Exploring the relationship between child temperament, maternal psychiatric symptoms, family environment and infant feeding.

OBJECTIVES: Infant temperament is assumed to be primarily innate. However, newer research suggests that maternal affection impacts ratings of temperament and environmental factors, including feeding method, can also influence infant temperament. This study investigates child temperament and its relationships with maternal psychiatric symptoms, environmental variables and feeding method longitudinally in a cohort of children followed from 6 to 72 months. Differences in temperament by feeding group are also investigated. We hypothesized that maternal psychiatric symptoms, environmental stressors, and impaired family dynamics would have negative impact on child temperament, whereas breastfeeding would have a positive impact on child temperament. METHOD: Mothers' ratings of child's temperament, own psychiatric symptomatology, environmental stresses and family cohesion were obtained in 504 mother-infant dyads via rating scales completed by mothers. Infants were breastfeed (BF), fed soy-based infant formula (SF) or dairy-based infant formula (MF). Linear mixed effect models investigated the relationship of variables on child's temperament while controlling for significant covariates and repeated measurements. RESULTS: Mothers in this study did not endorse clinical-level psychiatric symptomatology; however, when adjusted for significant covariates, higher psychiatric symptomatology significantly correlated with environmental stressors, impaired family dynamics and elevations in temperament ratings of infants' adaptability and mood. There were no lasting differences for temperament between feeding groups. However, some significant transient increases in rhythmicity and adaptability were found between SF and BF children. CONCLUSION: Positive relationships between family environment stressors and maternal psychiatric ratings were found. Transient differences were found in child temperament based upon feeding method.

Associations Between Maternal Physical Activity, Maternal Lipid Levels, and Infant Anthropometric Outcomes at Two Weeks of Age.

BACKGROUND: This study determined the relationship between physical activity (PA), circulating lipids throughout pregnancy and infant anthropometric outcomes at birth and 2 weeks of age. METHODS: Women (N = 234) with normal weight (NW, BMI 18.5-24.9 kg/m2) and with overweight and class I obesity (OW/OB, BMI 25-35 kg/m2) were categorized into high and low PA based on average cohort steps during pregnancy (8099 steps/day). Circulating fasting lipids were measured at each trimester. Standardized methods were used to obtain anthropometrics measures. Infant body composition was estimated by quantitative nuclear magnetic resonance (EchoMRI-AH small; ECHO Medical Systems). RESULTS: Women with NW who had higher activity had lower circulating triglycerides (TG) and total cholesterol (TC) levels at 12 weeks compared to women with NW and low activity (p < 0.05). Women with OW/OB and high activity level throughout pregnancy had lower circulating TG, and low density lipoprotein (LDL), at 12 weeks, lower LDL at 24 weeks, and lower TG at 36 weeks compared to the women with OW/OB who had low activity levels (p < 0.05). For children born to women with OW/OB, maternal circulating TG and LDL were most associated with infant anthropometrics at 2 weeks of age. CONCLUSION: This study supports that higher PA during pregnancy is associated with lower lipid levels throughout pregnancy with a greater effect size in women with OW/OB. Maternal lipids were associated with anthropometrics and infant body composition at two weeks of life in women with OW/OB.

Early infant feeding effect on growth and body composition during the first 6 years and neurodevelopment at age 72 months.

BACKGROUND: This study longitudinally characterized the developmental status, growth, and body composition of children who were fed human milk (breastfed, BF), cow's milk-based (MF), or soy protein-based (SF) infant formula from 3 to 12 months. METHODS: Standardized anthropometrics and dual-energy X-ray absorptiometry were used to characterize growth and body composition at 3, 6, 9, 12, 24, 36, 48, 60, and 72 months (NCT00616395). Preschool Language Scale-3, Children's Memory Scale Index (CMS), and Wechsler Preschool and Primary Scale of Intelligence were administered at age 72 months. Mixed-effects models adjusting for gestational age, birth weight, child race and sex, parental education, and maternal IQ were performed. RESULTS: Body Mass index (BMI) was significantly lower between 24 and 72 months in BF children compared to SF children. At 3 and 6 months, BF infants had significantly higher fat mass (FM) than SF infants, whereas BF children had significantly lower FM at 36 and 48 months than SF children. Delayed Recognition Index of the CMS was higher for SF than for MF participants (p = 0.009). There was no other significant difference in developmental outcomes between groups. CONCLUSIONS: In conclusion, BF, MF, and SF support adequate growth and development up to age 6 years. IMPACT: Although soy protein-based infant formula is reported to support normal infant growth and development compared to cow's milk-based formula and human milk, there are limited data on the effect of these feeding methods in school-aged children. This study suggests a significant difference in body composition, specifically BMI, after 24 months between infant feeding methods during the first year of life and in early childhood; however, all diets provide adequate nutrients to maintain normal development up to 72 months.

