Clinical analysis of newborn infants with congenital defects registered in ECEMC: Distribution by etiology and ethnic groups

Dismorfología y Genética ClínicaIn this chapter, the information gathered by ECEMC between January 1980 and December 2008 has been analysed. It corresponds to 2,463,134 consecutive newborn infants surveyed, among which 37,545 (1.52%) presented congenital defects detected during the first 3 days of life. When these were distributed by clinical presentation, all the groups showed a statistically significant diminishing trend since the base period, mainly attributable to the impact of termination of pregnancy after the diagnosis of foetal alterations. The distribution by clinical presentation was specifically analysed for 17 congenital defects which are usually monitored, this information being useful in the field of prenatal diagnosis. Blastogenic defects showed a statistically significant decrease in the study period, except in the last 6 years, which could be due to the influence of the immigrant population. All the infants registered were distributed by the causes of the defects, and those with syndromes were also distributed by etiology and frequency in the ECEMC data. Moreover, all infants with congenital defects were distributed by the organic system or area affected, and presented in 3 periods of time. Given the increase in the immigrant population in our country, the distribution of all infants with congenital defects by ethnic group is shown, with whites being distinguished as native or foreigner. This distribution by ethnic group is important for designing specific campaigns for prevention, education and information, according to their real needs. When analysing some selected defects in those groups, with respect to the group of native whites, a lower percentage of cases with neural tube defects was found among blacks; a higher percentage of cases with cardiovascular defects was registered among blacks, gipsies and arabs; a lower percentage of cases with hypospadias was observed among blacks and indoamericans, and a higher percentage of cases with postaxial polydactyly was found among blacks. This data provides useful information for identifying defects for which the gene frequencies of the native population could be modified by immigration, as well as to define specific needs of the different ethnic groups in Spain.N

Indicadores sociales e inserción laboral de la población extranjera en España y Andalucía

En este trabajo llevamos a cabo un esbozo sobre las dificultades existentes para la elaboración de indicadores sociales aplicados a los estudios de migraciones. Posteriormente se da cuenta de los indicadores existentes en materia de inserción sociolaboral en España y Andalucía en este campo. Por último se utilizan estos indicadores para analizar la inserción laboral en el ámbito nacional y andaluz. Se lleva a cabo una discusión sobre las posibilidades de aplicación de estos indicadores al ámbito local, lo que se ejemplifica a través de datos referidos a la provincia de Huelva. Esta comunicación forma parte de la ejecución de un proyecto de I+D financiado por el Ministerio de Ciencia y Tecnología sobre los itinerarios de inserción social y laboral de la población inmigrante en Huelva (Ref. SEC2002-04795) y del proyecto Equal Arena coordinado por la Consejería de Gobernación de la Junta de Andalucía (ES-ES333) sobre indicadores de inserción profesional.This paper sketches the difficulties for the elaboration of social indicators applied to the study of migrations. Later it explains the existing indicators in the matter of sociolaboral insertion in Spain and Andalusia in this field. Finally these indicators are used to analyze the labor insertion in the national scope and Andalusian. A discussion is carried out on the possibilities of application of these indicators to the local scope, which is exemplified through data referred to the province of Huelva. This communication forms part of the execution of a project of Scientific Reasearch and Technological Development financed by the Ministry of Science and Technology on the itineraries of social and labor insertion of the immigrant population in Huelva (Ref. SEC2002-04795) and of the Equal Arena project coordinated by the Consejería de Gobernación, Junta de Andalucía (Ref. ES-ES333) on indicators of professional insertio

Present situation in Spain regarding the etiologic diagnosis in foetuses from termination of pregnancy (ToP) due to congenital defects. Guidelines for a minimum protocol

