Stephanie M Engel

University of North Carolina at Chapel Hill, North Carolina, United States

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Publications (54)254.23 Total impact

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    ABSTRACT: Background: Phthalates are hypothesized to cause obesity, but few studies have assessed whether prenatal phthalate exposures are related to childhood body mass index (BMI). Methods: We included 707 children from three prospective cohort studies enrolled in the United States between 1998 and 2006 who had maternal urinary phthalate metabolite concentrations measured during pregnancy, and measures of weight and height at ages 4 to 7 years. We calculated age- and sex-standardized BMI z-scores and classified children with BMI percentiles ≥85 as overweight/obese. We used mixed effects regression models to estimate associations between a 1-standard deviation increase in natural log phthalate metabolite concentrations and BMI zscores and overweight/obesity. We estimated associations in multiple metabolite models adjusted for confounders, and evaluated heterogeneity of associations by child's sex, race/ethnicity, and cohort RESULTS:: Mono-3-carboxypropyl phthalate (MCPP) concentrations were positively associated with overweight/obese status in children (odds ratio [95% credible interval] = 2.1 [1.2, 4.0]) but not with BMI z-scores (beta = -0.02 [-0.15, 0.11]). We did not observe evidence of obesogenic effects for other metabolites. However, monoethyl phthalate (MEP) and summed di-(2-ethylhexyl) phthalate metabolites (∑DEHP) concentrations were inversely associated with BMI z-scores among girls (MEP beta = -0.14 [-0.28, 0.00]; ∑DEHP beta = -0.12 [-0.27, 0.02]). Conclusions: Maternal urinary MCPP, a non-specific metabolite of several phthalates, was positively associated with childhood overweight/obesity. Metabolites of diethyl phthalate and DEHP were associated with lower BMI in girls but not boys, suggesting prenatal exposures may have sexually dimorphic effects on physical development.
    No preview · Article · Jan 2016 · Epidemiology
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    ABSTRACT: Background: Organophosphorous (OP) pesticides are associated with reduced fetal growth in animals, but human studies are inconsistent. Objectives: We pooled data from four cohorts to examine associations of prenatal OP exposure with birth weight (n=1,169), length (n=1,152), and head circumference (n=1,143). Methods: Data were from the CHAMACOS, HOME, Columbia, and Mount Sinai birth cohorts. Concentrations of 3 diethyl phosphate (ΣDEP) and 3 dimethyl phosphate (ΣDMP) metabolites of OP pesticides (summed to six dialkyl phosphates (ΣDAPs)) were measured in maternal urine. Linear regression and mixed effects models were used to examine associations with birth outcomes. Results: We found no significant associations of ΣDEP, ΣDMP, or ΣDAPs with birth weight, length, or head circumference overall. However, among non-Hispanic Black women, increasing urinary ΣDAP and ΣDMP concentrations were associated with decreased birth length (β= -0.4 cm, 95% CI: -0.9, 0.0 and β= -0.4 cm, 95% CI: -0.8, 0.0, respectively for each 10-fold increase in metabolite concentration). Among infants with the PON1192RR genotype, ΣDAP and ΣDMP were negatively associated with length (β= -0.4 cm, 95% CI: -0.9, 0.0 and β= -0.5 cm, 95% CI: -0.9, -0.1). Conclusions: This study confirms previously reported associations of prenatal OP exposure among Black women with decreased infant size at birth, but finds no evidence of smaller birth weight, length, or head circumference among Whites or Hispanics. Contrary to our hypothesis, we found stronger inverse associations of DAPs and birth outcome in infants with the less susceptible PON1192RR genotype. The large pooled dataset facilitated exploration of interactions by race/ethnicity and PON1 genotype, but was limited by differences in study populations.
