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Birth Defects (birth + defects)
Kinds of Birth Defects Terms modified by Birth Defects Selected AbstractsThe cause and prevention of human birth defects: What have we learned in the past 50 years?CONGENITAL ANOMALIES, Issue 1 2001Robert L. Brent ABSTRACT This review article dealig with the subject of "The Cause and Prevention of Human Birth Defects" was prepared in celebration of the 40th anniversary of the Japanese Teratology Society. It begins with recollections of some of the important contributions of Japanese scientists in the fields of teratology and embryology and a summary of the many scientific and medical accomplishments of the past 50 years in the fields of teratology, genetics, developmental biology, epidemiology and genetics. The review includes a summary of the drugs, chemicals and physical agents that have been documented to result in congenital malformations and reproductive effects when pregnant women are exposed during pregnancy. The principles of teratology were also summarized and emphasize that 1) no teratogenic agent can be described qualitatively as a teratogen, since a teratogenic exposure must include not only the agent, but also the dose and the time in pregnancy when the exposure occurs. 2) Even agents that have been demonstrated to result in malformatins cannot produce every type of malformation. 3) Known teratogens can be presumptively identified by the spectrum of malformations they produce. 4) It is easier to exclude an agent as a cause of birth defects than to definitively conclude that it was responsible for birth defects. 5) When evaluating the risk of exposures, the dose is a crucial component in determining the risk. 6) Teratogenic agents follow a toxicological dose response curve. This means that each teratogen has a threshold dose, below which, there is no risk of teratogenensis, no matter when in pregnancy the exposure occurred. 7) The evaluation of a child with congenital malformations connot be adequately performed unless it is approached with the same scholarship and detail, as is any other complicated medical problem. 8) Each physician must recognize the consequences of providing erroneous reproductive risks to pregnant women exposed to drugs and chemicals during pregnancy or alleging that a child's malformations are due to an environmental agent without performing a complete and scholarly evaluation. [source] Teratogenic Effects of Antiepileptic Drugs: Use of an International Database on Malformations and Drug Exposure (MADRE)EPILEPSIA, Issue 11 2000Carla Arpino Summary: Purpose: The study goal was to assess teratogenic effects of antiepileptic drugs (AEDs) through the use of a surveillance system (MADRE) of infants with malformations. Methods: Information on all malformed infants (1990,1996) with maternal first-trimester drug exposure was collected by the International Clearinghouse for Birth Defects and Monitoring Systems (ICBDMS). Cases were defined as infants presenting with a specific malformation, and controls were defined as infants presenting with any other birth defect. Exposure was defined by the use of AEDs during the first trimester of pregnancy. The association of AEDs with malformations was then estimated by calculating the odds ratios with 95% confidence intervals and testing their homogeneity among registries. Results: Among 8005 cases of malformations, 299 infants were exposed in utero to AEDs. Of those exposed to monotherapy, 65 were exposed to phenobarbital, 10 to methylphenobarbital, 80 to valproic acid, 46 to carbamazepine, 24 to phenytoin, and 16 to other AEDs. Associations were found for spina bifida with valproic acid. Infants exposed to phenobarbital and to methylphenobarbital showed an increased risk of oral clefts. Cardiac malformations were found to be associated with phenobarbital, methylphenobarbital, valproic acid, and carbamazepine. Hypospadias was associated with valproic acid. Porencephaly and other specified anomalies of brain, anomalies of face, coarctation of aorta, and limb reduction defects were found to be associated with valproic acid. Conclusions: Using the MADRE system, we confirmed known teratogenic effects of AEDs. We also found increased risks for malformations that had never been reported associated with AEDs or for which the association was suggested by case reports. [source] Birth defects caused by mutations in human GLI3 and mouse Gli3 genesCONGENITAL ANOMALIES, Issue 1 2010Ichiro Naruse ABSTRACT GLI3 is the gene responsible for Greig cephalopolysyndactyly syndrome (GCPS), Pallister,Hall syndrome (PHS) and Postaxial polydactyly type-A (PAP-A). Genetic polydactyly mice such as Pdn/Pdn (Polydactyly Nagoya), XtH/XtH (Extra toes) and XtJ/XtJ (Extra toes Jackson) are the mouse homolog of GCPS, and Gli3tmlUrtt/Gli3tmlUrt is produced as the mouse homolog of PHS. In the present review, relationships between mutation points of GLI3 and Gli3, and resulting phenotypes in humans and mice are described. It has been confirmed that mutation in the upstream or within the zinc finger domain of the GLI3 gene induces GCPS; that in the post-zinc finger region including the protease cleavage site induces PHS; and that in the downstream of the GLI3 gene induces PAP-A. A mimicking phenomenon was observed in the mouse homolog. Therefore, human GLI3 and mouse Gli3 genes have a common structure, and it is suggested here that mutations in the same functional regions produce similar phenotypes in human and mice. The most important issue might be that GCPS and PHS exhibit an autosomal dominant trait, but mouse homologs, such as Pdn/Pdn, XtH/XtH, XtJ/XtJ and Gli3tmlUrt/Gli3tmlUrt, are autosomal recessive traits in the manifestation of similar phenotypes to human diseases. It is discussed here how the reduced amounts of the GLI3 protein, or truncated mutant GLI3 protein, disrupt