Integrating early stimulation and play at scale: study protocol for "MAHAY Mikolo", a multi-arm cluster-randomized controlled trial.

BACKGROUND: Hundreds of millions of children living in poverty worldwide are not reaching their full, developmental potential. Programs to promote nurturing and responsive caregiving, such as those in which community health workers (CHWs) conduct home visits to support optimal early childhood development (ECD), have been effective in small trials, but have not achieved similar success at scale. This study will explore two approaches to scale-up: converting a home-visiting model to a group-based model; and integrating the ECD curriculum into an existing government program. The objectives of the study are to: 1) Measure how the integration of ECD activities affects time and task allocation of CHWs and CHW psychosocial wellbeing; 2) Examine how the integration of ECD activities affects caregiver-child dyad participation in standard health and nutrition activities; and 3) Explore how the availability of age-appropriate play materials at home affects caregiver-child dyad participation rates in a group-based ECD program. METHODS: We will randomize 75 communities in rural Madagascar into three arms: 1) [C], which is the status quo (community-based health and nutrition program); 2) [T], which is C + ECD group sessions [T]; and 3) [T +], which is T with the addition of an enhanced play materials package for home use. All children between 6-30 months old at the time of the intervention launch will be eligible to participate in group activities. The intervention will last 12 months and is comprised of fortnightly group sessions in which the CHWs provide caregiver-child dyads with information relating to ECD; CHWs will also include structured time for caregivers to practice the play and child stimulation activities they have learned. We will administer monthly surveys to measure CHW time use and task allocation, and we will leverage administrative data to measure caregiver-child dyad participation in the group sessions. DISCUSSION: The results from the trial will provide the evidence base required to implement an integrated package of nutrition, health and ECD promotion activities at scale in Madagascar, and findings may be relevant in other low-income countries. TRIAL REGISTRATION: This trial is registered on the AEA Social Science Registry (AEARCTR-0004704) on November 15, 2019 and on ClinicalTrials.gov (NCT05129696) on November 22, 2021.

Lipid-Based Nutrient Supplementation Reduces Child Anemia and Increases Micronutrient Status in Madagascar: A Multiarm Cluster-Randomized Controlled Trial.

BACKGROUND: Iron deficiency anemia affects hundreds of millions of women and children worldwide and is associated with impaired infant outcomes. Small-quantity lipid-based nutrient supplement (LNS) have been found to reduce the prevalence of anemia and iron deficiency in some trials. OBJECTIVES: We evaluated the effectiveness of daily LNS supplementation on child anemia and micronutrient status in Madagascar within the context of an existing, scaled-up nutrition program. METHODS: We cluster-randomized 125 communities to (T0) a routine program with monthly growth monitoring and nutrition education; (T1) T0 + home visits for intensive nutrition counselling; (T2) T1 + LNS for children aged 6-18 mo; (T3) T2 + LNS for pregnant/lactating women; or (T4) T1 + parenting messages. Pregnant women and infants aged <12 mo were enrolled in 2014 and followed for 2 y. Child outcome measures included hemoglobin and anemia assessed using the HemoCue 301 system (n = 3561), and serum ferritin and soluble transferrin receptor as markers of iron status, retinol-binding protein as a marker of vitamin A status, and C-reactive protein and α-1 acid glycoprotein from a finger stick blood draw among a subsample (n = 387). We estimated mean difference using linear regression and prevalence ratios using modified Poisson regression accounting for the clustered design. All analyses were intention-to-treat. RESULTS: Children in the LNS groups (T2 and T3) had ∼40% lower prevalence of anemia and iron deficiency anemia and 25% lower prevalence of iron deficiency than children in the control group (T0) (P < 0.05 for all). There were no differences in any of the biomarkers when comparing children in the T4 group with those in T0; nor were there differences between T3 and T2. CONCLUSIONS: Our findings suggest the provision of LNS in the context of a large-scale program offers significant benefits on anemia and iron status in young children.This trial was registered at www.isrctn.com as ISRCTN14393738.

Caregiver perceptions of child development in rural Madagascar: a cross-sectional study.

