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Iron and Infant Development

A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Micronutrients and Human Health".

Deadline for manuscript submissions: closed (15 November 2023) | Viewed by 23136

Special Issue Editors


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Guest Editor
Department of Human Development Nursing Science, University of Illinois at Chicago, Chicago, IL, 60612, USA
Interests: mprovements in maternal and child health; nutritional status; infant development; pregnancy; human milk
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Department of Kinesiology and Nutrition Medicine, University of Illinois, Chicago, IL 60612, USA
Interests: obesity; inflammation and nutrient metabolism; iron in health and disease; intestinal cancers; dietary interventions; dietary assessment; reproductive health; cancer and reproductive health inequity

Special Issue Information

Dear Colleagues,

Iron deficiency is the most common single-nutrient disorder in the world and infants are particularly vulnerable due to their rapid growth and limited dietary sources of iron. Iron is critical for the development of multiple central nervous system processes that impact infant and child behavior and development. Infants who are born iron deficient are likely to experience persistent effects, including motor and neurocognitive developmental delays, that alter functioning into adulthood. Iron deficiency during infancy is not a lone driver of these developmental delays. Maternal iron deficiency anemia can negatively impact the iron endowment of the neonate. Maternal undernutrition can promote iron deficiency anemia, but emerging research also suggests maternal systemic inflammation may play an important role in iron metabolism during the perinatal period. Systemic inflammation, which may stem from infection, obesity, or psychological stress, may cause disruption to maternal and subsequently fetal iron nutrition. We welcome papers addressing these multilevel determinants of iron status, from genetics to environment, from the perinatal period to infancy. Topics can include iron endowment of the neonate at birth or during infancy and its deleterious effects on neurocognitive development, iron transfer across the placenta to the fetus and consequences for development in utero, and novel therapies or adjustments to existing therapies to address iron deficiency in utero and during infancy.

Prof. Dr. Mary Dawn Koenig
Prof. Dr. Lisa Tussing-Humphreys
Guest Editors

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Keywords

  • iron deficiency
  • infant development
  • infancy
  • pregnancy
  • iron
  • iron metabolism

Published Papers (8 papers)

