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OBJECTIVE: To explore the pattern of fetal cortical development in pregnancies complicated by pre-eclampsia (PE), with and without a small-for-gestational-age (SGA) fetus, compared to uncomplicated pregnancies. METHODS: This was a prospective observational study including singleton pregnancies complicated by normotensive SGA (birth weight < 10(th) centile) (n = 77), PE with an appropriate-for-gestational-age (AGA) fetus (n = 76) or PE with a SGA fetus (n = 67), and 128 uncomplicated pregnancies (normotensive AGA) matched by gestational age at ultrasound. All pregnancies underwent detailed neurosonography, using a transabdominal and transvaginal approach, at 31-35 weeks' gestation to assess the depth of the insula, Sylvian fissure, parieto-occipital sulcus, cingulate sulcus and calcarine sulcus. All measurements were adjusted for biparietal diameter (BPD). In addition, a grading score of cortical development was assigned to each brain structure, ranging from Grade 0 (no development) to Grade 5 (maximum development). Univariate and multiple regression analyses were conducted. RESULTS: Similar to findings in previous studies, normotensive pregnancies with a SGA fetus showed significant differences in cortical development compared with controls, with reduced Sylvian fissure depth adjusted for BPD (14.5 ± 2.4 vs 16.6 ± 2.3; P < 0.001) and increased insula depth adjusted for BPD (33.2 ± 2.0 vs 31.8 ± 2.0; P < 0.001). Interestingly, a similar cortical development pattern was observed in PE pregnancies with a SGA fetus and in PE pregnancies with an AGA fetus, manifested by reduced Sylvian fissure depth adjusted for BPD (14.2 ± 2.3 and 14.3 ± 2.3 vs 16.6 ± 2.3; P < 0.001 for both) and greater insula depth adjusted for BPD (33.2 ± 2.1 and 32.8 ± 1.7 vs 31.8 ± 2.0; P < 0.001 for both) compared with controls. No significant differences were observed in parieto-occipital, cingulate sulcus or calcarine sulcus depth across the study groups. The Sylvian fissure was scored as Grade 4 in significantly more (93.2% vs 59.5%) and as Grade 5 in significantly fewer (2.7% vs 37.3%) PE pregnancies with an AGA fetus compared with controls (P < 0.05 for both). These differences remained significant even after statistical adjustment for potential confounders, including ethnicity, low socioeconomic status, nulliparity, chronic hypertension, pregestational diabetes, assisted reproductive technologies, smoking and fetal gender, with the application of Benjamini-Hochberg procedure for multiple comparisons. CONCLUSIONS: PE with or without SGA is associated with a differential fetal cortical development pattern which is similar to that described previously in small fetuses. Future research is warranted to elucidate better the mechanism(s) underlying these changes. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Objective Stillbirth is a potentially preventable complication of pregnancy. Identifying women at high risk of stillbirth can guide decisions on the need for closer surveillance and timing of delivery in order to prevent fetal death. Prognostic models have been developed to predict the risk of stillbirth, but none has yet been validated externally. In this study, we externally validated published prediction models for stillbirth using individual participant data (IPD) meta-analysis to assess their predictive performance. Methods MEDLINE, EMBASE, DH-DATA and AMED databases were searched from inception to December 2020 to identify studies reporting stillbirth prediction models. Studies that developed or updated prediction models for stillbirth for use at any time during pregnancy were included. IPD from cohorts within the International Prediction of Pregnancy Complications (IPPIC) Network were used to validate externally the identified prediction models whose individual variables were available in the IPD. The risk of bias of the models and cohorts was assessed using the Prediction study Risk Of Bias ASsessment Tool (PROBAST). The discriminative performance of the models was evaluated using the C-statistic, and calibration was assessed using calibration plots, calibration slope and calibration-in-the-large. Performance measures were estimated separately in each cohort, as well as summarized across cohorts using random-effects meta-analysis. Clinical utility was assessed using net benefit. Results Seventeen studies reporting the development of 40 prognostic models for stillbirth were identified. None of the models had been previously validated externally, and the full model equation was reported for only one-fifth (20%, 8/40) of the models. External validation was possible for three of these models, using IPD from 19 cohorts (491 201 pregnant women) within the IPPIC Network database. Based on evaluation of the model development studies, all three models had an overall high risk of bias, according to PROBAST. In the IPD meta-analysis, the models had summary C-statistics ranging from 0.53 to 0.65 and summary calibration slopes ranging from 0.40 to 0.88, with risk predictions that were generally too extreme compared with the observed risks. The models had little to no clinical utility, as assessed by net benefit. However, there remained uncertainty in the performance of some models due to small available sample sizes. Conclusions The three validated stillbirth prediction models showed generally poor and uncertain predictive performance in new data, with limited evidence to support their clinical application. The findings suggest methodological shortcomings in their development, including overfitting. Further research is needed to further validate these and other models, identify stronger prognostic factors and develop more robust prediction models. (c) 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Background Fetal growth restriction (FGR) affects 7–10% of all pregnancies resulting in a higher risk of perinatal morbidity and mortality, long-term disabilities, and cognitive impairment. Due to its multifactorial etiology, changes in maternal lifestyle, including suboptimal maternal diet and stress, have increasingly been associated with its prevalence. We present a protocol for the Improving Mothers for a better PrenAtal Care Trial Barcelona (IMPACT BCN), which evaluates two different maternal lifestyle strategies (improved nutrition by promoting Mediterranean diet and stress reduction program based on mindfulness techniques) on perinatal outcomes. The primary objective is to reduce the prevalence of FGR. Secondary aims are to reduce adverse perinatal outcomes and to improve neurodevelopment and cardiovascular profile in children at 2 years of age. Methods A randomized parallel, open-blind, single-center trial following a 1:1:1 ratio will select and randomize high-risk singleton pregnancies for FGR (N=1218), according to the criteria of the Royal College of Obstetricians and Gynaecologists (19.0–23.6 weeks’ gestation), into three arms: Mediterranean diet, mindfulness-based stress reduction program, and usual care without any intervention. Compliance to the interventions will be randomly tested in 30% of participants with specific biomarkers. Maternal socio-demographic, clinical data, biological samples, and lifestyle questionnaires will be collected at enrollment and at the end of the interventions (34.0–36.6 weeks’ gestation), together with a fetoplacental ultrasound and magnetic resonance. Fetoplacental biological samples and perinatal outcomes will be recorded at delivery. Postnatal follow-up is planned up to 2 years of corrected age including neurodevelopmental tests and cardiovascular assessment. Intention-to-treat and population per-protocol analysis will be performed. Discussion This is the first randomized study evaluating the impact of maternal lifestyle interventions during pregnancy on perinatal outcomes. The maternal lifestyle interventions (Mediterranean diet and mindfulness-based stress reduction program) are supported by scientific evidence, and their compliance will be evaluated with several biomarkers. Trial registration ClinicalTrials.govNCT03166332. Registered on April 19, 2017