Could Biomarkers Direct Therapy for the Septic Patient?

Sepsis is a serious medical condition caused by a severe systemic inflammatory response to a bacterial, fungal, or viral infection that most commonly affects neonates and the elderly. Advances in understanding the pathophysiology of sepsis have resulted in guidelines for care that have helped reduce the risk of dying from sepsis for both children and older adults. Still, over the past three decades, a large number of clinical trials have been undertaken to evaluate pharmacological agents for sepsis. Unfortunately, all of these trials have failed, with the use of some agents even shown to be harmful. One key issue in these trials was the heterogeneity of the patient population that participated. What has emerged is the need to target therapeutic interventions to the specific patient's underlying pathophysiological processes, rather than looking for a universal therapy that would be effective in a "typical" septic patient, who does not exist. This review supports the concept that identification of the right biomarkers that can direct therapy and provide timely feedback on its effectiveness will enable critical care physicians to decrease mortality of patients with sepsis and improve the quality of life of survivors.

Pharmacologic targeting of sphingosine-1-phosphate receptor 1 improves the renal microcirculation during sepsis in the mouse.

Microvascular failure is hallmark of sepsis in humans and is recognized as a strong predictor of mortality. In the mouse subjected to cecal ligation and puncture (CLP) to induce a clinically relevant sepsis, renal microvascular permeability increases and peritubular capillary perfusion declines rapidly in the kidney leading to acute kidney injury (AKI). Sphingosine-1-phosphate (S1P) is a key regulator of microvascular endothelial function. To investigate the role of S1P in the development of microvascular permeability and peritubular capillary hypoperfusion in the kidney during CLP-induced AKI, we used a pharmacologic approach and a clinically relevant delayed dosing paradigm. Evans blue dye was used to measure renal microvascular permeability and intravital video microscopy was used to quantitate renal cortical capillary perfusion. The S1P receptor 1 (S1P1) agonist SEW2871 [5-[4-phenyl-5-(trifluoromethyl)-2-thienyl]-3-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazole] and S1P2 antagonist JTE-013 [N-(2,6-dichloro-4-pyridinyl)-2-[1,3-dimethyl-4-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridin-6-yl]-hydrazinecarboxamide] were administered at the time of CLP and produced a dose-dependent but partial reduction in renal microvascular permeability at 6 hours after CLP. However, neither agent improved capillary perfusion at 6 hours. With delayed administration at 6 hours after CLP, only SEW2871 reversed microvascular permeability when measured at 18 hours. Importantly, SEW2871 also restored capillary perfusion and improved renal function. These data suggest that S1P1 and S1P2 do not regulate the early decline in renal capillary perfusion. However, later in the course of sepsis, pharmacologic stimulation of S1P1, even when delaying therapy until after injury has occurred, improves capillary and renal function, suggesting this approach should be evaluated as an adjunct therapy during sepsis.

Loss of functional NADPH oxidase 2 protects against alcohol-induced bone resorption in female p47phox-/- mice.

