Lipid-based Nutritional Supplements Research Articles

Lipid-based Nutritional Supplement Impact on Energy Intake, Appetite, Glucose and Insulin Levels in Under-Weight Pregnant and Lactating Women with Preeclampsia.

To investigate the response of nutritional supplement (LNS-PLW) on appetite score, energy intake, insulin and glucose levels in preeclamptic women. Sixty under-weight preeclamptic primigravida were divided into two groups randomly and provided LNS-PLW/Placebo in the fasted state. Blood samples were collected at fasting state, after 30mins of supplementation, "ad libitum buffet" breakfast and lunch for glucose and insulin levels. Total energy intake was higher significantly in the LNS-PLW group, although during breakfast it was significantly reduced. The insulin and glucose concentration was significantly increased after 30min of supplementation in the LNS-PLW group. Intake of the LNS-PLW by pre-eclamptic women had short-term suppression on subsequent meal but improved total energy intake during trial.

Literature Review: Stunting Prevention with Environmental and Nutrition in the Prenatal Period

Background: Stunting increases the global public health burden by contributing 45% of all under-five deaths. Children who experience stunting as a result of someone not getting the right amount of nutritional intake for a long period of time (chronic). Thus, stunting can actually be prevented with adequate nutritional intake, especially in the First 1000 Days of Life. The target set by the government through the 2020-2024 National Medium-Term Development Plan (RPJMN) is to reduce the percentage of stunting by 14%. Stunting prevention is more effective in the prenatal period where 80% before stunting occurs, When compared to chasing from stunting to non-stunting, the success is only 20%. Purpose: This study aims to analyze stunting prevention with enviroinmental and nutrition in the prenatal period. Methods: The method used in this study is to use a literature study with a search method, combine the results of research and analyze facts from several scientific sources that are accurate and valid. Results: The results showed that 69% of households defecated in open areas. hazard defecation behavior can cause environmental pollution due to the spread of pathogenic germs from the anus. The kinds of nutritions better consumted by prenatal are Moringa leaves, The Tubaramure Food, iron folic acids (IFA), lipid based nutritional supplements (LNS). Conclusion: The meal preparation, amount of food, energy intake, and protein intake to prevent stunting. We noted there are many kinds of nutrition and supplements such as food from Moringa leaves, Moringa leaf extract supplementation, Moringa powder, and blood-added tablets, IFA, iron and folic acid supplements (IFA), iron supplements, folic acid (IFA), and lipid supplements given to pregnant women can significantly prevent stunting in children. Continuous education and monthly monitoring of pregnant women diet during pregnancy classes at the Posyandu are suggested to prevent stunting in children.

Short Term Effect of Lipid-Based Nutritional Supplement on Caloric Intake, Appetite, Glucose, and Insulin Levels in Moderately Malnourished Children

Background: Malnutrition is a major health problem specially effecting children under the age of 5 years. Malnutrition has serious outcomes such as suppressed immune system, delayed and stunted growth, slow wound healing etc. Objective: To look into the impact of a lipid-based nutritional supplement on caloric intake, appetite, glucose and insulin levels of school going children of age 5-10years. Methods: In this single blind randomized controlled trial, 38 children with BMI (Z score between-2 and -3SDS) were randomly allocated to Lipid based nutritional supplements & Placebo groups. They were given supplements (535kcal) /Placebo (92kcal). They were served ad libitum buffet meals (breakfast and lunch). The appetite responses were measured by marking the Likert scale questionnaire at 0, 30, 60, 120, 150, 180, 210 and 240 minutes. The total caloric intake was calculated for the ad libitum buffet breakfast and lunch. The insulin and glucose levels were measured using COBAS C3 analyzer. Result: On the trial day, there was no significant difference in total caloric intake between lipid based nutritional supplements LNS (766.3272.4) kcal and Placebo (806311.5) kcal. Appetite was measured using a Likert scale, but no significant differences were found between the two groups. There was also no significant difference between glucose in the LNS vs. PLACEBO, i.e. (929.13 vs.97.111.7) mg/dL and insulin (1.6±0.97 vs. 2.09±1.15) µU/mL in both the groups. Conclusion: In mildly underweight children the Lipid based nutritional supplements reduces the caloric intake from the regular habitual diet, which extends to the lunch time. This suppression of caloric intake might be related to the changes in appetite.

