Associations of maternal non-nutritive sweetener intake during pregnancy with offspring body mass index and body fat from birth to adolescence.

BACKGROUND/OBJECTIVE: The evidence that maternal non-nutritive sweetener (NNS) intake during pregnancy increases childhood obesity risk is conflicting. A potential reason for this is that all prior studies examined childhood body mass index (BMI) at only one timepoint and at different ages. We examined the extent to which NNS intake during pregnancy is associated with offspring BMI z-score and body fat longitudinally from birth to 18 years. SUBJECTS: A total of 1683 children from Project Viva, a prospective pre-birth cohort, were recruited from 1999 to 2002 in Massachusetts. METHODS: We assessed maternal NNS intake in the first and second trimesters of pregnancy using a semiquantitative food frequency questionnaire. Our outcomes were offspring BMI z-score, (at birth, infancy (median 6.3 months), early childhood (3.2 years), mid-childhood (7.7 years), and early adolescence (12.9 years)), sum of skinfolds (SS), fat mass index (FMI) measured by dual x-ray absorptiometry, and BMI z-score trajectory from birth to 18 years. We adjusted models for maternal pre-pregnancy BMI, age, race/ethnicity, education, parity, pre-pregnancy physical activity, smoking, and paternal BMI and education. RESULTS: A total of 70% of mothers were white and pre-pregnancy BMI was 24.6 ± 5.2 kg/m2. The highest quartile of NNS intake (Q4: 0.98 ± 0.91 servings/day) was associated with higher BMI z-score in infancy (ß 0.20 units; 95% CI 0.02, 0.38), early childhood (0.21; 0.05, 0.37), mid-childhood (0.21; 0.02, 0.40), and early adolescence (0.14; -0.07, 0.35) compared with Q1 intake (Q1: 0.00 ± 0.00 servings/day). Q4 was also associated with higher SS in early childhood (1.17 mm; 0.47, 1.88), mid-childhood (2.33 mm; 0.80, 3.87), and early adolescence (2.27 mm; -0.06, 4.60) and higher FMI in mid-childhood (0.26 kg/m2; -0.07, 0.59). Associations of maternal NNS intake with offspring BMI z-score became stronger with increasing age from 3 to 18 years (Pinteraction < 0.0001). CONCLUSIONS: Maternal NNS intake during pregnancy is associated with increased childhood BMI z-score and body fat from birth to teenage years. This is relevant given the escalating obesity epidemic, and popularity of NNS.

Development and Validation of a Prediction Model for Infant Fat Mass.

OBJECTIVES: To develop and validate a prediction model for fat mass in infants ≤12 kg using easily accessible measurements such as weight and length. STUDY DESIGN: We used data from a pooled cohort of 359 infants age 1-24 months and weighing 3-12 kg from 3 studies across Southern California and New York City. The training data set (75% of the cohort) included 269 infants and the testing data set (25% of the cohort) included 90 infants age 1-24 months. Quantitative magnetic resonance was used as the standard measure for fat mass. We used multivariable linear regression analysis, with backwards selection of predictor variables and fractional polynomials for nonlinear relationships to predict infant fat mass (from which lean mass can be estimated by subtracting resulting estimates from total mass) in the training data set. We used 5-fold cross-validation to examine overfitting and generalizability of the model's predictive performance. Finally, we tested the adjusted model on the testing data set. RESULTS: The final model included weight, length, sex, and age, and had high predictive ability for fat mass with good calibration of observed and predicted values in the training data set (optimism-adjusted R2: 92.1%). Performance on the test dataset showed promising generalizability (adjusted R2: 85.4%). The mean difference between observed and predicted values in the testing dataset was 0.015 kg (-0.043 to -0.072 kg; 0.7% of the mean). CONCLUSIONS: Our model accurately predicted infant fat mass and could be used to improve the accuracy of assessments of infant body composition for effective early identification, surveillance, prevention, and management of obesity and future chronic disease risk.

