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1.  Gestational weight gain among American Samoan women and its impact on delivery and infant outcomes 
Background
As obesity has increased worldwide, so have levels of obesity during pregnancy and excess gestational weight gain (GWG). The aim of this paper was to describe GWG among American Samoan women and examine the association between GWG and four adverse pregnancy and infant outcomes: cesarean delivery, small- and large-for-gestational age (SGA/LGA), and infant overweight/obesity.
Methods
Data were extracted from prenatal care records of 632 Samoan women. Mixed-effects growth models were used to produce individual weight-for-gestational week curves from which second and third trimester weight gain was estimated. Binary logistic regression was used to examine associations between GWG and the outcomes of interest.
Results
Most women were overweight/obese in early pregnancy (86%) and 78% exceeded the Institute of Medicine GWG guidelines. Greater GWG in the second trimester and early pregnancy weight were independently associated with increased odds of a c-section (OR 1.40 [95% CI: 1.08, 1.83]) and OR 1.51 [95% CI: 1.17, 1.95], respectively). Risk of delivering a LGA infant increased with greater third trimester weight gain and higher early pregnancy weight, while second trimester weight gain was negatively associated with SGA. Risk of infant overweight/obesity at 12 months increased with early pregnancy weight (OR: 1.23 [95% CI: 1.01, 1.51]) and infant birthweight.
Conclusions
The high levels of pregnancy obesity and excessive GWG in American Samoa suggest that it is important for physicians to encourage women into prenatal care early and begin education about appropriate GWG and the potential risks of excess weight gain for both the mother and baby.
doi:10.1186/s12884-015-0451-1
PMCID: PMC4324802  PMID: 25643752
American Samoa; Birth size; Cesarean delivery; Gestational weight gain; Obesity
2.  Accuracy of Brief Screening Tools for Identifying Postpartum Depression Among Adolescent Mothers 
Pediatrics  2014;133(1):e45-e53.
OBJECTIVE:
To evaluate the accuracy of the Edinburgh Postnatal Depression Scale (EPDS) and 3 subscales for identifying postpartum depression among primiparous adolescent mothers.
METHODS:
Mothers enrolled in a randomized controlled trial to prevent postpartum depression completed a psychiatric diagnostic interview and the 10-item EPDS at 6 weeks, 3 months, and 6 months postpartum. Three subscales of the EPDS were assessed as brief screening tools: 3-item anxiety subscale (EPDS-3), 7-item depressive symptoms subscale (EPDS-7), and 2-item subscale (EPDS-2) that resemble the Patient Health Questionnaire-2. Receiver operating characteristic curves and the areas under the curves for each tool were compared to assess accuracy. The sensitivities and specificities of each screening tool were calculated in comparison with diagnostic criteria for a major depressive disorder. Repeated-measures longitudinal analytical techniques were used.
RESULTS:
A total of 106 women contributed 289 postpartum visits; 18% of the women met criteria for incident postpartum depression by psychiatric diagnostic interview. When used as continuous measures, the full EPDS, EPDS-7, and EPDS-2 performed equally well (area under the curve >0.9). Optimal cutoff scores for a positive depression screen for the EPDS and EPDS-7 were lower (≥9 and ≥7, respectively) than currently recommended cutoff scores (≥10). At optimal cutoff scores, the EPDS and EPDS-7 both had sensitivities of 90% and specificities of >85%.
CONCLUSIONS:
The EPDS, EPDS-7, and EPDS-2 are highly accurate at identifying postpartum depression among adolescent mothers. In primary care pediatric settings, the EPDS and its shorter subscales have potential for use as effective depression screening tools.
doi:10.1542/peds.2013-1628
PMCID: PMC3876181  PMID: 24344102
teenage; pregnancy; screening; postpartum depression; validity
4.  Chocolate Consumption in Pregnancy and Reduced Likelihood of Preeclampsia 
Epidemiology (Cambridge, Mass.)  2008;19(3):459-464.
