ABSTRACT
Genome sequencing is a very attractive technology as it is also the idea of sequencing children at birth, with the aim to establish medical care and preventive actions during their whole life, tailored to the genome of each newborn. Part I of this article analyses limitations and opportunities of next generation sequencing technologies (NGS). Part II relates scientific knowledge with ethical, legal and social issues (ELSIs) concerning its application to a newborn screening program. This program is offered universally to a vulnerable and asymptomatic population and must be guided by principles of "do not harm" and to act in the "best interest of child". With this purpose, this article considers, first of all, ethical principles of bioethics and public health that govern newborn screening. Then it summarizes main issues of our legal framework. And finally, in social context, it analyzes influences of technological imperative, commercial actors and patient´s advocacy groups, as well as parent's perspective and psychosocial aspects. In this context, conclusion is that whole genome sequencing should not be implemented as universal newborn screening. Nevertheless, the use of NGS could be an opportunity to extend these programs, including treatable infantile diseases that cannot be detected with other technologies. That means realizing a directed approach in order to identify well known genomic variants, highly penetrant, that confer a high risk of preventable or treatable diseases for which treatment must begin at the neonatal period. The implementation of such directed genomic screening should follow current evidence based model for newborn screening. This model shows three features: recognition of the importance of the evaluation of empirical, epidemiological and clinical data before taking the decision to include a disease; evaluation of benefits and risks (proportionality) and evaluation of benefits and costs (distributive justice); and finally, consideration of public consensus, because this kind of decisions have a value that concerns society as a whole.
La secuenciación genómica es una tecnología extraordinariamente atractiva, tanto como lo es la idea de poder aplicarla a todos los recién nacidos, estableciendo con ello una etapa de cuidados médicos para toda la vida y acciones preventivas a medida del genoma de cada niño. En la parte I de este artículo se analizaron las limitaciones y oportunidades que presentan las tecnologías de secuenciación de nueva generación (NGS). La parte II relaciona el conocimiento científico con los aspectos éticos, legales y sociales (AELS) de su introducción en un programa de cribado neonatal de salud pública de aplicación universal a población vulnerable y asintomática, que debe ser guiada por los principios fundamentales de "no hacer daño" y de actuar "en el mejor interés del niño". Para ello se contemplan en primer lugar los principios éticos de la medicina y de la salud pública que rigen el cribado neonatal, a continuación se resumen los principales aspectos de nuestro marco legal al respecto y finalmente en el ámbito social se analizan la influencia del imperativo tecnológico, la de los actores comerciales, los grupos de apoyo de pacientes y por último la perspectiva de los padres y aspectos psicosociales. Las conclusiones son que en este contexto la secuenciación genómica completa no debe ser implementada como cribado neonatal universal, sin embargo el uso de las NGS podría ser una oportunidad para ampliar los programas incluyendo enfermedades infantiles tratables que no pudiesen ser detectadas con otros métodos. Realizando para ello una aproximación dirigida a enfermedades/genes concretos, a fin de identificar variantes genómicas bien conocidas, altamente penetrantes confiriendo riesgo elevado de enfermedad prevenible o tratable, para la cual el tratamiento deba iniciarse en el periodo neonatal. Su incorporación al cribado neonatal debería seguir el modelo actual basado en la evidencia, evaluando los datos empíricos, epidemiológicos y clínicos antes de tomar una decisión sobre la inclusión de una enfermedad, así como los beneficios y riesgos (proporcionalidad) y si los beneficios justifican los costes (justicia distributiva), tomando en consideración el consenso público en tanto que las decisiones tienen una carga de valores que conciernen a la sociedad en su conjunto.