BACKGROUND: Human capital (the knowledge, skills, and health that accumulate over life) can be optimized by investments in early childhood to promote cognitive and language development. Parents and caregivers play a crucial role in the promotion and support of cognitive development in their children. Thus, understanding caregiver perceptions of a child's capabilities and attributes, including intelligence, may enhance investments early in life. To explore this question, we asked caregivers to rank their child's intelligence in comparison with other children in the community, and compared this ranking with children's scores on an assessment of developmental abilities across multiple domains. METHODS: Our study examined cross-sectional data of 3361 children aged 16-42 months in rural Madagascar. Child intelligence, as perceived by their caregiver, was captured using a ladder ranking scale based on the MacArthur Scale for Subjective Social Status. Children's developmental abilities were assessed using scores from the Ages and Stages Questionnaire: Inventory (ASQ-I), which measures cognitive, language, and socio-emotional development. Ranked percentiles of the ASQ-I were generated within communities and across the whole sample. We created categories of under-estimation, matched, and over-estimation by taking the differences in rankings between caregiver-perceived child intelligence and ASQ-I. Child nutritional status, caregiver belief of their influence on child intelligence, and sociodemographic factors were examined as potential correlates of discordance between the measures using multinomial logistic regressions. RESULTS: We found caregiver perceptions of intelligence in Madagascar did not align consistently with the ASQ-I, with approximately 8% of caregivers under-estimating and almost 50% over-estimating their children's developmental abilities. Child nutritional status, caregiver belief of their influence on child intelligence, caregiver education, and wealth were associated with under- or over-estimation of children's developmental abilities. CONCLUSIONS: Our findings suggest parents may not always have an accurate perception of their child's intelligence or abilities compared with other children. The results are consistent with the limited literature on parental perceptions of child nutrition, which documents a discordance between caregiver perceptions and objective measures. Further research is needed to understand the common cues caregivers that use to identify child development milestones and how these may differ from researcher-observed measures in low-income settings. TRIAL REGISTRATION: Current Controlled Trials ISRCTN14393738 . Registered June 23, 2015.

Perils of scaling up: Effects of expanding a nutrition programme in Madagascar.

Scaling up integrated nutrition programmes from small, targeted interventions or pilot studies to large-scale government-run programmes can be challenging, with risks of changing the nature and quality of the interventions such that effectiveness is not sustained. In 1999, the Government of Madagascar introduced a nationwide, community-based, growth-monitoring and nutrition education programme, which was gradually scaled up throughout the country until 2011. Data from three nationally representative surveys, administered pre- and post-programme implementation, in participating and non-participating communities, were used to evaluate the effectiveness of the programme to reduce malnutrition in children under 5 after two phases of expansion (1999-2004 and 2004-2011). In our analyses, we compared "original" communities, who had initiated the programme during the first phase, and "new" communities, who initiated the programme during the second phase. "Original" communities demonstrated a significant effect on mean weight-for-age and on the prevalence of underweight by 2004; this effect was sustained at a reduced level through 2011. In contrast, "new" communities showed no benefits for any childhood nutritional outcomes. An explanation for these findings may be that community health workers in the "new" communities reported lower motivation and less use of key messages and materials than those in the "original" communities. Frontline workers reported increased workload and irregular pay across the board during the second phase of programme expansion. Our findings underscore the risk of losing effectiveness if programme quality is not maintained during scale-up. Key factors, such as training and motivation of frontline workers, are important to address when bringing a programme to scale.

A cluster-randomized, controlled trial of nutritional supplementation and promotion of responsive parenting in Madagascar: the MAHAY study design and rationale.