development of the limbs, head and face. [source] Assessing human germ-cell mutagenesis in the Postgenome Era: A celebration of the legacy of William Lawson (Bill) Russell,ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 2 2007Andrew J. Wyrobek Abstract Birth defects, de novo genetic diseases, and chromosomal abnormality syndromes occur in ,5% of all live births, and affected children suffer from a broad range of lifelong health consequences. Despite the social and medical impact of these defects, and the 8 decades of research in animal systems that have identified numerous germ-cell mutagens, no human germ-cell mutagen has been confirmed to date. There is now a growing consensus that the inability to detect human germ-cell mutagens is due to technological limitations in the detection of random mutations rather than biological differences between animal and human susceptibility. A multidisciplinary workshop responding to this challenge convened at The Jackson Laboratory in Bar Harbor, Maine. The purpose of the workshop was to assess the applicability of an emerging repertoire of genomic technologies to studies of human germ-cell mutagenesis. Workshop participants recommended large-scale human germ-cell mutation studies be conducted using samples from donors with high-dose exposures, such as cancer survivors. Within this high-risk cohort, parents and children could be evaluated for heritable changes in (a) DNA sequence and chromosomal structure, (b) repeat sequences and minisatellites, and (c) global gene expression profiles and pathways. Participants also advocated the establishment of a bio-bank of human tissue samples from donors with well-characterized exposure, including medical and reproductive histories. This mutational resource could support large-scale, multiple-endpoint studies. Additional studies could involve the examination of transgenerational effects associated with changes in imprinting and methylation patterns, nucleotide repeats, and mitochondrial DNA mutations. The further development of animal models and the integration of these with human studies are necessary to provide molecular insights into the mechanisms of germ-cell mutations and to identify prevention strategies. Furthermore, scientific specialty groups should be convened to review and prioritize the evidence for germ-cell mutagenicity from common environmental, occupational, medical, and lifestyle exposures. Workshop attendees agreed on the need for a full-scale assault to address key fundamental questions in human germ-cell environmental mutagenesis. These include, but are not limited to, the following: Do human germ-cell mutagens exist? What are the risks to future generations? Are some parents at higher risk than others for acquiring and transmitting germ-cell mutations? Obtaining answers to these, and other critical questions, will require strong support from relevant funding agencies, in addition to the engagement of scientists outside the fields of genomics and germ-cell mutagenesis. Environ. Mol. Mutagen., 2007. Published 2007 Wiley-Liss, Inc. [source] Birth defects in the child of a woman who had undergone a successful Kasai procedure for biliary atresiaANZ JOURNAL OF SURGERY, Issue 11 2009Abdelbasit Elsayed Ali MBBS, FRCS (Glasg), FRCS (Paed Surg) No abstract is available for this article. [source] Birth defects and preterm birth: Overlapping outcomes with a shared strategy for research and prevention,BIRTH DEFECTS RESEARCH, Issue 11 2009Siobhan M. Dolan First page of article [source] Contribution of birth defects to infant mortality in the United StatesBIRTH DEFECTS RESEARCH, Issue S1 2002Joann Petrini Background While overall infant mortality rates (IMR) have declined over the past several decades, birth defects have remained the leading cause of infant death in the United States. To illustrate how this leading cause of infant mortality impacts subgroups within the US population a descriptive analysis of the contribution of birth defects to infant mortality at the national and state level was conducted. Methods Descriptive analyses of birth defects-specific IMRs and proportionate infant mortality due to birth defects were conducted for the US using 1999 mortality data from the National Center for Health Statistics. In 1999, the change to ICD-10 impacted how cause-specific mortality rates were coded. Aggregated 1995-1998 state- birth defects infant death statistics were used for state comparisons. Results In 1999, birth defects accounted for nearly 1 in 5 infant deaths in the US. Variation in birth defects-specific IMRs were observed by maternal race with black infants having the highest rates when compared with other race groups. However, among black infants prematurity/low birthweight was the leading cause of death, followed by birth defects. There is substantial variation in state-specific birth defects IMRs and the state-specific proportion of infant deaths due to birth defects. Conclusions Birth defects remain the leading cause of infant death in the United States, despite the changes that resulted in 1999 from an update in the coding of cause of death from ICD-9 to ICD-10. While birth defects-specific IMRs provide an overall picture of fatal birth defects and a gauge of the impact of life-threatening anomalies, they represent only a fraction of the impact of birth defects, missing those who survive past infancy and those birth defects related losses in the antepartum period. Expansion and support of effective birth defects monitoring systems in each state that include the full spectrum of perinatal outcomes must be a priority. However, paralleling these efforts, analyses of this leading cause of infant mortality provide critical insight into perinatal health and should continue, with appropriate adjustments for the 1999 classification changes. Teratology 66:S3,S6, 2002. © 2002 Wiley-Liss, Inc. [source] Cell