Mother's age at menarche is associated with odds of preterm delivery: A case-control study.

OBJECTIVE: There is a secular trend towards earlier age of menarche in the US and globally. Earlier age at menarche (AAM) has been associated with metabolic disorders that increase risk for preterm delivery (PTD), yet no studies in the US have investigated whether AAM influences risk of PTD. This study tested the hypothesis that AAM is associated with PTD. DESIGN: A case-control study. SETTING: The Boston Medical Center (BMC) in Boston, Massachusetts. POPULATION OR SAMPLE: 8264 mother-newborn dyads enrolled at birth at BMC between 1998 and 2019, of which 2242 mothers had PTD (cases) and 6022 did not have PTD (controls). METHODS: Multivariable-adjusted logistic regression models and restricted cubic splines were used to examine the association between AAM and risk of PTD. The combined impact of AAM and age at delivery on the risk of PTD was also examined. MAIN OUTCOME MEASURES: Preterm delivery and gestational age (GA) was defined by maternal last menstrual period and early ultrasound documented in medical records. RESULTS: Maternal age at delivery was 28.1 ± 6.5 years and AAM was 12.85 ± 1.86 years. Multivariable-adjusted cubic spline suggested an inverse dose-response association of AAM with odds of PTD and, consistently, a positive association with GA. A 1-year earlier AAM was associated with 5% (95% CI 2%-8%) higher odds of PTD, after adjustment for maternal year of birth, parity, maternal place of birth, education, smoking status and Mediterranean-style diet score. The association between AAM and PTD was stronger among older mothers whose age at delivery was ≥35 years. CONCLUSIONS: Earlier AAM is associated with higher odds for PTD, and this association is stronger among women at advanced reproductive age.

A Marginalized Zero-Inflated Negative Binomial Model for Spatial Data: Modeling COVID-19 Deaths in Georgia.

Spatial count data with an abundance of zeros arise commonly in disease mapping studies. Typically, these data are analyzed using zero-inflated models, which comprise a mixture of a point mass at zero and an ordinary count distribution, such as the Poisson or negative binomial. However, due to their mixture representation, conventional zero-inflated models are challenging to explain in practice because the parameter estimates have conditional latent-class interpretations. As an alternative, several authors have proposed marginalized zero-inflated models that simultaneously model the excess zeros and the marginal mean, leading to a parameterization that more closely aligns with ordinary count models. Motivated by a study examining predictors of COVID-19 death rates, we develop a spatiotemporal marginalized zero-inflated negative binomial model that directly models the marginal mean, thus extending marginalized zero-inflated models to the spatial setting. To capture the spatiotemporal heterogeneity in the data, we introduce region-level covariates, smooth temporal effects, and spatially correlated random effects to model both the excess zeros and the marginal mean. For estimation, we adopt a Bayesian approach that combines full-conditional Gibbs sampling and Metropolis-Hastings steps. We investigate features of the model and use the model to identify key predictors of COVID-19 deaths in the US state of Georgia during the 2021 calendar year.

Pre-pregnancy body mass index and gut microbiota of mothers and children 5 years postpartum.

BACKGROUND: Maternal pre-pregnancy body mass index (BMI) has been linked to altered gut microbiota in women shortly after delivery and in their offspring in the first few years of life. But little is known about how long these differences persist. METHODS: We followed 180 mothers and children from pregnancy until 5-year postpartum in the Gen3G cohort (Canada, enrolled 2010-2013). At 5 years postpartum we collected stool samples from mothers and children and estimated the gut microbiota by 16 S rRNA sequencing (V4 region) using Illumina MiSeq, and assigning amplicon sequence variants (ASV). We examined whether overall microbiota composition (as measured by microbiota ß diversity) was more similar between mother-child pairs compared to between mothers or between children. We also assessed whether mother-child pair sharing of overall microbiota composition differed by the weight status of mothers before pregnancy and of children at 5-year. Furthermore, in mothers, we examined whether pre-pregnancy BMI, BMI 5-year postpartum, and change in BMI between time points was associated with maternal gut microbiota 5-year postpartum. In children, we further examined associations of maternal pre-pregnancy BMI and child 5-year BMI z-score with child 5-year gut microbiota. RESULTS: Mother-child pairs had greater similarity in overall microbiome composition compared to between mothers and between children. In mothers, higher pre-pregnancy BMI and 5-year postpartum BMI were associated with lower microbiota observed ASV richness and Chao 1 index; in children's gut microbiota, higher maternal pre-pregnancy BMI was weakly associated with lower microbiota Shannon index, whereas child's 5-year BMI z-score was associated with higher observed ASV richness. Pre-pregnancy BMI was also linked to differential abundances of several microbial ASVs in the Ruminococcaceae and Lachnospiraceae families, but no specific ASV had overlapping associations with BMI measures in both mothers and children. CONCLUSIONS: Pre-pregnancy BMI was associated with gut microbiota diversity and composition of mothers and children 5 years after birth, however, the nature and direction of most associations differed for mothers and children. Future studies are encouraged to confirm our findings and look into potential mechanisms or factors that may drive these associations.

