Associations Between Disinfection By-Product Exposures and Craniofacial Birth Defects.
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ABSTRACT:
SUBMITTER: Kaufman JA
PROVIDER: S-EPMC5927773 | biostudies-literature | 2018 Feb
REPOSITORIES: biostudies-literature
Publications
Associations Between Disinfection By-Product Exposures and Craniofacial Birth Defects.
Kaufman John A JA Wright J Michael JM Evans Amanda A Rivera-Núñez Zorimar Z Meyer Amy A Narotsky Michael G MG
Journal of occupational and environmental medicine 20180201 2
<h4>Objective</h4>The aim of this study was to examine associations between craniofacial birth defects (CFDs) and disinfection by-product (DBP) exposures, including the sum of four trihalomethanes (THM4) and five haloacetic acids (HAA5) (ie, DBP9).<h4>Methods</h4>We calculated first trimester adjusted odds ratios (aORs) for different DBPs in a matched case-control study of 366 CFD cases in Massachusetts towns with complete 1999 to 2004 THM and HAA data.<h4>Results</h4>We detected elevated aORs f ...[more]
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Project description:Epidemiological studies suggest that exposure to water disinfection by-products (DBPs) may increase the risk of certain birth defects. However, evidence for musculoskeletal defects (MSDs) is limited. Previous MSD studies have not examined DBPs beyond trihalomethanes (THMs) and have not separately examined limb or diaphragm defects which may have distinct developmental etiologies. We calculated adjusted odds ratios (aORs) in a registry-based case-control study of birth defects in Massachusetts with complete quarterly 1999-2004 data on four THMs and five haloacetic acids (HAAs). We matched 10 controls each to 187 MSD cases based on week of conception. Weight-averaged town-level first-trimester DBP exposures were individually assigned based on residence at birth. We adjusted THM models for exposure to the sum of five HAAs (HAA5), and HAA models for the sum of four THMs (THM4). We detected positive exposure-response associations for all grouped MSDs with THM4 quintiles (aOR range: 1.90-3.18) and chloroform quartiles (aOR range: 1.30-2.21), and for reduction of upper or lower limbs with chloroform quartiles (aOR range: 2.39-3.52). We detected elevated aORs for diaphragmatic hernia with DBP9 (sum of THM4 and HAA5), and chloroform and bromodichloromethane tertiles and an exposure-response relationship for THM4 tertiles (aOR range: 1.67-1.80). This is the first epidemiological study to examine HAAs in relation to MSDs. Given the indirect nature of our exposure assessment data and small case numbers, the exposure-response relationships that we detected for THM4 and chloroform warrant further investigation.
| S-EPMC7061532 | biostudies-literature
Project description:Epidemiological studies suggest that women exposed to disinfection by-products (DBPs) have an increased risk of delivering babies with cardiovascular defects (CVDs).We examined nine CVDs in relation to categorical DBP exposures including bromoform, chloroform, dibromochloromethane (DBCM), bromodichloromethane (BDCM), monobromoacetic acid (MBAA), dichloroacetic acid (DCAA), trichloroacetic acid (TCAA), and summary DBP measures (HAA5, THMBr, THM4, and DBP9).We calculated adjusted odds ratios (aORs) in a case-control study of birth defects in Massachusetts with complete quarterly 1999-2004 trihalomethane (THM) and haloacetic acid (HAA) data. We randomly matched 10 controls each to 904 CVD cases based on week of conception. Weight-averaged aggregate first-trimester DBP exposures were assigned to individuals based on residence at birth.We detected associations for tetralogy of Fallot and the upper exposure categories for TCAA, DCAA, and HAA5 (aOR range, 3.34-6.51) including positive exposure-response relationships for DCAA and HAA5. aORs consistent in magnitude were detected between atrial septal defects and bromoform (aOR = 1.56; 95% CI: 1.01, 2.43), as well as DBCM, chloroform, and THM4 (aOR range, 1.26-1.67). Ventricular septal defects (VSDs) were associated with the highest bromoform (aOR = 1.85; 95% CI: 1.20, 2.83), MBAA (aOR = 1.81; 95% CI: 0.85, 3.84), and DBCM (aOR = 1.54; 95% CI: 1.00, 2.37) exposure categories.To our knowledge, this is the first birth defect study to develop multi-DBP adjusted regression models as well as the first CVD study to evaluate HAA exposures and the second to evaluate bromoform exposures. Our findings, therefore, inform exposure specificity for the consistent associations previously reported between THM4 and CVDs including VSDs. Citation: Wright JM, Evans A, Kaufman JA, Rivera-Núñez Z, Narotsky MG. 2017. Disinfection by-product exposures and the risk of specific cardiac birth defects. Environ Health Perspect 125:269-277;?http://dx.doi.org/10.1289/EHP103.