Short Term Effect of Lipid-Based Nutritional Supplement on Caloric Intake, Appetite, Glucose, and Insulin Levels in Moderately Malnourished Children

Background: Malnutrition is a major health problem specially effecting children under the age of 5 years. Malnutrition has serious outcomes such as suppressed immune system, delayed and stunted growth, slow wound healing etc. Objective: To look into the impact of a lipid-based nutritional supplement on caloric intake, appetite, glucose and insulin levels of school going children of age 5-10years. Methods: In this single blind randomized controlled trial, 38 children with BMI (Z score between-2 and -3SDS) were randomly allocated to Lipid based nutritional supplements & Placebo groups. They were given supplements (535kcal) /Placebo (92kcal). They were served ad libitum buffet meals (breakfast and lunch). The appetite responses were measured by marking the Likert scale questionnaire at 0, 30, 60, 120, 150, 180, 210 and 240 minutes. The total caloric intake was calculated for the ad libitum buffet breakfast and lunch. The insulin and glucose levels were measured using COBAS C3 analyzer. Result: On the trial day, there was no significant difference in total caloric intake between lipid based nutritional supplements LNS (766.3272.4) kcal and Placebo (806311.5) kcal. Appetite was measured using a Likert scale, but no significant differences were found between the two groups. There was also no significant difference between glucose in the LNS vs. PLACEBO, i.e. (929.13 vs.97.111.7) mg/dL and insulin (1.6±0.97 vs. 2.09±1.15) µU/mL in both the groups. Conclusion: In mildly underweight children the Lipid based nutritional supplements reduces the caloric intake from the regular habitual diet, which extends to the lunch time. This suppression of caloric intake might be related to the changes in appetite.

Treatment outcomes and associated factors for hospitalization of children treated for acute malnutrition under the OptiMA simplified protocol: a prospective observational cohort in rural Niger.

Globally, access to treatment for severe and moderate acute malnutrition is very low, in part because different protocols and products are used in separate programs. New approaches, defining acute malnutrition (AM) as mid-upper arm circumference (MUAC) < 125 mm or oedema, are being investigated to compare effectiveness to current programs. Optimizing Malnutrition treatment (OptiMA) is one such strategy that treats AM with one product - ready-to-use therapeutic food, or RUTF - at reduced dosage as the child improves. This study aimed to determine whether OptiMA achieved effectiveness benchmarks established in the Nigerien National Nutrition protocol. A prospective cohort study of children in the rural Mirriah district evaluated outcomes among children 6-59 months with uncomplicated AM treated under OptiMA. In a parallel, unconnected program in one of the two trial sites, all non-malnourished children 6-23 months of age were provided small quantity lipid-based nutritional supplements (SQ-LNS). A multivariate logistic regression identified factors associated with hospitalization. From July-December 2019, 1,105 children were included for analysis. Prior to treatment, 39.3% of children received SQ-LNS. Recovery, non-response, and mortality rates were 82.3%, 12.6%, and 0.7%, respectively, and the hospitalization rate was 15.1%. Children who received SQ-LNS before an episode of AM were 43% less likely to be hospitalized (ORa=0.57; 0.39-0.85, p = 0.004). OptiMA had acceptable recovery compared to the Nigerien reference but non-response was high. Children who received SQ-LNS before treatment under OptiMA were less likely to be hospitalized, showing potential health benefits of combining simplified treatment protocols with food-based prevention in an area with a high burden of malnutrition such as rural Niger.

Effects of Oral Lipid-Based nutritional supplements on appetite, energy intake, and lipid profile of moderately underweight children.

Oral lipid-based nutritional supplements (LNS) are designed to ensure dietary adequacy and to improve malnourishment in children. Therefore, this study investigated the effects of 4 weeks of LNS on appetite, energy intake, and lipid profile of moderately underweight children (5-10 years old) with BMI-Z score between -2 and - 3 SDS, recruited in a single-blind randomized control trial. In addition to the regular dietary intake, fasting blood samples, anthropometric measurements, energy intake, and appetite responses were obtained before and after 4 weeks of LNS (535 kcal) or PLACEBO (92 kcal). After 4 weeks of supplementation mean energy intake (kcal) (p < .001), body weight (kg) (p < .001), BMI (kg/m2) (p < .01), mid-upper arm circumference (cm) (p < .01), total cholesterol (mg/dl) (p < .01) and fasting glucose (mg/dl) (p < .01) were raised significantly in the LNS group as compared to the PLACEBO group. No significant changes were detected in appetite responses (p > 0.05). In conclusion, LNS increases the overall energy intake, but does not affect the appetite but may induce hyperglycemia and hyperlipidemia.

