INTRODUCCIÓN La preeclampsia es una causa importante de morbilidad y mortalidad durante el embarazo a nivel mundial y una de las principales causas de mortalidad materna en Cuba. Es una enfermedad compleja y multifactorial; en ella no se debe subestimar la interacción de los factores genéticos y ambientales, cuando se persigue una evaluación adecuada de los riesgos para apoyar el asesoramiento genético preventivo y personalizado, así como una atención prenatal más eficaz para prevenir las complicaciones del embarazo.

OBJETIVO Determinar la contribución a la preeclampsia de la interacción entre un genoma predisponente y los factores ambientales adversos en mujeres embarazadas de un hospital materno de La Habana.

MÉTODOS Se presenta la fase exploratoria de un estudio de casos y controles realizado entre enero 2007 y diciembre 2009, a partir de los registros de las pacientes obstétricas del Hospital Universitario Eusebio Hernández, hospital materno de la provincia de La Habana. Se estudiaron 80 mujeres embarazadas con diagnóstico de preeclampsia y 160 controles. Las principales variables fueron: edad, paridad, estado nutricional (medido por el índice de masa corporal), consumo de alcohol, tabaquismo y antecedentes de preeclampsia en los familiares de la mujer embarazada (caso en estudio) o de su pareja. Se utilizaron las pruebas de chi cuadrado de Pearson y la prueba exacta de Fisher para evaluar la significación estadística de la asociación entre las variables y el riesgo relativo como medida de la fortaleza de la asociación. Se estudió la agregación familiar y se empleó un diseño de casos y controles para evaluar la interacción entre la genética y el ambiente, con el uso de modelos aditivos y multiplicativos.

RESULTADOS Entre los factores de riesgo ambientales estudiados, el consumo de alcohol mostró el mayor efecto sobre el riesgo de preeclampsia (OR 3.87, IC del 95%: 1.64–9.13). Se observó agregación familiar de la preeclampsia, con un incremento del riesgo tanto para los familiares de primer grado (OR 2.43, IC 95% 1.62–3.73) como para los de segundo grado (OR 1.89, IC del 95%: 1.34–2.68), así como para los familiares del esposo (OR 2.32, IC del 95%: 1.40–3.86). Hubo evidencia de interacción entre el consumo de alcohol y la historia familiar.

CONCLUSIONES Se demostró la agregación familiar de la enfermedad. Esta es la primera evidencia epidemiológica en Cuba de las contribuciones genéticas y ambientales al riesgo de preeclampsia. La agregación familiar constituida por los parientes del esposo demuestra la importancia del genoma fetal en la génesis de la preeclampsia. Cuando existe interacción de los factores de riesgo ambientales con los genéticos, el riesgo de preeclampsia es mayor, en comparación con los riesgos esperados basados en la acción independiente de estas variables.

PALABRAS CLAVE Preeclampsia, toxemia del embarazo, resultado del embarazo, medio ambiente, genética, interacción genoma–ambiente, epidemiología genética, Cuba

INTRODUCTION Pre-eclampsia is a major cause of morbidity and mortality during pregnancy worldwide and is among the leading causes of maternal mortality in Cuba. It is a complex, multifactoral disease, in which interaction of genetic and environmental factors should not be overlooked if the goal is proper risk assessment to support personalized preventive genetic counseling and more effective prenatal care to prevent pregnancy complications.

OBJECTIVE Determine the contribution to pre-eclampsia of interaction between a predisposing genome and adverse environmental factors in pregnant women in a Havana maternity hospital.

METHODS This was the exploratory phase of a hospital-based case-control study, using January 2007–December 2009 patient records from the Eusebio Hernández University Hospital, a provincial maternity hospital in Havana. Eighty pregnant women diagnosed with pre-eclampsia and 160 controls were studied. The main variables were age, parity, nutritional status (measured by BMI), alcohol use, tobacco use, and history of pre-eclampsia in relatives of the pregnant woman (proband) or of her partner. Pearson chi square and Fisher exact test were used to assess statistical significance of associations between variables and odds ratio as a measure of association strength. Familial aggregation was studied and a case-control design used to assess gene–environment interaction, using multiplicative and additive models.

