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Keele E. Wurst Charles Poole Sara A. Ephross Andrew F. Olshan 《Birth defects research. Part A, Clinical and molecular teratology》2010,88(3):159-170
BACKGROUND : Several studies have evaluated maternal first trimester paroxetine use and the prevalence of congenital defects, particularly cardiac defects. To synthesize current epidemiologic information, a meta‐analysis was conducted. METHODS : A systematic literature search was conducted for original research published from January 1, 1992, through September 30, 2008. Results were extracted using predefined criteria, and authors were contacted for additional information when necessary. Compiled results were evaluated for funnel plot asymmetry, heterogeneity, and study characteristic associations. Where appropriate, fixed‐effect summary estimates were calculated and sensitivity analyses performed. RESULTS : Twenty reports (11 including results for aggregated congenital and combined cardiac defects, six for aggregated congenital defects only, and three for combined cardiac defects only) met prespecified inclusion criteria. There was little evidence of funnel plot asymmetry or overall heterogeneity. Summary estimates were produced for combined cardiac defects (prevalence odds ratio [POR], 1.46; 95% confidence interval [CI], 1.17–1.82) and aggregated congenital defects (POR, 1.24; 95% CI, 1.08–1.43) and first trimester paroxetine use. Some study characteristics may be associated with differential POR estimates for paroxetine and either combined cardiac or aggregated congenital defects. CONCLUSIONS : This meta‐analysis found little evidence of publication bias or overall statistical heterogeneity and only weak evidence of associations with some study characteristics. Although subject to limitations, the summary estimate indicates an increased prevalence of combined cardiac defects with first trimester paroxetine use. The summary estimate also indicates an increased prevalence of aggregated congenital defects with paroxetine; however, this association may be explained, in part, by the increased prevalence of combined cardiac defects. Birth Defects Research (Part A), 2010. © 2009 Wiley‐Liss, Inc. 相似文献
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Bérard A Ramos E Rey E Blais L St-André M Oraichi D 《Birth defects research. Part B, Developmental and reproductive toxicology》2007,80(1):18-27
BACKGROUND: Conflicting findings with regard to the teratogenic risks of first trimester use of paroxetine have prompted the FDA, Health Canada, and the manufacturer of the drug to issue warnings against its use during pregnancy. Given that untreated depression during pregnancy can lead to deleterious effect on the mother and her unborn fetus, data on the relationship between the dose and the range of malformations is warranted. This study attempts to quantify the association between first trimester exposure to paroxetine and congenital cardiac malformations, adjusting for possible confounders, and to quantify the dose-response relationship between paroxetine use and cardiac defects. METHODS: The Medication and Pregnancy registry was used. This population-based registry was built by linking three administrative databases (RAMQ, Med-Echo, and ISQ), and includes all pregnancies in Quebec between 01/01/1997 and 06/30/2003. Date of entry in the registry is the date of the first day of the last menstrual period. To be eligible for this study, women had to: 1) be 15-45 years of age at entry; 2) be covered by the RAMQ drug plan >or=12 months before and during pregnancy; 3) be using only one type of antidepressant during the first trimester; and 4) have a live birth. Two nested case-control studies were carried out comparing the prevalence of paroxetine use in the first trimester of pregnancy to the prevalence of other antidepressant exposures during the same time period. Cases were defined as: 1) any major malformations; or 2) any cardiac malformations diagnosed in the first year of life; controls were defined as no major or minor malformations. Multivariate logistic regression techniques were used to analyze data. RESULTS: Among the 1,403 women meeting inclusion criteria, 101 infants with major congenital malformations were identified; 24 had cardiac malformations. Adjusting for possible confounders, the use of paroxetine (odds ratio [OR] = 1.38, 95% confidence interval [CI] = 0.49-3.92), and the use of other SSRIs (OR = 0.89, 95% CI = 0.28-2.84) during the first trimester of pregnancy did not increase the risk of congenital cardiac malformations compared with the use of non-SSRI antidepressants. When considering the dose, however, a dose-response relationship was observed, thus women exposed to >25 mg/day of paroxetine during the first trimester of pregnancy were at increased risk of having an infant with major congenital malformations (adjusted [adj] OR = 2.23, 95% CI = 1.19, 4.17), or major cardiac malformations (adj OR = 3.07, 95% CI = 1.00, 9.42). CONCLUSIONS: Gestational exposure to paroxetine is associated with major congenital malformations and major cardiac malformations for only first trimester exposure above 25 mg/day. 相似文献
