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Triple-crossover randomized controlled intervention trial to test whether reduced exposure to household NO2 or fine particles results in reduced symptoms among children with persistent asthma. Children (n = 126) aged 5–11 years with persistent asthma living in homes with gas stoves and levels of NO2 15 ppb or greater recruited in Connecticut and Massachusetts (2015–2019) participated in an intervention involving three air cleaners configured for: (1) NO2 reduction: sham particle filtration and real NO2 scrubbing; (2) particle filtration: HEPA filter and sham NO2 scrubbing; (3) control: sham particle filtration and sham NO2 scrubbing. Air cleaners were randomly assigned for 5-week treatment periods using a three-arm crossover design. Outcome was number of asthma symptom-days during final 14 days of treatment. Treatment effects were assessed using repeated measures, linear mixed models. Measured NO2 was lower (by 4 ppb, p <.0001) for NO2-reducing compared to control or particle-reducing treatments. NO2-reducing treatment did not reduce asthma morbidity compared to control. In analysis controlling for measured NO2, there were 1.8 (95% CI −0.3 to 3.9, p =.10) fewer symptom days out of 14 in the particle-reducing treatment compared to control. It remains unknown if using an air cleaner alone can achieve levels of NO2 reduction large enough to observe reductions in asthma symptoms. We observed that in small, urban homes with gas stoves, modest reductions in asthma symptoms occurred using air cleaners that remove fine particles. An intervention targeting exposures to both NO2 and fine particles is complicated and further research is warranted. NCT02258893. [ABSTRACT FROM AUTHOR]

On June 20, 2013, the American Journal of Epidemiology sponsored a symposium at the Society for Epidemiologic Research's 46th Annual Meeting in Boston, Massachusetts, entitled, “What Is the Role of Epidemiology in the Era of Molecular Biology and Genomics?” The future of epidemiology depends on innovation in generating interesting and important testable hypotheses that are relevant to population health. These new strategies will depend on new technology, both in measurement of agents and environment and in the fields of pathophysiology and outcomes, such as cellular epidemiology and molecular pathology. The populations to be studied, sample sizes, and study designs should be selected based on the hypotheses to be tested and include case-control, cohort, and clinical trials. Developing large mega cohorts without attention to specific hypotheses is inefficient, will fail to address many associations with high-quality data, and may well produce spurious results. [ABSTRACT FROM PUBLISHER]

Purpose: To estimate whether low-to-moderate prenatal alcohol exposure is associated with selected birth outcomes., Methods: Low-to-moderate prenatal alcohol drinking and effects on low birthweight, preterm delivery, intrauterine growth restriction, and selected neonatal outcomes were evaluated among 4496 women and singleton infants. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariable logistic regression, controlling for confounding variables., Results: Early pregnancy drinking was associated with reduced odds of low birthweight, OR, 0.66 (95% CI, 0.46-0.96) and birth length less than 10th percentile, OR, 0.74 (95% CI, 0.56-0.97). Drinking during the first 3 months showed lower odds for birth length and head circumference less than 10th percentile, OR, 0.56 (95% CI, 0.36-0.87) and OR, 0.69 (95% CI, 0.50-0.96), respectively. Third trimester drinking was associated with lower odds for low birthweight, OR, 0.56 (95% CI, 0.34-0.94) and preterm delivery, OR, 0.60 (95% CI, 0.42-0.87)., Conclusions: Our results suggest low-to-moderate alcohol exposure during early and late gestation is not associated with increased risk of low birthweight, preterm delivery, intrauterine growth restriction, and most selected perinatal outcomes., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Preeclampsia is a major pregnancy complication with cardiovascular manifestations. Recent studies suggest that chocolate consumption may benefit cardiovascular health., Methods: We studied the association of chocolate consumption with risk of preeclampsia in a prospective cohort study of 2291 pregnant women who delivered a singleton livebirth between September 1996 and January 2000. Chocolate consumption was measured by self report in the first and third trimesters, and by umbilical cord serum concentrations of theobromine, the major methylxanthine component of chocolate. Preeclampsia was assessed by detailed medical record review for 1943 of the women. We derived adjusted odds ratios (aOR) and 95% confidence intervals (CIs) from logistic regression models controlling for potential confounders., Results: Preeclampsia developed in 3.7% (n = 63) of 1681 women. Cord serum theobromine concentrations were negatively associated with preeclampsia (aOR = 0.31; CI = 0.11-0.87 for highest compared with lowest quartile). Self-reported chocolate consumption estimates also were inversely associated with preeclampsia. Compared with women consuming under 1 serving of chocolate weekly, women consuming 5+ servings per week had decreased risk: aOR = 0.81 with consumption in the first 3 months of pregnancy (CI = 0.37-1.79) and 0.60 in the last 3 months (0.30-1.24)., Conclusions: Our results suggest that chocolate consumption during pregnancy may lower risk of preeclampsia. However, reverse causality may also contribute to these findings.

