Search

Breastfeeding has many established benefits for mothers, children, and society at large; however, the vast majority of infants globally do not meet international breastfeeding recommendations. There are many complex reasons for suboptimal breastfeeding rates, including social and societal factors. Alongside increasing social media use worldwide, there is an expanding research focus on how social media use affects health behaviours, decisions and perceptions. The objective of this study was to systematically determine if and how breastfeeding is promoted and supported on the popular social media platform Instagram, which currently has over 700 million active users worldwide. To assess how Instagram is used to depict and portray breastfeeding, and how users share perspectives and information about this topic, we analysed 4,089 images and 8,331 corresponding comments posted with popular breastfeeding‐related hashtags (#breastfeeding, #breastmilk, #breastisbest, and #normalizebreastfeeding). We found that Instagram is being mobilized by users to publicly display and share diverse breastfeeding‐related content and to create supportive networks that allow new mothers to share experiences, build confidence, and address challenges related to breastfeeding. Discussions were overwhelmingly positive and often highly personal, with virtually no antagonistic content. Very little educational content was found, contrasted by frequent depiction and discussion of commercial products. Thus, Instagram is currently used by breastfeeding mothers to create supportive networks and could potentially offer new avenues and opportunities to "normalize," protect, promote, and support breastfeeding more broadly across its large and diverse global online community. [ABSTRACT FROM AUTHOR]

Background: A growing number of studies observe associations between the amount of green space around a mother's home and positive birth outcomes; however, the robustness of this association and potential pathways of action remain unclear. Objectives: To examine associations between mother's residential green space and term birth weight within the Canadian Healthy Infant Longitudinal Development (CHILD) study and examine specific hypothesized pathways. Methods: We examined 2510 births located in Vancouver, Edmonton, Winnipeg, and Toronto Canada. Green space was estimated around mother's residences during pregnancy using Landsat 30 m normalized difference vegetation index (NDVI). We examined hypothesized pathways of: (1) reduction of environmental exposure; (2) built environment features promoting physical activity; (3) psychosocial conditions; and (4) psychological influences. Linear regression was used to assess associations between green space and term birth weight adjusting first for a comprehensive set of confounding factors and then incrementally for pathway variables. Results: Fully adjusted models showed non-statistically significant increases in term birth weight with increasing green space. For example, a 0.1 increase in NDVI within 500 m was associated with a 21.5 g (95% CI − 4.6, 47.7) increase in term birth weight. Associations varied by city and were most robust for high-density locations. For the two largest cities (Vancouver and Toronto), we observed an increase in birth weight of 41.2 g (95% CI 7.8, 74.6) for a 0.1 increase in NDVI within 500 m. We did not observe substantial reductions in the green space effect on birth weight when adjusting for pathway variables. Conclusion: Our results highlight the need to further characterize the interactions between green space, urban density and climate related factors as well as the pathways linking residential green space to birth outcomes. [ABSTRACT FROM AUTHOR]

There is increasing evidence that interactions between microbes and their hosts not only play a role in determining health and disease but also in emotions, thought, and behavior. Built environments greatly influence microbiome exposures because of their built-in highly specific microbiomes coproduced with myriad metaorganisms including humans, pets, plants, rodents, and insects. Seemingly static built structures host complex ecologies of microorganisms that are only starting to be mapped. These microbial ecologies of built environments are directly and interdependently affected by social, spatial, and technological norms. Advances in technology have made these organisms visible and forced the scientific community and architects to rethink gene-environment and microbe interactions respectively. Thus, built environment design must consider the microbiome, and research involving host-microbiome interaction must consider the built-environment. This paradigm shift becomes increasingly important as evidence grows that contemporary built environments are steadily reducing the microbial diversity essential for human health, well-being, and resilience while accelerating the symptoms of human chronic diseases including environmental allergies, and other more life-altering diseases. New models of design are required to balance maximizing exposure to microbial diversity while minimizing exposure to human-associated diseases. Sustained trans-disciplinary research across time (evolutionary, historical, and generational) and space (cultural and geographical) is needed to develop experimental design protocols that address multigenerational multispecies health and health equity in built environments. [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]

Previous studies on the differences in gut microbiota between exclusively breastfed (EBF) and non-EBF infants have provided highly variable results. Here we perform a meta-analysis of seven microbiome studies (1825 stool samples from 684 infants) to compare the gut microbiota of non-EBF and EBF infants across populations. In the first 6 months of life, gut bacterial diversity, microbiota age, relative abundances of Bacteroidetes and Firmicutes, and predicted microbial pathways related to carbohydrate metabolism are consistently higher in non-EBF than in EBF infants, whereas relative abundances of pathways related to lipid metabolism, vitamin metabolism, and detoxification are lower. Variation in predicted microbial pathways associated with non-EBF infants is larger among infants born by Caesarian section than among those vaginally delivered. Longer duration of exclusive breastfeeding is associated with reduced diarrhea-related gut microbiota dysbiosis. Furthermore, differences in gut microbiota between EBF and non-EBF infants persist after 6 months of age. Our findings elucidate some mechanisms of short and long-term benefits of exclusive breastfeeding across different populations. Studies on the effects of breastfeeding on the infant gut microbiota have provided inconsistent results. Here, Ho et al. perform a meta-analysis of seven studies across different populations, supporting that exclusive breastfeeding is associated with short-term and long-term alterations in the infant gut microbiota. [ABSTRACT FROM AUTHOR]

Breastfeeding has many established health benefits, but its impact on asthma development is uncertain. Breastfeeding appears to have a positive and dose-dependent impact on respiratory health, particularly during early childhood and in high-risk populations; however, the strength and causality of these associations are unclear. It is challenging to compare results across studies due to methodological differences and biological variation. Resolving these inconsistencies will require well-designed, prospective studies that accurately capture asthma diagnoses and infant feeding exposures (including breastfeeding duration, exclusivity, and method of feeding), account for key confounders, evaluate dose effects, and consider effect modification and reverse causality. Mechanistic studies examining human milk bioactives and their impact on lung health and asthma development are beginning to emerge, and these will be important in establishing the causality and mechanistic basis of the observed associations between breastfeeding and asthma. In this review, we summarize current evidence on this topic, identify possible reasons for disagreement across studies, discuss potential mechanisms for a causal association, and provide recommendations for future research. [ABSTRACT FROM AUTHOR]