Design, development, and local production of lipid-based nutritional supplements to enhance the complementary feeding diet: A model for collaboration for a feeding trial in Bangladesh.

Background: Lipid-based nutrient supplements (LNS) are effective for treating childhood wasting and for preventing stunting, wasting, and anemia, but large-scale production and programmatic use are a barrier. Locally-developed and produced LNS may be more affordable and reduce logistical procurement and importation hurdles, while promoting private sector engagement and partnership. Methods: In northwestern Bangladesh, we conducted a community-based trial of complementary food supplementation to test its efficacy to reduce childhood stunting. Two locally-developed, small-quantity LNS (20g/day, rice-lentil and chick-pea based) were designed, developed first at small scale in the 'kitchen' laboratory under controlled conditions, followed by taking them to a local food manufacturer for larger production for the study.We describe here the partnership, required expertise and capacity, experiences, and lessons learned that made this uniquely complex undertaking possible Results:Key steps in the journey included addressing the dynamics of clear communication between partners, executing on carefully assigned tasks and roles, correcting course when needed, and maintaining timeliness and roadmaps. Knowledge of food science and technology was key in solving many food-production challenges that were encountered in taking the laboratory recipe to the factory. Factory production was established and had to meet quality and hygiene criteria set for young children. Conclusions: We provide documentation of this experience as a model to describe the various steps and considerations and what is entailed in local LNS production. We highlight the importance of a well-conceived collaboration with clear roles that created a 'win-win' situation for all partners for achieving common goals, establishing improved technology at the factory, and building new capacity to produce such products for children in a low resource setting. Key words: micronutrient, lipid-based nutrient supplements, maternal and child, malnutrition, multiagency collaboration.

MICRONUTRIENT STATUS AND ENERGY INTAKE IN MODERATE ACUTE MALNOURISHED CHILDREN AFTER INTAKE OF HIGH ENERGY NUTRITIONAL SUPPLEMENTS FOR FOUR WEEKS: A RANDOMIZED CONTROLLED STUDY

Background: Undernutrition including micronutrient deficiency results in adverse health-related outcomes in children of low-medium income countries. This study aims to explore the effect of four weeks of Lipid-based nutritional supplement (LNS) on energy intake, anthropometry and micronutrient status in moderate acute malnourished children. Methods Thirty-four children with mean age 7.08±1.47 years and a BMI Z score between -2 and -3 SDS were randomized into LNS and Placebo groups in a single blind randomized control trial. Energy intake, fasting blood samples, and anthropometric measurements were obtained prior to and after four weeks of LNS (535 kcal) or Placebo (92kcal) supplementation in addition to their habitual dietary intake. Results: During four weeks of supplementation, energy intake (kcal) [(611±155) to (987±224), p&lt;0.001)], weight (kg) [(17.5±2.83) to (18.1±3.24), p&lt; 0.001], mid-upper arm circumference (cm) [(14.8±0.91) to (15.1±0.84), p=0.005)] and BMI (kg/m2) [(12.9±0.33) to (13.3±0.45), p=0.002] was significantly improved in the LNS group compared to Placebo. A significant increase in hemoglobin (g/ml) [(12.2±1.14) to (13.7±1.69), p&lt;0.01] and iron levels (µg/dl) [(0.36±0.09) to (0.67±0.20), p&lt;0.001] were observed in the LNS group. No significant differences were detected in the copper and zinc levels. Conclusion: Lipid-based nutritional supplement is effective in improving energy intake, nutritional outcomes and iron but not copper and zinc. The trial was registered at www.isrctn.com under reference: ISRCTN147181521.

IMPACT OF LIPID-BASED NUTRITIONAL SUPPLEMENTATION IN PRIMI-GRAVIDAS AND ITS EFFECT ON MATERNAL, BIRTH AND INFANT OUTCOMES: A RANDOMIZED CONTROLLED TRIAL

