Birth defects research. Part A, Clinical and molecular teratology最新文献

{"title":"Effects of thyroxine exposure on the Twist 1 +/− phenotype: A test of gene–environment interaction modeling for craniosynostosis","authors":"Emily L. Durham,&nbsp;R. Nicole Howie,&nbsp;Laurel Black,&nbsp;Grace Bennfors,&nbsp;Trish E. Parsons,&nbsp;Mohammed Elsalanty,&nbsp;Jack C. Yu,&nbsp;Seth M. Weinberg,&nbsp;James J. Cray Jr.","doi":"10.1002/bdra.23543","DOIUrl":"10.1002/bdra.23543","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Craniosynostosis, the premature fusion of one or more of the cranial sutures, is estimated to occur in 1:1800 to 2500 births. Genetic murine models of craniosynostosis exist, but often imperfectly model human patients. Case, cohort, and surveillance studies have identified excess thyroid hormone as an agent that can either cause or exacerbate human cases of craniosynostosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Here we investigate the influence of <i>in utero</i> and <i>in vitro</i> exogenous thyroid hormone exposure on a murine model of craniosynostosis, <i>Twist 1 +/−</i>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>By 15 days post-natal, there was evidence of coronal suture fusion in the <i>Twist 1</i> +/− model, regardless of exposure. With the exception of craniofacial width, there were no significant effects of exposure; however, the <i>Twist 1 +/−</i> phenotype was significantly different from the wild-type control. <i>Twist 1 +/−</i> cranial suture cells did not respond to thyroxine treatment as measured by proliferation, osteogenic differentiation, and gene expression of osteogenic markers. However, treatment of these cells did result in modulation of thyroid associated gene expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings suggest the phenotypic effects of the genetic mutation largely outweighed the effects of thyroxine exposure in the <i>Twist 1</i> +/− model. These results highlight difficultly in experimentally modeling gene–environment interactions for craniosynostotic phenotypes. Birth Defects Research (Part A) 106:803–813, 2016. © 2016 Wiley Periodicals, Inc.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8983,"journal":{"name":"Birth defects research. Part A, Clinical and molecular teratology","volume":"106 10","pages":"803-813"},"PeriodicalIF":0.0,"publicationDate":"2016-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/bdra.23543","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34683106","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":"A 2015 global update on folic acid-preventable spina bifida and anencephaly","authors":"Annelise Arth,&nbsp;Vijaya Kancherla,&nbsp;Helena Pachón,&nbsp;Sarah Zimmerman,&nbsp;Quentin Johnson,&nbsp;Godfrey P. Oakley Jr","doi":"10.1002/bdra.23529","DOIUrl":"10.1002/bdra.23529","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Spina bifida and anencephaly are two major neural tube defects. They contribute substantially to perinatal, neonatal, infant, and under-five mortality and life-long disability. To monitor the progress toward the total prevention of folic acid-preventable spina bifida and anencephaly (FAP SBA), we examined their global status in 2015.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Based on existing data, we modeled the proportion of FAP SBA that are prevented in the year 2015 through mandatory folic acid fortification globally. We included only those countries with mandatory fortification that added at least 1.0 ppm folic acid as a fortificant to wheat and maize flour, and had complete information on coverage. Our model assumed mandatory folic acid fortification at 200 μg/day is fully protective against FAP SBA, and reduces the rate of spina bifida and anencephaly to a minimum of 0.5 per 1000 births.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Our estimates show that, in 2015, 13.2% (35,500 of approximately 268,700 global cases) of FAP SBA were prevented in 58 countries through mandatory folic acid fortification of wheat and maize flour. Most countries in Europe, Africa, and Asia were not implementing mandatory fortification with folic acid.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Knowledge that folic acid prevents spina bifida and anencephaly has existed for 25 years, yet only a small fraction of FAP SBA is being prevented worldwide. Several countries still have 5- to 20-fold epidemics of FAP SBA. Implementation of mandatory fortification with folic acid offers governments a proven and rapid way to prevent FAP SBA-associated disability and mortality, and to help achieve health-related Sustainable Development Goals. Birth Defects Research (Part A) 106:520–529, 2016. © 2016 Wiley Periodicals, Inc.