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.
doi:10.1097/EDE.0b013e31816a1d17
PMCID: PMC2782959  PMID: 18379424
5.  Correction of Systematic Bias in Ultrasound Dating in Studies of Small-for-Gestational-Age Birth: An Example From the Iowa Health in Pregnancy Study 
American Journal of Epidemiology  2012;176(5):443-455.
The authors examined whether early ultrasound dating (≤20 weeks) of gestational age (GA) in small-for-gestational-age (SGA) fetuses may underestimate gestational duration and therefore the incidence of SGA birth. Within a population-based case-control study (May 2002–June 2005) of Iowa SGA births and preterm deliveries identified from birth records (n = 2,709), the authors illustrate a novel methodological approach with which to assess and correct for systematic underestimation of GA by early ultrasound in women with suspected SGA fetuses. After restricting the analysis to subjects with first-trimester prenatal care, a nonmissing date of the last menstrual period (LMP), and early ultrasound (n = 1,135), SGA subjects’ ultrasound GA was 5.5 days less than their LMP GA, on average. Multivariable linear regression was conducted to determine the extent to which ultrasound GA predicted LMP dating and to correct for systematic misclassification that results after applying standard guidelines to adjudicate differences in these measures. In the unadjusted model, SGA subjects required a correction of +1.5 weeks to the ultrasound estimate. With adjustment for maternal age, smoking, and first-trimester vaginal bleeding, standard guidelines for adjudicating differences in ultrasound and LMP dating underestimated SGA birth by 12.9% and overestimated preterm delivery by 8.7%. This methodological approach can be applied by researchers using different study populations in similar research contexts.
doi:10.1093/aje/kws120
PMCID: PMC3499119  PMID: 22886591
bias (epidemiology); gestational age; infant, small for gestational age; pregnancy; premature birth; ultra-sonography
6.  Clinical Characteristics of Children with Autism Spectrum Disorder and Co-Occurring Epilepsy 
PLoS ONE  2013;8(7):e67797.
Objectives
To estimate the prevalence of epilepsy in children with Autism Spectrum Disorder (ASD) and to determine the demographic and clinical characteristics of children with ASD and epilepsy in a large patient population.
Methods
Cross-sectional study using four samples of children with ASD for a total of 5,815 participants with ASD. The prevalence of epilepsy was estimated from a population-based sample. Children with and without epilepsy were compared on demographic and clinical characteristics. Multivariate logistic regression was used to examine the association between demographic and clinical characteristics and epilepsy.
Results
The average prevalence of epilepsy in children with ASD 2–17 years was 12.5%; among children aged 13 years and older, 26% had epilepsy. Epilepsy was associated with older age, lower cognitive ability, poorer adaptive and language functioning, a history of developmental regression and more severe ASD symptoms. The association between epilepsy and the majority of these characteristics appears to be driven by the lower IQ of participants with epilepsy. In a multivariate regression model, only age and cognitive ability were independently associated with epilepsy. Children age 10 or older had 2.35 times the odds of being diagnosed with epilepsy (p<.001) and for a one standard deviation increase in IQ, the odds of having epilepsy decreased by 47% (p<.001).
Conclusion
This is among the largest studies to date of patients with ASD and co-occurring epilepsy. Based on a representative sample of children with ASD, the average prevalence of epilepsy is approximately 12% and reaches 26% by adolescence. Independent associations were found between epilepsy and older age and lower cognitive ability. Other risk factors, such as poor language and developmental regression, are not associated with epilepsy after controlling for IQ. These findings can help guide prognosis and alert clinicians to patients with ASD who are at increased risk for epilepsy.
doi:10.1371/journal.pone.0067797
PMCID: PMC3701630  PMID: 23861807
7.  Association of variants in innate immune genes with asthma and eczema 
Background
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.
Methods
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.
Results
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.