Background Recent trials have shown that avoiding peanuts during infancy increases the risk of peanut allergy; however, these studies did not address maternal peanut consumption. Objective We sought to investigate the relationship between maternal peanut consumption while breast-feeding, timing of direct peanut introduction, and peanut sensitization at age 7 years. Methods Secondary analysis of a nested cohort within the 1995 Canadian Asthma Primary Prevention Study intervention study was performed. Breast-feeding and maternal and infant peanut consumption were captured by repeated questionnaires during infancy. Skin prick testing for peanut sensitization was performed at age 7 years. Results Overall, 58.2% of mothers consumed peanuts while breast-feeding and 22.5% directly introduced peanuts to their infant by 12 months. At 7 years, 9.4% of children were sensitized to peanuts. The lowest incidence (1.7%) was observed among children whose mothers consumed peanuts while breast-feeding and directly introduced peanuts before 12 months. Incidence was significantly higher ( P < .05) if mothers consumed peanuts while breast-feeding but delayed introducing peanuts to their infant beyond 12 months (15.1%), or if mothers avoided peanuts themselves but directly introduced peanuts by 12 months (17.6%). Interaction analyses controlling for study group and maternal atopy confirmed that maternal peanut consumption while breast-feeding and infant peanut consumption by 12 months were protective in combination, whereas either exposure in isolation was associated with an increased risk of sensitization ( P interaction = .003). Conclusions In this secondary analysis, maternal peanut consumption while breast-feeding paired with direct introduction of peanuts in the first year of life was associated with the lowest risk of peanut sensitization, compared with all other combinations of maternal and infant peanut consumption. [ABSTRACT FROM AUTHOR]

Objective: To determine whether different modes of infant feeding are associated with childhood asthma, including differentiating between direct breastfeeding and expressed breast milk.Study Design: We studied 3296 children in the Canadian Healthy Infant Longitudinal Development birth cohort. The primary exposure was infant feeding mode at 3 months, reported by mothers and categorized as direct breastfeeding only, breastfeeding with some expressed breast milk, breast milk and formula, or formula only. The primary outcome was asthma at 3 years of age, diagnosed by trained healthcare professionals.Results: At 3 months of age, the distribution of feeding modes was 27% direct breastfeeding, 32% breastfeeding with some expressed breast milk, 26% breast milk and formula, and 15% formula only. At 3 years of age, 12% of children were diagnosed with possible or probable asthma. Compared with direct breastfeeding, any other mode of infant feeding was associated with an increased risk of asthma. These associations persisted after adjusting for maternal asthma, ethnicity, method of birth, infant sex, gestational age, and daycare attendance (some expressed breast milk: aOR, 1.64, 95% CI, 1.12-2.39; breast milk and formula, aOR, 1.73, 95% CI, 1.17-2.57; formula only: aOR, 2.14, 95% CI, 1.37-3.35). Results were similar after further adjustment for total breastfeeding duration and respiratory infections.Conclusions: Modes of infant feeding are associated with asthma development. Direct breastfeeding is most protective compared with formula feeding; indirect breast milk confers intermediate protection. Policies that facilitate and promote direct breastfeeding could have impact on the primary prevention of asthma. [ABSTRACT FROM AUTHOR]

The article discusses research on safety and effectiveness of probiotic supplementation during pregnancy or infancy for pediatric asthma and wheezing prevention. It acknowledges previous studies which suggest relation between asthma prevalence and infant gut microbiota disruption. It reports study procedures performed including participant selection, administration of probiotic supplements, and data analysis. The need for further studies into probiotics and childhood asthma is noted.

Background: Childhood obesity is a global health concern and can lead to lifetime cardiometabolic disease. New advances in metabolomics can provide biochemical insights into the early development of obesity, so we aimed to characterize serum metabolites associated with overweight and adiposity in early childhood and to stratify associations by sex. Methods: Nontargeted metabolite profiling was conducted in the Canadian CHILD birth cohort (discovery cohort) at age 5 years (n = 900) by multisegment injection-capillary electrophoresis-mass spectrometry. Clinical outcome was defined using novel combined measures of overweight (WHO-standardized body mass index ≥ 85th percentile) and/or adiposity (waist circumference ≥ 90th percentile). Associations between circulating metabolites and child overweight/adiposity (binary and continuous outcomes) were determined by multivariable linear and logistic regression, adjusting for covariates and false discovery rate, and by subsequent sex-stratified analysis. Replication was assessed in an independent replication cohort called FAMILY at age 5 years (n = 456). Results: In the discovery cohort, each standard deviation (SD) increment of branched-chain and aromatic amino acids, glutamic acid, threonine, and oxoproline was associated with 20–28% increased odds of overweight/adiposity, whereas each SD increment of the glutamine/glutamic acid ratio was associated with 20% decreased odds. All associations were significant in females but not in males in sex-stratified analyses, except for oxoproline that was not significant in either subgroup. Similar outcomes were confirmed in the replication cohort, where associations of aromatic amino acids, leucine, glutamic acid, and the glutamine/glutamic acid ratio with childhood overweight/adiposity were independently replicated. Conclusions: Our findings show the utility of combining measures of both overweight and adiposity in young children. Childhood overweight/adiposity at age 5 years has a specific serum metabolic phenotype, with the profile being more prominent in females compared to males. [ABSTRACT FROM AUTHOR]

An abstract of the article "Infant gut microbiota and the hygiene hypothesis of allergic disease," by Meghan B. Azad and colleagues is presented.

