The cost-effectiveness of small-quantity lipid-based nutrient supplements for prevention of child death and malnutrition and promotion of healthy development: modelling results for Uganda.

OBJECTIVE: Recent meta-analyses demonstrate that small-quantity lipid-based nutrient supplements (SQ-LNS) for young children significantly reduce child mortality, stunting, wasting, anaemia and adverse developmental outcomes. Cost considerations should inform policy decisions. We developed a modelling framework to estimate the cost and cost-effectiveness of SQ-LNS and applied the framework in the context of rural Uganda. DESIGN: We adapted costs from a costing study of micronutrient powder (MNP) in Uganda, and based effectiveness estimates on recent meta-analyses and Uganda-specific estimates of baseline mortality and the prevalence of stunting, wasting, anaemia and developmental disability. SETTING: Rural Uganda. PARTICIPANTS: Not applicable. RESULTS: Providing SQ-LNS daily to all children in rural Uganda (> 1 million) for 12 months (from 6 to 18 months of age) via the existing Village Health Team system would cost ∼$52 per child (2020 US dollars) or ∼$58·7 million annually. SQ-LNS could avert an average of > 242 000 disability-adjusted life years (DALYs) annually as a result of preventing 3689 deaths, > 160 000 cases of moderate or severe anaemia and ∼6000 cases of developmental disability. The estimated cost per DALY averted is $242. CONCLUSIONS: In this context, SQ-LNS may be more cost-effective than other options such as MNP or the provision of complementary food, although the total cost for a programme including all age-eligible children would be high. Strategies to reduce costs, such as targeting to the most vulnerable populations and the elimination of taxes on SQ-LNS, may enhance financial feasibility.

The association between plasma choline, growth and neurodevelopment among Malawian children aged 6-15 months enroled in an egg intervention trial.

Choline is an essential micronutrient that may influence growth and development; however, few studies have examined postnatal choline status and children's growth and development in low- and middle-income countries. The aim of this observational analysis was to examine associations of plasma choline with growth and development among Malawian children aged 6-15 months enrolled in an egg intervention trial. Plasma choline and related metabolites (betaine, dimethylglycine and trimethylamine N-oxide) were measured at baseline and 6-month follow-up, along with anthropometric (length, weight, head circumference) and developmental assessments (the Malawi Developmental Assessment Tool [MDAT], the Infant Orienting with Attention task [IOWA], a visual paired comparison [VPC] task and an elicited imitation [EI] task). In cross-sectional covariate-adjusted models, each 1 SD higher plasma choline was associated with lower length-for-age z-score (-0.09 SD [95% confidence interval, CI -0.17 to -0.01]), slower IOWA response time (8.84 ms [1.66-16.03]) and faster processing speed on the VPC task (-203.5 ms [-366.2 to -40.7]). In predictive models, baseline plasma choline was negatively associated with MDAT fine motor z-score at 6-month follow-up (-0.13 SD [-0.22 to -0.04]). There were no other significant associations of plasma choline with child measures. Similarly, associations of choline metabolites with growth and development were null except higher trimethylamine N-oxide was associated with slower information processing on the VPC task and higher memory scores on the EI task. In this cohort of children with low dietary choline intake, we conclude that there were no strong or consistent associations between plasma choline and growth and development.

Impacts of an egg complementary feeding trial on energy intake and dietary diversity in Malawi.

Complementary feeding diets in low- and middle-income countries are generally inadequate to meet requirements for growth and development. Food-based interventions may prevent nutrient inadequacies provided that they do not displace other nutrient-rich foods. We conducted a randomized controlled trial in rural Malawi in which 660 children aged 6 to 9 months were provided an egg a day for 6 months or assigned to a control group. Dietary intake of complementary foods and drinks was assessed at baseline, 3-month midline and 6-month endline visits using a tablet-based multipass 24-h recall. Up to two repeat recalls were collected at each time point in a subsample of 100 children per treatment group. At midline and endline, usual energy intake from eggs was about 30 kcal/day higher in the egg group compared with controls (p < 0.0001). Compared with controls, children in the egg group were over nine times more likely to consume eggs at midline and endline. There was a comparable, but nonsignificant, greater total usual energy intake from complementary foods of 30 kcal/day at midline (p = 0.128) and 36 kcal/day at endline (p = 0.087). There also was a displacement of 7 kcal/day in legumes and nuts in children at endline (p = 0.059). At midline and endline, more than 80% of children in the egg group consumed a minimally diverse diet compared with 53% at midline and 60% at endline in the control group. This study illustrates that mothers in the egg group fed eggs to young children on a regular basis without substantial displacement of other complementary foods.

