Laura E. Murray-Kolb

Prenatal Micronutrient Supplementation and Intellectual and Motor Function in Early School-aged Children in Nepal

CONTEXT Iron and zinc are important for the development of both intellectual and motor skills. Few studies have examined whether iron and zinc supplementation during gestation, a critical period of central nervous system development, affects childrens later functioning. OBJECTIVE To examine intellectual and motor functioning of children whose mothers received micronutrient supplementation during pregnancy. DESIGN, SETTING, AND PARTICIPANTS Cohort follow-up of 676 children aged 7 to 9 years in June 2007-April 2009 who had been born to women in 4 of 5 groups of a community-based, double-blind, randomized controlled trial of prenatal micronutrient supplementation between 1999 and 2001 in rural Nepal. Study children were also in the placebo group of a subsequent preschool iron and zinc supplementation trial. INTERVENTIONS Women whose children were followed up had been randomly assigned to receive daily iron/folic acid, iron/folic acid/zinc, or multiple micronutrients containing these plus 11 other micronutrients, all with vitamin A, vs a control group of vitamin A alone from early pregnancy through 3 months postpartum. These children did not receive additional micronutrient supplementation other than biannual vitamin A supplementation. MAIN OUTCOME MEASURES Childrens intellectual functioning, assessed using the Universal Nonverbal Intelligence Test (UNIT); tests of executive function, including go/no-go, the Stroop test, and backward digit span; and motor function, assessed using the Movement Assessment Battery for Children (MABC) and finger-tapping test. RESULTS The difference across outcomes was significant (Bonferroni-adjusted P < .001) for iron/folic acid vs control but not for other supplement groups. The mean UNIT T score in the iron/folic acid group was 51.7 (SD, 8.5) and in the control group was 48.2 (SD, 10.2), with an adjusted mean difference of 2.38 (95% confidence interval [CI], 0.06-4.70; P = .04). Differences were not significant between the control group and either the iron/folic acid/zinc (0.73; 95% CI, -0.95 to 2.42) or multiple micronutrient (1.00; 95% CI, -0.55 to 2.56) groups. In tests of executive function, scores were better in the iron/folic acid group relative to the control group for the Stroop test (adjusted mean difference in proportion who failed, -0.14; 95% CI, -0.23 to -0.04) and backward digit span (adjusted mean difference, 0.36; 95% CI, 0.01-0.71) but not for the go/no-go test. The MABC score was lower (better) in the iron/folic acid group compared with the control group but not after adjustment for confounders (mean difference, -1.47; 95% CI, -3.06 to 0.12; P = .07). Finger-tapping test scores were higher (mean difference, 2.05; 95% CI, 0.87-3.24; P = .001) in the iron/folic acid group. CONCLUSION Aspects of intellectual functioning including working memory, inhibitory control, and fine motor functioning among offspring were positively associated with prenatal iron/folic acid supplementation in an area where iron deficiency is prevalent. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00115271.

Iron deficiency: differential effects on monoamine transporters.

Abstract In this study, we extend previous work on iron deficiency and dopamine (DA) transporters to include an examination of central serotonin (5-HT) and noradrenergic (NE) transporters. Rats were fed either iron deficient (ID) or iron adequate (CN) diets from weaning until adulthood. In males, an additional group of iron deficient animals (IR) were given iron supplementation. DA, 5-HT, and NE transporter binding was done in situ on thin sections. ID males, but not females, decreased DA transporter binding in the nucleus accumbens, caudate putamen and substantia nigra by 20–40%. ID males also had a 20–30% reduction in 5-HT transporter binding in several areas (nucleus accumbens, olfactory tubercle, colliculus) while in ID females there was 15–25% increased serotonin transporter binding in the olfactory tubercle, zona incerta, anteroventral thalamic nucleus and vestibular nucleus. Iron deficiency reduced 3 H-nisoxetine binding to the NE transporter in locus ceruleus and anteroventral thalamic nucleus in males but not females. Only some of the changes observed in DA, serotonin and NE transporter binding were reversible by iron supplementation. These findings show that iron deficiency affects monoamine systems related to homeostasis and in most cases males appear to be more vulnerable than females.