Subject(s)
High-Throughput Nucleotide Sequencing , Neonatal Screening , Child , Genomics , Human Genetics , Humans , Infant, Newborn , Public Health , Spain , TechnologyABSTRACT
La secuenciación genómica es una tecnología extraordinariamente atractiva, tanto como lo es la idea de poder aplicarla a todos los recién nacidos, estableciendo con ello una etapa de cuidados médicos para toda la vida y acciones preventivas a medida del genoma de cada niño. En la parte I de este artículo se analizaron las limitaciones y oportunidades que presentan las tecnologías de secuenciación de nueva generación (NGS). La parte II relaciona el conocimiento científico con los aspectos éticos, legales y sociales (AELS) de su introducción en un programa de cribado neonatal de salud pública de aplicación universal a población vulnerable y asintomática, que debe ser guiada por los principios fundamentales de no hacer daño y de actuar en el mejor interés del niño. Para ello se contemplan en primer lugar los principios éticos de la medicina y de la salud pública que rigen el cribado neonatal, a continuación se resumen los principales aspectos de nuestro marco legal al respecto y finalmente en el ámbito social se analizan la influencia del imperativo tecnológico, la de los actores comerciales, los grupos de apoyo de pacientes y por último la perspectiva de los padres y aspectos psicosociales. Las conclusiones son que en este contexto la secuenciación genómica completa no debe ser implementada como cribado neonatal universal, sin embargo el uso de las NGS podría ser una oportunidad para ampliar los programas incluyendo enfermedades infantiles tratables que no pudiesen ser detectadas con otros métodos. Realizando para ello una aproximación dirigida a enfermedades/genes concretos, a fin de identificar variantes genómicas bien conocidas, altamente penetrantes confiriendo riesgo elevado de enfermedad prevenible o tratable, para la cual el tratamiento deba iniciarse en el periodo neonatal.(AU)
Genome sequencing is a very attractive technology as it is also the idea of sequencing children at birth, with the aim to establish medical care and preventive actions during their whole life, tailored to the genome of each newborn. Part I of this article analyses limitations and opportunities of next generation sequencing technologies (NGS). Part II relates scientific knowledge with ethical, legal and social issues (ELSIs) concerning its application to a newborn screening program. This program is offered universally to a vulnerable and asymptomatic population and must be guided by principles of do not harm and to act in the best interest of child. With this purpose, this article considers, first of all, ethical principles of bioethics and public health that govern newborn screening. Then it summarizes main issues of our legal framework. And finally, in social context, it analyzes influences of technological imperative, commercial actors and patient ́s advocacy groups, as well as parents perspective and psychosocial aspects. In this context, conclusion is that whole genome sequencing should not be implemented as universal newborn screening. Nevertheless, the use of NGS could be an opportunity to extend these programs, including treatable infantile diseases that cannot be detected with other technologies. That means realizing a directed approach in order to identify well known genomic variants, highly penetrant, that confer a high risk of preventable or treatable diseases for which treatment must begin at the neonatal period. The implementation of such directed genomic screening should follow current evidence based model for newborn screening.(AU)
Subject(s)
Humans , Human Genetics , Neonatal Screening , Whole Genome Sequencing , Infant, Newborn , Genome, Human , Genome Components , Genomics , Principle-Based Ethics , Spain , Public HealthABSTRACT
In 2003 at the ending of the Human Genome Project, it aroused the idea that all newborns could be sequenced and its genome archived in the clinical record, in order to manage risks of diseases and response to medicaments along his whole life. Eighteen years later, promises of genomic medicine and tremendous decrease of costs of next generation sequencing technologies, continues feeding this dream that shows important practical, ethical and social challenges and genomic sequencing is presented as the next historical change in newborn screening programs. In this paper we analyze challenges and opportunities of next generation sequencing technologies, their real costs, problems associated to management, storage and protection of the enormous amount of genomic data produced and finally, according to conclusions of recent researches, there are considered the conclusions in two contexts, sick newborn with diagnostic purposes and healthy asymptomatic newborns with public health purposes (newborn screening programs). In a second part of this article it will be considered ethical, legal and social issues (ELSI). Final objective is to contribute to scientific, professional, ethics and social debate in order to promote that genome sequencing in newborn don't be used indiscriminately constituting a risk, but properly done, as a partner in the promotion of health and prevention of consequences of genetic diseases.
En 2003, cuando finalizó el Proyecto Genoma Humano, surgió la idea de secuenciar el genoma a todos los recién nacidos, archivarlo en la historia clínica y usarlo a lo largo de toda la vida para manejar riesgos de enfermedades y respuesta a medicamentos. Dieciocho años más tarde, las promesas de la medicina genómica y el extraordinario abaratamiento de las tecnologías secuenciadoras, siguen alimentando este sueño que todavía plantea grandes desafíos prácticos, éticos y sociales y la secuenciación genómica se presenta como el próximo gran cambio histórico en los programas de cribado neonatal. En el presente artículo, se analizan los retos y oportunidades de las tecnologías secuenciadoras de nueva generación, sus costos reales, la problemática inherente a la gestión, almacenamiento y protección de la enorme cantidad de datos genómicos que generan y finalmente, en base a las conclusiones de investigaciones recientes, se considera el potencial y limitaciones de su aplicación en dos escenarios, el recién nacido enfermo con finalidades diagnósticas y el recién nacido sano, asintomático, con finalidades de salud pública(programas de cribado neonatal). En una segunda parte de este artículo se tendrán en cuenta los aspectos éticos, legales y sociales (AELS). El objetivo final es contribuir al debate científico, profesional, ético y social, promoviendo que la secuenciación genómica en el recién nacido no sea usada indiscriminadamente constituyendo un riesgo, sino que bien empleada sea una aliada en la promoción de la salud y prevención de las consecuencias de las enfermedades genéticas.
