Protocol for a randomised, multicentre, four-arm, double-blinded, placebo-controlled trial to assess the benefits and safety of iron supplementation with malaria chemoprevention to children in Malawi: IRMA trial.

INTRODUCTION: Approximately 40% of children aged 6-59 months worldwide are anaemic. Iron-containing multiple micronutrient powders (MNPs) and iron supplements (syrup/drops) are used to combat anaemia in children in different parts of the world. However, evidence for functional benefits of iron supplementation in children is scarce, and potential risks remain poorly defined, particularly concerning diarrhoea and malaria. This trial aims to determine if: (1) the efficacy of iron supplements or MNPs (containing iron) given with malaria chemoprevention is superior to malaria chemoprevention alone, or (2) if the efficacy of malaria chemoprevention alone is superior to placebo on child cognitive development. METHODS AND ANALYSIS: IRMA is a four-arm, parallel-group, double-blinded, placebo-controlled, triple-dummy, randomised trial in Southern Malawi. The study recruits 2168 infants aged 6 months, with an intervention period of 6 months and a post-intervention period of a further 6 months. Children are randomised into four arms: (1) No intervention (placebo); (2) malaria chemoprevention only; (3) MNPs and malaria chemoprevention; and (4) iron syrup and malaria chemoprevention. The primary outcome, cognitive development (Cognitive Composite Score (CogCS)), is measured at the end of the 6 months intervention. Secondary outcomes include CogCS at a further 6 months post-intervention, motor, language and behavioural development, physical growth and prevalence of anaemia and iron deficiency. Safety outcomes include incidence of malaria and other infections, and prevalence of malaria parasitaemia during and post-intervention period. ETHICS AND DISSEMINATION: The trial is approved by the National Health Sciences Research Committee (#19/01/2213) (Malawi) and the Human Research Ethics Committee (WEHI: 19/012) (Australia). Written informed consent in the local language is obtained from each participant before conducting any study-related procedure. Results will be shared with the local community and internationally with academic and policy stakeholders. TRIAL REGISTRATION NUMBER: ACTRN12620000386932.

Six-Year Follow-up of Childhood Stimulation on Development of Children With and Without Anemia.

BACKGROUND AND OBJECTIVES: Previously, in 30 Bangladeshi villages, 2 groups of children with iron-deficiency anemia (IDA) and nonanemic (NA) iron sufficiency aged 6 to 24 months participated in 2 parallel cluster randomized controlled trials of the effect of psychosocial stimulation on neurodevelopment. The intervention was composed of weekly play sessions at home for 9 months. All children with anemia received iron treatment of 6 months. The intervention improved the mental development of NA but not IDA groups. Six years after end line when the children were aged 8 to 9 years, we aimed to determine if benefits were sustained in the NA group or late-onset benefits emerged in the IDA group. METHODS: We relocated 372 (90%) of the initial 412 children from all the clusters (villages), and assessed their IQ with the Wechsler Abbreviated Scale of Intelligence-II, motor development, and school achievement including math, spelling, and reading. Analyses were by intention-to-treat, adjusting for clustering. RESULTS: There was a significant interaction between anemia groups (IDA/NA) and intervention on IQ. The intervention benefitted the NA group's Full-Scale IQ (effect size, 0.43 [95% confidence interval, 0.08-0.79]) and Perceptual Reasoning Index (effect size, 0.48 [95% confidence interval, 0.08-0.89]) but did not affect the IDA group's outcomes. No other outcomes were significant. CONCLUSIONS: The benefits from early childhood psychosocial stimulation on the NA group's IQ, 6 years after intervention ended, adds to the limited evidence on the sustainability of benefits in low- and middle-income countries. Reasons for lack of effect in children with anemia are unknown.

Effects of iron supplementation on neural indices of habituation in Bangladeshi children.