BACKGROUND: Over half of the world's children suffer from poor nutrition, and as a consequence they experience delays in physical and mental health, and cognitive development. There is little data evaluating the effects of delivery of lipid-based, nutrition supplementation on growth and development during pregnancy and early childhood within the context of a scaled-up program. Furthermore, there is limited evidence on effects of scaled-up, home-visiting programs that focus on the promotion of child development within the context of an existing, national nutrition program. METHODS/DESIGN: The MAHAY ("smart" in Malagasy) study uses a multi-arm randomized-controlled trial (RCT) to test the effects and cost-effectiveness of combined interventions to address chronic malnutrition and poor child development. The arms of the trial are: (T0) existing program with monthly growth monitoring and nutritional/hygiene education; (T1) is T0 + home visits for intensive nutrition counseling within a behavior change framework; (T2) is T1 + lipid-based supplementation (LNS) for children 6-18 months old; (T3) is T2 + LNS supplementation of pregnant/lactating women; and (T4) is T1 + intensive home visiting program to support child development. There are anticipated to be n = 25 communities in each arm (n = 1250 pregnant women, n = 1250 children 0-6 months old, and n = 1250 children 6-18 months old). Primary outcomes include growth (length/height-for-age z-scores) and child development (mental, motor and social development). Secondary outcomes include care-giver reported child morbidity, household food security and diet diversity, micro-nutrient status, maternal knowledge of child care and feeding practices, and home stimulation practices. We will estimate unadjusted and adjusted intention-to-treat effects. Study protocols have been reviewed and approved by the Malagasy Ethics Committee at the Ministry of Health in Madagascar and by the institutional review board at the University of California, Davis. This study is funded by the Strategic Impact Evaluation Fund (SIEF), the World Bank Innovation Grant, the Early Learning Partnership Grant, the Japan Scaling-up for Nutrition Trustfund, and Grand Challenges Canada. The implementation of the study is financed by Madagascar's National Nutrition Office. TRIAL REGISTRATION: Current Controlled Trials ISRCTN14393738 . Registered June 23, 2015.

Preventive small-quantity lipid-based nutrient supplements reduce severe wasting and severe stunting among young children: an individual participant data meta-analysis of randomized controlled trials.

BACKGROUND: Meta-analyses show that small-quantity lipid-based nutrient supplements (SQ-LNSs) reduce child wasting and stunting. There is little information regarding effects on severe wasting or stunting. OBJECTIVES: We aimed to identify the effect of SQ-LNSs on prevalence of severe wasting (weight-for-length z score < -3) and severe stunting (length-for-age z score < -3). METHODS: We conducted a 2-stage meta-analysis of individual participant data from 14 randomized controlled trials of SQ-LNSs provided to children 6-24 mo of age. We generated study-specific and subgroup estimates of SQ-LNS compared with control and pooled the estimates using fixed-effects models. We used random-effects meta-regression to examine study-level effect modifiers. In sensitivity analyses, we examined whether results differed depending on study arm inclusion criteria and types of comparisons. RESULTS: SQ-LNS provision led to a relative reduction of 31% in severe wasting [prevalence ratio (PR): 0.69; 95% CI: 0.55, 0.86; n = 34,373] and 17% in severe stunting (PR: 0.83; 95% CI: 0.78, 0.90; n = 36,795) at endline. Results were similar in most of the sensitivity analyses but somewhat attenuated when comparisons using passive control arms were excluded (PR: 0.74; 95% CI: 0.57, 0.96; n = 26,327 for severe wasting and PR: 0.88; 95% CI: 0.81, 0.95; n = 28,742 for severe stunting). Study-level characteristics generally did not significantly modify the effects of SQ-LNSs, but results suggested greater effects of SQ-LNSs in sites with greater burdens of wasting or stunting, or with poorer water quality or sanitation. CONCLUSIONS: Including SQ-LNSs in preventive interventions to promote healthy child growth and development is likely to reduce rates of severe wasting and stunting. This meta-analysis was registered at www.crd.york.ac.uk/PROSPERO as CRD42019146592.

Socioeconomic gradients and child development in a very low income population: evidence from Madagascar.

