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1.  Fine Particulate Matter and Risk of Preterm Birth in Connecticut in 2000–2006: A Longitudinal Study 
American Journal of Epidemiology  2013;179(1):67-74.
Several studies have examined associations between particulate matter with aerodynamic diameter of 2.5 µm or less (PM2.5) and preterm birth, but it is uncertain whether results were affected by individual predispositions (e.g., genetic factors, social conditions) that might vary considerably between women. We tested the hypothesis that a woman is at greater risk of preterm delivery when she has had elevated exposure to ambient PM2.5 during a pregnancy than when she has not by comparing pregnancies in the same woman. From 271,204 births, we selected 29,175 women who had vaginal singleton livebirths at least twice in Connecticut in 2000–2006 (n = 61,688 births). Analyses matched pregnancies to the same woman. Adjusted odds ratios per interquartile range (2.33-µg/m3) increase in PM2.5 in the first trimester, second trimester, third trimester, and whole pregnancy were 1.07 (95% confidence interval (CI): 1.00, 1.15), 0.96 (95% CI: 0.90, 1.03), 1.03 (95% CI: 0.97, 1.08), and 1.13 (95% CI: 1.01, 1.28), respectively. Among Hispanic women, the odds ratio per interquartile range increase in whole-pregnancy exposure was 1.31 (95% CI: 1.00, 1.73). Pregnancies with elevated PM2.5 exposure were more likely to result in preterm birth than were other pregnancies to the same woman at lower exposure. Associations were most pronounced in the first trimester and among Hispanic women.
PMCID: PMC3864709  PMID: 24068199
air pollution; environmental pollution; longitudinal studies; particulate matter; pregnancy; pregnancy outcomes; preterm birth
2.  PM2.5 exposure and birth outcomes: Use of satellite- and monitor-based data 
Air pollution may be related to adverse birth outcomes. Exposure information from land-based monitoring stations often suffers from limited spatial coverage. Satellite data offer an alternative data source for exposure assessment.
We used birth certificate data for births in Connecticut and Massachusetts, U.S. (2000-2006). Gestational exposure to PM2.5 was estimated from US Environmental Protection Agency monitoring data and from satellite data. Satellite data were processed and modeled using 2 methods – denoted satellite (1) and satellite (2) – before exposure assessment. Regression models related PM2.5 exposure to birth outcomes while controlling for several confounders. Birth outcomes were mean birth weight at term birth, low birth weight at term (LBW <2500g), small for gestational age (SGA, <10th percentile for gestational age and sex), and preterm birth (<37 weeks).
Overall, the exposure assessment method modified the magnitude of the effect estimates of PM2.5 on birth outcomes. Change in birth weight per inter-quartile range (2.41 μg/m3)-increase in PM2.5 was -6g (95% confidence interval = -8 to -5), -16g (-21 to -11) and -19g (-23 to -15), using the monitor, satellite (1) and satellite (2) methods, respectively. Adjusted odds ratios, based on the same 3 exposure methods, for term LBW were 1.01 (0.98 to 1.04), 1.06 (0.97 to 1.16), and 1.08 (1.01 to 1.16); for SGA, 1.03 (1.01 to 1.04), 1.06 (1.03 to 1.10) and 1.08 (1.04 to 1.11); and for preterm birth, 1.00 (0.99 to 1.02), 0.98 (0.94 to 1.03) and 0.99 (0.95 to 1.03).
Under exposure assessment methods, we found associations between PM2.5 exposure and adverse birth outcomes particularly for birth weight among term births and for SGA. These results add to the growing concerns that air pollution adversely affects infant health and suggest that analysis of health consequences based on satellite-based exposure assessment can provide additional useful information.
PMCID: PMC4009503  PMID: 24240652
3.  Sources of Fine Particulate Matter and Risk of Preterm Birth in Connecticut, 2000–2006: A Longitudinal Study 
Environmental Health Perspectives  2014;122(10):1117-1122.
Background: Previous studies have examined fine particulate matter (≤ 2.5 μm; PM2.5) and preterm birth, but there is a dearth of longitudinal studies on this topic and a paucity of studies that have investigated specific sources of this exposure.
