RESUMEN
This study was undertaken to find a strict, unbiased epidemiological delineation of the VATER non-random association of congenital malformations and, based on registry information, to identify a group of probable VATER association infants suitable for etiological analyses. Information on 5,260 infants with multiple malformations was collected from four large registers of congenital malformations. Data were analyzed using a statistical method in which various putative confounders were controlled for. Our results indicate the existence of a distinct group of malformations corresponding to the VATER association: esophageal atresia, anal atresia, upper preaxial limb reduction defects, and costo-vertebral malformations. A subdivision into an upper and a lower group of VATER association was indicated, with heart malformations associated with the upper group and kidney malformations associated with the lower group. Restricting the inclusion criteria for VATER association to the above mentioned core malformations, few infants seem to belong to the VATER association, thus limiting the possibilities of carrying out etiological analyses. A relatively large number of infants may belong to a family of related conditions among which VATER association is a subgroup. In the search for risk factors, a strict definition of the VATER association is needed in order to not dilute the study material with irrelevant cases. The present study provides such strict inclusion criteria.
Asunto(s)
Anomalías Múltiples/epidemiología , Anomalías Múltiples/etiología , Ano Imperforado , Interpretación Estadística de Datos , Femenino , Francia/epidemiología , Cardiopatías Congénitas , Humanos , Recién Nacido , Italia/epidemiología , Riñón/anomalías , Masculino , Sistema de Registros , América del Sur/epidemiología , Columna Vertebral/anomalías , Suecia/epidemiología , Síndrome , Fístula TraqueoesofágicaRESUMEN
Using a novel method for the analysis of infants with multiple malformations, we investigated the cluster of associated malformations called the OEIS (omphalocele, bladder exstrophy, imperforate anus, spine defect) complex among 5,260 infants with multiple malformations identified in four large registers of congenital malformations, corresponding to 5.84 million births. The existence of the OEIS complex was clearly demonstrated and malformations entering it could be defined. Other than the four classical malformations, omphalocele, bladder exstrophy, imperforate anus, and spine malformation, a strong association with spina bifida and intersex was stressed. Spine malformations occurred not only in the lumbosacral level but also more cranially, and an association also with upper spina bifida could be demonstrated. No specific association with any other malformation, including cardiac defects, was apparent. The OEIS complex is an unusually clearly defined entity among the various nonrandom associations which have been described.
Asunto(s)
Anomalías Múltiples/epidemiología , Ano Imperforado , Extrofia de la Vejiga , Hernia Umbilical , Disrafia Espinal , Anomalías Múltiples/clasificación , Estudios de Cohortes , Métodos Epidemiológicos , Francia/epidemiología , Humanos , Recién Nacido , Italia/epidemiología , América del Sur/epidemiología , Suecia/epidemiologíaRESUMEN
BACKGROUND: Infants with multiple malformations are important in birth defect epidemiology and malformation monitoring because human teratogens have often caused complex malformations. Various methods for the analysis of multimalformed infants have been tried. METHOD: By using data from four large registries of congenital malformations, 5256 infants were identified with two or more among 73 selected malformations. Pairwise associations between malformations were detected by multiple logistic regression analyses, and putative confounders (programme, maternal age, autopsy, etc.) were controlled for. For each significant pairwise association, further analyses were performed in order to find associations with a possible third malformation. RESULTS: The importance of controlling for several confounders was demonstrated. Several well-known associations were found, which supports the technique used. The interpretation of three-way associations was discussed. Results from the present study were compared with those obtained using some other methods. CONCLUSIONS: Different confounders can cause biased associations. The method presented in the paper takes this into consideration and is therefore more likely than previously used techniques to give unbiased information on the clustering of different malformations among multimalformed infants.
