Background: The HOX gene family consists of highly conserved transcription factors that specify the identity of the body segments along the anteroposterior axis of the embryo. Because the phenotypes of mice with targeted disruptions of Hox genes resemble some patterns of human malformations, mutations in HOX genes have been expected to be associated with a significant number of human malformations. Thus far, however, mutations have been documented in only three of the 39 human HOX genes (HOXD13, HOXA13, and HOXA11) partly because current knowledge on the complete coding sequence and genome structure is limited to only 20 of the 39 human HOX genes. Methods: Taking advantage of the human and mouse draft genome sequences, we attempted to characterize the remaining 19 human HOX genes by bioinformatic analysis including phylogenetic footprinting, the probabilistic prediction method, and comparison of genomic sequences with the complete set of the human anonymous cDNA sequences. Results: We were able to determine the full coding sequences of 19 HOX genes and their genome structure and successfully designed a complete set of PCR primers to amplify the entire coding region of each of the 39 HOX genes from genomic DNA. Conclusions: Our results indicate the usefulness of bioinformatic analysis of the draft genome sequences for clinically oriented research projects. It is hoped that the mutation panel provided here will serve as a launch-pad for a new discourse on the genetic basis of human malformations.
BACKGROUND:The live birth prevalence of Down syndrome is approximately 10 per 10,000 live births in the United States. Down syndrome prevalence has been reported to change over time and to vary by selected demographic factors.METHODS:Data from a population-based birth defects registry in Hawaii involving 363 Down syndrome cases delivered during 1986-97 were used to calculate overall prevalence and to investigate secular trends and differences by selected demographic factors.RESULTS:The total (live birth, fetal death, and elective termination) prevalence was 14.74 per 10,000 live births and fetal deaths. The unadjusted live birth prevalence was 8.67 per 10,000 live births. The adjusted live birth (live births and proportion of elective terminations expected to have resulted in live births) prevalence was 12.59 per 10,000 live births. No significant secular trends were observed for either total prevalence (P = 0.688) or adjusted live birth prevalence (P = 0.604). The total Down syndrome prevalence per 10,000 live births was highest for Far East Asians (22.01), followed by whites (17.06), Filipinos (15.94), and Pacific Islanders (9.21). Prevalence per 10,000 births was higher in metropolitan Honolulu (18.57) than in the rest of Hawaii (14.15). After adjusting for maternal age, however, the differences within the demographic groups were not statistically significant.CONCLUSIONS:The live birth prevalence of Down syndrome in Hawaii during 1986-97 was lower than reported in the literature. Prevalence did not change significantly over time. Any differences in prevalence by maternal race/ethnicity and place of residence appeared to result from differences in maternal age distribution.
TeratologyVolume 66, Issue 6 p. 273-273 Letter to the Editor Comment on antiepileptics and antipsychotics Gideon Koren, Corresponding Author Gideon Koren Motherisk Program, Hospital for Sick Children, Toronto, Ontario M5G 1X8, CanadaMotherisk Program, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, CanadaSearch for more papers by this author Gideon Koren, Corresponding Author Gideon Koren Motherisk Program, Hospital for Sick Children, Toronto, Ontario M5G 1X8, CanadaMotherisk Program, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, CanadaSearch for more papers by this author First published: 16 December 2002 https://doi.org/10.1002/tera.10115AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume66, Issue6December 2002Pages 273-273 RelatedInformation
Background: Congenital Heart Defects (CHD) are conditions that encompass more than 50 diagnoses and are due to developmental abnormalities early in fetal life. The King Faisal Specialist Hospital and Research Centre in the Kingdom of Saudi Arabia treats approximately 100 new cases per month. We recently developed a new CHD Registry that captures, stores and processes our data via the Internet.Methods: The Registry was developed using Hypertext Markup Language (HTML), Microsoft Active Server Pages and Microsoft Structured Query Language (SQL)Results: Details of CHD cases are captured in a World Wide Web (WWW) Registry, permitting any browser-enabled PC or Mac to participate fully in all registry functions, including data-entry, viewing, editing, searching, reporting, validating, charting, and exporting data subsets to statistics packages. It includes "administrative" features and an active security system. The paper forms have been designed to reflect the "look and feel" of the Web pages. Automatic validation procedures are also included.Conclusions: Our Registry has been in operation for 3 years. It serves 10 PCs and contains more than 3,000 registered cases of CHD. It is the first CHD Registry to be fully functional on the Internet. It is also the first dedicated CHD registry, and the first to routinely report on the full spectrum of CHD diagnoses. The WWW offers several logistical advantages to disease registries, especially those that represent large regions. It also offers the possibility of sharing resources between registries, facilitating the aggregation and analysis of disease data on a world-wide scale. This is useful for rare diseases such as CHD (see http://rc.kfshrc.edu.sa/chdr/demo/).
