Search

Cognitive deficits in human infants at risk for gestationally acquired perinatal iron deficiency suggest involvement of the developing hippocampus. To understand the plausible biological explanations for hippocampal injury in perinatal iron deficiency, a neurochemical profile of 16 metabolites in the iron-deficient rat hippocampus was evaluated longitudinally by [sup.1]H NMR spectroscopy at 9.4 T. Metabolites were quantified from an 11-24 [micro]L volume centered in the hippocampus in 18 iron-deficient and 16 iron-sufficient rats on postnatal day (PD) 7, PD10, PD14, PD21 and PD28. Perinatal iron deficiency was induced by feeding the pregnant dam an iron-deficient diet from gestational d 3 to PD7. The brain iron concentration of the iron-deficient group was 60% lower on PD7 and 19% lower on PD28 (P < 0.001 each). The concentration of 12 of the 16 measured metabolites changed over time between PD7 and PD28 in both groups (P < 0.001 each). Compared with the iron-sufficient group, phosphocreatine, glutamate, N-acetylaspartate, aspartate, [gamma]-aminobutyric acid, phosphorylethanolamine and taurine concentrations, and the phosphocreatine/creatine ratio were elevated in the iron-deficient group (P < 0.02 each). These neurochemical alterations suggest persistent changes in resting energy status, neurotransmission and myelination in perinatal iron deficiency. An altered neurochemical profile of the developing hippocampus may underlie some of the cognitive deficits observed in human infants with perinatal iron deficiency. J. Nutr. 133: 3215-3221, 2003. KEY WORDS: * hippocampus * iron * neurochemical profile * NMR spectroscopy * perinatal iron deficiency

Infants born preterm are more likely than ever to survive, but relatively little is known about the factors that influence their subsequent sociocognitive development. Responding to joint attention (RJA) is a pivotal skill that is likely supported by biological preparedness at birth and ex‐utero social experience. The goals of this study are to evaluate the relative roles of chronological age, gestation duration, and birthweight for early RJA and examine birthweight as a potential moderator of the associations between chronological age and RJA. This study leveraged a mixed longitudinal design of infants (N = 256, obs = 421) from 8 to 16 months of chronological age. Results show that chronological age and gestation duration both explain unique variation in RJA. Further, birthweight exhibits quadratic relations with RJA. Birthweight moderates the association between chronological age and RJA; infants born heavier demonstrate faster RJA growth compared to those born smaller. Findings suggest that birth weight, an index of nutrient sufficiency in utero and biological preparedness, may constrain or afford early RJA development, consistent with the Developmental Origins of Health and Disease (DoHAD) hypothesis. Findings inform our understanding of the roles of biological preparedness and experience in shaping RJA and help disaggregate potential mechanisms of prematurity‐related challenges to social cognitive development. [ABSTRACT FROM AUTHOR]

Fetal brain iron deficiency occurs in human pregnancies complicated by diabetes mellitus or intrauterine growth retardation. Because neurocognitive deficits are more common in the offspring of these pregnancies, we tested the hypothesis that perinatal brain iron deficiency predisposes the neonatal hippocampus, a structure important for memory processing, to injury. Brain iron concentration was reduced by 45% in 45 neonatal rats by maternal dietary iron restriction during gestation. Right-sided neuronal injury in four hippocampal subareas was induced by hypoxic-ischemic insult (ipsilateral carotid artery ligation and subsequent hypoxia on postnatal d 7) and was quantified histochemically on d 8 by cytochrome c oxidase activity (n = 30), and on d 14 by Nissl staining (n: 15). Acute right-sided cytochrome c oxidase activity loss occurred in CA1 (P - 0.02), CA3c (P < 0.001) and dentate gyrus (P < 0.001) in the iron-deficient group, whereas only CA1 (P = 0.003) was affected in the iron-sufficient group. Long-term right-sided Nissl substance loss occurred in CA1 (P = 0.001), CA3a,b (P < 0.001) and dentate gyrus (P: 0.008) in the iron-deficient group, but only in CA1 (P = 0.004) in the iron-sufficient group. No increase in right-sided free-iron staining was present in either group. Perinatal iron deficiency predisposes the neonatal hippocampus to a greater acute loss of neuronal metabolic activity after an hypoxic-ischemic event, suggesting compromised cellular energetics. The subsequently greater loss of hippocampal neuronal integrity suggests poorer recoverability after injury in the perinatal iron-deficient brain. KEY WORDS: cytochrome c oxidase; hippocampus; hypoxia-ischemia; iron; rats