Subject(s)
High-Throughput Nucleotide Sequencing , Neonatal Screening , Genomics , Human Genetics , Humans , Infant, Newborn , SpainABSTRACT
En 2003, cuando finalizó el Proyecto Genoma Humano, surgió la idea de secuenciar el genoma a todos los recién nacidos, archivarlo en la historia clínica y usarlo a lo largo de toda la vida para manejar riesgos de enfermedades y respuesta a medicamentos. Dieciocho años más tarde, las promesas de la medicina genómica y el extraordinario abaratamiento de las tecnologías secuenciadoras, siguen alimentando este sueño que todavía plantea grandes desafíos prácticos, éticos y sociales y la secuenciación genómica se presenta como el próximo gran cambio histórico en los programas de cribado neonatal. En el presente artículo, se analizan los retos y oportunidades de las tecnologías secuenciadoras de nueva generación, sus costos reales, la problemática inherente a la gestión, almacenamiento y protección de la enorme cantidad de datos genómicos que generan y finalmente, en base a las conclusiones de investigaciones recientes, se considera el potencial y limitaciones de su aplicación en dos escenarios, el recién nacido enfermo con finalidades diagnósticas y el recién nacido sano, asintomático, con finalidades de salud pública(programas de cribado neonatal). En una segunda parte de este artículo se tendrán en cuenta los aspectos éticos, legales y sociales (AELS). El objetivo final es contribuir al debate científico, profesional, ético y social, promoviendo que la secuenciación genómica en el recién nacido no sea usada indiscriminadamente constituyendo un riesgo, sino que bien empleada sea una aliada en la promoción de la salud y prevención de las consecuencias de las enfermedades genéticas.(AU)
In 2003 at the ending of the Human Genome Project, it aroused the idea that all newborns could be sequenced and its genome archived in the clinical record, in order to manage risks of diseases and response to medicaments along his whole life. Eighteen years later, promises of genomic medicine and tremendous decrease of costs of next generation sequencing technologies, continues feeding this dream that shows important practical, ethical and social challenges and genomic sequencing is presented as the next historical change in newborn screening programs. In this article we analyze challenges and opportunities of next generation sequencing technologies, their real costs, problems associated to management, storage and protection of the enormous amount of genomic data produced and finally, according to conclusions of recent researches, there are considered the conclusions in two contexts, sick newborn with diagnostic purposes and healthy asymptomatic newborns with public health purposes (newborn screening programs). In a second part of this article it will be considered ethical, legal and social issues (ELSI). Final objective is to contribute to scientific, professional, ethics and social debate in order to promote that genome sequencing in newborn dont be used indiscriminately constituting a risk, but properly done, as a partner in the promotion of health and prevention of consequences of genetic diseases.(AU)
Subject(s)
Humans , Infant, Newborn , Human Genetics , Genetic Testing , Neonatal Screening , Exome Sequencing , Whole Genome Sequencing , Public Health , Social Medicine , SpainABSTRACT
Decision making for the development of newborn screening programs is based on not only medical but also social concerns and involves different stakeholders. Part III of the article focuses on their role in the governance of the programs. First of all, we consider the proactive role that health authorities has played in the evolution to an evidentiary model of policy development currently based on evidence, just as in the preparation of an expert, impartial and transparent opinion on health policy and its coordination with the national health system. And, in accordance with this evidence and with the consensus, health autorities following quality criteria have made an attempt to achieve a more homogeneous approach of the neonatal screening program throughout the territory. Secondly, we address the role of several scientific and professional societies in newborn screening. Among them, it deserves to be mentioned the Spanish Society for Clinical Chemistry, currently Spanish Society of Laboratory Medicine (SEQCML), and its Commission of inborn errors of metabolism and the Spanish Society for Newborn Screening (AECNE), which since 1985 and for thirty three years collected the activity of newborn screening centers and established a forum for debate, sharing of knowledge and cooperation among screening centers and with health authorities. Since 1999, the Spanish Society for Inborn Errors of Metabolism (AECOM) exercises an important activity in the field of diagnosis treatment and follow up of patients. Finally, we consider the role of families and the psychosocial aspects of the programme, and the associative activity of patient organizations. In 1990 the Spanish federation of PKU and other disorders (FAEPKU) was found, renamed currently as The Spanish Federation of Inherited Metabolic Diseases; together with the Spanish Federation for Rare Diseases (FEDER), found in 1999, they both have clearly contributed to the patient's empowerment, supporting research and education and establishing a network of cooperation and support for patients and their families. Patient organizations collaborate with health authorities but they have not participated in policy decision making yet. During this half century, the evolution of newborn screening programs have been characterized for a spirit of improvement, by including the development of ethical, legal and social issues. Important technological challenges lie ahead and it will be necessary to know how to use them efficiently, proportionally and fairly in the best interest of newborns and by extension of their family and society.
