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Zinc is essential to supporting growth in young children especially for tissues undergoing rapid cellular differentiation and turnover, such as those in the immune system and gastrointestinal tract. Therapeutic zinc supplementation has been initiated in low-income countries as part of diarrhea treatment programs to support these needs for young children, but the effects of preventive supplemental zinc as a tablet or as a multiple micronutrient powder (MNP) on child growth and diarrheal disease are mixed and pose programmatic uncertainties. Thus, a randomized, double-blind community-based efficacy trial of five different doses, forms, and frequencies of preventive zinc supplementation vs. a placebo was designed for a study in children aged 9⁻11 months in an urban community in Dhaka, Bangladesh. The primary outcomes of this 24-week study are incidence of diarrheal disease and linear growth. Study workers will conduct in-home morbidity checks twice weekly; anthropometry will be measured at baseline, 12 weeks and 24 weeks. Serum zinc and other related biomarkers will be measured in a subsample along with an estimate of the exchangeable zinc pool size using stable isotope techniques in a subgroup. Therapeutic zinc will be provided as part of diarrhea treatment, in accordance with Bangladesh's national policy. Therefore, the proposed study will determine the additional benefit of a preventive zinc supplementation intervention. The protocol has been approved by the Institutional Review Boards (IRBs) of icddr,b and Children's Hospital Oakland Research Institute (CHORI). The IRB review process is underway at the University of Colorado Denver as well., Competing Interests: The authors declare no conflict of interest.

Aim: It is unknown whether maternal malnutrition reduces the effect of counselling on exclusive breastfeeding. This study evaluated the effect of breastfeeding counselling on the duration of exclusive breastfeeding, and whether the timing of prenatal food and different micronutrient supplements further prolonged this duration., Methods: Pregnant women in Matlab, Bangladesh, were randomised to receive daily food supplements of 600 kcal at nine weeks of gestation or at the standard 20 weeks. They also were allocated to either 30 mg of iron and 400 μg folic acid, or the standard programme 60 mg of iron and folic acid or multiple micronutrients. At 30 weeks of gestation, 3188 women were randomised to receive either eight breastfeeding counselling sessions or the usual health messages., Results: The median duration of exclusive breastfeeding was 135 days in the counselling group and 75 days in the usual health message group (p < 0.001). Prenatal supplements did not modify the effects of counselling. Women in the usual health message group who were randomised to multiple micronutrients exclusively breastfed for 12 days longer than mothers receiving the standard iron-folate combination (p = 0.003)., Conclusion: Breastfeeding counselling increased the duration of exclusive breastfeeding by 60 days. This duration was not influenced by the supplements., (©2016 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Background: Fetal nutritional insults may alter the later metabolic phenotype. We hypothesized that early timing of prenatal food supplementation and multiple micronutrient supplementation (MMS) would favourably influence childhood metabolic phenotype., Methods: Pregnant women recruited 1 January to 31 December 2002 in Matlab, Bangladesh, were randomized into supplementation with capsules of either 30 mg of iron and 400 μg of folic acid, 60 mg of iron and 400 μg of folic acid, or MMS containing a daily allowance of 15 micronutrients, and randomized to food supplementation (608 kcal) either with early invitation (9 weeks' gestation) or usual invitation (at 20 weeks). Their children (n = 1667) were followed up at 4.5 years with assessment of biomarkers of lipid and glucose metabolism, inflammation and oxidative stress., Results: Children in the group with early timing of food supplementation had lower cholesterol (difference -0.079 mmol/l, 95% confidence interval (CI) -0.156; -0.003), low-density lipoprotein (LDL) (difference -0.068 mmol/l, 95% CI -0.126; -0.011) and ApoB levels (difference -0.017 g/l, 95% CL -0.033; -0.001). MMS supplementation resulted in lower high-density lipoprotein (HDL) (difference -0.028 mmol/l, 95% CL -0.053; -0.002), lower glucose (difference -0.099 mmol/l, 95% CL -0.179; -0.019) and lower insulin-like growth factor 1 (IGF-1) (difference on log scale -0.141 µg/l, 95% CL -0.254; -0.028) than 60 mg iron and 400 μg folic acid. There were no effects on markers of inflammation or oxidative stress., Conclusions: Findings suggest that in a population where malnutrition is prevalent, nutrition interventions during pregnancy may modify the metabolic phenotype in the young child that could have consequences for later chronic disease risks., (© The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Knowledge about the impact of maternal food and micronutrient supplementation on infant micronutrient status is limited. We examined the effect of maternal food and micronutrient supplementation on infant micronutrient status in the Maternal and Infant Nutrition Interventions in Matlab Trial. Pregnant women (n = 4436) were randomized to Early or Usual promotion of enrollment in a food supplementation program. In addition, they were randomly allocated to 1 of the following 3 types of daily micronutrient supplements provided from wk 14 of gestation to 3 mo postpartum: 1) folic acid and 30 mg iron (Fe30Fol); 2) folic acid and 60 mg iron; or 3) a multiple micronutrient including folic acid and 30 mg iron (MMS). At 6 mo, infant blood samples (n = 1066) were collected and analyzed for hemoglobin and plasma ferritin, zinc, retinol, vitamin B-12, and folate. The vitamin B-12 concentration differed between the micronutrient supplementation groups (P = 0.049). The prevalence of vitamin B-12 deficiency was lower in the MMS group (26.1%) than in the Fe30Fol group (36.5%) (P = 0.003). The prevalence of zinc deficiency was lower in the Usual food supplementation group (54.1%) than in the Early group (60.2%) (P = 0.046). There were no other differential effects according to food or micronutrient supplementation groups. We conclude that maternal multiple micronutrient supplementation may have a beneficial effect on vitamin B-12 status in infancy.

