Peri-implantitis in patients without regular supportive therapy: Prevalence and risk indicators

Objectives: To determine the prevalence of peri-implant diseases in patients treated in a university setting without a regular peri-implant supportive therapy schedule, and to identify the risk indicators associated with peri-implantitis. Material and methods: A retrospective cohort study was made of patients with dental implants with at least 12 months of functional loading who did not receive regular peri-implant supportive therapy. Patient- and implant-related variables were retrieved, and clinical and radiological examinations were performed. Descriptive and bivariate analyses and multilevel logistic regression analyses were performed to identify factors associated with peri-implantitis. Results: A total of 213 implants in 88 patients were analyzed. The patient-level prevalence of peri-implantitis and peri-implant mucositis was 26.1% (95%CI: 16.7%-35.5%) and 44.3% (95%CI: 34.0%-54.6%), respectively. Peri-implant diseases were significantly more frequent when the width of the keratinized mucosa was < 2 mm (OR = 5.26; 95%CI: 1.24-22.26; p = 0.024), and when there was 12 month post-loading bone loss (OR = 2.96; 95%CI: 1.35-6.52; p = 0.007). Conclusions: Peri-implantitis is a common finding in patients without regular peri-implant supportive therapy (prevalence 16.7-35.5%). A thin peri-implant keratinized mucosa (< 2 mm) and a higher degree of bone remodeling after loading seem to be the main risk factors for peri-implantitis in this patient profile. Clinical relevance: Patients who do not engage in supportive peri-implant maintenance have a higher risk of peri-implantitis. A thin keratinized mucosa and bone loss during the first year of loading are predisposing factors for peri-implantitis

First-Trimester Sequential Screening for Preeclampsia Using Angiogenic Factors : Study Protocol for a Prospective, Multicenter, Real Clinical Setting Study

The incidence of preeclampsia (PE) is about 2-8%, making it one of the leading causes of perinatal morbidity and maternal mortality in the world. Early prophylactic low dose administration (150 mg) of acetylsalicylic acid is associated with a significant reduction in the incidence of early-onset PE, intrauterine growth restriction (IUGR), and neonatal mean stay in the intensive care unit (ICU). Universal implementation of a first-trimester screening system including angiogenic and antiangiogenic markers [the Placental Growth Factor (PlGF) and/or soluble fms-like Tyrosine Kinase-1 (sFlt-1)] has shown a prediction rate of 90% for early-onset PE but entails a high financial cost. The aim of this study is to determine the predictive and preventive capacity of a universal PE first-trimester two-step sequential screening model, determining the PlGF only in patients previously classified as intermediate risk by means of a multivariate model based on resources already used in the standard pregnancy control, in a real clinical setting. We hypothesize that this screening model will achieve similar diagnostic performance as the universal determination of PlGF but at a lower economic cost. This is a prospective, multicentric, cohort study in a real-world clinical setting. Every singleton pregnancy will be recruited at the routine first pregnancy visit. In a first step, the first-trimester risk of PE will be calculated using a multivariate Gaussian distribution model, based on medical history, mean blood pressure, Pregnancy-Associated Plasma Protein A (PAPP-A), and Uterine Artery Doppler Pulsatility Index (UTPI). Patients will be classified into three risk groups for PE: (1) risk ≥ 1/50, high-risk with no further testing (blinded PlGF); (2) risk between 1/51 and 1/500, medium-risk requiring further testing; and (3) risk ≤ 1/501, low-risk with no further testing. In a second step, the PlGF will only be determined in those patients classified as intermediate risk after this first step, and then reclassified into high- or low-risk groups. Prophylactic administration of aspirin (150 mg/day) will be prescribed only in high risk patients. As a secondary objective, sFlt-1 values will be blindly determined in patients with high and intermediate risk to assess its potential performance in the screening for PE. The study will be conducted in accordance with the principles of Good Clinical Practice. This study is approved by the Aragon Research Ethics Committee (CEICA) on 3 July 2020 (15/2020). , identifier: NCT04767438

Multicenter prospective clinical study to evaluate children short-term neurodevelopmental outcome in congenital heart disease (children NEURO-HEART): study protocol