Colonization of infants with Clostridium difficile is on the rise. Although better tolerated by infants than adults, it is a risk factor for future allergic disease. The present study describes associations between infant fecal immunoglobulin A (IgA) and colonization with C. difficile in 47 infants enrolled in the Canadian Healthy Infant Longitudinal Development (CHILD) study. C. difficile colonization was observed in over half (53%) of the infants. Median IgA was lower in infants colonized with C. difficile (10.9 μg versus 25.5 μg per g protein; p = 0.18). A smaller proportion of infants with IgA in the highest tertile were colonized with C. difficile compared to the other tertiles (31.3% versus 64.5%, p = 0.03). In unadjusted analysis, odds of colonization with C. difficile was reduced by 75% (OR 0.25 95% CI 0.07, 0.91 p = 0.04) among infants with IgA in the highest tertile compared to those in the other tertiles. Following adjustment for parity, birth mode and breastfeeding, this association was even stronger (aOR 0.17, 95% CI 0.03, 0.94, p = 0.04). Our study provides evidence that high fecal IgA, independent of breastfeeding, is associated with reduced likelihood of C. difficile colonization in infancy. [ABSTRACT FROM AUTHOR]

Objective: To identify factors associated with breast-feeding initiation and continuation in Canadian-born and non-Canadian-born women. Design: Prospective cohort of mothers and infants born from 2008 to 2012: the Canadian Healthy Infant Longitudinal Development (CHILD) Cohort Study. Setting: General community setting in four Canadian provinces. Participants: In total, 3455 pregnant women from Vancouver, Edmonton, Winnipeg and Toronto between 2008 and 2012. Results: Of 3010 participants included in the current study, the majority were Canadian-born (75·5 %). Breast-feeding initiation rates were high in both non-Canadian-born (95·5 %) and Canadian-born participants (92·7 %). The median breast-feeding duration was 10 months in Canadian-born participants and 11 months in non-Canadian-born participants. Among Canadian-born participants, factors associated with breast-feeding initiation and continuation were older maternal age, higher maternal education, living with their partner and recruitment site. Rooming-in during the hospital stay was also associated with higher rates of breast-feeding initiation, but not continuation at 6-month postpartum. Factors associated with non-initiation of breast-feeding and cessation at 6-month postpartum were maternal smoking, living with a current smoker, caesarean birth and early-term birth. Among non-Canadian-born participants, maternal smoking during pregnancy was associated with lower odds of breast-feeding initiation and lower odds of breast-feeding continuation at 6 months, and older maternal age and recruitment site were associated with breast-feeding continuation at 6 months. Conclusions: Although Canadian-born and non-Canadian-born women in the CHILD cohort have similar breast-feeding initiation rates, breast-feeding initiation and continuation are more strongly associated with socio-demographic characteristics in Canadian-born participants. Recruitment site was strongly associated with breast-feeding continuation in both groups and may indicate geographic disparities in breast-feeding rates nationally. [ABSTRACT FROM AUTHOR]

Background: Polyunsaturated fatty acids (PUFAs) may influence immune development. We examined the association of PUFAs in human milk with food sensitization and atopic dermatitis among breastfed infants. Methods: In a selected subgroup of 1109 mother‐infant dyads from the CHILD Cohort Study, human milk was analyzed by gas‐liquid chromatography to quantify PUFAs including arachidonic acid (ARA) and docosahexaenoic acid (DHA). At 1 year of age, food sensitization was determined by skin‐prick testing for egg, peanut, cow's milk, and soybean, and atopic dermatitis was diagnosed by pediatricians. Logistic regression analyses controlled for breastfeeding exclusivity, family history of atopy, and other potential confounders. Results: Overall, 184 infants (17%) were sensitized to one or more food allergens and 160 (14%) had atopic dermatitis. Sex‐specific associations were observed between these conditions and milk PUFAs. Girls receiving human milk with lower proportions of DHA had lower odds of food sensitization (aOR 0.35; 95% CI 0.12, 0.99 for lowest vs highest quintile), and a clear dose‐dependent association was observed for the ARA/DHA ratio (aOR 2.98; 95% CI 1.10, 8.06 for lowest vs highest quintile). These associations were not seen in boys. Similar sex‐specific tendencies were observed for atopic dermatitis. Conclusions: Human milk PUFA proportions and their ratios are associated with infant atopic conditions in a sex‐specific manner. In female infants, a higher ratio of ARA/DHA may reduce the risk of food sensitization and atopic dermatitis. Further research is needed to determine the underlying mechanisms and clinical relevance of this sex‐specific association. [ABSTRACT FROM AUTHOR]

Bacterial members of the infant gut microbiota and bacterial-derived short-chain fatty acids (SCFAs) have been shown to be protective against childhood asthma, but a role for the fungal microbiota in asthma etiology remains poorly defined. We recently reported an association between overgrowth of the yeast Pichia kudriavzevii in the gut microbiota of Ecuadorian infants and increased asthma risk. In the present study, we replicated these findings in Canadian infants and investigated a causal association between early life gut fungal dysbiosis and later allergic airway disease (AAD). In a mouse model, we demonstrate that overgrowth of P. kudriavzevii within the neonatal gut exacerbates features of type-2 and -17 inflammation during AAD later in life. We further show that P. kudriavzevii growth and adherence to gut epithelial cells are altered by SCFAs. Collectively, our results underscore the potential for leveraging inter-kingdom interactions when designing putative microbiota-based asthma therapeutics. [ABSTRACT FROM AUTHOR]

Background: Early-life stress is becoming an important determinant of immune system programming. Maternal prenatal distress is found to be associated with atopic disease in offspring but the separate effects of postnatal distress are not well-studied.Research Question: Does the likelihood of asthma and atopic dermatitis in children increase when they are exposed to maternal distress pre- and postnatally in a sex-specific manner?Study Design and Methods: Using data from a provincial newborn screen and health-care database for 12,587 children born in 2004, maternal distress (depression or anxiety) was defined as prenatal, self-limiting, recurrent, or late-onset postpartum. Atopic dermatitis (AD) and asthma at ages 5 years and 7 years of age were diagnosed by using hospitalization, physician visit, or prescription records. Associations between maternal distress and childhood asthma and AD were determined by using multiple logistic regression.Results: After adjusting for risk factors, a significant association between maternal prenatal (OR, 1.27; 95% CI, 1.11-1.46), recurrent postpartum (OR, 1.28; 95% CI, 1.11-1.48), and late-onset postpartum (OR, 1.19, 95% CI, 1.06-1.34) distress was found with AD at age 5 years. Asthma at age 7 years was also associated with maternal prenatal distress (OR, 1.57; 95% CI, 1.29-1.91) and late-onset postnatal distress (OR, 1.22; 95% CI, 1.01-1.46). Self-limiting postnatal distress was not found to be a risk factor for either atopic condition. Associations with AD or asthma were of a similar magnitude in boys and girls; the exception was recurrent postnatal distress, which increased risk for asthma in boys only.Interpretation: This population-based study provides evidence for sex-specific associations between maternal prenatal and postnatal distress, as well as the development of AD and asthma. The findings support recommendations for greater psychosocial support of mothers during pregnancy and early childhood to prevent childhood atopic disease. [ABSTRACT FROM AUTHOR]

