The Effects of Multiple Micronutrient Fortified Beverage and Responsive Caregiving Interventions on Early Childhood Development, Hemoglobin, and Ferritin among Infants in Rural Guatemala.

Undernutrition and a lack of learning opportunities can jeopardize long-term growth and development among infants in low- and middle-income countries. We conducted a 6-month 2 × 2 cluster-randomized trial to assess the effects of multiple micronutrient-fortified beverages and responsive caregiving interventions among infants 6-18 months in 72 community sectors in southwest Guatemala. We administered baseline and endline assessments of childhood development (Bayley Scales of Infant and Toddler Development) and socioemotional development (Brief Infant Toddler Socio-Emotional Assessment) and measured ferritin and hemoglobin on a subsample. The trial was analyzed using linear mixed models. At the baseline, the mean age (SD) was 13.0 (4.6) months, including 49% males, 32% who were stunted, 55% who were anemic, and 58% who were iron deficient. At the endline (n = 328/386, 85% retention), there was no synergistic effect on the fortified beverage and responsive caregiving intervention. Compared to the non-fortified beverage group, socioemotional development improved in the fortified beverage group. There were no intervention effects on other measures of child development, hemoglobin, or ferritin. In a setting with high rates of anemia and iron deficiency, a multiple micronutrient-fortified beverage improved infants' socioemotional development.

Associations between early introduction to complementary foods, subsequent cereal-added bottle feeding and daily macronutrient intake among infants.

Introducing complementary foods early during infancy has been associated with an increased risk of overweight later in life, but the pathway is an understudied topic. Hence the study was conducted with low-income and primarily minority mother-infant dyads to: 1) understand how the introduction of complementary foods prior to 4 months was associated with socio-demographic characteristics and food security status; 2) determine the association between early introduction to complementary foods and breastfeeding and adding cereal into the bottle in later infancy (i.e., at 6 and 9 months), and; 3) examine how adding infant cereal into the bottle was related to daily calorie and macronutrient intake in infancy. We conducted interviews with mothers (n = 201) at 4 months of age and 24-h feeding recalls at age 6 and 9 months. Results indicated that 29% of the infants were fed complementary foods before 4 months of age. Introducing complementary foods early was negatively associated with breastfeeding and positively associated with adding cereal into the bottle at 6-months. This practice was more common among those who experienced marginal to very low levels of food security. Comparing by race/ethnicity, Latinx mothers were significantly less likely to introduce solids early. After controlling for sex, infants fed cereal in the bottle were consuming significantly more calories compared to their counterparts. Specifically, adding cereal into the bottle resulted in approximately 10% additional daily calorie intake among infants. Understanding how these feeding practices affect appetite development and weight status during infancy is warranted.

Rethinking Responsive Feeding: Insights from Bangladesh.

Young children's growth is influenced by food and feeding behavior. Responsive feeding has been shown to promote healthy growth and development, to prevent under- and overfeeding, and to encourage children's self-regulation. However, most measures of responsive feeding do not incorporate bidirectional mother-infant responsivity or early learning principles and have not been validated against observations. To overcome these gaps, we laid the groundwork for a responsive feeding measure based on a community sample of 67 mothers and their 6-18-month-old children in Bangladesh. Children were weighed and measured. Mothers reported on their child's dietary intake and responded to a 38-item responsive feeding questionnaire developed through a 2-phase Delphi procedure. Based on a video-recorded feeding observation, mother-child dyads were categorized into proximal (43%) and distal (57%) responsivity groups. Using stepwise logistic regression, a 9-item model from the responsive feeding questionnaire had excellent fit (AUC = 0.93), sensitivity (90%), specificity (89%), positive predictive value (87%), and negative predictive value (93%). Proximal responsivity was characterized by maternal concerns about children's dietary intake. Distal responsivity was characterized by maternal perception of children's happy mood during feeding. Findings support responsive feeding as modulating between proximal and distal responsivity, promoting autonomy, self-regulation, and enabling children to acquire and practice healthy eating behaviors.

Grandi Byen-supporting child growth and development through integrated, responsive parenting, nutrition and hygiene: study protocol for a randomized controlled trial.

