Prenatal air pollution and children's autism traits score: Examination of joint associations with maternal intake of vitamin D, methyl donors, and polyunsaturated fatty acids using mixture methods.

Background: Maternal nutrient intake may moderate associations between environmental exposures and children's neurodevelopmental outcomes, but few studies have assessed joint effects. We aimed to evaluate whether prenatal nutrient intake influences the association between air pollutants and autism-related trait scores. Methods: We included 126 participants from the EARLI (Early Autism Risk Longitudinal Investigation, 2009-2012) cohort, which followed US pregnant mothers who previously had a child with autism. Bayesian kernel machine regression and traditional regression models were used to examine joint associations of prenatal nutrient intake (vitamins D, B12, and B6; folate, choline, and betaine; and total omega 3 and 6 polyunsaturated fatty acids, reported via food frequency questionnaire), air pollutant exposure (particulate matter <2.5 µm [PM2.5], nitrogen dioxide [NO2], and ozone [O3], estimated at the address level), and children's autism-related traits (measured by the Social Responsiveness Scale [SRS] at 36 months). Results: Most participants had nutrient intakes and air pollutant exposures that met US standards. Bayesian kernel machine regression mixture models and traditional regression models provided little evidence of individual or joint associations of nutrients and air pollutants with SRS scores or of an association between the overall mixture and SRS scores. Conclusion: In this cohort with a high familial likelihood of autism, we did not observe evidence of joint associations between air pollution exposures and nutrient intake with autism-related traits. Future work should examine the use of these methods in larger, more diverse samples, as our results may have been influenced by familial liability and/or relatively high nutrient intakes and low air pollutant exposures.

Opportunities for Examining Child Health Impacts of Early-Life Nutrition in the ECHO Program: Maternal and Child Dietary Intake Data from Pregnancy to Adolescence.

Background: Longitudinal measures of diet spanning pregnancy through adolescence are needed from a large, diverse sample to advance research on the effect of early-life nutrition on child health. The Environmental influences on Child Health Outcomes (ECHO) Program, which includes 69 cohorts, >33,000 pregnancies, and >31,000 children in its first 7-y cycle, provides such data, now publicly available. Objectives: This study aimed to describe dietary intake data available in the ECHO Program as of 31 August, 2022 (end of year 6 of Cycle 1) from pregnancy through adolescence, including estimated sample sizes, and to highlight the potential for future analyses of nutrition and child health. Methods: We identified and categorized ECHO Program dietary intake data, by assessment method, participant (pregnant person or child), and life stage of data collection. We calculated the number of maternal-child dyads with dietary data and the number of participants with repeated measures. We identified diet-related variables derived from raw dietary intake data and nutrient biomarkers measured from biospecimens. Results: Overall, 66 cohorts (26,941 pregnancies, 27,103 children, including 22,712 dyads) across 34 US states/territories provided dietary intake data. Dietary intake assessments included 24-h recalls (1548 pregnancies and 1457 children), food frequency questionnaires (4902 and 4117), dietary screeners (8816 and 23,626), and dietary supplement use questionnaires (24,798 and 26,513). Repeated measures were available for ∼70%, ∼30%, and ∼15% of participants with 24-h recalls, food frequency questionnaires, and dietary screeners, respectively. The available diet-related variables describe nutrient and food intake, diet patterns, and breastfeeding practices. Overall, 17% of participants with dietary intake data had measured nutrient biomarkers. Conclusions: ECHO cohorts have collected longitudinal dietary intake data spanning pregnancy through adolescence from a geographically, socioeconomically, and ethnically diverse US sample. As data collection continues in Cycle 2, these data present an opportunity to advance the field of nutrition and child health.

Examining infants' visual paired comparison performance in the US and rural Malawi.

Measures of attention and memory were evaluated in 6- to 9-month-old infants from two diverse contexts. One sample consisted of African infants residing in rural Malawi (N = 228, 118 girls, 110 boys). The other sample consisted of racially diverse infants residing in suburban California (N = 48, 24 girls, 24 boys). Infants were tested in an eye-tracking version of the visual paired comparison procedure and were shown racially familiar faces. The eye tracking data were parsed into individual looks, revealing that both groups of infants showed significant memory performance. However, how a look was operationally defined impacted some-but not other-measures of infant VPC performance. RESEARCH HIGHLIGHTS: In both the US and Malawi, 6- to 9-month-old infants showed evidence of memory for faces they had previously viewed during a familiarization period. Infant age was associated with peak look duration and memory performance in both contexts. Different operational definitions of a look yielded consistent findings for peak look duration and novelty preference scores-but not shift rate. Operationalization of look-defined measures is an important consideration for studies of infants in different cultural contexts.

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.

Plasma Choline Concentration Was Not Increased After a 6-Month Egg Intervention in 6-9-Month-Old Malawian Children: Results from a Randomized Controlled Trial.

BACKGROUND: Eggs are a rich source of choline, an essential nutrient important for child growth and development. In a randomized trial of 1 egg/d in young children in Ecuador, an egg intervention led to significant improvements in growth, which were partially mediated by increased plasma choline concentration. A similar trial in Malawi (clinicaltrials.gov: NCT03385252) found little improvement in child growth or development. OBJECTIVES: We aimed to evaluate the effect of 1 egg/d for 6 mo on plasma choline concentrations in Malawian children enrolled in a randomized trial. METHODS: Infants aged 6-9 mo in rural Malawi were randomly assigned to receive 1 egg/d (n = 331) or serve as a nonintervention control (n = 329) for 6 mo. Anthropometric, developmental, and dietary data were collected at baseline and 6-mo follow-up, along with a blood draw. Plasma choline, betaine, dimethylglycine, trimethylamine N-oxide (TMAO), and DHA were measured at both time points using ultrahigh performance liquid chromatography-tandem MS (n = 200 per group). Linear regression analysis was used to determine the difference in plasma choline and related metabolites between groups after 6 mo of intervention. RESULTS: Plasma choline, betaine, dimethylglycine, and DHA concentrations did not differ between groups at 6-mo follow-up. Plasma TMAO was significantly (26%; 95% CI: 7%, 48%) higher in the egg intervention group in a fully adjusted model. CONCLUSIONS: Provision of 1 egg/d for 6 mo did not result in increases in plasma choline or related metabolites, except TMAO. This could partially explain the lack of effect on growth and development. Additional interventions are needed to improve choline status, growth, and development in this population.

Choline and docosahexaenoic acid during the first 1000 days and children's health and development in low- and middle-income countries.

Choline and DHA are nutrients that, when provided during the first 1000 days from conception to age 2 years, may have beneficial effects on child neurodevelopment as well as related health factors, including birth outcomes and child growth, morbidity, and inflammation. Because these nutrients are found mainly in animal-source foods, they may be lacking in the diets of pregnant and lactating women and young children in low- and middle-income countries, potentially putting children at risk for suboptimal development and health. Prior reviews of these nutrients have mainly focused on studies from high-income countries. Here, a narrative review is presented of studies describing the pre- and postnatal roles of choline, docosahexaenoic acid, and a combination of the 2 nutrients on child neurodevelopment, birth outcomes, growth, morbidity, and inflammation in low- and middle-income countries. More studies are needed to understand the specific, long-term effects of perinatal choline and docosahexaenoic acid intake in various contexts.

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.