Las bases para la toma de decisiones acerca del desarrollo de los programas de cribado de Salud Pública no son exclusivamente médicas, sino también sociales. En esta parte III del artículo se contemplan los actores que intervienen en la gobernanza de los programas, cómo son las autoridades sanitarias, las sociedades científicas y profesionales, así como las familias y su movimiento asociativo. En primer lugar, se analiza el papel de las instituciones/autoridades sanitarias en el desarrollo de los programas y en la evolución del modelo para la toma de decisiones, hasta el actual basado en la evidencia, así como en la elaboración de una opinión experta, imparcial y transparente en política sanitaria y su coordinación en el marco del Sistema Nacional de Salud (SNS). Y, de acuerdo con dicha evidencia y con el consenso, las instituciones/autoridades sanitarias han tratado de conseguir un abordaje más homogéneo y conforme a criterios de calidad del programa de cribado neonatal en todo el territorio. A continuación, se aborda el papel de las sociedades científicas y profesionales, especialmente de la Sociedad Española de Química Clínica (actualmente Sociedad Española de Medicina de Laboratorio (SEQCML), a través de la Comisión de Errores Congénitos del Metabolismo, y de la Asociación Española de Cribado Neonatal (AECNE), que desde 1985 y durante 33 años recogieron los datos de actividad de los centros de cribado y establecieron un foro de debate, intercambio de conocimientos y colaboración entre ellos y con las autoridades sanitarias. De ellas, destaca el importante papel de la Asociación Española de Errores Congénitos del Metabolismo (AECOM) desde 1999 en el diagnóstico, seguimiento y tratamiento de los pacientes. Finalmente, se contempla el papel de las familias y los aspectos psicosociales del programa, así como la evolución del movimiento asociativo, con especial mención a la fundación en 1990 de la Federación Española de PKU y otros trastornos (FAEPKU) (que pasó después a llamarse la Federación Española de Enfermedades Metabólicas Hereditarias) y en 1999 de la Federación Española de Enfermedades Raras (FEDER). Estas asociaciones han contribuido notablemente al empoderamiento de los pacientes, a apoyar la investigación y la formación y a establecer una red de colaboración y soporte para los pacientes y sus familias. Y aunque están en contacto y colaboran con las autoridades sanitarias, hasta el momento no han participado en la elaboración de decisiones y en la gobernanza de los programas. El espíritu de superación y mejora ha marcado la evolución de los programas durante este medio siglo al incluir el desarrollo de sus aspectos éticos, legales y sociales. Se avecinan desafíos tecnológicos importantes y habrá que saber utilizarlos con eficiencia, proporcionalidad y justicia en el mejor interés del niño y, por extensión, de la familia y de la sociedad.
Subject(s)
Neonatal Screening/history , Health Policy , History, 20th Century , Humans , Infant, Newborn , Neonatal Screening/ethics , Neonatal Screening/legislation & jurisprudence , Social Responsibility , SpainABSTRACT
Varios miembros de diferentes asociaciones científicas y expertos de la reproducción han actualizado las recomendaciones de estudio genético e inmunológico en las parejas con disfunción en la reproducción con el fin de mejorar la asistencia sanitaria. El estudio se ha considerado altamente recomendable cuando la prueba diagnóstica es relevante para la toma de decisiones, moderada cuando estas han mostrado un resultado poco consistente y baja, cuando el beneficio de la prueba es incierto. Con la indicación de estas recomendaciones obtendremos una información relevante para el diagnóstico, pronóstico y tratamiento de la pareja con disfunción en la reproducción
In this article several members of diverse scientific associations and reproduction experts from Spain have updated different genetic and immunological procedure recommendations in couples affected by reproductive dysfunction with the goal of providing a set of useful guidelines for the clinic. The laboratory test has been considered as highly recommendable for making clinical decisions when the result of the diagnostic test is relevant, moderately recommendable when the results are of limited evidence because they are inconsistent, and low when the benefit of the test is uncertain. It is expected that these recommendations will provide some useful guidelines for the diagnosis, prognosis and treatment of couples presenting reproductive dysfunction
Subject(s)
Humans , Infertility/diagnosis , Immunologic Tests/methods , Genetic Testing/methods , Reproductive Techniques/ethics , Abortion, Habitual/genetics , Cytogenetic Analysis/methods , Reproductive Physiological Phenomena/genetics , Reproductive Physiological Phenomena/immunology , Practice Patterns, Physicians' , Genetic Counseling/organization & administration , Infertility, Male/genetics , Genetic Diseases, Inborn/prevention & controlABSTRACT
No disponible
Subject(s)
Humans , Genetic Testing/methods , Genetic Testing/standards , Products of Consumer Direct Sale , Direct-To-Consumer Screening and Testing/standards , Treatment Outcome , Societies/standards , Genetic Testing/ethics , Patient Comfort/standardsSubject(s)
Direct-To-Consumer Screening and Testing/ethics , Genetic Testing/ethics , Confidentiality , Direct-To-Consumer Screening and Testing/legislation & jurisprudence , Direct-To-Consumer Screening and Testing/psychology , Direct-to-Consumer Advertising/ethics , Direct-to-Consumer Advertising/legislation & jurisprudence , Ethics Committees , Ethics, Business , Genetic Testing/legislation & jurisprudence , Genetics, Medical , Government Agencies , Humans , Personal Autonomy , Precision Medicine , Risk , Societies, Scientific , Spain , Truth Disclosure , United Kingdom , United States , United States Food and Drug AdministrationABSTRACT
