Prevalence and Clustering of Congenital Heart Defects among Boys With Hypospadias

IMPORTANCE: Hypospadias is a common birth defect of the male urinary tract that may be isolated or may co-occur with other structural malformations, including congenital heart defects (CHDs). The risk for co-occurring CHDs among boys with hypospadias remains unknown, which limits screening and genetic testing strategies. OBJECTIVE: to characterize the risk of major CHDs among boys born with hypospadias. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used data from population-based birth defect surveillance programs on all male infants born in 11 US states from January 1, 1995, to December 31, 2014. Statistical analysis was performed from September 2, 2020, to March 25, 2022. EXPOSURE: Hypospadias. MAIN OUTCOMES AND MEASURES: Demographic and diagnostic data were obtained from 2 active state-based birth defect surveillance programs for primary analyses, the Texas Birth Defects Registry and the Arkansas Reproductive Health Monitoring System, with validation among 9 additional states in the National Birth Defects Prevention Network (NBDPN). Birth defect diagnoses were identified using the British Pediatric Association coding for hypospadias (exposure) and major CHDs (primary outcomes). Maternal covariates and birth year were also abstracted from the vital records. Poisson regression was used to estimate adjusted prevalence ratios and 95% CIs for major CHDs within Texas and Arkansas and combined using inverse variance-weighted meta-analysis. Findings were validated using the NBDPN. RESULTS: Among 3.7 million pregnancies in Texas and Arkansas, 1485 boys had hypospadias and a co-occurring CHD. Boys with hypospadias were 5.8 times (95% CI, 5.5-6.1) more likely to have a co-occurring CHD compared with boys without hypospadias. Associations were observed for every specific CHD analyzed among boys with hypospadias, occurred outside of chromosomal anomalies, and were validated in the NBDPN. An estimated 7.024% (95% CI, 7.020%-7.028%) of boys with hypospadias in Texas and 5.503% (95% CI, 5.495%-5.511%) of boys with hypospadias in Arkansas have a co-occurring CHD. In addition, hypospadias severity and maternal race and ethnicity were independently associated with the likelihood for hypospadias to co-occur with a CHD; boys in Texas with third-degree (ie, more severe) hypospadias were 2.7 times (95% CI, 2.2-3.4) more likely than boys with first-degree hypospadias to have a co-occurring CHD, with consistent estimates in Arkansas (odds ratio, 2.7; 95% CI, 1.4-5.3), and boys with hypospadias born to Hispanic mothers in Texas were 1.5 times (95% CI, 1.3-1.8) more likely to have a co-occurring CHD than boys with hypospadias born to non-Hispanic White mothers. CONCLUSIONS AND RELEVANCE: In this cohort study, boys with hypospadias had a higher prevalence of CHDs than boys without hypospadias. These findings support the need for consideration of additional CHD screening programs for boys born with hypospadias

Estimated Maternal Pesticide Exposure from Drinking Water and Heart Defects in Offspring

Our objective was to examine the relationship between estimated maternal exposure to pesticides in public drinking water and the risk of congenital heart defects (CHD). We used mixed-effects logistic regression to analyze data from 18,291 nonsyndromic cases with heart defects from the Texas Birth Defects Registry and 4414 randomly-selected controls delivered in Texas from 1999 through 2005. Water district-level pesticide exposure was estimated by linking each maternal residential address to the corresponding public water supply district’s measured atrazine levels. We repeated analyses among independent subjects from the National Birth Defects Prevention Study (NBDPS) (1620 nonsyndromic cases with heart defects and 1335 controls delivered from 1999 through 2005). No positive associations were observed between high versus low atrazine level and eight CHD subtypes or all included heart defects combined. These findings should be interpreted with caution, in light of potential misclassification and relatively large proportions of subjects with missing atrazine data. Thus, more consistent and complete monitoring and reporting of drinking water contaminants will aid in better understanding the relationships between pesticide water contaminants and birth defects

Vertical Nanowire TFET Diameter Influence on Intrinsic Voltage Gain for Different Inversion Conditions

In this work, the impact of the nanowire TFET diameter on analog parameters in "weak" and "strong inversion" conditions is analyzed. Its relation with the current conduction mechanism is also studied. A comparison of the analog performance among TFETs doped with different source doping profile (abrupt and nonabrupt) and MOSFETs was experimentally realized for larger diameter nanowires. Additionally the TFET evaluation was extrapolated for smaller diameters by numerical simulation. The transistor efficiency and the Early voltage were considered in order to calculate the intrinsic voltage gain (AV). Both effects influence AV degradation for TFETs with smaller diameters biased in "weak inversion". While larger TFET nanowires show better AV than MOSFETs under "strong inversion" bias, narrower nanowires present potentialities for low power and low voltage applications, since their AV is better than the corresponding values for larger diameters TFET nanowires under "weak inversion" bias

Maternal Occupational Exposure to Polycyclic Aromatic Hydrocarbons: Effects on Gastroschisis among Offspring in the National Birth Defects Prevention Study

Background: Exposure to polycyclic aromatic hydrocarbons (PAHs) occurs in many occupational settings. There is evidence in animal models that maternal exposure to PAHs during pregnancy is associated with gastroschisis in offspring; however, to our knowledge, no human studies examining this association have been conducted

Pesticide exposure and lymphohaematopoietic cancers: a case-control study in an agricultural region (Larissa, Thessaly, Greece)