BACKGROUND: In bone, NADPH oxidase (NOX)-derived reactive oxygen species (ROS) superoxide and/or hydrogen peroxide are an important stimulus for osteoclast differentiation and activity. Previously, we have demonstrated that chronic ethanol (EtOH) consumption generates excess NOX-dependent ROS in osteoblasts, which functions to stimulate nuclear factor kappa-ß receptor ligand (RANKL)-RANK signaling, thus increasing osteoclastogenesis and activity. This activity can be blocked by co-administration of EtOH with the pan-NOX inhibitor diphenylene idonium (DPI). METHODS: To test whether EtOH-induced bone loss is dependent on a functional NOX2 enzyme, 6-week-old female C57BL/6J-Ncf1/p47phox(-/-) (p47phox KO) and wild-type (WT) mice were pair-fed EtOH diets for 40 days. Bone loss was assessed by 3-point bending, micro-computed tomography and static histomorphometric analysis. Additionally, ST2 cultured cells were co-treated with EtOH and NOX inhibitors, DPI, gliotoxin, and plumbagin, after which changes in ROS production, and in RANKL and NOX mRNA expression were analyzed. RESULTS: In WT mice, EtOH treatment significantly reduced bone density and mechanical strength, and increased total osteoclast number and activity. In EtOH-treated p47phox KO mice, bone density and mechanical strength were completely preserved. EtOH p47phox KO mice had no changes in osteoclast numbers or activity, and no elevations in serum CTX or RANKL gene expression (p < 0.05). In both WT and p47phox KO mice, EtOH feeding reduced biochemical markers of bone formation (p < 0.05). In vitro EtOH exposure of ST2 cells increased ROS, which was blocked by pretreating with DPI or the NOX2 inhibitor gliotoxin. EtOH-induced RANKL and NOX2 gene expression were inhibited by the NOX4-specific inhibitor plumbagin. CONCLUSIONS: These data suggest that NOX2-derived ROS is necessary for EtOH-induced bone resorption. In osteoblasts, NOX2 and NOX4 appear to work in tandem to increase RANKL expression, whereas EtOH-mediated inhibition of bone formation occurs via a NOX2-independent mechanism.

Healthful Eating Behaviors among Couples Contribute to Lower Gestational Weight Gain.

Through longitudinal analysis from the GLOWING cohort study, we examined the independent and joint relationships between couples' eating behaviors and gestational weight gain (GWG). Pregnant persons (n = 218) and their non-pregnant partners (n = 157) completed an Eating Inventory. GWG was calculated as gestation weight at 36 weeks minus that at 10 weeks. General linear models were used to examine the relationships between GWG and the pregnant persons, non-pregnant partners, and couples (n = 137; mean of pregnant persons and non-pregnant partners) cognitive restraint (range 0-21), dietary disinhibition (range 0-18), and perceived hunger (range 0-14), with higher scores reflecting poorer eating behaviors. The adjusted models included race/ethnicity, education, income, marital status, and age. The pregnant persons and their non-pregnant partners' cognitive restraint, dietary disinhibition, and perceived hunger scores were 9.8 ± 4.7, 4.8 ± 3.2, and 4.4 ± 2.5 and 6.6 ± 4.6, 5.4 ± 3.4, and 4.7 ± 3.2, respectively. Higher cognitive restraint scores among the pregnant persons and couples were positively associated with GWG (p ≤ 0.04 for both). Stratified analyses revealed this was significant for the pregnant persons with overweight (p ≤ 0.04). The non-pregnant partners' eating behaviors alone were not significantly associated with GWG (p ≥ 0.31 for all). The other explored relationships between GWG and the couples' eating behaviors were insignificant (p ≥ 0.12 for all). Among the pregnant persons and couples, reduced GWG may be achieved with higher levels of restrained eating. Involving non-pregnant partners in programs to optimize GWG may be beneficial.

Maternal immune cell gene expression associates with maternal gut microbiome, milk composition and infant gut microbiome.

BACKGROUND: Pre-pregnancy overweight and obesity promote deleterious health impacts on both mothers during pregnancy and the offspring. Significant changes in the maternal peripheral blood mononuclear cells (PBMCs) gene expression due to obesity are well-known. However, the impact of pre-pregnancy overweight on immune cell gene expression during pregnancy and its association with maternal and infant outcomes is not well explored. METHODS: Blood samples were collected from healthy normal weight (NW, pre-pregnancy BMI 18.5-24.9) or overweight (OW, pre-pregnancy BMI 25-29.9) 2nd parity pregnant women at 12, 24 and 36 weeks of pregnancy. PBMCs were isolated from the blood and subjected to mRNA sequencing. Maternal and infant microbiota were analyzed by 16S rRNA gene sequencing. Integrative multi-omics data analysis was performed to evaluate the association of gene expression with maternal diet, gut microbiota, milk composition, and infant gut microbiota. RESULTS: Gene expression analysis revealed that 453 genes were differentially expressed in the OW women compared to NW women at 12 weeks of pregnancy, out of which 354 were upregulated and 99 were downregulated. Several up-regulated genes in the OW group were enriched in inflammatory, chemokine-mediated signaling and regulation of interleukin-8 production-related pathways. At 36 weeks of pregnancy healthy eating index score was positively associated with several genes that include, DTD1, ELOC, GALNT8, ITGA6-AS1, KRT17P2, NPW, POT1-AS1 and RPL26. In addition, at 36 weeks of pregnancy, genes involved in adipocyte functions, such as NG2 and SMTNL1, were negatively correlated to human milk 2'FL and total fucosylated oligosaccharides content collected at 1 month postnatally. Furthermore, infant Akkermansia was positively associated with maternal PBMC anti-inflammatory genes that include CPS1 and RAB7B, at 12 and 36 weeks of pregnancy. CONCLUSIONS: These findings suggest that prepregnancy overweight impacts the immune cell gene expression profile, particularly at 12 weeks of pregnancy. Furthermore, deciphering the complex association of PBMC's gene expression levels with maternal gut microbiome and milk composition and infant gut microbiome may aid in developing strategies to mitigate obesity-mediated effects.