Early Child Development Outcomes of a Randomized Trial Providing 1 Egg Per Day to Children Age 6 to 15 Months in Malawi.

BACKGROUND: Eggs are a rich source of nutrients important for brain development, including choline, riboflavin, vitamins B-6 and B-12, folate, zinc, protein, and DHA. OBJECTIVE: Our objective was to evaluate the effect of the consumption of 1 egg per day over a 6-mo period on child development. METHODS: In the Mazira Project randomized controlled trial, 660 children aged 6-9 mo were randomly allocated into an intervention or control group. Eggs were provided to intervention households during twice-weekly home visits for 6 mo. Control households were visited at the same frequency. At enrollment, blinded assessors administered the Malawi Developmental Assessment Tool (MDAT), and 2 eye-tracking tasks using a Tobii-Pro X2-60 eye tracker: a visual paired comparison memory task and an Infant Orienting with Attention task. At endline, 6-mo later, blinded assessors administered the MDAT and eye-tracking tasks plus an additional elicited imitation memory task. RESULTS: At endline, intervention and control groups did not significantly differ in any developmental score, with the exception that a smaller percentage of children were delayed in fine motor development in the intervention group (10.6%) compared with the control group (16.5%; prevalence ratio: 0.59, 95% CI: 0.38-0.91). Among 10 prespecified effect modifiers for the 8 primary developmental outcomes, we found 7 significant interactions demonstrating a consistent pattern that children who were less vulnerable, for example, those with higher household wealth and maternal education, showed positive effects of the intervention. Given multiple hypothesis testing, some findings may have been due to chance. CONCLUSION: The provision of 1 egg per day had no overall effect on child development in this population of children, however, some benefits may be seen among children in less vulnerable circumstances. This trial was registered at clinicaltrials.gov as NCT03385252.

Maternal Multiple Micronutrient Supplementation Stabilizes Mitochondrial DNA Copy Number in Pregnant Women in Lombok, Indonesia.

BACKGROUND: The Supplementation with Multiple Micronutrients Intervention Trial (SUMMIT) in Lombok, Indonesia showed that maternal multiple micronutrients (MMN), as compared with iron and folic acid (IFA), reduced fetal loss, early infant mortality, and low birth weight. Mitochondria play a key role during pregnancy by providing maternal metabolic energy for fetal development, but the effects of maternal supplementation during pregnancy on mitochondria are not fully understood. OBJECTIVE: The aim of this study was to assess the impact of MMN supplementation on maternal mitochondrial DNA copy number (mtDNA-CN). METHODS: We used archived venous blood specimens from pregnant women enrolled in the SUMMIT study. SUMMIT was a cluster-randomized double-blind controlled trial in which midwives were randomly assigned to distribute MMN or IFA to pregnant women. In this study, we selected 108 sets of paired baseline and postsupplementation samples (MMN = 54 and IFA = 54). Maternal mtDNA-CN was determined by real-time quantitative polymerase chain reaction in baseline and postsupplementation specimens. The association between supplementation type and change in mtDNA-CN was performed using rank-based estimation for linear models. RESULTS: In both groups, maternal mtDNA-CN at postsupplementation was significantly elevated compared with baseline (P < 0.001). The regression revealed that the MMN group had lower postsupplementation mtDNA-CN than the IFA group (ß = -4.63, P = 0.003), especially for women with mtDNA-CN levels above the median at baseline (ß = -7.49, P = 0.007). This effect was rapid, and observed within 33 d of initiation of supplementation (ß = -7.39, P = 0.017). CONCLUSION: Maternal MMN supplementation rapidly stabilized mtDNA-CN in pregnant women who participated in SUMMIT, indicating improved mitochondrial efficiency. The data provide a mechanistic basis for the beneficial effects of MMN on fetal growth and survival, and support the transition from routine IFA to MMN supplementation.This trial was registered at www.isrctn.com as ISRCTN34151616.