    Full-text · Article · Dec 2015 · Environmental Health Perspectives
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    ABSTRACT: Epidemiologists often wish to estimate quantities that are easy to communicate and correspond to the results of realistic public health scenarios. Methods from causal inference can answer these questions. We adopt the language of potential outcomes under Rubin's original Bayesian framework and show that the parametric g-formula is easily amenable to a Bayesian approach. We show that the frequentist properties of the Bayesian g-formula suggest it improves the accuracy of estimates of causal effects in small samples or when data may be sparse. We demonstrate our approach to estimate the effect of environmental tobacco smoke on body mass index z-scores among children aged 4-9 years who were enrolled in a longitudinal birth cohort in New York, USA. We give a general algorithm and supply SAS and Stan code that can be adopted to implement our computational approach in both time-fixed and longitudinal data.
    Preview · Article · Dec 2015
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    ABSTRACT: Epidemiological analyses of aggregated data are often used to evaluate theoretical health effects of natural disasters. Such analyses are susceptible to confounding by unmeasured differences between the exposed and unexposed populations. To demonstrate the difference-in-difference method our population included all recorded Florida live births that reached 20 weeks gestation and conceived after the first hurricane of 2004 or in 2003 (when no hurricanes made landfall). Hurricane exposure was categorized using ≥74 mile per hour hurricane wind speed as well as a 60 km spatial buffer based on weather data from the National Oceanic and Atmospheric Administration. The effect of exposure was quantified as live birth rate differences and 95 % confidence intervals [RD (95 % CI)]. To illustrate sensitivity of the results, the difference-in-differences estimates were compared to general linear models adjusted for census-level covariates. This analysis demonstrates difference-in-differences as a method to control for time-invariant confounders investigating hurricane exposure on live birth rates. Difference-in-differences analysis yielded consistently null associations across exposure metrics and hurricanes for the post hurricane rate difference between exposed and unexposed areas (e.g., Hurricane Ivan for 60 km spatial buffer [−0.02 births/1000 individuals (−0.51, 0.47)]. In contrast, general linear models suggested a positive association between hurricane exposure and birth rate [Hurricane Ivan for 60 km spatial buffer (2.80 births/1000 individuals (1.94, 3.67)] but not all models. Ecological studies of associations between environmental exposures and health are susceptible to confounding due to unmeasured population attributes. Here we demonstrate an accessible method of control for time-invariant confounders for future research.
    Preview · Article · Dec 2015 · Emerging Themes in Epidemiology
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    ABSTRACT: Background: Organophosphorus pesticides (OPs) are used in agriculture worldwide. Residential use was common in the United States prior to 2001. Objectives: To conduct a pooled analysis of four birth cohorts (n = 936) to evaluate associations of prenatal exposure to OPs with child development at 24 months. Methods: Using general linear models, we computed site-specific and pooled estimates of the association of total dialkyl (∑DAP), diethyl (∑DEP) and dimethylphosphate (∑DMP) metabolite concentrations in maternal prenatal urine with mental and psychomotor development indices (MDI/PDI), and evaluated heterogeneity by Center, race/ethnicity, and PON1 genotype. Results: There was significant heterogeneity in the Center-specific estimates of association for ∑DAP and ∑DMP and the MDI (p = 0.09, and p = 0.05 respectively), as well as heterogeneity in the race/ethnicity-specific estimates for ∑DAP (p = 0.06) and ∑DMP (p = 0.02) and the MDI. Strong MDI associations in the CHAMACOS population per 10-fold increase in ∑DAP (β = -4.17, 95% CI -7.00, -1.33) and ∑DMP (β = -3.64, 95% CI -5.97, -1.32) were influential, as were associations among Hispanics (β per 10-fold increase in ∑DAP = -2.91, 95% CI -4.71, -1.12). We generally found stronger negative associations of ∑DAP and ∑DEP with the 24 month MDI for carriers of the 192Q PON1 allele, particularly among blacks and Hispanics. Conclusions: Data pooling was complicated by Center-related differences in subject characteristics, eligibility, and changes in regulations governing residential use of OPs during the study periods. Pooled summary estimates of prenatal exposure to OPs and neurodevelopment should be interpreted with caution due to significant heterogeneity in associations by Center, race/ethnicity and PON1 genotype. Subgroups with unique exposure profiles or susceptibilities may be at higher risk for adverse neurodevelopment following prenatal exposure.
