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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]

Background: In clinical settings, wasting in childhood has primarily been assessed with the use of a weight-for-height z score (WHZ), and in community settings, it has been assessed via the midupper arm circumference (MUAC) with a cutoff <115 mm for severe wasting and <115-125 mm for moderate wasting. Our recent experience indicates that many wasted children were not identified when these cutoffs for MUAC were used. Objective: We determined the cutoffs for MUAC to detect wasting in Bangladeshi children aged 6-60 mo. Design: A secondary analysis was carried out on data from 27,767 children aged 6-59 mo. This analysis comprised 1) 9131 children across Bangladesh and 2) 18,636 children enrolled in a surveillance study in the Dhaka Hospital of icddr,b during 1996-2014. The area under the receiver operating curve was used to indicate the most appropriate choice for cutoffs that related MUAC with WHZ. Results: The mean ± SD age for the entire group was 21 ± 14 mo, WHZ was -1.18 ± 1.23, height-for-age z score was -1.63 ± 1.39, MUAC was 136 ± 14 mm, and 45% of subjects were girls. MUAC correlated with the WHZ (r: 0.618, P < 0.001). Age-stratified analyses revealed that, for ages 6-24 mo, MUAC cutoffs were <120 mm for a WHZ <-3 and <125 mm for a WHZ <-2 with a sensitivity of 72.9% and 63.2%, respectively, and a specificity of 84.7% and 85.3%, respectively; for ages 25-36 mo, MUAC cutoffs were <125 mm for a WHZ < - 3 and <135 mm for a WHZ <-2 with a sensitivity of 55.0% and 71.7%, respectively, and a specificity of 92.8% and 78.7% respectively; and for ages 37-60 mo, MUAC cutoffs were <135 mm for a WHZ < - 3 and <140 mm for a WHZ <-2 with a sensitivity of 71.4% and 70.4%, respectively, and a specificity of 84.6% and 80.3%, respectively. Conclusion: The respective cutoffs for MUAC to better capture the vulnerability and risk of severe (WHZ <- 3) and moderate (WHZ <-2) wasting would be <120 and <125 mm for ages 6-24 mo, <125 and <135 mm for ages 25-36 mo, and <135 and <140 mm for ages 37-60 mo. [ABSTRACT FROM AUTHOR]

We conducted a randomized, double-blind placebo controlled, community trial in rural Bangladesh in children 4-59 mo of age to compare the efficacy of a 5- and 10-d course of zinc therapy on the incidence and duration of diarrhea over the subsequent 90-d follow-up after initial treatment for an acute childhood diarrheal (ACD) episode. Children (n = 1622) with ACD were randomly allocated to either 5 or 10 d of zinc treatment. Female field workers visited each child daily, supervised the administration of zinc, recorded the duration of current episode, and the occurrence and duration of diarrhea over the subsequent 3 mo. The incidence of diarrhea over the 90 d of follow-up did not differ between the 5-d (1.08 ± 1.38 episodesl and 10-d 11.02 ± 1.35 episodesl groups (P = 0.35). Children in both groups experienced a comparable duration of diarrheal episodes (3.1 ± 5.6 d vs. 2.9 ± 5.6 d, 5-d vs. 10-d, respectively; P= 0.64) with a mean difference between groups within the defined range of equivalence. Time to onset of the first episode and the proportion children experiencing diarrhea during the 90-d follow-up also did not differ between groups. These findings suggest that among Bangladeshi children, a 5-d zinc treatment for ACD is as efficacious as 10 d in preventing diarrhea in the subsequent 3 mo. [ABSTRACT FROM AUTHOR]

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 Fe3OFol group 136.5%) (P = 0.003). The prevalence of zinc deficiency was lower in the Usual food supplementation group 154.1 %) 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. [ABSTRACT FROM AUTHOR]

There is a concern that exclusive breast-feeding (EBF) for 6 mo may lead to iron and zinc deficiency in low-birth weight (LBW) infants. We assessed the association between duration of EBF and infant iron and zinc status in the Maternal and Infant Nutrition Interventions in Matlab trial, Bangladesh, stratified for normal birth weigh (NBW) and LBW. Duration of EBF was classified into EBF <4 mo and EBF 4-6 mo based on monthly recalls of foods introduced to the infant. Blood samples collected at 6 mo were analyzed for plasma zinc (n = 1032), plasma ferritin (n = 10401, and hemoglobin (Hb) (n = 791). Infants EBF 4-6 mo had a higher mean plasma zinc concentration (9.9 ± 2.3 μmol/L) than infants EBF <4mo (9.5 ± 2.0 μmol/L) (P < 0.01). This association was apparent in only the NBW strata and was not reflected in a lower prevalence of zinc deficiency. Duration of EBF was not associated with concentration of plasma ferritin, Hb concentration, or prevalence of iron deficiency or anemia in any strata. Regardless of EBF duration, the prevalence of zinc deficiency, iron deficiency, and anemia was high in infants in this population and strategies to prevent deficiency are needed. [ABSTRACT FROM AUTHOR]