Background: Fungi constitute an important yet frequently neglected component of the human microbiota with a possible role in health and disease. Fungi and bacteria colonise the infant gastrointestinal tract in parallel, yet most infant microbiome studies have ignored fungi. Milk is a source of diverse and viable bacteria, but few studies have assessed the diversity of fungi in human milk. Results: Here we profiled mycobiota in milk from 271 mothers in the CHILD birth cohort and detected fungi in 58 (21.4%). Samples containing detectable fungi were dominated by Candida, Alternaria, and Rhodotorula, and had lower concentrations of two human milk oligosaccharides (disialyllacto-N-tetraose and lacto-N-hexaose). The presence of milk fungi was associated with multiple outdoor environmental features (city, population density, and season), maternal atopy, and early-life antibiotic exposure. In addition, despite a strong positive correlation between bacterial and fungal richness, there was a co-exclusion pattern between the most abundant fungus (Candida) and most of the core bacterial genera. Conclusion: We profiled human milk mycobiota in a well-characterised cohort of mother-infant dyads and provide evidence of possible host-environment interactions in fungal inoculation. Further research is required to establish the role of breastfeeding in delivering fungi to the developing infant, and to assess the health impact of the milk microbiota in its entirety, including both bacterial and fungal components. [ABSTRACT FROM AUTHOR]

Background: Comprehensive longitudinal studies are important for understanding the complex risk factors, pathways, exposures and interactions that lead to the development and persistence of asthma. We aimed to examine associations between use of household cleaning products in early life and childhood respiratory and allergic disease using data from the Canadian Healthy Infant Longitudinal Development (CHILD) Cohort Study.Methods: We summed responses from parental questionnaires that indicated the frequency of use of 26 household cleaning products in the homes of 2022 children from this birth cohort when they were 3-4 months of age to create a cumulative Frequency of Use Score (FUS). We used multivariable logistic regression models to assess whether frequent compared with less frequent use was associated with recurrent wheeze, atopy or asthma diagnosis, as defined by the questionnaire and clinical assessments at age 3 years. Data were collected between 2008 and 2015.Results: Children in homes with a higher frequency of use of cleaning products in infancy, as determined by an interquartile range increase, had higher odds of recurrent wheeze (adjusted odds ratio [OR] 1.35, 95% confidence interval [CI] 1.11-1.64), recurrent wheeze with atopy (adjusted OR 1.49, 95% CI 1.02-2.16) and asthma diagnosis (adjusted OR 1.37, 95% CI 1.09-1.70), but no increase in the odds of atopy at age 3 years (adjusted OR 1.14, 95% CI 0.96-1.35). Compared with the lowest tertile of FUS exposure, infants in the highest tertile had higher odds of acquiring asthma. Stratification of the results showed that females had higher ORs than males for all outcomes, although the p values for this sex difference did not reach statistical significance.Interpretation: Frequent use of household cleaning products in early life was associated with an increased risk for childhood wheeze and asthma but not atopy at age 3 years. Our findings add to the understanding of how early life exposures to cleaning products may be associated with the development of allergic airway disease and help to identify household behaviours as a potential area for intervention. [ABSTRACT FROM AUTHOR]

Rationale: Sleep duration is critical to growth, learning, and immune function development in infancy. Strategies to ensure that national recommendations for sleep duration in infants are met require knowledge of perinatal factors that affect infant sleep.Objectives: To investigate the mechanistic pathways linking maternal education and infant sleep.Methods: An observational study was conducted on 619 infants whose mothers were enrolled at the Edmonton site of the CHILD birth cohort. Infant sleep duration at three months was assessed using the Brief Infant Sleep Questionnaire. Maternal education was collected via maternal report. Prenatal and postnatal depression scores were obtained from the 20-item Center for Epidemiologic Studies Depression Scale (CES-D). Birth records and maternal report were the source of covariate measures. Mediation analysis (PROCESS v3.0) was used to examine the indirect effects of maternal education on infant sleep duration mediated through prenatal depression and birth mode.Measurements and Main Results: At three months of age, infants slept on average 14.1 h. Lower maternal education and prenatal depression were associated with significantly shorter infant sleep duration. Emergency cesarean section birth was associated with 1-hour shorter sleep duration at three months compared to vaginal birth [without intrapartum antibiotic prophylaxis] (β: -0.99 h; 95% CI: -1.51, -0.48). Thirty percent of the effect of lower maternal education on infant total sleep duration was mediated sequentially through prenatal depression and birth mode (Total Indirect Effects: -0.12, 95% CI: -0.22, -0.03, p < 0.05).Conclusions: Prenatal depression and birth mode sequentially mediate the effect of maternal education on infant sleep duration. [ABSTRACT FROM AUTHOR]