BACKGROUND: Iron deficiency and anemia have been associated with poor cognition in children, yet the effects of iron supplementation on neurocognition remain unclear. OBJECTIVE: We aimed to examine the effects of supplementation with iron on neural indices of habituation using auditory event-related brain potentials (ERPs). METHODS: This substudy was nested within a 3-arm, double-blind, double-dummy, individual randomized trial in Bangladesh, in which 3300 8-mo-old children were randomly selected to receive 3 mo of daily iron syrup (12.5 mg iron), multiple micronutrient powders (MNPs) (including 12.5 mg iron), or placebo. Children were assessed after 3 mo of intervention (mo 3) and 9 mo thereafter (mo 12). The neurocognitive substudy comprised a randomly selected subset of children from the main trial. Brain activity elicited during an auditory roving oddball task was recorded using electroencephalography to provide an index of habituation. The differential response to a novel (deviant) compared with a repeated (standard) sound was examined. The primary outcome was the amplitude of the mismatch response (deviant minusstandard tone waveforms) at mo 3. Secondary outcomes included the deviant and standard tone-evoked amplitudes, N2 amplitude differences, and differences in mean amplitudes evoked by deviant tones presented in the second compared with first half of the oddball sequence at mo 3 and 12. RESULTS: Data were analyzed from 329 children at month 3 and 363 at mo 12. Analyses indicated no treatment effects of iron interventions compared with placebo on the amplitude of the mismatch response (iron syrup compared with placebo: mean difference (MD) = 0.07µV [95% CI: -1.22, 1.37]; MNPs compared with placebo: MD = 0.58µV [95% CI: -0.74, 1.90]) nor any secondary ERP outcomes at mo 3 or 12, despite improvements in hemoglobin and ferritin concentrations from iron syrup and MNPs in this nested substudy. CONCLUSION: In Bangladeshi children with >40% anemia prevalence, iron or MNP interventions alone are insufficient to improve neural indices of habituation. This trial was registered at the Australian New Zealand Clinical Trials Registry as ACTRN12617000660381.

Scaling-up an early childhood parenting intervention by integrating into government health care services in rural Bangladesh: A cluster-randomised controlled trial.

AIMS: We evaluated the feasibility and effectiveness of utilising government health supervisors to train and supervise primary health care workers (HWs) in community clinics to deliver parenting sessions as part of their usual duties. METHODS: We randomly allocated 16 unions in the Mymensing district of Bangladesh 1:1 to an intervention or control group. HWs in clinics in the eight intervention unions (n = 59 health workers, n = 24 clinics) were trained to deliver a group-based parenting intervention, with training and supervision provided by government supervisors. In each of the 24 intervention clinics, we recruited 24 mothers of children aged 6-24 months to participate in the parenting sessions (n = 576 mother/child dyads). Mother/child dyads attended fortnightly parenting sessions at the clinic in groups of four to five participants for 6 months (13 sessions). We collected data on supervisor and HW compliance in implementing the intervention, mothers' attendance and the observed quality of parenting sessions in all intervention clinics and HW burnout at endline in all clinics. We randomly selected 32 clinics (16 intervention, 16 control) and 384 mothers (192 intervention, 192 control) to participate in the evaluation on mother-reported home stimulation, measured at baseline and endline. RESULTS: Supervisors and HWs attended all training, 46/59 health workers (78%) conducted the majority of parenting sessions, (only two HWs [3.4%] refused) and mothers' attendance rate was 86%. However, supervision levels were low: only 32/57 (56.1%) of HWs received at least one supervisory visit. Intervention HWs delivered the parenting sessions with acceptable levels of quality on most items. The intervention significantly benefitted home stimulation (effect size = 0.53SD, 95% confidence interval: 0.50, 0.56, p < 0.001). HW burnout was low in both groups. CONCLUSION: Integration into the primary health care service is a promising approach for scaling early childhood development programmes in Bangladesh, although further research is required to identify feasible methods for facilitator supervision.

Cost-effectiveness of universal iron supplementation and iron-containing micronutrient powders for anemia among young children in rural Bangladesh: analysis of a randomized, placebo-controlled trial.

