Iron Deficiency In Infants Research Articles

Food Based Complementary Feeding Strategies for Breastfed Infants: What's the Evidence that it Matters?

The period of complementary feeding represents a major portion of the 1000 day critical window and thus impacts a period of substantial and dynamic infant development. This review highlights and synthesizes findings of several recent studies conducted to evaluate food based strategies on outcomes related to micronutrient status, growth and neurocognitive development. Particular emphasis is placed on interventions using meat or fortified products to impact iron and zinc intakes, due to the dependence of breastfed infants on complementary food choices to meet requirements for these two critical micronutrients. Regular consumption of modest amounts of meat or fortified cereals provides adequate absorbed zinc to meet estimated physiologic requirements, whereas homeostatic adaptation to lower zinc intake from unfortified cereal/plant staples is inadequate to meet requirements. Iron fortification of cereals may be somewhat more effective than meat to improve iron status, but neither prevents iron deficiency in breastfed infants, even in westernized settings. Improvements in the quality of complementary foods have had very modest effects on linear growth in settings where stunting is prevalent. Maternal education is strongly associated with both linear growth and with child neurodevelopment. The determinants of early growth faltering are more complex and intractable than 'simple' dietary deficiencies of micronutrients. Solutions to growth faltering in young children most likely need to be multi-factorial, and almost certainly will need to start earlier than the complementary feeding period.

Iron and late preterm

Iron is essential for the Central Nervous System development, i.e. mielinization process and cellular differentiation as well as correct functioning of neurotransmitters [1]. Preterm infants show an increased risk of iron deficiency (ID) since 80% of the iron storage at birth is accumulated during the third trimester of pregnancy. Rapid child growth and elevated red cell turn over in the neonatal period may exaust iron storage after two months of age [2]. ID risk is greater in the breast-fed babies, since maternal milk does not contain an amount of iron sufficient to demands. However, ID prevalence equal to 14%, between the fourth and the eighth month of age [3], is also reported in the preterm infants who are nourished with milk formulas enriched with iron. Referred long-lasting effects of ID in infancy include reduced cognitive functions, motor performances and social-emotional development, as well as persisting neurophysiologic abnormalities [1]. As a consequence early iron supplementation is recommended for preterm and very-low-birth-weight infants [3]. Healthy late-preterm infants are often treated with the same modalities than term neonates. For these infants we lack strong evidence based recommendations about supplementation of iron, doses, time of beginning as well as duration of treatment. The RCT evidence to date does not suggest a definite threshold of birth-weight or gestational age at which iron supplementation becomes beneficial. Two methodologically sound trials suggest a benefit even for marginally low-birth-weight infants, whether term or preterm [4]. As recently reported, marginally low-birth-weight neonates showed a high prevalence of ID and Iron Deficiency Anemia (IDA) when evaluated at the age of six months, especially in the case of exclusive breast feeding to age six weeks [5]. Martial supplementation lowered ID and IDA prevalence without adverse effects. In conclusion, despite the amount of studies concerning ID in infancy, there is still a paucity of evidence about the effects of iron deficiency/overload with respect to growth , morbidity and neurodevelopmental outcomes in the different categories of neonates ,as well as about the reliability of the presently available iron methabolism markers.

A Study of the Effects of Latent Iron Deficiency on Measures of Cognition: A Pilot Randomised Controlled Trial of Iron Supplementation in Young Women

Rates of iron deficiency are high amongst healthy young women. Cognitive impairment occurs secondary to iron deficiency in infants and children, but evaluation of the impact on cognition among young women is inconsistent. The aim was to determine the suitability of the IntegNeuro test battery for assessing cognitive function in iron-deficient and iron-sufficient young women. A pilot double-blinded, placebo-controlled intervention trial was conducted in iron-deficient (serum ferritin ≤ 20 μg/L and haemoglobin > 120 g/L) and iron-sufficient young women (18–35 years). Cognitive function and haematological markers of iron status were measured at baseline and follow-up. Iron-deficient participants (n = 24) were randomised to receive placebo, 60 mg or 80 mg elemental iron daily supplements for 16 weeks. A control group of iron-sufficient participants (n = 8) was allocated to placebo. Change scores for Impulsivity and Attention were significantly greater in plasma ferritin improvers than in non-improvers (p = 0.004, p = 0.026). IntegNeuro was easy to administer and acceptable to young women. Based on the differences in Memory and Attention scores between iron-deficient participants on iron treatment and those on placebo, it was decided that between 26 and 84 participants would be required in each iron treatment group for an adequately powered extension of this pilot RCT.