Identifying Foods That Optimize Intake of Key Micronutrients During Pregnancy.

BACKGROUND: Most pregnant women in the United States are at risk of inadequate intake of vitamin A, vitamin D, folic acid, calcium, iron, and omega-3 fatty acids from foods alone. Very few United States dietary supplements provide sufficient doses of all 6 nutrients without inducing excess intake. OBJECTIVE: We aimed to identify energy-efficient foods that provide sufficient doses of these nutrients and could be consumed in lieu of dietary supplements to achieve the recommended intake in pregnancy. METHODS: In a previous analysis of 2,450 pregnant women, we calculated the range of additional intake needed to shift 90% of participants to intake above the estimated average requirement and keep 90% below the tolerable upper level for these 6 nutrients. Here, we identified foods and beverages from the 2019 to 2020 Food and Nutrient Database for Dietary Studies that provide target levels of these nutrients without exceeding the additional energy intake recommended for pregnancy beginning in the second trimester (340 kilocalories). RESULTS: We identified 2358 candidate foods meeting the target intake range for at least one nutrient. No candidate foods provided target amounts of all 6 nutrients. Seaweed (raw or cooked without fat) provided sufficient vitamin A, folate, calcium, iron, and omega-3s (5 of 6 nutrients) but would require an intake of >5 cups/d. Twenty-one other foods/beverages (mainly fish, vegetables, and beverages) provided target amounts of 4 of the 6 nutrients. Few foods met targets for vitamin D (n = 54) or iron (n = 93). CONCLUSIONS: Results highlight the difficulty in meeting nutritional requirements from diet alone and imply that dietary supplements are likely necessary to meet vitamin D and iron targets in pregnancy, as well as omega-3 fatty acid targets for individuals who do not consume fish products. Other foods could be added in limited amounts to help meet intake targets without exceeding caloric recommendations or nutrient safety limits.

A behavioral weight-loss intervention, but not metformin, decreases a marker of gut barrier permeability: results from the SPIRIT randomized trial.

BACKGROUND/OBJECTIVES: Lipopolysaccharide-binding protein (LBP), a biomarker of gut barrier permeability to lipopolysaccharides, is higher in adults with obesity and type 2 diabetes. Behavioral weight loss and metformin have distinct effects on the gut microbiome, but their impact on gut permeability to lipopolysaccharides is unknown. This study's objective was to determine the effects of a behavioral weight-loss intervention or metformin treatment on plasma LBP. SUBJECTS/METHODS: SPIRIT was a randomized trial of adults with overweight or obesity. Participants were randomized to one of three arms: metformin treatment, coach-directed behavioral weight loss on a DASH diet, or self-directed care (control). Of 121 participants, a random subset (n = 88) was selected to have LBP measured at baseline, 6 months, and 12 months post intervention. Intervention effects on LBP over time were assessed using generalized estimating equations (GEE). We also examined whether the intervention effects were modified by change in diet and weight. RESULTS: Arms were balanced by sex (83% female), race (51% white), and age (mean 60 years), with no differences in baseline LBP (median 4.23 µg/mL). At 1 year, mean weight change was -3.00% in the metformin arm, -3.02% in the coach-directed behavioral weight-loss arm, and +0.33% in the self-directed (control) arm. The corresponding change in LBP was +1.03, -0.98, +1.03 µg/mL. The behavioral weight-loss intervention reduced LBP compared to self-directed care (ß = -0.17, 95% CI: -0.33 to -0.01); no other between-arm comparisons were significant. Behavioral weight-loss participants who reduced dietary fat showed the greatest reductions in 6-month LBP (ß = -2.84, 95% CI: -5.17 to -0.50). CONCLUSIONS: Despite similar weight loss in the behavioral weight loss arm and the metformin arm, only the behavioral weight-loss intervention reduced LBP compared to control. Lifestyle weight-loss interventions that promote a DASH diet may be effective at reducing gut barrier permeability to lipopolysaccharides. CLINICAL TRIALS REGISTRATION NUMBER: NCT02431676, https://clinicaltrials.gov.

