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1.
J Perinatol ; 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31388117

RESUMO

OBJECTIVE: To examine the association between neonatal jaundice and autism spectrum disorder (ASD) and non-ASD developmental disorder (DD). STUDY DESIGN: We analyzed data from the Study to Explore Early Development, a US multisite, case-control study conducted from 2007 to 2011. Developmental assessment classified children aged 2-5 years into: ASD (n = 636), DD (n = 777), or controls (POP; n = 926). Neonatal jaundice (n = 1054) was identified from medical records and maternal interviews. We examined associations between neonatal jaundice and ASD and DD using regression models to obtain adjusted odds ratios (aOR). RESULTS: Our results showed interaction between gestational age and neonatal jaundice. Neonatal jaundice was associated with ASD at 35-37 weeks (aOR = 1.83, 95%CI 1.05, 3.19), but not ≥38 weeks gestation (aOR = 0.97, 95%CI 0.76, 1.24). Similar results were observed with DD. CONCLUSIONS: Further exploration of timing and severity of neonatal jaundice and ASD/DD is warranted.

2.
Cancer Epidemiol ; 61: 165-171, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31279991

RESUMO

BACKGROUND: There is evidence vitamin A plays a role in neuroblastoma. Not only is 13-cis-retinoic acid used as maintenance therapy for high-risk cases, but prenatal vitamin intake use may decrease neuroblastoma risk. We hypothesized that single nucleotide polymorphisms (SNPs) in vitamin A-related genes are may be associated with neuroblastoma risk and potentially be modified by vitamin A intake. METHODS: The Neuroblastoma Epidemiology in North America (NENA) study recruited 563 case-parent sets through the Children's Oncology Group's Childhood Cancer Research Network. We ascertained dietary nutrient intake through questionnaires and genotyped 463 SNPs in vitamin A-related genes from saliva DNA. Offspring and maternal log-additive risk ratios (RR) and stratum-specific RR for gene-environment interaction were estimated with a log-linear model. We avoided false positives due to multiple testing by using the false discovery rate (FDR). RESULTS: When all neuroblastoma cases were considered together, no offspring variants met the significance criteria (FDR Q-value < 0.2). One maternal SNP (rs12442054) was associated with decreased risk of neuroblastoma (RR: 0.61; 95% Confidence Interval (CI): 0.47-0.79, Q = 0.076). When the cases were categorized according to prognostic risk category and age at onset, nine offspring SNPs were significantly associated with intermediate-risk neuroblastoma. Maternal rs6776706 was associated with (RR: 0.49; 95% CI: 0.33-0.72, Q = 0.161) high-risk neuroblastoma and maternal rs11103603 (RR: 0.60; 95% CI: 0.45-0.79, Q = 0.127) was associated with neuroblastoma aged <1 year. For gene-environment interaction, maternal rs729147 was associated with decreased risk of neuroblastoma among mothers with vitamin A consumption above the recommendation. CONCLUSIONS: Although there is biologic plausibility for the role of vitamin A in neuroblastoma, we found weak evidence of a relationship between vitamin A related genes and neuroblastoma.