Asunto(s)
Anomalías Múltiples/epidemiología , Sistema de Registros/estadística & datos numéricos , Anomalías Múltiples/etiología , Análisis por Conglomerados , Europa (Continente)/epidemiología , Femenino , Muerte Fetal/epidemiología , Humanos , Recién Nacido , Masculino , Edad Materna , Oportunidad Relativa , Análisis de Regresión , Estudios Retrospectivos , América del Sur/epidemiologíaRESUMEN
The paternal ages of nonfamilial cases of achondroplasia (AC) (n = 78), thanatophoric dysplasia (TD) (n = 64), and osteogenesis imperfecta (OI) (n = 106), were compared with those of matched controls, from an Italian Indagine Policentrica Italiana sulle Malformazioni Congenite and a South American Estudio Colaborativo Latinoamericano de Malformaciones Congénitas series. The degree of paternal age effect on the origin of these dominant mutations differed among the three conditions. Mean paternal age was highly elevated in AC, 36.30 +/- 6.74 years in the IPIMC, and 37.19 +/- 10.53 years in the ECLAMC; less consistently elevated in TD, 33.60 +/- 7.08 years in the IPIMC, and 36.41 +/- 9.38 years in the ECLAMC; and only slightly elevated in OI in the ECLAMC, 31.15 +/- 9.25 years, but not in the IPIMC, 32.26 +/- 6.07 years. Increased maternal age or birth order in these conditions disappeared when corrected for paternal age. Approximately 50% of AC and TD cases, and only 30% of OI cases, were born to fathers above age 35 years. For AC and TD, the increase in relative incidence with paternal age fitted an exponential curve. The variability of paternal age effect in these new mutations could be due, among other reasons, to the high proportion of germ-line mosaicism in OI parents, or to the localization of the AC gene, mapped to the 4p16.3 region, in the neighborhood of an unstable DNA area.
Asunto(s)
Acondroplasia/genética , Osteogénesis Imperfecta/genética , Displasia Tanatofórica/genética , Acondroplasia/epidemiología , Adulto , Orden de Nacimiento , Estudios de Casos y Controles , Femenino , Mutación de Línea Germinal , Humanos , Recién Nacido , Italia/epidemiología , Masculino , Edad Materna , Persona de Mediana Edad , Mosaicismo , Osteogénesis Imperfecta/epidemiología , Edad Paterna , Embarazo , Sistema de Registros , Factores de Riesgo , América del Sur/epidemiología , Displasia Tanatofórica/epidemiologíaRESUMEN
Three large and comparable series of births were used to test the working hypothesis that if there is a real seasonal variation in the frequency of a given congenital malformation; it would have to be shown by adequate analysis; to be more overt in non-tropical areas; and to be six months out of phase in northern and southern hemispheres. The data set were hospital births from tropical (287,165 births) and non-tropical (582,585 births) South America, and from Italy (508,536 births). Sixteen well-defined malformation types were tested: anencephaly, spina bifida, cephalocoele, hydrocephaly, microtia, cleft palate, cleft lip, oesophageal atresia, anal atresia, hypospadias, pes equino-varus, pes talovalgus, postaxial polydactylyl, pre-axial polydactylyl, diaphragmatic hernia, and Down's syndrome. No seasonal variation was proven (p less than 0.01) for any malformation type in any of the three series of data by means of Walter and Elwood's test, or Hewitt et al's non-parametric test2 applied to seven instances with sample sizes smaller than 50 cases. Variations of borderline significance (p less than 0.05) included oesophageal atresia in tropical South America, none in non-tropical South America, and anencephaly in Italy. It is concluded that seasonal variation in the occurrence of congenital malformations is a rare phenomenon when tests are strictly used within their recommended limitations.
Asunto(s)
Anomalías Congénitas/epidemiología , Estaciones del Año , Humanos , Incidencia , Recién Nacido , Italia/epidemiología , América del Sur/epidemiologíaRESUMEN
The distribution of anticonvulsant drug therapy was studied in 318 malformed infants with known histories of maternal epilepsy. Data on the infants was collected from six birth defect monitoring programs in Europe and South America. Use of specific types of anticonvulsants varies widely among reporting countries. Heterogeneity of drug-malformation distribution, was analyzed to determine whether use of specific drugs were linked to specific malformations. A significant association was seen between maternal use of valproic acid and spina bifida, and a weaker, non-significant one between carbamazepine and spina bifida. Facial clefts were associated with both diphenylhydantoin and phenobarbitone use and also with polytherapy. These differences indicate that the actual drug used is significant for the teratogenic process. The technique may be useful in analysis of other drug-related teratogenic questions.