    Full-text · Article · Sep 2015 · Environmental Health Perspectives
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    ABSTRACT: Experimental animal studies and limited epidemiologic evidence suggest that prenatal exposure to phthalates may be obesogenic, with potential sex-specific effects of phthalates with anti-androgenic activity. We aimed to assess associations between prenatal phthalate exposures and childhood fat mass in a prospective cohort study. We measured phthalate metabolite concentrations in third trimester maternal urine in a cohort of women enrolled in New York City between 1998 and 2002 (N=404). Among 180 children (82 girls and 98 boys), we evaluated body composition using a Tanita scale at multiple follow-up visits between ages 4 and 9 years (363 total visits). We estimated associations of standard deviation differences or tertiles of natural log phthalate metabolite concentrations with percent fat mass using linear mixed effects regression models with random intercepts for repeated outcome measurements. We assessed associations in multiple metabolite models and adjusted for covariates including pre-pregnancy body mass index, gestational weight gain, maternal smoking during pregnancy, and breastfeeding. We did not observe associations between maternal urinary phthalate concentrations and percent body fat in models examining continuous exposures. Fat mass was 3.06 percent (95% CI: -5.99, -0.09%) lower among children in the highest tertile of maternal urinary concentrations of summed di-(2-ethylhexyl) phthalate (∑DEHP) metabolites compared to children in the lowest tertile. Though estimates were imprecise, there was little evidence that associations between maternal urinary phthalate concentrations and percent fat mass were modified by child's sex. Prenatal phthalate exposures were not associated with increased body fat among children aged 4 to 9 years, though high prenatal DEHP exposure may be associated with lower fat mass in childhood.
    No preview · Article · Aug 2015 · Environmental Health Perspectives
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    ABSTRACT: We discuss considerations that are essential when evaluating exposure to nonpersistent, semivolatile environmental chemicals such as phthalates and phenols (e.g., bisphenol A). A biomarker should be chosen to best represent usual personal exposures and not recent, adventitious, or extraneous exposures. Biomarkers should be selected to minimize contamination arising from collection, sampling, or analysis procedures. Pharmacokinetics should be considered; for example, nonpersistent, semivolatile chemicals are metabolized quickly, and urine is the compartment with the highest concentrations of metabolites. Because these chemicals are nonpersistent, knowledge of intraindividual reliability over the biologic window of interest is also required. In recent years researchers have increasingly used blood as a matrix for characterizing exposure to nonpersistent chemicals. However, the biologic and technical factors noted above strongly support urine as the optimal matrix for measuring nonpersistent, semivolatile, hydrophilic environmental agents. © 2015, Public Health Services, US Dept of Health and Human Services. All Rights Reserved.
    Full-text · Article · Jul 2015 · Environmental Health Perspectives
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    ABSTRACT: Exposures to environmental phenols and parabens may be harmful, especially in utero. Prior studies have demonstrated high within-person variability of urinary concentrations across pregnancy. We sought to measure phenol and paraben biomarker concentrations for the Norwegian Mother and Child Cohort (MoBa) study, assess within-person variability, and investigate any possible external phenol or paraben contamination of specimens. We collected three spot urines at approximately 17, 23, and 29 weeks' gestation in a hospital setting and added a preservative containing ethyl paraben. We measured urinary concentrations and within-person variability for phenols and parabens in a MoBa sample (n=45), including a subgroup of 15 participants previously randomly selected for a bisphenol-A (BPA) exposure study who had unusually high total BPA concentrations. Additionally, we compared reliability results for total, conjugated, and free concentrations of phenolic compounds. We detected total and free BPA, butyl paraben, propyl paraben, and methyl paraben in 100% of samples, total benzophenone-3 in 95% of samples, and infrequently detected free benzophenone-3 and total and free 2,4-dichlorophenol and 2,5-dichlorophenol. Intraclass correlation coefficients (ICCs) for total, conjugated, and free concentrations ranged from relatively low for BPA to moderate for propyl paraben. ICCs were generally similar overall and by subgroup. Using conjugated concentrations improved reliability estimates only for BPA. Measuring total and free concentrations, an approach which may be useful for future studies, allowed us to identify likely BPA and butyl paraben contamination of archived MoBa urine specimens.