3.
Environ Int ; 132: 104723, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31208937

RESUMO

BACKGROUND: DNA methylation (DNAm) may contribute to processes that underlie associations between air pollution and poor health. Therefore, our objective was to evaluate associations between DNAm and ambient concentrations of particulate matter (PM) ≤2.5, ≤10, and 2.5-10 µm in diameter (PM2.5; PM10; PM2.5-10). METHODS: We conducted a methylome-wide association study among twelve cohort- and race/ethnicity-stratified subpopulations from the Women's Health Initiative and the Atherosclerosis Risk in Communities study (n = 8397; mean age: 61.5 years; 83% female; 45% African American; 9% Hispanic/Latino American). We averaged geocoded address-specific estimates of daily and monthly mean PM concentrations over 2, 7, 28, and 365 days and 1 and 12 months before exams at which we measured leukocyte DNAm in whole blood. We estimated subpopulation-specific, DNAm-PM associations at approximately 485,000 Cytosine-phosphate-Guanine (CpG) sites in multi-level, linear, mixed-effects models. We combined subpopulation- and site-specific estimates in fixed-effects, inverse variance-weighted meta-analyses, then for associations that exceeded methylome-wide significance and were not heterogeneous across subpopulations (P < 1.0 × 10-7; PCochran's Q > 0.10), we characterized associations using publicly accessible genomic databases and attempted replication in the Cooperative Health Research in the Region of Augsburg (KORA) study. RESULTS: Analyses identified significant DNAm-PM associations at three CpG sites. Twenty-eight-day mean PM10 was positively associated with DNAm at cg19004594 (chromosome 20; MATN4; P = 3.33 × 10-8). One-month mean PM10 and PM2.5-10 were positively associated with DNAm at cg24102420 (chromosome 10; ARPP21; P = 5.84 × 10-8) and inversely associated with DNAm at cg12124767 (chromosome 7; CFTR; P = 9.86 × 10-8). The PM-sensitive CpG sites mapped to neurological, pulmonary, endocrine, and cardiovascular disease-related genes, but DNAm at those sites was not associated with gene expression in blood cells and did not replicate in KORA. CONCLUSIONS: Ambient PM concentrations were associated with DNAm at genomic regions potentially related to poor health among racially, ethnically and environmentally diverse populations of U.S. women and men. Further investigation is warranted to uncover mechanisms through which PM-induced epigenomic changes may cause disease.

4.
Neurotoxicology ; 73: 150-160, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30951742

RESUMO

Organophosphate esters (OPEs) are commonly used as plasticizers and flame retardants in consumer products, and exposure is relatively ubiquitous in most populations studied. This may be of concern as some OPEs may be neurotoxic, endocrine-disrupting, and interfere with behavioral development; however, observational evidence is limited. We used data from the Pregnancy, Infection, and Nutrition Study, a prospective birth cohort study, to investigate associations between maternal OPE metabolite concentrations during pregnancy and behavioral development in offspring. Women provided a urine sample during pregnancy that was analyzed for concentrations of OPE metabolites, including diphenyl phosphate (DPHP), bis(1,3-dichloro-2-propyl phosphate) (BDCIPP), isopropyl-phenyl phenyl phosphate (ip-PPP), and 1-hydroxyl-2-propyl bis(1-chloro-2-propyl) phosphate (BCIPHIPP). Offspring's behavioral development was assessed by the Behavioral Assessment System for Children (2nd Edition) (BASC-2) at approximately 36 months. Linear regression was used to estimate associations between tertiles in specific gravity-corrected OPE metabolite concentrations and children's scores on the BASC-2, adjusted for maternal age, maternal BMI, maternal race, maternal education, familial income, maternal depression, quality of the home environment, and sex. Higher BDCIPP concentrations were associated with higher scores on the Behavioral Symptoms Index (1st vs. 3rd tertile: ß = 3.03; 95% CI = 0.40, 5.67) and Externalizing Problems (1st vs. 3rd tertile: ß = 2.49; 95% CI: -0.12, 5.10) composites. Among BASC-2 scales, BDCIPP was most strongly associated with Withdrawal, Attention Problems, Depression, Hyperactivity, and Aggression. DPHP concentrations were also associated with higher scores on the Externalizing Problems and Behavioral Symptoms Index composites, but not as strongly as BDCIPP. Conversely, higher concentrations of ip-PPP were associated with fewer adverse behavioral symptoms, including an inverse association with the Internalizing Problems composite (1st vs. 3rd tertile: ß = -3.74; 95% CI = -6.75, -0.74) and constituent scales. BCIPHIPP was not strongly associated with any measured behavioral outcomes. Our results suggest that greater maternal exposure to tris(1,3-dichloro-2-propyl phosphate) (TDCIPP, parent compound of BDCIPP) and, to a lesser degree, triphenyl phosphate (TPHP, parent compound of DPHP) during pregnancy is associated with adverse behavioral development in children. Our study contributes to the growing body of evidence pertaining to adverse developmental effects of prenatal OPE exposure and highlights the need for further research to characterize risks associated with this ubiquitous family of chemicals.

