The impact of prenatal dog keeping on infant gut microbiota development.

INTRODUCTION: Prenatal and early-life dog exposure has been linked to reduced childhood allergy and asthma. A potential mechanism includes altered early immune development in response to changes in the gut microbiome among dog-exposed infants. We thus sought to determine whether infants born into homes with indoor dog(s) exhibit altered gut microbiome development. METHODS: Pregnant women living in homes with dogs or in pet-free homes were recruited in southeast Michigan. Infant stool samples were collected at intervals between 1 week and 18 months after birth and microbiome was assessed using 16S ribosomal sequencing. Perinatal maternal vaginal/rectal swabs and stool samples were sequenced from a limited number of mothers. Mixed effect adjusted models were used to assess stool microbial community trajectories comparing infants from dog-keeping versus pet-free homes with adjustment for relevant covariates. RESULTS: Infant gut microbial composition among vaginally born babies became less similar to the maternal vaginal/rectal microbiota and more similar to the maternal gut microbiota with age-related accumulation of bacterial species with advancing age. Stool samples from dog-exposed infants were microbially more diverse (p = .041) through age 18 months with enhanced diversity most apparent between 3 and 6 months of age. Statistically significant effects of dog exposure on ß-diversity metrics were restricted to formula-fed children. Across the sample collection period, dog exposure was associated with Fusobacterium genera enrichment, as well as enrichment of Collinsella, Ruminococcus, Clostridaceae and Lachnospiraceae OTUs. CONCLUSION: Prenatal/early-life dog exposure is associated with an altered gut microbiome during infancy and supports a potential mechanism explaining lessened atopy and asthma risk. Further research directly linking specific dog-attributable changes in the infant gut microbiome to the risk of allergic disorders is needed.

Early-life gut microbiota and attention deficit hyperactivity disorder in preadolescents.

BACKGROUND: Gut microbiota maturation coincides with nervous system development. Cross-sectional data suggest gut microbiota of individuals with and without attention deficit hyperactivity disorder (ADHD) differs. We hypothesized that infant gut microbiota composition is associated with later ADHD development in our on-going birth cohort study, WHEALS. METHODS: Gut microbiota was profiled using 16S ribosomal RNA and the internal transcribed spacer region 2 (ITS2) sequencing in stool samples from 1 month and 6 months of age. ADHD was defined by parent-reported or medical record doctor diagnosis at age 10. RESULTS: A total of 314 children had gut microbiota and ADHD data; 59 (18.8%) had ADHD. After covariate adjustment, bacterial phylogenetic diversity (p = 0.017) and bacterial composition (unweighted UniFrac p = 0.006, R2 = 0.9%) at age 6 months were associated with development of ADHD. At 1 month of age, 18 bacterial and 3 fungal OTUs were associated with ADHD development. At 6 months of age, 51 bacterial OTUs were associated with ADHD; 14 of the order Lactobacillales. Three fungal OTUs at 6 months of age were associated with ADHD development. CONCLUSIONS: Infant gut microbiota is associated with ADHD development in pre-adolescents. Further studies replicating these findings and evaluating potential mechanisms of the association are needed. IMPACT: Cross-sectional studies suggest that the gut microbiota of individuals with and without ADHD differs. We found evidence that the bacterial gut microbiota of infants at 1 month and 6 months of age is associated with ADHD at age 10 years. We also found novel evidence that the fungal gut microbiota in infancy (ages 1 month and 6 months) is associated with ADHD at age 10 years. This study addresses a gap in the literature in providing longitudinal evidence for an association of the infant gut microbiota with later ADHD development.

Infant gut bacterial community composition and food-related manifestation of atopy in early childhood.

