Añadir medicación oral a los ciclos de fiv en ciclo natural no aporta beneficio a los resultados clínicos / Adding oral medication does not have any benefit on natural-cycle ivf results

Introducción: En los últimos años, los tratamientos de FIV en ciclo natural y la FIV con estimulación ovárica “suave” están resurgiendo como una opción más segura, económica y cómoda para las pacien-tes. Definimos FIV en ciclo natural como el tratamiento en el que los ovocitos son obtenidos de un ciclo ovulatorio espontáneo. Cuando añadimos fármacos orales (citrato de clomifeno o letrozol), hablamos de estimulación “mínima”. El objetivo de este estudio es clarificar si la introducción de esta medicación es beneficiosa para las pacientes. Materials y métodos: Analizamos retrospectivamente los tratamientos de FIV en ciclo natural o con estimulación mínima llevados realizados en nuestro centro de enero 2016 a diciembre 2020.Resultados: Encontramos diferencias significativas entre los dos protocolos en el número de ovocitos obtenidos después de la punción folicular (1.03 vs 1.63, p<0.001), número de ovocitos maduros (0.9 vs 1.3, p < 0.01), ovocitos fecundados (0.7 vs 1.1, p < 0.01), y número de embriones disponibles para trans-ferencia (0.5 vs 0.7, p < 0.01). Sin embargo, no encontramos diferencias en la tasa de embarazo (26,3% vs 19,6%, p=0.251) ni en la tasa de recién nacido vivo (16.3% vs 14,3%, p=0.7806).Discusión: Añadir medicación oral a la FIV en ciclo natural no parece tener ningún impacto sobre los resultados clínicos del ciclo. Son necesarios más estudios, pero podríamos reconsiderar la necesidad de añadir esta medicación, ya que supone un mayor coste para los pacientes. (AU)

Introduction: In recent years, natural cycle IVF and minimal ovarian stimulation IVF had been under-going a revival, gaining recognition as safer, cheaper, and more comfortable options for patients. We define natural cicle IVF as the treatment in which oocytes are obtained from a spontaneous ovulatory cycle. When oral drugs are used (usually clomiphene citrate or letrozole), the process is referred to as minimal ovarian stimulation cycle IVF. The aim of this study is to clarify whether the introduction of oral medication is beneficial for patients.Methods: We retrospectively analysed all natural or minimal ovarian stimulation IVF treatments that took place in our clinic during the studied period (January 2016 - December 2020). Descriptive variables were analysed with a t-test, and a chi-square test was performed on result variables. Results: We found significant differences, between both protocols, in the number of oocytes obtained after oocyte retrieval (1.03 vs 1.63, p<0.001), number of mature oocytes (0.9 vs 1.3, p < 0.01), fertilized oocytes (0.7 vs 1.1, p < 0.01), and number of embryos available for transfer (0.5 vs 0.7, p < 0.01).Howe-ver, we did not found signficant differences in terms of pregnancy rate (26,3% vs 19,6%, p=0.251) or live birth rate (16.3% vs 14,3%, p=0.7806). (AU)

Predicción del crecimiento a los dos años utilizando las gráficas de Fenton e Intergrowth-21 en menores de 1.500 g / Growth outcome at 2 years using Fenton and Intergrowth-21st charts in infants less than 1500 g

Introducción: No existe consenso sobre qué gráfica neonatal es mejor utilizar en niños con muy bajo peso al nacer (MBPN). El objetivo del estudio fue comparar las gráficas de Fenton 2013 e Intergrowth-21st (IW-21) con base en su capacidad predictora de la somatometría a los dos años, así como analizar factores relacionados con talla baja a los dos años. Material y métodos: Cohorte de niños con MBPN nacidos entre 2002-2017. Se analizó la asociación entre la somatometría neonatal (z-score por Fenton e IW-21) y el riesgo de talla baja (< -2 desviación estándar [DS]), perímetro craneal < -2 DS y desnutrición a los 2 años (IMC < -2 DS) (gráficas OMS). Resultados: Se incluyeron 513 niños con una edad gestacional media de 30,05 ± 2,5 semanas. El z-score del peso al nacimiento y al alta por Fenton y por IW-21 resultaron útiles para predecir riesgo de talla baja y desnutrición a los dos años (sin diferencias en el AUC de las curvas ROC), siendo el z-score al alta útil además para predecir perímetro craneal < -2D. A los dos años, la prevalencia de talla baja, perímetro craneal < -2 DS, y desnutrición fue del 17,2, 4,1 y 6,1%, respectivamente. El bajo peso para la edad gestacional y la duración del ingreso neonatal se identificaron como factores de riesgo independientes para talla baja a los dos años. Conclusiones: El z-score peso al alta resulta útil para predecir riesgo de talla baja, desnutrición y perímetro craneal < -2 DS a los dos años en niños con muy bajo peso al nacer, sin diferencias estadísticas entre utilizar las gráficas de Fenton o IW-21. (AU)

