Multiple Micronutrient Interventions Research Articles

2015 The Challenges of Scaling Up Multiple Micronutrient Interventions

With eight hundred million still living in extreme poverty and hunger, the Millennium Development Goals (MDGs) were created with a vision of a world with less poverty, hunger and disease; improved survival prospects for mothers and children; greater primary education; equal opportunities and empowerment for women; and a healthier environment. While several countries have progressed towards achieving the MDGs, many interventions have nonetheless failed to improve the quality of life in a large number of the world’s countries (Figure 1). To be sure, despite enormous in-country and international efforts to achieve the first MDG of ending extreme poverty and hunger, an estimated 800 million people still face these challenges daily. One in seven children under the age of fi ve years is still underweight (i.e., they weigh less than 2 standard deviations of the population average for their age and sex), and one in four children worldwide, or approximately 161 million children, are still stunted (i.e., they are below 2 standard deviations in height for age and sex).

Perspective from 2021 The Challenges of Sustaining Multiple Micronutrient Interventions

In our original article in 2015, we focused on the process of scaling up micronutrient powders (MNPs). We defined scaling as a four-stage process that included: research and discovery; setting up a supply (value) chain; developing business models for implementation; and finally scaling up (original Figure 3). We defined scaling as the intentional process of taking an intervention that has been successful in one context, and expanding or replicating the relevant policies, programs, or projects to other locations so that the intervention can benefit more people in an equitable and sustainable way.

The Effects of Nutritional Interventions on the Cognitive Development of Preschool-Age Children: A Systematic Review.

The developing human brain requires all essential nutrients to form and to maintain its structure. Infant and child cognitive development is dependent on adequate nutrition. Children who do not receive sufficient nutrition are at high risk of exhibiting impaired cognitive skills. This systematic review aimed to examine the effects of nutritional interventions on cognitive outcomes of preschool-age children. PubMed, PsycInfo, Academic Search Complete, and Cochrane Library electronic databases were searched to identify Randomized Controlled Trials (RCTs) published after the year 2000. Studies assessing the effects of food-based, single, and multiple micronutrient interventions on the cognition of nourished and undernourished children aged 2–6 years were deemed eligible. A total of 12 trials were identified. Eight out of the twelve studies found significant positive effects on cognitive outcomes. Iron and multiple-micronutrients supplementation yield improvements in the cognitive abilities of undernourished preschool-age children. Increased fish consumption was found to have a beneficial effect in the cognitive outcomes of nourished children. On the other hand, B-vitamin, iodized salt, and guava powder interventions failed to display significant results. Findings of this review highlight the importance of adequate nutrition during preschool years, and the crucial role sufficient nutrition plays in cognitive development.

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

RationaleBrain 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. MethodsWe 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). ResultsThree 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. ConclusionsOur 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.

Myo-Inositol, Probiotics, and Micronutrient Supplementation From Preconception for Glycemia in Pregnancy: NiPPeR International Multicenter Double-Blind Randomized Controlled Trial.

OBJECTIVEBetter preconception metabolic and nutritional health are hypothesized to promote gestational normoglycemia and reduce preterm birth, but evidence supporting improved outcomes with nutritional supplementation starting preconception is limited.RESEARCH DESIGN AND METHODSThis double-blind randomized controlled trial recruited from the community 1,729 U.K., Singapore, and New Zealand women aged 18–38 years planning conception. We investigated whether a nutritional formulation containing myo-inositol, probiotics, and multiple micronutrients (intervention), compared with a standard micronutrient supplement (control), taken preconception and throughout pregnancy could improve pregnancy outcomes. The primary outcome was combined fasting, 1-h, and 2-h postload glycemia (28 weeks gestation oral glucose tolerance test).RESULTSBetween 2015 and 2017, participants were randomized to control (n = 859) or intervention (n = 870); 585 conceived within 1 year and completed the primary outcome (295 intervention, 290 control). In an intention-to-treat analysis adjusting for site, ethnicity, and preconception glycemia with prespecified P < 0.017 for multiplicity, there were no differences in gestational fasting, 1-h, and 2-h glycemia between groups (β [95% CI] loge mmol/L intervention vs. control −0.004 [−0.018 to 0.011], 0.025 [−0.014 to 0.064], 0.040 [0.004–0.077], respectively). Between the intervention and control groups there were no significant differences in gestational diabetes mellitus (24.8% vs. 22.6%, adjusted risk ratio [aRR] 1.22 [0.92–1.62]), birth weight (adjusted β = 0.05 kg [−0.03 to 0.13]), or gestational age at birth (mean 39.3 vs. 39.2 weeks, adjusted β = 0.20 [−0.06 to 0.46]), but there were fewer preterm births (5.8% vs. 9.2%, aRR 0.43 [0.22–0.82]), adjusting for prespecified covariates.CONCLUSIONSSupplementation with myo-inositol, probiotics, and micronutrients preconception and in pregnancy did not lower gestational glycemia but did reduce preterm birth.