The Role of Childhood Asthma in Obesity Development: A Nationwide US Multicohort Study.

RATIONALE: Asthma and obesity often co-occur. It has been hypothesized that asthma may contribute to childhood obesity onset. OBJECTIVES: To determine if childhood asthma is associated with incident obesity and examine the role of asthma medication in this association. METHODS: We studied 8,716 children between ages 6 and 18.5 years who were nonobese at study entry participating in 18 US cohorts of the Environmental influences on Child Health Outcomes program (among 7,299 children with complete covariate data mean [SD] study entry age = 7.2 [1.6] years and follow up = 5.3 [3.1] years). MEASUREMENTS AND MAIN RESULTS: We defined asthma based on caregiver report of provider diagnosis. Incident obesity was defined as the first documented body mass index ≥95th percentile for age and sex following asthma status ascertainment. Over the study period, 26% of children had an asthma diagnosis and 11% developed obesity. Cox proportional hazards models with sex-specific baseline hazards were fitted to assess the association of asthma diagnosis with obesity incidence. Children with asthma had a 23% (95% confidence intervals [CI] = 4, 44) higher risk for subsequently developing obesity compared with those without asthma. A novel mediation analysis was also conducted to decompose the total asthma effect on obesity into pathways mediated and not mediated by asthma medication use. Use of asthma medication attenuated the total estimated effect of asthma on obesity by 64% (excess hazard ratios = 0.64; 95% CI = -1.05, -0.23). CONCLUSIONS: This nationwide study supports the hypothesis that childhood asthma is associated with later risk of obesity. Asthma medication may reduce this association and merits further investigation as a potential strategy for obesity prevention among children with asthma.

Diet quality scores associated with improved cardiometabolic measures among African American adolescents.

BACKGROUND: The Reversing the Negative cardiovascular Effects on Weight (ReNEW) Clinic is a prospective cohort study in children and adolescents (≤21 years) at the Johns Hopkins Children's Center. METHODS: Cross-sectional analysis between diet quality using the Alternative Healthy Eating Index (AHEI-2010), pro-inflammatory potential using the Children's Dietary Inflammatory Index (C-DII), and cardiometabolic outcomes. AHEI-2010 and C-DII scores were assessed by median intake determined from the sample distribution and associated with cardiometabolic measures using linear regression models. Changes in measures were evaluated in a sub-sample of participants invited to attend follow-up visits due to the presence of hypertensive blood pressure (n = 33). RESULTS: Participants (n = 90) reported an average energy intake of 1790 kcal/day (SD ± 734), AHEI-2010 score of 55.04 (SD ± 9.86) (range: 0 to 110) and C-DII score of -0.12 (±0.86) (range -5 to 5). Participants with higher quality/anti-inflammatory diets trended towards more favorable cardiometabolic measures at baseline. Among the sub-sample (n = 33), there was a significant reduction in total energy (m = -302 kcal/day; p-value= 0.03) but no change in AHEI-2010 (p-value = 0.73) or C-DII score (p-value = 0.85) over follow-up. CONCLUSIONS: Despite stable diet quality scores, outpatient dietary and behavioral counseling may be an effective tool to reduce energy intake in youth with overweight/obesity and elevated blood pressure. IMPACT: Diet quality scores among obese, hypertensive, African American adolescents were low and reflect a pro-inflammatory diet. Reported intake was negligible for fruits, whole grains, nuts, and legumes, and well above the daily limit for sodium and saturated fat. Participants with high quality/anti-inflammatory diet quality scores trended toward improved cardiometabolic measures. Outpatient dietary counseling resulted in reduced total energy intake.

Mode of delivery, type of labor, and measures of adiposity from childhood to teenage: Project Viva.