Dietary modulation of human milk bioactives is associated with maternal FUT2 secretor phenotype: an exploratory analysis of carotenoids and polyphenol metabolites.

Introduction: Maternal diet modifies profiles of human milk oligosaccharides (HMOs), carotenoids, and polyphenols in human milk (HM). However, substantial variability in profiles exists between women, highlighting the complexity of non-dietary factors modulating these profiles. The objective of this study was to carry out a secondary analysis exploring the effect of maternal diet on HM carotenoids and polyphenols and relationships between dietary modulation of HM bioactives (carotenoids, polyphenols, and oligosaccharides) and maternal α1,2-fucosyltransferase 2 (FUT2) secretor phenotype. Methods: In this pilot study, 16 exclusively breastfeeding women with obesity were enrolled between 4 and 5 months postpartum. The women were provided a 4-week meal plan consistent with the 2020 Dietary Guidelines for Americans (DGA). HM was collected for 24 h at baseline and post-intervention. Maternal FUT2 secretor phenotype was determined by 2'-fucosyllactose concentration in HM (non-secretor: < 100 nmol/ml; secretor: ≥100 nmol/ml). Concentrations of carotenoids and HMOs were determined by LC and polyphenol metabolites by UPLC-MS/MS. Results: Thirteen women completed the study (6 secretors, 7 non-secretors). The change in HM concentrations of the HMOs lacto-N-tetraose (LNT, p = 0.007), lacto-N-fucopentaose II (LNFP II, p = 0.02), difucosyllacto-N-tetraose (DFLNT, p = 0.003), and disialyllacto-N-tetraose (DSLNT, p = 0.003) and polyphenol metabolites 4-hydroxybenzoic acid (4-HBA, p = 0.08) and ferulic acid (p = 0.02) over the intervention time frame was differentially associated with maternal secretor status. 4-HBA and ferulic acid positively correlated with HMOs LNT and DSLNT (rrm = 0.82-0.90, p = 0.03-0.06) for secretors but not for non-secretors. Only secretors demonstrated a negative correlation between 4-HBA and DFLNT (rrm = -0.94, p = 0.001). Discussion: The influence of maternal diet on composition of HMOs and polyphenol metabolites in HM differs based on maternal secretor status. Consideration of non-dietary factors is needed to evaluate differences in response of HM bioactives to dietary modulation.

Excessive Gestational Weight Gain, independent of BMI, is associated with Child Fat Mass Index at age 2 years in the Glowing Study.