Background: Few data exist for the effects of multiple micronutrient (MM) or food supplementation to undernourished pregnant women on their offsprings' development., Objective: We aimed to compare the effects on infant development of early (8-10 wk gestation) or usual ( approximately 17 wk gestation) supplementation with food and MM, 30 mg Fe + 400 microg folate, or 60 mg Fe + 400 microg folate., Design: A large, randomized, controlled trial of pregnancy supplementation was conducted in Bangladesh. A subsample of infants (n = 2853) were assessed on 2 problem-solving tests (support and cover tests), the motor index of the Bayley Scales of Infant Development, and Wolke's behavior ratings at 7 mo of age., Results: There were no significant effects of any intervention in the group as a whole. However, infants of undernourished mothers [body mass index (BMI; in kg/m2) < 18.5] who received early food supplementation performed slightly but significantly (P = 0.035) better on the support test than did infants of mothers who received usual food supplementation (z score: 0.17; 95% CI: 0.01, 0.33). There were no benefits in infants of higher-BMI mothers (P = 0.024 for BMI x food interaction). Children of low-BMI mothers who received MMs had slightly better motor scores (z score: 0.28; 95% CI: 0.08, 0.48) and activity ratings (z score: 0.24; 95% CI: 0.037, 0.45) than did those who received 30 mg Fe + 400 microg folate, whereas other children did not benefit (P = 0.05 for both motor scores and BMI x micronutrients and for activity and BMI x micronutrients)., Conclusions: Small benefits from early food and MM supplementation were found in infants of low-BMI but not of high-BMI mothers. However, the benefits were of doubtful functional importance, and longer follow-up is required to determine programmatic implications.

Background: Children in resource-limited settings remain vulnerable to zinc deficiency and its consequences.Objectives: To evaluate the effects of different doses, durations, and frequencies of zinc supplementation on the incidence of diarrhea and change in linear growth among young children.Methods: We conducted a randomized, partially double-blind, controlled, 6-arm, community-based efficacy trial in Dhaka, Bangladesh. Children aged 9-11 mo were randomly assigned to receive 1 of the following interventions for 24 wk: 1) standard micronutrient powder (MNP) containing 4.1 mg zinc and 10 mg iron, daily; 2) high-zinc (10 mg), low-iron (6 mg) (HiZn LoFe) MNP, daily; 3) HiZn (10 mg) LoFe (6 mg)/HiZn (10 mg), no-iron MNPs on alternating days; 4) dispersible zinc tablet (10 mg), daily; 5) dispersible zinc tablet (10 mg), daily for 2 wk at enrollment and 12 wk; 6) placebo powder, daily. Primary outcomes were incidence of diarrhea and change in length-for-age z-score (LAZ) over the 24-wk intervention period. Home visits were conducted twice weekly to assess diarrhea and other morbidity. Incidence and prevalence outcomes were compared among groups with Poisson regression; continuous outcomes were compared using ANCOVA.Results: A total of 2886 children were enrolled between February 2018 and July 2019. The mean incidence and prevalence of diarrhea among all participants was 1.21 episodes per 100 d and 3.76 d per 100 d, respectively. There were no differences in the incidence or prevalence of diarrhea across intervention groups. The decline in LAZ was slightly smaller among children in the daily HiZn LoFe MNP group compared with the placebo powder group (P < 0.05).Conclusions: The dose of zinc in MNPs as well as the duration and frequency of supplementation evaluated in this trial were not effective in reducing diarrhea; however, the daily HiZn LoFe MNP formulation offered modest improvements in linear growth among young children. This trial was registered at clinicaltrials.gov as NCT03406793. [ABSTRACT FROM AUTHOR]

Given the high prevalence of micronutrient deficiencies and infectious diseases in infants in developing countries, an evaluation of the efficacy of different micronutrient formulations on infant morbidity is a priority. The efficacy of weekly supplementation of four different micronutrient formulations on diarrhea and acute lower respiratory infection (ALRI) morbidity was evaluated in Bangladeshi infants. In a double-blind, randomized, controlled community trial, 799 infants aged 6 mo were randomly assigned to one of the following 5 groups: 1) 20 mg elemental iron with 1 mg riboflavin, 2) 20 mg elemental zinc with 1 mg riboflavin, 3) 20 mg iron and 20 mg zinc with 1 mg riboflavin, 4) a micronutrient mix (MM) containing 20 mg iron, 20 mg zinc, 1 mg riboflavin along with other minerals and vitamins and 5) a control treatment, 1 mg riboflavin only. Health workers visited each infant weekly until age 12 mo to feed the supplement and to collect data on diarrhea and ALRI morbidity. Hemoglobin, serum ferritin and serum zinc levels of a sample of infants were measured at 6 and 12 mo. Compared with the control group, at 12 mo, serum ferritin levels were higher in the iron + zinc group, and serum zinc levels were higher in the zinc and iron + zinc groups. Simultaneous supplementation with iron + zinc was associated with lower risk of severe diarrhea, 19% lower in all infants and 30% lower in less well-nourished infants with weight-for-age Z-score below -1. Iron + zinc supplementation was also associated with 40% lower risk of severe ALRI in less well-nourished infants. MM supplementation was associated with a 15% higher risk of diarrhea in all infants and 22% higher risk in less well-nourished infants. Intermittent simultaneous supplementation with iron + zinc seems promising; it will be useful to determine whether higher doses would provide greater benefits. [ABSTRACT FROM AUTHOR]