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Background:Almost a quarter of children under the age of five in low- and middle-income countries (LMICs) currently experience growth faltering. Early childhood stunting (height/length-for-age z-score < -2) is associated with a range of adverse later life outcomes including reduced cognitive development, poor school achievement and increased probability of living in poverty as adults. Few effective interventions are currently available to address stunting in LMICs. Methods: We will conduct a 2x2 cluster-randomized factorial trial with ~2300 caregiver-child dyads residing in 280 communities (clusters) located in Luapula, Lusaka, and Southern Provinces of Zambia. Clusters will be randomized into four groups each comprising 70 clusters with ~560 caregiver-child dyads: i) a control group ii) a growth charts only group; iii) a small quantity lipid-based nutrient supplements (SQ-LNS) only group; and iv) a growth charts + SQ-LNS group. Families in the growth charts groups (ii and iv) will receive a locally developed poster installed in their home that allows them to compare the height of their children to the World Health Organization’s international growth reference tables. The poster will also include health and nutrition messages for infants and young children in alignment with Ministry of Health recommended practices. Families in the SQ-LNS groups (iii and iv) will be given monthly rations (30 sachets) of SQ-LNS over a period of 18 months. Pediatric anthropometry and a caregiver survey will be conducted at baseline and endline. The primary study outcome is height-for-age z-score and stunting (HAZ < -2) after 18-months of intervention, when children will be between 24 and 36 months of age. Secondary outcomes will be anemia, weight-for-height, weight-for-age and child development. In a subsample we will also assess micronutrient status (Retinol-binding protein (RBP) for Vitamin A deficiency, ferritin for iron deficiency, and hemoglobin for anemia), inflammation (C-reactive protein (CRP), α1-acid glycoprotein (AGP)), biomarkers of environmental enteric dysfunction, the composition of the bacterial community in the gut microbiome and saccadic reaction time (SRT), an eye-tracking measure of neural function. Discussion:This study was designed to assess the impact of growth charts as well as the extent to which early childhood growth faltering can be mitigated through SQ-LNS supplementation in three purposely selected highly diverse areas of Zambia. Trial registration: This study is registered at clinicaltrials.gov as NCT0512042. https://clinicaltrials.gov/ct2/show/NCT05120427

Author(s): Jorgensen, Josh M; Young, Rebecca; Ashorn, Per; Ashorn, Ulla; Chaima, David; Davis, Jasmine CC; Goonatilleke, Elisha; Kumwenda, Chiza; Lebrilla, Carlito B; Maleta, Kenneth; Sadalaki, John; Totten, Sarah M; Wu, Lauren D; Zivkovic, Angela M; Dewey, Kathryn G | Abstract: BackgroundHuman milk oligosaccharides (HMOs) and bioactive proteins likely benefit infant health, but information on these relations is sparse.ObjectivesWe aimed to examine associations of milk content of HMOs and bioactive proteins with incidence and longitudinal prevalence of infant morbidity (any illness, fever, diarrhea, acute respiratory infection, and loss of appetite) and markers of inflammation [C-reactive protein (CRP) and α-1-acid glycoprotein (AGP)]. These are secondary analyses of a randomized controlled trial.MethodsBreast milk samples at 6nmo postpartum (nnn=n659) were analyzed to quantify absolute abundance of HMOs, relative abundance of fucosylated HMOs, sialylated HMOs, and 51 individual HMOs, and concentrations of 6 bioactive proteins (lactalbumin, lactoferrin, lysozyme, antitrypsin, IgA, and osteopontin). We examined associations of these constituents with infant morbidity from 6 to 7 and 6 to 12nmo, and CRP and AGP at 6 and 18nmo, considering maternal secretor status [presence or absence of the functional enzyme encoded by the fucosyltransferase 2 gene (FUT2) ] and adjusting for covariates and multiple hypothesis testing.ResultsIn secretors there were positive associations between total HMOs and longitudinal prevalence of fever (Pn=n0.032), between fucosylated HMOs and incidence of diarrhea (Pn=n0.026), and between lactoferrin and elevated CRP at 18nmo (Pn=n0.011). In nonsecretors, there were inverse associations between lactoferrin and incidence of fever (Pnn=n0.007), between osteopontin and longitudinal prevalence of lost appetite (Pnn=n0.038), and between fucosylated HMOs and incidence of diarrhea (Pn=n0.025), lost appetite (Pn=n0.019), and concentrations of AGP and CRP at 6nmo (Pn=n0.001 and 0.010); and positive associations between total HMOs and incidence of lost appetite (Pn=n0.024) and elevated CRP at 18nmo (Pnn=n0.026), between lactalbumin and incidence of diarrhea (Pn=n0.006), and between lactoferrin and elevated CRP at 18nmo (Pn=n0.015).ConclusionsCertain HMOs and bioactive proteins were associated with infant morbidity and inflammation, particularly in nonsecretors. Further research is needed to elucidate the causality of these relations.This trial was registered at clinicaltrials.gov as NCT01239693.