Clinical Intervention to Reduce Dietary Sugar Does Not Affect Liver Fat in Latino Youth, Regardless of PNPLA3 Genotype: A Randomized Controlled Trial.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) among Latinos is partially attributed to a prevalent C>G polymorphism in the patatin-like phospholipase 3 (PNPLA3) gene. Cross-sectional analyses in Latino children showed the association between dietary sugar and liver fat was exacerbated by GG genotype. Pediatric feeding studies show extreme sugar restriction improves liver fat, but no prior trial has examined the impact of a clinical intervention or whether effects differ by PNPLA3 genotype. OBJECTIVES: We aimed to test effects of a clinical intervention to reduce dietary sugar compared with standard dietary advice on change in liver fat, and secondary-endpoint changes in liver fibrosis, liver enzymes, and anthropometrics; and whether effects differ by PNPLA3 genotype (assessed retrospectively) in Latino youth with obesity (BMI ≥ 95th percentile). METHODS: This parallel-design trial randomly assigned participants (n = 105; mean baseline liver fat: 12.7%; mean age: 14.8 y) to control or sugar reduction (goal of ≤10% of calories from free sugar) for 12 wk. Intervention participants met with a dietitian monthly and received delivery of bottled water. Changes in liver fat, by MRI, were assessed by intervention group via general linear models. RESULTS: Mean free sugar intake decreased in intervention compared with control [11.5% to 7.3% compared with 13.9% to 10.7% (% energy), respectively; P = 0.02], but there were no significant effects on liver outcomes or anthropometrics (Pall > 0.10), and no PNPLA3 interactions (Pall > 0.10). In exploratory analyses, participants with whole-body fat mass (FM) reduction (mean ± SD: -1.9 ± 2.4 kg), irrespective of randomization, had significant reductions in liver fat compared with participants without FM reduction (median: -2.1%; IQR: -6.5% to -0.8% compared with 0.3%; IQR: -1.0% to 1.1%; P < 0.001). CONCLUSIONS: In Latino youth with obesity, a dietitian-led sugar reduction intervention did not improve liver outcomes compared with control, regardless of PNPLA3 genotype. Results suggest FM reduction is important for liver fat reduction, confirming clinical recommendations of weight loss and a healthy diet for pediatric NAFLD.This trial was registered at clinicaltrials.gov as NCT02948647.

Longitudinal Changes in Human Milk Oligosaccharides (HMOs) Over the Course of 24 Months of Lactation.

BACKGROUND: Human milk oligosaccharides (HMOs) are complex glycans that are highly abundant in human milk. While over 150 HMOs have been identified, it is unknown how individual HMOs change in concentration over 24 months of lactation. OBJECTIVES: To understand how HMO concentrations change over 24 months of lactation. METHODS: Breast milk samples were collected from participants in a longitudinal cohort study of Hispanic mother-infant pairs at 1, 6, 12, 18, and 24 months postpartum. Concentrations of 19 of the most abundant HMOs were measured using HPLC. Because the parent study is ongoing and not all participants have finished all time points yet, the sample sizes ranged per time point (n = 207 at 1 month; n = 109 at 6 months; n = 83 at 12 months; n = 59 at 18 months; and n = 28 at 24 months). Approximately 88% of participants were classified as HMO secretors-a genetic factor that affects concentrations of HMOs such as 2'fucosyllactose (2'FL) and lacto-N-fucopentaose I-while the remaining 12% were classified as nonsecretors. Mixed models were used to examine changes in HMO concentrations and relative abundances over the course of lactation. RESULTS: The majority of HMOs significantly decreased in concentration over the course of lactation. The exceptions were 2'FL, sialyl-lacto-N-tetraose b, and disialyl-lacto-N-tetraose, which did not change with time, and 3-fucosyllactose (3FL) and 3'-sialyllactose (3'SL), which significantly increased. The concentration of 3FL increased 10-fold, from 195 (IQR 138-415) µg/mL at 1 month to 1930 (1100-2630) µg/mL at 24 months, while 3'SL increased 2-fold, from 277 (198-377) µg/mL to 568 (448-708) µg/mL over the same time period. CONCLUSIONS: These results indicate that HMOs do not decrease in concentration uniformly across lactation. In particular, 3FL and 3'SL increased over the course of lactation in this cohort. Future studies are required to fully understand the functions of these HMOs.

Prenatal exposure to ambient air pollutants and early infant growth and adiposity in the Southern California Mother's Milk Study.