Summary: Childhood pneumonia and diarrhoeal disease cause almost half of all child deaths globally. Effective interventions against these conditions are available and could prevent about two-thirds of these deaths. We argue that part of the reason for the lack of success in delivering these interventions is the lack of attention to implementation challenges. We present a novel research priority setting model that shifts the emphasis from generation of new knowledge and publication to potential public-health outcomes, and propose a framework by which this new model can be put into operation. We believe that only in this way will proper attention be given to delivery of proven interventions to reduce the high childhood mortality caused by pneumonia and diarrhoea. [Copyright &y& Elsevier]

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 onBWby considering the duration of supplementation and whether the effect is modified by maternal postpartum weight (a proxy of prepregnancy weight) groups. Design:Acohort of undernourished pregnantwomen(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 (⩾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 andBWvaries with maternal postpartum weight.A large effect was observed after the season with food insecurity (mid- August to mid-November). [ABSTRACT FROM AUTHOR]

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,HOMEscore, 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. [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]

The 10-valent pneumococcal conjugate vaccine (PCV10) was introduced in March 2015 in Bangladesh. In this study, we aimed to estimate the impact of PCV10 on invasive pneumococcal disease (IPD) identified by blood cultures and severe pneumonia identified clinically and its effectiveness on invasive disease caused by vaccine serotypes. We conducted population-based surveillance among children aged 2- <24 months between April 2012 through March 2019 in Mirzapur, a rural sub-district of Bangladesh. We compared incidence of IPD and severe pneumonia before (April 2012 to March 2015) and after (April 2015 to March 2019) the introduction of PCV10. Vaccine effectiveness was measured using an indirect cohort analysis of data from four sentinel sites in which PCV10 vaccination status was compared between children with IPD caused by vaccine serotype vs. non-vaccine serotypes. We identified 24 IPD cases by blood culture and 1,704 severe pneumonia hospitalizations during the surveillance period. IPD incidence in under-2-year-old children fell 25 % (95 % CI: −1.2 % to 76 %; p-value = 0.59) from 106 cases per 100,000 child-years at baseline to 79.3 in April 2018- March 2019. Vaccine serotype-IPD incidence was lower (77 % reduction, 95 % CI: −0.45 % to 96 %; p-value = 0.068) in April 2018 - March 2019 than in the pre-vaccine period (85.7 cases to 19.8/100,000 child-years). A significant decline of 54.0 % (95 % CI: 47.0 % to 59.0 %; p-value < 0.001) was observed in hospitalizations due to severe pneumonia. From indirect cohort analysis, the effectiveness of PCV10 against vaccine serotype IPD was 37 % (95 % CI: −141.0 % to 83.5 %; p = 0.5) after the 1st dose and 63.1 % (95 % CI: −3.3 % to 85.9 %, p = 0.0411) after the 2nd or the 3rd dose. This study demonstrates that PCV10 introduction prevented hospitalizations with severe pneumonia and provided individual protection against vaccine serotypes. [ABSTRACT FROM AUTHOR]

Objective: To validate a rapid neurodevelopmental assessment tool for use by child care professionals to determine neurodevelopmental impairments (NDIs) in children ages 5-9 years (61-108 months) in Bangladesh. Study design: In a convenience sample of community children (n = 18), interrater reliability was determined between 6 testers. Validity was determined in 121 children by simultaneous administration of a test of adaptive behavior (AB) (ie, the Independent Behavior Assessment Scale, or Gold Standard I) and IQ tests (Wechsler Preschool and Primary Scales of Intelligence or the Wechsler Intelligence Scales for Children, or Gold Standard II) by child psychologists. Results: Interrater reliability was excellent (kappa = 1.00). Significantly lower scores were obtained on AB and IQ tests in those identified with “any (≥1) NDI” and most specific NDIs. Sensitivity and specificity for “any NDI” with (a) “significant difficulties” (defined as AB z-scores < −2 SD and/or IQ < 70) or (b) “mild difficulties included” (AB z scores < −1 SD and/or IQ < 85) were 84% and 57%; and 83% and 70%, respectively. Conclusion: The rapid neurodevelopmental assessment tool shows promise as a tool for use by a range of professionals for identifying NDIs in children of primary school age. Further refinement for identifying specific impairments is needed. [Copyright &y& Elsevier]

