Human Milk Oligosaccharide Concentrations and Infant Intakes Are Associated with Maternal Overweight and Obesity and Predict Infant Growth

Human milk oligosaccharides (HMOs) are bioactive molecules playing a critical role in infant health. We aimed to quantify the composition of HMOs of women with normal weight (18.5–24.9 kg/m2), overweight (25.0–29.9 kg/m2), or obesity (30.0–60.0 kg/m2) and determine the effect of HMO intake on infant growth. Human milk (HM) samples collected at 2 months (2 M; n = 194) postpartum were analyzed for HMO concentrations via high-performance liquid chromatography. Infant HM intake, anthropometrics and body composition were assessed at 2 M and 6 M postpartum. Linear regressions and linear mixed-effects models were conducted examining the relationships between maternal BMI and HMO composition and HMO intake and infant growth over the first 6 M, respectively. Maternal obesity was associated with lower concentrations of several fucosylated and sialylated HMOs and infants born to women with obesity had lower intakes of these HMOs. Maternal BMI was positively associated with lacto-N-neotetraose, 3-fucosyllactose, 3-sialyllactose and 6-sialyllactose and negatively associated with disialyllacto-N-tetraose, disialyllacto-N-hexaose, fucodisialyllacto-N-hexaose and total acidic HMOs concentrations at 2 M. Infant intakes of 3-fucosyllactose, 3-sialyllactose, 6-sialyllactose, disialyllacto-N-tetraose, disialyllacto-N-hexaose, and total acidic HMOs were positively associated with infant growth over the first 6 M of life. Maternal obesity is associated with changes in HMO concentrations that are associated with infant adiposity.

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The Impact of Maternal Obesity on Human Milk Macronutrient Composition: A Systematic Review and Meta-Analysis

Nutrients ◽

10.3390/nu12040934 ◽

2020 ◽

Vol 12 (4) ◽

pp. 934 ◽

Cited By ~ 3

Author(s):

Gabriela E. Leghi ◽

Merryn J. Netting ◽

Philippa F. Middleton ◽

Mary E. Wlodek ◽

Donna T. Geddes ◽

...

Keyword(s):

Human Milk ◽

Maternal Obesity ◽

Overweight And Obesity ◽

Cochrane Library ◽

Maternal Body Mass Index ◽

Qualitative Synthesis ◽

Lactating Women ◽

Maternal Overweight ◽

The Impact

Maternal obesity has been associated with changes in the macronutrient concentration of human milk (HM), which have the potential to promote weight gain and increase the long-term risk of obesity in the infant. This article aimed to provide a synthesis of studies evaluating the effects of maternal overweight and obesity on the concentrations of macronutrients in HM. EMBASE, MEDLINE/PubMed, Cochrane Library, Scopus, Web of Science, and ProQuest databases were searched for relevant articles. Two authors conducted screening, data extraction, and quality assessment independently. A total of 31 studies (5078 lactating women) were included in the qualitative synthesis and nine studies (872 lactating women) in the quantitative synthesis. Overall, maternal body mass index (BMI) and adiposity measurements were associated with higher HM fat and lactose concentrations at different stages of lactation, whereas protein concentration in HM did not appear to differ between overweight and/or obese and normal weight women. However, given the considerable variability in the results between studies and low quality of many of the included studies, further research is needed to establish the impact of maternal overweight and obesity on HM composition. This is particularly relevant considering potential implications of higher HM fat concentration on both growth and fat deposition during the first few months of infancy and long-term risk of obesity.

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The Impact of Maternal Obesity on Human Milk Macronutrient Composition: A Systematic Review and Meta-Analysis

Current Developments in Nutrition ◽

10.1093/cdn/nzab046_070 ◽

2021 ◽

Vol 5 (Supplement_2) ◽

pp. 773-773

Author(s):

Gabriela Leghi ◽

Merryn J Netting ◽

Philippa F Middleton ◽

Mary E Wlodek ◽

Donna T Geddes ◽

...