BACKGROUND: We aimed to assess the efficacy and safety of two neutralising monoclonal antibody therapies (sotrovimab [Vir Biotechnology and GlaxoSmithKline] and BRII-196 plus BRII-198 [Brii Biosciences]) for adults admitted to hospital for COVID-19 (hereafter referred to as hospitalised) with COVID-19.METHODS: In this multinational, double-blind, randomised, placebo-controlled, clinical trial (Therapeutics for Inpatients with COVID-19 [TICO]), adults (aged ≥18 years) hospitalised with COVID-19 at 43 hospitals in the USA, Denmark, Switzerland, and Poland were recruited. Patients were eligible if they had laboratory-confirmed SARS-CoV-2 infection and COVID-19 symptoms for up to 12 days. Using a web-based application, participants were randomly assigned (2:1:2:1), stratified by trial site pharmacy, to sotrovimab 500 mg, matching placebo for sotrovimab, BRII-196 1000 mg plus BRII-198 1000 mg, or matching placebo for BRII-196 plus BRII-198, in addition to standard of care. Each study product was administered as a single dose given intravenously over 60 min. The concurrent placebo groups were pooled for analyses. The primary outcome was time to sustained clinical recovery, defined as discharge from the hospital to home and remaining at home for 14 consecutive days, up to day 90 after randomisation. Interim futility analyses were based on two seven-category ordinal outcome scales on day 5 that measured pulmonary status and extrapulmonary complications of COVID-19. The safety outcome was a composite of death, serious adverse events, incident organ failure, and serious coinfection up to day 90 after randomisation. Efficacy and safety outcomes were assessed in the modified intention-to-treat population, defined as all patients randomly assigned to treatment who started the study infusion. This study is registered with ClinicalTrials.gov, NCT04501978.FINDINGS: Between Dec 16, 2020, and March 1, 2021, 546 patients were enrolled and randomly assigned to sotrovimab (n=184), BRII-196 plus BRII-198 (n=183), or placebo (n=179), of whom 536 received part or all of their assigned study drug (sotrovimab n=182, BRII-196 plus BRII-198 n=176, or placebo n=178; median age of 60 years [IQR 50-72], 228 [43%] patients were female and 308 [57%] were male). At this point, enrolment was halted on the basis of the interim futility analysis. At day 5, neither the sotrovimab group nor the BRII-196 plus BRII-198 group had significantly higher odds of more favourable outcomes than the placebo group on either the pulmonary scale (adjusted odds ratio sotrovimab 1·07 [95% CI 0·74-1·56]; BRII-196 plus BRII-198 0·98 [95% CI 0·67-1·43]) or the pulmonary-plus complications scale (sotrovimab 1·08 [0·74-1·58]; BRII-196 plus BRII-198 1·00 [0·68-1·46]). By day 90, sustained clinical recovery was seen in 151 (85%) patients in the placebo group compared with 160 (88%) in the sotrovimab group (adjusted rate ratio 1·12 [95% CI 0·91-1·37]) and 155 (88%) in the BRII-196 plus BRII-198 group (1·08 [0·88-1·32]). The composite safety outcome up to day 90 was met by 48 (27%) patients in the placebo group, 42 (23%) in the sotrovimab group, and 45 (26%) in the BRII-196 plus BRII-198 group. 13 (7%) patients in the placebo group, 14 (8%) in the sotrovimab group, and 15 (9%) in the BRII-196 plus BRII-198 group died up to day 90.INTERPRETATION: Neither sotrovimab nor BRII-196 plus BRII-198 showed efficacy for improving clinical outcomes among adults hospitalised with COVID-19.FUNDING: US National Institutes of Health and Operation Warp Speed.