Dismorfología y Genética ClínicaSince the passing of the Spanish law permitting termination of pregnancy (ToP) after the detection of foetal anomalies, in July 1985, the ECEMC has undertaken the commitment to register the maximum information regarding the cases of ToP due to congenital anomalies. This interest is not only prompted by the need of a proper surveillance of these pathologies, what is important for public health purposes, but also for getting an etiologic diagnosis for each case; although this is only possible by retrieving minimum clinical and non-clinical information, depending on each case. This is important, because not achieving an etiologic diagnosis implies not being able to provide the family with information regarding recurrence risk, the risk for possible carriers among their healthy children, and for future pregnancies, planning prenatal diagnosis, and pre-implantation diagnosis or assisted reproduction for certain pathologies. At present, in Spain, there is no official protocol for the study of foetuses from ToP with congenital anomalies, what precludes from getting prevention in all their different levels, starting by the possibility of having a correct diagnosis. To cover that need, and based on the experience of the ECEMC, we highlight a small protocol with the minimal data to be collected to increase the possibilities to reach to a proper diagnosis, and, therefore, provide the parents with complete information. From the point of view of the health practice, this is the correct way, not only for getting the diagnosis, but because this is the only way to also help to diminish the awful situation of couples undergoing ToP due to foetal malformations.N

Primary prevention as an essential factor ensuring sustainability of health systems: the example of congenital anomalies

Protection of early development contributes to health of next generations. Congenital anomalies (and other adverse reproductive outcomes) are an important public health issue and early indicator of public health risks, as early development is influenced by many risk factors (e.g., nutrition, lifestyles, pollution, infections, medications, etc). Effective primary prevention requires an integrated “One Health” approach, linking knowledge and action. This requires surveillance of health events and potential health-damaging factors, science-based risk analysis, citizens’ empowerment and education of health professionals. From the policy standpoint, joint budgeting mechanisms are needed to sustain with equity intersectoral actions (involving policy domains of health, social affairs, education, agriculture and environment). States should devote resources to strengthen registries and systematic data collection for surveillance of congenital anomalies, to better inform national prevention strategies. Investing in primary prevention based on scientific  evidence is essential to support sustainable and resilient health systems and sustainable development of the society

Characteristics of mothers following assisted reproductive technologies

Aspectos EpidemiológicosBackground: Assisted reproductive technologies (ART), such as in vitro fertilization, intracytoplasmic sperm injection (ICSI), assisted fecundation, and all the fertility treatments and procedures, have been successfully used to overcome infertility. Indeed, it has been estimated that between 1 and 4% of births in developed countries are conceived trough ART. But at the same time, rising concerns exist on their potential adverse effects on the embryo and fetal development. However, in spite of the huge amount of studies that have been published, big gaps in this knowledge still exist. To assess this association through epidemiological studies, it is necessary to recognize which maternal characteristics, among others, could confound the results. However, some of the maternal characteristics may be related with cultural and social aspects, as well as with other local influences. Therefore, it is advisable to identify those characteristics in the different populations. Objective and methods: Here we present the results of the analysis of several maternal characteristics on data from the cases and controls ´ mothers of the ECEMC database. The analysis included 20,233 mothers of consecutive live born infants with congenital defects, and 19,411 mothers of control infants. The studied characteristics were: maternal age ( 19, 20-30, 31-35, 36), level of education (primary, secondary, and university studies), body mass index (BMI) in three strata (30), maternal chronic diseases, maternal diabetes mellitus, hypertension, gestational diabetes, infectious diseases during pregnancy, tobacco and alcohol consumption while pregnant, multiple births, and caesarean section. Due to the number of analyses performed, the statistical significance was established in p<0.01. Results: We have observed that women undergoing ART are older, with higher educational levels, suffer more chronic diseases, higher frequency of gestational diabetes, and more infectious diseases than mothers with natural conceptions. Most of these results are observed either in cases´ mothers or controls´ mothers, but did no differ when we analyzed cases versus controls´ mothers, all of them using ART for conception. On the other hand, mothers following ART, are less smokers, do not have more frequency of both diabetes mellitus and hypertension. Regarding the BMI, the only statistically significant result is an increased frequency of women having a BMI of <25 among those following ART. Conclusions: Many of the studied characteristics can be confounder factors for epidemiological analyses to identify potential risks of ART to produce birth defects. In addition, although most of the results are similar to those observed in other studies, particularly in Sweden, some of the observed differences may be due to variations in social and educational aspects. Therefore, it is advisable to identify which maternal characteristics can be confounder factors in each population.N