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8983,"journal":{"name":"Birth defects research. Part A, Clinical and molecular teratology","volume":"106 7","pages":"520-529"},"PeriodicalIF":0.0,"publicationDate":"2016-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/bdra.23529","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34560362","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":"What is standing in the way of complete prevention of folate preventable neural tube defects?","authors":"James L. Mills,&nbsp;Aggeliki Dimopoulos,&nbsp;Regan L. Bailey","doi":"10.1002/bdra.23518","DOIUrl":"10.1002/bdra.23518","url":null,"abstract":"<p>It is well known that there is a large gap between the number of neural tube defects (NTDs) that could be prevented by folic acid and the number that are actually being prevented. Arth and colleagues demonstrate just how large that gap is (Arth et al., <span>2016</span>). The question is: why are so many potentially preventable NTDs not being prevented?</p><p>Campaigns recommending that women of childbearing age take folic acid supplements routinely and voluntary fortification programs have had only modest success at best (Khoshnood et al., <span>2015</span>). Therefore, mandatory fortification has been instituted in almost 80 countries (Food Fortification Initiative, 2016). As Arth et al. demonstrate, many countries have not embraced the mandatory fortification approach, despite the fact that it has prevented an average of 40 to 50% of NTDs (Castillo-Lancellotti et al., <span>2013</span>).</p><p>Concerns regarding the safety of folic acid fortification are one reason. Two major concerns are masking vitamin B12 deficiency and increasing cancer risk. It should be noted that the amount of folic acid people receive from fortified food in the United States, where fortification of enriched cereal grain products is mandatory, is an average of 163 micrograms per day in women of childbearing age, less than half the recommended dietary allowance (Tinker et al., <span>2010</span>). This is sufficient to prevent folate-related NTDs (Mosley et al., <span>2009</span>) but does not appear to cause masking of the hematological signs of vitamin B12 deficiency (Mills et al., <span>2003</span>). A large meta-analysis of participants in folic acid trials demonstrated that, after an average of 5 years of follow-up, the relative risk for incident cancer was 1.06 with a 95% confidence interval of 0.99 to 1.13 (Vollset et al., <span>2013</span>).</p><p>The authors noted that the 6% increase was not statistically significant and that trial participants were exposed to far higher doses than fortification would deliver. There was no significant increase in any individual cancers studied. Nonetheless, concerns persist regarding cancer risk (van Wijngaarden et al., <span>2014</span>) and other possible but unproved risks (National Toxicology Program, 2015). It is important to note that the amount of folic acid needed to prevent NTDs is far less than the amount likely to cause adverse effects (Mills and Dimopoulos, <span>2015</span>). Because NTDs are uncommon events and a small increase in cancer would affect a substantial number of people, some countries have been reluctant to require fortification. It should be noted, however, that mandatory fortification has caused a dramatic reduction in folate deficiency (Pfeiffer et al., <span>2012</span>); so the benefit is not limited to a small group.</p><p>Several other obstacles to mandatory fortification exist. Although European Union (EU) regulation No. 1925/2006 (European Commission, 2006) acknowledges the need for mandator","PeriodicalId":8983,"journal":{"name":"Birth defects research. Part A, Clinical and molecular teratology","volume":"106 7","pages":"517-519"},"PeriodicalIF":0.0,"publicationDate":"2016-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/bdra.23518","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34560361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In utero exposure to venlafaxine, a serotonin–norepinephrine reuptake inhibitor, increases cardiac anomalies and alters placental and heart serotonin signaling in the rat","authors":"Laetitia Laurent,&nbsp;Chunwei Huang,&nbsp;Sheila R. Ernest,&nbsp;Anick Berard,&nbsp;Cathy Vaillancourt,&nbsp;Barbara F. Hales","doi":"10.1002/bdra.23537","DOIUrl":"10.1002/bdra.23537","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Human studies are inconsistent with respect to an association between treatment with selective serotonin and serotonin–norepinephrine reuptake inhibitors (SSRI/SNRIs) and an increase in the incidence of congenital heart defects. Here we tested the hypothesis that <i>in utero</i> exposure to venlafaxine, a highly prescribed SNRI, increases the incidence of fetal heart defects and alters placental and fetal heart serotonin signaling in the rat.