BACKGROUND:Anal atresia is one of the more common birth defects affecting the gastrointestinal tract. This study examined the relationship between anal atresia and selected demographic and clinical factors in Hawaii.METHODS:Data were obtained from a population-based birth defects registry and included all cases of anal atresia identified in Hawaii among 1986-1999 deliveries.RESULTS:There were 124 cases of anal atresia, resulting in a rate of 4.38 per 10,000 live births and fetal deaths (95% confidence interval (CI) 3.65-5.23). Cases consisted of 115 (92.7%) live births, 6 (4.8%) fetal deaths, and 3 (2.4%) elective terminations. Chromosomal abnormalities were reported for 10 (8.1%) of the cases, 7 of which were trisomy 21. Family history of anal atresia was reported for 3 (2.4%) of the cases. No secular trend in anal atresia rates was identified (p=0.617). Risk of anal atresia was highest for the 25-29-year maternal age group and lower among younger and older maternal age groups. Risk for anal atresia was lower for females (relative risk (RR) 0.69 95% CI 0.51-0.91) and higher for live births with a birth weight less than 3,000 grams (RR 2.75, 95% CI 2.08-3.56) or less than 38 weeks' gestation (RR 3.90, 95% CI 2.88-5.15) and for multiple births (RR 3.34, 95% CI 1.44-6.57). Anal atresia rates did not vary significantly by maternal race/ethnicity, residence at delivery, gravidity, or prenatal care.CONCLUSIONS:Anal atresia risk was associated with maternal age, infant/fetus sex, birth weight, gestational age, and plurality but not maternal race/ethnicity, residence at delivery, gravidity, or prenatal care. Except for maternal age, these findings are consistent with the literature.
BACKGROUND:Pharmacological antagonism of VLA-4 (Very Late Antigen 4, alpha(4)beta(1) integrin) has become an attractive target for the treatment of predominantly eosinophil mediated disease states such as asthma, allergic rhinitis, multiple sclerosis, rheumatoid arthritis, diabetes, and inflammatory bowel disease. Gene knockouts of the alpha(4)-integrin subunit of VLA-4 or its cell surface ligand, VCAM-1, however, have been shown to result in embryo-lethality in homozygous null mice due to defects in chorio-allantoic or epi-myocardial fusion. Although gene knockout phenotypes are not always manifested by pharmacological antagonism, those studies suggested that VLA-4 antagonists might cause embryo-lethality or drug-induced malformations.METHODS:To test these concepts, early neurulating rat embryos were cultured by the methods of New ('78) after intra-coelomic microinjection of a VLA-4 blocking antibody or in the presence of small molecule VLA-4 antagonists.RESULTS:Defects in chorio-allantoic fusion were induced after microinjection of VLA4 blocking antibody and after continuous exposure to small molecule antagonists. In a minority of affected embryos chorio-allantoic fusion was completely blocked whereas the majority of affected embryos had only superficial chorio-allantoic fusion and the allantois was enlarged and edematous. Although the allantoic mesoderm covered the trophoblasts of the chorionic plate and contained blood vessels there was only minimal invasion of the trophoblasts by the allantoic mesoderm. The lowest observed effect level generally correlated with the IC(approximately 95), as determined in 90% plasma.DISCUSSION:Based on these data, VLA-4 antagonism might represent a significant risk to the developing embryo/fetus. In vitro exposure, however, is "constant" and does not take into account the elimination phase of these xenobiotics in vivo. Given the high concentrations required to elicit an effect, therapeutic blood levels in vivo may be several fold lower than those that affect the conceptus, depending on the tissue penetration of the compound and the route of administration. VLA-4 also exists in a range of conformations and activation states in vivo and the gene KOs and present studies do not define whether these developmental processes are dependent upon a particular activation state of VLA-4. Therefore, state-selective antagonists may have an improved embryonic safety profile. Additional studies will be required to determine potential effects of VLA-4 antagonists on embryo/fetal development in vivo.