Studies have demonstrated an association between phthalate exposure and childhood asthma, although results have been inconsistent. No epidemiological studies have examined exposure during the first year of life. To investigate the association between phthalate exposures in the home environment during the first year of life, and subsequent development of childhood asthma and related symptoms. This study used a case-cohort design including 436 randomly selected children and all additional cases of asthma at 5 years (n total = 129) and recurrent wheeze between 2 and 5 years (n total = 332) within the CHILD Cohort Study, a general population Canadian birth cohort of 3455 children. Phthalate exposure was assessed using house dust samples collected during a standardized home visit when children were 3-4 months of age. All children were assessed by specialist clinicians for asthma and allergy at 1, 3 and 5 years. Logistic regression was used to assess the association between exposure to five phthalates and asthma diagnosis at 5 years, and recurrent wheeze between 2 and 5 years, with further stratification by wheeze subtypes (late onset, persistent, transient) based on the timing of onset and persistence of wheeze symptoms. Di(2-ethylhexyl) phthalate (DEHP) had the highest concentration in dust (median subcohort = 217 μg/g), followed by benzyl butyl phthalate (BzBP) (20 μg/g). A nearly four-fold increase in risk of developing asthma was associated with the highest concentration quartile of DEHP (OR = 3.92, 95% CI: 1.87–8.24) including a positive dose-response relationship. A two-fold increase in risk of recurrent wheeze was observed across all quartiles compared to the lowest quartile of DEHP concentrations. Compared to other wheeze subtypes, stronger associations for DEHP were observed with the late onset wheezing subtype, while stronger associations for di-iso-butyl phthalate (DiBP) and BzBP were observed with the transient subtype. DEHP exposure at 3-4 months, at concentrations lower than other studies that reported an association, were associated with increased risks of asthma and recurrent wheeze among children at 5 years. These findings suggest the need to assess whether more stringent regulations are required to protect children's health, which can be informed by future work exploring the main sources of DEHP exposure. • DEHP, BzBP, DnBP, DiBP and DEP were detected in nearly all house dust samples. • Early life DEHP exposure was associated with a large increased risk of asthma at 5 years. • Early life DEHP exposure associated with increased risk of recurrent wheeze between 2 and 5 years. • Increased risk with DEHP observed at concentrations lower than other studies. [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.)

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., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

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 and microbial colonization during infancy occur within a critical time window for development, and both are thought to influence the risk of respiratory illness. However, the mechanisms underlying the protective effects of breastfeeding and the regulation of microbial colonization are poorly understood. Here, we profiled the nasal and gut microbiomes, breastfeeding characteristics, and maternal milk composition of 2,227 children from the CHILD Cohort Study. We identified robust colonization patterns that, together with milk components, predict preschool asthma and mediate the protective effects of breastfeeding. We found that early cessation of breastfeeding (before 3 months) leads to the premature acquisition of microbial species and functions, including Ruminococcus gnavus and tryptophan biosynthesis, which were previously linked to immune modulation and asthma. Conversely, longer exclusive breastfeeding supports a paced microbial development, protecting against asthma. These findings underscore the importance of extended breastfeeding for respiratory health and highlight potential microbial targets for intervention., Competing Interests: Declaration of interests M.B.A. receives research funding from the Canadian and US governments, the Bill and Melinda Gates Foundation, and the Garfield Weston Foundation. She holds a Canada Research Chair in Early Nutrition and the Developmental Origins of Health and Disease and is a fellow of the CIFAR Humans and the Microbiome program. She has consulted for DSM Nutritional Products, serves on the scientific advisory board for TinyHealth, and has received speaking honoraria from Prolacta Biosciences. She has contributed without remuneration to online courses on breast milk and the infant microbiome produced by Microbiome Courses. L.B. receives research funding from the United States National Institutes of Health and the Bill and Melinda Gates Foundation. L.B. is the UC San Diego Chair of Collaborative Human Milk Research endowed by the Family Larsson-Rosenquist Foundation in Switzerland. V.B. is currently an employee of F. Hoffman-La Roche Ltd.; however, the published work was done prior to her employment and does not involve/promote any of Roche’s materials or point of view., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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).)

Background: Atopic dermatitis (AD) is the most common chronic inflammatory skin disease in both pediatric and adult populations. The development of AD has been linked to antibiotic usage, which causes perturbation of the microbiome and has been associated with abnormal immune system function. However, imbalances in the gut microbiome itself associated with antibiotic usage have been inconsistently linked to AD., Objectives: This study aimed to elucidate the timing and specific factors mediating the relationship between systemic (oral or intravenous) antibiotic usage and AD., Methods: We used statistical modeling and differential analysis to link CHILD Cohort Study participants' history of antibiotic usage and early-life gut microbiome alterations to AD., Results: Here we report that systemic antibiotics during the first year of life, as compared to later, are associated with AD risk (adjusted odds ratio [aOR] = 1.81; 95% CI: 1.28-2.57; P < .001), with an increased number of antibiotic courses corresponding to a dose response-like increased risk of AD risk (1 course: aOR: 1.67; 95% CI: 1.17-2.38; 2 or more courses: aOR: 2.16; 95% CI: 1.30-3.59). Further, we demonstrate that microbiome alterations associated with both AD and systemic antibiotic usage fully mediate the effect of antibiotic usage on the development of AD (β indirect  = 0.072; P < .001). Alterations in the 1-year infant gut microbiome of participants who would later develop AD included increased Tyzzerella nexilis, increased monosaccharide utilization, and parallel decreased Bifidobacterium and Eubacterium spp, and fermentative pathways., Conclusions: These findings indicate that early-life antibiotic usage, especially in the first year of life, modulates key gut microbiome components that may be used as markers to predict and possibly prevent the development of AD., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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., (© 2024. The Author(s).)

Background: Epigenetic modifications, particularly DNA methylation (DNAm) in cord blood, are an important biological marker of how external exposures during gestation can influence the in-utero environment and subsequent offspring development. Despite the recognized importance of DNAm during gestation, comparative studies to determine the consistency of these epigenetic signals across different ethnic groups are largely absent. To address this gap, we first performed epigenome-wide association studies (EWAS) of gestational age (GA) using newborn cord blood DNAm comparatively in a white European (n = 342) and a South Asian (n = 490) birth cohort living in Canada. Then, we capitalized on established cord blood epigenetic GA clocks to examine the associations between maternal exposures, offspring characteristics and epigenetic GA, as well as GA acceleration, defined as the residual difference between epigenetic and chronological GA at birth., Results: Individual EWASs confirmed 1,211 and 1,543 differentially methylated CpGs previously reported to be associated with GA, in white European and South Asian cohorts, respectively, with a similar distribution of effects. We confirmed that Bohlin's cord blood GA clock was robustly correlated with GA in white Europeans (r = 0.71; p = 6.0 × 10 -54 ) and South Asians (r = 0.66; p = 6.9 × 10 -64 ). In both cohorts, Bohlin's clock was positively associated with newborn weight and length and negatively associated with parity, newborn female sex, and gestational diabetes. Exclusive to South Asians, the GA clock was positively associated with the newborn ponderal index, while pre-pregnancy weight and gestational weight gain were strongly predictive of increased epigenetic GA in white Europeans. Important predictors of GA acceleration included gestational diabetes mellitus, newborn sex, and parity in both cohorts., Conclusions: These results demonstrate the consistent DNAm signatures of GA and the utility of Bohlin's GA clock across the two populations. Although the overall pattern of DNAm is similar, its connections with the mother's environment and the baby's anthropometrics can differ between the two groups. Further research is needed to understand these unique relationships., (© 2024. The Author(s).)

