Common Genetic Variants Contribute to Risk of Transposition of the Great Arteries.

Rationale: Dextro-transposition of the great arteries (D-TGA) is a severe congenital heart defect which affects approximately 1 in 4,000 live births. While there are several reports of D-TGA patients with rare variants in individual genes, the majority of D-TGA cases remain genetically elusive. Familial recurrence patterns and the observation that most cases with D-TGA are sporadic suggest a polygenic inheritance for the disorder, yet this remains unexplored.

Embryonic lethal genetic variants and chromosomally normal pregnancy loss.

Objective: To examine whether rare damaging genetic variants are associated with chromosomally normal pregnancy loss and estimate the magnitude of the association.

Design: Case-control.

Setting: Cases were derived from a consecutive series of karyotyped losses at one New Jersey hospital.

Body size at birth, early-life growth and the timing of the menopausal transition and natural menopause.

Background: Whether birth weight and early-life growth are associated with age at menopause has not been resolved.

Methods: We conducted a prospective study in two U.S.

A cross-sectional study of water arsenic exposure and intellectual function in adolescence in Araihazar, Bangladesh.

Background: Exposure to inorganic arsenic (As) from drinking water is associated with modest deficits in intellectual function in young children; it is unclear whether deficits occur during adolescence, when key brain functions are more fully developed.

Objectives: We sought to determine the degree to which As exposure is associated with adolescent intelligence, and the contributory roles of lead, cadmium, manganese and selenium.

Methods: We recruited a cross-section of 726 14-16 year olds (mean age = 14.

The Congenital Heart Disease Genetic Network Study: Cohort description.

The Pediatric Cardiac Genomics Consortium (PCGC) designed the Congenital Heart Disease Genetic Network Study to provide phenotype and genotype data for a large congenital heart defects (CHDs) cohort. This article describes the PCGC cohort, overall and by major types of CHDs (e.g.

Child Intelligence and Reductions in Water Arsenic and Manganese: A Two-Year Follow-up Study in Bangladesh.

Background: Arsenic (As) exposure from drinking water is associated with modest intellectual deficits in childhood. It is not known whether reducing exposure is associated with improved intelligence.

Objective: We aimed to determine whether reducing As exposure is associated with improved child intellectual outcomes.

Life course exposure to smoke and early menopause and menopausal transition.

Objective: Early age at menopause is associated with increased risk of cardiovascular disease, stroke, osteoporosis, and all-cause mortality. Cigarette smoke exposure in adulthood is an established risk factor for earlier age at natural menopause and may be related to age at the menopausal transition. Using data from two US birth cohorts, we examined the association between smoke exposure at various stages of the life course (prenatal exposure, childhood exposure to parental smoking, and adult smoke exposure) and menopause status in 1,001 women aged 39 to 49 years at follow-up.

A cross-sectional study of well water arsenic and child IQ in Maine schoolchildren.

Background: In recent studies in Bangladesh and elsewhere, exposure to arsenic (As) via drinking water is negatively associated with performance-related aspects of child intelligence (e.g., Perceptual Reasoning, Working Memory) after adjustment for social factors.

Intermediate CGG repeat length at the FMR1 locus is not associated with hormonal indicators of ovarian age.

Objective: Premutation and intermediate CGG repeat length at the fragile X mental retardation 1 (FMR1) locus have been associated with premature ovarian failure. We tested whether intermediate length is associated with indicators of ovarian age in a sample of fertile women. Our primary measures of ovarian age were antimüllerian hormone (AMH) and follicle-stimulating hormone (FSH) levels.

The contribution of de novo and rare inherited copy number changes to congenital heart disease in an unselected sample of children with conotruncal defects or hypoplastic left heart disease.

Congenital heart disease (CHD) is the most common congenital malformation, with evidence of a strong genetic component. We analyzed data from 223 consecutively ascertained families, each consisting of at least one child affected by a conotruncal defect (CNT) or hypoplastic left heart disease (HLHS) and both parents. The NimbleGen HD2-2.

De novo mutations in histone-modifying genes in congenital heart disease.

Congenital heart disease (CHD) is the most frequent birth defect, affecting 0.8% of live births. Many cases occur sporadically and impair reproductive fitness, suggesting a role for de novo mutations.

The Congenital Heart Disease Genetic Network Study: rationale, design, and early results.

Congenital heart defects (CHD) are the leading cause of infant mortality among birth defects, and later morbidities and premature mortality remain problematic. Although genetic factors contribute significantly to cause CHD, specific genetic lesions are unknown for most patients. The National Heart, Lung, and Blood Institute-funded Pediatric Cardiac Genomics Consortium established the Congenital Heart Disease Genetic Network Study to investigate relationships between genetic factors, clinical features, and outcomes in CHD.

Incidence of subsequent pancreatic adenocarcinoma in patients with a history of nonpancreatic primary cancers.

Background: Several environmental risk factors are known to predispose individuals to pancreatic cancer, and up to 15% of pancreatic cancers have an inherited component. Understanding metachronous cancer associations can modify pancreas cancer risk. The objective of this study was to investigate the association of nonpancreatic cancers with subsequent pancreatic adenocarcinoma.

Arsenic exposure and motor function among children in Bangladesh.

Background: Several reports indicate that drinking water arsenic (WAs) and manganese (WMn) are associated with children's intellectual function. Very little is known, however, about possible associations with other neurologic outcomes such as motor function.

Methods: We investigated the associations of WAs and WMn with motor function in 304 children in Bangladesh, 8-11 years of age.