death in normal and abnormal developmentCONGENITAL ANOMALIES, Issue 1 2008Philip E. Mirkes ABSTRACT Research over the past 50 years has consistently documented that cell death is an integral part of both normal development and the etiology of birth defects; however, the significance of this cell death has been, until recently, unclear. Research published during the past 15 years has now shown that programmed cell death (PCD) and teratogen-induced cell death are genetically controlled processes (apoptosis) that play important roles in both normal and abnormal development. Therefore, the purpose of this review is to highlight what is known about PCD and teratogen-induced cell death and their relationships to the mechanisms of apoptosis and abnormal development. [source] Congenital malformations in infants whose mothers reported the use of folic acid in early pregnancy in Sweden.CONGENITAL ANOMALIES, Issue 4 2007A prospective population study ABSTRACT The use of folic acid prior to conception is generally recommended for the prevention of birth defects, notably neural tube defects. In a previous study from Sweden, based on interviews of women in early pregnancy, no such effect was found on the general malformation rate, but data for neural tube defects were scarce. Using data from the Swedish Medical Birth Register for the years 1995,2004, 20 891 women were identified who reported the use of folic acid in early pregnancy, but not of anticonvulsants. These women were compared to all other women who gave birth during the study period. Malformations in the infants born were identified from multiple sources. No reduction in the general malformation rate was seen among infants born to women who reported the use of folic acid (OR = 1.09, 95% CI 1.02,1.17) and no effect of neural tube defect rate was seen (RR = 1.35, 95% CI 0.82,2.22), based on 16 infants with neural tube defect whose mother reported the use of folic acid. No effect was seen on the rates of other malformations except for cardiac defects, where a statistically significant increased risk (notably for severe defects) was found (OR = 1.19, 95% CI 1.05,1.35). The effect of various deficiencies in data collection is discussed, but is unlikely to explain the lack of protective effect noticed. So far, it has not been possible to demonstrate a beneficial effect of folic acid supplementation on malformation risk in Sweden. A more complete ascertainment and detailed timing and dosage of folic acid use in a prospective study is recommended. [source] Patterns of chromosomal deletions identified by a birth defects registry, Hawaii, 1986,2003CONGENITAL ANOMALIES, Issue 2 2007Mathias B. Forrester ABSTRACT The aim of the investigation was to describe the chromosomal deletions identified by a birth defects registry with respect to the chromosomes involved, pregnancy outcome, method of diagnosis, inheritance, sex, and the diagnosis of major structural birth defects. Cases were derived from a population-based birth defects registry in Hawaii and comprised all infants and fetuses with chromosomal deletions delivered during 1986,2003. A total of 71 cases were identified through a statewide birth defects registry in Hawaii during 1986,2003. The chromosomes involved in the greatest proportion of deletions were chromosomes 22 (14.1%), 4 (11.3%), and 5 (11.3%). Live births accounted for 58 (81.7%) of the cases. Diagnosis was made by amniocentesis or chorionic villus sampling in 19 (26.8%) of the cases. Of the 18 cases with known inheritance, the deletion was inherited in 5 (27.8%) and de novo in 13 (72.2%). Males accounted for 28 (39.4%) and females for 43 (60.6%) of the cases. Major structural birth defects were identified in 51 (71.8%) of the cases. Chromosomal deletions do not appear to affect all chromosomes equally. Most of the chromosomal deletions that were detected occurred among live births and were de novo conditions. Infants and fetuses with chromosomal deletions are more likely to be females and to be associated with major structural birth defects. [source] Essential roles of Gli3 and sonic hedgehog in pattern formation and developmental anomalies caused by their dysfunctionCONGENITAL ANOMALIES, Issue 3 2006Jun Motoyama ABSTRACT Pattern formation along the body axis directs the proportion of different types of cells required for functional tissue structures. The secreted protein sonic hedgehog (Shh) and zinc finger transcription factor Gli3 are key players in pattern formation during brain and limb development; the antagonistic action of Shh towards Gli3 may be crucial for pattern formation. Recent findings from Shh/Gli3 double homozygous mutants suggest that a balance of both activities is required for the production of the normal proportion of different cell types during organogenesis. This conclusion contrasts with the alternative hypothesis that a Shh gradient directs the specification of several different cell types. The observations reviewed here offer a new perspective on understanding the pathogenesis of human birth defects caused by mutations of the Shh and Gli3 genes. [source] Descriptive epidemiology of anotia and microtia, Hawaii, 1986,2002CONGENITAL ANOMALIES, Issue 4 2005Mathias B. Forrester ABSTRACT The objective of this investigation was to describe the epidemiology of anotia and microtia with respect to various factors. The cases studied were all infants and fetuses with anotia or microtia identified by a population-based birth defects registry in Hawaii. The anotia and microtia rates were determined for selected factors and comparisons made among the subgroups by calculating the rate ratio (RR) and 95% confidence interval (CI). A total of 120 cases were identified, for a rate of 3.79 per 10 000 live births. The anotia and microtia rate increased during 1986,2002, although the trend was not significant (P = 0.715). Of 49 