BACKGROUND: Excessive gestational weight gain (eGWG) increases risk for pregnancy complications and future obesity for pregnant persons and children. Yet, it is unclear whether eGWG leads to higher child adiposity at 2 years, independent of pregnant person's body mass index while considering important covariates. Moreover, understanding the characteristics of pregnant persons experiencing eGWG will help design future targeted interventions. OBJECTIVE: The objectives of the analyses were to assess the association between eGWG and childhood adiposity at 2-years-old, while controlling for pregnant persons' body mass index (BMI) and other important covariates and to describe the characteristics of pregnant persons who experience eGWG during their second pregnancy. DESIGN: This is a secondary analysis of 221 pregnant persons and their 2-year-old children who were enrolled in the Glowing longitudinal observational study. PARTICIPANTS/SETTING: Participants were recruited between 2011- 2014 in central Arkansas. Participants were secundigravida persons with BMIs 18.5-35kg/m2, >20 years old, and who conceived without assistance. MAIN OUTCOME MEASURES: The main outcome measure was 2-year-old fat mass index measured by quantitative nuclear magnetic resonance. Secondary outcomes included: first pregnancy gestational weight gain (GWG), dietary and physical activity characteristics in between pregnancies, second pregnancy nausea levels, and motivation level to adhere to the GWG guidelines. STATISTICAL ANALYSIS PERFORMED: Multivariable regression analyses were used to examine the associations between GWG and childhood fat mass index at 2 years of age. Pearson correlations and Wilcoxon rank sum tests were used to identify the characteristics of pregnant persons who experienced eGWG. RESULTS: Pregnant persons' eGWG (ß = 0.503, P =0.03) was positively associated with child adiposity at age 2 years independent of maternal BMI (P = 0.3). Pregnant persons who experienced eGWG during their second pregnancy had greater odds of: eGWG in first pregnancies (OR = 7.5; P <0.001), dieting behavior (OR = 14.3; P =0.02), and low motivation to adhere to the GWG guidelines (OR = 11.2; P =0.009). Fewer participants had eGWG in their second pregnancy (52.5 %) compared to their first pregnancy (66.8%) which was different by BMI groups (BMI 18.5-24.9 kg/m2: 23.6% decrease in participants who gained eGWG, BMI 25-29.9 kg/m2: 20.0% decrease, and BMI ≥ 30 kg/m2: 37.9% decrease). CONCLUSIONS: EGWG among pregnant persons is associated with child adiposity at age 2-years. Pregnant persons who experienced eGWG during their second pregnancy reported low motivation to gain weight within guidelines, eGWG in first pregnancy, and reported prior dieting behavior. Future research focusing on patients with these characteristics may increase success of interventions designed to limit eGWG.

Childhood cardiometabolic risk factors associated with the perinatal environment of the maternal-paternal-child triad.

INTRODUCTION: Clustering of cardiometabolic risk factors in childhood significantly increases the risk of atherosclerotic cardiovascular disease later in life. Identification of modifiable parental factors that contribute to offspring cardiometabolic health is critical for the prevention of disease. The objective was to identify factors associated with child cardiometabolic risk factors at age 5 years. METHODS: Triads from a longitudinal cohort were recalled at 5 years (n = 68). Dietary intake, anthropometrics, physical activity and serum-based risk factors were collected. Best subset selection, linear and logistic regressions were used to identify triad variables associated with increased risk of cardiometabolic risk factor clustering at age 5 years. RESULTS: In this cohort, best subset modelling revealed that increased paternal fat mass, serum low-density lipoproteins and triglycerides, maternal dietary added sugar and being female were associated with increased odds of offspring having two or more cardiometabolic risk factors at age 5 years. CONCLUSIONS: Dietary and exercise interventions prior to conception targeting paternal adiposity and dyslipidaemia as well as maternal dietary habits could decrease children's cardiometabolic risk in later life.

A Mediterranean diet plan in lactating women with obesity reduces maternal energy intake and modulates human milk composition - a feasibility study.

Introduction: Maternal obesity is associated with increased concentrations of human milk (HM) obesogenic hormones, pro-inflammatory cytokines, and oligosaccharides (HMOs) that have been associated with infant growth and adiposity. The objective of this pilot study was to determine if adherence to a Mediterranean meal plan during lactation modulates macronutrients and bioactive molecules in human milk from mothers with obesity. Methods: Sixteen healthy, exclusively breastfeeding women with obesity (body mass index ≥30 kg/m2) enrolled between 4 and 5 months postpartum. The women followed a 4-week Mediterranean meal plan which was provided at no cost. Maternal and infant anthropometrics, HM composition, and infant intakes were measured at enrollment and at weeks 2 and 4 of the intervention. Thirteen mother-infant dyads completed the study. Additionally, participants from an adjacent, observational cohort who had obesity and who collected milk at 5 and 6 months postpartum were compared to this cohort. Results: Participants' healthy eating index scores improved (+27 units, p < 0.001), fat mass index decreased (-4.7%, p < 0.001), and daily energy and fat intake were lower (-423.5 kcal/day, p < 0.001 and-32.7 g/day, p < 0.001, respectively) following the intervention. While HM macronutrient concentrations did not change, HM leptin, total human milk oligosaccharides (HMOs), HMO-bound fucose, Lacto-N-fucopentaose (LNFP)-II, LNFP-III, and difucosyllacto-N-tetrose (DFLNT) concentrations were lower following the intervention. Infant intakes of leptin, tumor necrosis factor (TNF)-α, total HMOs, HMO-bound fucose, LNFP-III and DFLNT were lower following the intervention. Specific components of the maternal diet (protein and fat) and specific measures of maternal diet quality (protein, dairy, greens and beans, fruit and vegetables) were associated with infant intakes and growth. Discussion: Adherence to a Mediterranean meal plan increases dietary quality while reducing total fat and caloric intake. In effect, body composition in women with obesity improved, HM composition and infants' intakes were modulated. These findings provide, for the first time, evidence-based data that enhancing maternal dietary quality during lactation may promote both maternal and child health. Longer intervention studies examining the impact of maternal diet quality on HM composition, infant growth, and infant development are warranted.