Effect of gravity on volume of placental transfusion: a multicentre, randomised, non-inferiority trial

Delayed cord clamping allows for the passage of blood from the placenta to the baby and reduces the risk of iron deficiency in infancy. To hold the infant for more than 1 min at the level of the vagina (as is presently recommended), on the assumption that gravity affects the volume of placental transfusion, is cumbersome, might result in low compliance, and interferes with immediate contact of the infant with the mother. We aimed to assess whether gravity affects the volume of placental transfusion We did a multicentre non-inferiority trial at three university-affiliated hospitals in Argentina. We obtained informed consent from healthy mothers with normal term pregnancies admitted early in labour. Vigorous babies born vaginally were randomly assigned in a 1:1 ratio by computer-generated blocks and sequentially numbered sealed opaque envelopes to be held for 2 min before clamping the umbilical cord, at the level of the vagina (introitus group) or on the mother's abdomen or chest (abdomen group). Newborn babies were weighed immediately after birth and after cord clamping. The primary outcome was the difference in weight (as a proxy of placental transfusion volume). The prespecified non-inferiority margin was 18 g (20%). We used t test and χ(2) test for group comparison, and used a multivariable linear regression analysis to control for covariables. This trial is registered with ClinicalTrials.gov, number NCT01497353. Between Aug 1, 2011, and Aug 31, 2012, we allocated 274 newborn babies to the introitus group and 272 to the abdomen group. 77 newborn babies in the introitus group and 78 in the abdomen group were ineligible after randomisation (eg, caesarean section, forceps delivery, short umbilical cord or nuchal cord). Mean weight change was 56 g (SD 47, 95% CI 50-63) for 197 babies in the introitus group compared with 53 g (45, 46-59) for 194 babies in the abdomen group, supporting non-inferiority of the two approaches (difference 3 g, 95% CI -5.8 to 12.8; p=0.45). We did not note any serious adverse events during the study. Position of the newborn baby before cord clamping does not seem to affect volume of placental transfusion. Mothers could safely be allowed to hold their baby on their abdomen or chest. This change in practice might increase obstetric compliance with the procedure, enhance maternal-infant bonding, and decrease iron deficiency in infancy. Foundation for Maternal and Child Health (FUNDASAMIN).

G247(P) Profile of Profoundly anaemic children presenting to DGH

IntroductionAnaemia is the most common problem in children. Majority of the children are managed in the primary care settings. We had a 3 and a half year old girl presenting...

Linking infant iron status, brain function, and looking behavior during a memory task (810.36)

No definition of iron deficiency (ID) exists for infants under 12 mo, but young infants (4‐6 mo) are at risk of anemia and depleted iron stores. Nutritional insults during peak brain development (late gestation thru early infancy) may affect long‐term memory. Previous human studies used global cognitive measures, and cannot link ID to impaired memory via specific brain abnormalities. This study examined the links between iron status (hemoglobin (Hb), ferritin, transferrin receptor and body iron), memory function, and brain activity in 40 infants, aged 4‐6 mo. Memory performance was assessed via a Paired Comparison (PC) task and brain function via a similar task with synchronous electroencephalography (EEG). Mixed and logistic regression models were used to estimate the effect (OR) of iron status on 1) amplitude and latency of EEG peaks related to memory; 2) novelty preference and look duration in the PC. Covariates include quality of mother‐infant interactions and infant age, gender, and SES. Nearly 10% of infants were anemic (Hb <110 g/L) and over 70% had mild anemia (Hb 110‐120 g/L). Over 60% of infants showed novelty preference in the PC. This work will inform a definition of ID in infants <12 mo.Grant Funding Source: Supported by the USDA/NIFA (Hatch# 2012‐13‐228) and NSF Graduate Research Fellowship (JEH)

