Multimodal machine learning for modeling infant head circumference, mothers' milk composition, and their shared environment.

Links between human milk (HM) and infant development are poorly understood and often focus on individual HM components. Here we apply multi-modal predictive machine learning to study HM and head circumference (a proxy for brain development) among 1022 mother-infant dyads of the CHILD Cohort. We integrated HM data (19 oligosaccharides, 28 fatty acids, 3 hormones, 28 chemokines) with maternal and infant demographic, health, dietary and home environment data. Head circumference was significantly predictable at 3 and 12 months. Two of the most associated features were HM n3-polyunsaturated fatty acid C22:6n3 (docosahexaenoic acid, DHA; p = 9.6e-05) and maternal intake of fish (p = 4.1e-03), a key dietary source of DHA with established relationships to brain function. Thus, using a systems biology approach, we identified meaningful relationships between HM and brain development, which validates our statistical approach, gives credence to the novel associations we observed, and sets the foundation for further research with additional cohorts and HM analytes.

The protective associations of breastfeeding with infant overweight and asthma are not dependent on maternal FUT2 secretor status.

Breastfeeding supplies infant gut bacteria with human milk oligosaccharides (HMOs) as a nutrient source. HMO profiles are influenced by the FUT2 gene, which encodes an enzyme affecting the fucosylation of milk sugars. 20 to 40% of individuals have a "non-secretor" polymorphism that inactivates the FUT2 gene, resulting in variable HMO proportions in milk. This has engendered a concerning, yet unfounded, perception that non-secretor milk is "inferior." To address this untested hypothesis, we re-analyzed two datasets in which we previously showed that breastfeeding was protective against early life asthma and excessive infant weight gain in the Canadian CHILD Cohort Study. Using stratified regression models, we found that the protective association of exclusive breastfeeding and infant asthma was not modified by maternal secretor status (secretors aOR: 0.53, 95% CI 0.31 to 0.92; non-secretors aOR: 0.36, 95% CI 0.12 to 1.04; p for interaction = 0.50, N = 2086 children). Similarly, the association of breastfeeding with lower infant BMI and weight gain velocity did not vary by maternal secretor status (infant BMI: secretors aß -0.47, 95% CI -0.66 to -0.29; non-secretors aß -0.46, 95% CI -0.78 to -0.13; p for interaction = 0.60; N = 1971 infants). Our results indicate that secretor and non-secretor mothers can equally promote infant growth and respiratory health through breastfeeding. These findings run contrary to the idea that non-secretor milk is an inferior food source, and instead reify the importance of breastfeeding for all infants. The results of this study can inform feeding recommendations that are applicable to all infants, regardless of maternal secretor status.

Cohort profile: investigating SARS-CoV-2 infection and the health and psychosocial impact of the COVID-19 pandemic in the Canadian CHILD Cohort.

The coronavirus disease 2019 (COVID-19) pandemic has affected all Canadian families, with some impacted differently than others. Our study aims to: (1) determine the prevalence and transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among Canadian families, (2) identify predictors of infection susceptibility and severity of SARS-CoV-2, and (3) identify health and psychosocial impacts of the COVID-19 pandemic. This study builds upon the CHILD Cohort Study, an ongoing multi-ethnic general population prospective cohort consisting of 3,454 Canadian families with children born in Vancouver, Edmonton, Manitoba, and Toronto between 2009 and 2012. During the pandemic, CHILD households were invited to participate in the CHILD COVID-19 Add-On Study involving: (1) brief biweekly surveys about COVID-19 symptoms and testing; (2) quarterly questionnaires assessing COVID-19 exposure and testing, vaccination status, physical and mental health, and pandemic-driven life changes; and (3) in-home biological sampling kits to collect blood and stool. In total, 1,462 households (5,378 participants) consented to the CHILD COVID-19 Add-On Study: 2,803 children (mean±standard deviation [SD], 9.0±2.7 years; range, 0-17 years) and 2,576 adults (mean±SD, 43.0±6.5 years; range, 18-85 years). We will leverage the wealth of pre-pandemic CHILD data to identify risk and resilience factors for susceptibility and severity to the direct and indirect pandemic effects. Our short-term findings will inform key stakeholders and knowledge users to shape current and future pandemic responses. Additionally, this study provides a unique resource to study the long-term impacts of the pandemic as the CHILD Cohort Study continues.

Parental cardiorespiratory conditions and offspring fracture: A population-based familial linkage study.

BACKGROUND: The role of parental cardiorespiratory conditions on fracture risk is unclear. We examined the associations between parental cardiorespiratory conditions and offspring fracture risk. METHODS: In this population-based retrospective cohort study, we identified 279,085 offspring aged≥40 years between April 1, 1997 and December 31, 2015 with successful linkage to 273,852 mothers and 254,622 fathers. Parental cardiorespiratory conditions, including cerebral vascular disease, congestive heart failure, hypertension, ischemic heart disease, myocardial infarction, chronic obstructive pulmonary disease (COPD) and peripheral vascular disease, were ascertained using physician and hospital records dating back to 1979. The outcome was offspring incident major osteoporotic fracture (MOF). RESULTS: During an average of 11.8 years of offspring follow-up, we identified 8762 (3.1%) incident MOF. Either parent congestive heart failure (adjusted hazard ratio [HR]: 1.13; 95% confidence interval [CI] 1.07-1.19) and COPD (adjusted HR: 1.12; 95% CI 1.07-1.17) were independently associated with increased offspring MOF risk; all their false discovery rates were <0.001. Similar risk estimates were observed when analyses were performed for fathers only, mothers only or both parents, in multivariable models with and without adjustment for offspring cardiorespiratory conditions, and stratified by offspring sex and offspring incident fracture site. Parental cerebrovascular disease, hypertension, ischemic heart disease and myocardial infarction were not associated with offspring MOF. CONCLUSIONS: Parental congestive heart failure and parental COPD are independent risk factors for offspring MOF.