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.

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.

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.

Prevalence of dementia and factors associated with dementia in rural Bangladesh: data from a cross-sectional, population-based study.

BACKGROUND: There are currently no published reports of dementia prevalence or factors associated with dementia occurrence in Bangladesh. The aims are to report the prevalence of definite and questionable dementia in rural Bangladesh, and examine factors potentially associated with dementia occurrence, including sociodemographic, clinical, social, and nutritional factors. METHODS: We used data from a population-based, cross-sectional study from Matlab, in rural Bangladesh, on 471 persons aged 60+ years. Participants underwent a clinical examination including diagnosis of somatic disorders, and a structured interview including questions about sociodemographic and social factors. Nutritional status was measured with the Mini Nutritional Assessment, and blood tests were conducted to assess a range of nutritional and clinical aspects. Age- and sex-specific dementia prevalence was calculated. Crude and adjusted logistic regression was used to examine associations between dementia and clinical, social, and nutritional factors. Dementia was diagnosed using a two-step procedure by physicians according to DSM-IV criteria. RESULTS: The prevalence of questionable dementia was 11.5% and definite dementia was 3.6%. Dementia prevalence increased with increasing years of age (adjusted OR: 1.04; 95% CI = 1.002-1.1) and decreased with more years of education (adjusted OR: 0.8; 95% CI = 0.6-0.99). Being malnourished increased the odds of dementia almost six-fold (adjusted OR: 5.9; 95% CI = 1.3-26.3), while frequent participation in social activities was associated with a decreased odds (adjusted OR: 0.5; 95% CI = 0.2-0.9). CONCLUSIONS: The prevalence of dementia in rural Bangladesh is similar to other countries in the South Asia region, but lower than reports from other world regions. Malnutrition is strongly associated with dementia occurrence, and is a relevant area for future research within low-income countries.

Febrile illness and pro-inflammatory cytokines are associated with lower neurodevelopmental scores in Bangladeshi infants living in poverty.

BACKGROUND: An estimated one-third of children younger than 5 years in low- and middle-income countries fail to meet their full developmental potential. The first year of life is a period of critical brain development and is also when most of the morbidity from infection is suffered. We aimed to determine if clinical and biological markers of inflammation in the first year of life predict cognitive, language, and motor outcomes in children living in an urban slum in Bangladesh. METHODS: Children living in Dhaka, Bangladesh were observed from birth until 24 months of age. Febrile illness was used as a clinical marker of inflammation and elevated concentrations of inflammation-related cytokines (IL-1ß, IL-6, TNF-α, IL-4, IL-10) in sera collected from a subset of the cohort (N = 127) at 6 months of age were used as biomarkers of inflammation. Psychologists assessed cognitive, language, and motor development using a culturally adapted version of the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) at 12 (N = 398) and 24 months of age (N = 210). We tested for the ability of febrile illness and elevated cytokine levels to predict developmental outcomes, independent of known predictors of stunting, family income, and maternal education. RESULTS: Every additional 10 days of fever was associated with a 1.9 decrease in language composite score and a 2.1 decrease in motor composite score (p = 0.005 and 0.0002, respectively). Elevated levels of the pro-inflammatory cytokines IL-1ß (> 7.06 pg/mL) and IL-6 (> 10.52 pg/mL) were significantly associated with a 4.9 and 4.3 decrease in motor score, respectively. Conversely, an elevated level of the Th-2 cytokine IL-4 (> 0.70 pg/mL) was associated with a 3.6 increase in cognitive score (all p < 0.05). CONCLUSIONS: Clinical and biological markers of inflammation in the first year of life were significantly associated with poor neurodevelopmental outcomes. Conversely, a Th2-like response was associated with a better outcome. These findings suggest that markers of inflammation could serve as prognostic indicators and potentially lead to immune-based therapies to prevent developmental delays in at-risk children.

Association between maternal haemoglobin status during pregnancy and children's mental and psychomotor development at 18 months of age: Evidence from rural Bangladesh.

BACKGROUND: Anaemia is commonly caused by iron deficiency and screened by haemoglobin (Hb) concentration in blood. There is a scarcity of longitudinal data on the relationship between maternal Hb levels during pregnancy and neurodevelopment in children. OBJECTIVE: To measure the relationship of maternal Hb concentrations during pregnancy on early child development. METHODS: This prospective cohort study included 1,720 mother-child dyads in rural Bangladesh. Maternal Hb concentrations were measured at 14 and 30 weeks of gestation. The child's Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) at 18 months of age were measured using Bayley Scales of Infant and Toddler Development (BSID-II). Data on socio-demographic characteristics, anthropometrics, mothers' IQ and children's home stimulation were also collected. Bivariate and multivariable-adjusted linear regression analyses were used to explore associations of maternal Hb with child development. RESULTS: Mean Hb concentrations at 14 and 30 weeks of gestation were 116.6 g/L (±12.7) and 114.7 g/L (±12.7), respectively. Mean MDI and PDI scores among 18-month-old children were 78.9 (±12.4) and 93.8 (±13.7), respectively. Maternal 14-week Hb concentration was correlated with PDI (r = 0.06; p < 0.05) and 30-week Hb concentrations was correlated with MDI (r = 0.05; p < 0.05). Multivariable adjusted linear regression analysis showed that an increase in 14-week Hb concentrations increased the PDI scores among boys (ß = 0.09; 95% CI: 0.02, 0.16). Hb concentrations at 30 weeks of gestation were not associated with MDI or PDI scores. CONCLUSION: Higher maternal Hb concentrations at 14 weeks of gestation were associated with higher PDI among 18-month-old boys in Bangladesh.