Conclusion
Our findings suggest that innate immune genes contribute to the pathogenesis of asthma and eczema, and that these diseases likely have different genetic determinants.
doi:10.1111/j.1399-3038.2011.01243.x
PMCID: PMC3412627  PMID: 22192168
asthma; Bayesian network; genetic association; eczema; innate immunity
8.  Sexual Risk Behaviors Among HIV-Infected South African Men and Women with Their Partners in a Primary Care Program: Implications for Couples-Based Prevention 
AIDS and Behavior  2012;16(1):139-150.
We studied 1163 sexually-active HIV-infected South African men and women in an urban primary care program to understand patterns of sexual behaviors and whether these behaviors differed by partner HIV status. Overall, 40% reported a HIV-positive partner and 60% a HIV-negative or status unknown partner; and 17.5% reported >2 sex acts in the last 2 weeks, 16.4% unprotected sex in the last 6 months, and 3.7% >1 sex partner in the last 6 months. Antiretroviral therapy (ART) was consistently associated with decreased sexual risk behaviors, as well as with reporting a HIV-negative or status unknown partner. The odds of sexual risk behaviors differed by sex; and were generally higher among participants reporting a HIV-positive partner, but continued among those with a HIV-negative or status unknown partner. These data support ART as a means of HIV prevention. Engaging in sexual risk behaviors primarily with HIV-positive partners was not widely practiced in this setting, emphasizing the need for couples-based prevention.
doi:10.1007/s10461-011-9941-y
PMCID: PMC3184366  PMID: 21476005
HIV; AIDS; South Africa; Sexual risk behavior; ART
9.  Effects of Ambient Pollen Concentrations on Frequency and Severity of Asthma Symptoms Among Asthmatic Children 
Background
Previous studies on the associations between ambient pollen exposures and daily respiratory symptoms have produced inconsistent results. We investigated these relationships in a cohort of asthmatic children, using pollen exposure models to estimate individual ambient exposures.
Methods
Daily symptoms of wheeze, night symptoms, shortness of breath, chest tightness, persistent cough and rescue medication use were recorded in a cohort of 430 children age 4-12 years with asthma in Connecticut, Massachusetts and New York. Daily ambient exposures to tree, grass, weed and all-type pollen were estimated using mixed effects models. We stratified analyses by asthma maintenance medication and sensitization to grass or weed pollens. Separate logistic regression analysis using generalized estimating equations were performed for each symptom outcome and pollen type. We adjusted analyses for maximum daily temperature, maximum 8-hr average ozone, fine particles (PM2.5), season and antibiotic use.
Results
Associations were observed among children sensitized to specific pollens; these associations varied by use of asthma maintenance medication. Exposures to even relatively low levels of weed pollen (6-9 grains/m3) were associated with increased shortness of breath, chest tightness, rescue medication use, wheeze, and persistent cough, compared with lower exposure among sensitized children taking maintenance medication. Grass pollen exposures ≥2 grains/m3 were associated with wheeze, night symptoms, shortness of breath and persistent cough compared with lower exposure among sensitized children who did not take maintenance medication.
Conclusion
Even low-level pollen exposure was associated with daily asthmatic symptoms.
doi:10.1097/EDE.0b013e31823b66b8
PMCID: PMC3246281  PMID: 22082997
10.  Genome-wide association study identifies a maternal copy-number deletion in PSG11 enriched among preeclampsia patients 
Background
Specific genetic contributions for preeclampsia (PE) are currently unknown. This genome-wide association study (GWAS) aims to identify maternal single nucleotide polymorphisms (SNPs) and copy-number variants (CNVs) involved in the etiology of PE.
Methods
A genome-wide scan was performed on 177 PE cases (diagnosed according to National Heart, Lung and Blood Institute guidelines) and 116 normotensive controls. White female study subjects from Iowa were genotyped on Affymetrix SNP 6.0 microarrays. CNV calls made using a combination of four detection algorithms (Birdseye, Canary, PennCNV, and QuantiSNP) were merged using CNVision and screened with stringent prioritization criteria. Due to limited DNA quantities and the deleterious nature of copy-number deletions, it was decided a priori that only deletions would be selected for assay on the entire case-control dataset using quantitative real-time PCR.
