Teratology最新文献

{"title":"Orofacial clefts and spina bifida: N-acetyltransferase phenotype, maternal smoking, and medication use.","authors":"Iris A L M van Rooij,&nbsp;Pascal M W Groenen,&nbsp;Merel van Drongelen,&nbsp;René H M Te Morsche,&nbsp;Wilbert H M Peters,&nbsp;Régine P M Steegers-Theunissen","doi":"10.1002/tera.10096","DOIUrl":"https://doi.org/10.1002/tera.10096","url":null,"abstract":"<p><strong>Background: </strong>Orofacial clefts and spina bifida are midline defects with a multifactorial etiology. Maternal smoking and medication use periconceptionally have been studied as risk factors for these malformations. The biotransformation enzyme N-acetyltransferase 2 (NAT2), plays a part in the inactivation of toxic compounds in cigarette smoke and medication. We investigated maternal NAT2 phenotype and the interaction with smoking and medication use periconceptionally on orofacial cleft and spina bifida risk in offspring.</p><p><strong>Methods: </strong>In this case-control study of 45 mothers of orofacial cleft children, 39 mothers of spina bifida children and 73 control mothers, NAT2 acetylator status was determined by measuring urinary caffeine metabolites.</p><p><strong>Results: </strong>Slow NAT2 acetylators showed no increased risk for orofacial cleft (OR = 1.0, 95% CI: 0.4-2.3) or spina bifida offspring (OR = 0.7, 95% CI: 0.3-1.7) compared to fast NAT2 acetylators. More mothers with orofacial cleft and spina bifida offspring smoked cigarettes (36% and 23% respectively) and used medication periconceptionally (38% and 44% respectively) compared to control mothers (smoking:18%, medication use:19%). No interaction between maternal NAT2 acetylator status and smoking or medication use was observed for orofacial cleft and spina bifida risk.</p><p><strong>Conclusions: </strong>Maternal smoking and medication use is associated with orofacial cleft risk as well as medication use is with spina bifida. The maternal NAT2 acetylator status, however, was not associated with an increased risk for orofacial cleft or spina bifida offspring, nor in combination with periconceptional smoking or medication use.</p>","PeriodicalId":22211,"journal":{"name":"Teratology","volume":"66 5","pages":"260-6"},"PeriodicalIF":0.0,"publicationDate":"2002-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/tera.10096","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22081252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk factors for heart disease associated with abnormal sidedness.","authors":"Karen S Kuehl,&nbsp;Christopher Loffredo","doi":"10.1002/tera.10099","DOIUrl":"https://doi.org/10.1002/tera.10099","url":null,"abstract":"<p><strong>Background: </strong>The purpose of this study is to obtain information on potential familial and environmental risk factors for liveborn cases of heart disease associated with abnormal visceral and vascular sidedness, heterotaxy heart disease, so that hypotheses about this congenital cardiovascular malformation (CCVM) and its risk factors can be generated. We describe the characteristics of infants with heterotaxy heart malformations and case-control comparisons of interview data obtained on parental socio-demographic characteristics, occupational and household environmental exposures.</p><p><strong>Methods: </strong>Cases and controls are drawn from the Baltimore Washington Infant Study (BWIS) a population based case control study of CCVM diagnosed in the region from 1981-89.</p><p><strong>Results: </strong>Maternal diabetes (OR = 5.5, 95% CI = 1.6-19.1) and family history of malformations (OR = 5.1, 95% CI = 2.0-12.9) are strongly associated with cardiac disorders of sidedness. Cocaine use by mothers during the first trimester is associated with heterotaxy heart disease with odds of 3.7 (95% CI = 1.3-10.7). Cases of isolated dextrocardia shared risk factors with other heterotaxy malformations. The odds of a twin proband having heterotaxy heart disease is 4.8 (95% CI = 1.9-11.8) compared to singleton births. Twin probands are predominantly monozygotic twins in contrast to twin probands in other congenital cardiovascular malformations.</p><p><strong>Conclusions: </strong>Our findings are consistent with a role for multiple genetic factors in the development of left-right axis formation and with variable cardiac phenotypes according to gene expression and possible gene-environment interactions. Association with monozygotic twinning and with parental cocaine use may point to additional mechanistic clues for future research.</p>","PeriodicalId":22211,"journal":{"name":"Teratology","volume":"66 5","pages":"242-8"},"PeriodicalIF":0.0,"publicationDate":"2002-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/tera.10099","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22081950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"13C-NMR study of hypoglycemia-induced glycolytic changes in embryonic mouse heart.","authors":"Gautam S Ghatnekar,&nbsp;Hanna S Gracz,&nbsp;Ida W Smoak","doi":"10.1002/tera.10103","DOIUrl":"https://doi.org/10.1002/tera.10103","url":null,"abstract":"<p><strong>Background: </strong>Glucose metabolites can be detected in embryonic mouse tissues using 13C-NMR spectroscopy. The advantage of this method is in its chemical specificity and the ability to follow metabolic changes.