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Background: Undernutrition during pregnancy increases the risk of giving birth to a small vulnerable newborn. Small-quantity lipid-based nutrient supplements (SQ-LNSs) contain both macro- and micronutrients and can help prevent multiple nutritional deficiencies., Objectives: We examined the effects of SQ-LNSs provided during pregnancy compared with 1) iron and folic acid or standard of care (IFA/SOC) or 2) multiple micronutrient supplements (MMSs) and identified characteristics that modified the estimates of effects of SQ-LNSs on birth outcomes., Methods: We conducted a 2-stage meta-analysis of individual participant data from 4 randomized controlled trials of SQ-LNSs provided during pregnancy (n = 5273). We generated study-specific and subgroup estimates of SQ-LNS compared with IFA/SOC or MMS and pooled the estimates. In sensitivity analyses, we examined whether the results differed depending on methods for gestational age dating, birth anthropometry, or study design., Results: SQ-LNSs (compared with IFA/SOC) increased birth weight [mean difference: +49 g; 95% confidence interval (CI): 26, 71 g] and all birth anthropometric z-scores (+0.10-0.13 standard deviation); they reduced risk of low birth weight by 11%, newborn stunting by 17%, newborn wasting by 11%, and small head size by 15%. Only 2 trials compared SQ-LNSs and MMSs; P values for birth outcomes were >0.10 except for head circumference (e.g., z-score for gestational age: +0.11; 95% CI: -0.01, 0.23). Effect estimates for SQ-LNSs compared with IFA/SOC were greater among female infants and, for certain outcomes, among mothers with body mass index <20 kg/m 2 , inflammation, malaria, or household food insecurity. Effect estimates for SQ-LNSs compared with MMSs were greater for certain outcomes among female infants, first-born infants, and mothers <25 y., Conclusions: SQ-LNSs had positive impacts on multiple outcomes compared to IFA/SOC, but further research directly comparing SQ-LNSs and MMSs is needed. Targeting SQ-LNSs to vulnerable subgroups may be worth considering., Clinical Trial Registry: This study was registered at PROSPERO as CRD42021283391., Competing Interests: Conflict of interest N.F.K. is on the Editorial Board of the American Journal of Clinical Nutrition and played no role in the Journal’s evaluation of the manuscript., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Little is known about costs and cost effectiveness of interventions that integrate wasting prevention into screening for child wasting., Objectives: This study's objective was to estimate the cost and cost-effectiveness of an intervention that integrated behavior change communication (BCC) and small-quantity lipid-based nutrient supplements (SQ-LNS) into platforms for wasting screening in Burkina Faso (a facility-based platform, where BCC was enhanced compared with standard care) and Mali (a community-based platform, with standard BCC)., Methods: Activity-based costing was used to estimate the cost per child-contact for the intervention and the comparison group, which did not receive the intervention. Costs were ascertained from accounting records, interviews, surveys, and observations. The number of child-contacts was calculated using population size estimates and average attendance rates for each service. Costs per disability-adjusted life year (DALY) averted were estimated using a Markov model populated with data from the parent trials on impact of wasting incidence and treatment coverage., Results: In the intervention group in Burkina Faso, the cost per child-contact of facility-based screening was $0.85 of enhanced BCC was $4.28, and of SQ-LNS was $8.86. In Mali, the cost per child-contact of community-based screening was $0.57, standard BCC was $0.72, and SQ-LNS was $4.14. Although no SQ-LNS costs were incurred in the comparison groups (hence lower total costs), costs per child-contact for screening and BCC were higher because coverage of these services was lower. The intervention package cost $1073 per DALY averted in Burkina Faso and $747 in Mali., Conclusions: Integration of wasting prevention into screening for child wasting led to higher total costs but lower unit costs than standard screening due to increased coverage. Greater cost-effectiveness could be achieved if BCC were strengthened and led to improved caregiver health and nutrition practices and if screening triggered appropriate use of services and higher treatment coverage., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Although there is growing global momentum behind food systems strategies to improve planetary and human health-including nutrition-there is limited evidence of what types of food systems interventions work. Evaluating these types of interventions is challenging due to their complex and dynamic nature and lack of fit with standard evaluation methods. In this article, we draw on a portfolio of 6 evaluations of food systems interventions in Africa and South Asia that were intended to improve nutrition. We identify key methodological challenges and formulate recommendations to improve the quality of such studies. We highlight 5 challenges: a lack of evidence base to justify the intervention, the dynamic and multifaceted nature of the interventions, addressing attribution, collecting or accessing accurate and timely data, and defining and measuring appropriate outcomes. In addition to more specific guidance, we identify 6 cross-cutting recommendations, including a need to use multiple and diverse methods and flexible designs. We also note that these evaluation challenges present opportunities to develop new methods and highlight several specific needs in this space., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The coronavirus disease 2019 (COVID-19) pandemic has had large negative effects on countries' economies and individual well-being throughout the world, particularly in low- and middle-income countries. Pandemic-related changes in behavior and government restrictions in Kenya may have negatively affected food supply chains and household food access; however, the empirical evidence is currently limited., Objectives: The study explored changes in informal milk markets, dairy consumption, and food insecurity among low-income households in urban and periurban Nairobi, Kenya, following the start of the COVID-19 pandemic in the country., Methods: Baseline data on milk sales and consumption were collected in late 2019 from dairy vendors operating in the informal sector and their dairy customers. We conducted 2 longitudinal telephone surveys with the same study participants in July and September-October 2020, respectively., Results: At the first follow-up, the volume of milk sold by informal vendors had dropped by 30% compared with their baseline level, and the volume of milk from informal markets consumed by households decreased by 23%. By the second follow-up, the volume of milk sold and consumed had recovered somewhat but remained lower than the volume observed 1 y prior in the same season. Large reductions in the consumption of other animal-sourced products were also observed. The rate of food insecurity increased by 16 and 11 percentage points in the first and second follow-up periods, respectively, compared with baseline., Conclusions: The evidence, therefore, suggests that the timing of the pandemic and the related restrictions were associated with a decrease in the supply and consumption of milk from informal markets in Nairobi and a decrease in the food security of periurban consumers., (© 2023 The Author(s).)

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., (Copyright © 2022 American Society for Nutrition.)

Researchers conducting randomised controlled trials (RCTs) of complex interventions face design and analytical challenges that are not fully addressed in existing guidelines. Further guidance is needed to help ensure that these trials of complex interventions are conducted to the highest scientific standards while maximising the evidence that can be extracted from each trial. The key challenge is how to manage the multiplicity of outcomes required for the trial while minimising false positive and false negative findings. To address this challenge, we formulate three principles to conduct RCTs: (1) outcomes chosen should be driven by the intent and programme theory of the intervention and should thus be linked to testable hypotheses; (2) outcomes should be adequately powered and (3) researchers must be explicit and fully transparent about all outcomes and hypotheses before the trial is started and when the results are reported. Multiplicity in trials of complex interventions should be managed through careful planning and interpretation rather than through post hoc analytical adjustment. For trials of complex interventions, the distinction between primary and secondary outcomes as defined in current guidelines does not adequately protect against false positive and negative findings. Primary outcomes should be defined as outcomes that are relevant based on the intervention intent and programme theory, declared (ie, registered), and adequately powered. The possibility of confirmatory causal inference is limited to these outcomes. All other outcomes (either undeclared and/or inadequately powered) are secondary and inference relative to these outcomes will be exploratory., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: Poor birth outcomes are an important global public health problem. Social assistance programs that provide cash or in-kind transfers, such as food or vouchers, hold potential to improve birth outcomes but the evidence on their effectiveness has not been reviewed., Objectives: We systematically reviewed studies that used experimental or quasi-experimental methods to evaluate the impacts of social assistance programs on outcomes in low- and middle-income countries., Methods: The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system was used to assess the certainty of the evidence for birth weight and neonatal mortality (most common outcomes reported). We summarized the evidence on hypothesized nutrition and health pathways of impact., Results: We included 6 evaluations of 4 different cash transfer programs and 1 evaluation of a community-based participatory learning and action program that provided food and cash transfers. The 4 studies that assessed birth weight impacts found significant (P < 0.05) effects ranging from 31 to 578 g. Out of 3 studies that assessed neonatal mortality impacts, 2 found significant effects ranging from 0.6 to 3.1 deaths/1000 live births. The certainty of the evidence for both outcomes was rated as very low due to several methodological limitations. In terms of potential pathways, some studies documented positive effects on maternal diet, antenatal care (ANC) utilization, and delivery in a health facility., Conclusions: Better-designed evaluations are needed to strengthen the evidence base on these programs. Evaluation studies should elucidate underlying mechanisms of impact by including outcomes related to maternal diet, ANC seeking, use of skilled delivery, and women's empowerment in nutrition and health domains. Studies should also assess potential unintended negative consequences of social assistance, such as reduced birth spacing and excess pregnancy weight gain., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