Keyword(s):

Human Milk ◽

Maternal Obesity ◽

Meta Analysis ◽

Overweight And Obesity ◽

Qualitative Assessment ◽

Cochrane Library ◽

Qualitative Synthesis ◽

Lactating Women ◽

Maternal Overweight ◽

The Impact

Abstract Objectives This article aimed to provide a synthesis of studies evaluating the effects of maternal overweight and obesity, including body mass index (BMI) and other measures of adiposity, on the concentrations of macronutrients (fat, protein and lactose) in human milk (HM). Methods EMBASE, MEDLINE/PubMed, Cochrane Library, Scopus, Web of Science and ProQuest databases were searched for relevant articles. Two authors conducted screening, data extraction and quality assessment independently. Meta-analyses of eligible studies were conducted using Review Manager software version 5.3. Results A total of 31 studies (5078 lactating women) were included in the qualitative synthesis and 9 studies (872 lactating women) in the quantitative synthesis. The meta-analysis indicated that maternal overweight and obesity were associated with higher concentrations of fat in mature HM (p = 0.01) and lactose in colostrum (p = 0.002). While the qualitative analyses broadly supported the findings of the meta-analysis, the qualitative assessment identified considerable variability in the results between studies and low quality of many of the included studies, making it difficult to draw robust conclusions. Conclusions Overall, maternal BMI and adiposity measurements were associated with differences in the concentrations of fat and lactose in HM, however the direction of change was dependent on the stage of lactation, whereas protein concentration in HM did not appear to differ between overweight and/or obese and normal weight women. This is particularly relevant considering potential implications of higher HM fat concentration on both growth and fat deposition during the first few months of infancy and long-term risk of obesity. Funding Sources GEL was supported by a FOODplus Early Life Nutrition Scholarship, The University of Adelaide. BSM received a Career Development Award from the National Health and Medical Research Council of Australia (NHMRC).

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Maternal Obesity and Risk of Early-onset Neonatal Bacterial Sepsis: Nationwide Cohort and Sibling-controlled Studies

Clinical Infectious Diseases ◽

10.1093/cid/ciaa783 ◽

2020 ◽

Author(s):

Eduardo Villamor ◽

Mikael Norman ◽

Stefan Johansson ◽

Sven Cnattingius

Keyword(s):

Early Onset ◽

Maternal Obesity ◽

Group B Streptococcus ◽

Population Based ◽

Normal Weight ◽

Overweight And Obesity ◽

Bacterial Sepsis ◽

Term Infants ◽

Cesarean Section Delivery ◽

Maternal Overweight

Abstract Background Maternal overweight and obesity are related to risks of pregnancy and delivery complications that, in turn, are associated with newborn infections. We examined the associations between early pregnancy body mass index (BMI; kg/m2) and risk of early-onset neonatal bacterial sepsis (EOS). Methods We conducted a nationwide population-based retrospective cohort study of 1 971 346 live singleton infants born in Sweden between 1997 and 2016. Outcome was a culture-confirmed EOS diagnosis. We estimated hazard ratios (HR) of EOS according to BMI using proportional hazard models, and identified potential mediators. Among term infants, we conducted sibling-controlled analyses. Results EOS risk per 1000 live births was 1.48; 0.76 in term and 15.52 in preterm infants. Compared with infants of normal-weight mothers (BMI, 18.5–24.9), the adjusted HR (95% confidence interval [CI]) of EOS for BMI categories <18.5, 25.0–29.9, 30.0–34.9, 35.0–39.9, and ≥40.0 were, respectively, 1.07 (.83–1.40), 1.19 (1.08–1.32), 1.70 (1.49–1.94), 2.11 (1.73–2.58), and 2.50 (1.86–3.38). Maternal overweight and obesity increased the risk of EOS by group B Streptococcus, Staphylococcus aureus, and Escherichia coli. Half of the association was mediated through preeclampsia, cesarean section delivery, and preterm delivery. A dose-response association was consistently apparent in term infants only. In sibling-controlled analyses, every kilogram per meter squared interpregnancy BMI change was associated with a mean 8.3% increase in EOS risk (95% CI, 1.7%–15.3%; P = .01). Conclusions Risk of EOS increases with maternal overweight and obesity severity, particularly in term infants.