    Full-text · Article · Mar 2015 · Environmental Health Perspectives
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    ABSTRACT: To estimate gestational age-specific risks of fetal death in pregnancies complicated by preeclampsia. Population-based cohort study comprising all singleton births (N=554,333) without preexisting chronic hypertension recorded in the Norwegian Medical Birth Registry from 1999 to 2008. Additional data come from a subset of preeclamptic pregnancies enrolled in the Norwegian Mother and Child Cohort Study with available medical records (n=3,037). The risk of fetal death, expressed per 1,000 fetuses exposed to preeclampsia, was calculated using a life table approach. Preeclampsia was recorded in 3.8% (n=21,020) of all pregnancies. Risk of stillbirth was 3.6 per 1,000 overall and 5.2 per 1,000 among pregnancies with preeclampsia (relative risk 1.45, 95% confidence interval [CI] 1.20-1.76). However, relative risk of stillbirth was markedly elevated with preeclampsia in early pregnancy. At 26 weeks of gestation, there were 11.6 stillbirths per 1,000 pregnancies with preeclampsia compared with 0.1 stillbirths per 1,000 pregnancies without (relative risk 86, 95% CI 46-142). Fetal risk with preeclampsia declined as pregnancy advanced, but at 34 weeks of gestation remained more than sevenfold higher than pregnancies without preeclampsia. For clinical purposes, the fetal risk of death associated with preeclampsia begins when preeclampsia becomes clinically apparent. Using a method that takes into account the clinical diagnosis of preeclampsia and the population of fetuses at risk, we find a remarkably high relative risk of fetal death among pregnancies diagnosed with preeclampsia in the preterm period. LEVEL OF EVIDENCE:: II.
    No preview · Article · Mar 2015 · Obstetrics and Gynecology
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    ABSTRACT: Preeclampsia and preterm delivery are serious complications of pregnancy and leading causes of perinatal mortality and morbidity worldwide. Dietary factors might be associated with these adverse outcomes. We investigated whether adherence to the New Nordic Diet (NND) was associated with preeclampsia and preterm delivery risks in the Norwegian Mother and Child Cohort Study (MoBa). Participants were recruited from all over Norway during the period 1999-2008. A previously constructed diet score assessing meal frequency, and the consumption of Nordic fruits, root vegetables, cabbages, potatoes, oatmeal porridge, whole grains, wild fish, game, berries, milk and water, was used to assess NND adherence. Associations between NND adherence and the outcomes were estimated in adjusted multivariate logistic regression models. Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated. A total of 72,072 women was included in the study. High versus low NND adherence was associated with lower risk of total preeclampsia (OR 0.86; 95 % CI 0.78-0.95) and early preeclampsia (OR 0.71; 95 % CI 0.52-0.96). High compared with low NND adherence was associated with a lower risk of spontaneous preterm delivery among nulliparous women (OR 0.77; 95 % CI 0.66-0.89), whereas multiparous women with high NND adherence had a marginally significant higher risk of preterm delivery (OR 1.24; 95 % CI 1.00-1.53). High NND adherence was associated with a lower relative risk of preeclampsia and of spontaneous preterm delivery among nulliparous women; however, among multiparous women there was a higher relative risk of preterm delivery.
