINDI) Cohort

The Importance of Iron To Support Optimum Cognitive Development

Mitochondria at Work: New Insights into Regulation and Dysregulation of Cellular Energy Supply and Metabolism

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