Background: Early identification of children at risk of asthma can have significant clinical implications for effective intervention and treatment. This study aims to disentangle the relative timing and importance of early markers of asthma., Methods: Using the CHILD Cohort Study, 132 variables measured in 1754 multi-ethnic children were included in the analysis for asthma prediction. Data up to 4 years of age was used in multiple machine learning models to predict physician-diagnosed asthma at age 5 years. Both predictive performance and variable importance was assessed in these models., Results: Early-life data (≤1 year) has limited predictive ability for physician-diagnosed asthma at age 5 years (area under the precision-recall curve (AUPRC) < 0.35). The earliest reliable prediction of asthma is achieved at age 3 years, (area under the receiver-operator curve (AUROC) > 0.90) and (AUPRC > 0.80). Maternal asthma, antibiotic exposure, and lower respiratory tract infections remained highly predictive throughout childhood. Wheezing status and atopy are the most important predictors of early childhood asthma from among the factors included in this study., Conclusions: Childhood asthma is predictable from non-biological measurements from the age of 3 years, primarily using parental asthma and patient history of wheezing, atopy, antibiotic exposure, and lower respiratory tract infections., Impact: Machine learning models can predict physician-diagnosed asthma in early childhood (AUROC > 0.90 and AUPRC > 0.80) using ≥3 years of non-biological and non-genetic information, whereas prediction with the same patient information available before 1 year of age is challenging. Wheezing, atopy, antibiotic exposure, lower respiratory tract infections, and the child's mother having asthma were the strongest early markers of 5-year asthma diagnosis, suggesting an opportunity for earlier diagnosis and intervention and focused assessment of patients at risk for asthma, with an evolving risk stratification over time., (© 2024. The Author(s).)

Background: Human milk fatty acids derive from maternal diet, body stores, and mammary synthesis and may reflect women's underlying cardiometabolic health. We explored whether human milk fatty acid composition was associated with maternal cardiometabolic disease (CMD) during pregnancy and up to 5 years postpartum. Materials and Methods: We analyzed data from the prospective CHILD Cohort Study on 1,018 women with no preexisting CMD who provided breast milk samples at 3-4 months postpartum. Milk fatty acid composition was measured using gas-liquid chromatography. Maternal CMD (diabetes or hypertension) was classified using questionnaires and birth records as no CMD (reference outcome group; 81.1%), perinatal CMD (developed and resolved during the perinatal period; 14.9%), persistent CMD (developed during, and persisted beyond, the perinatal period; 2.9%), and incident CMD (developed after the perinatal period; 1.1%). Multinomial logistic regression was used to model associations between milk fatty acid composition (individual, summary, ratios, and patterns identified using principal component analysis) and maternal CMD, adjusting for pre-pregnancy anthropometry and race/ethnicity. Results: Medium-chain saturated fatty acids (MC-SFA), lauric (C12:0; odds ratio [OR] = 0.73, 95% confidence interval [CI] = 0.60-0.89) and myristic acid (C14:0; OR = 0.80, 95% CI = 0.66-0.97), and the high MC-SFA principal component pattern (OR = 0.86, 95% CI = 0.76-0.96) were inversely associated with perinatal CMD. Long-chain polyunsaturated fatty acids adrenic acid (C22:4n-6) was positively associated with perinatal (OR = 1.21, 95% CI = 1.01-1.44) and persistent CMD (OR = 1.56, 95% CI = 1.08-2.25). The arachidonic (C20:4n-6)-to-docosahexaenoic acid (C22:6n-3) ratio was inversely associated with incident CMD (OR = 0.52, 95% CI = 0.28-0.96). Conclusions: These exploratory findings highlight a potential novel utility of breast milk for understanding women's cardiometabolic health.

We performed whole-genome sequencing (WGS) in 327 children with cerebral palsy (CP) and their biological parents. We classified 37 of 327 (11.3%) children as having pathogenic/likely pathogenic (P/LP) variants and 58 of 327 (17.7%) as having variants of uncertain significance. Multiple classes of P/LP variants included single-nucleotide variants (SNVs)/indels (6.7%), copy number variations (3.4%) and mitochondrial mutations (1.5%). The COL4A1 gene had the most P/LP SNVs. We also analyzed two pediatric control cohorts (n = 203 trios and n = 89 sib-pair families) to provide a baseline for de novo mutation rates and genetic burden analyses, the latter of which demonstrated associations between de novo deleterious variants and genes related to the nervous system. An enrichment analysis revealed previously undescribed plausible candidate CP genes (SMOC1, KDM5B, BCL11A and CYP51A1). A multifactorial CP risk profile and substantial presence of P/LP variants combine to support WGS in the diagnostic work-up across all CP and related phenotypes., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Competing Interests: Competing interests: None declared.

Objective: Breastfeeding is associated with reduced postpartum depression, stronger parent-child relationships, and fewer behavioral disorders in early childhood. We tested the mediating roles of postpartum depression and parent-child relationship in the association between breastfeeding practices and child behavior., Study Design: We used standardized questionnaire data from a subset of the CHILD Cohort Study (n = 1,573) to measure postpartum depression at 6 months, 1 year and 2 years, parent-child relationship 1 year and 2 years, and child behavior at 5 years using the Child Behavior Checklist (range 0-100). Breastfeeding practices were measured at 3 months (none, partial, some expressed, all direct at the breast), 6 months (none, partial, exclusive), 12 months, and 24 months (no, yes). Confounders included birth factors, maternal characteristics, and socioeconomic status., Results: Breast milk feeding at 3 or 6 months was associated with - 1.13 (95% CI: -2.19-0.07) to -2.14 (95% CI: -3.46, -0.81) lower (better) child behavior scores. Reduced postpartum depression at 6 months mediated between 11.5% and 16.6% of the relationship between exclusive breast milk feeding at 3 months and better child behavior scores. Together, reduced postpartum depression at 1 year and reduced parent-child dysfunction at 2 years mediated between 21.9% and 32.1% of the relationship between breastfeeding at 12 months and better child behavior scores., Conclusion: Postpartum depression and parent-child relationship quality partially mediate the relationship between breastfeeding practices and child behavior. Breastfeeding, as well as efforts to support parental mental health and parent-child relationships, may help to improve child behavior., (© 2024. The Author(s).)