Objectives: Some Asian countries have been reluctant to adopt Haemophilus influenzae type b (Hib) conjugate vaccination because of uncertainty over disease burden. We assessed the impact of introduction of Hib conjugate vaccine into the Expanded Program on Immunization in Bangladesh on purulent and laboratory-confirmed H influenzae meningitis. Study design: Within a well-defined catchment area around 2 surveillance hospitals in Dhaka, Bangladesh, we compared the incidence of Hib meningitis confirmed by culture, latex agglutination, and polymerase chain reaction assay among infants 1 year before and 1 year after introduction of Hib conjugate vaccine. We adjusted the incidence rate for the proportion of children who sought care at the surveillance hospitals. Results: Among infants, the incidence of confirmed Hib meningitis decreased from 92-16 cases per 100 000 within 1 year of vaccine introduction (vaccine preventable incidence = 76; 95% CI 18, 135 per 100 000). The incidence of purulent meningitis decreased from 1659-1159 per 100 000 (vaccine preventable incidence = 500; 95% CI: 203, 799 per 100 000). During the same time period, there was no significant difference in the incidence of meningitis due to Streptococcus pneumoniae. Conclusions: Introduction of conjugate Hib conjugate vaccine into Bangladesh Expanded Program on Immunization markedly reduced the burden of Hib and purulent meningitis. [Copyright &y& Elsevier]

Objective: To measure physical and neurologic impact of Haemophilus influenzae type b (Hib) meningitis on surviving children through short- and long-term follow-up. Study design: Cases of Hib meningitis, diagnosed at a tertiary level pediatric hospital, were subjected to short- and long-term follow-up and compared with age, sex, and area of residence matched healthy controls. Follow-up assessments included thorough physical and neurodevelopmental assessments using a standardized protocol by a multidisciplinary team. Results: Assessments of short-term follow-up cohort (n = 64) revealed hearing, vision, mental, and psychomotor deficits in 7.8%, 3%, 20%, and 25% of the cases, respectively. Deficits were 10%, 1.4%, 21%, and 25% in long-term follow-up cohort (n = 71), in that order. Mental and psychomotor deficits were found in 2% of the controls, none of whom had vision or hearing deficits. Conclusions: In addition to risk of death, Hib meningitis in children causes severe disabilities in survivors. These data facilitated a comprehensive understanding of the burden of Hib meningitis, specifically in developing countries where disabled children remain incapacitated because of lack of resources and facilities. The evidence generated from this study is expected to provide a compelling argument in favor of introduction and continuation of Hib conjugate vaccine in the national immunization program for children. [Copyright &y& Elsevier]

The essential element manganese (Mn) might be toxic at excess exposure. We assessed the impact of elevated Mn exposure through drinking water during pregnancy on birth size in a population-based cohort( n = 1695) in rural Bangladesh. Concentrations of water Mn (median = 236 μg/L, range = 7.1–6336; n = 1177) and erythrocyte Mn (median = 30 μg/kg, range = 6.3–114; n = 758) were measured using ICP-MS. In regression analyses, newborns of women in the highest tertile of water Mn (median = 1495 μg/L) were 0.49 cm (0.20 SD) shorter ( B = −0.42; 95% CI: −0.77, −0.08) than those in the lowest tertile (56 μg/L). The inverse association was significant in girls and also in boys of mothers with lowest hemoglobin values, likely due to higher absorption of Mn. Manganese concentrations in water and erythrocytes did not correlate, and the associations of the latter with birth size were less obvious. This study suggests that consumption of water with highly elevated Mn levels during pregnancy may impair fetal growth. [ABSTRACT FROM AUTHOR]

Strong leadership has been highlighted as a common element of success within countries that have made rapid progress in tackling child and maternal undernutrition. Yet little is known of what contributes to nutrition leaders’ success or lack of it in particular policy environments. This study of 89 individuals identified as influential within child and maternal undernutrition policy and programming in Bangladesh, Ethiopia, Kenya and India sheds light on why particular individuals have been effective in contributing towards positive changes in nutrition policy, and how they operate in the wider policy/political sphere. We employ a framework working outwards from individual capabilities, knowledge and motivations, through to wider political economy considerations and the narratives and knowledge structuring individual capacity. We argue that only by locating individuals within this wider political economy can we begin to appreciate the range of strategies and avenues for influence (or constraints to that influence) that individual leaders employ and encounter. [ABSTRACT FROM AUTHOR]