BACKGROUND: Cesarean delivery has been linked with childhood obesity. Few studies have examined if this association is attenuated if there is labor prior to delivery. The objective of this current analysis was to examine the association of cesarean vs. vaginal delivery with measures of childhood adiposity, and whether the association differs by labor type (spontaneous, induced, or absent) preceding cesarean delivery. METHODS: We ascertained delivery mode and type of labor from medical records in 1443 mother-child dyads from Project Viva with adiposity measures from at least one follow-up visit (3369 total observations) in early childhood (median age 3.2 y), mid-childhood (median 7.7 y), or early teen (median 12.9 y). Child adiposity outcomes were CDC age- and sex-specific body mass index (BMI) z-scores, sum of subscapular and triceps skinfold thicknesses (SS + TR; mm), and waist circumference (cm). We used linear regression models with generalized estimating equation estimates and adjusted for maternal age, education, race/ethnicity, prepregnancy BMI, rate of gestational weight gain, and child sex and age at outcome. RESULTS: A total of 333 (23%) women delivered via cesarean, including 155 (11%) with spontaneous labor, 74 (5%) with induced labor, 99 (7%) with no labor, and 5 (<1%) with unknown labor status. Compared to vaginal-delivered children, cesarean-delivered children had higher BMI-z (0.15, 95% CI: 0.04, 0.26); and non-significantly higher waist circumference (0.50 cm, 95% CI: -0.34, 1.34) and SS + TR (0.47 mm, 95% CI: -0.52, 1.46). Cesarean deliveries that were preceded by spontaneous labor were not associated with childhood BMI-z (0.08, 95% CI: -0.07, 0.23), waist circumference (-0.12 cm, 95% CI: -1.09, 0.85), or SS + TR (-0.25 mm, 95% CI: -1.44, 0.93), as compared to vaginal deliveries. CONCLUSION: Cesarean delivery was associated with higher childhood BMI-z, and although waist circumference and SS + TR trended in the same direction, these associations were not significant. Cesarean delivery preceded by spontaneous labor was not associated with adiposity outcomes.

Higher Diet Quality in African-American Adolescents Is Associated with Lower Odds of Metabolic Syndrome: Evidence from the NHANES.

BACKGROUND: Development of clinical risk factors linked to metabolic syndrome (MetS) in adolescence is associated with higher incidence of atherosclerotic cardiovascular events in adulthood. Given the increasing burden of obesity and MetS in African-American (AA) youth, there is a need to establish the relation of MetS with modifiable risk factors such as diet quality, because these data may enhance preventative and treatment approaches. OBJECTIVES: The purpose of this study was to assess diet quality, measured by the Alternative Healthy Eating Index 2010 (AHEI-2010) and the Dietary Approaches to Stop Hypertension (DASH) pattern score, in AA adolescents and youth (aged 12-21 y) from the NHANES, and to investigate the association of diet quality with MetS and its components. METHODS: This study is a cross-sectional analysis of NHANES data from the 2005-2016 cycles (n = 2459). Survey-weighted logistic regression models were used to assess the association of diet quality with the prevalence of MetS and individual cardiometabolic components [overweight/obesity, hypertensive blood pressure (BP), impaired fasting glucose, low HDL cholesterol, hypertriglyceridemia]. RESULTS: The mean ± SD AHEI-2010 score was 38.9 ± 9.7 and DASH pattern score was 21.8 ± 4.4, which is equivalent to 35% adherence to recommendations to achieve an optimal diet quality and 45% adherence to the DASH-style dietary pattern, respectively. Compared with those within the lowest quartile of DASH pattern score, individuals in the fourth quartile group had 0.63 (95% CI: 0.41, 0.97) times the odds of having hypertensive BP. Among individuals with complete clinical measures (n = 1007), individuals within the highest-quartile AHEI-2010 group had 0.25 (95% CI: 0.06, 0.99) times the odds of having MetS compared with those within the lowest quartile. CONCLUSIONS: Diet quality in US AA youth is low. Higher DASH pattern scores were associated with lower odds of hypertensive BP and higher AHEI-2010 scores were associated with lower odds of MetS.

Higher Carbohydrate Amount and Lower Glycemic Index Increase Hunger, Diet Satisfaction, and Heartburn in Overweight and Obese Adults in the OmniCarb Randomized Clinical Trial.

