Maternal Obesity and MicroRNAs in Breast Milk: Implications for Infant Developmental Programming.

Programming, metabolic syndrome, and NAFLD: The challenge of transforming a vicious cycle into a virtuous cycle

BackgroundAlthough most inflammatory bowel disease (IBD) medications are considered safe during pregnancy, their impact on microRNAs (miRNAs) in breast milk is largely unknown. MiRNAs in milk, carried by milk-derived extracellular vesicles (MDEs), are transmitted to the newborn’s gut to regulate genes. Aberrant miRNA expression profiles have been found in IBD within tissue, blood, and feces, but data on mother’s milk are scarce.MethodsWe collected breast milk samples from 32 mothers with Crohn’s disease (CD), 14 mothers with ulcerative colitis (UC), and 44 healthy controls. We analyzed miRNA expression through qualitative real-time polymerase chain reaction and Affymetrix miRNA chips. Target genes of differentially expressed miRNAs were predicted using miRATBase. Statistical analyses were conducted using GraphPad Prism software with Mann–Whitney tests.ResultsMilk-derived extracellular vesicles from mothers with IBD showed altered miRNA profiles compared to controls. Specifically, miR-21 and miR-320 were downregulated, while Let-7a was upregulated in IBD mothers. The expression patterns varied between CD and UC, with significantly lower MiR-21 in UC and higher Let-7a in CD. Additionally, anti-tumor necrosis factor treatment during pregnancy was associated with reduced miR-21 and miR-148a levels in MDEs. Pathway analysis revealed that these miRNAs are involved in immune regulation, particularly interleukin signaling pathways.ConclusionsThis study highlights that miRNAs in breast milk are differentially expressed in mothers with IBD, influenced by the disease and its treatments. These findings emphasize the impact of maternal health on milk composition and potential implications for infant immune development. Understanding these findings may guide personalized treatment strategies for mothers and promote breastfeeding among mothers with IBD.

Objective To explore the expression levels of immune-related microRNA-146b(miR-146b), microRNA-155(miR-155) and microRNA-30b(miR-30b) in human breast milk and its relationship with maternal and infant's health. Methods One hundred and thirty-four mothers and their infants from obstetrical department were recruited in the study after delivery.The subjects were divided into 2 groups, breast feeding group(n=86) and formula-fee-ding group(n=48), and were followed up 3 months after delivery.Breast milk samples were collected at 2-5 days after delivery(colostrum) and 3 months after delivery(mature milk). The expression levels of microRNAs in milk samples were detected by real-time PCR.The relationship between levels of microRNAs and maternal and infant-related factors was analyzed. Results 1.MiR-146b, miR-155 and miR-30b expressions were abundant both in human colostrums(5.950±0.823, 3.899±0.920, 4.057±0.604) and mature milk(4.840±0.805, 2.128±0.969, 4.929±0.566). The levels of miR-146b and miR-155 were higher in colostrum than that of mature milk(t=7.716, 10.215, all P<0.01), while the level of miR-30b was higher in mature milk than that of colostrums(t=-8.626, P<0.01).2.Additionally, the level of miR-30b was negatively correlated with maternal pre-pregnancy body mass index(r=-0.298, P<0.01).3.The levels of miR-146b and miR-30b were higher in mothers giving birth by vaginal delivery than those who underwent cesarean section(t=2.356, 3.108, all P<0.05).4.The levels of miR-146b and miR-155 were higher in colostrum-fed girls than boys(t=-2.204, -2.985, all P<0.05).5.The level of miR-146b in mature milk was negatively correlated with 3-month-old infant's Z score of body weight(r=-0.425, P<0.05) and body length(r=-0.569, P<0.01).6.During follow-up, the incidence of baby eczema in breast feeding group(8.82%, 3/34 cases) was lower than that in formula milk feeding group(29.17%, 14/48 cases) (χ2 = 5.012, P=0.025). Conclusions The levels of immunocompetent microRNAs in human milk are influenced by the lactation period, maternal pre-pregnancy body mass index, mode of delivery and infant sex.The immune-related microRNAs in human milk could be involved in the regulation of infant's immunity and growth. Key words: Human milk; Immunity; MicroRNA-146b; MicroRNA-155; MicroRNA-30b; Maternal and infant health