BACKGROUND: Immunoglobulin E-mediated food allergy (IgE-FA) has emerged as a global public health concern. Immune dysregulation is an underlying mechanism for IgE-FA, caused by "dysbiosis" of the early intestinal microbiota. We investigated the association between infant gut bacterial composition and food-related atopy at age 3-5 years using a well-characterized birth cohort. METHODS: The study definition of IgE-FA to egg, milk, or peanut was based on physician panel retrospective review of clinical and questionnaire data collected from birth through age 3-5 years. Using 16S rRNA sequencing, we profiled the bacterial gut microbiota present in stool specimens collected at 1 and 6 months of age. RESULTS: Of 447 infants with data for analysis, 44 (9.8%) met physician panel review criteria for IgE-FA to ≥1 of the three allergens. Among children classified as IgE-FA at 3-5 years, infant stool samples showed significantly less diversity of the gut microbiota compared with the samples of children classified as no IgE-FA at age 3-5 years, especially for milk and peanut (all covariate-adjusted p's for alpha metrics <.007). Testing of individual operational taxonomic units (OTUs) revealed 6-month deficiencies in 31 OTUs for IgE-FA compared with no IgE-FA, mostly in the orders Lactobacillales, Bacteroidales, and Clostridiales. CONCLUSIONS: Variations in gut microbial composition in infant stool were associated with a study definition of IgE-FA at 3-5 years of age. This included evidence of a lack of bacterial diversity, deficiencies in specific OTUs, and delayed microbial maturation. Results support dysbiosis in IgE-FA pathogenesis.

Pediatric asthma incidence rates in the United States from 1980 to 2017.

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.

Participant-level characteristics differ by recruitment setting when evaluating a behavioral intervention targeting adolescents with asthma.

OBJECTIVE: 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. METHODS: 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). RESULTS: Compared to school-based trial participants, ED participants had significantly more acute-care visits for asthma (p < 0.001) and more caregiver depression (p < 0.001). Clinic-based participants were more likely to have computer/ internet access than participants from the school-based trial (p < 0.001). Both ED and clinic participants were more likely to report controller medication (p's < 0.001) and higher teen emotional support (p's < 0.01) when compared to the schools, but were less likely to report Medicaid (p's < 0.014) and exposure to environmental tobacco smoke (p < 0.001). CONCLUSION: 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.

Association between cesarean delivery types and obesity in preadolescence.

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 preadolescent 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). The 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 preadolescent 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.

The impact of traditional literacy and education on health literacy in adolescents with asthma.

Introduction: People with low health literacy have poorer self-management of chronic diseases like asthma. Studies of parent health literacy and education level on the management of children's chronic illnesses reveal inconclusive results. We hypothesized a correlation between parent and adolescent health literacy in teens with asthma. Methods: Sociodemographic data were obtained; health literacy was assessed on adolescents and parents with three instruments: Rapid Estimate of Adolescent/Adult Literacy in Medicine (REALM), Single Item Literacy Screener (SILS) and Newest Vital Sign (NVS). Agreement between scores was examined by calculating weighted kappa statistics and performing Bowkers test of symmetry. Results: In all, 243 adolescents and 203 parents completed health literacy assessments yielding 198 paired observations. 9th-12th graders, 60.6% female, 72.7% African-American (AA), mean age: 15.3 years (±0.9). Parent education ranged from < high school (19.1%) to college graduate (24.0%). Agreement between adolescent and parent scores was poor: REALM (κw = 0.26), SILS (κw = 0.12), and NVS (κw = 0.29) and disagreement did not significantly differ by race. Positive correlations of moderate strength (overall and between racial groups) were found between reading scores and both REALM and NVS scores, and between REALM and NVS scores. Due to the inverse relationship of SILS scores with health literacy level, SILS scores (overall and between racial groups) were weakly and negatively correlated with reading scores, REALM and NVS. Conclusion: Correlation between education level and traditional literacy suggests that these are contributing factors to the health literacy of adolescents with asthma. Correlation between adolescent and caregiver health literacy was not supported.

Rural Asthma: Current Understanding of Prevalence, Patterns, and Interventions for Children and Adolescents.

PURPOSE OF REVIEW: Asthma is the most common chronic illness of children and adolescents in the USA. While asthma has been understood to disproportionately affect urban dwellers, recent investigations have revealed rural pediatric asthma prevalence to be very similar to urban and to be more closely correlated with socioeconomic and environmental factors than geographic location or population density. RECENT FINDINGS: Rural children experience factors unique to location that impact asthma development and outcomes, including housing quality, cigarette smoke exposure, and small/large-scale farming. Additionally, there are challenging barriers to appropriate asthma care that frequently are more severe for those living in rural areas, including insurance status, lack of primary care providers and pulmonary specialists, knowledge deficits (both patient and provider), and a lack of culturally tailored asthma interventions. Interventions designed to address rural pediatric asthma disparities are more likely to be successful when targeted to specific challenges, such as the use of school-based services or telemedicine to mitigate asthma care access issues. Continued research on understanding the complex interaction of specific rural environmental factors with host factors can inform future interventions designed to mitigate asthma disparities.