Maternal-Infant Supplementation with Small-Quantity Lipid-Based Nutrient Supplements Does Not Affect Child Blood Pressure at 4-6 Y in Ghana: Follow-up of a Randomized Trial.

BACKGROUND: In the International Lipid-Based Nutrient Supplements (iLiNS)-DYAD-Ghana trial, prenatal small-quantity lipid-based nutrient supplements (LNSs) had a positive effect on birth weight. Birth weight may be inversely related to blood pressure (BP) later in life. OBJECTIVES: We examined the effect of the intervention on BP at 4-6 y of age, and maternal and child factors related to BP. METHODS: The iLiNS-DYAD-Ghana study was a partially double-blind, randomized controlled trial which assigned women (n = 1320) ≤20 weeks of gestation to daily supplementation with: 1) iron and folic acid during pregnancy and 200 mg Ca for 6 mo postpartum , 2) multiple micronutrients during pregnancy and postpartum, or 3) LNSs during pregnancy and postpartum plus LNSs for infants from 6 to 18 mo of age. At 4-6 y of age (n = 858, 70% of live births), we compared BP, a secondary outcome, between non-LNS and LNS groups and examined whether BP was related to several factors including maternal BP, child weight-for-age z score (WAZ), and physical activity. RESULTS: Non-LNS and LNS groups did not differ in systolic (99.2 ± 0.4 compared with 98.5 ± 0.6 mm Hg; P = 0.317) or diastolic (60.1 ± 0.3 compared with 60.0 ± 0.4 mm Hg; P = 0.805) BP, or prevalence of high BP (systolic or diastolic BP ≥90th percentile of the US National Heart, Lung, and Blood Institute reference: 31% compared with 28%; P = 0.251). BP at 4-6 y of age was positively related to birth weight; this relation was largely mediated through concurrent WAZ in a path model. Concurrent WAZ and maternal BP were the factors most strongly related to child BP. CONCLUSIONS: Despite greater birth weight in the LNS group, there was no intervention group difference in BP at 4-6 y. In this preschool population at high risk of adult hypertension based on BP at 4-6 y, high maternal BP and child WAZ were key factors related to BP. This trial was registered at clinicaltrials.gov as NCT00970866.

Maternal and Infant Lipid-Based Nutritional Supplementation Increases Height of Ghanaian Children at 4-6 Years Only if the Mother Was Not Overweight Before Conception.

BACKGROUND: Few studies have evaluated the long-term effects of nutritional supplementation during the first 1000 d of life. We previously reported that maternal and child lipid-based nutrient supplements (LNS) increased child length by 18 mo. OBJECTIVE: The aim of this study was to examine the effects of LNS on later growth and body composition at 4-6 y of age. DESIGN: This was a follow-up of children in the International Lipid-based Nutrient Supplements (iLiNS)-DYAD trial in Ghana. Women (n = 1320) at ≤20 weeks of gestation were randomly assigned to: 1) iron and folic acid during pregnancy and 200 mg calcium/d for 6 mo postpartum, 2) multiple micronutrients (1-2 RDA of 18 vitamins and minerals) during both periods, or 3) maternal LNS during both periods plus child LNS from 6 to 18 mo. At 4-6 y, we compared height, height-for-age z score (HAZ), and % body fat (deuterium dilution method) between the LNS group and the 2 non-LNS groups combined. RESULTS: Data were available for 961 children (76.5% of live births). There were no significant differences between LNS compared with non-LNS groups in height [106.7 compared with 106.3 cm (mean difference, MD, 0.36; P = 0.226)], HAZ [-0.49 compared with -0.57 (MD = 0.08; P = 0.226)], stunting (< -2 SD) [6.5 compared with 6.3% (OR = 1.00; P = 0.993)], or % body fat [15.5 compared with 15.3% (MD = 0.16; P = 0.630)]. However, there was an interaction with maternal prepregnancy BMI (kg/m2) (P-interaction = 0.046 before correction for multiple testing): among children of women with BMI < 25 , LNS children were taller than non-LNS children (+1.1 cm, P = 0.017), whereas there was no difference among children of women with BMI ≥ 25 (+0.1 cm; P = 0.874). CONCLUSIONS: There was no overall effect of LNS on height at 4-6 y in this cohort, which had a low stunting rate, but height was greater in the LNS group among children of nonoverweight/obese women. There was no adverse impact of LNS on body composition. This trial was registered at clinicaltrials.gov as NCT00970866.