BACKGROUND: Prior epidemiological and animal work has linked in utero exposure to ambient air pollutants (AAP) with accelerated postnatal weight gain, which is predictive of increased cardiometabolic risk factors in childhood and adolescence. However, few studies have assessed changes in infant body composition or multiple pollutant exposures. Therefore, the objective of this study was to examine relationships between prenatal residential AAP exposure with infant growth and adiposity. METHODS: Residential exposure to AAP (particulate matter < 2.5 and 10 microns in aerodynamic diameter [PM2.5, PM10]; nitrogen dioxide [NO2]; ozone [O3]; oxidative capacity [Oxwt: redox-weighted oxidative potential of O3 and NO2]) was modeled by spatial interpolation of monitoring stations via an inverse distance-squared weighting (IDW2) algorithm for 123 participants from the longitudinal Mother's Milk Study, an ongoing cohort of Hispanic mother-infant dyads from Southern California. Outcomes included changes in infant growth (weight, length), total subcutaneous fat (TSF; calculated via infant skinfold thickness measures) and fat distribution (umbilical circumference, central to total subcutaneous fat [CTSF]) and were calculated by subtracting 1-month measures from 6-month measures. Multivariable linear regression was performed to examine relationships between prenatal AAP exposure and infant outcomes. Models adjusted for maternal age, pre-pregnancy body mass index, socioeconomic status, infant age, sex, and breastfeeding frequency. Sex interactions were tested, and effects are reported for each standard deviation increase in exposure. RESULTS: NO2 was associated with greater infant weight gain (ß = 0.14, p = 0.02) and TSF (ß = 1.69, p = 0.02). PM10 and PM2.5 were associated with change in umbilical circumference (ß = 0.73, p = 0.003) and TSF (ß = 1.53, p = 0.04), respectively. Associations of Oxwt (pinteractions < 0.10) with infant length change, umbilical circumference, and CTSF were modified by infant sex. Oxwt was associated with attenuated infant length change among males (ß = -0.60, p = 0.01), but not females (ß = 0.16, p = 0.49); umbilical circumference among females (ß = 0.92, p = 0.009), but not males (ß = -0.00, p = 0.99); and CTSF among males (ß = 0.01, p = 0.03), but not females (ß = 0.00, p = 0.51). CONCLUSION: Prenatal AAP exposure was associated with increased weight gain and anthropometric measures from 1-to-6 months of life among Hispanic infants. Sex-specific associations suggest differential consequences of in utero oxidative stress. These results indicate that prenatal AAP exposure may alter infant growth, which has potential to increase childhood obesity risk.

Carbohydrate composition in breast milk and its effect on infant health.

PURPOSE OF REVIEW: This narrative review presents the current state of available evidence regarding the role of breast milk carbohydrates on infant outcomes, with a primary focus on growth and body composition. RECENT FINDINGS: To date, there is a paucity of available data that exists in this realm. The current literature focuses on the role of two carbohydrate fractions in breast milk, and their relationships with infant outcomes in the first six months of life: oligosaccharides and fructose. A small but growing body of research indicates robust associations of both oligosaccharides and fructose in breast milk with infant weight and length, as well as bone, fat, and lean mass. There is also emerging evidence to support the role of these same carbohydrate fractions in breast milk in infant cognitive development. SUMMARY: The present state of the science suggests that oligosaccharides and fructose in breast milk play a role in infant growth and body composition and introduces intriguing associations of these two carbohydrate fractions with infant cognitive development as well.

Consumption of the Artificial Sweetener Acesulfame Potassium throughout Pregnancy Induces Glucose Intolerance and Adipose Tissue Dysfunction in Mice.