Objectives: Our aim was to assess whether anthropogenic sources are associated with risk of preterm birth, comparing successive pregnancies to the same woman.
Methods: Birth certificates were used to select women who had vaginal singleton live births at least twice in Connecticut during 2000–2006 (n = 23,123 women, n = 48,208 births). We procured 4,085 daily samples of PM2.5 on Teflon filters from the Connecticut Department of Environmental Protection for six cities in Connecticut. Filters were analyzed for chemical composition, and Positive Matrix Factorization was used to determine contributions of PM2.5 sources. Risk estimates were calculated with conditional logistic regression, matching pregnancies to the same women.
Results: Odds ratios of preterm birth per interquartile range increase in whole pregnancy exposure to dust, motor vehicle emissions, oil combustion, and regional sulfur PM2.5 sources were 1.01 (95% CI: 0.93, 1.09), 1.01 (95% CI: 0.92, 1.10), 1.00 (95% CI: 0.89, 1.12), and 1.09 (95% CI: 0.97, 1.22), respectively.
Conclusion: This was the first study of PM2.5 sources and preterm birth, and the first matched analysis, that better addresses individual-level confounding potentially inherent in all past studies. There was insufficient evidence to suggest that sources were statistically significantly associated with preterm birth. However, elevated central estimates and previously observed associations with mass concentration motivate the need for further research. Future studies would benefit from high source exposure settings and longitudinal study designs, such as that adopted in this study.
Citation: Pereira G, Bell ML, Lee HJ, Koutrakis P, Belanger K. 2014. Sources of fine particulate matter and risk of preterm birth in Connecticut, 2000–2006: a longitudinal study. Environ Health Perspect 122:1117–1122;
PMCID: PMC4181926  PMID: 24911470
4.  Pregnant Women With Posttraumatic Stress Disorder and Risk of Preterm Birth 
JAMA psychiatry  2014;71(8):897-904.
Posttraumatic stress disorder (PTSD) occurs in about 8% of pregnant women. Stressful conditions, including PTSD, are inconsistently linked to preterm birth. Psychotropic treatment has been frequently associated with preterm birth. Identifying whether the psychiatric illness or its treatment is independently associated with preterm birth may help clinicians and patients when making management decisions.
To determine whether a likely diagnosis of PTSD or antidepressant and benzodiazepine treatment during pregnancy is associated with risk of preterm birth. We hypothesized that pregnant women who likely had PTSD and women receiving antidepressant or anxiolytic treatment would be more likely to experience preterm birth.
Longitudinal, prospective cohort study of 2654 women who were recruited before 17 completed weeks of pregnancy from 137 obstetrical practices in Connecticut and Western Massachusetts.
Posttraumatic stress disorder, major depressive episode, and use of antidepressant and benzodiazepine medications.
Preterm birth, operationalized as delivery prior to 37 completed weeks of pregnancy. Likely psychiatric diagnoses were generated through administration of the Composite International Diagnostic Interview and the Modified PTSD Symptom Scale. Data on medication use were gathered at each participant interview.
Recursive partitioning analysis showed elevated rates of preterm birth among women with PTSD. A further split of the PTSD node showed high rates for women who met criteria for a major depressive episode, which suggests an interaction between these 2 exposures. Logistic regression analysis confirmed risk for women who likely had both conditions (odds ratio [OR], 4.08 [95% CI, 1.27–13.15]). For each point increase on the Modified PTSD Symptom Scale (range, 0–110), the risk of preterm birth increased by 1% to 2%. The odds of preterm birth are high for women who used a serotonin reuptake inhibitor (OR, 1.55 [95% CI, 1.02–2.36]) and women who used a benzodiazepine medication (OR, 1.99 [95% CI, 0.98–4.03]).
Women with likely diagnoses of both PTSD and a major depressive episode are at a 4-fold increased risk of preterm birth; this risk is greater than, and independent of, antidepressant and benzodiazepine use and is not simply a function of mood or anxiety symptoms.
