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.

Factors associated with children's cognitive, language, and motor development in deprived urban settings in Bangladesh.

BACKGROUND: Children's development is multifactorial. Although there have been several studies exploring the association of children's development with maternal, child, and environmental factors, we are unaware of any study that assessed those factors in children whose mothers were enrolled in a social safety net programme in low- and middle-income countries. This study aimed to identify the factors associated with disadvantaged children's cognitive, language, and motor development at age 6-16 months in deprived settings of urban Bangladesh and to identify relative importance of these factors of children's development. We also explored if there were any gender differences in child development. METHODS: This cross-sectional study was conducted in a deprived setting of urban Bangladesh. Bayley III was used for assessing children's cognitive, language, and motor development. Multivariable linear regression model was used to find the factors associated with children's development, and dominance analysis was used to explore the relative importance of the factors. RESULTS: Out of the total 599 mother-child dyads, 303 (50.58%) were girls. The factors associated with children's development were length-for-age Z-score (cognitive: B = 1.21 [95% CI = 0.31, 2.11], P = 0.008; language: 1.67 [0.79, 2.55] P < 0.001; motor: 2.15 [1.01, 3.29] P < 0.001) and home environment (cognitive: 0.58 [0.27, 0.89] P < 0.001; language: 0.59 [0.27, 0.92], P < 0.001; motor: 0.44 [0.09, 0.79] P = 0.013). Girls had higher cognitive (1.90 [0.17, 3.6], P = 0.031) and language (2.53 [0.55, 4.51], P = 0.013) development compared with boys. Families with a higher number of under five children within the households had lower language (-1.57 [-2.78, -0.36], P = 0.011) development. Violence against the mother and the families' food security status were not associated with the children's development. Children's length-for-age Z-score (27%) and home stimulation environment (23%) were the most important factors of cognitive development. CONCLUSION: Children's nutritional status and home environment are important factors for disadvantaged children's development in deprived urban settings of Bangladesh. Both early child development-focussed parenting and nutrition interventions should be considered when designing child development programmes in urban settings in low- and middle-income countries.

Supplementation With Iron Syrup or Iron-Containing Multiple Micronutrient Powders Alters Resting Brain Activity in Bangladeshi Children.

BACKGROUND: Anemia and iron deficiency have been associated with poor child cognitive development. A key rationale for the prevention of anemia using supplementation with iron has been the benefits to neurodevelopment. However, little causal evidence exists for these gains. OBJECTIVES: We aimed to examine effects of supplementation with iron or multiple micronutrient powders (MNPs) on brain activity measures using resting electroencephalography (EEG). METHODS: Children included in this neurocognitive substudy were randomly selected from the Benefits and Risks of Iron Supplementation in Children study, a double-blind, double-dummy, individually randomized, parallel-group trial in Bangladesh, in which children, starting at 8 mo of age, received 3 mo of daily iron syrup, MNPs, or placebo. Resting brain activity was recorded using EEG immediately after intervention (month 3) and after a further 9-month follow-up (month 12). We derived EEG band power measures for delta, theta, alpha, and beta frequency bands. Linear regression models were used to compare the effect of each intervention with that of placebo on the outcomes. RESULTS: Data from 412 children at month 3 and 374 at month 12 were analyzed. At baseline, 43.9% were anemic and 26.7% were iron deficient. Immediately after intervention, iron syrup, but not MNPs, increased the mu alpha-band power, a measure that is associated with maturity and the production of motor actions (iron vs. placebo: mean difference = 0.30; 95% CI: 0.11, 0.50 µV2; P = 0.003; false discovery rate adjusted P = 0.015). Despite effects on hemoglobin and iron status, effects were not observed on the posterior alpha, beta, delta, and theta bands, nor were effects sustained at the 9-month follow-up. CONCLUSIONS: The effect size for immediate effects on the mu alpha-band power is comparable in magnitude with psychosocial stimulation interventions and poverty reduction strategies. However, overall, we did not find evidence for long-lasting changes in resting EEG power spectra from iron interventions in young Bangladeshi children. This trial was registered at www.anzctr.org.au 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.

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.