Using formative research to design context-specific animal source food and multiple micronutrient powder interventions to improve the consumption of micronutrients by infants and young children in Tanzania, Kenya, Bangladesh and Pakistan.

Optimal complementary feeding practices including consumption of multiple micronutrient powders (MNP) are recommended to improve micronutrient intake by infants and young children (IYC) 6–23 months. Formative research was used to design the behaviour change strategy to improve IYC micronutrient intake for the multicountry ENRICH project in rural impoverished areas of Tanzania, Kenya, Bangladesh and Pakistan. Employing a qualitative approach with multiple methods and guided by a social ecological framework, the study was conducted in several phases: data collection in the community, household and health facilities, initial analysis and household trials (HHT). Results found limited use of animal source foods (ASF) for feeding IYC and MNP largely unavailable. Although cost constrained access to ASF, potential more affordable context‐specific ASF options were identified in each setting. Caregivers associated ASF with many positive attributes for IYC, but barriers to feeding them included lack of caregiver time and knowledge of specific preparation techniques, and limited advice from health workers. Feeding practices were identified that used time‐efficient, specific preparations for eggs and other ASF, and demonstrated good initial acceptability and feasibility during HHT. Testing MNP in HHT found good initial feasibility and acceptability and provided an understanding of the facilitators and constraints for preparing, feeding and promoting MNP. In conclusion, formative research led to the design of context‐specific ASF and MNP complementary feeding promotion strategies to improve IYC consumption of micronutrients by identifying the practices, benefits, motivations and alternative actions to overcome the barriers in each setting.

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.

Maternal Multiple Micronutrient Supplementation Stabilizes Mitochondrial DNA Copy Number in Pregnant Women in Lombok, Indonesia

ABSTRACTBackgroundThe Supplementation with Multiple Micronutrients Intervention Trial (SUMMIT) in Lombok, Indonesia showed that maternal multiple micronutrients (MMN), as compared with iron and folic acid (IFA), reduced fetal loss, early infant mortality, and low birth weight. Mitochondria play a key role during pregnancy by providing maternal metabolic energy for fetal development, but the effects of maternal supplementation during pregnancy on mitochondria are not fully understood.ObjectiveThe aim of this study was to assess the impact of MMN supplementation on maternal mitochondrial DNA copy number (mtDNA-CN).MethodsWe used archived venous blood specimens from pregnant women enrolled in the SUMMIT study. SUMMIT was a cluster-randomized double-blind controlled trial in which midwives were randomly assigned to distribute MMN or IFA to pregnant women. In this study, we selected 108 sets of paired baseline and postsupplementation samples (MMN = 54 and IFA = 54). Maternal mtDNA-CN was determined by real-time quantitative polymerase chain reaction in baseline and postsupplementation specimens. The association between supplementation type and change in mtDNA-CN was performed using rank-based estimation for linear models.ResultsIn both groups, maternal mtDNA-CN at postsupplementation was significantly elevated compared with baseline (P < 0.001). The regression revealed that the MMN group had lower postsupplementation mtDNA-CN than the IFA group (β = −4.63, P = 0.003), especially for women with mtDNA-CN levels above the median at baseline (β = −7.49, P = 0.007). This effect was rapid, and observed within 33 d of initiation of supplementation (β = −7.39, P = 0.017).ConclusionMaternal MMN supplementation rapidly stabilized mtDNA-CN in pregnant women who participated in SUMMIT, indicating improved mitochondrial efficiency. The data provide a mechanistic basis for the beneficial effects of MMN on fetal growth and survival, and support the transition from routine IFA to MMN supplementation.This trial was registered at www.isrctn.com as ISRCTN34151616.