Our objectives were to document and examine socioeconomic gradients across a comprehensive set of child development measures in a population living in extreme poverty, and to interpret these gradients in light of findings from the neuroscience literature. We assessed a nationally representative sample of 3-6-year-old children (n = 1332) from 150 communities of Madagascar using standard tests of development. We found that children whose families were in the top wealth quintile or whose mothers had secondary education performed significantly better across almost all measures of cognitive and language development and had better linear growth compared with children of women in the lowest wealth quintile or women with no education. These differences between children of low and high socioeconomic position were greatest for receptive language, working memory, and memory of phrases. The mean difference in the scores between children in the highest and lowest socioeconomic status categories doubled between age 3 and age 6, and the biggest gaps across socioeconomic position by age 6 were in receptive language and sustained attention. Our results suggest that even within the context of extreme poverty, there are strong associations between family socioeconomic status and child development outcomes among preschool children, and that the language and executive function domains exhibit the largest gradients.

Characteristics that modify the effect of small-quantity lipid-based nutrient supplementation on child anemia and micronutrient status: an individual participant data meta-analysis of randomized controlled trials.

BACKGROUND: Small-quantity lipid-based nutrient supplements (SQ-LNSs) have been shown to reduce the prevalence of child anemia and iron deficiency, but effects on other micronutrients are less well known. Identifying subgroups who benefit most from SQ-LNSs could support improved program design. OBJECTIVES: We aimed to identify study-level and individual-level modifiers of the effect of SQ-LNSs on child hemoglobin (Hb), anemia, and inflammation-adjusted micronutrient status outcomes. METHODS: We conducted a 2-stage meta-analysis of individual participant data from 13 randomized controlled trials of SQ-LNSs provided to children 6-24 mo of age (n = 15,946). We generated study-specific and subgroup estimates of SQ-LNSs compared with control, and pooled the estimates using fixed-effects models. We used random-effects meta-regression to examine potential study-level effect modifiers. RESULTS: SQ-LNS provision decreased the prevalence of anemia (Hb < 110 g/L) by 16% (relative reduction), iron deficiency (plasma ferritin < 12 µg/L) by 56%, and iron deficiency anemia (IDA; Hb < 110 g/L and plasma ferritin <12 µg/L) by 64%. We observed positive effects of SQ-LNSs on hematological and iron status outcomes within all subgroups of the study- and individual-level effect modifiers, but effects were larger in certain subgroups. For example, effects of SQ-LNSs on anemia and iron status were greater in trials that provided SQ-LNSs for >12 mo and provided 9 (as opposed to <9) mg Fe/d, and among later-born (than among first-born) children. There was no effect of SQ-LNSs on plasma zinc or retinol, but there was a 7% increase in plasma retinol-binding protein (RBP) and a 56% reduction in vitamin A deficiency (RBP < 0.70 µmol/L), with little evidence of effect modification by individual-level characteristics. CONCLUSIONS: SQ-LNSs can substantially reduce the prevalence of anemia, iron deficiency, and IDA among children across a range of individual, population, and study design characteristics. Policy-makers and program planners should consider SQ-LNSs within intervention packages to prevent anemia and iron deficiency.This trial was registered at www.crd.york.ac.uk/PROSPERO as CRD42020156663.

Small-quantity lipid-based nutrient supplements for children age 6-24 months: a systematic review and individual participant data meta-analysis of effects on developmental outcomes and effect modifiers.

BACKGROUND: Small-quantity (SQ) lipid-based nutrient supplements (LNSs) provide many nutrients needed for brain development. OBJECTIVES: We aimed to generate pooled estimates of the effect of SQ-LNSs on developmental outcomes (language, social-emotional, motor, and executive function), and to identify study-level and individual-level modifiers of these effects. METHODS: We conducted a 2-stage meta-analysis of individual participant data from 14 intervention against control group comparisons in 13 randomized trials of SQ-LNSs provided to children age 6-24 mo (total n = 30,024). RESULTS: In 11-13 intervention against control group comparisons (n = 23,588-24,561), SQ-LNSs increased mean language (mean difference: 0.07 SD; 95% CI: 0.04, 0.10 SD), social-emotional (0.08; 0.05, 0.11 SD), and motor scores (0.08; 95% CI: 0.05, 0.11 SD) and reduced the prevalence of children in the lowest decile of these scores by 16% (prevalence ratio: 0.84; 95% CI: 0.76, 0.92), 19% (0.81; 95% CI: 0.74, 0.89), and 16% (0.84; 95% CI: 0.76, 0.92), respectively. SQ-LNSs also increased the prevalence of children walking without support at 12 mo by 9% (1.09; 95% CI: 1.05, 1.14). Effects of SQ-LNSs on language, social-emotional, and motor outcomes were larger among study populations with a higher stunting burden (≥35%) (mean difference: 0.11-0.13 SD; 8-9 comparisons). At the individual level, greater effects of SQ-LNSs were found on language among children who were acutely malnourished (mean difference: 0.31) at baseline; on language (0.12), motor (0.11), and executive function (0.06) among children in households with lower socioeconomic status; and on motor development among later-born children (0.11), children of older mothers (0.10), and children of mothers with lower education (0.11). CONCLUSIONS: Child SQ-LNSs can be expected to result in modest developmental gains, which would be analogous to 1-1.5 IQ points on an IQ test, particularly in populations with a high child stunting burden. Certain groups of children who experience higher-risk environments have greater potential to benefit from SQ-LNSs in developmental outcomes.This trial was registered at www.crd.york.ac.uk/PROSPERO as CRD42020159971.

