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Miller F.W.,U.S. National Institutes of Health | Pollard K.M.,Scripps Research Institute | Parks C.G.,Epidemiology Branch | Germolec D.R.,National Toxicology Program | And 4 more authors.
Journal of Autoimmunity | Year: 2012

Increasing evidence supports a role for the environment in the development of autoimmune diseases, as reviewed in the accompanying three papers from the National Institute of Environmental Health Sciences Expert Panel Workshop. An important unresolved issue, however, is the development of criteria for identifying autoimmune disease phenotypes for which the environment plays a causative role, herein referred to as environmentally associated autoimmune diseases. There are several different areas in which such criteria need to be developed, including: 1) identifying the necessary and sufficient data to define environmental risk factors for autoimmune diseases meeting current classification criteria; 2) establishing the existence of and criteria for new environmentally associated autoimmune disorders that do not meet current disease classification criteria; and 3) identifying in clinical practice specific environmental agents that induce autoimmune disease in individual patients. Here we discuss approaches that could be useful for developing criteria in these three areas, as well as factors that should be considered in evaluating the evidence for criteria that can distinguish individuals with such disorders from individuals without such disorders with high sensitivity and specificity. Current studies suggest that multiple lines of complementary evidence will be important and that in many cases there will be clinical, serologic, genetic, epigenetic, and/or other laboratory features that could be incorporated as criteria for environmentally associated autoimmune diseases to improve diagnosis and treatment and possibly allow for preventative strategies in the future. © 2012.


Parikh L.I.,MedStar Washington Hospital Center | Reddy U.M.,U.S. National Institutes of Health | Mannisto T.,Epidemiology Branch | Mendola P.,Epidemiology Branch | And 5 more authors.
American Journal of Obstetrics and Gynecology | Year: 2014

Objective To determine neonatal morbidity rates for early term birth compared with full term birth by precursor leading to delivery. Study Design This was a retrospective study of 188,809 deliveries from 37 0/7 to 41 6/7 weeks of gestation with electronic medical record data from 2002 to 2008. Precursors for delivery were categorized as spontaneous labor, premature rupture of membranes indicated, and no recorded indication. After excluding anomalies, rates of neonatal morbidities by precursor were compared at each week of delivery. Results Early term births (37 0/7-38 6/7 weeks) accounted for 34.1% of term births. Overall, 53.6% of early term births were due to spontaneous labor, followed by 27.6% indicated, 15.5% with no recorded indication, and 3.3% with premature rupture of membranes. Neonatal intensive care unit admission and respiratory morbidity were lowest at or beyond 39 weeks compared with the early term period for most precursors, although indicated deliveries had the highest morbidity compared with other precursors. The greatest difference in morbidity was between 37 and 39 weeks for most precursors, although most differences in morbidities between 38 and 39 weeks were not significant. Respiratory morbidity was higher at 37 than 39 weeks regardless of route of delivery. Conclusion Given the higher neonatal morbidity at 37 compared with 39 weeks regardless of delivery precursor, our data support recent recommendations for designating early term to include 37 weeks. Prospective data is urgently needed to determine the optimal timing of delivery for common pregnancy complications. © 2014 Mosby, Inc. All rights reserved.


PubMed | Inc and., National Health Research Institute, Biostatistics and Bioinformatics Branch., Epidemiology Branch and Epidemiology Branch.
Type: | Journal: Pediatrics | Year: 2017