Associations of Nutritional and Social Exposures in Utero, Early, and Later Childhood with Cognitive, Motor, and Social-Emotional Development in Indonesia (OR10-03-19)

ObjectivesTo determine the association of biomedical and socio-environmental risk factors during pregnancy, early, and later childhood with cognitive (IQ), motor, social-emotional (SE), and executive function (EF) at age 3.5 and 9–12 y in Indonesia. MethodsChildren born to pregnant women enrolled in the Supplementation with Multiple Micronutrients Intervention Trial (SUMMIT) in 2001–2004 participated in follow-up studies at age 3.5 y in 2006 and 9–12 y in 2013. We assessed 359 children at both time points for outcomes of IQ, motor, SE and EF. We also assessed predictors of outcomes including biomedical risks (small for gestational age at birth: SGA; height-for-age z-score: HAZ; and child hemoglobin: Hb) and socio-environmental risks (HOME Inventory; maternal depression: MD). We calculated the residuals of earlier risks predicting the later scores, e.g., the residual of SGA at birth predicting HAZ at 3.5 y (rHAZ1), representing the deviation of HAZ at 3.5 y from the child’s expected HAZ based on SGA. In Model 1, we entered SGA, representing in utero exposures. In Model 2, we added indicators at 3.5 y (rHAZ1, Hb, HOME, MD). In Model 3, we added indicators at 9–12 y (rHAZ2, rHb, rHOME, rMD) and the corresponding 3.5 y IQ, motor, SE, or EF scores. ResultsThe coefficients for outcomes at early and later time points (Figure 1) show that SGA was not associated with any scores. Early (3.5 y) childhood rHAZ1 was associated with early IQ, motor, and EF, but was not independently associated with later (9–12 y) IQ, motor, or EF. Later childhood rHAZ2 was not associated with any scores. Early childhood HOME was independently associated with both early and later IQ, motor, and EF, while later childhood rHOME was not associated with any scores. Early Hb was not associated with any scores and later rHb was associated with motor scores only. MD during early childhood and rMD during later childhood were independently associated with later childhood SE. ConclusionsThese findings support the importance of early and continual intervention throughout childhood to support healthy growth and even more importantly maternal mental health and nurturing home environments. This is essential for longer-term IQ, motor, SE, and EF. Funding SourcesGrand Challenges Canada, Allen & Turner Foundations, UNICEF, Centre for Health and Human Development, USAID-Indonesia, USDA NIFA #CA-D-NTR-2493-H. Supporting Tables, Images and/or Graphs▪

Increased mitochondrial DNA copy number in maternal peripheral blood is associated with low birth weight in Lombok, Indonesia

Fetal development depends on maternal metabolic energy from mitochondria. We investigated the association of maternal mitochondrial function, represented by mitochondrial DNA copy number (mtDNA-CN) of venous blood, with child birth weight (BW) from 528 randomly selected mothers enrolled in the Supplementation with Multiple Micronutrients Intervention Trial (ISRCTN 34151616). Real-time quantitative PCR of archived blood specimens and regression analysis adjusting for other primary determinants of BW showed that loge mtDNA-CN was inversely associated with BW (β = −204.6, p < 0.001), particularly in the third trimester (β = −376.8, p<0.001). Maternal mtDNA-CN may be a marker for low BW and fetal growth restriction.

Cost-effectiveness of prenatal food and micronutrient interventions on under-five mortality and stunting: Analysis of data from the MINIMat randomized trial, Bangladesh.

