Characterisation and validation of lactation information from structured electronic health records for use in pharmacoepidemiological studies.

BACKGROUND: Breastfeeding information stored within electronic health records (EHR) has recently been used for pharmacoepidemiological research, however the data are primarily collected for clinical care. OBJECTIVES: To characterise breastfeeding information recorded in structured fields in EHR during infant and postpartum health care visits, and to assess the validity of lactation status based on EHR data versus maternal report at research study visits. METHODS: We assessed breastfeeding information recorded in structured fields in EHR from one health system for a subset of 211 patients who were also enrolled in a study on breast milk composition between 2014 and 2017 that required participants to exclusively breastfeed their infants until at least 1 month of age. We assessed the frequency of breastfeeding information in EHR during the first 12 months of age and compared lactation status based on EHR with maternal report at 1 and 6-month study visits (reference standard). RESULTS: The median number of breastfeeding records in the EHR per infant was six (interquartile range 3) with most observations clustering in the first few weeks of life and around well-infant visits. At the 6-month study visit, 93.8% of participants were breastfeeding and 80.1% were exclusively breastfeeding according to maternal report. Sensitivity of EHR data for identifying ever breastfeeding was at or near 100%, and sensitivity for identifying ever exclusive breastfeeding was 98.0% (95% CI: 95.0%, 99.2%). Sensitivities were 97.3% (95% CI: 93.9%, 98.9%) for identifying any breastfeeding and 94.4% (95% CI: 89.7%, 97.0%) for exclusive breastfeeding, and positive predictive values were 99.5% (95% CI: 97.0%, 99.9%) for any breastfeeding and 95.0% (95% CI: 90.4%, 97.4%) for exclusive breastfeeding. CONCLUSIONS: Breastfeeding information in structured EHR fields have the potential to accurately classify lactation status. The validity of these data should be assessed in populations with a lower breastfeeding prevalence.

Assembly, stability, and dynamics of the infant gut microbiome are linked to bacterial strains and functions in mother's milk.

The establishment of the gut microbiome in early life is critical for healthy infant development. Although human milk is recommended as the sole source of nutrition for the human infant, little is known about how variation in milk composition, and especially the milk microbiome, shapes the microbial communities in the infant gut. Here, we quantified the similarity between the maternal milk and the infant gut microbiome using 507 metagenomic samples collected from 195 mother-infant pairs at one, three, and six months postpartum. We found that the microbial taxonomic overlap between milk and the infant gut was driven by bifidobacteria, in particular by B. longum. Infant stool samples dominated by B. longum also showed higher temporal stability compared to samples dominated by other species. We identified two instances of strain sharing between maternal milk and the infant gut, one involving a commensal (B. longum) and one a pathobiont (K. pneumoniae). In addition, strain sharing between unrelated infants was higher among infants born at the same hospital compared to infants born in different hospitals, suggesting a potential role of the hospital environment in shaping the infant gut microbiome composition. The infant gut microbiome at one month compared to six months of age was enriched in metabolic pathways associated with de-novo molecule biosynthesis, suggesting that early colonisers might be more versatile and metabolically independent compared to later colonizers. Lastly, we found a significant overlap in antimicrobial resistance genes carriage between the mother's milk and their infant's gut microbiome. Taken together, our results suggest that the human milk microbiome has an important role in the assembly, composition, and stability of the infant gut microbiome.

Body composition after implementation of an enhanced parenteral nutrition protocol in the neonatal intensive care unit: a randomised pilot trial.

BACKGROUND: Very low birthweight (VLBW) infants are at risk for growth failure and poor neurodevelopment. Optimised parenteral nutrition may help promote optimal growth and development, but concerns that provision of enhanced nutrition may contribute to increased early adiposity and later metabolic disease remain. AIM: To determine associations between provision of an early enhanced parenteral nutrition protocol or standard parenteral nutrition protocol and growth and body composition for VLBW preterm infants in the neonatal intensive care unit. SUBJECTS: This is a secondary analysis of data from a clinical trial aimed at assessing the feasibility and safety of randomising VLBW preterm infants to Standard (n = 45) or Intervention (n = 42) parenteral nutrition groups between August 2017 and June 2019. METHODS: We evaluated associations between weekly infant growth and body composition measurements from n = 55 infants (Standard = 29, Intervention = 26) that were clinically stable enough to have body composition measurements taken before discharge using mixed effects linear regression models. RESULT: No statistically significant associations between nutrition group and infant growth or body composition measures were observed (p >.05). CONCLUSION: In this pilot trial, enhanced parenteral nutrition in the first week of life was not associated with significant differences in infant growth or body composition during hospitalisation.