TeratologyVolume 66, Issue 6 p. 274-274 Letter to the Editor Response to Gideon Koren's letter Thomas Shepard, Corresponding Author Thomas Shepard [email protected] Department of Pediatrics, University of Washington, Seattle, Washington 98195Department of Pediatrics, University of Washington, Seattle, WA 98195Search for more papers by this author Thomas Shepard, Corresponding Author Thomas Shepard [email protected] Department of Pediatrics, University of Washington, Seattle, Washington 98195Department of Pediatrics, University of Washington, Seattle, WA 98195Search for more papers by this author First published: 16 December 2002 https://doi.org/10.1002/tera.10114AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. LITERATURE CITED Amore BM, Kalhorn TF, Skiles GL, Hunter AP, Bennett GD, Finnell RH, Nelson SD, Slattery JT. 1997. Characterization of carbamazepine metabolism in a mouse model of carbamazepine teratogenicity. Drug Metabol Disposit 25: 953–962. CASPubMedWeb of Science®Google Scholar Blum S, Dial SL, Terry KK, Grafton TF, Hansen DK. 1996. Effect of rat hepatic S-9 fractions on CBZ-induced embryotoxicity in vitro. Teratology 53: 105–106. Google Scholar Volume66, Issue6December 2002Pages 274-274 ReferencesRelatedInformation
BACKGROUNDThe conduct of human research in the teratogenicity of drugs, chemicals, radiation and infections is needed in order to close critical gaps in knowledge.METHODSWe reviewed the various aspects of the ethics of conducting prospective human research in teratogenicity.RESULTSSuch research should respect the confidentiality of pregnant women and their families. Because this research is observational, interpretation of results is difficult, and the study design should strive to meet the highest possible scientific standards attainable in the particular research conditions. It should also be acknowledged that confidentiality cannot be always adhered to (e.g., if the interview reveals risks to minors).CONCLUSIONSIn general, the benefit risk ratio in this type of research is very favorable, although in specific cases the research follow-up may induce fears (e.g., drugs of abuse) in the woman being interviewed.
BACKGROUND:We present a case of partial facial duplication in a male infant.METHODS:The clinical, radiological, and laboratory findings for this patient are described, followed by a review of the literature.RESULTS:Craniofacial duplication is a rare form of conjoined twinning and presents in a wide spectrum, from dicephalus to diprosopus to partial facial duplication. Many of these cases can be diagnosed prenatally. Prenatal assessment of our patient revealed only agenesis of the corpus callosum.CONCLUSIONS:The pathogenesis is believed to involve duplication of the notochord. Where there are more severe associated anomalies, the prognosis is poor. Partial facial duplication, as in our case, is associated with fewer anomalies, and the prognosis is better. Symmetry and an excess of tissue, rather than deficiency, favor a positive result.
BACKGROUND The formation of the neural tube (neurulation) involves two mechanisms: primary and secondary neurulation. In chicks, there is also an overlap zone, where both mechanisms work together. Homocysteine (Hcy) may have an important teratogenic role in neural tube defects (NTD) when folic acid levels are considered normal. Recently, Hcy capability to generate NTD and modify neural crest cell migration has been demonstrated in chick embryos. This study was aimed to evaluate the effects of Hcy on neurulation and the development of the dorsal root ganglia (DRG). METHODS Chick embryos were treated with L-Hcy thiolactone 20 micromol to produce the highest rate of survival with embryos carrying neural tube defect (NTD) in the spine. Embryos at stages (st) 3-10 were treated and harvested at st 18-23. Only externally normal embryos or those carrying spinal NTD embryos were considered. RESULTS Histological sections of Hcy-treated embryos showed: open spina bifida (39% of embryos), more than one tube forming the spinal cord (26%), disorganized spinal cord (26%), always affecting lumbosacral regions, probably in the overlap zone. Additionally, 32% of embryos had small and continuous DRG, associated with a slimmed roof plate. Three-dimensional reconstruction showed unsegmented DRG until the C8 ganglion level. There was a 75% reduction of C3 DRG cells in treated embryos in comparison to untreated ganglia. CONCLUSION Hcy teratogenicity in avian embryos affected the neural tube in the overlap zone, secondary neurulation and the cervical DRG.