IntroductionNutrition interventions may have favourable as well as unfavourable effects. The Maternal and Infant Nutrition Interventions in Matlab (MINIMat), with early prenatal food and micronutrient supplementation, reduced infant mortality and were reported to be very cost-effective. However, the multiple micronutrients (MMS) supplement was associated with an increased risk of stunted growth in infancy and early childhood. This unfavourable outcome was not included in the previous cost-effectiveness analysis. The aim of this study is to evaluate whether the MINIMat interventions remain cost-effective in view of both favourable (decreased under-five-years mortality) and unfavourable (increased stunting) outcomes.MethodPregnant women in rural Bangladesh, where food insecurity still is prevalent, were randomized to early (E) or usual (U) invitation to be given food supplementation and daily doses of 30 mg, or 60 mg iron with 400 μg of folic acid, or MMS with 15 micronutrients including 30 mg iron and 400 μg of folic acid. E reduced stunting at 4.5 years compared with U, MMS increased stunting at 4.5 years compared with Fe60, while the combination EMMS reduced infant mortality compared with UFe60. The outcome measure used was disability adjusted life years (DALYs), a measure of overall disease burden that combines years of life lost due to premature mortality (under five-year mortality) and years lived with disability (stunting). Incremental cost effectiveness ratios were calculated using cost data from already published studies.ResultsBy incrementing UFe60 (standard practice) to EMMS, one DALY could be averted at a cost of US$24.ConclusionWhen both favourable and unfavourable outcomes were included in the analysis, early prenatal food and multiple micronutrient interventions remained highly cost effective and seem to be meaningful from a public health perspective.

Multiple-micronutrient supplementation: Evidence from large-scale prenatal programmes on coverage, compliance and impact.

Micronutrient deficiencies during pregnancy pose important challenges for public‐health, given the potential adverse outcomes not only during pregnancy but across the life‐course. Provision of iron‐folic acid (IFA) supplements is the strategy most commonly practiced and recommended globally. How to successfully implement IFA and multiple micronutrient supplementation interventions among pregnant women and to achieve sustainable/permanent solutions to prenatal micronutrient deficiencies remain unresolved issues in many countries. This paper aims to analyse available experiences of prenatal IFA and multiple micronutrient interventions to distil learning for their effective planning and large‐scale implementation. Relevant articles and programme‐documentation were comprehensively identified from electronic databases, websites of major‐agencies and through hand‐searching of relevant documents. Retrieved documents were screened and potentially relevant reports were critically examined by the authors with the aim of identifying a set of case studies reflecting regional variation, a mix of implementation successes and failures, and a mix of programmes and large‐scale experimental studies. Information on implementation, coverage, compliance, and impact was extracted from reports of large‐scale interventions in Central America, Southeast Asia, South Asia, and Sub‐Saharan Africa. The WHO/CDC Logic‐Model for Micronutrient Interventions in Public Health was used as an organizing framework for analysing and presenting the evidence. Our findings suggest that to successfully implement supplementation interventions and achieve sustainable‐permanent solutions efforts must focus on factors and processes related to quality, cost‐effectiveness, coverage, utilization, demand, outcomes, impacts, and sustainability of programmes including strategic analysis, management, collaborations to pilot a project, and careful monitoring, midcourse corrections, supervision and logistical‐support to gradually scaling it up.

Prenatal food and micronutrient interventions in rural Bangladesh remain cost‐effective when assessing both favorable and unfavorable outcomes: Cost‐effectiveness analysis of the MINIMat trial on under five‐mortality and stunting.

BackgroundFew studies analyze the cost‐effectiveness of nutrition interventions in low‐income countries, possibly deterring large‐scale implementation. Nutrition interventions may have favorable as well as unfavorable effects. The Maternal and Infant Nutrition Interventions in Matlab (MINIMat) with early prenatal food and micronutrient supplementation reduced infant mortality and were reported to be very cost‐effective. However, the multiple micronutrients (MMS) resulted in an increased risk of stunted growth in infancy and early childhood. This unfavorable outcome was not included in the previous cost‐effectiveness analysis. The aim of this study is to evaluate whether the MINIMat interventions remain cost‐effective in view of both favorable (decreased under‐five year mortality) and unfavorable (increased stunting) outcomes.MethodPregnant women in rural Bangladesh, where food insecurity still is prevalent, were randomized to early (E) or usual (U) invitation to food supplementation and daily doses of 30 mg, or 60 mg iron with 400 μgm of folic acid, or MMS with 15 micronutrients including 30 mg iron and 400 μgm of folic acid. E reduced stunting at 4.5 years compared with U, MMS compared with Fe60 increased stunting at 4.5 years while the combination EMMS reduced infant mortality compared with UFe60. The outcome measure used was disability adjusted life years (DALY), a measure of overall disease burden that combines years of life lost due to premature mortality (under five‐year mortality) and years lived with disability (stunting). Incremental cost effectiveness ratios were calculated using cost data from already published studies.ResultsBy incrementing UFe60F to EMMS, one DALY could be averted at a cost of US$26.ConclusionWhen both favorable and unfavorable outcomes were included in the analysis early prenatal food and multiple micronutrient interventions remained highly cost effective and seem to be meaningful from a public health perspective.

