Low nutritional value of complementary foods is associated with high incidence of childhood growth stunting in low-income countries. This study was done to test a hypothesis that dietary complementation with lipid-based nutrient supplements (LNS) promotes linear growth and reduces the incidence of severe stunting among at-risk infants. A total of 840 6-month-old healthy infants in rural Malawi were enrolled to a randomised assessor-blinded trial. The participants received 12-month supplementation with nothing, milk-LNS, soy-LNS, or corn-soy blend (CSB). Supplements provided micronutrients and approximately 280 kcal energy per day. Outcomes were incidence of severe and very severe stunting [length-for-age z-score, (LAZ) < -3.00 and <-3.50, respectively], and change in LAZ. The incidence of severe stunting was 11.8%, 8.2%, 9.1% and 15.5% (P = 0.098) and that of very severe stunting 7.4%, 2.9%, 8.0% and 6.4% (P = 0.138) in control, milk-LNS, soy-LNS and CSB groups, respectively. Between 9 and 12 months of age, the mean change in LAZ was -0.15, -0.02, -0.12 and -0.18 (P = 0.045) for control, milk-LNS, soy-LNS and CSB groups, respectively. There was no significant between-group difference in linear growth during other age-intervals. Although participants who received milk-LNS had the lowest incidence of severe and very severe stunting, the differences between the groups were smaller than expected. Thus, the results do not provide conclusive evidence on a causal association between the LNS supplementation and the lower incidence of stunting. Exploratory analyses suggest that provision of milk-LNS, but not soy-LNS promotes linear growth among at-risk infants mainly between 9 and 12 months of age.

Objective

Safety of home fortificants in children is uncertain in areas where infections are common. We tested the hypothesis that provision of lipid-based nutrient supplements (LNS) containing Fe does not increase infectious morbidity in children.

Design

Randomized controlled trial. Infants were randomised to receive 10, 20 or 40 g LNS/d; or no supplement until age 18 months. All LNS contained 6 mg Fe/d. Morbidity outcomes (serious adverse events, non-scheduled visits and guardian-reported morbidity episodes) were compared between control and intervention groups using a non-inferiority margin of 20 %.

Setting

Namwera and Mangochi catchment areas in rural Malawi.

Subjects

Infants aged 6 months (n 1932).

Results

The enrolled 1932 infants contributed 1306 child-years of follow-up. Baseline characteristics were similar across groups. Compared with the control group, the relative risk (95 % CI) of serious adverse events was 0·71 (0·48, 1·07), 0·67 (0·48, 0·95) and 0·91 (0·66, 1·25) in 10, 20 and 40 g LNS/d groups, respectively. The incidence rate ratio (95 % CI) of non-scheduled visits due to malaria was 1·10 (0·88, 1·37), 1·08 (0·89, 1·31) and 1·21 (1·00, 1·46), and of guardian-reported morbidity episodes was 1·04 (0·96, 1·11), 1·03 (0·97, 1·10) and 1·04 (0·97, 1·10), in the respective LNS groups.

Conclusions

Provision of 10 and 20 g LNS/d containing 6 mg Fe/d did not increase morbidity in the children. Provision of 40 g LNS/d did not affect guardian-reported illness episodes but may have increased malaria-related non-scheduled visits.

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 < 0.01) and maternal height (P < 0.01) and negatively associated with maternal education and age (P < 0.01). There was a non-significant (P = 0.063) inverse association between energy from non-breast milk sources and breast milk intake. In this rural Malawian population, infant weight is the main predictor of breast milk intake, even after the first 6 months of life.

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.

Background

Although poor complementary feeding is associated with poor child growth, nutrition interventions only have modest impact on child growth, due to high burden of infections. We aimed to assess the association of malaria with linear growth, hemoglobin, iron status, and development in children aged 6-18 months in a setting of high malaria and undernutrition prevalence.

Methods

Prospective cohort study, conducted in Mangochi district, Malawi. We enrolled six-months-old infants and collected weekly data for 'presumed' malaria, diarrhea, and acute respiratory infections (ARI) until age 18 months. Change in length-for-age z-scores (LAZ), stunting, hemoglobin, iron status, and development were assessed at age 18 months. We used ordinary least squares regression for continuous outcomes and modified Poisson regression for categorical outcomes.