Background: Maternal obesity is associated with increased risk of pediatric obesity and the mechanisms that account for these observations remain poorly characterized. Pre-pregnancy BMI (ppBMI) is associated with variation in human milk composition, suggesting that human milk metabolites may affect infant growth and risk of obesity. Objective: The purpose of this study was to leverage clinical metabolomics to understand the impact of ppBMI on human milk composition in a longitudinal birth cohort. Methods: Clinical data (n=83) for this study included normal weight (NW, pre-pregnant BMI &amp;lt;25.0 kg/m2) and obese (Ob, pre-pregnant BMI &amp;gt;30.0 kg/m2) maternal infant dyads at 3rd trimester (34-38 weeks) and followed for 12-months postpartum. Human milk samples were collected at 2-weeks and metabolomics data was generated by untargeted high-resolution liquid chromatography mass spectrometry. T-test was performed using the R statistical software to test for differences in human milk metabolomics. Results: We found that maternal obesity was associated with changes in 170 human milk metabolites. Specifically, we found ppBMI was associated with reduced levels of human milk carbohydrates (deoxyribose, p=0.03), lipids (undecanoic acid, p=0.03), and phytochemical (pipecolate, p=0.02) compounds. We also found that ppBMI was associated with increased levels of lipids (dodecylaldehyde, p=0.02), nucleic acids (uridine, p=0.04) and peptides (ornithine, p=0.0003). Conclusion: Our results demonstrate that maternal ppBMI was associated with changes in human milk composition and may represent a potential milk-dependent mechanism for mother-child transmission of obesity risk. Disclosure L. DeCicco: None. T.J. Garrett: None. D.J. Lemas: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (K01DK115632)

The present study investigates the influence of selected infant and maternal factors on the energy and macronutrient composition of mature human milk (HM). The study enrolled 77 mothers at 4–8 weeks postpartum. Each mother provided 1 sample of HM. Each extracted HM sample was formed by mixing four subsamples of HM, each of which were obtained in one predefined 6-h periods of the day. Among maternal factors, the analysis included: anthropometric data before and after pregnancy; weight gain in pregnancy; body composition, assessed using the Maltron BioScan 920-II to analyze bioimpedance; and dietary intake, assessed with three-day dietary records. Among the neonatal factors, birth weight and length, number of daily feedings and type of delivery were included. The composition of HM, including energy content, protein, fat and carbohydrate concentrations, was analyzed using the Miris human milk analyzer. Pearson’s and Spearman’s correlation coefficients and multivariable logistic regression models were used to analyze the association between the selected maternal and infant factors and HM milk composition. It was found that total protein content of HM was correlated with pre-pregnancy BMI (Spearman rho = 0.238; p = 0.037), current lean body mass (Spearman rho = −0.293, p = 0.01) and total water content (Spearman rho = −0.315, p = 0.005). Carbohydrates were the only macronutrients whose composition was significantly affected by the infant factors. It was reported that higher carbohydrate content was associated with male sex (OR = 4.52, p = 0.049). Our results show that maternal and infant factors, especially maternal pre-pregnancy and current nutritional status and infant sex, interact and affect HM composition, suggesting that macronutrient and energy content in HM may be determined in pregnancy and may have unique compositional profile for every mother–infant dyad.