Iron Deficiency is Not Associated with Increased Blood Cadmium in Infants

ObjectivesTo determine whether blood cadmium concentration is elevated in iron-deficient infants.MethodsBlood cadmium and serum ferritin concentrations, serum iron/total iron-binding capacity (Fe/TIBC) and complete blood counts were measured in 31 iron deficient and 36 control infants, aged 6–24 months. All 31 iron-deficient infants received iron supplementation for 1–6 months.ResultsBlood cadmium concentrations were measured again in 19 of the iron deficient infants after their ferritin levels returned to the normal range. The mean blood cadmium concentration did not differ significantly in iron deficient and control infants. The mean blood cadmium concentration in the 19 iron-deficient infants was not significantly altered by ferric hydroxide treatment, while their hemoglobin, ferritin, and Fe/TIBC (%) concentrations were significantly higher after than before treatment.ConclusionThese findings indicate that iron deficiency does not increase blood cadmium concentrations in infants, in contrast with the effects of iron deficiency on manganese and lead concentrations.

Effect of delayed vs early umbilical cord clamping on iron status and neurodevelopment at age 12 months: a randomized clinical trial.

Prevention of iron deficiency in infancy may promote neurodevelopment. Delayed cord clamping (DCC) can prevent iron deficiency during the first 6 months of life. However, no data are available on long-term effects on infant outcomes in relation to time for umbilical cord clamping. To investigate effects of DCC, as compared with early cord clamping (ECC), on infant iron status and neurodevelopment at age 12 months in a European setting. Randomized clinical trial of 382 full-term infants born after a low-risk pregnancy at a Swedish county hospital. Follow-up at 12 months included evaluation of iron status (ferritin level, transferrin saturation, transferrin receptor level, reticulocyte hemoglobin level, and mean cell volume) and parental assessment of neurodevelopment by the Ages and Stages Questionnaire, second edition (ASQ). Infants were randomized to DCC (≥180 seconds after delivery) or ECC (≤10 seconds after delivery). The main outcome was iron status at age 12 months; the secondary outcome was ASQ score. In total, 347 of 382 infants (90.8%) were assessed. The DCC and ECC groups did not differ in iron status (mean ferritin level, 35.4 vs 33.6 ng/mL, respectively; P = .40) or neurodevelopment (mean ASQ total score, 229.6 vs 233.1, respectively; P = .42) at age 12 months. Predictors of ferritin levels were infant sex and ferritin in umbilical cord blood. Predictors of ASQ score were infant sex and breastfeeding within 1 hour after birth. For both outcomes, being a boy was associated with lower results. Interaction analysis showed that DCC was associated with an ASQ score 5 points higher among boys (mean [SD] score, 229 [43] for DCC vs 224 [39] for ECC) but 12 points lower among girls (mean [SD] score, 230 [39] for DCC vs 242 [36] for ECC), out of a maximum of 300 points (P = .04 for the interaction term). Delayed cord clamping did not affect iron status or neurodevelopment at age 12 months in a selected population of healthy term-born infants. However, it may not be possible to demonstrate minor effects on neurodevelopment with the size of the study population and the chosen method for assessment. The current data indicate that sex may influence the effects on infant development after DCC in different directions. The magnitude and biological reason for this finding remain to be investigated. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01245296.

Iron deficiency increases blood concentrations of neurotoxic metals in children.

Iron deficiency affects approximately one-third of the world's population, occurring most frequently in children aged 6 months to 3 years. Mechanisms of iron absorption are similar to those of other divalent metals, particularly manganese, lead, and cadmium, and a diet deficient in iron can lead to excess absorption of manganese, lead, and cadmium. Iron deficiency may lead to cognitive impairments resulting from the deficiency itself or from increased metal concentrations caused by the deficiency. Iron deficiency combined with increased manganese or lead concentrations may further affect neurodevelopment. We recently showed that blood manganese and lead concentrations are elevated among iron-deficient infants. Increased blood manganese and lead levels are likely associated with prolonged breast-feeding, which is also a risk factor for iron deficiency. Thus, babies who are breast-fed for prolonged periods should be given plain, iron-fortified cereals or other good sources of dietary iron.