Varios miembros de diferentes asociaciones científicas y expertos de la reproducción han actualizado las recomendaciones de estudio genético e inmunológico en las parejas con disfunción en la reproducción con el fin de mejorar la asistencia sanitaria. El estudio se ha considerado altamente recomendable cuando la prueba diagnóstica es relevante para la toma de decisiones, moderada cuando estas han mostrado un resultado poco consistente y baja, cuando el beneficio de la prueba es incierto. Con la indicación de estas recomendaciones obtendremos una información relevante para el diagnóstico, pronóstico y tratamiento de la pareja con disfunción en la reproducción
In this article several members of diverse scientific associations and reproduction experts from Spain have updated different genetic and immunological procedure recommendations in couples affected by reproductive dysfunction with the goal of providing a set of useful guidelines for the clinic. The laboratory test has been considered as highly recommendable for making clinical decisions when the result of the diagnostic test is relevant, moderately recommendable when the results are of limited evidence because they are inconsistent, and low when the benefit of the test is uncertain. It is expected that these recommendations will provide some useful guidelines for the diagnosis, prognosis and treatment of couples presenting reproductive dysfunction
Subject(s)
Humans , Male , Female , Reproduction/genetics , Tissue and Organ Procurement/methods , Reproduction/immunology , Prognosis , Reproduction/ethics , Infertility, Male/genetics , Epigenesis, GeneticABSTRACT
In this article several members of diverse scientific associations and reproduction experts from Spain have updated different genetic and immunological procedure recommendations in couples affected by reproductive dysfunction with the goal of providing a set of useful guidelines for the clinic. The laboratory test has been considered as highly recommendable for making clinical decisions when the result of the diagnostic test is relevant, moderately recommendable when the results are of limited evidence because they are inconsistent, and low when the benefit of the test is uncertain. It is expected that these recommendations will provide some useful guidelines for the diagnosis, prognosis and treatment of couples presenting reproductive dysfunction.
Subject(s)
Infertility, Female/genetics , Infertility, Female/immunology , Infertility, Male/genetics , Infertility, Male/immunology , Chromosome Aberrations , Donor Conception/standards , Epigenesis, Genetic , Female , Genetic Diseases, Inborn/diagnosis , Genetic Testing/classification , Genetic Testing/standards , Humans , Male , Reproduction/ethics , Sex FactorsABSTRACT
This study is part of the BioMadrid Project, a bio-monitoring study designed to assess pollutants in the environment surrounding children born in the Madrid region. Our aim in this report is to evaluate the association between prenatal lead exposure and fetal development using three biological samples (maternal and paternal blood lead at around 34 weeks of gestation as well as cord blood lead levels), three biomarkers of effect in cord blood peripheral lymphocytes (micronucleus in binucleated cells, nucleoplasmic bridges, and nuclear buds), and different anthropometrical characteristics at birth. Maternal and cord blood lead were not associated with newborn measurements or genotoxicity biomarkers. In contrast, increases in father blood lead were coupled with lower weight (mean difference (MD), -110.8 g; 95% confidence intervals (95%CI), -235.6 to 6.00; p < 0.10) and shorter abdominal (MD, -0.81 cm; 95%CI, -1.64 to 0.00; p < 0.05) and cephalic (MD, -0.32 cm; 95%CI, -0.65 to 0.00; p < 0.05) circumferences at birth as well as with the presence of nucleoplasmic bridges (odds ratio, 1.03; 95%CI, 1.00 to 1.06; p < 0.05) and nuclear buds (odds ratio, 1.02; 95%CI, 0.99 to 1.04; p < 0.10). These associations were mainly confined to female babies, in whom paternal lead was also inversely associated with length. Our results support the hypothesis that paternal lead exposure may be affecting the development of newborns.
Subject(s)
Environmental Exposure , Environmental Monitoring/methods , Environmental Pollutants/blood , Fetal Blood/chemistry , Lead/blood , Paternal Exposure , Adult , Biomarkers/blood , Female , Humans , Infant , Infant, Newborn , Lead/chemistry , Male , Pregnancy , Spain , Urban PopulationABSTRACT
BACKGROUND: In Spain, few studies have evaluated prenatal exposure to heavy metals. The objective of this study was to describe lead, mercury and cadmium concentrations in blood from a sample of newborn-mother-father trios, as well as to investigate the association between metals in cord blood and parental variables. We also explored the relationship between cord blood metal concentrations and child characteristics at birth. METHODS: Metal correlations among family members were assessed using Spearman Rank Correlation Coefficient. Linear regression was used to explore the association between parental variables and log-transformed cord blood lead and cord blood mercury concentrations. In the case of cadmium, tobit regression was used due to the existence of samples below the detection limit. The association between cord blood metal concentrations and child characteristics at birth was evaluated using linear regression. RESULTS: Geometric means for lead, mercury and cadmium were 14.09 µg/L, 6.72 µg/L and 0.27 µg/L in newborns; 19.80 µg/L, 3.90 µg/L and 0.53 µg/L in pregnant women; and 33.00 µg/L, 5.38 µg/L and 0.49 µg/L in men. Positive correlations were found between metal concentrations among members of the trio. Lead and cadmium concentrations were 15% and 22% higher in newborns from mothers who smoked during pregnancy, while mercury concentrations were 25% higher in newborns from mothers with greater fish intake. Cord-blood lead levels showed seasonal periodicity, with lower concentrations observed in winter. Cord blood cadmium concentrations over 0.29 µg/L were associated with lower 1-minute and 5-minute Apgar scores. CONCLUSIONS: These results reinforce the need to establish biomonitoring programs in Spain, and provide support for tobacco smoke and fish consumption as important preventable sources of heavy metal exposure in newborns. Additionally, our findings support the hypothesis that cadmium exposure might be deleterious to fetal development.