Background and aims: Parental obesity is one of the important factors that is strongly linked with the development of offspring obesity. When both parents are obese, the risk of offspring being obese is greater than when one parent is obese. Irrespective of the exposure time of parental overweight and obesity, studies have consistently found that parental overweight and obesity is positively associated with offspring overweight and obesity. Few longitudinal birth-cohort studies have examined pre-pregnancy parental overweight or obesity and whether it is positively associated with offspring overweight and obesity in the long term. Additionally, there are limited studies reporting on the association of prenatal parental obesity with offspring body mass index (BMI) change, and even less is known about the association between long-term post-partum parental BMI change and the risk of offspring obesity. The aim of the current study is to investigate the association between parental obesity and offspring obesity over the life course, using data from birth-cohort studies. This study examines the longitudinal association between prenatal parental BMI and offspring BMI and adiposity in infancy, childhood, adolescence and adulthood. This study also investigates the association between prenatal parental BMI and offspring BMI change in childhood, adolescence and adulthood. Finally, this study adds to research examining the association between 21 years maternal post-partum weight change (PPWC) and the risk of adulthood obesity in offspring. Methods: Data are from two cohorts-Universiti Sains Malaysia Pregnancy Cohort which consists of 145 respondents who provided details of pre-pregnancy parental weight and height and weight and length of offspring at the 12-month follow-up; and the Mater-University of Queensland Study of Pregnancy (MUSP) which consists of 1494 participants with complete weight and height for pre-pregnancy paternal–maternal and offspring weight and height at 5, 14 and 21 years. A series of models were used to test the association between prenatal parental BMI and offspring outcomes to adjust the potential covariates obtained from either cohorts (e.g. maternal factors: gestational weight gain; offspring factors: birth weight, TV watching hours at 14 years). Multiple linear regression, logistic regression and multinomial regression were used (continuous or categorical predictors) to examine the association between pre-pregnancy parental BMI and its categories, and offspring BMI and its categories. Multiple imputation was used to address the issue of missing values in covariates. Generalized estimating equation models were used to examine the longitudinal parental–offspring BMI association in infants and were again used to determine the differential effect size of prenatal parental BMI on childhood, adolescence and adulthood. Finally, we analysed the association between 21 years maternal postpartum BMI change and offspring BMI and waist circumference (WC at 21 years using multiple linear regression and multinomial logistic regression. Results: Major findings are as follows: 1) A significant association was found between maternal BMI and child’s weight for age z-score (WAZ), weight for height z-score (WHZ) and BMI for age z-score (BAZ) at 12 months; although it was attenuated in the fully adjusted model. 2) After adjustment for confounders, for each unit increase in paternal and maternal BMI, the BMI of young adult offspring increased by 0.33 kg/m2 and 0.35 kg/m2, and the waist circumference (WC) increased by 0.76 cm and 0.62 cm, respectively. Offspring at 21 years were at six times more at risk of being overweight/obese (OW/OB) when both parents were OW/OB, compared to offspring of normal-weight parents. 3) A total of 14.7% of the offspring experienced BMI change from normal at 5 years to OW/OB at 14 years, 15.3% from normal at 14 years to OW/OB at 21 years. Overall, the strength of the association of parental BMI with offspring BMI was stronger as offspring became older. When both parents were OW/OB, these associations were stronger than when one parent was OW/OB. 4) In two decades, mothers who had highest weight change were associated with adult offspring’s risk of OW/OB and abdominal obesity with odds of 1.47 (95%CI: 1.08–2.00) and 1.50 (95%CI: 1.10–2.02), respectively. Conclusions: These findings suggest that parental BMI before pregnancy has a long-term association with offspring BMI from early childhood to adulthood. We found mother–offspring and father–offspring associations were of similar strength and direction. There was no offspring male–female differential association. Our study further demonstrated that parental pre-pregnancy nutritional status is an important predictor in early life that influences offspring overweight and obesity throughout life. Intervening to reduce the prevalence of overweight or obesity in early life by targeting parents may have potential benefits. Encouraging adults to maintain a healthy lifestyle in this challenging obesogenic environment may benefit both themselves and subsequent generations. Studies are warranted to further explore parental lifestyle (dietary and physical activities) before pregnancy and the impact of intervention to improve parental lifestyle on offspring outcomes in the long term.

BackgroundColostrum is well known to have excellent nutritional value for newborns. The aim of this study was to investigate the dynamic expression pattern of microRNA in human colostrum and mature milk. Furthermore, we identified the specific microRNA in human colostrum and analyzed the regulatory function of human colostrum.MethodsWe collected breast milk samples from 18 lactating volunteers. The expression of microRNA in breast milk was detected by microarray analysis. The expression differences were characterized by log2FC (|log2fold change| >1.58) and associated P values (P<0.05). Furthermore, the prediction of microRNA targets, bioinformatics analysis and network generation were carried out using network database.ResultsOur results showed that during the human lactation process, the composition of microRNAs in human milk changes dynamically. Compared to the microRNA expression profile in human mature milk, the expression levels of 49 microRNAs were significantly different and 67 microRNAs were specifically expressed in human colostrum. Based on the results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, the predicted target mRNAs of the identified colostrum-specific microRNAs were involved in the regulation of distinct biological processes, such as signal transduction, positive regulation of GTPase activity, and protein phosphorylation. Moreover, the predicted mRNA targets were from large spectrums of signaling pathways, such as the MAPK, Ras, Hippo, Wnt, and mTOR signaling pathways, as well as the longevity regulating pathway.ConclusionsOur study illuminates the landscape of microRNA expressions in human colostrum and mature milk, and emphasizes the value of microRNAs as nutritional additives in milk-related commercial products.

The rise of preeclampsia rates: The contribution of increasing maternal obesity

Maternal high fat diet programming of the endocrine system

Breast milk (BM) provides the optimal combination of essential nutrients and bioactive molecules for infant growth and development. However, accumulating evidence from our group and others indicates that maternal factors such as obesity can alter BM composition, potentially affecting offspring health outcomes. Bile acids (BA), both primary and secondary, have been identified in human BM but the precise composition and their role in BM remain largely underexplored. In this study, we analyzed BA profiles in BM and plasma in lactating mothers with obesity or not, across two independent clinical cohorts. BM and plasma samples were collected from breastfeeding women classified as normal-weight (N) or with obesity (O). BA concentrations were quantified by reverse phase liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). BAs were present in BM, primarily as glyco- and tauro-conjugated of the primary BAs cholic (CA) and chenodeoxycholic acid (CDCA), though at lower levels than in plasma under normal-weight conditions. Maternal obesity led to a marked increase in total BM BA levels while plasma BA concentrations and composition remained unchanged. Additionally, BM BA levels were positively correlated with maternal pre-pregnancy BMI, circulating leptin (a marker of adiposity), and insulin levels. Our findings identify maternal obesity as a significant modifier of BM BA composition, with potential implications for neonatal digestion, maturation and health. Further research is warranted to elucidate the impact of these alterations on infant health and development.