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 Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

The Brazilian government's decision to open the Amazon biome to sugarcane expansion reignited EU concerns regarding the sustainability of Brazil's sugar sector, hindering the ratification of the EU-Mercosur trade agreement. Meanwhile, in the EU, certain conventional biofuels face stricter controls, whilst uncertainty surrounding the commercialisation of more sustainable advanced-biofuels renders bioethanol as a short- to medium-term fix. This paper examines Brazil's land-use changes and associated greenhouse gas emissions arising from an EU driven ethanol import policy and projections for other 13 biocommodities. Results suggest that Brazil's sugarcane could satisfy growing ethanol demand and comply with EU environmental criteria, since almost all sugarcane expansion is expected to occur on long-established pasturelands in the South and Midwest. However, expansion of sugarcane is also driven by competition for viable lands with other relevant commodities, mainly soy and beef. As a result, deforestation trends in the Amazon and Cerrado biomes linked to soy and beef production could jeopardize Brazil's contribution to the Paris agreement with an additional 1 ± 0.3 billion CO 2 eq tonnes above its First NDC target by 2030. Trade talks with a narrow focus on a single commodity could thus risk unsustainable outcomes, calling for systemic sustainability benchmarks, should the deal be ratified.

It has been suggested that rainfall in the Amazon decreases if forest loss exceeds some threshold, but the specific value of this threshold remains uncertain. Here, we investigate the relationship between historical deforestation and rainfall at different geographical scales across the Southern Brazilian Amazon (SBA). We also assess impacts of deforestation policy scenarios on the region's agriculture. Forest loss of up to 55-60% within 28 km grid cells enhances rainfall, but further deforestation reduces rainfall precipitously. This threshold is lower at larger scales (45-50% at 56 km and 25-30% at 112 km grid cells), while rainfall decreases linearly within 224 km grid cells. Widespread deforestation results in a hydrological and economic negative-sum game, because lower rainfall and agricultural productivity at larger scales outdo local gains. Under a weak governance scenario, SBA may lose 56% of its forests by 2050. Reducing deforestation prevents agricultural losses in SBA up to US$ 1 billion annually.

Background: Little is known about the impact of food-assisted maternal and child health programs (FA-MCHN) on child wasting., Objectives: We assessed the impact of Tubaramure, a FA-MCHN program in Burundi, on child (0 to 24 months) wasting and the differential impacts by socio-economic characteristics and age. The program targeted women and their children during the first 1000 days and included 1) food rations, 2) strengthening and promotion of use of health services, and 3) behavior change communication (BCC)., Methods: We conducted a 4-arm, cluster-randomized, controlled trial (2010-2012). Clusters were defined as "collines" (communities). Impact was estimated using repeated cross-sectional data (n = ∼2620 children in each round). Treatment arms received household and individual (mother or child in the first 1000 days) food rations (corn-soy blend and micronutrient-fortified vegetable oil) from pregnancy to 24 months (T24 arm), from pregnancy to 18 months (T18), or from birth to 24 months (TNFP). All beneficiaries received the same BCC for the first 1000 days. The control arm received no rations or BCC., Results: Wasting (weight-for-length Z-score <2 SD) increased from baseline to follow-up in the control group (from 6.5% to 8%), but Tubaramure had a significant (P < 0.05) protective effect on wasting [treatment arms combined, -3.3 percentage points (pp); T18, -4.5 pp] and on the weight-for-length z-score (treatment arms combined, +0.15; T24, +0.20; T18, +0.17). The effects were limited to children whose mother and household head had no education, and who lived in the poorest households. The largest effect was found in children 6 to 12 months of age: the group with the highest wasting prevalence., Conclusions: FA-MCHN programs in highly food-insecure regions can protect the most disadvantaged children from wasting. These findings are particularly relevant in the context of the economic crisis due to the coronavirus disease 2019 pandemic, which is expected to dramatically increase child wasting., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Child acute malnutrition (AM) is an important cause of child mortality. Accurately estimating its burden requires cumulative incidence data from longitudinal studies, which are rarely available in low-income settings. In the absence of such data, the AM burden is approximated using prevalence estimates from cross-sectional surveys and the incidence correction factor $K$, obtained from the few available cohorts that measured AM. We estimated $K$ factors for severe acute malnutrition (SAM) and moderate acute malnutrition (MAM) from AM incidence and prevalence using representative cross-sectional baseline and longitudinal data from 2 cluster-randomized controlled trials (Innovative Approaches for the Prevention of Childhood Malnutrition-PROMIS) conducted between 2014 and 2017 in Burkina Faso and Mali. We compared K estimates using complete (weight-for-length z score, mid-upper arm circumference (MUAC), and edema) and partial (MUAC, edema) definitions of SAM and MAM. $K$ estimates for SAM were 9.4 and 5.7 in Burkina Faso and in Mali, respectively; K estimates for MAM were 4.7 in Burkina Faso and 5.1 in Mali. The MUAC and edema-based definition of AM did not lead to different $K$ estimates. Our results suggest that $K$ can be reliably estimated when only MUAC and edema-based data are available. Additional studies, however, are required to confirm this finding in different settings., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Recovery from nutritionally induced height deficits continues to garner attention. The current literature on catch-up growth, however, has 2 important limitations: wide-ranging definitions of catch-up growth are used, and it remains unclear whether children can recover from the broader consequences of undernutrition. We addressed these shortcomings by reviewing the literature on the criteria for catch-up in linear growth and on the potential to recover from undernutrition early in life in 3 domains: linear growth, developmental epigenetics, and child brain and neurocognitive development. Four criteria must be met to demonstrate catch-up growth in height: after a period in which a growth-inhibiting condition (criterion 1) causes a reduction in linear growth velocity (criterion 2), alleviation of the inhibiting condition (criterion 3) leads to higher-than-normal velocity (criterion 4). Accordingly, studies that are observational, do not use absolute height, or have no alleviation of an inhibiting condition cannot be used to establish catch-up growth. Adoption and foster care, which provide dramatic improvements in children's living conditions not typically attained in nutrition interventions, led to some (but incomplete) recovery in linear growth and brain and neurocognitive development. Maternal nutrition around the time of conception was shown to have long-term (potentially permanent) effects on DNA methylation in the offspring. Undernourishment early in life may thus have profound irreversible effects. Scientific, program, and policy efforts should focus on preventing maternal and child undernutrition rather than on correcting its consequences or attempting to prove they can be corrected., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

Background: Food-assisted maternal and child health and nutrition programs are a widely used approach to address undernutrition. Little is known about the effects of these programs' combined household and individual food rations on household and individual food consumption. Tubaramure in Burundi targeted women and children during the first 1000 d of life, and included: 1) food rations (corn-soy blend and micronutrient-fortified vegetable oil); 2) health services strengthening and promotion of their use; and 3) behavior change communication on nutrition, hygiene, and health practices., Objectives: The objectives were: 1) to assess Tubaramure's impact on household food consumption and food security, maternal dietary diversity, and infant and young child feeding practices; 2) to explore the role of the food rations; and 3) assess 6-8 mo impacts around 8 mo after the end of the program., Methods: We used a 4-arm cluster-randomized controlled repeated cross-sectional design (11,906 observations). The treatment arms received the same food ration but differed in the ration timing and duration: 1) the first 1000 d; 2) from pregnancy through 17.9 mo of age; or 3) from birth through 23.9 mo of age., Results: Tubaramure significantly (P < 0.05) improved the percentage of food secure households [from 4.5 to 7.3 percentage points (pp)], and increased household energy consumption (from 17% to 20%) and micronutrient consumption. The program had a positive effect on maternal dietary diversity (+0.4 food groups, P < 0.05) and increased the proportion of children aged 6-23.9 mo consuming ≥4 food groups (from 8.0 to 9.6 pp, P < 0.05). The effects on many outcomes were attributable to the food rations. Postprogram effects (P < 0.05) were found on household food security, maternal dietary diversity, and younger sibling's complementary feeding practices., Conclusions: Programs such as Tubaramure have the potential to improve food security and household and individual energy and micronutrient consumption in severely resource-constrained populations, as seen in rural Burundi. This trial was registered at clinicaltrials.gov as NCT01072279., (Copyright © The Author(s) 2019.)