PMCID: PMC4134929  PMID: 24920287
5.  Household levels of nitrogen dioxide and pediatric asthma severity 
Epidemiology (Cambridge, Mass.)  2013;24(2):320-330.
Adverse respiratory effects in children with asthma are associated with exposures to nitrogen dioxide (NO2). Levels indoors can be much higher than outdoors. Primary indoor sources of NO2 are gas stoves, which are used for cooking by one-third of US households. We investigated effects of indoor NO2 exposure on asthma severity among an ethnically and economically diverse sample of children, controlling for season and indoor allergen exposure.
Children aged 5–10 years with active asthma (n=1,342), were recruited through schools in urban and suburban Connecticut and Massachusetts (2006–2009) for a prospective, year-long study with seasonal measurements of NO2 and asthma severity. Exposure to NO2 was measured passively for four, month-long, periods with Palmes tubes. Asthma morbidity was concurrently measured by a severity score and frequency of wheeze, night symptoms and use of rescue medication. We used adjusted, hierarchical ordered logistic regression models to examine associations between household NO2 exposure and health outcomes.
Every 5 ppb increase in NO2 exposure above a threshold of 6 ppb was associated with a dose-dependent increase in risk of higher asthma severity score (odds ratio= 1.37 [95% confidence interval= 1.01 – 1.89]), wheeze (1.49 [1.09 – 2.03]), night symptoms (1.52 [1.16 – 2.00]) and rescue medication use (1.78 [1.33 – 2.38]).
Asthmatic children exposed to NO2 indoors, at levels well below the US Environmental Protection Agency outdoor standard (53 ppb), are at risk for increased asthma morbidity. Risks are not confined to inner-city children, but occur at NO2 concentrations common in urban and suburban homes.
PMCID: PMC3686297  PMID: 23337243
Epidemiology (Cambridge, Mass.)  2012;23(5):677-685.
Major depressive disorder as well as the use of serotonin reuptake inhibitors in pregnancy have been associated with preterm birth. Studies that have attempted to separate effects of illness from treatment have been inconclusive. We sought to explore the separate effects of serotonin reuptake inhibitor use and major depressive episodes in pregnancy on risk of preterm birth.
We conducted a prospective cohort study of 2793 pregnant women, oversampled for a recent episode of major depression or use of a serotonin reuptake inhibitor. We extracted data on birth outcomes from hospital charts and used binary logistic regression to model preterm birth (<37 weeks’ gestation). We used ordered logistic regression to model early (<34 weeks’ gestation) or late (34-36 weeks) preterm birth, and we used nominal logistic regression to model preterm birth antecedents (spontaneous preterm labor/preterm premature rupture of membranes/preterm for medical indications/term).
Use of a serotonin reuptake inhibitor, both with (odds ratio=2.1 [95% confidence interval=1.0—4.6]) and without (1.6=[1.0—2.5]) a major depressive episode, was associated with preterm birth. A major depressive episode without serotonin reuptake inhibitor use (1.2; [0.68—2.1]) had no clear effect on preterm risk. None of these exposures was associated with early preterm birth. Use of serotonin reuptake inhibitors in pregnancy was associated with increases in spontaneous but not medically indicated preterm birth.
Serotonin reuptake inhibitor use increased risk of preterm birth. Although the effect of a major depressive episode alone was unclear, symptomatic women undergoing antidepressant treatment had elevated risk.
PMCID: PMC3415566  PMID: 22627901
7.  Contributing Indications to the Rising Cesarean Delivery Rate 
Obstetrics and gynecology  2011;118(1):29-38.
To examine physician-documented indications for cesarean delivery in order to investigate the specific indications contributing to this increase.
We analyzed rates of primary and repeat cesarean delivery, including indications for the procedure, among 32,443 live births at a major academic hospital between 2003–2009. Time trends for each indication were modeled to estimate the absolute and cumulative annualized relative risk of cesarean by indication over time and the relative contribution of each indication to the overall increase in primary cesarean delivery rate.
