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To estimate the age-specific incidence of uterine leiomyomas identified by transvaginal ultrasonography among participants in SELF (Study of Environment, LifestyleFibroids).SELF is a longitudinal cohort study of individuals aged 23-35 years who self-identified as Black. Participants were recruited from the Detroit, Michigan, area and underwent up to five transvaginal ultrasonograms over a period of up to 10 years to identify uterine leiomyomas. We randomly imputed incidence dates between the last ultrasonogram date in which no leiomyomas were detected and the date of the ultrasonogram in which leiomyomas were first detected. We used Poisson regression to estimate age-specific incidence rates per 1,000 person-years with 95% CIs. The rates were then compared with those of the BWHS (Black Women's Health Study) and the NHS II (Nurses' Health Study II)-two prospective cohort studies based on self-reported leiomyoma diagnoses.In this cohort, 1,693 participants completed a baseline interview and ultrasonogram. We excluded 385 (22.7%) participants with leiomyomas detected during baseline, seven participants whose ultrasonograms were poor quality, and 60 participants with only a baseline ultrasonogram. Among the remaining 1,241 participants, the overall incidence rate was 53.9 cases per 1,000 person-years (95% CI 48.6-59.6). The age-specific incidence rates (cases/1,000 person-years) were: younger than 30 years: 49.7, 95% CI 40.9-59.9; 30-34 years: 55.2, 95% CI 47.0-64.3; and 35-39 years: 58.2, 95% CI 47.3-70.9. Among participants aged younger than 30 years, the incidence rate in SELF was more than double that of the BWHS or the NHS II.The high age-specific leiomyoma incidence rates in this prospective ultrasound-based study indicate that many young Black individuals with leiomyomas go undiagnosed. These data suggest that individuals could benefit from ultrasound screening when they experience symptoms compatible with leiomyomas (eg, heavy menstrual bleeding, anemia, pelvic pain).

Background Wheeze and allergic sensitization are the strongest early-life predictors of childhood asthma development; the molecular origins of these early-life phenotypes are poorly understood. Objectives We sought to identify metabolites associated with early-life wheeze, allergic sensitization, and childhood asthma. Methods We conducted a nested case-control study using Environmental influences on Child Health Outcomes Program cohorts for discovery and independent replication. Wheeze and allergic sensitization were defined by number of wheeze episodes and positive specific IgE at age 1 year, respectively. Asthma was defined as physician diagnosis of asthma at age 5 or 6 years. We used untargeted metabolomics, controlling for observed and latent confounding factors, to assess associations between the plasma metabolome and early-life wheeze, allergy, and childhood asthma. Results Eighteen plasma metabolites were associated with first-year wheeze in the discovery cohort (n = 338). Z,Z unconjugated bilirubin (UCB) and its related metabolites exhibited a dose-response relationship with wheeze frequency; UCB levels were 13% (β = 0.87; 95% CI, 0.74-1.02) and 22% (β = 0.78; 95% CI, 0.68-0.91) lower in children with 1 to 3 and 4+ wheeze episodes compared with those who never wheezed, respectively. UCB levels were also associated with childhood asthma (β = 0.82; 95% CI, 0.68-0.98). Similar trends were observed in 2 independent cohorts. UCB was significantly negatively correlated with eicosanoid- and oxidative stress–related metabolites. There were no significant associations between metabolites and allergic sensitization. Conclusions We identified a novel inverse, dose-dependent association between UCB and recurrent wheeze and childhood asthma. Inflammatory lipid mediators and oxidative stress byproducts inversely correlated with UCB, suggesting that UCB modulates pathways critical to the development of early-life recurrent wheeze and childhood asthma.

Rationale: Birth cohort studies have identified several temporal patterns of wheezing, only some of which are associated with asthma. Whether 17q12-21 genetic variants, which are closely associated...

Background/Objectives: The association between mode of delivery and childhood obesity remains inconclusive. Because few studies have separated C-section types (planned or unplanned C-section), our objective was to assess how these subtypes relate to pre-adolescent obesity. Subjects/Methods: The study consisted of 570 maternal-child pairs drawn from the WHEALS birth cohort based in Detroit, Michigan. Children were followed-up at 10 years of age where a variety of anthropometric measurements were collected. Obesity was defined based on BMI percentile (≥95th percentile), as well as through gaussian finite mixture modeling on the anthropometric measurements. Risk ratios (RRs) and 95% confidence intervals (CIs) for obesity comparing planned and unplanned C-sections to vaginal deliveries were computed, which utilized inverse probability weights to account for loss to follow-up and multiple imputation for covariate missingness. Mediation models were fit to examine the mediation role of breastfeeding. Results: After adjusting for marital status, maternal race, prenatal tobacco smoke exposure, maternal age, maternal BMI, any hypertensive disorders during pregnancy, gestational diabetes, prenatal antibiotic use, child sex, parity, and birthweight z-score, children born via planned C-section had 1.77 times higher risk of obesity (≥95th percentile), relative to those delivered vaginally ((95% CI)=(1.16,2.72); p=0.009). No association was found comparing unplanned C-section to vaginal delivery (RR (95% CI)=0.75 (0.45, 1.23); p=0.25). Results were similar but slightly stronger when obesity was defined by anthropometric class (RR (95% CI)=2.78 (1.47, 5.26); p=0.002). Breastfeeding did not mediate the association between mode of delivery and obesity. Conclusions: These findings indicate that children delivered via planned C-section—but not unplanned C-section—have a higher risk of pre-adolescent obesity, suggesting that partial labor or membrane rupture (typically experienced during unplanned C-section delivery) may offer protection. Additional research is needed to understand the biological mechanisms behind this effect, including whether microbiological differences fully or partially account for the association.

