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RationaleAsthma and obesity often co-occur. It has been hypothesized that asthma may contribute to childhood obesity onset.ObjectivesTo determine if childhood asthma is associated with incident obesity and examine the role of asthma medication in this association.MethodsWe 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 resultsWe 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).ConclusionsThis 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.

The particularly interdisciplinary nature of human microbiome research makes the organization and reporting of results spanning epidemiology, biology, bioinformatics, translational medicine and statistics a challenge. Commonly used reporting guidelines for observational or genetic epidemiology studies lack key features specific to microbiome studies. Therefore, a multidisciplinary group of microbiome epidemiology researchers adapted guidelines for observational and genetic studies to culture-independent human microbiome studies, and also developed new reporting elements for laboratory, bioinformatics and statistical analyses tailored to microbiome studies. The resulting tool, called 'Strengthening The Organization and Reporting of Microbiome Studies' (STORMS), is composed of a 17-item checklist organized into six sections that correspond to the typical sections of a scientific publication, presented as an editable table for inclusion in supplementary materials. The STORMS checklist provides guidance for concise and complete reporting of microbiome studies that will facilitate manuscript preparation, peer review, and reader comprehension of publications and comparative analysis of published results.

BackgroundInadequate or excessive intake of micronutrients in pregnancy has potential to negatively impact maternal/offspring health outcomes.ObjectiveThe 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.MethodsFifteen 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.ResultsRisk 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).ConclusionsImproved 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.

Although the COVID-19 pandemic is caused by a single virus, the rest of the human microbiome appears to be involved in the disease and could influence vaccine responses while offering opportunities for microbiome-directed therapeutics. The newly formed Microbiome Centers Consortium (MCC) surveyed its membership and identified four ways to leverage the strengths and experience of microbiome centers in the response to the COVID-19 pandemic. To meet these needs, the MCC will provide a platform to coordinate clinical and environmental research, assist with practical obstacles, and help communicate the connections between the microbiome and COVID-19. We ask that microbiome researchers join us in these efforts to address the ongoing pandemic.

Gut microbial diversity changes throughout the human life span and is known to be associated with host sex. We investigated the association of age, sex, and gut bacterial alpha diversity in three large cohorts of adults from four geographical regions: subjects from the United States and United Kingdom in the American Gut Project (AGP) citizen-science initiative and two independent cohorts of Colombians and Chinese. In three of the four cohorts, we observed a strong positive association between age and alpha diversity in young adults that plateaued after age 40 years. We also found sex-dependent differences that were more pronounced in younger adults than in middle-aged adults, with women having higher alpha diversity than men. In contrast to the other three cohorts, no association of alpha diversity with age or sex was observed in the Chinese cohort. The association of alpha diversity with age and sex remained after adjusting for cardiometabolic parameters in the Colombian cohort and antibiotic usage in the AGP cohort. We further attempted to predict the microbiota age in individuals using a machine-learning approach for the men and women in each cohort. Consistent with our alpha-diversity-based findings, U.S. and U.K. women had a significantly higher predicted microbiota age than men, with a reduced difference being seen above age 40 years. This difference was not observed in the Colombian cohort and was observed only in middle-aged Chinese adults. Together, our results provide new insights into the influence of age and sex on the biodiversity of the human gut microbiota during adulthood while highlighting similarities and differences across diverse cohorts. IMPORTANCE Microorganisms in the human gut play a role in health and disease, and in adults higher gut biodiversity has been linked to better health. Since gut microorganisms may be pivotal in the development of microbial therapies, understanding the factors that shape gut biodiversity is of utmost interest. We performed large-scale analyses of the relationship of age and sex to gut bacterial diversity in adult cohorts from four geographic regions: the United States, the United Kingdom, Colombia, and China. In the U.S., U.K., and Colombian cohorts, bacterial biodiversity correlated positively with age in young adults but plateaued at about age 40 years, with no positive association being found in middle-aged adults. Young, but not middle-aged, adult women had higher gut bacterial diversity than men, a pattern confirmed via supervised machine learning. Interestingly, in the Chinese cohort, minimal associations were observed between gut biodiversity and age or sex. Our results highlight the patterns of adult gut biodiversity and provide a framework for future research.