Results
The top four SNP candidates had an allelic or genotypic p-value between 10-5 and 10-6, however, none surpassed the Bonferroni-corrected significance threshold. Three recurrent rare deletions meeting prioritization criteria detected in multiple cases were selected for targeted genotyping. A locus of particular interest was found showing an enrichment of case deletions in 19q13.31 (5/169 cases and 1/114 controls), which encompasses the PSG11 gene contiguous to a highly plastic genomic region. All algorithm calls for these regions were assay confirmed.
Conclusions
CNVs may confer risk for PE and represent interesting regions that warrant further investigation. Top SNP candidates identified from the GWAS, although not genome-wide significant, may be useful to inform future studies in PE genetics.
doi:10.1186/1471-2393-12-61
PMCID: PMC3476390  PMID: 22748001
Copy-number variant; Genome-wide association study; Microarray analysis; Preeclampsia; Single nucleotide polymorphism
11.  Sexual risk behaviors among HIV-infected South Indian couples in the HAART era: implications for reproductive health and HIV care delivery 
AIDS care  2011;23(6):722-733.
The current study examines sexual behaviors among HIV-infected Indians in primary care, where access to highly active antiretroviral therapy (HAART) has recently increased. Between January to April 2008, we assessed the sexual behaviors of 247 HIV-infected South Indians in care. Multivariable logistic regression models were used to determine predictors of being in a HIV-seroconcordant primary relationship, being sexually active, and reporting unprotected sex. Over three-fourths (80%) of participants were HAART-experienced. Among the 58% of participants who were currently in a seroconcordant relationship, one-third were serodiscordant when first tested for HIV. Approximately two-thirds (63.2%) of participants were sexually active; 9.0% reported unprotected sex. In the multivariable analyses, participants who were in a seroconcordant primary relationship were more likely to have children, use alcohol, report unprotected sex, and have been enrolled in care for >12 months. Sexually active participants were more likely to be on HAART, have a prior tuberculosis diagnosis, test Herpes simplex type 2 antibody seropositive, and have low general health perceptions. Participants who reported unprotected sex were more likely to be in a seroconcordant relationship, be childless, want to have a child, and use alcohol. We did not document an association between HAART and unprotected sex. Among HIV-infected Indians in primary care, predictors of unprotected sex included alcohol use and desire for children. Prevention interventions for Indian couples should integrate reproductive health and alcohol use counseling at entry into care.
doi:10.1080/09540121.2010.525616
PMCID: PMC3095699  PMID: 21293990
HIV; AIDS; sexual behavior; HAART; India
12.  Morbidity and Mortality among Infants Born to HIV-Infected Women in South Africa: Implications for Child Health in Resource-Limited Settings 
Journal of Tropical Pediatrics  2010;57(2):109-119.
Background: We examined correlates of infant morbidity and mortality within the first 3 months of life among HIV-exposed infants receiving post-exposure antiretroviral prophylaxis in South Africa. Methods: We conducted a prospective cohort study of 848 mother–child dyads. Multivariable Cox proportional hazards models were used. Results: The main causes of infant morbidity were gastrointestinal and respiratory infections. Morbidity was higher with infant HIV infection (HR: 2.61; 95% CI: 1.40–4.85; p = 0.002) and maternal plasma viral load (PVL) >100 000 copies ml−1 (HR: 1.87; 95% CI: 1.01–3.48; p = 0.048), and lower with maternal age <20 years (HR: 0.25; 95% CI: 0.07–0.88; p = 0.031). Mortality was higher with infant HIV infection (HR: 4.10; 95% CI: 1.18–14.31; p = 0.027) and maternal PVL >100 000 copies ml−1 (HR: 6.93; 95% CI: 1.64–29.26; p = 0.008). Infant feeding status did not influence the risk of morbidity nor mortality. Conclusions: Future interventions that minimize pediatric HIV infection and reduce maternal viremia, which are the main predictors of child health soon after birth, will impact positively on infant health outcomes.
doi:10.1093/tropej/fmq061
PMCID: PMC3107462  PMID: 20601692
South Africa; mother-to-child transmission; breast-feeding; infant HIV-1 infection; mortality; morbidity
13.  Prenatal Factors for Childhood Blood Pressure Mediated by Intrauterine and/or Childhood Growth? 
Pediatrics  2011;127(3):e713-e721.