5.
Autism Res ; 12(6): 967-975, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30969030

RESUMO

Previous studies have shown complications of pregnancy, often examined in aggregate, to be associated with autism spectrum disorder (ASD). Results for specific complications, such as maternal diabetes and hypertension, have not been uniformly consistent and should be investigated independently in relation to ASD in a large community-based sample. The Study to Explore Early Development (SEED), a US multisite case-control study, enrolled children born in 2003-2006 at 2-5 years of age. Children were classified into three groups based on confirmation of ASD (n = 698), non-ASD developmental delay (DD; n = 887), or controls drawn from the general population (POP; n = 979). Diagnoses of any diabetes or hypertensive disorder during pregnancy were identified from prenatal medical records and maternal self-report. Logistic regression models estimated adjusted odds ratios (aOR) and confidence intervals (CI) adjusting for maternal age, race/ethnicity, education, smoking during pregnancy, and study site. Models for hypertension were additionally adjusted for parity and plurality. Among 2,564 mothers, we identified 246 (9.6%) with any diabetes and 386 (15.1%) with any hypertension in pregnancy. After adjustment for covariates, any diabetes during pregnancy was not associated with ASD (aOR = 1.10 [95% CI 0.77, 1.56]), but any hypertension was associated with ASD (aOR = 1.69 [95% CI 1.26, 2.26]). Results were similar for DD, and any diabetes (aOR = 1.29 [95% CI 0.94, 1.78]) or any hypertension (aOR = 1.71 [95% CI 1.30, 2.25]). Some pregnancy complications, such as hypertension, may play a role in autism etiology and can possibly serve as a prompt for more vigilant ASD screening efforts. Autism Res 2019, 12: 967-975. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: We studied if common complications in pregnancy are associated with autism spectrum disorder (ASD) in a large sample of mothers and children. Our results show an association between conditions marked by high blood pressure and ASD, but no association with conditions marked by high blood sugar and ASD. Associations were similar for children who had a developmental disorder that was not ASD, suggesting that this relationship may not be specific to ASD.

6.
Epidemiology ; 30(1): 130-144, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30299402

RESUMO

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is the most common neurobehavioral disorder in children, yet its etiology is poorly understood. Early thyroid hormone disruption may contribute to the development of ADHD. Disrupted maternal thyroid hormone function has been associated with adverse neurodevelopmental outcomes in children. Among newborns, early-treated congenital hypothyroidism has been consistently associated with later cognitive deficits. METHODS: We systematically reviewed literature on the association between maternal or neonatal thyroid hormones and ADHD diagnosis or symptoms. We searched Embase, Pubmed, Cinahl, PsycInfo, ERIC, Medline, Scopus, and Web of Science for articles published or available ahead of print as of April 2018. RESULTS: We identified 28 eligible articles: 16 studies of maternal thyroid hormones, seven studies of early-treated congenital hypothyroidism, and five studies of neonatal thyroid hormones. The studies provide moderate evidence for an association between maternal thyroid hormone levels and offspring ADHD, some evidence for an association between early-treated congenital hypothyroidism and ADHD, and little evidence for an association between neonatal thyroid hormone levels and later ADHD. CONCLUSIONS: The reviewed articles suggest an association between maternal thyroid function and ADHD, and possibly between early-treated congenital hypothyroidism and ADHD. Study limitations, however, weaken the conclusions in our systematic review, underlining the need for more research. Importantly, there was much variation in the measurement of thyroid hormone function and of ADHD symptoms. Recommendations for future research include using population-based designs, attending to measurement issues for thyroid hormones and ADHD, considering biologically relevant covariates (e.g., iodine intake), and assessing nonlinear dose-responses.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Troca Materno-Fetal , Glândula Tireoide/metabolismo , Hormônios Tireóideos/metabolismo , Criança , Hipotireoidismo Congênito/epidemiologia , Feminino , Humanos , Recém-Nascido , Gravidez
7.
JAMA Pediatr ; 2018 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-30508164