The Impact of Excessive Weight on Breastfeeding Intention, Initiation, and Duration.

Background: Breastfeeding is widely recognized as the optimal feeding method for infants. However, breastfeeding goals are often unmet, especially in mothers with excessive weight. Potential factors associated with unmet goals could be disparities in care for women with higher body mass index (BMI) or mental health symptomology. Methods: Women enrolled in a longitudinal study were stratified by BMI into three groups: mothers with normal weight (18.5-24.9 kg/m2, n = 101), with overweight (25-29.9 kg/m2, n = 78), and with obesity (OB; 30-35 kg/m2, n = 48). Breastfeeding intention and standardized mental health questionnaires were administered at gestational weeks 12 and 36. The prevalence of initiation and duration of breastfeeding were determined based on self-reported breastfeeding start and end dates. Wilcoxon tests, pairwise proportion test, Cox proportional hazards regression, and linear regression were used. Results: Higher maternal weight status (OB) was significantly associated with lower breastfeeding intention and duration. As expected, higher breastfeeding intention scores were associated with significantly longer breastfeeding duration. Higher scores on the Beck Depression Inventory (BDI), associated with a greater number of depression symptoms, mediated the negative impact of weight status on breastfeeding intention. Conclusions: breastfeeding outcomes are negatively associated with maternal weight status and prenatal mental health with the relationship between the two being interconnected, despite subclinical scores on the BDI. Further research is needed to explore the role of mental health on breastfeeding outcomes. From these findings, targeted prenatal interventions for women with excessive weight and depressive symptoms would likely promote and improve breastfeeding outcomes. ClinicalTrials.gov: www.clinicaltrials.gov, ID #NCT01131117.

A longitudinal observational study of skeletal development between ages 3 mo and 6 y in children fed human milk, milk formula, or soy formula.

BACKGROUND: Early infant feeding can affect skeletal development. Most children are fed with breast milk, dairy-based infant formula, or soy-based infant formula during the first year of life. The National Health and Nutrition Examination Survey 2003-2010 reports that 12% of the US infants consume soy-based infant formula. Despite potential effects of soy-associated isoflavones on skeletal development, studies investigating bone metabolism and structural and functional bone indices in children are lacking. OBJECTIVE: The aim of this observational study was to investigate early effects of soy-based infant formula (SF group) intake on bone metabolism and structure during the first 6 y of life comparing with those of infants fed with breast milk (BF group) and dairy-based infant formula (MF group). METHODS: A total of 433 healthy infants were followed up from 3 mo to 6 y of age. Children's skeletal development was assessed using dual-energy X-ray absorptiometry (DXA; N = 433) and peripheral quantitative computed tomography (pQCT; n = 78). The urinary biomarkers of bone metabolism (N-terminal telopeptide of type I collagen [NTx] and osteocalcin) were evaluated using immunoassays at 6, 24, 60, and 72 mo. RESULTS: No statistically significant group differences were observed in bone mineral density (BMD) between the BF, MF, and SF groups, assessed using DXA or pQCT. At 6 y of age, children in the SF group showed significantly greater whole-body bone mineral content measured using DXA than those in the MF group. Six-month-old boys in the SF group demonstrated significantly greater levels of NTx than those in the MF group and significantly greater osteocalcin levels than those in the BF group. CONCLUSIONS: Together, these data suggest that although infants at age 6 mo in the SF group showed some enhanced bone metabolism compared with those in the BF and MF groups, as indicated by the urinary biomarkers, no differences in bone metabolism or BMD were noted between ages 2 and 6 y. This trial was registered at clinicaltrials.gov as NCT00616395.

Infant intakes of human milk branched chain amino acids are negatively associated with infant growth and influenced by maternal body mass index.

