Parental and child genetic burden of glycaemic dysregulation and early-life cognitive development: an Asian and European prospective cohort study.

Insulin resistance and glucose metabolism have been associated with neurodevelopmental disorders. However, in the metabolically more susceptible Asian populations, it is not clear whether the genetic burden of glycaemic dysregulation influences early-life neurodevelopment. In a multi-ethnic Asian prospective cohort study in Singapore (Growing Up in Singapore Towards healthy Outcomes (GUSTO)), we constructed child and parental polygenic risk scores (PRS) for glycaemic dysregulation based on the largest genome-wide association studies of type 2 diabetes and fasting glucose among Asians. We found that child PRS for HOMA-IR was associated with a lower perceptual reasoning score at ~7 years (ß = -0. 141, p-value = 0.024, 95% CI -0. 264 to -0. 018) and a lower WIAT-III mean score at ~9 years (ß = -0.222, p-value = 0.001, 95% CI -0.357 to -0.087). This association were consistent in direction among boys and girls. These inverse associations were not influenced by parental PRS and were likely mediated via insulin resistance rather than mediators such as birth weight and childhood body mass index. Higher paternal PRS for HOMA-IR was suggestively associated with lower child perceptual reasoning at ~7 years (ß = -0.172, p-value = 0.002, 95% CI -0.280 to -0.064). Replication analysis in a European cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort, showed that higher child PRS for fasting glucose was associated with lower verbal IQ score while higher maternal PRS for insulin resistance was associated with lower performance IQ score in their children at ~8.5 years. In summary, our findings suggest that higher child PRS for HOMA-IR was associated with lower cognitive scores in both Asian and European replication cohorts. Differential findings between cohorts may be attributed to genetic and environmental factors. Further investigation of the functions of the genetic structure and ancestry-specific PRS and a more comprehensive investigation of behavioural mediators may help to understand these findings better.

COVID-19-Related Life Experiences, Outdoor Play, and Long-term Adiposity Changes Among Preschool- and School-Aged Children in Singapore 1 Year After Lockdown.

IMPORTANCE: Despite the potential for COVID-19 infection control-related events to have an effect on child well-being, comprehensive assessments of postlockdown changes and persistent outcomes are lacking. OBJECTIVE: To survey the extent of COVID-19 lockdown-related lifestyle changes, their differences by child age and family socioeconomic status, and the potential association with child adiposity 1 year after lockdown. DESIGN, SETTING, AND PARTICIPANTS: A self-administered, electronic survey was introduced to 2 ongoing child cohorts (the Singapore Preconception Study of Long-term Maternal and Child Outcomes [S-PRESTO] cohort of preschool children aged 1-4.5 years and the Growing Up in Singapore Towards Healthy Outcomes [GUSTO] cohort of primary school children aged 9-10.7 years) from July 8, 2020, to September 5, 2020, which was 1 to 3 months after the end of strict universal movement restrictions (duration of 73 days ending on June 19, 2020). All active participants from S-PRESTO and GUSTO, 2 population-based, longitudinal, parent-offspring cohorts in Singapore, were invited to participate and monitored through June 15, 2021. EXPOSURES: Exposures included family income before and after the COVID-19 lockdown, changes in child outdoor play or exercise, and COVID-19-related life events; all data were self-reported by parents and school-aged children 1 to 3 months after the lockdown. MAIN OUTCOMES AND MEASURES: Primary outcomes were self-reported COVID-19-related life events and changes in child online socialization, outdoor play or exercise, and intrafamily relationships. Study staff measured children's weight, height, and skinfold thickness before and up to 1 year after lockdown. Body mass indices (calculated as weight in kilograms divided by height in meters squared) and World Health Organization-standardized scores were computed. Differences before and after lockdown were compared using baseline-adjusted linear regression. RESULTS: A total of 604 parents (53% of active cohort participants) and 356 school-aged children completed the survey and were similar to source cohorts. This represents 373 of 761 eligible children in the GUSTO cohort (mean [SD] age, 9.9 [0.4] years; 197 girls [52.8%]) and 231 of 370 eligible children in the S-PRESTO cohort (mean [SD] age, 2.6 [0.8] years; 121 boys [52.6%]). The COVID-19-related life changes were prevalent and varied (eg, 414 of 600 children [69.0%] reported changes in social activities). More than one-third of primary school-aged children (122 of 356 [34.3%]) and one-quarter of preschool-aged children (56 of 229 [24.5%]) eliminated any outdoor play after the lockdown. Lower family income before the lockdown was associated with increased odds of elimination of outdoor play (adjusted odds ratio per 1000 Singapore dollars [$730 US dollars] decrease, 1.09; 95% CI, 1.01-1.19). Complete elimination of outdoor activity (vs continued outdoor activity) was associated with an increase in body mass index of 0.48 (95% CI, 0.03-0.94) and a body mass index z score of 0.18 units (95% CI, 0-0.37) in school-aged children approximately 1 year after lockdown. CONCLUSIONS AND RELEVANCE: Results of this cohort study suggest that 1 to 3 months after a brief, strict lockdown, a large proportion of parents and school-aged children reported elimination of outdoor play, which was more prevalent in lower-income families. Future research to better understand clinical implications and ways to mitigate lockdown outcomes is essential.

The socioeconomic landscape of the exposome during pregnancy.

BACKGROUND: While socioeconomic position (SEP) is consistently related to pregnancy and birth outcome disparities, relevant biological mechanisms are manifold, thus necessitating more comprehensive characterization of SEP-exposome associations during pregnancy. OBJECTIVES: We implemented an exposomic approach to systematically characterize the socioeconomic landscape of prenatal exposures in a setting where social segregation was less distinct in a hypotheses-generating manner. METHODS: We described the correlation structure of 134 prenatal exogenous and endogenous sources (e.g., micronutrients, hormones, immunomodulatory metabolites, environmental pollutants) collected in a diverse, population-representative, urban, high-income longitudinal mother-offspring cohort (N = 1341; 2009-2011). We examined the associations between maternal, paternal, household, and areal level SEP indicators and 134 exposures using multiple regressions adjusted for precision variables, as well as potential effect measure modification by ethnicity and nativity. Finally, we generated summary SEP indices using Multiple Correspondence Analysis to further explore possible curved relationships. RESULTS: Individual and household SEP were associated with anthropometric/adiposity measures, folate, omega-3 fatty acids, insulin-like growth factor-II, fasting glucose, and neopterin, an inflammatory marker. We observed paternal education was more strongly and consistently related to maternal exposures than maternal education. This was most apparent amongst couples discordant on education. Analyses revealed additional non-linear associations between areal composite SEP and particulate matter. Environmental contaminants (e.g., per- and polyfluoroalkyl substances) and micronutrients (e.g., folate and copper) showed opposing associations by ethnicity and nativity, respectively. DISCUSSION: SEP-exposome relationships are complex, non-linear, and context specific. Our findings reinforce the potential role of paternal contributions and context-specific modifiers of associations, such as between ethnicity and maternal diet-related exposures. Despite weak presumed areal clustering of individual exposures in our context, our approach reinforces subtle non-linearities in areal-level exposures.