Human microbiome variation associated with race and ethnicity emerges as early as 3 months of age.

Human microbiome variation is linked to the incidence, prevalence, and mortality of many diseases and associates with race and ethnicity in the United States. However, the age at which microbiome variability emerges between these groups remains a central gap in knowledge. Here, we identify that gut microbiome variation associated with race and ethnicity arises after 3 months of age and persists through childhood. One-third of the bacterial taxa that vary across caregiver-identified racial categories in children are taxa reported to also vary between adults. Machine learning modeling of childhood microbiomes from 8 cohort studies (2,756 samples from 729 children) distinguishes racial and ethnic categories with 87% accuracy. Importantly, predictive genera are also among the top 30 most important taxa when childhood microbiomes are used to predict adult self-identified race and ethnicity. Our results highlight a critical developmental window at or shortly after 3 months of age when social and environmental factors drive race and ethnicity-associated microbiome variation and may contribute to adult health and health disparities.

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.

Food insecurity in Detroit: exploring the relationship between patient-reported food insecurity and proximity to healthful grocery stores.

OBJECTIVE: The objective of the current study was to determine if patients of a large health care system in Detroit who self-identify as food insecure live further away from healthy grocery stores compared with food secure patients. Second, we explored whether food insecurity and distance to healthy grocery stores are related to ecological measures of vehicle availability in the area of residence. DESIGN: A secondary data analysis that uses baseline data from a pilot intervention/feasibility study. SETTING: Detroit, Michigan, USA. PARTICIPANTS: Patients of Henry Ford Health System were screened for food insecurity to determine eligibility for a pilot intervention/feasibility study (i.e. Henry's Groceries for Health), conducted through a collaboration with Gleaners Community Foodbank of Southeastern Michigan. Only patients residing in Detroit city limits (including Highland Park and Hamtramck) were included in the secondary analysis. Of the 1,100 patients included in the analysis, 336 (31 %) were food insecure. RESULTS: After accounting for socio-demographic factors associated with food insecurity, we did not find evidence that food insecure patients lived further away from healthier grocery stores, nor was this modified by ecological measures of vehicle access. However, some neighbourhoods were identified as having a significantly higher risk of food insecurity. CONCLUSIONS: Food insecure patients in Detroit are perhaps limited by social and political determinants and not their immediate neighbourhood geography or physical access to healthy grocery stores. Future research should explore the complexity in linkages between household socio-economic factors, socio-cultural dynamics and the neighbourhood food environment.

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.

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.

Association between asthma symptom scores and perceived stress and trait anxiety in adolescents with asthma.

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 (ß = 4.82, p < 0.001), nocturnal awakening due to asthma (ß = 4.47, p < 0.001), activity limitation (ß = 2.78, p = 0.005), and shortness of breath (ß = 1.73, p = 0.014). These associations remained significant after adjusting for gender, race, and the body mass index percentile. Trait anxiety had significant associations with nocturnal awakening (ß = 9.28, p = 0.002) and symptoms on awakening (ß = 8.74, p = 0.002). Associations remained significant after adjusting for gender, race, and body mass index percentile. 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.

Birth Mode, Breastfeeding, Pet Exposure, and Antibiotic Use: Associations With the Gut Microbiome and Sensitization in Children.

PURPOSE OF REVIEW: The infant gut microbiota has become a focus of multiple epidemiologic and cohort studies. This microbiome is derived from the mother (via the vaginal canal, maternal skin contact, breastfeeding, and possibly in utero microbial transfer) and is likely influenced by multiple external factors. It is now believed by some experts that colonization and formation of the newborn and alterations of gut microbiota in children are dependent on earlier alterations of the microbiota of mothers during or perhaps even before pregnancy. This review will focus on specific factors (pet keeping, breastfeeding, antibiotic use, and mode of delivery) that influence the infant gut microbiome and atopy. RECENT FINDINGS: This is a review of recent literature describing how pet keeping, breastfeeding, antibiotic use, and mode of delivery influences and changes the infant gut microbiome and atopy. General trends in gut microbiota differences have emerged in different birth cohorts when each external factor is analyzed, but consistency between studies is difficult to replicate. The aforementioned factors do not seem to confer an overwhelming risk for development of atopy alone. This review provides a comprehensive review of early life environmental factors and their influence on the infant gut microbiome and atopy.