OBJECTIVE:
Some prenatal factors may program an offspring's blood pressure, but existing evidence is inconclusive and mechanisms remain unclear. We examined the mediating roles of intrauterine and childhood growth in the associations between childhood systolic blood pressure (SBP) and 5 potentially modifiable prenatal factors: maternal smoking during pregnancy; prepregnancy BMI; pregnancy weight gain; chronic hypertension; and preeclampsia-eclampsia.
METHODS:
The sample contained 30 461 mother-child pairs in the Collaborative Perinatal Project. Prenatal data were extracted from obstetric forms, and children's SBP was measured at 7 years of age. Potential mediation by intrauterine growth restriction (IUGR) and childhood growth was examined by the causal step method.
RESULTS:
Heavy maternal smoking during pregnancy was significantly associated with higher offspring SBP (adjusted mean difference versus nonsmoking: 0.73 mm Hg [95% confidence interval (CI): 0.32–1.14]), which attenuated to null (0.13 [95% CI: −0.27–0.54]) after adjustment for changes in BMI from birth to 7 years of age. Prepregnancy overweight-obesity was significantly associated with higher offspring SBP (versus normal weight: 0.89 mm Hg [95% CI: 0.52–1.26]), which also attenuated to null (−0.04 mm Hg [95% CI: −0.40–0.31]) after adjustment for childhood BMI trajectory. Adjustment for BMI trajectory augmented the association between maternal pregnancy weight gain and offspring SBP. Adjustment for childhood weight trajectory similarly changed these associations. However, all these associations were independent of IUGR.
CONCLUSIONS:
Childhood BMI and weight trajectory, but not IUGR, may largely mediate the associations of maternal smoking during pregnancy and prepregnancy BMI with an offspring's SBP.
doi:10.1542/peds.2010-2000
PMCID: PMC3065147  PMID: 21300676
blood pressure; pregnancy; fetal development; infant; small for gestational age; child development; obesity
14.  Association between placental morphology and childhood systolic blood pressure 
Hypertension  2010;57(1):48-55.
We tested hypotheses that disproportionately large placental size and vascular lesions were associated with high systolic blood pressure (SBP); and these associations might be more evident with age. The sample included 13,273 out of 40,666 full-term singletons in the Collaborative Perinatal Project. Placentas were examined by pathologists blinded of pregnancy courses and outcomes. The 4-month and 7-year SBP were measured with palpation and auscultation methods, respectively. We found that placental weight (adjusted mean difference corresponding to an increase by 1 standard deviation, 0.50 [95% confidence interval, 0.33 to 0.68]) and placenta-fetus weight ratio (0.37 [95% CI, 0.19 to 0.54]) was positively associated with 7-year SBP, but not associated with 4-month SBP. Placental largest and smallest diameters, and area were negatively associated with 4-month SBP, but positively with 7-year SBP. Placental thickness was negatively associated with 4-month SBP only. Placental volume was negatively associated with 4-month SBP (−0.60 [95% CI, −0.85 to −0.35]), but positively associated with 7-year SBP (0.48 [95% CI, 0.30 to 0.67]). Thrombi in cord vessels (adjusted mean difference vs absence, 2.73 [95% CI, −0.03 to 5.50]) and decidual vessels (2.58 [95% CI, 0.24 to 4.91]), villous microinfarcts (1.63 [95% CI, 0.71 to 2.55]), necrosis at the decidual margin (1.57 [95% CI, 0.54 to 2.59]) and basalis (3.44 [95% CI, 1.55 to 5.32]) were associated with higher 4-month SBP only. We conclude that placental inefficiency, reflected by disproportionately large weight and size, predicts long-term blood pressure, while vascular resistance and lesions may only influence short-term blood pressure.
doi:10.1161/HYPERTENSIONAHA.110.162792
PMCID: PMC3074204  PMID: 21079045
placenta; placental insufficiency; placental circulation; fetal development; blood pressure
15.  Effects of endotoxin exposure on childhood asthma risk are modified by a genetic polymorphism in ACAA1 
BMC Medical Genetics  2011;12:158.