BACKGROUND:The HOX gene family consists of highly conserved transcription factors that specify the identity of the body segments along the anteroposterior axis of the embryo. Because the phenotypes of mice with targeted disruptions of Hox genes resemble some patterns of human malformations, mutations in HOX genes have been expected to be associated with a significant number of human malformations. Thus far, however, mutations have been documented in only three of the 39 human HOX genes (HOXD13, HOXA13, and HOXA11) partly because current knowledge on the complete coding sequence and genome structure is limited to only 20 of the 39 human HOX genes.METHODS:Taking advantage of the human and mouse draft genome sequences, we attempted to characterize the remaining 19 human HOX genes by bioinformatic analysis including phylogenetic footprinting, the probabilistic prediction method, and comparison of genomic sequences with the complete set of the human anonymous cDNA sequences.RESULTS:We were able to determine the full coding sequences of 19 HOX genes and their genome structure and successfully designed a complete set of PCR primers to amplify the entire coding region of each of the 39 HOX genes from genomic DNA.CONCLUSIONS:Our results indicate the usefulness of bioinformatic analysis of the draft genome sequences for clinically oriented research projects. It is hoped that the mutation panel provided here will serve as a launchpad for a new discourse on the genetic basis of human malformations.
TeratologyVolume 66, Issue 1 p. 4-5 Letter to the Editor Case-control study confirms the diagnosis-specific risk of maternal diabetes: Reply to Harold Kalter Christopher A. Loffredo, Corresponding Author Christopher A. Loffredo [email protected] Cancer Genetics and Epidemiology Program, Department of Oncology, Georgetown University, Washington, DCLombardi Cancer Center, Room S-153, Georgetown University, 3800 Reservoir Road, Washington, DC 20007Search for more papers by this authorCharlotte Ferencz, Charlotte Ferencz Department of Epidemiology & Preventive Medicine, University of Maryland, Baltimore, MDSearch for more papers by this author Christopher A. Loffredo, Corresponding Author Christopher A. Loffredo [email protected] Cancer Genetics and Epidemiology Program, Department of Oncology, Georgetown University, Washington, DCLombardi Cancer Center, Room S-153, Georgetown University, 3800 Reservoir Road, Washington, DC 20007Search for more papers by this authorCharlotte Ferencz, Charlotte Ferencz Department of Epidemiology & Preventive Medicine, University of Maryland, Baltimore, MDSearch for more papers by this author First published: 28 June 2002 https://doi.org/10.1002/tera.10045Citations: 2AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. LITERATURE CITED Ferencz C, Rubin JD, Loffredo CA, Magee CA. 1993. Epidemiology of congenital heart disease: the Baltimore–Washington Infant Study, 1981–89. Mt. Kisco, NY: Futura Publishing Co. Google Scholar Ferencz C, Loffredo CA, Correa-Villaseñor A, Wilson PD. 1997. Genetic and environmental risk factors of major cardiovascular malformations. Armonk, NY: Futura Publishing Co. Google Scholar Kuehl KS, Loffredo CA, Ferencz C. 1999. Failure to diagnose congenital heart disease in infancy. Pediatrics 103: 743–747. 10.1542/peds.103.4.743 CASPubMedWeb of Science®Google Scholar Loffredo CA, Wilson PD, Ferencz C. 2001. Maternal diabetes: an independent risk factor for major cardiovascular malformations with increased mortality of affected infants. Teratology 64: 98–106. 10.1002/tera.1051 CASPubMedWeb of Science®Google Scholar Loffredo, CA. 2001. The epidemiology of cardiovascular malformations: prevalence and risk factors. Am J Med Genet (Semin Med Genet) 97: 319–325. 10.1002/1096-8628(200024)97:4<319::AID-AJMG1283>3.0.CO;2-E Web of Science®Google Scholar Citing Literature Volume66, Issue1July 2002Pages 4-5 ReferencesRelatedInformation
TeratologyVolume 65, Issue 3 p. 105-105 Letter to the Editor The biology of cardiovascular malformations—At last! Reply to Dr. English Charlotte Ferencz, Corresponding Author Charlotte Ferencz cferencz@epi.umaryland.edu Department of Epidemiology and Preventive Medicine, University of Maryland, School of Medicine Baltimore, MD660 W. Redwood Street, Baltimore MD 21201Search for more papers by this author Charlotte Ferencz, Corresponding Author Charlotte Ferencz cferencz@epi.umaryland.edu Department of Epidemiology and Preventive Medicine, University of Maryland, School of Medicine Baltimore, MD660 W. Redwood Street, Baltimore MD 21201Search for more papers by this author First published: 15 February 2002 https://doi.org/10.1002/tera.10027AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume65, Issue3March 2002Pages 105-105 RelatedInformation