</p><p><strong>Methods: </strong>In this study, CD-1 mice were mated and embryos excised on gestational day (GD) 10.5 (plug = GD 0.5). Hearts were isolated and cultured in 150 mg/dl glucose (normoglycemic medium) or 40 mg/dl glucose (hypoglycemic medium) for 6 hr. 13C-labeled glucose comprised 62%-64% of total glucose in the culture medium. Pre- and postculture media were treated with deuterated water (D2O), and 13C spectra were obtained using a Bruker Avance 500 MHz spectrometer operating at 11.744 tesla (125.7 MHz for 13C). NMR spectra demonstrated resonances for 13C-glucose in preculture normoglycemic and hypoglycemic media. Postculture spectra for normoglycemic and hypoglycemic media demonstrated 13C-glucose signals as well as a signal for 13C-lactate. Area under the curve (AUC) was measured for the [1-(13)C-glucose] resonance from preculture media and the [3-(13)C-lactate] resonance from postculture media. The ratios of AUC for postculture [3-(13)C-lactate] to preculture [1-(13)C-glucose] were calculated and found to be higher in hypoglycemic than in normoglycemic media.</p><p><strong>Results: </strong>Our results confirm earlier findings using radiolabeled substrates and suggest that 13C-NMR spectroscopy can be used to study glucose metabolism in isolated embryonic hearts exposed to hypoglycemia.</p><p><strong>Conclusions: </strong>NMR effectively measures glucose and its metabolite, lactate, in the same spectrum and thus determines metabolic flux in the isolated embryonic heart after exposure to hypoglycemia and normoglycemia. This method could evaluate glucose metabolism in embryonic tissues following other teratogenic exposures.</p>","PeriodicalId":22211,"journal":{"name":"Teratology","volume":"66 5","pages":"267-72"},"PeriodicalIF":0.0,"publicationDate":"2002-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/tera.10103","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22081253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decline of neural tube defects cases after a folic acid campaign in Nuevo León, México.","authors":"Laura Martínez de Villarreal,&nbsp;Jesús Z Villarreal Pérez,&nbsp;Patricia Arredondo Vázquez,&nbsp;Ricardo Hernández Herrera,&nbsp;Ma Del Roble Velazco Campos,&nbsp;Roberto Ambriz López,&nbsp;José Luis Herrera Ramírez,&nbsp;Jesús Manuel Yañez Sánchez,&nbsp;Juan José Morales Villarreal,&nbsp;Manuel Treviño Garza,&nbsp;Adriana Limón,&nbsp;Abel Guzmán López,&nbsp;Mario Bárcenas,&nbsp;Juan Ramón Cepeda García,&nbsp;Andrés Sánchez Domínguez,&nbsp;Rogelio Hernández Nuñez,&nbsp;Jorge Luis García Ayala,&nbsp;Jorge Garza Martínez,&nbsp;Mario Tijerina González,&nbsp;Carlos García Alvarez,&nbsp;Roberto Negrete Castro","doi":"10.1002/tera.10094","DOIUrl":"https://doi.org/10.1002/tera.10094","url":null,"abstract":"<p><strong>Background: </strong>Nuevo León is a state in northeastern Mexico, near the border of Texas. Mean mortality rate from 1996-98 due to anencephaly cases was 0.6/1,000. In 1999 a surveillance program for the registry and prevention of neural tube defects (NTD) cases was initiated.</p><p><strong>Methods: </strong>Cases were obtained from hospitals and OB-GYN clinics by immediate notification, death certificates, or fetal death registries. Only isolated cases of NTD were included. In August 1999 a folic acid campaign was initiated with the free distribution of the vitamin to low-income women with a recommendation to take a 5.0-mg pill once a week. Number of cases and rates from 1999 to 2001 were compared (chi(2) test).</p><p><strong>Results: </strong>After 2 years there has been a significant reduction in the number of cases and rates. In 1999 there were 95 NTD cases and in the years 2000 and 2001 there were only 59 and 55 respectively (P < 0.001). NTD rate decreased from 1.04/1,000 in 1999 to 0.58/1,000 in 2001. Anencephaly and spina bifida rates decreased from 0.55/1,000 to 0.29/1,000 and from 0.47/1,000 to 0.22/1,000 respectively, from 1999-2001. Decrease of female cases was higher than male cases for both phenotypes.</p><p><strong>Conclusion: </strong>After 2 years there was a 50% decrease in the incidence of anencephaly and spina bifida cases with a significant reduction of infant mortality and disability. These results encourage us to propose the use of a single tablet of 5.0-mg of folic acid per week as an alternative to supplementation on a daily basis.