Background: Emotional disorders, including depression and anxiety, are more prevalent in individuals with asthma than in the general population and are associated with poor asthma outcomes. Identification of patients with increased levels of stress and anxiety may be helpful when treating asthma and during asthma counseling. Objective: To further characterize the relationship between asthma symptoms and perceived stress and trait anxiety in an adolescent population. Methods: Adolescents (N = 335) ages 14‐17 years were recruited to examine the effect of stress on health measures. They were included in the present analysis if they reported current asthma, defined as self-reported clinician-diagnosed asthma plus one or more episodes of asthma in the past year. Asthma symptoms were assessed on a 7-point scale by using a standardized questionnaire that targets nocturnal awakening due to asthma, symptoms on awakening, activity limitation, shortness of breath, time spent wheezing, and short-acting bronchodilator use. Stress was measured by using the Perceived Stress Scale (PSS), and trait anxiety was measured by using the State-Trait Anxiety Inventory. Linear regression was used to associate asthma symptoms with PSS and trait anxiety. Results: Thirty-eight adolescents (11.3%), with mean ± standard deviation age 16.7 ± 0.9 years, reported current asthma. Four of the six asthma symptom assessments had significant associations with PSS: symptoms on awakening (β = 4.82, p < 0.001), nocturnal awakening due to asthma (β = 4.47, p Conclusion: Asthma symptom severity is associated with increased perceived stress and trait anxiety. Adolescents with asthma may represent a population that is particularly vulnerable to perceived stress and anxiety, which highlights the importance of considering these factors in asthma counseling.

Background: African ancestry is associated with a higher prevalence and greater severity of asthma than European ancestries, yet genetic studies of the most common locus associated with childhood-onset asthma, 17q12–21, in African Americans have been inconclusive. The aim of this study was to leverage both the phenotyping of the Children's Respiratory and Environmental Workgroup (CREW) birth cohort consortium, and the reduced linkage disequilibrium in African Americans, to fine map the 17q12–21 locus. Methods: We first did a genetic association study and meta-analysis using 17q12–21 tag single-nucleotide polymorphisms (SNPs) for childhood-onset asthma in 1613 European American and 870 African American children from the CREW consortium. Nine tag SNPs were selected based on linkage disequilibrium patterns at 17q12–21 and their association with asthma, considering the effect allele under an additive model (0, 1, or 2 effect alleles). Results were meta-analysed with publicly available summary data from the EVE consortium (on 4303 European American and 3034 African American individuals) for seven of the nine SNPs of interest. Subsequently, we tested for expression quantitative trait loci (eQTLs) among the SNPs associated with childhood-onset asthma and the expression of 17q12–21 genes in resting peripheral blood mononuclear cells (PBMCs) from 85 African American CREW children and in upper airway epithelial cells from 246 African American CREW children; and in lower airway epithelial cells from 44 European American and 72 African American adults from a case-control study of asthma genetic risk in Chicago (IL, USA). Findings: 17q12–21 SNPs were broadly associated with asthma in European Americans. Only two SNPs (rs2305480 in gasdermin-B [GSDMB] and rs8076131 in ORMDL sphingolipid biosynthesis regulator 3 [ORMDL3]) were associated with asthma in African Americans, at a Bonferroni-corrected threshold of p

Background Previous analyses in the WHEALS birth cohort demonstrated that black children are more likely to experience allergic outcomes than white children by age 2 years. The results could not be explained by a host of variables. Objective Assess whether racial disparities persisted to age 10 years and determine whether any differences could be explained by a panel of variables related to early life exposures in WHEALS. Methods At age 10 years, WHEALS children (n = 481) completed skin prick testing, spirometry and methacholine challenge, and a physician examination for eczema and asthma. Allergen-specific immunoglobulin Es (sIgE) and total IgE were measured. Inverse probability weighting with logistic and linear regression models was used to assess associations between race (black or white) and the outcomes. Results Black children fared worse than white children with respect to each outcome. Black children were more likely to have eczema, asthma, sensitization (≥1 sIgE ≥ 0.35 IU/L) and at least 1 positive skin pick test; however, some variability was present in the magnitudes of association within subgroups defined by delivery mode, sex of the child, prenatal indoor dog exposure, and firstborn status. In some subgroups, black children were also more likely to have higher total IgE and worse pulmonary function test measures (PC 20 ≤ 25 mg/mL, % predicted forced vital capacity [FVC], forced expiratory volume in 1 second [FEV1]/FVC, forced expiratory flow from 25% to 75% of vital capacity [FEF25-75]). Confounding did not explain these differences. Conclusion Racial differences persisted in this cohort through age 10 years. Future studies should include potentially important, but rarely studied factors such as segregation and structural racism, because these factors could explain the observed racial differences.

Highlights • Classification and regression tree analysis identified patterns in participation. • White people, >43 years old, with A1c > 8.9 and with Medicaid had lowest contact. • People with Medicaid, 8.1 had lowest intake session attendance. • Older males with A1c ≤ 8.3% had the highest rate (66.0%) of completing their plan., Diabetes self-management education and support (DSMES) can help people achieve optimal disease control, yet these services often remain underutilized. People referred to these programs by their provider can become disengaged in the program at several key steps. This study applies Classification and Regression Tree analysis to 3796 people with diabetes at a single health system based in the Detroit metropolitan area who were referred for DSMES provided by the health system to determine demographic patterns of those who were successfully contacted to schedule program intake appointments, those who did not attend their intake appointment, and those who began but did not complete their personalized DSMES program. White people > 43 years of age, those with a prior A1C value > 8.9 and those with Medicaid insurance had the highest rate of not being successfully contacted for their intake appointment. Those who did not attend their intake appointment tended to have Medicaid insurance, be younger than 48 years, and have A1C > 8.1. Within the Medicare or private insurance groups, those who did not attend were more likely to be female, of Black race and not partnered. Older males with a lower A1C (≤8.3%) had the lowest rate (34.0%) of failing to complete their DSMES plan. The data showed that almost half of those referred were not successfully contacted. The overall low completion rate of 13.2% confirms the need to examine factors predictive of participation and completion. This study highlights process improvement changes to improve personalization of outreach and engagement.

