Julio Nazer H

Malformaciones congénitas en Chile y Latino América: Una visión Epidemiológica del ECLAMC del período 1995-2008

Background: The Latin American Study of Congenital Malformations (ECLAMC) hasperformed an epidemiologica! surveillance of congenital malformations since 1967. This allows to detectany unexpected change in the incidence of malformations, possibly caused by a new environmental teratogenic agent. Aim: To report a summary ofthe results thusfar obtained in this study. Material ana Methods: The ECLAMC database was analyzed and all Uve births and stillbirths ofmore than 500 grams in the period 1995-2008, were analyzed. Results: There were 2,409,407 births in the nine participant countries. Ofthese 31,516 (1.3%) were stillbirths. The global rate of congenital malformations in this sample was 2.7%. In the studied period, there was a significant reduction in the rates of anencephaly and spina bifida in Chile and Argentina. In the rest ofthe countries, the global rates of malformations increased. Venezuela had the higher rate of teenage pregnancies (25%), followed by Colombia (23%). Chile had the higherpercentage ofwomen aged 35years or moregiving birth (14%), followed by Uruguay (13%). However, Chile had the higher rate of Down syndrome and Uruguay, the lowest (24.7 and 13.6per 10000). Conclusions: There is a tendency towards an increase in the rates of congenital malformations in this sample, with significant differences among countries.

ECLAMC: Estudio de 30 años de vigilancia epidemiológica de defectos de tubo neural en Chile y en Latinoamérica

Background: There is an urgent need to assess the impact, on the incidence of neural tube defects, of the recently implanted flour fortification with folic acid in Chile. The Collaborative Study of Congenital Malformations in Latin America (ECLAMC) has carried out an uninterrupted register of congenital malformations in the last thirty years Aim: To assess the epidemiology of neural tube defects in Chile and determine the most adequate base period to evaluate the effects of Folic acid fortification. Material and methods: analysis of ECLAMC database that has registered all births over 500 g from 1967. Results: From 1967 to 1999, there were 434.624 births in 18 hospitals in Chile and 3.586.569 births in 155 hospitals in the rest of Latin America. The rate of neural tube defects in Chile was 17.03 per 10.000, significantly higher than the rest of ECLAMC (14.88 per 10.000). The prevalence of neural tube defects has a statistically significant secular tendency to increase in the study period and is higher among stillbirths, newborns with a birth weight of less than 1500 g, women and offspring of mothers aged less than 19 years old. Conclusions: The period 1982-1999 is considered the best period for reference comparisons of the effects folic acid supplementation (Rev Med Chile 2001; 129: 531-9)

Incidencia de labio leporino y paladar hendido en la Maternidad del Hospital Clínico de la Universidad de Chile y en las maternidades chilenas participantes en el Estudio Colaborativo Latino Americano de Malformaciones Congénitas (ECLAMC) período 1991-1999

Background: ECLAMC is a registry, aimed to assess the incidence of congenital malformations, that started in 1967 and Chile incorporated to it in 1969. Aim: To report the incidence of cleft lip/palate, updated to 1999 in the University of Chile Maternity Hospital and other Chilean hospitals participating in the ECLAMC. Patients and methods: A review of the ECLAMC database that registers all births or stillbirths of more than 500 g. Results: The incidence of orofacial cleft, at the University of Chile Maternity Hospital, in the period 1991-1999 was 17.8 per 10000 (12.6 for cleft lip and 5.2 for cleft palate). The incidence in the rest of participating hospitals was 12.04 and 4.6 respectively. Males had a higher incidence of cleft lip and 80% of children with cleft palate, had other malformations, most of them as part of a syndrome (13 and 18 trisomy, holoproscencephalia, Pierre Robin, Apert en EE syndromes, anencephaly etc). In three of 12 children with cleft lip but without cleft palate, there was a relative with the same malformation. Conclusions: It is proposed that both entities, cleft lip with or without cleft palate and cleft palate without cleft lip, are two etiopathogenically different conditions (Rev Med Chile 2001; 129: 285-93).

Effects of folic acid fortification in the rates of malformations at birth in Chile

After the start of folic acidfortification a significant reduction in the rates of anencephalia, spina bifida anddiaphragmatic hernia, was observed. The rates of all other malformations remained stable orincreased. The rates of all malformations at the University of Chile Clinical Hospital had asteady increase until 2005 and were significantly higher than in the rest of hospitalsparticipating in ECLAMC.

The association between maternal age and congenital malformations

An overallprevalence of malformations of 8,4% was detected at the hospital. There is a significantly lowerfrequency of mothers aged less than 20 years than in the rest of Chile. Mothers aged between 20and 29 years have the lower frequency of malformed children. Women aged less than 20 yearsand over 39 years of age, account for 56% of malformed children. Maternal ages and the ratesof malformations, increased in a parallel fashion at a rate of 0.2 years and 2.2 malformedchildren per 1,000 born alive, per calendar year, respectively.