OBJECTIVE: To find out the effect of Lipid based nutritional supplement (LNS) on body composition, hematological findings, maternal, birth and infant outcomes in underweight primi-gravidas. METHODS: This single-blinded randomized controlled clinical trial was executed in the tertiary care hospitals of Khyber Pakhtunkhwa province, Pakistan from April 2018 to August 2019. Forty primi-gravidas recruited in the study were randomized into LNS and placebo groups. LNS group received 75 gms of high energy nutritional supplement, named “MAAMTA”, on daily basis from their first antenatal visit till delivery in addition to their conventional antenatal treatment. Fasting blood samples were taken and body composition was measured at baseline visit, 16th week of gestation and post-natally. For the measurement of hematological parameters neonates cord blood was obtained. Data of 36 participants (LNS group n=19; placebo group n=17) were available for final analysis. RESULTS: Majority (n=33/36; 91.7%) had normal vaginal deliveries (n=18/19 in LNS group &amp; n=15/17 in placebo group). Frequency of Cesarean section was 1/19 (5.3%) in LNS group and 2/17 (11.8%) in placebo group. No case of abortion was reported. Mean crown heel length (CHL) was 47.11±2.747 cm in LNS group and 44.24±2.359 cm in placebo group (p=0.002). Mean fronto-occipital circumference was 35.11±1.663 cm and 32.41±7.859 cm in the LNS and placebo groups respectively (p=0.153). No difference was observed between the groups in maternal gestational weight gain per visit, prevalence of maternal anemia, maternal mortality &amp; neonatal birth weight. CONCLUSION: The prenatal use of LNS increases the CHL of the neonates of underweight primi-gravidas.

Costs of Implementing an Integrated Package of Maternal and Pediatric Interventions Including SQ-LNS in Rural Niger.

In January 2015, the Alliance for International Medical Action and Bien Être de la Femme et de l'Enfant au Niger launched the 1000 Days Program in Mirriah District, Niger, to provide an integrated package of maternal and pediatric preventive and curative interventions. A new component of the package was the provision of small-quantity lipid-based nutritional supplements (SQ-LNS) for children 6 to 23 months. The objective of this study was to estimate the costs associated with providing the 1000 days package. Activity-based costing was used to estimate the total costs of the 10 activities included in the 1000 days package and also the incremental costs of new interventions, those beyond the standard of care. The total cost of the 1000 Days Program was US$2.31 million for 9000 mother-child pairs. The average cost per pair was US$257 or US$103 per year. Incremental costs for new interventions accounted for 56% of program costs. Small-quantity lipid-based nutritional supplement represented 30% of incremental costs. A combination of efficiency measures could lower program costs by 15%. This study is the first to estimate the costs of an integrated, preventative-curative package of maternal-child health interventions with SQ-LNS. Implementing the 1000 days package across Niger will be challenging with only the country's domestic health resources. Efficiency measures and creative financing arrangements, including support from external partners, should be explored. The approach and results described can inform future resource mobilization, financing, and budgeting efforts to scale the 1000 days or similar programs.

Heat Stress-Associated Growth Retardation in the First 1000 Days Is Mitigated by Preconception Nutritional Supplementation

Abstract Objectives Understanding the interactions between nutrition and climate-driven health outcomes is increasingly necessary. Employing data from the Women First trial conducted in Thatta, Pakistan, we examined the interactions between maternal nutritional deficits and heat stress (HS) on birth outcomes. Methods Women of child-bearing age either consumed a small quantity lipid-based nutrition supplement (sqLNS) prior to conception (Arm 1), from 12 wk of gestation until delivery (Arm 2); or were not supplemented with sqLNS (Arm 3). At the Pakistan site, samples sizes with birth outcomes obtained within 48 h of delivery for Arms 1, 2 and 3 were 157,150 and 138, respectively. Daily maximal air temperatures were used to were compute the average daily maximal temperatures (Tmax) for each infant over four 90-day windows representing each trimester of gestation and 3 mo preconception. The number of days in each period when the Tmax was &amp;gt; 39°C was computed to assess ‘heat stress days’. Results Linear regression models assessing the associations between heat exposure and outcome variables (gestational age adjusted Z-scores of birth length (LGAZ), birth weight (WGAZ) and head circumference (HCGAZ) revealed a striking negative association of both ambient temperature and HS days in the first trimester on birth length (LGAZ) and head circumference (HCGAZ) (p &amp;lt; 0.005). For each 5°C increase in the Tmax in the first trimester, LGAZ decreased by 0.15 z-scores and HCGAZ decreased by 0.11 z-scores. Heat exposure (Tmax) in the second trimester also associated with HCGAZ (p = 0.02 and z-score of −0.11 for every 5°C) but not with birth length or birth weight. RNA-sequencing of placenta indicated a robust association of 1st trimester HS with genes involved in protein targeting to ER, protein biosynthesis, and cytoplasmic translation. Finally, while non-intervention groups (Arms 2 and 3) showed a robust negative association of excessive HS with LGAZ (p &amp;lt; 0.05), preconception intervention with sqLNS (Arm 1) significantly mitigated heat-associated decreases in birth length. Conclusions These findings indicate that excessive HS in the first trimester is associated with decreased linear growth in utero. Importantly, sqLNS mitigated growth restriction in newborns implicating nutritional status as a driving force in resilience to HS. Funding Sources Supported by The BMGF and NICHD.