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Breast Milk Supply of MicroRNA Associated with Leptin and Adiponectin Is Affected by Maternal Overweight/Obesity and Influences Infancy BMI

Nutrients ◽

10.3390/nu11112589 ◽

2019 ◽

Vol 11 (11) ◽

pp. 2589 ◽

Cited By ~ 2

Author(s):

Rocío Zamanillo ◽

Juana Sánchez ◽

Francisca Serra ◽

Andreu Palou

Keyword(s):

Breast Milk ◽

Target Genes ◽

Maternal Obesity ◽

Infant Growth ◽

Normal Weight ◽

Milk Supply ◽

Milk Samples ◽

Lactating Mothers ◽

Maternal Overweight ◽

Over Time

Breast milk constitutes a dietary source of leptin, adiponectin and microRNAs (miRNAs) for newborns. Expression of miRNAs previously associated with maternal obesity, leptin or adiponectin function were assessed and their impact on infant weight analyzed. Milk samples were collected (at month 1, 2, and 3) from a cohort of 59 healthy lactating mothers (38 normal-weight and 21 overweight/obese (BMI ≥ 25)), and infant growth was followed up to 2 years of age. Thirteen miRNAs, leptin and adiponectin were determined in milk. Leptin, adiponectin and miRNA showed a decrease over time of lactation in normal-weight mothers that was altered in overweight/obesity. Furthermore, negative correlations were observed in normal-weight mothers between the expression of miRNAs in milk and the concentration of leptin or adiponectin, but were absent in overweight/obesity. Moreover, miRNAs negatively correlated with infant BMI only in normal-weight mothers (miR-103, miR-17, miR-181a, miR-222, miR-let7c and miR-146b). Interestingly, target genes of milk miRNAs differently regulated in overweight/obesity could be related to neurodevelopmental processes. In conclusion, a set of miRNAs present in breast milk, in close conjunction with leptin and adiponectin, are natural bioactive compounds with the potential to modulate infant growth and brain development, an interplay that is disturbed in the case of maternal overweight/obesity.

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Infant Intakes of Human Milk Amino Acids Are Associated With Maternal Obesity and Infant Growth

Current Developments in Nutrition ◽

10.1093/cdn/nzab046_107 ◽

2021 ◽

Vol 5 (Supplement_2) ◽

pp. 810-810

Author(s):

Jessica Saben ◽

Clark Sims ◽

Lindsay Pack ◽

Renny Lan ◽

Aline Andres

Keyword(s):