BACKGROUND: Universal provision of iron supplements or iron-containing multiple micronutrient powders (MNPs) is widely used to prevent anemia in young children in low- and middle-income countries. The BRISC (Benefits and Risks of Iron Interventions in Children) trial compared iron supplements and MNPs with placebo in children <2 y old in rural Bangladesh. OBJECTIVES: We aimed to assess the cost-effectiveness of iron supplements or iron-containing MNPs among young children in rural Bangladesh. METHODS: We did a cost-effectiveness analysis of MNPs and iron supplements using the BRISC trial outcomes and resource use data, and programmatic data from the literature. Health care costs were assessed from a health system perspective. We calculated incremental cost-effectiveness ratios (ICERs) in terms of US$ per disability-adjusted life-year (DALY) averted. To explore uncertainty, we constructed cost-effectiveness acceptability curves using bootstrapped data over a range of cost-effectiveness thresholds. One- and 2-way sensitivity analyses tested the impact of varying key parameter values on our results. RESULTS: Provision of MNPs was estimated to avert 0.0031 (95% CI: 0.0022, 0.0041) DALYs/child, whereas iron supplements averted 0.0039 (95% CI: 0.0030, 0.0048) DALYs/child, over 1 y compared with no intervention. Incremental mean costs were $0.75 (95% CI: 0.73, 0.77) for MNPs compared with no intervention and $0.64 ($0.62, $0.67) for iron supplements compared with no intervention. Iron supplementation dominated MNPs because it was cheaper and averted more DALYs. Iron supplementation had an ICER of $1645 ($1333, $2153) per DALY averted compared with no intervention, and had a 0% probability of being the optimal strategy at cost-effectiveness thresholds of $200 (reflecting health opportunity costs in Bangladesh) and $985 [half of gross domestic product (GDP) per capita] per DALY averted. Scenario and sensitivity analyses supported the base case findings. CONCLUSIONS: These findings do not support universal iron supplementation or micronutrient powders as a cost-effective intervention for young children in rural Bangladesh. This trial was registered at anzctr.org.au as ACTRN1261700066038 and trialsearch.who.int as U1111-1196-1125.

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.

Integrating a Group-Based, Early Childhood Parenting Intervention Into Primary Health Care Services in Rural Bangladesh: A Cluster-Randomized Controlled Trial.

Background: Over 250 million children globally do not reach their developmental potential. We tested whether integrating a group-based, early childhood parenting program into government healthcare clinics improved children's development, growth, and behavior. Methods: We conducted a cluster-randomized controlled trial in 40 community clinics in the Kishorganj district of Bangladesh. We randomly assigned clinics (1:1) to deliver a group-based parenting interventions or to a comparison group that received no intervention. Participants were children aged 5-24 months, with weight-for-age z-score of ≤ -1.5 SDs of the WHO standards, living within a thirty-minute walking distance from the clinic (n = 419 intervention, 366 control). Government health staff facilitated parenting sessions in the clinic with groups of four mother/child dyads fortnightly for one year as part of their routine duties. Primary outcomes measured at baseline and endline were child development assessed using the Bayley scales, child behaviors during the test by tester ratings, and child growth. The trial is registered at ClinicalTrials.gov, NCT02208531. Findings: 91% of children were tested at endline (396 intervention, 319 control). Multilevel analyses showed significant benefits of intervention to child cognition (effect size 0.85 SDs, 95% CI: 0.59, 1.11), language (0.69 SDs, 0.43, 0.94), and motor development (0.52 SDs, 0.31, 0.73), and to child behaviors during the test (ranging from 0.36 SDs, 0.14, 0.58, to 0.53 SDs, 0.35, 0.71). There were no significant effects on growth. Conclusion: A scalable parenting intervention, integrated into existing government health services and implemented by government health staff, led to significant benefits to child development and behavior.

