Modelling stunting in LiST: the effect of applying smoothing to linear growth data

Background: The Lives Saved Tool (LiST) is a widely used resource for evidence-based decision-making regarding health program scale-up in low- and middle-income countries. LiST estimates the impact of specified changes in intervention coverage on mortality and stunting among children under 5 years of age. We aimed to improve the estimates of the parameters in LiST that determine the rate at which the effects of interventions to prevent stunting attenuate as children get older.Methods: We identified datasets with serial measurements of children\u27s lengths or heights and used random effects models and restricted cubic splines to model the growth trajectories of children with at least six serial length/height measurements. We applied WHO growth standards to both measured and modelled (smoothed) lengths/heights to determine children\u27s stunting status at multiple ages (1, 6, 12, 24 months). We then calculated the odds ratios for the association of stunting at one age point with stunting at the next ( stunting-to-stunting ORs ) using both measured and smoothed data points. We ran analyses in LiST to compare the impact on intervention effect attenuation of using smoothed rather than measured stunting-to-stunting ORs.Results: A total of 21,786 children with 178,786 length/height measurements between them contributed to our analysis. The odds of stunting at a given age were strongly related to whether a child is stunted at an earlier age, using both measured and smoothed lengths/heights, although the relationship was stronger for smoothed than measured lengths/heights. Using smoothed lengths/heights, we estimated that children stunted at 1 month have 45 times the odds of being stunted at 6 months, with corresponding odds ratios of 362 for the period 6 to 12 months and 175 for the period 12 to 24 months. Using the odds ratios derived from the smoothed data in LiST resulted in a somewhat slower attenuation of intervention effects over time, but substantial attenuation was still observed in the LiST outputs. For example, in Mali the effect of effectively eliminating SGA births reduced prevalence of stunting at age 59 months from 44.4% to 43.7% when using odds ratios derived from measured lengths/heights and from 44.4% to 41.9% when using odds ratios derived from smoothed lengths/heights.Conclusions: Smoothing of children\u27s measured lengths/heights increased the strength of the association between stunting at a given age and stunting at an earlier age. Using odds ratios based on smoothed lengths/heights in LiST resulted in a small reduction in the attenuation of intervention effects with age and thus some increase in the estimated benefits, and may better reflect the true benefits of early nutritional interventions

Monitoring and evaluation design of Malawi's Right Foods at the Right Time nutrition program

Abstract Child stunting is a public health problem in Malawi. In 2014, the Government of Malawi launched the Right Foods at the Right Time (RFRT) program in Ntchisi district delivering nutrition social and behavior change communication, a small-quantity lipid-based nutrient supplement to children 6–23 months, and nutrition sensitive activities. Monitoring and evaluation (M&E) systems are key aspects of successful program implementation. We describe these and the methodology for an impact evaluation that was conducted for this program. Two monitoring systems using traditional and electronic platforms were established to register and track program delivery and processes including number of eligible beneficiaries, worker performance, program participation, and to monitor input, output, and outcome indicators. The impact evaluation used comparative cross-sectional and longitudinal designs to assess impact on anthropometric and infant and young child feeding outcomes. Three cross-sectional surveys (base-, mid-, and end-line) and two longitudinal cohorts of children followed in 6-month intervals from 6 to 24 months of age, were conducted in sampled households in the program and a neighboring comparison district. Additional M&E included qualitative studies, a process evaluation, and a cost-effectiveness study. The current paper describes lessons from this program's M&E, and demonstrates how multiple implementation research activities can inform course-correction and program scale-up

Modelling stunting in LiST: the effect of applying smoothing to linear growth data.

BACKGROUND: The Lives Saved Tool (LiST) is a widely used resource for evidence-based decision-making regarding health program scale-up in low- and middle-income countries. LiST estimates the impact of specified changes in intervention coverage on mortality and stunting among children under 5 years of age. We aimed to improve the estimates of the parameters in LiST that determine the rate at which the effects of interventions to prevent stunting attenuate as children get older. METHODS: We identified datasets with serial measurements of children's lengths or heights and used random effects models and restricted cubic splines to model the growth trajectories of children with at least six serial length/height measurements. We applied WHO growth standards to both measured and modelled (smoothed) lengths/heights to determine children's stunting status at multiple ages (1, 6, 12, 24 months). We then calculated the odds ratios for the association of stunting at one age point with stunting at the next ("stunting-to-stunting ORs") using both measured and smoothed data points. We ran analyses in LiST to compare the impact on intervention effect attenuation of using smoothed rather than measured stunting-to-stunting ORs. RESULTS: A total of 21,786 children with 178,786 length/height measurements between them contributed to our analysis. The odds of stunting at a given age were strongly related to whether a child is stunted at an earlier age, using both measured and smoothed lengths/heights, although the relationship was stronger for smoothed than measured lengths/heights. Using smoothed lengths/heights, we estimated that children stunted at 1 month have 45 times the odds of being stunted at 6 months, with corresponding odds ratios of 362 for the period 6 to 12 months and 175 for the period 12 to 24 months. Using the odds ratios derived from the smoothed data in LiST resulted in a somewhat slower attenuation of intervention effects over time, but substantial attenuation was still observed in the LiST outputs. For example, in Mali the effect of effectively eliminating SGA births reduced prevalence of stunting at age 59 months from 44.4% to 43.7% when using odds ratios derived from measured lengths/heights and from 44.4% to 41.9% when using odds ratios derived from smoothed lengths/heights. CONCLUSIONS: Smoothing of children's measured lengths/heights increased the strength of the association between stunting at a given age and stunting at an earlier age. Using odds ratios based on smoothed lengths/heights in LiST resulted in a small reduction in the attenuation of intervention effects with age and thus some increase in the estimated benefits, and may better reflect the true benefits of early nutritional interventions