Surveillance of congenital anomalies in Spain in the last 23 years (period 1980-2002)

Resultados de Vigilancia Epidemiológica de los defectos congénitos sobre los datos del ECEMCWe have analysed data from the ECEMC database, gathered in the period 1980-2002, during which a total of 1,838,654 newborn infants were surveyed. The ECEMC programme covered 25.6% of total births occurred in Spain in 2001. We have calculated the global frequency of infants with congenital anomalies in different periods of time (before or after the passing of the law permitting voluntary interruption of gestation -VIG- following prenatal detection of anomalies). This allows to figure out the baseline frequency of congenital anomalies (corresponding to the period 1980-1985), and to assess the impact of VIG on the birth prevalence by comparing the baseline frequency of congenital anomalies with the frequency registered after 1985. The global frequency is decreasing over the years, and in 11 out of 17 Spanish Autonomic Regions we have also observed significant decreases of the frequency along the time. All those decreases are attributable to VIG. We have also studied the time distribution of the frequency of some selected anomalies, as well as their geographical distribution, and both are highly influenced by VIG. Nevertheless, the information on VIG is rather scarce. We consider that if it is not registered on a routine basis, it will be impossible to perform analytic studies on the causes of birth defects and to evaluate any preventive measure. Another question that will have to be approached in years to come is the distribution of birth defects depending on the country the parents come from, as immigration from other countries is increasing in Spain. Finally, we consider that even though the birth prevalence of these pathologies is decreasing as a consequence of the prenatal diagnosis and the possibility of voluntarily interrupting the gestation, it is necessary to search for primary prevention measures in order to get infants being born healthy.N

Epidemiological surveillance of congenital anomalies in Spain: Analysis of the data from the ECEMC’s Registry in the period 1980-2008

Aspectos EpidemiológicosThe Spanish Collaborative Study of Congenital Malformations (ECEMC) is a programme for research on congenital anomalies. It was created in 1976 by Prof. Martínez-Frías, as a hospital-based, case-control registry of newborn infants in Spain. Since its foundation, it has surveyed a total population of more than 2.6 million births, and studied more than 39,900 consecutive infants with congenital anomalies. According to the most recent data, the coverage of the registry reaches 21.55% of total births in Spain. The global frequency of infants with congenital defects has significantly decreased along the time, from 2.22% in the base period (1980-1985), to 1.03% in 2008. This significant decrease is mainly attributable to the impact of prenatal diagnosis and further interruption of some affected pregnancies, which is legal in Spain since 1985. Such a decrease has been observed in most of the Spanish Autonomic Regions (see Fig. 1) and participating hospitals, being statistically significant in many of them. The only Autonomic Region in which an increase was detected is Extremadura, where the base frequency was quite low due to a small coverage of births, in a period during which the most complicated pregnancies, and infants with serious birth defects, had to be referred to other regions (a situation that has changed since the basal period). From the periodic analysis of the frequency of a group of 33 defects selected due to their relatively high base frequency or morbidity/ mortality that they bear, only the heart/great vessels defects, and unilateral renal agenesis, have increased along the time, possibly as a result of increasing facilities for their diagnosis. The temporal-spatial analyses mostly detected decreases in the frequency of many of the defects studied in several Spanish Autonomic Regions. However, there were also some increases. Specifically, in the frequency of anophthalmia/microphthalmia in the Región de Murcia, cleft palate in Aragón, oesophageal atresia/stenosis in Galicia, and anal-rectal atresia/stenosis in Canarias. Regarding anophthalmia/ microphthalmia in the Región de Murcia, after excluding one case with a chromosomal abnormality and another one with familial Waardenburg syndrome, the increase lost its statistical significance, and apparently there was not any common denominator among the other cases registered, apart from the area of birth. With respect to the increase of oesophageal atresia/stenosis in Galicia, this was due to the birth of 4 cases in 2008, without any known common characteristic from which a causal relationship could be inferred. This defect will be subject to a special surveillance during the next months. Concerning the increase of cleft palate in Aragón, there was not any sign of a common cause restricted to this geographical area either. The last increase was based on the birth of 3 clinically different cases with anal atresia in Canarias, and no causal agent could be specifically linked to this area. From this report, it is clear the crucial role of the ECEMC system in the epidemiological surveillance of congenital anomalies in Spain, given its long experience since 1976, its huge database, the network of hospitals established, and the close and dynamic collaboration between its participants. This has enabled not only to calculate the birth frequency of congenital defects in Spain on a consecutive series on non-selected newborn infants, in a live and active system, but also to study their evolution along the time, and their geographical distribution, as well as their clinical diagnosis.N