BACKGROUND: Sugar-sweetened beverage consumption is associated with metabolic dysfunction. Artificially sweetened beverages (ASBs) are often promoted as an alternative. However, evidence for the safety of ASB consumption during pregnancy is lacking. OBJECTIVES: The effects of sugar-sweetened beverage and ASB consumption during pregnancy in mice were examined, and we hypothesized that both sugar-sweetened beverages and ASBs would impair maternal metabolic function. METHODS: Pregnant female C57BL/6J mice received control drinking water (CD), high-fructose corn syrup (Fr; 20% kcal intake; 335 mM), or the artificial sweetener acesulfame potassium (AS; 12.5 mM) in their drinking water, from gestational day (GD) 0.5 (n = 8/group). Body weights and food and water intakes were assessed every second day, an oral-glucose-tolerance test (OGTT) was performed at GD 16.5, and mice were culled at GD 18.5. RT-PCR was carried out on adipose tissue, liver, and gut. Adipose tissue morphology was assessed using histological methods. In a separate cohort of animals, pregnancy length was assessed. Repeated-measures ANOVA was performed for the OGTT and weight gain data. All other data were analyzed by 1-way ANOVA. RESULTS: Fr and AS significantly impaired glucose tolerance, as demonstrated by OGTT (21% and 24% increase in AUC, respectively; P = 0.0006). Fr and AS reduced expression of insulin receptor (39.5% and 33% reduction, respectively; P = 0.02) and peroxisome proliferator-activated receptor γ (45.2% and 47%, respectively; P = 0.039), whereas Fr alone reduced expression of protein kinase B (36.9% reduction; P = 0.048) and resulted in an increase in adipocyte size and leptin concentrations (40% increase; P = 0.03). AS, but not Fr, reduced male fetal weight (16.5% reduction; P = 0.04) and female fetal fasting blood glucose concentration at cull (20% reduction; P = 0.02) compared with CD. AS significantly reduced the length of pregnancy compared with the CD and Fr groups (1.25 d shorter; P = 0.02). CONCLUSIONS: Fr and AS consumption were associated with maternal metabolic dysfunction in mice. AS was also associated with reduced fetal growth and fetal hypoglycemia. Therefore, ASBs may not be a beneficial alternative to sugar-sweetened beverages during pregnancy.

Nutritional Supplementation for the Prevention and/or Treatment of Gestational Diabetes Mellitus.

PURPOSE OF REVIEW: Gestational diabetes mellitus (GDM) is a common pregnancy complication that has short- and long-term health implications for both the mother and child. While lifestyle modifications, insulin therapy, and oral agents such as metformin are effective, they can be difficult to adhere to, and there remain concerns over long-term effects of oral agents on the infant. Further, GDM has no proven preventive strategies, which could be more effective than treatment postdiagnosis. Nutritional supplements are an appealing, potentially safer, and better tolerated alternative to pharmaceuticals to treat and/or prevent GDM. Here, we review the existing evidence for nutritional supplementation for treatment and prevention of GDM. RECENT FINDINGS: There is limited evidence that myo-inositol, vitamins D and B6, magnesium, selenium, zinc, fatty acids, and probiotics might be beneficial for the prevention or treatment of GDM. There are very few studies for each nutrient, and the existing studies tend to have few participants. Where multiple studies of a nutrient exist, often those studies were conducted within the same country, limiting the generalizability of the findings, or alternatively there was no consensus across findings. There is limited evidence that nutritional supplementation of myo-inositol, vitamins D and B6, magnesium, selenium, zinc, fatty acids, and probiotics could improve glycemic control or prevent GDM. Our understanding is constrained by the small number of studies, small sample sizes in most studies, and by lack of consistency across findings. Further large, high-quality, randomized controlled trials are required to determine the efficacy of nutritional supplements to treat or prevent GDM.

Effect of sildenafil citrate treatment in the eNOS knockout mouse model of fetal growth restriction on long-term cardiometabolic outcomes in male offspring.