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17 pages, 571 KiB  
Article
Feasibility Study of Lactobacillus Plantarum 299v Probiotic Supplementation in an Urban Academic Facility among Diverse Pregnant Individuals
by Nefertiti OjiNjideka Hemphill, Lacey Pezley, Alana Steffen, Gloria Elam, Michelle A. Kominiarek, Angela Odoms-Young, Nicollette Kessee, Alyshia Hamm, Lisa Tussing-Humphreys and Mary Dawn Koenig
Nutrients 2023, 15(4), 875; https://doi.org/10.3390/nu15040875 - 9 Feb 2023
Cited by 5 | Viewed by 2832 | Correction
Abstract
(1) Background: Despite iron intake recommendations, over a quarter of pregnant individuals have iron deficiency. Lactobacillus plantarum 299v enhances iron absorption in non-pregnant populations and may have positive effects in pregnancy among those with sufficient iron stores; however, no studies have evaluated the [...] Read more.
(1) Background: Despite iron intake recommendations, over a quarter of pregnant individuals have iron deficiency. Lactobacillus plantarum 299v enhances iron absorption in non-pregnant populations and may have positive effects in pregnancy among those with sufficient iron stores; however, no studies have evaluated the effect of Lp299v on maternal and neonatal iron status among individuals at risk for iron deficiency anemia in pregnancy. Thus, this study aims to assess the feasibility and preliminary efficacy of daily oral Lp299v maternal supplementation among diverse pregnant individuals. (2) Methods: In this double-blind placebo-controlled randomized supplementation feasibility study, participants were randomized to probiotic Lp299v + prenatal vitamin with iron or placebo + prenatal vitamin with iron from 15–20 weeks of gestation through delivery. (3) Results: Of the 20 enrolled and randomized participants, 58% (7/12) from the Lp299v group and 75% (6/8) from the placebo group were retained. Adherence to supplementation was 72% for Lp299v/placebo and 73% for the prenatal vitamin. A slower decline in maternal hematological and iron parameters across pregnancy was observed in the Lp299v group compared to placebo. (4) Conclusions: Lp299v may be a tolerable therapy during pregnancy and has the potential to affect maternal and neonatal hematological and iron status. Full article
(This article belongs to the Special Issue Iron and Infant Development)
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18 pages, 2467 KiB  
Article
Trace Element Interactions, Inflammatory Signaling, and Male Sex Implicated in Reduced Growth Following Excess Oral Iron Supplementation in Pre-Weanling Rats
by Shasta A. McMillen, Eric B. Nonnecke and Bo Lönnerdal
Nutrients 2022, 14(19), 3913; https://doi.org/10.3390/nu14193913 - 21 Sep 2022
Cited by 1 | Viewed by 1957
Abstract
Iron supplements are frequently provided to infants in high-income countries despite low incidence of iron deficiency. There is growing concern regarding adverse health and development outcomes of excess iron provision in early life. Excess iron may directly damage developing organs through the formation [...] Read more.
Iron supplements are frequently provided to infants in high-income countries despite low incidence of iron deficiency. There is growing concern regarding adverse health and development outcomes of excess iron provision in early life. Excess iron may directly damage developing organs through the formation of reactive oxygen species, alter systemic inflammatory signaling, and/or dysregulate trace mineral metabolism. To better characterize the in vivo effects of excess iron on development, we utilized a pre-weanling rat pup model. Lewis rat litters were culled to eight pups (four males and four females) and randomly assigned to daily supplementation groups receiving either vehicle control (CON; 10% w/v sucrose solution) or ferrous sulfate (FS) iron at one of the following doses: 10, 30, or 90 mg iron/kg body weight—FS-10, FS-30, and FS-90, respectively—from postnatal day (PD) 2 through 9. FS-90 litters, but not FS-30 or FS-10, failed to thrive compared to CON litters and had smaller brains on PD 10. Among the groups, FS-90 liver iron levels were highest, as were white blood cell counts. Compared to CON, circulating MCP-1 and liver zinc were increased in FS-90 pups, whereas liver copper was decreased. Growth defects due to excess FS provision in pre-weanling rats may be related to liver injury, inflammation, and altered trace mineral metabolism. Full article
(This article belongs to the Special Issue Iron and Infant Development)
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12 pages, 1342 KiB  
Article
Prevalence of and Risk Factors for Iron Deficiency in Twin and Singleton Newborns
by Rebecca K. Campbell, Catalin S. Buhimschi, Guomao Zhao, Cielo Dela Rosa, Bethany T. Stetson, Carl H. Backes and Irina A. Buhimschi
Nutrients 2022, 14(18), 3854; https://doi.org/10.3390/nu14183854 - 17 Sep 2022
Cited by 3 | Viewed by 2715
Abstract
Iron deficiency (ID) in utero and in infancy can cause irreversible neurocognitive damage. Iron status is not routinely tested at birth, so the burden of neonatal ID in the United States is unknown. Infants born from twin or higher-order pregnancies may be at [...] Read more.
