Search

A sensitive and reliable biomarker of zinc status has yet to be identified, but observational research suggests that the exchangeable zinc pool (EZP) size may be a possible biomarker. This randomized, placebo-controlled trial aimed to compare the change in EZP size from baseline to endline in 174 children who were preventatively supplemented with 10 mg of zinc as part of a multiple micronutrient power (MNP) or as a standalone dispersible tablet for 24 weeks versus a placebo powder. The effects of systemic inflammation on EZP size were also evaluated. Zinc stable isotopes were administered intravenously to children at baseline and endline, and the EZP was measured by the urine extrapolation method. A total of 156 children completed the study with the zinc dispersible tablet group having the greatest increase in EZP (14.1 mg) over 24 weeks when compared with the MNP group (6.8 mg) (p < 0.01) or placebo group (2.0 mg) (p < 0.001). Median EZP size was not different between children with normal or elevated serum inflammatory markers. EZP size was responsive to longitudinal zinc supplementation and reflected the expected difference in bioavailability for two forms of supplementation. The apparent absence of an effect of inflammation on EZP size may offer an advantage for use as a biomarker for group comparisons between different interventions.

Background: Iron-deficiency is the most common nutritional deficiency globally. Due to the high iron requirements for pregnancy, it is highly prevalent and severe in pregnant women. There is strong evidence that maternal iron deficiency anaemia increases the risk of adverse perinatal outcomes. However, most of the evidence is from observational epidemiological studies except for a very few randomised controlled trials. IFA supplements have also been found to reduce the preterm delivery rate and neonatal mortality attributable to prematurity and birth asphyxia. These results combined indicate that IFA supplements in populations of iron-deficient pregnant women could lead to a decrease in the number of neonatal deaths mediated by reduced rates of preterm delivery. In this paper, we describe the protocol of a community-based cluster randomised controlled trial that aims to evaluate the impact of maternal antenatal IFA supplements on perinatal outcomes., Methods/design: The effect of the early use of iron-folic acid supplements on neonatal mortality will be examined using a community based, cluster randomised controlled trial in five districts with 30,000 live births. In intervention clusters trained BRAC village volunteers will identify pregnant women & provide iron-folic acid supplements. Groundwater iron levels will be measured in all study households using a validated test kit. The analysis will follow the intention to treat principle. We will compare neonatal mortality rates & their 95% confidence intervals adjusted for clustering between treatment groups in each groundwater iron-level group. Cox proportional hazards mixed models will be used for mortality outcomes & will include groundwater iron level as an interaction term in the mortality model., Discussion: This paper aims to describe the study protocol of a community based randomised controlled trial evaluating the impact of the use of iron-folic acid supplements early in pregnancy on the risk of neonatal mortality. This study is critical because it will determine if antenatal IFA supplements commenced in the first trimester of pregnancy, rather than later, will significantly reduce neonatal deaths in the first month of life, and if this approach is cost-effective., Trial Registration: This trial has been registered with the Australian New Zealand Clinical Trials Registry (ANZCTR) on 31 May 2012. The registration ID is ACTRN12612000588897 .

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.)

Background: Antenatal vitamin D3 (vitD3) supplementation significantly increases maternal and neonatal 25-hydroxyvitamin D3 (25(OH)D3) concentration, yet the effect of an improvement in maternal-fetal vitamin D status on the neonatal immune response is unclear., Method: To assess the effect of prenatal vitD3 supplementation on cord blood T cell function, healthy pregnant Bangladeshi women (n = 160) were randomized to receive either oral 35,000 IU/week vitD3 or placebo from 26 to 29 weeks of gestation to delivery. In a subset of participants (n = 80), cord blood mononuclear cells (CBMC) were cultured, non-adherent lymphocytes were isolated to assess T cell cytokine responses to phytohemagglutinin (PHA) and anti-CD3/anti-CD28 (iCD3/iCD28), measured by multiplex assay. In 12 participants, lymphocyte gene expression profiles were analyzed by PCR array., Result: In supplemented group, increased concentrations of IL-10 (P < 0.000) and TNF-α (P = 0.05) with iCD3/iCD28 stimulation and IFN-γ (p = 0.05) with PHA stimulation were obtained compared to placebo group. No differences in the gene expression profile were noted between the two groups. However, PHA stimulation significantly induced the expression of genes encoding Th1 and Th2 cytokines and down-regulated a number of genes involved in T-cell development, proliferation and differentiation of B cells, signal transduction pathway, transcriptional regulation and pattern recognition receptors (PRRs) in the vitamin D group (vitD group)., Conclusion: Third-trimester high-dose vitD3 supplementation in healthy pregnant women had balanced effects on biomarkers of cord blood Th1 and Th2 responses., Trial Registration: ClinicalTrials.gov ( NCT01126528 ).

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: National nutrition programs in Bangladesh have included prenatal food supplementation to reduce maternal and child malnutrition. The knowledge base is weak regarding the effect of prenatal food supplementation on the birth weight (BW) of infants in populations in whom low BW is prevalent and regarding any variation in effect based on maternal nutritional status., Objective: We examined whether observational data support an effect of daily prenatal food supplementation on BW by considering the duration of supplementation and whether the effect is modified by maternal postpartum weight (a proxy of prepregnancy weight) groups., Design: A cohort of undernourished pregnant women (n = 777) who received prenatal food supplementation (608 kcal/d) was followed. The association between the uptake of food supplements and BW was analyzed after adjustment for potential confounders (n = 619 with complete information). Differential effects in lower and higher maternal postpartum weight groups were examined., Results: The average BW was 2521 g. On average, the women received daily supplements for 4 mo, which resulted in an increase in BW of 118 g (1.0 g/d). The strongest effect was found for births occurring in January and February. There was a linear dose-response relation between duration of supplementation and BW for women with higher postpartum weights (> or = 42 kg, above the median). In women with lower weights (< 42 kg, below median), a shorter duration of supplementation (< 4 mo) had no such dose-response relation with BW, but there was a linear dose-response relation for longer durations of supplementation., Conclusions: The association between duration of prenatal food supplementation and BW varies with maternal postpartum weight. A large effect was observed after the season with food insecurity (mid-August to mid-November).