Homogeneous development of temporal bone structures is explained by their ontogenic origin; tegmen tympani (TT) and superior semicircular canal (SSC) are related with the glenoid fossa at the temporomandibular joint (TMJ). Therefore, our objective was to determine a possible relationship between TT status (dehiscence or integrity) and the roof of the glenoid fossa (RGF) thickness; SSC status has also been considered. This cross-sectional descriptive study was conducted in two tertiary hospitals on 95 patients (109 ears) presenting hypoacusia, facial palsy, vertigo, tinnitus, and other single or combined symptoms, and submitted to a thin-section multidetector-row computed axial tomography (CT) scan. A significant interaction effect of TT × SSC statuses on RGF thickness was found (p = 0.049). A significant difference in RGF thickness was found only for SSC integrity status between TT integrity and TT dehiscence (p = 0.004). The TT dehiscence increased the risk for RGF dehiscence 12.047 times (p = 0.002). There is an interaction effect of the statuses of both TT and SSC on the thickness of the RGF, instead of an independent effect of the TT status. When RGF dehiscence is found, TT and SSC statuses should be assessed, to discard associated dehiscences.

Eight lactating Italian Friesian cows were housed in individual respiration chambers in a repeated Latin square design to determine their dry matter intake (DMI) and their milk and methane production, as well as to collect the total feces and urine to determine the N and energy balances. Four diets, based on the following forages (% of dry matter, DM), were tested: corn silage (CS, 49.3), alfalfa silage (AS, 26.8), wheat silage (WS, 20.0), and a typical hay-based Parmigiano Reggiano cheese production diet (PR, 25.3 of both alfalfa and Italian ryegrass hay). The greatest DMI was observed for cows fed PR (23.4 vs. 20.7 kg/d, the average of the other 3 diets). The DM digestibility was lower for PR (64.5 vs. 71.7%, the average of the other diets). The highest ash-free neutral detergent fiber digestibility values were obtained for CS (50.7%) and AS (47.4%). In the present study, no differences in milk production were observed between diets, although PR showed a higher milk yield trend. The highest milk urea N concentration (mg/dL) was found for the cows fed the WS diet (13.8), and the lowest was observed for the cows fed AS (9.24). The highest milk urea N concentration for the cows fed WS was also correlated with the highest urinary N excretion (g/d), which was found for the cows fed that same diet (189 vs. 147 on average for the other diets). The protein digestibility was higher for the cows fed the CS and WS diets (on average 68.5%) than for the cows fed AS and PR (on average 57.0%); dietary soybean inclusion was higher for CS and WS than for AS and PR. The rumen fermentation pattern was affected by the diet; the cows fed the PR diet showed a higher rumen pH and decreased propionate production than those fed CS, due to the lower nonfiber carbohydrate content and higher ash-free neutral detergent fiber content of the PR diet than the CS diet. Feeding cows with PR diet increased the acetate:propionate ratio in comparison with the CS diet (3.30 vs. 2.44 for PR and CS, respectively). Cows fed the PR diet produced a greater daily amount of methane and had a greater methane energy loss (% of digestible energy intake) than those fed the CS diet (413 vs. 378 g/d and 8.67 vs. 7.70%), but no differences were observed when methane was expressed as grams per kilogram of DMI or grams per kilogram of milk. The PR diet resulted in a smaller net energy for lactation content than the CS diet (1.36 vs. 1.70 Mcal/kg of DM for the PR and CS diets, respectively). Overall, our research suggests that a satisfactory milk production can be attained by including different high-quality forages in balanced diets without any negative effect on milk production or on the methane emissions per kilogram of milk.

The aim of the present study was to evaluate, through a survey conducted on commercial farms, the global warming potential (GWP) of different lactating cow total mixed rations (TMR) and to identify the best dietary strategies to increase feed efficiency (FE) and reduce enteric CH4 emission. A total of 171 dairy herds were selected: data about dry matter intake (DMI), lactating cow TMR composition, and milk production and composition were provided by farmers. Diet GWP (kg of CO2 equivalents; CO2eq) was calculated as sum of GWP (kg of CO2eq) of each included ingredient, considering inputs needed at field level, feed processing, and transport. For soybean solvent meal, land use change was included in the assessment. Enteric methane production (g/d) was estimated [using the equation CH4 (g/d) = 2.54 + 19.14 × DMI] to calculate CH4 emission for kilograms of fat- and protein-corrected milk (FPCM). The data set was analyzed by generalized linear model and logistic analysis using SAS 9.4 (SAS Institute Inc., Cary, NC). The frequency distribution showed wide variation among farms for GWP (kg of CO2eq) of TMR: approximately 25% of the surveyed farms showed a diet GWP of 15 kg of CO2eq, 20% showed a GWP of 13 kg of CO2eq, and 16.7% showed a GWP of 17 kg of CO2eq. The variation among farms was due to the feedstuffs used. Among feedstuffs, soybean meal (SBM) had the highest correlation with the GWP of the TMR as shown by the following equation: TMR GWP (kg of CO2eq) = 2.49 × kg of SBM + 6.9 (R2 = 0.547). Moreover, diets with inclusion of SBM >15% of dry matter (DM) did not result in higher milk production than diets with a lower inclusion of SBM (≤15%). Average daily milk production of cows was 29.8 [standard deviation (SD) 4.83] kg with fat and protein contents of 3.86% (SD 0.22) and 3.40% (SD 0.14), respectively. The average DMI (kg/d) of lactating cows was 22.3 (SD 2.23). Logistic analysis demonstrated that corn silage ≤30% of diet DM was associated with higher FE. Almost 50% of farms had an average value of 15.0 g of CH4/kg of FPCM and about 30% of farms had an average of 12.5 g of CH4/kg of FPCM. The results demonstrated that lower enteric CH4 production was related to inclusion (% of diet DM) of ≤12% alfalfa hay and >30% corn silage. Diets with >34% neutral detergent fiber had higher CH4 production (>14.0 g/kg of FPCM) than those with lower neutral detergent fiber content. In contrast, lower enteric CH4 production (≤14.0 g/kg of FPCM) was related to diets characterized by net energy of lactation (NEL) >1.61 Mcal/kg and >4% ether extract. The variability in TMR GWP shows significant potential for reducing the GWP of a diet through choice and inclusion levels of ingredients (mainly SBM) and the possibility of decreasing methane enteric emission associated with milk production on a commercial scale.

