Sustained effects of small-quantity lipid-based nutrient supplements provided during the first 1000 days on child growth at 9-11 y in a randomized controlled trial in Ghana.

BACKGROUND: There is limited research on whether nutritional supplementation in the first 1000 d affects long-term child outcomes. We previously demonstrated that pre- and postnatal small-quantity lipid-based nutrient supplements (SQ-LNS) increased birth weight and child length at 18 mo of age in Ghana. OBJECTIVES: We aimed to investigate the effect of pre- and postnatal SQ-LNS on child growth and blood pressure at 9-11 y. METHODS: In the International Lipid-Based Nutrient Supplements (iLiNS)-DYAD-Ghana trial, 1320 females ≤20 weeks of gestation were randomly assigned to receive daily: iron and folic acid (IFA) during pregnancy and placebo during 6 mo postpartum or multiple micronutrients (MMNs) during pregnancy and 6 mo postpartum, or SQ-LNS during pregnancy and 6 mo postpartum and for their children aged from 6 to 18 mo. We re-enrolled 966 children aged 9-11 y and assessed child blood pressure, height-for-age z-score (HAZ), body mass index (BMI)-for-age z-score, waist-to-height ratio, triceps skinfold, and midupper arm circumference. We compared SQ-LNS with control (IFA + MMN) groups adjusting for child's age. RESULTS: Mean (standard deviation [SD]) HAZ in SQ-LNS and control group was -0.04 (0.96) and -0.16 (0.99); P = 0.060. There were no indications of group differences in the other outcomes (P > 0.10). Effects on HAZ varied by child sex (P-interaction = 0.075) and maternal prepregnancy BMI (kg/m2; P-interaction = 0.007). Among females, HAZ was higher in the SQ-LNS [0.08 (1.04)] than in the control group [-0.16 (1.01)] (P = 0.010); among males, SQ-LNS [-0.16 (0.85)] and control groups [-0.16 (0.96)] did not differ (P = 0.974). Among children of females with BMI of <25, HAZ was higher in the SQ-LNS [-0.04 (1.00)] than in the control group [-0.29 (0.94)] (P = 0.004); among females with BMI of ≥25, SQ-LNS [-0.04 (0.91)] and control groups [0.07 (1.00)] did not differ (P = 0.281). CONCLUSIONS: There is a sustained impact of prenatal and postnatal SQ-LNS on linear growth among female children and children whose mothers were not overweight. This trial was registered at clinicaltrials.gov as NCT00970866 (https://clinicaltrials.gov/ct2/show/record/NCT00970866).

The cost-effectiveness of small-quantity lipid-based nutrient supplements for prevention of child death and malnutrition and promotion of healthy development: modelling results for Uganda.

OBJECTIVE: Recent meta-analyses demonstrate that small-quantity lipid-based nutrient supplements (SQ-LNS) for young children significantly reduce child mortality, stunting, wasting, anaemia and adverse developmental outcomes. Cost considerations should inform policy decisions. We developed a modelling framework to estimate the cost and cost-effectiveness of SQ-LNS and applied the framework in the context of rural Uganda. DESIGN: We adapted costs from a costing study of micronutrient powder (MNP) in Uganda, and based effectiveness estimates on recent meta-analyses and Uganda-specific estimates of baseline mortality and the prevalence of stunting, wasting, anaemia and developmental disability. SETTING: Rural Uganda. PARTICIPANTS: Not applicable. RESULTS: Providing SQ-LNS daily to all children in rural Uganda (> 1 million) for 12 months (from 6 to 18 months of age) via the existing Village Health Team system would cost ∼$52 per child (2020 US dollars) or ∼$58·7 million annually. SQ-LNS could avert an average of > 242 000 disability-adjusted life years (DALYs) annually as a result of preventing 3689 deaths, > 160 000 cases of moderate or severe anaemia and ∼6000 cases of developmental disability. The estimated cost per DALY averted is $242. CONCLUSIONS: In this context, SQ-LNS may be more cost-effective than other options such as MNP or the provision of complementary food, although the total cost for a programme including all age-eligible children would be high. Strategies to reduce costs, such as targeting to the most vulnerable populations and the elimination of taxes on SQ-LNS, may enhance financial feasibility.

Prenatal and postnatal small-quantity lipid-based nutrient supplements and children's social-emotional difficulties at ages 9-11 y in Ghana: follow-up of a randomized controlled trial.