Human Cytomegalovirus in breast milk is associated with milk composition, the infant gut microbiome, and infant growth.

Human cytomegalovirus (CMV) is a highly prevalent herpesvirus that is often transmitted to the neonate via breast milk. Postnatal CMV transmission can have negative health consequences for preterm and immunocompromised infants, but any effects on healthy term infants are thought to be benign. Furthermore, the impact of CMV on the composition of the hundreds of bioactive factors in human milk has not been tested. Here, we utilize a cohort of exclusively breastfeeding full term mother-infant pairs to test for differences in the milk transcriptome and metabolome associated with CMV, and the impact of CMV in breast milk on the infant gut microbiome and infant growth. We find upregulation of the indoleamine 2,3- dioxygenase (IDO) tryptophan-to-kynurenine metabolic pathway in CMV+ milk samples, and that CMV+ milk is associated with decreased Bifidobacterium in the infant gut. Our data indicate a complex relationship between milk CMV, milk kynurenine, and infant growth; with kynurenine positively correlated, and CMV viral load negatively correlated, with infant weight-for-length at 1 month of age. These results suggest CMV transmission, CMV-related changes in milk composition, or both may be modulators of full term infant development.

Parental factors that impact the ecology of human mammary development, milk secretion, and milk composition-a report from "Breastmilk Ecology: Genesis of Infant Nutrition (BEGIN)" Working Group 1.

The goal of Working Group 1 in the Breastmilk Ecology: Genesis of Infant Nutrition (BEGIN) Project was to outline factors influencing biological processes governing human milk secretion and to evaluate our current knowledge of these processes. Many factors regulate mammary gland development in utero, during puberty, in pregnancy, through secretory activation, and at weaning. These factors include breast anatomy, breast vasculature, diet, and the lactating parent's hormonal milieu including estrogen, progesterone, placental lactogen, cortisol, prolactin, and growth hormone. We examine the effects of time of day and postpartum interval on milk secretion, along with the role and mechanisms of lactating parent-infant interactions on milk secretion and bonding, with particular attention to the actions of oxytocin on the mammary gland and the pleasure systems in the brain. We then consider the potential effects of clinical conditions including infection, pre-eclampsia, preterm birth, cardiovascular health, inflammatory states, mastitis, and particularly, gestational diabetes and obesity. Although we know a great deal about the transporter systems by which zinc and calcium pass from the blood stream into milk, the interactions and cellular localization of transporters that carry substrates such as glucose, amino acids, copper, and the many other trace metals present in human milk across plasma and intracellular membranes require more research. We pose the question of how cultured mammary alveolar cells and animal models can help answer lingering questions about the mechanisms and regulation of human milk secretion. We raise questions about the role of the lactating parent and the infant microbiome and the immune system during breast development, secretion of immune molecules into milk, and protection of the breast from pathogens. Finally, we consider the effect of medications, recreational and illicit drugs, pesticides, and endocrine-disrupting chemicals on milk secretion and composition, emphasizing that this area needs much more research attention.

Human milk variation is shaped by maternal genetics and impacts the infant gut microbiome.

Human milk is a complex mix of nutritional and bioactive components that provide complete nutrition for the infant. However, we lack a systematic knowledge of the factors shaping milk composition and how milk variation influences infant health. Here, we used multi-omic profiling to characterize interactions between maternal genetics, milk gene expression, milk composition, and the infant fecal microbiome in 242 exclusively breastfeeding mother-infant pairs. We identified 487 genetic loci associated with milk gene expression unique to the lactating mammary gland, including loci that impacted breast cancer risk and human milk oligosaccharide concentration. Integrative analyses uncovered connections between milk gene expression and infant gut microbiome, including an association between the expression of inflammation-related genes with IL-6 concentration in milk and the abundance of Bifidobacteria in the infant gut. Our results show how an improved understanding of the genetics and genomics of human milk connects lactation biology with maternal and infant health.

Enhanced Parenteral Nutrition Is Feasible and Safe in Very Low Birth Weight Preterm Infants: A Randomized Trial.