The heart is a central organ in the fetal adaptation to an adverse environment. Fetal cardiac changes may persist postnatally and increase the risk of cardiovascular disease in adulthood. Knowledge about fetal cardiac structural as well as functional remodeling has radically improved over the last few years. As it occurs in postnatal life, the fetal heart remodels - changing its structure and shape - to adapt to an insult. Several conditions have been reported to be associated with fetal cardiac remodeling including intrauterine growth restriction, diabetes, exposure to antiretroviral drugs, conception by assisted reproductive technologies, pulmonary stenosis, and other congenital heart diseases. Here we summarized the main observable patterns of cardiac remodeling, i.e., globular shape, hypertrophy without dilation, and hypertrophy with cardiomegaly. We discuss the potential pathophysiology behind different types of remodeling. Defining precisely the distinct patterns of fetal cardiac remodeling is critical for advancing in the understanding of fetal cardiovascular programming and its consequences on adult health, and potentially for the design of preventive strategies that might have an impact on long-term cardiovascular health. ispartof: FETAL DIAGNOSIS AND THERAPY vol:47 issue:5 pages:337-344 ispartof: location:Switzerland status: published

We aimed to explore fetal cortical brain development by neurosonography in fetuses conceived by assisted reproductive technology (ART), including frozen and fresh embryo transfer (ET), compared with those conceived spontaneously (SC), and to investigate its association with infant neurobehavior at 12 months of age.This was a prospective cohort study of 210 singleton pregnancies, including 70 SC pregnancies, 70 conceived by in-vitro fertilization (IVF) following frozen ET and 70 conceived by IVF after fresh ET. Fetal neurosonography was performed at 32 ± 2 gestational weeks to assess cortical development. Sulci depths were measured offline and normalized by biparietal diameter (BPD). Ages and Stages Questionnaires (ASQ) were completed postnatally, at 12 ± 1 months of corrected age. Neurosonographic findings were adjusted by regression analysis for maternal age, ethnicity, parity, fetal sex and fetal-weight centile and gestational age at scan, and ASQ scores were adjusted for maternal age, ethnicity, parity, educational level and employment status, gestational age at birth, breastfeeding, infant sex and infant age at the ASQ evaluation.Overall, in comparison to the SC fetuses, fetuses conceived by ART showed statistically significant differences in cortical development, with reduced parieto-occipital sulci depth adjusted for BPD (mean ± SD: fresh ET, 12.5 ± 2.5 vs frozen ET, 13.4 ± 2.6 vs SC, 13.4 ± 2.6, P 0.001), cingulate sulci depth adjusted for BPD (median (interquartile range (IQR)): fresh ET, 5.8 (4.2-7.4) vs frozen ET, 5.8 (4.1-7.5) vs SC, 6.5 (4.8-7.8), P = 0.001) and calcarine sulci depth adjusted for BPD (median (IQR): fresh ET, 13.5 (10.1-16.1) vs frozen ET, 14.5 (12.1-15.8) vs SC, 16.4 (14.3-17.9), P 0.001), together with lower Sylvian fissure grading score. Changes in cortical development were more pronounced in the fresh ET than in the frozen ET group. ART infants showed lower ASQ scores as compared to SC infants, particularly in the fresh ET group (mean ± SD global ASQ Z-score: fresh ET, -0.3 ± 0.4 vs frozen ET, -0.2 ± 0.4 vs SC, 0 ± 0.4, P 0.001).Fetuses conceived by ART show a distinctive pattern of cortical development and suboptimal infant neurodevelopment, with more pronounced changes in those conceived following fresh ET. These findings support the existence of in-utero brain reorganization associated with ART and warrant follow-up studies to assess its long-term persistence. © 2022 The Authors. Ultrasound in ObstetricsGynecology published by John WileySons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