RESULTS Among the environmental risk factors studied, alcohol showed the strongest effect on pre-eclampsia risk (OR 3.87, 95% CI 1.64–9.13). Familial pre-eclampsia clustering was observed; risk was increased for both first-degree (OR 2.43, 95% CI 1.62–3.73) and second-degree (OR 1.89, 95% CI 1.34–2.68) relatives as well as for husband’s relatives (OR 2.32, 95% CI 1.40–3.86). There was evidence of interaction between alcohol consumption and family history.

CONCLUSIONS Familial aggregation of the disorder was demonstrated, the first Cuban epidemiological evidence of genetic and enviromental contributions to pre-eclampsia risk. Familial clustering among the husband’s relatives demonstrates the fetal genome’s importance in genesis of pre-eclampsia. The interaction of environmental risk factors with genetic ones produces increased pre-eclampsia risk, compared to expectations based on independent action of these variables.

KEYWORDS Pre-eclampsia, toxemia of pregnancy, pregnancy outcome, environment, genetics, genome–environment interaction, genetic epidemiology, Cuba

Introduction One of the most sensitive disabilities in human beings is intellectual disability. In April, 2003, a 10-month study was completed of all persons in Cuba with mental retardation (MR), producing results that included epidemiological variables on a national scale.

Objective Through follow-up research, this paper describes and analyzes 4 prenatal factors associated with MR: Down syndrome (DS), fragile X syndrome (FXS), consanguinity, and maternal alcohol use during pregnancy, in order to provide recommendations for health system decision-makers on consolidating prevention strategies at the community level and improving individual attention to persons with MR.

Materials & Methods All studies were carried out on the basis of strict ethical principles. Data for the 4 prenatal factors was gleaned from the national study’s database. Additional data on affected individuals was obtained through home visits. A previously developed screening instrument was used for clinical genetic analysis to classify possible MR causal factors as prenatal, perinatal, postnatal, psychosis, and unclassifiable. Prenatal included causal factors such as: genetic (by clinical genetic examination, metabolic screening in urine, and routine karyotypes); nonspecific (evidence of prenatal causal factor without diagnosis of genetic or environmental etiology); and environmental (prenatal medical history of biological, physical, or chemical teratogens, endocrine-metabolic diseases, or other maternal diseases known to affect fetal neurodevelopment). Frequency, prevalence, and percentages were reported using a descriptive statistical method. Impact of interventions and actions over time were also compared.

Results MR prevalence in Cuba is 1.25%, lower than the value of 2%-3% reported in developed countries. National prevalence of DS was found to be 4.3 per 10,000 population, representing 22.1% of persons with MR attributed to an ascertained genetic cause. FXS prevalence in a population of individuals of both sexes with MR, initially classified as nonspecific prenatal, psychosis, and unclassifiable, was 2.5 per 1,000 of that population; however, in males of the same population, prevalence was 3.7 per 1,000. At this first stage, such results indicate that this syndrome contributes biologically to the 1.46:1 male/female ratio among the 140,489 individuals with MR. Maternal alcohol use during pregnancy was found in 4.22% of persons with MR and consanguinity was present in 6.89% of the population with MR (10.9% of persons with mild prenatal MR and 14.2% with severe MR). This national data is subdivided by regions and provinces in this paper.

Conclusions Prevalence of MR in Cuba is lower than reference values for developed countries. Knowledge generated by this study about 4 specific causes of MR constitutes pioneering research in the Cuban context, contributing to the field of medical genetics. The results offer the basis for formulation of new scientific contributions related to MR genetics as well as preventive approaches to such genetic factors as consanguinity and to environmental factors such as maternal alcohol use during pregnancy, which affect or target embryo-fetal development of the nervous system.

Keywords Epidemiology; Mental retardation; Down syndrome; Fragile X syndrome; Consanguinity; Maternal alcohol use; Immunohistochemical test; Molecular genetics; Cytogenetics; Genetic (Abstract)