Measurement of Saccharin and trans-Resveratrol Metabolites in Urine as Adherence Markers for Small Quantity Lipid-Based Nutrient Supplement Consumption.

Saccharin and trans-resveratrol were incorporated into small quantity lipid-based nutritional supplements (SQ-LNS) to be evaluated as the markers of consumption for nutritional intervention studies. Forty-seven healthy women consumed a single supplement with either 8.6 mg of saccharin or 5 mg of trans-resveratrol, and urine was collected for 4 h. A rapid 11 min method employing multiple reaction monitoring and ultrahigh performance liquid chromatography coupled to a triple quadrupole mass spectrometer was developed to measure saccharin and resveratrol metabolites in urine simultaneously. The linear dynamic range of the method was from 3 to 1000 ng mL–1, with the correlation coefficient of 0.999 and limits of quantification from 15.28 to 53.03 ng mL–1. Sample preparation was simple dilution with an average recovery of 97.8%. Ion suppression was observed with urine concentrations >10%. Mean levels of saccharin and resveratrol-3-O-sulfate in urine were 5.481 ± 4.359 and 3.440 ± 4.160 nmol L–1, respectively. We developed and validated a method to measure saccharin and trans-resveratrol metabolites in urine to objectively corroborate the consumption of SQ-LNS for the first time in nutrition intervention studies.

Ending malnutrition in all its forms requires scaling up proven nutrition interventions and much more: a 129-country analysis

BackgroundSustainable Development Goal (SDG) 2.2 calls for an end to all forms of malnutrition, with 2025 targets of a 40% reduction in stunting (relative to 2012), for wasting to occur in less than 5% of children, and for a 50% reduction in anaemia in women (15–49 years). We assessed the likelihood of countries reaching these targets by scaling up proven interventions and identified priority interventions, based on cost-effectiveness.MethodsFor 129 countries, the Optima Nutrition model was used to compare 2019–2030 nutrition outcomes between a status quo (maintained intervention coverage) scenario and a scenario where outcome-specific interventions were scaled up to 95% coverage over 5 years. The average cost-effectiveness of each intervention was calculated as it was added to an expanding package of interventions.ResultsOf the 129 countries modelled, 46 (36%), 66 (51%) and 0 (0%) were on track to achieve the stunting, wasting and anaemia targets respectively. Scaling up 18 nutrition interventions increased the number of countries reaching the SDG 2.2 targets to 50 (39%), 83 (64%) and 7 (5%) respectively. Intermittent preventative treatment of malaria during pregnancy (IPTp), infant and young child feeding education, vitamin A supplementation and lipid-based nutrition supplements for children produced 88% of the total impact on stunting, with average costs per case averted of US$103, US$267, US$556 and US$1795 when interventions were consecutively scaled up, respectively. Vitamin A supplementation and cash transfers produced 100% of the total global impact on prevention of wasting, with average costs per case averted of US$1989 and US$19,427, respectively. IPTp, iron and folic acid supplementation for non-pregnant women, and multiple micronutrient supplementation for pregnant women produced 85% of the total impact on anaemia prevalence, with average costs per case averted of US$9, US$35 and US$47, respectively.ConclusionsPrioritising nutrition investment to the most cost-effective interventions within the country context can maximise the impact of funding. A greater focus on complementing nutrition-specific interventions with nutrition-sensitive ones that address the social determinants of health is critical to reach the SDG targets.

Impact Evaluation of a Comprehensive Nutrition Program for Reducing Stunting in Children Aged 6–23 Months in Rural Malawi