General intelligence is associated with subclinical inflammation in Nepalese children: A population-based plasma proteomics study

AbstractImproving child cognition in impoverished countries is a public health priority. Yet, biological pathways and associated biomarkers of impaired cognition remain poorly understood and largely unknown, respectively. This study aimed to explore and quantify associations between functional plasma protein biomarkers and childhood intellectual test performance. We applied proteomics to quantify proteins in plasma samples of 249 rural Nepalese children, 6–8years of age who, 1year later at 7–9years of age, were administered the Universal Nonverbal Intelligence Test (UNIT). Among 751 plasma proteins quantified, 22 were associated with UNIT scores, passing a false discovery rate threshold of 5.0% (q<0.05). UNIT scores were higher by 2.3–9.2 points for every 50% increase in relative abundance of two insulin-like growth factor binding proteins (IGFBPs), six subclasses of apolipoprotein (Apo) and transthyretin, and lower by 4.0–15.3 points for each 50% increase in relative abundance of 13 proteins predominantly involved in inflammation. Among them, IGFBP-acid labile subunit, orosomucoid 1 (ORM1), Apo C-I, and pyruvate kinase isoenzymes M1/M2 jointly explained 37% of the variance in UNIT scores. After additional adjustment for height-for-age Z-score and household socio-economic status as indicators of long-term nutritional and social stress, associations with 6 proteins involved in inflammation, including ORM1, α-1-antichymotrypsin, reticulocalbin 1, and 3 components of the complement cascade, remained significant (q<0.05). Using untargeted proteomics, stable, constitutive facets of subclinical inflammation were associated with lower developmental test performance in this rural South Asian child population. Plasma proteomics may offer opportunities to identify functional, antecedent biomarkers of child cognitive development

Plasma Proteome Biomarkers of Inflammation in School Aged Children in Nepal

<div><p>Inflammation is a condition stemming from complex host defense and tissue repair mechanisms, often simply characterized by plasma levels of a single acute reactant. We attempted to identify candidate biomarkers of systemic inflammation within the plasma proteome. We applied quantitative proteomics using isobaric mass tags (iTRAQ) tandem mass spectrometry to quantify proteins in plasma of 500 Nepalese children 6–8 years of age. We evaluated those that co-vary with inflammation, indexed by α-1-acid glycoprotein (AGP), a conventional biomarker of inflammation in population studies. Among 982 proteins quantified in >10% of samples, 99 were strongly associated with AGP at a family-wise error rate of 0.1%. Magnitude and significance of association varied more among proteins positively (n = 41) than negatively associated (n = 58) with AGP. The former included known positive acute phase proteins including C-reactive protein, serum amyloid A, complement components, protease inhibitors, transport proteins with anti-oxidative activity, and numerous unexpected intracellular signaling molecules. Negatively associated proteins exhibited distinct differences in abundance between secretory hepatic proteins involved in transporting or binding lipids, micronutrients (vitamin A and calcium), growth factors and sex hormones, and proteins of largely extra-hepatic origin involved in the formation and metabolic regulation of extracellular matrix. With the same analytical approach and the significance threshold, seventy-two out of the 99 proteins were commonly associated with CRP, an established biomarker of inflammation, suggesting the validity of the identified proteins. Our findings have revealed a vast plasma proteome within a free-living population of children that comprise functional biomarkers of homeostatic and induced host defense, nutrient metabolism and tissue repair, representing a set of plasma proteins that may be used to assess dynamics and extent of inflammation for future clinical and public health application.</p></div

Cellular localizati4on and molecular/biological functions of plasma proteins associated with α-1-acid glycoprotein (AGP) in 6–8 year old children in rural Nepal.^a

<p>Cellular localizati4on and molecular/biological functions of plasma proteins associated with α-1-acid glycoprotein (AGP) in 6–8 year old children in rural Nepal.<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0144279#t004fn001" target="_blank">^a</a></p

Plasma proteins negatively associated with plasma alpha-1-acid glycoprotein (AGP) in 6–8 year old children in rural Nepal, ordered by <i>P</i>.^a

<p>Plasma proteins negatively associated with plasma alpha-1-acid glycoprotein (AGP) in 6–8 year old children in rural Nepal, ordered by <i>P</i>.<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0144279#t003fn001" target="_blank">^a</a></p

Volcano plot of plasma proteins associated with plasma α-1-acid glycoprotein (AGP) in 6–8 year old children in rural Nepal.

<p>Plot (A) and (C) are enlarged rectangles in plot (B). (A) Plasma proteins negatively associated with AGP, presented by gene symbol (n = 58); (B) Plasma proteins associated with AGP were colored in red and blue (n = 99); (C) Plasma proteins positively associated with AGP, presented by gene symbol (n = 41). x- and y-axes are logarithmic.</p