Congenital heart disease; Neurodevelopment; Predictive markersCardiopatía congénita; Desarrollo neurológico; Marcadores predictivosCardiopaties congènites; Neurodesenvolupament; Marcadors predictiusBackground: Congenital heart disease (CHD) is the most prevalent congenital malformation affecting 1 in 100 newborns. While advances in early diagnosis and postnatal management have increased survival in CHD children, worrying long-term outcomes, particularly neurodevelopmental disability, have emerged as a key prognostic factor in the counseling of these pregnancies. Methods: Eligible participants are women presenting at 20 to < 37 weeks of gestation carrying a fetus with CHD. Maternal/neonatal recordings are performed at regular intervals, from the fetal period to 24 months of age, and include: placental and fetal hemodynamics, fetal brain magnetic resonance imaging (MRI), functional echocardiography, cerebral oxymetry, electroencephalography and serum neurological and cardiac biomarkers. Neurodevelopmental assessment is planned at 12 months of age using the ages and stages questionnaire (ASQ) and at 24months of age with the Bayley-III test. Target recruitment is at least 150 cases classified in three groups according to three main severe CHD groups: transposition of great arteries (TGA), Tetralogy of Fallot (TOF) and Left Ventricular Outflow Tract Obstruction (LVOTO). Discussion: The results of NEURO-HEART study will provide themost comprehensive knowledge until date of children’s neurologic prognosis in CHD and will have the potential for developing future clinical decisive tools and improving preventive strategies in CHD.RETICS funded by the PN 2018-2021 (Spain), ISCIII- Sub-Directorate General for Research Assessment and Promotion and the European Regional Development Fund (FEDER), reference RD16/002

First-Trimester Sequential Screening for Preeclampsia Using Angiogenic Factors: Study Protocol for a Prospective, Multicenter, Real Clinical Setting Study

IntroductionThe incidence of preeclampsia (PE) is about 2–8%, making it one of the leading causes of perinatal morbidity and maternal mortality in the world. Early prophylactic low dose administration (150 mg) of acetylsalicylic acid is associated with a significant reduction in the incidence of early-onset PE, intrauterine growth restriction (IUGR), and neonatal mean stay in the intensive care unit (ICU). Universal implementation of a first-trimester screening system including angiogenic and antiangiogenic markers [the Placental Growth Factor (PlGF) and/or soluble fms-like Tyrosine Kinase-1 (sFlt-1)] has shown a prediction rate of 90% for early-onset PE but entails a high financial cost. The aim of this study is to determine the predictive and preventive capacity of a universal PE first-trimester two-step sequential screening model, determining the PlGF only in patients previously classified as intermediate risk by means of a multivariate model based on resources already used in the standard pregnancy control, in a real clinical setting. We hypothesize that this screening model will achieve similar diagnostic performance as the universal determination of PlGF but at a lower economic cost.Methods and AnalysisThis is a prospective, multicentric, cohort study in a real-world clinical setting. Every singleton pregnancy will be recruited at the routine first pregnancy visit. In a first step, the first-trimester risk of PE will be calculated using a multivariate Gaussian distribution model, based on medical history, mean blood pressure, Pregnancy-Associated Plasma Protein A (PAPP-A), and Uterine Artery Doppler Pulsatility Index (UTPI). Patients will be classified into three risk groups for PE: (1) risk ≥ 1/50, high-risk with no further testing (blinded PlGF); (2) risk between 1/51 and 1/500, medium-risk requiring further testing; and (3) risk ≤ 1/501, low-risk with no further testing. In a second step, the PlGF will only be determined in those patients classified as intermediate risk after this first step, and then reclassified into high- or low-risk groups. Prophylactic administration of aspirin (150 mg/day) will be prescribed only in high risk patients. As a secondary objective, sFlt-1 values will be blindly determined in patients with high and intermediate risk to assess its potential performance in the screening for PE.Ethics and DisseminationThe study will be conducted in accordance with the principles of Good Clinical Practice. This study is approved by the Aragon Research Ethics Committee (CEICA) on 3 July 2020 (15/2020).Clinical Trial RegistrationClinicalTrials.gov, identifier: NCT04767438