Subject(s)
Environmental Pollutants/adverse effects , Fetal Blood/chemistry , Maternal-Fetal Exchange , Metals, Heavy/blood , Pregnancy Outcome , Premature Birth , Adult , Cadmium/blood , Cohort Studies , Environmental Monitoring/methods , Female , Fetal Development/physiology , Gestational Age , Humans , Infant, Newborn , Lead/blood , Linear Models , Male , Maternal Exposure/adverse effects , Mercury/blood , Multivariate Analysis , Needs Assessment , Paternal Exposure/adverse effects , Pilot Projects , Pregnancy , Spain , Urban PopulationABSTRACT
Micronuclei are structures similar to a nucleus but small size and localized in the cytoplasm. A micronucleus contents chromosome fragments or whole chromosomes. The micronucleus test is considered a biomarker for early induced genetic damage. Micronucleus test with cytochalasin B (CBMN test) is used to evaluate genotoxic effects induced by physical and chemical environmental agents, and to estimate the genetic damage induced in population groups exposed to such agents. After the study of large groups of control population, it is estimated that CBMN test can be used as a marker of health status with ability to establish a cancer risk. Finally, recent studies about the onset of cancer, based on single catastrophic events able to originate a cancer, such as chromothripsis or chromoanagenesis, are going to understand through an anomalous replication of DNA within the micronucleus.
Subject(s)
Micronucleus Tests , Neoplasms/diagnosis , Neoplasms/genetics , HumansABSTRACT
BACKGROUND: Although breastfeeding is the ideal way of nurturing infants, it can be a source of exposure to toxicants. This study reports the concentration of Hg, Pb and Cd in breast milk from a sample of women drawn from the general population of the Madrid Region, and explores the association between metal levels and socio-demographic factors, lifestyle habits, diet and environmental exposures, including tobacco smoke, exposure at home and occupational exposures. METHODS: Breast milk was obtained from 100 women (20 mL) at around the third week postpartum. Pb, Cd and Hg levels were determined using Atomic Absorption Spectrometry. Metal levels were log-transformed due to non-normal distribution. Their association with the variables collected by questionnaire was assessed using linear regression models. Separate models were fitted for Hg, Pb and Cd, using univariate linear regression in a first step. Secondly, multivariate linear regression models were adjusted introducing potential confounders specific for each metal. Finally, a test for trend was performed in order to evaluate possible dose-response relationships between metal levels and changes in variables categories. RESULTS: Geometric mean Hg, Pb and Cd content in milk were 0.53 µg L(-1), 15.56 µg L(-1), and 1.31 µg L(-1), respectively. Decreases in Hg levels in older women and in those with a previous history of pregnancies and lactations suggested clearance of this metal over lifetime, though differences were not statistically significant, probably due to limited sample size. Lead concentrations increased with greater exposure to motor vehicle traffic and higher potato consumption. Increased Cd levels were associated with type of lactation and tended to increase with tobacco smoking. CONCLUSIONS: Surveillance for the presence of heavy metals in human milk is needed. Smoking and dietary habits are the main factors linked to heavy metal levels in breast milk. Our results reinforce the need to strengthen national food safety programs and to further promote avoidance of unhealthy behaviors such as smoking during pregnancy.