Benefits and Risks of Iron Interventions in Infants in Rural Bangladesh.

BACKGROUND: Universal provision of iron supplements (drops or syrup) or multiple micronutrient powders to young children in low-to-middle-income countries where anemia is prevalent is recommended by the World Health Organization and widely implemented. The functional benefits and safety of these interventions are unclear. METHODS: We conducted a three-group, double-blind, double-dummy, individually randomized, placebo-controlled trial to assess the immediate and medium-term benefits and risks of 3 months of daily supplementation with iron syrup or iron-containing multiple micronutrient powders, as compared with placebo, in 8-month-old children in rural Bangladesh. The primary outcome was cognitive development, as assessed by the cognitive composite score on the Bayley Scales of Infant and Toddler Development, third edition, immediately after completion of the assigned 3-month regimen; scores range from 55 to 145, with higher scores indicating better cognitive performance. Secondary outcomes included the cognitive composite score at 9 months after completion of the assigned regimen; behavioral, language, and motor development, as well as growth and hematologic markers, immediately after completion and at 9 months after completion; and safety. RESULTS: We randomly assigned 3300 infants to receive iron syrup (1101 infants), multiple micronutrient powders (1099), or placebo (1100) daily. After completion of the assigned 3-month regimen, no apparent effect on the cognitive composite score was observed with iron syrup as compared with placebo (mean between-group difference in change in score from baseline, -0.30 points; 95% confidence interval [CI], -1.08 to 0.48) or with multiple micronutrient powders as compared with placebo (mean between-group difference in change in score from baseline, 0.23 points; 95% CI, -0.55 to 1.00). No apparent effect on any other developmental or growth outcome was observed immediately after completion of the assigned regimen or at 9 months after completion. At 9 months after completion of the assigned regimen, the prevalences of anemia, iron deficiency, and iron deficiency anemia increased in all three trial groups but remained lower among the children who received iron syrup or multiple micronutrient powders than among those who received placebo. The risk of serious adverse events and incidence of symptoms of infection were similar in the three trial groups. CONCLUSIONS: In this trial involving infants in Bangladesh, 3 months of daily supplementation with iron syrup or multiple micronutrient powders did not appear to have an effect on child development or other functional outcomes as compared with placebo. (Funded by the National Health and Medical Research Council of Australia; BRISC Australian New Zealand Clinical Trials Registry number, ACTRN12617000660381.).

Thirty-five years later: Long-term effects of the Matlab maternal and child health/family planning program on older women's well-being.

Family planning programs are believed to have substantial long-term benefits for women's health and well-being, yet few studies have established either extent or direction of long-term effects. The Matlab, Bangladesh, maternal and child health/family planning (MCH/FP) program afforded a 12-y period of well-documented differential access to services. We evaluate its impacts on women's lifetime fertility, adult health, and economic outcomes 35 y after program initiation. We followed 1,820 women who were of reproductive age during the differential access period (born 1938-1973) from 1978 to 2012 using prospectively collected data from the Matlab Health and Demographic Surveillance System and the 1996 and 2012 Matlab Health and Socioeconomic Surveys. We estimated intent-to-treat single-difference models comparing treatment and comparison area women. MCH/FP significantly increased contraceptive use, reduced completed fertility, lengthened birth intervals, and reduced age at last birth, but had no significant positive impacts on health or economic outcomes. Treatment area women had modestly poorer overall health (+0.07 SD) and respiratory health (+0.12 SD), and those born 1950-1961 had significantly higher body mass index (BMI) in 1996 (0.76 kg/m2) and 2012 (0.57 kg/m2); fewer were underweight in 1996, but more were overweight or obese in 2012. Overall, there was a +2.5 kg/m2 secular increase in BMI. We found substantial changes in lifetime contraceptive and fertility behavior but no long-term health or economic benefits of the program. We observed modest negative health impacts that likely result from an accelerated nutritional transition among treated women, a transition that would, in an earlier context, have been beneficial.