Introduction: There is no consensus on which neonatal chart is best to use in very low birth weight (VLBW) infants. The aim of the study was to compare the Fenton 2013 and Intergrowth-21st (IW-21) charts based on their predictive ability for somatometry at 2 years, as well as to analyze factors related to short stature at 2 years. Material and methods: Cohort of children with VLBW born in 2002–2017. Association between neonatal somatometry (z-score by Fenton and IW-21) and risk of short stature (< −2 DS), head circumference < −2 DS and malnutrition at 2 years (BMI < −2 DS) was analyzed (WHO charts). Results: 513 children with a mean gestational age of 30.05 ± 2.5 weeks were included. Birth and discharge weight z-score by Fenton and IW-21 were useful for predicting risk of short stature and malnutrition at 2 years (without differences in the AUC of the ROC curves). Weight z-score at discharge was also useful for predicting head circumference < −2 DS. At 2 years, prevalence of short stature, head circumference < −2 DS, and malnutrition was 17.2, 4.1, and 6.1%, respectively. Low weight for gestational age and length of stay were identified as independent risk factors for short stature at 2 years. Conclusions: Discharge weight z-score is useful for predicting risk of short stature, malnutrition and head circumference < −2 DS at 2 years in very low birth weight children, with no statistical difference between using Fenton or IW-21 charts. (AU)

Growth outcome at 2 years using Fenton and Intergrowth-21st charts in infants less than 1500 g.

INTRODUCTION: There is no consensus on which neonatal chart is best to use in very low birth weight (VLBW) infants. The aim of the study was to compare the Fenton 2013 and Intergrowth-21st (IW-21) charts based on their predictive ability for somatometry at 2 years, as well as to analyze factors related to short stature at 2 years. MATERIAL AND METHODS: Cohort of children with VLBW born between 2002 and 2017. Association between neonatal somatometry (z-score by Fenton and IW-21) and risk of short stature (<-2 DS), head circumference <-2 DS and malnutrition at 2 years (BMI < -2 DS) was analyzed (WHO charts). RESULTS: 513 children with a mean gestational age of 30.05 ± 2.5 weeks were included. Birth and discharge weight z-score by Fenton and IW-21 were useful for predicting risk of short stature and malnutrition at 2 years (without differences in the AUC of the ROC curves). Weight z-score at discharge was also useful for predicting head circumference < -2 DS. At 2 years, prevalence of short stature, head circumference < -2 DS, and malnutrition was 17.2, 4.1, and 6.1%, respectively. Low weight for gestational age and length of stay were identified as independent risk factors for short stature at 2 years. CONCLUSIONS: Discharge weight z-score is useful for predicting risk of short stature, malnutrition and head circumference < -2 DS at 2 years in very low birth weight children, with no statistical difference between using Fenton or IW-21 charts.

Neuropsychological Development and New Criteria for Extrauterine Growth Restriction in Very Low-Birth-Weight Children.

BACKGROUND: Controversy between short-term neonatal growth of very low birth-weight preterm (VLBW) and neurodevelopment may be affected by criteria changes of extrauterine growth restriction (EUGR). OBJECTIVE: to determine if new EUGR criteria imply modifications in the relationship between old criteria and results of neuropsychological tests in preterm children. PATIENTS AND METHODS: 87 VLBW at 5-7 years of age were studied. Neuropsychological assessment included RIST test (Reynolds Intellectual Sctreening Test) and NEPSY-II (NE neuro, PSY psycolgy assessment) tests. The relationships between these tests and the different growth parameters were analyzed. RESULTS: RIST index was correlated with z-score Fenton's weight (p = 0.004) and length (p = 0.003) and with z-score IGW-21's (INTERGRWTH-21 Project) weight (p = 0.004) and length (p = 0.003) at neonatal discharge, but not with z-score difference between birth and neonatal discharge in weight, length, and HC for both. We did not find a statistically significant correlation between Fenton or IGW-21 z-scores and scalar data of NEPSY-II subtasks. CONCLUSION: In our series, neonatal growth influence on neuropsychological tests at the beginning of primary school does not seem robust, except for RIST test. New EUGR criteria do not improve the predictive ability of the old ones.

Extrauterine Growth Restriction in Very Low Birth Weight Infants: Concordance Between Fenton 2013 and INTERGROWTH-21st Growth Charts.