RESUMO

Importance: Metformin is an emerging option for treating gestational diabetes (GDM). However, because metformin crosses the placenta, patients and clinicians are concerned with its long-term effect on child health. Objective: To estimate the association of treating GDM with metformin vs insulin with child growth and development. Design, Setting, and Participants: Population-based cohort study of New Zealand women treated with metformin or insulin for GDM from 2005 to 2012 and their children. This study linked national health care data to create a cohort of mothers and their children, including data from maternity care, pharmaceutical dispensing, hospitalizations, demographic records, and the B4 School Check (B4SC) preschool health assessment. Women treated pharmacologically with metformin or insulin during pregnancy were included. We excluded pregnancies with evidence of diabetes and deliveries prior to 2013. Liveborn infants were linked to their B4SC results. Data were analyzed between January 2017 and May 2018. Exposures: Pharmacologic treatment for GDM with metformin or insulin, measured using pharmaceutical claims data. Main Outcomes and Measures: Child growth (weight and height) and Strengths and Difficulties Questionnaire (SDQ) scores for behavioral development. All outcomes were derived from the B4SC screening program. Linear and log-binomial regression with inverse probability of treatment weighting was used to estimate the association of child growth and psychosocial outcomes with metformin vs insulin treatment for GDM. Results: In both treatment groups, the mean (SD) maternal age was 32 (5) years. A large proportion of mothers who were treated with insulin identified as New Zealand European (867 [44.9%]) while 756 mothers (28.9%) identified as New Zealand European. Approximately one-third of mothers who were treated with metformin (n = 639) identified as Asian. We identified 3928 pregnancies treated with metformin (n = 1996) or insulin (n = 1932). After adjustment, we observed no meaningful difference in weight for height z scores between children exposed to metformin compared with insulin (mean difference, -0.10; 95% CI, -0.20 to 0.01). Risk of being 85th percentile or greater for weight for height was similar between treatment groups (adjusted risk ratio, 0.92; 95% CI, 0.83-1.02). Mean SDQ scores were not meaningfully different between the treatment groups, Children of metformin-treated mothers were not significantly more likely to have parent-reported SDQ scores of 14 or more (adjusted risk ratio, 1.13; 95% CI, 0.88-1.46) than those of insulin-treated mothers. Conclusions and Relevance: Our study compares long-term outcomes among school-aged children following maternal use of metformin vs insulin treatment for GDM. Children of metformin-treated mothers were indistinguishable on growth and developmental assessments from those of insulin-treated mothers. These results will help inform future GDM treatment guidelines.

8.
Environ Res ; 169: 33-40, 2018 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-30408751

RESUMO

Organophosphate esters (OPEs) are a class of chemicals commonly used as flame retardants and plasticizers. OPEs are applied to a wide variety of consumer products and have a propensity to leach from these products. Consequently, OPEs are ubiquitous contaminants in many human environments and human exposure is pervasive. Accumulating evidence suggests that OPEs are capable of interfering with childhood cognitive development through both neurologic- and endocrine-mediated mechanisms. However, observational evidence of cognitive effects is limited. We used data collected in the third phase of the Pregnancy, Infection, and Nutrition Study to investigate cognitive effects of prenatal exposure to OPEs. In a spot prenatal maternal urine sample, we measured the following OPE metabolites: diphenyl phosphate (DPHP), bis(1,3-dichloro-2-propyl phosphate) (BDCIPP), isopropyl-phenyl phenyl phosphate (ip-PPP), and 1-hydroxyl-2-propyl bis(1-chloro-2-propyl) phosphate (BCIPHIPP). We assessed children's language and multi-faceted and overall cognitive development between two and three years of age using the MacArthur-Bates Communicative Development Inventories (MB-CDI) and the Mullen Scales of Early Learning (MSEL). We used linear regression to estimate the change in children's scores on these developmental assessments per interquartile range (IQR) increase in log-transformed, specific-gravity-corrected prenatal OPE metabolite concentrations, adjusted for maternal age, education, income, race/ethnicity, BMI, and child's sex. A total of 149 children had both OPE metabolite measurements and MB-CDI scores, and 227 children had both OPE metabolite measurements and MSEL scores. We observed that higher concentrations of ip-PPP (ng/ml) were associated with lower scores on the MSEL Cognitive Composite Score (ß = -2.61; 95% CI: -5.69, 0.46), and separately on two of the four MSEL Scales that comprise the Cognitive Composite, specifically the Fine Motor Scale (ß = -3.08; 95% CI: -5.26, -0.91) and the Expressive Language Scale (ß = -1.21; 95% CI: -2.91, 0.49). We similarly observed that prenatal ip-PPP concentrations were inversely associated with age-standardized scores on the MB-CDI Vocabulary assessment (ß = -1.19; 95% CI: -2.53, 0.16). Other OPE metabolites were not strongly associated with performance on either assessment. Our results suggest that isopropylated triarylphosphate isomers, the presumed parent compounds of ip-PPP, may adversely impact cognitive development, including fine motor skills and early language abilities. Our study contributes to the growing body of observational evidence that suggests prenatal exposure to OPEs may adversely affect cognitive development.