Characteristics that modify the effect of small-quantity lipid-based nutrient supplementation on child growth: an individual participant data meta-analysis of randomized controlled trials.

BACKGROUND: Meta-analyses show that small-quantity lipid-based nutrient supplements (SQ-LNSs) reduce child stunting and wasting. Identification of subgroups who benefit most from SQ-LNSs may facilitate program design. OBJECTIVES: We aimed to identify study-level and individual-level modifiers of the effect of SQ-LNSs on child growth outcomes. METHODS: We conducted a 2-stage meta-analysis of individual participant data from 14 randomized controlled trials of SQ-LNSs provided to children 6-24 mo of age (n = 37,066). We generated study-specific and subgroup estimates of SQ-LNS compared with control and pooled the estimates using fixed-effects models. We used random-effects meta-regression to examine study-level effect modifiers. In sensitivity analyses, we examined whether results differed depending on study arm inclusion criteria and types of comparisons. RESULTS: SQ-LNS provision decreased stunting (length-for-age z score < -2) by 12% (relative reduction), wasting [weight-for-length (WLZ) z score < -2] by 14%, low midupper arm circumference (MUAC) (<125 mm or MUAC-for-age z score < -2) by 18%, acute malnutrition (WLZ < -2 or MUAC < 125 mm) by 14%, underweight (weight-for-age z score < -2) by 13%, and small head size (head circumference-for-age z score < -2) by 9%. Effects of SQ-LNSs generally did not differ by study-level characteristics including region, stunting burden, malaria prevalence, sanitation, water quality, duration of supplementation, frequency of contact, or average compliance with SQ-LNS. Effects of SQ-LNSs on stunting, wasting, low MUAC, and small head size were greater among girls than among boys; effects on stunting, underweight, and low MUAC were greater among later-born (than among firstborn) children; and effects on wasting and acute malnutrition were greater among children in households with improved (as opposed to unimproved) sanitation. CONCLUSIONS: The positive impact of SQ-LNSs on growth is apparent across a variety of study-level contexts. Policy-makers and program planners should consider including SQ-LNSs in packages of interventions to prevent both stunting and wasting.This trial was registered at www.crd.york.ac.uk/PROSPERO as CRD42019146592.

The aggregate income losses from childhood stunting and the returns to a nutrition intervention aimed at reducing stunting.

We undertake two calculations, one for all developing countries, the other for 34 developing countries that together account for 90% of the world's stunted children. The first asks how much lower a country's per capita income is today as a result of having a fraction of its workforce been stunted in childhood. We use a development accounting framework, relying on micro-econometric estimates of the effects of childhood stunting on adult wages through their effects on years of schooling, cognitive skills, and height, parsing out the relative contribution of each set of returns to avoid double counting. We estimate that, on average, the per capita income penalty from stunting is between 5-7%, depending on the assumption. In our second calculation we estimate the economic value and the costs associates with scaling up a package of nutrition interventions using the same methodology and set of assumptions used in the first calculation. We take a package of 10 nutrition interventions that has data on both effects and costs, and we estimate the rate-of-return to gradually introducing this program over a period of 10 years in 34 countries that together account for 90% of the world's stunted children. We estimate a rate-of-return of 12%, and a benefit-cost ratio of 5:1-6:1.

