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The human milk microbiota (HMM) is thought to influence the long-term health of offspring. However, its role in asthma and atopy and the impact of host genomics on HMM composition remain unclear. Through the CHILD Cohort Study, we followed 885 pregnant mothers and their offspring from birth to 5 years and determined that HMM was associated with maternal genomics and prevalence of childhood asthma and allergic sensitization (atopy) among human milk-fed infants. Network analysis identified modules of correlated microbes in human milk that were associated with subsequent asthma and atopy in preschool-aged children. Moreover, reduced alpha-diversity and increased Lawsonella abundance in HMM were associated with increased prevalence of childhood atopy. Genome-wide association studies (GWASs) identified maternal genetic loci (e.g., ADAMTS8 , NPR1, and COTL1) associated with HMM implicated with asthma and atopy, notably Lawsonella and alpha-diversity. Thus, our study elucidates the role of host genomics on the HMM and its potential impact on childhood asthma and atopy. [Display omitted] • Network clusters of correlated microbes are identified in human milk • Host genomics are associated with human milk microbes and network clusters • Some heritable milk microbes are associated with childhood asthma and atopy • Microbe-associated loci have been linked to human milk traits and gut microbiota Fang et al. report associations between host genomics and human milk microbiota (HMM) among 885 mothers of the CHILD Cohort Study. Exposure to some of these heritable milk microbes may promote or protect the later development of childhood asthma and food/inhalant sensitization among milk-fed infants. [ABSTRACT FROM AUTHOR]

Background: Despite global public health organizations endorsing breastfeeding or human milk (HM) as the optimal source of nutrition for infants, detailed knowledge of how HM composition influences infant growth is lacking. In this commentary we summarize and interpret the key findings of a large systematic review on HM components and child growth (N = 141 articles included). We highlight the most consistent associations, discuss study quality issues, explore socio-economic and time trends in this body of research, and identify gaps and future research directions. Key Findings of Systematic Review: We grouped HM components into three categories: micronutrients (28 articles), macronutrients (57 articles), and bioactives (75 articles). Overall, we struggled to find consistent associations between HM components and infant growth. The majority of studies (85%) were of moderate or low-quality, with inconsistent HM collection and analysis strategies being identified as the most substantial quality concerns. Additional quality issues included failing to account for potential confounding by factors such as breastfeeding exclusivity and maternal body mass index. Considerations for Future Human Milk Research: Many opportunities exist for the future of HM research. Using untargeted metabolomics will expand our understanding of HM components beyond previously defined and well-understood components. Machine learning will allow researchers to investigate HM as an integrated system, rather than a collection of individual components. Future research on HM composition should incorporate evidence-based HM sampling strategies to encompass circadian variation as well as infant consumption. Additionally, researchers need to focus on developing high quality growth data using consistent growth metrics and definitions. Building multidisciplinary research teams will help to ensure that outcomes are meaningful and clinically relevant. Conclusion: Despite a large body of literature, there is limited quality evidence on the relationship between HM composition and infant growth. Future research should engage in more accurate collection of breastfeeding data, use standardized HM collection strategies and employ assays that are validated for HM. By systematically evaluating the existing literature and identifying gaps in existing research methods and practice, we hope to inspire standardized methods and reporting guidelines to support robust strategies for examining relationships between HM composition and child growth. [ABSTRACT FROM AUTHOR]

Background: A lack of safety data on postpartum medication use presents a potential barrier to breastfeeding and may result in infant exposure to medications in breastmilk. The type and extent of medication use by lactating women requires investigation. Methods: Data were collected from the CHILD Cohort Study which enrolled pregnant women across Canada between 2008 and 2012. Participants completed questionnaires regarding medications and non-prescription medications used and breastfeeding status at 3, 6 and 12 months postpartum. Medications, along with self-reported reasons for medication use, were categorized by ontologies [hierarchical controlled vocabulary] as part of a large-scale curation effort to enable more robust investigations of reasons for medication use. Results: A total of 3542 mother-infant dyads were recruited to the CHILD study. Breastfeeding rates were 87.4%, 75.3%, 45.5% at 3, 6 and 12 months respectively. About 40% of women who were breastfeeding at 3 months used at least one prescription medication during the first three months postpartum; this proportion decreased over time to 29.5% % at 6 months and 32.8% at 12 months. The most commonly used prescription medication by breastfeeding women was domperidone at 3 months (9.0%, n = 229/2540) and 6 months (5.6%, n = 109/1948), and norethisterone at 12 months (4.1%, n = 48/1180). The vast majority of domperidone use by breastfeeding women (97.3%) was for lactation purposes which is off-label (signifying unapproved use of an approved medication). Non-prescription medications were more often used among breastfeeding than non-breastfeeding women (67.6% versus 48.9% at 3 months, p < 0.0001), The most commonly used non-prescription medications were multivitamins and Vitamin D at 3, 6 and 12 months postpartum. Conclusions: In Canada, medication use is common postpartum; 40% of breastfeeding women use prescription medications in the first 3 months postpartum. A diverse range of medications were used, with many women taking more than one prescription and non-prescription medicines. The most commonly used prescription medication by breastfeeding women were domperidone for off-label lactation support, signalling a need for more data on the efficacy of domperidone for this indication. This data should inform research priorities and communication strategies developed to optimize care during lactation. [ABSTRACT FROM AUTHOR]