BACKGROUND: Provision of small-quantity lipid-based nutrient supplements (SQ-LNSs) during early life improves growth and development. In the International Lipid-Based Nutrient Supplements DYAD-Ghana trial, prenatal and postnatal SQ-LNS reduced social-emotional difficulties at age 5 y, with greater effects among children in less-enriched home environments. OBJECTIVES: We aimed to investigate the effect of prenatal and postnatal SQ-LNS on children's social-emotional problems at age 9-11 y. METHODS: In 2009-2011, 1320 pregnant women ≤20 wk gestation were randomly assigned to receive the following daily until 6 mo postpartum: 1) iron and folic acid until delivery, then placebo, 2) multiple micronutrients (MMNs), or 3) SQ-LNS (20 g/d). Children in group 3 received SQ-LNS from 6 to 18 mo. In 2021, we evaluated children's social-emotional outcomes with 6 assessment tools that used caregiver, teacher, and/or self-report to measure socioemotional difficulties, conduct problems, temperament, mood, anxiety, and emotion management. RESULTS: We assessed outcomes in 966 children, comprising 79.4% of 1217 participants eligible for re-enrolment. No significant differences were found between the SQ-LNS and control (non-LNS groups combined) groups. Few children (<2%) experienced high parent-reported social-emotional difficulties at 9-11 y, in contrast to the high prevalence at age 5 in this cohort (25%). Among children in less-enriched early childhood home environments, the SQ-LNS group had 0.37 SD (-0.04 to 0.82) lower self-reported conduct problems than the control group (P-interaction = 0.047). CONCLUSIONS: Overall positive effects of SQ-LNS on social-emotional development previously found at age 5 y are not sustained to age 9-11 y; however, there is some evidence of positive effects among children in less-enriched environments. The lack of effects may be owing to low prevalence of social-emotional problems at preadolescence, resulting in little potential to benefit from early nutritional intervention at this age in this outcome domain. Follow-up during adolescence, when social-emotional problems more typically onset, may yield further insights. This trial was registered at clinicaltrials.gov as NCT00970866. https://clinicaltrials.gov/ct2/show/record/NCT00970866.

Effectiveness of Digital Mental Health Tools to Reduce Depressive and Anxiety Symptoms in Low- and Middle-Income Countries: Systematic Review and Meta-analysis.

BACKGROUND: Depression and anxiety contribute to an estimated 74.6 million years of life with disability, and 80% of this burden occurs in low- and middle-income countries (LMICs), where there is a large gap in care. OBJECTIVE: We aimed to systematically synthesize available evidence and quantify the effectiveness of digital mental health interventions in reducing depression and anxiety in LMICs. METHODS: In this systematic review and meta-analysis, we searched PubMed, Embase, and Cochrane databases from the inception date to February 2022. We included randomized controlled trials conducted in LMICs that compared groups that received digital health interventions with controls (active control, treatment as usual, or no intervention) on depression or anxiety symptoms. Two reviewers independently extracted summary data reported in the papers and performed study quality assessments. The outcomes were postintervention measures of depression or anxiety symptoms (Hedges g). We calculated the pooled effect size weighted by inverse variance. RESULTS: Among 11,196 retrieved records, we included 80 studies in the meta-analysis (12,070 participants n=6052, 50.14% in the intervention group and n=6018, 49.85% in the control group) and 96 studies in the systematic review. The pooled effect sizes were -0.61 (95% CI -0.78 to -0.44; n=67 comparisons) for depression and -0.73 (95% CI -0.93 to -0.53; n=65 comparisons) for anxiety, indicating that digital health intervention groups had lower postintervention depression and anxiety symptoms compared with controls. Although heterogeneity was considerable (I2=0.94 for depression and 0.95 for anxiety), we found notable sources of variability between the studies, including intervention content, depression or anxiety symptom severity, control type, and age. Grading of Recommendations, Assessments, Development, and Evaluation showed that the evidence quality was overall high. CONCLUSIONS: Digital mental health tools are moderately to highly effective in reducing depression and anxiety symptoms in LMICs. Thus, they could be effective options to close the gap in depression and anxiety care in LMICs, where the usual mental health care is minimal. TRIAL REGISTRATION: PROSPERO CRD42021289709; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=289709.

The association between plasma choline, growth and neurodevelopment among Malawian children aged 6-15 months enroled in an egg intervention trial.