<p>Abstract</p> <p>Background</p> <p>The causality of lymphohaematopoietic cancers (LHC) is multifactorial and studies investigating the association between chemical exposure and LHC have produced variable results. The aim of this study was to investigate the relationships between exposure to pesticides and LHC in an agricultural region of Greece.</p> <p>Methods</p> <p>A structured questionnaire was employed in a hospital-based case control study to gather information on demographics, occupation, exposure to pesticides, agricultural practices, family and medical history and smoking. To control for confounders, backward conditional and multinomial logistic regression analyses were used. To assess the dose-response relationship between exposure and disease, the chi-square test for trend was used.</p> <p>Results</p> <p>Three hundred and fifty-four (354) histologically confirmed LHC cases diagnosed from 2004 to 2006 and 455 sex- and age-matched controls were included in the study. Pesticide exposure was associated with total LHC cases (OR 1.46, 95% CI 1.05-2.04), myelodysplastic syndrome (MDS) (OR 1.87, 95% CI 1.00-3.51) and leukaemia (OR 2.14, 95% CI 1.09-4.20). A dose-response pattern was observed for total LHC cases (P = 0.004), MDS (P = 0.024) and leukaemia (P = 0.002). Pesticide exposure was independently associated with total LHC cases (OR 1.41, 95% CI 1.00 - 2.00) and leukaemia (OR 2.05, 95% CI 1.02-4.12) after controlling for age, smoking and family history (cancers, LHC and immunological disorders). Smoking during application of pesticides was strongly associated with total LHC cases (OR 3.29, 95% CI 1.81-5.98), MDS (OR 3.67, 95% CI 1.18-12.11), leukaemia (OR 10.15, 95% CI 2.15-65.69) and lymphoma (OR 2.72, 95% CI 1.02-8.00). This association was even stronger for total LHC cases (OR 18.18, 95% CI 2.38-381.17) when eating simultaneously with pesticide application.</p> <p>Conclusions</p> <p>Lymphohaematopoietic cancers were associated with pesticide exposure after controlling for confounders. Smoking and eating during pesticide application were identified as modifying factors increasing the risk for LHC. The poor pesticide work practices identified during this study underline the need for educational campaigns for farmers.</p

Diabetes and Obesity-Related Genes and the Risk of Neural Tube Defects in the National Birth Defects Prevention Study

Few studies have evaluated genetic susceptibility related to diabetes and obesity as a risk factor for neural tube defects (NTDs). The authors investigated 23 single nucleotide polymorphisms among 9 genes (ADRB3, ENPP1, FTO, LEP, PPARG, PPARGC1A, SLC2A2, TCF7L2, and UCP2) associated with type 2 diabetes or obesity. Samples were obtained from 737 NTD case-parent triads included in the National Birth Defects Prevention Study during 1999–2007. Log-linear models were used to evaluate maternal and offspring genetic effects. After application of the false discovery rate, there were 5 significant maternal genetic effects. The less common alleles at the 4 FTO single nucleotide polymorphisms showed a reduction of NTD risk (for rs1421085, relative risk (RR) = 0.73 (95% confidence interval (CI): 0.62, 0.87); for rs8050136, RR = 0.79 (95% CI: 0.67, 0.93); for rs9939609, RR = 0.79 (95% CI: 0.67, 0.94); and for rs17187449, RR = 0.80 (95% CI: 0.68, 0.95)). Additionally, maternal LEP rs2071045 (RR = 1.31, 95% CI: 1.08, 1.60) and offspring UCP2 rs660339 (RR = 1.32, 95% CI: 1.06, 1.64) were associated with NTD risk. Furthermore, the maternal genotype for TCF7L2 rs3814573 suggested an increased NTD risk among obese women. These findings indicate that maternal genetic variants associated with glucose homeostasis may modify the risk of having an NTD-affected pregnancy

MI-GWAS: a SAS platform for the analysis of inherited and maternal genetic effects in genome-wide association studies using log-linear models

<p>Abstract</p> <p>Background</p> <p>Several platforms for the analysis of genome-wide association data are available. However, these platforms focus on the evaluation of the genotype inherited by affected (i.e. case) individuals, whereas for some conditions (e.g. birth defects) the genotype of the mothers of affected individuals may also contribute to risk. For such conditions, it is critical to evaluate associations with both the maternal and the inherited (i.e. case) genotype. When genotype data are available for case-parent triads, a likelihood-based approach using log-linear modeling can be used to assess both the maternal and inherited genotypes. However, available software packages for log-linear analyses are not well suited to the analysis of typical genome-wide association data (e.g. including missing data).</p> <p>Results</p> <p>An integrated platform, Maternal and Inherited Analyses for Genome-wide Association Studies <b>(</b>MI-GWAS) for log-linear analyses of maternal and inherited genetic effects in large, genome-wide datasets, is described. MI-GWAS uses SAS and LEM software in combination to appropriately format data, perform the log-linear analyses and summarize the results. This platform was evaluated using existing genome-wide data and was shown to perform accurately and relatively efficiently.</p> <p>Conclusions</p> <p>The MI-GWAS platform provides a valuable tool for the analysis of association of a phenotype or condition with maternal and inherited genotypes using genome-wide data from case-parent triads. The source code for this platform is freely available at <url>http://www.sph.uth.tmc.edu/sbrr/mi-gwas.htm</url>.</p

Maternal occupational exposure to polycyclic aromatic hydrocarbons and congenital heart defects among offspring in the national birth defects prevention study

There is evidence in experimental model systems that exposure to polycyclic aromatic hydrocarbons (PAHs) results in congenital heart defects (CHDs); however, to our knowledge, this relationship has not been examined in humans. Therefore, we conducted a case-control study assessing the association between estimated maternal occupational exposure to PAHs and CHDs in offspring