Development is a multi-faceted process; achieving development goals thus requires a multi-sectoral approach. For over two decades, our research group of economists and nutritionists has designed and implemented randomized trials to assess the effectiveness of multisectoral programs in improving nutrition, food security, and other measures of well-being, largely at the request of developing country governments, development partners, and non-governmental organizations. Our approach addresses three perceived pitfalls of RCTs: the "black box" nature of RCTs, limited external validity, and challenges in translation of results to impacts at scale. We address these concerns by identifying and assessing programmatic pathways to impact with quantitative and qualitative methods; studying similar programs implemented by different organizations across various settings; and working closely with implementing partners in the design, research, and dissemination processes to inform adaptation and scale-up of programs and policies., (© 2019 The Authors.)

Evidence on the cost-effectiveness of multisectoral maternal and child health and nutrition programmes is scarce. We conducted a prospective costing study of two food-assisted maternal and child health and nutrition programmes targeted to pregnant women and children during the first 1,000 days (pregnancy to 2 years). Each was paired with a cluster-randomized controlled trial to evaluate impact and compare the optimal quantity and composition of food rations (Guatemala, five treatment arms) and their optimal timing and duration (Burundi, three treatment arms). We calculated the total and per beneficiary cost, conducted cost consequence analyses, and estimated the cost savings from extending the programme for 2 years. In Guatemala, the programme model with the lowest cost per percentage point reduction in stunting provided the full-size family ration with an individual ration of corn-soy blend or micronutrient powder. Reducing family ration size lowered costs but failed to reduce stunting. In Burundi, providing food assistance for the full 1,000 days led to the lowest cost per percentage point reduction in stunting. Reducing the duration of ration eligibility reduced per beneficiary costs but was less effective. A 2-year extension could have saved 11% per beneficiary in Guatemala and 18% in Burundi. We found that investments in multisectoral nutrition programmes do not scale linearly. Programmes providing smaller rations or rations for shorter durations, although less expensive per beneficiary, may not provide the necessary dose to improve (biological) outcomes. Lastly, delivering effective programmes for longer periods can generate cost savings by dispersing start-up costs and lengthening peak operating capacity., (© 2019 The Authors Maternal & Child Nutrition Published by John Wiley & Sons Ltd.)

Strain gage sensors have been used to evaluate the local behavior of structures; however, there are limited studies for its application in bridge dynamic feature identification. In this study, fiber Bragg grating strain gages were installed on the lower chord members of a bridge, and dynamic features were identified successfully using strain gage readings when vehicles passed over the bridge. The results were also verified using a finite element model. The innovation presented in this article is the use of fiber Bragg grating strain gage readings to identify the dynamic features of a long-span, steel-girder bridge. To clarify the effect of truck dynamic load, the load spectrum of the truck is characterized. This article introduces a new method for identifying the dynamic parameters of bridges.

Background: Food-assisted maternal and child health and nutrition (FA-MCHN) programs are widely used to reduce household food insecurity and maternal and child undernutrition in low- and middle-income countries. These programs, however, may unintentionally lead to excessive energy intake and unhealthy weight gain, especially in food-secure populations., Objective: We evaluated the impact of an FA-MCHN program implemented in Guatemala on maternal weight from pregnancy to 24 mo postpartum. The program was earlier shown to reduce stunting., Methods: We used a longitudinal, cluster-randomized controlled trial with arms varying in family ration size [full (FFR), reduced (RFR), none (NFR)] and individual maternal ration type [corn-soy blend (CSB), lipid-based nutrient supplement (LNS), micronutrient powder (MNP)]: A: FFR + CSB; B: RFR + CSB; C: NFR + CSB; D: FFR + LNS; E: FFR + MNP; F: control. Weight was measured during pregnancy and at 1, 4, 6, 9, 12, 18, and 24 mo postpartum. We used linear mixed models controlling for pregnancy weight with random cluster and mother effects. Data on 3535 women were analyzed., Results: Significant (P < 0.05) or marginally significant (P < 0.10) effects of 0.50-0.65 kg were found at all time points (except 9 mo) in arm A. Similar-sized effects were found in arms B (1, 4, 6, and 12 mo) and C (1 and 12 mo). Marginally significant effects (0.51-0.66 kg) were found in arm D (1, 6, 9, and 12 mo); in arm E, marginally significant effects (0.48-0.75 kg) were found from 6 to 24 mo., Conclusions: The effect on maternal postpartum weight is of concern because of the high existing prevalence of overweight. Programs need to include "double-duty" objectives and actions, to ensure that addressing child undernutrition does not exacerbate the problem of unhealthy weight gain. This trial was registered at clinicaltrials.gov as NCT01072279., (Copyright © American Society for Nutrition 2019.)

Background: Child development is affected by multiple factors throughout pregnancy and childhood. Multisectoral programs addressing these factors may improve children's development., Objective: We evaluated the impact of a food-assisted multisectoral nutrition program (Tubaramure) on children's (4-41.9 mo) motor and language development. Tubaramure was targeted to Burundian women and children in the first 1000 d and provided micronutrient-fortified food rations; nutrition, health, and hygiene behavior change communication; and health system-strengthening activities., Methods: Program impact was assessed using a cluster-randomized controlled trial with repeated cross-sections: 2010 (baseline, children 4-41.9 mo), 2012 (follow-up during implementation, children 4-23.9 mo), and 2014 (follow-up postimplementation, children 24-41.9 mo). Sixty villages were randomly assigned to 4 groups with varying timing and duration of food rations: pregnancy-24 mo; pregnancy-18 mo; 0-24 mo; and control, no direct Tubaramure benefits. Treatment groups were pooled and compared with control using difference-in-difference estimates. We examined impact pathways by assessing program impacts on intermediary variables and their associations with development outcomes., Results: At first follow-up, Tubaramure positively affected language (0.4 milestones, P < 0.05) but not motor development among children aged 4-23.9 mo. Among the 12-23.9 mo age subgroup, the program positively affected language (0.7 milestones, P < 0.01) and motor (0.6 milestones, P = 0.08) development. At second follow-up, among children aged 24-41.9 mo, Tubaramure marginally affected motor development (0.4 milestones, P = 0.09). In age subgroup analyses, program impacts were limited to children aged 24-29.9 mo [0.4 motor (P = 0.09) and 1.0 language (P < 0.01) milestones]. Pathway analyses revealed significant positive impacts on diet, health, and nutritional indicators of children aged 12-23.9 mo and health and nutritional indicators of children aged 24-29.9 mo, supporting the plausibility of program impacts on child development., Conclusions: Tubaramure had small positive impacts on children's motor and language development through multiple pathways, demonstrating the role multisectoral nutrition programs can play in improving children's development. This trial was registered at clinicaltrials.gov as NCT01072279., (Copyright © American Society for Nutrition 2019.)