Fetal growth restriction (FGR) is associated with an increased risk of hypertension, insulin resistance, obesity and cardiovascular disease in adulthood. Currently there are no effective treatments to reverse the course of FGR. This study used the eNOS knockout mouse (eNOS-/-), a model of FGR, to determine the ability of sildenafil, a potential new treatment for FGR, to improve cardiovascular and metabolic outcomes in adult offspring following a complicated pregnancy. Pregnant eNOS-/- and C57BL/6J control dams were randomised to sildenafil treatment (0.2 mg/ml in drinking water) or placebo at day 12.5 of gestation until birth. After weaning, male offspring were randomised to either a high fat (HFD; 45% kcal from fat) or normal chow diet (ND), and raised to either postnatal day 90 or 150. Growth and body composition, glucose tolerance, insulin resistance, systolic blood pressure and vascular function were analysed at both time-points. eNOS-/- offspring were significantly smaller than their C57BL/6J controls at weaning and P90 (p < 0.01); at P150 they were a similar weight. Total adipose tissue deposition at P90 was significantly increased only in eNOS-/- mice fed a HFD (p < 0.001). At P150 both C57BL/6J and eNOS-/- offspring fed a HFD demonstrated significant adipose tissue deposition (p < 0.01), regardless of maternal treatment. Both diet and maternal sildenafil treatment had a significant effect on glucose tolerance. Glucose tolerance was significantly impaired in eNOS-/- mice fed a HFD (p < 0.01); this was significant in offspring from both sildenafil and vehicle treated mothers at P90 and P150. Glucose tolerance was also impaired in C57BL/6J mice fed a HFD at both P90 and P150 (p < 0.01), but only in those also exposed to sildenafil. In these C57BL/6J mice, sildenafil was associated with impaired insulin sensitivity at P90 (p = 0.020) but increased insulin resistance at P150 (p = 0.019). Exposure to sildenafil was associated with a significant increase in systolic blood pressure in eNOS-/- mice compared with their C57BL/6J diet controls at P150 (p < 0.05). Exposure to sildenafil had differing effects on vascular function in mesenteric arteries; it increased vasodilation in response to ACh in C57BL/6J mice, but was associated with a more constrictive phenotype in eNOS-/- mice. eNOS-/- mice demonstrate a number of impaired outcomes consistent with programmed cardiometabolic disease, particularly when faced with the 'second hit' of a HFD. Exposure to sildenafil treatment during pregnancy did not increase fetal growth or significantly improve adult metabolic or cardiac outcomes. Maternal sildenafil treatment was, however, associated with small impairments in glucose handling and an increase in blood pressure. This study highlights the importance of understanding the long-term effects of treatment during pregnancy in offspring from both complicated and healthy control pregnancies.

The Pathophysiology of Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is a serious pregnancy complication, in which women without previously diagnosed diabetes develop chronic hyperglycemia during gestation. In most cases, this hyperglycemia is the result of impaired glucose tolerance due to pancreatic ß-cell dysfunction on a background of chronic insulin resistance. Risk factors for GDM include overweight and obesity, advanced maternal age, and a family history or any form of diabetes. Consequences of GDM include increased risk of maternal cardiovascular disease and type 2 diabetes and macrosomia and birth complications in the infant. There is also a longer-term risk of obesity, type 2 diabetes, and cardiovascular disease in the child. GDM affects approximately 16.5% of pregnancies worldwide, and this number is set to increase with the escalating obesity epidemic. While several management strategies exist-including insulin and lifestyle interventions-there is not yet a cure or an efficacious prevention strategy. One reason for this is that the molecular mechanisms underlying GDM are poorly defined. This review discusses what is known about the pathophysiology of GDM, and where there are gaps in the literature that warrant further exploration.

Adverse Effects of Infant Formula Made with Corn-Syrup Solids on the Development of Eating Behaviors in Hispanic Children.

Few studies have investigated the influence of infant formulas made with added corn-syrup solids on the development of child eating behaviors. We examined associations of breastmilk (BM), traditional formula (TF), and formula containing corn-syrup solids (CSSF) with changes in eating behaviors over a period of 2 years. Feeding type was assessed at 6 months in 115 mother−infant pairs. Eating behaviors were assessed at 12, 18 and 24 months. Repeated Measures ANCOVA was used to determine changes in eating behaviors over time as a function of feeding type. Food fussiness and enjoyment of food differed between the feeding groups (p < 0.05) and changed over time for CSSF and TF (p < 0.01). Food fussiness increased from 12 to 18 and 12 to 24 months for CSSF and from 12 to 24 months for TF (p < 0.01), while it remained stable for BM. Enjoyment of food decreased from 12 to 24 months for CSSF (p < 0.01), while it remained stable for TF and BM. There was an interaction between feeding type and time for food fussiness and enjoyment of food (p < 0.01). Our findings suggest that Hispanic infants consuming CSSF may develop greater food fussiness and reduced enjoyment of food in the first 2 years of life compared to BM-fed infants.

Interleukin-1 Receptor-1 Deficiency Impairs Metabolic Function in Pregnant and Non-Pregnant Female Mice.