Author(s): Jorgensen, Josh M; Young, Rebecca; Ashorn, Per; Ashorn, Ulla; Chaima, David; Davis, Jasmine CC; Goonatilleke, Elisha; Kumwenda, Chiza; Lebrilla, Carlito B; Maleta, Kenneth; Prado, Elizabeth L; Sadalaki, John; Totten, Sarah M; Wu, Lauren D; Zivkovic, Angela M; Dewey, Kathryn G | Abstract: BackgroundHuman milk oligosaccharides (HMOs) and bioactive breast milk proteins have many beneficial properties. Information is sparse regarding associations between these milk constituents and infant growth and development in lower-income countries.ObjectivesWe aimed to examine associations of milk content of HMOs and bioactive proteins at 6 mo postpartum with infant growth and motor and cognitive development. These are secondary analyses of a randomized controlled trial in rural Malawi.MethodsBreast milk samples were analyzed at 6 mo (nn=n659) for general categories of HMOs (total HMOs, fucosylated HMOs, and sialylated HMOs), 51 individual HMOs, and 6 bioactive proteins (lactalbumin, lactoferrin, lysozyme, antitrypsin, IgA, and osteopontin). We examined associations of the relative abundances of HMOs and concentrations of bioactive proteins with infant growth from 6 to 12 mo [change in length-for-age (ΔLAZ), weight-for-age, weight-for-length, and head circumference z-scores] as well as ability to stand or walk alone at 12 mo, and motor and language skills, socioemotional development, executive function, and working memory at 18 mo. Analyses were adjusted for covariates and multiple hypothesis testing.ResultsAmong all participants, there were inverse associations of IgA and lactoferrin concentrations with motor skills (Pn=n0.018 and P =n0.044), and a positive association of lactalbumin concentration with motor skills (Pn=n0.038). Among secretors only [fucosyltransferase 2 gene (FUT2) positive], there were positive associations of absolute abundance of HMOs with ΔLAZ (Pn=n0.035), and relative abundance of fucosylated and sialylated HMOs with language at 18 mo (Pnln0.001 and Pn=n0.033, respectively), and inverse associations of osteopontin with standing and walking at 12 mo (Pn=n0.007 and 0.002, respectively). Relative abundances of several individual HMOs were associated with growth and development, mostly among secretors.ConclusionsCertain bioactive breast milk proteins and HMOs are associated with infant growth and motor and cognitive development. Further studies are needed to determine if a causal relation exists.This trial was registered at clinicaltrials.gov as NCT01239693.

Background Malnutrition is a public health problem in many developing countries, Zambia inclusive. According to the Zambia Demographic and Health Survey, the stunting rate in children under five years old is at 40% while underweight is at 15% and wasting at 6%. The purpose of this study was to establish whether childcare practices have an influence on the nutritional status of children aged 6 to 23 months in Lusaka district. Methods A cross sectional study was employed targeting 239 children resident in Munali constituency in Zambia. A researcher administered questionnaire was used to collect data on demographic characteristics, hygiene practices, health seeking behaviour and food consumption pattern. Child anthropometric measurements were taken using calibrated scales and height/length boards for weight and length/height respectively. SPSS version 20 was used to analyse data. WHO AnthroPlus was used to generate anthropometric indices. Bivariate analysis used to establish associations between variables and logistic regression was used to establish predictors of stunting. Results Prevalence of wasting, underweight and stunting was 3.8%, 9.6% and 25.5%, respectively. Stunting was more prevalent among male than female children, (p-value = 0.015). Child care practices that were associated with stunting included: breastfeeding (p-value = 0.002), education level of caregiver (p-value = 0.013), type of toilet used (p – value = 0.004), child morbidity (p – value = 0.040), use of insecticide treated mosquito net (p – value = 0.012). Predictors of stunting included breastfeeding and child morbidity. Breastfeeding before the survey was associated with a reduction in risk of stunting among children (p-value = 0.009, OR = 0.347, 95% CI (0.156 – 0.769)). Surprisingly morbidity two weeks prior to the study was also associated with a reduction in the likelihood of stunting (p-value = 0.009, OR = 0.350, 95% CI (0.166 – 0.773)). Conclusion The study revealed high levels of stunting. Childcare practices that had a significant relationship to nutritional status of the children were: breastfeeding night before survey, type of toilet used, use of insecticide treated mosquito net, education level of caregiver and child morbidity. Key words: childcare, stunting, underweight, wasting, Zambia