Breast Milk Transforming Growth Factor ß Is Associated With Neonatal Gut Microbial Composition.

BACKGROUND AND OBJECTIVES: 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. METHODS: 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)ß1, TGFß2, and IL-10 were assayed using enzyme-linked immunosorbent assays, whereas neonatal gut microbiome was profiled using 16S rRNA sequencing. RESULTS: Individually, immunomodulators TGFß1 and TGFß2 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 TGFß1 and TGFß2, however, were not independent of one another, and the effect of TGFß2 was stronger than that of TGFß1. Higher levels of TGFß2 were associated with the increased relative abundance of several bacteria, including members of Streptococcaceae and Ruminococcaceae, and lower relative abundance of distinct Staphylococcaceae taxa. CONCLUSIONS: Breast milk TGFß concentration explains a portion of variability in gut bacterial microbiota composition among breast-fed neonates. Whether TGFß 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.

Exploring racial differences in IgE-mediated food allergy in the WHEALS birth cohort.

BACKGROUND: Suspected food allergies are the cause of more than 200,000 visits to the emergency department annually. Racial differences in the prevalence of food allergy have also been reported, but the evidence is less conclusive. Researchers continue to struggle with the identification of food allergy for epidemiologic studies. OBJECTIVE: To explore racial differences in IgE-mediated food allergy (IgE-FA) in a birth cohort. METHODS: We used a panel of board-certified allergists to systematically identify IgE-FA to egg, milk, or peanut in a multiethnic birth cohort in which patient medical history, patient symptoms, and clinical data were available through 36 months of age. RESULTS: Of the 590 infants analyzed, 52.9% were male and 65.8% African American. Sensitization (serum specific IgE >0.35 IU/mL) to the food allergens was significantly higher for African American children compared with non-African American children as has been previously reported. No statistically significant racial/ethnic differences in IgE-FA were observed; however, a higher proportion of African American children were designated as having peanut allergy, and the percentage of African American children with an IgE level greater than 95% predictive decision points for peanut was 1.7% vs 0.5% for non-African American children. With the use of logistic regression, race/ethnicity was not significantly associated with IgE-FA (adjusted odds ratio, 1.12; 95% confidence interval, 0.58-2.17; P = .75) but was associated with sensitization to more than 1 of the food allergens (adjusted odds ratio, 1.80; 95% confidence interval, 1.22-2.65; P = .003). CONCLUSION: We did not observe an elevated risk of IgE-FA for African American children, although established differences in sensitization were observed. Racial/ethnic differences in sensitization must be taken into consideration when investigating disparities in asthma and allergy.

Initiating an online asthma management program in urban emergency departments: the recruitment experience.

BACKGROUND: The emergency department could represent a means of identifying patients with asthma who could benefit from asthma interventions. OBJECTIVE: To assess the initiation of a Web-based tailored asthma intervention in the emergency department of 2 urban tertiary care hospitals. METHODS: In addition to awareness strategies for emergency department staff (eg, attending nursing huddles, division meetings, etc), recruitment experiences are described for 2 strategies: (1) recruitment during an emergency department visit for acute asthma and (2) recruitment from patient listings (mail or telephone). Patient enrollment was defined as baseline completion, randomization, and completion of the first of 4 online sessions. RESULTS: Of 499 eligible patients 13 to 19 years old visiting the emergency department for asthma during the study period, 313 (63%) were contacted in the emergency department (n = 65) or by mail or telephone (n = 350). Of these, 121 (38.6%) were randomized. Mean age of the study sample was 15.4 years and 88.4% were African American. Refusal rates for emergency department recruitment and mail or telephone were 18.5% (12 of 65) and 16.6% (58 of 350), respectively. On average, emergency department enrollment took 44 to 67 minutes, including downtime. When surveyed, emergency department providers were more positive about awareness activities and emergency department recruitment than were research staff. CONCLUSION: Emergency department recruitment was feasible but labor intensive. Refusal rates were similar for the 2 strategies. Targeting patients with acute asthma in the emergency department is one way of connecting with youth at risk of future acute events.

Future Research Directions in Asthma. An NHLBI Working Group Report.