9.
J Rheumatol ; 2018 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-30008449

RESUMO

OBJECTIVE: To estimate the effects of preconceptional cardiovascular (CV) health, measured by American Heart Association (AHA) guidelines, on pregnancy outcomes in women with systemic lupus erythematosus (SLE). METHODS: The study included patients in the Hopkins Lupus Pregnancy Cohort. Body mass index (BMI), total cholesterol, and blood pressure (BP) in the most recent clinic visit prior to conception or first trimester were used to determine CV health (ideal, intermediate, or poor health) based on AHA definitions. Outcomes included preterm birth, gestational age at birth, and small for gestational age (SGA). Multivariable linear and logistic regression models with generalized estimating equations estimated the association of each CV health factor and outcome. RESULTS: The analysis included 309 live births. There were 95 preterm births (31%), and of the 293 pregnancies with birth weights, 18% were SGA. Ideal BMI, total cholesterol, and BP were reported in 56%, 85%, and 51% of pregnancies, respectively. Intermediate BMI was associated with decreased odds of SGA (OR 0.26, 95% CI 0.11-0.63), adjusted for race and prednisone use. Intermediate/poor total cholesterol was associated with increased odds of preterm birth (OR 2.21, 95% CI 1.06-4.62). Intermediate/poor BP was associated with decreased gestational age at birth (ß -0.96, 95% CI -1.62 to -0.29). CONCLUSION: Poor/intermediate preconception CV health affects pregnancy outcomes of preterm birth and SGA infants among women with SLE. Efforts to maintain BMI, total cholesterol, and BP within the recommended ideal range prior to pregnancy is important to improve pregnancy outcomes in women with SLE.

10.
BMJ ; 361: k2167, 2018 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-29925546

RESUMO

OBJECTIVE: To use mendelian randomisation to investigate whether 25-hydroxyvitamin D concentration has a causal effect on gestational hypertension or pre-eclampsia. DESIGN: One and two sample mendelian randomisation analyses. SETTING: Two European pregnancy cohorts (Avon Longitudinal Study of Parents and Children, and Generation R Study), and two case-control studies (subgroup nested within the Norwegian Mother and Child Cohort Study, and the UK Genetics of Pre-eclampsia Study). PARTICIPANTS: 7389 women in a one sample mendelian randomisation analysis (751 with gestational hypertension and 135 with pre-eclampsia), and 3388 pre-eclampsia cases and 6059 controls in a two sample mendelian randomisation analysis. EXPOSURES: Single nucleotide polymorphisms in genes associated with vitamin D synthesis (rs10741657 and rs12785878) and metabolism (rs6013897 and rs2282679) were used as instrumental variables. MAIN OUTCOME MEASURES: Gestational hypertension and pre-eclampsia defined according to the International Society for the Study of Hypertension in Pregnancy. RESULTS: In the conventional multivariable analysis, the relative risk for pre-eclampsia was 1.03 (95% confidence interval 1.00 to 1.07) per 10% decrease in 25-hydroxyvitamin D level, and 2.04 (1.02 to 4.07) for 25-hydroxyvitamin D levels <25 nmol/L compared with ≥75 nmol/L. No association was found for gestational hypertension. The one sample mendelian randomisation analysis using the total genetic risk score as an instrument did not provide strong evidence of a linear effect of 25-hydroxyvitamin D on the risk of gestational hypertension or pre-eclampsia: odds ratio 0.90 (95% confidence interval 0.78 to 1.03) and 1.19 (0.92 to 1.52) per 10% decrease, respectively. The two sample mendelian randomisation estimate gave an odds ratio for pre-eclampsia of 0.98 (0.89 to 1.07) per 10% decrease in 25-hydroxyvitamin D level, an odds ratio of 0.96 (0.80 to 1.15) per unit increase in the log(odds) of 25-hydroxyvitamin D level <75 nmol/L, and an odds ratio of 0.93 (0.73 to 1.19) per unit increase in the log(odds) of 25-hydroxyvitamin D levels <50 nmol/L. CONCLUSIONS: No strong evidence was found to support a causal effect of vitamin D status on gestational hypertension or pre-eclampsia. Future mendelian randomisation studies with a larger number of women with pre-eclampsia or more genetic instruments that would increase the proportion of 25-hydroxyvitamin D levels explained by the instrument are needed.

