[Prenatal rescue dose of betamethasone in the preterm infant with intrauterine growth restriction]. / Dosis prenatal de rescate de betametasona en el prematuro con restricción del crecimiento intrauterino.

Antenatal corticosteroids reduce mortality and respiratory distress syndrome (RDS) in preterm newborns. These benefits decrease after a week of administration, recommending a rescue therapy if there is a new threat of premature delivery. Repeated administration of antenatal corticosteroids may have deleterious effects and their benefits are controversial in intrauterine growth restriction (IUGR). OBJECTIVE: to verify the effects in the IUGR population of antenatal betamethasone rescue therapy on neonatal morbidity and mortality, RDS, and neurodevelopment at 2 years. PATIENTS AND METHOD: Retrospective study including ≤ 34 weeks and ≤ 1,500g preterm newborns divided according to antenatal betamethasone exposure: Single-cycle (2 doses) vs Rescue therapy (3 doses). Subgroups were created for those ≥ 30 weeks. Both cohorts were followed up to 24 months of corrected age. The Ages & Stages Questionnaires (ASQ)® was administered to assess neurodevelopment. RESULTS: 62 preterm infants with a diagnosis of IUGR were included. The rescue therapy group compared with the single-dose group showed no differences in morbidity and mortality and less intubation rate at birth (p = 0.02), with no differences in respiratory support at 7 days of life. Preterm newborns ≥ 30 weeks exposed to rescue therapy showed higher morbidity and mortality (p = 0.03) and bronchopulmonary dysplasia (BPD) (p = 0.02), showing no differences in RDS. The rescue therapy group showed worse mean scores on the ASQ-3 scale, with no significant differences in cerebral palsy or sensory deficits. CONCLUSIONS: Rescue therapy reduces intubation at birth but does not reduce morbidity and mortality. However, at > 30 weeks, this benefit is not observed and the IUGR population exposed to rescue therapy presented more BPD and lower scores on the ASQ-3 scale at 2 years. Future studies should be aimed at the individualization of antenatal corticosteroid therapy.

[Embryology and genetics of primary vesicoureteral reflux and associated renal dysplasia]. / Embriología y genética del reflujo vesicoureteral primario y de la displasia renal asociada.

OBJECTIVES: The main reasons of this review are: To determine some of the embryological and genetic mechanisms of vesicoureteral reflux (VUR) and associated congenital reflux nephropathy (NR); recognize different patterns of familiar clustering and identify appropriate cases where genetic counselling and investigations might be indicated; and finally, to establish the association of these phenomena (VUR and NR). METHODS: Bibliographic search of related articles until June 2007. RESULTS: There are two kinds of primary VUR: isolated VUR and syndromic VUR; the last one has an inherited Mendelian transmission and we know the mechanisms. Epidemiological studies seem to demonstrate that isolated VUR also presents familiar clustering and its inheritance pattern is the main object of interest in some studies; most authors support the hypothesis that VUR is genetically heterogeneous and is caused by a number of different genes acting with random environmental effects. There are lots of candidate implicated genes. The characteristics of VUR (incomplete penetrance, variability of expression, spontaneous resolution...) make difficult to configure a selection of patients subsidiary of genetic study. Despite different treatment options, the incidence of renal chronic failure secondary to VUR has not decreased. Some of the candidate genes identified regulate the position of ureteral budding, a critical step in both kidney and urinary tract development. Analysis of data from humans and mice suggests that some of the renal damage associated with VUR is congenital and is due to a kidney malformation. Therefore, in these cases, the association of VUR and renal failure may be caused by a genetic defect affecting the formation of the kidney and the urinary tract and not by evolution of VUR. Investigation in animals is fundamental to know more about this issue (candidate genes and VUR-NR association). CONCLUSION: It is important to learn patterns of familiar clustering of isolated and syndromic VUR to offer genetic counselling if possible. For this reason, we should be screening carefully all patients suffering from VUR. It is known that limitations in actual indications of genetic study exist. Prenatal diagnosis may be realized if there is a syndromic VUR with known mutation, invariable expressivity or if clinical manifestations involve risk of death. Epidemiological data and laboratory studies may give us guidance to elicit new cases of nephropathy associated to severe VUR.