Importance Asthma is the leading chronic illness in US children, but most descriptive epidemiological data are focused on prevalence. Objective To evaluate childhood asthma incidence rates across the nation by core demographic strata and parental history of asthma. Design, Setting, and Participants For this cohort study, a distributed meta-analysis was conducted within the Environmental Influences on Child Health Outcomes (ECHO) consortium for data collected from May 1, 1980, through March 31, 2018. Birth cohort data of children from 34 gestational weeks of age or older to 18 years of age from 31 cohorts in the ECHO consortium were included. Data were analyzed from June 14, 2018, to February 18, 2020. Exposures Caregiver report of physician-diagnosed asthma with age of diagnosis. Main Outcome and Measures Asthma incidence survival tables generated by each cohort were combined for each year of age using the Kaplan-Meier method. Age-specific incidence rates for each stratum and asthma incidence rate ratios by parental family history (FH), sex, and race/ethnicity were calculated. Results Of the 11 404 children (mean [SD] age, 10.0 [0.7] years; 5836 boys [51%]; 5909 White children [53%]) included in the primary analysis, 7326 children (64%) had no FH of asthma, 4078 (36%) had an FH of asthma, and 2494 (23%) were non-Hispanic Black children. Children with an FH had a nearly 2-fold higher incidence rate through the fourth year of life (incidence rate ratio [IRR], 1.94; 95% CI, 1.76-2.16) after which the rates converged with the non-FH group. Regardless of FH, asthma incidence rates among non-Hispanic Black children were markedly higher than those of non-Hispanic White children during the preschool years (IRR, 1.58; 95% CI, 1.31-1.86) with no FH at age 4 years and became lower than that of White children after age 9 to 10 years (IRR, 0.67; 95% CI, 0.50-0.89) with no FH. The rates for boys declined with age, whereas rates among girls were relatively steady across all ages, particularly among those without an FH of asthma. Conclusions and Relevance Analysis of these diverse birth cohorts suggests that asthma FH, as well as race/ethnicity and sex, were all associated with childhood asthma incidence rates. Black children had much higher incidences rates but only during the preschool years, irrespective of FH. To prevent asthma among children with an FH of asthma or among Black infants, results suggest that interventions should be developed to target early life.

Background Few studies have examined longitudinal asthma incidence rates (IRs) from a public health surveillance perspective. Objective Our aim was to calculate descriptive asthma IRs in children over time with consideration for demographics and parental asthma history. Methods Data from 9 US birth cohorts were pooled into 1 population covering the period from 1980 to 2017. The outcome was earliest parental report of a doctor diagnosis of asthma. IRs per 1,000 person-years were calculated. Results The racial/ethnic backgrounds of the 6,283 children studied were as follows: 55% European American (EA), 25.5% African American (AA), 9.5% Mexican-Hispanic American (MA) and 8.5% Caribbean-Hispanic American (CA). The average follow-up was 10.4 years (SD = 8.5 years; median = 8.4 years), totaling 65,291 person-years, with 1789 asthma diagnoses yielding a crude IR of 27.5 per 1,000 person-years (95% CI = 26.3-28.8). Age-specific rates were highest among children aged 0 to 4 years, notably from 1995 to 1999, with a decline in EA and MA children in 2000 to 2004 followed by a decline in AA and CA children in 2010 to 2014. Parental asthma history was associated with statistically significantly increased rates. IRs were similar and higher in AA and CA children versus lower but similar in EA and MA children. The differential rates by sex from birth through adolescence principally resulted from a decline in rates among males but relatively stable rates among females. Conclusions US childhood asthma IRs varied dramatically by age, sex, parental asthma history, race/ethnicity, and calendar year. Higher rates in the 0- to 4-year-olds group, particularly among AA/CA males with a parental history of asthma, as well as changes in rates over time and by demographic factors, suggest that asthma is driven by complex interactions between genetic susceptibility and variation in time-dependent environmental and social factors.

Childhood sensitization patterns have been previously found to be related to variable risk of early life allergic disease in several birth cohorts.To determine whether these risks persist into later childhood.In the birth cohort of the Wayne County Health, Environment, Allergy and Asthma Longitudinal Study, previous latent class analysis based on sensitization to 10 allergens found the following 4 early life sensitization patterns at age 2 years: "highly sensitized," "milk/egg dominated," "peanut and inhalant(s)," and "low to no sensitization." At an age 10 study-specific visit, children were evaluated by an allergist for current asthma and atopic dermatitis through a physical examination and interviews with the child and parent or guardian. Total and specific immunoglobulin E (IgE), spirometry, and methacholine challenge were also completed.Compared with children sensitized to none or 1 allergen, children sensitized to 4 or more food and inhalant allergens at age 2 had the highest risk of current asthma (relative risk [RR], 4.42; 95% confidence interval [CI], 2.58-7.59; P.001) and bronchial hyperresponsiveness (RR, 1.77; 95% CI, 1.29-2.42; P.001). In addition, they had the highest levels of total IgE (geometric mean, 800 IU/mL; 95% CI, 416-1536) among the 4 groups. Risk of current atopic dermatitis did not depend on pattern of sensitization but remained increased for children with any sensitization (RR, 2.23; 95% CI, 1.40-3.55; P.001). No differences in spirometry (forced expiratory volume in 1 second, forced expiratory flow between 25% and 75%, and forced expiratory volume in 1 second/forced vital capacity) were identified.The previously reported importance of a specific pattern of sensitization in early life (sensitization to ≥4 inhalant and food allergens) continues to be associated with an increased risk of asthma, bronchial hyperresponsiveness, and high total IgE at age 10 years.