| S-EPMC5289901 | biostudies-other
Project description:BACKGROUND:Water and water-based beverages constitute a major part of daily fluid intake for pregnant women, yet few epidemiologic studies have investigated the role of water consumption on birth outcomes. METHODS:We used data from the National Birth Defects Prevention Study to conduct a case-control study investigating associations between maternal water consumption during pregnancy and birth defects (BD). We used interview data on water consumption during the first trimester of pregnancy in 14,454 cases (major BDs n ? 50) and 5,063 controls. Total water consumption was analyzed as a continuous variable and in quartiles. We evaluated the role of dietary quality and sugar sweetened beverage consumption. Logistic regression models were used to assess effects of water consumption on risk of BDs with adjustment for relevant covariates. RESULTS:Mean daily maternal water consumption among controls was 4.4 eight-ounce glasses. We observed decreases in estimated risk associated with increases in water consumption for several BDs, including neural tube defects (spina bifida), oral clefts (cleft lip), musculoskeletal defects (gastroschisis, limb deficiencies), and congenital heart defects (hypoplastic left heart syndrome, right-sided obstructions, pulmonary valve stenosis). Our results were generally unchanged when an indicator for overall dietary quality was included; however, there was evidence of effect measure modification by heavy consumption of sugar-sweetened beverages for some defects, but not all. CONCLUSION:These analyses suggest the importance of sufficient water consumption during early pregnancy, above and beyond it being a marker of higher diet quality. Additional analyses are warranted to understand the biological mechanism for this association. Birth Defects Research 109:193-202, 2017. © 2016 Wiley Periodicals, Inc.
| S-EPMC6193258 | biostudies-literature
Project description:BackgroundCauses of most birth defects are largely unknown. Genetics, maternal factors (e.g., age, smoking) and environmental exposures have all been linked to some birth defects, including neural tube, oral cleft, limb reduction, and gastroschisis; however, the contribution of cumulative exposures across several environmental domains in association with these defects is not well understood.MethodsThe Environmental Quality Index (EQI) and its domains (air, water, land, sociodemographic, built) were used to estimate county-level cumulative environmental exposures from 2006-2010 and matched to birth defects identified from Texas Birth Defects Registry and live birth records from births in years 2007-2010 (N = 1,610,709). Poisson regression models estimated prevalence ratios (PR) and 95% confidence intervals (CI) for associations between 10 birth defects and the EQI.ResultsWe observed some positive associations between worst environmental quality and neural tube, anencephaly, spina bifida, oral cleft, cleft palate, cleft lip with and without cleft palate, and gastroschisis [PR range: 1.12-1.55], but near null associations with limb reduction defects. Among domain specific results, we observed the strongest positive associations with the sociodemographic domain across birth defects but varied positive associations among the air and water domains, and negative or null associations with the land and built domains. Overall, few exposure-response patterns were evident.ConclusionsOur results highlight the complexities of cumulative, simultaneous environmental exposures in the prevalence rates of 10 selected birth defects. We were able to explore the impact of overall and domain specific environmental quality on birth defects and identify potential domain specific drivers of these associations.
| S-EPMC8091812 | biostudies-literature
Project description:BackgroundEarly life antibiotic treatment is one likely exposure influencing allergy risk. The objective was to investigate associations between pre- and postnatal antibiotic exposures and the development of allergic manifestations until age 18 months.MethodsWe included 1387 mother-child dyads from the prospective, population-based NorthPop birth cohort study. Data on antibiotic exposures in pregnancy and childhood were collected by web-based questionnaires. Until the child turned 18 months old, parents (n = 1219) reported symptoms of wheeze, eczema, and physician-diagnosed asthma; parents (n = 1025) reported physician-diagnosed food allergy. At age 18 months, serum immunoglobulin E levels to inhalant (Phadiatop) and food (Food mix fx5) allergens were determined. Associations were estimated using bivariable and multivariable logistic regressions.ResultsPrenatal antibiotic exposure was positively associated with food sensitization in the crude (OR 1.82, 95% CI 1.01-3.26) but not in the adjusted analyses (aOR 1.58, 0.82-3.05). A borderline significant association was found between prenatal exposure and wheeze (aOR 1.56, 0.95-2.57). Postnatal antibiotics were positively associated with wheeze (aOR 2.14, 1.47-3.11), asthma (aOR 2.35, 1.32-4.19), and eczema (aOR 1.49, 1.07-2.06). Postnatal antibiotics were negatively associated with food sensitization (aOR 0.46, 95% CI 0.25-0.83) but not with food allergy nor sensitization to inhalants.ConclusionPre- and postnatal antibiotic exposure demonstrated positive associations with allergic manifestations and the former also with food sensitization. In contrast, there was a negative association between postnatal antibiotics and food sensitization. Food sensitization is often transient but may precede respiratory allergies. Future studies should investigate the relationship between antibiotic exposure and food sensitization later in childhood.