Background
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.
Methods
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.
Results
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.
Conclusion
Our findings suggest that protective effects of endotoxin exposure on asthma may vary depending upon the presence or absence of a polymorphism in ACAA1.
doi:10.1186/1471-2350-12-158
PMCID: PMC3252252  PMID: 22151743
16.  Predictors of Nonadherence to Highly Active Antiretroviral Therapy Among HIV-Infected South Indians in Clinical Care: Implications for Developing Adherence Interventions in Resource-Limited Settings 
AIDS Patient Care and STDs  2010;24(12):795-803.
Abstract
In light of the increasing availability of generic highly active antiretroviral therapy (HAART) in India, further data are needed to examine variables associated with HAART nonadherence among HIV-infected Indians in clinical care. We conducted a cross-sectional analysis of 198 HIV-infected South Indian men and women between January and April 2008 receiving first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based HAART. Nonadherence was defined as taking less than 95% of HAART doses in the last 1 month, and was examined using multivariable logistic regression models. Half of the participants reported less than 95% adherence to HAART, and 50% had been on HAART for more than 24 months. The median CD4 cell count was 435 cells per microliter. An increased odds of nonadherence was found for participants with current CD4 cell counts greater than 500 cells per microliter (adjusted odds ratio [AOR]: 2.22 [95% confidence interval {CI}: 1.04–4.75]; p = 0.038), who were on HAART for more than 24 months (AOR: 3.07 [95% CI: 1.35–7.01]; p = 0.007), who reported alcohol use (AOR: 5.68 [95%CI: 2.10-15.32]; p = 0.001), who had low general health perceptions (AOR: 3.58 [95%CI: 1.20-10.66]; p = 0.021), and who had high distress (AOR: 3.32 [95%CI: 1.19-9.26]; p = 0.022). This study documents several modifiable risk factors for nonadherence in a clinic population of HIV-infected Indians with substantial HAART experience. Further targeted culturally specific interventions are needed that address barriers to optimal adherence.
doi:10.1089/apc.2010.0153
PMCID: PMC3011993  PMID: 21091232
17.  Decreased sexual risk behavior in the era of HAART among HIV-infected urban and rural South Africans attending primary care clinics 
AIDS (London, England)  2010;24(17):2687-2696.
Objective
In light of increasing access to highly active antiretroviral treatment (HAART) in sub-Saharan Africa, we conducted a longitudinal study to assess the impact of HAART on sexual risk behaviors among HIV-infected South Africans in urban and rural primary care clinics.
Design
Prospective observational cohort study.
Methods
We conducted a cohort study at rural and urban primary care HIV clinics in South Africa consisting of 1544 men and 4719 women enrolled from 2003–2010, representing 19703 clinic visits. The primary outcomes were being sexually active, unprotected sex, and >1 sex partner and were evaluated at six monthly intervals. Generalized estimated equations assessed the impact of HAART on sexual risk behaviors.
Results
Among 6263 HIV-infected men and women, over a third (37.2%) initiated HAART during study follow-up. In comparison to pre-HAART follow-up, visits while receiving HAART were associated with a decrease in those reporting being sexually active (AOR: 0.86 [95% CI: 0.78–0.95]). Unprotected sex and having >1 sex partner were reduced at visits following HAART initiation compared to pre-HAART visits (AOR: 0.40 [95% CI: 0.34–0.46] and AOR: 0.20 [95% CI: 0.14–0.29], respectively).
