Gregory A. Reinhart’s research while affiliated with Georgia Southern University and other places

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.

Background: Anemia is a global public health problem that undermines childhood development. India provides

Objectives To determine the long-term impact of a micronutrient fortified supplement on stunting rates and micronutrient status in young children living in rural Guatemala, which has the highest stunting prevalence in Latin America. Methods A parallel, open label randomised control trial in rural children aged 6–72 months (Registration NCT01643187). After growth screening, all children < 1SD for either weight for height (WHZ), height for age (HAZ), or weight for age (WAZ) were randomly allocated using 7:3 ratio, stratified by locality and age to receive either the test drink, Chispuditos®, a corn/soy beverage fortified with 21 vitamins or de-lactosed milk (control). Both drinks were isoproteic (4g/drink) and had similar energy content (test drink 147 kcal, milk 117 kcal) but the tst drink had higher micronutrient content (e.g., 9 mg zinc, 12.5 mg iron vs 1.5 mg zinc, 1.9 mg iron in control). They were supplied for 18 months and monthly visits were conducted to test for adherence. Results A total of 1238 children were screened, 971 met the criteria and 681 were allocated to test drink and 290 to control. At baseline, malnutrition prevalence of stunting (HAZ < -2SD), for test vs control was 48.4% vs 47.9%, 5.5% vs 6.7% for wasting (WHZ < -2SD) and 19.9% vs 18.7% for underweight (WAZ < -2SD). 73% of children reported to consume at least half of allocated drinks/day. After 18 months of intervention, the prevalence and relative risks [RR (95% CI)] for stunting in the test: control were 40.6:40.7% [RR 0.99 (0.84, 1.19)]; similarly, no differences were seen in WAZ, WHZ nor micronutrient status. Conclusions In this trial in rural Guatemalan children, long term supplementation with a micronutrient enriched drink had no impact on either stunting or micronutrient status. These results differ form long-term studies in urban Guatemalan nurseries. The present study suggest that fortified foods alone are not enough to reduce stunting rates in this setting when fed during an 18 month period. Funding Sources The Mathile Institute for the Advancement of Human Nutrition funded this study.

Objectives To assess the effectiveness of a nutrition intervention with a multi-micronutrient fortified corn-soy blend (MMC) (ChapuditosTM) vs. standard of care (SOC) in anemia and hemoglobin (Hb) in 6 to 12-mo-old infants from four rural municipalities in La Libertad, El Salvador. Methods A two-arm, clustered randomized evaluation was implemented between September 2015 and November 2017. A total of n = 384 infants met eligibility criteria: ages 6 to ≤ 12 mo, permanent resident of study locations, no genetic, health conditions or disability, parental consent, having attended 2 consecutive well-child visits. Clinicaltrials.gov registration NCT02567981. A total of n = 195 received SOC: 3 lb of corn-soy blend with dry milk with 18 micronutrients including 1.8 mg of zinc and 3.6 mg of iron per serving, equivalent to 30 daily servings; + 100,000 IU of vitamin A every 6 mo, and 12.5 mg of elemental iron per day via ferrous sulphate. A total of n = 189 received “MMC”: 3 lb of corn-soy blend with 21 micronutrients and high concentrations of chelated zinc (9 mg) and iron (12 mg) per serving, equivalent to 72 daily servings. Capillary blood was drawn at baseline (Bl) and 3 mo. Linear and generalized linear mixed models with binary outcomes were used to assess Bl – 3 mo changes in Hb and anemia, respectively. Models were adjusted by age, sex, Bl outcomes, and cluster. Both nutrition interventions were provided at the scheduled well-child visits. Results Preliminary analyses showed that Hb tended to improve from Bl to 3 mo in both groups [Bl-MMC = 10.47g/dL; 95% CI (10.32–10.61), Bl-SOC = 10.26 g/dL; 95% CI (10.12–10.40); 3 mo MMC = 10.88g/dL; 95% CI (10.72–11.04); 3 mo-SOC = 10.43g/dL; 95% CI (10.28–10.60)]. Changes in Hb were significant for the MMC vs. SOC group, [mean difference = 0.41g/dL, P ≤ 0.001; and 0.180g/dL, P = 0.228, respectively]. The odds of anemia were 63% lower in the MMC group, relative to SOC, [OR: 0.37, 95% CI (0.17–0.82)]. Conclusions A multi-micronutrient cereal with 21 micronutrients and elevated concentrations of chelated zinc and iron may be an effective alternative to current practices in alleviating anemia and improving Hb in this population. Consolidating different multiple-micronutrient delivery methods into one product may simplify provision and adherence, resulting in improved anemia and Hb status. Funding Sources This study was funded by the Mathile Institute for the Advancement of Human Nutrition.