BACKGROUND: Poor child growth and development outcomes stem from complex relationships encompassing biological, behavioral, social, and environmental conditions. However, there is a dearth of research on integrated approaches targeting these interwoven factors. The Grandi Byen study seeks to fill this research gap through a three-arm longitudinal randomized controlled trial which will evaluate the impact of an integrated nutrition, responsive parenting, and WASH (water, sanitation and hygiene) intervention on holistic child growth and development. METHODS: We will recruit 600 mother-infant dyads living in Cap-Haitien, Haiti and randomize them equally into one of the following groups: 1) standard well-baby care; 2) nutritional intervention (one egg per day for 6 months); and 3) multicomponent Grandi Byen intervention (responsive parenting, nutrition, WASH + one egg per day for 6 months). Primary outcomes include child growth as well as cognitive, language, motor, and social-emotional development. The study also assesses other indicators of child health (bone maturation, brain growth, diarrheal morbidity and allergies, dietary intake, nutrient biomarkers) along with responsive parenting as mediating factors influencing the primary outcomes. An economic evaluation will assess the feasibility of large-scale implementation of the interventions. DISCUSSION: This study builds on research highlighting the importance of responsive parenting interventions on overall child health, as well as evidence demonstrating that providing an egg daily to infants during the complementary feeding period can prevent stunted growth. The multicomponent Grandi Byen intervention may provide evidence of synergistic or mediating effects of an egg intervention with instruction on psychoeducational parenting and WASH on child growth and development. Grandi Byen presents key innovations with implications for the well-being of children living in poverty globally. TRIAL REGISTRATION: NCT04785352 . Registered March 5, 2021 at https://clinicaltrials.gov/.

A Randomized Multiple Micronutrient Powder Point-of-Use Fortification Trial Implemented in Indian Preschools Increases Expressive Language and Reduces Anemia and Iron Deficiency.

BACKGROUND: Anemia is a global public health problem that undermines childhood development. India provides government-sponsored integrated nutrition/child development preschools. OBJECTIVES: This double-masked, cluster-randomized controlled trial examines whether point-of-use multiple micronutrient powder (MNP) compared with placebo fortification of preschool meals impacts child development and whether effects vary by preschool quality (primary outcome) and biomarkers of anemia and micronutrients (secondary outcomes). We also measured growth and morbidity. METHODS: We randomly assigned 22 preschools in rural India to receive MNP/placebo fortification. We administered baseline and endline blood sampling and measures of childhood development (Mullen Scales of Early Learning, inhibitory control, social-emotional), anthropometry, and morbidity to preschoolers (aged 29-49 mo). Preschools added MNP/placebo to meals 6 d/wk for 8 mo. We conducted linear mixed-effects regression models accounting for preschool clustering and repeated measures. We evaluated child development, examining effects in high- compared with low-quality preschools using the Early Childhood Environment Rating Scale-Revised and the Home Observation for the Measurement of the Environment Inventory, modified for preschools. RESULTS: At baseline, mean age ± SD was 36.6 ± 5.7 mo, with 47.8% anemic, 41.9% stunted, and 20.0% wasted. Baseline expressive/receptive language scores were higher in high-quality compared with low-quality preschools (P = 0.02 and P = 0.03, respectively). At endline (91% retention, n = 293/321), we found MNP compared with placebo effects in expressive language (Cohen's standardized effect d = 0.4), inhibitory control (d = 0.2), and social-emotional (d = 0.3) in low-quality, not high-quality, preschools. MNP had significantly greater reduction of anemia and iron deficiency compared with placebo (37% compared with 13.5% and 41% compared with 1.2%, respectively). There were no effects on growth or morbidity. CONCLUSIONS: Providing multiple micronutrient-fortified meals in government-sponsored preschools is feasible; reduced anemia and iron deficiency; and, in low-quality preschools, increased preschoolers' expressive language and inhibitory control and reduced developmental disparities. Improving overall preschool quality by incorporating multiple components of nurturing care (responsive care, learning, and nutrition) may be necessary to enhance preschoolers' development. This trial was registered at clinicaltrials.gov as NCT01660958.

Zinc deficiency associated with anaemia among young children in rural Guatemala.