Conclusions
Sexual risk behavior significantly decreased following HAART initiation among HIV-infected South African men and women in primary care programs. The further expansion of antiretroviral treatment programs could enhance HIV prevention efforts in Africa.
doi:10.1097/QAD.0b013e32833e78d4
PMCID: PMC3130627  PMID: 20808202
South Africa; HAART; antiretroviral therapy; sexual behavior; HIV transmission; AIDS; HIV
18.  Integrated Exposure Modeling: A Model Using GIS and GLM 
Statistics in medicine  2010;29(1):116-129.
Traffic exhaust is a source of air contaminants that have adverse health effects. Quantification of traffic as an exposure variable is complicated by aerosol dispersion related to variation in layout of roads, traffic density, meteorology, and topography. A statistical model is presented which uses Geographic Information Systems (GIS) technology to incorporate variables into a generalized linear model that estimates distribution of traffic-related pollution. Exposure from a source is expressed as an integral of a function proportional to average daily traffic and a nonparametric dispersion function which takes the form of a step, polynomial or spline model. The method may be applied using standard regression techniques for fitting generalized linear models. Modifiers of pollutant dispersion such as wind direction, meteorology, and landscape features can also be included. Two examples are given to illustrate the method. The first employs data from a study in which NO2 (a known pollutant from automobile exhaust) was monitored outside of 138 Connecticut homes, providing a model for estimating NO2 exposure. In a second example, estimated levels of nitrogen dioxide (NO2) from the model, as well as a separate spatial model, were used to analyze traffic-related health effects in a study of 761 infants.
doi:10.1002/sim.3732
PMCID: PMC3182125  PMID: 19823976
Traffic; Dispersion models; Geographic Information Systems; Generalized Linear Models; Splines
19.  Does Chocolate Intake During Pregnancy Reduce the Risks of Preeclampsia and Gestational Hypertension? 
Annals of epidemiology  2010;20(8):584-591.
Purpose
Chocolate consumption is associated with favorable levels of blood pressure and other cardiovascular disease risk markers. We analyzed a prospective cohort study to determine if regular chocolate intake during pregnancy is associated with reduced risks of preeclampsia and gestational hypertension (GH).
Methods
Subjects were recruited from 13 prenatal care practices in Connecticut (1988-1991). In-person interviews were administered at <16 weeks gestation to ascertain risk factors for adverse pregnancy outcomes. Hospital delivery and prenatal records were abstracted to classify preeclampsia (n=58), GH (n=158), and normotensive pregnancies (n=2351). Chocolate consumption (servings/week) during the 1st and 3rd trimesters was ascertained at initial interview and immediately postpartum, respectively. Consumers of <1 serving/week comprised the referent group. Adjusted odds ratios (aOR) were estimated using logistic regression.
Results
Chocolate intake was more frequent among normotensives (80.7%) than preeclamptics (62.5%) or GH women (75.8%), and associated with reduced odds of preeclampsia (1st trimester: aOR=0.55, 95% CI: 0.32-0.95; 3rd trimester: aOR=0.56, 95% CI: 0.32-0.97). Only 1st trimester intake was associated with reduced odds of GH (aOR=0.65, 95% CI: 0.45-0.87).
Conclusions
These findings provide additional evidence of the benefits of chocolate. Prospective studies are needed to confirm and delineate protective effects of chocolate intake on risk of preeclampsia.
doi:10.1016/j.annepidem.2010.05.010
PMCID: PMC2901253  PMID: 20609337
Chocolate; Gestational Hypertension; Preeclampsia; Pregnancy
21.  Association of pediatric asthma severity with exposure to common household dust allergens 
Environmental research  2009;109(6):768-774.
Background
Reducingexposure to household dust inhalant allergens has been proposed as one strategy to reduce asthma.
Objective
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.
Methods
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.
Results
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).
Conclusion
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.
doi:10.1016/j.envres.2009.04.010
PMCID: PMC2706291  PMID: 19473655
pediatric asthma; household dust allergens; Der p1; dust mite; pet allergens
22.  Indoor Combustion and Asthma 
doi:10.1016/j.iac.2008.03.011
PMCID: PMC2760246  PMID: 18572104
23.  Respiratory symptoms among infants at risk for asthma: association with surfactant protein A haplotypes 
BMC Medical Genetics  2007;8:15.