Choline is an essential micronutrient that may influence growth and development; however, few studies have examined postnatal choline status and children's growth and development in low- and middle-income countries. The aim of this observational analysis was to examine associations of plasma choline with growth and development among Malawian children aged 6-15 months enrolled in an egg intervention trial. Plasma choline and related metabolites (betaine, dimethylglycine and trimethylamine N-oxide) were measured at baseline and 6-month follow-up, along with anthropometric (length, weight, head circumference) and developmental assessments (the Malawi Developmental Assessment Tool [MDAT], the Infant Orienting with Attention task [IOWA], a visual paired comparison [VPC] task and an elicited imitation [EI] task). In cross-sectional covariate-adjusted models, each 1 SD higher plasma choline was associated with lower length-for-age z-score (-0.09 SD [95% confidence interval, CI -0.17 to -0.01]), slower IOWA response time (8.84 ms [1.66-16.03]) and faster processing speed on the VPC task (-203.5 ms [-366.2 to -40.7]). In predictive models, baseline plasma choline was negatively associated with MDAT fine motor z-score at 6-month follow-up (-0.13 SD [-0.22 to -0.04]). There were no other significant associations of plasma choline with child measures. Similarly, associations of choline metabolites with growth and development were null except higher trimethylamine N-oxide was associated with slower information processing on the VPC task and higher memory scores on the EI task. In this cohort of children with low dietary choline intake, we conclude that there were no strong or consistent associations between plasma choline and growth and development.

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.

Plasma Choline Concentration Was Not Increased After a 6-Month Egg Intervention in 6-9-Month-Old Malawian Children: Results from a Randomized Controlled Trial.

BACKGROUND: Eggs are a rich source of choline, an essential nutrient important for child growth and development. In a randomized trial of 1 egg/d in young children in Ecuador, an egg intervention led to significant improvements in growth, which were partially mediated by increased plasma choline concentration. A similar trial in Malawi (clinicaltrials.gov: NCT03385252) found little improvement in child growth or development. OBJECTIVES: We aimed to evaluate the effect of 1 egg/d for 6 mo on plasma choline concentrations in Malawian children enrolled in a randomized trial. METHODS: Infants aged 6-9 mo in rural Malawi were randomly assigned to receive 1 egg/d (n = 331) or serve as a nonintervention control (n = 329) for 6 mo. Anthropometric, developmental, and dietary data were collected at baseline and 6-mo follow-up, along with a blood draw. Plasma choline, betaine, dimethylglycine, trimethylamine N-oxide (TMAO), and DHA were measured at both time points using ultrahigh performance liquid chromatography-tandem MS (n = 200 per group). Linear regression analysis was used to determine the difference in plasma choline and related metabolites between groups after 6 mo of intervention. RESULTS: Plasma choline, betaine, dimethylglycine, and DHA concentrations did not differ between groups at 6-mo follow-up. Plasma TMAO was significantly (26%; 95% CI: 7%, 48%) higher in the egg intervention group in a fully adjusted model. CONCLUSIONS: Provision of 1 egg/d for 6 mo did not result in increases in plasma choline or related metabolites, except TMAO. This could partially explain the lack of effect on growth and development. Additional interventions are needed to improve choline status, growth, and development in this population.

Choline and docosahexaenoic acid during the first 1000 days and children's health and development in low- and middle-income countries.

Choline and DHA are nutrients that, when provided during the first 1000 days from conception to age 2 years, may have beneficial effects on child neurodevelopment as well as related health factors, including birth outcomes and child growth, morbidity, and inflammation. Because these nutrients are found mainly in animal-source foods, they may be lacking in the diets of pregnant and lactating women and young children in low- and middle-income countries, potentially putting children at risk for suboptimal development and health. Prior reviews of these nutrients have mainly focused on studies from high-income countries. Here, a narrative review is presented of studies describing the pre- and postnatal roles of choline, docosahexaenoic acid, and a combination of the 2 nutrients on child neurodevelopment, birth outcomes, growth, morbidity, and inflammation in low- and middle-income countries. More studies are needed to understand the specific, long-term effects of perinatal choline and docosahexaenoic acid intake in various contexts.

Maternal depression is the predominant persistent risk for child cognitive and social-emotional problems from early childhood to pre-adolescence: A longitudinal cohort study.