Amino Acids ◽

Human Milk ◽

Early Life ◽

Maternal Obesity ◽

Child Growth ◽

Infant Growth ◽

Formula Milk ◽

Mixed Effect ◽

The Impact ◽

Maternal Bmi

Abstract Objectives Branched chain amino acids (AA) (BCAAs: leucine (Leu), isoleucine (Ile), and valine) and aromatic AA (AAAs: phenylalanine (Phe) and tyrosine (Tyr)) have been hypothesized to take part in early-life metabolic programing. To date studies testing the effect of early-life AA consumption on metabolic programing have been focused on formula milk proteins, where increased consumption was associated with obesity risk. However, a knowledge gap exists regarding how variations in human milk (HM) free AA concentrations might impact child growth. Here, we aimed to characterize HM free AA concentrations and infant intakes of HM AAs from women with obesity (OB) compared to those with normal weight (NW). We hypothesized that infants born to women with OB would consume greater amounts of HM BCAAs and AAAs, which would be positively associated with their growth. Methods HM samples were collected at 0.5 months (0.5M; n = 151), 2 months (2M; n = 129), and 6 months (6M; n = 93) postpartum from NW (body mass index (BMI) = 18.5 – 24.9 kg/m2) and OB (BMI > 30 kg/m2) mothers. HM free AA were quantified at each timepoint via mass spectrometry. Infant HM intake, anthropometrics and body composition were assessed at each timepoint. Linear mixed effect models examined the relationships between maternal BMI and HM AA composition, HM AA intake, and infant growth over the first 6Ms postpartum. Models were adjusted for maternal race, breastfeeding exclusivity, infant sex and infant age. Results Concentrations of Ile, Leu, and AAAs were higher (p < 0.05) across all timepoints in HM from women with OB compared to those with NW. Infant intakes, normalized to kg body weight, of these AAs were only significantly higher at 2M. Maternal BMI was negatively associated (p < 0.05) with infant intakes of HM asparagine, cystine, and histidine and positively associated with Ile, Leu, and AAAs intakes across timepoints. Infant intakes of HM Ile (b = −0.083), Leu (b = −0.045), and proline (b = -0.024) were negative predictors of infant weight-for-age z-scores over the first 6M postpartum (p < 0.05). Conclusions Maternal obesity is associated with increased BCAA and AAA infant exposures over the first 6M of life. However, the impact of these AAs on infant growth are not consistent with observations made with infant formulas. Funding Sources USDA ARS Project # 6026-51,000-010-05S and 6026-51,000-012-06S.

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

Nutrients ◽

10.3390/nu13041091 ◽

2021 ◽

Vol 13 (4) ◽

pp. 1091

Author(s):

Kruti B. Shah ◽

Steven D. Chernausek ◽

Lori D. Garman ◽

Nathan P. Pezant ◽

Jasmine F. Plows ◽

...

Keyword(s):

Body Composition ◽

Human Milk ◽

Fat Mass ◽

Maternal Obesity ◽

Normal Weight ◽

The Body ◽

Fat Free Mass ◽

Negatively Associated ◽

Maternal Overweight ◽

The Impact

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.

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Effect of maternal high body mass index on outcome of pregnancy in women with recurrent miscarriages

Indian Journal of Forensic and Community Medicine ◽

10.18231/j.ijfcm.2021.048 ◽

2021 ◽

Vol 8 (4) ◽

pp. 237-241

Author(s):

Malangori Parande ◽

Tanvi V Wagh ◽

Anjali V Wagh ◽

Nandkumar Salunke

Keyword(s):

Gestational Diabetes ◽

Preterm Delivery ◽

Maternal Obesity ◽

Tertiary Care ◽

Overweight And Obesity ◽

Care Hospital ◽

Pregnancy Induced Hypertension ◽

Recurrent Miscarriages ◽

Induced Hypertension ◽

Maternal Overweight

The epidemic of obesity is spreading worldwide and subsequently, rate of obesity during pregnancy has also increased. Maternal overweight and obesity are widely associated with adverse pregnancy outcomes. Recurrent miscarriage is an important reproductive health issue, because it affects many couples. So the present study is planned to study the relationship between maternal obesity and pregnancy outcome in women with recurrent miscarriages. Observational Cross sectional study was conducted in a tertiary care hospital. 111 Postnatal women between 18 to 44 years of age with history of two or more miscarriages less than 20 weeks of gestation in previous pregnancy were included in the study. First trimester weight at the first visit (registration) was recorded, BMI was calculated & women were divided into obese and non obese groups. The outcome of present pregnancy was noted as Mode of delivery, Gestational diabetes mellitus, Pregnancy induced hypertension, Preterm delivery etc. Statistical tests were used to quantify the risk. Gestational diabetes (OR= 13.6) and pregnancy induced hypertension (OR=4.2) were significantly associated with obesity in women with recurrent miscarriages. [At 95% CI] The incidence of LSCS and preterm delivery was more in overweight and obese mothers, though not statistically significant. Maternal obesity significantly contributes to poor prognosis for the mother and the baby during delivery. Hence the women of this group should be regarded as ‘high risk’ and counselling and the risk assessment should be done during ANC visits.