| S-EPMC9544930 | biostudies-literature
Project description:Birth defects prevalence may vary seasonally, but previous studies have focused on a few commonly occurring phenotypes. We performed a phenome-wide association study (PheWAS) in order to evaluate the associations between season of conception and a broad range of birth defects. Date of conception was estimated for all livebirths and birth defect cases in Texas from 1999-2015 using data from vital records, provided by the Texas Department of State Health Services Center for Health Statistics. Birth defects diagnoses were obtained from the Texas Birth Defects Registry, a statewide, active surveillance system. We estimated prevalence ratios (PRs) for phenotypes with ≥50 cases according to conception in spring (March-May), summer (June-August) or fall (September-November) relative to winter (December-February), using Poisson regression. Season of conception was associated with 5% of birth defects studied in models adjusted for maternal age, education, race/ethnicity, and number of previous livebirths. Specifically, summer conception was associated with any monitored birth defect (PR 1.03, 95% CI 1.02-1.04) and five specific phenotypes, most notably Hirschsprung disease (PR 1.46, 95% CI 1.22-1.75). These findings suggest that seasonally variable exposures influence the development of several birth defects and may assist in identifying novel environmental risk factors.
| S-EPMC7579376 | biostudies-literature
Project description:Mutations in the Notch1 receptor and delta-like 3 (Dll3) ligand cause global disruptions in axial segmental patterning. Genetic interactions between members of the notch pathway have previously been shown to cause patterning defects not observed in single gene disruptions. We examined Dll3-Notch1 compound mouse mutants to screen for potential gene interactions. While mice heterozygous at either locus appeared normal, 30% of Dll3-Notch1 double heterozygous animals exhibited localized, stochastic segmental anomalies similar to human congenital vertebral defects. Unexpectedly, double heterozygous mice also displayed statistically significant decreases in mandibular height and elongated maxillary hard palate. Examination of somite-stage embryos and perinatal anatomy and histology did not reveal any organ defects, so we used microarray-based analysis of Dll3 and Notch1 mutant embryos to identify gene targets that may be involved in notch-regulated segmental or craniofacial development. Therefore, Dll3-Notch1 double heterozygous mice model human congenital scoliosis and craniofacial disorders. Keywords: genotype comparison
2007-07-01 | GSE8027 | GEO
Project description:BackgroundIngestion of disinfection byproducts has been associated with bladder cancer in multiple studies. Although associations with other routes of exposure have been suggested, epidemiologic evidence is limited.ObjectivesWe evaluated the relationship between bladder cancer and total, chlorinated, and brominated trihalomethanes (THMs) through various exposure routes.MethodsIn a population-based case–control study in New England (n=(1,213) cases; n=(1,418) controls), we estimated lifetime exposure to THMs from ingestion, showering/bathing, and hours of swimming pool use. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression adjusted for confounders.ResultsAdjusted ORs for bladder cancer comparing participants with exposure above the 95th percentile with those in the lowest quartile of exposure (based on the distribution in controls) were statistically significant for average daily intake mg/d of total THMs [OR=1.53 (95% CI: 1.01, 2.32), p-trend=0.16] and brominated THMs [OR=1.98 (95% CI: 1.19, 3.29), p-trend=0.03]. For cumulative intake mg, the OR at the 95th percentile of total THMs was 1.45 (95% CI: 0.95, 2.2), p-trend=0.13; the ORs at the 95th percentile for chlorinated and brominated THMs were 1.77 (95% CI: 1.05, 2,.99), p-trend=0.07 and 1.78 (95% CI: 1.05, 3.00), p-trend=0.02, respectively. The OR in the highest category of showering/bathing for brominated THMs was 1.43 (95% CI: 0.80, 2.42), p-trend=0.10. We found no evidence of an association for bladder cancer and hours of swimming pool use.ConclusionsWe observed a modest association between ingestion of water with higher THMs (>95th?percentile?vs.<25th?percentile) and bladder cancer. Brominated THMs have been a particular concern based on toxicologic evidence, and our suggestive findings for multiple metrics require further study in a population with higher levels of these exposures. Data from this population do not support an association between swimming pool use and bladder cancer. https://doi.org/10.1289/EHP89.