The cesarean delivery rate increased from 26% to 36.5% between 2003 and 2009; 50.0% of the increase was attributable to an increase in primary cesarean delivery. Among the documented indications, nonreassuring fetal status, arrest of dilation, multiple gestation, pre-eclampsia, suspected macrosomia, and maternal request increased over time, while arrest of descent, malpresentation, maternal-fetal indications, and other obstetric indications (eg, cord prolapse, placenta previa) did not increase. The relative contributions of each indication to the total increase in primary cesarean rate were: Non-reassuring fetal status (32%), labor arrest disorders (18%), multiple gestation (16%), suspected macrosomia (10%), pre-eclampsia (10%), maternal request (8%), maternal-fetal conditions (5%), and other obstetric conditions (1%).
Primary cesarean births accounted for 50% of the increasing cesarean rate. Among primary cesareans, more subjective indications (nonreassuring fetal status and arrest of dilation) contributed larger proportions than more objective indications (malpresentation, maternal-fetal, and obstetric conditions).
PMCID: PMC3751192  PMID: 21646928
8.  The relationship between air pollution and low birth weight: effects by mother’s age, infant sex, co-pollutants, and pre-term births 
Previously we identified associations between the mother’s air pollution exposure and birth weight for births in Connecticut and Massachusetts from 1999–2002. Other studies also found effects, though results are inconsistent. We explored potential uncertainties in earlier work and further explored associations between air pollution and birth weight for PM10, PM2.5, CO, NO2, and SO2. Specifically we investigated: (1) whether infants of younger (≤24 years) and older (≥40 years) mothers are particularly susceptible to air pollution’s effects on birth weight; (2) whether the relationship between air pollution and birth weight differed by infant sex; (3) confounding by co-pollutants and differences in pollutants’ measurement frequencies; and (4) whether observed associations were influenced by inclusion of pre-term births. Findings did not indicate higher susceptibility to the relationship between air pollution and birth weight based on the mother’s age or the infant’s sex. Results were robust to exclusion of pre-term infants and co-pollutant adjustment, although sample size decreased for some pollutant pairs. These findings provide additional evidence for the relationship between air pollution and birth weight, and do not identify susceptible sub-populations based on infant sex or mother’s age. We conclude with discussion of key challenges in research on air pollution and pregnancy outcomes.
PMCID: PMC3735236  PMID: 23930137
air pollution; birth weight; carbon monoxide; nitrogen dioxide; particulate matter; PM10; PM2.5; pregnancy; sensitivity analysis; sulfur dioxide
9.  Relationship Between Birth Weight and Exposure to Airborne Fine Particulate Potassium and Titanium During Gestation 
Environmental research  2012;117:83-89.
Airborne particles are linked to numerous health impacts, including adverse pregnancy outcomes. Most studies of particles examined total mass, although the chemical structure of particles varies widely. We investigated whether mother’s exposure to potassium (K) and titanium (Ti) components of airborne fine particulate matter (PM2.5) during pregnancy was associated with birth weight or risk of low birth weight (<2500 gm) for term infants. The study population was 76,788 infants born in four counties in Connecticut and Massachusetts, US, for August 2000-February 2004. Both K and Ti were associated with birth weight. An interquartile range (IQR) increase K was associated with an 8.75% (95% confidence interval (CI): 1.24–16.8%) increase in risk of low birth weight. An IQR increase in Ti was associated with a 12.1% (95% CI: 3.55–21.4%) increase in risk of low birth weight, with an estimate of 6.41% (95% CI: −5.80–20.2%) for males and 16.4% (95% CI: 5.13–28.9%) for females. Results were robust to sensitivity analysis of first births only, but not adjustment by co-pollutants. Disentangling the effects of various chemical components is challenging because of the covariance among some components due to similar sources. Central effect estimates for infants of African-American mothers were higher than those of white mothers, although the confidence intervals overlapped. Our results indicate that exposure to airborne potassium and titanium during pregnancy is associated with lower birth weight. Associations may relate to chemical components of sources producing K and Ti.
PMCID: PMC3418490  PMID: 22705336
air pollution; pregnancy; PM2.5; low birth weight; titanium; potassium
10.  Association of variants in innate immune genes with asthma and eczema 
The innate immune pathway is important in the pathogenesis of asthma and eczema. However, only a few variants in these genes have been associated with either disease. We investigate the association between polymorphisms of genes in the innate immune pathway with childhood asthma and eczema. In addition, we compare individual associations with those discovered using a multivariate approach.