In a cohort of pregnant women patterns of allergic sensitization in adulthood were not found to differ between women with current asthma starting before or after 15 years of age.

Background Mounting evidence suggests both vitamin D and the early life gut microbiome influence childhood health outcomes. However, little is known about how these two important exposures are related. We aimed to examine associations between plasma 25-hydroxyvitamin D (25[OH]D) levels during pregnancy or at delivery (cord blood) and infant gut microbiota. Methods Maternal and cord blood 25[OH]D levels were assessed in a sample of pregnant women. Compositional analyses adjusted for race were run on the gut microbiota of their offspring at 1 and 6 months of age. Results Mean prenatal 25(OH)D level was 25.04 ± 11.62 ng/mL and mean cord blood 25(OH)D level was 10.88 ± 6.77 ng/mL. Increasing prenatal 25(OH)D level was significantly associated with decreased richness (p = 0.028) and diversity (p = 0.012) of the gut microbiota at 1 month of age. Both prenatal and cord 25(OH)D were significantly associated with 1 month microbiota composition. A total of 6 operational taxonomic units (OTUs) were significantly associated with prenatal 25(OH)D level (four positively and two negatively) while 11 OTUs were significantly associated with cord 25(OH)D (10 positively and one negatively). Of these, OTU 93 (Acinetobacter) and OTU 210 (Corynebacterium), were consistently positively associated with maternal and cord 25(OH)D; OTU 64 (Ruminococcus gnavus) was positively associated with prenatal 25(OH)D but negatively associated with cord 25(OH)D. Conclusions Prenatal maternal and cord blood 25(OH)D levels are associated with the early life gut microbiota. Future studies are needed to understand how vitamin D and the microbiome may interact to influence child health.

In this first of a two-part series on introductory biostatistics, we briefly describe common designs. The advantages and disadvantages of six design types are highlighted. The randomized clinical trial is the gold standard to which other designs are compared. We present the benefits of randomization and discuss the importance of power and sample size. Sample size and power calculations for any design need to be based on meaningful effects of interest. We give examples of how the effect of interest and the sample size interrelate. We also define concepts helpful to the statistical inference process. When drawing conclusions from a completed study, P values, point estimates, and confidence intervals will all assist the researcher. Finally, the issue of multiple comparisons is briefly explored. The second paper in this series will describe basic analytical techniques and discuss some common mistakes in the interpretation of data.

The recruitment setting plays a key role in the evaluation of behavioral interventions. We evaluated a behavioral intervention for urban adolescents with asthma in three randomized trials conducted separately in three different settings over the course of 8 years. We hypothesized that characteristics of trial participants recruited from the ED and clinic settings would be significantly different from that of youth participating in the school-based trials. The intervention evaluated was Puff City, a web-based program that uses tailoring to improve asthma management behaviors.The present analysis includes youth aged 13-19 years who reported a physician diagnosis of asthma and symptoms at trial baseline. In the three trials, all participants were randomized post-baseline to a web-based, tailored intervention (treatment) or generic web-based asthma education (control).Compared to school-based trial participants, ED participants had significantly more acute-care visits for asthma (Compared to participants in the school-based trials, participants recruited from ED and clinic settings differed significantly in terms of healthcare use, as well as psychosocial and sociodemographic factors. These factors can inform intervention content, and may impact external validity of behavioral interventions for asthma.

Research has largely reported that dog exposure is associated with reduced allergic disease risk. Responsible mechanism(s) are not understood. The goal was to investigate whether introducing a dog into the home changes the home dust microbiota. Families without dogs or cats planning to adopt a dog and those who were not were recruited. Dust samples were collected from the homes at recruitment and 12 months later. Microbiota composition and taxa (V4 region of the 16S rRNA gene) were compared between homes that did and did not adopt a dog. A total of 91 dust samples from 54 families (27 each, dog and no dog; 17 dog and 20 no dog homes with paired samples) were analyzed. A significant dog effect was seen across time in both unweighted UniFrac and Canberra metrics (both P = .008), indicating dog introduction may result in rapid establishment of rarer and phylogenetically related taxa. A significant dog-time interaction was seen in both weighted UniFrac (P < .001) and Bray-Curtis (P = .002) metrics, suggesting that while there may not initially be large relative abundance shifts following dog introduction, differences can be seen within a year. Therefore, dog introduction into the home has both immediate effects and effects that emerge over time.

Many studies suggest a role for cholesterol in cancer development. Serum cholesterol levels have been observed to be low in newly diagnosed lymphoma cases. The objective of these analyses was to examine the time-varying relationship of cholesterol with lymphomagenesis in the 10 years prior to diagnosis by lymphoma subtype. Participants were selected from the combined membership of six National Cancer Institute-funded Cancer Research Network health plans from 1998 to 2008, excluding members with human immunodeficiency virus, cancer (except lymphoma), or organ transplants. Incident lymphoma cases within this population were ascertained and matched with up to five controls. Total serum cholesterol, high-density lipoprotein, and low-density lipoprotein were collected from plan databases. Multilevel, multivariable longitudinal models were fit after choosing the best polynomial order by deviance statistics for selected lymphoma histotypes to examine pre-diagnosis cholesterol trajectories: Hodgkin lymphoma (n = 519) and all non-Hodgkin lymphomas combined (n = 12,635) as well as six subtypes of the latter. For all categories, lymphoma cases had statistically significantly lower estimated total serum cholesterol, high-density lipoprotein, and low-density lipoprotein levels than controls in the years prior to diagnosis/index date. Between-group differences were most pronounced 3–4 years prior to diagnosis, when cases’ cholesterol levels declined steeply. This analysis is the first to examine changes in serum cholesterol for a decade prior to lymphoma diagnosis. A drop in cholesterol levels was evident several years before diagnosis. Our results suggest that cholesterol-related pathways have an important relationship with lymphomagenesis and low cholesterol could be a preclinical lymphoma marker.

