Higher infant blood lead levels with longer duration of breastfeeding.

OBJECTIVE: To determine whether longer breastfeeding is associated with higher infant lead concentrations. STUDY DESIGN: Data were analyzed from 3 studies of developmental effects of iron deficiency in infancy: Costa Rica (1981-1984), Chile (1991-1996), and Detroit (2002-2003). The relation between duration of breastfeeding and lead levels was assessed with Pearson product-moment or partial correlation coefficients. RESULTS: More than 93% of the Costa Rica and Chile samples was breastfed (179 and 323 breastfed infants, respectively; mean weaning age, 8-10 months), as was 35.6% of the Detroit sample (53 breastfed infants; mean weaning age, 4.5 months). Lead concentrations averaged 10.8 microg/dL (Costa Rica, 12-23 months), 7.8 microg/dL (Chile, 12 months), and 2.5 microg/dL (Detroit, 9-10 months). Duration of breastfeeding as sole milk source and total breastfeeding correlated with lead concentration in all samples (r values = 0.14-0.57; P values = .06-<.0001). CONCLUSIONS: Longer breastfeeding was associated with higher infant lead concentration in 3 countries, in 3 different decades, in settings differing in breastfeeding patterns, environmental lead sources, and infant lead levels. The results suggest that monitoring lead concentrations in breastfed infants be considered.

Caco-2 intestinal epithelial cells absorb soybean ferritin by mu2 (AP2)-dependent endocytosis.

Iron deficiency, a condition currently affecting approximately 3 billion people, persists in the 21st century despite half a millennium of medical treatment. Soybean ferritin (SBFn), a large, stable protein nanocage around a mineral with hundreds of iron and oxygen atoms, is a source of nutritional iron with an unknown mechanism for intestinal absorption. Iron absorption from SBFn is insensitive to phytate, suggesting an absorption mechanism different from for the ferrous transport. Here, we investigated the mechanism of iron absorption from mineralized SBFn using Caco-2 cells (polarized in bicameral inserts) as an intestinal cell mode and analyzed binding, internalization and degradation with labeled SBFn ((131)I or fluorescent labels), confocal microscopy, and immunoanalyses to show: 1) saturable binding to the apical cell surface; dissociation constant of 7.75 +/- 0.88 nmol/L; 2) internalization of SBFn that was dependent on temperature, concentration, and time; 3) entrance of SBFn iron into the labile iron pool (calcein quenching); 4) degradation of the SBFn protein cage; and 5) assembly peptide 2 (AP2)-/clathrin-dependent endocytosis (sensitivity of SBFn uptake to hyperosmolarity, acidity, and RNA interference to the mu(2) subunit of AP2), and resistance to filipin, a caveolar endocytosis inhibitor. The results support a model of SBFn endocytosis through the apical cell membrane, followed by protein cage degradation, mineral reduction/dissolution, and iron entry to the cytosolic iron pool. The large number of iron atoms in SBFn makes iron transport across the cell membrane a much more efficient event for SBFn than for single iron atoms as heme or ferrous ions.

Iron deficiency in infancy: applying a physiologic framework for prediction.

BACKGROUND: Infants aged 6-24 mo are at high risk of iron deficiency. Numerous studies worldwide have sought to identify predictors of iron deficiency in this age group. OBJECTIVE: The objectives of the study were to apply a physiologic model to identify risk factors for iron deficiency and to consider those risk factors under different conditions of iron supplementation. We predicted that factors related to iron status at birth (lower gestational age and lower birth weight), postnatal needs for iron (more rapid growth), and bioavailable iron (more cow milk) would be major risk factors. DESIGN: The physiologic framework was assessed in 1657 Chilean infants (aged 12 mo) with birth weights >or=3 kg who were randomly assigned at age 6 mo to high or low iron supplementation or no added iron. Based on venous blood, the analysis used mean corpuscular volume and concentrations of hemoglobin, free erythrocyte protoporphyrin, and ferritin. Logistic regression models were used to identify predictors of iron deficiency anemia and iron deficiency without anemia. RESULTS: The prevalence of iron deficiency (>or=2 abnormal iron measures) was 34.9% at age 12 mo. Of 186 infants with hemoglobin concentrations <110 g/L, 158 (84.9%) were iron deficient. The only consistent (and the strongest) predictor of iron deficiency or iron deficiency anemia was lower 6-mo hemoglobin. Factors related to poorer iron status at birth (lower birth weight, shorter gestation though full-term, or both) were predictors in the no-added-iron and high-iron groups. Otherwise, predictors varied by iron supplementation. CONCLUSION: Variations in predictors of iron deficiency or iron deficiency anemia according to iron supplementation suggest that direct comparisons across studies are tenuous at best without data on early iron status and certainty that specific conditions are comparable.

