Dataset Information

The impact of maternal obesity and breast milk inflammation on developmental programming of infant growth.

ABSTRACT:

Background

Little is known about how maternal obesity impacts breast milk (BM) composition and how BM composition may impact growth. We sought to determine the role of maternal body mass index (BMI) on BM inflammatory and oxidative stress markers and to delineate the role of these BM markers on infant growth.

Methods

This was a secondary analysis of 40 mother-infant dyads. We first assessed the association between maternal BMI and BM marker (omega-6:omega-3 polyunsaturated fatty acid ratio (n-6:n-3 PUFA), leptin, interleukin (IL)-8, IL-6, IL-1? and malondialdehyde (MDA)) concentration at one (V1) and four (V4) months postpartum. We then examined the association between BM markers on infant growth trajectory from birth to seven months.

Results

Higher maternal BMI was associated with higher BM n-6:n-3 PUFA (V1 ??=?0.12, 95% CI 0.01, 0.2; V4 ??=?0.13, 95% CI 0.01, 0.3) and leptin (V1 ??=?107, 95% CI 29, 184; V4 ??=?254, 95% CI 105, 403) concentrations. Infants exposed to high BM n-6:n-3 PUFA had higher BMI z-scores over time (p?=?0.01). Higher BM leptin was associated with lower infant percent fat mass at V4 (??=?-9, 95% CI -17, -0.6). Infants exposed to high BM IL-8, IL-6, or IL-1? had higher weight z-scores over time (IL-8 p?ConclusionsHigher maternal BMI is associated with higher BM n-6:n-3 PUFA and leptin concentrations. In addition, higher BM n-6:n-3 PUFA and inflammatory cytokines were associated with accelerated weight gain in infancy.

SUBMITTER: Enstad S

PROVIDER: S-EPMC7855210 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The impact of maternal obesity and breast milk inflammation on developmental programming of infant growth.

Enstad Samantha S Cheema Sukhinder S Thomas Raymond R Fichorova Raina N RN Martin Camilia R CR O'Tierney-Ginn Perrie P Wagner Carol L CL Sen Sarbattama S

European journal of clinical nutrition 20200819 1

<h4>Background</h4>Little is known about how maternal obesity impacts breast milk (BM) composition and how BM composition may impact growth. We sought to determine the role of maternal body mass index (BMI) on BM inflammatory and oxidative stress markers and to delineate the role of these BM markers on infant growth.<h4>Methods</h4>This was a secondary analysis of 40 mother-infant dyads. We first assessed the association between maternal BMI and BM marker (omega-6:omega-3 polyunsaturated fatty a ...[more]

PMID: 32814855

Similar Datasets

Project description:BackgroundThe epigenetic effects of transmission of certain regulatory molecules, such as miRNAs, through maternal milk on future generations, are still unknown and have not been fully understood yet. We hypothesized that breastfeeding regularly by adoptive-mother may cause transmission of miRNAs as epigenetic regulating factors to the infant, and the marriage of milk-siblings may cause various pathologies in the future generations.ResultsA cross-fostering model using a/a and A vy /a mice had been established. F2 milk-sibling and F2 control groups were obtained from mating of milk-siblings or unrelated mice. Randomized selected animals in the both F2 groups were sacrificed for miRNA expression studies and the remainings were followed for phenotypic changes (coat color, obesity, hyperglycemia, liver pathology, and life span). The lifespan in the F2 milk-sibling group was shorter than the control group (387 vs 590 days, p = 0.011) and they were more obese during the aging period. Histopathological examination of liver tissues revealed abnormal findings in F2 milk-sibling group. In order to understand the epigenetic mechanisms leading to these phenotypic changes, we analyzed miRNA expression differences between offspring of milk-sibling and control matings and focused on the signaling pathways regulating lifespan and metabolism. Bioinformatic analysis demonstrated that differentially expressed miRNAs were associated with pathways regulating metabolism, survival, and cancer development such as the PI3K-Akt, ErbB, mTOR, and MAPK, insulin signaling pathways. We further analyzed the expression patterns of miR-186-5p, miR-141-3p, miR-345-5p, and miR-34c-5p and their candidate target genes Mapk8, Gsk3b, and Ppargc1a in ovarian and liver tissues.ConclusionOur findings support for the first time that the factors modifying the epigenetic mechanisms may be transmitted by breast milk and these epigenetic interactions may be transferred transgenerationally. Results also suggested hereditary epigenetic effects of cross-fostering on future generations and the impact of mother-infant dyad on epigenetic programming.