BACKGROUND: The Dietary Approaches to Stop Hypertension (DASH) diet, a high-carbohydrate diet, is highly recommended based on its cardiovascular risk benefits, yet adherence remains persistently low. How subjective impressions of this diet contribute to adherence has not been thoroughly explored. The OmniCarb trial, which compared DASH-style diets varying in glycemic index (GI) and carbohydrate amount, surveyed subjective impressions of such diets. OBJECTIVES: We examined the effects of GI and carbohydrate amount on qualitative aspects of diet acceptability through secondary outcomes in the OmniCarb trial. METHODS: OmniCarb was a randomized, crossover trial of 4 DASH-style diets varying by GI (≥65 compared with ≤45) and carbohydrate amount (40% compared with 58% kcal) in overweight or obese (BMI ≥25 kg/m2) adults (n = 163). Participants consumed each diet in random order over 5-wk periods, separated by 2-wk washouts. At baseline and the end of each feeding period, participants rated hunger, diet satisfaction, and gastrointestinal symptoms (diarrhea/loose stools, constipation, bloating, nausea, and heartburn). RESULTS: Participant mean age was 52 y, with 52% women, 51% non-Hispanic black, and 56% obese (BMI ≥30). Compared with baseline, all intervention diets decreased heartburn, increased diarrhea/loose stools, and increased bloating, but did not significantly affect constipation or nausea. Compared with lower carbohydrate diets, higher carbohydrate diets increased hunger (RR: 1.16; 95% CI: 1.04, 1.30), increased diet satisfaction (RR: 1.10; 95% CI: 1.01, 1.20), and increased heartburn (RR: 1.49; 95% CI: 1.09, 2.04). Compared with lower GI diets, higher GI diets did not affect hunger (RR: 0.92; 95% CI: 0.83, 1.02), decreased diet satisfaction (RR: 0.83; 95% CI: 0.75, 0.92), and did not affect heartburn (RR: 0.89; 95% CI: 0.70, 1.13). There were no between-diet differences for diarrhea/loose stools, constipation, bloating, and nausea. CONCLUSIONS: Although a higher carbohydrate amount in DASH-style diets can increase diet satisfaction, it can also decrease satiety and increase heartburn in adults with overweight or obesity.This trial is registered at clinicaltrials.gov as NCT00608049.

Disparities in Risks of Inadequate and Excessive Intake of Micronutrients during Pregnancy.

BACKGROUND: Inadequate or excessive intake of micronutrients in pregnancy has potential to negatively impact maternal/offspring health outcomes. OBJECTIVE: The aim was to compare risks of inadequate or excessive micronutrient intake in diverse females with singleton pregnancies by strata of maternal age, race/ethnicity, education, and prepregnancy BMI. METHODS: Fifteen observational cohorts in the US Environmental influences on Child Health Outcomes (ECHO) Consortium assessed participant dietary intake with 24-h dietary recalls (n = 1910) or food-frequency questionnaires (n = 7891) from 1999-2019. We compared the distributions of usual intake of 19 micronutrients from food alone (15 cohorts; n = 9801) and food plus dietary supplements (10 cohorts with supplement data; n = 7082) to estimate the proportion with usual daily intakes below their age-specific daily Estimated Average Requirement (EAR), above their Adequate Intake (AI), and above their Tolerable Upper Intake Level (UL), overall and within sociodemographic and anthropometric subgroups. RESULTS: Risk of inadequate intake from food alone ranged from 0% to 87%, depending on the micronutrient and assessment methodology. When dietary supplements were included, some women were below the EAR for vitamin D (20-38%), vitamin E (17-22%), and magnesium (39-41%); some women were above the AI for vitamin K (63-75%), choline (7%), and potassium (37-53%); and some were above the UL for folic acid (32-51%), iron (39-40%), and zinc (19-20%). Highest risks for inadequate intakes were observed among participants with age 14-18 y (6 nutrients), non-White race or Hispanic ethnicity (10 nutrients), less than a high school education (9 nutrients), or obesity (9 nutrients). CONCLUSIONS: Improved diet quality is needed for most pregnant females. Even with dietary supplement use, >20% of participants were at risk of inadequate intake of ≥1 micronutrients, especially in some population subgroups. Pregnancy may be a window of opportunity to address disparities in micronutrient intake that could contribute to intergenerational health inequalities.

Delivery mode and altered infant growth at 1 year of life in India.

BACKGROUND: Cesarean section (C-section) delivered infants are more likely to be colonized by opportunistic pathogens, resulting in altered growth. We examined whether C-section (elective/emergency) vs vaginal delivery was associated with altered weight and linear growth at 1 year of life. METHODS: A total of 638 mother-infant pairs were included from MAASTHI cohort 2016-2019. Information on delivery mode was obtained from medical records. Based on WHO child growth standards, body mass index-forage z-score (BMI z) and length-for-age z-score (length z) were derived. We ran multivariable linear and Poisson regression models before and after multiple imputation. RESULTS: The rate of C-section was 43.4% (26.5%: emergency, 16.9%: elective). Percentage of infant overweight was 14.9%. Compared to vaginal delivery, elective C-section was associated with ß = 0.57 (95% CI 0.20, 0.95) higher BMI z. Also infants born by elective C-section had RR = 2.44 (95% CI 1.35, 4.41) higher risk of being overweight; no such association was found for emergency C-section. Also, elective C-section delivery was associated with reduced linear growth at 1 year after multiple imputation (ß = -0.38, 95% CI -0.76, -0.01). CONCLUSIONS: Elective C-section delivery might contribute to excess weight and also possibly reduced linear growth at 1 year of age in children from low- and middle-income countries. IMPACT: Our study, in a low-income setting, suggests that elective, but not emergency, C-section is associated with excess infant BMI z at 1 year of age and elective C (C-section) was also associated with altered linear growth but only in multiple imputation analyses. Elective C-section was associated with a higher risk of being overweight at 1 year of age. Our results indicate that decreasing medically unnecessary elective C-section deliveries may help limit excess weight gain and stunted linear growth among infants.