In utero metal exposures measured in deciduous teeth and birth outcomes in a racially-diverse urban cohort.

A growing number of studies have examined associations of metal exposures with birth outcomes, however, results from these studies have been inconsistent, and hampered by methodological limitations. We measured direct fetal exposure to three metals (lead, manganese and zinc) during the second and third trimester and examined its association with birth weight and gestational age at delivery. Participants in the Wayne County Health, Environment, Allergy and Asthma Longitudinal Study (WHEALS), a population-based birth cohort established between September 2003 and December 2007, were invited to donate teeth to the study. Lead, manganese and zinc during the second and third trimesters were measured via high-resolution microspatial mapping of dentin growth rings, a validated biomarker for prenatal metal exposure. Gestational age at delivery and infant birth weight were obtained from the delivery medical record. A total of 145 children had tooth metal measurements and birth outcome data. Mean birth weight was 3431 ±â€¯472 g and mean gestational age at delivery was 39.0 ±â€¯1.3 weeks. Overall, there was a positive association between second (ß = 0.21, 95% CI: 0.05, 0.37, P = 0.01) and third trimester (ß = 0.21, 95% CI: 0.05, 0.37, P = 0.01) tooth manganese and birth weight Z-score; this remained statistically significant after covariate adjustment. There was also a negative association between second trimester tooth lead level and birth weight Z-score (ß = -0.20, 95% CI: -0.38, -0.02, P = 0.02), however, this was attenuated after adjusting for covariates. Mixture analysis revealed similar findings. There was evidence for a sex-specific effect of manganese with birth weight Z-score, with the association stronger in female compared to male infants. Overall, we found evidence suggesting that higher in utero manganese is associated with larger birth weight Z-scores and that these associations may vary by infant sex.

Prenatal pet keeping and caregiver-reported attention deficit hyperactivity disorder through preadolescence in a United States birth cohort.

BACKGROUND: While the keeping of pets has been shown to protect against childhood allergic disease and obesity, less is known regarding potential associations of prenatal pet keeping and attention deficit hyperactivity disorder (ADHD). We sought to examine the associations between prenatal dog or cat keeping with caregiver-reported ADHD in preadolescents in the Wayne County Health, Environment, Allergy and Asthma Longitudinal Study (WHEALS) birth cohort (N = 1258). METHODS: At an interview with the caregiver at child age 10-12 years, caregivers reported if the WHEALS child had ever been diagnosed with ADHD. Similarly, during an interview with the mother prenatally, pet keeping (defined as dog or cat kept inside ≥1 h/day) was ascertained. Logistic regression models were fit to examine the association of prenatal pet keeping (dog keeping and cat keeping, separately) with ADHD. RESULTS: A subset of 627 children were included in the analyses: 93 who had ADHD and 534 with neurotypical development. After accounting for confounders and loss to follow-up, maternal prenatal dog exposure was associated with 2.23 times (95% CI: 1.15, 4.31; p = 0.017) greater odds of ADHD among boys. Prenatal dog keeping was not statistically significantly associated with ADHD in girls (odds ratio = 0.27, 95% CI: 0.06, 1.12; p = 0.070). Prenatal cat keeping was not associated with ADHD. CONCLUSIONS: In boys, but not girls, maternal prenatal dog keeping was positively associated with ADHD. Further study to confirm these findings and to identify potential mechanisms of this association (e.g., modification of the gut microbiome, exposure to environmental toxicants or pet-related medications) is needed.

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.

Maternal COVID-19 exposure and placental characteristics.

INTRODUCTION: The impact of COVID-19 on the placenta is poorly described, particularly among minority women. MATERIALS AND METHODS: This is a retrospective case-control study. Micro- and macroscopic placental pathologic findings were compared for 15 COVID-19 positive and 36 negative mothers. Cases and controls were frequency matched on gestational age, race, maternal comorbidities, and delivery type. Data from the electronic medical record were supplemented with independent review of microscopic slides. RESULTS: Placentas from cases and controls were similar except the median distance from the site of the cord insertion to the nearest disk margin was statistically significantly shorter among placentas from COVID-19 positive cases (3.5 versus 6.0 cm, p = 0.006). Case status was not associated with an increased risk of placental pathologies. CONCLUSION: There are few pathologic differences between placentas of COVID-19 positive and negative mothers. Additional studies are needed to investigate the role of timing of infection.