| S-EPMC5743617 | biostudies-literature
Project description:Mutations in the Notch1 receptor and delta-like 3 (Dll3) ligand cause global disruptions in axial segmental patterning. Genetic interactions between members of the notch pathway have previously been shown to cause patterning defects not observed in single gene disruptions. We examined Dll3-Notch1 compound mouse mutants to screen for potential gene interactions. While mice heterozygous at either locus appeared normal, 30% of Dll3-Notch1 double heterozygous animals exhibited localized, stochastic segmental anomalies similar to human congenital vertebral defects. Unexpectedly, double heterozygous mice also displayed statistically significant decreases in mandibular height and elongated maxillary hard palate. Examination of somite-stage embryos and perinatal anatomy and histology did not reveal any organ defects, so we used microarray-based analysis of Dll3 and Notch1 mutant embryos to identify gene targets that may be involved in notch-regulated segmental or craniofacial development. Therefore, Dll3-Notch1 double heterozygous mice model human congenital scoliosis and craniofacial disorders. Experiment Overall Design: Given the reduced penetrance and stochastic nature of the segmental and craniofacial defects in Dll3-Notch1 double heterozygous animals, we next sought to identify candidate genes that may be down or up-regulated in Dll3 and Notch1 homozygous mutant embryos during development of these structures. We carried out microarray analysis using Affymetrix MOE430 microarrays, comparing 9.5 dpc homozygous embryos in duplicate to littermates with wild-type alleles at both loci, and comparing with heterozygous littermate embryos. Affymetrix analysis software (Microarray Suite 5.0) was used to determine whether gene probes were present, marginal or absent. Probes with present flags in replicates of Dll3, Notch1, or embryos with wild-type alleles at both loci were considered present for further analysis. Altogether, out of 22,690 probe sets on the MOE430A array, we identified 12,820 probes that were present in replicates of at least one genotypic group. To identify genes that were increased or decreased in expression in mutant embryos, we carried out robust multichip average (RMA) normalization of microarray data sets using the RMA module of Genespring GX 7.3 (Agilent). After RMA normalization, housekeeping genes such as Gapdh showed steady expression (probe AFFX-GapdhMur/M32599_M_at, normalized expression 1.00 ± 0.02). As a general indicator of variability between samples, we calculated Pearsonâs correlation coefficients. We found that the correlations between duplicates were moderately high: wild-type embryos (0.623), Dll3 embryos (0.584), Notch1 embryos (0.531).
2008-06-15 | E-GEOD-8027 | biostudies-arrayexpress
Project description:Although the descriptive epidemiology of atrioventricular septal defects (AVSDs), a group of serious congenital heart defects (CHDs), has been recently reported, non-genetic risk factors have not been consistently identified. Using data (1997-2005) from the National Birth Defects Prevention Study, an ongoing multisite population-based case-control study, the association between selected non-genetic factors and non-syndromic AVSDs was examined. Data on periconceptional exposures to such factors were collected by telephone interview from 187 mothers of AVSD case infants and 6,703 mothers of unaffected infants. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated from logistic regression models. Mothers who reported cigarette smoking during the periconceptional period were more likely to have infants with AVSDs compared with non-smokers, independent of maternal age, periconceptional alcohol consumption, infant gestational age, family history of CHDs, and study site (aOR 1.5, 95% CI 1.1-2.4). The association was strongest in mothers who smoked more than 25 cigarettes/day. In addition, mothers with periconceptional passive smoke exposure were more likely to have infants with AVSDs than unexposed mothers, independent of maternal age, active periconceptional smoking, infant gestational age, and family history of CHDs (aOR 1.4, 95% CI 1.0-2.0). No associations were observed between AVSDs and maternal history of a urinary tract infection or pelvic inflammatory disease, maternal use of a wide variety of medications, maternal occupational exposure, parental drug use, or maternal alcohol consumption. If the results of this preliminary study can be replicated, minimizing maternal active and passive smoke exposure may decrease the incidence of AVSDs.
| S-EPMC4462202 | biostudies-literature