specific structural birth defects examined, four were found to be significantly more common in the presence of anotia and microtia. When compared with Caucasians, the anotia and microtia rates were higher among Far East Asians (RR 1.79, 95% CI 0.89,3.68), Pacific Islanders (RR 2.26, 95% CI 1.24,4.32), and Filipinos (RR 2.34, 95% CI 1.23,4.64). The defects were less common among females (RR 0.64, 95% CI 0.43,0.93) and more common with multiple birth (RR 3.72, 95% CI 1.66,7.33), birth weight <,2500 g (RR 3.35, 95% CI 2.04,5.30), and gestational age <38 weeks (RR 2.27, 95% CI 1.49,3.40). In conclusion, the rate for anotia and microtia increased in Hawaii during the study period. The rates for only a few structural birth defects were substantially greater than expected in association with anotia and microtia. Anotia and microtia rates varied significantly according to maternal race/ethnicity, infant sex, plurality, birth weight, and gestational age. [source] Assisted reproductive technologies and birth defectsCONGENITAL ANOMALIES, Issue 2 2005Kohei Shiota ABSTRACT In vitro fertilization (IVF) and other assisted reproductive technologies (ART) are effective treatments for infertility and are widely provided at infertility clinics. Although IVF and related ART procedures are generally considered safe, some studies have suggested an excess occurrence of major malformations, low birth-weight and other perinatal complications in babies conceived by ART. Further, it was recently reported that IVF and intracytoplasmic sperm injection (ICSI) are associated with imprinting disorders in the offspring such as Beckwith-Wiedemann syndrome and Angelman syndrome. Here we review the human and animal studies investigating the potential risks of ART, and discuss the need for further investigation. [source] Evaluating the accuracy of Malformations Surveillance Program in detecting virilization due to congenital adrenal hyperplasiaCONGENITAL ANOMALIES, Issue 1 2005Julie Travitz ABSTRACT Malformations surveillance programs of newborn infants have been developed as a method for identifying serious and relatively common birth defects. The virilization of newborn infants with the classic 21-hydroxylase form of congenital adrenal hyperplasia must be identified early if the associated metabolic crisis in the perinatal period is to be prevented. We compared the detection of virilization associated with 21-hydroxylase congenital adrenal hyperplasia in infants by three methods: an ,active' malformations surveillance of medical records at a large urban hospital; routine medical care by examining physicians; and newborn biochemical screening of blood samples. The experience at a large maternity center in Boston, since 1972, showed that pediatricians often recognized affected females (6/6), but not males (0/2); the state newborn screening program, begun in 1990, identified correctly all affected males and females. The Active Malformations Surveillance Program was the least effective screening method, identifying four of six affected females and neither of the affected males. The low rate of detecting affected females by the Surveillance Program was attributed to a failure to sensitize the research assistants to the importance of physicians' notations regarding the signs and symptoms of virilization. The failure of examining physicians, and thereby, the malformations surveillance program, to detect virilized newborn males was due to the lack of consistent associated physical features. These comparisons between these three methods of detection can be used to design and improve malformations surveillance programs. [source] The cause and prevention of human birth defects: What have we learned in the past 50 years?CONGENITAL ANOMALIES, Issue 1 2001Robert L. Brent ABSTRACT This review article dealig with the subject of "The Cause and Prevention of Human Birth Defects" was prepared in celebration of the 40th anniversary of the Japanese Teratology Society. It begins with recollections of some of the important contributions of Japanese scientists in the fields of teratology and embryology and a summary of the many scientific and medical accomplishments of the past 50 years in the fields of teratology, genetics, developmental biology, epidemiology and genetics. The review includes a summary of the drugs, chemicals and physical agents that have been documented to result in congenital malformations and reproductive effects when pregnant women are exposed during pregnancy. The principles of teratology were also summarized and emphasize that 1) no teratogenic agent can be described qualitatively as a teratogen, since a teratogenic exposure must include not only the agent, but also the dose and the time in pregnancy when the exposure occurs. 2) Even agents that have been demonstrated to result in malformatins cannot produce every type of malformation. 3) Known teratogens can be presumptively identified by the spectrum of malformations they produce. 4) It is easier to exclude an agent as a cause of birth defects than to definitively conclude that it was responsible for birth defects. 5) When evaluating the risk of exposures, the dose is a crucial component in determining the risk. 6) Teratogenic agents follow a toxicological dose response curve. This means that each teratogen has a threshold dose, below which, there is no risk of teratogenensis, no matter when in pregnancy the exposure occurred. 7) The evaluation of a child with congenital malformations connot be adequately performed unless it is approached with the same scholarship and detail, as is any other complicated medical problem. 