Influence of a small fraction of individuals with enhanced mutations on a population genetic pool

Computer simulations of the Penna ageing model suggest that already a small fraction of births with enhanced number of new mutations can negatively influence the whole population.Comment: 10 pages including 6 figures; draf

Birth defect and risk factor surveillance in the northern and southwestern Netherlands

Objective: To survey the associations between several risk factors and birth defects, in order to detect potential new teratogens.Methods: Data of the two Dutch European Registration of Congenital Anomalies (EUROCAT) registries collected before January 1, 1998 were used to perform X2 tests for a large number of risk factors and birth defects. Defects caused by chromosomal or monogenic disorders were analyzed separately.Results: Cross- tabulations of 80 groups of birth defects with 303 risk factors were studied. Of these, 126 combinations had a p value under 0.05, and 34 had a p value under 0.001. Of these 34 associations, some are known in the literature, some were found before in the same databases and some were new associations.Conclusions: This is a good method for generating new hypotheses for associations between risk factors and birth defects. It can be a start for new, more in-depth studies of potential teratogens. Copyright (C) 2000 S. Karger AG, Basel.</p

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

Maternal occupational exposure to solvents and gastroschisis in offspring-National Birth Defects Prevention Study 1997-2011

Objectives: The aim of this study was to assess the association between maternal occupational exposure to solvents and gastroschisis in offspring. Methods: We used data from the National Birth Defects Prevention Study, a large population-based case-control study of major birth defects conducted in 10 US states from 1997 to 2011. Infants with gastroschisis were ascertained by active birth defects surveillance systems. Control infants without major birth defects were selected from vital records or birth hospital records. Self-reported maternal occupational histories were collected by telephone interview. Industrial hygienists reviewed this information to estimate exposure to aromatic, chlorinated and petroleum-based solvents from 1 month before conception through the first trimester of pregnancy. Cumulative exposure to solvents was estimated for the same period accounting for estimated exposure intensity and frequency, job duration and hours worked per week. ORs and 95% CIs were estimated to assess the association between exposure to any solvents or solvent classes, and gastroschisis risk. Results: Among 879 cases and 7817 controls, the overall prevalence of periconceptional solvent exposure was 7.3% and 7.4%, respectively. Exposure to any solvent versus no exposure to solvents was not associated with gastroschisis after adjusting for maternal age (OR 1.00, 95% CI 0.75 to 1.32), nor was an association noted for solvent classes. There was no exposure-response relationship between estimated cumulative solvent exposure and gastroschisis after adjusting for maternal age. Conclusion: Our study found no association between maternal occupational solvent exposure and gastroschisis in offspring. Further research is needed to understand risk factors for gastroschisis

Is maternal employment site a source of exposure misclassification in studies of environmental exposures and birth outcomes? A simulation-based bias analysis of haloacetic acids in tap water and hypospadias

Background: In population research, exposure to environmental contaminants is often indirectly assessed by linking residence to geocoded databases of environmental exposures. We explored the potential for misclassification of residence-based environmental exposure as a result of not accounting for the workplace environments of employed pregnant women using data from a National Birth Defects Prevention Study (NBDPS) analysis of drinking water haloacetic acids and hypospadias. Methods: The original analysis used NBDPS data from women with haloacetic acid exposure information in eight states who delivered an infant with second- or third-degree hypospadias (cases) or a male infant without a birth defect (controls) between 2000 and 2005. In this bias analysis, we used a uniform distribution to randomly select 11%-14% of employed women that were assumed to change municipal water systems between home and work and imputed new contaminant exposures for tap water beverages consumed at work among the selected women using resampled values from the control population. Multivariable logistic regression was used to estimate the association between hypospadias and haloacetic acid ingestion with the same covariates and exposure cut-points as the original study. We repeated this process across 10,000 iterations and then completed a sensitivity analysis of an additional 10,000 iterations where we expanded the uniform distribution (i.e., 0%, 28%). Results: In both simulations, the average results of the 10,000 iterations were nearly identical to those of the initial study. Conclusions: Our results suggest that household estimates may be sufficient proxies for worksite exposures to haloacetic acids in tap water

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

Maternal exposure to disinfection by-products and risk of hypospadias in the national birth defects prevention study (2000–2005)

The purpose of this study was to estimate the association between 2nd and 3rd degree hypospadias and maternal exposure to disinfection by-products (DBPs) using data from a large case-control study in the United States. Concentration estimates for total trihalomethanes (TTHMs), the sum of the five most prevalent haloacetic acids (HAA5), and individual species of each were integrated with data on maternal behaviors related to water use from the National Birth Defects Prevention Study (NBDPS) to create three different exposure metrics: (1) household DBP concentrations; (2) estimates of DBP ingestion; (3) predicted uptake (i.e., internal dose) of trihalomethanes (THMs) via ingestion, showering, and bathing. The distribution of DBP exposure was categorized as follows: (Q1/referent) < 50%; (Q2) ≥ 50% to < 75%; and (Q3) ≥ 75%. Logistic regression was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Generally, null associations were observed with increasing TTHM or HAA5 exposure. An increased risk was observed among women with household bromodichloromethane levels in the second quantile (aOR: 1.8; 95% CI: 1.2, 2.7); however, this association did not persist after the inclusion of individual-level water-use data. Findings from the present study do not support the hypothesis that maternal DBP exposures are related to the occurrence of hypospadias

Congenital anomalies in newborns to women employed in jobs with frequent exposure to organic solvents - a register-based prospective study

<p>Abstract</p> <p>Background</p> <p>The foetal effects of occupational exposure to organic solvents in pregnancy are still unclear. Our aim was to study the risk of non-chromosomal congenital anomalies at birth in a well-defined population of singletons born to women employed as painters and spoolers in early pregnancy, compared to women in non-hazardous occupations.</p> <p>Method</p> <p>The study population for this prospective cohort study was singleton newborns delivered to working mothers in the industrial community of Mončegorsk in the period 1973-2005. Occupational information and characteristics of the women and their newborns was obtained from the local population-based birth register.</p> <p>Results</p> <p>The 597 women employed as painters, painter-plasterers or spoolers had 712 singleton births, whereof 31 (4.4%) were perinatally diagnosed with 37 malformations. Among the 10 561 newborns in the group classified as non-exposed, 397 (3.9%) had one or more malformations. The overall prevalence in the exposed group was 520/10 000 births [95% confidence limits (CL): 476, 564], and 436/10 000 births (95% CL: 396, 476) in the unexposed. Adjusted for young maternal age, smoking during pregnancy, maternal congenital malformation and year of birth, the odds ratio (OR) was 1.24 (95% CL: 0.85, 1.82); for multiple anomalies it was 1.54 (95% CL: 0.66, 3.59).</p> <p>The largest organ-system specific difference in prevalence between the two groups was observed for malformations of the circulatory system: 112/10 000 (95% CL: 35, 190) in the exposed group, and 42/10 000 (95% CL: 29, 54) in the unexposed, with an adjusted OR of 2.03 (95% CL: 0.85, 4.84). The adjusted ORs for malformations of the genital organs and musculoskeletal system were 2.24 (95% CI: 0.95, 5.31) and 1.12 (95% CI: (0.62, 2.02), respectively.</p> <p>Conclusion</p> <p>There appeared to be a higher risk of malformations of the circulatory system and genital organs at birth among newborns to women in occupations with organic solvent exposure during early pregnancy (predominantly employed as painters). However, the findings were not statistically conclusive. Considering that these two categories of malformations are not readily diagnosed perinatally, the difference in prevalence between the exposed and unexposed may have been underestimated.</p