An Energy-Reduced Mediterranean Diet, Physical Activity, and Body Composition

[ENG]Importance Strategies targeting body composition may help prevent chronic diseases in persons with excess weight, but randomized clinical trials evaluating lifestyle interventions have rarely reported effects on directly quantified body composition. OBJECTIVE To evaluate the effects of a lifestyle weight-loss intervention on changes in overall and regional body composition. DESIGN, SETTING, AND PARTICIPANTS The ongoing Prevención con Dieta Mediterránea-Plus (PREDIMED-Plus) randomized clinical trial is designed to test the effect of the intervention on cardiovascular disease prevention after 8 years of follow-up. The trial is being conducted in 23 Spanish research centers and includes men and women (age 55-75 years) with body mass index between 27 and 40 and metabolic syndrome. The trial reported herein is an interim subgroup analysis of the intermediate outcome body composition after 3-year follow-up, and data analysis was conducted from February 1 to November 30, 2022. Of 6874 total PREDIMED-Plus participants, a subsample of 1521 individuals, coming from centers with access to a dual energy x-ray absorptiometry device, underwent body composition measurements at 3 time points. INTERVENTION Participants were randomly allocated to a multifactorial intervention based on an energy-reduced Mediterranean diet (MedDiet) and increased physical activity (PA) or to a control group based on usual care, with advice to follow an ad libitum MedDiet, but no physical activity promotion. MAIN OUTCOMES AND MEASURES The outcomes (continuous) were 3-year changes in total fat and lean mass (expressed as percentages of body mass) and visceral fat (in grams), tested using multivariable linear mixed-effects models. Clinical relevance of changes in body components (dichotomous) was assessed based on 5% or more improvements in baseline values, using logistic regression. Main analyses were performed in the evaluable population (completers only) and in sensitivity analyses, multiple imputation was performed to include data of participants lost to follow-up (intention-to-treat analyses). RESULTS A total of 1521 individuals were included (mean [SD] age, 65.3 [5.0] years; 52.1% men). In comparison with the control group (n=761), participants in the intervention arm (n=760) showed greater reductions in the percentage of total fat (between group differences after 1-year, −0.94% [95% CI, −1.19 to −0.69]; 3 years, −0.38% [95% CI, −0.64 to −0.12] and visceral fat storage after 1 year, -126 g [95% CI, −179 to −73.3 g]; 3 years, −70.4 g [95% CI, −126 to −15.2 g] and greater increases in the percentage of total lean mass at 1 year, 0.88% [95% CI, 0.63%-1.12%]; 3-years 0.34% [95%CI, 0.09%-0.60%]). The intervention group was more likely to show improvements of 5% or more in baseline body components (absolute risk reduction after 1 year, 13% for total fat mass, 11% for total lean mass, and 14% for visceral fat mass; after 3-years: 6% for total fat mass, 6% for total lean mass, and 8% for visceral fat mass). The number of participants needed to treat was between 12 and 17 to attain at least 1 individual with possibly clinically meaningful improvements in body composition. CONCLUSIONS AND RELEVANCE The findings of this trial suggest a weight-loss lifestyle intervention based on an energy-reduced MedDiet and physical activity significantly reduced total and visceral fat and attenuated age-related losses of lean mass in older adults with overweight or obesity and metabolic syndrome. Continued follow-up is warranted to confirm the long-term consequences of these changes on cardiovascular clinical end points.S