Previous studies identified associations between maternal obesity and childhood neurodevelopment, but few examined paternal obesity despite potentially distinct genetic/epigenetic effects related to developmental programming.Upstate KIDS (2008-2010) recruited mothers from New York State (excluding New York City) at 4 months postpartum. Parents completed the Ages and Stages Questionnaire (ASQ) when their children were 4, 8, 12, 18, 24, 30, and 36 months of age corrected for gestation. The ASQ is validated to screen for delays in 5 developmental domains (ie, fine motor, gross motor, communication, personal-social functioning, and problem-solving ability). Analyses included 3759 singletons and 1062 nonrelated twins with 1 ASQs returned. Adjusted odds ratios (aORs) and 95% confidence intervals were estimated by using generalized linear mixed models accounting for maternal covariates (ie, age, race, education, insurance, marital status, parity, and pregnancy smoking).Compared with normal/underweight mothers (BMI <25), children of obese mothers (26% with BMI 30) had increased odds of failing the fine motor domain (aOR 1.67; confidence interval 1.12-2.47). The association remained after additional adjustment for paternal BMI (1.67; 1.11-2.52). Paternal obesity (29%) was associated with increased risk of failing the personal-social domain (1.75; 1.13-2.71), albeit attenuated after adjustment for maternal obesity (aOR 1.71; 1.08-2.70). Children whose parents both had BMI 35 were likely to additionally fail the problem-solving domain (2.93; 1.09-7.85).Findings suggest that maternal and paternal obesity are each associated with specific delays in early childhood development, emphasizing the importance of family information when screening child development.


Liu R.,Epidemiology Branch | Umbach D.M.,National Health Research Institute | Peddada S.D.,National Health Research Institute | Xu Z.,Epidemiology Branch | And 3 more authors.
Neurology | Year: 2015

Objective: To examine potential sex differences in nonmotor symptoms (NMS) among drug-naive patients with Parkinson disease (PD), and to identify NMS that can best differentiate patients with early PD from controls. Methods: Our cross-sectional analysis included 414 newly diagnosed, untreated patients with PD (269 men and 145 women) and 188 healthy controls (121 men and 67 women) in the Parkinson's Progression Markers Initiative Study. NMS were measured using well-validated instruments covering sleep, olfactory, neurobehavioral, autonomic, and neuropsychological domains. Results: Male and female patients with PD were fairly comparable on motor presentations but differed on several nonmotor features. Male patients with PD had significantly more pronounced deficits in olfaction (p 0.02) and in certain cognitive measurements (all p < 0.01) than female patients, whereas female cases experienced higher trait anxiety (p 0.02). Multiple stepwise logistic regression analysis showed that the combination of NMS measures-University of Pennsylvania Smell Identification Test (UPSIT), Montreal Cognitive Assessment (MoCA), Scales for Outcomes in Parkinson's Disease-Autonomic (SCOPA-AUT), and state anxiety from the State-Trait Anxiety Inventory-effectively differentiated patients with PD from controls with an area under the receiver operating characteristic curve (AUC) of 0.913 (95% confidence interval [CI]: 0.89-0.94). UPSIT, MoCA, and SCOPA-AUT were the most predictive NMS measurements in men (AUC 0.919; 95% CI: 0.89-0.95) as compared to UPSIT, MoCA, and REM Sleep Behavior Disorder Screening Questionnaire in women (AUC 0.903; 95% CI: 0.86-0.95). Conclusions: Our analysis revealed notable sex differences in several nonmotor features of patients with de novo PD. Furthermore, we found a parsimonious NMS combination that could effectively differentiate de novo cases from healthy controls. © 2015 American Academy of Neurology.


Dragomir A.D.,University of North Carolina at Chapel Hill | Schroeder J.C.,University of North Carolina at Chapel Hill | Connolly A.,University of North Carolina at Chapel Hill | Kupper L.L.,University of North Carolina at Chapel Hill | And 3 more authors.
Reproductive Sciences | Year: 2010

Objective: To compare potential risk factors for uterine leiomyomata (UL) subtypes among premenopausal African American and Caucasian women. Methods: This cross-sectional study included 986 premenopausal women, aged 35 to 49 years old, from the National Institute of Environmental Health Sciences (NIEHS) Uterine Fibroid Study (UFS). Uterine leiomyomata were subtyped as submucosal, intramural/subserosal, and diffuse, based on ultrasound examinations. Results: For both ethnic groups, age, age at menarche, body mass index, and current physical activity had similar associations across the 3 UL subtypes. Inverse associations with pregnancies after age 24 appeared to be stronger for the submucosal subtype. Current smoking was associated only with diffuse UL (adjusted odds ratio [aOR] = 1.97, 95% CI: 1.11, 3.51 in African Americans, aOR = 3.00, 95% CI: 1.07, 8.38 in Caucasians). Conclusions: Although the 2 focal UL subtypes had similar risk factor profiles, the diffuse UL subtype appeared to have a distinctive risk profile with regard to current smoking. Further study of the diffuse heterogeneity seen with uterine ultrasound is needed. © The Author(s) 2010.