Effects of nutritional supplementation and home visiting on growth and development in young children in Madagascar: a cluster-randomised controlled trial.

BACKGROUND: Evidence from efficacy trials suggests that lipid-based nutrient supplementation (LNS) and home visits can be effective approaches to preventing chronic malnutrition and promoting child development in low-income settings. We tested the integration of these approaches within an existing, large-scale, community-based nutrition programme in Madagascar. METHODS: We randomly allocated 125 programme sites to five intervention groups: standard-of-care programme with monthly growth monitoring and nutrition education (T0); T0 plus home visits for intensive nutrition counselling through an added community worker (T1); T1 plus LNS for children aged 6-18 months (T2); T2 plus LNS for pregnant or lactating women (T3); or T1 plus fortnightly home visits to promote and encourage early stimulation (T4). Pregnant women (second or third trimester) and infants younger than 12 months were enrolled in the trial. Primary outcomes were child growth (length-for-age and weight-for-length Z scores) and development at age 18-30 months. Analyses were by intention to treat. The trial was registered with the ISRCTN registry, number ISRCTN14393738. FINDINGS: The study enrolled 3738 mothers: 1248 pregnant women (250 women in each of the T0, T1, T2, and T4 intervention groups and 248 in the T3 intervention group) and 2490 children aged 0-11 months (497 children in T0, 500 in T1, 494 in T2, 499 in T3, and 500 in T4) at baseline who were assessed at 1-year and 2-year intervals. There were no main effects of any of the intervention groups on any measure of anthropometry or any of the child development outcomes in the full sample. However, compared with children in the T0 intervention group, the youngest children (<6 months at baseline) in the T2 and T3 intervention groups who were fully exposed to the child LNS dose had higher length-for-age Z scores (a significant effect of 0·210 SD [95% CI -0·004 to 0·424] for T2 and a borderline effect of 0·216 SD [0·043 to 0·389] for T3) and lower stunting prevalence (-9·0% [95% CI -16·7 to -1·2] for T2 and -8·2% [-15·6 to -0·7] for T3); supplementing mothers conferred no additional benefit. INTERPRETATION: LNS for children for a duration of 12 months only benefited growth when it began at an early age, suggesting the need to supplement infants at age 6 months in a very low-income context. The lack of effect of the early stimulation messages and home visits might be due to little take-up of behaviour-change messages and delivery challenges facing community health workers. FUNDING: Eunice Kennedy Shriver National Institutes of Child Health and Human Development, Strategic Impact Evaluation Fund, World Bank Innovation Grant, Early Learning Partnership Grant, World Bank Research Budget, Japan Nutrition Trust Fund, Power of Nutrition, and the National Nutrition Office of Madagascar.

Performance of a receptive language test among young children in Madagascar.

Language tests developed and validated in one country may lose their desired properties when translated for use in another, possibly resulting in misleading estimates of ability. Using Item Response Theory (IRT) methodology, we assess the performance of a test of receptive vocabulary, the U.S.-validated Peabody Picture Vocabulary Test-Third Edition (PPVT-III), when translated, adapted, and administered to children 3 to 10 years of age in Madagascar (N = 1372), in the local language (Malagasy). Though Malagasy is considered a single language, there are numerous dialects spoken in Madagascar. Our findings were that test scores were positively correlated with age and indicators of socio-economic status. However, over half (57/96) of items evidenced unexpected response variation and/or bias by local dialect spoken. We also encountered measurement error and reduced differentiation among person abilities when we used the publishers' recommended stopping rules, largely because we lost the original item ordering by difficulty when we translated test items into Malagasy. Our results suggest that bias and testing inefficiency introduced from the translation of the PPVT can be significantly reduced with the use of methods based on IRT at both the pre-testing and analysis stages. We explore and discuss implications for cross-cultural comparisons of internationally recognized tests, such as the PPVT.