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Jardins per a la salut

Facultat de Farmàcia, Universitat de Barcelona. Ensenyament: Grau de Farmàcia. Assignatura: Botànica farmacèutica. Curs: 2014-2015. Coordinadors: Joan Simon, Cèsar Blanché i Maria Bosch.Els materials que aquí es presenten són el recull de les fitxes botàniques de 128 espècies presents en el Jardí Ferran Soldevila de l’Edifici Històric de la UB. Els treballs han estat realitzats manera individual per part dels estudiants dels grups M-3 i T-1 de l’assignatura Botànica Farmacèutica durant els mesos de febrer a maig del curs 2014-15 com a resultat final del Projecte d’Innovació Docent «Jardins per a la salut: aprenentatge servei a Botànica farmacèutica» (codi 2014PID-UB/054). Tots els treballs s’han dut a terme a través de la plataforma de GoogleDocs i han estat tutoritzats pels professors de l’assignatura. L’objectiu principal de l’activitat ha estat fomentar l’aprenentatge autònom i col·laboratiu en Botànica farmacèutica. També s’ha pretès motivar els estudiants a través del retorn de part del seu esforç a la societat a través d’una experiència d’Aprenentatge-Servei, deixant disponible finalment el treball dels estudiants per a poder ser consultable a través d’una Web pública amb la possibilitat de poder-ho fer in-situ en el propi jardí mitjançant codis QR amb un smartphone

Adelante / Endavant

Séptimo desafío por la erradicación de la violencia contra las mujeres del Institut Universitari d’Estudis Feministes i de Gènere "Purificación Escribano" de la Universitat Jaume