Human resources and curricula content for early child development implementation: multicountry mixed methods evaluation.

OBJECTIVE: The WHO recommends responsive caregiving and early learning (RCEL) interventions to improve early child development (ECD), and to achieve the Sustainable Development Goals' vision of a world where all children thrive. Implementation of RCEL programmes in low and middle-income countries (LMIC) requires evidence to inform decisions about human resources and curricula content. We aimed to describe human resources and curricula content for implementation of RCEL projects across diverse LMICs, using data from the Grand Challenges Canada Saving Brains ECD portfolio. SETTING: We evaluated 32 RCEL projects across 17 LMICs on four continents. PARTICIPANTS: Overall, 2165 workers delivered ECD interventions to 25 909 families. INTERVENTION: Projects were either stand-alone RCEL or RCEL combined with health and nutrition, and/or safety and security. PRIMARY AND SECONDARY OUTCOMES: We undertook a mixed methods evaluation of RCEL projects within the Saving Brains portfolio. Quantitative data were collected through standardised reporting tools. Qualitative data were collected from ECD experts and stakeholders and analysed using thematic content analysis, informed by literature review. RESULTS: Major themes regarding human resources included: worker characteristics, incentivisation, retention, training and supervision, and regarding curricula content: flexible adaptation of content and delivery, fidelity, and intervention duration and dosage. Lack of an agreed standard ECD package contributed to project heterogeneity. Incorporation of ECD into existing services may facilitate scale-up but overburdened workers plus potential reductions in service quality remain challenging. Supportive training and supervision, inducement, worker retention, dosage and delivery modality emerged as key implementation decisions. CONCLUSIONS: This mixed methods evaluation of a multicountry ECD portfolio identified themes for consideration by policymakers and programme leaders relevant to RCEL implementation in diverse LMICs. Larger studies, which also examine impact, including high-quality process and costing evaluations with comparable data, are required to further inform decisions for implementation of RCEL projects at national and regional scales.

Effects of adding psychosocial stimulation for children of lactating mothers using an unconditional cash transfer platform on neurocognitive behavior of children in rural Bangladesh: protocol for a cluster randomized controlled trial.

BACKGROUND: There is sufficient evidence that psychosocial stimulation (PS) benefits children's neurocognitive behavior, however, there is no information on how it works when delivered through an Unconditional Cash Transfer (UCT) platform for poor rural population in developing countries. The objective of this study is to measure effects of adding PS for children of lactating mothers enrolled to receive UCT with health education (HE) on neurocognitive behavior of children in rural Bangladesh. METHODS: The study will be conducted at 11 unions of Ullapara sub-district in Bangladesh. The study is a cluster randomized controlled trial with three-arms; (i) PS and UCT with HE (ii) UCT with HE and iii) Comparison arm. The cluster will be considered as an old Ward of a Union, the lowest tier of local government system in rural Bangladesh. There are three old Wards in a union. These three clusters will be randomized to one of the three arms. Similarly, randomization will be done for each 11 Unions and then 11 clusters will be assigned to an arm. Eighteen participants will be recruited from each cluster randomly (n = 196 in each arm). The intervention designed for one year includes UCT with HE for the poor as a safety net program in rural Bangladesh with or without PS. An age-based curriculum of PS is already available for Bangladeshi children and this will be administered by trained local women; play leaders (PL) in intervention clusters. The government of Bangladesh is providing UCT of taka 500 ($6.25) as maternity allowance per month with HE. The primary outcomes will be cognitive, motor and language composite scores measured by Bayley-III and behavior using Wolke's behavior rating scale. The secondary outcomes will be children and mothers' growth, family food security status, health seeking behavior, mothers' depressive symptoms and self-esteem and violence against mothers. DISCUSSION: The study will provide a unique opportunity to assess an integrated early childhood development intervention using UCT platform to mitigate developmental delays in poor vulnerable children of rural Bangladesh. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT03281980, registered on September 13, 2017.