    No preview · Article · Sep 2014 · European Journal of Epidemiology
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    ABSTRACT: Background The Norwegian Mother and Child Cohort Study (MoBa), a prospective population-based pregnancy cohort, is a valuable database for studying causes of pre-eclampsia. Pre-eclampsia data in MoBa come from the Medical Birth Registry of Norway (MBRN); thus, we wanted to study the validity of MBRN pre-eclampsia registration for MoBa women.Methods We selected all MoBa pregnancies with pre-eclampsia registered in the MBRN (n = 4081) and a random control group (n = 2000) without pre-eclampsia registrations. After excluding two delivery units not participating in MoBa and one no longer operating, units were asked to provide copies of antenatal charts with blood pressure and urinary measurements from all antenatal visits during pregnancy, and hospital discharge codes from the delivery stay. We received data for 5340 pregnancies delivered 1999–2010 (87% of all eligible). We calculated positive predictive value (PPV), and sensitivity and specificity of MBRN registration, using hypertension and proteinuria on the antenatal charts and/or hospital discharge codes indicating pre-eclampsia as gold standard.ResultsOverall PPV was 83.9% [95% CI 82.7, 85.1] and was higher when women were primiparous, or delivered preterm or low birthweight infants. Severe pre-eclampsia in the MBRN was found to be a true severe pre-eclampsia in 70% of cases. Extrapolating to the total MoBa population, the estimated sensitivity was low – 43.0% (38.7, 48.2) – while specificity was high – 99.2% (99.2, 99.3). False negative cases seemed to have mild forms of pre-eclampsia.ConclusionsPPV and specificity of pre-eclampsia registration in the MBRN during 1999–2010 was satisfactory, while sensitivity was low.
    No preview · Article · Aug 2014 · Paediatric and Perinatal Epidemiology
  • Melissa A Furlong · Stephanie M Engel · Dana Boyd Barr · Mary S Wolff
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    ABSTRACT: Prenatal exposure to organophosphate pesticides (OPs) has been associated with adverse neurodevelopmental outcomes in childhood, including low IQ, pervasive developmental disorder (PDD), attention problems and ADHD. Many of these disorders involve impairments in social functioning. Thus, we investigated the relationship between biomarkers of prenatal OP exposure and impaired reciprocal social behavior in childhood, as measured by the Social Responsiveness Scale (SRS). Using a multi-ethnic urban prospective cohort of mother-infant pairs in New York City recruited between 1998 and 2002 (n=404) we examined the relation between third trimester maternal urinary levels of dialkylphosphate (ΣDAP) OP metabolites and SRS scores among 136 children who returned for the 7-9year visit. Overall, there was no association between OPs and SRS scores, although in multivariate adjusted models, associations were heterogeneous by race and by sex. Among blacks, each 10-fold increase in total diethylphosphates (ΣDEP) was associated with poorer social responsiveness (β=5.1 points, 95% confidence interval (CI) 0.8, 9.4). There was no association among whites or Hispanics, or for total ΣDAP or total dimethylphosphate (ΣDMP) biomarker levels. Additionally, stratum-specific models supported a stronger negative association among boys for ΣDEPs (β=3.5 points, 95% CI 0.2, 6.8), with no notable association among girls. Our results support an association of prenatal OP exposure with deficits in social functioning among blacks and among boys, although this may be in part reflective of differences in exposure patterns.
    No preview · Article · Jun 2014 · Environment International
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    ABSTRACT: ProblemInflammatory biomarkers are associated with preeclampsia (PE) and poor fetal growth; however, genetic epidemiologic studies have been limited by reduced gene coverage and the exclusion of African American mothers.Method of studyCases and controls (N = 1646) from a pregnancy cohort were genotyped for 503 tagSNPs in 40 genes related to inflammation. Gene-set analyses were stratified by race and were followed by a single SNP analysis within significant gene sets.ResultsGene-level associations were found for IL6 and KLRD1 for term small for gestational age (SGA) among African Americans. LTA/TNF and TBX21 were associated with PE among European Americans. The strongest association was for PE among European Americans for an upstream regulator of TNF with RR = 1.8 (95% CI 1.1–2.7).Conclusion Although previous studies have suggested null associations, increased tagging and stratification by genetic ancestry suggests important associations between IL6 and term SGA for African Americans, and a TNF regulator and PE among European Americans (N = 149).