Purpose: We sought to examine associations among measures of caffeine exposure, including maternal urine, umbilical cord blood, and maternal self report., Methods: Pregnant women were recruited from 56 obstetric practices and 15 clinics associated with six hospitals in Connecticut and Massachusetts between September 1996 and January 2000; 3633 women were enrolled. Maternal urine throughout pregnancy and umbilical cord blood samples were analyzed for caffeine, paraxanthine, theophylline, and theobromine. Maternal caffeine intake was assessed throughout pregnancy., Results: Urinary and cord blood biomarkers were correlated with reported intake throughout pregnancy (range r = 0.35-0.66; p < 0.0001). Infants of smokers had greater cord blood concentrations of paraxanthine, reflecting faster caffeine metabolism in smokers, and cord blood paraxanthine levels were more strongly correlated with intake in smokers., Conclusion: Maternal self reported intake may still be the optimal and most valid measure of antenatal caffeine exposure, since biomarkers do not reflect exposure over pregnancy.

Studies investigating antenatal caffeine consumption and reproductive outcomes show conflicting results, and most studies have used maternal self-reported caffeine consumption to estimate fetal exposure. This study (n=1,606) was specifically designed to test the association of caffeine and its primary metabolites in umbilical cord blood with intrauterine growth restriction (IUGR). Pregnant women were recruited from 56 obstetric practices and 15 clinics affiliated with six hospitals in Connecticut and Massachusetts between September 1996 and January 2000. In an adjusted model including caffeine only, levels in all quartiles were associated with reduced risk of IUGR. In adjusted analyses including paraxanthine and caffeine, serum paraxanthine levels in the highest quartile were associated with increased risk of IUGR (adjusted odds ratio=3.29, 95% confidence interval: 1.17, 9.22); caffeine remained protective. These conflicting findings suggest that cytochrome P-450 1A2 (CYP1A2) metabolic activity may be associated with IUGR, so the ratio of paraxanthine to caffeine was then modeled. The likelihood of IUGR increased 21% for every one standard deviation change in the ratio (adjusted odds ratio=1.21, 95% confidence interval: 1.07, 1.37), suggesting that CYP1A2 activity, and not the absolute levels of paraxanthine, influences fetal growth. No associations were observed between caffeine or any metabolites and preterm delivery.