The effects of supplementing maternal and infant diets with lipid-based nutrient supplements on physical activity and sedentary behaviour at preschool age in Ghana.

Evidence on whether nutritional supplementation affects physical activity (PA) during early childhood is limited. We examined the long-term effects of lipid-based nutrient supplements (LNS) on total PA, moderate-to-vigorous PA (MVPA) and sedentary behaviour (SB) of children at 4-6 years using an accelerometer for 1 week. Their mothers were enrolled in the International Lipid-based Nutrient Supplement-DYAD randomised controlled trial in Ghana, assigned to daily LNS or multiple micronutrients (MMN) during pregnancy through 6 months postpartum or Fe and folic acid (IFA) during pregnancy and placebo for 6 months postpartum. From 6 to 18 months, children in the LNS group received LNS; the other two groups received no supplements. Analysis was done with intention to treat comparing two groups: LNS v. non-LNS (MMN+ IFA). Of the sub-sample of 375 children fitted with accelerometers, 353 provided sufficient data. Median vector magnitude (VM) count was 1374 (interquartile range (IQR) 309), and percentages of time in MVPA and SB were 4·8 (IQR 2) and 31 (IQR 8) %, respectively. The LNS group (n 129) had lower VM (difference in mean -73 (95 % CI -20, -126), P = 0·007) and spent more time in SB (LNS v. non-LNS: 32·3 v. 30·5 %, P = 0·020) than the non-LNS group (n 224) but did not differ in MVPA (4·4 v. 4·7 %, P = 0·198). Contrary to expectations, provision of LNS in early life slightly reduced the total PA and increased the time in SB but did not affect time in MVPA. Given reduced social-emotional difficulties in the LNS group previously reported, including hyperactivity, one possible explanation is less restless movement in the LNS group.

Associations between antenatal depression and neonatal outcomes in Malawi.

Studies from several low- and middle-income countries have shown that antenatal depression may be a risk factor for poor neonatal outcomes. However, those studies conducted in sub-Saharan Africa have not consistently demonstrated this association. We set out to investigate whether antenatal depression is associated with shorter duration of pregnancy and reduced newborn size in rural Malawi. Pregnant women recruited from four antenatal clinics to the International Lipid-Based Nutrient Supplements Project-DYAD-Malawi (iLiNS-DYAD-M) randomised controlled trial of nutrient supplementation were screened for antenatal depression in the second or third trimester using a locally validated version of the Self Reporting Questionnaire (SRQ). Outcomes were duration of pregnancy, birthweight, newborn length for age z-score (LAZ), head circumference z-score, and mid-upper arm circumference (MUAC). Other potential confounding factors and predictors of birth outcome were measured and adjusted for in the analysis. 1,391 women were enrolled to the trial. 1,006/1,391 (72.3%) of these women completed an SRQ and gave birth to a singleton infant whose weight was measured within 2 weeks of birth. 143/1,006 (14.2%) scored SRQ ≥ 8, indicating likely depression. Antenatal depression was not associated with birth weight, duration of pregnancy, newborn LAZ, or head-circumference Z-score. There was an inverse association with newborn MUAC (adjusted mean difference - 0.2 cm (95% CI -0.4 to 0, p = 0.021) the significance of which is unclear. The study was conducted within a randomised controlled trial of nutritional supplementation and there was a high proportion of missing data in some enrolment sites; this may have affected the validity of our findings.