BACKGROUND: Branched-chain amino acids (BCAAs: isoleucine, leucine, and valine) and aromatic amino acids (AAAs: phenylalanine and tyrosine) are hypothesized to influence early-life obesity risk. OBJECTIVE: To assess HM free amino acid (AA) concentrations and infant intakes of HM AAs from women with obesity (OB) compared to those with normal weight (NW) and determine the relationships between HM AA consumption and infant growth. METHODS: HM samples were collected at 0.5 (n = 151), 2 (n = 129), and 6 (n = 93) months postpartum from mothers with NW (body mass index [BMI] = 18.5-24.9 kg/m2 ) and OB (BMI > 30 kg/m2 ). HM AAs were quantified via mass spectrometry. Infant HM intake, anthropometrics and body composition were assessed. Linear mixed-effects models (LMEM) examined the relationships between maternal BMI and HM AA intakes, and HM AA intake and infant growth over the first 6 months postpartum after adjusting for maternal and infant characteristics. RESULTS: Maternal BMI was positively associated with infant intakes of isoleucine, leucine, and AAAs across timepoints. HM AA intakes were positively associated with weight-for-length z-score, fat mass index, and fat-free mass index in infants (p < 0.05). CONCLUSIONS: Maternal BMI led to differences in HM AA composition, which was associated with infant body composition.

Breastfeeding duration modifies the association between maternal weight status and offspring dietary palmitate oxidation.

BACKGROUND: Offspring of obese rodents develop a metabolic phenotype that favors fat deposition. Data regarding the impact of maternal obesity programing of offspring fuel usage in humans is scarce. OBJECTIVE: The objective of this study was to explore the association between maternal weight status and dietary palmitate oxidation (DPO) in 2-y-old offspring, taking into consideration potential confounders and modifiers. METHODS: Women (n = 56) were enrolled by the first trimester of gestation. Maternal physical activity (PA; measured with accelerometers) at enrollment and gestational weight gain (GWG) were measured. Offspring sex, race, and breastfeeding (BF) duration were self-reported. Human milk (HM) composition was determined at 6 mo postpartum. At age 2 y, dietary quality [healthy eating index (HEI)] and parental feeding practices [Child Feeding Questionnaire (CFQ)] were assessed. DPO in 2-y-olds (2-yo-DPO) was measured using deuterated palmitic acid. Generalized linear regression analysis was used to model the associations of 2-yo-DPO with maternal weight status [normal weight (NW), BMI <25 (in kg/m2) compared with excessive weight (EW), BMI ≥25]. RESULTS: DPO was higher in offspring of women with EW compared with NW (2.1 ± 1.2%/h compared with 1.4 ± 0.7%/h, P = 0.03). Maternal weight status interacted with BF duration in association with 2-yo-DPO (log ß: 0.05, P = 0.04). Specifically, 2-yo-DPO was higher in the EW compared with NW group if BF duration was ≥9 mo. HM insulin (log ß: 0.35, P = 0.002) and HM leptin (log ß: 0.81, P = 0.001) concentrations directly associated with 2-yo-DPO. PA (log ß: 0.06, P = 0.013), parental feeding restriction (log ß: 0.05, P < 0.0001), and male sex (log ß: 0.54, P < 0.001) were positively associated with 2-yo-DPO. HEI was negatively associated with 2-yo-DPO (log ß:-0.03, P < 0.0001). CONCLUSIONS: Higher 2-yo-DPO in offspring of women with EW compared with NW were driven by BF duration. Higher HM insulin and leptin concentrations in women with EW may explain these finding. More studies are needed to confirm these results. This trial was registered at clinicaltrials.gov as NCT03281850.

Associations between maternal obesity and offspring gut microbiome in the first year of life.

BACKGROUND: Maternal obesity is an important determinant of offspring obesity risk, which may be mediated via changes in the infant microbiome. OBJECTIVES: We examined infant faecal microbiome, short-chain fatty acids (SCFA), and maternal human milk oligosaccharides (HMO) in mothers with overweight/obese body mass index (BMI) (OW) compared with normal weight (NW) (Clinicaltrials.gov NCT01131117). METHODS: Infant stool samples at 1, 6, and 12 months were analysed by 16S rRNA sequencing. Maternal (BODPOD) and infant (quantitative nuclear magnetic resonance [QMR]) adiposity were measured. HMOs at 2 months postpartum and faecal SCFAs at 1 month were also assessed. Statistical analyses included multivariable and mixed linear models for assessment of microbiome diversity, composition, and associations of taxonomic abundance with metabolic and anthropometric variables. RESULTS: At 1 month, offspring of women with obesity had lower abundance of SCFA-producing bacteria (including Ruminococcus and Turicibacter) and lower faecal butyric acid levels. Lachnospiraceae abundance was lower in OW group at 6 months, and infant fat mass was negatively associated with the levels of Sutterella. Gradient boosting machine models indicated that higher α-diversity and specific microbial taxa at 1 month predicted elevated adiposity at 12 months with overall accuracy of 76.5%. Associations between maternal HMO concentrations and infant bacterial taxa differed between NW and OW groups. CONCLUSIONS: Elevated maternal BMI is associated with relative depletion of butyrate-producing microbes and faecal butyrate in the early infant faecal microbiome. Overall microbial richness may aid in prediction of elevated adiposity in later infancy.