11.
Comput Stat Data Anal ; 122: 135-155, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29867285

RESUMO

Nonparametric regression models do not require the specification of the functional form between the outcome and the covariates. Despite their popularity, the amount of diagnostic statistics, in comparison to their parametric counter-parts, is small. We propose a goodness-of-fit test for nonparametric regression models with linear smoother form. In particular, we apply this testing framework to smoothing spline ANOVA models. The test can consider two sources of lack-of-fit: whether covariates that are not currently in the model need to be included, and whether the current model fits the data well. The proposed method derives estimated residuals from the model. Then, statistical dependence is assessed between the estimated residuals and the covariates using the HSIC. If dependence exists, the model does not capture all the variability in the outcome associated with the covariates, otherwise the model fits the data well. The bootstrap is used to obtain p-values. Application of the method is demonstrated with a neonatal mental development data analysis. We demonstrate correct type I error as well as power performance through simulations.

12.
J Cancer Surviv ; 12(4): 592-600, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29785559

RESUMO

PURPOSE: Annually, > 45,000 US women are diagnosed with cancer during adolescence and young adulthood (AYA). Since 2006, national guidelines have recommended fertility counseling for cancer patients. We examined childbirth after AYA cancer by calendar period, cancer diagnosis, and maternal characteristics. METHODS: We identified a cohort of women with an incident invasive AYA cancer diagnosis at ages 15-39 during 2000-2013 in North Carolina. Cancer records were linked with statewide birth certificates through 2014. Hazard ratios (HR) and 95% confidence intervals (CI) for first post-diagnosis live birth were calculated using Cox proportional hazards regression. RESULTS: Among 17,564 AYA cancer survivors, 1989 had ≥ 1 birth after diagnosis during 98,397 person-years. The 5- and 10-year cumulative incidence of live birth after cancer was 10 and 15%, respectively. AYA survivors with a post-diagnosis birth were younger at diagnosis, had lower stage disease, and had less often received chemotherapy than those without a birth. The 5-year cumulative incidence of post-diagnosis birth was 10.0% for women diagnosed during 2007-2012, compared to 9.4% during 2000-2005 (HR = 1.01; 0.91, 1.12), corresponding to periods before and after publication of American Society of Clinical Oncology fertility counseling guidelines in 2006. CONCLUSIONS: Despite advances in fertility preservation options and recognition of fertility counseling as a part of high-quality cancer care, the incidence of post-diagnosis childbirth has remained stable over the last 15 years. IMPLICATIONS FOR CANCER SURVIVORS: Our study uses statewide data to provide recent, population-based estimates of how often AYA women have biological children after a cancer diagnosis.

13.
Environ Health Perspect ; 126(5): 057004, 2018 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-29790729

RESUMO

BACKGROUND: There is growing concern that phthalate exposures may have an impact on child neurodevelopment. Prenatal exposure to phthalates has been linked with externalizing behaviors and executive functioning defects suggestive of an attention-deficit hyperactivity disorder (ADHD) phenotype. OBJECTIVES: We undertook an investigation into whether prenatal exposure to phthalates was associated with clinically confirmed ADHD in a population-based nested case-control study of the Norwegian Mother and Child Cohort (MoBa) between the years 2003 and 2008. METHODS: Phthalate metabolites were measured in maternal urine collected at midpregnancy. Cases of ADHD (n=297) were obtained through linkage between MoBa and the Norwegian National Patient Registry. A random sample of controls (n=553) from the MoBa population was obtained. RESULTS: In multivariable adjusted coexposure models, the sum of di-2-ethylhexyl phthalate metabolites (∑DEHP) was associated with a monotonically increasing risk of ADHD. Children of mothers in the highest quintile of ∑DEHP had almost three times the odds of an ADHD diagnosis as those in the lowest [OR=2.99 (95% CI: 1.47, 5.49)]. When ∑DEHP was modeled as a log-linear (natural log) term, for each log-unit increase in exposure, the odds of ADHD increased by 47% [OR=1.47 (95% CI: 1.09, 1.94)]. We detected no significant modification by sex or mediation by prenatal maternal thyroid function or by preterm delivery. CONCLUSIONS: In this population-based case-control study of clinical ADHD, maternal urinary concentrations of DEHP were monotonically associated with increased risk of ADHD. Additional research is needed to evaluate potential mechanisms linking phthalates to ADHD. https://doi.org/10.1289/EHP2358.