One in four children younger than age five in Guatemala experiences anaemia (haemoglobin <11.0 g/dl). This study characterized the factors and micronutrient deficiencies associated with anaemia in a baseline cross-sectional sample of 182 Guatemalan infants/toddlers and 207 preschoolers, using generalized linear mixed models. Associations between anaemia and maternal, child and household variables, and biomarkers (soluble transferrin receptor, ferritin, zinc, folate, vitamin B12, C-reactive protein, and α1-acid glycoprotein) were explored. Rates of anaemia were 56% among infants/toddlers and 12.1% among preschoolers. In children with anaemia, rates of iron deficiency (low ferritin based on inflammation status, and/or high soluble transferrin receptor, ≥1.97 mg/L) and zinc deficiency (serum zinc <65 µg/dl) were 81.1% and 53.7%, respectively. Folate deficiency (either plasma folate <3 ng/ml or erythrocyte folate <100 ng/ml) was 3.3%. Vitamin B12 deficiency (plasma vitamin B12 <148 pmol/L) was 7.5%. For infants and toddlers (<24 months), the odds ratio of anaemia was lower when higher number of adults lived in the household (OR = 0.69; 95% CI [0.53, 0.90]), and higher when children were zinc deficient (OR = 3.40; 95% CI [1.54, 7.47]). For preschoolers (36-60 months), the odds ratio of anaemia was lower for every additional month of age (OR = 0.90; 95% CI [0.81, 1.00]). Findings suggest that micronutrient deficiencies coexist in Guatemalan rural children, and zinc deficiency is associated with anaemia in children <24 months, highlighting the need of continued multidisciplinary interventions with multiple micronutrients. Further research examining how household composition, feeding practices, and accessibility to micronutrient supplements and to animal source foods is needed to incorporate strategies to improve the nutritional status of Guatemalan children.

Maternal mental health and infant dietary patterns in a statewide sample of Maryland WIC participants.

The study's objective was to examine the relation between maternal mental health and infant dietary intake. A cross-sectional, population-based telephone survey was employed within a statewide sample of Maryland Special Supplemental Nutrition Program for Women, Infants and Children participants. A 24-h diet recall was performed using the United States Department of Agriculture Automated Multiple-Pass Method. Analyses presented were based on 689 mother-infant pairs. Overall, 36.5% of mothers reported introducing solids to their infants early (<4 months of age), and 40% reported adding cereal to their infant's bottle. Among 0-6-month-old infants, higher infant energy intake was associated with symptoms of maternal stress [ß=0.02; confidence interval (CI): 0.01, 0.04], depression (ß=0.04; CI: 0.01, 0.06) and overall maternal psychological distress (ß=0.02; CI: 0.003, 0.03). With early introduction of solids in the model, the significant associations between infant energy intake and maternal stress and maternal psychological distress became marginal (P's=0.06-0.10). The association between infant energy intake and maternal depression remained significant (ß=0.03; CI: 0.01, 0.06). Among 4-6-month-old infants, intakes of breads and cereals were higher among mothers who reported more symptoms of stress (ß=0.12; CI: 0.04, 0.23), depression (ß=0.19; CI: 0.03, 0.34), anxiety (ß=0.15; CI: 0.02, 0.27) and overall psychological distress (ß=0.04; CI: 0.01, 0.07). Among 7-12-month-old infants, dietary intake was not related to mental health symptoms. Findings suggest poorer infant feeding practices and higher infant dietary intake during the first 6 months of age in the context of maternal mental health symptoms. Further research is needed to evaluate these effects on child dietary habits and growth patterns over time.

Integrating nutrition and early child-development interventions among infants and preschoolers in rural India.

