Intrauterine growth restriction and later cardiovascular function

Intrauterine growth restriction is one of the most common obstetric conditions, affecting 7-10% of fetuses. Affected fetuses are actually exposed in utero to an adverse environment during the highly critical time of development and may face life-long health consequences such as increased cardiovascular risk in adulthood. Already in utero, fetuses affected by growth restriction show remodeled hearts with signs of systolic and diastolic dysfunction. Cardiovascular remodeling persist into postnatal life, from the neonatal period to adolescence, suggesting a primary fetal cardiac programming that might explain the increased cardiovascular risk later in life. In this review we summarize the current evidence on fetal cardiovascular programming in fetuses affected by growth restriction, its consequences later and possible strategies from which they could benefit to reduce their cardiovascular risk

Enfrentamiento terapéutico del trastorno por déficit atencional en una población infantil escolar perteneciente a la Región Metropolitana de Chile

Indexación: ScieloAn evaluation was made of a retrospective evolution presented by the patients from to 14 years and 11 month old (average 9,2 years old), with a diagnostic of attentional hyperactive disorder (AHD), treated with metilfenidate in Huechuraba during the year 2007. A revision of every clinic history showed the principal results: a high positive response (higher than the 76% of the measured parameters). The evaluated parameters were, academic response, self report of subjective opinion from the patient, opinion from the tutor of the child in relationships with his/her conduct at home and teacher's evaluations of the child conduct at school. No differences were found between the evolution of the clinic parameters, in children with and without comorbilities. It was found a 52, 7% of comorbility. Specific learning disease, adaptative disorder, anxious disorder, and depression were more frequent diagnoses. This study concludes that the high percent of success in the treatment of the student group is similar to the one found in literature. The presence of comorbility won't cause to down of the treatment efficiency. This is conditioned by the presence of psychosocial factors like maternal psychopathology and familiar violence.Se realizó una evaluación restrospectiva de la evolución presentada por los pacientes desde 6 a 14 años 11 meses de edad (edad media de 9,2 años) con diagnóstico de Trastorno por déficit atencional (TDA) bajo tratamiento con metilfenidato en la comuna de Huechuraba durante el año 2007. Se hizo la revisión y el análisis de cada ficha clínica, encontrándose como principales resultados el alto porcentaje de mejoría, igual o mayor al 76% de los parámetros medidos, consistentes en evolución del rendimiento académico; autoreporte de sensación subjetiva del niño; reporte del cuidador principal en relación a la conducta del niño (a) en el hogar y evaluación del profesor en cuanto su conducta en el colegio. No se encontraron diferencias entre la evolución de los parámetros clínicos entre los niños con comorbilidad y sin comorbilidad, se encontró un 52,7% de esta, siendo los diagnósticos más frecuentes Trastorno específico del aprendizaje, trastorno adaptativo, trastorno ansioso y del ánimo. Se concluye que el alto porcentaje de éxito del tratamiento en el grupo estudiado es similar al encontrado en la literatura; que la presencia de comorbilidad no condiciona la disminución de la eficiencia del tratamiento y que esta es condicionada por presencia de factores psicosociales como psicopatología materna y violencia intrafamiliar.http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-92272009000100005&nrm=is

Usefulness of circulating microRNAs for the prediction of early preeclampsia at first-trimester of pregnancy

To assess the usefulness of circulating microRNAs (miRNAs) as non-invasive molecular biomarkers for early prediction of preeclampsia, a differential miRNA profiling analysis was performed in first-trimester pooled sera from 31 early preeclampsia patients, requiring delivery before 34 weeks of gestation, and 44 uncomplicated pregnancies using microfluidic arrays. Among a total of 754 miRNAs analyzed, the presence of 63 miRNAs (8%) was consistently documented in the sera from preeclampsia and control samples. Nevertheless, only 15 amplified miRNAs (2%) seemed to be differentially, although modestly, represented (fold change range: 0.4-1.4). After stem loop RT-qPCR from individual samples, the statistical analysis confirmed that none of the most consistent and differentially represented miRNAs (3 overrepresented and 4 underrepresented) were differentially abundant in serum from preeclamptic pregnancies compared with serum from normal pregnancies. Therefore, maternal serum miRNA assessment at first-trimester of pregnancy does not appear to have any predictive value for early preeclampsia