Infant iron status affects iron absorption in Peruvian breastfed infants at 2 and 5 mo of age

Effects of prenatal iron supplementation on maternal postpartum iron status and early infant iron homeostasis remain largely unknown. We examined iron absorption and growth in exclusively breastfed infants in relation to fetal iron exposure and iron status during early infancy. Longitudinal, paired iron-absorption (⁵⁸Fe) studies were conducted in 59 exclusively breastfed Peruvian infants at 2-3 mo of age (2M) and 5-6 mo of age (5M). Infants were born to women who received ≥ 5100 or ≤ 1320 mg supplemental prenatal Fe. Iron status was assessed in mothers and infants at 2M and 5M. Infant iron absorption from breast milk averaged 7.1% and 13.9% at 2M and 5M. Maternal iron status (at 2M) predicted infant iron deficiency (ID) at 5M. Although no infants were iron deficient at 2M, 28.6% of infants had depleted iron stores (ferritin concentration <12 μg/L) by 5M. Infant serum ferritin decreased (P < 0.0001), serum transferrin receptor (sTfR) increased (P < 0.0001), and serum iron decreased from 2M to 5M (P < 0.01). Higher infant sTfR (P < 0.01) and breast-milk copper (P < 0.01) predicted increased iron absorption at 5M. Prenatal iron supplementation had no effects on infant iron status or breast-milk nutrient concentrations at 2M or 5M. However, fetal iron exposure predicted increased infant length at 2M (P < 0.01) and 5M (P < 0.05). Fetal iron exposure affected early infant growth but did not significantly improve iron status or absorption. Young, exclusively breastfed infants upregulated iron absorption when iron stores were depleted at both 2M and 5M.

Iron deficiency and anemia in iron-fortified formula and human milk-fed preterm infants until 6 months post-term

An iron intake of >2 mg/kg/d is recommended for preterm infants. We hypothesized that human milk (HM)-fed preterm infants require iron supplementation after discharge, whereas iron-fortified formulae (IFF; 0.8-1.0 mg iron/100 ml) may provide sufficient dietary iron until 6 months post-term. At term age, 3 and 6 months post-term, ferritin (μg/l) was measured in 92 IFF-fed infants (gestational age (median (interquartile range)) 30.7 (1.4) weeks, birth weight 1,375 (338) gram) and 46 HM-fed infants (gestational age 30.0 (1.7) weeks, birth weight 1,400 (571) gram). Iron intake (mg/kg/d) between term age and 6 months post-term was calculated. Iron was supplemented to 71.7% of HM-fed and 83.7% of IFF-fed infants between term age and 3 months post-term and to 13% of HM-fed and 0% of IFF-fed infants between 3 and 6 months post-term. IFF-fed infants had an iron intake from supplements and formula of 2.66 (1.22) mg/kg/d between term age and 3 months post-term and 1.19 (0.32) mg/kg/d between 3 and 6 months post-term. At 3 and 6 months post-term, the incidence of ferritin <12 μg/l was higher in HM-fed compared to IFF-fed infants (23.8 vs. 7.8% and 26.3 vs. 9.5%, P < 0.02). This observational study demonstrates that ferritin <12 μg/l is more prevalent in HM-fed infants until 6 months post-term. This may be due to early cessation of additional iron supplementation. We speculate that additional iron supplementation is not necessary in preterm infants fed IFF (0.8-1.0 mg iron/100 ml), as they achieve ferritin ≥12 μg/l without additional iron supplements between 3 and 6 months post-term.

Effects of iron therapy on blood lead concentrations in infants

To determine whether blood lead concentration is elevated in iron-deficient infants, blood lead and serum ferritin concentrations, serum iron/transferring iron-binding capacity (Fe/TIBC) and complete blood counts were measured in 30 iron deficient and 35 control infants, aged 6–24 months. All 30 iron-deficient infants received iron supplementation (ferric hydroxide-polymaltose complex, 6mg/kg Fe3+/day) for 1–6 months. Blood lead concentrations were measured in 18 of the iron deficient infants after their ferritin levels returned to the normal range. The geometric mean blood lead concentration was higher in iron deficient than in control infants (1.846 vs. 1.416μg/dL). After iron therapy, the blood lead levels of iron-deficient infants decreased significantly compared with pre-treatment levels (1.785 vs. 2.386μg/dL), and the hemoglobin and ferritin concentrations increased significantly. These findings indicate that iron deficiency increases blood lead concentrations in infants with very low blood lead concentrations.