Postnatal growth restriction has high prevalence in very low birth weight (VLBW) preterm neonates, and this could affect their long-term prognosis. Nowadays, there is no consensus on how to monitor growth in these neonates. Objective: This study aimed to compare prevalence of intra- and extrauterine growth restriction (IUGR and EUGR) in a sample of VLBW infants according to the Fenton 2013 charts and INTERGROWTH-21st (IW-21) standards and to analyze concordance between both in the different EUGR definitions criteria (cross-sectional, dynamic, and true). Patients and Methods: An observational retrospective study of 635 VLBW preterm was performed. The study was carried out in Central University Hospital of Asturias. Body measurements (weight, length, and head circumference) were collected at birth and at hospital discharge and expressed in z-scores for the two references (Fenton 2010 and IW-21). Kappa concordance was calculated. Results: Kappa concordance between Fenton and IW-21 was 0.887 for IUGR and 0.580 for static EUGR. Prevalence was higher according to Fenton in IUGR (36.5 vs. 35.1%), in static EUGR (73.8 vs. 59.3%), and in dynamic EUGR (44.3 vs. 29.3%). Despite observing low prevalence of EUGR when IW-21 was used to define EUGR, a statistical association between neonatal morbidity and diagnosis of EUGR was observed. Conclusion: The Fenton and IW-21 concordance for IUGR is good. IW-21 is more restrictive than Fenton in EUGR. Patients diagnosed by IW-21 as EUGR are more likely to have neonatal morbidity, especially if we use EUGR dynamic definition. In our study, we cannot conclude that one graph is better than the other.

Composición nutricional de la leche materna donada según el periodo de lactancia / Nutritional composition of donor human milk according to lactation period

INTRODUCCIÓN: cuando no se dispone de leche materna propia, la leche materna donada es la mejor alternativa para asegurar los requerimientos nutricionales de los recién nacidos prematuros o enfermos. OBJETIVOS: conocer el contenido de macronutrientes de la leche materna donada y cómo varían estos en los distintos periodos de la lactancia. MATERIAL Y MÉTODOS: se analizó de forma retrospectiva la composición nutricional de 822,423 litros de leche materna donada, procedentes de 160 donantes del banco de leche materna de un hospital de tercer nivel entre el 1 de febrero de 2017 y el 31 de diciembre de 2019. RESULTADOS: el contenido en lípidos y carbohidratos se mantiene constante a lo largo de la lactancia; sin embargo, el contenido proteico disminuye inicialmente para luego volver a aumentar a partir del segundo año de lactancia. CONCLUSIONES: los bancos de leche materna deben conocer las variaciones del contenido en macronutrientes de la leche donada para optimizar la nutrición del recién nacido prematuro

INTRODUCTION: when own mother's breast milk is unavailable, donor human milk is the best option to guarantee the nutritional requirements of preterm or ill newborns. OBJECTIVES: to analyze the macronutrient composition of donor breast milk and its evolution over lactation periods. MATERIAL AND METHODS: we retrospectively analyzed the nutritional composition of 822.423 L of donor breast milk from 160 donors at the human milk bank of a third-level hospital between February 1, 2017 and December 31, 2019. RESULTS: lipid and carbohydrate composition remains constant throughout lactation. However, protein content decreases initially to increase again starting in the second year of lactation. CONCLUSIONS: donor human milk banks should be aware of the variations in macronutrient composition donor human milk shows in order to optimize nutrition for preterm newborns

[Nutritional composition of donor human milk according to lactation period]. / Composición nutricional de la leche materna donada según el periodo de lactancia.

INTRODUCTION: Introduction: when own mother´s breast milk is unavailable, donor human milk is the best option to guarantee the nutritional requirements of preterm or ill newborns. Objectives: to analyze the macronutrient composition of donor breast milk and its evolution over lactation periods. Material and methods: we retrospectively analyzed the nutritional composition of 822.423 L of donor breast milk from 160 donors at the human milk bank of a third-level hospital between February 1, 2017 and December 31, 2019. Results: lipid and carbohydrate composition remains constant throughout lactation. However, protein content decreases initially to increase again starting in the second year of lactation. Conclusions: donor human milk banks should be aware of the variations in macronutrient composition donor human milk shows in order to optimize nutrition for preterm newborns.

INTRODUCCIÓN: Introducción: cuando no se dispone de leche materna propia, la leche materna donada es la mejor alternativa para asegurar los requerimientos nutricionales de los recién nacidos prematuros o enfermos. Objetivos: conocer el contenido de macronutrientes de la leche materna donada y cómo varían estos en los distintos periodos de la lactancia. Material y métodos: se analizó de forma retrospectiva la composición nutricional de 822,423 litros de leche materna donada, procedentes de 160 donantes del banco de leche materna de un hospital de tercer nivel entre el 1 de febrero de 2017 y el 31 de diciembre de 2019. Resultados: el contenido en lípidos y carbohidratos se mantiene constante a lo largo de la lactancia; sin embargo, el contenido proteico disminuye inicialmente para luego volver a aumentar a partir del segundo año de lactancia. Conclusiones: los bancos de leche materna deben conocer las variaciones del contenido en macronutrientes de la leche donada para optimizar la nutrición del recién nacido prematuro.