Main findings: Observational studies reported that low haemoglobin concentration during pregnancy is associated with poor neurodevelopmental outcomes among offspring; however, population-based longitudinal data are scarce.Added knowledge: Our study conducted in rural Bangladesh suggests that higher maternal haemoglobin levels in early pregnancy (14 weeks of gestation) are positively associated with psychomotor performance in boys.Global health impact for policy and action: The study finding provides evidence to inform public health policies aimed at improving maternal and child health outcomes, particularly in regions with high rates of anaemia during pregnancy.

Psychosocial stimulation benefits development in nonanemic children but not in anemic, iron-deficient children.

Young children with iron deficiency anemia (IDA) usually have poor development, but there is limited information on their response to psychosocial intervention. We aimed to compare the effects of psychosocial stimulation on the development of children with IDA and children who were neither anemic nor iron deficient (NANI). NANI (n = 209) and IDA (n = 225) children, aged 6-24 mo, from 30 Bangladeshi villages were enrolled in the study. The villages were then randomized to stimulation or control, and all children with IDA received 30 mg iron daily for 6 mo. Stimulation comprised 9 mo weekly play sessions at home. We assessed children's development at baseline and after 9 mo by using the Psychomotor Development Index (PDI) and the Mental Development Index (MDI) of the Bayley Scales of Infant Development-II, and rated their behavior during the test. When we controlled for socioeconomic background, the IDA and NANI groups did not differ in their Bayley scores and behavior at baseline. After 9 mo, the IDA group had improved in iron status compared with baseline but had lower PDI scores and were less responsive to the examiner than the NANI group. Random-effects multilevel regressions of the final Bayley scores of the IDA and NANI groups showed that stimulation improved children's MDI [B ± SE = 5.7 ± 1.9 (95% CI: 2.0, 9.4), P = 0.003], and the interaction between iron status and stimulation showed a suggestive trend (P = 0.10), indicating that children with IDA and NANI responded differently to stimulation, with the NANI group improving more than the IDA group. In addition to iron treatment, children with IDA may require more intense or longer interventions than NANI children.

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.

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.

Inequality in early childhood: risk and protective factors for early child development.

Inequality between and within populations has origins in adverse early experiences. Developmental neuroscience shows how early biological and psychosocial experiences affect brain development. We previously identified inadequate cognitive stimulation, stunting, iodine deficiency, and iron-deficiency anaemia as key risks that prevent millions of young children from attaining their developmental potential. Recent research emphasises the importance of these risks, strengthens the evidence for other risk factors including intrauterine growth restriction, malaria, lead exposure, HIV infection, maternal depression, institutionalisation, and exposure to societal violence, and identifies protective factors such as breastfeeding and maternal education. Evidence on risks resulting from prenatal maternal nutrition, maternal stress, and families affected with HIV is emerging. Interventions are urgently needed to reduce children's risk exposure and to promote development in affected children. Our goal is to provide information to help the setting of priorities for early child development programmes and policies to benefit the world's poorest children and reduce persistent inequalities.

Effects of psychosocial stimulation on improving home environment and child-rearing practices: results from a community-based trial among severely malnourished children in Bangladesh.

BACKGROUND: Parenting programmes are effective in enhancing parenting practices and child development. This study evaluated the effects of a intervention with psychosocial stimulation (PS) on the quality of the home environment and mothers' child-rearing practices in a community-based trial with severely malnourished Bangladeshi children. METHOD: Severely underweight children (n = 507), 6-24 months of age, were randomly assigned to five groups: PS; food supplementation (FS); PS + FS; clinic-control (CC); and, hospital-control (CH). PS included fortnightly follow-up visits for six months at community clinics where a play leader demonstrated play activities and gave education on child development and child rearing practices. FS comprised cereal-based supplements (150-300 kcal/day) for three months. All groups received medical care, micronutrient supplements and growth monitoring. Mothers were given the Home Observation for Measurement of the Environment (HOME) inventory and a questionnaire on parenting at baseline and after six months to assess the outcome. RESULTS: 322 children completed the study. After six months of intervention the PS + FS and PS groups benefitted in the total HOME score (depending on the comparison group, effect sizes varied from 0.66 to 0.33 SD) The PS + FS and PS groups also benefitted in two HOME subscales: maternal involvement (effect sizes: 0.8 to 0.55 SD) and play materials, (effect sizes: 0.46 to 0.6 SD), and child-rearing practices scores (effect size: 1.5 to 1.1 SD). The PS + FS group benefitted 4.0 points in total HOME score compared with CH, 4.8 points compared with CC and 4.5 points compared with FS (p < 0.001 for all). The PS group benefitted 2.4 points compared with CH (p = 0.035), 3.3 points compared with CC (p = 0.004), and 2.9 points compared with FS (p = 0.006). Child-rearing practice scores of the PS + FS group improved 7.7, 6.4 and 6.6 points and the PS group improved 8.5, 7.2 and 7.4 points more than CH, CC and FS, respectively (p < 0.001 for all). CONCLUSIONS: Child-rearing practices of mothers of severely malnourished children and the quality of their home environment can be improved through community-based psychosocial stimulation with or without food supplementation. This may be of importance to promote child development.