16 pages, 6 figures, 3 tables, supplementary data https://doi.org/10.1016/j.ajog.2022.03.048, Background: COVID-19 presents a spectrum of signs and symptoms in pregnant women that might resemble preeclampsia. Differentiation between severe COVID-19 and preeclampsia is difficult in some cases. Objective: To study biomarkers of endothelial damage, coagulation, innate immune response, and angiogenesis in preeclampsia and COVID-19 in pregnancy in addition to in vitro alterations in endothelial cells exposed to sera from pregnant women with preeclampsia and COVID-19. Study Design: Plasma and sera samples were obtained from pregnant women with COVID-19 infection classified into mild (n=10) or severe (n=9) and from women with normotensive pregnancies as controls (n=10) and patients with preeclampsia (n=13). A panel of plasmatic biomarkers was assessed, including vascular cell adhesion molecule-1, soluble tumor necrosis factor-receptor I, heparan sulfate, von Willebrand factor antigen (activity and multimeric pattern), α2-antiplasmin, C5b9, neutrophil extracellular traps, placental growth factor, soluble fms-like tyrosine kinase-1, and angiopoietin 2. In addition, microvascular endothelial cells were exposed to patients’ sera, and changes in the cell expression of intercellular adhesion molecule 1 on cell membranes and von Willebrand factor release to the extracellular matrix were evaluated through immunofluorescence. Changes in inflammation cell signaling pathways were also assessed by of p38 mitogen-activated protein kinase phosphorylation. Statistical analysis included univariate and multivariate methods. Results: Biomarker profiles of patients with mild COVID-19 were similar to those of controls. Both preeclampsia and severe COVID-19 showed significant alterations in most circulating biomarkers with distinctive profiles. Whereas severe COVID-19 exhibited higher concentrations of vascular cell adhesion molecule-1, soluble tumor necrosis factor-α receptor I, heparan sulfate, von Willebrand factor antigen, and neutrophil extracellular traps, with a significant reduction of placental growth factor compared with controls, preeclampsia presented a marked increase in vascular cell adhesion molecule-1 and soluble tumor necrosis factor-α receptor I (significantly increased compared with controls and patients with severe COVID-19), with a striking reduction in von Willebrand factor antigen, von Willebrand factor activity, and α2-antiplasmin. As expected, reduced placental growth factor, increased soluble fms-like tyrosine kinase-1 and angiopoietin 2, and a very high soluble fms-like tyrosine kinase-1 to placental growth factor ratio were also observed in preeclampsia. In addition, a significant increase in C5b9 and neutrophil extracellular traps was also detected in preeclampsia compared with controls. Principal component analysis demonstrated a clear separation between patients with preeclampsia and the other groups (first and second components explained 42.2% and 13.5% of the variance), mainly differentiated by variables related to von Willebrand factor, soluble tumor necrosis factor-receptor I, heparan sulfate, and soluble fms-like tyrosine kinase-1. Von Willebrand factor multimeric analysis revealed the absence of von Willebrand factor high-molecular-weight multimers in preeclampsia (similar profile to von Willebrand disease type 2A), whereas in healthy pregnancies and COVID-19 patients, von Willebrand factor multimeric pattern was normal. Sera from both preeclampsia and severe COVID-19 patients induced an overexpression of intercellular adhesion molecule 1 and von Willebrand factor in endothelial cells in culture compared with controls. However, the effect of preeclampsia was less pronounced than the that of severe COVID-19. Immunoblots of lysates from endothelial cells exposed to mild and severe COVID-19 and preeclampsia sera showed an increase in p38 mitogen-activated protein kinase phosphorylation. Patients with severe COVID-19 and preeclampsia were statistically different from controls, suggesting that both severe COVID-19 and preeclampsia sera can activate inflammatory signaling pathways. Conclusion: Although similar in in vitro endothelial dysfunction, preeclampsia and severe COVID-19 exhibit distinctive profiles of circulating biomarkers related to endothelial damage, coagulopathy, and angiogenic imbalance that could aid in the differential diagnosis of these entities, With the institutional support of the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000928-S)

Behavioural and metabolic risk factors are responsible for the greatest burden of disease; an unhealthy diet, along with abdominal obesity, are risk factors related to Non-communicable diseases (NCDs).Data concerning food patterns were determined by the application of an interview-type instrument, used to assess the daily and weekly frequency of consumption; cardiovascular risk was assessed using waist circumference, and nutritional status via Body Mass Index. Student's t test was applied to evaluate the differences between variables and the Pearson's chi-square test for the association of variables.Dietary energy intake (kcal/capita/day) was 3000 kcal, with an average distribution of 12.2% (proteins), 46.9% (carbohydrates), and 40.9% (total fats). The 78% of the sample suffered from malnutrition by excess. About 37.5% had Non-Communicable Diseases, with high blood pressure being the most frequent disease among both genders, with the highest prevalence among women, along with diabetes mellitus and dyslipidaemia. Depending on the nutritional status, the presence of obesity is associated with high cardiovascular risk (p = 0.000), greater energy availability (p = 0.012), and an increased occurrence of non-communicable diseases (p = 0.004).Malnutrition by excess figures support the global alert for obesity and overweight, which are considered to be a pandemic; in addition, Chiloé is not immune to the increasing trend of processed and ultra-processed food consumption.

Objective: Second- and third-trimester SARS-CoV-2 infections may have an increased risk of obstetric complications. However, data on first-trimester infections are scarce. We sought to characterize the clinical and inflammatory presentations and pregnancy outcomes of first-trimester infections. Methods: A population-based multicenter study including 817 singleton pregnancies with SARS-CoV-2 serologic testing at 8-14 weeks between March and May 2020. Blood count, uterine artery Doppler, and pregnancy-associated plasma protein A (PAPP-A) were performed in all women. Placental growth factor (PlGF), soluble fms-like tyrosine kinase 1 (sFlt-1), IL-6, and ferritin were determined in positive women. Obstetric outcomes were evaluated. Results: The prevalence of first-trimester infection was 15.2% (n = 124). 72.6% of positive women were asymptomatic. Symptomatic women had higher rates of lymphopenia (1.91 × 109/L vs. 2.16 × 109/L, p = 0.017) and increased levels of IL-6 (9.1% vs. 1.2%, p = 0.051), but lower rates of decreased ferritin (6.3% vs. 19.8%, p = 0.015). PAPP-A was higher in symptomatic women compared with asymptomatic and negative women (1.44 [IQR 0.90-1.82] vs. 1.08 [IQR 0.66-1.61] p = 0.014, vs. 1.08 [IQR 0.77-1.55] p = 0.019, respectively). Obstetric outcomes were not increased. Conclusions: First-trimester SARS-CoV-2 infections are mostly asymptomatic, with a mild increase of inflammatory markers in symptomatic women. Obstetric complications were not increased, but PAPP-A levels were higher in symptomatic women. © 2022