Precocious infant fecal microbiome promotes enterocyte barrier dysfuction, altered neuroendocrine signaling and associates with increased childhood obesity risk.

Early life gut microbiome composition has been correlated with childhood obesity, though microbial functional contributions to disease origins remain unclear. Here, using an infant birth cohort (n = 349) we identify a distinct fecal microbiota composition in 1-month-old infants with the lowest rate of exclusive breastfeeding, that relates with higher relative risk for obesity and overweight phenotypes at two years. Higher-risk infant fecal microbiomes exhibited accelerated taxonomic and functional maturation and broad-ranging metabolic reprogramming, including reduced concentrations of neuro-endocrine signals. In vitro, exposure of enterocytes to fecal extracts from higher-risk infants led to upregulation of genes associated with obesity and with expansion of nutrient sensing enteroendocrine progenitor cells. Fecal extracts from higher-risk infants also promoted enterocyte barrier dysfunction. These data implicate dysregulation of infant microbiome functional development, and more specifically promotion of enteroendocrine signaling and epithelial barrier impairment in the early-life developmental origins of childhood obesity.

Impact of Spirometry Race-Correction on Preadolescent Black and White Children.

BACKGROUND: Race-correction for Black patients is standard practice in spirometry testing. History suggests that these corrections are at least partially a result of racist assumptions regarding lung anatomy among Black individuals, which can potentially lead to less frequent diagnoses of pulmonary diseases in this population. OBJECTIVE: To evaluate the impact of race-correction in spirometry testing among Black and White preadolescents, and examine the frequency of current asthma symptoms in Black children who were differentially classified depending on whether race-corrected or race-uncorrected reference equations were deployed. METHODS: Data from Black and White children who completed a clinical examination at age 10 years from a Detroit-based unselected birth cohort were analyzed. Global Lung Initiative 2012 reference equations were applied to spirometry data using both race-corrected and race-uncorrected (ie, population-average) equations. Abnormal results were defined as values less than the fifth percentile. Asthma symptoms were assessed concurrently using the International Study of Asthma and Allergies in Childhood questionnaire, while asthma control was assessed using the Asthma Control Test. RESULTS: The impact of race-correction on forced expiratory volume in 1 second (FEV1)/forced vital capacity ratio was minimal, but abnormal classification of FEV1 results more than doubled among Black children when race-uncorrected equations were used (7% vs 18.1%) and were almost 8 times greater based on forced vital capacity classification (1.5% vs 11.4%). More than half of Black children differentially classified on FEV1 (whose FEV1 was classified as normal with race-corrected equations but abnormal with race-uncorrected equations) experienced asthma symptoms in the past 12 months (52.6%), which was significantly higher than the percentage of Black children consistently classified as normal (35.5%, P = .049), but similar to that of Black children consistently classified as abnormal using both race-corrected and race-uncorrected equations (62.5%, P = .60). Asthma Control Test scores were not different based on classification. CONCLUSIONS: Race-correction had an extensive impact on spirometry classification in Black children, and differentially classified children had a higher rate of asthma symptoms than children consistently classified as normal. Spirometry reference equations should be reevaluated to be aligned with current scientific perspectives on the use of race in medicine.

Prenatal physical activity and the gut microbiota of pregnant women: results from a preliminary investigation.