Research shows that lambs with an iron deficiency take up iron in the red blood cells in preference to other areas of the body, including the brain, heart and skeletal muscle. Experiments designed to demonstrate iron loss recovery mechanisms in twin lambs with chronic phlebotomies are described. Atomic absorption spectroscopy techniques are used to measure tissue iron and hemoproteins.

Long-term growth failure and altered body composition are common consequences of bronchopulmonary dysplasia (BPD). We hypothesized that these chronic findings are preceded by uncompensated, acute early growth failure. The purpose of this study was to evaluate the effects of developing bronchopulmonary dysplasia on body composition and growth of very-low-birth-weight (VLBW) infants during the first six postnatal weeks. Arm muscle and fat accretion and changes in weight, length and head circumference were evaluated in 16 very-low-birth-weight infants who developed bronchopulmonary dysplasia and compared with 16 birth-weight-matched control infants without bronchopulmonary dysplasia. During the 1st wk, both groups experienced similarly low nutritional intakes, wasting of arm muscle and fat stores, and reduced weight, length and head circumference growth velocities, compared with intrauterine growth standards. Between wk 2 and 4, infants with developing bronchopulmonary dysplasia consumed less protein and energy (P < 0.05), accreted less arm fat and muscle (P < 0.05), and grew more slowly than control infants in all measured variables (P < 0.05). When infants with bronchopulmonary dysplasia had achieved full enteral feedings and had similar protein-energy intakes to control infants, they demonstrated similar rates of growth and arm muscle and fat accretion, but did not demonstrate catch-up growth. These data support the speculation that early reductions in muscle and fat accretion and growth velocity contribute to the long-term growth failure in infants with bronchopulmonary dysplasia. Prevention may require greater attention to defining and delivering optimal nutritional therapy to physiologically unstable premature infants in the immediate postnatal period. INDEXING KEY WORDS: bronchopulmonary dysplasia; fat accretion; muscle accretion; growth; humans

Scatchard analysis of the binding of 125I, and transferrin receptor (TR) immunoreactivity measurement in pregnant diabetic mothers to determine the influence of fetal iron demand on placental TR reveal that fetal iron demand affects the modulation of placental TR expression and results in fetal hypoxia, hyperinsulinemia and high erythropoiesis. Placental syncytiotrophoblastic TR expression increases and corresponds to low cord serum ferritin levels, indicating that the fetus uses high placental iron transport and mobilizes fetal iron stores to increase erythropoiesis. TR staining reveals that fetal hyperinsulinemia plays a primary or secondary role in TR expression.