    No preview · Article · Apr 2014 · American Journal Of Reproductive Immunology
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    ABSTRACT: Exposure to certain phenols is ubiquitous due to their use in many consumer and personal care products. However, predictors of exposure have not been well characterized in most populations. To identify predictors of exposure and assess reproducibility of phenol concentrations across serial spot urine samples among Chinese adults. We measured 2,4-dichlorophenol, 2,5-dichlorophenol, butyl paraben, methyl paraben, propyl paraben, benzophenone-3, bisphenol A, and triclosan in urine collected during 1997-2006 among 50 participants of the Shanghai Women's Health Study cohort and during 2002-2006 among 50 participants of the Shanghai Men's Health Study cohort. We investigated predictors of concentrations using the Satterthwaite t-test and assessed reproducibility among serial samples using intraclass correlation coefficients (ICC) and Spearman correlation coefficients (SCC). Creatinine-corrected phenol concentrations were generally higher among women than men. Participants who took medicine in the past 24 hours had higher concentrations of propyl paraben. Cigarette smoking was associated with lower concentrations of propyl and methyl parabens among men. Bottled water consumption was associated with higher bisphenol A, 2,4-dichlorophenol, and 2,5-dichlorophenol concentrations among women. Among men, reproducibility across serial samples was moderate for 2,4-dichlorophenol and 2,5-dichlorophenol (ICC=0.54-0.60, SCC=0.43-0.56), but lower for other analytes (ICC=0.20-0.29). Reproducibility among women was low (ICC=0.13-0.39), but increased when restricted to morning-only urine samples. Among these 100 Shanghai residents, urinary phenol concentrations varied by sex, smoking, and consumption of bottled water. Our results suggest that a single urine sample may be adequate for ranking exposure to the precursors of 2,4-dichlorophenol and 2,5-dichlorophenol among men and, under certain circumstances, among women.
    Full-text · Article · Mar 2014 · Environmental Health Perspectives
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    ABSTRACT: Although epigenetic regulation plays a critical role in embryonic development, few studies have examined the relationship of epigenome-wide methylation with fetal growth. Using the Infinium HumanMethylation450 BeadChip (Illumina, Inc., San Diego, California) in a substudy of 1,046 infants from the Norwegian Mother and Child Cohort Study (MoBa) enrolled between 1999 and 2008, we examined epigenome-wide cord blood DNA methylation in relation to birth weight. In multivariable-adjusted robust linear regression models, we identified differential methylation at 19 cytosine-guanine dinucleotides (CpGs) associated with either decreased (AT-rich interactive domain 5B (MRF1-like) (ARID5B), 2 CpGs) or increased (x-ray repair complementing defective repair in Chinese hamster cells 3 (XRCC3), 4 CpGs) birth weight. ARID5B knockout mice have less adipose tissue and significantly lower weight in the postnatal period. XRCC3 plays a key role in the maintenance of chromosome stability and the repair of DNA damage. Although there are fewer data on the other implicated genes, many of these genes have been shown to have roles in developmental processes. This constitutes the largest and most robust study of birth weight using an epigenome-wide methylation platform and offers potential insights into epigenetic mechanisms of fetal growth.