SCOPE: Glucose intolerance during pregnancy is associated with short- and long-term maternal and offspring health consequences. In young male mice, knockout of the major pro-inflammatory mediator interleukin-1-receptor-1 (IL1R1) protects against high-fat diet (HFD)-induced glucose intolerance and metabolic dysfunction. This phenotype has not been examined during pregnancy. The hypothesis that IL1R1 depletion will protect females against HFD-induced glucose intolerance and metabolic dysfunction before, during, and post pregnancy is tested. METHODS AND RESULTS: C57BL/6J control and IL1R1 knockout (IL1R1-/- ) mice are randomized to either a control diet (10% kcal from fat) or HFD (45% kcal from fat), and three distinct cohorts are established: nulliparous, pregnant, and postpartum females. Contrary to the authors' hypothesis, it is found that IL1R1-/- does not protect against glucose intolerance in nulliparous or pregnant females, and while control HFD animals see a resolution of glucose tolerance postpartum, IL-1R1-/- mice remain impaired. These effects are accompanied by adipocyte hypertrophy, hyperleptinemia, and increased adipose tissue inflammatory gene expression. Maternal genotype differentially affects fetal growth in male and female fetuses, demonstrating sexual dimorphism in this genotype prior to birth. CONCLUSIONS: These findings suggest that IL1R1 signaling is important for normal metabolic functioning in females, during and outside of pregnancy.

Risk of Micronutrient Inadequacy among Hispanic, Lactating Mothers: Preliminary Evidence from the Southern California Mother's Milk Study.

Micronutrients are dietary components important for health and physiological function, and inadequate intake of these nutrients can contribute to poor health outcomes. The risk of inadequate micronutrient intake has been shown to be greater among low-income Hispanics and postpartum and lactating women. Therefore, we aimed to determine the risk of nutrient inadequacies based on preliminary evidence among postpartum, Hispanic women. Risk of micronutrient inadequacy for Hispanic women (29-45 years of age) from the Southern California Mother's Milk Study (n = 188) was assessed using 24 h dietary recalls at 1 and 6 months postpartum and the estimated average requirement (EAR) fixed cut-point approach. Women were considered at risk of inadequate intake for a nutrient if more than 50% of women were consuming below the EAR. The Chronic Disease Risk Reduction (CDRR) value was also used to assess sodium intake. These women were at risk of inadequate intake for folate and vitamins A, D, and E, with 87.0%, 93.4%, 43.8%, and 95% of women consuming less than the EAR for these nutrients, respectively. Lastly, 71.7% of women consumed excess sodium. Results from this preliminary analysis indicate that Hispanic women are at risk of inadequate intake of important micronutrients for maternal and child health.

Specific amino acids but not total protein attenuate postpartum weight gain among Hispanic women from Southern California.

There is a high prevalence of obesity and type 2 diabetes in the United States, particularly among Hispanic women, which may be partly explained by failure to lose gestational weight during the postpartum period. Previous work indicates that protein and amino acids may protect against weight gain; therefore, this study examined the impact of dietary protein and amino acid intake on changes in postpartum weight and the percent of women meeting the Estimated Average Requirement (EAR) for these dietary variables among Hispanic women from the Southern California Mother's Milk Study (n = 99). Multivariable linear regression analysis was used to examine the associations between protein and amino acid intake with change in weight after adjusting for maternal age, height, and energy intake. Women's weight increased from prepregnancy to 1-month and 6-months postpartum (71.1 ± 14.6 vs. 73.1 ± 13.1 vs. 74.5 ± 14.6 kg, p < .0001). Although dietary protein was not associated with weight change (ß = -1.09; p = .13), phenylalanine (ß = -1.46; p = .04), tryptophan (ß = -1.71; p = .009), valine (ß = -1.34; p = .04), isoleucine (ß = -1.26; p = .045), and cysteine (ß = -1.52; p = .02) intake were inversely associated with weight change. Additionally, fewer women met the EAR values for cysteine (11.1%), phenylalanine (60.6%), and methionine (69.7%), whereas most women met the EAR values for tryptophan (92.9%), valine (96.0%), and isoleucine (94.9%). Study results indicate that several essential and conditionally essential amino acids were associated with postpartum weight loss, with a significant portion of women not meeting recommended intake levels for some of these amino acids. These results highlight the importance of postpartum maternal diet as a potential modifiable risk factor.

Early life gut microbiota is associated with rapid infant growth in Hispanics from Southern California.