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.

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.

Effects of community-based follow-up care in managing severely underweight children.

OBJECTIVE: The aim of the present study was to assess the effects of community-based follow-up care, food supplementation, and/or psychosocial stimulation on the recovery of severely underweight children. PATIENTS AND METHODS: A total of 507 severely underweight children (weight-for-age z score <-3) ages 6 to 24 months hospitalized at the International Center for Diarrheal Disease Research, Bangladesh, were randomly assigned to 1 of the following regimens for 3 months once they recovered from diarrhea: fortnightly follow-up care at the International Center for Diarrheal Disease Research, Bangladesh Hospital, including growth monitoring, health education, and micronutrient supplementation (group H-C, n = 102); fortnightly follow-up at community clinics, using the same treatment regimen as group H-C (group C-C, n = 99); community-based follow-up as per group C-C plus cereal-based supplementary food (SF) (group C-SF, n = 101); follow-up as per group C-C plus psychosocial stimulation (PS) (group C-PS, n = 102); or follow-up as per group C-C plus both SF and PS (group C-SF + PS, n = 103). RESULTS: There were no significant differences in baseline characteristics by treatment group. Attendance at scheduled follow-up visits was greater in groups C-SF, C-SF + PS, and C-PS than in C-C and H-C; P < 0.05. Rates of weight gain were greater in groups C-SF + PS, C-SF, and C-PS (0.88-1.01 kg) compared with groups C-C and H-C (0.63-0.76 kg), P < 0.05. Three-factor analysis of covariance of the effects of treatment components indicated that weight gain and change in weight-for-age z score and weight-for-length z score were greater in groups that received SF (P < 0.05) and linear growth was greater among children managed in the community (P = 0.002). CONCLUSIONS: Positioning follow-up services in the community increases follow-up visits and promotes greater linear growth; providing SF, with or without PS, increases clinic attendance and enhances nutritional recovery. Community-based service delivery, especially including SF, permits better rehabilitation of greater numbers of severely underweight children.

Intestinal mucosal permeability of severely underweight and nonmalnourished Bangladeshi children and effects of nutritional rehabilitation.

OBJECTIVE: Lactulose/mannitol (L/M) intestinal permeability tests were completed to compare the intestinal function of severely underweight children recovering from diarrhea and other illnesses and of nonmalnourished children from the same communities, and to evaluate the effects of food supplementation, with or without psychosocial stimulation, on the changes in intestinal function among the underweight children. PATIENTS AND METHODS: Seventy-seven malnourished children completed intestinal permeability studies at baseline and 3 months after receiving 1 of the following randomly assigned treatment regimens: group-C--fortnightly follow-up at community-based follow-up units, including growth monitoring and promotion, health education, and micronutrient supplementation, n = 17; group-SF--same as group-C plus supplementary food (SF) to provide 150 to 300 kcal/day, n = 23; group-PS--same as group-C plus psychosocial stimulation (PS), n = 17; or group-SF + PS--same as group-C plus SF and PS, n = 20. Seventeen nonmalnourished children were included as comparison subjects. RESULTS: The malnourished children's mean ± SD initial age was 13.1 ± 4.0 months, their mean weight-for-age z score was -3.82 ± 0.61, and their median (interquartile range) urinary L/M recovery ratio was 0.16 (0.10-0.28). Eighty-four percent of the children had L/M ≥ 0.07, suggestive of impaired intestinal function. The median L/M of the malnourished children was significantly greater than that of 17 relatively well-nourished children (median 0.09; interquartile range 0.05-0.12; P = 0.001). There were no significant differences in baseline characteristics of the severely malnourished children by treatment group. Following treatment, the L/M ratio improved in all of the groups (P < 0.001), but there were no significant differences in these changes by treatment group. There was a significant positive association between weight gain and the magnitude of improvement in L/M ratio (r = 0.30, P = 0.012). CONCLUSIONS: Intestinal mucosal function, as measured by sugar permeability, is impaired among severely underweight children. Intestinal permeability improves in relation to weight gain, but intestinal mucosal recovery is not specifically related to the types or amount of food supplementation or PS provided in this trial.