Background: Cardiomyopathy is a clinically and genetically heterogeneous heart condition that can lead to heart failure and sudden cardiac death in childhood. While it has a strong genetic basis, the genetic aetiology for over 50% of cardiomyopathy cases remains unknown., Methods: In this study, we analyse the characteristics of tandem repeats from genome sequence data of unrelated individuals diagnosed with cardiomyopathy from Canada and the United Kingdom (n = 1216) and compare them to those found in the general population. We perform burden analysis to identify genomic and epigenomic features that are impacted by rare tandem repeat expansions (TREs), and enrichment analysis to identify functional pathways that are involved in the TRE-associated genes in cardiomyopathy. We use Oxford Nanopore targeted long-read sequencing to validate repeat size and methylation status of one of the most recurrent TREs. We also compare the TRE-associated genes to those that are dysregulated in the heart tissues of individuals with cardiomyopathy., Findings: We demonstrate that tandem repeats that are rarely expanded in the general population are predominantly expanded in cardiomyopathy. We find that rare TREs are disproportionately present in constrained genes near transcriptional start sites, have high GC content, and frequently overlap active enhancer H3K27ac marks, where expansion-related DNA methylation may reduce gene expression. We demonstrate the gene silencing effect of expanded CGG tandem repeats in DIP2B through promoter hypermethylation. We show that the enhancer-associated loci are found in genes that are highly expressed in human cardiomyocytes and are differentially expressed in the left ventricle of the heart in individuals with cardiomyopathy., Interpretation: Our findings highlight the underrecognized contribution of rare tandem repeat expansions to the risk of cardiomyopathy and suggest that rare TREs contribute to ∼4% of cardiomyopathy risk., Funding: Government of Ontario (RKCY), The Canadian Institutes of Health Research PJT 175329 (RKCY), The Azrieli Foundation (RKCY), SickKids Catalyst Scholar in Genetics (RKCY), The University of Toronto McLaughlin Centre (RKCY, SM), Ted Rogers Centre for Heart Research (SM), Data Sciences Institute at the University of Toronto (SM), The Canadian Institutes of Health Research PJT 175034 (SM), The Canadian Institutes of Health Research ENP 161429 under the frame of ERA PerMed (SM, RL), Heart and Stroke Foundation of Ontario & Robert M Freedom Chair in Cardiovascular Science (SM), Bitove Family Professorship of Adult Congenital Heart Disease (EO), Canada Foundation for Innovation (SWS, JR), Canada Research Chair (PS), Genome Canada (PS, JR), The Canadian Institutes of Health Research (PS)., Competing Interests: Declaration of interests SM holds the Heart and Stroke Foundation of Canada/Robert M Freedom Chair in Cardiovascular Science and serves on the Advisory Board for Bristol Myers Squibb and Tenaya Therapeutics. EO holds the Bitove Family Professorship of Adult Congenital Heart Disease. SWS is on the Scientific Advisory Committees of Population Bio, Inc. and Deep Genomics and serves as a Highly Cited Academic Advisor for the King Abdulaziz University. SWS and RY hold patent entitled “Genome-wide Detection of DNA Repeats Expanded in Disease” (WO2021119840A1). PM is a Senior Medical Director at Maternal Newborn Child Youth Strategic Clinical Network (Alberta Health Services) and was supported for attending Clinical Microbiology and Infectious Diseases, Long COVID and ENRICH meetings. TJM received support from CIHR, PSI and SickKids Foundation, CAMH and GSK. ES received support from COVID-19 Immune Task Force, Children's Hospital Foundation and CIHR, and is on the American Academy of Allergy, Asthma, and Immunology Credentials Committee. JR is supported by Canada Foundation for Innovation and received support for attending Ultima Biosciences and 10x Genomics meetings. Illumina, Inc. provided sequencing reagents for the CHILD cohort study. CHILD cohort study was supported by CIHR, AllerGen NCE, Alberta Health, Public Health Agency of Canada and Women's and Children's Health Research. Other authors declare that they have no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The gut microbiome undergoes primary ecological succession over the course of early life before achieving ecosystem stability around 3 years of age. These maturational patterns have been well-characterized for bacteria, but limited descriptions exist for other microbiota members, such as fungi. Further, our current understanding of the prevalence of different patterns of bacterial and fungal microbiome maturation and how inter-kingdom dynamics influence early-life microbiome establishment is limited., Results: We examined individual shifts in bacterial and fungal alpha diversity from 3 to 12 months of age in 100 infants from the CHILD Cohort Study. We identified divergent patterns of gut bacterial or fungal microbiome maturation in over 40% of infants, which were characterized by differences in community composition, inter-kingdom dynamics, and microbe-derived metabolites in urine, suggestive of alterations in the timing of ecosystem transitions. Known microbiome-modifying factors, such as formula feeding and delivery by C-section, were associated with atypical bacterial, but not fungal, microbiome maturation patterns. Instead, fungal microbiome maturation was influenced by prenatal exposure to artificially sweetened beverages and the bacterial microbiome, emphasizing the importance of inter-kingdom dynamics in early-life colonization patterns., Conclusions: These findings highlight the ecological and environmental factors underlying atypical patterns of microbiome maturation in infants, and the need to incorporate multi-kingdom and individual-level perspectives in microbiome research to improve our understandings of gut microbiome maturation patterns in early life and how they relate to host health. Video Abstract., (© 2024. The Author(s).)

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., (© 2024. The Author(s).)