Integrating an early childhood development programme into Bangladeshi primary health-care services: an open-label, cluster-randomised controlled trial.

BACKGROUND: Poor development in young children in developing countries is a major problem. Child development experts are calling for interventions that aim to improve child development to be integrated into health services, but there are few robust evaluations of such programmes. Previous small Bangladeshi trials that used individual play sessions with mothers and their children (at home or in clinics), which were predominantly run by employed women, found moderate improvements on child development. We aimed to integrate an early childhood development programme into government clinics that provide primary health care and to evaluate the effects of this intervention on child cognition, language, and motor development, growth, and behaviour in a subsample of the children. METHODS: In this open-label cluster-randomised controlled trial, we recruited individuals from community clinics in Narsingdi district, Bangladesh. These clinics were randomly selected from a larger sample of eligible clinics, and they were assigned (1:1) to either deliver an intervention of 25 sessions, in which mothers of eligible children were shown how to support their child's development through play and interactions, or to deliver no intervention (control group). Participants were underweight children, defined as a weight-for-age Z score of -2 SDs of the WHO standard, who were aged 5-24 months and who lived near the clinic (defined as a walk of less than 30 min). Government health workers ran these sessions at the clinics as part of their routine work, and mothers and children attended fortnightly in pairs (instead of individual weekly home visits that were specified in the original programme). A subsample of children from each clinic was randomly selected for impact evaluation, and these children were assessed on the Bayley Scales of Infant and Toddler Development for their cognitive, language, and motor performance and for their behaviour with Wolke's ratings, before and after implementation of the intervention. The primary outcomes were the performance of this evaluation subsample on the Bayley and Wolke scales and their anthropometric measurements (weight, length or height, and head circumference) after 1 year of the intervention. This study is registered with ClinicalTrials.gov, number NCT02208531. FINDINGS: Between Nov 29, 2014, and April 30, 2015, 12 054 children in 90 clinics were screened, and between six and 25 underweight children were enrolled from each clinic. From the 2423 (20%) underweight children, we excluded 656 (27%) children who lived more than 30-min walking distance from the community clinics, and 30 (1%) children whose mothers did not consent to participate. We therefore enrolled 1737 (72%) children from these 90 clinics. After randomisation, the control group clinics included 878 (51%) children (who all received no intervention) and the intervention group clinics included 859 (49%) children (who all received the child development programme sessions). Eight children from each clinic (360 [41%] children from the control group clinics and 358 [42%] children from the intervention group clinics) were randomly selected for inclusion in the evaluation subsample. Between Feb 24, 2016, and Sept 7, 2016, 344 (96%) children in control group clinics and 343 (96%) children in intervention group clinics were assessed for the primary outcome. 16 (5%) children in the control group clinics and 15 (4%) children in the intervention group clinics did not provide all data and were not included in final analyses. An intention-to-treat analysis showed that the intervention significantly improved children's cognition (effect size 1·3 SDs, 95% CI 1·1 to 1·5; p=0·006), language (1·1 SDs, 0·9 to 1·2; p=0·01), and motor composite scores (1·2 SDs, 1·0 to 1·3; p=0·006) and behaviour ratings (ranging from 0·7 SDs, 0·5 to 0·9; p=0·02; to 1·1 SDs, 1·0 to 1·2; p=0·007), but the intervention had no significant effect on growth (p values ranged from 0·05 to 0·74). Three (1%) children in the intervention group died, but their deaths were not related to the intervention. INTERPRETATION: The extent and range of benefits of our intervention are encouraging. Health workers ran most of the sessions effectively and attendance was good, which is promising for scale-up of the intervention model. However, researchers trained and supervised the health workers, and the next step will be to determine whether the Bangladeshi ministry of health can perform these tasks. In future programmes, more attention needs to be paid to the nutrition of the children. FUNDING: Grand Challenges Canada (Saving Brains).

Prioritizing research for integrated implementation of early childhood development and maternal, newborn, child and adolescent health and nutrition platforms.