Background: Recent public health lead crises in urban areas emphasize the need to better understand exposure to environmental toxicants, particularly in higher risk groups. Although African-American children have the highest prevalence of elevated blood lead levels in the United States, little is known about when this trajectory of disproportionate burden of lead exposure first emerges. Objectives: Using tooth-matrix biomarkers that directly measure fetal and early childhood metal levels, the primary goal of this study was to determine if there were racial disparities in lead levels during fetal development and early childhood. Manganese, an essential nutrient that modifies the neurotoxic effects of lead, was also measured. Methods: Pregnant women served by the Henry Ford Health System and living in a predefined geographic area in and around Detroit, Michigan, were recruited during the second trimester or later into the Wayne County Health, Environment, Allergy and Asthma Longitudinal Study (WHEALS), a population-based birth cohort. Offspring born between September 2003 and December 2007 were studied in childhood. Child race was parent-reported. Lead and manganese during the second and third trimesters, early postnatal life (birth through age 1year) and early childhood (age 1 through time of tooth shedding, which ranges from 6 to 12years) were measured via high-resolution microspatial mapping of dentin growth rings, a validated biomarker for prenatal and childhood metal exposure. Results: African-American children (N=71) had 2.2 times higher lead levels in the second and third trimesters (both p

Breast milk is a complex bioactive fluid that varies across numerous maternal and environmental conditions. Although breast-feeding is known to affect neonatal gut microbiome, the milk components responsible for this effect are not well-characterized. Given the wide range of immunological activity breast milk cytokines engage in, we investigated 3 essential breast milk cytokines and their association with early life gut microbiota.A total of 52 maternal-child pairs were drawn from a racially diverse birth cohort based in Detroit, Michigan. Breast milk and neonatal stool specimens were collected at 1-month postpartum. Breast milk transforming growth factor (TGF)β1, TGFβ2, and IL-10 were assayed using enzyme-linked immunosorbent assays, whereas neonatal gut microbiome was profiled using 16S rRNA sequencing.Individually, immunomodulators TGFβ1 and TGFβ2 were significantly associated with neonatal gut microbial composition (R = 0.024, P = 0.041; R = 0.026, P = 0.012, respectively) and increased richness, evenness, and diversity, but IL-10 was not. The effects of TGFβ1 and TGFβ2, however, were not independent of one another, and the effect of TGFβ2 was stronger than that of TGFβ1. Higher levels of TGFβ2 were associated with the increased relative abundance of several bacteria, including members of Streptococcaceae and Ruminococcaceae, and lower relative abundance of distinct Staphylococcaceae taxa.Breast milk TGFβ concentration explains a portion of variability in gut bacterial microbiota composition among breast-fed neonates. Whether TGFβ acts in isolation or jointly with other bioactive components to alter bacterial composition requires further investigation. These findings contribute to an increased understanding of how breast-feeding affects the gut microbiome-and potentially immune development-in early life.

Growing evidence suggests that antibiotic use is associated with childhood body mass index (BMI), potentially via mechanisms mediated by gut microbiome alterations. Less is known on the potential role of prenatal antimicrobial use in offspring obesity risk. We examined whether prenatal antibiotic or antifungal use was associated with BMI at the age of 2 years in 527 birth cohort participants. Antimicrobial use was obtained from the prenatal medical record. Height and weight were measured at the age of 2 years. Overweight/obesity was defined as a BMI ⩾85th percentile. A total of 303 (57.5%) women used antibiotics and 101 (19.2%) used antifungals during pregnancy. Prenatal antifungal use was not associated with child BMI at the age of 2 years. In the fully adjusted model, prenatal antibiotic use was associated with a 0.20±0.10 (P=0.046) higher mean BMI Z-score at the age of 2 years. Associations between prenatal antibiotic use and childhood BMI varied by trimester of exposure, with first or second-trimester exposure more strongly associated with larger BMI at the age of 2 years for both BMI Z-score (interaction P=0.032) and overweight/obesity (interaction P=0.098) after covariate adjustment. Prenatal antibiotic, but not antifungal, use is associated with larger BMI at the age of 2 years; associations were stronger for antibiotic exposures in earlier trimesters. Future studies examining whether these associations are due to alterations in the maternal and/or infant microbiome are necessary. Children who are overweight at the age of 2 years are at higher risk for being overweight as they age; prenatal antibiotic use is a potentially modifiable exposure that could reduce childhood obesity.

Background Infant feeding practices are thought to shape food acceptance and preferences. However, few studies have evaluated whether these affect child diet later in life. Objective The study objective was to examine the association between infant feeding practices and dietary patterns (DPs) in school-aged children. Design A secondary analysis of data from a diverse prospective birth cohort with 10 years of follow-up (WHEALS [Wayne County Health Environment Allergy and Asthma Longitudinal Study]) was conducted. Participants/setting Children from the WHEALS (Detroit, MI, born 2003 through 2007) who completed a food screener at age 10 years were included (471 of 1,258 original participants). Main outcome measures The main outcome was DPs at age 10 years, identified using the Block Kids Food Screener. Statistical analysis performed Latent class analysis was applied for DP identification. Breastfeeding and age at solid food introduction were associated with DPs using a 3-step approach for latent class modeling based on multinomial logistic regression models. Results The following childhood DPs were identified: processed/energy-dense food (35%), variety plus high intake (41%), and healthy (24%). After weighting for loss to follow-up and covariate adjustment, compared with formula-fed children at 1 month, breastfed children had 0.41 times lower odds of the processed/energy-dense food DP vs the healthy DP (95% CI 0.14 to 1.25) and 0.53 times lower odds of the variety plus high intake DP (95% CI 0.17 to 1.61), neither of which were statistically significant. Results were similar, but more imprecise, for breastfeeding at 6 months. In addition, the association between age at solid food introduction and DP was nonsignificant, with each 1-month increase in age at solid food introduction associated with 0.81 times lower odds of the processed/energy-dense food DP relative to the healthy DP (95% CI 0.64 to 1.02). Conclusions A significant association between early life feeding practices and dietary patterns at school age was not detected. Large studies with follow-up beyond early childhood that can also adjust for the multitude of potential confounders associated with breastfeeding are needed.