Maternal multiple micronutrient supplementation and other biomedical and socioenvironmental influences on children's cognition at age 9-12 years in Indonesia: follow-up of the SUMMIT randomised trial.

Brain and cognitive development during the first 1000 days from conception are affected by multiple biomedical and socioenvironmental determinants including nutrition, health, nurturing, and stimulation. An improved understanding of the long-term influence of these factors is needed to prioritise public health investments to optimise human development. We did a follow-up study of the Supplementation with Multiple Micronutrients Intervention Trial (SUMMIT), a double-blind, cluster-randomised trial of maternal supplementation with multiple micronutrients (MMN) or iron and folic acid (IFA) in Indonesia. Of 27 356 live infants from birth to 3 months of age in 2001-04, we re-enrolled 19 274 (70%) children at age 9-12 years, and randomly selected 2879 from the 18 230 who were attending school at a known location. Of these, 574 children were oversampled from mothers who were anaemic or malnourished at SUMMIT enrolment. We assessed the effects of MMN and associations of biomedical (ie, maternal and child anthropometry and haemoglobin and preterm birth) and socioenvironmental determinants (ie, parental education, socioeconomic status, home environment, and maternal depression) on general intellectual ability, declarative memory, procedural memory, executive function, academic achievement, fine motor dexterity, and socioemotional health. The SUMMIT trial was registered, number ISRCTN34151616. Children of mothers given MMN had a mean score of 0·11 SD (95% CI 0·01-0·20, p=0·0319) higher in procedural memory than those given IFA, equivalent to the increase in scores with half a year of schooling. Children of anaemic mothers in the MMN group scored 0·18 SD (0·06-0·31, p=0·0047) higher in general intellectual ability, similar to the increase with 1 year of schooling. Overall, 18 of 21 tests showed a positive coefficient of MMN versus IFA (p=0·0431) with effect sizes from 0·00-0·18 SD. In multiple regression models, socioenvironmental determinants had coefficients of 0·00-0·43 SD and 22 of 35 tests were significant at the 95% CI level, whereas biomedical coefficients were 0·00-0·10 SD and eight of 56 tests were significant, indicating larger and more consistent impact of socioenvironmental factors (p<0·0001). Maternal MMN had long-term benefits for child cognitive development at 9-12 years of age, thereby supporting its role in early childhood development, and policy change toward MMN. The stronger association of socioenvironmental determinants with improved cognition suggests present reproductive, maternal, neonatal, and child health programmes focused on biomedical determinants might not sufficiently enhance child cognition, and that programmes addressing socioenvironmental determinants are essential to achieve thriving populations. Grand Challenges Canada Saving Brains Program.

Feeding the brain – The effects of micronutrient interventions on cognitive performance among school-aged children: A systematic review of randomized controlled trials

Micronutrients are essential for brain development with deficiencies in specific nutrients linked to impaired cognitive function. Interventions are shown to be beneficial to children's mental development, particularly in subjects who were micronutrient-deficient at baseline but results on healthy subjects remain inconsistent. This systematic review evaluated the effect of micronutrient inventions on different cognitive domains. Studies conducted in both developing and developed countries, and trials that investigate the effect of both single and multiple micronutrient intervention were reviewed. Systematic searches of Medline, CINAHL Plus and Academic Search database were undertaken to identify trials published after year 2000. Randomized controlled trials (RCTs) that evaluate the effect of micronutrients on cognitive performance or academic performance among children aged 4-18 years were included. 19 trials were identified from 18 articles. The major cognitive outcomes assessed included fluid intelligence, crystallized intelligence, short-term memory, long-term memory, cognitive processing speed, attention and concentration, and school performance. Eight of ten trials assessing fluid intelligence reported significant positive effects of micronutrient supplementation among micronutrient-deficient children, especially those who were iron-deficient or iodine-deficient at baseline. The effects of micronutrient interventions on other domains were inconsistent. Improvement in fluid intelligence among micronutrient-deficient children was consistently reported. Further research is needed to provide more definite evidence on the beneficial effects of micronutrient inventions on other cognitive domains and the effects in healthy subjects.