This article describes the development, design, and implementation of an integrated randomized double-masked placebo-controlled trial (Project Grow Smart) that examines how home/preschool fortification with multiple micronutrient powder (MNP) combined with an early child-development intervention affects child development, growth, and micronutrient status among infants and preschoolers in rural India. The 1-year trial has an infant phase (enrollment age: 6-12 months) and a preschool phase (enrollment age: 36-48 months). Infants are individually randomized into one of four groups: placebo, placebo plus early learning, MNP alone, and MNP plus early learning (integrated intervention), conducted through home visits. The preschool phase is a cluster-randomized trial conducted in Anganwadi centers (AWCs), government-run preschools sponsored by the Integrated Child Development System of India. AWCs are randomized into MNP or placebo, with the MNP or placebo mixed into the children's food. The evaluation examines whether the effects of the MNP intervention vary by the quality of the early learning opportunities and communication within the AWCs. Study outcomes include child development, growth, and micronutrient status. Lessons learned during the development, design, and implementation of the integrated trial can be used to guide large-scale policy and programs designed to promote the developmental, educational, and economic potential of children in developing countries.

Integrated strategies needed to prevent iron deficiency and to promote early child development.

Iron deficiency (ID) and iron deficiency anemia (IDA) are global public health problems that differentially impact pregnant women and infants in low and middle income countries. IDA during the first 1000 days of life (prenatally through 24 months) has been associated with long term deficits in children's socio-emotional, motor, cognitive, and physiological functioning. Mechanisms linking iron deficiency to children's development may include alterations to dopamine metabolism, myelination, and hippocampal structure and function, as well as maternal depression and unresponsive caregiving, potentially associated with maternal ID. Iron supplementation trials have had mixed success in promoting children's development. Evidence suggests that the most effective interventions to prevent iron deficiency and to promote early child development begin early in life and integrate strategies to ensure adequate iron and nutritional status, along with strategies to promote responsive mother-child interactions and early learning opportunities.

Iron deficiency and iron-deficiency anemia in the first two years of life: strategies to prevent loss of developmental potential.

This article examines the association of iron deficiency (ID) and iron deficiency anemia (IDA) with children's development and behavior, with the goal of providing recommendations to prevent the developmental loss associated with these conditions. Children's risk for ID and IDA is particularly high during the second 6 months of life when prenatal stores are depleted. Longitudinal studies from infancy through adolescence and early adulthood suggest that socioemotional development is uniquely vulnerable to ID and IDA, perhaps being associated with shared neural pathways, and the effects of early iron deficiencies may be irreversible. In addition to direct effects on brain function, ID and IDA may also affect child development indirectly through non-responsive mother-child interactions. Maternal ID is a global problem that may contribute to high rates of maternal depression and non-responsive caregiving. Intervention trials illustrate that children benefit from both nutritional intervention and early learning interventions that promote responsive mother-child interactions. Recommendations to reduce the developmental loss associated with ID and IDA are to reduce the incidence of these conditions by efforts to prevent premature birth, delay cord clamping, ensure adequate maternal iron status, provide iron-rich complementary foods, and ensure access to postnatal interventions that promote responsive mother-infant interaction patterns and early learning opportunities for infants.

B12 in fetal development.

Vitamin B12 (cobalamin) is necessary for development of the fetus and child. Pregnant women who are vegetarian or vegan, have Crohn's or celiac disease, or have undergone gastric bypass surgery are at increased risk of B12 deficiency. Low serum levels of B12 have been linked to negative impacts in cognitive, motor, and growth outcomes. Low cobalamin levels also may be related to depression in adults. Some studies indicate that B12 supplementation may improve outcomes in children, although more research is needed in this area. Overall, the mechanisms of B12 action in development remain unclear. Further studies in this area to elucidate the pathways of cobalamin influence on development, as well as to prevent B12 deficiency in pregnant women and children are indicated.

Randomized trial of the effect of zinc supplementation on the mental health of school-age children in Guatemala.