Background: Community management of acute malnutrition (CMAM) is a highly efficacious approach for treating acute malnutrition (AM) in children who would otherwise be at significantly increased risk of mortality. In program settings, however, CMAM's effectiveness is limited because of low screening coverage of AM, in part because of the lack of perceived benefits for caregivers. In Burkina Faso, monthly screening for AM of children <2 years of age is conducted during well-baby consultations (consultation du nourrisson sain [CNS]) at health centers. We hypothesized that the integration of a preventive package including age-appropriate behavior change communication (BCC) on nutrition, health, and hygiene practices and a monthly supply of small-quantity lipid-based nutrient supplements (SQ-LNSs) to the monthly screening would increase AM screening and treatment coverage and decrease the incidence and prevalence of AM., Methods and Findings: We used a cluster-randomized controlled trial and allocated 16 health centers to the intervention group and 16 to a comparison group. Both groups had access to standard CMAM and CNS services; caregivers in the intervention group also received age-appropriate monthly BCC and SQ-LNS for children >6 months of age. We used two study designs: (1) a repeated cross-sectional study of children 0-17 months old (n = 2,318 and 2,317 at baseline and endline 2 years later) to assess impacts on AM screening coverage, treatment coverage, and prevalence; (2) a longitudinal study of 2,113 children enrolled soon after birth and followed up monthly for 18 months to assess impacts on AM screening coverage, treatment coverage, and incidence. Data were analyzed as intent to treat. Level of significance for primary outcomes was α = 0.016 after adjustment for multiple testing. Children's average age was 8.8 ± 4.9 months in the intervention group and 8.9 ± 5.0 months in the comparison group at baseline and, respectively, 0.66 ± 0.32 and 0.67 ± 0.33 months at enrollment in the longitudinal study. Relative to the comparison group, the intervention group had significantly higher monthly AM screening coverage (cross-sectional study: +18 percentage points [pp], 95% CI 10-26, P < 0.001; longitudinal study: +23 pp, 95% CI 17-29, P < 0.001). There were no impacts on either AM treatment coverage (cross-sectional study: +8.0 pp, 95% CI 0.09-16, P = 0.047; longitudinal study: +7.7 pp, 95% CI -1.2 to 17, P = 0.090), AM incidence (longitudinal study: incidence rate ratio = 0.98, 95% CI 0.75-1.3, P = 0.88), or AM prevalence (cross-sectional study: -0.46 pp, 95% CI -4.4 to 3.5, P = 0.82). A study limitation is the referral of AM cases (for ethical reasons) by study enumerators as part of the monthly measurement in the longitudinal study that may have attenuated the detectable impact on AM treatment coverage., Conclusions: Adding a preventive package to CMAM delivered at health facilities in Burkina Faso increased participation in monthly AM screening, thus overcoming a major impediment to CMAM effectiveness. The lack of impact on AM treatment coverage and on AM prevalence and incidence calls for research to address the remaining barriers to uptake of preventive and treatment services at the health center and to identify and test complementary approaches to bring integrated preventive and CMAM services closer to the community while ensuring high-quality implementation and service delivery., Trial Registration: ClinicalTrials.gov NCT02245152., Competing Interests: The authors have declared that no competing interests exist.

Background: Community-based management of acute malnutrition (CMAM) has been widely adopted to treat childhood acute malnutrition (AM), but its effectiveness in program settings is often limited by implementation constraints, low screening coverage, and poor treatment uptake and adherence. This study addresses the problem of low screening coverage by testing the impact of distributing small-quantity lipid-based nutrient supplements (SQ-LNSs) at monthly screenings held by community health volunteers (CHVs). Screening sessions included behavior change communication (BCC) on nutrition, health, and hygiene practices (both study arms) and SQ-LNSs (one study arm). Impact was assessed on AM screening and treatment coverage and on AM incidence and prevalence., Methods and Findings: A two-arm cluster-randomized controlled trial in 48 health center catchment areas in the Bla and San health districts in Mali was conducted from February 2015 to April 2017. In both arms, CHVs led monthly AM screenings in children 6-23 months of age and provided BCC to caregivers. The intervention arm also received a monthly supply of SQ-LNSs to stimulate caregivers' participation and supplement children's diet. We used two study designs: i) a repeated cross-sectional study (n = approximately 2,300) with baseline and endline surveys to examine impacts on AM screening and treatment coverage and prevalence (primary study outcomes) and ii) a longitudinal study of children enrolled at 6 months of age (n = 1,132) and followed monthly for 18 months to assess impact on AM screening and treatment coverage and incidence (primary study outcomes). All analyses were done by intent to treat. The intervention significantly increased AM screening coverage (cross-sectional study: +40 percentage points [pp], 95% confidence interval [CI]: 32, 49, p < 0.001; longitudinal study: +28 pp, 95% CI: 23, 33, p < 0.001). No impact on treatment coverage or AM prevalence was found. Children in the intervention arm, however, were 29% (95% CI: 8, 46; p = 0.017) less likely to develop a first AM episode (incidence) and, compared to children in comparison arm, their overall risk of AM (longitudinal prevalence) was 30% (95% CI: 12, 44; p = 0.002) lower. The intervention lowered CMAM enrollment by 10 pp (95% CI: 1.9, 18; p = 0.016), an unintended negative impact likely due to CHVs handing out preventive SQ-LNSs to caregivers of AM children instead of referring them to the CMAM program. Study limitations were i) the referral of AM cases by our research team (for ethical reasons) during monthly measurements in the longitudinal study might have interfered with usual CMAM activities and ii) the outcomes presented by child age also reflect seasonal variations because of the closed cohort design., Conclusions: Incorporating SQ-LNSs into monthly community-level AM screenings and BCC sessions was highly effective at improving screening coverage and reducing AM incidence, but it did not improve AM prevalence or treatment coverage. Future evaluation and implementation research on CMAM should carefully assess and tackle the remaining barriers that prevent AM cases from being correctly diagnosed, referred, and adequately treated., Trial Registration: ClinicalTrials.gov NCT02323815., Competing Interests: All authors have declared that no competing interests exist.

Linear growth is increasingly used as the sole or primary outcome for evaluating interventions, but impact is often not seen. Sometimes there is interest in whether children catch up to where they otherwise would have been had detrimental conditions not occurred, but the literature is confusing because of claims for evidence of catch-up growth based on inappropriate methods. This article examines the use of linear growth measures to evaluate intervention impact and catch-up. Focus on linear growth as a measure of impact has resulted in a lack of demonstrable intervention effects, evaluations that do not use measures responsive to nutrition-sensitive and integrated interventions, insufficient emphasis on adolescent girls and women before conception and children after the first 1000 d, and insufficient investment in developing other measures. Nutrition interventions may benefit children but may not discernibly affect linear growth deficits in immediate or intermediate periods. Interventions intended to affect one domain may have positive or negative impacts on others. Child nutrition and growth are part of early childhood development; the focus should be on improving conditions in which children grow and develop throughout childhood and adolescence because poor conditions in a population affect all children. To assess the impact of nutrition interventions, it is important to use a broad set of measures and indicators of outcomes and immediate and underlying determinants. The 4 criteria for demonstrating catch-up in growth, which are much more stringent than those for demonstrating intervention impact, require demonstration of the following: 1) an inhibiting condition and 2) reduced velocity during 1 period, 3) followed by alleviation of or compensation for the inhibiting condition, and 4) higher-than-normal velocity during a subsequent period. Partial catch-up growth is sometimes possible when constraints are removed, but whether it is beneficial to the child is not clear. Research is needed to develop, refine, and validate measures and indicators for the purposes intended., (Copyright © American Society for Nutrition 2019.)

The past decade has seen an unprecedented increase in attention to undernutrition, and drastically reducing child stunting has become a global development objective. The strong focus on linear growth retardation and stunting has enabled successful advocacy for nutrition, but with this focus has come some confusion and misunderstanding about the meaning of linear growth retardation and stunting among researchers, donors, and agencies active in nutrition. Motivated by the belief that a sharp focus will further accelerate progress in reducing undernutrition, we critically reviewed the evidence. The global attention to stunting is based on the premise that any intervention aimed at improving linear growth will subsequently lead to improvements in the correlates of linear growth retardation and stunting. Current evidence and understanding of mechanisms does not support this causal thinking, with 2 exceptions: linear growth retardation is a cause of difficult births and poor birth outcomes. Linear growth retardation is associated with (but does not cause) delayed child development, reduced earnings in adulthood, and chronic diseases. We thus propose distinguishing 2 distinctly different meanings of linear growth retardation and stunting. First, the association between linear growth retardation (or stunting) and other outcomes makes it a useful marker. Second, the causal links with difficult births and poor birth outcomes make linear growth retardation and stunting outcomes of intrinsic value. In many cases a focus on linear growth retardation and stunting is not necessary to improve the well-being of children; in many other cases, it is not sufficient to reach that goal; and for some outcomes, promoting linear growth is not the most cost-efficient strategy. We appeal to donors, program planners, and researchers to be specific in selecting nutrition outcomes and to target those outcomes directly., (© 2019 American Society for Nutrition.)