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Timed-pregnant Sprague Dawley rats were gavaged daily with venlafaxine hydrochloride (0, 3, 10, 30, or 100 mg/kg/day) from gestation day 8 to 20. On gestation day 21, fetuses were examined for external and internal malformations; placentas and fetal hearts were collected for the analysis of gene expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Venlafaxine had no effect on the number of live fetuses, fetal body weights, or external morphology in the absence of maternal toxicity. However, venlafaxine significantly increased the placental index (fetal body/placental weight ratio) and the incidence of fetal cardiac anomalies. Venlafaxine exposure decreased placental expression of the serotonin transporter (SERT/<i>Slc6a4</i>) at the transcript and protein levels. In contrast, venlafaxine increased SERT expression in the hearts of female, but not male, fetuses. Expression of the serotonin 2B receptor (5-HT_2B/<i>Htr2b</i>) and of fibroblast growth factor 8 was induced in fetal hearts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p><i>In utero</i> venlafaxine exposure altered the placental index and induced fetal cardiac anomalies in rats. We propose that the increased incidence of cardiac anomalies is mediated through alterations in serotonin signaling in the placenta and fetal heart. Birth Defects Research (Part A), 2016. © 2016 Wiley Periodicals, Inc. Birth Defects Research (Part A) 106:1044–1055, 2016. © 2016 Wiley Periodicals, Inc.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8983,"journal":{"name":"Birth defects research. Part A, Clinical and molecular teratology","volume":"106 12","pages":"1044-1055"},"PeriodicalIF":0.0,"publicationDate":"2016-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/bdra.23537","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34544248","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":"Further evidence for deletions in 7p14.1 contributing to nonsyndromic cleft lip with or without cleft palate","authors":"Johanna Klamt,&nbsp;Andrea Hofmann,&nbsp;Anne C. Böhmer,&nbsp;Ann-Kathrin Hoebel,&nbsp;Lina Gölz,&nbsp;Jessica Becker,&nbsp;Alexander M. Zink,&nbsp;Markus Draaken,&nbsp;Alexander Hemprich,&nbsp;Martin Scheer,&nbsp;Gül Schmidt,&nbsp;Markus Martini,&nbsp;Michael Knapp,&nbsp;Elisabeth Mangold,&nbsp;Franziska Degenhardt,&nbsp;Kerstin U. Ludwig","doi":"10.1002/bdra.23539","DOIUrl":"10.1002/bdra.23539","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Nonsyndromic cleft with or without cleft palate (nsCL/P) is a common birth defect. Although genome-wide association studies (GWAS) have identified numerous risk variants, a considerable fraction of the genetic heritability remains unknown. The aim of the present study was to replicate a previous finding that <i>de novo</i> deletions in a 62 kb region of chromosome 7p14 are a risk factor for nsCL/P, using an independent cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data from a published case–control GWAS cohort of 399 patients and 1318 controls were used. Copy number variant (CNV) detection in the 62 kb candidate region of 7p14 was performed using QuantiSNP. Putative CNVs in probands were verified and validated by quantitative polymerase chain reaction. Segregation analyses were performed in family members for whom DNA was available.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Within the 62 kb candidate region, a deletion of 7.4 kb showed association with nsCL/P (13/387 cases, 20/1300 controls, <i>p</i>_lowest = 0.024, odds ratio = 2.22). In all families with a sporadic case (<i>n</i> = 3), the deletion occurred <i>de novo</i>. In multiplex families, both incomplete segregation and incomplete penetrance were observed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The present data support the hypothesis that deletions at 7p14 are a common risk factor for nsCL/P. Genome-wide CNV analyses in nsCL/P cohorts are warranted to explore the functional relevance of these deletions and their contribution to nsCL/P, and to determine exact breakpoints. Birth Defects Research (Part A) 106:767–772, 2016. © 2016 Wiley Periodicals, Inc.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8983,"journal":{"name":"Birth defects research. Part A, Clinical and molecular teratology","volume":"106 9","pages":"767-772"},"PeriodicalIF":0.0,"publicationDate":"2016-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/bdra.23539","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34641758","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":"Prevalence, characteristics, and survival of children with esophageal atresia: A 32-year population-based study including 1,417,724 consecutive newborns.","authors":"M. Cassina, Michele Ruol, R. Pertile, P. Midrio, S. Piffer, V. Vicenzi, M. Saugo, C. Stocco, P. Gamba, M. Clementi","doi":"10.1002/bdra.23493","DOIUrl":"https://doi.org/10.1002/bdra.23493","url":null,"abstract":"BACKGROUND\u0000Esophageal atresia (EA) is a congenital malformation of the upper gastrointestinal tract with an estimated prevalence varying from 1 in 2500 to 1 in 4500 births. The aim of this study was to describe the epidemiology of EA between 1981 and 2012 and evaluate patients' survival.