    No preview · Article · Feb 2014 · American journal of epidemiology
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    ABSTRACT: Perfluoroalkyl substances (PFAS) are persistent and ubiquitous environmental contaminants, and human exposure to these substances may be related to preeclampsia, a common pregnancy complication. Previous studies have found serum concentrations of PFAS to be positively associated with pregnancy-induced hypertension and preeclampsia in a population with high levels of exposure to perfluorooctanoate. Whether this association exists among pregnant women with background levels of PFAS exposure is unknown. Using data from the Norwegian Mother and Child Cohort Study conducted by the Norwegian Institute of Public Health, we carried out a study of nulliparous pregnant women enrolled in 2003-2007 (466 cases, 510 noncases) to estimate associations between PFAS concentrations and an independently validated diagnosis of preeclampsia. We measured levels of 9 PFAS in maternal plasma extracted midpregnancy; statistical analyses were restricted to 7 PFAS that were quantifiable in more than 50% of samples. In proportional hazards models adjusted for maternal age, prepregnancy body mass index (weight (kg)/height (m)(2)), educational level, and smoking status, we observed no strongly positive associations between PFAS levels and preeclampsia. We found an inverse association between preeclampsia and the highest quartile of perfluoroundecanoic acid concentration relative to the lowest quartile (hazard ratio = 0.55, 95% confidence interval: 0.38, 0.81). Overall, our findings do not support an increased risk of preeclampsia among nulliparous Norwegian women with background levels of PFAS exposure.
    No preview · Article · Feb 2014 · American journal of epidemiology
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    ABSTRACT: Triclosan (TCS) is a synthetic antibacterial chemical that is used in personal care products and is measurable in urine. Urinary TCS has been associated with allergy in children in Norway and the United States. A reasonable degree of temporal reliability of TCS urinary concentrations has been reported among US children as well as for Puerto Rican pregnant women. We examined the reliability of TCS measures in urine among Norwegian pregnant women. TCS was measured in spot urine samples collected in gestational weeks 17, 23, and 29 from 45 women in The Norwegian Mother and Child Cohort Study (MoBa) enrolled in 2007 and 2008. Spearman's rank correlation coefficient (rs) and intraclass correlation coefficient (ICC) statistics were calculated. Fifty-six percent of the 45 women had a least one sample with a value above the method limit of detection (2.3 μg/l). The correlation coefficients were 0.61 for TCS concentrations at 17 and 23 weeks and 0.49 for concentrations at 17 and 29 weeks. For the three time points, the ICC was 0.49. The reliability of TCS concentrations in repeated urine samples from pregnant Norwegian women was reasonably good, suggesting a single urine sample can adequately represent TCS exposure during pregnancy.Journal of Exposure Science and Environmental Epidemiology advance online publication, 29 January 2014; doi:10.1038/jes.2013.95.
    Full-text · Article · Jan 2014 · Journal of Exposure Science and Environmental Epidemiology
  • Melissa A. Furlong · Stephanie M. Engel · Dana Boyd Barr · Mary S. Wolff
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    ABSTRACT: Prenatal exposure to organophosphate pesticides (OPs) has been associated with adverse neurodevelopmental outcomes in childhood, including low IQ, pervasive developmental disorder (PDD), attention problems and ADHD. Many of these disorders involve impairments in social functioning. Thus, we investigated the relationship between biomarkers of prenatal OP exposure and impaired reciprocal social behavior in childhood, as measured by the Social Responsiveness Scale (SRS). Using a multi-ethnic urban prospective cohort of mother–infant pairs in New York City recruited between 1998 and 2002 (n = 404) we examined the relation between third trimester maternal urinary levels of dialkylphosphate (ΣDAP) OP metabolites and SRS scores among 136 children who returned for the 7–9 year visit. Overall, there was no association between OPs and SRS scores, although in multivariate adjusted models, associations were heterogeneous by race and by sex. Among blacks, each 10-fold increase in total diethylphosphates (ΣDEP) was associated with poorer social responsiveness (β = 5.1 points, 95% confidence interval (CI) 0.8, 9.4). There was no association among whites or Hispanics, or for total ΣDAP or total dimethylphosphate (ΣDMP) biomarker levels. Additionally, stratum-specific models supported a stronger negative association among boys for ΣDEPs (β = 3.5 points, 95% CI 0.2, 6.8), with no notable association among girls. Our results support an association of prenatal OP exposure with deficits in social functioning among blacks and among boys, although this may be in part reflective of differences in exposure patterns.