Using a novel method, case control based association testing (C2BAT), 569 single nucleotide polymorphisms (SNPs) in 44 innate immune genes were tested for association with asthma and eczema in children from the Boston Home Allergens and Asthma Study and the Connecticut Childhood Asthma Study. The screening algorithm was used to identify the top SNPs associated with asthma and eczema. We next investigated the interaction of innate immune variants with asthma and eczema risk using Bayesian networks.
After correction for multiple comparisons, 7 SNPs in 6 genes (CARD25, TGFB1, LY96, ACAA1, DEFB1, and IFNG) were associated with asthma (adjusted p-value<0.02), while 5 SNPs in 3 different genes (CD80, STAT4, and IRAKI) were significantly associated with eczema (adjusted p-value < 0.02). None of these SNPs were associated with both asthma and eczema. Bayesian network analysis identified 4 SNPs that were predictive of asthma and 10 SNPs that predicted eczema. Of the genes identified using Bayesian networks, only CD80 was associated with eczema in the single-SNP study. Using novel methodology that allows for screening and replication in the same population, we have identified associations of innate immune genes with asthma and eczema. Bayesian network analysis suggests that additional SNPs influence disease susceptibility via SNP interactions.
Our findings suggest that innate immune genes contribute to the pathogenesis of asthma and eczema, and that these diseases likely have different genetic determinants.
PMCID: PMC3412627  PMID: 22192168
asthma; Bayesian network; genetic association; eczema; innate immunity
11.  Review of research on residential mobility during pregnancy: consequences for assessment of prenatal environmental exposures 
Studies on environmental exposures during pregnancy often have limited residential history (e.g., at delivery), potentially introducing exposure misclassification. We reviewed studies reporting residential mobility during pregnancy to summarize current evidence and discuss research implications. A meaningful quantitative combination of results (e.g., meta-analysis), was infeasible owing to variation in study designs. Fourteen studies were identified, of which half were from the US. Most were case-control studies examining birth defects. Residential history was typically assessed after delivery. Overall mobility rates were 9–32% and highest in the second trimester. Mobility generally declined with age, parity, and socioeconomic status, although not consistently. Married mothers moved less frequently. Findings were dissimilar by race, smoking, or alcohol use. On the basis of the few studies reporting distance moved, most distances were short (median often <10 km). Results indicate potential misclassification for environmental exposures estimated with incomplete residential information. This misclassification could be associated with potential confounders, such as socioeconomics, thereby affecting risk estimates. As most moves were short distances, exposures that are homogenous within a community may be well estimated with limited residential data. Future research should consider the implications of residential mobility during pregnancy in relation to the exposure’s spatial heterogeneity and factors associated with the likelihood of moving and distance moved.
PMCID: PMC3543155  PMID: 22617723
residential mobility; pregnancy; air pollution
13.  Urban Land-Use and Respiratory Symptoms in Infants 
Environmental research  2011;111(5):677-684.
Children’s respiratory health has been linked to many factors, including air pollution. The impacts of urban land-use on health are not fully understood, although these relationships are of key importance given the growing populations living in urban environments.
We investigated whether the degree of urban land-use near a family’s residence is associated with severity of respiratory symptoms like wheeze among infants.
Wheeze occurrence was recorded for the first year of life for 680 infants in Connecticut for 1996–1998 from a cohort at risk for asthma development. Land-use categories were obtained from the National Land Cover Database. The fraction of urban land-use near each subject’s home was related to severity of wheeze symptoms using ordered logistic regression, adjusting for individual-level data including smoking in the household, race, gender, and socio-economic status. Nitrogen dioxide (NO2) exposure was estimated using integrated traffic exposure modeling. Different levels of urban land-use intensity were included in separate models to explore intensity-response relationships. A buffer distance was selected based on the log-likelihood value of models with buffers of 100–2,000m by 10m increments.