\u0000\u0000\u0000METHODS\u0000This study used data from a population-based Italian Congenital Malformation Registry. The survival status was ascertained by linking the registry records, vital records and the regional registries of patients. Kaplan-Meier methods were used to estimate survival probabilities up to 25 years and Cox proportional hazards regression was used to evaluate factors that affected survival.\u0000\u0000\u0000RESULTS\u0000A total of 407 cases of EA were identified among 1,417,724 total births. After the exclusion of cases with chromosomal anomalies, 49.9% of the patients presented with at least one associated congenital anomaly. The 25-year survival probability was 85.1% (95% confidence interval [CI], 80.8-89.4), with most deaths occurring during the first months of life. Patients' characteristics associated with decreased survival probability were low birth weight (hazard ratio, 3.7; 95% CI, 1.7-8.3) and presence of additional major defects (hazard ratio, 2.8; 95% CI, 1.3-6.0). A significant improvement in survival over the decades was observed for patients with nonisolated EA.\u0000\u0000\u0000CONCLUSION\u0000This study detected a significant improvement in survival of individuals with EA over the past decades and identified the strongest predictors of mortality. These results will be important for the planning of the clinical management and formulation of prognosis when EA is diagnosed in a newborn. Birth Defects Research (Part A) 106:542-548, 2016. © 2016 Wiley Periodicals, Inc.","PeriodicalId":8983,"journal":{"name":"Birth defects research. Part A, Clinical and molecular teratology","volume":"4 1","pages":"542-8"},"PeriodicalIF":0.0,"publicationDate":"2016-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87529575","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":"Obituary: Dr. Ed Lammer.","authors":"R. Finnell, G. Shaw","doi":"10.1002/bdra.23524","DOIUrl":"https://doi.org/10.1002/bdra.23524","url":null,"abstract":"","PeriodicalId":8983,"journal":{"name":"Birth defects research. Part A, Clinical and molecular teratology","volume":"1 1","pages":"515-6"},"PeriodicalIF":0.0,"publicationDate":"2016-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79840233","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":"When the right (Drug) should be left: Prenatal drug exposure and heterotaxy syndrome.","authors":"Nicole R. van Veenendaal, C. Kusters, R. Oostra, J. Bergman, J. Cobben","doi":"10.1002/bdra.23497","DOIUrl":"https://doi.org/10.1002/bdra.23497","url":null,"abstract":"BACKGROUND\u0000Recent studies reported an association between prenatal propylthiouracil exposure and birth defects, including abnormal arrangement across the left-right body axis, suggesting an association with heterotaxy syndrome.\u0000\u0000\u0000METHODS\u0000This case-control and case-finding study used data from 1981 to 2013 from the EUROCAT birth defect registry in the Northern Netherlands. First, we explored prenatal exposures in heterotaxy syndrome (cases) and Down syndrome (controls). Second, we describe the specific birth defects in offspring of mothers using propylthiouracil (PTU) prenatally.\u0000\u0000\u0000RESULTS\u0000A total of 66 cases with heterotaxy syndrome (incidence 12.1 per 100,000 pregnancies) and 783 controls with Down syndrome (143.3 per 100,000 pregnancies) were studied. No differences in intoxication use during pregnancy were found between cases and controls, including smoking (28.0% vs. 22.7%; p = 0.40), alcohol (14.0% vs. 26.9%; p = 0.052), and recreational drugs (0 vs. 0.3%; p = 1.00). We found an association between heterotaxy syndrome and prenatal drug exposure to follitropin-alfa (5.6% vs. 1.1%; p = 0.04), and drugs used in nicotine dependence (3.7% vs. 0.2%; p = 0.02). Five mothers used PTU during pregnancy and gave birth to a child with trisomy 18, renal abnormalities, or hypospadias and cardiac defects.\u0000\u0000\u0000CONCLUSION\u0000This study identified follitropin-alfa and drugs used in nicotine dependence as possible teratogens of heterotaxy syndrome. Our data suggest the possibility that there is an increased risk of birth defects (including renal, urological, and cardiac abnormalities) in children born among mothers taking PTU prenatally, but not for heterotaxy syndrome. Birth Defects Research (Part A) 106:573-579, 2016. © 2016 Wiley Periodicals, Inc.","PeriodicalId":8983,"journal":{"name":"Birth defects research. Part A, Clinical and molecular teratology","volume":"10 1","pages":"573-9"},"PeriodicalIF":0.0,"publicationDate":"2016-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77045764","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":"Mechanism of pancreatic and liver malformations in human fetuses with short-rib polydactyly syndrome.","authors":"C. Loo, T. Pereira, M. Ramsing, I. Vogel, O. B. Petersen, G. Ramm","doi":"10.1002/bdra.23495","DOIUrl":"https://doi.org/10.1002/bdra.23495","url":null,"abstract":"BACKGROUND\u0000The short-rib polydactyly (SRP) syndromes are rare skeletal dysplasias caused by abnormalities in primary cilia, sometimes associated with visceral malformations.