Breast-feeding and mental and motor development at 51/2 years.

OBJECTIVE: Breast-feeding is associated with better child development outcomes, but uncertainty remains primarily due to the close relationship between breast-feeding and socioeconomic status. This study assesses the issue in a low socioeconomic status sample where breast-feeding was close to universal. METHODS: Seven hundred eighty-four Chilean children were followed longitudinally from infancy. All but four were initially breastfed, 40% nursed beyond 12 months, and infant growth was normal. Child development was assessed at 5(1/2) years by a cognitive, language, and motor test battery. The duration of breast-feeding as the sole milk source was analyzed as a continuous variable, adjusting for a comprehensive set of background factors. RESULTS: The relationship between breast-feeding and most 5(1/2)-year developmental outcomes was nonlinear, with poorer outcome for periods of breast-feeding as the sole milk source for <2 months or >8 months--statistically significant for language, motor, and one comprehensive cognitive test, with a suggestive trend for IQ. CONCLUSIONS: The observed nonlinear relationships showed that breast-feeding as the sole milk source for <2 months or >8 months, compared with 2-8 months, was associated with poorer development in this sample. The latter finding requires replication in other samples where long breast-feeding is common and socioeconomic status is relatively homogeneous.

The usefulness of elemental iron for cereal flour fortification: a SUSTAIN Task Force report. Sharing United States Technology to Aid in the Improvement of Nutrition.

Fortification of cereal flours may be a useful public health strategy to combat iron deficiency. Cereal flours that are used shortly after production (e.g., baking flour) can be fortified with soluble iron compounds, such as ferrous sulfate, whereas the majority of flours stored for longer periods is usually fortified with elemental iron powders to avoid unacceptable sensory changes. Elemental iron powders are less well absorbed than soluble iron compounds and they vary widely in their absorption depending on manufacturing method and physicochemical characteristics. Costs vary with powder type, but elemental iron powders are generally less expensive than ferrous sulfate. This review evaluates the usefulness of the different elemental iron powders based on results from in vitro studies, rat assays, human bioavailability studies, and efficacy studies monitoring iron status in human subjects. It concludes that, at the present time, only electrolytic iron powder can be recommended as an iron fortificant. Because it is only approximately half as well absorbed as ferrous sulfate, it should be added to provide double the amount of iron.

Effect of iron-deficiency anemia on cognitive skills and neuromaturation in infancy and childhood.

Iron-deficiency anemia in infancy has been consistently shown to negatively influence performance in tests of psychomotor development. In most studies of short-term follow-up, lower scores did not improve with iron therapy, despite complete hematologic replenishment. The negative impact on psychomotor development of iron-deficiency anemia (IDA) in infancy has been well documented in more than a dozen studies during the last two decades. Two studies will be presented here to further support this assertion. Additionally, we will present some data referring to longer follow-up at 5 and 10 years as well as data concerning recent descriptions of the neurologic derangements that may underlie these behavioral effects. To evaluate whether these deficits may revert after long-term observation, a cohort of infants was re-evaluated at 5 and 10 years of age. Two studies have examined children aged 5 years who had anemia as infants using comparable tools of cognitive development showing persisting and consistent important disadvantages in those who were formerly anemic. These tests were better predictors of future achievement than psychomotor scores. These children were again examined at 10 years and showed lower school achievement and poorer fine-hand movements. Studies of neurologic maturation in a new cohort of infants aged 6 months included auditory brain stem responses and naptime 18-lead sleep studies. The central conduction time of the auditory brain stem responses was slower at 6, 12, and 18 months and at 4 years, despite iron therapy beginning at 6 months. During the sleep-wakefulness cycle, heart-rate variability--a developmental expression of the autonomic nervous system--was less mature in anemic infants. The proposed mechanisms are altered auditory-nerve and vagal-nerve myelination, respectively, as iron is required for normal myelin synthesis.