Results

Of the 2723 children enrolled, 2016 (74.0%) had complete measurements. The mean (standard deviation) incidences of 'presumed' malaria, diarrhea, and ARI, respectively were: 1.4 (2.0), 4.6 (10.1), and 8.3 (5.0) episodes/child year. Prevalence of stunting increased from 27.4 to 41.5% from 6 to 18 months. 'Presumed' malaria incidence was associated with higher risk of stunting (risk ratio [RR] = 1.04, 95% confidence interval [CI] = 1.01 to 1.07, p = 0.023), anemia (RR = 1.02, 95%CI = 1.00 to 1.04, p = 0.014) and better socio-emotional scores (B = - 0.21, 95%CI = - 0.39 to - 0.03, p = 0.041), but not with change in LAZ, haemoglobin, iron status or other developmental outcomes. Diarrhea incidence was associated with change in LAZ (B = - 0.02; 95% CI = - 0.03 to - 0.01; p = 0.009), stunting (RR = 1.02; 95% CI = 1.01 to 1.03; p = 0.005), and slower motor development. ARI incidence was not associated with any outcome except for poorer socio-emotional scores.

Conclusion

In this population of young children living in a malaria-endemic setting, with active surveillance and treatment, 'presumed' malaria is not associated with change in LAZ, hemoglobin, or iron status, but could be associated with stunting and anemia. Diarrhea was more consistently associated with growth than was malaria or ARI. The findings may be different in contexts where active malaria surveillance and treatment is not provided.

Trial registration

NCT00945698 (July 24, 2009) and NCT01239693 (November 11, 2010).

Pregnant and post-partum women require increased nutrient intake and optimal cognition, which depends on adequate nutrition, to enable reasoning and learning for caregiving. We aimed to assess (a) differences in maternal cognition and caregiving between women in Malawi who received different nutritional supplements, (b) 14 effect modifiers, and (c) associations of cognition and caregiving with biomarkers of iron, Vitamin A, B-vitamin, and fatty acid status. In a randomized controlled trial (n = 869), pregnant women daily received either multiple micronutrients (MMN), 20 g/day lipid-based nutrient supplements (LNS), or a control iron/folic acid (IFA) tablet. After delivery, supplementation continued in the MMN and LNS arms, and the IFA control group received placebo until 6 months post-partum, when cognition (n = 712), caregiving behaviour (n = 669), and biomarkers of nutritional status (n = 283) were assessed. In the full group, only one difference was significant: the IFA arm scored 0.22 SD (95% CI [0.01, 0.39], p = .03) higher than the LNS arm in mental rotation. Among subgroups of women with baseline low hemoglobin, poor iron status, or malaria, those who received LNS scored 0.4 to 0.7 SD higher than the IFA arm in verbal fluency. Breastmilk docosahexaenoic acid and Vitamin B12 concentrations were positively associated with verbal fluency and digit span forward (adjusting for covariates ps < .05). In this population in Malawi, maternal supplementation with MMN or LNS did not positively affect maternal cognition or caregiving. Maternal docosahexaenoic acid and B12 status may be important for post-partum attention and executive function.

Background

Since the adoption of United Nations' Sustainable Goal 4.2 to ensure that all children have access to quality early child development (ECD) so that they are ready for primary education, the demand for valid ECD assessments has increased in contexts where they do not yet exist. The development of early language ability is important for school readiness. Our objective was to evaluate the validity of a method to develop vocabulary checklists in new languages to assess early language development, based on the MacArthur-Bates Communicative Development Inventories.

Methods

Through asking mothers of young children what words their children say and through pilot testing, we developed 100-word vocabulary checklists in multilingual contexts in Malawi and Ghana. In Malawi, we evaluated the validity of the vocabulary checklist among 29 children age 17-25 months compared to three language measures assessed concurrently: Developmental Milestones Checklist-II (DMC-II) language scale, Malawi Developmental Assessment Tool (MDAT) language scale, and the number of different words (NDW) in 30-min recordings of spontaneous speech. In Ghana, we assessed the predictive validity of the vocabulary checklist at age 18 months to forecast language, pre-academic, and other skills at age 4-6 years among 869 children. We also compared the predictive validity of the vocabulary checklist scores to that of other developmental assessments administered at age 18 months.

Results

In Malawi, the Spearman's correlation of the vocabulary checklist score with DMC-II language was 0.46 (p = 0.049), with MDAT language was 0.66 (p = 0.016) and with NDW was 0.50 (p = 0.033). In Ghana, the 18-month vocabulary checklist score showed the strongest (rho = 0.12-0.26) and most consistent (8/12) associations with preschool scores, compared to the other 18-month assessments. The largest coefficients were the correlations of the 18-month vocabulary score with the preschool cognitive factor score (rho = 0.26), language score (0.25), and pre-academic score (0.24).

Conclusions

We have demonstrated the validity of a method to develop vocabulary checklists in new languages, which can be used in multilingual contexts, using a feasible adaptation process requiring about 2 weeks. This is a promising method to assess early language development, which is associated with later preschool language, cognitive, and pre-academic skills.

Background

Small-quantity (SQ) lipid-based nutrient supplements (LNSs) provide many nutrients needed for brain development.