Iron deficiency (ID) in utero and in infancy can cause irreversible neurocognitive damage. Iron status is not routinely tested at birth, so the burden of neonatal ID in the United States is unknown. Infants born from twin or higher-order pregnancies may be at elevated risk of inadequate nutrient endowment at birth. The present study sought to compare the burden of neonatal ID in cord blood serum samples from twin (n = 54) and singleton pregnancies (n = 24). Iron status (serum ferritin (SF), soluble transferrin receptor (sTfR), hepcidin) and inflammation (C-reactive protein (CRP) and interleukin-6 (IL-6)) biomarker concentrations were measured by immunoassay. The prevalence of ID (SF < 76 ng/mL) among twins was 21% (23/108) and among singletons 20% (5/24). Gestational age at birth, maternal race and infant sex predicted SF levels. Maternal anemia (hemoglobin < 11 g/dL) was observed in 40% of mothers but was not associated with neonatal iron biomarkers. More research is needed to identify risk factors and regulatory mechanisms for inadequate fetal iron accrual to identify higher risk pregnancies and neonates for screening and intervention. Full article
(This article belongs to the Special Issue Iron and Infant Development)
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26 pages, 9015 KiB  
Article
Multiple Indicators of Undernutrition, Infection, and Inflammation in Lactating Women Are Associated with Maternal Iron Status and Infant Anthropometry in Panama: The MINDI Cohort
by Doris González-Fernández, Elizabeta Nemeth, Emérita del Carmen Pons, Odalis Teresa Sinisterra, Delfina Rueda, Lisa Starr, Veena Sangkhae, Enrique Murillo, Marilyn E. Scott and Kristine G. Koski
Nutrients 2022, 14(17), 3497; https://doi.org/10.3390/nu14173497 - 25 Aug 2022
Cited by 4 | Viewed by 2170
Abstract
Maternal infections, nutrient deficiencies, and inflammation (MINDI) co-exist in lactating indigenous women in Panama, but their impact on maternal iron status and infant growth is unknown. For this secondary analysis of cross-sectional data of lactating mothers from our MINDI cohort, we investigated associations [...] Read more.
Maternal infections, nutrient deficiencies, and inflammation (MINDI) co-exist in lactating indigenous women in Panama, but their impact on maternal iron status and infant growth is unknown. For this secondary analysis of cross-sectional data of lactating mothers from our MINDI cohort, we investigated associations of MINDI variables with maternal anemia, elevated serum transferrin receptor (sTfR), low serum iron, hepcidin, ferritin, and infant weight-for-age (WAZ), length-for-age (LAZ), and head-circumference-for-age (HCAZ) Z-scores in 99 mother-infant dyads. A bootstrapping resampling procedure preselected covariates for inclusion in multivariable regressions models from chronic maternal infections and nutritional status [folate, vitamins A, D, retinol-binding protein (RBP), insulin-growth factor-1 (IGF-1)] and inflammation [C-reactive protein (CRP), cytokines, platelet indices] indicators. Anemia was prevalent (53.5%) but underestimated due to widespread low plasma volume (<2.2 L, 79.9%) and was associated with indicators of malnutrition [lower IGF-1, body mass index (BMI), vitamin D, and intake of green/leafy vegetables], but not inflammation. Higher CRP was associated with lower serum iron, and higher hepcidin and ferritin, whereas maternal platelets were associated with lower HCAZ (β = −0.22), WAZ (β = −0.17), and LAZ (β = −0.17). Higher LAZ was also associated with maternal serum vitamin D (β = 0.23), whereas maternal iron supplementation lowered LAZ (β = −0.22). Assessment of iron status in this MINDI cohort is complex and supplementation strategies must consider consequences for both the mother and the infant. Full article
(This article belongs to the Special Issue Iron and Infant Development)
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20 pages, 2600 KiB  
Article
High Iron Exposure from the Fetal Stage to Adulthood in Mice Alters Lipid Metabolism
by Minju Kim, Yeon-hee Kim, Sohyun Min and Seung-Min Lee
Nutrients 2022, 14(12), 2451; https://doi.org/10.3390/nu14122451 - 13 Jun 2022
Cited by 2 | Viewed by 2877
Abstract
Iron supplementation is recommended during pregnancy and fetal growth. However, excess iron exposure may increase the risk of abnormal fetal development. We investigated the potential side effects of high iron levels in fetuses and through their adult life. C57BL/6J pregnant mice from 2 [...] Read more.
Iron supplementation is recommended during pregnancy and fetal growth. However, excess iron exposure may increase the risk of abnormal fetal development. We investigated the potential side effects of high iron levels in fetuses and through their adult life. C57BL/6J pregnant mice from 2 weeks of gestation and their offspring until 30 weeks were fed a control (CTRL, FeSO4 0 g/1 kg) or high iron (HFe, FeSO4 9.9 g/1 kg) diets. HFe group showed higher iron accumulation in the liver with increased hepcidin, reduced TfR1/2 mRNAs, and lowered ferritin heavy chain (FTH) proteins in both liver and adipose tissues despite iron loading. HFe decreased body weight, fat weight, adipocyte size, and triglyceride levels in the blood and fat, along with downregulation of lipogenesis genes, including PPARγ, C/EBPα, SREBP1c, FASN, and SCD1, and fatty acid uptake and oxidation genes, such as CD36 and PPARα. UCP2, adiponectin, and mRNA levels of antioxidant genes such as GPX4, HO-1, and NQO1 were increased in the HFe group, while total glutathione was reduced. We conclude that prolonged exposure to high iron from the fetal stage to adulthood may decrease fat accumulation by altering ferritin expression, adipocyte differentiation, and triglyceride metabolism, resulting in an alteration in normal growth. Full article
(This article belongs to the Special Issue Iron and Infant Development)