Transgenerational transmission of small for gestational age

Objective: To evaluate the transgenerational transmission of small for gestational age. Methods: Cohort study including a random sample of 2,043 offspring of deliveries occurring from 1975 to 1993. Of 623 offspring -now adults- that agreed to participate, 152 adults (72 born small-for-gestational age (SGA) and 80 with appropriate intrauterine growth) reported to have at least one child. Multiple regression analysis was used to determine the presence of SGA (defined as a birthweight < 10th percentile) or placental mediated disease (defined as the presence of SGA, preeclampsia or gestational hypertension) in the following generation. Results: Descendants from SGA adults presented lower birthweight percentile (median 26 [interquartile range 7-52] vs. 43 [19-75]; p<0.001) and higher prevalence of SGA (40.3% vs. 16.3%; p=0.001) and placental mediated disease (43.1% vs. 17.5%; p=0.001). After adjustment for confounder variables, parental SGA background was associated with an almost three-fold increased risk of subsequent SGA or any placental mediated disease in the following generation. This association was stronger in SGA mothers as compared to fathers. Conclusions: Our data provides evidence suggesting a transgenerational transmission of SGA highlighting the importance of public health strategies for preventing intrauterine growth impairment

Hemopexin and α1-microglobulin heme scavengers with differential involvement in preeclampsia and fetal growth restriction

Hemopexin and α1-microglobulin act as scavengers to eliminate free heme-groups responsible for hemoglobin-induced oxidative stress. The present study evaluated maternal and fetal plasma concentrations of these scavengers in the different phenotypes of placenta-mediated disorders. Singleton pregnancies with normotensive fetal growth restriction [FGR] (n = 47), preeclampsia without FGR (n = 45) and preeclampsia with FGR (n = 51) were included prospectively as well as uncomplicated pregnancies (n = 49). Samples were collected at delivery and ELISA analysis was applied to measure the hemopexin and α1-microglobulin concentrations. In maternal blood in preeclampsia with and without FGR, hemopexin was significantly lower (p = 0.003 and p<0.001, respectively) and α1-microglobulin was significantly higher (p<0.001 in both) whereas no difference existed in normotensive FGR mothers compared to controls. In contrast, in fetal blood in growth restricted fetuses with and without preeclampsia, both hemopexin and α1-microglobulin were significantly lower (p<0.001 and p = 0.001 for hemopexin, p = 0.016 and p = 0.013 for α1-microglobulin, respectively) with no difference in fetuses from preeclampsia without FGR in comparison to controls. Thus, hemopexin and α1-microglobulin present significantly altered concentrations in maternal blood in the maternal disease -preeclampsia- and in cord blood in the fetal disease -FGR-, which supports their differential role in placenta-mediated disorders in accordance with the clinical presentation of these disorders

Maternal proteomic profiling reveals alterations in lipid metabolism in late-onset fetal growth restriction

Fetal growth restriction defined as the failure to achieve the fetal genetic growth potential is a major cause of perinatal morbidity and mortality. The role of maternal adaptations to placental insufficiency in this disorder is still not fully understood. We aimed to investigate the biological processes and protein-protein interactions involved in late-onset fetal growth restriction in particular. We applied 2D nano LC-MS/MS proteomics analysis on maternal blood samples collected at the time of delivery from 5 singleton pregnancies with late-onset fetal growth restriction and 5 uncomplicated pregnancies. Data were analyzed using R package 'limma' and Ingenuity Pathway Analysis. 25 proteins showed significant changes in their relative abundance in late-onset fetal growth restriction (p value < 0.05). Direct protein-protein interactions network demonstrated that Neurogenic locus notch homolog protein 1 (NOTCH1) was the most significant putative upstream regulator of the observed profile. Gene ontology analysis of these proteins revealed the involvement of 14 canonical pathways. The most significant biological processes were efflux of cholesterol, efflux of phospholipids, adhesion of blood cells, fatty acid metabolism and dyslipidemia. Future studies are warranted to validate the potential role of the detected altered proteins as potential therapeutic targets in the late-onset form of fetal growth restriction