OBJECTIVE: The objective of this study was to determine the feasibility and safety of enhanced early (PN) (early initiation of intralipids and faster advancement of glucose infusion rate) during the first week of life for very low birth weight (VLBW) preterm infants. METHODS: 90 VLBW preterm infants (<32 weeks gestational age at birth) admitted to the University of Minnesota Masonic Children's Hospital between August 2017 and June 2019 were included. Enrolled infants were stratified by gestational age-groups and randomized to either the enhanced nutrition protocol (intervention group) or the standard PN protocol (standard group). Welch's two-sample t tests were used to investigate differences in calorie and protein intake, insulin use, days of hyperglycemia, hyperbilirubinemia, and hypertriglyceridemia, and proportion of bronchopulmonary dysplasia, necrotizing enterocolitis, and death between groups. RESULTS: Intervention and standard groups were similar in baseline characteristics. The intervention group received higher weekly mean caloric intake (102.6 [SD 24.9] kcal/kg/day versus 89.7 [SD 30.2] kcal/kg/day; p = 0.001) and higher mean caloric intake on days of life 2-4 (p < 0.05 for all). Both groups received the recommended protein intake (≥4 g/kg/day). There were no significant differences in safety or feasibility outcomes between groups (all p values >0.12). CONCLUSION: Utilization of an enhanced nutrition protocol during the first week of life resulted in increased caloric intake and was feasible with no evidence of harm. Follow-up of this cohort is needed to determine if enhanced PN will result in improved growth and neurodevelopment.

Revisiting One-Carbon Metabolites in Human Breast Milk: Focus on S-Adenosylmethionine.

Breastfeeding is the gold standard for early nutrition. Metabolites from the one-carbon metabolism pool are crucial for infant development. The aim of this study is to compare the breast-milk one-carbon metabolic profile to other biofluids where these metabolites are present, including cord and adult blood plasma as well as cerebrospinal fluid. Breast milk (n = 142), cord blood plasma (n = 23), maternal plasma (n = 28), aging adult plasma (n = 91), cerebrospinal fluid (n = 92), and infant milk formula (n = 11) samples were analyzed by LC-MS/MS to quantify choline, betaine, methionine, S-adenosylmethionine, S-adenosylhomocysteine, total homocysteine, and cystathionine. Differences between groups were visualized by principal component analysis and analyzed by Kruskal-Wallis test. Correlation analysis was performed between one-carbon metabolites in human breast milk. Principal component analysis based on these metabolites separated breast milk samples from other biofluids. The S-adenosylmethionine (SAM) concentration was significantly higher in breast milk compared to the other biofluids and was absent in infant milk formulas. Despite many significant correlations between metabolites in one-carbon metabolism, there were no significant correlations between SAM and methionine or total homocysteine. Together, our data indicate a high concentration of SAM in breast milk, which may suggest a strong demand for this metabolite during infant early growth while its absence in infant milk formulas may indicate the inadequacy of this vital metabolic nutrient.

Randomized Trial of Early Enhanced Parenteral Nutrition and Later Neurodevelopment in Preterm Infants.

Retrospective studies indicate that the parenteral provision of calories, proteins, and lipids in the first week of life is associated with improved later neurodevelopment. We aimed to determine whether infants randomized to an enhanced parenteral nutrition protocol had improved developmental outcomes at 4, 12, or 24 months corrected age (CA). In total, 90 preterm infants (<32 weeks gestational age and <1500 g) were randomized to receive enhanced parenteral nutrition (PN) or standard PN during the first week of life. The enhanced group received a higher glucose infusion rate and intralipids. Neurodevelopmental outcomes included pattern-reversal visually evoked potentials (VEP) at 4 months CA (n = 33) and the Bayley Scales of Infant Development (BSID) at 12 (n = 46) and 24 (n = 29) months CA. P100 latency was longer in the intervention group, indicating slower processing speed (145 vs. 178 ms, p = 0.01). This association did not hold in multivariable analysis adjusting for potentially confounding variables. BSID scores were not associated with enhanced PN. Higher enteral energy and protein intake regardless of randomization group were associated with faster processing speed at 4 months CA (p ≤ 0.02 for both). Enhanced early PN was not associated with improved neurodevelopment; however, first-week enteral caloric and protein intake were associated with improved speed of processing.

Training the MCH workforce: the Time for Change is now.