Effect of a dietary and exercise intervention in women with overweight and obesity undergoing fertility treatments: protocol for a randomized controlled trial.

BACKGROUND: Distinct molecular, inflammatory, and metabolic signatures are present in oocytes and follicular fluid derived from women with obesity when compared to those derived from normal weight women, which suggest existing signals that may program future offspring for metabolic diseases. This study aims to assess the feasibility and efficacy of a peri-conception nutrition and exercise intervention on mitigating obesity-associated changes in oocyte gene expression profiles and follicular fluid metabolites. METHODS: This single blinded randomized control trial will include 120 women with a BMI of 25-45 kg/m2, ≥21 years of age, and undergoing in vitro fertilization (IVF) treatments. Participants will be randomized to standard of care (N = 60) or an intervention group (N = 60) in a block design by polycystic ovary syndrome status. The intervention will combine a dietary component (Mediterranean meal plan) with exercise prescription following the Physical Activity Guidelines for Americans. Participants will be assessed pre- and post-intervention. The standard of care group will be offered to join the intervention group if the IVF treatments are unsuccessful as a cross over design. Recruitment is anticipated to start in July of 2021. Primary outcomes will include single oocyte gene expression profiles and follicular fluid metabolites. Mann-Whitney U nonparametric tests will be used to assess potential differences for each stratum. Follicular fluid and serum metabolites will be analyzed using a one-factor Analysis of Covariance (ANCOVA) at four levels, pair-wise comparisons using Tukey-Kramer post-hoc tests will be used to identify groups whose means differ significantly while retaining the family-wise error rate at 5%. When the design is balanced, two-way Analysis of Variance (ANOVA), or non-parametric Friedman test will be used in data analysis. Additionally, general linear models and ANCOVA may be used to control for covariates. Significance will be set at p < 0.05. Findings will be disseminated via peer-reviewed manuscripts and presentations at scientific conferences. DISCUSSION: This study will provide novel data and key information on the impact of a dietary and exercise intervention on oocyte gene expression and follicular fluid content. Results will demonstrate the potential of such intervention in mitigating obesity-induced changes in oocyte gene expression and follicular fluid metabolites. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT04273048 ): submitted November 13, 2019; posted February 17, 2020.

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.

Associations between Maternal Diet, Body Composition and Gut Microbial Ecology in Pregnancy.

Maternal body composition, gestational weight gain (GWG) and diet quality influence offspring obesity risk. While the gut microbiome is thought to play a crucial role, it is understudied in pregnancy. Using a longitudinal pregnancy cohort, maternal anthropometrics, body composition, fecal microbiome and dietary intake were assessed at 12, 24 and 36 weeks of gestation. Fecal samples (n = 101, 98 and 107, at each trimester, respectively) were utilized for microbiome analysis via 16S rRNA amplicon sequencing. Data analysis included alpha- and beta-diversity measures and assessment of compositional changes using MaAsLin2. Correlation analyses of serum metabolic and anthropometric markers were performed against bacterial abundance and predicted functional pathways. α-diversity was unaltered by pregnancy stage or maternal obesity status. Actinobacteria, Lachnospiraceae, Akkermansia, Bifidobacterium, Streptococcus and Anaerotuncus abundances were associated with gestation stage. Maternal obesity status was associated with increased abundance of Lachnospiraceae, Bilophila, Dialister and Roseburia. Maternal BMI, fat mass, triglyceride and insulin levels were positively associated with Bilophila. Correlations of bacterial abundance with diet intake showed that Ruminococcus and Paraprevotella were associated with total fat and unsaturated fatty acid intake, while Collinsella and Anaerostipes were associated with protein intake. While causal relationships remain unclear, collectively, these findings indicate pregnancy- and maternal obesity-dependent interactions between dietary factors and the maternal gut microbiome.