Objectives

We aimed to generate pooled estimates of the effect of SQ-LNSs on developmental outcomes (language, social-emotional, motor, and executive function), and to identify study-level and individual-level modifiers of these effects.

Methods

We conducted a 2-stage meta-analysis of individual participant data from 14 intervention against control group comparisons in 13 randomized trials of SQ-LNSs provided to children age 6-24 mo (total n = 30,024).

Results

In 11-13 intervention against control group comparisons (n = 23,588-24,561), SQ-LNSs increased mean language (mean difference: 0.07 SD; 95% CI: 0.04, 0.10 SD), social-emotional (0.08; 0.05, 0.11 SD), and motor scores (0.08; 95% CI: 0.05, 0.11 SD) and reduced the prevalence of children in the lowest decile of these scores by 16% (prevalence ratio: 0.84; 95% CI: 0.76, 0.92), 19% (0.81; 95% CI: 0.74, 0.89), and 16% (0.84; 95% CI: 0.76, 0.92), respectively. SQ-LNSs also increased the prevalence of children walking without support at 12 mo by 9% (1.09; 95% CI: 1.05, 1.14). Effects of SQ-LNSs on language, social-emotional, and motor outcomes were larger among study populations with a higher stunting burden (≥35%) (mean difference: 0.11-0.13 SD; 8-9 comparisons). At the individual level, greater effects of SQ-LNSs were found on language among children who were acutely malnourished (mean difference: 0.31) at baseline; on language (0.12), motor (0.11), and executive function (0.06) among children in households with lower socioeconomic status; and on motor development among later-born children (0.11), children of older mothers (0.10), and children of mothers with lower education (0.11).

Conclusions

Child SQ-LNSs can be expected to result in modest developmental gains, which would be analogous to 1-1.5 IQ points on an IQ test, particularly in populations with a high child stunting burden. Certain groups of children who experience higher-risk environments have greater potential to benefit from SQ-LNSs in developmental outcomes.This trial was registered at www.crd.york.ac.uk/PROSPERO as CRD42020159971.

Background

Small-quantity lipid-based nutrient supplements (SQ-LNS) reduce child stunting and provide many of the fatty acids and micronutrients that are necessary for rapid brain development that occurs during infancy and early childhood. Positive effects of SQ-LNS on developmental outcomes have been found in some trials, but not others.

Objectives

Our objectives were to generate pooled estimates of the effect of SQ-LNS, compared to control groups that received no intervention or an intervention without any nutritional supplement, on developmental outcomes (language, social-emotional, motor, and executive function), and to identify study-level and individual-level modifiers of these effects.

Methods

We conducted a two-stage meta-analysis of individual participant data from 14 intervention versus control group comparisons in 13 randomized trials of SQ-LNS provided to infants and young children age 6 to 24 months in 9 low- or middle-income countries (total n=30,024). We generated study-specific estimates of SQ-LNS vs. control groups (including main effects and subgroup estimates for individual-level effect modifiers) and pooled the estimates using fixed-effects models. We used random effects meta-regression to examine potential study-level effect modifiers.

Results

In 11-13 intervention versus control group comparisons (n=23,588-24,561), SQ-LNS increased mean language (mean difference: 0.07 standard deviations; 95% CI: 0.04, 0.10), social-emotional (0.08; 0.05, 0.11), and motor scores (0.08; 0.05, 0.11) and reduced the prevalence of children in the lowest decile of these scores by 17% (prevalence ratio: 0.83, 95% CI 0.76, 0.91), 19% (0.81; 0.74, 0.90), and 16% (0.84; 0.77, 0.92), respectively. SQ-LNS also increased the prevalence of children walking without support at 12 months by 9% (1.09; 1.05, 1.14). Effects of SQ-LNS on language, social-emotional, and motor outcomes were larger among study populations with a higher burden (≥ 35%) of child stunting at 18 months (mean difference 0.11-0.13 SD; 8-9 comparisons) than in populations with lower stunting burden (estimates near zero). At the individual level, greater effects of SQ-LNS were found on language among children who were acutely malnourished (mean difference: 0.31) at baseline; on language (0.12), motor (0.11), and executive function (0.06) among children in households with lower socio-economic status; and on motor development among later-born children (0.11), children of older mothers (0.10), and children of mothers with lower education (0.11).

Conclusions

SQ-LNS provided daily to children in the range of 6-24 months of age can be expected to result in modest, but potentially important, developmental gains, particularly in populations with high child stunting burden. Certain groups of children who experience higher risk environments, such as those from poor households or with poor baseline nutritional status, have greater potential to benefit from SQ-LNS in developmental outcomes. This study was registered at www.crd.york.ac.uk/PROSPERO as CRD42020159971.