Background: Effects of nitrogen dioxide (NO2) on respiratory health have been the subject of extensive research. The outcomes of these studies were not consistent. Exposure to nitrous acid, which is a primary product of combustion, and is also formed when NO2 reacts with water, may play an important role in respiratory health. We estimate the independent effects of exposure to nitrogen dioxide and nitrous acid on respiratory symptoms during the first year of life., Methods: Nitrogen dioxide and nitrous acid concentrations were measured once (1996-1998) in the homes of 768 infants who were at risk for developing asthma. Infants were living in southern New England. The frequency of respiratory symptoms in these children was recorded during the first year of life., Results: Infants living in homes with an NO2 concentration exceeding 17.4 ppb (highest quartile) had a higher frequency of days with wheeze (rate ratio = 2.2; 95% confidence interval = 1.4-3.4), persistent cough (1.8; 1.2-2.7), and shortness of breath (3.1; 1.8-5.6) when compared with infants in homes that had NO2 concentrations lower than 5.1 ppb (lowest quartile), controlling for nitrous acid concentration. Nitrous acid exposure was not independently associated with respiratory symptoms., Conclusions: Among infants at risk for developing asthma, the frequency of reported respiratory symptoms in the first year of life was associated with levels of NO2 not currently considered to be harmful., (Copyright 2004 Lippincott Williams and Wilkins)

Context: Exposure to ozone and particulate matter of 2.5 microm or less (PM2.5) in air at levels above current US Environmental Protection Agency (EPA) standards is a risk factor for respiratory symptoms in children with asthma., Objective: To examine simultaneous effects of ozone and PM2.5 at levels below EPA standards on daily respiratory symptoms and rescue medication use among children with asthma., Design, Setting, and Participants: Daily respiratory symptoms and medication use were examined prospectively for 271 children younger than 12 years with physician-diagnosed, active asthma residing in southern New England. Exposure to ambient concentrations of ozone and PM2.5 from April 1 through September 30, 2001, was assessed using ozone (peak 1-hour and 8-hour) and 24-hour PM2.5. Logistic regression analyses using generalized estimating equations were performed separately for maintenance medication users (n = 130) and nonusers (n = 141). Associations between pollutants (adjusted for temperature, controlling for same- and previous-day levels) and respiratory symptoms and use of rescue medication were evaluated., Main Outcome Measures: Respiratory symptoms and rescue medication use recorded on calendars by subjects' mothers., Results: Mean (SD) levels were 59 (19) ppb (1-hour average) and 51 (16) ppb (8-hour average) for ozone and 13 (8) microg/m3 for PM2.5. In copollutant models, ozone level but not PM2.5 was significantly associated with respiratory symptoms and rescue medication use among children using maintenance medication; a 50-ppb increase in 1-hour ozone was associated with increased likelihood of wheeze (by 35%) and chest tightness (by 47%). The highest levels of ozone (1-hour or 8-hour averages) were associated with increased shortness of breath and rescue medication use. No significant, exposure-dependent associations were observed for any outcome by any pollutant among children who did not use maintenance medication., Conclusion: Asthmatic children using maintenance medication are particularly vulnerable to ozone, controlling for exposure to fine particles, at levels below EPA standards.

Objective: To prospectively examine in pregnant women whether asthma or asthma therapy influenced preterm delivery, intrauterine grown restriction (IUGR), or birthweight., Methods: We enrolled 873 pregnant women with a history of asthma, of whom 778 experienced asthma symptoms or took medication, and 1333 women with no asthma history, including 884 women with neither asthma diagnosis nor symptoms and 449 with symptoms but no diagnosis. Asthma symptoms, medication, and severity were classified according to 2002 Global Initiative for Asthma guidelines., Results: Preterm delivery was not associated with asthma diagnosis, severity, or symptoms but was associated with use of controller medications, independent of symptoms, specifically oral steroids and theophylline. Gestation was reduced by 2.22 weeks in women using oral steroids daily (P =.001) and 1.11 weeks after theophylline (P =.002). We observed a 24% (5-47%) increased risk for IUGR with each increased symptom step, which increased further in symptomatic women with no asthma diagnosis (31%, 4-65%) compared with women with neither asthma nor symptoms., Conclusions: We found no effect of asthma symptoms or severity on preterm delivery but observed increased risks associated with use of oral steroid and theophylline. Intrauterine growth restriction was associated with asthma severity, which possibly reflects a hypoxic fetal effect. Women with asthma symptoms but no diagnosis were at particular risk of undermedication and delivering IUGR infants. These observations support guidelines that advocate active management of pregnant patients with mild or moderate asthma with beta(2) agonists, with oral steroids added only if severity increases. Symptomatic patients without an asthma diagnosis might need to be equally managed.