15.
Environ Int ; 115: 79-88, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29550712

RESUMO

BACKGROUND: Prenatal environmental phenol and phthalate exposures may alter immune or inflammatory responses leading to respiratory and allergic disease. OBJECTIVES: We estimated associations of prenatal environmental phenol and phthalate biomarkers with respiratory and allergic outcomes among children in the Mount Sinai Children's Environmental Health Study. METHODS: We quantified urinary biomarkers of benzophenone-3, bisphenol A, paradichlorobenzene (as 2,5-dichlorophenol), triclosan, and 10 phthalate metabolites in third trimester maternal samples and assessed asthma, wheeze, and atopic skin conditions via parent questionnaires at ages 6 and 7 years (n = 164 children with 240 observations). We used logistic regression to estimate covariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) per standard deviation difference in natural log biomarker concentrations and examined effect measure modification by child's sex. RESULTS: Associations of prenatal 2,5-dichlorophenol (all outcomes) and bisphenol A (asthma outcomes) were modified by child's sex, with increased odds of outcomes among boys but not girls. Among boys, ORs for asthma diagnosis per standard deviation difference in biomarker concentration were 3.00 (95% CI: 1.36, 6.59) for 2,5-dichlorophenol and 3.04 (95% CI: 1.38, 6.68) for bisphenol A. Wheeze in the past 12 months was inversely associated with low molecular weight phthalate metabolites among girls only (OR: 0.27, 95% CI: 0.13, 0.59) and with benzophenone-3 among all children (OR: 0.65, 95% CI: 0.44, 0.96). CONCLUSIONS: Prenatal bisphenol A and paradichlorobenzene exposures were associated with pediatric respiratory outcomes among boys. Future studies may shed light on biological mechanisms and potential sexually-dimorphic effects of select phenols and phthalates on respiratory disease development.

16.
Ann Rheum Dis ; 77(6): 855-860, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29463519

RESUMO

OBJECTIVE: Prior studies found conflicting results about whether lupus is likely to flare during or after pregnancy. Using a large cohort of pregnant and non-pregnant women with lupus, we estimated the effect of pregnancy on disease flares in systemic lupus erythematosus. METHODS: Data were collected in the Hopkins Lupus Cohort 1987-2015. Women aged 14-45 years with >1 measurement of disease activity were included. The time-varying exposures were classified as pregnancy, postpartum or non-pregnant/non-postpartum periods. Flares were defined as: (1) change in Physician Global Assessment (PGA)≥1 from previous visit and (2) change in Safety of Estrogens in Lupus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI)≥4 from previous visit. A stratified Cox model estimated HRs with bootstrap 95% CIs. RESULTS: There were 1349 patients, including 398 pregnancies in 304 patients. There was an increased rate of flare defined by PGA during pregnancy (HR: 1.59; 95% CI 1.27 to 1.96); however, this effect was modified by hydroxychloroquine (HCQ) use, with the HR of flares in pregnancy compared with non-pregnant/non-postpartum periods estimated to be 1.83 (95% CI 1.34 to 2.45) for patients with no HCQ use and 1.26 (95% CI 0.88 to 1.69) for patients with HCQ use. The risk of flare was similarly elevated among non-HCQ users in the 3 months postpartum, but not for women taking HCQ after delivery. CONCLUSIONS: Our study supports and extends previous findings that the incidence of flare is increased during pregnancy and within the 3 months postpartum. Continuing HCQ, however, appeared to mitigate the risk of flare during and after pregnancy.

17.
Stat Methods Med Res ; 27(10): 3183-3204, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29298607

RESUMO

Epidemiologists often wish to estimate quantities that are easy to communicate and correspond to the results of realistic public health interventions. 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 are sparse. We demonstrate an approach to estimate the effect of environmental tobacco smoke on body mass index among children aged 4-9 years who were enrolled in a longitudinal birth cohort in New York, USA. We provide an algorithm and supply SAS and Stan code that can be adopted to implement this computational approach more generally.