We aimed to determine if the newborn gut microbiota is an underlying determinant of early life growth trajectories. 132 Hispanic infants were recruited at 1-month postpartum. The infant gut microbiome was characterized using 16S rRNA amplicon sequencing. Rapid infant growth was defined as a weight-for-age z-score (WAZ) change greater than 0.67 between birth and 12-months of age. Measures of infant growth included change in WAZ, weight-for-length z-score (WLZ), and body mass index (BMI) z-scores from birth to 12-months and infant anthropometrics at 12-months (weight, skinfold thickness). Of the 132 infants, 40% had rapid growth in the first year of life. Multiple metrics of alpha-diversity predicted rapid infant growth, including a higher Shannon diversity (OR = 1.83; 95% CI: 1.07-3.29; p = .03), Faith's phylogenic diversity (OR = 1.41, 95% CI: 1.05-1.94; p = .03), and richness (OR = 1.04, 95% CI: 1.01-1.08; p = .02). Many of these alpha-diversity metrics were also positively associated with increases in WAZ, WLZ, and BMI z-scores from birth to 12-months (pall<0.05). Importantly, we identified subsets of microbial consortia whose abundance were correlated with these same measures of infant growth. We also found that rapid growers were enriched in multiple taxa belonging to genera such as Acinetobacter, Collinsella, Enterococcus, Neisseria, and Parabacteroides. Moreover, measures of the newborn gut microbiota explained up to an additional 5% of the variance in rapid growth beyond known clinical predictors (R2 = 0.37 vs. 0.32, p < .01). These findings indicate that a more mature gut microbiota, characterized by increased alpha-diversity, at as early as 1-month of age, may influence infant growth trajectories in the first year of life.

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.

Timing of food consumption in Hispanic adolescents with obesity.

BACKGROUND: Little is known about the normal eating time periods in adolescents with obesity and how these patterns change throughout development. As the obesity epidemic continues to rise in adolescence, it becomes imperative to understand developmentally appropriate eating behaviours and to create weight management strategies that build on those innate patterns and preferences. The purpose of this study was to determine the most common habitual eating windows observed in adolescents with obesity. METHODS: Participants were 101 Hispanic adolescents (mean age 14.8 ± 2.1 years; 48 male/53 female) with obesity (BMI ≥95th percentile) who were recruited as part of a larger clinical trial. Dietary intake and meal timing was determined using multiple pass 24-hours recalls. Histograms were utilized to determine the natural distribution of percent consumption of total kilocalories, carbohydrates and added sugar per hour. RESULTS: The majority of total kilocalories (65.4%), carbohydrates (65.3%) and added sugar (59.1%) occurred between 11:00 and 19:00. Adolescents were 2.5 to 2.9 times more likely to consume kilocalories, carbohydrates, and added sugar during the 8-hour window between 11:00 am and 19:00 pm than other time windows examined (all P < .001). The consumption of these calories did not differ between weekdays and weekend (P > .05) or by sex. CONCLUSIONS: In this cohort, more than 60% of calories, carbohydrates and added sugar were consumed between 11:00 am and 19:00 pm, which is concordant with an afternoon/evening chronotype that is common in adolescents. Our findings support this 8-hour period as a practical window for weight loss interventions that target pre-specified eating periods in this population.

PNPLA3 Genotype, Arachidonic Acid Intake, and Unsaturated Fat Intake Influences Liver Fibrosis in Hispanic Youth with Obesity.

Non-alcoholic fatty liver disease impacts 15.2% of Hispanic adolescents and can progress to a build-up of scared tissue called liver fibrosis. If diagnosed early, liver fibrosis may be reversible, so it is necessary to understand risk factors. The aims of this study in 59 Hispanic adolescents with obesity were to: (1) identify potential biological predictors of liver fibrosis and dietary components that influence liver fibrosis, and (2) determine if the association between dietary components and liver fibrosis differs by PNPLA3 genotype, which is highly prevalent in Hispanic adolescents and associated with elevated liver fat. We examined liver fat and fibrosis, genotyped for PNPLA3 gene, and assessed diet via 24-h diet recalls. The prevalence of increased fibrosis was 20.9% greater in males, whereas participants with the GG genotype showed 23.7% greater prevalence. Arachidonic acid was associated with liver fibrosis after accounting for sex, genotype, and liver fat (ß = 0.072, p = 0.033). Intakes of several dietary types of unsaturated fat have different associations with liver fibrosis by PNPLA3 genotype after accounting for sex, caloric intake, and liver fat. These included monounsaturated fat (ßCC/CG = -0.0007, ßGG = 0.03, p-value = 0.004), polyunsaturated fat (ßCC/CG = -0.01, ßGG = 0.02, p-value = 0.01), and omega-6 (ßCC/CG = -0.0102, ßGG = 0.028, p-value = 0.01). Results from this study suggest that reduction of arachidonic acid and polyunsaturated fatty acid intake might be important for the prevention of non-alcoholic fatty liver disease progression, especially among those with PNPLA3 risk alleles.