Embriología y genética del reflujo vesicoureteral primario y de la displasia renal asociada / Embryology and genetics of primary vesicoureteral reflux and associated renal dysplasia

Objetivo: Realizar una aproximación a la embriología y genética del reflujo vesicoureteral (RVU) y de la nefropatía de reflujo (NR). Reconocer los patrones de asociación familiar del RVU y tratar de ver en qué casos se deberían considerar estudios genéticos a estos pacientes y, en tal caso, qué tipo de estudios. Por último, estudiar qué tipo de asociación presentan estos dos fenómenos (RVU y NR). Métodos: Revisión bibliográfica de artículos relacionados hasta junio de 2007. Resultados: Se reconocen dos tipos de RVU primario según la presentación: aislado y sindrómico; de este último se conocen sus mecanismos de transmisión y sigue patrones de herencia mendeliana. Los estudios epidemiológicos ponen de manifiesto que el RVU aislado también presenta asociación familiar, y es objeto de estudio el patrón de herencia del mismo; la mayoría de los autores sostienen la idea de que se trata de un fenómeno genéticamente heterogéneo en el que interactúan diferentes genes y efectos medioambientales. Son múltiples los genes candidatos implicados. Las características del RVU (expresividad y penetrancia variables, resolución espontánea) hacen difícil seleccionar aquellos pacientes subsidiarios de estudio genético. A pesar del tratamiento del RVU, la incidencia de fallo renal crónico secundario al mismo no ha descendido. Algunos de los genes candidatos en estudio para el RVU se han identificado como reguladores de la embriogénesis de la yema ureteral, paso clave para el desarrollo del riñón y tracto urinario. Análisis en ratones y humanos sugieren que parte del daño renal asociado al RVU es congénito y debido a una malformación congénita; por lo que la asociación entre RVU y fallo renal puede deberse a un defecto genético del desarrollo y no a la mala evolución del paciente con RVU. La investigación en animales es un paso clave para profundizar en los conocimientos en este tema (genes candidatos y asociación de RVU con NR). Conclusiones: Es importante conocer los patrones de asociación familiar del RVU (aislado y sindrómico) para dar consejo genético cuando sea posible. Por ello, en todo paciente con RVU, son necesarias una anamnesis y exploración específicas y dirigidas. La indicación actual de estudio genético tiene limitaciones. Se realizará diagnóstico prenatal si existe RVU sindrómico con mutación conocida, expresividad fija y penetrancia completa o si las manifestaciones conllevan riesgo vital. Los datos epidemiológicos y estudios de laboratorio nos orientan a la posibilidad de nefropatía congénita asociada en casos de RVU grave (AU)

Objectives: The main reasons of this review are: To determine some of the embryological and genetic mechanisms of vesicoureteral reflux (VUR) and associated congenital reflux nephropathy (NR); recognize different patterns of familiar clustering and identify appropriate cases where genetic counselling and investigations might be indicated; and finally, to establish the association of these phenomena (VUR and NR). Methods: Bibliographic search of related articles until June 2007. Results: There are two kinds of primary VUR: isolated VUR and syndromic VUR; the last one has an inherited Mendelian transmission and we know the mechanisms. Epidemiological studies seem to demonstrate that isolated VUR also presents familiar clustering and its inheritance pattern is the main object of interest in some studies; most authors support the hypothesis that VUR is genetically heterogeneous and is caused by a number of different genes acting with random environmental effects. There are lots of candidate implicated genes. The characteristics of VUR (incomplete penetrance, variability of expression, spontaneous resolution…) make difficult to configure a selection of patients subsidiary of genetic study. Despite different treatment options, the incidence of renal chronic failure secondary to VUR has not decreased. Some of the candidate genes identified regulate the position of ureteral budding, a critical step in both kidney and urinary tract development. Analysis of data from humans and mice suggests that some of the renal damage associated with VUR is congenital and is due to a kidney malformation. Therefore, in these cases, the association of VUR and renal failure may be caused by a genetic defect affecting the formation of the kidney and the urinary tract and not by evolution of VUR. Investigation in animals is fundamental to know more about this issue (candidate genes and VUR-NR association). Conclusion: It is important to learn patterns of familiar clustering of isolated and syndromic VUR to offer genetic counselling if possible. For this reason, we should be screening carefully all patients suffering from VUR. It is known that limitations in actual indications of genetic study exist. Prenatal diagnosis may be realized if there is a syndromic VUR with known mutation, invariable expressivity or if clinical manifestations involve risk of death. Epidemiological data and laboratory studies may give us guidance to elicit new cases of nephropathy associated to severe VUR (AU)