Increasing survival of metastatic breast cancer through locoregional surgery.

BACKGROUND: Surgery for the primary tumor in metastatic breast cancer is usually not recommended, assuming that local therapy provides no advantage. Recent reports suggest a survival improvement after locoregional treatment, but this is still controversial. We aimed to evaluate the effectiveness of locoregional treatment in primary metastatic breast cancer and to determine associated factors. METHODS: A retrospective analysis of 39 women with de-novo metastatic breast cancer at La Paz University Hospital, from January 2012 to June 2016, grouped by locoregional treatment (n=23) or not (n=16). Multivariate assessment of prognostic factors was performed using Cox regression analysis. RESULTS: Mean tumor size was 6 cm. Eighteen patients (46.2%) had multifocal tumors, 29 (74.4%) multicentric and 10 (25.7%) bilateral breast cancer. Eighteen patients (46.2%) had an oligometastatic disease and 21 (53.8%) multiorgan metastatic disease. The average time from diagnosis to surgery was 7.7 months, without delay in the start of systemic treatment compared to the no-surgery group. The main surgical procedure was mastectomy in 18 (78.3%) patients. Half of the patients survived 48 months (95% CI: 39-57). In the multivariate analysis, we have not detailed differences in survival by age, chemotherapy, neoadjuvancy, number of systemic treatment lines, radiotherapy, and tumor histology or grade. However, surgery (HR=0.2; 95% CI: 0.07-0.57) and high tumor burden (HR=2.96, 95% CI: 1.23-7.13) have acted as a protective and a risk factor respectively. CONCLUSIONS: Our cohort supports that locoregional treatment in selected patients with de-novo MBC significantly improved survival, so it might be considered in combination with systemic therapy.

Protocol for the BRECAR study: a prospective cohort follow-up on the impact of breast reconstruction timing on health-related quality of life in women with breast cancer.

INTRODUCTION: The completion of postmastectomy breast reconstruction (BR) in women with breast cancer can last from months to years, and to our knowledge, there is a lack of studies that analyse how the different types and times of reconstruction impact on the patient's quality of life and psychosocial adjustment.The primary aim of the BREast Cancer Reconstruction (BRECAR Study) is twofold. First, to describe health-related quality of life (HRQoL), overall satisfaction with surgery and psychological impact (body image, self-esteem, depression and anxiety) on women who will have undergone a mastectomy with planned BR, considering the varied timing of BR procedures (immediate BR (iBR), delayed BR (dBR) and two-stage BR (2sBR)). To measure the impact on surgical outcomes, we will obtain data prior to and after surgery (6-9 and at 18 months of follow-up). Second, to analyse sociodemographic, clinical and psychosocial factors associated with HRQoL, satisfaction with surgery and psychological impact. METHODS AND ANALYSIS: A prospective, observational, clinical cohort study of women diagnosed with breast cancer who have an indication for mastectomy treated at La Paz University Hospital (Madrid, Spain).Patients will be classified into one of three groups under conditions of routine clinical practice, based on the type of BR planned: the iBR group, the dBR group and the 2sBR group.Under typical clinical practice conditions, we will perform three visits: baseline visit (presurgery), V1 (6-9 months after diagnosis) and V2 (18 months after diagnosis). A sample size of 210 patients is estimated. ETHICS AND DISSEMINATION: The study protocol and informed consent form have been reviewed and approved by the Institutional Review Board of La Paz Hospital (no. PI-2036). Dissemination of results will be via journal articles and conference presentations.

Effects of growth hormone treatment on growth plate, bone, and mineral metabolism of young rats with uremia induced by adenine.

This corrects the article DOI: 10.1038/pr.2017.95.

Effects of growth hormone treatment on growth plate, bone, and mineral metabolism of young rats with uremia induced by adenine.

BackgroundIn a model of growth retardation secondary to chronic kidney disease (CKD) induced by adenine, this study explores the effects of growth hormone (GH) therapy on growth plate and mineral metabolism.MethodsWeaning female rats receiving a 0.5% adenine diet during 21 days, untreated (AD) or treated with GH (ADGH) for 1 week, were compared with control rats receiving normal diet, either ad libitum or pair-fed with AD animals. AD and ADGH rats had similarly elevated serum concentrations of urea nitrogen, parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF23).ResultsUremia induced by adenine caused growth retardation and disturbed growth cartilage chondrocyte hypertrophy. We demonstrated marked expression of aquaporin 1 in the growth plate, but its immunohistochemical signal and the expression levels of other proteins potentially related with chondrocyte enlargement, such as Na-K-2Cl cotransporter, insulin-like growth factor 1 (IGF-1), and IGF-1 receptor, were not different among the four groups of rats. The distribution pattern of vascular endothelial growth factor was also similar. AD rats developed femur bone structure abnormalities analyzed by micro-computerized tomography.ConclusionGH treatment accelerated longitudinal growth velocity, stimulated the proliferation and enlargement of chondrocytes, and did not modify the elevated serum PTH or FGF23 concentrations or the abnormal bone structure.