PURPOSE: To determine whether physical activity (PA), specifically meeting the recommended 150 minutes of moderate-intensity PA per week, is associated with gut microbiota composition in pregnant women. METHODS: In an ongoing birth cohort study, questions from the Behavioral Risk Factor Surveillance System, which provides data on PA variables, were used to determine whether pregnant women met or exceeded the PA recommendations. To profile the composition of gut bacterial microbiota, 16S rRNA sequencing was performed on stool samples obtained from pregnant women. Differences in alpha diversity metrics (richness, Pielou's evenness, and Shannon's diversity) according to PA were determined using linear regression, whereas beta diversity relationships (Canberra and Bray-Curtis) were assessed using Permutational multivariate analysis of variance (PERMANOVA). Differences in relative taxon abundance were determined using DESeq2. RESULTS: The complete analytical sample included 23 women that were evaluated for both PA and 16S rRNA sequencing data (median age [Q1; Q3] = 30.5 [26.6; 34.0] years; 17.4% Black), and 11 (47.8%) met or exceeded the PA recommendations. Meeting or exceeding the PA recommendations during pregnancy was not associated with gut microbiota richness, evenness, or diversity, but it was related to distinct bacterial composition using both Canberra (p = 0.005) and Bray-Curtis (p = 0.022) distances. Significantly lower abundances of Bacteroidales, Bifidobacteriaceae, Lactobacillaceae, and Streptococcaceae were observed in women who met or exceeded the PA recommendations (all false discovery rates adjusted, p < 0.02). CONCLUSION: Pregnant women who met or exceeded the PA recommendations showed altered gut microbiota composition. This study forms the basis for future studies on the impact of PA on gut microbiota during pregnancy.

Comparison of methanol fixation versus cryopreservation of the placenta for metabolomics analysis.

Methods for collection of placental tissue at room temperature for metabolic profiling are described. Specimens were excised from the maternal side of the placenta and immediately flash frozen or fixed and stored for 1, 6, 12, 24, or 48 h in 80% methanol. Untargeted metabolic profiling was performed on both the methanol-fixed tissue and the methanol extract. Data were analyzed using Gaussian generalized estimating equations, two sample t-tests with false discovery rate (FDR) corrections, and principal components analysis. Methanol-fixed tissue samples and methanol extracts had a similar number of metabolites (p = 0.45, p = 0.21 in positive vs. negative ion mode). In positive ion mode, when compared to flash frozen tissue, both the methanol extract and methanol-fixed tissue (6 h) had a higher number of metabolites detected (146 additional metabolites, pFDR = 0.020; 149 additional metabolites, pFDR = 0.017; respectively), but these associations were not found in negative ion mode (all pFDR ≥ 0.05). Principle components analysis demonstrated separation of the metabolite features in the methanol extract, but similarity between methanol-fixed tissue and flash frozen tissue. These results show that placental tissue samples collected in 80% methanol at room temperature can yield similar metabolic data to flash frozen specimens.

Association between prenatal antimicrobial use and offspring attention deficit hyperactivity disorder.

BACKGROUND: Gut-brain cross-talk may play an important role in modulating neurodevelopment. Few studies have examined the association between antimicrobials that influence infant gut microbiota assemblage and attention deficit hyperactivity disorder (ADHD). OBJECTIVE: To examine the association between maternal prenatal antimicrobial use and ADHD in offspring at 10 years of age. METHODS: Data are from the Wayne County Health, Environment, Allergy and Asthma Longitudinal Study, a racially and socioeconomically diverse birth cohort in metropolitan Detroit, Michigan. Maternal antimicrobial use was extracted from the medical record. ADHD diagnoses were based on parental report at the 10-year study visit. Poisson regression models with robust error variance were used to calculate risk ratios (RR). Cumulative frequency of exposure to antibiotics, and effect modification were also evaluated. RESULTS: Among the 555 children included in the analysis, 108 were diagnosed with ADHD. During pregnancy, 54.1% of mothers used antibiotics while 18.7% used antifungals. Overall, there was no evidence of an association between prenatal antibiotic exposure and ADHD (RR [95% CI] = 0.98 [0.75, 1.29]), but there was an increased risk of ADHD among those with mothers using 3+ courses of antibiotics (RR [95%CI] = 1.58 [1.10, 2.29]). Prenatal exposure to antifungals was associated with a 1.6 times higher risk of ADHD (RR [95% CI] = 1.60 [1.19, 2.15]). In examining effect modification by child sex for antifungal use, there was no evidence of an association among females (RR [95% CI] = 0.97 [0.42, 2.23]), but among males, prenatal antifungal use was associated with 1.82 times higher risk of ADHD (RR [95% CI] = 1.82 [1.29, 2.56]). CONCLUSIONS: Maternal prenatal antifungal use and frequent prenatal antibiotic use are associated with an increased risk of ADHD in offspring at age 10. These findings highlight the importance of the prenatal environment and the need for careful use of antimicrobials.