Subject(s)
Cadmium/analysis , Lead/analysis , Mercury/analysis , Milk, Human/chemistry , Environmental Exposure , Feeding Behavior , Female , Humans , Life Style , Metals, Heavy/analysis , Occupational Exposure , Pregnancy , Socioeconomic Factors , Spain , Tobacco Smoke Pollution , Young AdultABSTRACT
Cytogenetic aberrations are a biomarker for early effect that indicate the cell or the organism has undergone chromosomal damage as a result of his exposure to an external mutagenic/carcinogenic agent. The story begins with the description of the cytogenetic effects of ionizing radiation in 1927, but was not until 1956, with the description of the cytogenetic technique in humans, when genotoxic effects induced by mutagenic or carcinogenic chemical and physical agents are known. Induced chromosomal damage in humans by genotoxic agents is analyzed in human cells in vitro to check the genotoxicity of a suspected agent or in vivo in lymphocytes of individuals exposed to a genotoxic agent. The biomarker may be chromosomal breakage, sister chromatids exchanges, or micronucleus when the exposure has been recent, or chromosomal translocations for delayed or continuing exposures. The above, has allowed establishing that genotoxic damage accumulates with age and lifestyles such as smoking or occupational exposures. Recently, after checking the health status and survival of several European cohorts of normal individuals who years earlier were analyzed their cytogenetics biomarkers, has been established the cancer predictive value of the biomarker chromosome aberrations.
Subject(s)
Cytogenetic Analysis , Health Status , Chromosome Aberrations , Genetic Markers , Humans , Mutagenicity Tests , Translocation, GeneticSubject(s)
Chromosome Aberrations , Chromosomes, Human, Pair 5 , Chromosomes, Human, Pair 8 , Multiple Myeloma/complications , Multiple Myeloma/genetics , Myelodysplastic Syndromes/complications , Myelodysplastic Syndromes/genetics , Trisomy , Aged , Chromosome Banding , Chromosome Deletion , Cytogenetics , Female , Humans , KaryotypingABSTRACT
Monitoring cytogenetic damage is frequently used to assess population exposure to environmental mutagens. The cytokinesis-block micronucleus assay is one of the most widely used methods employed in these studies. In the present study we used this assay to assess the baseline frequency of micronuclei in a healthy population of father-pregnant woman-newborn trios drawn from two Madrid areas. We also investigated the association between micronucleus frequency and specific socioeconomic, environmental, and demographic factors collected by questionnaire. Mercury, arsenic, lead, and cadmium blood levels were measured by atomic absorption spectrometry. The association between micronucleated cell frequency and the variables collected by questionnaire, as well as, the risk associated with the presence of elevated levels of metals in blood, was estimated using Poisson models, taking the number of micronucleated cells in 1,000 binucleated cells (MNBCs) as the dependent variable. Separate analyses were conducted for the 110 newborns, 136 pregnant women, and 134 fathers in whom micronuclei could be assessed. The mean number of micronucleated cells per 1,000 binucleated cells was 3.9, 6.5, and 6.1 respectively. Our results show a statistically significant correlation in MNBC frequency between fathers and mothers, and between parents and newborns. Elevated blood mercury levels in fathers were associated with significantly higher MNBC frequency, compared with fathers who had normal mercury levels (RR:1.21; 95%CI:1.02-1.43). This last result suggests the need to implement greater control over populations which, by reason of their occupation or life style, are among those most exposed to this metal.
Subject(s)
Environmental Exposure/analysis , Micronuclei, Chromosome-Defective/statistics & numerical data , Adult , Arsenic/blood , Biomarkers/blood , Cadmium/blood , Cytogenetic Analysis , Demography , Environmental Pollutants/blood , Environmental Pollutants/toxicity , Female , Humans , Infant, Newborn , Lead/blood , Male , Mercury/blood , Micronucleus Tests , Pregnancy , Socioeconomic Factors , Spain/epidemiologyABSTRACT
Siempre se debe garantizar un asesoramiento genético apropiado a la pareja, tanto antes como después del estudio genético. Las pruebas genéticas se han clasificado como pruebas altamente recomendables, recomendables u opcionales, según su resultado modifique el pronóstico. La indicación de las pruebas genéticas en la mujer con alteraciones en la reproducción se ha clasificado sobre la base de la historia clínica personal y familiar y puede abarcar el cariotipo en sangre periférica, el estudio molecular del gen CFTR (cystic fibrosis transmembrane conductance regulator), de X frágil, del factor II, del factor V y de metilentetrahidrofolatoreductasa (MTHFR). Respecto a los varones con alteraciones en la reproducción, cualquier estudio genético debe ir precedido por un estudio andrológico, que debe incluir al menos una historia clínica personal, familiar y el análisis de semen. Se puede indicar el cariotipo en sangre periférica, el estudio molecular de CFTR, las microdeleciones en el cromosoma Y, la hibridación fluorescente in situ (FISH, por sus siglas en inglés) en espermatozoides, el estudio de meiosis en tejido testicular y la fragmentación del ADN (AU)
