Consumption of multiple micronutrient supplements (MMS) during pregnancy offers additional benefits compared with iron-folic acid (IFA) supplementation, but the tablets are more expensive. We estimated the effects, costs, and cost-effectiveness of hypothetically replacing IFA supplements with MMS for 1 year in Bangladesh and Burkina Faso. Using baseline demographic characteristics from LiST and effect sizes from a meta-analysis, we estimated the marginal effects of replacing IFA with MMS on mortality, adverse birth outcomes, and disability-adjusted life years (DALYs) averted. We calculated the marginal tablet costs of completely replacing MMS with IFA (assuming 180 tablets per covered pregnancy). Replacing IFA with MMS could avert over 15,000 deaths and 30,000 cases of preterm birth annually in Bangladesh and over 5000 deaths and 5000 cases of preterm birth in Burkina Faso, assuming 100% coverage and adherence. We estimated the cost per death averted to be US$175-185 in Bangladesh and $112-125 in Burkina Faso. Cost per DALY averted ranged from $3 to $15, depending on the country and consideration of subgroup effects. Our estimates suggest that this policy change would cost-effectively save lives and reduce life-long disabilities. Improvements in program delivery and supplement adherence would be expected to improve the cost-effectiveness of replacing IFA with MMS.

Objective

We aimed to identify factors (child diet, physical activity; maternal BMI) associated with body composition of Ghanaian pre-school children.

Design

Longitudinal analysis of the International Lipid-Based Nutrient Supplements (iLiNS)-DYAD-Ghana randomized trial, which enrolled 1320 pregnant women at ≤20 weeks' gestation and followed them and their infants until 6 and 18 months postpartum, respectively. At follow-up, child age 4-6 years, we collected data on body composition (by 2H dilution), physical activity and diet, extracted dietary patterns using factor analysis, and examined the association of children's percentage body fat with maternal and child factors by regression analysis.

Setting

Eastern Region, Ghana.

Participants

Children 4-6 years of age.

Results

The analysis included 889 children with percentage body fat and dietary data at follow-up. We identified two major dietary patterns, a snacking and a cooked foods pattern. Percentage body fat was positively associated (standardized β (se)) with maternal BMI at follow-up (0·10 (0·03); P = 0·003) and negatively associated with physical activity (-0·15 (0·05); P = 0·003, unadjusted for child gender), but not associated with the snacking (0·06 (0·03); P = 0·103) or cooked foods (-0·05 (0·07); P = 0·474) pattern. Boys were more active than girls (1470 v. 1314 mean vector magnitude counts/min; P < 0·0001) and had lower percentage body fat (13·8 v. 16·9 %; P < 0·0001).

Conclusions

In this population, maternal overweight and child physical activity, especially among girls, may be key factors for addressing child overweight/obesity. We did not demonstrate a relationship between the dietary patterns and body fatness, which may be related to limitations of the dietary data available.

Objectives

To investigate several basic psychometric properties, including construct, convergent and discriminant validity, of the tablet-based Rapid Assessment of Cognitive and Emotional Regulation (RACER) among children aged 4-6 years in Ghana.

Methods

We investigated whether RACER tasks administered to children in Ghana could successfully reproduce expected patterns of performance previously found in high-income countries on similar tasks assessing inhibitory control (e.g., slower responses on inhibition trials), declarative memory (e.g., higher accuracy on previously seen items), and procedural memory (e.g., faster responses on sequence blocks). Next, we assessed the validity of declarative memory and inhibitory control scores by examining associations of these scores with corresponding paper-based test scores and increasing child age. Lastly, we examined whether RACER was more sensitive than paper-based tests to environmental risk factors common in low- and middle-income countries (LMICs).

Results

Of the 966 children enrolled, more than 96% completed the declarative memory and inhibitory control tasks; however, around 30% of children were excluded from data analysis on the procedural memory task due to missing more than half of trials. The performance of children in Ghana replicated previously documented patterns of performance. RACER inhibitory control accuracy score was significantly correlated with child age (r (929) = .09, p = .007). However, our findings did not support other hypotheses.

Conclusions

The high task completion rates and replication of expected patterns support that certain RACER sub-tasks are feasible for measuring child cognitive development in LMIC settings. However, this study did not provide evidence to support that RACER is a valid tool to capture meaningful individual differences among children aged 4-6 years 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.

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 (β = 0.12, 95% CI = 0.05, 0.19), ΔLAZ from 6 to 18 months (β = 0.16, 95% CI = 0.04, 0.28), and Hb at 18 months (β = 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.

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.

Background

Adequate nutrition is necessary for brain development during pregnancy and infancy. Few randomized controlled trials of supplementation during these periods have measured later developmental outcomes.

Objective

Our objective was to investigate the effects of provision of prenatal and postnatal lipid-based nutrient supplements (LNS) on child development at preschool age.