Johnson-McMillin syndrome (JMS): description of the first patient in Spain.

Dismorfología y Genética ClínicaThe JMS (OMIM: 147770) is a rare autosomal dominant neuroectodermal disorder characterized by alopecia, ear malformations, conductive hearing loss, anosmia/hyposmia, and hypogonadotropic hypogonadism. Morover, some additional features have been described so far (congenital heart defect, cleft palate, mild facial asymmetry, tendency to caries, and mental retardation). Herein we report on a patient with this condition who exhibits many of the features previously described, including alopecia, malformed auricles, conductive hearing loss, facial asymmetry, and developmental delay. Interestingly, she also has features that have not been reported yet, such as preauricular pits and tags, broad depressions at the external lateral areas close to the eyes, and an abnormal left lower eyelid. This phenotype supports the involvement of the ectoderm and neuroectoderm of the first two branchial arches in the embryologic basis of this condition. Indeed, alopecia, dental anomalies, defects of the choanae, part of the palatal valves, hypothalamic axis and hypogonadotropic hypogonadism, of epidermic origin, are derived from the ectoderm. Other defects as craniofacial alterations, including inner ear, preauricular tags, ear pits, and even microtia, and facial palsy, are derived from the neural crest, as also are the cardiac malformations. As far as we have known, the patient described here, represents the first case published from SpainN

Clinical-epidemiological analysis of the newborn infants with congenital defects registered by ECEMC: Distribution by etiology and ethnic groups.

Dismorfología y Genética ClínicaIt is presented here the analysis of the main clinical aspects of the infants with congenital defects registered by ECEMC (Spanish Collaborative Study of Congenital Malformations) between 1980 and 2010. Among a total of 2,648,286 newborns surveyed, 39,434 (1.49%) had congenital defects detected during the first 3 days of life. This group of infants with congenital anomalies was distributed according to the clinical presentation of their defects as isolated (73.94%), multiply malformed (13.53%), and syndromes (12.53%). The etiologic distribution of infants with congenital anomalies in the ECEMC showed a 20.47% of genetic cause, 20.28% multifactorial, 1.35% produced by environmental causes, and the etiology of the defects was unknown in the remaining 57.90%. The secular distribution of the 3 main groups of clinical presentation (isolated, multiply malformed and syndromes) was studied and all of them showed a decreasing trend along the years, probably as a consequence of the impact of the interruption of pregnancy of some affected foetuses. The different types of syndromes identified and their minimal frequency values are also presented, separated by type of cause (Tables 4-10). Finally, the proportion of cases with birth defects by ethnic groups, first including (Graph 8) and then excluding (Graph 9) two groups of whites, the autochthones and the immigrant whites group. Due to the small samples in most non-white groups, the differences are not statistically significant, except for a significant higher frequency among Gypsies than in the white groups (both native and foreigner), the black group, and the one of Other (including mix groups).N