Basso O.,Epidemiology Branch | Basso O.,McGill University | Wilcox A.J.,Epidemiology Branch
Epidemiology | Year: 2011

Background: Preterm delivery has a variety of causes, with each of these presumably carrying its own mortality risk. To the extent that they add to the risk of mortality, the various pathologic factors triggering preterm delivery will confound the causal contribution of gestational age to mortality, inflating the observed rates of gestational-age-specific mortality. We have previously estimated that about half of the mortality of US preterm singletons may be due to unmeasured pathologies that increase mortality risk and also cause preterm birth. In this paper, we examine the impact that rare factors may have, at least in theory, on preterm mortality. Methods: We constructed a simple model of gestational-age-specific mortality, in which we arbitrarily selected a function to represent the mortality due to immaturity alone ("baseline" risk). We then added "unmeasured" confounding factors that cause mortality and also cause preterm birth. This construct allowed us to calculate, in simple scenarios, the proportion of preterm mortality that could be caused by unmeasured confounding. Results: We found that rare pathologies with moderate-to-strong effects can substantially contribute to preterm mortality. The presence of such rare factors can also produce an intersection of gestational-age-specific mortality curves when stratifying by known risk factors. Conclusions: It is possible that a few relatively rare factors may account for a large fraction of preterm mortality. The search for such factors should be a primary focus of future research on preterm delivery. Copyright © 2011 by Lippincott Williams & Wilkins.


News Article | September 27, 2016
Site: www.chromatographytechniques.com

Expecting mothers experiencing nausea and vomiting during pregnancy may find some comfort in the results of a recent study that backs up the notion that morning sickness is a sign of a healthy pregnancy. Researchers at the National Institute of Child Health and Development examined data from women already enrolled in a larger study that analyzed the effects of taking aspirin on pregnancy loss and live birth. Out of the 1,200 women enrolled in the “Effects of Aspirin in Gestation and Reproduction Trial” from June 2007 to July 2011, 797 became pregnant. The study, published in the journal JAMA Internal Medicine, also focused on women who already lost at least one pregnancy. The participants kept a diary daily during their first trimester, which rated their morning sickness symptoms. In the second and third trimesters, the women completed monthly questionnaires about their symptoms. Overall, the results showed that women who experienced morning sickness were 50 to 75 percent less likely to experiencing a loss. To break it down further, about 18 percent of the women reported experiencing nausea at week two, and three percent had nausea with vomiting. By week eight, that number jumped to 57 percent and 27 percent, respectively. Those who experienced just nausea by week eight were 50 percent less likely to lose the pregnancy, and participants who endured vomiting were 75 percent less likely. Nearly 24 percent, or 188 of the 797 women, lost their pregnancy. “It’s a common thought that nausea indicates a healthy pregnancy, but there wasn’t a lot of high-quality evidence to support this belief,” said the study’s first author, Stefanie N. Hinkle, Ph.D, a staff scientist in NICHD’s Epidemiology Branch. “Our study evaluates symptoms from the earliest weeks of pregnancy, immediately after conception, and confirms that there is a protective association between nausea and vomiting and a lower risk of pregnancy loss.” The NICHD researchers overcame limitations seen in previous research by enrolling women as they were trying to conceive to track the pregnancy from the very beginning. They were also able to rule out other contributing factors such as alcohol or smoking, as well as fetal characteristics that may play a role in development. "These findings overcome prior analytic and design limitations and represent the most definitive data available to date indicating the protective association of nausea and vomiting in early pregnancy and the risk for pregnancy loss," the researchers explain in their paper. The researchers theorize that sickness during pregnancy may indicate viable placental tissue, because the tissue has released a sufficient amount of hormones—but the rapid change also produces a nauseous side effect. On the other hand, the researchers explain, if a woman is not experiencing any nausea, it could mean that not enough hormones were released and the placental tissue is less viable. But the team cautions women from making any generalizations from the study results, noting that every individual is different and not all pregnancies are the same.