Distinctive patterns of placental lesions in preeclampsia versus fetal growth restriction and their association with fetoplacental Doppler

OBJECTIVES: The aim of this study was to describe placental histopathological findings in a large cohort of pregnancies complicated by preeclampsia and/or fetal growth restriction, and to investigate its association with fetoplacental Doppler. METHODS: This was a prospective observational study including pregnancies complicated by: 1) normotensive FGR defined as birthweight 95th centile for uterine and umbilical artery, or <5th centile for middle cerebral artery and CPR. Placental lesions were categorized to vascular (maternal/fetal side), inflammatory and other lesions according to the 2014 Amsterdam Placental Workshop Group Consensus Statement. Univariate and multiple regression analysis were performed for the comparison between the study groups. Logistic regression was used to determine abnormal Doppler association with placental lesions. RESULTS: Maternal side vascular lesions are significantly higher in PE compared to controls and normotensive FGR (PE&FGR: 73%, PE: 46%, FGR: 38% vs. controls: 31%; p=0.01) including 2 types of lesions: developmental (PE&FGR: 13%, PE: 5%, FGR: 3% vs. controls: 2%, p<0.001) and malperfusion (PE&FGR: 70%, PE: 39%, FGR: 32% vs. controls: 25%, p=0.001). In contrast, fetal side developmental lesions are significantly higher in normotensive FGR compared to controls and PE (PE&FGR: 0%, PE: 3%, FGR: 8% vs. controls 2%, p=0.001). All cases displayed lower prevalence of infectious lesions, with a high prevalence of immune lesions in PE&FGR (PE&FGR: 17.5%, PE: 7.8%, FGR: 9.8% vs. controls 9.4%, p=0.001). All fetoplacental Doppler parameters are associated with maternal side vascular lesions -mainly malperfusion- [uterine arteries mean PI (Odds ratio(OR)=2.45, 95% confidence interval (CI): 1.51 - 3.97), umbilical artery PI (OR=2.05, 95% CI: 1.02 - 4.47), middle cerebral artery PI (OR=2.75, 95% CI: 1.4 - 5.42), CPR (OR=1.75, 95% CI: 1.04 - 2.95)]. This association was evident mainly in the FGR groups -with and without PE-, being nonsignificant in controls or PE without FGR. No significant associations were observed between fetoplacental Doppler parameters and other placental lesions in any of the study groups. CONCLUSIONS: PE and FGR exhibit different patterns of placental histopathological lesions in accordance with the clinical manifestation of the placental disorder (maternal vs. fetal). Fetoplacental Doppler shows an association with placental malperfusion lesions in the maternal side, reinforcing its use as a surrogate of placental insufficiency

Postoperative Pancreatic Fistula. Is Minimally Invasive Surgery Better than Open? A Systematic Review and Meta-analysis

Background/Aim: Minimally invasive pancreatico-duodenectomy (PD) is gaining popularity. The aim of this study was to compare the incidence of postoperative pancreatic fistula (POPF) after minimally invasive versus open procedures. Materials and Methods: Following the PRISMA statement, literature research was conducted focusing on papers comparing the incidence of POPF after open pancreaticoduodenectomy (OPD) versus minimally invasive pancreaticoduodenectomy (MIPD). Results: Twenty-one papers were included in this meta -analysis, for a total of 4,448 patients. A total of 2,456 patients (55.2%) underwent OPD, while 1,992 (44.8%) underwent MIPD. Age, ASA score III patients, incidence of pancreatic ductal adenocarcinoma and duct diameter were significantly lower in the MIPD group. No statistically significant differences were found between the OPD and MIPD regarding the incidence of major complications (15.6% vs. 17.0%, respectively, p=0.55), mortality (3.7% vs. 2.4%, p=0.81), and POPF rate (14.3% vs. 12.9%, p=0.25). Conclusion: MIPD and OPD had comparable rates of postoperative complications, postoperative mortality, and POPF