INTRODUCTION: Maternal and child health (MCH) services are critical for vulnerable populations. Workforce shortages, poor retention, and gaps in necessary trainings impede the capacity of public health systems to address needs. This manuscript characterizes the current MCH workforce, MCH program applicants and graduates, and describe findings within a national context to devise elements of a recruitment and retention strategy. METHODS: Data were obtained for public health program applicants, first-destination employment outcomes, and worker perceptions and demographics. Data were stratified according to the MCH and total public health workforce and by local, state, and national totals. Data were characterized by degree type, discipline, demographics, and employment outcomes. RESULTS: MCH staff constitute 11% of the state and local governmental public health workforce. MCH staff are approximately as diverse, have higher educational attainment, and are more likely to hold nursing degrees than the rest of the public health workforce. Yet, just 14% of MCH staff hold any type of public health degree. The MCH pipeline from academia appears modestly sized, with approximately 5% of applicants between 2017 and 2021 applying to a MCH master's degree. DISCUSSION: The MCH workforce has a lower proportion of formal training or degrees in public health, though trends seem to indicate improvements. However, it is critical that a multi-faceted recruitment and retention strategy be coordinated by a broad range of stakeholders. These efforts will serve to improve the capability and capacity of the public health system to address critical needs of increasingly diverse MCH populations. SIGNIFICANCE: In order to modernize and reimagine the academic-public health pipeline, it is critical to better understand how many applicants and graduates exist within Maternal and Child Health programs across the US, and their characteristics. This manuscript connects that information with the most recently available public health workforce information on demographics, workplace perceptions, and intent to leave among staff at state and local health departments. Data presented in this paper allow the most comprehensive characterization of the MCH academia->practice pipeline to-date, identifies a fundamental disconnect in those career pathways, and offers options to repair that break.

Testing the Institute of Medicine (IOM) recommendations on maternal reproductive health and associated neonatal characteristics in a transitional, Mediterranean population.

BACKGROUND: High pre-pregnancy body mass index (BMI) and excessive gestational weight gain (GWG) are significant risk factors for maternal and neonatal health. AIM: To assess pre-pregnancy BMI and GWG during pregnancy and their association with different maternal and neonatal characteristics in the transitional Mediterranean population from the Eastern Adriatic islands. SUBJECTS AND METHODS: Two hundred and sixty-two mother-child dyads from the CRoatian Islands' Birth Cohort Study (CRIBS) were included in the study. Chi-square test, ANOVA, and regression analysis were used to test the association between selected characteristics. RESULTS: In total, 22% of women entered pregnancy as overweight/obese and 46.6% had excessive GWG. Pre-pregnancy overweight and obesity were significantly associated with elevated triglycerides uric acid levels, and decreased HDL cholesterol in pregnancy. Excessive GWG was associated with elevated fibrinogen and lipoprotein A levels. Women with high pre-pregnancy BMI and GWG values were more likely to give birth to babies that were large for gestational age (LGA), additionally confirmed in the multiple logistic regression model. CONCLUSION: High maternal pre-pregnancy BMI and excessive GWG were both significantly associated with deviated biochemical parameters and neonatal size. More careful monitoring of maternal nutritional status can lead to better pre- and perinatal maternal healthcare.

Gestational Diabetes Mellitus Is Associated with Differences in Human Milk Hormone and Cytokine Concentrations in a Fully Breastfeeding United States Cohort.

It is unclear whether gestational diabetes mellitus (GDM) alters breast milk composition. We prospectively examined associations of GDM status with concentrations of six potentially bioactive elements (glucose, insulin, C-reactive protein (CRP), interleukin-6 (IL-6), leptin, and adiponectin) in human milk. These were measured at both 1 and 3 months postpartum in 189 fully breastfeeding women. Mixed-effects linear regression assessed GDM status-related differences in these milk bioactives, adjusting for demographics, maternal factors, and diet. At 1 and 3 months postpartum, milk CRP was higher (1.46 ± 0.31 ng/mL; p < 0.001 and 1.69 ± 0.31 ng/mL; p < 0.001) in women with GDM than in women without GDM, whereas milk glucose (−5.23 ± 2.22 mg/dL; p = 0.02 and −5.70 ± 2.22; p = 0.01) and milk insulin (−0.38 ± 0.17 µIU/mL; p = 0.03 and −0.53 ± 0.17; p = 0.003) were lower in women with GDM. These significant associations remained similar after additional adjustment for maternal weight status and its changes. No difference was found for milk IL-6, leptin, and adiponectin. There was no evidence of association between these milk bioactive compounds and 1 h non-fasting oral glucose challenge serum glucose in the women without GDM. This prospective study provides evidence that potentially bioactive elements of human milk composition are altered in women with GDM.

