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.

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.

Effects of airgun discharges used in seismic surveys on development and mortality in nauplii of the copepod Acartia tonsa.

Seismic surveys are conducted worldwide to explore for oil and gas deposits and to map subsea formations. The airguns used in these surveys emit low-frequency sound waves. Studies on zooplankton responses to airguns report a range of effects, from none to substantial mortality. A field experiment was conducted to assess mortality and naupliar body length of the calanoid copepod Acartia tonsa when exposed to the discharge of two 40-inch airguns. Nauplii were placed in plastic bags and attached to a line at a depth of 6 m. For each treatment, three bags of nauplii were exposed to one of three treatments for 2.5 h: Airgun array discharge, a boat control, or a silent control. After exposure, nauplii were kept in filtered seawater in the laboratory without food. Immediate mortality in the nauplii was approximately 14% compared to less than 4% in the silent and boat control. Similarly, there was higher mortality in the airgun exposed nauplii up to six days after exposure compared to the control treatments. Nearly all of the airgun exposed nauplii were dead after four days, while >50% of the nauplii in the control treatments were alive at six days post-exposure. There was an interaction between treatment and time on naupliar body length, indicating lower growth in the nauplii exposed to the airgun discharge (growth rates after 4 days: 1.7, 5.4, and 6.1 µm d-1 in the airgun exposed, silent control, and boat control, respectively). These experiments indicate that the output of two small airguns affected mortality and growth of the naupliar stages of Acartia tonsa in close vicinity to the array.

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.

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.

Stability of Human-Milk Oligosaccharide Concentrations Over 1 Week of Lactation and Over 6 Hours Following a Standard Meal.

BACKGROUND: Our previous studies revealed that human-milk oligosaccharides (HMOs) have health benefits for nursing infants and their concentrations change dynamically over 24 mo of lactation. Yet, the extent to which HMOs vary over the short term (days) and in response to acute factors such as maternal diet is unclear. OBJECTIVE: The purpose of this study was to determine the stability of HMO concentrations over 7 d and in response to a standard meal and sugar-sweetened beverage (SSB) over 6 h. METHODS: In this ancillary study, lactating mothers were enrolled at 6 wk postpartum. Participants received in-person instructions and materials to complete procedures at home. In the 1-wk experiment (n = 11), mothers pumped a milk sample at 07:00 h for 7 consecutive days. In the 6-h experiment (n = 35), mothers pumped a milk sample after an overnight fast at 06:00 h and then consumed a standard meal plus SSB provided by the study team. Mothers pumped a milk sample every hour for 6 consecutive hours. Samples were analyzed for the 19 most abundant HMOs. Repeated-measures ANOVA was used to test changes in HMO concentrations over time, reported as F(dftime, dferror) = F value, P value. RESULTS: Concentrations of all assayed HMOs were stable over 7 consecutive days, including, for example, the most widely studied HMOs in relation to infant health: 2'-fucosyllactose (2'FL) [F(2,17) = 0.39, P = 0.65], disialyl-lacto-N-tetraose (DSLNT) [F(4, 37) = 0.60, P = 0.66], and lacto-N-neotetraose (LNnT) [F(3, 32) = 1.5, P = 0.23]. Concentrations of all assayed HMOs were stable in response to a standard meal plus SSB. For example, fasted baseline concentrations of 2'FL, DSLNT, and LNnT were 2310 ± 1620 µg/mL, 560 ± 290 µg/mL, and 630 ± 290 µg/mL, respectively, and there were no changes in 2'FL [F(4, 119) = 1.9, P = 0.13], DSLNT [F(4, 136) = 0.39, P = 0.83], and LNnT [F(4, 120) = 0.64, P = 0.63] over 6 consecutive hours. CONCLUSIONS: HMO concentrations are stable over 1 wk of lactation and are not acutely affected by a standard meal plus SSB in mothers.

Applying genetic technologies to combat infectious diseases in aquaculture.

Disease and parasitism cause major welfare, environmental and economic concerns for global aquaculture. In this review, we examine the status and potential of technologies that exploit genetic variation in host resistance to tackle this problem. We argue that there is an urgent need to improve understanding of the genetic mechanisms involved, leading to the development of tools that can be applied to boost host resistance and reduce the disease burden. We draw on two pressing global disease problems as case studies-sea lice infestations in salmonids and white spot syndrome in shrimp. We review how the latest genetic technologies can be capitalised upon to determine the mechanisms underlying inter- and intra-species variation in pathogen/parasite resistance, and how the derived knowledge could be applied to boost disease resistance using selective breeding, gene editing and/or with targeted feed treatments and vaccines. Gene editing brings novel opportunities, but also implementation and dissemination challenges, and necessitates new protocols to integrate the technology into aquaculture breeding programmes. There is also an ongoing need to minimise risks of disease agents evolving to overcome genetic improvements to host resistance, and insights from epidemiological and evolutionary models of pathogen infestation in wild and cultured host populations are explored. Ethical issues around the different approaches for achieving genetic resistance are discussed. Application of genetic technologies and approaches has potential to improve fundamental knowledge of mechanisms affecting genetic resistance and provide effective pathways for implementation that could lead to more resistant aquaculture stocks, transforming global aquaculture.