The Relative Association of Bio‐Medical and Socio‐Environmental Risk Factors with School‐Age Child Cognition in Indonesia

Child cognitive, motor, and socio‐emotional development is affected by multiple bio‐medical and socio‐environmental factors. A better understanding of the influence and interplay of these factors is needed to inform the strategic design and integration of child development programs with existing reproductive, maternal, neonatal and child health (RMNCH) programs.We assessed the cognitive, motor, and socio‐emotional function of 2879 9–12‐year‐old children whose mothers had participated in the Supplementation with Multiple Micronutrients Intervention Trial (SUMMIT). In multiple regression models, we assessed the relative effect size of seven bio‐medical risk factors and five socio‐environmental risk factors on each of seven cognitive, motor, and socio‐emotional scores. Six factors were measured before birth, two at birth, and four at school‐age follow‐up.The socio‐environmental factors showed stronger and more consistent associations with school‐age cognitive, motor, and socio‐emotional scores, as compared to the bio‐medical factors. Pre‐term birth, born small for gestation age, maternal anemia, and low maternal mid‐upper arm circumference and height during pregnancy were not significantly associated with any score. Child anemia at follow‐up was significantly associated with fine motor dexterity only. Children whose mothers received multiple micronutrient supplements during pregnancy and postpartum scored higher in procedural memory only. Post‐natal growth in height was significantly associated with general intellectual ability and academic achievement. In contrast, each of the socio‐environmental factors was significantly associated with three to five of the seven scores. Children in low SES households scored significantly lower in general intellectual ability, declarative memory, executive function, academic achievement, and fine motor dexterity. Both maternal and paternal education were associated with general intellectual ability, executive function, and academic achievement, while maternal education was also associated with declarative memory and fine motor dexterity. Nurturing and stimulation from the environment (HOME Inventory score) was significantly associated with general intellectual ability, declarative memory, executive function, academic achievement, and fine motor dexterity. Maternal depression was strongly associated with child socio‐emotional development, and was the only significant predictor of this score. Children of depressed mothers also scored lower in declarative memory.In order to achieve thriving populations, coverage of existing RMNCH interventions to prevent these bio‐medical conditions needs to be improved. Even with improved coverage of existing interventions, additional interventions addressing socio‐environmental risk factors are also needed.Support or Funding InformationFunded by Grand Challenges Canada Saving Brains

The Challenges of Scaling Up Multiple Micronutrient Interventions

The Challenges of Scaling Up Multiple Micronutrient Interventions

Multiple Micronutrients And Early Learning Interventions Promote Infant Micronutrient Status And Development

BackgroundMalnutrition and lack of early learning (EL) opportunities are major causes for children not reaching their developmental potential. &#x0D;ObjectiveTo evaluate the impact of multiple micronutrient powder (MNP) and EL intervention on infants' micronutrient status and development.&#x0D;Methods497 infants (6‐12 mos) were enrolled from 26 villages in rural India and randomized using a 2X2 design to receive MNP (iron, zinc, vitamins A,B2,B12, C and folic acid ) vs. placebo (B2) and EL vs. control. The EL intervention was based on the UNICEF‐developed Care for Child Development and delivered through biweekly home visits. Baseline, post‐intervention (6 mos) and follow‐up (12 mos) evaluations included 2ml venous blood and Mullens Scales of Early Learning. Data were analyzed using 2‐way ANOVA, adjusting for baseline, with MNP X EL interactions to assess intervention synergy. &#x0D;ResultsNo baseline differences (66% anemic (Hb&lt;11 g/dL), 31% inadequate iron stores (ferritin&gt;12 µg/L), 20% stunted (HAZ&lt;‐2), 19% underweight (WAZ&lt;‐2). At follow‐up, the prevalence of micronutrient (MN) deficiencies was significantly lower in the MNP group. Significant interactions in motor and language performance showed that children who received either or both interventions had better scores than children who received neither. Table 1. Percent MN Deficiencies at Follow‐Up * p &amp;lt; .05 MNP Placebo Infant % % Hemoglobin (&amp;lt; 11g/dL) * 50.2 74.2 Ferritin (&amp;lt;12 ug/L) * 32.6 81.6 Transferrin receptor (&amp;gt; 2mg/L) * 44.1 81.7 Vitamin B12 (&amp;lt;200p/mL) * 2.6 9.1 Zinc (&amp;lt;65 ug/dL) 2.1 1.8 Table 2. MNP x EL Interaction at Post Intervention: Mean (SE) * p&amp;lt;.05 MNP Placebo EL Control EL Control Gross Motor 50.2 (1.0) 51.8 (1.0) 51.7 (1.0) 48.7 (1.0) * Language 38.9 (0.6) 39.3 (0.6) 40.3 (0.6) 48.1 (0.6) * ConclusionHome MNP and EL can improve infant MN status and development.