</p>","PeriodicalId":22211,"journal":{"name":"Teratology","volume":"66 5","pages":"249-56"},"PeriodicalIF":0.0,"publicationDate":"2002-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/tera.10094","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22081951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An in ovo chicken model to study the systemic and localized teratogenic effects of valproic acid.","authors":"Amy I Whitsel,&nbsp;Casey B Johnson,&nbsp;Cynthia J Forehand","doi":"10.1002/tera.10093","DOIUrl":"https://doi.org/10.1002/tera.10093","url":null,"abstract":"<p><strong>Background: </strong>The antiepileptic valproic acid (VPA) is a teratogen whose embryopathic mechanism(s) remain uncertain. Elucidating potential cellular and molecular effects of VPA is complicated by systemic application paradigms. We developed an in ovo model to reproduce the teratogenic effects of VPA and a localized VPA application procedure to determine whether VPA can selectively effect abnormal development in one region of the embryo.</p><p><strong>Methods: </strong>VPA was applied topically to chicken embryos in ovo at different embryonic stages. Embryos were later evaluated for gross and skeletal anomalies. Pax-2 and Pax-6 protein expression in the developing eye was also evaluated because VPA-induced eye anomalies are similar to those seen by the disruption of Pax-2 and Pax-6. For localized application, a thin sheet of the synthetic polymer Elvax was impregnated with VPA. A small piece of the VPA-impregnated polymer was applied directly to the presumptive wing bud region in Stage 10-17 embryos. Embryos were examined for gross and skeletal anomalies. Sham controls were employed for all experiments.</p><p><strong>Results: </strong>Chicken embryos exposed to VPA in ovo demonstrated increased mortality, growth delay and anomalies similar to ones previously seen in humans: neural tube, cardiovascular, craniofacial, limb and skeletal. Pax-2 and Pax-6 protein expression was qualitatively diminished in the eye. Localized wing bud VPA exposure caused structural abnormalities in the developing wing in the absence of other anomalies in the embryos. These wing defects were similar to those observed after topical whole-embryo VPA application.</p><p><strong>Conclusions: </strong>These results indicate that at least one mechanism for the teratogenicity of VPA involves a direct effect on developing tissue. The nature of the abnormalities observed implies that this effect may be mediated by disruption of genes that regulate pattern formation.</p>","PeriodicalId":22211,"journal":{"name":"Teratology","volume":"66 4","pages":"153-63"},"PeriodicalIF":0.0,"publicationDate":"2002-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/tera.10093","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22043483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"8-Iso-PGF(2alpha) administration generates dysmorphogenesis and increased lipid peroxidation in rat embryos in vitro.","authors":"Parri Wentzel,&nbsp;Ulf J Eriksson","doi":"10.1002/tera.10068","DOIUrl":"https://doi.org/10.1002/tera.10068","url":null,"abstract":"<p><strong>Background: </strong>Diabetic pregnancy displays increased incidence of congenital malformations and elevated levels of lipid peroxides in the offspring. The aim of the present work was to study if exogenous administration of one lipid peroxide, the isoprostane 8-iso-PGF(2alpha), is teratogenic per se in rat embryos in vitro, and if such teratological effects may be diminished by supplementation of an antioxidative agent, i.e., N-acetylcysteine or superoxide dismutase, to the culture medium.</p><p><strong>Methods: </strong>Day-9 embryos were cultured in vitro for 48 hr and subjected to 8-iso-PGF(2alpha) with and without N-acetylcysteine or superoxide dismutase.</p><p><strong>Results: </strong>Addition of 2 micromol/l of the isoprostane 8-iso-PGF(2alpha) to the culture medium caused high malformation rate, decreased protein and DNA contents, decreased somite number and crown-rump-length as well as marked accumulation of the isoprostane in the embryonic tissues. Adding N-acetylcysteine or superoxide dismutase to the culture medium with isoprostane normalized almost all morphological and biochemical parameters, including the elevated tissue concentration of 8-iso-PGF(2alpha).</p><p><strong>Conclusions: </strong>Results indicate that the isoprostane (8-iso-PGF(2alpha)) serves both as an oxidative stress indicator and a teratogenic agent. The findings support earlier studies of enhanced oxidative stress and increased malformation rate in embryos exposed to a diabetes-like environment, and suggest prevention of dysmorphogenesis by administration of antioxidative agents.