Background
We examined the association between single nucleotide polymorphisms (SNPs) in loci encoding surfactant protein A (SFTPA) and risk of wheeze and persistent cough during the first year of life among a cohort of infants at risk for developing asthma.
Methods
Between September 1996 and December 1998, mothers of newborn infants were invited to participate if they had an older child with clinician-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. Due to the association of SFTPA polymorphisms and race/ethnicity, analyses were restricted to 221 white infants for whom whole blood and respiratory data were available. Ordered logistic regression models were used to examine the association between respiratory symptom frequency and SFTPA haplotypes.
Results
The 6A allele haplotype of SFTPA1, with an estimated frequency of 6% among our study infants, was associated with an increased risk of persistent cough (OR 3.69, 95% CI 1.71, 7.98) and wheeze (OR 4.72, 95% CI 2.20, 10.11). The 6A/1A haplotype of SFTPA, found among approximately 5% of the infants, was associated with an increased risk of persistent cough (OR 3.20, 95% CI 1.39, 7.36) and wheeze (OR 3.25, 95% CI 1.43, 7.37).
Conclusion
Polymorphisms within SFTPA loci may be associated with wheeze and persistent cough in white infants at risk for asthma. These associations require replication and exploration in other ethnic/racial groups.
doi:10.1186/1471-2350-8-15
PMCID: PMC1852548  PMID: 17407567
24.  Association of Indoor Nitrogen Dioxide Exposure with Respiratory Symptoms in Children with Asthma 
Rationale: Chronic exposure to indoor nitrogen dioxide (NO2) is a public health concern. Over half of U.S. households have a source of NO2, and experimental data suggest potential for adverse respiratory effects.
Objective: To examine associations of indoor NO2 exposure with respiratory symptoms among children with asthma.
Methods: NO2 was measured using Palmes tubes, and respiratory symptoms in the month before sampling were collected during home interviews of mothers of 728 children with active asthma. All were younger than 12 yr, lived at the sampled home for at least 2 mo, and had asthma symptoms or used maintenance medication within the previous year.
Measurements: Respiratory symptoms (wheeze, persistent cough, shortness of breath, chest tightness).
Results: Mean (SD) NO2 was 8.6 (9.1) ppb in homes with electric ranges and 25.9 (18.1) ppb in homes with gas stoves. In models stratified by housing type (a factor associated with socioeconomic status), gas stove presence and elevated NO2 were each significantly associated with respiratory symptoms, controlling for age, ethnicity, medication, mold/mildew, water leaks, and season of sampling. Among children in multifamily housing, exposure to gas stoves increased likelihood of wheeze (odds ratio [OR], 2.27; 95% confidence interval [95% CI], 1.15, 4.47), shortness of breath (OR, 2.33; 95% CI, 1.12, 5.06), and chest tightness (OR, 4.34; 95% CI, 1.76, 10.69), whereas each 20-ppb increase in NO2 increased both likelihood of any wheeze (OR, 1.52; 95% CI, 1.04, 2.21) or chest tightness (OR, 1.61; 95% CI, 1.04, 2.49), and days of wheeze (rate ratio (RR), 1.33; 95% CI, 1.05, 1.68) or chest tightness (RR, 1.51; 95% CI, 1.18, 1.91).
Conclusion: Exposure to indoor NO2 at levels well below the Environmental Protection Agency outdoor standard (53 ppb) is associated with respiratory symptoms among children with asthma in multifamily housing.
doi:10.1164/rccm.200408-1123OC
PMCID: PMC2662932  PMID: 16254270
asthma; children; gas stoves; indoor environment; nitrogen dioxide; respiratory symptoms
25.  Association of surfactant protein A polymorphisms with otitis media in infants at risk for asthma 
BMC Medical Genetics  2006;7:68.
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 6A4/1A5haplotype 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.
doi:10.1186/1471-2350-7-68
PMCID: PMC1557482  PMID: 16884531

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