ABSTRACT
Resumen OBJETIVO: Determinar si la exposición al ondansetrón en el primer trimestre del embarazo se asocia, en general, con mayor riesgo de malformaciones orofaciales, cardiopatías congénitas, defectos del septo interventricular, de labio o paladar hendidos. MÉTODOLOGÍA: Revisión sistemática y metanálisis de estudios aleatorizados, cohortes y casos y controles publicados en las bases de datos de PubMed, EMBASE y LILACS. RESULTADOS: Se incluyeron 15 estudios: 11 de cohorte y 4 de casos y controles, con 245,679 mujeres expuestas al ondansetrón en el primer trimestre del embarazo. No se encontró una asociación estadísticamente significativa con malformaciones congénitas en general (RM 1.1; IC95%: 0.99-1.22; I2: 72%), con cardiopatías congénitas (RM 1.05; IC95%: 0.95-1.19; I2: 78%) y con comunicación interventricular (RM 1.2; IC95%: 0.97-1.45; I2: 85%). Se encontró un pequeño aumento en el riesgo de defectos orofaciales en general (RM 1.17; IC95%: 1.04-1.32; I2:0%), no se encontró un riesgo mayor de defecto de labio (RM 1.01; IC95%: 0.84-1.21; I2%: 0%) ni de paladar hendido (RM 1.16; IC95%: 0.9-1.5; I2: 31%). CONCLUSIÓN: Los resultados muestran que el tratamiento con ondansetrón en el primer trimestre del embarazo no se asocia con un aumento de malformaciones congénitas en general, ni con un incremento de cardiopatías, labio o paladar hendido, pero sí con incremento leve del riesgo de malformaciones orofaciales.
Abstract OBJECTIVE: To determine whether ondansetron exposure in the first trimester is associated with an increased risk of any congenital malformations. As secondary outcomes, determine if it is associated with a higher overall risk of congenital heart disease, interventricular septal defects, orofacial malformations, cleft lip defect (with or without palate) or cleft palate. METHODOLOGY: A systematic review with meta-analysis was carried out. The search was carried out in the following databases: PUBMED, EMBASE and LILACS, randomized studies, cohorts and cases and controls were chosen. RESULTS: 15 studies were included, 11 cohort studies and four case-control studies, with 245,679 women exposed to ondansetron in the first trimester. No statistically significant association was found with overall congenital malformations (OR, 1.1; 95%, CI 0.99-1.22 I2: 72%), nor with congenital heart diseases (OR, 1.05; 95%, CI 0.95-1.19 I2: 78%) not with ventricular septal defects (OR, 1.2 95% CI 0.97 - 1.45 I2: 85%). A small increased risk was found for overall orofacial defects (OR, 1.17 95% CI 1.04 - 1.32 I2:0%), no increased risk was found for lip defect (with or without palate) (OR, 1.01 CI 95% 0.84 -1.21 I2%: 0%) or cleft palate (OR, 1.16 95% CI 0.9 - 1.5 I2: 31%). CONCLUSION: The results show that the use of ondansetron in the first trimester is not associated with an increase in overall congenital malformations, nor with an increase in heart disease, cleft lip and/or palate, but there is a slight increase in the risk of orofacial malformations.
ABSTRACT
BACKGROUND: Thoracic transplantation is considered for patients with Eisenmenger syndrome (ES) who have refractory right ventricular failure despite optimal therapy for pulmonary arterial hypertension. This study compared the outcomes of bilateral lung transplantation (BLT) with cardiac defect repair vs combined heart-lung transplantation (HLT). RESEARCH QUESTION: This study presents an updated analysis using a US national registry to evaluate the outcomes of patients diagnosed with ES who underwent HLT or BLT with repair of cardiac defects. STUDY DESIGN AND METHODS: This study identified patients with ES who underwent thoracic transplantation from 1987 to 2018 from the United Network for Organ Sharing database. Survival curves were estimated by using the Kaplan-Meier method and were compared by using the log-rank test. RESULTS: During the study period, 442 adults with ES underwent thoracic transplantation (316 HLTs and 126 BLTs). Following BLT, overall survival 1, 5, and 10 years' posttransplant was 63.1%, 38.5%, and 30.2%, respectively. Following HLT, overall survival 1, 5, and 10 years' posttransplant was 68.0%, 47.3%, and 30.5% (P = .6). When survival analysis was stratified according to type of defect, patients with an atrial septal defect had better survival following BLT than following HLT (88.3% vs 63.2% 1 year posttransplant, P < .01; 71.1% vs 49.8% 3 years' posttransplant, P < .01; and 37.4% vs 29.9% 10 years' posttransplant, P = .08). Patients with a ventricular septal defect (VSD) exhibited better survival following HLT than following BLT (78.2% vs 49.6% 1 year posttransplant, P < .01; 55.6% vs 34.3% 5 years' posttransplant, P < .01; and 35.7% vs 26.5% 10 years' posttransplant, P = .03). The most common cause of mortality in patients with VSD undergoing BLT was cardiac ventricular failure. INTERPRETATION: This study suggests that the best transplant option for patients with VSD remains HLT, which prevents subsequent development of ventricular failure. BLT with cardiac defect repair should be considered as the first-line treatment option in patients with ES due to an uncorrected atrial septal defect. These patients can be considered to have isolated and reversible right ventricular failure akin to patients with advanced pulmonary arterial hypertension.