Introduction: Observational studies have documented an association between aflatoxin (AF) exposure and reduced linear growth in infants and young children. Our objective was to assess the effectiveness of reducing AF exposure on child linear growth and serum AF levels in rural areas in Eastern Kenya., Methods: A cluster randomised controlled design was used (28 intervention and 28 control clusters). The intervention arm received a swapping (contaminated maize was replaced with safe maize) and a stockist intervention (households were encouraged to purchase from a stockist supplied with clean maize). Women in the fifth to final month of pregnancy were invited to enrol in the study. Outcomes were child length-for-age Z-score (LAZ), the prevalence of stunting and child serum AFB 1 -lysine adduct level 24 (endline, primary outcomes) and 11 to 19 months (midline, secondary outcomes) after trial commencement, respectively. The trial was registered with socialscienceregistry.org., Results: Of the 1230 unborn children enrolled in the study, 881 (72%) were included in the LAZ and 798 (65%) in the serum AFB 1 analysis. The intervention significantly reduced endline ln serum AFB 1 -lysine adduct levels (intervention effect-0.273, 95% CI -0.547 to 0.001; one-sided p=0.025), but had no effect on endline LAZ or stunting (mean LAZ at endline was -1.64). At midline, the intervention increased LAZ by 0.16 (95% CI -0.009 to 0.33; one-sided p=0.032) and reduced stunting by seven percentage points (95% CI -0.125 to -0.007; one-sided p=0.015), but had no impact on serum AFB 1 levels., Conclusion: Improving access to AF-free maize substantially reduced endline serum AF, but had no effect on child linear growth. The midline analysis suggests that AF may affect linear growth at younger ages., Trial Registration Number: AEARCTR-0000105., Competing Interests: Competing interests: None declared.

Aflatoxins are a group of naturally occurring mycotoxins, which can lead to death and are a known cause of hepatocellular carcinoma. AF exposure has been hypothesised to lead to stunted growth in children, but separating the AF effect from other determinants of linear growth retardation is difficult. The study used secondary data from an efficacy trial conducted in young children in southern Mexico to test the comparative efficacy of a milk-based multiple micronutrient-fortified food, a multiple micronutrient syrup, or a multiple micronutrient powder. The effect of serum AFB 1 -lysine adduct level on incremental growth was tested using a longitudinal mixed model, controlling for key individual, maternal, and household-level covariates. AFB 1 -lysine adduct was detectable in all but 2 of the 347 children in the study (median exposure: 0.82 pg/mg albumin). AF exposure was associated (p < .05) with greater linear growth: an increase equivalent to the sample interquartile range (~0.5 pg AFB 1 -lysine/mg albumin) was associated (p < .05) with an increase in the child's height-for-age deficit of 1.5 to 2.0 mm in the 4 months from baseline (average age 8 months) to follow-up (average age 12 months); the magnitude of the difference in the 10-month follow-up was smaller and not statistically significant. This study documents that low-dose AF exposure was associated with greater child linear growth. Given its toxicity and carcinogenicity, our results do not change the urgent need to drastically reduce human AF exposure. Our findings show that the association between AF exposure and linear growth is more complex than previously thought., (© 2018 John Wiley & Sons Ltd.)

Background: Food-assisted maternal and child health and nutrition (FA-MCHN) programs are widely used to address undernutrition, but little is known about their effectiveness in improving child linear growth., Objective: We assessed the impact of Burundi's Tubaramure FA-MCHN program on linear growth. The program targeted women and their children during the first 1000 d and included 1) food rations, 2) strengthening of health services and promotion of their use, and 3) behavior change communication (BCC). A second objective was to assess the differential effect when varying the timing and duration of receiving food rations., Methods: We used a 4-arm, cluster-randomized controlled study to assess program impact with the use of cluster fixed-effects double-difference models with repeated cross-sectional data (baseline and follow-up 4 y later with ∼3550 children in each round). Treatment arms received food rations (corn-soy blend and micronutrient-fortified vegetable oil) for the first 1000 d (T24), from pregnancy through the child reaching 18 mo (T18), or from birth through the child reaching 24 mo ["no food during pregnancy" (TNFP)]. All treatment arms received BCC for the first 1000 d. The control arm received no food rations or BCC., Results: Stunting (height-for-age z score <2 SDs) increased markedly from baseline to follow-up, but Tubaramure had a significant (P < 0.05) beneficial effect in the T24 [7.4 percentage points (pp); P < 0.05], T18 (5.7 pp; P < 0.05), and TNFP (4.6; P = 0.09) arms; the differences in effect across arms were not significant (P > 0.01). Secondary analyses showed that the effect was limited to children whose mother and head of household had some primary education and who lived in households with above-median assets., Conclusions: FA-MCHN programs are an effective development tool to improve child linear growth and can protect children from political and economic shocks in vulnerable countries such as Burundi. A better understanding of how to improve the nutritional status of children in the worst-off households is needed. This trial was registered at www.clinicaltrials.gov as NCT01072279.

Evidence on the nutritional status and diets of adolescents in low- and middle-income countries is scant. We characterized the nutritional status (body mass index Z-scores (BMIZs)) and nutrient intakes of adolescent boys and girls in rural areas in Bangladesh using the 2011-2012 BIHS data, used regression models to identify the socioeconomic determinants of these outcomes, and household fixed effects models to assess whether the gap between boys and girls changed with women's education and empowerment and household wealth. The adolescents' BMIZ and adequacy of their nutrient intakes were suboptimal. Gender differences varied by outcome and were not systematically in favor of boys. Household wealth was associated with higher BMIZ and probability of adequate energy and micronutrient intakes. Women's education and empowerment were mostly not associated with the study outcomes and did not modify gender differences. There is an urgent need to invest in improving the diets of adolescent boys and girls in Bangladesh. The limited role of women's education and empowerment in improving adolescent nutrition suggests that resources may be too constrained. It may also reflect deeply rooted beliefs about adolescent nutrition and differences between boys and girls that would need to be addressed to improve their nutrition., (© 2018 New York Academy of Sciences.)

Evidence on the impact of weather shocks on child nutrition focuses on linear growth retardation (stunting) and thus, associates the effect of a short-term measure (weather events) on a cumulative measure (attained height). Relatively little is known on how weather shocks predict increases in wasting in a population. This study explores whether deviation in rainfall in Ethiopia, a drought prone country, is a sensitive indicator of future increases in wasting. Around 12% of children 0-23 months were wasted, but we found no consistent association between the rainfall shock variables and child weight-for-height Z-scores. The results indicate that monitoring rainfall does not provide a practical early warning to use for scaling up financing and management of preventative measures without additional information to increase precision.

In the present study, we investigate the concept of the targeted delivery of pharmaceutical drug aerosols in an anatomically realistic geometry of the human upper and central respiratory system. The geometry considered extends from the mouth inlet to the eighth generation of the bronchial bifurcations and is identical to the phantom model used in the experimental studies of Banko et al. (2015 Exp. Fluids 56 , 1-12 (doi:10.1007/s00348-015-1966-y)). In our computer simulations, we combine the transitional Reynolds-averaged Navier-Stokes (RANS) and the wall-resolved large eddy simulation (LES) methods for the air phase with the Lagrangian approach for the particulate (aerosol) phase. We validated simulations against recently obtained magnetic resonance velocimetry measurements of Banko et al. (2015 Exp. Fluids 56 , 1-12. (doi:10.1007/s00348-015-1966-y)) that provide a full three-dimensional mean velocity field for steady inspiratory conditions. Both approaches produced good agreement with experiments, and the transitional RANS approach is selected for the multiphase simulations of aerosols transport, because of significantly lower computational costs. The local and total deposition efficiency are calculated for different classes of pharmaceutical particles (in the 0.1 μm≤ d p ≤10 μm range) without and with a paramagnetic core (the shell-core particles). For the latter, an external magnetic field is imposed. The source of the imposed magnetic field was placed in the proximity of the first bronchial bifurcation. We demonstrated that both total and local depositions of aerosols at targeted locations can be significantly increased by an applied magnetization force. This finding confirms the possible potential for further advancement of the magnetic drug targeting technique for more efficient treatments for respiratory diseases., Competing Interests: We have no competing interests.

In bridge health monitoring, tiltmeters have been used for measuring rotation and curvature; however, their application in dynamic parameter identification has been lacking. This study installed fiber Bragg grating (FBG) tiltmeters on the bearings of a bridge and monitored the dynamic rotational angle. The dynamic features, including natural frequencies and mode shapes, have been identified successfully. The innovation presented in this paper is the first-time use of FBG tiltmeter readings to identify the natural frequencies of a long-span steel girder bridge. The identified results have been verified using a bridge finite element model. This paper introduces a new method for the dynamic monitoring of a bridge using FBG tiltmeters. Limitations and future research directions are also discussed in the conclusion., Competing Interests: The authors declare no conflict of interest.