The association of early linear growth and haemoglobin concentration with later cognitive, motor, and social-emotional development at preschool age in Ghana.

It is important to identify the periods during childhood when exposure to environmental risk factors results in long-term neurodevelopmental deficits. Stunting and anaemia may be sensitive indicators of exposure to such risks. In a prospective cohort enrolled before birth, we investigated the association of developmental scores at 4-6 years with (a) birth length and linear growth during three postnatal periods and (2) haemoglobin (Hb) concentration at three time points. Children were participants in a follow-up study of a randomized controlled trial of nutritional supplementation in Ghana. At 4-6 years, cognitive, motor, and social-emotional developments were assessed using standard tests adapted for this population. We estimated the associations of length-for-age z-score (LAZ) at birth and postnatal linear growth (n = 710) and Hb (n = 617) with developmental scores in regression models, using multistage least squares analysis to calculate uncorrelated residuals for postnatal growth. Cognitive development at 4-6 years was significantly associated with LAZ at birth (ß = 0.12, 95% CI = 0.05, 0.19), ΔLAZ from 6 to 18 months (ß = 0.16, 95% CI = 0.04, 0.28), and Hb at 18 months (ß = 0.13, 95% CI = 0.06, 0.20), but not with ΔLAZ during 0-6 months, ΔLAZ from 18 months to 4-6 years, Hb at 6 months, or Hb at 4-6 years. No evidence of associations with motor or social-emotional development were found. These results suggest that in similar contexts, the earlier periods prior to birth and up to 18 months are more sensitive to risk factors for long-term cognitive development associated with LAZ and Hb compared with later childhood. This may inform the optimal timing of interventions targeting improved cognitive development.

The association of malaria morbidity with linear growth, hemoglobin, iron status, and development in young Malawian children: a prospective cohort study.

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).

Associations of maternal nutrition during pregnancy and post-partum with maternal cognition and caregiving.

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.

Association between breast milk intake at 9-10 months of age and growth and development among Malawian young children.

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 (ß = -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.

Predictors and pathways of language and motor development in four prospective cohorts of young children in Ghana, Malawi, and Burkina Faso.

BACKGROUND: Previous reviews have identified 44 risk factors for poor early child development (ECD) in low- and middle-income countries. Further understanding of their relative influence and pathways is needed to inform the design of interventions targeting ECD. METHODS: We conducted path analyses of factors associated with 18-month language and motor development in four prospective cohorts of children who participated in trials conducted as part of the International Lipid-Based Nutrient Supplements (iLiNS) Project in Ghana (n = 1,023), Malawi (n = 675 and 1,385), and Burkina Faso (n = 1,122). In two cohorts, women were enrolled during pregnancy. In two cohorts, infants were enrolled at 6 or 9 months. In multiple linear regression and structural equation models (SEM), we examined 22 out of 44 factors identified in previous reviews, plus 12 additional factors expected to be associated with ECD. RESULTS: Out of 42 indicators of the 34 factors examined, 6 were associated with 18-month language and/or motor development in 3 or 4 cohorts: child linear and ponderal growth, variety of play materials, activities with caregivers, dietary diversity, and child hemoglobin/iron status. Factors that were not associated with child development were indicators of maternal Hb/iron status, maternal illness and inflammation during pregnancy, maternal perceived stress and depression, exclusive breastfeeding during 6 months postpartum, and child diarrhea, fever, malaria, and acute respiratory infections. Associations between socioeconomic status and language development were consistently mediated to a greater extent by caregiving practices than by maternal or child biomedical conditions, while this pattern for motor development was not consistent across cohorts. CONCLUSIONS: Key elements of interventions to ensure quality ECD are likely to be promotion of caregiver activities with children, a variety of play materials, and a diverse diet, and prevention of faltering in linear and ponderal growth and improvement in child hemoglobin/iron status.