BackgroundHuman milk dynamically adapts its composition of immunoglobulins (Igs), cytokines, and other proteins as lactation progresses, influencing the infant’s immune development and protection. Understanding how maternal factors, such as parity, influence the composition of human milk can provide strategies aimed at enhancing infant immune protection and reducing early-life infections. This study aims to investigate whether the immune composition of human milk differs based on parity, and if so, how these changes are related to infections in early life.MethodsThe study included 75 healthy mother-infant pairs from the MAMI cohort (Clinical Trial Registry NCT03552939), with milk samples collected from the same mothers at days 7 and 15 postpartum, during transitional lactation stage. Igs, cytokines, and adipokines were quantified using multiplex immunoassays and ELISA. A comparison was conducted between primiparous and multiparous mothers regarding both the overall and individual composition of immune components in human milk at each time point, as well as their evolution throughout the transitional phase.ResultsInfants from multiparous mothers recorded higher infection rates in early life than those of primiparous mothers. Some human milk immune components also differed by parity, with multiparous mothers exhibiting higher levels of IgA, total IgG, IgG1, IgG2, IgG3, IgE, and IL-23 at the beginning of the transitional phase (day 7), as well as higher IL-18 and IL-21 levels toward its end (day 15), compared to primiparous mothers. Additionally, the evolutionary pattern in levels of Igs, cytokines, and adipokines throughout the transitional milk stage also differed. Moreover, in multiparous mothers, higher levels of IgG, particularly IgG1 and IgG2 (day 7), as well as IL-18 and IL-22 (day 15), were associated with reduced infant infections, highlighting their potential protective role.ConclusionsParity is a maternal factor that influences some immune components of human milk during the transitional stage and may be linked to the susceptibility of infants to infections during the first 6 months of life. Future studies aimed at analyzing the impact of the parity factor, among others, on the progression of immune components in human milk may contribute to a better understanding and improved strategies for newborn health.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13006-025-00770-0.

Maternal Obesity is Negatively Associated with Breastfeeding Success among Hispanic but Not Black Women

Maternal obesity during pregnancy as a risk for early-life asthma

BackgroundInfant cognitive development is influenced by maternal factors that range from obesity to early feeding and breast milk composition. Animal studies suggest a role for human milk oligosaccharide (HMO), 2’-fucosyllactose (2’FL), on learning and memory, yet no human studies have examined its impact on infant cognitive development relative to other HMOs and maternal factors.ObjectiveTo determine the impact of 2’FL from breast milk feeding on infant cognitive development at 24 months of age relative to maternal obesity and breast milk feeding frequency.Methods and materialsHispanic mother-infant pairs (N = 50) were recruited across the spectrum of pre-pregnancy BMI. Breast milk was collected at 1 and 6 months, and feedings/day were reported. Nineteen HMOs were analyzed using high-performance liquid chromatography, with initial interest in 2’FL. Infant cognitive development score was assessed with the Bayley-III Scale at 24 months. Linear regressions were used for prediction, and bootstrapping to determine mediation by 2’FL.ResultsMaternal pre-pregnancy BMI was not related to feedings/day or HMOs, but predicted poorer infant cognitive development (β = -0.31, P = 0.03). Feedings/day (β = 0.34) and 2’FL (β = 0.59) at 1 month predicted better infant cognitive development (both P≤ 0.01). The association of feedings/day with infant cognitive development was no longer significant after further adjustment for 2’FL (estimated mediation effect = 0.13, P = 0.04). There were no associations of feedings/day and 2’FL at 6 months with infant cognitive development.ConclusionsOur findings suggest that maternal factors influence infant cognitive development through multiple means. Though maternal obesity may be a separate negative influence, greater frequency of breast milk feeding at 1 month contributed to infant cognitive development through greater exposure to 2’FL relative to other HMOs. The influence of 2’FL was not significant at 6 months, indicating that early exposure to 2’FL may be a critical temporal window for positively influencing infant cognitive development.

Maternal obesity and the human milk metabolome: associations with infant body composition and postnatal weight gain