Arsenic and manganese exposure and children's intellectual function.

Recently, epidemiologic studies of developmental neurotoxicology have been challenged to increase focus on co-exposure to multiple toxicants. Earlier reports, including our own work in Bangladesh, have demonstrated independent associations between neurobehavioral function and exposure to both arsenic (As) and manganese (Mn) in school-aged children. Our earlier studies, however, were not designed to examine possible interactive effects of exposure to both As and Mn.

Skewed X chromosome inactivation and trisomic spontaneous abortion: no association.

Several studies suggest that highly skewed X chromosome inactivation (HSXI) is associated with recurrent spontaneous abortion. We hypothesized that this association reflects an increased rate of trisomic conceptions due to anomalies on the X chromosome that lead both to HSXI and to a diminished oocyte pool. We compared the distribution of X chromosome inactivation (XCI) skewing percentages (range: 50%-100%) among women with spontaneous abortions in four karyotype groups-trisomy (n = 154), chromosomally normal male (n = 43), chromosomally normal female (n = 38), nontrisomic chromosomally abnormal (n = 61)-to the distribution for age-matched controls with chromosomally normal births (n = 388).

Environmental lead exposure, maternal thyroid function, and childhood growth.

Prenatal and early-life exposure to lead is hypothesized to have a range of adverse effects on childhood health. Drawing on data collected from a population-based prospective cohort study of a highly exposed town and a low exposed town in Kosovo, Yugoslavia we assessed whether elevated maternal blood lead (BPb) concentrations during pregnancy were associated with reduced childhood measures of attained height and BMI or growth rate, and whether the associations, if any, were mediated by maternal thyroid hormone concentration at mid-pregnancy. There was no association between blood lead levels and height or BMI in either town.

The autism epidemic: fact or artifact?

Objective: We provide an illustration of how changes in methodological factors may produce variations in the frequency of autistic disorder (AD) over time and project how much of the observed increase in the frequency of AD may be explained by methodological factors.

Method: Using a prediction analysis, we calculate how broadening diagnostic criteria, younger age at diagnosis, and improved efficiency of case ascertainment could produce temporal trends in the incidence and prevalence of AD, measured by calendar year and by year of birth, in a hypothetical population of children 0 to 18 across the years 1950 to 2020.

Results: Time trend studies report an increase as large as 11.

Water arsenic exposure and intellectual function in 6-year-old children in Araihazar, Bangladesh.

Background: We recently reported results of a cross-sectional investigation of intellectual function in 10-year-olds in Bangladesh, who had been exposed to arsenic from drinking water in their home wells.

Objectives: We present results of a similar investigation of 301 randomly selected 6-year-olds whose parents participated in our ongoing prospective study of the health effects of As exposure in 12,000 residents of Araihazar, Bangladesh.

Methods: Water As and manganese concentrations of tube wells at each home were obtained by surveying all study region wells.

Preliminary open trial of interpersonal counseling for subsyndromal depression following miscarriage.

Miscarriage occurs in 10-20% of clinically recognized pregnancies and is associated with two- to fourfold increases in depressive symptoms. No counseling programs for depressed miscarrying women have been manualized or evaluated for safety and efficacy. We investigated whether depressive symptoms decline substantially among miscarrying women receiving one to six weekly sessions of manualized, telephone-administered interpersonal counseling (IPC), a variant of interpersonal psychotherapy (IPT) in an open trial.

Pilot randomized controlled trial of interpersonal counseling for subsyndromal depression following miscarriage.

Objective: Miscarriage, which occurs in 10% to 20% of clinically recognized pregnancies, is associated with an increased risk for subsyndromal depression. We examined whether Interpersonal Counseling (IPC) was superior to treatment as usual (TAU) in reducing subsyndromal depression among miscarrying women and, secondarily, superior to TAU in improving role functioning.

Method: Nineteen of 20 eligible women participated in a randomized controlled trial of 1 to 6 weekly telephone sessions of IPC versus TAU, which consisted of whatever lay counseling or professional care women sought on their own initiative, from October 2001 to April 2002.

X-chromosome inactivation and ovarian age during the reproductive years.

Objective: To explore whether skewed X-chromosome inactivation (XCI) is related to indicators of ovarian age.

Design: The XCI skewing percent and indicators of ovarian age were measured in women with recent pregnancy losses and women with recent livebirths. All analyses adjust for chronologic age and pregnancy outcome.

Water manganese exposure and children's intellectual function in Araihazar, Bangladesh.

Exposure to manganese via inhalation has long been known to elicit neurotoxicity in adults, but little is known about possible consequences of exposure via drinking water. In this study, we report results of a cross-sectional investigation of intellectual function in 142 10-year-old children in Araihazar, Bangladesh, who had been consuming tube-well water with an average concentration of 793 microg Mn/L and 3 microg arsenic/L. Children and mothers came to our field clinic, where children received a medical examination in which weight, height, and head circumference were measured.

Alcohol, caffeine and smoking in relation to age at menopause.

Objectives: Exposures which might influence age at natural menopause have been extensively studied but, with the exception of cigarette smoking, results have been inconsistent. We sought to determine: (i) whether alcohol and caffeine intake are associated with age at menopause; (ii) whether the association of cigarette smoking with age at menopause is confined to current smokers.

Methods: Analyses drew on longitudinal data from 494 women, aged 44-60 in 1993, of whom 159 experienced menopause before intake or during follow-up.