Chronic kidney disease induced by adenine: a suitable model of growth retardation in uremia.

Growth retardation is a major manifestation of chronic kidney disease (CKD) in pediatric patients. The involvement of the various pathogenic factors is difficult to evaluate in clinical studies. Here, we present an experimental model of adenine-induced CKD for the study of growth failure. Three groups (n = 10) of weaning female rats were studied: normal diet (control), 0.5% adenine diet (AD), and normal diet pair fed with AD (PF). After 21 days, serum urea nitrogen, creatinine, parathyroid hormone (PTH), weight and length gains, femur osseous front advance as an index of longitudinal growth rate, growth plate histomorphometry, chondrocyte proliferative activity, bone structure, aorta calcifications, and kidney histology were analyzed. Results are means ± SE. AD rats developed renal failure (serum urea nitrogen: 70 ± 6 mg/dl and creatinine: 0.6 ± 0.1 mg/dl) and secondary hyperparathyroidism (PTH: 480 ± 31 pg/ml). Growth retardation of AD rats was demonstrated by lower weight (AD rats: 63.3 ± 4.8 g, control rats: 112.6 ± 4.7 g, and PF rats: 60.0 ± 3.8 g) and length (AD rats: 7.2 ± 0.2 cm, control rats: 11.1 ± 0.3 cm, and PF rats: 8.1 ± 0.3 cm) gains as well as lower osseous front advances (AD rats: 141 ± 13 µm/day, control rats: 293 ± 16 µm/day, and PF rats: 251 ± 10 µm/day). The processes of chondrocyte maturation and proliferation were impaired in AD rats, as shown by lower growth plate terminal chondrocyte height (21.7 ± 2.3 vs. 26.2 ± 1.9 and 23.9 ± 1.3 µm in control and PF rats) and proliferative activity index (AD rats: 30 ± 2%, control rats: 38 ± 2%, and PF rats: 42 ± 3%). The bone primary spongiosa structure of AD rats was markedly disorganized. In conclusion, adenine-induced CKD in young rats is associated with growth retardation and disturbed endochondral ossification. This animal protocol may be a useful new experimental model to study growth in CKD.

Growth hormone improves growth retardation induced by rapamycin without blocking its antiproliferative and antiangiogenic effects on rat growth plate.

Rapamycin, an immunosuppressant agent used in renal transplantation with antitumoral properties, has been reported to impair longitudinal growth in young individuals. As growth hormone (GH) can be used to treat growth retardation in transplanted children, we aimed this study to find out the effect of GH therapy in a model of young rat with growth retardation induced by rapamycin administration. Three groups of 4-week-old rats treated with vehicle (C), daily injections of rapamycin alone (RAPA) or in combination with GH (RGH) at pharmacological doses for 1 week were compared. GH treatment caused a 20% increase in both growth velocity and body length in RGH animals when compared with RAPA group. GH treatment did not increase circulating levels of insulin-like growth factor I, a systemic mediator of GH actions. Instead, GH promoted the maturation and hypertrophy of growth plate chondrocytes, an effect likely related to AKT and ERK1/2 mediated inactivation of GSK3ß, increase of glycogen deposits and stabilization of ß-catenin. Interestingly, GH did not interfere with the antiproliferative and antiangiogenic activities of rapamycin in the growth plate and did not cause changes in chondrocyte autophagy markers. In summary, these findings indicate that GH administration improves longitudinal growth in rapamycin-treated rats by specifically acting on the process of growth plate chondrocyte hypertrophy but not by counteracting the effects of rapamycin on proliferation and angiogenesis.

Rapamycin induces growth retardation by disrupting angiogenesis in the growth plate.

Rapamycin, a potent immunosuppressant used in renal transplantation, has been reported to impair longitudinal growth in experimental studies. Rapamycin is both antiproliferative and antiangiogenic; therefore, it has the potential to disrupt vascular endothelial growth factor (VEGF) action in the growth plate and to interfere with insulin-like growth factor I (IGF-I) signaling. To further investigate the mechanisms of rapamycin action on longitudinal growth, we gave the 4-week-old rats rapamycin daily for two weeks. Compared with a vehicle-treated group, rapamycin-treated animals were severely growth retarded and had marked alterations in the growth plate. Vascular invasion was disturbed in the rapamycin group, there was a significant reduction in osteoclast cells near the chondro-osseus junction, and there was lower VEGF protein and mRNA expression in the terminal chondrocytes of the growth cartilage. Compared with the control group, the rapamycin group had higher levels of circulating IGF-I as well as the mRNAs for IGF-I and of the receptors of IGF-I and growth hormone in the liver but not in the growth cartilage. Thus our findings explain the adverse effect of rapamycin on growth plate dynamics. This should be taken into account when the drug is administered to children.