Unsupervised Segmentation of Fetal Brain MRI using Deep Learning Cascaded Registration

Accurate segmentation of fetal brain magnetic resonance images is crucial for analyzing fetal brain development and detecting potential neurodevelopmental abnormalities. Traditional deep learning-based automatic segmentation, although effective, requires extensive training data with ground-truth labels, typically produced by clinicians through a time-consuming annotation process. To overcome this challenge, we propose a novel unsupervised segmentation method based on multi-atlas segmentation, that accurately segments multiple tissues without relying on labeled data for training. Our method employs a cascaded deep learning network for 3D image registration, which computes small, incremental deformations to the moving image to align it precisely with the fixed image. This cascaded network can then be used to register multiple annotated images with the image to be segmented, and combine the propagated labels to form a refined segmentation. Our experiments demonstrate that the proposed cascaded architecture outperforms the state-of-the-art registration methods that were tested. Furthermore, the derived segmentation method achieves similar performance and inference time to nnU-Net while only using a small subset of annotated data for the multi-atlas segmentation task and none for training the network. Our pipeline for registration and multi-atlas segmentation is publicly available at https://github.com/ValBcn/CasReg.Comment: 17 pages, 8 figures, 5 tables, paper submitted to IEEE transaction on medical imagin

Premature placental aging in term small-for-gestational-age and fetal-growth-restricted fetuses

Objective The aim of this study was to perform a comprehensive assessment of the placental aging process through senescence and apoptotic markers in late-onset small fetuses classified as SGA or FGR. Study Design A prospective nested case-control study in singleton pregnancies delivering at term including 21 normally grown fetuses and 36 small fetuses classified into SGA (if birthweight was between the 3rd and 9th centile and normal fetoplacental Doppler; n=18) and FGR (if birthweight <3rd centile and/or abnormal cerebroplacental ratio or uterine artery Doppler; n=18). Telomerase activity, telomere length and RNA expression of senescence (Sirtuin 1,3,6) and apoptotic markers (p53, p21, BAX, Caspase 3 and 9) were analyzed in placental samples collected at birth. Results Compared with normally grown fetuses, both SGA and FGR presented signs of accelerated placental aging including lower telomerase activity (controls mean±SD 12.8% ± 6.6 vs SGA 7.98% ± 4.2 vs FGR 7.79% ± 4.6, p=0.008), shorter telomeres (controls 1.20 T/S ± 0.6 vs SGA 1.08 T/S ± 0.9 vs FGR 0.66 T/S ± 0.5, p=0.017), and reduced Sirtuin1 RNA expression (controls 1.55 2-' ' Ct ± 0.8 vs SGA 0.91 2-' ' Ct ± 0.8vs FGR 0.63 2-' ' Ct ± 0.5, p<0.001) together with increased p53 RNA expression (controls median(IQR) 1.072-' ' Ct (3.2) vs SGA 5.39 2-' ' Ct (15) vs FGR 3.75 2-' ' Ct (7.8), p=0.040), with a significant linear tendency across severity stages. In addition, FGR cases presented signs of apoptosis with increased RNA levels of Caspase 3 (controls 0.94 2-' ' Ct (1.1) vs FGR 3.98 2-' ' Ct (30), p=0.031) and Caspase 9 (controls 1.21 2-' ' Ct (4.0) vs FGR 3.87 2-' ' Ct (8.7), p=0.037) as compared to controls