BACKGROUND: Existing health and nutrition services present potential platforms for scaling up delivery of early childhood development (ECD) interventions within sensitive windows across the life course, especially in the first 1000 days from conception to age 2 years. However, there is insufficient knowledge on how to optimize implementation for such strategies in an integrated manner. In light of this knowledge gap, we aimed to systematically identify a set of integrated implementation research priorities for health, nutrition and early child development within the 2015 to 2030 timeframe of the Sustainable Development Goals (SDGs). METHODS: We applied the Child Health and Nutrition Research Initiative method, and consulted a diverse group of global health experts to develop and score 57 research questions against five criteria: answerability, effectiveness, deliverability, impact, and effect on equity. These questions were ranked using a research priority score, and the average expert agreement score was calculated for each question. FINDINGS: The research priority scores ranged from 61.01 to 93.52, with a median of 82.87. The average expert agreement scores ranged from 0.50 to 0.90, with a median of 0.75. The top-ranked research question were: i) "How can interventions and packages to reduce neonatal mortality be expanded to include ECD and stimulation interventions?"; ii) "How does the integration of ECD and MNCAH&N interventions affect human resource requirements and capacity development in resource-poor settings?"; and iii) "How can integrated interventions be tailored to vulnerable refugee and migrant populations to protect against poor ECD and MNCAH&N outcomes?". Most highly-ranked research priorities varied across the life course and highlighted key aspects of scaling up coverage of integrated interventions in resource-limited settings, including: workforce and capacity development, cost-effectiveness and strategies to reduce financial barriers, and quality assessment of programs. CONCLUSIONS: Investing in ECD is critical to achieving several of the SDGs, including SDG 2 on ending all forms of malnutrition, SDG 3 on ensuring health and well-being for all, and SDG 4 on ensuring inclusive and equitable quality education and promotion of life-long learning opportunities for all. The generated research agenda is expected to drive action and investment on priority approaches to integrating ECD interventions within existing health and nutrition services.

Different Context but Similar Cognitive Structures: Older Adults in Rural Bangladesh.

Most research in cognitive aging is based on literate participants from high-income and Western populations. The extent to which findings generalize to low-income and illiterate populations is unknown. The main aim was to examine the structure of between-person differences in cognitive functions among elderly from rural Bangladesh. We used data from the Poverty and Health in Aging (PHA) project in Bangladesh. The participants (n = 452) were in the age range 60-92 years. Structural equation modeling was used to estimate the fit of a five-factor model (episodic recall, episodic recognition, verbal fluency, semantic knowledge, processing speed) and to examine whether the model generalized across age, sex, and literacy. This study demonstrates that an established model of cognition is valid also among older persons from rural Bangladesh. The model demonstrated strong (or scalar) invariance for age, and partial strong invariance for sex and literacy. Semantic knowledge and processing speed showed weak (or metric) sex invariance, and semantic knowledge demonstrated also sensitivity to illiteracy. In general, women performed poorer on all abilities. The structure of individual cognitive differences established in Western populations also fits a population in rural Bangladesh well. This is an important prerequisite for comparisons of cognitive functioning (e.g., declarative memory) across cultures. It is also worth noting that absolute sex differences in cognitive performance among rural elderly in Bangladesh differ from those usually found in Western samples.

Prevalence of depressive symptoms and suicidal thoughts among elderly persons in rural Bangladesh.