A 10% increase in urban land-use within the selected 1,540m buffer of each infant’s residence was associated with 1.09-fold increased risk of wheeze severity (95% confidence interval, 1.02–1.16). Results were robust to alternate buffer sizes. When NO2, representing traffic pollution, was added to the model, results for urban land-use were no longer statistically significant, but had similar central estimates. Higher urban intensity showed higher risk of prevalence and severity of wheeze symptoms.
Urban land-use was associated with severity of wheeze symptoms in infants. Findings indicate that health effect estimates for urbanicity incorporate some effects of traffic-related emissions, but also involve other factors. These may include differences in housing characteristics or baseline healthcare status.
PMCID: PMC3114197  PMID: 21530957
Wheeze Symptom; Land-Use; Infants’ health; Traffic; Urbanicity
15.  Antibiotic Exposure by 6 Months and Asthma and Allergy at 6 Years: Findings in a Cohort of 1,401 US Children 
American Journal of Epidemiology  2010;173(3):310-318.
Many studies have reported that antibiotic use may be associated with increased risk of childhood asthma. Respiratory tract infections in small children may be difficult to distinguish from early symptoms of asthma, and studies may have been confounded by “protopathic” bias, where antibiotics are used to treat early symptoms of asthma. These analyses of a cohort including 1,401 US children assess the association between antibiotic use within the first 6 months of life and asthma and allergy at 6 years of age between 2003 and 2007. Antibiotic exposure was associated with increased risk of asthma (adjusted odds ratio = 1.52, 95% confidence interval (CI): 1.07, 2.16). The odds ratio if asthma was first diagnosed after 3 years of age was 1.66 (95% CI: 0.99, 2.79) and, in children with no history of lower respiratory infection in the first year of life, the odds ratio was 1.66 (95% CI: 1.12, 3.46). The adverse effect of antibiotics was particularly strong in children with no family history of asthma (odds ratio = 1.89, 95% CI: 1.00, 3.58) (Pinteraction = 0.03). The odds ratio for a positive allergy blood or skin test was 1.59 (95% CI: 1.10, 2.28). The results show that early antibiotic use was associated with asthma and allergy at 6 years of age, and that protopathic bias was unlikely to account for the main findings.
PMCID: PMC3105273  PMID: 21190986
anti-bacterial agents; asthma; child; cohort studies; hypersensitivity
16.  Effects of endotoxin exposure on childhood asthma risk are modified by a genetic polymorphism in ACAA1 
BMC Medical Genetics  2011;12:158.
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.
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.
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.
Our findings suggest that protective effects of endotoxin exposure on asthma may vary depending upon the presence or absence of a polymorphism in ACAA1.
PMCID: PMC3252252  PMID: 22151743
17.  Modeling effects of traffic and landscape characteristics on ambient nitrogen dioxide levels in Connecticut 
An integrated exposure model was developed that estimates nitrogen dioxide (NO2) concentration at residences using geographic information systems (GIS) and variables derived within residential buffers representing traffic volume and landscape characteristics including land use, population density and elevation. Multiple measurements of NO2 taken outside of 985 residences in Connecticut were used to develop the model. A second set of 120 outdoor NO2 measurements as well as cross-validation were used to validate the model. The model suggests that approximately 67% of the variation in NO2 levels can be explained by: traffic and land use primarily within 2 km of a residence; population density; elevation; and time of year. Potential benefits of this model for health effects research include improved spatial estimations of traffic-related pollutant exposure and reduced need for extensive pollutant measurements. The model, which could be calibrated and applied in areas other than Connecticut, has importance as a tool for exposure estimation in epidemiological studies of traffic-related air pollution.
PMCID: PMC2976574  PMID: 21076636
traffic-related air pollution; exposure modeling; outdoor nitrogen dioxide; traffic volume; land use
18.  Effect of Pregnancy on Maternal Asthma Symptoms and Medication Use 
Obstetrics and gynecology  2010;115(3):559-567.
To examine whether factors related to the patient or her treatment influence asthma severity during pregnancy.