Impacto de las cardiopatías congénitas en el sistema nervioso central

Esta tesis es el resumen de tres trabajos realizados siguiendo una misma línea de trabajo en relación al papel de los factores angigogénicos en el neurodesarrollo de los fetos con cardiopatía congénita (CC). Estudio 1: Complicaciones derivadas de la insuficiencia placentaria en gestantes portadoras de fetos con CC. Introducción: Estudios recientes reportaron un desequilibrio angiogénico en la circulación materna y fetal en las gestaciones con CC sugiriendo una placentación alterada. Objetivos: Evaluar si las gestantes con fetos con CC tiene una mayor incidencia de complicaciones derivadas de la insuficiencia placentaria. Métodos: Se compararon los resultados perinatales de gestantes con CC y una población de bajo riesgo. Resultados: Se incluyeron 279 gestaciones con fetos con CC. Se observó una incidencia significativamente mayor de preeclampsia en el grupo con CC (5,7% frente a 1,2% p <0,0001). El 9,7% de los fetos con CC tenían un peso al nacer menor del p3. SAe observó una mayor incidencia de muerte intraútero en el grupo con CC (2,5% vs 0,4%). Estudio 2: Cambios longitudinales en las biometrías y la hemodinámica cerebroplacentaria en fetos con CC. Objetivos: Determinar el comportamiento a lo largo de la gestación de las biometrías fetales y la hemodinámica cerebroplacentaria en fetos con CC. Métodos: Se midieron las biometrías fetales y distintos parámetros Doppler en fetos con CC. Las evaluaciones se realizaron desde el diagnóstico (<25 semanas) hasta el parto. Los fetos con CC se clasificaron en 3 grupos de acuerdo con el patrón esperado de oxigenación cerebral. Resultados: Se realizaron 444 ecografías en 119 fetos con CC. Los fetos con CC presentaron unas biometrías cefálicas más pequeñas al diagnóstico (BPD -1,32-0,99Zs, HC -0,79-1,02Zs), que se mantuvieron durante toda la gestación. El Doppler de las UtA y de la UA mostró un aumento significativo hacia el final de la gestación. La MCA y el CPR presentaron diferencias significativas en el comportamiento longitudinal entre los distintos grupos de CC. Estudio 3: Expresión cerebral de distintos genes angiogénicos en las CC. Introducción: La existencia de un desequilibrio angiogénico ha surgido como una posible vía en la patogénesis de los mecanismos prenatales que condicionan un neurodesarrollo anómalo en los pacientes con CC. Objetivo: Analizar diferencias en la expresión de distintos factores angiogénicos/antiangiogénicos y genes de hipoxia crónica en el tejido cerebral de fetos con CC en comparación con controles. Métodos: Se determinó el perfil de expresión génica por PCR cuantitativa en el tejido cerebral de 2 áreas diferentes: la corteza frontal y los ganglios basales y el hipotálamo, obtenidos a partir de 15 con CC y 12 fetos controles. Resultados: Se observó una expresión aumentada del ARNm de los factores angiogénicos/antiangiogénicos en los fetos con CC en comparación con los controles, en la corteza frontal (sFlt-1, 48%, p = 0,0431) y en los ganglios basales y el hipotálamo (sFlt-1, 72%, p = 0,0369 y VEGF - A, 60%, p = 0,0432). Conclusiones: 1. Las gestaciones con CC presentan una mayor incidencia de complicaciones relacionadas con la insuficiencia placenta. 2. Los fetos con CC presentan unas biometrías cefálicas menores desde el segundo trimestre. Confirmando la aparición temprana de mecanismos que pueden conducir a un peor neurodesarrollo en estos niños. 3. El aumento progresivo de las resistencia en las UtA i la UA a lo largo de la gestación, sugiere un grado progresivo de insuficiencia placentaria. 4. En el tejido cerebral de los fetos con CC existe una regulación antiangigogénica, sugiriendo que estos fetos tienen una angiogénesis anormal, que puede contribuir a una perfusión cerebral anómala, así como a un neurodesarrollo anormal.This thesis is the summary of three studies carried out along the same line of work in relation to the role of angiogenic factors in the neurological development of foetuses with congenital heart diseases (CHD). Study 1: Placenta-related complications in women carrying a foetus with congenital heart disease Introduction: Recent studies pointed to an intrinsically angiogenic imbalance in CHD in the maternal and foetal circulation suggestive of impaired placentation. Objectives: To assess whether pregnant women with a CHD foetus are at greater risk of placenta-related complications. Methods: Perinatal results of women with a CDH foetus were compared with those of a nonselected population followed up at our centre. Results: 279 pregnancies with CHD foetuses were included. A significantly higher incidence of pre-eclampsia was observed in the CHD group compared with the normal population (5.7% vs 1.2% p< 0.0001). 9.7% of foetuses with CHD had < 3rd birth weight percentile compared with 3% for the normal population. A higher incidence of stillbirth was also observed in the CHD group compared with the normal population (2.5% vs 0.4%). Study 2: Longitudinal changes in fetal biometries and cerebroplacental haemodynamics in fetuses with congenital heart disease. Objectives: To determine the longitudinal behaviour of fetal biometries and cerebroplacental haemodynamics throughout gestation in fetuses with CHD. Methods: Fetal biometries and Doppler haemodynamic were serially measured in a cohort of consecutive fetuses diagnosed with CHD. Evaluations were made at various time points, from diagnosis (<25 weeks) to delivery. CHD fetuses were classified in 3 groups according to the expected pattern of brain blood supply. Results: 444 ultrasound examinations were performed on 119 CHD fetuses. CHD fetuses presented a small head at diagnosis (BPD -1.32 - 0.99 Zs, HC -0.79 - 1.02 Zs), which remained small throughout gestation. UtA and UA Doppler showed a significant increase towards the end of pregnancy, whereas no significant changes were observed in MCA or CPR with gestational age. Both MCA and CPR presented significant differences in longitudinal behaviour between CHD groups. Study 3: Brain angiogenic gene-expression in congenital heart disease Introduction: Increasing evidence support prenatal appearance of mechanisms that lead to poor neurodevelopmental outcome. Angiogenic unbalance has emerged as a possible contributor pathway in the pathogenesis of CHD. Objective: To analyze if differences exists in the expression of antiangiogenic and angiogenic factors as well as the genes of chronic hypoxia in cerebral tissue of euploid CHD compared to control fetuses. Methods: Gene expression profile was determined by real-time PCR quantification in brain tissue from 2 different areas: frontal cortex and basal ganglia and hypothalamus, obtained from 15 CHD and 12 control fetuses. Results: Both antiangiogenic/angiogenic factor mRNA expressions were significantly increased in the CHD group compared to controls in frontal cortex (sFlt-1, 48%, p=0.0431) and in basal ganglia and hypothalamus (sFlt-1, 72%, p=0.0369 and VEGF-A, 60%, p=0.0432). Conclusions: 1. Women carrying a foetus with CHD have a high risk of placenta-related complications (pre-eclampsia and IUGR). 2. CHD fetuses had smaller head biometries from the second trimester of pregnancy. Our results support the early onset appearance of mechanisms that could lead to a poorer neurodevelopment later in life in CHD cases. 3. CHD fetuses had and increasing resistance in UtA and UA Doppler suggestive of progressing degree of placental impairment. 4. An overall dysregulation of angiogenesis with a net balance towards an anti-angiogenic environment was observed in the cerebral tissue from fetuses with CHD, suggesting that CHD cases have an intrinsically-angiogenic impairment that could contribute to impaired brain perfusion and abnormal neurological development later in life