Bacterial, fungal, and interkingdom microbiome features of exclusively breastfeeding dyads are associated with infant age, antibiotic exposure, and birth mode.

The composition and function of early life gut bacterial communities (microbiomes) have been proposed to modulate health for the long term. In addition to bacteria, fungi (mycobiomes) also colonize the early life gut and have been implicated in health disorders such as asthma and obesity. Despite the potential importance of mycobiomes in health, there has been a lack of study regarding fungi and their interkingdom interactions with bacteria during infancy. The goal of this study was to obtain a more complete understanding of microbial communities thought to be relevant for the early life programming of health. Breastmilk and infant feces were obtained from a unique cohort of healthy, exclusively breastfeeding dyads recruited as part of the Mothers and Infants Linked for Healthy Growth (MILk) study with microbial taxa characterized using amplicon-based sequencing approaches. Bacterial and fungal communities in breastmilk were both distinct from those of infant feces, consistent with niche-specific microbial community development. Nevertheless, overlap was observed among sample types (breastmilk, 1-month feces, 6-month feces) with respect to the taxa that were the most prevalent and abundant. Self-reported antibacterial antibiotic exposure was associated with micro- as well as mycobiome variation, which depended upon the subject receiving antibiotics (mother or infant), timing of exposure (prenatal, peri- or postpartum), and sample type. In addition, birth mode was associated with bacterial and fungal community variation in infant feces, but not breastmilk. Correlations between bacterial and fungal taxa abundances were identified in all sample types. For infant feces, congruency between bacterial and fungal communities was higher for older infants, consistent with the idea of co-maturation of bacterial and fungal gut communities. Interkingdom connectedness also tended to be higher in older infants. Additionally, higher interkingdom connectedness was associated with Cesarean section birth and with antibiotic exposure for microbial communities of both breastmilk and infant feces. Overall, these results implicate infant age, birth mode, and antibiotic exposure in bacterial, fungal and interkingdom relationship variation in early-life-relevant microbiomes, expanding the current literature beyond bacteria.

Bone Mass Accrual in First Six Months of Life: Impact of Maternal Diabetes, Infant Adiposity, and Cord Blood Adipokines.

The perinatal period is a time of substantial bone mass accrual with many factors affecting long-term bone mineralization. Currently it is unclear what effect maternal gestational/type 2 diabetes has on infant bone mass accrual. This is a prospective study of offspring of Native American and Hispanic mothers with normoglycemia (n = 94) and gestational diabetes or type 2 diabetes (n = 64). Infant anthropometrics were measured at birth, 1, and 6 months of age. Cord blood leptin, high-molecular weight adiponectin (HMWA), pigment epithelium-derived factor (PEDF), vascular epithelium growth factor (VEGF), endoglin, and C-peptide were measured by ELISA. Infants had bone mineral density measurement at 1 month or/and 6 months of age using dual-energy x-ray absorptiometry scan. Mothers with diabetes were older (31 ± 6 years vs 25 ± 4 years) and had higher pre-pregnancy BMI (32.6 ± 5.8 vs 27.2 ± 6.4 kg/m2) than control mothers. Mean HbA1C of mothers with diabetes was 5.9 ± 1.0% compared to 5.1 ± 0.3% in controls early in pregnancy. Infants born to mothers with diabetes (DM-O) were born at a slightly lower gestational age compared to infants born to control mothers (Con-O). There was no difference in total body less head bone mineral content (BMC) or bone mineral density (BMD) between DM-O and Con-O. For both groups together, bone area, BMD, and BMC tracked over the first 6 months of life (r: 0.56, 0.38, and 0.48, respectively). Percent fat was strongly and positively correlated with BMC at 1 month of age (r = 0.44; p < 0.001) and BMC at both 1 and 6 months of age correlated strongly with birth weight. There were no associations between infant bone mass and cord blood leptin, PEDF, or VEGF, while C-peptide had a significant correlation with BMC at 1 and 6 months only in DM-O (p = 0.01 and 0.03, respectively). Infants born to mothers with well-controlled gestational/type 2 diabetes have normal bone mass accrual. Bone mineral content during this time is highly correlated with indices of infant growth and the association of bone mineral indices with percent body fat suggests that bone-fat crosstalk is operative early in life.