Multiple-micronutrient fortification technology development and evaluation: from lab to market.

At the World Summit for Children (New York, 1990), a resolution was passed to eliminate vitamin A and iodine deficiencies and significantly reduce iron-deficiency anemia by the year 2000. In responding to this urgent call, we developed a unique multiple-micronutrient fortification delivery system called "GrowthPlus/CreciPlus." Using this technology, a fortified powder fruit drink has been formulated and extensively evaluated. One serving of the product delivers the following US recommended dietary allowances: 20-30% of iron; 10-35% of vitamin A; 25-35% of iodine; 100-120% of vitamin C; 25-35% of zinc; 15-35% of folate; and 10-50% of vitamins E, B2, B6, and B12. This was accomplished through (a) identifying and selecting the right fortificants, and (b) understanding their chemical and physical properties that contribute to multiple problems (product acceptability, stability, and bioavailability). Data from a home-use test showed fortification with the "Multiple-Fortification Technology" has no effect on the appearance and taste of the eventually consumed powder fruit drink. One-year stability studies demonstrated that iodine and the vitamins have adequate stability. Bioavailability evaluation by using double-isotope labeling technique showed that the iron from the fortified powder drink has excellent bioavailability (23.4% +/- 6.7). In conclusion, a powder fruit drink has been clinically demonstrated to deliver multiple micronutrients, which include adequate levels of bioavailable iron, vitamin A, iodine, zinc, vitamin C, and B vitamins, without compromising taste, appearance, and bioavailability. The critical limiting step in the micronutrient fortification program is the production and distribution of the multiple-micronutrient-fortified product. The fortified powder drink was marketed in Venezuela under the brand name NutriStar.

Rapid drop in infant blood lead levels during the transition to unleaded gasoline use in Santiago, Chile.

This study was conducted to relate blood lead levels in infants to changes in lead emissions in Santiago, Chile, a heavily polluted setting where leaded gasoline began to be replaced with unleaded gasoline in 1993. Over an 18-mo period, 422 infants had blood lead levels, cotinine, and iron status determined at 12 mo. Blood lead levels fell at an average rate of 0.5 microg/dl every 2 mo, from 8.3 to 5.9 microg/dl, as the city experienced a net fall of 30% in the quantity of leaded gasoline sold. Time progression, car ownership, serum cotinine, and type of housing were significantly associated with a blood lead level > or = 10 microg/dl. In this study, the authors demonstrated that infant blood lead levels, even if relatively low, can drop very rapidly in conjunction with decreases in environmental lead exposure.

Iron bioavailability in corn-masa tortillas is improved by the addition of disodium EDTA.

Corn-masa flour flat bread tortillas are the main staple of Mexican and Central American populations. Due to high concentrations of inhibitors of iron absorption, the bioavailability from this matrix is unknown. We wanted to determine the most suitable fortificant that would efficaciously improve iron bioavailability. In tortillas prepared with commercial precooked, lime-treated, corn-masa flour, we examined the in vitro solubility of the following forms of iron: native iron with and without Na2EDTA, elemental reduced iron plus Na2EDTA, ferrous fumarate with and without Na2EDTA, bisglycine iron, ferrous sulfate and NaFeEDTA. We also examined the in vivo bioavailability in humans with double radioiron erythrocyte incorporation of ferrous fumarate with and without Na2EDTA, bisglycine iron, NaFeEDTA and native iron plus Na2EDTA, beans and rice. In vitro, solubility ranged from 1% in iron forms without Na2EDTA to 19.4% for NaFeEDTA. Forms of iron with Na2EDTA had intermediate values. In vivo radioiron studies showed that iron forms without Na2EDTA also had low bioavailability (< or =1%). NaFeEDTA had the highest bioavailability (5.3%). The bioavailability of all iron forms improved significantly when tested with Na2EDTA (<0.05). Adding Na2EDTA to ferrous fumarate increased bioavailability from 0.87% to 2.9% (P < 0.001). We conclude that NaFeEDTA is the form of iron best absorbed, but alternatively, ferrous fumarate plus Na2EDTA comprises a feasible option as a fortificant.