Added sugar and sugar-sweetened beverages are associated with increased postpartum weight gain and soluble fiber intake is associated with postpartum weight loss in Hispanic women from Southern California.

BACKGROUND: Obesity prevalence remains high in the United States, and there is an increased risk among women who do not lose their gestational weight gain during the postpartum period. Indicators of dietary carbohydrate quality including added sugar consumption, glycemic load, and glycemic index have been linked with weight gain, whereas fiber may protect against obesity. However, these dietary factors have not been examined during the postpartum period. OBJECTIVES: The aim of this study was to determine whether dietary sugars and fiber intake were associated with changes in postpartum weight. METHODS: We examined Hispanic women from the longitudinal Southern California Mother's Milk Study (n = 99) at 1 and 6 mo postpartum. Maternal assessments included height, weight, and dietary intake based on 24-h diet recalls. We used multivariable linear regression to examine the relation between maternal diet and change in postpartum weight after adjusting for maternal age, height, and energy intake. RESULTS: Higher intake of added sugar was associated with postpartum weight gain (ß: 0.05; 95% CI: 0.004, 0.10; P = 0.05). In addition, a half 8-ounce (8 fluid ounces = 236.6 mL) serving per day increase in soft drinks was associated with a 1.52-kg increase in weight (95% CI: 0.70, 2.34 kg; P < 0.001). A high glycemic index (ß: 0.25; 95% CI: 0.07, 0.42; P = 0.006) and glycemic load (ß: 0.04; 95% CI: 0.002, 0.08; P = 0.04) were associated with postpartum weight gain. Higher soluble fiber was associated with a decrease in postpartum weight (ß: -0.82 kg; 95% CI: -1.35, -0.29 kg; P = 0.003) and the negative effects of added sugar, sugary beverages, and high-glycemic-index and -load diets were partially attenuated after adjusting for soluble fiber intake. CONCLUSIONS: Increased consumption of added sugar, sugar-sweetened beverages, and high-glycemic diets were associated with greater weight gain in the first 6 mo postpartum. In addition, increased consumption of soluble fiber was associated with postpartum weight loss, which may partially offset the obesogenic effects of some dietary sugars.

Human Milk Oligosaccharides and Hispanic Infant Weight Gain in the First 6 Months.

OBJECTIVE: The aim of this study was to determine whether human milk oligosaccharides (HMOs) at 1 month predicted infant weight gain at 6 months and whether associations varied by HMO secretor status. METHODS: Participants were 157 Hispanic mother-infant pairs. Human milk samples were collected at 1 month. Nineteen individual HMOs were analyzed using high-performance liquid chromatography, and secretor status was determined by the presence of 2'-fucosyllactose or lacto-N-fucopentaose (LNFP) I. Infant weight was measured at 1 and 6 months. Path analysis was used to test effects of HMO composition on infant weight gain, adjusting for maternal age, prepregnancy BMI, and infant age, sex, and birth weight. RESULTS: In the total sample, higher LNFPII predicted lower infant weight gain (g1 = -4.1, P = 0.004); this was observed in both nonsecretor (g1 = -3.0, P = 0.006) and secretor groups (g1 = -4.7, P = 0.014). In the nonsecretor group, higher lacto-N-neotetraose (g1 = 7.6, P = 0.011) and disialyllacto-N-tetraose (g1 = 14.3, P = 0.002) predicted higher infant weight gain. There were no other associations in the secretor group. CONCLUSIONS: Our data suggest that higher LNFPII in human milk may decrease obesity risk across all infants, whereas higher lacto-N-neotetraose and disialyllacto-N-tetraose may increase obesity risk in infants of nonsecretors only.