Niu L.,University of Cincinnati | Xu Z.,Epidemiology Branch | Taylor J.A.,Epidemiology Branch | Taylor J.A.,U.S. National Institutes of Health
Bioinformatics | Year: 2016

Motivation: The Illumina HumanMethylation450 BeadChip has been extensively utilized in epigenome-wide association studies. This array and its successor, the MethylationEPIC array, use two types of probes - Infinium I (type I) and Infinium II (type II) - in order to increase genome coverage but differences in probe chemistries result in different type I and II distributions of methylation values. Ignoring the difference in distributions between the two probe types may bias downstream analysis. Results: Here, we developed a novel method, called Regression on Correlated Probes (RCP), which uses the existing correlation between pairs of nearby type I and II probes to adjust the beta values of all type II probes. We evaluate the effect of this adjustment on reducing probe design type bias, reducing technical variation in duplicate samples, improving accuracy of measurements against known standards, and retention of biological signal. We find that RCP is statistically significantly better than unadjusted data or adjustment with alternative methods including SWAN and BMIQ. Availability: We incorporated the method into the R package ENmix, which is freely available from the Bioconductor website (https://www.bioconductor.org/packages/release/bioc/html/ENmix.html). © 2016 Published by Oxford University Press 2016.


Higa D.H.,Prevention Research Branch | Marks G.,Epidemiology Branch | Crepaz N.,Prevention Research Branch | Liau A.,Indiana University | Lyles C.M.,Prevention Research Branch
Current HIV/AIDS Reports | Year: 2012

Retaining HIV-diagnosed persons in care is a national priority, but little is known on what intervention strategies are most effective for promoting retention in care. We conducted a systematic search and qualitatively reviewed 13 published studies and three recent conference presentations to identify evidence-informed retention strategies. We extracted information on study design, methods, and intervention characteristics. Strengths-based case management that encourages clients to recognize and use their own internal abilities to access resources and solve problems offered strong evidence for retention in care. Other evidence-informed strategies included peer navigation, reducing structural- and system-level barriers, including peers as part of a health care team, displaying posters and brochures in waiting rooms, having medical providers present brief messages to patients, and having clinics stay in closer contact with patients across time. Opportunities for additional intervention strategies include using community-based organizations as a setting for engaging HIV-infected persons about the importance ofregular care and involving patients' significant others in retention in care interventions. © 2012 Springer Science+Business Media, LLC (outside the USA).


Gust D.A.,Epidemiology Branch | Kretsinger K.,Epidemiology Branch | Gaul Z.,Epidemiology Branch | Pals S.,Epidemiology Branch | And 4 more authors.
Sexually Transmitted Diseases | Year: 2011

Background/Purpose: To understand whether information from the African clinical trials about the partially protective effect of male circumcision against human immunodeficiency virus (HIV) infection could influence adults to circumcise a newborn son. Methods: Using the 2008 ConsumerStyles panel survey data, multiple regression analysis was performed to identify correlates of (1) inclination toward circumcising a newborn son and (2) being influenced to have a newborn son circumcised if it would reduce the chance of becoming HIV infected later in life. Results: Response rate was 50.6% (10,108/19,996). Approximately 12% reported not being inclined to circumcise a newborn son. Higher odds of not being inclined to circumcise a newborn son were associated with Hispanic and "other" race/ethnicity, being an uncircumcised man and a man not reporting circumcision status, postgraduate education, region, and negative health-related attitudes. Lower odds were associated with black race and less number of household members. Fifty-three percent of respondents reported that information about the protective effect of circumcision would make them more likely to have a newborn son circumcised. Higher odds of being influenced to have a newborn son circumcised were associated with being ≥45 years of age, black race, living in a household with fewer than 5 members, having high school or some college education, region, and positive health-related attitudes; lower odds were associated with being an uncircumcised man and lower income. Conclusions: Our findings suggest that providing educational information about the HIV prevention and benefit of circumcision may increase the inclination to circumcise a newborn son for some people. © 2011 American Sexually Transmitted Diseases Association All rights reserved.

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