Fortifying complementary foods with lipid-based nutrient supplements (LNS) may improve energy and nutrient intakes of infants at risk for undernutrition. We aimed to determine the relative validity of an interactive 24-h recall (i-24-HR) for assessing the impact of an LNS intervention on dietary intakes of energy and nutrients among rural Malawian 9–10-month-old infants (n 132) participating in the International Lipid‐Based Nutrient Supplements Dose (iLiNS-DOSE) trial. Dietary data were collected for the same day via i-24-HR and weighed food records. Inter-method agreements were estimated overall and by intervention group, using Bland–Altman plots and paired t tests; measurement error models (differential error); and percentage of food omissions and intrusions were estimated. Overall, inter-method differences in mean intakes of energy and most nutrients were not significant. When stratified by group, recalled energy intakes were under-estimated (−368 kJ; P=0·01) in the control but not in the intervention group (−42 kJ; P=0·6). This differential reporting error was related to an over-estimation of recalled LNS (8·1 v. 4·5 g; PPP30 % eating occasions) omissions were milk/fish/eggs, starchy roots/vegetables and sweetened snacks. Common intrusions were milk/yogurt. Starchy staples and LNS were recalled when consumed (>85 %) (i.e. matched). These results emphasise the importance of considering differential error when interpreting dietary results in LNS trials.

Exclusive breastfeeding is recommended during the first 6 months of life; thereafter, continued breastfeeding along with nutritious complementary foods is recommended. Continued breastfeeding contributes a substantial proportion of nutrient needs and promotes healthy growth and development, but the quantity of breast milk consumed may be highly variable and little is known about the factors associated with breast milk intake after 6 months of age. The present study was conducted to assess factors associated with breast milk intake of Malawian infants at 9-10 months of age. Breast milk intake was measured using the dose-to-mother deuterium oxide dilution method in a subsample of 358 Malawian infants who were participating in a randomized controlled trial of lipid-based nutrient supplements. Regression analysis was used to assess associations between breast milk intake and several maternal and infant variables. Mean (standard deviation) breast milk intake was 752 (244) g day(-1) . In multiple regression, breast milk intake was positively associated with infant weight (+62 g per kg body weight, P

World Health Organization recommends exclusive breastfeeding for infants for the first 6 months of life, followed by introduction of nutritious complementary foods alongside breastfeeding. Breast milk remains a significant source of nourishment in the second half of infancy and beyond; however, it is not clear whether more breast milk is always better. The present study was designed to determine the association between amount of breast milk intake at 9-10 months of age and infant growth and development by 12-18 months of age. The study was nested in a randomized controlled trial conducted in Malawi. Regression analysis was used to determine associations between breast milk intake and growth and development. Mean (SD) breast milk intake at 9-10 months of age was 752 (244) g/day. Mean (SD) length-for-age z-score at 12 months and change in length-for-age z-score between 12 and 18 months were -1.69 (1.0) and -0.17 (0.6), respectively. At 18 months, mean (SD) expressive vocabulary score was 32 (24) words and median (interquartile range) skills successfully performed for fine, gross, and overall motor skills were 21 (19-22), 18 (16-19), and 38 (26-40), respectively. Breast milk intake (g/day) was not associated with either growth or development. Proportion of total energy intake from breast milk was negatively associated with fine motor (β = -0.18, p = .015) but not other developmental scores in models adjusted for potential confounders. Among Malawian infants, neither breast milk intake nor percent of total energy intake from breast milk at 9-10 months was positively associated with subsequent growth between 12 and 18 months, or development at 18 months.