The CHILD Cohort Study is an active multi-center longitudinal, prospective, population pregnancy cohort study following Canadian infants from fetal life until adulthood. We hypothesized that early life physical and psychosocial environments interact with biological factors (e.g. immunologic, genetic, physiologic, and metabolic) influencing burdensome non-communicable disease outcomes, including asthma and allergic disorders, growth and development, cardio-metabolic health, and neurodevelopmental outcomes that manifest during the life-course. Detailed clinical and physiologic phenotyping at strategic intervals was complemented by environmental sampling, actigraphy and global positioning system measures, biological sampling including gut, breastmilk and nasal microbiome, nutritional studies, genetics, and epigenetic profiling. Of 3,454 families recruited from 2008 to 2012, study retention was 96.0% at 1-year, 93.2% at 5-years and 90.7% at 8-years. Data collection during the SARS-2 COVID-19 pandemic was partially completed via virtual visits. A sub-cohort was implemented, capturing detailed information on the prevalence and predictors of SARS-CoV-2 infection and the health and psychosocial impact of the pandemic on Canadian families. The 13-year clinical assessment launched in 2022 will be completed in 2025. Ultimately, the CHILD Cohort Study provides a data science platform designed to enable a deep understanding of early life factors associated with the development of chronic non-communicable diseases and multimorbidity., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Maternal diet may modulate human milk microbiota, but the effects of nutritional supplements are unknown. We examined the associations of prenatal diet and supplement use with milk microbiota composition. Mothers reported prenatal diet intake and supplement use using self-administered food frequency and standardised questionnaires, respectively. The milk microbiota was profiled using 16S rRNA gene sequencing. Associations of prenatal diet quality, dietary patterns, and supplement use with milk microbiota diversity and taxonomic structure were examined using Wilcoxon signed-rank tests and multivariable models adjusting for relevant confounders. A subset of 645 mothers participating in the CHILD Cohort Study (originally known as the Canadian Healthy Infant Longitudinal Development Study) provided one milk sample between 2 and 6 months postpartum and used prenatal multivitamin supplements ≥4 times a week. After adjusting for confounders, vitamin C supplement use was positively associated with milk bacterial Shannon diversity ( β = 0.18, 95% CI = 0.05, 0.31) and Veillonella and Granulicatella relative abundance ( β = 0.54; 95% CI = 0.05, 1.03 and β = 0.44; 95% CI = 0.04, 0.84, respectively), and negatively associated with Finegoldia relative abundance ( β = -0.31; 95% CI = -0.63, -0.01). Fish oil supplement use was positively associated with Streptococcus relative abundance ( β = 0.26; 95% CI = 0.03, 0.50). Prenatal diet quality and dietary patterns were not associated with milk microbiota composition. Prenatal vitamin C and fish oil supplement use were associated with differences in the milk microbiota composition. Future studies are needed to confirm our findings and elucidate mechanisms linking maternal supplement use to milk microbiota and child health., Competing Interests: The authors report no conflicts of interest., (© The Author(s) 2024.)

Breastfeeding provides many health benefits, but its impact on respiratory health remains unclear. This study addresses the complex and dynamic nature of the mother-milk-infant triad by investigating maternal genomic factors regulating human milk oligosaccharides (HMOs), and their associations with respiratory health among human milk-fed infants. Nineteen HMOs are quantified from 980 mothers of the CHILD Cohort Study. Genome-wide association studies identify HMO-associated loci on chromosome 19p13.3 and 19q13.33 (lowest P = 2.4e-118), spanning several fucosyltransferase (FUT) genes. We identify novel associations on chromosome 3q27.3 for 6'-sialyllactose (P = 2.2e-9) in the sialyltransferase (ST6GAL1) gene. These, plus additional associations on chromosomes 7q21.32, 7q31.32 and 13q33.3, are replicated in the independent INSPIRE Cohort. Moreover, gene-environment interaction analyses suggest that fucosylated HMOs may modulate overall risk of recurrent wheeze among preschoolers with variable genetic risk scores (P < 0.01). Thus, we report novel genetic factors associated with HMOs, some of which may protect the respiratory health of children., (© 2024. The Author(s).)

Competing Interests: Competing interests: None declared.