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16 pages, 2691 KiB  
Article
Low Hemoglobin Levels Are Associated with Reduced Psychomotor and Language Abilities in Young Ugandan Children
by Margaret Nampijja, Agnes M. Mutua, Alison M. Elliott, John Muthii Muriuki, Amina Abubakar, Emily L. Webb and Sarah H. Atkinson
Nutrients 2022, 14(7), 1452; https://doi.org/10.3390/nu14071452 - 30 Mar 2022
Cited by 6 | Viewed by 5940
Abstract
Children living in Sub-Saharan Africa are vulnerable to developmental delay, particularly in the critical first five years due to various adverse exposures including disease and nutritional deficiencies. Anemia and iron deficiency (ID) are highly prevalent in pregnant mothers and young children and are [...] Read more.
Children living in Sub-Saharan Africa are vulnerable to developmental delay, particularly in the critical first five years due to various adverse exposures including disease and nutritional deficiencies. Anemia and iron deficiency (ID) are highly prevalent in pregnant mothers and young children and are implicated in abnormal brain development. However, available evidence on the association between anemia, ID and neurodevelopment in sub-Saharan Africa is limited. Using data from the Entebbe Mother and Baby Study prospective birth cohort, we examined the effect of maternal and child hemoglobin (Hb) levels and child iron status on developmental scores in 933 and 530 pre-school Ugandan children respectively. Associations between Hb levels, iron status and developmental scores were assessed using regression analyses adjusting for potential confounders. Lower maternal and child Hb levels were associated with reduced psychomotor scores at 15 months, while only lower Hb levels in infancy were associated with reduced language scores. We found no evidence that anemia or ID was associated with cognitive or motor scores at five years. This study emphasizes the importance of managing anemia in pregnancy and infancy and highlights the need for further studies on the effects of anemia and ID in children living in Sub-Saharan Africa. Full article
(This article belongs to the Special Issue Iron and Infant Development)
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16 pages, 1481 KiB  
Article
Prenatal Iron Deficiency and Choline Supplementation Interact to Epigenetically Regulate Jarid1b and Bdnf in the Rat Hippocampus into Adulthood
by Shirelle X. Liu, Amanda K. Barks, Scott Lunos, Jonathan C. Gewirtz, Michael K. Georgieff and Phu V. Tran
Nutrients 2021, 13(12), 4527; https://doi.org/10.3390/nu13124527 - 17 Dec 2021
Cited by 5 | Viewed by 2852
Abstract
Early-life iron deficiency (ID) causes long-term neurocognitive impairments and gene dysregulation that can be partially mitigated by prenatal choline supplementation. The long-term gene dysregulation is hypothesized to underlie cognitive dysfunction. However, mechanisms by which iron and choline mediate long-term gene dysregulation remain unknown. [...] Read more.
Early-life iron deficiency (ID) causes long-term neurocognitive impairments and gene dysregulation that can be partially mitigated by prenatal choline supplementation. The long-term gene dysregulation is hypothesized to underlie cognitive dysfunction. However, mechanisms by which iron and choline mediate long-term gene dysregulation remain unknown. In the present study, using a well-established rat model of fetal-neonatal ID, we demonstrated that ID downregulated hippocampal expression of the gene encoding JmjC-ARID domain-containing protein 1B (JARID1B), an iron-dependent histone H3K4 demethylase, associated with a higher histone deacetylase 1 (HDAC1) enrichment and a lower enrichment of acetylated histone H3K9 (H3K9ac) and phosphorylated cAMP response element-binding protein (pCREB). Likewise, ID reduced transcriptional capacity of the gene encoding brain-derived neurotrophic factor (BDNF), a target of JARID1B, associated with repressive histone modifications such as lower H3K9ac and pCREB enrichments at the Bdnf promoters in the adult rat hippocampus. Prenatal choline supplementation did not prevent the ID-induced chromatin modifications at these loci but induced long-lasting repressive chromatin modifications in the iron-sufficient adult rats. Collectively, these findings demonstrated that the iron-dependent epigenetic mechanism mediated by JARID1B accounted for long-term Bdnf dysregulation by early-life ID. Choline supplementation utilized a separate mechanism to rescue the effect of ID on neural gene regulation. The negative epigenetic effects of choline supplementation in the iron-sufficient rat hippocampus necessitate additional investigations prior to its use as an adjunctive therapeutic agent. Full article
(This article belongs to the Special Issue Iron and Infant Development)
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1 pages, 179 KiB  
Correction
Correction: OjiNjideka Hemphill et al. Feasibility Study of Lactobacillus Plantarum 299v Probiotic Supplementation in an Urban Academic Facility among Diverse Pregnant Individuals. Nutrients 2023, 15, 875
by Nefertiti OjiNjideka Hemphill, Lacey Pezley, Alana Steffen, Gloria Elam, Michelle A. Kominiarek, Angela Odoms-Young, Nicollette Kessee, Alyshia Hamm, Lisa Tussing-Humphreys and Mary Dawn Koenig
Nutrients 2023, 15(15), 3339; https://doi.org/10.3390/nu15153339 - 27 Jul 2023
Viewed by 565
Abstract
There was an error in the original publication [...] Full article
(This article belongs to the Special Issue Iron and Infant Development)
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