18.
Int J Cancer ; 142(10): 1994-2002, 2018 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-29266267

RESUMO

Reproductive outcomes are an important survivorship concern for women diagnosed with cancer as adolescents and young adults (AYAs). We examined the incidence of live birth and the prevalence of adverse birth outcomes according to tumor and treatment characteristics among AYAs with breast cancer. Women diagnosed with breast cancer at ages 15-39 during 2000-2013 were identified using the North Carolina Central Cancer Registry (n = 4,978). Cancer registry records were linked to state birth certificate files from 2000 to 2014 to identify births to women with and without a breast cancer history. The breast cancer cohort was followed until live birth, death, age 46, or December 31, 2014, whichever occurred first. For each birth to breast cancer survivors (n = 338), we sampled 20 births to women without a recorded cancer diagnosis, with frequency matching on maternal age and year of delivery. The cumulative incidence of live births after breast cancer was 8% at 10 years. Births were less common among women treated with chemotherapy. Overall, the prevalence of preterm birth, low birth weight, small-for-gestational age (SGA) and Cesarean delivery did not differ substantially between births to women with and without breast cancer. However, births to women with ER-negative disease were more likely to be preterm (PR = 1.84; 95% CI: 1.11-3.06). In this population-based study, <10% of AYA breast cancer survivors had a live birth within 10 years of their diagnosis. The increase in risk of preterm delivery among ER-negative survivors in our cohort warrants further investigation in larger studies.

19.
Child Psychiatry Hum Dev ; 49(4): 534-550, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29177988

RESUMO

Neurodevelopmental outcomes including behavior, executive functioning, and IQ exhibit complex correlational structures, although they are often treated as independent in etiologic studies. We performed a principal components analysis of the behavioral assessment system for children, the behavior rating inventory of executive functioning, and the Wechsler scales of intelligence in a prospective birth cohort, and estimated associations with early life characteristics. We identified seven factors: (1) impulsivity and externalizing, (2) executive functioning, (3) internalizing, (4) perceptual reasoning, (5) adaptability, (6) processing speed, and (7) verbal intelligence. Prenatal fish consumption, maternal education, preterm birth, and the home environment were important predictors of various neurodevelopmental factors. Although maternal smoking was associated with more adverse externalizing, executive functioning, and adaptive composite scores in our sample, of the orthogonally-rotated factors, smoking was only associated with the impulsivity and externalizing factor ([Formula: see text] - 0.82, 95% CI - 1.42, - 0.23). These differences may be due to correlations among outcomes that were accounted for by using a phenotypic approach. Dimension reduction may improve upon traditional approaches by accounting for correlations among neurodevelopmental traits.

20.
Cancer Causes Control ; 29(2): 289-295, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29196836

RESUMO

PURPOSE: A cancer diagnosis in adolescence and young adulthood (AYA, ages 15-39) may affect future pregnancy outcomes. Previous studies have reported an increased risk of preterm delivery (< 37 weeks of gestation) after maternal cancer treatment. In this analysis, we evaluated whether non-cancer characteristics modify the association between an AYA cancer history and preterm birth. METHODS: North Carolina Central Cancer Registry records (2000-2013) were linked to state birth certificate files (2000-2014) to identify births to AYA cancer survivors (n = 1,980). A comparison cohort of births to women without a cancer diagnosis was selected from birth certificate files (n = 11,860). Log-binomial regression was used to estimate risk ratios (RR) and 95% confidence intervals (CI) for preterm delivery. Effect modification by early prenatal care (1st trimester; yes/no), race/ethnicity (white/black/other), previous live births (0/1+), maternal age (< 25/25-29/30-34/35+), smoking during pregnancy (any/none), and education (high school or less/some college/Bachelor's degree or higher) was evaluated using likelihood ratio tests (LRT). RESULTS: Overall, preterm births were more common among AYA survivors than the comparison group (RR = 1.24, CI 1.07-1.43). The association was stronger among those who did not receive early prenatal care (RR = 1.73, CI 1.26-2.37) than among those who did (RR = 1.15, CI 0.98-1.35; LRT p = 0.03). Maternal age < 25 was also associated with a greater increase in preterm birth (< 25: RR = 1.80, CI 1.27-2.54; LRT p = 0.07). Associations did not vary strongly by other factors evaluated. CONCLUSIONS: An AYA cancer diagnosis may be associated with an increased risk of preterm birth, particularly among women who are younger and receive late or no prenatal care.

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