8) Each physician must recognize the consequences of providing erroneous reproductive risks to pregnant women exposed to drugs and chemicals during pregnancy or alleging that a child's malformations are due to an environmental agent without performing a complete and scholarly evaluation. [source] Valproic acid-induced congenital malformations: Clinical and experimental observationsCONGENITAL ANOMALIES, Issue 4 2000R. Padmanabhan ABSTRACT With a large number of epileptic women being in the childbearing age group, complications of pregnancy in epileptic patients are of concern. Epileptic women are treated with antiepileptic drugs (AED) whether they are pregnant or not. Contrary to prevailing opinion, recent data suggest that epilepsy per se contributes significantly to birth defects possibly because of the same genetic susceptibility that predisposes to epilepsy. Many of these defects closely resemble those attributed to exposure to AED. The syndromes attributed to various AED also considerably overlap with each other. Valproic acid (VPA) induces several minor and major malformations. The relative risk for spina bifida in VPA exposed pregnancies is nearly 20 times higher than that for the general population and about 10 times higher than that attributed to other anticonvulsants. Fetuses of experimental animals treated with VPA during pregnancy exhibit exencephaly unlike the human offspring in whom VPA induces spina bifida. The cranial and spinal malformations observed in humans and laboratory animals indicate that VPA has a preferentially deleterious effect on the neural crest. Several AEDs including VPA tend to lower maternal plasma folate levels. In view of the beneficial effects of periconceptional folate supplementation in prevention of neural tube defects (NTD), future research should be directed at the role of folate in the possible alleviation of VPA-induced NTD. It is also necessary to continue prospective studies to monitor the old and new AED prescribed and to evaluate the role of interactions between drugs used in combinations. [source] Prevention of fetal alcohol spectrum disorders,DEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 3 2009R. Louise Floyd Abstract Alcohol use among women of childbearing age is a leading, preventable cause of birth defects and developmental disabilities in the United States. Although most women reduce their alcohol use upon pregnancy recognition, some women report drinking during pregnancy and others may continue to drink prior to realizing they are pregnant. These findings emphasize the need for effective prevention strategies for both pregnant and nonpregnant women who might be at risk for an alcohol-exposed pregnancy (AEP). This report reviews evidence supporting alcohol screening and brief intervention as an effective approach to reducing problem drinking and AEPs that can lead to fetal alcohol spectrum disorders. In addition, this article highlights a recent report of the National Task Force on Fetal Alcohol Syndrome and Fetal Alcohol Effect that describes effective interventions to reduce alcohol use and AEPs, and outlines recommendations on promoting and improving these strategies. Utilizing evidence-based alcohol screening tools and brief counseling for women at risk for an AEP and other effective population-based strategies can help achieve future alcohol-free pregnancies. © 2009 Wiley-Liss, Inc. Dev Disabil Res Rev 2009;15:193,199. [source] Epidemiology of Down syndromeDEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 3 2007Stephanie L. Sherman Abstract Down syndrome (DS) is the most commonly identified genetic form of mental retardation and the leading cause of specific birth defects and medical conditions. Traditional epidemiological studies to determine the prevalence, cause, and clinical significance of the syndrome have been conducted over the last 100 years. DS has been estimated to occur in ,1 in 732 infants in the United States, although there is some evidence that variability in prevalence of estimates exist among racial/ethnic groups. Progress has been made in characterizing the specific types of chromosome errors that lead to DS and in identifying associated factors that increase the risk of chromosome 21 malsegregation, i.e., advanced maternal age and recombination. Studies to examine the variability of the presence of specific DS-associated birth defects and medical conditions provide evidence for genetic and environmental modifiers. Here, we provide a brief survey of studies that address the current state of the field and suggest gaps in research that can soon be filled with new multidisciplinary approaches and technological advances. © 2007 Wiley-Liss, Inc. MRDD Research Reviews 2007;13:221,227. [source] From segment to somite: Segmentation to epithelialization analyzed within quantitative frameworksDEVELOPMENTAL DYNAMICS, Issue 6 2007Paul M. Kulesa Abstract One of the most visually striking patterns in the early developing embryo is somite segmentation. Somites form as repeated, periodic structures in pairs along nearly the entire caudal vertebrate axis. The morphological process involves short- and long-range signals that drive cell rearrangements and cell shaping to create discrete, epithelialized segments. Key to developing novel strategies to prevent somite birth defects that involve axial bone and skeletal muscle development is understanding how the molecular choreography is coordinated across multiple spatial scales and in a repeating temporal manner. Mathematical models have emerged as useful tools to integrate spatiotemporal data and simulate model mechanisms to provide unique insights into somite pattern formation. In this short review, we present two quantitative frameworks that address the morphogenesis from segment to somite and discuss recent data of segmentation and epithelialization. Developmental Dynamics 236:1392,1402, 2007. © 2007 Wiley-Liss, Inc. [source] Reprogramming of genetic networks during initiation of the Fetal Alcohol Syndrome,DEVELOPMENTAL DYNAMICS, Issue 2 2007Maia L. Green Abstract Fetal Alcohol Spectrum Disorders (FASD) are birth defects that