Project description:Background: Maternal pre-pregnancy BMI is a critical factor influencing the composition of breast milk. Breast milk has abundant extracellular vesicles (EVs) containing various biological molecules (cargo), including miRNAs. EVs are not degraded in the gastrointestinal system and circulation; thus, breast milk EVs (bEVs) interact with other organs in breastfed infants and modify the gene expression of recipient cells using miRNAs. In maternal obesity, miRNAs in bEVs are deregulated, which might be associated with adverse health outcomes in infants. In this study, we examined 798 miRNAs to determine which miRNAs are altered in the bEVs of obese mothers and their potential impact on breastfed infants. Methods: We recruited healthy nursing mothers who were either obese (BMI≥30) or lean (BMI<25) based on their pre-pregnancy BMI, and delivered a singleton baby in the prior six months. EVs were isolated from breast milk with ultracentrifugation. bEV characteristics were examined by flow cytometry and fluorescence imaging of EV markers. A total of 798 miRNAs were screened using a NanoString human miRNA panel to find deregulated miRNAs in bEVs of obese mothers compared to lean mothers. Results: We included 65 nursing mothers: 47 lean and 18 obese mothers based on pre-pregnancy BMI. After bEV isolation, we confirmed the expression of general EV markers. Out of 37 EV markers, CD326 was the most highly expressed marker in bEVs. From miRNA analysis using NanoString, we found that the most abundant miRNAs include miR-30b-5p, miR-494-3p, and let-7 families, and the list of top 10 miRNAs was not different between lean and obese mothers. Target genes of the top 10 miRNAs were associated with the EGFR, ErbB, and FoxO signaling pathway. Nineteen miRNAs were deregulated in bEVs of obese mothers (adjusted p < 0.05 cut-off), including miR-575, miR-548g-3p, miR-582-3p, and miR-652-5p. The target genes of these miRNAs are associated with lipid metabolism, inflammatory diseases, and nervous/cardiovascular system development. Conclusion: In this study, we demonstrated altered miRNAs in bEVs of obese mothers and identified the pathways of their potential target genes. Our findings will provide insight for future studies investigating the role of bEVs in breastfed infants.

Project description:Maternal and pediatric obesity has risen dramatically over recent years, and is a known predictor of adverse long-term metabolic outcomes in offspring. However, which particular aspects of obese pregnancy promote such outcomes is less clear. While maternal obesity increases both maternal and placental inflammation, it is still unknown whether this is a dominant mechanism in fetal metabolic programming. In this study, we utilized the Fat-1 transgenic mouse to test whether increasing the maternal n-3/n-6 tissue fatty acid ratio could reduce the consequences of maternal obesity-associated inflammation and thereby mitigate downstream developmental programming. Eight-week-old WT or hemizygous Fat-1 C57BL/6J female mice were placed on a high-fat diet (HFD) or control diet (CD) for 8 weeks prior to mating with WT chow-fed males. Only WT offspring from Fat-1 mothers were analyzed. WT-HFD mothers demonstrated increased markers of infiltrating adipose tissue macrophages (P<0.02), and a striking increase in 12 serum pro-inflammatory cytokines (P<0.05), while Fat1-HFD mothers remained similar to WT-CD mothers, despite equal weight gain. E18.5 Fetuses from WT-HFD mothers had larger placentas (P<0.02), as well as increased placenta and fetal liver TG deposition (P<0.01 and P<0.02, respectively) and increased placental LPL TG-hydrolase activity (P<0.02), which correlated with degree of maternal insulin resistance (r?=?0.59, P<0.02). The placentas and fetal livers from Fat1-HFD mothers were protected from this excess placental growth and fetal-placental lipid deposition. Importantly, maternal protection from excess inflammation corresponded with improved metabolic outcomes in adult WT offspring. While the offspring from WT-HFD mothers weaned onto CD demonstrated increased weight gain (P<0.05), body and liver fat (P<0.05 and P<0.001, respectively), and whole body insulin resistance (P<0.05), these were prevented in WT offspring from Fat1-HFD mothers. Our results suggest that reducing excess maternal inflammation may be a promising target for preventing adverse fetal metabolic outcomes in pregnancies complicated by maternal obesity.