The prevalence of stunting in central rural Malawi is ∼50%, which prompted a multipronged nutrition program in 1 district from 2014 to 2016. The program distributed a daily, fortified, small-quantity lipid-based nutritional supplement, providing 110kcal and 2.6g of protein to children aged 6-23mo, and behavior change messages around optimal infant and young child feeding (IYCF) and water, sanitation, and hygiene. Our objective was to perform an impact evaluation of the program using a neighboring district as comparison. Using a quasi-experimental study design, with cross-sectional baseline (January-March, 2014; n=2404) and endline (January-March, 2017; n=2453) surveys, we evaluated the program's impact using a neighboring district as comparison. Impact on stunting was estimated using propensity score weighted difference-in-differences regression analyses to account for baseline differences between districts. No differences in mean length-for-age z-score or prevalence of stunting were found at endline. However, mean weight, weight-for-length z-score, and mid-upper arm circumference were higher at endline by 150g, 0.22, and 0.19cm, respectively, in the program compared with the comparison district (all P<0.05). Weekly reports of high fever and malaria were also lower by 6.4 and 4.7 percentage points, respectively, in the program compared with the comparison district (both P<0.05). There was no impact on anemia. Children's dietary diversity score improved by 0.17, and caregivers' infant and young child feeding and hand-washing practices improved by 8-11% in the program compared with the comparison district (all P<0.05). An impact evaluation of a comprehensive nutrition program in rural Malawi demonstrated benefit for child ponderal growth and health, improved maternal IYCF and hand-washing practices, but a reduction in stunting prevalence was not observed.

Longitudinal Changes of One-Carbon Metabolites and Amino Acid Concentrations during Pregnancy in the Women First Maternal Nutrition Trial.

ABSTRACTBackgroundMaternal dietary restriction and supplementation of one-carbon (1C) metabolites can impact offspring growth and DNA methylation. However, longitudinal research of 1C metabolite and amino acid (AA) concentrations over the reproductive cycle of human pregnancy is limited.ObjectiveTo investigate longitudinal 1C metabolite and AA concentrations prior to and during pregnancy and the effects of a small-quantity lipid-based nutrition supplement (LNS) containing >20 micronutrients and prepregnancy BMI (ppBMI).MethodsThis study was an ancillary study of the Women First Trial (NCT01883193, clinicaltrials.gov) focused on a subset of Guatemalan women (n = 134), 49% of whom entered pregnancy with a BMI ≥25 kg/m2. Ninety-five women received LNS during pregnancy (+LNS group), while the remainder did not (−LNS group). A subset of women from the Pakistan study site (n = 179) were used as a replication cohort, 124 of whom received LNS. Maternal blood was longitudinally collected on dried blood spot (DBS) cards at preconception, and at 12 and 34 wk gestation. A targeted metabolomics assay was performed on DBS samples at each time point using LC-MS/MS. Longitudinal analyses were performed using linear mixed modeling to investigate the influence of time, LNS, and ppBMI.ResultsConcentrations of 23 of 27 metabolites, including betaine, choline, and serine, changed from preconception across gestation after application of a Bonferroni multiple testing correction (P < 0.00185). Sixteen of those metabolites showed similar changes in the replication cohort. Asymmetric and symmetric dimethylarginine were decreased by LNS in the participants from Guatemala. Only tyrosine was statistically associated with ppBMI at both study sites.ConclusionsTime influenced most 1C metabolite and AA concentrations with a high degree of similarity between the 2 diverse study populations. These patterns were not significantly altered by LNS consumption or ppBMI. Future investigations will focus on 1C metabolite changes associated with infant outcomes, including DNA methylation. This trial was registered at clinicaltrials.gov as NCT01883193.

Differential DNA Methylation of Human Metastable Epialleles in Guatemalan Infants at Birth Due to Timing of a Maternal Lipid-Based Nutrition Supplement and Pre-Pregnancy BMI (P11-139-19)

Abstract Objectives Human metastable epialleles (MEs) are specific regions that are systemically methylated (lack tissue specificity), stable over time, and variably expressed between individuals. DNA methylation (DNAme) of MEs have been previously reported to be altered by maternal nutritional status at the time of conception. Here, we examined DNAme of MEs from a subset of Guatemalan mother/infant dyads as part of the Women First study, an international RCT that tested whether timing of a daily lipid-based nutrition supplement (LNS) improved birth length. The 3 study arms are: women consumed LNS ≥ 3 months prior to conception until delivery (Arm 1, N = 45); women consumed the same LNS commencing at 12 weeks gestation until delivery (Arm 2, N = 45); or no LNS (Arm 3, N = 44). The purpose of this study was to test if the timing of maternal LNS and pre-pregnancy BMI (ppBMI, BMI range = 20.1 – 38.4 kg/m2) led to differential DNAme of MEs in infants at birth. Methods Bisulfite-converted DNAme libraries were constructed using NimbleGen SeqCap Epi CpGiant probes from amnion tissue collected at birth. Individuals were sequenced via 2 × 150 paired end reads using the Illumina NovaSeq sequencer. Subjects that passed quality control (131/142 subjects) were used in subsequent statistical analyses. A linear model was used to test for the interaction between maternal LNS and ppBMI on infant DNAme for each base pair site within 296 previously identified candidate ME regions. The number of methylated base pairs per region ranged from 1 – 737. A significance level adjusting for the 296 regions was set at P ≤ 0.000169. Results We identified 6 ME regions with significant interactions, demonstrating differential ME DNAme due to intervention arm was dependent on ppBMI values. Our analyses also identified 3 CpGs associated with ppBMI regardless of LNS status and 1 CpG associated with LNS regardless of ppBMI suggesting a role for independent effects of maternal LNS and ppBMI on ME DNAme. Conclusions Our findings indicate that timing of maternal LNS and ppBMI contribute to DNAme of candidate MEs in infants at birth, suggesting epigenetic influences due to in utero exposures. Future analyses will identify genes associated with changes in ME DNAme and the role of DNAme on infant growth. Funding Sources Bill &amp; Melinda Gates Foundation and National Institutes of Health.

