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

BackgroundPrevious 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.MethodsWe 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.ResultsOut 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.ConclusionsKey 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

What can eye-tracking tell us?

Background: Early development of neurocognitive functions in infants can be compromised by poverty, malnutrition and lack of adequate stimulation. Optimal management of neurodevelopmental problems in infants requires assessment tools that can be used early in life, and are objective and applicable across economic, cultural and educational settings. Objective and design: The present study examined the feasibility of infrared eye tracking as a novel and highly automated technique for assessing visual-orienting and sequence-learning abilities as well as attention to facial expressions in young (9-month-old) infants. Techniques piloted in a high-resource laboratory setting in Finland (N=39) were subsequently field-tested in a community health centre in rural Malawi (N=40). Results: Parents' perception of the acceptability of the method (Finland 95%, Malawi 92%) and percentages of infants completing the whole eye-tracking test (Finland 95%, Malawi 90%) were high, and percentages of valid test trials (Finland 69-85%, Malawi 68-73%) satisfactory at both sites. Test completion rates were slightly higher for eye tracking (90%) than traditional observational tests (87%) in Malawi. The predicted response pattern indicative of specific cognitive function was replicated in Malawi, but Malawian infants exhibited lower response rates and slower processing speed across tasks. Conclusions: High test completion rates and the replication of the predicted test patterns in a novel environment in Malawi support the feasibility of eye tracking as a technique for assessing infant development in low-resource setting. Further research is needed to the test-retest stability and predictive validity of the eye-tracking scores in low-income settings

Infections and systemic inflammation are associated with lower plasma concentration of insulin-like growth factor I among Malawian children

Background: Insulin-like growth factor I (IGF-I) is the most important hormonal promoter of linear growth in infants and young children. Objectives: The objectives of this study were to compare plasma IGF-I concentration in a low- compared with a high-income country and characterize biological pathways leading to reduced IGF-I concentration in children in a low-income setting. Methods: We analyzed plasma IGF-I concentration from 716 Malawian and 80 Finnish children at 6-36 mo of age. In the Malawian children, we studied the association between IGF-I concentration and their environmental exposures; nutritional status; systemic and intestinal inflammation; malaria parasitemia and viral, bacterial, and parasitic enteric infections; as well as growth at 18 mo of age. We then conducted a pathway analysis to identify direct and indirect associations between these predictors and IGF-I concentration. Results: The mean IGF-I concentrations were similar in Malawi and Finland among 6-mo-old infants. At age 18 mo. the mean +/- SD concentration was almost double among the Finns compared with the Malawians [24.2 +/- 11.3 compared with 12.5 +/- 7.7 ng/mL., age- and sex-adjusted difference in mean (95% CI): 11.8 (9.9. 13.7) ng/mL; P <0.01]. Among 18-mo-old Malawians, plasma IGF-I concentration was inversely associated with systemic inflammation, malaria parasitemia, and intestinal Shigella. Campylobacter, and enterovirus infection and positively associated with the children's weight-for-length z score (WLZ), female sex, maternal height, mother's education, and dry season. Seasonally, mean plasma IGF-I concentration was highest in June and July and lowest in December and January, coinciding with changes in children's length gain and preceded by similar to 2 mo by the changes in their WLZ. Conclusions: The mean plasma IGF-I concentrations are similar in Malawi and Finland among 6-mo-old infants. Thereafter, mean concentrations rise markedly in Finland but not in Malawi. Systemic inflammation and clinically nonapparent infections are strongly associated with lower plasma IGF-I concentrations in Malawi through direct and indirect pathways.Peer reviewe

Child Aflatoxin Exposure is Associated with Poor Child Growth Outcomes : A Prospective Cohort Study in Rural Malawi

Background: Aflatoxin (AF) exposure is associated with child growth faltering in cross-sectional studies, with limited findings from longitudinal studies. Objectives: To evaluate the relationship between maternal AF B1-lysine adduct concentration, child AF B1-lysine adduct concentration, and child growth in the first 30 mo of life. Methods: AF B1-lysine adduct was measured in mother-child dyad plasma samples using isotope dilution mass spectrometry. Using linear regression, we assessed the relationship between AF B1-lysine adduct concentration and child weight, height, and head and mid-upper arm circumferences at 1 wk, 6, 12, 18, 24, and 30 mo of age. Results: In adjusted models, maternal prenatal AF B1-lysine adduct (pg/μL) was positively associated with newborn anthropometric outcomes; largest beta coefficients for associations between standardized values were for newborn weight-for-age z-score [β = 0.13; 95% confidence interval (CI): 0.02, 0.24; P < 0.05 and β = 0.11; 95% CI: 0.00, 0.22; P < 0.05 for second and third trimester AF, respectively]. Child AF B1-lysine adduct (pg/μL) at 6 mo was negatively associated with head circumference-for-age z-score at 6, 18, 24, and 30 mo, with beta coefficients ranging from β = –0.15; 95% CI: –0.28, –0.02 to β = –0.17; 95% CI: –0.31, –0.03; P < 0.05); 18-mo AF was negatively associated with anthropometric outcomes at 18, 24, and 30 mo, most consistently with length-for-age z-score (β = –0.18; 95% CI: –0.32, –0.04, β = –0.21; 95% CI: –0.35, –0.07, β = –0.18; 95% CI: –0.32, –0.03 at 18, 24 and 30 mo, respectively). Conclusions: Child AF exposure was associated with impaired child growth, but maternal AF exposure was not. Exposure during infancy was linked to persistent deficit in head circumference, implying reduced brain size lasting beyond the age of 2 years. Exposure at 18 mo was linked to persistent linear growth deficit. Further research should elucidate mechanisms through which AF affects child growth.Peer reviewe