The effect of dog exposure on the risk of children developing allergic disease remains controversial. Many analyses have not considered that associations may vary within population subgroups.To examine whether associations between living with a dog in the first year of life and allergic outcomes vary within subgroups selected a priori (race, gender and delivery mode).Black (n = 496) and White (n = 196) children enrolled in the WHEALS birth cohort study had a clinical examination at age 2 years to assess eczema and allergen-specific IgE (sIgE) and perform skin prick testing (SPT). Whether the child lived with an indoor dog in the first year of life was assessed through interview, as was doctor diagnosis of asthma at ages 3-6 years.Living with a dog was associated with decreased odds of having ≥ 1 positive SPT (OR = 0.56, 95% CI: 0.34, 0.91) and having eczema (OR = 0.34, 95% CI: 0.20, 0.60). The association with SPT was stronger in those children born via caesarean section (c-section) vs. vaginally (OR = 0.29, 95% CI: 0.12, 0.74 vs. OR = 0.76, 95% CI: 0.43, 1.37, respectively, interaction P = 0.087) and in those who were firstborn vs. not (OR = 0.27, 95% CI: 0.11, 0.67 vs. OR = 0.82, 95% CI: 0.45, 1.47, respectively, interaction P = 0.044). The association with eczema was stronger in children born vaginally compared with those born via caesarean section (OR = 0.17, 95% CI: 0.06, 0.43 vs. OR = 0.65, 95% CI: 0.31, 1.35, respectively, interaction P = 0.025) and was stronger in Black vs. White children (OR = 0.30, 95% CI: 0.15, 0.61 vs. OR = 0.78, 95% CI: 0.29, 2.11, respectively, interaction P = 0.12). Dog keeping was not significantly inversely associated with having ≥ 1 elevated sIgE and only approached statistical significance with asthma.Results likely vary between studies due to variability of specific exposure-outcome associations in subgroups defined by other factors as well as the relative distributions of those subgroups. Important allergic disorder associations will be missed without subgroup analyses.

Gut microbiota bacterial depletions and altered metabolic activity at 3 months are implicated in childhood atopy and asthma. We hypothesized that compositionally distinct human neonatal gut microbiota (NGM) exist, and are differentially related to relative risk (RR) of childhood atopy and asthma. Using stool samples (n = 298; aged 1-11 months) from a US birth cohort and 16S rRNA sequencing, neonates (median age, 35 d) were divisible into three microbiota composition states (NGM1-3). Each incurred a substantially different RR for multisensitized atopy at age 2 years and doctor-diagnosed asthma at age 4 years. The highest risk group, labeled NGM3, showed lower relative abundance of certain bacteria (for example, Bifidobacterium, Akkermansia and Faecalibacterium), higher relative abundance of particular fungi (Candida and Rhodotorula) and a distinct fecal metabolome enriched for pro-inflammatory metabolites. Ex vivo culture of human adult peripheral T cells with sterile fecal water from NGM3 subjects increased the proportion of CD4+ cells producing interleukin (IL)-4 and reduced the relative abundance of CD4+CD25+FOXP3+ cells. 12,13-DiHOME, enriched in NGM3 versus lower-risk NGM states, recapitulated the effect of NGM3 fecal water on relative CD4+CD25+FOXP3+ cell abundance. These findings suggest that neonatal gut microbiome dysbiosis might promote CD4+ T cell dysfunction associated with childhood atopy.

Purpose Measurement of socioeconomic status (SES) is traditionally based on education, income, and occupation. This information may not be readily available from adolescents participating in research. Methods Using data from school-based randomized trial of an asthma intervention targeting urban adolescents, we compared percent poverty in zip code of residence (% poverty), median housing value, and parental income and education, to teen responses on the Home Affluence Scale for Children (HASC), which included home, car, and computer ownership for the family and eligibility for free school lunch. The association of HASC with measures of asthma control was also assessed. Results Of 422 adolescents, 390 (92%) responded to HASC items (mean HASC = 2.5). HASC was associated with mother's education and household income (both P

Early patterns of gut colonization may predispose children to adult disease. Exposures in utero and during delivery are associated with the infant gut microbiome. Although ~35% of women carry group B strep (GBS; Streptococcus agalactiae) during pregnancy, it is unknown if GBS presence influences the infant gut microbiome. As part of a population-based, general risk birth cohort, stool specimens were collected from infant’s diapers at research visits conducted at ~1 and 6 months of age. Using the Illumina MiSeq (San Diego, CA) platform, the V4 region of the bacterial 16S rRNA gene was sequenced. Infant gut bacterial community compositional differences by maternal GBS status were evaluated using permutational multivariate analysis of variance. Individual operational taxonomic units (OTUs) were tested using a zero-inflated negative binomial model. Data on maternal GBS and infant gut microbiota from either 1 (n=112) or 6-month-old stool (n=150) specimens was available on 262 maternal-child pairs. Eighty women (30.5%) were GBS+, of who 58 (72.5%) were given intrapartum antibiotics. After adjusting for maternal race, prenatal antifungal use and intrapartum antibiotics, maternal GBS status was statistically significantly associated with gut bacterial composition in the 6 month visit specimen (Canberra R2=0.008, P=0.008; Unweighted UniFrac R2=0.010, P=0.011). Individual OTU tests revealed that infants of GBS+ mothers were significantly enriched for specific members of the Clostridiaceae, Ruminococcoceae, and Enterococcaceae in the 6 month specimens compared with infants of GBS- mothers. Whether these taxonomic differences in infant gut microbiota at 6 months lead to differential predisposition for adult disease requires additional study.