Fisiopatología e impacto de la deficiencia de hierro y la anemia en las mujeres gestantes y en los recién nacidos/infantes

La deficiencia de hierro es el trastorno de deficiencia más prevalente; y la anemia por deficiencia de hierro es la forma de anemia más frecuente en las mujeres gestantes. Son causas menores de la anemia la deficiencia de folato y de la vitamina B12; así como las hemoglobinopatías y la anemia hemolítica. Se define a la anemia como niveles de hemoglobina &lt;110 g/L en el primer y en el tercer trimestre y &lt;105 g/L en el segundo trimestre de la gestación. El diagnóstico se basa en la medición de los valores de la hemoglobina, así como en un perfil hematológico completo y la determinación de los niveles plasmáticos de ferritina, los cuales pueden sustentarse en la saturación de la transferrina en el plasma y el receptor soluble de transferrina en el suero (sTfR, soluble transferrin receptor). En las mujeres no gestantes en edad reproductiva, un 40% tiene valores de ferritina por debajo de 30 μg/L, lo cual indica que las reservas de hierro o son pequeñas o están ausentes; y, en consecuencia, tienen un pobre nivel del hierro con respecto a un embarazo futuro. Los requerimientos para la absorción del hierro aumentan durante la gestación, de 0,8 mg/día en el primer trimestre a 7,5 mg/día en el tercer trimestre, siendo el promedio 4,4 mg/día. En cuanto a la edad reproductiva, un 40% de las mujeres en Escandinavia y posiblemente hasta un 80% de las mujeres peruanas (dependiendo de su condición social y su lugar de residencia) tienen niveles bajos de hierro con respecto a un embarazo futuro. En el Perú, la prevalencia de la anemia en las mujeres no gestantes de edad reproductiva es 22%, y en las mujeres gestantes es de 27%. La prevalencia de la anemia en el tercer trimestre puede variar desde 14 hasta 52% en las mujeres que no toman suplementos de hierro (dependiendo del país y de la condición social); y de 0 a 25% en las mujeres que toman suplementos de hierro (dependiendo de las dosis del citado elemento). La deficiencia de hierro y la anemia poseen consecuencias severas en las mujeres gestantes, estando asociadas con una menor capacidad para trabajar, fatiga, debilidad y disturbios psíquicos, condiciones que en su totalidad afectan la calidad de vida tanto a nivel físico como psíquico. En el feto/en el recién nacido la deficiencia de hierro puede tener consecuencias serias para el desarrollo de las funciones cerebrales. Incrementa la prevalencia de nacimientos prematuros y la frecuencia de peso bajo al nacer, así como la mortalidad perinatal. Los niños nacidos de madres con deficiencia de hierro tienen un menor desarrollo cognitivo, motor, socio-emocional y neurofisiológico, así como menores valores del cociente de inteligencia en comparación con los infantes y niños nacidos de madres con niveles normales de hierro. La anemia por deficiencia de hierro posee consecuencias serias en las mujeres y en los fetos/neonatos; y requiere una intervención eficiente con una profilaxis y/o tratamiento con hierro. En el futuro, los sistemas de cuidado de la salud prenatal deberán dedicar más esfuerzos para erradicar este problema tan significativo. Palabras clave: Anemia; deficiencia de hierro; embarazo.

Infant Emotional Withdrawal: A Precursor of Affective and Cognitive Disturbance in Fetal Alcohol Spectrum Disorders

Our aim was to test the hypothesis that emotional withdrawal is an early indicator of affective disorder in infants heavily exposed prenatally to alcohol, which is independent of alcohol-related effects on mother-infant interaction and temperament and discriminated between children later diagnosed with fetal alcohol syndrome (FAS) and partial FAS (PFAS) and predicted cognitive and affective outcomes at 5 and 9years. The sample consisted of Cape Coloured (mixed ancestry) infants, whose mothers were interviewed during pregnancy regarding their alcohol consumption using a timeline follow-back approach. Infant emotional withdrawal (n=85) was assessed on the Alarm Distress Baby Scale at 6.5months. Mother-infant interaction was evaluated from video recordings during free play and infant feeding at 6.5months (n=127). Infant temperament was assessed by maternal report on the EAS Temperament Survey at 13months (n=119). Sociodemographic and psychological correlates of maternal alcohol use and infant iron deficiency were examined as potential confounders. The children were diagnosed for FAS/PFAS by expert dysmorphologists at 5years, cognitive and affective function at 5 and 9years. Prenatal alcohol exposure was associated with increased infant emotional withdrawal and decreased activity, but unrelated to mother-infant interaction or any other temperament measures. Children later diagnosed with FAS and PFAS at 5years exhibited more emotional withdrawal and less responsivity and activity as infants. Infant withdrawal, responsivity, quality of interaction, and maternal sensitivity also predicted poorer IQ and affective response at 5 and 9years. When all 4 infant affective measures were examined simultaneously in a regression analysis, only infant emotional withdrawal persisted as a significant predictor of 9-year IQ. This study is the first to document a direct effect of fetal alcohol exposure on emotional withdrawal in infancy. These data link prenatal alcohol to a specific aspect of infant affective function not attributable to mother-infant interaction, infant temperament, or other socioemotional aspects of the infant's environment and identify infant emotional withdrawal as an early indicator of affective disturbance, particularly in children later diagnosed with FAS and PFAS.