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. [ABSTRACT FROM AUTHOR]

Objective: The gut microbiome has been associated with visceral fat (VAT) in European and Asian populations; however, associations with VAT and with ectopic fats among African-ancestry individuals are not known. Our objective was to investigate cross-sectional associations of fecal microbiota diversity and composition with VAT and ectopic fat, as well as body mass index (BMI), among middle-aged and older African Caribbean men. Methods: We included in our analysis n = 193 men (mean age = 62.2 ± 7.6 years; mean BMI = 28.3 ± 4.9 kg/m2) from the Tobago Health Study. We assessed fecal microbiota using V4 16s rRNA gene sequencing. We evaluated multivariable-adjusted associations of microbiota features (alpha diversity, beta diversity, microbiota differential abundance) with BMI and with computed tomography-measured VAT and ectopic fats (pericardial and intermuscular fat; muscle and liver attenuation). Results: Lower alpha diversity was associated with higher VAT and BMI, and somewhat with higher pericardial and liver fat. VAT, BMI, and pericardial fat each explained similar levels of variance in beta diversity. Gram-negative Prevotellaceae and Negativicutes microbiota showed positive associations, while gram-positive Ruminococcaceae microbiota showed inverse associations, with ectopic fats. Conclusions: Fecal microbiota features associated with measures of general adiposity also extend to metabolically pernicious VAT and ectopic fat accumulation in older African-ancestry men. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background and Objectives: Breastfeeding during infancy is associated with healthier beverage consumption later in childhood, but little is known about this relation during infancy. This was a longitudinal study of breastfeeding and less healthy beverage consumption during the first year of life, in a birth cohort study conducted 2013–2018 in the Southeastern United States (n = 666). Methods: We estimated monthly rates of 100% juice and sugar‐sweetened beverage (SSB) consumption comparing infants who were exclusively or partially breastfed, versus those who were not, in multivariable adjusted models. Results: Mothers had a median age of 26.5 years, 71% identified as Black/African‐American, and 61% reported household incomes <$20 000/year. The prevalence of any breastfeeding during the first month was 78.2% and 18.7% at month 12. By age 12 months, infants consumed juice a mean (SD) 9.1 (10.1) times per week and SSBs 3.6 (9.5) times per week. Breastfed infants had a 38% lower incidence rate of weekly juice consumption (95% CI 52%, 15%, p = 0.003) and a 57% lower incidence rate of weekly SSB consumption (95% CI 76%, 22%, p = 0.006), compared with infants who were not breastfed. Conclusions: Research on early‐life correlates of dietary health should focus on the earliest beverages, given evidence that consumption of obesogenic beverages may begin prior to age 1 year. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic created an unprecedented global health crisis. Recent studies suggest that socially vulnerable communities were disproportionately impacted, although findings are mixed. To quantify social vulnerability in the US, many studies rely on the Social Vulnerability Index (SVI), a county-level measure comprising 15 census variables. Typically, the SVI is modelled in an additive manner, which may obscure non-linear or interactive associations, further contributing to inconsistent findings. As a more robust alternative, we propose a negative binomial Bayesian kernel machine regression (BKMR) model to investigate dynamic associations between social vulnerability and COVID-19 death rates, thus extending BKMR to the count data setting. The model produces a 'vulnerability effect' that quantifies the impact of vulnerability on COVID-19 death rates in each county. The method can also identify the relative importance of various SVI variables and make future predictions as county vulnerability profiles evolve. To capture spatio-temporal heterogeneity, the model incorporates spatial effects, county-level covariates, and smooth temporal functions. For Bayesian computation, we propose a tractable data-augmented Gibbs sampler. We conduct a simulation study to highlight the approach and apply the method to a study of COVID-19 deaths in the US state of South Carolina during the 2021 calendar year. [ABSTRACT FROM AUTHOR]

ObjectivesThere is biological crosstalk between insulin signaling and bone remodeling pathways, and wrist circumference and bone area were recently found to associate with insulin resistance independent of body mass index (BMI) in overweight/obese children. We aimed to expand on this work by using more specific measures of adiposity for adjustment and examining children with broader range of BMI.MethodsWe used serial data (1,051 total measures) on 313 non-Hispanic white youth (ages 8-18 y) from the Fels Longitudinal Study with homeostasis model assessment of insulin resistance (HOMA-IR) as the outcome. Internal standard deviation score (SDS) for wrist breadth was evaluated as a predictor of HOMA-IR (log-transformed) before and after adjusting for internal-sample SDSs for BMI, waist circumference (WC), and total body fat (TBF) from dual energy X-ray absorptiometry, in addition to age, sex, Tanner stage, and birth year, using generalized estimating equations.ResultsBefore additional adiposity adjustment, we found a significant positive association between wrist breadth SDS and log-transformed HOMA-IR (β = 0.13; 95%CI: 0.09-0.17), which remained significant after adjusting for TBF SDS (β = 0.09; 95%CI: 0.05-0.13; P < 0.001), BMI SDS (β = 0.06; 95%CI: 0.02-0.10; P = 0.007), and WC SDS (β = 0.06; 95%CI: 0.02-0.09; P = 0.005).ConclusionsFurther work is needed to determine whether simple frame size measures such as wrist breadth may be useful markers of metabolic risk.