Changes in Chemical Composition and Copepod Toxicity during Petroleum Photo-oxidation.

Photoproducts can be formed rapidly in the initial phase of a marine oil spill. However, their toxicity is not well understood. In this study, oil was irradiated, chemically characterized, and tested for toxicity in three copepod species (Acartia tonsa, Temora longicornis, and Calanus finmarchicus). Irradiation led to a depletion of polycyclic aromatic hydrocarbons (PAHs) and n-alkanes in oil residues, along with an enrichment in aromatic and aliphatic oil photoproducts. Target lipid model-based calculations of PAH toxicity units predicted that PAH toxicities were lower in water-accommodated fractions (WAFs) of irradiated oil residues ("irradiated WAFs") than in WAFs of dark-control samples ("dark WAFs"). In contrast, biomimetic extraction (BE) measurements showed increased bioaccumulation potential of dissolved constituents of irradiated WAFs compared to dark WAFs, mainly driven by photoproducts present in irradiated oil. In line with the BE results, copepod mortality increased in irradiated WAFs compared to dark WAFs. However, low copepod toxicities were observed for WAFs produced with photo-oxidized oil slicks collected during the Deepwater Horizon oil spill. The results of this study suggest that while oil photoproducts have the potential to be a significant source of copepod toxicity, dilution and dispersion of these higher solubility products appear to help mitigate their toxicity at sea.

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.

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.

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.

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.

Gene expression and epigenetic responses of the marine Cladoceran, Evadne nordmanni, and the copepod, Acartia clausi, to elevated CO2.

Characterizing the capacity of marine organisms to adapt to climate change related drivers (e.g., pCO2 and temperature), and the possible rate of this adaptation, is required to assess their resilience (or lack thereof) to these drivers. Several studies have hypothesized that epigenetic markers such as DNA methylation, histone modifications and noncoding RNAs, act as drivers of adaptation in marine organisms, especially corals. However, this hypothesis has not been tested in zooplankton, a keystone organism in marine food webs. The objective of this study is to test the hypothesis that acute ocean acidification (OA) exposure alters DNA methylation in two zooplanktonic species-copepods (Acartia clausii) and cladocerans (Evadne nordmanii). We exposed these two species to near-future OA conditions (400 and 900 ppm pCO2) for 24 h and assessed transcriptional and DNA methylation patterns using RNA sequencing and Reduced Representation Bisulfite Sequencing (RRBS). OA exposure caused differential expression of genes associated with energy metabolism, cytoskeletal and extracellular matrix functions, hypoxia and one-carbon metabolism. Similarly, OA exposure also caused altered DNA methylation patterns in both species but the effect of these changes on gene expression and physiological effects remains to be determined. The results from this study form the basis for studies investigating the potential role of epigenetic mechanisms in OA induced phenotypic plasticity and/or adaptive responses in zooplanktonic organisms.

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.

Human Milk Exosomal MicroRNA: Associations with Maternal Overweight/Obesity and Infant Body Composition at 1 Month of Life.

Among all the body fluids, breast milk is one of the richest sources of microRNAs (miRNAs). MiRNAs packaged within the milk exosomes are bioavailable to breastfeeding infants. The role of miRNAs in determining infant growth and the impact of maternal overweight/obesity on human milk (HM) miRNAs is poorly understood. The objectives of this study were to examine the impact of maternal overweight/obesity on select miRNAs (miR-148a, miR-30b, miR-29a, miR-29b, miR-let-7a and miR-32) involved in adipogenesis and glucose metabolism and to examine the relationship of these miRNAs with measures of infant body composition in the first 6 months of life. Milk samples were collected from a cohort of 60 mothers (30 normal-weight [NW] and 30 overweight [OW]/obese [OB]) at 1-month and a subset of 48 of these at 3 months of lactation. Relative abundance of miRNA was determined using real-time PCR. The associations between the miRNAs of interest and infant weight and body composition at one, three, and six months were examined after adjusting for infant gestational age, birth weight, and sex. The abundance of miR-148a and miR-30b was lower by 30% and 42%, respectively, in the OW/OB group than in the NW group at 1 month. miR-148a was negatively associated with infant weight, fat mass, and fat free mass, while miR-30b was positively associated with infant weight, percent body fat, and fat mass at 1 month. Maternal obesity is negatively associated with the content of select miRNAs in human milk. An association of specific miRNAs with infant body composition was observed during the first month of life, suggesting a potential role in the infant's adaptation to enteral nutrition.