Search for ethnic, geographic, and other factors in the epidemiology of Down syndrome in South America: analysis of data from the ECLAMC project, 1967-1997.

We have analyzed data on 3,157 cases of Down syndrome (DS) from nine South American countries in consecutive series of hospital live births over a 30-year period, with particular emphasis on possible ethnic or geographic variations in maternal age-adjusted incidence. The data constitute the largest series of DS cases assembled to date from an area lacking advanced health care systems. Absolute incidence rates were estimated from total hospital live births; relative rates were estimated from matched case-control data using conditional logistic regression. Maternal age-adjusted rates were closely similar to those reported elsewhere, and showed little or no dependency on other factors investigated, including paternal age, birth order, ancestral origin, country of birth, maternal educational level, maternal ABO and Rhesus blood groups, interval to and outcome of mother's previous pregnancy, and parental consanguinity. The absence of an effect of high birth order was particularly notable because of the relatively large number of grand multipara resulting from high fertility in this population. The study adds to a body of evidence suggesting that maternal age-adjusted DS rates vary little across human populations, and are therefore unlikely to be greatly influenced by genetic or environmental factors that differ between them. An unusual finding was of a markedly lower sex ratio (98 males per 100 females) than has been reported in other DS samples.

Survival of children with Down syndrome in South America. ECLAMC-Downsurv Group. Latin American Collaborative Study of Congenital Malformations.

The first step of all healthcare actions aimed at promoting an appropriate quality of life for infants affected by Down syndrome (DS) is to ensure their survival. This investigation was aimed at estimating the infant mortality rate of infants affected with DS in urban populations of South America. Thirty-three hospitals included in the Latin American Collaborative Study of Congenital Malformations (ECLAMC) distributed in 23 cities of 5 South American countries followed 360 liveborn DS cases born during the 1988-1992 period. Families were recontacted after the infant should have reached the age of one year. The collected data included information about health status; i.e., frequency and dates of diagnosed illnesses and hospital admissions, and, in case of death, information on date, place and cause of death, and illness immediately before death. Information about the interviews included place, date, and name of the interviewer. A closed questionnaire was employed by the interviewers, mostly physicians, nurses, and social workers. Life table analysis up to the age of one year was performed by the actuarial survival method. The overall mean survival at age one year was 0.736 (SE=0.023). Thirty-three (9.2%) of the 360 cases died neonatally, and 62 (17.2%) within the remaining 2-to-12-month interval. The probability of survival at one year of age did not differ between public (209 cases; mean 0.718; SE=0.031) and private (151 cases; mean: 0.762; SE=0.035) (chi2:0.87; df:1; P >0.05) health systems. The 150 DS cases with a congenital heart defect (CHD) had a significantly lower P robability of survival at the age of one year (mean: 0.660; SE: 0.039) than did the 210 cases without CHD (mean: 0.790; SE: 0.028) (chi2:6.67; df:1; P <0.01). The death rate in the first year of life for DS cases without a detected cardiac defect (21%) is significantly higher than that reported in developed countries; namely, 16% from Italy, 11% from Canada, 10% from England, and 7% from Denmark.

Unintended pregnancies in women delivering at 18 South American hospitals. NFP-ECLAMC Group. Latin American Collaborative Study of Congenital Malformations.

Unintended pregnancies are accepted as associated with social, maternal and perinatal risks, but few data exist in South America. In a selected network of hospitals participating in the ECLAMC (Spanish acronym for Latin American Collaborative Study of Congenital Malformations), the frequency of unintended pregnancies was 49.8% in 5155 mothers of normal liveborns, as interviewed in the post-partum period (1992-1994). Compared with the intended pregnancy group, these mothers were more frequently multiparous, conceived easily, had a surprisingly higher mean maternal age, lower educational level, and Black ancestors. The frequency of mistimed pregnancies was the highest among primiparae. No adverse perinatal outcome could be found with regard to low birthweight (< 2500 g), prematurity (< 37 weeks), and early neonatal death. The rates of Caesarean delivery, twinning and sex ratio were similar in intended and unintended groups. Logistic regression analysis showed that maternal education could be a confounding factor associated with other maternal variables. The rate of unintended pregnancies in the present study is significantly higher than that described for other regions. Knowledge of the characteristics of women experiencing unintended pregnancies would allow proper public health strategies.

Thalidomide, a current teratogen in South America.

Thalidomide, mainly used for the treatment of leprosy, is a current teratogen in South America, and it is reasonable to assume that at present this situation is affecting many births in underdeveloped countries. Moreover, the potential re-marketing of thalidomide for the treatment of a large variety of diseases may extend the problem to the developed world. When the drug is available, the control of its intake during early pregnancy is very difficult since most pregnancies are unintended. The ongoing occurrence of thalidomide embryopathy cases went undetected by the ECLAMC, due to several factors: (1) low populational coverage through this monitoring system; (2) pre-existence of the teratogen with its effects present in both baseline (expected) and monitored (observed) materials; and (3) lack of a defined phenotype to be monitored. Thus, if thalidomide re-enters the market throughout the world, due to the wide range of new applications, occurrence of phocomelia alone might not be sufficient to detect its effects. By a case-reference approach, the ECLAMC registered 34 thalidomide embryopathy cases born in South America after 1965 whose birthplaces correspond to endemic areas for leprosy. Phocomelia was found in five of eleven fully described cases. Thus, phocomelia alone is neither specific nor sufficient to serve as a suitable phenotype to survey the teratogenic effects of thalidomide. Therefore, a thalidomide-like phenotype, defined as any bilateral upper and/or lower limb reduction defect of the preaxial and/or phocomelia types, should be included in the routine surveillance of birth defects in all programmes.