BACKGROUND:This study was conducted to: (1) determine whether women who have had a neural tube defect (NTD) affected pregnancy know about recommendations for NTD recurrence prevention; (2) educate them about the recommendations; and (3) ensure that they have access to folic acid prior to another pregnancy.METHODS:Colorado women who had an NTD affected pregnancy in 1999 or later were interviewed about their knowledge and use of folic acid, provided with verbal information about folic acid and NTD prevention, and offered written information and a voucher for free folic acid.RESULTS:Thirty-two of 68 women who had an NTD affected pregnancy were interviewed. Of these, 22 (69%) were aware of the 0.4 mg. folic acid recommendation for women of child bearing age who have not had an NTD affected pregnancy (MMWR, '91). Only 15 (47%) of the women knew about the U.S. Public Health Service recommendation (MMWR, '92) to consume 4.0 mg of folic acid prior to another pregnancy for NTD recurrence prevention. Twenty-five (78%) of the women reported taking a multivitamin or folic acid daily.CONCLUSIONS:Nine years after national folic acid recommendations, a majority of interviewed women (53%) with NTD affected pregnancies did not know about the recommendation to consume 4.0 mg of folic acid for NTD recurrence prevention. This sample of women are receptive to information about folic acid. Health care providers and public health officials should ensure that education about folic acid is provided in an effective and timely manner to women with NTD-affected pregnancies.
TeratologyVolume 66, Issue 3 p. 103-104 Letter to the Editor Unusual intrauterine sex hormone profiles as a potential cause of sex ratios typical of some malformations: Reply to Dr. James Joseph M. Lary, Corresponding Author Joseph M. Lary Epidemiologist Emeritus National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia2914 Yorktown Drive, Tuscaloosa, AL 35406Search for more papers by this author Joseph M. Lary, Corresponding Author Joseph M. Lary Epidemiologist Emeritus National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia2914 Yorktown Drive, Tuscaloosa, AL 35406Search for more papers by this author First published: 13 August 2002 https://doi.org/10.1002/tera.10080Citations: 4AboutRelatedInformationPDFPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessClose modalShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume66, Issue3September 2002Pages 103-104 RelatedInformation
Background: Nonsyndromic orofacial clefts have an estimated incidence of 1/1000 live births. Population genetic and embryologic studies suggest that cleft palate only (CPO) may be a distinct clinical entity from cleft lip with or without cleft palate (CL/P). Both CPO and CL/P are thought to be multifactorial in etiology, with evidence indicating that genetic, environmental, and developmental determinants may all play a role. The ARNT2 gene localizes to a conserved linkage group on mouse chromosome 7 that is syntenic with human chromosome 15q23-25. This chromosomal region was previously identified as a teratogen-induced clefting susceptibility locus in a genome-wide scan of AXB and BXA recombinant inbred mice. Arnt2 is expressed in the first branchial arch in mice. The teratogen 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) acts through the aryl hydrocarbon receptor (Ahr) pathway to produce dose-dependent CPO and thymic wasting in mice exposed in utero. Arnt2 and Ahr proteins dimerize in vitro. TCDD exposure is also associated with orofacial clefting in children of parents involved in agricultural work.Methods: To determine whether ARNT2 influences human craniofacial development, we identified the human ARNT2 gene and conducted genomic structural analysis. Mutational screening was performed in infants with nonsyndromic CPO or CL/P who were identified by the Iowa Birth Defects Registry.Results: A common amino acid polymorphism was detected but, no obvious disease-causing mutations were detected by SSCP analysis. The microsatellite marker, GATA89D04 (D15S823) was identified within intron 11 of the human ARNT2 gene, and linkage disequilibrium of nonsyndromic CPO and CL/P parent-infant trios was conducted.Conclusions: No association was demonstrated with CPO (n = 45) and CL/P (n = 37). (C) 2002 Wiley-Liss, Inc.