Bioactive compounds in mothers milk affecting offspring outcomes: A narrative review.

BACKGROUND: Compared to the exhaustive study of transgenerational programming of obesity and diabetes through exposures in the prenatal period, postnatal programming mechanisms are understudied, including the potential role of breast milk composition linking maternal metabolic status (body mass index and diabetes) and offspring growth, metabolic health and future disease risk. METHODS: This narrative review will principally focus on four emergent bioactive compounds [microRNA's (miRNA), lipokines/signalling lipids, small molecules/metabolites and fructose] that, until recently were not known to exist in breast milk. The objective of this narrative review is to integrate evidence across multiple fields of study that demonstrate the importance of these compositional elements of breast milk during lactation and the subsequent effect of breast milk components on the health of the infant. RESULTS: Current knowledge on the presence of miRNA's, lipokines/signalling lipids, small molecules/metabolites and fructose in breast milk and their associations with infant outcomes is compelling, but far from resolved. Two themes emerge: (1) maternal metabolic phenotypes are associated with these bioactives and (2) though existing in milk at low concentrations, they are also associated with offspring growth and body composition. CONCLUSION: Breast milk research is gaining momentum though we must remain focused on understanding how non-nutritive bioactive components are affected by the maternal phenotype, how they subsequently impact infant outcomes. Though early, there is evidence to suggest fructose is associated with fat mass in the 1st months of life whereas 12,13 diHOME (brown fat activator) and betaine are negatively associated with early adiposity and growth.

Gestational Diabetes Mellitus Is Associated with Altered Abundance of Exosomal MicroRNAs in Human Milk.

PURPOSE: Human milk (HM) is a unique biological fluid that is enriched with a variety of factors, including microRNAs (miRNAs) that potentially provide both short- and long-term benefits to the infants. miRNAs are packaged within exosomes, making them bioavailable to infants. Gestational diabetes mellitus (GDM) may affect the abundance of exosomal miRNAs in HM, providing a mechanism for growth and adiposity variation in infants of mothers with GDM in early life. Therefore, the purposes of this study were to examine the impact of GDM on select miRNAs (miRNA-148a, miRNA-30b, miRNA-let-7a, and miRNA-let-7d) involved in metabolism and to examine the association of these miRNAs with measures of infant body composition in the first 6 months of life. METHODS: Milk samples were collected from a cohort of 94 mothers (62 mothers without GDM and 32 mothers with GDM) matched on body mass index strata at 1 month post partum. miRNA abundance was measured by real-time polymerase chain reaction. Linear regression models were used to examine potential differences in miRNA abundance in women with and without GDM, testing associations between miRNA abundance and infant growth and body composition measures from 1 to 6 months. FINDINGS: The abundances of miRNA-148a, miRNA-30b, miRNA-let-7a, and miRNA-let-7d were reduced in milk from mothers with GDM. Independent of GDM status, higher maternal diet quality was associated with increased abundance of each of the measured miRNAs. miRNA-148a was negatively associated with infant weight, percentage of body fat, and fat mass, whereas miRNA-30b was positively associated with infant weight and fat mass at 1 month of age. There was no association of milk miRNA-148a and miRNA-30b with infant weight at 1 month of age or with body composition measures at 3 months of age; however, miRNA-148a was negatively associated with infant weight at 6 months of age. IMPLICATIONS: If supported by randomized dietary supplementation or other intervention trials, HM miRNAs may be a therapeutic target to mitigate risk of metabolic outcomes in offspring of women with GDM.

Maternal Psychological Distress and Lactation and Breastfeeding Outcomes: a Narrative Review.