result from maternal alcohol use. We used a non a priori approach to prioritize candidate pathways during alcohol-induced teratogenicity in early mouse embryos. Two C57BL/6 substrains (B6J, B6N) served as the basis for study. Dosing pregnant dams with alcohol (2× 2.9 g/kg ethanol spaced 4 hr on day 8) induced FASD in B6J at a higher incidence than B6N embryos. Counter-exposure to PK11195 (4 mg/kg) significantly protected B6J embryos but slightly promoted FASD in B6N embryos. Microarray transcript profiling was performed on the embryonic headfold 3 hr after the first maternal alcohol injection (GEO data series accession GSE1074). This analysis revealed metabolic and cellular reprogramming that was substrain-specific and/or PK11195-dependent. Mapping ethanol-responsive KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways revealed down-regulation of ribosomal proteins and proteasome, and up-regulation of glycolysis and pentose phosphate pathway in B6N embryos; and significant up-regulation of tight junction, focal adhesion, adherens junction, and regulation of the actin cytoskeleton (and near-significant up-regulation of Wnt signaling and apoptosis) pathways in both substrains. Expression networks constructed computationally from these altered genes identified entry points for EtOH at several hubs (MAPK1, ALDH3A2, CD14, PFKM, TNFRSF1A, RPS6, IGF1, EGFR, PTEN) and for PK11195 at AKT1. Our findings are consistent with the growing view that developmental exposure to alcohol alters common signaling pathways linking receptor activation to cytoskeletal reorganization. The programmatic shift in cell motility and metabolic capacity further implies cell signals and responses that are integrated by the mitochondrial recognition site for PK11195. Developmental Dynamics 236:613,631, 2007. © 2007 Wiley-Liss, Inc. [source] Recent advances in craniofacial morphogenesisDEVELOPMENTAL DYNAMICS, Issue 9 2006Yang Chai Abstract Craniofacial malformations are involved in three fourths of all congenital birth defects in humans, affecting the development of head, face, or neck. Tremendous progress in the study of craniofacial development has been made that places this field at the forefront of biomedical research. A concerted effort among evolutionary and developmental biologists, human geneticists, and tissue engineers has revealed important information on the molecular mechanisms that are crucial for the patterning and formation of craniofacial structures. Here, we highlight recent advances in our understanding of evo,devo as it relates to craniofacial morphogenesis, fate determination of cranial neural crest cells, and specific signaling pathways in regulating tissue,tissue interactions during patterning of craniofacial apparatus and the morphogenesis of tooth, mandible, and palate. Together, these findings will be beneficial for the understanding, treatment, and prevention of human congenital malformations and establish the foundation for craniofacial tissue regeneration. Developmental Dynamics 235:2353,2375, 2006. © 2006 Wiley-Liss, Inc. [source] Impact of congenital talipes equinovarus etiology on treatment outcomesDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 7 2008Christina A Gurnett MD Although congenital talipes equinovarus (CTEV) is often idiopathic, additional birth defects occur in some patients that may have an impact on the treatment of this disorder. The purpose of this study was to determine the prevalence of associated malformations, chromosomal abnormalities, or known genetic syndromes, and to compare treatment outcomes of children with idiopathic CTEV with children with non-idiopathic CTEV. Of 357 children evaluated, 273 (76%) had idiopathic CTEV (179 males, 94 females; mean age 2y 1mo [SD 1y 2mo], range 0,18y) and 84 (24%) had non-idiopathic CETV (51 males, 33 females; mean age 2y 5mo [SD 2y], range 0,16y). Disorders affecting the nervous system were found in 46 (54%) children with non-idiopathic CTEV. In a subgroup of patients treated entirely at our institution (n=196), children with non-idiopathic CTEV (n=47) required more casts for correction than those with idiopathic CTEV (n=149; 5.3 vs 4.6; p=0.016). There was also a greater risk of recurrence in non-idiopathic CTEV (14.9% vs 4%; p=0.009), but no significant difference in the need for extensive surgery (2.7% vs 8.5%; p=0.096). Treatment was initiated at a mean age of 13 weeks (range 1wk to 2y 6mo) for both idiopathic and non-idiopathic patients, and treatment was assessed during a minimum 2-year follow-up. Non-idiopathic CTEV can be successfully treated with the Ponseti method of serial casting, with low recurrence rates or need for surgery. [source] Folic acid and prevention of birth defectsDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 6 2002Don C Van Dyke MD First page of article [source] Navigating toward Fetal and Maternal Health: The Challenge of Treating Epilepsy in PregnancyEPILEPSIA, Issue 10 2004Torbjörn Tomson Summary:, A rational approach to the treatment of women of childbearing potential with epilepsy has been hampered by the lack of conclusive data on the comparative teratogenic potential of different antiepileptic drugs (AEDs). Although, several cohort studies on birth defects associated with AED use during pregnancy have been published, these have generally failed to demonstrate differences in malformation rates between AEDs, probably mainly due to insufficient power. In particular, pregnancies with new generation AEDs have been too few. In recent years, pregnancy registries have been introduced to overcome this problem,EURAP (an international collaboration), the North American, and the U.K. AED and pregnancy registries are observational studies that prospectively assess pregnancy outcome after AED exposure using slightly different methods. Each has enlisted 3,5,000 pregnancies in women with epilepsy, and