The poor bioavailability of elemental iron in corn masa flour is not affected by disodium EDTA.

The most sustainable way to eradicate iron deficiency is through food fortification. Elemental iron powders are commonly utilized as fortificants due to their low cost and few sensory problems. However, their bioavailability is unknown. Our goals were to measure the bioavailability of elemental iron in Mexican style corn masa flour tortillas and to evaluate the effects of Na(2)EDTA. We used a stable isotope of H(2)-reduced iron powder, with and without Na(2)EDTA in tortillas prepared with corn masa flour. Two groups of 5- to 7-y-old children (n = 12/group) were fed tortillas to which was added 3 mg/100 g of H(2)-reduced (58)Fe with a mean particle size of 15 micro m. In one group, Na(2)EDTA was incorporated at a ratio of 1:2 mol/mol. The next day, (57)Fe ascorbate was given as a reference dose. After 14 d, blood samples were analyzed for isotopic enrichment. When normalized to 40% absorption of the reference dose, the geometric mean (+/-range 1 SD) bioavailability of reduced iron in tortilla was 3.8% (2.7-5.3). The addition of Na(2)EDTA, tended to increase it (P = 0.18) to 5.1% (2.8-9.2). This observed low absorption was compounded by the use of iron isotopes with smaller particle size (mean diameter 15 micro m) than typical of commercial elemental iron powder (<45 micro m). We conclude that H(2)-reduced iron powder is an ineffective fortificant in corn tortillas.

Behavioral and developmental effects of preventing iron-deficiency anemia in healthy full-term infants.

OBJECTIVE: To determine the behavioral and developmental effects of preventing iron-deficiency anemia in infancy. METHODS: Healthy full-term Chilean infants who were free of iron-deficiency anemia at 6 months were assigned to high- or low-iron groups or to high- or no-added-iron groups. Behavioral/developmental outcomes at 12 months of age included overall mental and motor test scores and specific measures of motor functioning, cognitive processing, and behavior. There were no differences between high- and low-iron groups in the prevalence of iron-deficiency anemia or behavioral/developmental outcome, and they were combined to form an iron-supplemented group (n = 1123) for comparison with the no-added-iron group (n = 534). RESULTS: At 12 months, iron-deficiency anemia was present in 3.1% and 22.6% of the supplemented and unsupplemented groups, respectively. The groups differed in specific behavioral/developmental outcomes but not on global test scores. Infants who did not receive supplemental iron processed information slower. They were less likely to show positive affect, interact socially, or check their caregivers' reactions. A smaller proportion of them resisted giving up toys and test materials, and more could not be soothed by words or objects when upset. They crawled somewhat later and were more likely to be tremulous. CONCLUSIONS: The results suggest that unsupplemented infants responded less positively to the physical and social environment. The observed differences seem to be congruent with current understanding of the effects of iron deficiency on the developing brain. The study shows that healthy full-term infants may receive developmental and behavioral benefits from iron supplementation in the first year of life.

Fine particulate matter and wheezing illnesses in the first year of life.