Iron deficiency and child and maternal health

BACKGROUND Iron deficiency is most commonly found in women of reproductive age and infants worldwide, but the influence of maternal iron deficiency on infant development is underexplored. OBJECTIVE The objective was to examine the relation between maternal iron status and mother-child interactions in a randomized, double-blind, intervention trial conducted in South Africa. DESIGN Women were recruited into the study from a health clinic at 6-8 wk postpartum and were classified as either iron-deficient anemic (IDA) or iron-sufficient after blood analysis. IDA mothers received iron supplements of 125 mg FeSO(4) (IDA-Fe; n = 34) or placebo (IDA-PL; n = 30) daily from 10 wk to 9 mo postpartum. The control group (n = 31) consisted of iron-sufficient mothers. Free-play mother-child interaction sessions were videotaped in the clinic at 10 wk (n = 80) and 9 mo (n = 66) postpartum and coded per the Emotional Availability Scales (4 maternal scales: sensitivity, structuring, nonintrusiveness, and nonhostility; 2 infant scales: responsiveness and involvement). RESULTS At 10 wk, scores for maternal sensitivity and child responsiveness were significantly greater in the control group than in the IDA groups (P = 0.028 and 0.009, respectively). At 9 mo, the control and IDA-Fe groups no longer differed. These 2 groups scored significantly better on the maternal sensitivity, structuring, and nonhostility scales and on the child responsiveness scale than did the IDA-PL group (P = 0.007-0.032), whose iron status remained low. CONCLUSION These data indicate that maternal iron deficiency negatively affects mother-child interactions and that iron supplementation protects against these negative effects.

Nutritional guidance is needed during dietary transition in early childhood.

Objective. To assess dietary nutritional quality during dietary transition to a modified adult-style diet in the second year of life. Design. A total of 55 children from 12 to 18 months old and their parents were studied. Dietary intake and indices of growth were measured monthly. Dietary data were collected monthly and tabulated using the Minnesota Nutrient Data System. Data were evaluated using repeated-measures analysis of variance, time trend, and correlational analyses. Results. Mean energy intake increased from 12 to 18 months of age (926 ± 24 kcal to 1062 ± 33 kcal) with contributions from energy-yielding macronutrients remaining relatively constant. Throughout the study, fat intakes were below 30% of energy for 22% to 33% of the sample. Micronutrient intake patterns were diverse with intake for some nutrients (vitamins A, C, B6, B12, and D and calcium) remaining above recommended levels despite changes over the course of the study. Folate intakes increased from 79% of the recommended value at 12 months old to ∼100% at 18 months old. Zinc and vitamin E intakes were well below recommended levels throughout the study, and iron decreased markedly from 96% of the recommended level at 12 months old to 76% at 18 months old. Applications/Conclusions. These data show that intakes of some key nutrients are low during the period of dietary transition in early childhood, and intakes for some nutrients actually decrease despite increases in energy intake. Furthermore, because a considerable portion of children studied were consuming low-fat diets, it is clear that many parents are not following the only pediatric nutrition recommendations that currently exist. These findings argue strongly for the development of dietary guidance that not only addresses fat restriction, but also assists parents in selecting diets that support optimum growth and development in young children. nutrient intake, infants, dietary density.

Iron Status and Neuropsychological Consequences in Women of Reproductive Age: What Do We Know and Where Are We Headed?