There is evidence on benefits of psychosocial stimulation (PS) and cash transfer programmes in low- and middle-income countries on children's development. We integrated PS into an unconditional cash transfer (UCT) programme for poor Bangladeshi mothers to examine the effects on children's development. This cluster randomized controlled trial was conducted in rural Bangladesh from July 2017 to December 2018 in 33 clusters, with 11 clusters randomly assigned to each of the three arms, namely i) PS + UCT ii) UCT-only and iii) Comparison. We enrolled poor mothers and child (6–16 months) dyads eligible to receive maternity allowance by the Government of Bangladesh. Trained local women imparted training to mothers to provide psychosocial stimulation to their children for one year. Children's cognitive, language and motor development were measured with Bayley-III, behaviour with Wolke's ratings and maternal self-esteem with Rosenberg self-esteem scale. The analysis was intention-to-treat. Of the 594 mother-child dyads, 40 (6·8%) were lost to follow-up. Compared to UCT-only, children in the PS + UCT had significant improvement in cognitive (B = 2.96, 95% CI: 0.46–5.47, Effect Size [ES] 0.24SD) and language (2.73, 0.39–5.00, ES 0.21SD) scores and were more responsive to examiner (0.30, 0.06–0.52, ES 0.27SD), while compared to comparison group, they had significantly higher cognitive (3.37, 1.27–6.19, ES 0.32SD), language (2.82, 0.53–5.10, ES 0.24SD) and motor (2.65, 0.24–5.06, ES 0.22SD) scores and were more responsive to examiner (0.30, 0.08–0.52, ES 0.26 SD). The mothers' self-esteem was significantly higher in PS + UCT (2.46, 0.94–3.98, ES 0.48 SD) and UCT-only (1.67, 0.02–3.20, ES 0.32 SD) compared to the comparison group. PS integrated into an UCT programme benefited children's neurodevelopment and UCT improved mother's self-esteem. UCT programme may be an important platform for child stimulation programmes for rural poor populations. • Integrated parenting and unconditional cash benefit rural children's development. • Unconditional cash transfer alone improves mother's self-esteem in rural settings. • Further research is required to see if the intervention work for urban population. [ABSTRACT FROM AUTHOR]

Abstract: We piloted a low-cost approach to measure the disease burden of Streptococcus pneumoniae, Hib and Salmonella Typhi by leveraging the existing infrastructure of high performing microbiology laboratories at two large paediatric hospitals in Dhaka Bangladesh, and assessing the hospital utilization of the catchment population of these hospitals for different syndromes. S. Typhi was the most common bacterium identified in culture and accounted for an estimated 211 hospitalizations per 100,000 children <5 years of age per year. Meningitis due to S. pneumoniae was the most common cause of mortality accounting for 8.0 deaths per 100,000 children <5 years of age per year. This low-cost approach can provide data to support vaccine introduction and the health impact of newly introduced vaccines. [Copyright &y& Elsevier]

While reductions in infectious disease have resulted in impressive declines in child mortality in Bangladesh, drowning is becoming proportionately more important as a major cause of death, accounting for at least 19% of deaths of children between 1 and 4 years of age in trend analysis since 2000. Little is known about indigenous beliefs and behaviors associated with drowning, which may be critical to preventing child-related drowning deaths. Qualitative research was carried out over 13 months in Matlab, Bangladesh to describe the indigenous explanatory model of drowning and to identify behavioral factors increasing the risk for drowning deaths. Methods included cognitive mapping procedures as well as open-ended interviews with families who had lost a child or experienced a near-death due to drowning and families with at least one child under 5 years living near a body of water. Along with diarrhea, fever, and pneumonia, drowning is perceived as a leading cause of child death. Causal explanations are primarily associated with “evil spirits” believed to entice young children to water or bewitch mothers so that they forget about the child. Another primary interpretation relates to a water goddess known to prey on small children. When a young child is discovered in water, parents refrain from rescuing the child due to a belief that if a parent touches a drowning child, the child will die. After the child is removed from the water, traditional practices that have no known benefit are employed. The research identified locally constructed beliefs and practices such as refraining from touching the child that may increase the incidence of drowning deaths. Future efforts are required to address these beliefs and assess the feasibility, cultural acceptability and effectiveness of strategies designed to prevent drowning. [Copyright &y& Elsevier]