Symptom and medication data were collected by in-person and telephone interviews. Women were recruited before 24 weeks of gestation through private obstetricians and hospital clinics. Eight hundred seventy-two women had physician-diagnosed asthma, 686 were active asthmatics, and 641 with complete data were analyzed. The Global Initiative for Asthma measured severity. Cumulative logistic regression models for repeated measures assessed changes in asthma severity during each month of pregnancy.
Two factors had significant and profound effects on the course of asthma: prepregnancy severity and use of medication according to Global Initiative for Asthma guidelines. Although several factors were analyzed (race, age, atopic status, body mass index, parity, fetal sex, and smoking), none were significant risk factors for changes in asthma severity, measured in a clinically important way as a one-step change in Global Initiative for Asthma category. Women with milder asthma received most benefit from appropriate treatment, 62% decreased risk for worsening asthma among those with intermittent asthma (0.38, 95% confidence interval 0.23–0.64) and 52% decreased risk among those with mild persistent asthma (odds ratio 0.48, 95% confidence interval 0.28–0.84). Month or trimester of gestation was not consistently associated with changes in asthma severity.
Asthma severity during pregnancy is similar to severity in the year before pregnancy, provided patients continue to use their prescribed medication. If women discontinue medication, even mild asthma is likely to become significantly more severe.
PMCID: PMC3176497  PMID: 20177287
20.  Prenatal Exposure to Fine Particulate Matter and Birth Weight 
Epidemiology (Cambridge, Mass.)  2010;21(6):884-891.
Exposure to fine particles (PM2.5) during pregnancy has been linked to lower birth weight; however, the chemical composition of PM2.5 varies widely. The health effects of PM2.5 constituents are unknown.
We investigated whether PM2.5 mass, constituents, and sources are associated with birth weight for term births. PM2.5 filters collected in 3 Connecticut counties and 1 Massachusetts county from August 2000 through February 2004 were analyzed for more than 50 elements. Source apportionment was used to estimate daily contributions of PM2.5 sources, including traffic, road dust/crustal, oil combustion, salt, and regional (sulfur) sources. Gestational and trimester exposure to PM2.5 mass, constituents, and source contributions were examined in relation to birth weight and risk of small-at-term birth (term birth <2500 g) for 76,788 infants.
Road dust and related constituents such as silicon and aluminum were associated with lower birth weight, as were the motor-vehicle-related species such as elemental carbon and zinc, and the oil-combustion-associated elements vanadium and nickel. An interquartile range increase in exposure was associated with low birthweight for zinc (12% increase in risk), elemental carbon (13%), silicon (10%), aluminum (11%), vanadium (8%), and nickel (11%). Analysis by trimester showed effects of third-trimester exposure to elemental carbon, nickel, vanadium, and oil-combustion PM2.5.
Exposures of pregnant women to higher levels of certain PM2.5 chemical constituents originating from specific sources are associated with lower birth weight.
PMCID: PMC3055585  PMID: 20811286
21.  Association of pediatric asthma severity with exposure to common household dust allergens 
Environmental research  2009;109(6):768-774.
Reducingexposure to household dust inhalant allergens has been proposed as one strategy to reduce asthma.
To examine the dose response relationships and health impact of five common household dust allergens on disease severity, quantified using both symptom frequency and medication use, in atopic and non-atopic asthmatic children.
Asthmatic children (N=300) aged 4–12 years were followed for one year. Household dust samples from two indoor locations were analyzed for allergens including dust mite (Der p 1, Der f 1), cat (Fel d 1), dog (Can f 1), cockroach (Bla g 1). Daily symptoms and medication use were collected in monthly telephone interviews. Annual disease severity was examined in models including allergens, specific IgE sensitivity and adjusted for age, gender, atopy, ethnicity, and mother’s education.
Der p 1 house dust mite allergen concentration of 2.0 + μg/g from the main room and the child’s bed was related to increased asthma severity independent of allergic status (respectively, OR 2.93, 95% CI 1.37, 6.30 for 2.0 –10.0 μg/g and OR 2.55 95% CI 1.13, 5.73 for ≥ 10.0 μg/g). Higher pet allergen levels were associated with greater asthma severity, but only for those sensitized (cat OR 2.41 95% CI 1.19, 4.89; dog OR 2.06 95% CI 1.01, 4.22).