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Won‐Jun Jang Sung Keun Jung Tam Thuy Lu Vo Chul‐Ho Jeong 《Journal of cellular and molecular medicine》2019,23(2):1106-1115
The concept of drug repositioning has recently received considerable attention in the field of oncology. In the present study, we propose that paroxetine can be used as a potent anticancer drug. Paroxetine, one of the selective serotonin reuptake inhibitors (SSRIs), has been widely prescribed for the treatment of depression and anxiety disorders. Recently, SSRIs have been reported to have anticancer activity in various types of cancer cells; however, the underlying mechanisms of their action are not yet known. In this study, we investigated the potential anticancer effect of paroxetine in human colorectal cancer cells, HCT116 and HT‐29. Treatment with paroxetine reduced cell viability, which was associated with marked increase in apoptosis, in both the cell lines. Also, paroxetine effectively inhibited colony formation and 3D spheroid formation. We speculated that the mode of action of paroxetine might be through the inhibition of two major receptor tyrosine kinases – MET and ERBB3 – leading to the suppression of AKT, ERK and p38 activation and induction of JNK and caspase‐3 pathways. Moreover, in vivo experiments revealed that treatment of athymic nude mice bearing HT‐29 cells with paroxetine remarkably suppressed tumour growth. In conclusion, paroxetine is a potential therapeutic option for patients with colorectal cancer. 相似文献
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Matthew E. Oster Tiffany Riehle‐Colarusso Adolfo Correa 《Birth defects research. Part A, Clinical and molecular teratology》2010,88(1):1-8
BACKGROUND : Congenital rubella syndrome (CRS) has long been characterized by the triad of deafness, cataract, and cardiovascular malformations (CVMs). While initial reports identified patent ductus arteriosus (PDA) as the primary CVM in CRS, the exact nature of the CVMs found in CRS has not been well established. METHODS : We searched the English literature from 1941 through 2008 to identify studies that used cardiac catheterization or echocardiography to evaluate the CVMs in CRS. RESULTS : Of the 121 patients in the 10 studies with catheterization data, 78% had branch pulmonary artery stenosis, and 62% had a PDA. In 49% of cases, both branch pulmonary artery stenosis and PDA were present, whereas isolated branch pulmonary artery stenosis and isolated PDA were found in 29 and 13% of cases, respectively. Of the 12 patients in the 10 studies with echocardiographic data, PDA was more common than branch pulmonary artery stenosis, but this finding is greatly limited by the small numbers of patients and limitations of echocardiography. Although published studies of CVMs in CRS have in general reported PDA as the CVM phenotype most commonly associated with CRS, among CRS cases evaluated by catheterization, branch pulmonary artery stenosis was actually more common than PDA. Moreover, although the combination of branch pulmonary artery stenosis and PDA was more common than either branch pulmonary artery stenosis or PDA alone, isolated branch pulmonary artery stenosis was twice as common as isolated PDA. CONCLUSION : Among children with suspected CRS, clinical evaluations for the presence of CVMs should include examinations for both branch pulmonary artery stenosis and PDA. Birth Defects Research (Part A), 2010. © 2009 Wiley‐Liss, Inc. 相似文献
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Xia Cao Yukai Du 《Birth defects research. Part A, Clinical and molecular teratology》2013,97(11):750-754
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Källén B Finnström O Nygren KG Olausson PO 《Birth defects research. Part A, Clinical and molecular teratology》2005,73(3):162-169
BACKGROUND: The possible excess of congenital malformations in infants born after in vitro fertilization (IVF) has been much discussed in the literature, with controversial conclusions. This population based study is aimed at analyzing the presence of congenital malformations in a large group of infants born after IVF and to compare malformation risk both with that of all infants born and according to IVF method used. METHODS: Infants born after IVF during the period 1982-2001 were ascertained from all IVF clinics in Sweden. The presence of congenital malformations was identified from three national health registers: the Swedish Medical Birth Register, the Swedish Registry of Congenital Malformations, and the Swedish Hospital Discharge Register. The IVF children were compared with all children born in Sweden during the same period and recorded in the Swedish Medical Birth Register. RESULTS: Among 16,280 IVF children (30% conceived after intracytoplasmatic sperm injection [ICSI]) a 42% excess of any congenital malformation was found, explainable by parental characteristics and in some cases by the high rate of multiple births. Among these children, 8% had a congenital malformation, and 5% had a relatively severe condition. For neural tube defects, choanal atresia, and alimentary tract atresia, an additional risk increase was seen. There was no difference in malformation rate according to IVF method except for an excess of hypospadias after ICSI. CONCLUSIONS: An increased risk for congenital malformations occurs after IVF, similar for the different IVF techniques used, and mainly a consequence of parental characteristics. A few specific conditions show an extra increase in risk. 相似文献