RATIONALE: Brain development occurs rapidly during early childhood and continues throughout middle childhood. Early and later windows of opportunity exist to alter developmental trajectories. Few studies in low- and middle-income countries have examined the importance of the timing of exposure to risks for poor pre-adolescent cognitive and social-emotional outcomes. METHODS: We assessed 359 children who participated in two follow-up studies of the Supplementation with Multiple Micronutrients Intervention Trial conducted in Indonesia in 2001-2004: at 3.5 years in 2006 and 9-12 years in 2012-2014. Using structural equation models, we examined indicators of early childhood (3.5 y) and pre-adolescent (9-12 y) exposure to risks (child height-for-age z-score [HAZ], hemoglobin [Hb], maternal depressive symptoms [MDS], home environment [HOME]), with two developmental outcomes: cognitive ability and social-emotional problems. We characterized patterns of change by calculating residuals of indicators measured earlier (3.5 y) predicting the same indicators measured later (9-12 y), for example, the residual of 3.5 y MDS predicting 9-12 y MDS (rMDS). RESULTS: Three early risk indicators (HOME, Hb, and MDS) were indirectly associated with pre-adolescent cognitive scores through early cognitive scores (HOME: 0.15, [95% CI 0.09, 0.21]; Hb: 0.08 [0.04, 0.12], MDS: -0.07 [-0.12, -0.02]). Pre-adolescent cognitive scores were also associated with change in MDS (rMDS: -0.13 [-0.23, -0.02]) and Hb (rHb: 0.10 [0.00, 0.20]) during middle childhood. For pre-adolescent social-emotional problems, both early childhood MDS (0.31 [0.19, 0.44]) and change in MDS during middle childhood (rMDS: 0.48 [0.37, 0.60]) showed strong direct associations with this outcome. CONCLUSIONS: Our findings confirm those of previous studies that prevention of risk exposures during early childhood is likely to support long-term child development. It also adds evidence to a previously scarce literature for the middle childhood period. Prevention of maternal depressive symptoms and child anemia during middle childhood should be assessed for effectiveness to support child development.

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.

Small-quantity lipid-based nutrient supplements for the prevention of child malnutrition and promotion of healthy development: overview of individual participant data meta-analysis and programmatic implications.

Small-quantity lipid-based nutrient supplements (SQ-LNSs) were designed to provide multiple micronutrients within a food base that also provides energy, protein, and essential fatty acids, targeted towards preventing malnutrition in vulnerable populations. Previous meta-analyses demonstrated beneficial effects of SQ-LNSs on child growth, anemia, and mortality. To further examine the efficacy and effectiveness of SQ-LNSs, and explore study-level and individual-level effect modifiers, we conducted an individual participant data meta-analysis of 14 randomized controlled trials of SQ-LNSs provided to children 6-24 mo of age (n > 37,000). We examined growth, development, anemia, and micronutrient status outcomes. Children who received SQ-LNSs had a 12-14% lower prevalence of stunting, wasting, and underweight; were 16-19% less likely to score in the lowest decile for language, social-emotional, and motor development; had a 16% lower prevalence of anemia; and had a 64% lower prevalence of iron-deficiency anemia compared with control group children. For most outcomes, beneficial effects of SQ-LNSs were evident regardless of study-level characteristics, including region, stunting burden, malaria prevalence, sanitation, water quality, duration of supplementation, frequency of contact, or average reported compliance with SQ-LNSs. For development, the benefits of SQ-LNSs were greater in populations with higher stunting burden, in households with lower socioeconomic status, and among acutely malnourished children. For hemoglobin and iron status, benefits were greater in populations with higher anemia prevalence and among acutely malnourished children, respectively. Thus, targeting based on potential to benefit may be worthwhile for those outcomes. Overall, co-packaging SQ-LNSs with interventions that reduce constraints on response, such as the prevention and control of prenatal and child infections, improving health care access, and promotion of early child development, may lead to greater impact. Policymakers and program planners should consider including SQ-LNSs in strategies to reduce child mortality, stunting, wasting, anemia, iron deficiency, and delayed development. This study was registered at www.crd.york.ac.uk/PROSPERO as CRD42019146592, CRD42020159971, and CRD42020156663.

The principles of Nurturing Care promote human capital and mitigate adversities from preconception through adolescence.