Blood Manganese Concentration is Elevated in Infants with Iron Deficiency

The present study was done to determine whether blood Mn concentration is elevated in iron-deficient infants. Thirty-one infants with iron deficiency and thirty-six control subjects (6-24 months of age) were tested for blood Mn concentration, complete blood counts, serum ferritin, and serum iron/transferring iron-binding capacity (Fe/TIBC). All the 31 iron-deficient infants were treated with iron supplement; however, 19 of them underwent blood Mn checkup again in compliance with follow-up schedule when their ferritin levels returned to the normal range. Iron therapies were done for 1-6 months (mean, 2.8; standard deviation, 1.6) using ferric hydroxide-polymaltose complex (6 mg/kg Fe(3+) daily). Infants with iron deficiency had a higher mean blood Mn concentration than controls (2.550 vs. 1.499 μg/dL, respectively). After iron therapy, the blood Mn levels of iron-deficient infants significantly decreased compared to their pre-therapy levels (2.045 vs. 2.971 μg/dL, respectively), and their hemoglobin and ferritin levels significantly increased. After adjustment for covariates (e.g., age and breast-feeding), multiple linear regression models showed that increased blood Mn levels were significantly associated with low serum ferritin and hemoglobin levels, whereas with Fe/TIBC there was only a tendency. Our results indicate that iron deficiency increases blood Mn levels in infants, presumably by increasing Mn absorption.

Impact of Multiple Prenatal Risk Factors on Newborn Iron Status at Delivery

Maternal anemia and several complications of pregnancy can affect fetal iron acquisition. Because it is unknown whether the effects of demographic and maternal risk factors (RF) are summative, we examined cord iron status in newborns with multiple RF for acquiring iron deficiency. Cord blood indices from healthy control newborns with and without RF for newborn or infant iron deficiency were studied. Newborns with greater RF had poorer erythrocyte and storage iron status. Poorest status was seen if mothers with comorbid obesity and diabetes delivered large-for-gestation newborns. Findings highlight the importance of identifying RF.

Iron status and developmental scores in 6‐year‐olds highlights ongoing need to tackle iron deficiency in infants

To investigate iron status and developmental scores at 6 years of age in a population with decreased prevalence of iron deficiency in infancy. Iron status at 6 years and tracking from 12 months were also studied. Children (n = 143) born in Iceland in 2005 were followed up at the age of six. Motor and verbal development was assessed by a parental questionnaire, and iron status was assessed by Hb, MCV and serum ferritin (SF). Iron depletion was defined as SF <15 μg/L and deficiency as MCV <76 fL and SF <15 μg/L. Iron depletion was observed in 5.6% of 6-year-olds, and 1.4% were iron deficient. Self-help (subset in motor development) differed by -4.14 (95% CI = -7.61, -0.67), between those iron depleted at 12 months (n = 6) and those nondepleted (n = 102), adjusted for maternal education. The combined motor developmental score seemed lower in iron depleted infants, although of borderline significance (p = 0.066). MCV concentration tracked from 12 months to 6 years (r = 0.31, p < 0.002), but Hb and SF did not. Improved iron status at 12 months and 6 years has diminished the public health threat associated with iron depletion in the population studied, but iron depletion and development still associate weakly. Action to prevent iron depletion in infancy remains important.