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.

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.

Objectives: Nutritional deficiency and lack of early learning opportunities contribute to the loss of developmental potential. The objective is to evaluate the effects of an integrated nutrition and early learning intervention (ELI) on micronutrient status and the development of infants in rural India. Methods: 513 infants (6-12mo) were enrolled from 26 villages in rural India and randomized using a 2 × 2 design to receive multiple micronutrient powders (MNP containing iron, zinc, vitamins A, B2, B12, C and folic acid) vs. placebo (B2) and EL vs. control. The ELI was based on the UNICEF-developed Care for Child Development. Baseline (BL), post-intervention (6 mo) and follow-up (12 mo) evaluations included Mullens Scales of Early Learning, anthropometry, and 2 ml venous blood (BL & 12 mo). Data were analyzed using linear mixed effects regression models with random village/subject intercepts accounting for site of recruitment and repeated measures. For biomarker outcomes, main effects of MNP was assessed. P-values of <0.05 considered statistically significant. For child development outcomes, main effects of MNP and ELI were analyzed separately, and three-way interactions (MNP*ELI*midline or MNP*ELI*end line) were tested. Results: At baseline, the mean age of mothers was 22.9y (SD = 2.9) and 99.6% were married. Most mothers (84.2%) had attended some schooling. Mean infant age was 8.6 mo (SD = 2.2); 53.0% were male. Anemia prevalence was 66.4%. No significant baseline differences were found. At end line, infants in the MNP group had significantly higher hemoglobin (11 g/dl vs.10 g/dl) and ferritin (18.2ug/l vs.11.5 ug/l) values compared to infants in the placebo groups, respectively. Infants in the MNP group (mean = 39.5; SE = 0.6) versus placebo group (mean = 37.7; SE = 0.6) also scored significantly higher in expressive language and marginally higher in visual reception (mean = 42.5; SE = 0.5; P = 0.06) and social-emotional behavior (mean = 24.1; SE = 0.2; P = 0.052), compared to the placebo (mean = 41.1; E = 0.6, mean = 23.5; SE = 0.2, respectively). Significant interactions in visual reception and expressive language performance showed that children who received either or both interventions had better scores than children who received neither. Conclusions: Home MNP and EL interventions can improve infant MN status and development. Funding sources: Mathile Institute for the Advancement of Human Nutrition, Nutrition International, Sackler Institute for Nutrition Science of the New York Academy of Science.

Objectives: In low and middle-income countries, early child development (ECD) is associated with stunting, but the association with length-for-age z-scores (LAZ) is understudied. The objective is to examine whether the association with ECD among infants extends beyond stunting to LAZ and whether it is altered by nurturance or inflammation. Methods: Sample: 513 infants (mean age 8.6 months, SD 2.2), 20% stunted (LAZ < -2) participated in a randomized controlled trial of micronutrient powder (MNP) in rural India. Following baseline, infants were re-evaluated at 6- and 12-months. LAZ was calculated from measured length, inflammation (C-reactive protein, CRP) from blood draw; nurturance from home observation (HOME Inventory), and ECD from Mullens Early Learning Scale (visual reception, fine/gross motor and receptive/expressive language). Linear mixed effects models were conducted, accounting for repeated measures and clustering, adjusted for child age, anemia, maternal education, household assets, and intervention. LAZ interactions with CRP and HOME scores were tested. Results: LAZ was significantly positively associated with all ECD domains over time. HOME was positively associated with visual reception and expressive language (Table 1). HOME interactions were marginal for fine motor (P = 0.058) and significant for receptive language (P = 0.015). For HOME scores < -1 SD, LAZ was positively related to fine motor and receptive language, for HOME scores >1 SD, LAZ was not related to ECD (Figure 1). CRP was not related to ECD and CRP interaction was not significant. Conclusions: The positive association between LAZ and ECD illustrates vulnerability prior to the threshold of stunting. Maternal nurturance is positively associated with multiple domains of infants' ECD and attenuates relations between LAZ and receptive language and fine motor. Inflammation (measured by CRP) is not associated with ECD. Linear growth within normal and nurturant caregiving are needed to promote ECD. Funding sources: Mathile Institute for the Advancement of Human Nutrition, Nutrition International, Sackler Institute for Nutrition Science of the New York Academy of Sciences.