Prevalencia al nacimiento de malformaciones congénitas y de menor peso de nacimiento en hijos de madres adolescentes

:The births occurred in a hospital between 1982 and 2001, were analyzed using the Latin Amer-ican Collaborative Study for Congenital Malformations (ECLAMC) data base. Mothers were clas-sified as teenagers when their age ranged between 10 and 19 years old and older when their agewas over 20 years old. All women were subdivided as cases and controls.

Malformaciones congénitas en los hijos de madres diabéticas

The offspring of diabetic mothers have a 10 times higher frequency of congenital malformations and 5 times higher frequency of spontaneous abortions. Since the discovery of insulin, the prognosis of pregnancies has improved, both for the mother and the offspring. However, the prevalence of congenital malformations at birth has not decreased significantly. The embriological process that leads to anomalies in the offspring of diabetic mothers probably occurs between 6 and 8 weeks of gestation. According to animal experiments, hyperglycemia, ketones and free radicals may be involved in the genesis of malfomations, but different strains of rats respond differently to these potential teratogenic agents. Possibly, a higher genetic susceptibility towards congenital malformations also plays a role in diabetic women. Therefore, although the intimate mechanism producing malformations in the offspring of diabetic women is not known, several strategies to decrease the prevalence of malformations in these women, such as the use of antioxidants, are being tested

Estudio epidemiológico global del síndrome de Down

Introduccion: El ECLAMC (Estudio Colaborativo Latino Americano de Malformaciones Congenitas) fue creado en 1967. Actualmente, lo integran 180 hospitales de 76 ciudades de 9 paises Latino Americanos y ha acumulado mas de 4,5 millones de nacimientos. El Hospital Clinico de la Universidad de Chile (HCUCH) ingreso en 1967 y despues otros 12 establecimientos chilenos. Objetivos: Verificar si la frecuencia de sindrome de Down (SD) esta aumentando en Chile y Latino America y como se ha visto modificada en los paises en que esta permitido el aborto electivo. Pacientes y Metodo: Se estudio 3 muestras: Todos los nacimientos del HCUCH desde 1972 a 2009; de los hospitales chilenos activos y de los 180 hospitales de 9 paises Latinoamericanos. Se comparo las frecuencias de SD de Chile y del ECLAMC con otros paises que participan en el Internacional Clearinghouse for Birth Defects Monitoring System. Resultados: La frecuencia del SD en el HCUCH aumento significativamente de 1,03 por mil nacimientos en 1972 a 2,93 por mil en 2009. Las frecuencias en los hospitales chilenos son muy homogeneas, todas mas altas que el promedio del ECLAMC: 1,88 por mil. El promedio chileno para el periodo 1998-2005 fue de 2,47 por mil. Con un rango de 1,88 por mil del HCUCH y 2,86 por mil del Hospital de Curico. En el resto del mundo se ha asistido a una disminucion significativa de las tasas de SD, siendo las mas bajas la de Iran: 0,32 por mil y Espana 0,60 por mil nacimientos vivos. Conclusion: En Chile, las tasas de SD son mayores al promedio del ECLAMC 2,47 por mil existiendo una tendencia al aumento de ellas lo mismo que en Latino America, donde el promedio para el periodo 20012005 fue de 2,89 por mil. En Europa y Asia las tasas han disminuido a cifras extremas, Iran 0,32 por mil y Espana 0,60 por mil.

Malformaciones congénitas en Chile.: Un problema emergente (período 1995-1999)

Background: The Latin American collaborative study of congenital malformations (ECLAMC) is a surveillance program designed to monitor the frequency of congenital malformations and detect abrupt changes in their frequency, look for the cause of such change and implement primary prevention measures. Aim: To construct a secular trend curve with the frequency of congenital malformations in Chile. Material and methods: Using the ECLAMC protocol, every malformed newborn or stillbirth, weighting more than 500 g at birth is registered using a standard protocol, and the next non malformed child of the same sex born in the same hospital is assigned as control. Using the gathered data, secular trend curves of congenital malformations were constructed. Results: Between 1982 and 1999, there is a secular tendency in the rate of congenital malformations and maternal age, with a correlation coefficient of 0.8 and slope of 13.5 (p<0.05). The rates of congenital malformations at the moment of birth are higher at the University of Chile Clinical Hospital than in the rest of Chilean hospitals and other Latin American Hospitals. Anencephalia is a defect with a high frequency in Concepcion and spina bifida has a high frequency in Rancagua, Vina del Mar, Concepcion and Valdivia. There is an impressive increase in malformations dependent on prenatal diagnosis such as kidney agenesis, polycystic kidney and diaphragmatic hernia. Conclusions: Congenital malformations are having an increasing importance as causes of morbidity or mortality in the newborn. (Rev Med Chile 2001; 129: 895-904).

Prevalencia de nacimiento de microtia-anotia: Maternidad del Hospital Clínico de la Universidad de Chile, período 1983-2005

The prevalence of microtia-anotia in the period 1982-2001 was 8.7 per10,000 born alive. Chilean hospitals have an uniform prevalence of 5.2 per 10,000 born alive. Thirtyseven percent presented as isolated malformations and the rest were associated to other defects. Eightysix percent of non isolated cases were part of a syndrome. Sixty eight percent were mild or moderateforms and the rest, severe forms. Two cases were stillborns and two newborns died before hospitaldischarge.