The impact of maternal diet fortification with lipid-based nutrient supplements on postpartum depression in rural Malawi: a randomised-controlled trial.

Perinatal depression is highly prevalent in low-and-middle-income countries and has been linked to poor child health. Suboptimal maternal nutrition may be a risk factor for perinatal depression. In this randomised-controlled trial conducted in rural Malawi, we set out to test the hypothesis that women taking a fatty acid-rich lipid-based nutrient supplement (LNS) would have fewer depressive symptoms postpartum than those taking iron-folate (IFA) or multiple-micronutrient (MMN) capsules. Women were recruited from antenatal clinics and randomised to receive LNS or MMN during pregnancy and for 6 months postpartum, or IFA during pregnancy only. Maternal depressive symptoms were measured using validated translations of the Self Reporting Questionnaire (SRQ) and Edinburgh Postnatal Depression Scale (EPDS), antenatally (SRQ only) and at 6 months postpartum (SRQ and EPDS). Analysis was by modified intention to treat. One thousand three hundred and ninety one women were randomised (LNS = 462, MMN = 466, IFA = 463). The groups were similar across a range of baseline variables. At 6 months postpartum, 1078 (77.5%) had SRQ completed; mean (SD) scores were LNS 1.76(2.73), MMN 1.92(2.75), IFA 1.71(2.66), P = 0.541. One thousand and fifty seven (76.0%) had EPDS completed; mean (SD) scores were LNS 5.77(5.53), MMN 5.43(4.97), IFA 5.52(5.18), P = 0.676. There were no statistically significant differences between the groups on SRQ or EPDS scores (continuous or dichotomised) in unadjusted or adjusted models. In conclusion, fortification of maternal diet with LNS compared with MMN or IFA did not reduce postnatal depressive symptoms in this study.

Effects of an intervention on infant growth and development: evidence for different mechanisms at work.

Millions of children in low-income and middle-income countries falter in linear growth and neurobehavioral development early in life. This faltering may be caused by risk factors that are associated with both growth and development, such as insufficient dietary intake and infection in infancy. Alternatively, these risk factors may be indicative of an environment that constrains both linear growth and development through different mechanisms. In a cluster-randomized trial in Burkina Faso, we previously found that provision of lipid-based nutrient supplements plus malaria and diarrhoea treatment from age 9 to 18 months resulted in positive effects of ~0.3 standard deviation on length-for-age z-score (LAZ) and of ~0.3 standard deviation on motor, language and personal-social development scores at age 18 months. In this paper, we examined whether the effect of the intervention on developmental scores was mediated by the effect on LAZ, or, alternatively, whether the intervention had independent effects on growth and development. For motor, language, and personal-social z-scores, the effect of the intervention decreased from 0.32 to 0.21, from 0.33 to 0.27 and from 0.35 to 0.29, respectively, when controlling for change in LAZ from 9 to 18 months. All effects remained significant. These results indicate that the intervention had independent positive effects on linear growth and development, suggesting that these effects occurred through different mechanisms. © 2016 John Wiley & Sons Ltd.

Provision of Lipid-Based Nutrient Supplements from Age 6 to 18 Months Does Not Affect Infant Development Scores in a Randomized Trial in Malawi.

Objectives Undernutrition during early life contributes to more than 200 million children globally not fulfilling their developmental potential. Our objective was to determine whether dietary supplementation with several formulations of lipid-based nutrient supplements (LNS), which differed in dose per day and milk content, positively affect infant development in Malawi. Methods We randomly assigned 1932 infants age 6 months to receive one of the following for 12 months: 10, 20 g, or 40 g/day milk-containing LNS, 20 g or 40 g/day milk-free LNS, or no supplement until 18 months of age (control group). We assessed motor, language, socio-emotional, and executive function at age 18 months. Primary analysis was by intention-to-treat and we also examined 13 potential effect modifiers, including the child's initial nutritional status and level of developmental stimulation. The study is registered as clinical trial NCT00945698. Results We found no significant differences between intervention groups in any scores. The difference in mean z-scores between children in the control group and children in the intervention groups ranged from -0.08 to 0.04 for motor development (p = 0.76), -0.05 to 0.01 for language development (p = 0.97), -0.15 to 0.11 for socio-emotional development (p = 0.22), and -0.02 to 0.20 for executive function (p = 0.24). We did not find that initial nutritional status, developmental stimulation, or other factors modified the effect LNS versus control group. Conclusions for Practice Our results suggest that in a population such as this one, provision of LNS from age 6 to 18 months would not affect motor, language, socio-emotional, or executive function skills at age 18 months.