Does birth mode modify associations of maternal pre-pregnancy BMI and gestational weight gain with the infant gut microbiome?

BACKGROUND: Mother-to-newborn transmission of obesity-associated microbiota may be modified by birth mode (vaginal vs. Cesarean delivery). Prospective data to test this hypothesis are still sparse. OBJECTIVE: To examine prospective associations of maternal pre-pregnancy BMI and gestational weight gain with the infant gut microbiome by birth-mode strata. SUBJECTS/METHODS: In 335 mother-infant pairs in the New Hampshire Birth Cohort, we ascertained data from questionnaires and medical records, and generated microbiome data from 6-week-old infants' stool using Illumina 16s rRNA gene sequencing (V4-V5 region). Analyses were stratified by birth mode and conducted before and after adjusting for potential confounders, which included maternal age, education, parity, and Mediterranean diet score. RESULTS: Among 335 mothers, 56% had normal pre-pregnancy BMI ( < 25, referent), 27% were overweight (BMI 25-30), and 18% obese (BMI > 30). Among the 312 mothers with weight gain data, 10% had inadequate weight gain, 30% adequate (referent), and 60% excess. Birth mode modified associations of pre-pregnancy BMI with several genera, including the most abundant genus, Bacteroides (P for interaction = 0.05). In the vaginal-delivery group, maternal overweight or obesity was associated with higher infant gut microbiome diversity and higher relative abundance of 15 operational taxonomic units (OTUs), including overrepresentation of Bacteroides fragilis, Escherichia coli, Veillonella dispar, and OTUs in the genera Staphylococcus and Enterococcus. In the Cesarean-delivered group, there were no significant associations of pre-pregnancy BMI with infant microbiome (alpha) diversity or OTUs. Gestational weight gain was not associated with differential relative abundance of infant gut microbial OTUs or with measures of microbial diversity in infants delivered vaginally or by Cesarean section. CONCLUSIONS: Among vaginally-delivered infants, maternal overweight and obesity was associated with altered infant gut microbiome composition and higher diversity. These associations were not observed in Cesarean-delivered infants, whose microbiome development differs from vaginally-delivered infants. Our study provides additional evidence of birth-mode dependent associations of maternal body weight status with the infant gut microbiota. The role of these associations in mediating the intergenerational cycle of obesity warrants further examination.

Understanding childhood obesity in the US: the NIH environmental influences on child health outcomes (ECHO) program.

BACKGROUND: Few resources exist for prospective, longitudinal analysis of the relationships between early life environment and later obesity in large diverse samples of children in the United States (US). In 2016, the National Institutes of Health launched the Environmental influences on Child Health Outcomes (ECHO) program to investigate influences of environmental exposures on child health and development. We describe demographics and overweight and obesity prevalence in ECHO, and ECHO's potential as a resource for understanding how early life environmental factors affect obesity risk. METHODS: In this cross-sectional study of 70 extant US and Puerto Rico cohorts, 2003-2017, we examined age, race/ethnicity, and sex in children with body mass index (BMI) data, including 28,507 full-term post-birth to <2 years and 38,332 aged 2-18 years. Main outcomes included high BMI for age <2 years, and at 2-18 years overweight (BMI 85th to <95th percentile), obesity (BMI ≥ 95th percentile), and severe obesity (BMI ≥ 120% of 95th percentile). RESULTS: The study population had diverse race/ethnicity and maternal demographics. Each outcome was more common with increasing age and varied with race/ethnicity. High BMI prevalence (95% CI) was 4.7% (3.5, 6.0) <1 year, and 10.6% (7.4, 13.7) for 1 to <2 years; overweight prevalence increased from 13.9% (12.4, 15.9) at 2-3 years to 19.9% (11.7, 28.2) at 12 to <18 years. ECHO has the statistical power to detect relative risks for 'high' BMI ranging from 1.2 to 2.2 for a wide range of exposure prevalences (1-50%) within each age group. CONCLUSIONS: ECHO is a powerful resource for understanding influences of chemical, biological, social, natural, and built environments on onset and trajectories of obesity in US children. The large sample size of ECHO cohorts adopting a standardized protocol for new data collection of varied exposures along with longitudinal assessments will allow refined analyses to identify drivers of childhood obesity.