Asthma is a common chronic disease without cure. Our understanding of asthma onset, pathobiology, classification, and management has evolved substantially over the past decade; however, significant asthma-related morbidity and excess healthcare use and costs persist. To address this important clinical condition, the NHLBI convened a group of extramural investigators for an Asthma Research Strategic Planning workshop on September 18-19, 2014, to accelerate discoveries and their translation to patients. The workshop focused on (1) in utero and early-life origins of asthma, (2) the use of phenotypes and endotypes to classify disease, (3) defining disease modification, (4) disease management, and (5) implementation research. This report summarizes the workshop and produces recommendations to guide future research in asthma.

Race-specific Association of Caesarean-Section Delivery with Body Size at Age 2 Years.

OBJECTIVE: African American children are at higher risk of obesity than White children and African American women are more likely to undergo caesarean-section (CS) delivery than White women. CS is associated with childhood obesity; however, little is known whether this relationship varies by race. We examined if the association of CS with obesity at age 2 years varied by race. DESIGN: Longitudinal birth cohort. SETTING: Birth cohort conducted in a health care system in metropolitan Detroit, Michigan with follow-up at age 2 years. PARTICIPANTS: 639 birth cohort participants; 367 children (57.4%) were born to African American mothers and 230 (36.0%) children were born via CS. MAIN OUTCOME MEASURES: Obesity defined as body mass index ≥95th percentile at age 2 years. RESULTS: Slightly more children of African American (n=37; 10.1%) than non-African American mothers (n=18; 6.6%) were obese (P=.12). There was evidence of effect modification between race and delivery mode with obesity at age 2 years (interaction P=.020). In children of African American mothers, CS compared to vaginal birth was associated with a significantly higher odds of obesity (aOR=2.35 (95% CI: 1.16, 4.77), P=.017). In contrast, delivery mode was not associated with obesity at age 2 years in children of non-African American mothers (aOR=.47 (95% CI: .13, 1.71), P=.25). CONCLUSIONS: There is evidence for a race-specific effect of CS on obesity at age 2 years; potential underlying mechanisms may be racial differences in the developing gut microbiome or in epigenetic programming. Future research is needed to determine if this racial difference persists into later childhood.

Association between vitamin D levels and allergy-related outcomes vary by race and other factors.

BACKGROUND: Allergy-related studies that include biological measurements of vitamin D preceding well-measured outcomes are needed. OBJECTIVE: We sought to examine the associations between early-life vitamin D levels and the development of allergy-related outcomes in the racially diverse Wayne County Health, Environment, Allergy, and Asthma Longitudinal Study birth cohort. METHODS: 25-Hydroxyvitamin D (25[OH]D) levels were measured in stored blood samples from pregnancy, cord blood, and age 2 years. Logistic regression models were used to calculate odds ratios (ORs) with 95% CIs for a 5 ng/mL increase in 25(OH)D levels for the following outcomes at age 2 years: eczema, skin prick tests (SPTs), increased allergen-specific IgE level (≥ 0.35 IU/mL), and doctor's diagnosis of asthma (3-6 years). RESULTS: Prenatal 25(OH)D levels were inversely associated with eczema (OR, 0.85; 95% CI, 0.75-0.96). The association was stronger in white children (white children: OR, 0.79; 95% CI, 0.57-1.09; black children: OR, 0.96; 95% CI, 0.82-1.12), although this was not statistically significant. Cord blood 25(OH)D levels were inversely associated with having 1 or more positive SPT responses and aeroallergen sensitization. Both associations were statistically significant in white children (positive SPT response: OR, 0.50; 95% CI, 0.32-0.80; ≥ 1 aeroallergen sensitization: OR, 0.50; 95% CI, 0.28-0.92) in contrast with black children (positive SPT response: OR, 0.88; 95% CI, 0.68-1.14; ≥ 1 aeroallergen sensitization: OR, 0.85; 95% CI, 0.65-1.11). 25(OH)D levels measured concurrently with outcome assessment were inversely associated with aeroallergen sensitization (OR, 0.79; 95% CI, 0.66-0.96) only among black children (white children: OR, 1.21; 95% CI, 0.87-1.69). CONCLUSIONS: Prenatal and cord blood 25(OH)D levels were associated with some allergy-related outcomes, with a general pattern indicating that children with higher 25(OH)D levels tend to have fewer allergy-related outcomes.

Comparison of asthma prevalence among African American teenage youth attending public high schools in rural Georgia and urban Detroit.