In order to improve the care and follow up of couples with impaired reproduction, several scientific societies and experts have established specific recommendations for genetic testing in the evaluation of reproductive disorders in couples with impaired reproduction. Appropriate genetic counselling must be given to the couple before and after the genetic testing. Genetic tests have been classified as highly recommended, recommended or optional depending on whether the results have changed the prognosis of the corresponding pathology. The indication for genetic testing in women with impaired reproduction is classified on the basis of personal and family medical history and can include the karyotype in peripheral blood, the molecular study of CFTR, Fragile X, factor II, factor V and MTHRF. As regards men with impaired reproduction, every genetic study should be preceded by an andrological study, which must include at least the personal and family history and a semen analysis. A medical indication can be made for the karyotype in peripheral blood, the molecular study of CFTR, microdeletions on the Y chromosome, FISH sperm FISH, meiosis in testicular tissue studies, and DNA fragmentation (AU)
Subject(s)
Humans , Male , Female , Sexual Partners/classification , Reproduction/genetics , Cytogenetics/methods , Cytogenetic Analysis/trends , Cytogenetic Analysis , Gametogenesis/genetics , Karyotype/methods , In Situ Hybridization, Fluorescence/methods , In Situ Hybridization, Fluorescence , DNA Fragmentation , Societies/ethics , Societies, Medical/ethics , Societies, Medical/standards , /analysis , Reproductive Techniques , Surveys and Questionnaires , Cystic Fibrosis/diagnosis , Chromosome Fragility/genetics , Fragile X Syndrome/diagnosis , MeiosisABSTRACT
In Spain environmental surveillance has mainly relied on measures of selected pollutants in air, water, food and soil. A study was conducted in Madrid to assess the feasibility of implementing a surveillance system of exposure among the general population to specific environmental pollutants, using bio-markers. The project was basically focused on the environment surrounding newborns. Hence, the study population was made up of 145 triplets of pregnant women at around 8 months' gestation, their partners, and newborns from two areas, representing the two main types of urban environments in the region, i.e., the City of Madrid and its outlying metropolitan belt. Multiple biologic substrates were collected from each participant in order to assess the most suitable samples for an environmental surveillance system. The selected contaminants represent the main agents to which a population like that of Madrid is exposed every day, including certain heavy metals, persistent organic pollutants and polycyclic aromatic hydrocarbons, as well as micronuclei in peripheral blood, a commonly used unspecific index of cytogenetic damage. In addition, passive air samplers were placed around subjects' place of residence. This paper reports in detail on the design and response rates, summarizes field work results, and discusses some lessons learned.
Subject(s)
Environmental Exposure , Environmental Monitoring/methods , Environmental Pollutants/analysis , Public Health , Adolescent , Adult , Biomarkers , Child , Cohort Studies , Feasibility Studies , Female , Humans , Infant , Infant, Newborn , Male , Micronucleus Tests , Middle Aged , Parents , Pilot Projects , Pregnancy , Socioeconomic Factors , Spain , Surveys and Questionnaires , Urban PopulationABSTRACT
In Spain environmental surveillance has mainly relied on measuresof selected pollutants in air, water, food and soil. A studywas conducted in Madrid to assess the feasibility of implementinga surveillance system of exposure among the generalpopulation to specific environmental pollutants, using biomarkers.The project was basically focused on the environmentsurrounding newborns. Hence, the study population was madeup of 145 triplets of pregnant women at around 8 months gestation,their partners, and newborns from two areas, representingthe two main types of urban environments in the region,i.e., the City of Madrid and its outlying metropolitan belt.Multiple biologic substrates were collected from each participantin order to assess the most suitable samples for an environmentalsurveillance system. The selected contaminantsrepresent the main agents to which a population like that ofMadrid is exposed every day, including certain heavy metals,persistent organic pollutants and polycyclic aromatic hydrocarbons,as well as micronuclei in peripheral blood, a commonlyused unspecific index of cytogenetic damage. In addition,passive air samplers were placed around subjects placeof residence. This paper reports in detail on the design andresponse rates, summarizes field work results, and discussessome lessons learned(AU)
En España, la vigilancia medioambiental se basa principalmenteen medidas de ciertos contaminantes en muestrasde aire, agua, alimentos y suelos. En Madrid se ha realizadoun estudio para valorar la posibilidad de poner en marchaun sistema de vigilancia de exposiciones a contaminantesambientales en la población general utilizando biomarcadores.El proyecto ha tenido como eje el estudio del entornode los recién nacidos. Por tanto, la población de estudio laconstituyen 145 ®tríos» formados por mujeres en su octavomes de embarazo, sus parejas y los recién nacidos de dosáreas geográficas, que representan los dos principales entornosurbanos de la región, es decir, Madrid capital y su áreametropolitana. Se recogieron múltiples sustratos biológicosde cada participante con el objeto de valorar las muestrasmás adecuadas para un sistema de vigilancia de exposicionesambientales. Los contaminantes elegidos representan losprincipales agentes tóxicos a los que una población como lade Madrid está expuesta diariamente, e incluyen metales pesados,contaminantes orgánicos persistentes e hidrocarburosaromáticos policíclicos; se ha añadido también una medidainespecífica de daño citogenético, los micronúcleos ensangre periférica. Además, se han colocado muestreadorespasivos de aire en los alrededores del domicilio de los participantes.Este artículo describe en detalle el diseño del estudioy la tasa de respuesta, resume los resultados del trabajode campo y comenta algunas enseñanzas prácticas deéste(AU)