Lipid-Based Nutrient Supplements Plus Malaria and Diarrhea Treatment Increase Infant Development Scores in a Cluster-Randomized Trial in Burkina Faso.

BACKGROUND: Adequate nutrition is necessary for the rapid brain development that occurs during infancy. OBJECTIVES: We tested the hypothesis that the provision of small-quantity, lipid-based nutrient supplements (SQ-LNSs) plus malaria and diarrhea treatment positively affects infant development. We also tested the effect of various doses of zinc provided in SQ-LNSs or in a tablet. METHODS: In a partially masked, cluster-randomized controlled trial, communities in rural Burkina Faso were stratified by selected characteristics and then randomly assigned within strata to the intervention (IC; 25 communities, 2435 children) or the nonintervention (NIC; 9 communities, 785 children) cohorts. IC children were randomly assigned to 4 groups. As secondary outcomes, a subsample of 3 of these 4 groups (n = 747) and of the NIC (n = 376) were assessed for motor, language, and personal-social development at age 18 mo by using the Developmental Milestones Checklist II. The 3 IC groups received 20 g SQ-LNSs/d containing 0 or 10 mg added zinc with a placebo tablet or 20 g SQ-LNSs/d containing 0 mg added zinc with a tablet containing 5 mg Zn. All IC groups received treatment of malaria and diarrhea from age 9 to 18 mo. Data collectors and participants were aware of allocation to the IC or NIC but did not know the particular IC subgroup. RESULTS: Children in the IC scored 0.34 (95% CI: 0.21, 0.46), 0.30 (95% CI: 0.15, 0.44), and 0.32 (95% CI: 0.16, 0.48) SDs higher in motor, language, and personal-social development, respectively, than did children in the NIC (All P < 0.001). Children who received different amounts of zinc did not differ significantly in any of the scores. No effect on caregiver-child interaction was found. CONCLUSION: In rural Burkina Faso, the provision of SQ-LNSs to infants from age 9 to 18 mo, regardless of added zinc content, plus malaria and diarrhea treatment positively affected motor, language, and personal-social development at age 18 mo. This trial was registered at clinicaltrials.gov as NCT00944281.

Extending the Developmental Milestones Checklist for use in a different context in Sub-Saharan Africa.

AIM: Sub-Saharan Africa bears a disproportionate amount of global diseases related to neurodevelopmental delays in infancy, including malnutrition, malaria and HIV. Evaluating interventions to prevent such delays requires developmental assessment tools appropriate for Sub-Saharan Africa. This study aimed to develop and evaluate such a tool. METHODS: The Developmental Milestones Checklist (DMC) was developed in Kenya to provide motor, language and personal-social scores for children aged from 3 to 24 months. We developed an extended version (DMC-II) in Burkina Faso, West Africa, and then evaluated the reliability and sensitivity of the scores to age and nutritional and environmental measures. RESULTS: The internal, interinterviewer and test-retest reliability of the DMC-II scores were >0.7. In 214 children aged 11.6-25.4 months, each score correlated with age (rs > 0.7). In 1123 children aged 16.8-19.9 months, the scores were sensitive to stunting, wasting and underweight (effect sizes 0.31-0.87 SD). The scores also showed expected correlations with measures of play materials in the home and activities with caregivers (rs = 0.13-0.41). CONCLUSION: The DMC-II is easily used by trained fieldworkers with no previous experience in developmental assessment. It is a practical, reliable and sensitive tool for evaluating motor, language and personal-social development in different contexts in Sub-Saharan Africa.