Project description:Background & aimsBreastfeeding is beneficial for mothers and infants. Underlying mechanisms and biochemical mediators thus need to be investigated to develop and support improved infant nutrition practices promoting the child health. We analysed the relation between maternal breast milk composition and infant metabolism.Methods196 pairs of mothers and infants from a European research project (PreventCD) were studied. Maternal milk samples collected at month 1 and month 4 after birth were analysed for macronutrient classes, hormone, and fatty acid (FA) content. Phospholipids, acylcarnitines, and amino acids were measured in serum samples of 4-month old infants. Associations between milk components and infant metabolites were analysed with spearman correlation and linear mixed effect models (LME). P-values were corrected for multiple testing (PLME).ResultsMonth 1 milk protein content was strongly associated with infant serum lyso-phosphatidylcholine (LPC) 14:0 (PLME = 0.009). Month 1 milk insulin was associated to infant acetylcarnitine (PLME = 0.01). There were no associations between milk protein content and serum amino acids and milk total fat content and serum polar lipids. Middle- and odd-chain FA% in breast milk at both ages were significantly related to serum LPC and sphingomyelins (SM) species in infant serum (all PLME<0.05), while FA% 20:5n-3 and 22:6n-3 percentages were significantly associated to serum LPC 22:6 (PLME = 1.91×10-4/7.93×10-5) in milk only at month 4. Other polyunsaturated fatty acids and hormones in milk showed only weak associations with infant serum metabolites.ConclusionsInfant serum LPC are influenced by breast milk FA composition and, intriguingly, milk protein content in early but not late lactation. LPC 14:0, previously found positively associated with obesity risk, was the serum metabolite which was the most strongly associated to milk protein content. Thus, LPC 14:0 might be a key metabolite not only reflecting milk protein intake in infants, but also relating high protein content in milk or infant formula to childhood obesity risk.

Project description:Abstract Objectives Fatty acid esters of hydroxy fatty acids (FAHFAs) are a novel class of endogenous lipids with suspected anti-inflammatory and anti-diabetic properties in adults. They have been reported to be present in breast milk (BM), but there is no data about their role in infant growth and nutrition. Our objective was to determine the role of maternal body mass index (BMI) on BM FAHFA composition and to delineate the association of these BM fatty acids on infant growth and adiposity. Methods This is a secondary analysis of a randomized controlled trial of maternal vitamin D supplementation during lactation (NCT00412074). We included 40 control mother-infant dyads who had BM samples at one (V1) and four (V4) months and outcome data available. At V1 and V4, maternal and infant anthropometrics were measured, dual energy absorptiometry (DXA) scans conducted, and BM samples collected. BM lipids were measured using established methods of UHPLC-C30RP/HRAM mass spectrometry. Our primary infant growth outcomes were percentage of fat and lean mass, fat mass index, and fat-free mass index. Redundancy analysis (RDA) was used to analyze the relation between individual lipids, maternal BMI, and infant growth. Focusing on V1 measurements, we computed the unadjusted associations between maternal BMI with BM lipids; BM lipids with infant growth using Pearson's correlations; and the adjusted associations of BM lipids at V1 with infant growth using linear regression with adjustment for relevant covariates. Results The mean maternal BMI was 29 kg/m2. There was no correlation between maternal BMI and reported dietary intake of fat. Higher maternal BMI was associated with a higher concentration of saturated and monounsaturated FAHFAs, and a lower concentration of polyunsaturated FAHFAs in BM at V1. In an unadjusted model, saturated and monounsaturated FAHFAs were associated with higher infant fat mass and lower lean mass. The converse was seen with polyunsaturated FAHFAs which were associated with lower infant fat mass and higher lean mass. In a fully adjusted model, these associations were attenuated but the overall pattern persisted (Table 1). Conclusions Maternal BMI influences the FAHFA composition of BM. In turn, BM FAHFA composition may play a role in programming infant growth patterns. Funding Sources The Nutritional Obesity Research Consortium Grant. Supporting Tables, Images and/or Graphs

Dataset Information

The impact of maternal obesity and breast milk inflammation on developmental programming of infant growth.

Background

Methods

Results

Publications

The impact of maternal obesity and breast milk inflammation on developmental programming of infant growth.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure