Investigating the Impact of Maternal Residential Mobility on Identifying Critical Windows of Susceptibility to Ambient Air Pollution during Pregnancy

© 2018 The Author(s). Identifying periods of increased vulnerability to air pollution during pregnancy with respect to the development of adverse birth outcomes can improve understanding of possible mechanisms of disease development and provide guidelines for protection of the child. Exposure to air pollution during pregnancy is typically based on the mother's residence at delivery, potentially resulting in exposure misclassification and biasing the estimation of critical windows of pregnancy. In this study, we determined the impact of maternal residential mobility during pregnancy on defining weekly exposure to particulate matter less than or equal to 10 µm in aerodynamic diameter (PM 10) and estimating windows of susceptibility to term low birth weight. We utilized data sets from 4 Connecticut birth cohorts (1988-2008) that included information on all residential addresses between conception and delivery for each woman. We designed a simulation study to investigate the impact of increasing levels of mobility on identification of critical windows. Increased PM 10 exposure during pregnancy weeks 16-18 was associated with an increased probability of term low birth weight. Ignoring residential mobility when defining weekly exposure had only a minor impact on the identification of critical windows for PM 10 and term low birth weight in the data application and simulation study. Identification of critical pregnancy windows was robust to exposure misclassification caused by ignoring residential mobility in these Connecticut birth cohorts

Low-Level Ozone Exposure and Respiratory Symptoms in Infants

OBJECTIVE: Recent studies indicate that the U.S. Environmental Protection Agency (EPA) ozone standards may not protect sensitive individuals. In this study we examined respiratory effects of ozone in infants who may be vulnerable, particularly if they are children of asthmatic mothers. DESIGN: Women delivering babies at one of five hospitals in southwestern Virginia between 1994 and 1996 were invited to participate in a cohort study; 780 women enrolled. Ambient air quality data (ozone and particulate matter) were collected at a central monitoring site. PARTICIPANTS: This analysis is of 691 infants followed for approximately 83 days between 10 June and 31 August 1995 and/or 1996; they contributed a total of 52,421 infant-days of follow-up. Mothers were interviewed at enrollment and approximately biweekly to report infants’ daily symptoms. Repeated measures logistic regression models were run separately for wheeze, difficulty breathing, and cough. Ozone metrics included 24-hr average, peak 1-hr, and maximum 8-hr average. Analyses were repeated for the 61 infants whose mothers had asthma. RESULTS: For every interquartile-range increase in same-day 24-hr average ozone, likelihood of wheeze increased 37% [95% confidence interval (CI), 2–84%]. Among infants of asthmatic mothers, same-day 24-hr average ozone increased likelihood of wheeze 59% (95% CI, 1–154%) and of difficulty breathing 83% (95% CI, 42–136%). Maximum 8-hr ozone and peak 1-hr ozone were associated with difficulty breathing, but not wheeze, in infants of asthmatic mothers. Ozone was not associated with cough. CONCLUSIONS: At levels of ozone exposure near or below current U.S. EPA standards, infants are at increased risk of respiratory symptoms, particularly infants whose mothers have physician-diagnosed asthma

Effects of endotoxin exposure on childhood asthma risk are modified by a genetic polymorphism in ACAA1

<p>Abstract</p> <p>Background</p> <p>Polymorphisms in the endotoxin-mediated TLR4 pathway genes have been associated with asthma and atopy. We aimed to examine how genetic polymorphisms in innate immunity pathways interact with endotoxin to influence asthma risk in children.</p> <p>Methods</p> <p>In a previous analysis of 372 children from the Boston Home Allergens and the Connecticut Childhood Asthma studies, 7 SNPs in 6 genes (CARD15, TGFB1, LY96, ACAA1, DEFB1 and IFNG) involved in innate immune pathways were associated with asthma, and 5 SNPs in 3 genes (CD80, STAT4, IRAK2) were associated with eczema. We tested these SNPs for interaction with early life endotoxin exposure (n = 291), in models for asthma and eczema by age 6.</p> <p>Results</p> <p>We found a significant interaction between endotoxin and a SNP (rs156265) in ACAA1 (p = 0.0013 for interaction). Increased endotoxin exposure (by quartile) showed protective effects for asthma in individuals with at least one copy of the minor allele (OR = 0.39 per quartile increase in endotoxin, 95% CI 0.15 to 1.01). Endotoxin exposure did not reduce the risk of asthma in children homozygous for the major allele.</p> <p>Conclusion</p> <p>Our findings suggest that protective effects of endotoxin exposure on asthma may vary depending upon the presence or absence of a polymorphism in ACAA1.</p

Association of surfactant protein A polymorphisms with otitis media in infants at risk for asthma

BACKGROUND: Otitis media is one of the most common infections of early childhood. Surfactant protein A functions as part of the innate immune response, which plays an important role in preventing infections early in life. This prospective study utilized a candidate gene approach to evaluate the association between polymorphisms in loci encoding SP-A and risk of otitis media during the first year of life among a cohort of infants at risk for developing asthma. METHODS: Between September 1996 and December 1998, women were invited to participate if they had at least one other child with physician-diagnosed asthma. Each mother was given a standardized questionnaire within 4 months of her infant's birth. Infant respiratory symptoms were collected during quarterly telephone interviews at 6, 9 and 12 months of age. Genotyping was done on 355 infants for whom whole blood and complete otitis media data were available. RESULTS: Polymorphisms at codons 19, 62, and 133 in SP-A1, and 223 in SP-A2 were associated with race/ethnicity. In logistic regression models incorporating estimates of uncertainty in haplotype assignment, the 6A(4)/1A(5)haplotype was protective for otitis media among white infants in our study population (OR 0.23; 95% CI 0.07,0.73). CONCLUSION: These results indicate that polymorphisms within SP-A loci may be associated with otitis media in white infants. Larger confirmatory studies in all ethnic groups are warranted