Timing of complementary feeding is associated with gut microbiota diversity and composition and short chain fatty acid concentrations over the first year of life.

BACKGROUND: Early introduction of complementary foods has been associated with various immune disorders, oxidative stress, and obesity in childhood. The gut microbiota and the short chain fatty acids (SCFAs) they produce are postulated to be on the causal pathway. The objective of this study was to determine if early complementary feeding (i.e. consumption of solids or non-water/formula liquids at or before 3 months) is prospectively associated with infant gut microbiota composition, diversity and SCFAs at 3 and 12 months of age in the Nurture birth cohort. RESULTS: Mother-infant dyads in the early complementary feeding group (n = 18) had similar baseline characteristics to those in the later feeding group (n = 49). We assessed differential abundance of microbial taxa (measured by 16S rRNA gene sequencing of the V4 region) by timing of complementary feeding using beta-binomial regression models (considering a two-sided FDR corrected p-value of < 0.05 as significant), and we fittted linear regression models to assess the association between early complementary feeding and SCFA concentrations (quantified using gas chromatography). After multivariable adjustment for breastfeeding, delivery method, birth weight, and gestational age, there were 13 differentially abundant microbial amplicon sequence variants (ASVs) by timing of introduction to complementary foods at 3 months and 20 ASVs at 12 months. Infants introduced to complementary foods early (vs. later) had higher concentrations of the SCFA butyric acid (mean difference = 0.65, 95% CI: 0.27, 1.04, p < 0.01) and total SCFAs (mean difference = 38.8, 95% CI: 7.83, 69.7) at 12 months. Bilophila wadsworthia and Lachnospiraceae Roseburia were associated with early (vs. later) complementary feeding and with higher butyric acid concentrations at 3 and 12 months, respectively. CONCLUSIONS: Our findings are consistent with the hypothesis that early (vs. later) introduction to complementary foods is associated with altered gut microbiota composition and butyric acid concentrations measured in stool until at least 1 year of age. Further research is needed to determine if these changes mediate future development of metabolic and immune conditions.

Prospective Association Between Manganese in Early Pregnancy and the Risk of Preeclampsia.

BACKGROUND: Manganese, an essential micronutrient, has been found in lower concentrations among women with preeclampsia in cross-sectional and case-control studies without establishment of a temporal relationship. METHODS: We evaluated the prospective association of manganese (in red blood cells) in first trimester of pregnancy with incidence of preeclampsia (ascertained by reviewing medical records) among 1,312 women in eastern Massachusetts (Project Viva, 1999-2002). We used log-binomial regression to examine the manganese-preeclampsia relationship, adjusting for maternal age, race/ethnicity, parity, prepregnancy body mass index, blood pressure, and hematocrit. RESULTS: The median (25th, 75th percentile) manganese concentrationin red blood cells was 16.2 ng/g (13.1, 20.4) and 48 (4%) women developed preeclampsia. We observed an inverse dose-response relationship between manganese and preeclampsia. Compared with women in the lowest tertile, women in the middle manganese tertile had 0.81 times the risk of preeclampsia (95% CI: 0.43, 1.5) and those in the highest tertile had 0.50 (95% CI: 0.25, 0.99) times the risk. CONCLUSIONS: Our results provide insight into a potentially modifiable way to prevent preeclampsia.

Effects of the DASH Diet and Sodium Intake on Bloating: Results From the DASH-Sodium Trial.

INTRODUCTION: Bloating is one of the most common gastrointestinal complaints. Evidence has linked fiber and sodium to bloating; however, randomized trials examining these diet components are lacking. Here, we used a randomized trial to examine the effects of the high-fiber DASH diet and dietary sodium intake on abdominal bloating. We hypothesized that both the high-fiber DASH diet and higher sodium intake would increase bloating. METHODS: The DASH-Sodium trial (1998-1999) randomized healthy adults to a high-fiber (32 g/d) DASH or low-fiber (11 g/d) Western diet (control). On their assigned diet, participants ate 3 sodium levels (50, 100, and 150 mmol/d at 2100 kcal) in 30-day periods in random order, with 5-day breaks between each period. The participants reported the presence of bloating at baseline and after each feeding period. Statistical analyses included log-binomial models to evaluate the risk of bloating. RESULTS: Of 412 participants (mean age 48 years; 57% women; 57% black), 36.7% reported bloating at baseline. Regardless of the diet, high sodium intake increased the risk of bloating (risk ratio = 1.27; 95% confidence interval: 1.06-1.52; P = 0.01). The high-fiber DASH diet also increased the risk of bloating over all sodium levels (risk ratio = 1.41; 95% confidence interval: 1.22-1.64; P < 0.001). The effect of high-fiber DASH on bloating was greater in men than in women (P for interaction = 0.001). DISCUSSION: Higher dietary sodium increased bloating, as did the high-fiber DASH diet. Although healthful high-fiber diets may increase bloating, these effects may be partially mitigated by decreasing dietary sodium intake. Future research is needed to explore mechanisms by which sodium intake and diet can influence bloating.