Higher levels of Der p 1 and pet allergens were associated with asthma severity, but Der p 1 remained an independent risk factor after accounting for pet allergens and regardless of Der p 1 specific IgE status.
PMCID: PMC2706291  PMID: 19473655
pediatric asthma; household dust allergens; Der p1; dust mite; pet allergens
22.  Typical Somatic Symptoms of Pregnancy and Their Impact on a Diagnosis of Major Depressive Disorder 
General hospital psychiatry  2009;31(4):327-333.
We sought to determine whether trimester of pregnancy influences the ability to diagnose major depressive disorder (MDD).
838 subjects completed a Composite International Diagnostic Interview and the Edinburgh Postnatal Depression Scale (EPDS) before 17 weeks pregnant, at 26−30 weeks of pregnancy and 4−12 weeks postpartum. Subjects responded to a checklist of MDD symptoms regardless of stem question endorsement. We compared rates of symptom expression by response (Y/N) to stem questions, and trimester, using logit analysis. Receiver Operating Curves determined optimal EPDS thresholds.
Most symptoms from the DSM-IV checklist were endorsed significantly more often in the first compared to later trimesters (Odds Ratios ranged from 1.39−14.16 for the first vs. later trimesters), independent of response to depression stem questions or medication treatment. Despite this, stem positive and stem negative groups differed significantly for 10 out of 13 symptoms (Odds Ratios 2.29−6.89), independent of trimester. The EPDS had an optimal cutoff of 10 and showed acceptable predictive value.
Pregnant women commonly experience somatic and other symptoms in this first trimester but depressed women still differ from those who are not depressed. “Appetite increase,” “oversleeping” and “increase in energy” (e.g. agitation). were uninformative with regard to an MDD diagnosis.
PMCID: PMC2748743  PMID: 19555792
Mood disorders/unipolar; Obstetrics and Gynecology; Pregnancy; Women
23.  Evaluation of a social support measure that may indicate risk of depression during pregnancy 
Journal of affective disorders  2008;114(1-3):216-223.
Strong social support has been linked with positive mental health and better birth outcomes for pregnant women. Our aim was to replicate the psychometric properties of the Kendler Social Support Interview modified for use in pregnant women and to establish the inventory’s relationship to depression in pregnancy.
The modified Kendler Social Support Interview (MKSSI) was evaluated using principal components analysis. The association with depression was used as an indicator of external validity and was assessed by logistic regression.
Data from 783 subjects were analyzed. One large principal component, termed “global support,” (eigenvalue=6.086) represented 22.5% of the total variance. However, 6 of the 27 items (frequency of contact with spouse, siblings, other relatives, and friends, and attendance at church and clubs) had low levels of association (<0.4) and thus were excluded from suggested items for a total score. Varimax rotation of the remaining 21 items resulted in subscales that fell into expected groupings: mother, father, siblings, friends, etc. One unit and two unit increases in the global support score were associated with 58.3% (OR=0.417, 95% CI=0.284-0.612) and 82.6% (OR=0.174, 95% CI=0.081-0.374) reductions in odds for depression, respectively.
The ability of this social support scale to predict future depression in pregnancy has not yet been established due to cross-sectional design.
The MKSSI is reliable and valid for use in evaluating social support and its relationship to depression in pregnant women.
PMCID: PMC2654337  PMID: 18765164
Social support; Pregnancy; Depression; Women; Psychometrics
24.  Chocolate Consumption in Pregnancy and Reduced Likelihood of Preeclampsia 
Epidemiology (Cambridge, Mass.)  2008;19(3):459-464.
Preeclampsia is a major pregnancy complication with cardiovascular manifestations. Recent studies suggest that chocolate consumption may benefit cardiovascular health.
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.
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).
Our results suggest that chocolate consumption during pregnancy may lower risk of preeclampsia. However, reverse causality may also contribute to these findings.
PMCID: PMC2782959  PMID: 18379424
25.  Indoor Combustion and Asthma 
PMCID: PMC2760246  PMID: 18572104

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