BACKGROUND: Recent evidence implicates fine particulate matter (PM2.5), principally from vehicular exhaust, as a major cause of increased mortality and morbidity. However, there are limited data on the impact of PM2.5 on infant respiratory illnesses. METHODS: We conducted a cohort study of 504 infants recruited at 4 months of age from primary health care units in southeastern Santiago, Chile. Project physicians followed infants through the first year of life via monthly check-ups and by appointments on demand. We obtained data for fine particulate matter, sulfur dioxide (SO2), and nitrogen dioxide (NO2) from the governmental monitoring network. RESULTS: The most frequent diagnosis during follow-up was wheezing bronchitis, occurring 19.5 times per 100 infants per month. After adjusting for sex, socioeconomic level, family history of asthma, minimum temperature, and number of older siblings, we found that an increase of 10 microg/m of PM2.5 24-hour average was related to a 5% increase (95% confidence interval 0-9%) in the risk for wheezing bronchitis (1-day lag). This association was present for different lags, with a maximum observed for a 9-day lag (9%; 6-12%). No consistent association was detected with NO2 or SO2 ambient levels. Lower socioeconomic status and having older siblings were also associated with the risk of wheezing bronchitis. The association of PM2.5 and wheezing bronchitis was stronger among infants with a family history of asthma than among infants without. CONCLUSIONS: Air pollution in the form of fine particulates, mostly from vehicular exhaust, may adversely affect infants' respiratory health with potential for chronic effects later in life.

Causas y consecuencias de la deficiencia de hierro / Causes and consequences of iron deficiency

La deficiencia de hierro es la deficiencia nutricional más prevalente y la principal causa de anemia a escala mundial. Además de las manifestaciones propias de la anemia, se han descrito otras manifestaciones no hematológicas tales como: disminución de la capacidad de trabajo físico y de la actividad motora espontánea, alteraciones de la inmunidad celular y de la capacidad bactericida de los neutrófilos, disminución de la termogénesis, alteraciones funcionales e histológicas del tubo digestivo, falla en la movilización de la vitamina A hepática, mayor riesgo de parto prematuro, bajo peso de nacimiento y de morbilidad perinatal, menor transferencia de hierro al feto, una disminución de la velocidad de crecimiento, alteraciones conductuales y del desarrollo mental y motor, velocidad de conducción más lenta de los sistemas sensoriales auditivo y visual, y reducción del tono vagal. La prevención de la deficiencia de hierro incluye cambios en los hábitos alimentarios, fortificación de los alimentos y la suplementación con hierro.

Crecimiento en talla del lactante chileno de bajo estrato socieconómico: 1978-1992 / Growth on terms of length of chilean infants of low socieconomic stratum: 1978-1992

En Chile, la desnutrición en la infancia se refleja más por el retraso del crecimiento en talla que por la relación peso/edad. Este estudio tiene como objetivo presentar la evolución del crecimiento en talla, entre 1978 y 1992, de lactantes de bajo nivel socieconómico. De tres estudios de intervención nutricional, se seleccionaron lactantes con peso de nacimiento >3000g y talla de nacimiento >0.5z Los lactantes según alimentación láctea se asignaron a: Grupo LV (desde antes del cuarto mes de vida) y el grupo LME (lactancia materna hasta después del sexto mes como única fuente lactea). La talla al nacer de los lactantes LV de la cohorte 1978-80 es de z + 0.21 y al año de z - 0.65, en promedio perdieron 0,86 z de talla. En cambio, en las lactantes de las cohortes 1982-86 y 1988-92 la talla cae de z - 0.37 (delta = 0.52 z) y de z + 0.16 a z - 0.19 (delta = 0.45 z) entre el nacimiento y el año de vida, respectivamente. Similar comportamiento presentan las tallas de los lactantes LME. En las tres cohortes, los lactantes tuvieron un adecuado aporte calórico-protéico, las curvas de crecimiento de peso-para la-talla se mantuvieron por sobre z + 0.5 durante todo el primer año de vida. Al analizar las pendientes de las curvas de crecimiento en talla de las tres cohortes se observó una disminución significativa de las pendientes a través del tiempo para los niños LV (p<0.001) como para los niños LME (p<0.001). La prueba de regresión lineal múltiple mostró asociación significativa entre z talla al año y peso de nacimiento (p<0.05), talla de nacimiento (p<0.0001) e índice socieconómico (p<0.0001). Se concluye que la evolución del crecimiento en talla en el primer año de vida del lactante chileno ha ido mejorando a través del tiempo, principalmente debido a una mejoría del nivel de vida de la población