Functional Significance of Early-Life Iron Deficiency: Outcomes at 25 Years

To evaluate adulthood function following chronic iron deficiency in infancy. At 25 years, we compared 33 subjects with chronic iron deficiency in infancy to 89 who were iron-sufficient before and/or after iron therapy. Outcomes included education, employment, marital status, and physical and mental health. Adjusting for sex and socioeconomic status, a higher proportion of the group with chronic iron deficiency did not complete secondary school (58.1% vs 19.8% in iron-sufficient group; Wald value = 8.74; P = .003), were not pursuing further education/training (76.1% vs 31.5%; Wald value = 3.01; P = .08; suggestive trend), and were single (83.9% vs 23.7%, Wald value = 4.49; P = .03). They reported poorer emotional health and more negative emotions and feelings of dissociation/detachment. Results were similar in secondary analyses comparing the chronic iron-deficient group with subjects in the iron-sufficient group who had been iron-deficient before treatment in infancy. Path analysis showed direct paths for chronic iron deficiency in infancy and being single and more detachment/dissociation at 25 years. There were indirect paths for chronic iron deficiency and not completing secondary school via poorer cognitive functioning in early adolescence and more negative emotions via behavior problems in adolescence, indicating a cascade of adverse outcomes. The observational nature of this study limits our ability to draw causal inference, even when controlling for background factors. Nonetheless, our results indicate substantial loss of human potential. There may be broader societal implications, considering that many adults worldwide had chronic iron deficiency in infancy. Iron deficiency can be prevented or treated before it becomes chronic or severe.

Relationships between infant morbidity, iron deficiency and growth

ObjectiveTo examine how caregiver infant morbidity reports relate to biomarkers of inflammation, iron deficiency and infant growth.MethodsAmong 497 infants age 6–12 months, morbidity was collected by 15 day caregiver recall. Biomarkers for iron deficiency (ID; ferritin&lt; 12) and inflammation (CRP: C ‐ reactive protein &gt;; 10mg/L); and anthropometry (measured weight and length) were collected. Stunting (HAZ&lt;−2), wasting (WHZ &lt;−2), and underweight (WAZ&lt;−2) were computed using WHO standards. Chi‐square and multivariate logistic regression, adjusting for maternal anthropometry and education, child age, and household assets, were conducted.ResultsAmong infants, 20% were stunted, 10% were wasted, 19% were underweight, 28% were ID, and 56% had an elevated CRP. Maternal reports of infant fever (35%) was related to elevated CRP and ID (p&lt; 0.05), cough (28%) and diarrhea (11%) were related to elevated CRP (p&lt; 0.05). In multivariate logistic models, ID (OR: 2.33; CI: 1.15–4.73) and fever (OR: 2.69; CI: 1.31–5.49) were related to wasting, and elevated CRP was related to stunting (OR=1.96; CI: 1.18–3.25)ConclusionFindings suggest that caregiver reports of recent infant morbidity relate to biomarkers of inflammation and ID, and that all three relate to poor growth in infantsResearch Support; Mathile Institute &amp; Micronutrient Initiative

Effects of Iron Supplementation of LBW Infants on Cognition and Behavior at 3 Years

Low birth weight (LBW) infants are at increased risk of cognitive and behavioral problems and at risk for iron deficiency, which is associated with impaired neurodevelopment. We hypothesized that iron supplementation of LBW infants would improve cognitive scores and reduce behavioral problems. In a randomized controlled trial, 285 marginally LBW (2000-2500 g) infants received 0, 1, or 2 mg/kg/day of iron supplements from 6 weeks to 6 months of age. At 3.5 years of age, these infants and 95 normal birth weight controls were assessed with a psychometric test (Wechsler Preschool and Primary Scale of Intelligence) and a questionnaire of behavioral problems (Child Behavior Checklist; CBCL). There were no significant differences in IQ between the LBW groups or LBW infants versus controls. Mean (SD) full-scale IQ was 105.2 (14.5), 104.2 (14.7), and 104.5 (12.7) in the placebo, 1 mg, and 2 mg groups, respectively (P = .924). However, for behavioral problems, there was a significant effect of intervention. The prevalence of children with CBCL scores above the US subclinical cutoff was 12.7%, 2.9%, and 2.7% in the placebo, 1-mg, and 2-mg groups, respectively (P = .027), compared with 3.2% in controls. Relative risk (95% confidence interval) for CBCL score above cutoff in placebo-treated children versus supplemented was 4.5 (1.4-14.2). Early iron supplementation of marginally LBW infants does not affect cognitive functions at 3.5 years of age but significantly reduces the prevalence of behavioral problems. The study suggests a causal relation between infant iron deficiency and later behavioral problems.