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Changes in PPAR-γ Expression Are Associated with microRNA Profiles during Fetal Programming due to Maternal Overweight and Obesity

Gynecologic and Obstetric Investigation ◽

10.1159/000517116 ◽

2021 ◽

pp. 1-12

Author(s):

Noemí Gaytán-Pacheco ◽

Victoria Lima-Rogel ◽

Alejandro Méndez-Mancilla ◽

Francisco Escalante-Padrón ◽

Juan Carlos Toro-Ortíz ◽

...

Keyword(s):

Cell Cultures ◽

Maternal Obesity ◽

Normal Weight ◽

Overweight And Obesity ◽

Epigenetic Changes ◽

Maternal Weight ◽

Ppar Γ ◽

Microrna Profile ◽

In Cells

Background: There has been a global increase in the prevalence of obesity in pregnant women in recent years. Animal studies have shown that intrauterine environment associated with maternal obesity leads to epigenetic changes. However, the effects of epigenetic changes occurring before birth in response to maternal conditions have not been clearly characterized in humans. Objective: The aim of the study was to analyze peroxisome proliferator-activated receptor (PPAR)-γ expression in cell cultures from newborns from mothers with overweight and obesity, in response to in vitro metabolic challenges and their relationship with microRNA profile and cytokine expression. Methods/Study design: The profile of circulating microRNAs from 72 mother-child pairs (including healthy infants born to normal weight [n = 35], overweight [n = 25], and obese [n = 12] mothers) was determined through real-time PCR, and the PPAR-γ expression in peripheral blood mononuclear cell cultures from offspring was analyzed after in vitro challenges. Results: miR-146a, miR-155, and miR-378a were upregulated in overweight mothers, while miR-378a was upregulated in obese mothers compared to normal weight mothers. In children from overweight mothers, miR-155 and miR-221 were downregulated and miR-146a was upregulated, while offspring of mothers with obesity showed downregulation of miR-155, miR-221, and miR-1301. These microRNAs have direct or indirect relation with PPAR-γ expression. In vitro exposure to high triglyceride and exposure to miR-378a induced a higher expression of PPAR-γ in cells from offspring of mothers with overweight and obesity. In contrast, cells from offspring of mothers with obesity cultured with high glucose concentrations showed PPAR-γ downregulation. IL-1ß, IL-6, and TNF-α expression in cells of offspring of overweight and obese mothers differed from that of offspring of normal weight mothers. Limitation of our study is the small sample size. Conclusion: The blood microRNA profile, and in vitro PPAR-γ and inflammatory cytokine expression in cells of newborn infants are associated with maternal obesity indicating that epigenetic marks may be established during intrauterine development. Key Message: Neonatal microRNA profile is associated with maternal weight. Neonatal microRNA profile is independent of maternal microRNA profile. PPAR-γ expression in newborn cell cultures is affected by maternal weight

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A comparative study of the effect of body mass index on pregnancy outcomes in normal and overweight women

International Journal of Reproduction Contraception Obstetrics and Gynecology ◽

10.18203/2320-1770.ijrcog20171426 ◽

2017 ◽

Vol 6 (4) ◽

pp. 1550

Author(s):

Seeniammal P. ◽

Chellamma V. K. ◽

Umadevi N.