American families who wish to adopt Romanian orphans should be aware that these children suffer from many physical, psychological and emotional disorders because of their prolonged stay in orphanages. Researchers who visited these orphanages after the fall of the Ceausescu regime found children living in appalling conditions with little human contact. A study of 65 Romanian children adopted by American families found that only 15% were physically and developmentally normal. Evidence of past or present hepatitis B infection was present in over half. One-third had intestinal parasites, most commonly Giardia. None were HIV-positive. In many, height, weight and head size had been compromised as a result of malnutrition. These children were most likely adopted because they were the most healthy children observed. Indeed, none had been found in the asylums for 'incurables'., Objective.--To determine the medical condition of Romanian adoptees and the effects of the Romanian orphanage system on their health. Design.--Case series. Setting.--The international adoption clinics at the University of Minnesota, Minneapolis, and the New England Medical Center, Tufts University, Boston, Mass. Participants.--Sixty-five Romanian adoptees who were brought to the United States during a 12-month period beginning in October 1990. Main Outcome Measures.--Incidence of hepatitis B, intestinal parasites, tuberculosis, syphilis, human immunodeficiency virus type 1, growth failure, and developmental delay. Results.--Although the adopted children were presumably chosen from the most vital and attractive adoptees, only 15% were judged to be physically healthy and developmentally normal. Fifty-three percent had serological evidence of past or present hepatitis B infection, and 20% of screened children tested positive for hepatitis B surface antigen. In children aged 7 months or older, the overall prevalence of chronic hepatitis B was 23%. Intestinal parasites were found in 33% of subjects, and 45% of infected children had two or more pathogens identified. All the children tested for human immunodeficiency virus type 1 were negative. Two patterns of growth failure were observed that resembled the two subtypes of psychosocial short stature that occur in association with prolonged psychological harassment or emotional deprivation. Infants&apos; length, weight, head circumference, and weight-for-height were adversely affected by institutionalization. Older children&apos;s height was reduced. Only 10% of children older than 12 months were developmentally normal. Conclusion.--Romanian adoptees are an extraordinarily high-risk pediatric group as a consequence of decades of government-sanctioned child neglect and abuse. (JAMA. 1992;268:3446-3451)

Background Prenatal alcohol exposure (PAE) is associated with postnatal iron deficiency (ID), which has been shown to exacerbate deficits in growth, cognition, and behavior seen in fetal alcohol spectrum disorders. However, the mechanisms underlying PAE-related ID remain unknown. Objectives We aimed to examine biochemical measures of iron homeostasis in the mother, placenta, neonate, and 6.5-month-old infant. Methods In a prenatally recruited, prospective longitudinal birth cohort in South Africa, 206 gravidas (126 heavy drinkers and 80 controls) were interviewed regarding alcohol, cigarette, and drug use and diet at 3 prenatal visits. Hemoglobin, ferritin, and soluble transferrin receptor (sTfR) were assayed twice during pregnancy and urinary hepcidin:creatinine was assayed once. Infant ferritin and hemoglobin were measured at 2 weeks and 6.5 months and sTfR was measured at 6.5 months. Histopathological examinations were conducted on 125 placentas and iron transport assays (iron regulatory protein-2, transferrin receptor-1, divalent metal transporter-1, ferroportin-1, and iron concentrations) were conducted on 63. Results In multivariable regression models, prenatal drinking frequency (days/week) was related to higher maternal hepcidin and to sequestration of iron into storage at the expense of erythropoiesis in mothers and neonates, as evidenced by a lower hemoglobin (g/dL)-to-log(ferritin) (ug/L) ratio [mothers: raw regression coefficient (β) = −0.21 (95% CI: −0.35 to −0.07); neonates: β = −0.15 (95% CI: −0.24 to −0.06)]. Drinking frequency was also related to decreased placental ferroportin-1:transferrin receptor-1 (β = −0.57 for logged values; 95% CI: −1.03 to −0.10), indicating iron-restricted placental iron transport. At 6.5 months, drinking frequency was associated with lower hemoglobin (β = −0.18; 95% CI: −0.33 to −0.02), and increased prevalences of ID (β = 0.09; 95% CI: 0.02–0.17) and ID anemia (IDA) (β = 0.13; 95% CI: 0.04–0.23). In causal inference analyses, the PAE-related increase in IDA was partially mediated by decreased neonatal hemoglobin:log(ferritin), and the decrease in neonatal hemoglobin:log(ferritin) was partially mediated by decreased maternal hemoglobin:log(ferritin). Conclusions In this study, greater PAE was associated with an unfavorable profile of maternal-fetal iron homeostasis, which may play mechanistic roles in PAE-related ID later in infancy. [ABSTRACT FROM AUTHOR]