IMPORTANCE: Being born small for gestational age (SGA) is a leading cause of perinatal morbidity and mortality with no effective prevention or therapy. Maternal suboptimal nutrition and high stress levels have been associated with poor fetal growth and adverse pregnancy outcomes. OBJECTIVE: To investigate whether structured interventions based on a Mediterranean diet or mindfulness-based stress reduction (stress reduction) in high-risk pregnancies can reduce the percentage of newborns who were born SGA and other adverse pregnancy outcomes. DESIGN, SETTING, AND PARTICIPANTS: Parallel-group randomized clinical trial conducted at a university hospital in Barcelona, Spain, including 1221 individuals with singleton pregnancies (19-23 weeks’ gestation) at high risk for SGA. Enrollment took place from February 1, 2017, to October 10, 2019, with follow-up until delivery (final follow-up on March 1, 2020). INTERVENTIONS: Participants in the Mediterranean diet group (n = 407) received 2 hours monthly of individual and group educational sessions and free provision of extra-virgin olive oil and walnuts. Individuals in the stress reduction group (n = 407) underwent an 8-week stress reduction program adapted for pregnancy, consisting of weekly 2.5-hour sessions and 1 full-day session. Individuals in the usual care group (n = 407) received pregnancy care per institutional protocols. MAIN OUTCOMES AND MEASURES: The primary end point was the percentage of newborns who were SGA at delivery, defined as birth weight below the 10th percentile. The secondary end point was a composite adverse perinatal outcome (at least 1 of the following: preterm birth, preeclampsia, perinatal mortality, severe SGA, neonatal acidosis, low Apgar score, or presence of any major neonatal morbidity). RESULTS: Among the 1221 randomized individuals (median [IQR] age, 37 [34-40] years), 1184 (97%) completed the trial (392 individuals assigned to the Mediterranean diet group, 391 to the stress reduction group, and 401 to the usual care group). SGA occurred in 88 newborns (21.9%) in the control group, 55 (14.0%) in the Mediterranean diet group (odds ratio [OR], 0.58 [95% CI, 0.40-0.84]; risk difference [RD], −7.9 [95% CI, −13.6 to −2.6]; P = .004), and 61 (15.6%) in the stress reduction group (OR, 0.66 [95% CI, 0.46-0.94]; RD, −6.3 [95% CI, −11.8 to −0.9]; P = .02). The composite adverse perinatal outcome occurred in 105 newborns (26.2%) in the control group, 73 (18.6%) in the Mediterranean diet group (OR, 0.64 [95% CI, 0.46-0.90]; RD, −7.6 [95% CI, −13.4 to −1.8]; P = .01), and 76 (19.5%) in the stress reduction group (OR, 0.68 [95% CI, 0.49-0.95]; RD, −6.8 [95% CI, −12.6 to −0.3]; P = .02). CONCLUSIONS AND RELEVANCE: In this randomized trial conducted at a single institution in Spain, treating pregnant individuals at high risk for SGA with a structured Mediterranean diet or with mindfulness-based stress reduction, compared with usual care, significantly reduced the percentage of newborns with birth weight below the 10th percentile. Due to important study limitations, these findings should be considered preliminary and require replication, as well as assessment in additional patient populations, before concluding that these treatments should be recommended to patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03166332

Importance: An intraoperative higher level of positive end-expiratory positive pressure (PEEP) with alveolar recruitment maneuvers improves respiratory function in obese patients undergoing surgery, but the effect on clinical outcomes is uncertain. Objective: To determine whether a higher level of PEEP with alveolar recruitment maneuvers decreases postoperative pulmonary complications in obese patients undergoing surgery compared with a lower level of PEEP. Design, Setting, and Participants: Randomized clinical trial of 2013 adults with body mass indices of 35 or greater and substantial risk for postoperative pulmonary complications who were undergoing noncardiac, nonneurological surgery under general anesthesia. The trial was conducted at 77 sites in 23 countries from July 2014-February 2018; final follow-up: May 2018. Interventions: Patients were randomized to the high level of PEEP group (n = 989), consisting of a PEEP level of 12 cm H2O with alveolar recruitment maneuvers (a stepwise increase of tidal volume and eventually PEEP) or to the low level of PEEP group (n = 987), consisting of a PEEP level of 4 cm H2O. All patients received volume-controlled ventilation with a tidal volume of 7 mL/kg of predicted body weight. Main Outcomes and Measures: The primary outcome was a composite of pulmonary complications within the first 5 postoperative days, including respiratory failure, acute respiratory distress syndrome, bronchospasm, new pulmonary infiltrates, pulmonary infection, aspiration pneumonitis, pleural effusion, atelectasis, cardiopulmonary edema, and pneumothorax. Among the 9 prespecified secondary outcomes, 3 were intraoperative complications, including hypoxemia (oxygen desaturation with Spo2 ≤92% for >1 minute). Results: Among 2013 adults who were randomized, 1976 (98.2%) completed the trial (mean age, 48.8 years; 1381 [69.9%] women; 1778 [90.1%] underwent abdominal operations). In the intention-to-treat analysis, the primary outcome occurred in 211 of 989 patients (21.3%) in the high level of PEEP group compared with 233 of 987 patients (23.6%) in the low level of PEEP group (difference, -2.3% [95% CI, -5.9% to 1.4%]; risk ratio, 0.93 [95% CI, 0.83 to 1.04]; P =.23). Among the 9 prespecified secondary outcomes, 6 were not significantly different between the high and low level of PEEP groups, and 3 were significantly different, including fewer patients with hypoxemia (5.0% in the high level of PEEP group vs 13.6% in the low level of PEEP group; difference, -8.6% [95% CI, -11.1% to 6.1%]; P