Background: Evidence suggests that both preventive and curative nutrition interventions are needed to tackle child acute malnutrition (AM) in developing countries. In addition to reducing the incidence of AM, providing preventive interventions may also help increase attendance (and coverage) of AM screening, a major constraint in the community-based management of child acute malnutrition (CMAM) model. There is a paucity of evidence-based strategies to deliver integrated preventive and curative interventions effectively and affordably at scale. The aim of the Innovative Approaches for the Prevention of Childhood Malnutrition (PROMIS) study is to assess the feasibility, quality of implementation, effectiveness and cost-effectiveness of an integrated child malnutrition prevention and treatment intervention package implemented through a community-based platform in Mali and a facility-based platform in Burkina Faso., Methods/design: The PROMIS intervention entails a comprehensive preventive package offered on a monthly basis to caregivers of children, while children are screened for acute malnutrition (AM). The package consists of behavior change communication on essential nutrition and hygiene actions, and monthly preventive doses of small quantity lipid-based nutrient supplements (SQ-LNS) for children aged 6 to 23.9 months. Positive AM cases are referred to treatment services offered by first-line health services according to the CMAM model. The PROMIS intervention will be evaluated using a mixed methods approach. The impact study encompasses two types of study design: i) repeated cross-sectional surveys conducted at baseline and at endline after 24 months of program implementation and ii) a longitudinal study with a monthly follow-up for 18 months. Primary study impact measures include the incidence and endpoint prevalence of AM, AM screening coverage and treatment compliance. A process evaluation will assess the feasibility and quality of implementation of the intervention guided by country specific program impact pathways (PIPs). Cost-effectiveness analysis will assess the economic feasibility of the intervention., Discussion: The PROMIS study assesses the effectiveness of an innovative model to integrate prevention and treatment interventions for greater and more sustainable impacts on the incidence and prevalence of AM using a rigorous, theory-based randomized control trial approach. This type of programmatic research is urgently needed to help program implementers, policy makers, and investors prioritize, select and scale-up the best program models to prevent and treat AM and achieve the World Health Assembly goal of reducing childhood wasting to less than 5% globally by the year 2025., Trial Registration: Clinicaltrials.gov NCT02323815 (registered on December 18, 2014) and NCT02245152 (registered on September 16, 2014).

Background: Metabolic stress associated with negative energy balance in high producing dairy cattle and obesity in women is a risk factor for decreased fertility. Non-esterified fatty acids (NEFA) are involved in this pathogenesis as they jeopardize oocyte and embryo development. Growing evidence indicates that maternal metabolic disorders can disturb epigenetic programming, such as DNA methylation, in the offspring. Oocyte maturation and early embryo development coincide with methylation changes and both are sensitive to adverse environments. Therefore, we investigated whether elevated NEFA concentrations affect establishment and maintenance of DNA methylation in oocytes and embryos, subsequently altering transcriptomic profiles and developmental competence of resultant blastocysts., Results: Bovine oocytes and embryos were exposed to different NEFA concentrations in separate experiments. In the first experiment, oocytes were matured in vitro for 24 h in medium containing: 1) physiological ("BASAL") concentrations of oleic (OA), palmitic (PA) and stearic (SA) acid or 2) pathophysiological ("HIGH COMBI") concentrations of OA, PA and SA. In the second experiment, zygotes were cultivated in vitro for 6.5 days under BASAL or HIGH COMBI conditions. Developmental competence was evaluated by assessing cleavage and blastocyst rate. Overall gene expression and DNA methylation of resultant blastocysts were analyzed using microarray. DNA methylation data were re-evaluated by pyrosequencing. HIGH COMBI-exposed oocytes and embryos displayed a lower competence to develop into blastocysts compared to BASAL-exposed counterparts (19.3% compared to 23.2% and 18.2% compared to 25.3%, respectively) (P < 0.05). HIGH COMBI-exposed oocytes and embryos resulted in blastocysts with altered DNA methylation and transcriptomic fingerprints, compared to BASAL-exposed counterparts. Differences in gene expression and methylation were more pronounced after exposure during culture compared to maturation suggesting that zygotes are more susceptible to adverse environments. Main gene networks affected were related to lipid and carbohydrate metabolism, cell death, immune response and metabolic disorders., Conclusions: Overall, high variation in methylation between blastocysts made it difficult to draw conclusions concerning methylation of individual genes, although a clear overview of affected pathways was obtained. This may offer clues regarding the high rate of embryonic loss and metabolic diseases during later life observed in offspring from mothers displaying lipolytic disorders.

Background: Food assistance programs may alter food choices, but factors determining households' decisions regarding food acquisition, preparation, and consumption in the context of food aid are not well understood., Objective: This study aimed to understand how the Programa Comunitario Materno Infantil de Diversificación Alimentaria (Mother-Child Community Food Diversification Program; PROCOMIDA), a food-assisted maternal and child health and nutrition program in rural Alta Verapaz, Guatemala, altered household food choices., Methods: We conducted semistructured interviews and focus groups with 63 households in 3 participating (n = 32 households) and 3 control (n = 31) villages. A last-day food recall (without estimating quantities) and food-frequency questionnaire that used food cards assessed dietary choices. Qualitative analysis used thematic a priori and emergent coding; food group consumption frequencies were analyzed by using 2-level, logistic, mixed modeling, and chi-square testing while accounting for community clustering., Results: Compared with control households, PROCOMIDA changed household food choices through a combination of providing food resources (with monthly food rations) and new knowledge and skills related to health and food (in the program's behavior change communication component) while reinforcing existing knowledge and beliefs. PROCOMIDA families consumed rice, red beans, and oil more frequently than did control families (differences of 2.20 (P < 0.001), 2.68 (P < 0.001), and 1.64 (P = 0.038) times/wk, respectively); these foods were in the rations. PROCOMIDA families also ate chicken, local plants, and some vegetables more frequently. The importance of these foods was emphasized in the behavioral change communication component; these foods may have been more accessible because provision of food rations freed resources., Conclusion: Our findings suggest that if a program provides food free of cost to rural indigenous families in the context of a maternal and child nutrition and health program, it may be important to include a well-designed behavioral change communication component to improve household food choices., (© 2016 American Society for Nutrition.)

Background: Despite their popularity, food-assisted maternal and child health and nutrition (MCHN) programs have not been evaluated rigorously, and evidence of their impacts on maternal and child outcomes is scant., Objective: This study estimated the impact of Tubaramure, a food-assisted MCHN program implemented by Catholic Relief Services and partners in eastern Burundi, on hemoglobin and anemia (primary outcome) in children aged 0-23.9 mo and their mothers and explored the impact pathways. The program targeted women and their children during their first 1000 d of life and included 1) food rations, 2) strengthening and promotion of the use of health services, and 3) behavior change communication., Methods: This was a cluster-randomized controlled study to assess program impact by using cluster fixed-effects double-difference models with repeated cross-sectional data (baseline and follow-up 2 y later). We explored impact pathways by estimating impact on intermediary factors addressed by Tubaramure that are known determinants of hemoglobin and anemia and by regressing hemoglobin and anemia on each determinant to assess the plausibility that the effect operated through each determinant., Results: Hemoglobin decreased and anemia increased markedly from baseline to follow-up, but Tubaramure had a significant (P < 0.05) beneficial effect on both children [6.1 percentage points (pps)] and mothers who had given birth in the previous 3 mo (34.9 pps). The program also had significant (P < 0.05) impacts on factors along the hypothesized impact pathways: dietary diversity, consumption of iron-rich foods, morbidity, and fever for child hemoglobin and dietary diversity, consumption of iron-rich foods, and current bed-net use for maternal anemia., Conclusions: We showed, for the first time to our knowledge, that a food-assisted MCHN program had a positive impact on anemia and hemoglobin in both mothers and children. The plausible pathways identified highlight the importance of addressing multiple determinants of anemia. This trial was registered at clinicaltrials.gov as NCT01072279., (© 2016 American Society for Nutrition.)