</p>","PeriodicalId":22211,"journal":{"name":"Teratology","volume":"66 4","pages":"164-8"},"PeriodicalIF":0.0,"publicationDate":"2002-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/tera.10068","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22043484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of maternal smoking and maternal reproductive history in the etiology of hypospadias in the offspring.","authors":"Karin Källén","doi":"10.1002/tera.10092","DOIUrl":"https://doi.org/10.1002/tera.10092","url":null,"abstract":"<p><strong>Background: </strong>This study was undertaken to evaluate some possible risk factors for hypospadias with special regard to parity, subfertility and maternal smoking.</p><p><strong>Methods: </strong>With the use of the Swedish health registries, 3,262 infants with a diagnosis of hypospadias were identified among 1,413,811 infants born in 1983-96 with prospectively collected smoking exposure during pregnancy. Odds ratios (OR) and 95% confidence intervals (CI) were calculated after adjustment for various possible confounders.</p><p><strong>Results: </strong>A negative association between hypospadias and maternal smoking was found (OR: 0.83 95% CI: 0.76-0.90), but this association was only observed among mothers of Parity 1 or 4+, and the possibility of the results being due to confounding was suspected. Primiparity (vs. Parity 2) was positively associated with hypospadias (OR: 1.29 95% CI: 1.19-1.40), and so was subfertility (defined here as at least 1 year of attempts to conceive) (OR for subfertility: 1.16 95% CI: 1.01-1.33). The OR for smoking and primiparity, respectively, were of the same magnitude irrespective of whether subfertility was present or not, and no evidence was found that subfertility in the parents of infants with hypospadias seriously confounded the analyses.</p><p><strong>Conclusions: </strong>No explanation was found for the negative association between maternal smoking and hypospadias or the positive association between primiparity and hypospadias. Possible causal mechanisms are discussed.</p>","PeriodicalId":22211,"journal":{"name":"Teratology","volume":"66 4","pages":"185-91"},"PeriodicalIF":0.0,"publicationDate":"2002-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/tera.10092","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22043487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Buthionine sulfoximine embryotoxicity is associated with prolonged AP-1 activation.","authors":"Terence R S Ozolins,&nbsp;Wafa Harrouk,&nbsp;Tonia Doerksen,&nbsp;Jacquetta M Trasler,&nbsp;Barbara F Hales","doi":"10.1002/tera.10084","DOIUrl":"https://doi.org/10.1002/tera.10084","url":null,"abstract":"<p><strong>Background: </strong>Many teratogens induce oxidative stress, altering redox status and redox signaling; this has led to the suggestion that developmental toxicants act by disturbing redox status. The goal of these studies was to determine the consequences of altering glutathione homeostasis during organogenesis on embryo development, total DNA methylation, and activator protein-1 (AP-1) DNA binding activity and gene expression.</p><p><strong>Methods: </strong>Gestational day 10.5 rat embryos were cultured in vitro for up to 44 hour in the presence of L-buthionine-S,R-sulfoximine (BSO), an irreversible inhibitor of gamma-glutamyl-cysteine synthetase, the rate limiting step in glutathione biosynthesis. Effects of BSO on total, oxidized and reduced glutathione, embryo development, DNA methylation, AP-1 DNA binding activity and gene expression were investigated.</p><p><strong>Results: </strong>Significant depletion of glutathione by BSO was first noted at 6 hr in the embryo and at 3 hr in the yolk sac; total glutathione in the conceptus was depleted to the same extent after treatment with either 0.1 or 1.0 mM BSO. Exposure to 0.1 mM BSO did not cause a significant increase in embryotoxicity, although some impairment of growth and development was observed. In contrast, exposure to 1.0 mM BSO severely inhibited growth and development, significantly increasing the incidence of swollen hindbrains and of blebs in the forebrain, limb and maxillary regions. No significant treatment-related differences in total DNA methylation were observed. Interestingly, AP-1 DNA binding activity was similar in control and 0.1 mM BSO-treated conceptuses; however, exposure to 1.0 mM BSO increased AP-1 DNA binding at 6, 24, and 44 hr. The expression of several AP-1 family genes and of gamma-glutamylcysteine synthetase was induced in embryos cultured with 1.0 mM BSO.</p><p><strong>Conclusion: </strong>Exposure of embryos in vitro to BSO at a concentration that was embryotoxic induced prolonged AP-1 DNA binding activity and altered gene expression. These data suggest that AP-1 induction may serve as a biomarker of embryo stress.