Effect of Maternal Multiple Micronutrients Supplementation on the Apgar Score of Indonesian Neonates

IntroductionMaternal multiple micronutrients (MMN) supplementation as compared to iron‐folic acid (IFA) can increase birth weight and decrease infant mortality, but the physiological basis remains unclear. We examined Apgar scores to assess the impact of MMN on the dynamic process of neonatal adaptation after birth.MethodsWe selected 3667 singleton live births from the Supplementation with Multiple Micronutrients Intervention Trial (SUMMIT) of maternal MMN versus IFA (ISRCTN34151616) with Apgar scores at the 1st and 5th minute, after excluding those with midline anomaly, inborn diseases and if not a spontaneous vaginal birth. Mixed effect multiple linear regression models were used to adjust for clustered randomization, covariates and interactions.ResultsOverall, there were no significant differences between Apgar scores of children from the MMN and IFA groups at the 1st (adjusted β ‐0.416, 95% CI ‐0.339‐0.047) or 5th minute (adjusted β 0.077, 95% CI ‐0.097‐0.252), or changes from 1 to 5 minutes (adjusted β 0.003, 95% CI ‐0.065‐0.072), nor were there effects on specific component scores. In subgroup analysis, MMN decreased the 1st minute score for full term and small for gestational (SGA) neonates, and MMN increased improvement from 1 to 5minutes in full term and SGA neonates, and those born of well‐nourished mothers (upper arm circumference &gt; 23.5 cm).DiscussionWe observed certain subgroups of neonates of mothers given MMN tended toward lower 1st minute Apgar scores and greater improvement of Apgar scores from the 1st to 5th minute. MMN supplementation may enhance the dynamic adaptive processes of certain neonates after delivery, thereby improving infant survival.

The long term impact of maternal multiple micronutrient supplementation, infant nutrition and health on visual acuity of 9‐12 year old children in Indonesia

The impact of the prenatal nutrition and neonatal health on visual acuity (VA) remains unknown. We investigated the long term relative impact of maternal multiple micronutrient (MMN) versus iron‐folic acid (IFA) supplementation on VA of 9‐12 years old school children, and explored the long term effects of birth weight, preterm birth, and stunting on VA. We assessed VA of 3,398 children of mothers who had participated in the Supplementation with Multiple Micronutrients Intervention Trial (SUMMIT), a cluster‐randomized trial of MMN versus IFA in Indonesia. Multivariate logistic regression was used to assess whether of MMN, child age, gender, socio‐economic status (SES), preterm birth, birth weight or stunting were related to VA. There was no siginificant long term impact of maternal MMN supplementation on VA in school age children. We found significant effects of birth weight on VA of the left eye (p=0.03) and left eye with pinhole assessments (p=0.01), and effects of stunting on VA of the left eye (p=0.04) and for both eyes (p=0.04), and of SES on VA for the right eye (p=0.04). No significant effects were observed for preterm birth, age and gender. There were no siginificant effects of maternal MMN and IFA supplementation on VA in 9‐12 years old school children, but there were significant effects of birth weight, stunting and SES on VA.