Background/Objectives: Murine models show that plastics, via their chemical constituents (e.g., phthalates), influence microbiota, metabolism, and growth. However, research on plastics in humans is lacking. Here, we examine how the frequency of plastic bottle exposure is associated with fecal microbiota, short-chain fatty acids (SCFAs), and anthropometry in the first year of life. Subjects/Methods: In 442 infants from the prospective Nurture birth cohort, we examined the association of frequency of plastic bottle feeding at 3 months with anthropometric outcomes (skinfolds, length-for-age, and weight-for-length) at 12 months of age and growth trajectories between 3 and 12 months. Furthermore, in a subset of infants (n = 70) that contributed fecal samples at 3 months and 12 months of age, we examined plastic bottle frequency in relation to fecal microbiota composition and diversity (measured by 16S rRNA gene sequencing of V4 region), and fecal SCFA concentrations (quantified using gas chromatography mass spectrometry). Results: At 3 months, 67.6% of infants were plastic bottle fed at every feeding, 15.4% were exclusively breast milk fed, and 48.9% were exclusively formula fed. After adjustment for potential confounders, infants who were plastic bottle fed less than every feeding compared to those who were plastic bottle fed at every feeding at 3 months did not show differences in anthropometry over the first 12 months of life, save for lower length-for-age z-score at 12 months (adjusted β = −0.45, 95% CI: −0.76, −0.13). Infants who were plastic bottle fed less than every feeding versus every feeding had lower fecal microbiota alpha diversity at 3 months (mean difference for Shannon index: −0.59, 95% CI: −0.99, −0.20) and lower isovaleric acid concentration at 3 months (mean difference: −2.12 μmol/g, 95% CI: −3.64, −0.60), but these results were attenuated following adjustment for infant diet. Plastic bottle frequency was not strongly associated with microbiota diversity or SCFAs at 12 months after multivariable adjustment. Frequency of plastic bottle use was associated with differential abundance of some bacterial taxa, however, significance was not consistent between statistical approaches. Conclusions: Plastic bottle frequency at 3 months was not strongly associated with measures of adiposity or growth (save for length-for-age) over the first year of life, and while plastic bottle use was associated with some features of fecal microbiota and SCFAs in the first year, these findings were attenuated in multivariable models with infant diet. Future research is needed to assess health effects of exposure to other plastic-based products and objective measures of microplastics and plastic constituents like phthalates. [ABSTRACT FROM AUTHOR]

Background: In utero exposure to heavy metals lead (Pb), mercury (Hg), and cadmium (Cd) may be associated with higher childhood blood pressure (BP), whereas trace elements selenium (Se) and manganese (Mn) may have protective antioxidant effects that modify metal-BP associations. Objectives: We examined the individual and joint effects of in utero exposure to Pb, Hg, Cd, Se, and Mn on childhood BP. Methods: We used data from the Boston Birth Cohort (enrolled 2002-2013). We measured heavy metals and trace elements in maternal red blood cells collected 24-72 h after delivery. We calculated child BP percentile per the 2017 American Academy of Pediatrics Clinical Practice Guideline. We used linear regression models to estimate the association of each metal, and Bayesian kernel machine regression (BKMR) to examine metal coexposures, with child BP between 3 to 15 years of age. Results: Our analytic sample comprised 1,194 mother-infant pairs (61% non-Hispanic Black, 20% Hispanic). Hg and Pb were not associated with child systolic BP (SBP). Se and Mn were inversely associated with child SBP percentiles, which, on average, were 6.23 points lower with a doubling of Se (95% CI: -11.51, -0.96) and 2.62 points lower with a doubling of Mn (95% CI: -5.20, -0.04). BKMR models showed similar results. Although Cd was not associated with child SBP overall, the inverse association between Mn and child SBP was stronger at higher levels of Cd (p-interaction = 0.04). Consistent with this finding, in utero exposure to cigarette smoke modified the Mn-child SBP association. Among children whose mothers smoked during pregnancy, a doubling of Mn was associated with a 10.09-point reduction in SBP percentile (95% CI: -18.03, -2.15), compared with a 1.49-point reduction (95% CI: -4.21, 1.24) in children whose mothers did not smoke during pregnancy (p- interaction = 0.08). Conclusion: Se and Mn concentrations in maternal red blood cells collected 24-72 h after delivery were associated with lower child SBP at 3 to 15 years of age. There was an interaction between Mn and Cd on child SBP, whereby the protective association of Mn on child SBP was stronger among mothers who had higher Cd. The association of Mn and child SBP was also modified by maternal cigarette smoking--a source of Cd--during pregnancy. Optimizing in utero Se levels, as well as Mn levels in women who had high Cd or smoked during pregnancy, may protect offspring from developing high BP during childhood. https://doi.org/10.1289/EHP8325, Introduction High blood pressure (BP) is the leading modifiable risk factor for cardiovascular diseases (CVD) (Virani et al. 2020) and is responsible for 7.8 million deaths per year worldwide (Forouzanfar [...]