Whether caffeine consumption during pregnancy represents a fetal hazard remains uncertain. The authors report on a large prospective study designed to examine this question. In 1996-2000, 2,291 mothers with singleton livebirths in Connecticut and Massachusetts were evaluated after their first prenatal visit and were questioned about caffeine consumption and important confounding factors. Urine samples were provided to analyze urinary caffeine, cotinine, and creatinine levels. Mothers were followed throughout pregnancy to monitor changes in consumption. Pregnancy outcomes were obtained from medical records. Self-reports of caffeine consumption in the first and third trimesters were not associated with intrauterine growth retardation, low birth weight, or preterm delivery. For every 1 mg/g creatinine increase in urinary caffeine, risk of intrauterine growth retardation was essentially unchanged (odds ratio (OR) = 0.96, 95% confidence interval (CI): 0.85, 1.08). In contrast, a 0.005 mg/g creatinine increase in urinary cotinine significantly increased risk (OR = 1.003, 95% CI: 1.001, 1.005). Mean birth weight was reduced by reported caffeine consumption (-28 g per 100 mg of caffeine consumed daily, 95% CI: -0.10, -0.46, p = 0.001) but not mean gestational age. Decaffeinated coffee did not increase risk for any perinatal outcome. This small decrease in birth weight, observed for maternal caffeine consumption, is unlikely to be clinically important except for women consuming >/=600 mg of caffeine daily (approximately six 10-ounce (1 ounce = 28.3 g) cups of coffee).

Home exposures to aeroallergens are an important environmental factor in allergic sensitization and in the development and exacerbation of asthma. We assessed variations in home concentrations of dust mite, cockroach, cat, and dog allergens in dust collected in the main living areas of asthmatics' homes by family income, mother's education, dwelling type, population density, household population density, and ethnicity in Connecticut and south-central Massachusetts. Dust samples were collected at the time of home interview in 999 homes as part of an ongoing longitudinal birth cohort study of 1,002 infants and their asthmatic siblings. The analysis employed lower and upper cut points for group 1 dust mite (> or = 2.0 microg/g and > or = 10 microg/g), cockroach (> or = 1.0 U/g and > or = 4.0 U/g), cat (> or = 1.0 microg/g and > or = 8.0 ug/g), and dog (> or = 2.0 microg/g and > or = 10.0 microg/g) allergens. Subject residences were geocoded to assess population density from the U.S. Census, and multiple logistic regression was used to control for confounding. The portion of homes at the lower cut point for dust mite, cockroach, cat, and dog allergens were 46.9%, 24.9%, 42.2%, and 35.6%, respectively; the upper cut point for each of the allergens was reached in 22.4%, 13.4%, 21.0%, and 22.9% of the homes, respectively. In all, 86.0% of the homes had at least one allergen at the lower cut point, and 58.0% had at least one allergen at the upper cut point. Forty-nine percent of the homes had two or more allergens at the lower cut point, and 19.7% had two or more allergens at the upper cut point. Higher education of the mother, higher household income, living in a single-family home in a less densely populated area with fewer people per room, and being a white household were associated with elevated dust mite, cat, and dog allergens and low cockroach allergen. In contrast, low income, living in a multifamily home in a high population density area with a higher occupancy rate per room, and being a Hispanic or black household were associated with elevated cockroach allergens and low concentrations of dust mite, cat, and dog allergens. Although the presence of an individual allergen is more likely associated with one or more socioeconomic or ethnic factors, most homes typically have multiple allergen burdens in excess of concentrations thought to be associated with sensitization and exacerbation of asthma. Mite and cockroach allergens have distinct and opposite associations with socioeconomic factors and population density.