BACKGROUND Presently, bone ossification is assessed by the study of single-stained fetal bones (alizarin red-S) or double-stained bones and cartilaginous structures (alcian blue followed by alizarin red-S). Both methods, especially double-staining, are labor-intensive, time-consuming, and provide qualitative information regarding skeleton ossification. Quantitative evaluation of ossification is more difficult and is usually based on determination of calcium and other minerals in the bone by means of atomic absorption spectrometry. Here we introduce a simple new method that allows quantitative determination of skeleton ossification before routine staining examination. METHODS Fetuses delivered by laparotomy on the 16th and 21st day of gestation as well as 1-day-old rat pups were examined. The fetuses and pups were prenatally subcutaneously exposed to sodium valproate or to physiological saline. Lateral, prone, and supine digital radiograms of each fetus were taken using the Digora-Soredex digital radiography system and the Planmeca Intra intraoral X-ray machine. According to the best visualization, the data concerning vertebra were analyzed. All the fetuses were then routinely double-stained using alcian blue and alizarin red-S. RESULTS Malformations of axial skeleton (rib, sternum, and thoracic and sacral vertebra) were found in valproate-treated groups. Unlike cartilage malformations, the bone changes were detected in similar frequency in radiological and staining methods. Differences in densities according to the degree of ossification in the vertebral arches and bodies at different levels of the vertebral column, between drug-treated and negative control groups were noted. CONCLUSIONS The preliminary results suggest that digital radiography examination is a useful method in determining delaying of skeleton ossification not detectable by other methods. It balances qualitative and quantitative aspects of the presently used methods and is also simple, objective, fast, and relatively inexpensive.
BACKGROUND:Systemic lupus erythematosus (SLE) with or without evidence of antiphospholipid antibodies (aPA) and antiphospholipid syndrome (APS) is associated with a high rate of spontaneous abortions. The placenta is thought to be the site of pathological damage in many of these abortions. To test this hypothesis, we studied the effects of sera obtained from women with SLE with or without treatment on human placental explants in culture.METHODS:We cultured 5.5- to 7.5-week-old human placental explants in a culture medium containing F-12 DMEM and 10% FCS or in 90% human serum obtained from nonpregnant women with SLE prior to or after treatment. Culture was carried out for 96 hr. At the end of the culture period, we studied the secretion of the placental hormones estrogen (E2), progesterone (PGN), and human chorionic gonadotropin (hCG). In addition, we studied the proliferation rate (using PCNA staining) and the rate of apoptosis (using ApoTag) of the trophoblastic cells.RESULTS:Placentae grew better in normal human serum than in a chemically defined medium of F-12 DMEM and 10% FCS. Enhanced growth and higher secretion rates for hCG and estradiol (E2) were manifested in placentae cultured in control sera with no change in PGN secretion. Secretion rates of hCG and PGN (but not of E2 in the treated group) by placental explants were similar to that of controls. However, the serum levels prior to culture were not measured. Further, explants in serum from untreated women with SLE produced a significant decrease in the proliferation rate of the trophoblastic cells and an increase of apoptosis. Treatment significantly reduced the apoptotic rate and increased cell proliferation, but the cell proliferation rate was still lower than that noted in controls.CONCLUSIONS:We conclude that sera from women with SLE may directly damage the developing placenta reducing proliferation and enhancing apoptosis. Successful treatment of the women reduces that damage.