A comprehensive evidence-based framework is needed to guide policies and programmes that enable children and adolescents to accrue the human capital required to meet the Sustainable Development Goals (SDGs). This paper proposes a comprehensive, multisectoral, multilevel life-course conceptualisation of human capital development by building on the Nurturing Care Framework (NCF), originally developed for the foundational period of growth and development through the age 3 years. Nurturing care (NC) comprises stable environments that promote children's health and nutrition, protect from threats, and provide opportunities for learning and responsive, emotionally supportive and developmentally enriching relationships. NC is fostered by families, communities, services, national policies and beyond. The principles apply across the life course, endorse equity and human rights, and promote long-term human capital. This paper presents an evidence-based argument for the extension of the NCF from preconception through adolescence (0-20 years), organised into six developmental periods: preconception/prenatal, newborn/birth, infancy/toddlerhood, preschool, middle childhood and adolescence. The proposed framework advances human capital within each developmental period by promoting resilience and adaptive developmental trajectories while mitigating negative consequences of adversities.Attaining the SDGs depends on strengthening human capital formation, extending throughout childhood and adolescence and supported by NC. Embedded in enabling laws, policies and services, the dynamic NCF components can mitigate adversities, enhance resilience and promote the well-being of marginalised groups. The life-course extension of the NCF is strategically positioned to enhance human capital, to attain the SDGs and to ensure that children or adolescents are not left behind in reaching their developmental potential.

Impacts of an egg complementary feeding trial on energy intake and dietary diversity in Malawi.

Complementary feeding diets in low- and middle-income countries are generally inadequate to meet requirements for growth and development. Food-based interventions may prevent nutrient inadequacies provided that they do not displace other nutrient-rich foods. We conducted a randomized controlled trial in rural Malawi in which 660 children aged 6 to 9 months were provided an egg a day for 6 months or assigned to a control group. Dietary intake of complementary foods and drinks was assessed at baseline, 3-month midline and 6-month endline visits using a tablet-based multipass 24-h recall. Up to two repeat recalls were collected at each time point in a subsample of 100 children per treatment group. At midline and endline, usual energy intake from eggs was about 30 kcal/day higher in the egg group compared with controls (p < 0.0001). Compared with controls, children in the egg group were over nine times more likely to consume eggs at midline and endline. There was a comparable, but nonsignificant, greater total usual energy intake from complementary foods of 30 kcal/day at midline (p = 0.128) and 36 kcal/day at endline (p = 0.087). There also was a displacement of 7 kcal/day in legumes and nuts in children at endline (p = 0.059). At midline and endline, more than 80% of children in the egg group consumed a minimally diverse diet compared with 53% at midline and 60% at endline in the control group. This study illustrates that mothers in the egg group fed eggs to young children on a regular basis without substantial displacement of other complementary foods.

Associations of human milk oligosaccharides and bioactive proteins with infant growth and development among Malawian mother-infant dyads.

BACKGROUND: Human milk oligosaccharides (HMOs) and bioactive breast milk proteins have many beneficial properties. Information is sparse regarding associations between these milk constituents and infant growth and development in lower-income countries. OBJECTIVES: We aimed to examine associations of milk content of HMOs and bioactive proteins at 6 mo postpartum with infant growth and motor and cognitive development. These are secondary analyses of a randomized controlled trial in rural Malawi. METHODS: Breast milk samples were analyzed at 6 mo (n = 659) for general categories of HMOs (total HMOs, fucosylated HMOs, and sialylated HMOs), 51 individual HMOs, and 6 bioactive proteins (lactalbumin, lactoferrin, lysozyme, antitrypsin, IgA, and osteopontin). We examined associations of the relative abundances of HMOs and concentrations of bioactive proteins with infant growth from 6 to 12 mo [change in length-for-age (ΔLAZ), weight-for-age, weight-for-length, and head circumference z-scores] as well as ability to stand or walk alone at 12 mo, and motor and language skills, socioemotional development, executive function, and working memory at 18 mo. Analyses were adjusted for covariates and multiple hypothesis testing. RESULTS: Among all participants, there were inverse associations of IgA and lactoferrin concentrations with motor skills (P = 0.018 and P = 0.044), and a positive association of lactalbumin concentration with motor skills (P = 0.038). Among secretors only [fucosyltransferase 2 gene (FUT2) positive], there were positive associations of absolute abundance of HMOs with ΔLAZ (P = 0.035), and relative abundance of fucosylated and sialylated HMOs with language at 18 mo (P < 0.001 and P = 0.033, respectively), and inverse associations of osteopontin with standing and walking at 12 mo (P = 0.007 and 0.002, respectively). Relative abundances of several individual HMOs were associated with growth and development, mostly among secretors. CONCLUSIONS: Certain bioactive breast milk proteins and HMOs are associated with infant growth and motor and cognitive development. Further studies are needed to determine if a causal relation exists.This trial was registered at clinicaltrials.gov as NCT01239693.