Objective To observe the occurrence of pregnancy in women undergoing minimally invasive and open myomectomy for symptoms attributed to uterine fibroids and who desire future pregnancy. Methods We performed a retrospective chart review of women who had undergone myomectomy at least two years previously within the Henry Ford Health System in Detroit, MI. We reviewed the subsequent fertility outcomes according to the fertility goals identified by each woman. Results During the seven-year observation window, 310 women underwent myomectomy and 124 (40%) of these women desired pregnancy. Forty-nine women desiring pregnancy (40%) conceived, and 30 (61% of those who conceived) delivered a viable infant from their first pregnancy. In addition, two women had a live birth after a miscarriage, and one had a live birth after an ectopic pregnancy. Five women had a second live-born baby. There were no differences in the occurrence of pregnancy or pregnancy outcome according to surgical approach, patient age or race, number of uterine incisions, or whether the endometrial cavity was entered. In addition, five of 186 women who did not have a fertility goal (3%) conceived, and one woman delivered two babies. Conclusion Myomectomy performed to preserve fertility resulted in approximately one in four women having a live birth, independent of surgical technique.

The infant gut's ability to suppress immunologic reactions to food proteins could be influenced by levels of TGFβ in breast milk. We hypothesized that lower levels of TGFβ(1) in the breast milk (BM) of mothers in the WHEALS birth cohort are associated with atopy at infant age 2-3 yrs.We used data collected during infancy in addition to the results of skin prick tests (SPT+) and measures of specific IgE0.35 IU/ml (spIgE) to milk, egg, and peanut at infant age 2-3 years. Infants were classified as food allergic (FA) based on parental report of infant symptoms/diagnoses and information from clinical assessments.Data for 304 cohort members were analyzed. Among non-black infants, BM-TGFβ(1) was lower for those classified as FA (vs. no FA) and those SPT+ (vs., SPT-), geometric mean = 1100 pg/ml vs. 1417pg/ml, p = 0.081; and 1100 pg/ml vs. 1415pg/ml, p = 0.064, respectively. Among infants of non-atopic mothers, BM-TGFβ(1) was lower for those with elevated (vs. not elevated) sIgE, geometric mean = 1347 pg/ml vs. 1651 pg/ml, p = 0.047. Using logistic regression, adjusted odds ratios describing the association of BM-TGFβ1 to the presence of atopic indicators in the infant were in the hypothesized direction only for non-black infants of non-atopic mothers: aORs for FA, sIgE and SPT+ were 0.08, 0.34, and 0.26 respectively; p = 0.091, 0.13, and 0.23.Immune benefit of BM-TGFβ(1) could inform prevention strategies. Evidence of an association appears greatly influenced by infant race and maternal atopy. More research can determine if these relationships represent a modifiable risk factor for the development of food allergy in certain subgroups.

Asthma definitions vary widely across research studies and feature a trade-off between inclusivity and precision. Harmonizing definitions across multiple asthma birth cohort studies highlights these challenges.

It is unknown whether family members with detectable specific immunoglobulin E (sIgE) and/or allergic symptoms to pets are more or less likely to reside in a household with pets. We cross-sectionally investigated potential relationships between family members’ allergic sensitization and symptoms to dogs and cats and current household pet-keeping practices, using birth cohort data. Blood samples taken from children enrolled in a birth cohort and their biological mothers and fathers, when the children were aged 18 years, were assessed for sIgE to dog and cat allergens. Interviews assessed subjects’ self-reported pet exposure symptoms, current household pet-keeping practices, and socioeconomic characteristics. Overall, household dog or cat keeping was not associated with sIgE to these animals and/or self-reported allergic symptoms in the presence of these animals, even after controlling for factors such as education and household income. In subgroup analyses, current household dog keeping among dog-symptomatic teens (n 40) was significantly lower than among teens who were not dog symptomatic (n 289), at 48.8 and 61.1%, respectively (p 0.036). Current household cat keeping was significantly lower among cat-symptomatic mothers (n 27) compared with mothers who were not cat symptomatic (n 120), at 24.3 and 37.0%, respectively (p 0.015). However, when considering those who were both sensitized and reported symptoms, only the mother and cat-keeping associations persisted (p 0.049). When cat-sensitized mothers report allergic symptoms to cats, these pets may be less likely to be kept in homes. Elevated dog and cat allergen sIgE does not appear to be associated with the keeping of these pets. (Allergy Asthma Proc 34:504 –510, 2013; doi: 10.2500/aap.2013.34.3698)

Exclusive breastfeeding during the first month of life and vaginal delivery may mitigate the transmission of atopy from mother to child. These results could have implications for potential targeted prevention strategies in high-risk offspring of atopic mothers.

Introduction Microbial-related exposures in early life stimulate immune development and may protect against allergic disease manifestations later in life. Parental pacifier sucking in early life may offer protection through the transfer of beneficial oral microbes from parent to offspring. Methods Using maternal-child pairs from the Microbes, Allergy, Asthma and Pets cohort(N=141), we investigated whether pacifier cleaning methods reported at 6-months of age were associated with differences in serum total IgE over the first 18 months of life(cord, 6-months, and 18-months). Linear mixed effect models were used to model log-transformed total IgE trajectories. Results Of 128 mothers completing an interview at 6 months, 74(58%) reported current child pacifier use. Of these 74, 30(41%) reported pacifier cleaning by sterilization, 53(72%) reported handwashing the pacifier, and 9(12%) reported parental pacifier sucking. Pacifier sterilization or handwashing were not associated with serum total IgE trajectory. A significant time interaction was detected for pacifier sucking(p=0.079), indicating that the trajectory shape differed between children of pacifier-sucking versus non-pacifier sucking parents. Specifically, parental pacifier sucking appeared to suppress serum IgE levels beginning around 10 months(p=0.048), and continued to diverge through 18 months(p=0.014). Conclusions These results show an association between parental pacifier sucking and lower early-life total IgE production. Further research is needed to assess whether these differences are due to the transfer of parental oral microbes, and if allergic disease risk later in life is sustained. These findings support a previous Swedish study reporting a protective effect of parental pacifier sucking on the risk of allergic diseases in children. Difference in total IgE trajectory by parental sucking of pacifiers - among children who used pacifiers at 6-months of age.