Human milk (HM) provides a plethora of nutritional and non-nutritional compounds that support infant development. For many compounds, concentrations vary substantially among mothers and across lactation, and their impact on infant growth is poorly understood. We systematically searched MEDLINE, Embase, the Cochrane Library, Scopus, and Web of Science to synthesize evidence published between 1980 and 2022 on HM components and anthropometry through 2 y of age among term-born infants. Outcomes included weight-for-length, length-for-age, weight-for-age, body mass index (in kg/m 2 )-for-age, and growth velocity. From 9992 abstracts screened, 144 articles were included and categorized based on their reporting of HM micronutrients, macronutrients, or bioactive components. Micronutrients (vitamins and minerals) are reported here, based on 28 articles involving 2526 mother-infant dyads. Studies varied markedly in their designs, sampling times, geographic and socioeconomic settings, reporting practices, and the HM analytes and infant anthropometrics measured. Meta-analysis was not possible because data were sparse for most micronutrients. The most-studied minerals were zinc (15 articles, 1423 dyads) and calcium (7 articles, 714 dyads). HM iodine, manganese, calcium, and zinc concentrations were positively associated with several outcomes (each in ≥2 studies), whereas magnesium (in a single study) was negatively associated with linear growth during early lactation. However, few studies measured HM intake, adjusted for confounders, provided adequate information about complementary and formula feeding, or adequately described HM collection protocols. Only 4 studies (17%) had high overall quality scores. The biological functions of individual HM micronutrients are likely influenced by other HM components; yet, only 1 study analyzed data from multiple micronutrients simultaneously, and few addressed other HM components. Thus, available evidence on this topic is largely inconclusive and fails to address the complex composition of HM. High-quality research employing chronobiology and systems biology approaches is required to understand how HM components work independently and together to influence infant growth and to identify new avenues for future maternal, newborn, or infant nutritional interventions., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Among exclusively breastfed infants, human milk (HM) provides complete nutrition in the first mo of life and remains an important energy source as long as breastfeeding continues. Consisting of digestible carbohydrates, proteins, and amino acids, as well as fats and fatty acids, macronutrients in human milk have been well studied; however, many aspects related to their relationship to growth in early life are still not well understood. We systematically searched Medline, EMBASE, the Cochrane Library, Scopus, and Web of Science to synthesize evidence published between 1980 and 2022 on HM components and anthropometry through 2 y of age among term-born healthy infants. From 9992 abstracts screened, 57 articles reporting observations from 5979 dyads were included and categorized based on their reporting of HM macronutrients and infant growth. There was substantial heterogeneity in anthropometric outcome measurement, milk collection timelines, and HM sampling strategies; thus, meta-analysis was not possible. In general, digestible carbohydrates were positively associated with infant weight outcomes. Protein was positively associated with infant length, but no associations were reported for infant weight. Finally, HM fat was not consistently associated with any infant growth metrics, though various associations were reported in single studies. Fatty acid intakes were generally positively associated with head circumference, except for docosahexaenoic acid. Our synthesis of the literature was limited by differences in milk collection strategies, heterogeneity in anthropometric outcomes and analytical methodologies, and by insufficient reporting of results. Moving forward, HM researchers should accurately record and account for breastfeeding exclusivity, use consistent sampling protocols that account for the temporal variation in HM macronutrients, and use reliable, sensitive, and accurate techniques for HM macronutrient analysis., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Human milk (HM) contains macronutrients, micronutrients, and a multitude of other bioactive factors, which can have a long-term impact on infant growth and development. We systematically searched MEDLINE, EMBASE, Cochrane Library, Scopus, and Web of Science to synthesize evidence published between 1980 and 2022 on HM components and anthropometry through 2 y of age among term-born infants. From 9992 abstracts screened, 141 articles were included and categorized based on their reporting of HM micronutrients, macronutrients, or bioactive components. Bioactives including hormones, HM oligosaccharides (HMOs), and immunomodulatory components are reported here, based on 75 articles from 69 unique studies reporting observations from 9980 dyads. Research designs, milk collection strategies, sampling times, geographic and socioeconomic settings, reporting practices, and outcomes varied considerably. Meta-analyses were not possible because data collection times and reporting were inconsistent among the studies included. Few measured infant HM intake, adjusted for confounders, precisely captured breastfeeding exclusivity, or adequately described HM collection protocols. Only 5 studies (6%) had high overall quality scores. Hormones were the most extensively examined bioactive with 46 articles (n = 6773 dyads), compared with 13 (n = 2640 dyads) for HMOs and 12 (n = 1422 dyads) for immunomodulatory components. Two studies conducted untargeted metabolomics. Leptin and adiponectin demonstrated inverse associations with infant growth, although several studies found no associations. No consistent associations were found between individual HMOs and infant growth outcomes. Among immunomodulatory components in HM, IL-6 demonstrated inverse relationships with infant growth. Current research on HM bioactives is largely inconclusive and is insufficient to address the complex composition of HM. Future research should ideally capture HM intake, use biologically relevant anthropometrics, and integrate components across categories, embracing a systems biology approach to better understand how HM components work independently and synergistically to influence infant growth., Competing Interests: Conflict of interest M(M)B, SMR, and MBA have contributed to online courses on breast milk and the infant microbiome produced by Microbiome Courses. SMR has also served as the scientific advisor for SimpliFed and as a consultant for TraverseScience®. She is a current employee of Prolacta Bioscience®; her contribution to this review occurred prior to this employment. JMM has received support from the Bill & Melinda Gates Foundation and serves on the Council on Research for the American Academy of Nutrition and Dietetics. DC is supported by a Canadian Nurses Foundation Scholarship. DTG is funded by an unrestricted research grant from Medela AG. She is also currently funded by Telethon Child Health Grants and the Australian National Health and Medical Research Council. LHA has research grants from the Bill & Melinda Gates Foundation. MBA is supported by a Canada Research Chair and is a CIFAR Fellow in the Humans and the Microbiome Program; she has consulted for DSM and is a scientific advisor to TinyHealth. LB is UC San Diego Chair of Collaborative Human Milk Research endowed by the Family Larsson-Rosenquist Foundation and also receives support from the USNational Institutes of Health and The Bill & Melinda Gates Foundation. AID, MG, RR, KKS, SM, PPP, CM, FJ, PK, DH, and KGE have no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)