Maternal biomarker patterns for metabolism and inflammation in pregnancy are influenced by multiple micronutrient supplementation and associated with child biomarker patterns and nutritional status at 9-12 years of age.

Maternal nutritional status influences fetal development and long-term risk for adult non-communicable diseases. However, the underlying mechanisms remain poorly understood. We examined whether biomarkers for metabolism and inflammation during pregnancy were associated with maternal health and with child biomarkers and health at 9-12 years of age in 44 maternal-child dyads from the Supplementation with Multiple Micronutrients Intervention Trial (SUMMIT, ISRCTN34151616) in Lombok, Indonesia. Archived blood for each dyad from maternal enrollment, later in pregnancy, postpartum, and from children at 9-12 years comprised 132 specimens. Multiplex microbead immunoassays were used to quantify vitamin D-binding protein (D), adiponectin (A), retinol-binding protein 4 (R), C-reactive protein (C), and leptin (L). Principal component analysis (PCA) revealed distinct variance patterns, i.e. principal components (PC), for baseline pregnancy, bp.pc1.D↓A↓R↓ and bp.pc2.C↓L↑; combined follow-up during pregnancy and postpartum, dp-pp.pc1.D↑↓A↑R↑↓L↓ and dp-pp.pc2.A↑C↑L↑; and children, ch.pc1.D↑R↑C↑ and ch.pc2.D↓A↑L↑. Maternal multiple micronutrient (MMN) supplementation led to an association of baseline maternal bp.pc2.C↓L↑ with decreased post-supplementation maternal dp-pp.pc2.A↑C↑L↑ (p = 0.022), which was in turn associated with both increased child ch.pc1.D↑R↑C↑ (p = 0.036) and decreased child BMI z-score (BMIZ) (p = 0.022). Further analyses revealed an association between maternal dp-pp.pc1.D↑↓A↑R↑↓L↓ and increased child BMIZ (p = 0.036). Child ch.pc1.D↑R↑C↑ was associated with decreased birth weight (p = 0.036) and increased child BMIZ (p = 0.002). Child ch.pc2.D↓A↑L↑ was associated with increased child BMIZ (p = 0.005), decreased maternal height (p = 0.030) and girls (p = 0.002). A pattern of elevated maternal adiponectin and leptin in pregnancy was associated with increased C-reactive protein, vitamin A, and D binding proteins pattern in children, suggesting biomarkers acting in concert may have qualitative as well as quantitative influence beyond single biomarker effects. Patterns in pregnancy proximal to birth were more associated with child status. In addition, child patterns were more associated with child status, particularly child BMI. MMN supplementation affects maternal biomarker patterns of metabolism and inflammation in pregnancy, and potentially in the child. However, child nutrition conditions after birth may have a greater impact on metabolism and inflammation.

Early Child Development Outcomes of a Randomized Trial Providing 1 Egg Per Day to Children Age 6 to 15 Months in Malawi.

BACKGROUND: Eggs are a rich source of nutrients important for brain development, including choline, riboflavin, vitamins B-6 and B-12, folate, zinc, protein, and DHA. OBJECTIVE: Our objective was to evaluate the effect of the consumption of 1 egg per day over a 6-mo period on child development. METHODS: In the Mazira Project randomized controlled trial, 660 children aged 6-9 mo were randomly allocated into an intervention or control group. Eggs were provided to intervention households during twice-weekly home visits for 6 mo. Control households were visited at the same frequency. At enrollment, blinded assessors administered the Malawi Developmental Assessment Tool (MDAT), and 2 eye-tracking tasks using a Tobii-Pro X2-60 eye tracker: a visual paired comparison memory task and an Infant Orienting with Attention task. At endline, 6-mo later, blinded assessors administered the MDAT and eye-tracking tasks plus an additional elicited imitation memory task. RESULTS: At endline, intervention and control groups did not significantly differ in any developmental score, with the exception that a smaller percentage of children were delayed in fine motor development in the intervention group (10.6%) compared with the control group (16.5%; prevalence ratio: 0.59, 95% CI: 0.38-0.91). Among 10 prespecified effect modifiers for the 8 primary developmental outcomes, we found 7 significant interactions demonstrating a consistent pattern that children who were less vulnerable, for example, those with higher household wealth and maternal education, showed positive effects of the intervention. Given multiple hypothesis testing, some findings may have been due to chance. CONCLUSION: The provision of 1 egg per day had no overall effect on child development in this population of children, however, some benefits may be seen among children in less vulnerable circumstances. This trial was registered at clinicaltrials.gov as NCT03385252.