Frecuencia de los defectos del tubo neural en Asturias: impacto del diagnóstico prenatal / Prevalence of neural tube defects in Asturias (Spain): impact of prenatal diagnosis

ObjetivoDescribir la frecuencia de defectos del tubo neural (DTN) –anencefalia, espina bífida y encefalocele—en Asturias, su evolución temporal y el impacto del diagnóstico prenatal.MétodosSe estudiaron los casos de DTN en nacidos y abortos inducidos durante el período 1990–2004, utilizando la base de datos del Registro de Defectos Congénitos de Asturias, de base poblacional. Se calcularon las tasas de prevalencia total y al nacimiento.ResultadosLa prevalencia total de DTN fue de 12,2 casos por 10.000 nacidos (5,9 anencefalias, 5,0 espinas bífidas y 1,3 encefaloceles) y mostró una tendencia ligeramente descendente, con un descenso significativo de la espina bífida, mientras que las cifras de anencefalia y encefalocele se mantuvieron estables. Finalizaron en aborto inducido tras el diagnóstico prenatal el 88% de los casos (anencefalia 96,7%; espina bífida 80%; encefalocele 84,6%), lo que determinó una prevalencia al nacimiento muy baja (1,4 DTN por 10.000 nacidos).ConclusionesEn Asturias, en los últimos 15 años se ha producido un descenso selectivo en la prevalencia total de espina bífida de causa no aclarada. La prevención secundaria, mediante los programas de diagnóstico prenatal y la consiguiente interrupción del embarazo, fue el motivo del marcado descenso de la frecuencia en los nacidos; la simple recomendación de suplementación periconcepcional con ácido fólico no parece haber logrado el efecto buscado(AU)

ObjectiveTo describe the frequency and prevalence trend for neural tube defects (NTD) (anencephaly, spina bifida and encephalocele) in Asturias (Spain), as well as the impact of prenatal diagnosis programs.MethodsAll cases of NTD in births and induced abortions were studied, using data from the Registry of Congenital Defects of Asturias for 1990-2004. Total and birth prevalence rates were calculated.ResultsThe prevalence of NTD for 1990–2004 was 12.2 per 10,000 births (5.9 anencephaly, 5.0 spina bifida and 1.3 encephalocele) and showed a slightly decreasing trend due to a significant decline in spina bifida prevalence. The prevalence of anencephaly and encephalocele remained stable. The percentage of induced abortions after prenatal diagnosis among all NTD was 88% (anencephaly 96.7%, spina bifida 80% and encephalocele 84.6%), leading to a very low birth prevalence (1.4 per 10,000) for the entire period.ConclusionsThe total prevalence of spina bifida has decreased in the last 15 years in Asturias. Secondary prevention through prenatal diagnosis and interruption of affected pregnancies have resulted in a marked decrease in NTD at birth. The recommendation of periconceptional use of folic acid seems not to have achieved the desired effect (AU)

Frecuencia y tendencia temporal de los defectos congénitos en Asturias. La necesidad de la vigilancia clinicoepidemiológica / Prevalence and secular trend of congenital defects in Asturias, Spain. The need for clinical-epidemiological surveillance

ObjetivoLos defectos congénitos son la segunda causa de muerte perinatal e infantil, y la tercera entre los 2 y 5 años de edad en Asturias. Además, generan una importante morbilidad. El objetivo de nuestro estudio fue conocer la frecuencia global de los defectos congénitos en Asturias y su forma de presentación.MétodosSe analizaron los datos del Registro de Defectos Congénitos de Asturias (RDCA), de base poblacional, durante el período 1990–2004. Los datos se refieren a nacidos y abortos inducidos después del diagnóstico prenatal, y se presentan como prevalencias al nacimiento y total (incluye los abortos inducidos).ResultadosSe registraron 3.035 casos de defectos congénitos entre 103.452 nacidos, con una prevalencia total de 2,9 casos por 100 nacidos y una prevalencia al nacimiento del 2,5%. Estas frecuencias presentaron una tendencia al aumento. Fueron 2.516 (82,9%) neonatos, 46 (1,5%) mortinatos y 473 (15,6%) abortos inducidos. El diagnóstico prenatal fue aumentando durante el citado período. Un 63% presentó un defecto aislado o una secuencia, un 17% un síndrome y el 20% restante defectos múltiples sin un patrón sindrómico conocido. Los defectos más frecuentes y graves fueron los del tubo neural (12,2 casos por 10.000 nacidos), las anomalías del corazón (75,2 por 10.000) y las cromosómicas (34,4 por 10.000).ConclusionesLa experiencia de 15 años del RDCA pone de manifiesto la necesidad de estos sistemas de información para evaluar los programas de diagnóstico prenatal, planificar adecuadamente los recursos de atención a las mujeres embarazadas que pudieran estar afectadas, así como a los recién nacidos, y asegurar la vigilancia epidemiológica de los defectos congénitos en relación con las exposiciones medioambientales y medicamentosas, y con las técnicas de reproducción asistida(AU)