The Effect of a Preconception Nutrition Supplement on One Carbon Metabolites (P24-028-19)

Abstract Objectives Studies in both animals and humans have shown that maternal dietary restriction and supplementation of one carbon (1C) metabolites (methyl donors), such as methionine and choline, can impact offspring growth, insulin resistance, and DNA methylation. However, there has been limited longitudinal research of 1C metabolite concentrations over the reproduction cycle of human pregnancy. The purpose of this study was to investigate if 1C metabolite concentrations change prior to and during pregnancy and if a preconception lipid-based nutrition supplement (LNS) influences such changes. Methods This study was a secondary analysis as part of the Women First study (clinicaltrials.gov, NCT01883193), a large, randomized controlled trial investigating whether the timing of maternal LNS initiation would impact fetal growth and development. The study arms were supplementation at least 3 months prior to conception (Arm 1), supplementation at ∼12 weeks of gestation (Arm 2), or no supplementation (Arm 3). Dried blood spot (DBS) cards were collected at study enrollment prior to conception, and at 12 and 34 weeks gestation. A targeted 1C metabolite assay (27 metabolites) was performed on a subset of DBS samples from Guatemalan women (n = 134) at each time point using liquid chromatography/tandem mass spectrometry. Longitudinal analyses were performed using linear mixed modeling to investigate the influence of time and LNS on these metabolites. Results The concentrations of two metabolites were changed by intervention status: asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA). Twenty-one of 27 metabolites significantly changed from preconception and across gestation after correcting for multiple testing using the Bonferroni correction (P &lt; 0.00185). Conclusions Preconception LNS significantly decreased the level of ADMA, a metabolite which has been implicated in intrauterine growth restriction and preeclampsia. More work is needed to determine whether this intervention could influence development of these conditions. Funding Sources Bill &amp; Melinda Gates Foundation, National Institutes of Health.

Differences in Birth Size Associated with Preconception Maternal Nutrition Intervention Persist in Postnatal Growth Through 6 Months (OR10-05-19)

ObjectivesNewborn size, including length, has been associated with later growth. Preconception nutrition supplementation in Women First (WF) trial (clinicaltrials.gov NCT01883193) was associated with higher newborn length and lower rates of stunting. The objective was to examine postnatal growth outcomes through 6 mo in the WF offspring. MethodsSubjects were 2450 infants from the WF sites in Democratic Republic of Congo (DRC), Guatemala, India, and Pakistan with the 3 WF arms maintained: Arm 1 started a lipid-based nutrition supplement ≥ 3 mo prior to conception; Arm 2 started same supplement at ∼11 wk gestation; and Arm 3 received no trial supplements. Maternal supplementation was discontinued at delivery. Anthropometric measurements were obtained at birth, 0.5, 1, 3, and 6 mo; Z-scores were calculated from WHO Child Growth Standards. Primary and secondary outcomes were analyzed using longitudinal generalized estimating equations accounting for the correlation of repeated measures over time and study cluster. Intervention effects were evaluated within each site as well as overall, adjusting for site and baseline maternal covariates that differed by arm. Statistical interaction between arm and infant sex was evaluated and included if significant. ResultsLongitudinal growth (length and weight) curves from 0–6 mo demonstrated differences by intervention arm, with Arms 1 and 2 more favorable compared to Arm 3 (Table + LAZ in Figure). Relative risks (RR) for stunting were significantly lower for Arms 1 and 2 (vs. Arm 3) (Table). Site-specific analyses revealed some site differences warranting further exploration. ConclusionsWithout any postnatal intervention, differences in fetal growth evident at birth persisted at 6 months. Funding SourcesBill & Melinda Gates Foundation; NIH, NICHD & ODS. Supporting Tables, Images and/or Graphs▪▪