Iron deficiency disproportionately affects infants, children, and women of reproductive age. It is more prevalent in developing countries but continues to be a problem in developed countries. Included among the consequences of iron deficiency are changes in cognitive performance, emotions, and behavior. Although the behavioral and developmental sequelae of iron deficiency in young children have received much interest, data on the consequences of iron deficiency in women of reproductive age are just beginning to emerge. Interest in this area increased as a result of the findings that brain iron is much more fluid than previously thought and iron-deficient animals experience nondevelopment-dependent brain alterations. These findings, coupled with the symptoms often reported by iron-deficient women (lethargy, inability to concentrate, difficulty with memory, etc.), have led researchers to begin to explore the relation between iron and neuropsychological outcomes in this population. This paper reviews findings from studies that have examined the brain functional consequences of iron deficiency in women of reproductive age. Additional consideration is given to the fact that detriments to cognition and behavior in a woman of reproductive age may have negative implications beyond the womans health; specifically, they may negatively influence her children. Therefore, the roles that cognitive and behavioral changes in these women have on their childrens development is also reviewed. The paper concludes with a discussion on ways to use technological advances (especially in neuroimaging techniques) to help us elucidate the role of iron in the brains of women of reproductive age.

Preschool Micronutrient Supplementation Effects on Intellectual and Motor Function in School-aged Nepalese Children

OBJECTIVE To examine intellectual and motor functioning of children who received micronutrient supplementation from 12 to 35 months of age. DESIGN Cohort follow-up of children 7 to 9 years of age who participated in a 2 × 2 factorial, placebo-controlled, randomized trial from October 2001 through January 2006. SETTING Rural Nepal. PARTICIPANTS A total of 734 children 12 to 35 months of age at supplementation and 7 to 9 years of age at testing. INTERVENTIONS Children received iron plus folic acid (12.5 mg of iron and 50 μg of folic acid); zinc (10 mg); iron plus folic acid and zinc; or placebo. MAIN OUTCOME MEASURES Intellectual, motor, and executive function. RESULTS In both the unadjusted and adjusted analyses, iron plus folic acid supplementation had no effect overall or on any individual outcome measures being tested. In the unadjusted analysis, zinc supplementation had an overall effect, although none of the individual test score differences were significant. In the adjusted analysis, the overall difference was not significant. CONCLUSION In rural Nepal, we found that iron plus folic acid or zinc supplementation during the preschool years had no effect on aspects of intellectual, executive, and motor function at 7 to 9 years of age, suggesting no long-term developmental benefit of iron or zinc supplementation during 12 to 35 months of age.

Iron Nutrition and Premenopausal Women: Effects of Poor Iron Status on Physical and Neuropsychological Performance

Iron is a nutritionally essential trace element that functions through incorporation into proteins and enzymes, many of which contribute to physical and neuropsychological performance. Poor iron status, including iron deficiency (ID; diminished iron stores) and iron deficiency anemia (IDA; poor iron stores and diminished hemoglobin), affects billions of people worldwide. This review focuses on physical and neuropsychological outcomes associated with ID and IDA in premenopausal women, as the prevalence of ID and IDA is often greater in premenopausal women than other population demographics. Recent studies addressing the physiological effects of poor iron status on physical performance, including work productivity, voluntary activity, and athletic performance, are addressed. Similarly, the effects of iron status on neurological performance, including cognition, affect, and behavior, are summarized. Nutritional countermeasures for the prevention of poor iron status and the restoration of decrements in performance outcomes are described.