OBJECTIVES: 1) to estimate the probability of inadequate amino acid intake among infants 9–10 months of age in rural Malawi 2) to evaluate whether dietary amino acid intake or protein quality are associated with length gain from 6 to 12 months of age METHODS: We assessed total amino acid intake from breast milk and complementary foods in 285 infants. Breast milk intake and complementary foods were estimated using dose-to-mother deuterium oxide dilution method and repeat 4-pass interactive 24-hour recall interviews, respectively. Amino acid composition values were taken from FAO human milk profile, Tanzania Food Composition table and International Minilist. Protein quality was estimated using Digestible Indispensable Amino Acid Score (DIAAS). Probability of intake below Estimated Average Requirement (EAR) for each amino acid was estimated using National Cancer Institute (NCI) method. We estimated protein quality of complementary food using median DIAAS. We assumed a DIAAS of ≥0.75 to represent a diet or food with good protein quality. Relationships between amino acid intake or protein quality with length gain were assessed using regression models. Length was measured at 6 and 12 months of age and length for age z-score (LAZ) velocity was calculated (ΔLAZ/months). RESULTS: The probability of inadequate amino acid intake from breast milk and complementary food that included a lipid-based nutrient supplement (LNS) was 3% for lysine, 0% for tryptophan, threonine, valine, histidine, isoleucine, leucine, sulfur containing amino acids (SAA), and aromatic amino acids (AAA). Without LNS, the probability was 7% for lysine and 0–2% for the other amino acids. The median (interquartile range) DIAAS for complementary food with and without LNS was 0.70 (0.28) and 0.64 (0.32), respectively. Dietary amino acid intake and protein quality were not significantly associated with length gain velocity from 6 to 12 months even after adjusting for confounding factors. CONCLUSIONS: The prevalence of inadequate amino acid intake in 9–10 months old infants in rural Malawi is very low. However, in conditions of frequent clinical or sub-clinical infections this situation may be different. Linear growth at 6–12 months does not appear to be limited by dietary amino acid intake or protein quality in this setting. FUNDING SOURCES: The Bill & Melinda Gates Foundation.

© 2015 Stewart et al. Background: Prenatal micronutrient supplements have been found to increase birth weight, but mechanisms for increased growth are poorly understood. Our hypotheses were that 1) women who receive lipid-based nutrient supplements (LNS) during pregnancy would have lower mean salivary cortisol concentration at 28 wk and 36 wk gestation compared to the multiple micronutrient (MMN) and iron-folic acid (IFA) supplement groups and 2) both salivary cortisol and perceived stress during pregnancy would be associated with shorter duration of gestation and smaller size at birth. Methods: Women were enrolled in the trial in early pregnancy and randomized to receive LNS, MMN, or iron-folic acid (IFA) supplements daily throughout pregnancy. At enrollment, 28 wk and 36 wk gestation, saliva samples were collected and their cortisol concentration was measured. Self-report of perceived stress was measured using questionnaires. Gestation duration was indicated by ultrasound dating and newborn anthropometric measurements (weight, length, head circumference) provided indicators of intrauterine growth. Results: Of the 1391 women enrolled in the trial, 1372, 906 and 1049 saliva samples were collected from women at baseline, 28 wk and 36 wk, respectively. There were no significant differences in mean cortisol concentrations by intervention group at 28 wk or 36 wk gestation. Cortisol concentrations were negatively associated with duration of gestation (Baseline: β = -0.05, p = 0.039; 36 wk: β = -0.04, p = 0.037) and birth weight (28 wk: β = -0.08, p = 0.035; 36 wk: β = -0.11, p = 0.003) but not associated with length-for-age or head circumference-for-age z-scores. Perceived stress at 36 wk was significantly associated with shorter newborn LAZ (p = 0.001). There were no significant associations with the risk of small for gestational age, preterm birth, or low birth weight. Conclusions: Maternal salivary cortisol concentration was strongly associated with birth weight and duration of gestation in rural Malawi, but these data do not support the hypothesis that LNS provision to pregnant women would influence their salivary cortisol concentrations. Trial registration: Clinicaltrials.gov identifier NCT01239693.

Exclusive breastfeeding is recommended during the first 6 months of life; thereafter, continued breastfeeding along with nutritious complementary foods is recommended. Continued breastfeeding contributes a substantial proportion of nutrient needs and promotes healthy growth and development, but the quantity of breast milk consumed may be highly variable and little is known about the factors associated with breast milk intake after 6 months of age. The present study was conducted to assess factors associated with breast milk intake of Malawian infants at 9–10 months of age. Breast milk intake was measured using the dose‐to‐mother deuterium oxide dilution method in a subsample of 358 Malawian infants who were participating in a randomized controlled trial of lipid‐based nutrient supplements. Regression analysis was used to assess associations between breast milk intake and several maternal and infant variables. Mean (standard deviation) breast milk intake was 752 (244) g day(–1). In multiple regression, breast milk intake was positively associated with infant weight (+62 g per kg body weight, P