Keyword(s):

Comparative Study ◽

Maternal Obesity ◽

Gestational Hypertension ◽

Fetal Outcome ◽

Overweight And Obesity ◽

Health Concern ◽

Accurate Information ◽

Obese Women ◽

Increased Risk ◽

Maternal Overweight

Background: Maternal obesity has been reported as a risk factor for various antepartum, intrapartum, postpartum and neonatal complications. Increasing rates of overweight among pregnant women are a significant public health concern with various implications for prenatal care and supervision of delivery. Therefore, the present study is to determine the adverse materno-fetal outcome in primigravid overweight and obese women delivering singleton babies.Methods: A prospective comparative study was conducted for a year at IMCH, Medical College, Calicut. Primigravid women with a singleton uncomplicated pregnancy with cephalic presentation at ≥37 weeks of gestation with accurate information regarding height and weight recorded at the booking visit were included in the study. Comparisons were made between 100 women with BMI >25 and 200 women with BMI 18.5-24.9. Statistical analysis was done using SPSS version 16.0. Data was analysed by Pearson Chi square test and Fisher’s exact test.Results: Overweight mothers are at increased risk quoted as relative risk (RR) and 95% confidence intervals (CI) of adverse materno-fetal outcomes. Gestational hypertension RR 2.39 (CI 1.65-3.47), Gestational diabetes RR 2.67(CI 0.95-7.48), induction of labour RR 2.35 (CI 1.4-3.95), Cesarean section RR 5.73 (CI 3.76-8.73), macrosomia RR 14 (CI 1.75-112.23), NICU admissions RR 4.51(CI 2.61-7.84),perineal lacerations RR 4.72 (CI 1.15-20.4), wound infection RR 2.97 (CI 1.06-8.41), and prolonged hospital stay.Conclusions: It is clearly evident from the study that maternal overweight and obesity is associated with adverse materno-fetal outcome.

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

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqy334 ◽

2019 ◽

Vol 110 (1) ◽

pp. 111-120 ◽

Cited By ~ 22

Author(s):

Elvira Isganaitis ◽

Sarah Venditti ◽

Tucker J Matthews ◽

Carles Lerin ◽

Ellen W Demerath ◽

...

Keyword(s):

Body Composition ◽

Weight Gain ◽

Childhood Obesity ◽

Human Milk ◽

False Discovery Rate ◽

Maternal Obesity ◽

Milk Composition ◽

False Discovery ◽

Postnatal Weight Gain ◽

Maternal Bmi

ABSTRACTBackgroundMaternal obesity is a risk factor for childhood obesity; this is a major public health concern given that ∼40% of pregnant women are either overweight or obese. Whether differences in milk composition in lean compared with obese women contribute to childhood obesity is unclear.ObjectivesWe aimed to analyze relationships between maternal obesity and human milk metabolites, infant body composition, and postnatal weight gain.MethodsThis was a prospective study in which mothers intending to breastfeed exclusively, and their newborn infants, were enrolled at delivery (n = 35 mother–infant pairs). We excluded mothers with diabetes, other medical conditions, or pregnancy complications. Participants were grouped by maternal prepregnancy BMI <25 (lean) or ≥25 kg/m2 (overweight/obese). We analyzed infant body composition by dual-energy X-ray absorptiometry and used untargeted liquid chromatography–gas chromatography–mass spectrometry to measure the milk content of 275 metabolites at 1 and 6 mo postpartum.ResultsAt 1 mo postpartum, 10 metabolites differed between overweight/obese and lean groups with nominal P < 0.05, but none was altered with a false discovery rate <0.25. Many differentially abundant metabolites belonged to the same chemical class; e.g., 4/10 metabolites were nucleotide derivatives, and 3/10 were human milk oligosaccharides. Milk adenine correlated positively with both continuously distributed maternal BMI and with infant adiposity and fat accrual. Analysis of milk composition at 6 mo postpartum revealed 20 differentially abundant metabolites (P < 0.05) in overweight/obese compared with lean women, including 6 metabolites with a false discovery rate of <0.25. At both 1 and 6 mo, human milk abundance of 1,5-anhydroglucitol, which has not previously been described in milk, was positively associated with maternal BMI.ConclusionsMaternal obesity is associated with changes in the human milk metabolome. While only a subset of metabolites correlated with both maternal and infant weight, these point to potential milk-dependent mechanisms for mother–child transmission of obesity. This trial was registered at www.clinicaltrials.gov as NCT02535637.

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