TeratologyVolume 66, Issue 2 p. 61-62 Letters to the Editor Classification of drugs for teratogenic risk: An anachronistic way of counseling Paul Merlob, Corresponding Author Paul Merlob [email protected] Beilinson Teratology Information Service, Department of Neonatology, and Drug Information Center, Rabin Medical Center, Beilinson Campus, Petah Tiqva and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelDepartment of Neonatology, Rabin Medical Center, Beilinson Campus, Petah Tiqva 49 100, IsraelSearch for more papers by this authorBracha Stahl, Bracha Stahl Beilinson Teratology Information Service, Department of Neonatology, and Drug Information Center, Rabin Medical Center, Beilinson Campus, Petah Tiqva and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelSearch for more papers by this author Paul Merlob, Corresponding Author Paul Merlob [email protected] Beilinson Teratology Information Service, Department of Neonatology, and Drug Information Center, Rabin Medical Center, Beilinson Campus, Petah Tiqva and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelDepartment of Neonatology, Rabin Medical Center, Beilinson Campus, Petah Tiqva 49 100, IsraelSearch for more papers by this authorBracha Stahl, Bracha Stahl Beilinson Teratology Information Service, Department of Neonatology, and Drug Information Center, Rabin Medical Center, Beilinson Campus, Petah Tiqva and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelSearch for more papers by this author First published: 22 July 2002 https://doi.org/10.1002/tera.10069Citations: 15AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. LITERATURE CITED Addis A, Sharabi S, Bonati M. 2000. Risk classification systems for drug use during pregnancy. Are they a reliable source of information? Drug Safety 23: 245–253. Alvan G, Danielsson BR, Kihlström I, Lundborg P, Prame B, Ridley E, Sannerstedt R. 1995. Classification of drugs for teratogenic risk. Eur J Clin Pharmacol 48: 177–178. American Academy of Pediatrics. 2000. Committee on drugs. Use of psychoactive medication during pregnancy and possible effects on the fetus and newborn. Pediatrics 105: 880–887. Australian Drug Evaluation Committee. 1989. Medicines in pregnancy. An Australian categorization of risk. Canberra: Australian Government Publishing Service. Beilinson Teratology Information Service. 1993. BELTIS Newsletter 1: 27–29. Beilinson Teratology Information Service. 1994. BELTIS Newsletter 2: 35–36. Briggs GG, Freeman RK, Yaffe SJ. 1994. Drugs in pregnancy and lactation. 4th Ed. Baltimore: Williams and Wilkins. FASS (Swedish System of Approved Drugs). 1993. Classification of medical products for use during pregnancy and lactation. The Swedish system. Stockholm: LINFO, Drug Information Ltd. Friedman JM, Little BB, Brent RL, Cordero JF, Hanson JW, Shepard TH. 1990. Potential human teratogenicity of frequently prescribed drugs. Obstet Gynecol 75: 594–599. McElhatton PR, Garbis HM, Elefant E, Vial T, Bellemin B, Mastroiacovo P, Arnon J, Rodriguez-Pinilla E, Schaefer C, Pexieder T, Merlob P, Dal Verme S. 1996. The outcome of pregnancy in 689 women exposed to therapeutic doses of antidepressants. A collaborative study of the European Network of Teratology Information Services (ENTIS). Reprod Toxicol 10: 285–294. Pastuszak A, Schick-Boschetto B, Zuber G, Feldkamp M, Pinelli M, Sihn S, Donnenfeld A, McCormack M, Leen-Mitchell M, Woodland C, et al. 1993. Pregnancy outcome following first trimester exposure to fluoxetine (Prozac). JAMA 269: 2246–2248. Schaefer C, Amoura-Elefant E, Vial T, Ornoy A, Garbis H, Robert E, Rodriguez-Pinilla E, Pexieder T, Prapas N, Merlob P. 1996. Pregnancy outcome after prenatal quinolone exposure. Evaluation of a case registry of the European Network of Teratology Information Services (ENTIS). Eur J Obstet Gynecol Reprod Biol 69: 83–89. Shader RS, Greenblatt DJ. 1995. More on drugs and pregnancy. J Clin Psychopharmacol 15: 1–2. Teratology Society Public Affairs Committee. 1994. FDA classification of drugs for teratogenic risk. Teratology 49: 446–447. Citing Literature Volume66, Issue2August 2002Pages 61-62 ReferencesRelatedInformation