Impacto de las cardiopatías congénitas en el sistema nervioso central /

Esta tesis es el resumen de tres trabajos realizados siguiendo una misma línea de trabajo en relación al papel de los factores angigogénicos en el neurodesarrollo de los fetos con cardiopatía congénita (CC). Estudio 1: Complicaciones derivadas de la insuficiencia placentaria en gestantes portadoras de fetos con CC. Introducción: Estudios recientes reportaron un desequilibrio angiogénico en la circulación materna y fetal en las gestaciones con CC sugiriendo una placentación alterada. Objetivos: Evaluar si las gestantes con fetos con CC tiene una mayor incidencia de complicaciones derivadas de la insuficiencia placentaria. Métodos: Se compararon los resultados perinatales de gestantes con CC y una población de bajo riesgo. Resultados: Se incluyeron 279 gestaciones con fetos con CC. Se observó una incidencia significativamente mayor de preeclampsia en el grupo con CC (5,7% frente a 1,2% p 0,0001). El 9,7% de los fetos con CC tenían un peso al nacer menor del p3. SAe observó una mayor incidencia de muerte intraútero en el grupo con CC (2,5% vs 0,4%). Estudio 2: Cambios longitudinales en las biometrías y la hemodinámica cerebroplacentaria en fetos con CC. Objetivos: Determinar el comportamiento a lo largo de la gestación de las biometrías fetales y la hemodinámica cerebroplacentaria en fetos con CC. Métodos: Se midieron las biometrías fetales y distintos parámetros Doppler en fetos con CC. Las evaluaciones se realizaron desde el diagnóstico ( 25 semanas) hasta el parto. Los fetos con CC se clasificaron en 3 grupos de acuerdo con el patrón esperado de oxigenación cerebral. Resultados: Se realizaron 444 ecografías en 119 fetos con CC. Los fetos con CC presentaron unas biometrías cefálicas más pequeñas al diagnóstico (BPD -1,32-0,99Zs, HC -0,79-1,02Zs), que se mantuvieron durante toda la gestación. El Doppler de las UtA y de la UA mostró un aumento significativo hacia el final de la gestación. La MCA y el CPR presentaron diferencias significativas en el comportamiento longitudinal entre los distintos grupos de CC. Estudio 3: Expresión cerebral de distintos genes angiogénicos en las CC. Introducción: La existencia de un desequilibrio angiogénico ha surgido como una posible vía en la patogénesis de los mecanismos prenatales que condicionan un neurodesarrollo anómalo en los pacientes con CC. Objetivo: Analizar diferencias en la expresión de distintos factores angiogénicos/antiangiogénicos y genes de hipoxia crónica en el tejido cerebral de fetos con CC en comparación con controles. Métodos: Se determinó el perfil de expresión génica por PCR cuantitativa en el tejido cerebral de 2 áreas diferentes: la corteza frontal y los ganglios basales y el hipotálamo, obtenidos a partir de 15 con CC y 12 fetos controles. Resultados: Se observó una expresión aumentada del ARNm de los factores angiogénicos/antiangiogénicos en los fetos con CC en comparación con los controles, en la corteza frontal (sFlt-1, 48%, p = 0,0431) y en los ganglios basales y el hipotálamo (sFlt-1, 72%, p = 0,0369 y VEGF - A, 60%, p = 0,0432). Conclusiones: 1. Las gestaciones con CC presentan una mayor incidencia de complicaciones relacionadas con la insuficiencia placenta. 2. Los fetos con CC presentan unas biometrías cefálicas menores desde el segundo trimestre. Confirmando la aparición temprana de mecanismos que pueden conducir a un peor neurodesarrollo en estos niños. 3. El aumento progresivo de las resistencia en las UtA i la UA a lo largo de la gestación, sugiere un grado progresivo de insuficiencia placentaria. 