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Keren Agay‐Shay Michael Friger Shai Linn Ammatzia Peled Yona Amitai Chava Peretz 《Birth defects research. Part A, Clinical and molecular teratology》2012,94(6):438-448
BACKGROUND Congenital malformations (CMs) are a leading cause of infant disability. Geophysical patterns such as 2‐year, yearly, half‐year, 3‐month, and lunar cycles regulate much of the temporal biology of all life on Earth and may affect birth and birth outcomes in humans. Therefore, the aim of this study was to evaluate and compare trends and periodicity in total births and CM conceptions in two Israeli populations. METHODS Poisson nonlinear models (polynomial) were applied to study and compare trends and geophysical periodicity cycles of weekly births and weekly prevalence rate of CM (CMPR), in a time‐series design of conception date within and between Jews and Muslims. The population included all live births and stillbirths (n = 823,966) and CM (three anatomic systems, eight CM groups [n = 2193]) in Israel during 2000 to 2006. Data were obtained from the Ministry of Health. RESULTS We describe the trend and periodicity cycles for total birth conceptions. Of eight groups of CM, periodicity cycles were statistically significant in four CM groups for either Jews or Muslims. Lunar month and biennial periodicity cycles not previously investigated in the literature were found to be statistically significant. Biennial cycle was significant in total births (Jews and Muslims) and syndactyly (Muslims), whereas lunar month cycle was significant in total births (Muslims) and atresia of small intestine (Jews). CONCLUSION We encourage others to use the method we describe as an important tool to investigate the effects of different geophysical cycles on human health and pregnancy outcomes, especially CM, and to compare between populations. Birth Defects Research (Part A) 2012. © 2012 Wiley Periodicals, Inc. 相似文献
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Goldschmidt B Lopes CA Moura M Fasano DM Andrade MC Cysne LB Gonçalves MB Bravin JS Kugelmeier T Viana CF Silva FA Marinho AM 《Journal of medical primatology》2008,37(4):173-176
BACKGROUND: Agnathia is a rare malformation characterized by the absence of the mandible. METHODS: A male rhesus monkey with malformations was found dead and studied by internal examination, radiographs and histopathology. RESULTS: A case of a rare first branchial arch anomaly with agenesis of the mandible and tongue is presented. The animal also had visceral deformities. However, ears were normal in shape and only slightly low in position. The craniofacial malformations may reflect incomplete separation of the first branchial arch into its maxillary and mandibular processes. CONCLUSIONS: The association between the craniofacial and other corporal anomalies is unclear. 相似文献
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Objective: This study determined whether obese women have an increased risk of cardiovascular defects in their offspring compared with average weight women. Research Methods and Procedures: In a case‐control study, prospectively collected information was obtained from Swedish medical health registers. The study included 6801 women who had infants with a cardiovascular defect and, as controls, all delivered women (N = 812, 457) during the study period (1992 to 2001). Infants with chromosomal anomalies or whose mothers had pre‐existing diabetes were excluded. Obesity was defined as BMI >29 kg/m2, and morbid obesity was defined as BMI >35 kg/m2. Comparisons were made with average weight women (BMI = 19.8 to 26 kg/m2). Results: In the group of obese mothers, there was an increased risk for cardiovascular defects compared with the average weight mothers [adjusted odds ratio (OR) = 1.18; 95% CI, 1.09 to 1.27], which was slightly more pronounced for the severe types of cardiovascular defects (adjusted OR = 1.23; 95% CI, 1.05 to 1.44). With morbid obesity, the OR for cardiovascular defects was 1.40 (95% CI, 1.22 to 1.64), and for severe cardiovascular defects, the OR was 1.69 (95% CI, 1.27 to 2.26). There was an increased risk for all specific defects studied among the obese women, but only ventricular septal defects and atrial septal defects reached statistical significance. Discussion: In this sample, a positive association was found between maternal obesity in early pregnancy and congenital heart defects in the offspring. A suggested explanation is undetected type 2 diabetes in early pregnancy, but other explanations may exist. 相似文献