</p>","PeriodicalId":22211,"journal":{"name":"Teratology","volume":"66 4","pages":"192-200"},"PeriodicalIF":0.0,"publicationDate":"2002-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/tera.10084","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22043488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Septation of the anorectal and genitourinary tracts in the human embryo: crucial role of the catenoidal shape of the urorectal sulcus.","authors":"Daniel S Rogers,&nbsp;Charles N Paidas,&nbsp;Robert F Morreale,&nbsp;Grover M Hutchins","doi":"10.1002/tera.10041","DOIUrl":"https://doi.org/10.1002/tera.10041","url":null,"abstract":"<p><strong>Background: </strong>Previous studies of the tracheoesophageal sulcus and the sulci of the developing heart have suggested that the catenoidal or saddle-shaped configuration of the sulcus had mechanical properties that were important to developmental processes by causing regional growth limitation. We examined the development of the human perineal region to determine if a similar configuration exists in relation to the urorectal septum. We wished to re-examine the controversial issue of the role of the urorectal sulcus in the partitioning of the cloaca.</p><p><strong>Methods: </strong>Digitally scanned photomicrographs of serial histologic sections of embryos from Carnegie stages 13, 15, 18, and 22, obtained from the Carnegie Embryological Collection were used. Each image was digitally stacked, aligned, and isolated using image-editing software. Images were compiled using 3-D image-visualization software (T-Vox), into full 3-D voxel-based volume renderings. Similarly, digital models were made of the urogenital sinus, anorectum, cloaca, allantois, mesonephric ducts, ureters, and kidneys by isolating their associated epithelium in each histologic section and compiling the data in T-Vox. Methods were developed to create registration models for determining the exact position and orientation of outlined structures within the embryos.</p><p><strong>Results: </strong>Models were oriented and resectioned to determine the configuration of the urorectal sulcus. The results show that the urorectal sulcus maintains a catenoidal configuration during the developmental period studied and, thus, would be expected to limit caudal growth of the urorectal septum.</p><p><strong>Conclusion: </strong>The observations support the concept that the urorectal septum is a passive structure that does not actively divide the cloaca into urogenital and anorectal components.</p>","PeriodicalId":22211,"journal":{"name":"Teratology","volume":"66 4","pages":"144-52"},"PeriodicalIF":0.0,"publicationDate":"2002-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/tera.10041","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22043482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integration of DNA sample collection into a multi-site birth defects case-control study.","authors":"Sonja A Rasmussen,&nbsp;Edward J Lammer,&nbsp;Gary M Shaw,&nbsp;Richard H Finnell,&nbsp;Robert E McGehee,&nbsp;Margaret Gallagher,&nbsp;Paul A Romitti,&nbsp;Jeffrey C Murray","doi":"10.1002/tera.10086","DOIUrl":"https://doi.org/10.1002/tera.10086","url":null,"abstract":"<p><strong>Background: </strong>Advances in quantitative analysis and molecular genotyping have provided unprecedented opportunities to add biological sampling and genetic information to epidemiologic studies. The purpose of this article is to describe the incorporation of DNA sample collection into the National Birth Defects Prevention Study (NBDPS), an ongoing case-control study in an eight-state consortium with a primary goal to identify risk factors for birth defects.</p><p><strong>Methods: </strong>Babies with birth defects are identified through birth defects surveillance systems in the eight participating centers. Cases are infants with one or more of over 30 major birth defects. Controls are infants without defects from the same geographic area. Epidemiologic information is collected through an hour-long interview with mothers of both cases and controls. We added the collection of buccal cytobrush DNA samples for case-infants, control-infants, and their parents to this study.</p><p><strong>Results: </strong>We describe here the methods by which the samples have been collected and processed, establishment of a centralized resource for DNA banking, and quality control, database management, access, informed consent, and confidentiality issues.</p><p><strong>Conclusions: </strong>Biological sampling and genetic analyses are important components to epidemiologic studies of birth defects aimed at identifying risk factors. The DNA specimens collected in this study can be used for detection of mutations, study of polymorphic variants that confer differential susceptibility to teratogens, and examination of interactions among genetic risk factors. Information on the methods used and issues faced by the NBDPS may be of value to others considering the addition of DNA sampling to epidemiologic studies.</p>","PeriodicalId":22211,"journal":{"name":"Teratology","volume":"66 4","pages":"177-84"},"PeriodicalIF":0.0,"publicationDate":"2002-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/tera.10086","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22043486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}