Path Analyses of Risk Factors for Linear Growth Faltering in Four Prospective Cohorts of Young Children in Ghana, Malawi and Burkina Faso

Stunting prevalence is an indicator of a country’s progress towards United Nations’ Sustainable Development Goal 2, which is to end hunger and achieve improved nutrition. Accelerating progress towards reducing stunting requires a deeper understanding of the factors that contribute to linear growth faltering. We conducted path analyses of factors associated with 18-month length-for-age z-score (LAZ) in four prospective cohorts of children who participated in trials conducted as part of the International Lipid-Based Nutrient Supplements Project in Ghana (n=1039), Malawi (n=684 and 1504) and Burkina Faso (n=2619). In two cohorts, women were enrolled during pregnancy. In two other cohorts, infants were enrolled at 6 or 9 months. We examined the association of 42 indicators of environmental, maternal, caregiving and child factors with 18-month LAZ. Using structural equation modelling, we examined direct and indirect associations through hypothesised mediators in each cohort. Out of 42 indicators, 2 were associated with 18-month LAZ in three or four cohorts: maternal height and body mass index (BMI). Six factors were associated with 18-month LAZ in two cohorts: length for gestational age z-score (LGAZ) at birth, pregnancy duration, improved household water, child dietary diversity, diarrhoea incidence and 6-month or 9-month haemoglobin concentration. Direct associations were more prevalent than indirect associations, but 30%–62% of the associations of maternal height and BMI with 18-month LAZ were mediated by LGAZ at birth. Factors that were not associated with LAZ were maternal iron status, illness and inflammation during pregnancy, maternal stress and depression, exclusive breast feeding during 6 months post partum, feeding frequency and child fever, malaria and acute respiratory infections. These findings may help in identifying interventions to accelerate progress towards reducing stunting; however, much of the variance in linear growth status remained unaccounted for by these 42 individual-level factors, suggesting that community-level changes may be needed to achieve substantial progress

Small-Quantity Lipid-Based Nutrient Supplements Increase Infants' Plasma Essential Fatty Acid Levels in Ghana and Malawi : A Secondary Outcome Analysis of the iLiNS-DYAD Randomized Trials

INTRODUCTION: Small-quantity (SQ) lipid-based nutrient supplements (LNSs) may influence infants' plasma fatty acid (FA) profiles, which could be associated with short- and long-term outcomes. OBJECTIVES: We aimed to determine the impact of SQ-LNS consumption on infants' plasma FA profiles in Ghana and Malawi. METHODS: Ghanaian (n = 1320) and Malawian (n = 1391) women ≤20 weeks pregnant were assigned to consume 60 mg iron and 400 μg folic acid daily until delivery [iron and folic acid (IFA) group], multiple-micronutrient supplements (MMNs) until 6 months postpartum (MMN group), or SQ-LNSs (∼7.8 linoleic acid:α-linolenic acid ratio) until 6 months postpartum (LNS group). LNS group infants received SQ-LNS from 6 to 18 months of age. We compared infant plasma FAs by intervention group in subsamples (n = 379 in Ghana; n = 442 in Malawi) at 6 and 18 months using ANOVA and Poisson regression models. Main outcomes were mean percentage compositions (%Cs; percentage of FAs by weight) of α-linolenic acid (ALA), linoleic acid (LA), EPA, DHA, and arachidonic acid (AA). RESULTS: At 6 months, LNS infants had greater mean ± SD ALA %Cs in Ghana (0.23 ± 0.08; IFA, 0.21 ± 0.06; MMN, 0.21 ± 0.07; P = 0.034) and Malawi (0.42 ± 0.16; IFA, 0.38 ± 0.15; MMN, 0.38 ± 0.14; P = 0.034) and greater AA values in Ghana (6.25 ± 1.24; IFA, 6.12 ± 1.13; MMN, 5.89 ± 1.24; P = 0.049). At 18 months, LNS infants had a tendency towards greater ALA (0.32 ± 0.16; IFA, 0.24 ± 0.08; MMN, 0.24 ± 0.10; P = 0.06) and LA (27.8 ± 3.6; IFA, 26.9 ± 2.9; MMN, 27.0 ± 3.1; P = 0.06) in Ghana, and greater ALA (0.45 ± 0.18; IFA, 0.39 ± 0.18; MMN, 0.39 ± 0.18; P < 0.001) and LA (29.7 ± 3.5; IFA, 28.7 ± 3.3; MMN, 28.6 ± 3.4; P = 0.011) in Malawi. The prevalence of ALA below the population-specific 10th percentile was lower in the LNS group compared to the MMN group, but not the IFA group. Groups did not differ significantly in plasma EPA or DHA levels. CONCLUSIONS: SQ-LNS increased infants' plasma essential FA levels in Ghana and Malawi, which may have implications for health and developmental outcomes. These trials were registered at clinicaltrials.gov as NCT00970866 and NCT01239693.acceptedVersionPeer reviewe