Background Environmental allergens may induce the generation of allergen-specific IgE (sIgE) and IgG4 (sIgG4). Some studies report an association of sIgG4 to protection against allergic symptoms after exposure to the relevant allergen. Objective We examined the relationship of dog and cat sIgE and sIgG4 levels to self-reported allergic symptoms on pet contact. Methods Participants 18 years of age in the Detroit Childhood Allergy Study cohort were asked whether they experienced symptoms on exposure to cats and dogs. Serum was assayed for cat and dog sIgE and sIgG4. Geometric means, ratios of cat and dog sIgE, sIgG4, and ratios of sIgG4/sIgE were compared between symptomatic and asymptomatic teens with the use of Wilcoxon rank sum tests. Ratios of sIgG4/sIgE, adjusted for presence of sIgE (≥0.35 kU/mL), were analyzed with logistic regression. Results Data on 500 participants were analyzed. Compared with asymptomatic teens, teens symptomatic with cat exposure had higher cat sIgE, sIgG4, and lower ratio of sIgG4/sIgE. Teens symptomatic after dog exposure had higher dog sIgE levels and lower sIgG4/sIgE, but similar levels of sIgG4 compared with asymptomatic participants. Increasing cat and dog sIgG4/sIgE ratios were associated with a lower likelihood of reporting allergic symptoms (cat: adjusted odds ratio, 0.8; 95% CI, 0.6-0.9; dog: adjusted odds ratio, 0.8; 95% CI, 0.7-1.0). Conclusion sIgG4 levels to cat and dog allergens correlate with lower rates of pet-induced allergic symptoms when interpreted in the context of concomitant sIgE. However, sIgG4 appears to have little utility as an isolated marker to indicate that pet exposure will be well tolerated.

Problem Uterine leiomyomata are the most common reproductive tumor in women, and their cause is not known. Methods of Study Plasma samples from 155 women (74 with and 81 without ultrasound-confirmed leiomyoma) from a new study of leiomyoma risk factors in the Detroit, Michigan area, were examined for any cross-sectional associations between commonly examined cytokines and leiomyoma presence. Results Associations varied by season of sample collection defined a priori as winter (December–February) and non-winter seasons. In the winter months, interleukin (IL)13 and IL17 were positively and IP10 was inversely associated with having a leiomyoma. In the non-winter samples, VEGF, G-CSF, and IP10 were positively associated and Monocyte chemotactic protein-1, IL13, and IL17 were inversely associated with having a leiomyoma. Associations were not changed by adjustment for age or BMI. Conclusions These data suggest that new insight into leiomyoma formation may be acquired through investigation of the immune system.

Asthma interventions targeting urban adolescents are rare, despite a great need. Motivating adolescents to achieve better self-management of asthma is challenging, and the literature suggests that certain subgroups are more resistant than others. We conducted a school-based, randomized controlled trial (RCT) to evaluate Puff City, a Web-based, tailored asthma intervention, which included a referral coordinator, and incorporated theory-based strategies to target urban teens with characteristics previously found to be associated with lack of behavior change.To identify eligible teens, we administered questionnaires on asthma diagnoses and symptoms to ninth through 12th graders of participating schools during a scheduled English class. We randomized eligible, consenting students to Puff City (treatment) or generic asthma education (control).We randomized 422 students (98% African-American, mean age = 15.6 years). At 12-month follow-up, adjusted odds ratios (aORs) (95% confidence intervals) indicated intervention benefit for treatment teens for symptom-days and restricted activity days (analyzed as categorical variables) as aOR = .49 (.24-.79), p = .006 and .53 (.32-.86), p = .010, respectively. Among teens meeting baseline criteria for rebelliousness, treatment teens reported fewer symptom-days, symptom-nights, school absences, and restricted activity days: aOR = .30 (.11-.80), .29 (.14-.64), .40 (.20-.78), and .23 (.10-.55); all p.05. Among teens reporting low perceived emotional support, treatment students reported only fewer symptom-days than controls: aOR = .23 (.06-.88), p = .031. We did not observe statistically significant differences in medical care use.Results suggest that a theory-based, tailored approach, with a referral coordinator, can improve asthma management in urban teens. Puff City represents a viable strategy for disseminating an effective intervention to high-risk and hard-to-reach populations.

The joint impact of pregnancy, environmental, and sociocultural exposures on early life gut microbiome is not yet well-characterized, especially in racially and socioeconomically diverse populations. Gut microbiota of 298 children from a Detroit-based birth cohort were profiled using 16S rRNA sequencing: 130 neonates (median age = 1.2 months) and 168 infants (median age = 6.6 months). Multiple factors were associated with neonatal gut microbiome composition in both single- and multi-factor models, with independent contributions of maternal race-ethnicity, breastfeeding, mode of delivery, marital status, exposure to environmental tobacco smoke, and indoor pets. These findings were consistent in the infants, and networks demonstrating the shared impact of factors on gut microbial composition also showed notable topological similarity between neonates and infants. Further, latent groups defined by these factors explained additional variation, highlighting the importance of combinatorial effects. Our findings also have implications for studies investigating the impact of the early life gut microbiota on disease.