the North American and the U.K. have released preliminary observations. Thus the U.K. registry reported a higher malformation rate with valproate, 5.9% (4.3,8.2%; 95% CI), than with carbamazepine, 2.3% (1.4,3.7%), and lamotrigine, 2.1% (1.0,4.0%). Most of the more recent cohort studies have also identified a nonsignificant trend toward a higher teratogenicity with valproate. These signals need to be interpreted with some caution since none of the studies to date have fully assessed the impact of possible confounders, such as type of epilepsy, family history of birth defects, etc. However, with increasing number of pregnancies it should be possible in the near future for the pregnancy registries to take such confounding factors into account and thus make more reliable assessments of the causal relationship between exposure to specific AEDs and teratogenic risks. While awaiting more conclusive results, it appears reasonable to be cautious in prescribing valproate to women considering to become pregnant if other suitable treatment alternatives, and with less teratogenic potential, are available. Any attempt to change treatment should, however, be accomplished well before conception. The importance of maintained seizure control must also be kept in mind, and the woman who needs valproate to control her seizures should not be discouraged from pregnancy, provided that counseling at the best of available knowledge is given. [source] Differential parental transmission of markers in RUNX2 among cleft case-parent trios from four populationsGENETIC EPIDEMIOLOGY, Issue 6 2008Jae Woong Sull Abstract Isolated cleft lip with or without cleft palate (CL/P) is among the most common human birth defects, with a prevalence around 1 in 700 live births. The Runt-related transcription factor 2 (RUNX2) gene has been suggested as a candidate gene for CL/P based largely on mouse models; however, no human studies have focused on RUNX2 as a risk factor for CL/P. This study examines the association between markers in RUNX2 and isolated, nonsyndromic CL/P using a case-parent trio design, while considering parent-of-origin effects. Case-parent trios from four populations (77 from Maryland, 146 from Taiwan, 35 from Singapore, and 40 from Korea) were genotyped for 24 single nucleotide polymorphisms (SNPs) in the RUNX2 gene. We performed the transmission disequilibrium test on individual SNPs. Parent-of-origin effects were assessed using the transmission asymmetry test and the parent-of-origin likelihood ratio test (PO-LRT). When all trios were combined, the transmission asymmetry test revealed a block of 11 SNPs showing excess maternal transmission significant at the P<0.01 level, plus one SNP (rs1934328) showing excess paternal transmission (P=0.002). For the 11 SNPs showing excess maternal transmission, odds ratios of being transmitted to the case from the mother ranged between 3.00 and 4.00. The parent-of-origin likelihood ratio tests for equality of maternal and paternal transmission were significant for three individual SNPs (rs910586, rs2819861, and rs1934328). Thus, RUNX2 appears to influence risk of CL/P through a parent-of-origin effect with excess maternal transmission. Genet. Epidemiol. 2008. © 2008 Wiley-Liss, Inc. [source] Factors Affecting Plan Choice and Unmet Need among Supplemental Security Income Eligible Children with DisabilitiesHEALTH SERVICES RESEARCH, Issue 5p1 2005Jean M. Mitchell Objective. To evaluate factors affecting plan choice (partially capitated managed care [MC] option versus the fee-for-service [FFS] system) and unmet needs for health care services among children who qualified for supplemental security income (SSI) because of a disability. Data Sources. We conducted telephone interviews during the summer and fall of 2002 with a random sample of close to 1,088 caregivers of SSI eligible children who resided in the District of Columbia. Research Design. We employed a two-step procedure where we first estimated plan choice and then constructed a selectivity correction to control for the potential selection bias associated with plan choice. We included the selectivity correction, the dummy variable indicating plan choice and other exogenous regressors in the second stage equations predicting unmet need. The dependent variables in the second stage equations include: (1) having an unmet need for any service or equipment; (2) having an unmet need for physician or hospital services; (3) having an unmet need for medical equipment; (4) having an unmet need for prescription drugs; (5) having an unmet need for dental care. Principal Findings. More disabled children (those with birth defects, chronic conditions, and/or more limitations in activities of daily living) were more likely to enroll in FFS. Children of caregivers with some college education were more likely to opt for FFS, whereas children from higher income households were more prone to enroll in the partially capitated MC plan. Children in FFS were 9.9 percentage points more likely than children enrolled in partially capitated MC to experience an unmet need for any type of health care services (p<.01), while FFS children were 4.5 percentage points more likely than partially capitated MC enrollees to incur a medical equipment unmet need (p<.05). FFS children were also more likely than partially capitated MC enrollees to experience unmet needs for prescription drugs and dental care, however these differences were only marginally significant. Conclusions. We speculate that the case management services available under the MC option, low Medicaid FFS reimbursements and provider availability account for some of the differences in unmet need that exist between partially capitated MC and FFS enrollees. [source] Study of four genes belonging to the folate pathway: transcobalamin 2 is involved in the onset of non-syndromic cleft lip with or without cleft