BACKGROUND: Low intakes of good-quality complementary foods (CFs) contribute to undernutrition and consequently negatively affect health, growth, and development. Lipid-based nutrient supplements (LNSs) are designed to ensure dietary adequacy in micronutrients and essential fatty acids and to provide some energy and high-quality protein. In populations in which acute energy deficiency is rare, the dose-dependent effect of LNSs on CF intakes is unknown. OBJECTIVE: The objective of this study was to evaluate the difference in energy and macronutrient intakes from CF between a control (no supplement) group and 3 groups that received 10, 20, or 40 g LNS/d. METHODS: We collected repeated interactive 24-h dietary recalls from caregivers of rural Malawian 9- to 10-mo-old infants (n = 748) to estimate dietary intakes (LNS and all non-breast-milk foods) of energy and macronutrients and their dietary patterns. All infants were participating in a 12-mo randomized controlled trial to investigate the efficacy of various doses of LNS for preventing undernutrition. RESULTS: Dietary energy intakes were significantly higher among infants in the LNS intervention groups than in the control group (396, 406, and 388 kcal/d in the 10-, 20-, and 40-g LNS/d groups, respectively, compared with 345 kcal/d; each pairwise P < 0.05), but no significant differences were found in energy intakes between groups who were administered the different LNS doses (10 g LNS/d compared with 20 g LNS/d: P = 0.72; 10 g LNS/d compared with 40 g LNS/d: P ≥ 0.67; 20 g LNS/d compared with 40 g LNS/d: P = 0.94). Intakes of protein and fat were significantly higher in the LNS intervention groups than in the control group. No significant intergroup differences were found in median intakes of energy from non-LNS CFs (357, 347, and 296 kcal/d in the 10-, 20-, and 40-g LNS/d groups, respectively, compared with 345 kcal/d in the control group; P = 0.11). CONCLUSION: LNSs in doses of 10-40 g/d increase intakes of energy and macronutrients among 9- to 10-mo-old Malawian infants, without displacing locally available CFs. This trial was registered at clinicaltrials.gov as NCT00945698.

BACKGROUND: Complementing infant diets with lipid-based nutrient supplements (LNSs) has been suggested to improve growth and reduce morbidity but the daily quantity and the milk content of LNSs affect their cost. OBJECTIVE: We tested the hypotheses that the change in mean length-for-age z score (LAZ) for infants provided with 10-40 g LNSs/d from ages 6 to 18 mo would be greater than that for infants receiving no dietary intervention at the same age and that provision of LNSs that did not contain milk would be as good as milk-containing LNSs in promoting linear growth. METHODS: We enrolled in a randomized single-blind trial 6-mo-old infants who were allocated to 1 of 6 groups to receive 10 20 or 40 g LNSs/d containing milk powder; 20 or 40 g milk-free LNSs/d; or no supplement until 18 mo of age. The primary outcome was change in LAZ. RESULTS: Of the 1932 enrolled infants 78 (4.0%) died and 319 (16.5%) dropped out during the trial. The overall reported supplement consumption was 71.6% of days with no difference between the groups (P = 0.26). The overall mean +/- SD length and LAZ changes were 13.0 +/- 2.1 cm and -0.45 +/- 0.77 z score units respectively which did not differ between the groups (P = 0.66 for length and P = 0.74 for LAZ). The difference in mean LAZ change in the no-milk LNS group compared with the milk LNS group was -0.02 (95% CI: -0.10 0.06; P = 0.72). CONCLUSION: Our results do not support the hypothesis that LNS supplementation during infancy and childhood promotes length gain or prevents stunting between 6 and 18 mo of age in Malawi. This trial was registered at clinicaltrials.gov as NCT00945698. (c) 2015 American Society for Nutrition.

BACKGROUND The potential for small-quantity lipid-based nutrient supplements (LNS) to promote growth and development after 6 mo of age is currently being investigated. Because infants self-regulate energy intake, consumption of LNS may reduce breast milk intake and potentially decrease the beneficial effects of breast milk. OBJECTIVE The objective was to test the hypothesis that the breast milk intake of 9- to 10-mo-old rural Malawian infants receiving LNS would not be lower than that of infants receiving no supplementation. DESIGN This was a substudy of the International Lipid-based Nutrient Supplements (iLiNS) DOSE trial, in which 6-mo-old infants were randomly assigned to receive 10, 20, or 40 g LNS/d containing 56, 117, or 241 kcal/d, respectively, or no LNS until 18 mo of age. A subset was randomly selected to estimate breast milk intake at 9-10 mo of age with the dose-to-mother deuterium oxide dilution method. The noninferiority margin was