BACKGROUND: The high prevalence of asthma among urban African American (AA) populations has attracted research attention, whereas the prevalence among rural AA populations is poorly documented. OBJECTIVE: We sought to compare the prevalence of asthma among AA youth in rural Georgia and urban Detroit, Michigan. METHODS: The prevalence of asthma was compared in population-based samples of 7297 youth attending Detroit public high schools and in 2523 youth attending public high schools in rural Georgia. Current asthma was defined as a physician diagnosis and symptoms in the previous 12 months. Undiagnosed asthma was defined as multiple respiratory symptoms in the previous 12 months without a physician diagnosis. RESULTS: In Detroit, 6994 (95.8%) youth were AA compared with 1514 (60.0%) in Georgia. Average population density in high school postal codes was 5628 people/mile(2) in Detroit and 45.1 people/mile(2) in Georgia. The percentages of poverty and of students qualifying for free or reduced lunches were similar in both areas. The prevalence of current diagnosed asthma among AA youth in Detroit and Georgia was similar: 15.0% (95% CI, 14.1-15.8) and 13.7% (95% CI, 12.0-17.1) (P = .22), respectively. The prevalence of undiagnosed asthma in AA youth was 8.0% in Detroit and 7.5% in Georgia (P = .56). Asthma symptoms were reported more frequently among those with diagnosed asthma in Detroit, whereas those with undiagnosed asthma in Georgia reported more symptoms. CONCLUSIONS: Among AA youth living in similar socioeconomic circumstances, asthma prevalence is as high in rural Georgia as it is in urban Detroit, suggesting that urban residence is not an asthma risk factor.

Birth weight and asthma incidence by asthma phenotype pattern in a racially diverse cohort followed through adolescence.

OBJECTIVE: Low birth weight (LBW) has been shown to be an independent risk factor for asthma. We hypothesized that LBW would have its greatest impact on early onset disease. METHODS: A racially diverse cohort of children born from 1983 to 1985 at two hospitals, one urban and one suburban in the same metropolitan area, and oversampled for babies weighing ≤2500 g, was identified retrospectively when the children were 6 years of age and followed periodically. At the age 17 years study visit, cohort members and their parent/guardians were separately interviewed face-to-face regarding the subject's history of asthma using the standardized ISAAC questionnaire. We measured the cumulative incidence of asthma from birth through adolescence defined by age of diagnosis and persistence/remittance. RESULTS: Six-hundred and eighty teens (82.6% of the original cohort) were included in the analyses, 387 with LBW and 293 of normal birth weight. The prevalence of physician-diagnosed "Current Asthma" was associated with LBW (p = 0.003 for trend), with patterns stronger in males and whites. LBW was associated most strongly with Late Onset Persistent asthma (current asthma that was diagnosed after 8 years); p for trend 0.032. This trend was again most evident in males and whites. None of the asthma categories classified as "remittent" were statistically associated with LBW. CONCLUSIONS: LBW was not associated with diagnosed asthma that remitted before age 17 years. LBW was associated with asthma diagnosis in mid-childhood that persisted through adolescence, suggesting that the asthmagenic effects of LBW can become evident post the early years of childhood and persist into adulthood.

Does pet-keeping modify the association of delivery mode with offspring body size?

Caesarean-section (CS) delivery increases risk of childhood obesity, and is associated with a distinct early-life gut microbiome, which may contribute to obesity. Household pets may alter human gut microbiome composition. We examined if pet-keeping modified the association of CS with obesity at age 2 years in 639 Wayne County Health, Environment, Allergy and Asthma Longitudinal Study birth cohort participants. Pet-keeping was defined as having a dog or cat (indoors ≥1 h/day) at child age 2 years. We used logistic regression to test for an interaction between CS and pet-keeping with obesity (BMI ≥ 95th percentile) at age 2 years, adjusted for maternal obesity. A total of 328 (51.3 %) children were male; 367 (57.4 %) were African American; 228 (35.7 %) were born by CS; and 55 (8.6 %) were obese. After adjusting for maternal obesity, CS-born children had a non-significant (P = 0.25) but elevated 1.4 (95 % CI 0.8, 2.5) higher odds of obesity compared to those born vaginally. There was evidence of effect modification between current pet-keeping and delivery mode with obesity at age 2 years (interaction P = 0.054). Compared to children born vaginally without a pet currently in the home, children born via CS without a pet currently in the home had a statistically significant (P = 0.043) higher odds (odds ratio 2.00; 95 % CI 1.02, 3.93) of being obese at age 2 years. Pets modified the CS-BMI relationship; whether the underlying mechanism is through effects on environmental or gut microbiome requires specific investigation.