ObjectiveCongenital defects remain the second cause of perinatal and infant death and the third cause between the second and fifth years of life in Asturias. These anomalies generate substantial morbidity. The aim of the present study was to describe the population-based frequency of congenital defects in Asturias and their forms of presentation.MethodsData from the population-based Registry of Congenital Defects of Asturias for 1990–2004 were analyzed. The data related to live births, stillbirths and induced abortions after prenatal diagnosis and are presented as birth prevalence and total prevalence (including induced abortions).ResultsThe total number of births was 103,452 and there were 3,035 cases of congenital defects, representing a total prevalence of 2.9 cases per 100 births and a birth prevalence of 2.5%. These figures showed a tendency to increase throughout the study period. A total of 2,516 (82.9%) cases were live births, 46 (1.5%) were stillbirths and 473 (15.6%) were induced abortions. Prenatal diagnosis increased throughout the period. Sixtythree percent of total cases showed an isolated defect, 17% a recognized syndrome and the remaining 20% had multiple malformations without a syndromic pattern. The most frequent and severe defects registered were neural tube defects (12.2 per 10,000 births), chromosomal abnormalities (34.4 per 10,000), and cardiac defects (75.2 per 10,000).ConclusionsThe 15-year experience of the Registry of Congenital Defects of Asturias reveals the utility of this type of database to evaluate prenatal screening programs, plan the resources needed in affected pregnant women and infants, and perform epidemiological surveillance of congenital defects in relation to environmental risks, drug exposure and assisted reproduction techniques(AU)

Alterations of growth plate and abnormal insulin-like growth factor I metabolism in growth-retarded hypokalemic rats: effect of growth hormone treatment.

Hypokalemic tubular disorders may lead to growth retardation which is resistant to growth hormone (GH) treatment. The mechanism of these alterations is unknown. Weaning female rats were grouped (n = 10) in control, potassium-depleted (KD), KD treated with intraperitoneal GH at 3.3 mg x kg(-1) x day(-1) during the last week (KDGH), and control pair-fed with KD (CPF). After 2 wk, KD rats were growth retarded compared with CPF rats, the osseous front advance (+/-SD) being 67.07 +/- 10.44 and 81.56 +/- 12.70 microm/day, respectively. GH treatment did not accelerate growth rate. The tibial growth plate of KD rats had marked morphological alterations: lower heights of growth cartilage (228.26 +/- 23.58 microm), hypertrophic zone (123.68 +/- 13.49 microm), and terminal chondrocytes (20.8 +/- 2.39 microm) than normokalemic CPF (264.21 +/- 21.77, 153.18 +/- 15.80, and 24.21 +/- 5.86 microm). GH administration normalized these changes except for the distal chondrocyte height. Quantitative PCR of insulin-like growth factor I (IGF-I), IGF-I receptor, and GH receptor genes in KD growth plates showed downregulation of IGF-I and upregulation of IGF-I receptor mRNAs, without changes in their distribution as analyzed by immunohistochemistry and in situ hybridization. GH did not further modify IGF-I mRNA expression. KD rats had normal hepatic IGF-I mRNA levels and low serum IGF-I values. GH increased liver IGF-I mRNA, but circulating IGF-I levels remained reduced. This study discloses the structural and molecular alterations induced by potassium depletion on the growth plate and shows that the lack of response to GH administration is associated with persistence of the disturbed process of chondrocyte hypertrophy and depressed mRNA expression of local IGF-I in the growth plate.

[Prevalence of neural tube defects in Asturias (Spain): impact of prenatal diagnosis]. / Frecuencia de los defectos del tubo neural en Asturias: impacto del diagnóstico prenatal.