BACKGROUND: Depression, if broadly defined, is the commonest late-life mental disorder. We examined the distribution of depressive symptoms and suicidal thoughts, across age, sex, literacy, and marital status, among elderly individuals residing in rural Bangladesh and participating in a population-based study on health and aging. METHODS: Prevalence figures of depressive symptoms were assessed with SRQ20 (n = 625), and possible social network and economic associations were examined. Morbidity accounts of depressive symptoms and suicidal thoughts were examined for a subsample that also underwent complete medical examination (n = 471). RESULTS: We selected for analyses the items that corresponded to DSM-IV criteria and constructed a dichotomous variable. The prevalence was 45%, and most pronounced among the oldest women (70%). The overall prevalence of suicidal thoughts was 23%. Being a woman, illiterate or single were all risk factors for depressive symptoms and suicidal thoughts. These associations remained unaccounted for by the social network and economic variables. Co-residing with a child and having a high quality of contact were protective of both depressive symptoms and suicidal thoughts. The main findings were replicated in the subsample, where it was found that morbidities were also associated with the outcomes, independently of the four main predictors. CONCLUSIONS: Prevalence figures for depressive symptoms among elderly in rural Bangladesh are high. Demographic, social network, and morbidity factors are independently associated with both depressive symptoms and suicidal thoughts. This is the first study to report prevalence figures for depressive symptoms in this population.

Selenium status in pregnancy influences children's cognitive function at 1.5 years of age.

BACKGROUND & AIMS: Selenium deficiency has been shown to affect the neurological development in animals, but human research in this area is scarce. We aimed to assess the impact of selenium status during pregnancy on child development at 1.5 years of age. METHODS: This prospective cohort study was nested into a food and micronutrient supplementation trial (MINIMat) conducted in rural Bangladesh. Using inductively coupled plasma mass spectrometry, we measured selenium concentrations in erythrocyte fraction of blood collected from 750 mothers at gestational week 30, and calculated µg per g hemoglobin. A revised version of Bayley Scales of Infant Development was used to assess children's mental and psychomotor development. A Bangladeshi version of MacArthur's Communicative Development Inventory was used to assess language comprehension and expression. Linear regression analyses adjusted for multiple covariates were used to assess the associations. RESULTS: Maternal erythrocyte selenium concentrations varied considerably, from 0.19 to 0.87 µg/g hemoglobin (median 0.46 µg/g hemoglobin), and were associated with developmental measures. An increase in erythrocyte selenium by 0.50 µg/g hemoglobin was associated with an increase in children's language comprehension by 3.7 points (0.5 standard deviations; 95% confidence interval: 0.40, 7.1; p = 0.028). The same increase in erythrocyte selenium corresponded to an increase in the girls' psychomotor development by 12 points (0.9 standard deviation; 95% confidence interval: 4.3, 19; p = 0.002), but much less in boys. CONCLUSIONS: Low prenatal selenium status seems to be disadvantageous for children's psychomotor and language development. Further studies are needed to elucidate the underlying mechanisms of these effects.

Cognitive deficit and poverty in the first 5 years of childhood in Bangladesh.

OBJECTIVE: We aimed to determine the timing and size of the cognitive deficit associated with poverty in the first 5 years of life and to examine the role of parental characteristics, pre- and postnatal growth, and stimulation in the home in Bangladeshi children. We hypothesized that the effect of poverty on cognition begins in infancy and is mainly mediated by these factors. METHODS: We enrolled 2853 singletons, a subsample from a pregnancy supplementation trial in a poor rural area. We assessed mental development at 7, 18, and 64 months; anthropometry at birth, 12, 24, and 64 months; home stimulation at 18 and 64 months; and family's socioeconomic background. In multiple regression analyses, we examined the effect of poverty at birth on IQ at 64 months and the extent that other factors mediated the effect. RESULTS: A mean cognitive deficit of 0.2 (95% confidence interval -0.4 to -0.02) z scores between the first and fifth wealth quintiles was apparent at 7 months and increased to 1.2 (95% confidence interval -1.3 to -1.0) z scores of IQ by 64 months. Parental education, pre- and postnatal growth in length, and home stimulation mediated 86% of the effects of poverty on IQ and had independent effects. Growth in the first 2 years had larger effects than later growth. Home stimulation had effects throughout the period. CONCLUSIONS: Effects of poverty on children's cognition are mostly mediated through parental education, birth size, growth in the first 24 months, and home stimulation in the first 5 years.