    No preview · Article · Jan 2014
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    ABSTRACT: Perfluoroalkyl substances (PFASs) are widespread and persistent environmental pollutants. Previous studies, primarily among non-pregnant individuals, suggest positive associations between PFAS levels and certain blood lipids. If there is a causal link between PFAS concentrations and elevated lipids during pregnancy, this may suggest a mechanism by which PFAS exposure leads to certain adverse pregnancy outcomes, including preeclampsia. This cross-sectional analysis included 891 pregnant women enrolled in the Norwegian Mother and Child (MoBa) Cohort Study in 2003-2004. Non-fasting plasma samples were obtained at mid-pregnancy and analyzed for nineteen PFASs. Total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, and triglycerides were measured in plasma. Linear regression was used to quantify associations between each PFAS exposure and each lipid outcome. A multiple PFAS model was also fitted. Seven PFASs were quantifiable in >50% of samples. Perfluorooctane sulfonate (PFOS) concentration was associated with total cholesterol, which increased 4.2mg/dL per inter-quartile shift (95% CI=0.8, 7.7) in adjusted models. Five of the seven PFASs studied were positively associated with HDL cholesterol, and all seven had elevated HDL associated with the highest quartile of exposure. Perfluoroundecanoic acid showed the strongest association with HDL: HDL increased 3.7mg/dL per inter-quartile shift (95% CI=2.5, 4.9). Plasma concentrations of PFASs were positively associated with HDL cholesterol, and PFOS was positively associated with total cholesterol in this sample of pregnant Norwegian women. While elevated HDL is not an adverse outcome per se, elevated total cholesterol associated with PFASs during pregnancy could be of concern if causal.
    No preview · Article · Nov 2013 · Environment international
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    ABSTRACT: Inflammation is implicated in preterm birth, but genetic studies of inflammatory genes have yielded inconsistent results. Maternal DNA from 1,646 participants in the Pregnancy, Infection, and Nutrition Cohort, enrolled in Orange and Wake counties, North Carolina (1995–2005), were genotyped for 432 tag single-nucleotide polymorphisms (SNPs) in 30 candidate genes. Gene-level and SNP associations were modeled within strata of genetic ancestry. Six genes were associated with preterm birth among European Americans: interleukin 12A (IL12A); colony-stimulating factor 2 (CSF2); interferon γ receptor 2 (IFNGR2); killer cell immunoglobulin–like receptor, three domain, long cytoplasmic tail, 2 (KIR3DL2); interleukin 4 (IL4); and interleukin 13 (IL13). Of these, relatively strong single-SNP associations were seen in IFNGR2 and KIR3DL2. Among the 4 genes related to natural killer cell function, 2 (IL12A and CSF2) were consistently associated with reduced risk of prematurity for both European and African Americans. SNPs tagging a locus control region for IL4 and IL13 were associated with an increased risk of spontaneous preterm birth for European Americans (rs3091307; risk ratio = 1.9; 95% confidence interval: 1.4, 2.5). Although gene-level associations were detected only in European Americans, single-SNP associations among European and African Americans were often similar in direction, though estimated with less precision among African Americans. In conclusion, we identified novel associations between variants in the natural killer cell immune pathway and prematurity in this biracial US population.
    Full-text · Article · Aug 2013 · American journal of epidemiology

Publication Stats

2k Citations
254.23 Total Impact Points

Institutions

  • 2011-2015
    • University of North Carolina at Chapel Hill
      • Department of Epidemiology
      North Carolina, United States
  • 2006-2012
    • Icahn School of Medicine at Mount Sinai
      • Department of Preventive Medicine
      Borough of Manhattan, New York, United States