Determinación cuantitativa de hemoglobina fecal por fluorimetría / Cuantitative determination of fecal hemoglobina through fluorometry

Con el propósito de determinar cuantitativamente hemoglobina fecal oculta (HbFc), se montó una microtécnica fluorimétrica denominada HemoQuant. El método consiste en incubar la deposición con ácido oxálico caliente y extraer la HbFc con solventes orgánicos. Así la hem ( no fluorescente) es convertida en porfirina (fluorescente). Además se determinan las porfirinas degradadas por las bacterias intestinales, por acción de ácido cítrico caliente. Estas reacciones permiten que el HemoQuant no produzca falsos positivos ni negativos, ya que mide todo el hem que ha entrado al intestino. Se obtuvo una sensibilidad de 0,005 mg Hb/g de deposición y una reproducibilidad medida como coeficiente de variación para el estándar de 1,72% intra-día y 5,23% inter-día y para las muestras de deposición un 4,05% intra-día y 14,35% inter-día. La recuperabilidad fue de 91,3+-3,8%. Se concluye que la técnica tiene una alta sensibilidad, especificidad y recuperabilidad

Factores que modifican el estado de nutrición de hierro: contenido de taninos de infusiones de hierbas / Factors that may influence nutritional iron status: Tannins in herbal infusions

Los taninos son compuestos naturales que se encuentran abundantemente en hierbas, maderas y frutas. Debido a sus numerosos radicalos hidroxilos se unen fuertemente a metales como Fe,Cu y Zn, propiedad que les confiere la capacidad de ser fuertes inhbidores de la absorción gastrointestinal de estos minerales. El propósito de este trabajo fue determinar el contenido de taninos presente en infusiones de hierbas habitualmente consumidas en Chile y otros países sudamericanos. La determinación de taninos se realizó a partir de infusiones preparadas con hierbas desecadas mediante la técnica de Folin Denis. La yerba mate, el té y el oréganos resultaron ser las hierbas con mayor contenido de taninos (117, 100 y 84 mg ácido tánico/g de muestra seca). Niveles intermedios la coca, el matico, el boldo, el palto, el laurel, el naranjo y el hinojo entre 20 y 40 mg de ácido tánico/g). El paico, el cedrón, el apio y la manzanilla contienen los niveles más bajos de taninos (<10 mg/g). Se concluye que las infusiones de hierba consumidas más frecuentemente con las comidas las concentraciones de taninos más altas, lo que podría estar influyendo en la biodisponibilidad del hierro de la dieta

Hemoglobin-fortified biscuits: bioavailability and its effect on iron nutriture in school children

En Chile, los escolares reciben diariamente 30g de galletas de harina de trigo en un Programa de Desayunos Escolares. Estas galletas fueron fortificadas con 6% de hemoglobulina de vacuno. La biodisponibilidad del hiero, determinada mediante una técnica dobleisotópica, mostró una elevada absorción del hierro hemínico en las galletas fortificadas (19.7%). En un estudio piloto, aun grupo de 215 escolares se les administró diariamente la galleta fortificada (30g) durante dos períodos escolares, comparando-se sus estrado nutricional férrico con 212 niños que recibieron galletas no fortificadas. Las aceptabilidad de la galleta fortificada fue excelente. Al inicio ambos grupos presentaron una nutrición de hierro comparablemente buena. Al término del primer y segundo período escolar, el grupo fortificado acusó promedios de ferritina sérica más elevados. Los depósitos de hierro eran suficientes (ferritina sérica > ou = 20 µg/lt) en el 92 y n79% de los sujetos fortificados, y controles, respectivamente (P < 0.004). La alta biodisponibilidad del hierro de esta galleta, sus óptimas condiciones organolépticas y su efecto sobre la nutrición de hierro, hacen de este producto una alternativa promisoria para la prevención de la deficiencia de hierro