palate,,HUMAN MUTATION, Issue 3 2006Marcella Martinelli Abstract Cleft lip with or without cleft palate (CL/P) is the most common inborn craniofacial anomaly. Affected individuals require extensive medical and psychosocial support. Although CL/P has a complex and poorly understood etiology, increasing evidence of folate pathway involvement has been collected. So far, only the MTHFR gene has been extensively investigated as a risk factor for CL/P, while little has been done to test genetic variations in the folate biosynthetic pathways that may influence the infant's susceptibility to these birth defects. To date, this paper presents the first attempt to verify the involvement of four genes belonging to the folate pathway in nonsyndromic cleft onset. We used a case-parent triad design to test for linkage disequilibrium in the case of seven SNPs mapping on four different genes: transcobalamin 1 and 2 (TCN1 and TCN2), methionine synthase (MTR), and MTR reductase (MTRR). Our finding suggests that TCN2 is involved in causing CL/P. Indeed, significant overtransmission of the C allele was observed at the polymorphism c.776C>G (p.Pro259Arg) to the affected offspring (P=0.01). Results obtained with additional TCN2 polymorphisms suggest that c.776C>G may be functionally related to CL/P. However, because conflicting data exist with regard to the effect of the polymorphism in transcobalamin 2 function or in perturbing plasma levels of key molecules in the folate pathway, further investigation is warranted to confirm our data. © 2006 Wiley-Liss, Inc. [source] Parenting and attachment among toddlers with congenital anomalies: Examining the Strange Situation and attachment Q-sortINFANT MENTAL HEALTH JOURNAL, Issue 6 2002Melissa Clements This study assessed parent and child predictors of attachment in a sample of 72 toddlers with neurological (e.g., cerebral palsy) and non-neurological (e.g., cleft lip and palate) birth defects and their mothers. Parenting quality (e.g., sensitivity) was expected to be more important in predicting the attachment relationship than type and severity of child medical condition. Parenting and indices of severity of child condition were measured via researcher observation. Attachment was measured via the Strange Situation and parent reported Attachment Q-sort. Parenting quality was better for children with more severe appearance disfigurements. Strange Situation and Q-sort assessments of attachment were not significantly related. Children with neurological impairments were at greater risk for developing insecure attachments than were children with non-neurological conditions. Parenting quality also directly predicted Strange Situation assessed attachment security and Q-sort comfort seeking/exploration but not standard Q-sort criterion scores. Parenting quality partially mediated the relation between child medical condition and attachment security. Results suggest child medical factors influence parenting, and thereby, child attachment. ©2002 Michigan Association for Infant Mental Health. [source] History, heresy and radiology in scientific discoveryJOURNAL OF MEDICAL IMAGING AND RADIATION ONCOLOGY, Issue 5 2009J McCredie Summary Nowadays, most drugs reach the market after research has established their pharmacology, safety and efficacy. That was not always the case 50 years ago. Thalidomide was used before its target cell or mode of action were known. Commencing with the thalidomide catastrophe , an epidemic of gross birth defects (1958,1962) , thalidomide's origins are revisited to show how this drug came to be made and sold in the 1950s. Thalidomide intersected with Australian radiology in the 1970s. The site and mode of action of the drug was deduced from X-rays of thalidomide-induced bone defects, which have classical radiological signs of sensory neuropathic osteoarthropathy. The longitudinal reduction deformities follow the distribution of segmental sensory innervation of the limb skeleton, indicating neural crest as the target organ. Injury to one level of neural crest halts normal neurotrophism and deletes the dependent segment , a previously unrecognised embryonic mechanism that explains most non-genetic birth defects. The final common pathway is neural crest injury and failure of normal neurotrophism to result in longitudinal reduction deformities, for example, phocomelia. [source] Toxoplasma gondii, HCV, and HBV seroprevalence and co-infection among HIV-positive and -negative pregnant women in Burkina FasoJOURNAL OF MEDICAL VIROLOGY, Issue 6 2006Jacques Simpore Abstract Toxoplasma gondii (T. gondii) infections can cause serious complications in HIV-infected pregnant women, leading to miscarriage, stillbirth, birth defects (e.g., mental retardation, blindness, epilepsy etc.) and could favor or enhance the mother-to-child transmission of HCV, HBV, and HIV vertical transmission. From May 20, 2004 to August 3, 2005, 336 18,45 years aged pregnant women, were enrolled for an investigation of the prevalence of serum antibodies against T. gondii, HCV, HBV, and HIV using ELISA. The prevalence of T. gondii, HCV, and HBV in pregnant women was 25.3%, 5.4%, and 9.8%, respectively and the HIV serostatus (61.6%) seems to be associated with greater prevalence rates of both T. gondii (28.5% vs. 20.2%) and HBV (11.6% vs. 7.0%). Without taking into account HIV, only 65.5% (220 of 336) of the women were not infected with these agents. The co-infection rate between HIV-infected and -negative women was different statistically: T. gondii/HBV 0.048 versus 0.015, T. gondii/HCV 0.014 versus 0.008, and HCV/HBV 0.005 versus 0.008, respectively. The elevated co-infection rate in HIV-positive women demonstrated that they are exposed to T. gondii, HCV, and HBV infections prevalently by sexual contact. J. Med. Virol. 78:730,733, 2006. © 2006 Wiley-Liss, Inc. [source] | |||||||||||||||||||||||||||||||