Objective: The aim of this study was to examine associations of gut microbiome diversity and composition with directly measured regional fat distribution, including central fat, in a large community‐based cohort. Methods: A cross‐sectional investigation was conducted in the Baltimore Longitudinal Study of Aging (N = 815, 55.2% female, 65.9% White). The fecal microbiome was assessed using whole‐genome shotgun metagenomic sequencing, and trunk and leg fat was measured using dual x‐ray absorptiometry. Multivariable‐adjusted associations of regional fat measures, BMI, or waist circumference with microbiome alpha diversity metrics, microbiome beta diversity metrics, and species differential abundance (verified using two compositional statistical approaches) were examined. Results: Trunk fat, leg fat, BMI, and waist circumference all significantly explained similar amounts of variance in microbiome structure. Differential abundance testing identified 11 bacterial species significantly associated with at least one measure of body composition or anthropometry. Ruminococcus gnavus was strongly and consistently associated with trunk fat mass, which is congruent with prior literature. Conclusions: Microbiome diversity and composition, in particular higher abundance of Ruminococcus gnavus, were associated with greater trunk fat, in addition to other measures of obesity. Longitudinal studies are needed to replicate these findings, and if replicated, randomized trials are needed to determine whether interventions targeting microbiome features such as abundance of Ruminococcus gnavus can lead to reductions in trunk fat and its metabolic sequelae. [ABSTRACT FROM AUTHOR]

Little is known about the most effective strategies to recruit male Latino smokers to cessation research studies. The purpose of this study was to identify efficient and cost-effective research recruitment strategies for this priority population. (Contains 4 tables.)

Background: No studies have examined whether the cord blood metabolome-a reflection of in utero metabolism-influences blood pressure (BP) in children.Objectives: To examine prospective associations of cord blood metabolites with systolic BP (SBP), diastolic BP (DBP), and risk of elevated BP in childhood and adolescence.Methods: In the Boston Birth Cohort, we measured metabolites in cord blood plasma, and SBP and DBP at clinic visits between 3 and 18 years. We examined associations of cord metabolites with SBP and DBP percentiles using linear mixed models and with elevated BP using mixed-effects Poisson regression.Results: Our study included 902 mother-child dyads (60% Black, 23% Hispanic, 45% female). Children were followed for a median of 9.2 (interquartile range, 6.7-11.7) years, and the median number of BP observations per child was 7 (interquartile range, 4-11). After false discovery rate correction, 3 metabolites were associated with SBP, 96 with DBP, and 24 with elevated BP; 2 metabolites (1-methylnicotinamide, dimethylguanidino valeric acid) were associated with all 3 outcomes, and 21 metabolites were associated with both DBP and elevated BP. After multivariable adjustment, 48 metabolites remained significantly associated with DBP. Metabolites that showed the strongest associations with SBP, DBP, and elevated BP included nucleotides (eg, xanthosine, hypoxanthine, xanthine) and acylcarnitines (eg, C6 and C7 carnitines), which represent fatty acid oxidation and purine metabolism pathways.Conclusions: In our urban and predominantly racial/ethnic minority cohort, we provide evidence that metabolomic alterations in utero, in particular, acylcarnitine- and purine-metabolism metabolites, may be involved in the early life origins of hypertension. [ABSTRACT FROM AUTHOR]

We conducted a scoping review to map available evidence about the health impact of gut microbiota-derived metabolites. We searched PubMed and Embase for studies that assessed the health impact of ten metabolites on any health condition: deoxycholate or deoxycholic acid (DCA), lithocholate or lithocholic acid (LCA), glycolithocholate or glycolithocholic acid, glycodeoxycholate or glycodeoxycholic acid, tryptamine, putrescine, d-alanine, urolithins, N-acetylmannosamine, and phenylacetylglutamine. We identified 352 eligible studies with 168,072 participants. Most (326, 92.6%) were case–control studies, followed by cohort studies (14, 4.0%), clinical trials (8, 2.3%), and cross-sectional studies (6, 1.7%). Most studies assessed the following associations: DCA on hepatobiliary disorders (64 studies, 7976 participants), colorectal cancer (19 studies, 7461 participants), and other digestive disorders (27 studies, 2463 participants); LCA on hepatobiliary disorders (34 studies, 4297 participants), colorectal cancers (14 studies, 4955 participants), and other digestive disorders (26 studies, 2117 participants); putrescine on colorectal cancers (16 studies, 94,399 participants) and cancers excluding colorectal and hepatobiliary cancers (42 studies, 4250 participants). There is a need to conduct more prospective studies, including clinical trials. Moreover, we identified metabolites and conditions for which systemic reviews are warranted to characterize the direction and magnitude of metabolite-disease associations. [ABSTRACT FROM AUTHOR]