PURPOSE: Despite recommendations from the World Health Organization and the American Academy of Pediatrics to exclusively breastfeed infants for their first 6 months of life, 75% of women do not meet exclusive breastfeeding guidelines, and 60% do not meet their own breastfeeding goals. Numerous observational studies have linked maternal psychological distress (eg, perceived stress, anxiety, and depression) with nonoptimal breastfeeding outcomes, such as decreased proportion and duration of exclusive breastfeeding. The physiological mechanisms underlying these associations, however, remain unclear. METHODS: For this narrative review, we evaluated the evidence of relationships between maternal psychological distress and lactation and breastfeeding outcomes in pregnancy and post partum and the possible physiological mechanisms that facilitate these relationships. We searched PubMed using the following terms: stress, anxiety, depression, breastfeeding, and lactation. Additional search by hand was conducted to ensure a thorough review of the literature. FINDINGS: Among the studies examined, methods used to assess maternal psychological distress were not uniform, with some studies examining perceived distress via a variety of validated tools and others measuring biological measures of distress, such as cortisol. Evidence supports a role for psychological distress in multiple breastfeeding outcomes, including delayed secretory activation and decreased duration of exclusive breastfeeding. One physiological mechanism proposed to explain these relationships is that psychological distress may impair the release of oxytocin, a hormone that plays a critical role in milk ejection during lactation. Continued impairment of milk ejection may lead to decreased milk production because of incomplete emptying of the breast during each feed. Maternal distress may also yield elevated levels of serum cortisol and decreased insulin sensitivity, which are associated with decreased milk production. The relationship between psychological distress and breastfeeding is likely to be bidirectional, however, in that breastfeeding appears to reduce maternal distress, again possibly via effects on the pleasure or reward pathway and calming effects of oxytocin on the mother. This finding suggests that interventions to support lactation and breastfeeding goals in women who score high on measures of psychological distress would be beneficial for both maternal and infant well-being. IMPLICATIONS: Evidence to date suggests that maternal psychological distress may impair lactation and breastfeeding outcomes, but stronger study designs and rigorous assessment methods are needed. A better understanding of the physiological mechanisms leading to impaired lactation may assist in the development of early interventions for mothers experiencing distress. In addition, stress-reducing programs and policies should be investigated for their potential to improve breastfeeding outcomes.

Human Milk Glucose, Leptin, and Insulin Predict Cessation of Full Breastfeeding and Initiation of Formula Use.

Objective: We aimed to investigate prospective associations between milk bioactives related to metabolic health (glucose, insulin, leptin, C reactive protein [CRP], and interleukin 6 [IL-6]) and incident formula initiation at 3 and 6 months postpartum. Design: This study included 363 mother-infant dyads who were fully breastfed at 1 month and participated in the prospective Mothers and Infants Linked for Healthy Growth study from pregnancy to 6 months postpartum. Associations between milk glucose, leptin, insulin, CRP, and IL-6 at 1 and 3 months and incident formula feeding (FF) at 3 and 6 months, respectively, were tested using multiple logistic regression, adjusting for numerous potential confounders such as maternal age and prepregnancy body mass index. Results: At 3 months postpartum, 1-month glucose (odds ratio [OR] 0.45 [95% confidence interval (CI): 0.27-0.75], p ≤ 0.01) and smaller decreases in glucose from 1 to 3 months (OR 0.51 [95% CI: 0.28-0.92], p = 0.03) were associated with lower odds of FF, whereas 1-month leptin (OR 2.30 [95% CI: 1.30-4.07], p < 0.01) and larger increase in insulin (OR 1.86 [95% CI: 1.23-2.81], p < 0.01) and leptin (OR 2.17 [95% CI: 1.29-3.68], p < 0.01) from 1 to 3 months were associated with increased odds of FF. At 6 months, insulin increases (OR 2.08 [95% CI: 1.03-4.17], p = 0.04) were associated with higher odds of FF. Conclusions: In a cohort of women with established lactation, 1-month milk glucose, insulin, and leptin predicted initiation of FF at 3 months. Early milk composition may provide a window into mammary gland function, allowing identification of women at risk of not meeting their breastfeeding goals.

Maternal Dietary Intake of Total Fat, Saturated Fat, and Added Sugar Is Associated with Infant Adiposity and Weight Status at 6 mo of Age.