Objective: Given the public health importance of improving dietary behavior in chronic disease prevention in low- and middle-income countries it is crucial to understand the factors influencing dietary behavior in these settings. This study tested the validity of a conceptual framework linking individual and environmental factors to dietary behavior among Ecuadorian adolescents aged 10-16 years., Methods: A cross-sectional survey was conducted in 784 school-going Ecuadorian adolescents in urban and rural Southern Ecuador. Participants provided data on socio-economic status, anthropometry, dietary behavior and its determining factors. The relationships between individual (perceived benefits and barriers, self-efficacy, habit strength, and a better understanding of healthy food) and environmental factors (physical environment: accessibility to healthy food; social environment: parental permissiveness and school support), and their association with key components of dietary behavior (fruit and vegetables, sugary drinks, breakfast, and unhealthy snack intake) were assessed using structural equation modeling., Results: The conceptual model performed well for each component of eating behavior, indicating acceptable goodness-of-fit for both the measurement and structural models. Models for vegetable intake and unhealthy snacking showed significant and direct effects of individual factors (perceived benefits). For breakfast and sugary drink consumption, there was a direct and positive association with socio-environmental factors (school support and parental permissiveness). Access to healthy food was associated indirectly with all eating behaviors (except for sugary drink intake) and this effect operated through socio-environmental (parental permissiveness and school support) and individual factors (perceived benefits)., Conclusion: Our study demonstrated that key components of adolescents' dietary behaviors are influenced by a complex interplay of individual and environmental factors. The findings indicate that the influence of these factors varied by type of dietary behavior.

Aflatoxins (AFs) are hepatocarcinogenic mycotoxins that can contaminate grains and oil seeds in tropical and sub-tropical areas and have been detected in maize and peanut products of Haiti. The first objective was to assess human exposure to AFs among Haitians at an urban hospital (GHESKIO) and a rural health centre (HCBH). The second objective was to test the association between AF exposure and reported dietary intake of potentially contaminated foods, such as maize, peanut products and milk. Measurement of urinary AFM1 by HPLC revealed that among 367 participants 14% and 22% at GHESKIO and HCBH, respectively, had detectable AFM1. The maximum and median AFM1 concentrations for all detected samples were 700 pg AFM1 ml(-1) and 11.7 pg ml(-1), respectively. Detection of AFM1 was significantly associated with peanut consumption (p < 0.05). Controlling for diet and age group in a logit model, patients who reported peanut consumption the day of the survey and patients from HCBH had greater log odds of excreting detectable AFM1 (p < 0.001 and 0.002, respectively); females had lower log odds (p = 0.020). Recalled frequency of consuming non-dairy animal-sourced foods, an indicator of diet quality, approached significance (p = 0.056) as an inverse predictor of urinary AFM1 detection. The findings augur the need for interventions that will improve food safety in Haiti and limit exposure to AFs, particularly among rural communities.

Background: Since the development of in vitro embryo production in cattle, different supplements have been added to culture media to support embryo development, with serum being the most popular. However, the addition of serum during embryo culture can induce high birthweights and low viability in calves (Large Offspring Syndrome). Analysis of global gene expression in bovine embryos produced under different conditions can provide valuable information to optimize culture media for in vitro embryo production., Results: We used RNA sequencing to examine the effect of in vitro embryo production, in either serum-containing or serum-free media, on the global gene expression pattern of individual bovine blastocysts. Compared to in vivo derived embryos, embryos produced in serum-containing medium had five times more differentially expressed genes than embryos produced in serum-free conditions (1109 vs. 207). Importantly, in vitro production in the presence of serum appeared to have a different impact on the embryos according to their sex, with male embryos having three times more genes differentially expressed than their female counterparts (1283 vs. 456). On the contrary, male and female embryos produced in serum-free conditions showed the same number (191 vs. 192) of genes expressed differentially; however, only 44 of those genes were common in both comparisons. The pathways affected by in vitro production differed depending on the type of supplementation. For example, embryos produced in serum-containing conditions had a lower expression of genes related to metabolism while embryos produced in serum-free conditions showed aberrations in genes involved in lipid metabolism., Conclusions: Serum supplementation had a major impact on the gene expression pattern of embryos, with male embryos being the most affected. The transcriptome of embryos produced in serum-free conditions showed a greater resemblance to that of in vivo derived embryos, although genes involved in lipid metabolism were altered. Male embryos appeared to be most affected by suboptimal in vitro culture, i.e. in the presence of serum.

Background: Notwithstanding the growing concern about the negative impact of aflatoxin (AF) on human health, there is a dearth of evidence on the socio-economic determinants of AF exposure in low and middle income countries., Objectives: We used detailed socio-economic data to quantify to what extent socio-economic characteristics explained differences in serum AFB1-lysine adduct level in adult women from a rural area in Kenya's Eastern Province., Methods: We first explored the relationship between serum aflatoxin level and a number of household, farm, and individual characteristics using cross-sectional data on 884 mothers (pregnant or with a child under 24 months). We then used regression analyses to estimate the extent to which the combined characteristics could predict serum aflatoxin levels. We finally used the estimated regression models to predict changes in AF level when changing a women's characteristics from the most disadvantaged group (setting all socio-economic characteristics to the lowest tertile) to the most advantaged group (highest tertile)., Results: AF was detected in all women. The median level of serum AB1-lysine adduct was 7.47 pg/mg albumin. Higher exposure levels were significantly associated with poverty: predicted serum aflatoxin levels in women living in the worst socio-economic conditions were 4.7-7.1 times higher than those with the best socio-economic status., Conclusions: The results of our study, the first to show the significant association between poverty and aflatoxin exposure, highlight the need to better understand the strategies used by better-off families to mitigate AF exposure., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Evidence from studies conducted in nutritionally deprived children in low- and middle-income countries (LIMC) in past decades showed little or no population-level catch-up in linear growth (mostly defined as reductions in the absolute height deficit) after 2 years of age. Recent studies, however, have reported population-level catch-up growth in children, defined as positive changes in mean height-for-age z-scores (HAZ). The aim of this paper was to assess whether population-level catch-up in linear growth is found when height-for-age difference (HAD: child's height compared to standard, expressed in centimeters) is used instead of HAZ. Our premise is that HAZ is inappropriate to measure changes in linear growth over time because they are constructed using standard deviations from cross-sectional data., Methods: We compare changes in growth in populations of children between 2 and 5 years using HAD vs. HAZ using cross-sectional data from 6 Demographic and Health Surveys (DHS) and longitudinal data from the Young Lives and the Consortium on Health-Orientated Research in Transitional Societies (COHORTS) studies., Results: Using HAD, we find not only an absence of population-level catch-up in linear growth, but a continued deterioration reflected in a decrease in mean HAD between 2 and 5 years; by contrast, HAZ shows either no change (DHS surveys) or an improvement in mean HAZ (some of the longitudinal data). Population-level growth velocity was also lower than expected (based on standards) in all four Young Lives data sets, confirming the absence of catch-up growth in height., Discussion: We show no evidence of population-level catch-up in linear growth in children between 2 to 5 years of age when using HAD (a measure more appropriate than HAZ to document changes as populations of children age), but a continued deterioration reflected in a decrease in mean HAD., Conclusions: The continued widening of the absolute height deficit after 2 years of age does not challenge the critical importance of investing in improving nutrition during the first 1000 days (i.e., from conception to 2 years of age), but raises a number of research questions including how to prevent continued deterioration and what is the potential of children to benefit from nutrition interventions after 2 years of age. Preventing, rather than reversing linear growth retardation remains the priority for reducing the global burden of malnutritionworldwide.

Due to the increased interest in preantral follicular physiology, non-invasive retrieval and morphological classification are crucial. Therefore, this study aimed: (1) to standardize a minimally invasive isolation protocol, applicable to three ruminant species; (2) to morphologically classify preantral follicles upon retrieval; and (3) to describe morphological features of freshly retrieved follicles compared with follicle characteristics using invasive methods. Bovine, caprine and ovine ovarian cortex strips were retrieved from slaughterhouse ovaries and dispersed. This suspension was filtered, centrifuged, re-suspended and transferred to a Petri dish, to which 0.025 mg/ml neutral red (NR) was added to assess the viability of the isolated follicles. Between 59 and 191 follicles per follicle class and per species were collected and classified by light microscopy, based on follicular cell morphology. Subsequently, follicle diameters were measured. The proposed isolation protocol was applicable to all three species and showed a significant, expected increase in diameter with developmental stage. With an average diameter of 37 ± 5 μm for primordial follicles, 47 ± 6.3 μm for primary follicles and 67.1 ± 13.1 μm for secondary follicles, no significant difference in diameter among the three species was observed. Bovine, caprine and ovine follicles (63, 59 and 50% respectively) were graded as viable upon retrieval. Using the same morphological characteristics as determined by invasive techniques [e.g. haematoxylin-eosin (HE) sections], cumulus cell morphology and follicle diameter could be used routinely to classify freshly retrieved follicles. Finally, we applied a mechanical, minimally invasive, follicle isolation protocol and extended it to three ruminant species, yielding viable preantral follicles without compromising further in vitro processing and allowing routine follicle characterization upon retrieval.