A Randomized Trial of Iron-Biofortified Pearl Millet in School Children in India

BACKGROUND Iron deficiency is the most widespread nutritional deficiency in the world. OBJECTIVE The objective of this randomized efficacy trial was to determine the effects of iron-biofortified pearl millet (Fe-PM) on iron status compared with control pearl millet (Control-PM). METHODS A randomized trial of biofortified pearl millet (Pennisetum glaucum), bred to enhance iron content, was conducted in 246 children (12-16 y) for 6 mo in Maharashtra, India. Iron status [hemoglobin, serum ferritin (SF), soluble transferrin receptor (sTfR), and total body iron (TBI)], inflammation (C-reactive protein and α-1 acid glycoprotein), and anthropometric indices were evaluated at enrollment and after 4 and 6 mo. Hodges-Lehmann-Sen 95% CIs were used to examine the effect of the Fe-PM on iron status compared with commercially available Control-PM. Linear and binomial regression models were used to evaluate the effects of Fe-PM on iron status and incidence of anemia and iron deficiency, compared with Control-PM. RESULTS At baseline, 41% of children were iron deficient (SF <15 μg/L) and 28% were anemic (hemoglobin <12.0 g/dL). Fe-PM significantly increased SF concentrations and TBI after 4 mo compared with Control-PM. Among children who were iron deficient at baseline, those who received Fe-PM were 1.64 times more likely to become iron replete by 6 mo than were those receiving Control-PM (RR: 1.64, 95% CI: 1.07, 2.49, P = 0.02). The effects of Fe-PM on iron status were greater among children who were iron deficient at baseline than among children who were not iron deficient at baseline. CONCLUSIONS Fe-PM significantly improved iron status in children by 4 mo compared with Control-PM. This study demonstrated that feeding Fe-PM is an efficacious approach to improve iron status in school-age children and it should be further evaluated for effectiveness in a broader population context. This trial was registered at clinicaltrials.gov as NCT02152150.

Associations between women's autonomy and child nutritional status: a review of the literature

Around the world, many women continue to experience low levels of autonomy. Recent literature has reported that the health consequences of low maternal autonomy extend beyond mothers and translate into health consequences for their children, and may be an important causal factor in child malnutrition. This review summarises the current knowledge of the relationship between maternal autonomy and childrens nutritional status (defined as any measure that reflects the nutritional state of the body, such as birthweight or anthropometric scores) and child-feeding practices. The review also includes both discussion of the limitations found in the literature and directions for future research. A systematic review of the literature was conducted. Results of the studies included in the review strongly suggest that raising maternal autonomy is an important goal for improving childrens nutritional status, yet gaps in the current knowledge exist, further confounded by issues with how autonomy is measured and limitations of cross-cultural comparability. A thorough understanding of the consequences of restricting womens autonomy will inform programmes and policy worldwide, and speed progress towards both empowering women and alleviating the global burden of child malnutrition.

Preschool Iron-Folic Acid and Zinc Supplementation in Children Exposed to Iron-Folic Acid in Utero Confers No Added Cognitive Benefit in Early School-Age

In Nepal, antenatal iron-folic acid supplementation improved aspects of intellectual, executive, and fine motor function among school-age children. We examined the impact of added zinc to the maternal antenatal supplement (M-IFAZn) and preschool supplementation from 12 to 36 mo with iron-folic acid (C-IFA) ± zinc (C-IFAZn) on cognitive outcomes compared to maternal iron-folic acid (M-IFA) alone. Children 7-9 y old (n = 780) who participated in early childhood micronutrient supplementation trial during 2001-2004 and whose mothers participated in an antenatal micronutrient supplementation between 1999 and 2001 were followed for cognitive assessments in 2007-2009. Using multivariate analysis of variance and adjusting for confounders, M-IFA with child supplementation (either C-IFA or C-IFAZn) did not impact scores on the tests of general intelligence (Universal Nonverbal Intelligence Test), and executive function (Stroop and go/no go tests) relative to the M-IFA alone. However, children in the C-IFAZn group had slightly lower scores on the backward digit span (-0.29, 95% CI: -0.55, -0.04) and Movement Assessment Battery for Children (1.33, 95% CI: 0.26, 2.40) relative to the referent group, whereas both C-IFA (-1.92, 95% CI: -3.12, -0.71) and C-IFAZn (-1.78, 95% CI: -2.63, -0.92) produced somewhat lower finger tapping test scores (fine motor skills). The combination of M-IFAZn and C-IFA or C-IFAZn did not lead to any outcome differences relative to M-IFA alone. Preschool iron-folic acid ± zinc to children exposed to iron-folic acid in utero or addition of zinc to maternal iron-folic acid conferred no additional benefit to cognitive outcomes assessed in early school age. The late timing of supplementation during preschool may explain the lack of impact of iron and/or zinc.