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Sharpe-Stimac M Wang Y Druschel CM Cross PK 《Birth defects research. Part A, Clinical and molecular teratology》2004,70(9):597-602
BACKGROUND: One of the objectives of the New York State birth defect surveillance system, the New York State Congenital Malformations Registry (CMR), is to identify children in need of special programs and assist prevention/intervention programs and services with evaluation. In 1999, the CMR started a statewide mass-mailing program to inform parents of children with major birth defects about programs and support groups that might be helpful to them. A follow-up survey by mail was conducted in 2002 to evaluate the usefulness of the mailing program. METHODS: The survey was mailed between September and December of 2001 to parents of children born in 2001 and reported to the CMR with selected major birth defects. Non-respondents were followed-up by telephone. RESULTS: Of the 226 eligible families, 54% (122) responded to the survey. Approximately 66% of responding parents stated that the information provided by the mailing program was helpful, and 48% had contacted and/or used the programs and services listed in the information sheets. Parents with children younger than 6 months of age at the time of mailing were more likely to find the information helpful, compared to parents with children 6 months of age or older. The majority of responding parents had contacted and/or used the Early Intervention Program. CONCLUSION: The findings from the current survey show that the statewide information-mailing program administered by CMR is helpful and useful to the families of children with major birth defects in New York State. 相似文献
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P.E. Peterson J.J. Short R. Tarara C. Valverde E. Rothgarn A.G. Hendrickx 《Journal of medical primatology》1997,26(5):267-275
Abstract: This paper summarizes the spontaneous incidence of congenital defects in the rhesus and cynomolgus macaque colonies (Macaca mulatta and M. fascicularis) at the California Regional Primate Research Center. The computerized database used in this analysis included fetuses, term infants, juveniles, and adults that underwent a necropsy procedure over a 14-year period (1983–1996). The calculated malformation rates were 0.9% (40/4,390) and 0.3% (3/965) for the rhesus and cynomolgus monkey, respectively. Most of the observed malformations in both species affected the musculoskeletal and the cardiovascular systems, while a smaller number of defects were observed in the gastrointestinal, urogenital, endocrine, and central nervous systems. Inbreeding did not contribute to the spontaneous malformation incidence and there was no predilection for sex (male vs. female) or housing (indoors vs. outdoors) among the malformed cases. This spontaneous malformation database in our macaque colony aids in the interpretation of defects that occur in an experimental study as well as in the ongoing assessment of a healthy nonhuman primate breeding colony. 相似文献
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Suzanne M. Gilboa Kyung A. Lee Mary E. Cogswell Flavia K. Traven Lorenzo D. Botto Tiffany Riehle‐Colarusso Adolfo Correa Coleen A. Boyle the National Birth Defects Prevention Study 《Birth defects research. Part A, Clinical and molecular teratology》2014,100(9):647-657
BACKGROUND In a recent study, high maternal periconceptional intake of vitamin E was found to be associated with risk of congenital heart defects (CHDs). To explore this association further, we investigated the association between total daily vitamin E intake and selected birth defects. METHODS: We analyzed data from 4525 controls and 8665 cases from the 1997 to 2005 National Birth Defects Prevention Study. We categorized estimated periconceptional energy‐adjusted total daily vitamin E intake from diet and supplements into quartiles (referent, lowest quartile). Associations between quartiles of energy‐adjusted vitamin E intake and selected birth defects were adjusted for demographic, lifestyle, and nutritional factors. RESULTS: We observed a statistically significant association with the third quartile of vitamin E intake (odds ratio [OR], 1.17; 95% confidence interval [CI], 1.01–1.35) and all CHDs combined. Among CHD sub‐types, we observed associations with left ventricular outflow tract obstruction defects, and its sub‐type, coarctation of the aorta and the third quartile of vitamin E intake. Among defects other than CHDs, we observed associations between anorectal atresia and the third quartile of vitamin E intake (OR, 1.66; 95% CI, 1.01–2.72) and hypospadias and the fourth quartile of vitamin E intake (OR, 1.42; 95% CI, 1.09–1.87). CONCLUSION: Selected quartiles of energy‐adjusted estimated total daily vitamin E intake were associated with selected birth defects. However, because these few associations did not exhibit exposure‐response patterns consistent with increasing risk associated with increasing intake of vitamin E, further studies are warranted to corroborate our findings. Birth Defects Research (Part A), 100:647–657, 2014. © 2014 Wiley Periodicals, Inc. 相似文献