Methods

We conducted a follow-up study of 966 children aged 4-6 y in 2016, born to women who participated in the International Lipid-Based Nutrient Supplements-DYAD trial conducted in Ghana in 2009-2014, representing 79% of eligible children. Women ≤20 weeks of gestation were randomized to daily LNS or multiple micronutrient (MMN) capsules during pregnancy through 6 mo postpartum or iron and folic acid (IFA) capsules during pregnancy and calcium placebo capsules during 6 mo postpartum. Children in the LNS group received LNS from 6 to 18 mo. Primary outcomes of this follow-up study were (1) a cognitive factor score based on a test battery adapted from several standard tests, 2) fine motor score (9-hole pegboard test), and (3) social-emotional difficulties (Strengths and Difficulties Questionnaire; SDQ). Eight secondary outcomes were calculated in specific domains (e.g., language, SDQ prosocial). Analysis was by a complete case intention to treat in a 2-group comparison: LNS compared with non-LNS (MMN + IFA).

Results

Children in the LNS group had significantly lower social-emotional difficulties z-scores than children in the non-LNS group (adjusted for child age β = -0.12, 95% CI: -0.25, 0.02, P = 0.087; fully adjusted β = -0.16, 95% CI: -0.29, -0.03, P = 0.013). The effect of LNS on social-emotional difficulties score was larger among children living in households with lower home environment scores (P-interaction = 0.081). No other outcomes differed between the 2 intervention groups.

Conclusions

Provision of LNS during the first 1000 d of development improved behavioral function, particularly for children from low nurturing and stimulation households, but did not affect cognition at preschool age in this setting. Trial Registration: clinicaltrials.gov, Identifier NCT00970866.

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.

Pregnancy and breastfeeding make demands on maternal nutrient stores. The extent of depletion and the degree to which nutrient stores are replenished between pregnancies has implications for a mother's nutritional status at conception of the subsequent child and therefore that child's birth outcomes and growth. Using follow-up data collected several years after a randomized effectiveness trial conducted in rural Bangladesh and a randomized efficacy trial conducted in semiurban Ghana, we evaluated the impact of maternal supplementation with small-quantity lipid-based nutrient supplements (LNS) or multiple micronutrients (MMN) through pregnancy (the index pregnancy) and 6 months postpartum on the growth status of the next living younger sibling conceived and born after the index pregnancy. In both Bangladesh (n = 472 younger siblings) and Ghana (n = 327 younger siblings), there were no overall differences in the growth status or the prevalence of undernutrition among younger siblings whose mothers had received LNS (or MMN, Ghana only) during and after the index pregnancy compared with the younger siblings of mothers who had received iron plus folic acid (IFA) during the index pregnancy (Ghana) or during and for 3 months after the index pregnancy (Bangladesh). These findings do not indicate that preconception nutrition interventions do not improve child growth. Rather, they suggest that any benefits of maternal LNS or MMN supplementation during one pregnancy and for 6 months postpartum are unlikely to extend to the growth of her next child beyond any effects due to IFA alone.

Background

The impact of feeding a slightly sweet nutrient supplement early in life on later sweet taste preference is unknown.

Objective

We tested the hypothesis that the level of sucrose most preferred by 4-6-y-old children exposed to a slightly sweet lipid-based nutrient supplement (LNS) early in life would not be higher than that of children never exposed to LNS.

Design

We followed up children born to women (n = 1,320) who participated in a randomized trial in Ghana. In one group, LNS was provided to women on a daily basis during pregnancy and the first 6 mo postpartum and to their infants from age 6 to 18 mo (LNS group). The control groups received daily iron and folic acid or multiple micronutrients during pregnancy and the first 6 mo postpartum, with no infant supplementation (non-LNS group). At age 4-6 y, we randomly selected a subsample of children (n = 775) to assess the concentration of sucrose most preferred using the Monell 2-series, forced-choice, paired-comparison tracking procedure. We compared LNS with non-LNS group differences using a noninferiority margin of 5% weight/volume (wt/vol).

Results

Of the 624 children tested, most (61%) provided reliable responses. Among all children, the mean ± SD sucrose solution most preferred (% wt/vol) was 14.6 ± 8.6 (LNS group 14.9 ± 8.7; non-LNS group 14.2 ± 8.4). However, among children with reliable responses, it was 17.0 ± 10.2 (LNS group 17.5 ± 10.4; non-LNS group 16.5 ± 10.0). The upper level of the 95% CI of the difference between groups did not exceed the noninferiority margin in either the full sample or those with reliable responses, indicating that the LNS group did not have a higher sweet preference than the non-LNS group.

Conclusion

Exposure to a slightly sweet nutrient supplement early in life did not increase the level of sweet taste most preferred during childhood. This trial was registered at clinicaltrials.gov as NCT00970866.