BACKGROUND: Rates of mental illness in children are increasing throughout the world. Observational studies of depression, anxiety, and attention-deficit hyperactivity disorder suggest that zinc is an alternative treatment. OBJECTIVE: We examined the effect of zinc supplementation on the mental health of school-age children in Guatemala. DESIGN: From January to October 2006, we conducted a 6-mo randomized, double-blind, controlled trial comparing zinc supplementation (10 mg ZnO/d for 5 d/wk) with a placebo (10 mg glucose) in 674 Guatemalan children in grades 1-4. Outcome measures included internalizing (ie, depression and anxiety) and externalizing (ie, hyperactivity and conduct disorder) problem behaviors, positive behaviors (ie, socialization and leadership), and serum zinc concentrations. RESULTS: Zinc and placebo groups did not differ significantly in any behavioral measures at baseline or at follow-up. At baseline, 21.4% of children had serum zinc concentrations <65 µg/dL. At follow-up, both groups improved significantly, and zinc concentrations were higher in the zinc group. Increases in serum zinc concentrations were inversely associated with decreases in depressive symptoms (estimate: -0.01 points per µg Zn/dL; P = 0.01), anxiety (estimate: -0.012 points per µg Zn/dL; P = 0.02), internalizing symptoms (estimate: -0.021 points per µg Zn/dL; P = 0.02), and social skills (estimate: -0.019 points per µg Zn/dL; P = 0.01) in adjusted models that were controlled for child age, sex, socioeconomic status, household, and treatment group. CONCLUSIONS: Six months of zinc supplementation did not induce differences in mental health outcomes between zinc and placebo groups. However, increases in serum zinc concentrations were associated with decreases in internalizing symptoms (ie, depression and anxiety) in a community-based sample of children at risk of zinc deficiency. This trial was registered at clinicaltrials.gov as NCT00283660.

Iron supplementation in early childhood: health benefits and risks.

The prevalence of iron deficiency among infants and young children living in developing countries is high. Because of its chemical properties--namely, its oxidative potential--iron functions in several biological systems that are crucial to human health. Iron, which is not easily eliminated from the body, can also cause harm through oxidative stress, interference with the absorption or metabolism of other nutrients, and suppression of critical enzymatic activities. We reviewed 26 randomized controlled trials of preventive, oral iron supplementation in young children (aged 0-59 mo) living in developing countries to ascertain the associated health benefits and risks. The outcomes investigated were anemia, development, growth, morbidity, and mortality. Initial hemoglobin concentrations and iron status were considered as effect modifiers, although few studies included such subgroup analyses. Among iron-deficient or anemic children, hemoglobin concentrations were improved with iron supplementation. Reductions in cognitive and motor development deficits were observed in iron-deficient or anemic children, particularly with longer-duration, lower-dose regimens. With iron supplementation, weight gains were adversely affected in iron-replete children; the effects on height were inconclusive. Most studies found no effect on morbidity, although few had sample sizes or study designs that were adequate for drawing conclusions. In a malaria-endemic population of Zanzibar, significant increases in serious adverse events were associated with iron supplementation, whereas, in Nepal, no effects on mortality in young children were found. More research is needed in populations affected by HIV and tuberculosis. Iron supplementation in preventive programs may need to be targeted through identification of iron-deficient children.

Iron and zinc supplementation promote motor development and exploratory behavior among Bangladeshi infants.

BACKGROUND: Iron and zinc deficiency are prevalent during infancy in low-income countries. OBJECTIVES: The objectives were to examine whether a weekly supplement of iron, zinc, iron+zinc, or a micronutrient mix (MM) of 16 vitamins and minerals would alter infant development and behavior. DESIGN: The participants were 221 infants from rural Bangladesh at risk of micronutrient deficiencies. Development and behavior were evaluated at 6 and 12 mo of age by using the Bayley Scales of Infant Development II and the Home Observation Measurement of Environment (HOME) scale. In this double-blind trial, the infants were randomly assigned to 1 of 5 treatment conditions: iron (20 mg), zinc (20 mg), iron+zinc, MM (16 vitamins and minerals, including iron and zinc), or riboflavin weekly from 6 to 12 mo. Multivariate analyses were conducted to examine the change in development and behavior for each supplementation group, with control for maternal education, HOME score, months breastfed, anemia, growth at 6 mo, and change in growth from 6 to 12 mo. RESULTS: Iron and zinc administered together and with other micronutrients had a beneficial effect on infant motor development. Iron and zinc administered individually and in combination had a beneficial effect on orientation-engagement. Two-thirds of the infants were mildly anemic, no treatment effects on hemoglobin concentration were observed, and hemoglobin was not associated with measures of development or behavior. CONCLUSION: The beneficial effects of weekly iron and zinc supplementation on motor development and orientation-engagement suggest that infants benefit from these minerals when administered together.