Because infants and young children in many developing countries are deficient in both iron and zinc, and zinc can affect iron metabolism, evaluation of optimum strategies to simultaneously supplement iron and zinc is an important public health priority. This study evaluated the efficacy of weekly supplementation of iron or zinc or both on iron, zinc, and copper status in Bangladeshi infants. In a double-blind, randomized, controlled community trial, 6-mo-old infants were assigned to receive weekly supplements of 1 mg riboflavin (control, n = 82) or 1 mg riboflavin + 20 mg iron (n = 83), 20 mg zinc (n = 83), or both (n = 85) for 6 mo. Hemoglobin, serum ferritin, transferrin receptor, zinc, and copper concentrations were measured at baseline and at the end of intervention. Serum Zn increased in both groups receiving zinc; the increase was greatest among children with low baseline serum zinc concentration. Iron status indicators did not differ among the groups before or after 6 mo of supplementation. Supplementation with either zinc or iron decreased serum copper after 6 mo. Joint supplementation did not alter the individual effects of iron or zinc supplementation in these Bangladeshi children. However, the dosing regimen may not have been adequate to achieve the desired biochemical effects.

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.

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]

Exclusive breastfeeding (EBF) for the first 6 months has established benefits, yet had slow improvements globally. Little is known about electronic job aid‐assisted counselling to support EBF. As a secondary outcome of a cluster randomized controlled trial in Bangladesh, we assessed the effect of electronic job aid‐supported nutrition counselling and practical demonstration on EBF. We randomized pregnant women to one of five study arms in the trial and followed mother–child dyads until 2 years of age. Community health workers (CHWs) provided breastfeeding counselling with or without prenatal and complementary nutrient supplements in all four intervention arms. The comparison arm continued with the usual practice where mothers could receive nutrition counselling at routine antenatal and postnatal care, and during careseeking for childhood illnesses. We assessed breastfeeding indicators at birth and monthly until the child was 6 months old, in both intervention and comparison arms. To evaluate the effect of nutrition counselling on breastfeeding, we combined all four intervention arms and compared them with the comparison arm. Intervention newborns had half the risk (relative risk [RR]: 0.54, 95% confidence interval [CI]: 0.39, 0.76) of receiving prelacteal feeds than those in the comparison arm. EBF declined steeply in the comparison arm after 3 months of age. EBF was 16% higher in the intervention than the comparison arm at 4 months (RR: 1.16, 95% CI: 1.08, 1.23) and 22% higher at 5 months of age (RR: 1.22, 95% CI: 1.12, 1.33). Maternal background and household characteristics did not modify the intervention effect, and we observed no difference in EBF among caesarean versus vaginal births. Breastfeeding counselling and practical demonstration using an electronic job aid by CHWs are promising interventions to improve EBF and are scalable into existing community‐based programmes. Key messages: Using an electronic job aid, repeated, one‐to‐one counselling and practical demonstration to mothers by locally recruited CHWs reduced prelacteal feeding and improved EBF practice by delaying the early introduction of complementary food.The positive effect of counselling on EBF remains similar with or without nutrient supplementation.Electronic job aid supported counselling to promote breastfeeding should be integrated into existing community‐based maternal and child health programmes. [ABSTRACT FROM AUTHOR]

Little is known about the usefulness of biomarkers to study the influence of prenatal nutrition supplementation in improving child growth. Anthropometry is not always straightforward to understand how nutrition might impact growth, especially in settings with high rates of malnutrition and infections. We examined the effects of prenatal supplementation on growth and growth biomarkers and the relationship between anthropometric measures and growth biomarkers of children at 4.5 and 9 years of age. Children were enrolled from a longitudinal cohort, where mothers were randomized into daily supplementation with either early‐food (≤9 gestation week [GW]) or usual‐food (~20 GW) (608 kcal 6 days/week); they were further randomized to receive 30‐mg or 60‐mg iron with 400‐μg folic acid, or multiple micronutrients (MM) in rural Bangladesh. Anthropometric data were collected from mothers at GW8 and children at 4.5 (n = 640) and 9 years (n = 536). Fasting blood was collected from children at each age. Early‐food supplementation showed reduced stunting and underweight at 4.5 and 9 years age respectively compared to usual‐food. Prenatal supplementations did not have any effect on growth biomarkers except for STAT5b expression which was lower in the early‐food compared to the usual‐food group (β = −0.21; 95 CI% = −0.36, −0.07). Plasma concentrations of 25‐hydroxy vitamin D and calcium were both inversely associated with weight‐for‐age and body mass index‐for‐age Z‐scores at 9 years, particularly in early‐food and MM groups. Although there was minimal effect on child growth by prenatal supplementations, the associations of biomarkers with anthropometric indices were predominantly driven by timing of food or MM supplementations. [ABSTRACT FROM AUTHOR]