Objectives To develop and validate a specific protocol for SARS-CoV-2 detection in breast milk matrix and to determine the impact of maternal SARS-CoV-2 infection on the presence, concentration and persistence of specific SARS-CoV-2 antibodies. Design and patients This is a prospective, multicentre longitudinal study (April–December 2020) in 60 mothers with SARS-CoV-2 infection and/or who have recovered from COVID-19. A control group of 13 women before the pandemic were also included. Setting Seven health centres from different provinces in Spain. Main outcome measures Presence of SARS-CoV-2 RNA in breast milk, targeting the N1 region of the nucleocapsid gene and the envelope (E) gene; presence and levels of SARS-CoV-2-specific immunoglobulins (Igs)—IgA, IgG and IgM—in breast milk samples from patients with COVID-19. Results All breast milk samples showed negative results for presence of SARS-CoV-2 RNA. We observed high intraindividual and interindividual variability in the antibody response to the receptor-binding domain of the SARS-CoV-2 spike protein for each of the three isotypes IgA, IgM and IgG. Main Protease (MPro) domain antibodies were also detected in milk. 82.9% (58 of 70) of milk samples were positive for at least one of the three antibody isotypes, with 52.9% of these positive for all three Igs. Positivity rate for IgA was relatively stable over time (65.2%–87.5%), whereas it raised continuously for IgG (from 47.8% for the first 10 days to 87.5% from day 41 up to day 206 post-PCR confirmation). Conclusions Our study confirms the safety of breast feeding and highlights the relevance of virus-specific SARS-CoV-2 antibody transfer. This study provides crucial data to support official breastfeeding recommendations based on scientific evidence. Trial registration number NCT04768244., This study has been supported by a research grant from Fundación La Marató-TV3 (MilkCORONA, ref 202106).

Introduction: Tobacco Consumption (TC) is one of the main causes of the deterioration of health. The objetive this study is to test the association of smoking with anthropometry, diet and sleep quality among Chilean university students. Cross-sectional study. University students (n=1454) from the North, South and Central parts of Chile were evaluated. A self-assessment survey was used to evaluate healthy and unhealthy eating habits, nutritional status was evaluated by Body Mass Index (BMI). And two surveys of sleep: the Questionnaire of Insomnia and the Epworth scale. Finally, he was consulted about tobacco Consumption. 30% of students consume tobacco, they have a higher score in unhealthy food consumption, less frequent weekly consumption, less daily fruit consumption, higher alcohol consumption and daily junk food consumption compared to non-consuming students. Men who consume tobacco present greater insomnia, sleep latency and daytime sleepiness compared to non-consumers; and women who consume tobacco have a higher weight and BMI. When performing the logistic regression, tobacco consumption is positively associated with alcohol consumption, whereas fish and vegetable consumption negatively. In conclusions, the students of both sexes who smoke have higher unfavorable health factors and quality of life, Journal of Preventive Medicine and Hygiene, Vol. 62 No. 2 (2021): 2021622

Objective: Second- and third-trimester SARS-CoV-2 infections may have an increased risk of obstetric complications. However, data on first-trimester infections are scarce. We sought to characterize the clinical and inflammatory presentations and pregnancy outcomes of first-trimester infections. Methods: A population-based multicenter study including 817 singleton pregnancies with SARS-CoV-2 serologic testing at 8–14 weeks between March and May 2020. Blood count, uterine artery Doppler, and pregnancy-associated plasma protein A (PAPP-A) were performed in all women. Placental growth factor (PlGF), soluble fms-like tyrosine kinase 1 (sFlt-1), IL-6, and ferritin were determined in positive women. Obstetric outcomes were evaluated. Results: The prevalence of first-trimester infection was 15.2% (n = 124). 72.6% of positive women were asymptomatic. Symptomatic women had higher rates of lymphopenia (1.91 × 109/L vs. 2.16 × 109/L, p = 0.017) and increased levels of IL-6 (9.1% vs. 1.2%, p = 0.051), but lower rates of decreased ferritin (6.3% vs. 19.8%, p = 0.015). PAPP-A was higher in symptomatic women compared with asymptomatic and negative women (1.44 [IQR 0.90–1.82] vs. 1.08 [IQR 0.66–1.61] p = 0.014, vs. 1.08 [IQR 0.77–1.55] p = 0.019, respectively). Obstetric outcomes were not increased. Conclusions: First-trimester SARS-CoV-2 infections are mostly asymptomatic, with a mild increase of inflammatory markers in symptomatic women. Obstetric complications were not increased, but PAPP-A levels were higher in symptomatic women.