Cognitive and motor development among small-for-gestational-age infants: impact of zinc supplementation, birth weight, and caregiving practices.

OBJECTIVE: Infants who are born small for gestational age (SGA) are at risk for developmental delays, which may be related to deficiencies in zinc, an essential trace metal, or to deficiencies in their ability to elicit caregiver responsiveness (functional isolation hypothesis). The objective of this study was to evaluate at 6 and 10 months of age the impact of a 9-month supplementation trial of 5 mg of zinc on the development and behavior of infants who were born SGA and to evaluate infants' ability to elicit responsive caregiver behavior. METHODS: A randomized, controlled trial of zinc supplementation was conducted among 200 infants in a low-income, urban community in Delhi, India. Infants were recruited when they were full term (>36 weeks) and SGA (birth weight <10th percentile weight-for-gestational age). Infants were randomized to receive daily supplements of a micronutrient mix (folate, iron, calcium, phosphorus, and riboflavin) with or without 5 mg of zinc sulfate. The supplement was administered by field workers daily from 30 days to 9 months of age. At 6 and 10 months, infant development and behavior were measured in a clinical setting using the Bayley Scales of Infant Development II. Caregiver responsiveness, observed on an Indian version of the Home Observation for Measurement of the Environment scale, was measured during a home visit at 10 months. During both the clinic and home visits, caregivers reported on their infant's temperament. RESULTS: There were no direct effects of zinc supplementation on the infants' development or behavior at either 6 or 10 months. In a subgroup analysis among the zinc-supplemented infants, lower birth weight infants were perceived to be more temperamentally difficult than higher weight infants; in the control group, birth weight was not associated with temperament. Heavier birth weight infants had better scores on all measures of development and behavior at 6 months and on changes in mental and motor development from 6 to 10 months, compared with lighter birth weight infants. Boys had better weight gain and higher scores on mental development and emotional regulation than girls. Infants who were from families of higher socioeconomic status (indexed by parental education, house size, and home ownership) had higher scores on mental development and orientation/engagement (exploratory behavior) than infants who were from families of lower socioeconomic status. In keeping with the functional isolation hypothesis, caregiver responsiveness was associated with infant irritability, controlling for socioeconomic status, gender, birth weight, and weight gain. Responsive mothers were more likely to perceive their infants to be temperamentally easy than less responsive mothers. CONCLUSION: Possible explanations for the lack of effects of zinc supplementation on infant development and behavior include 1) subtle effects of zinc supplementation that may not have been detected by the Bayley Scales, 2) interference with other nutritional deficiencies, or 3) no impact of zinc deficiency on infants' development and behavior. The link between birth weight and irritability among infants in the zinc supplementation group suggests that the response to zinc supplementation may differ by birth weight, with irritability occurring among the most vulnerable infants. Longer term follow-up studies among zinc-supplemented infants are needed to examine whether early supplementation leads to developmental or behavioral changes that have an impact on school-age performance. The relationship between infant irritability and low maternal responsiveness lends support to the functional isolation hypothesis and the importance of asking caregivers about infant temperament.

The evidence linking zinc deficiency with children's cognitive and motor functioning.

The role of zinc in children's cognitive and motor functioning is usually assessed by the response to supplementation in populations thought to be zinc deficient. A review of published zinc-supplementation trials that examined behavior and development identified one trial in fetuses, six trials in infants and toddlers and three trials in school-age children. The three studies that examined activity reported that zinc supplementation was associated with more activity. Of the five studies that examined motor development in infants and toddlers, one found improvements among very low-birth-weight infants, one found improvements in the quality of motor development and three found no impact. Of the four studies that examined mental development in infants and toddlers, three found no impact of zinc supplementation and one found that zinc-supplemented children had lower scores than control children. Among school-age children, one study found no impact of zinc supplementation on cognitive performance and two found a beneficial impact of neuropsychological processes, specifically reasoning. The evidence linking zinc deficiency to children's cognitive and motor functioning suggests a relationship among the most vulnerable children but lacks a clear consensus, highlighting the need for additional research into the timing of zinc deficiency and the co-occurrence with other micronutrient deficiencies.