OBJECTIVE: To describe the frequency and prevalence trend for neural tube defects (NTD) (anencephaly, spina bifida and encephalocele) in Asturias (Spain), as well as the impact of prenatal diagnosis programs. METHODS: All cases of NTD in births and induced abortions were studied, using data from the Registry of Congenital Defects of Asturias for 1990-2004. Total and birth prevalence rates were calculated. RESULTS: The prevalence of NTD for 1990-2004 was 12.2 per 10,000 births (5.9 anencephaly, 5.0 spina bifida and 1.3 encephalocele) and showed a slightly decreasing trend due to a significant decline in spina bifida prevalence. The prevalence of anencephaly and encephalocele remained stable. The percentage of induced abortions after prenatal diagnosis among all NTD was 88% (anencephaly 96.7%, spina bifida 80% and encephalocele 84.6%), leading to a very low birth prevalence (1.4 per 10,000) for the entire period. CONCLUSIONS: The total prevalence of spina bifida has decreased in the last 15 years in Asturias. Secondary prevention through prenatal diagnosis and interruption of affected pregnancies have resulted in a marked decrease in NTD at birth. The recommendation of periconceptional use of folic acid seems not to have achieved the desired effect.

Frecuencia del síndrome de Down en Asturias y tendencia temporal, 1990-2004 / Prevalence and secular trend of Down syndrome in Asturias (Spain), 1990-2004

Fundamento y objetivo: El síndrome de Down (SD) es la cromosomopatía más frecuente y se asocia a importante morbilidad. El objetivo de este estudio fue conocer la frecuencia de SD y otras cromosomopatías en Asturias y su evolución temporal. Material y método: Se analizaron los datos del Registro de Defectos Congénitos de Asturias (RDCA), de base poblacional, incluidos los casos diagnosticados en nacidos y abortos inducidos (AI) entre 1990 y 2004. Resultados: En 103.452 nacidos se registraron 356 cromosomopatías (176 nacidos y 180 AI), con una prevalencia total de 22 casos por 10.000 nacidos en 1990 y 48,6 en 2004. El SD fue la más frecuente, con 210 casos y una prevalencia total de 13 casos/10.000 en 1990 y 29,1 en 2004. Un 63% de los nacidos con SD presentaron anomalías asociadas. Conclusiones: Los cambios en la edad materna y los programas de diagnóstico prenatal han influido en la evolución temporal de prevalencia de SD (AU)

Background and objective: Down syndrome (DS) is the most frequent chromosomal abnormality and bears a severe associated morbidity. Our goal was to describe trends in the prevalence of DS in Asturias (Spain). Material and methods: Data from the Registry of Congenital Defects were analyzed, including births and induced abortions, between 1990 and 2004. Results: Out of a total 103 452 births, 356 chromosomal anomalies had been registered (176 births and 180 induced abortions) and there were 210 DS (119 live births, two stillbirths and 89 induced abortions). Total prevalence assessment showed an important upward trend over time in both cases. The prevalence of total chromosomal abnormalities increased from 22 cases per 10 000 births in 1990 to 48,6 in 2004 and the DS prevalence increased from 13 to 29,1. Furthermore, 63% of DS births presented one or more associated defects, cardiac and digestive tract defects being the most frequent. Conclusions: Changes in maternal age and prenatal screening have influenced DS prevalence and trends (AU)

[Prevalence and secular trend of congenital defects in Asturias, Spain. The need for clinical-epidemiological surveillance]. / Frecuencia y tendencia temporal de los defectos congénitos en Asturias. La necesidad de la vigilancia clinicoepidemiológica.

OBJECTIVE: Congenital defects remain the second cause of perinatal and infant death and the third cause between the second and fifth years of life in Asturias. These anomalies generate substantial morbidity. The aim of the present study was to describe the population-based frequency of congenital defects in Asturias and their forms of presentation. METHODS: Data from the population-based Registry of Congenital Defects of Asturias for 1990-2004 were analyzed. The data related to live births, stillbirths and induced abortions after prenatal diagnosis and are presented as birth prevalence and total prevalence (including induced abortions). RESULTS: The total number of births was 103,452 and there were 3,035 cases of congenital defects, representing a total prevalence of 2.9 cases per 100 births and a birth prevalence of 2.5%. These figures showed a tendency to increase throughout the study period. A total of 2,516 (82.9%) cases were live births, 46 (1.5%) were stillbirths and 473 (15.6%) were induced abortions. Prenatal diagnosis increased throughout the period. Sixtythree percent of total cases showed an isolated defect, 17% a recognized syndrome and the remaining 20% had multiple malformations without a syndromic pattern. The most frequent and severe defects registered were neural tube defects (12.2 per 10,000 births), chromosomal abnormalities (34.4 per 10,000), and cardiac defects (75.2 per 10,000). CONCLUSIONS: The 15-year experience of the Registry of Congenital Defects of Asturias reveals the utility of this type of database to evaluate prenatal screening programs, plan the resources needed in affected pregnant women and infants, and perform epidemiological surveillance of congenital defects in relation to environmental risks, drug exposure and assisted reproduction techniques.