BACKGROUND: Whether current dietary guidelines are appropriate for pregnancy and lactation has not been well studied. Many women of reproductive age are not meeting recommendations for dietary components such as fat, added sugar, and fiber. OBJECTIVES: To assess associations between maternal dietary components during pregnancy and lactation and infant growth and adiposity at 6 mo of age. METHODS: Mother-infant dyads (n = 349) from the prospective, observational Mothers and Infants Linked for Healthy Growth study were included (100% fully breastfed for 1 mo; 75% to 6 mo). Daily intake of fat, fiber, and added sugar was obtained using the National Cancer Institute Diet History Questionnaire II during the third trimester of pregnancy and at 1 and 3 mo postpartum. Furthermore, intakes were categorized as meeting/exceeding 2015-2020 Dietary Guidelines for Americans. Multiple linear regression models adjusted for numerous potential confounders tested relations between dietary components and infant adiposity (via DXA) and growth parameters. Regression coefficients (ß) for continuous variables were expressed per SD to allow for comparison of effect sizes. RESULTS: Maternal intake of total fat and saturated fat was positively associated with infant percent body fat (%BF) (ß: 0.84 per SD, P = 0.04; ß: 0.96 per SD, P = 0.01, respectively). Added sugar intake was positively associated with infant weight-for-length z score (ß: 0.16 per SD, P = 0.02), and excessive added sugar intake was positively associated with %BF at 6 mo (ß: 0.75 per SD, P = 0.05). CONCLUSIONS: In a predominantly fully breastfeeding cohort of women, maternal intake of fat and added sugar during pregnancy and lactation were associated with small increases in infant adiposity and relative weight at 6 mo. Additional research is needed to determine if these relations persist later in infancy and if such elevations in adiposity are important for long-term obesity risk.

Increasing breast milk betaine modulates Akkermansia abundance in mammalian neonates and improves long-term metabolic health.

Accelerated postnatal growth is a potentially modifiable risk factor for future obesity. To study how specific breast milk components contribute to early growth and obesity risk, we quantified one-carbon metabolism-related metabolites in human breast milk and found an inverse association between milk betaine content and infant growth. This association was replicated in an independent and geographically distinct cohort. To determine the potential role of milk betaine in modulating offspring obesity risk, we performed maternal betaine supplementation experiments in mice. Higher betaine intake during lactation increased milk betaine content in dams and led to lower adiposity and improved glucose homeostasis throughout adulthood in mouse offspring. These effects were accompanied by a transient increase in Akkermansia spp. abundance in the gut during early life and a long-lasting increase in intestinal goblet cell number. The link between breast milk betaine and Akkermansia abundance in the gut was also observed in humans, as infants exposed to higher milk betaine content during breastfeeding showed higher fecal Akkermansia muciniphila abundance. Furthermore, administration of A. muciniphila to mouse pups during the lactation period partially replicated the effects of maternal breast milk betaine, including increased intestinal goblet cell number, lower adiposity, and improved glucose homeostasis during adulthood. These data demonstrate a link between breast milk betaine content and long-term metabolic health of offspring.

Epigenetically mediated electrocardiographic manifestations of sub-chronic exposures to ambient particulate matter air pollution in the Women's Health Initiative and Atherosclerosis Risk in Communities Study.

BACKGROUND: Short-duration exposure to ambient particulate matter (PM) air pollution is associated with cardiac autonomic dysfunction and prolonged ventricular repolarization. However, associations with sub-chronic exposures to coarser particulates are relatively poorly characterized as are molecular mechanisms underlying their potential relationships with cardiovascular disease. MATERIALS AND METHODS: We estimated associations between monthly mean concentrations of PM < 10 µm and 2.5-10 µm in diameter (PM10; PM2.5-10) with time-domain measures of heart rate variability (HRV) and QT interval duration (QT) among U.S. women and men in the Women's Health Initiative and Atherosclerosis Risk in Communities Study (nHRV = 82,107; nQT = 76,711). Then we examined mediation of the PM-HRV and PM-QT associations by DNA methylation (DNAm) at three Cytosine-phosphate-Guanine (CpG) sites (cg19004594, cg24102420, cg12124767) with known sensitivity to monthly mean PM concentrations in a subset of the participants (nHRV = 7,169; nQT = 6,895). After multiply imputing missing PM, electrocardiographic and covariable data, we estimated associations using attrition-weighted, linear, mixed, longitudinal models adjusting for sociodemographic, behavioral, meteorological, and clinical characteristics. We assessed mediation by estimating the proportions of PM-HRV and PM-QT associations mediated by DNAm. RESULTS: We found little evidence of PM-HRV association, PM-QT association, or mediation by DNAm. CONCLUSIONS: The findings suggest that among racially/ethnically and environmentally diverse U.S. populations, sub-chronic exposures to coarser particulates may not exert appreciable, epigenetically mediated effects on cardiac autonomic function or ventricular repolarization. Further investigation in better-powered studies is warranted, with additional focus on shorter duration exposures to finer particulates and non-electrocardiographic outcomes among relatively susceptible populations.