Lipid-Based Nutrient Supplements During Pregnancy and Lactation Did Not Affect Human Milk Oligosaccharides and Bioactive Proteins in a Randomized Trial.

BACKGROUND: Human milk oligosaccharides (HMOs) and bioactive proteins are beneficial to infant health. Recent evidence suggests that maternal nutrition may affect the amount of HMOs and proteins in breast milk; however, the effect of nutrient supplementation on HMOs and bioactive proteins has not yet been well studied. OBJECTIVE: We aimed to determine whether lipid-based nutrient supplements (LNSs) affect milk bioactive protein and HMO concentrations at 6 mo postpartum in women in rural Malawi. These are secondary outcomes of a previously published randomized controlled trial. METHODS: Women were randomly assigned to consume either an iron and folic acid capsule (IFA) daily from ≤20 wk gestation until delivery, followed by placebo daily from delivery to 6 mo postpartum, or a multiple micronutrient (MMN) capsule or LNS daily from ≤20 wk gestation to 6 mo postpartum. Breast milk concentrations of total HMOs, sialylated HMOs, fucosylated HMOs, lactoferrin, lactalbumin, lysozymes, antitrypsin, immunoglobulin A, and osteopontin were analyzed at 6 mo postpartum (n = 647). Between-group differences in concentrations and in proportions of women classified as having low concentrations were tested. RESULTS: HMO and bioactive protein concentrations did not differ between groups (P > 0.10 for all comparisons). At 6 mo postpartum, the proportions of women with low HMOs or bioactive proteins were not different between groups except for osteopontin. A lower proportion of women in the IFA group had low osteopontin compared with the LNS group after adjusting for covariates (OR: 0.5; 95% CI: 0.3, 0.9; P = 0.016). CONCLUSION: The study findings do not support the hypothesis that supplementation with an LNS or MMN capsule during pregnancy and postpartum would increase HMO or bioactive milk proteins at 6 mo postpartum among Malawian women. This trial was registered at clinicaltrials.gov as NCT01239693

Association between asymptomatic infections and linear growth in 18–24-month-old Malawian children

Inadequate diet and frequent symptomatic infections are considered major causes of growth stunting in low-income countries, but interventions targeting these risk factors have achieved limited success. Asymptomatic infections can restrict growth, but little is known about their role in global stunting prevalence. We investigated factors related to length-for-age Z-score (LAZ) at 24 months by constructing an interconnected network of various infections, biomarkers of inflammation (as assessed by alpha-1-acid glycoprotein [AGP]), and growth (insulin-like growth factor 1 [IGF-1] and collagen X biomarker [CXM]) at 18 months, as well as other children, maternal, and household level factors. Among 604 children, there was a continuous decline in mean LAZ and increased mean length deficit from birth to 24 months. At 18 months of age, the percentage of asymptomatic children who carried each pathogen was: 84.5% enterovirus, 15.5% parechovirus, 7.7% norovirus, 4.6% rhinovirus, 0.6% rotavirus, 69.6% Campylobacter, 53.8% Giardia lamblia, 11.9% malaria parasites, 10.2% Shigella, and 2.7% Cryptosporidium. The mean plasma IGF-1 concentration was 12.5 ng/ml and 68% of the children had systemic inflammation (plasma AGP concentration >1 g/L). Shigella infection was associated with lower LAZ at 24 months through both direct and indirect pathways, whereas enterovirus, norovirus, Campylobacter, Cryptosporidium, and malaria infections were associated with lower LAZ at 24 months indirectly, predominantly through increased systemic inflammation and reduced plasma IGF-1 and CXM concentration at 18 months.publishedVersionPeer reviewe