4. En el tejido cerebral de los fetos con CC existe una regulación antiangigogénica, sugiriendo que estos fetos tienen una angiogénesis anormal, que puede contribuir a una perfusión cerebral anómala, así como a un neurodesarrollo anormal.This thesis is the summary of three studies carried out along the same line of work in relation to the role of angiogenic factors in the neurological development of foetuses with congenital heart diseases (CHD). Study 1: Placenta-related complications in women carrying a foetus with congenital heart disease Introduction: Recent studies pointed to an intrinsically angiogenic imbalance in CHD in the maternal and foetal circulation suggestive of impaired placentation. Objectives: To assess whether pregnant women with a CHD foetus are at greater risk of placenta-related complications. Methods: Perinatal results of women with a CDH foetus were compared with those of a nonselected population followed up at our centre. Results: 279 pregnancies with CHD foetuses were included. A significantly higher incidence of pre-eclampsia was observed in the CHD group compared with the normal population (5.7% vs 1.2% p 0.0001). 9.7% of foetuses with CHD had 3rd birth weight percentile compared with 3% for the normal population. A higher incidence of stillbirth was also observed in the CHD group compared with the normal population (2.5% vs 0.4%). Study 2: Longitudinal changes in fetal biometries and cerebroplacental haemodynamics in fetuses with congenital heart disease. Objectives: To determine the longitudinal behaviour of fetal biometries and cerebroplacental haemodynamics throughout gestation in fetuses with CHD. Methods: Fetal biometries and Doppler haemodynamic were serially measured in a cohort of consecutive fetuses diagnosed with CHD. Evaluations were made at various time points, from diagnosis ( 25 weeks) to delivery. CHD fetuses were classified in 3 groups according to the expected pattern of brain blood supply. Results: 444 ultrasound examinations were performed on 119 CHD fetuses. CHD fetuses presented a small head at diagnosis (BPD -1.32 - 0.99 Zs, HC -0.79 - 1.02 Zs), which remained small throughout gestation. UtA and UA Doppler showed a significant increase towards the end of pregnancy, whereas no significant changes were observed in MCA or CPR with gestational age. Both MCA and CPR presented significant differences in longitudinal behaviour between CHD groups. Study 3: Brain angiogenic gene-expression in congenital heart disease Introduction: Increasing evidence support prenatal appearance of mechanisms that lead to poor neurodevelopmental outcome. Angiogenic unbalance has emerged as a possible contributor pathway in the pathogenesis of CHD. Objective: To analyze if differences exists in the expression of antiangiogenic and angiogenic factors as well as the genes of chronic hypoxia in cerebral tissue of euploid CHD compared to control fetuses. Methods: Gene expression profile was determined by real-time PCR quantification in brain tissue from 2 different areas: frontal cortex and basal ganglia and hypothalamus, obtained from 15 CHD and 12 control fetuses. Results: Both antiangiogenic/angiogenic factor mRNA expressions were significantly increased in the CHD group compared to controls in frontal cortex (sFlt-1, 48%, p=0.0431) and in basal ganglia and hypothalamus (sFlt-1, 72%, p=0.0369 and VEGF-A, 60%, p=0.0432). Conclusions: 1. Women carrying a foetus with CHD have a high risk of placenta-related complications (pre-eclampsia and IUGR). 2. CHD fetuses had smaller head biometries from the second trimester of pregnancy. Our results support the early onset appearance of mechanisms that could lead to a poorer neurodevelopment later in life in CHD cases. 3. CHD fetuses had and increasing resistance in UtA and UA Doppler suggestive of progressing degree of placental impairment. 4. An overall dysregulation of angiogenesis with a net balance towards an anti-angiogenic environment was observed in the cerebral tissue from fetuses with CHD, suggesting that CHD cases have an intrinsically-angiogenic impairment that could contribute to impaired brain perfusion and abnormal neurological development later in life