\u0000\u0000\u0000METHODS\u0000The pathogenesis of ductal plate malformation (DPM) varies in different syndromes and has not been investigated in SRP. We have studied liver development in five SRP fetuses and pancreatic development in one SRP fetus, with genetically confirmed mutations in cilia related genes, with and without DPMs, using the immunoperoxidase technique, and compared these to other syndromes with DPM.\u0000\u0000\u0000RESULTS\u0000Acetylated tubulin expression was abnormal in DPM in SRP, Meckel syndrome, and autosomal recessive polycystic kidney disease (ARPKD), confirming ciliary anomalies. SDF-1 was abnormally expressed in SRP and two of three cases of autosomal dominant polycystic kidney disease (ADPKD) but not ARPKD or Meckel. Increased density of quiescent hepatic stellate cells was seen in SRP, Meckel, one of three cases of ARPKD, and two of three cases of ADPKD with aberrant hepatocyte expression of keratin 19 in SRP and ADPKD. Immunophenotypic abnormalities were present even in fetal liver without fully developed DPMs. The SRP case with DPM and pancreatic malformations showed abnormalities in the pancreatic head (influenced by mesenchyme from the septum transversum, similar to liver) but not pancreatic body (influenced by mesenchyme adjacent to the notochord).\u0000\u0000\u0000CONCLUSION\u0000In SRP, there are differentiation defects of hepatocytes, cholangiocytes, and liver mesenchyme and, in rare cases, pancreatic mesenchymal anomalies. The morphological changes were subtle in early gestation but immunophenotypic abnormalities were present. Mesenchymal-epithelial interactions may contribute to the malformations. Birth Defects Research (Part A) 106:549-562, 2016. © 2016 Wiley Periodicals, Inc.","PeriodicalId":8983,"journal":{"name":"Birth defects research. Part A, Clinical and molecular teratology","volume":"1 1","pages":"549-62"},"PeriodicalIF":0.0,"publicationDate":"2016-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84027714","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":"Childhood cancer in children with congenital anomalies in Oklahoma, 1997 to 2009.","authors":"Amanda E. Janitz, B. Neas, Janis E Campbell, Anne E Pate, J. Stoner, S. Magzamen, J. Peck","doi":"10.1002/bdra.23494","DOIUrl":"https://doi.org/10.1002/bdra.23494","url":null,"abstract":"BACKGROUND\u0000Data-linkage studies have reported an association between congenital anomalies and childhood cancer. However, few studies have focused on the differences in the effect of congenital anomalies on cancer as a function of attained age. We aimed to examine associations between anomalies and childhood cancer as a function of attained age among children born in Oklahoma.\u0000\u0000\u0000METHODS\u0000Data were obtained from the Oklahoma State Department of Health from 1997 to 2009 (n = 591,235). We linked Vital Statistics records for singleton deliveries to the Oklahoma Birth Defects Registry and the Oklahoma Central Cancer Registry using name and birth date. To assess the relation between anomalies and childhood cancer, we used Cox regression analysis allowing for a nonproportional hazards for anomalies as a function of age.\u0000\u0000\u0000RESULTS\u0000There were 23,368 (4.0%) children with anomalies and 531 (0.1%) children with cancer. When considering 3-year age intervals, we detected an increased hazard of any childhood cancer in children with anomalies compared with those without anomalies before 1 year of age (hazard ratio, 14.1; 95% confidence interval, 8.3-23.7) and at 3 years of age (hazard ratio, 2.3; 95% confidence interval, 1.6-3.2). The increased hazard declined with increasing time since birth, with the effect diminished by 6 years of age.\u0000\u0000\u0000CONCLUSION\u0000Our results were consistent with previous studies indicating an increased rate of childhood cancer among children with anomalies at younger ages. Furthermore, our study added a methodological refinement of assessing the effect of anomalies as a function of attained age. Birth Defects Research (Part A) 106:633-642, 2016. © 2016 Wiley Periodicals, Inc.","PeriodicalId":8983,"journal":{"name":"Birth defects research. Part A, Clinical and molecular teratology","volume":"22 1","pages":"633-42"},"PeriodicalIF":0.0,"publicationDate":"2016-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86512182","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}