A simple model for the estimation of congenital malformation frequency in racially mixed populations

É proposto um modelo simples, fazendo uso do método da máxima verossimilhança, para estimar as freqüências de malformaçöes em grupos raciais, baseado em dados obtidos em serviços hospitalares. Este modelo usa as proporçöes de mistura racial e a freqüência observada da malformaçäo. O método foi aplicado a dois defeitos: polidactilia pós-axial e lábio leporino, cujas freqüências säo reconhecidamente heterogêneas entre grupos raciais. As estimativas obtidas em cada grupo racial foram as esperadas para estas malformaçöes, o que prova a aplicabilidade do método.

Limb reduction defects in South America.

OBJECTIVE: Limb reduction defects were considered as possible indicators of environmental teratogenesis; it was suggested that also invasive prenatal procedures could increase the risk for limb reduction defects. The purpose of this work is to give a baseline frequency for limb reduction defects, using data from a population not exposed to prenatal diagnosis procedures. DESIGN: Using data collected in the period 1967 to 1992 within the frame of the Latin American Collaborative Study of Congenital Malformations which clinically examined 2,917,074 newborn infants, a total of 1715 with limb reduction defects were found. All cases were classified and analysed in 25 categories. Geographic differences in recorded rates were tested by chi 2 for homogeneity. Secular trends were analysed using chi 2 test for linear trends. RESULTS: The overall birth prevalence rate of limb reduction defects among liveborn infants was 4.91(per 10,000 births) (3.05 for isolated and 1.85 for associated cases). For stillbirths, the total prevalence was 26.73/10,000 (5.53 for isolated and 21.20 for associated cases). The inclusion of the brachydactylies increased those figures to 5.55/10,000 (3.39 for isolated and 2.16 for associated cases), and 27.42, respectively, (5.53 for isolated and 21.89 for associated cases). When isolated and associated cases were considered together, a geographic heterogeneity was found in pre-axial limb reduction defects; there was also some heterogeneity for amputations. A maternal age effect was found for the isolated hypoplasias. Standardising by maternal age, the overall prevalence of limb reduction in liveborn infants was 5.66 per 10,000 (95% CI = 5.38-5.93). An increasing trend was suggested by the isolated form of distal amputations which involved hands, feet, or digits. CONCLUSIONS: Our data suggest that clustering limb reduction defects in wide groups as transverse and longitudinal may lead to heterogeneous entities. When a possible association is suspected, it would be preferable to present and analyse data in the most discriminant form available. Due to the maternal age effect, it would be advisable to standardise the rates of transversal limb reduction defects by this variable.

Safety of tetanus toxoid in pregnant women: a hospital-based case-control study of congenital anomalies.

Reported are the results of the Latin American Collaborative Study of Congenital Malformations (ECLAMC), a hospital-based case-control study of 34,293 malformed and 34,477 matched nonmalformed newborn controls. No statistical differences were found between the malformed and control groups, exposed or not exposed to tetanus toxoid.

Epidemiological study of congenital talipes calcaneovalgus.

Among 671,494 children born in South American hospitals participating in the Collaborative Latin American Study of Congenital Malformations (ECLAMC), 284 had talipes calcaneovalgus, corresponding to an incidence of 4.2 per 10,000 live births. Genetic and environmental risk factors were investigated in the sample of malformed newborns with talipes calcaneovalgus and in matched control babies. An excess number of females was found among the newborns with talipes calcaneovalgus. Talipes calcaneovalgus patients did not differ from the matched controls in terms of ethnic groups, inbreeding coefficient, time between gestations or multiple births. However, the data suggested that breech delivery and primiparae mothers are higher risk factors for this newborn malformation.

Epidemiologia de los nevos pigmentados congenitos: III - Heredabilidad. / Epidemiology of congenital pigmented nevus: III - Heredity

La frecuencia de nevos pigmentados congenitos (NPC) en una serie de nacimientos consecutivos, entre los anos 1967 y 1979, fue 283/30.091 = 0,94%, sin existir diferencias por sexo. Esta frecuencia registrada esta viciada por subregistro, estimandose que la frecuencia real de los NPC debe estar entre 1,5 y 2,0%. Este subregistro afecta principalmente a los NPC leves (unicos, menores de 10 mm, de textura normal), por lo que la proporcion de nevos "graves" debe ser interpretado de acuerdo a la tasa global de incidencia esta 12 veces mayor que la de la poblacion en general. Esta agregacion familiar parece deberse a un mecanismo de herencia multifactorial de alta heredabilidad (H2 = 83,5%), sin indicacion de efectos de dominancia

Epidemiologia de los nevos pigmentados congenitos: III - Heredabilidad. / Epidemiology of congenital pigmented nevus: III - Heredity

La frecuencia de nevos pigmentados congenitos (NPC) en una serie de nacimientos consecutivos, entre los anos 1967 y 1979, fue 283/30.091 = 0,94%, sin existir diferencias por sexo. Esta frecuencia registrada esta viciada por subregistro, estimandose que la frecuencia real de los NPC debe estar entre 1,5 y 2,0%. Este subregistro afecta principalmente a los NPC leves (unicos, menores de 10 mm, de textura normal), por lo que la proporcion de nevos "graves" debe ser interpretado de acuerdo a la tasa global de incidencia esta 12 veces mayor que la de la poblacion en general. Esta agregacion familiar parece deberse a un mecanismo de herencia multifactorial de alta heredabilidad (H2 = 83,5%), sin indicacion de efectos de dominancia