Elevated non-esterified fatty acids (NEFAs) have been recognized as an important link between lipolytic metabolic conditions and impaired fertility in high-yielding dairy cows. However, NEFA effects on the oviductal micro-environment currently remain unknown. We hypothesize that elevated NEFAs may contribute to the complex pathology of subfertility by exerting a negative effect on bovine oviductal epithelial cell (BOEC) physiology. Therefore, the objectives of this study were to elucidate direct NEFA effects on BOEC physiology in three different in vitro cell culture systems. Bovine oviductal epithelial cells (four replicates) were mechanically isolated, pooled, and cultured as conventional monolayers, as explants, and in a polarized cell culture system with Dulbecco's modified Eagle's medium/F12-based culture medium. Bovine oviductal epithelial cells were exposed to an NEFA mixture of oleic, stearic, and palmitic acids for 24 hours at both physiological and pathologic concentrations. A control (0 μM NEFA) and a solvent control (0 μM NEFA + 0.45% ethanol) group were implemented. Bovine oviductal epithelial cells physiology was assessed by means of cell number and viability, a sperm binding assay, transepithelial electric resistance (TER), and a wound-healing assay. Bovine oviductal epithelial cell morphology was assessed by scanning electron microscopy on cell polarity, presence of microvilli and cilia, and monolayer integrity. Bovine oviductal epithelial cell number was negatively affected by increasing NEFAs, however, cell viability was not. Sperm binding affinity significantly decreased with increasing NEFAs and tended (P = 0.051) to be more affected by the direction of NEFA exposure in the polarized cell culture system. The absolute TER increase after NEFA exposure in the control (110 ± 11 Ω.cm(2)) was significantly higher than that in all the other treatments and was also different depending on the exposure side. Bidirectional exposed monolayers were even associated with a significant TER reduction (-15 ± 10 Ω.cm(2); P < 0.05). Cell proliferation capacity showed a decreased cell migration with increasing NEFA concentrations but was irrespective of the exposure side. Bovine oviductal epithelial cell morphology was not affected. In conclusion, in an in vitro setting, NEFAs exert a negative effect on BOEC physiology but not morphology. Ultimately, these physiological alterations in its microenvironment may result in suboptimal development of the pre-implantation embryo and a reduced reproductive outcome in dairy cattle., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Recent increases in the number of successful cancer treatments have stimulated interest in fertility preservation strategies in women of reproductive age and in prepubertal girls. However, research on the application of such programs under clinical conditions suffers from the scarce availability of human tissue for research purposes and from concurrent relevant ethical issues. To partly address this problem, this review focuses on the possibilities of ruminant in vitro models providing additional insights into several aspects of fertility preservation, ranging from preantral follicle collection to oocyte and follicle cryopreservation, to noninvasive quality assessment, and to follicle culture. After a brief introduction, we discuss currently available techniques involved in (human) fertility preservation, together with their inherent advantages and limitations. On the basis of literature, we describe specific points for improvement or urgent additional research, such as (1) the lack of noninvasive methods to assess viability and developmental capacity of preantral follicles (either isolated or "in situ"); (2) autotransplantation and cryopreservation of ovarian cortex and follicles; (3) ischemia, follicular burnout, and graft rejection as major causes of preantral follicle loss; and (4) the development of routine in vitro follicle culture methods. Within each section, an overview is given of similar available techniques in (ruminant) assisted reproduction, with suggestions as to where and how these research models might contribute to fill the identified gaps. After the identification of the remaining issues in the development of integrated fertility preservation strategies, available ruminant in vitro models are introduced, described, and matched to these challenges to define common grounds for reproductive research. Ruminant in vitro models are increasingly considered as being very relevant for human preimplantation reproductive research. Because ruminant in vitro models are not hampered by restrictive ethical constraints, they will undoubtedly boost research progress in fertility preservation. At the end of the review, future common research goals are proposed through which human and animal scientists can meet and hasten the development of integrated fertility preservation strategies., (Copyright © 2015 Elsevier Inc. All rights reserved.)

To provide new insights in the molecular mechanism controlling preantral follicular development and to unravel the needs to support in vitro follicular development of early-stage preantral follicles (PAFs), there is a need for alternative in vitro bovine follicle culture methods. In this study, we aimed to characterize follicular dynamics using an IVC system of isolated and individually cultured bovine early PAFs during 10 days to generate individual follicle follow-up data. Preantral follicles (<50 μm) were isolated from slaughterhouse ovaries and cultured individually for 10 days. Individual follicle morphology, growth, survival, quality, and cell proliferation were evaluated in time by combining noninvasive and invasive assessment methods. The PAFs were light microscopically evaluated during culture to assess follicular dynamics, stained with neutral red to determine follicle viability, stained with 4',6-diamidino-2-phenylindole and terminal deoxynucleotidyl transferase dUTP nick end labeling to evaluate cell proliferation and follicle quality, and processed for histologic evaluation to assess follicle morphology. On the basis of their morphology, follicles were subdivided in three categories, with category 1 follicles showing the best morphologic features. On Day 0, only category 1 follicles were selected, but follicle categories were reassigned on evaluation Days 1, 2, 4, 7, or 10. Although 67% of the follicles survived 10 days of IVC, the number of follicles exhibiting a normal morphology decreased significantly from Day 7 onward and the apoptotic index increased significantly from Day 10. Both category 1 and 2 follicles showed a significant increase in follicular diameter (Day 10: 21.80 ± 0.86 and 11.82 ± 0.80, respectively). This increase in follicular diameter showed to be correlated with an increase in the total cell number. In conclusion, this culture system showed to support follicular development until Day 10, although the proportion of follicles showing normal morphologic features and the follicular quality decreased after 10 days of IVC. Follicles maintaining their category 1 morphologic features over time seem to be of a better quality and show a higher developmental competence as compared to category 2 and 3 follicles., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: With food security now a top priority for many governments and for the global development community, there is heightened awareness of the need to improve our understanding and measurement of food security., Objective: To bring clarity in the assessment of the food access dimension of food security at the household and individual level., Methods: For the most commonly used indicators, we reviewed their original purpose and construction, at what levels (household or individual) they were designed to be used, what components (quality, quantity, safety, and cultural acceptability) they were intended to reflect, and whether or not they have been tested for validity and comparability across contexts., Results: We identified nine indicators and grouped them in three broad categories: experience-based, coping strategies, and dietary diversity. The indicators only capture the quantity and quality components of food access; none of the indicators capture information on safety or cultural acceptability of food access. Household Dietary Diversity (HDDS) and Food Consumption Score (FCS) are often considered indicators of both quantity and quality, but they have not been validated for the latter., Conclusions: We recommend the use of experience-based indicators, HDDS, or FCS to assess household access to energy; experience-based indicators to assess household access to diet quality (defined qualitatively as not having to adopt practices that favor acquiring cheaper, less appealing, and less micronutrient-dense foods); and individual dietary diversity scores for women or children to assess individual access to diet quality, defined as micronutrient adequacy., (© The Author(s) 2015.)

Developmental toxicity testing could greatly benefit from the availability of an in vitro alternative model based on the use of animal embryos that have better human-like physiology than the currently-used alternative models. These current models are insufficient, as extrapolation of the results can be challenging. Therefore, an in vitro bovine embryo culture system was used to expose individual morulae to test substances, and to study developmental characteristics up to the blastocyst stage. Cadmium was chosen as the reference toxicant to investigate the sensitivity of the bovine morulae to various concentrations and exposure times. Oocytes from slaughterhouse-obtained bovine ovaries, were maturated, fertilised and cultured up until the morula stage. Morulae were exposed to different cadmium concentrations for 18 or 70 hours, and developmental competence, embryo quality and the expression of cadmium exposure-related genes were evaluated. Cadmium exposure hampered embryonic developmental competence and quality. Compared with the 18-hour exposure, the 70-hour exposure induced a 20-fold higher toxic response with regard to developmental competence and a more 'cadmium-typical' transcript expression. The bovine morula might be a promising tool for toxicity testing as, following exposure, the embryos reacted in a sensitive and 'cadmium-typical' manner to our reference toxicant., (2015 FRAME.)