Formative Research Helped Identify Acceptable, Locally Available Foods to Mix with Unsweetened Small-quantity Lipid-based Nutrient Supplement in Mexico (P10-030-19)

ObjectivesAppropriate utilisation of home fortificants such as small-quantity lipid-based nutrition supplements (SQ-LNS) requires providing clear and acceptable instructions of use for the target audience. We conducted formative research to identify locally available foods that could be recommended to mix with unsweetened SQ-LNS in Mexico. MethodsThirteen caregivers of 7 to 23 month-old children participated in a SQ-LNS tasting session and guided group discussion at a hospital in a semi-urban area in Morelos, Mexico. After sampling the SQ-LNS, caregivers were asked to select 1 or more of the 9 common complementary foods available to mix with 1 sachet of SQ-LNS (20 g). The common complementary foods available, identified from previous research, were: cooked rice, mashed beans, plain yogurt, strawberry-flavoured yogurt, the sweetened dairy snack Danonino, two types of commercial baby food (carrot and pear), banana, and oatmeal. Caregivers tasted and rated the organoleptic properties of SQ-LNS mixed with each of the foods. Subsequently, we conducted a home feeding session in which caregivers selected 1 of the top 4 foods preferred during the tasting session to mix with SQ-LNS (n = 8). ResultsThe preferred foods for mixing SQ-LNS in the tasting session were mashed beans (n = 5), cooked rice (n = 2), Danonino (n = 2) and unsweetened yogurt (n = 2). Caregivers preferred these foods because they were considered better in masking the taste of the supplement. During the home feeding session, half of the caregivers selected Danonino to mix with SQ-LNS, and none selected unsweetened yogurt. Some caregivers considered that varying the type of foods used to mix with SQ-LNS could be a useful strategy to improve acceptance and adherence to daily supplementation. ConclusionsProviding multiple examples of locally available and acceptable complementary foods to mix with SQ-LNS might be necessary to promote daily supplement use in the study context. Formative research is useful for developing recommendations for SQ-LNS use that take into account the customs and preferences of the target population. Funding SourcesThe study was funded by the Government of Canada, as part of the Business Platform for Nutrition Research hosted by the Global Alliance for Improved Nutrition.

Thymic size is increased by infancy, but not pregnancy, nutritional supplementation in rural Gambian children: a randomized clinical trial

BackgroundThymic size in early infancy predicts subsequent survival in low-income settings. The human thymus develops from early gestation, is most active in early life and is highly sensitive to malnutrition. Our objective was to test whether thymic size in infancy could be increased by maternal and/or infant nutritional supplementation.MethodsThe Early Nutrition and Immune Development (ENID) Trial was a randomized 2 × 2 × 2 factorial, partially blinded trial of nutritional supplementation conducted in rural Gambia, West Africa. Pregnant women (N = 875) were randomized to four intervention groups (iron-folate (standard care), multiple micronutrients, protein energy or protein energy + multiple micronutrients at ‘booking’ (mean gestational age at enrolment = 13.6 weeks, range 8–20 weeks) until delivery. The iron-folate and multiple micronutrient arms were administered in tablet form and the protein energy arms as a lipid-based nutritional supplement. All intervention arms contained 60 mg iron and 400 μg folic acid per daily dose. From 24 to 52 weeks of age, infants from all groups were randomized to receive a daily lipid-based nutritional supplement, with or without additional micronutrients. Thymic size was assessed by ultrasonography at 1, 8, 24 and 52 weeks of infant age, and a volume-related thymic index calculated. Detailed data on infant growth, feeding status and morbidity were collected.ResultsA total of 724 (82.7%) mother-infant pairs completed the trial to infant age 52 weeks. Thymic size in infancy was not significantly associated with maternal supplement group at any post-natal time point. Infants who received the daily LNS with additional micronutrients had a significantly larger thymic index at 52 weeks of age (equivalent to an 8.0% increase in thymic index [95% CI 2.89, 13.4], P = 0.002). No interaction was observed between maternal and infant supplement groups.ConclusionsA micronutrient-fortified lipid-based supplement given in the latter half of infancy increased thymic size, a key mediator of immune function. Improving the micronutrient status of infants from populations with marginal micronutrient status may improve immune development and survival.Trial registrationISRCTN registry (controlled-trials.com) Identifier: ISRCTN49285450