Does cesarean delivery impact infant weight gain and adiposity over the first year of life?

BACKGROUND: Potentially driven by the lack of mother-to-infant transmission of microbiota at birth, cesarean delivery has been associated with higher risk of offspring obesity. Yet, no studies have examined when delivery-mode differences in adiposity begin to emerge. In this study, we examine differences in infant weight and adiposity trajectories from birth to 12 months by delivery mode. METHODS: From 2013 to 2015, we recruited pregnant women into the Nurture Study and followed up their 666 infants. We ascertained maternal delivery method and infant birth weight from medical records. We measured weight, length, and skinfold thicknesses (subscapular, triceps, abdominal) when infants were 3, 6, 9, and 12 months of age. The main outcome, infant weight-for-length z score, was derived based on the WHO Child Growth Standards. We used linear regression models to assess the difference at each time point and used linear mixed models to examine the growth rate for infant weight and adiposity trajectories. We controlled for maternal age, race, marital status, education level, household income, smoking status, maternal pre-pregnancy body mass index, and infant birth weight. RESULTS: Of the 563 infants in our final sample, 179 (31.8%) were cesarean delivered. From birth to 12 months, the rate of increase in weight-for-length z score was 0.02/month (p = 0.03) greater for cesarean-delivered than vaginally-delivered infants. As a result of more rapid growth, cesarean-delivered infants had higher weight-for-length z score (0.26, 95% CI: 0.05, 0.47) and sum of subscapular and triceps (SS + TR) skinfold thickness (0.95 mm, 95% CI: 0.30, 1.60)-an indicator for overall adiposity-at 12 months, compared to vaginally-delivered infants. CONCLUSIONS: Compared to vaginal delivery, cesarean delivery was associated with greater offspring rate of weight gain over the first year and differences in adiposity that appear as early as 3 months of age. Monitoring cesarean-delivered infants closely for excess weight gain may help guide primordial prevention of obesity later in life.

Association of prenatal antibiotics with measures of infant adiposity and the gut microbiome.

BACKGROUND: Prenatal antibiotic exposure has been associated with an altered infant gut microbiome composition and higher risk of childhood obesity, but no studies have examined if prenatal antibiotics simultaneously alter the gut microbiome and adiposity in infants. METHOD: In this prospective study (Nurture: recruitment 2013-2015 in North Carolina, United States), we examined in 454 infants the association of prenatal antibiotic exposure (by any prenatal antibiotic exposure; by trimester of pregnancy; by number of courses; by type of antibiotics) with infant age- and sex-specific weight-for-length z score (WFL-z) and skinfold thicknesses (subscapular, triceps, abdominal) at 12 months of age. In a subsample, we also examined whether prenatal antibiotic exposure was associated with alterations in the infant gut microbiome at ages 3 and 12 months. RESULTS: Compared to infants not exposed to prenatal antibiotics, infants who were exposed to any prenatal antibiotics had 0.21 (95% confidence interval [CI] 0.02, 0.41) higher WFL-z at 12 months, and 0.28 (95% CI 0.02, 0.55) higher WFL-z if they were exposed to antibiotics in the second trimester, after adjustment for potential confounders, birth weight, and gestational age. We also observed a dose-dependent association (P-value for trend = 0.006) with infants exposed to ≥ 3 courses having 0.41 (95% CI 0.13, 0.68) higher WFL-z at 12 months. After further adjustment for delivery method, only second-trimester antibiotic exposure remained associated with higher infant WFL-z (0.27, 95% CI 0.003, 0.54) and subscapular skinfold thickness (0.49 mm, 95% CI 0.11, 0.88) at 12 months. Infants exposed to second-trimester antibiotics versus not had differential abundance of 13 bacterial amplicon sequence variants (ASVs) at age 3 months and 17 ASVs at 12 months (false discovery rate adjusted P-value < 0.05). CONCLUSIONS: Prenatal antibiotic exposure in the second trimester was associated with an altered infant gut microbiome composition at 3 and 12 months and with higher infant WFL-z and subscapular skinfold thickness at 12 months.