IMPORTANCE: Being born small for gestational age (SGA), approximately 10% of all births, is associated with increased risk of cardiovascular mortality in adulthood, but mechanistic pathways are unclear. Cardiac remodeling and dysfunction occur in fetuses SGA and children born SGA, but it is uncertain whether and how these changes persist into adulthood. OBJECTIVE: To evaluate baseline cardiac function and structure and exercise capacity in young adults born SGA. DESIGN, SETTING, AND PARTICIPANTS: This cohort study conducted from January 2015 to January 2018 assessed a perinatal cohort born at a tertiary university hospital in Spain between 1975 and 1995. Participants included 158 randomly selected young adults aged 20 to 40 years born SGA (birth weight below the 10th centile) or with intrauterine growth within standard reference ranges (controls). Participants provided their medical history, filled out questionnaires regarding smoking and physical activity habits, and underwent incremental cardiopulmonary exercise stress testing, cardiac magnetic resonance imaging, and a physical examination, with blood pressure, glucose level, and lipid profile data collected. EXPOSURE: Being born SGA. MAIN OUTCOMES AND MEASURES: Cardiac structure and function assessed by cardiac magnetic resonance imaging, including biventricular end-diastolic shape analysis. Exercise capacity assessed by incremental exercise stress testing. RESULTS: This cohort study included 81 adults born SGA (median age at study, 34.4 years [IQR, 30.8-36.7 years]; 43 women [53%]) and 77 control participants (median age at study, 33.7 years [interquartile range (IQR), 31.0-37.1 years]; 33 women [43%]). All participants were of White race/ethnicity and underwent imaging, whereas 127 participants (80% of the cohort; 66 control participants and 61 adults born SGA) completed the exercise test. Cardiac shape analysis showed minor changes at rest in right ventricular geometry (DeLong test z, 2.2098; P = .02) with preserved cardiac function in individuals born SGA. However, compared with controls, adults born SGA had lower exercise capacity, with decreased maximal workload (mean [SD], 180 [62] W vs 214 [60] W; P = .006) and oxygen consumption (median, 26.0 mL/min/kg [IQR, 21.5-33.5 mL/min/kg vs 29.5 mL/min/kg [IQR, 24.0-36.0 mL/min/kg]; P = .02). Exercise capacity was significantly correlated with left ventricular mass (ρ = 0.7934; P

Preeclampsia (PE) and fetal growth restriction (FGR) are both placenta-mediated disorders with unclear pathogenesis. Metabolomics of maternal and fetal pairs might help in understanding these disorders. We recruited prospectively pregnancies with normotensive FGR, PE without FGR, PE + FGR and uncomplicated pregnancies as controls. Nuclear magnetic resonance metabolomics were applied on plasma samples collected at delivery. Advanced lipoprotein, glycoprotein and choline profiling was performed using the Liposcale test. The software package Dolphin was used to quantify 24 low-molecular-weight metabolites. Statistical analysis comprised the comparison between each group of complicated pregnancies versus controls, considering 5% false discovery rate correction. Lipid profiles were altered in accordance with the clinical presentation of these disorders. Specifically, PE mothers and FGR fetuses (with or without FGR or PE, respectively) exhibited a pro-atherogenic and pro-inflammatory profile, with higher concentrations of triglycerides, remnant cholesterol (VLDL, IDL) and Glc/GalNAc-linked and lipid-associated glycoproteins compared to controls. Low-molecular-weight metabolites were extensively disturbed in preeclamptic mothers, with or without FGR. Growth restricted fetuses in the presence of PE showed changes in low-molecular-weight metabolites similar to their mothers (increased creatine and creatinine), while normotensive FGR fetuses presented scarce differences, consistent with undernutrition (lower isoleucine). Further research is warranted to clarify maternal and fetal adaptations to PE and FGR.

To assess the added value of Doppler parameters, maternal history, and intrapartum clinical characteristics for the prediction of emergency delivery due to non-reassuring fetal status in low-risk pregnancies.This was a prospective cohort of low-risk pregnancies undergoing ultrasound assessment at 40 weeks' gestation within 7 days of delivery. The main outcome was emergency cesarean section due to non-reassuring fetal status. The association between Doppler parameters, intrapartum clinical characteristics, and maternal history was performed by logistic regression. The predictive performance of the constructed models was assessed by receiver operating characteristic (ROC) curve analysis and the area under the curve (AUC).From 403 included pregnancies, 18.6% (In low-risk pregnant woman at term, the addition of MCA Z-score to a previous model comprising maternal history and intrapartum clinical findings, significantly improves the prediction of emergency delivery due to non-reassuring fetal status.

OBJECTIVE: To evaluate the transgenerational transmission of small-for-gestational age (SGA). METHODS: This was a cohort study of a random sample of 2043 offspring delivered between 1975 and 1993 at Hospital Sant Joan de Déu in Barcelona. Exclusion criteria were multiple pregnancy, aneuploidy or genetic syndrome, major birth defects, severe mental disease and macrosomia. Eligible individuals were contacted and those with at least one offspring were included in the study. Participants were classified according to the presence of SGA (defined as birth weight < 10(th) percentile) at birth. Multiple regression analysis was used to determine the presence of SGA or placenta-mediated disease (defined as the presence of SGA, pre-eclampsia, gestational hypertension and/or placental abruption) in the following generation. RESULTS: Of 623 individuals who agreed to participate, 152 (72 born SGA and 80 born appropriate-for-gestational age (AGA)) were reported to have at least one child. Descendants of SGA individuals presented with a lower birth-weight percentile (median, 26 (interquartile range (IQR), 7-52) vs 43 (IQR, 19-75); P < 0.001) and a higher prevalence of SGA (40.3% vs 16.3%; P = 0.001) and placenta-mediated disease (43.1% vs 17.5%; P = 0.001) than did the offspring of AGA individuals. After adjustment for confounding variables, parental SGA background was associated with an almost three-fold increased risk of subsequent SGA or any placenta-mediated disease in the following generation. This association was stronger in SGA mothers than in SGA fathers. CONCLUSIONS: Our data provide evidence suggesting a transgenerational transmission of SGA, highlighting the importance of public health strategies for preventing intrauterine growth impairment. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Fetal growth restriction is one of the most common obstetric complications, affecting 7-10% of all pregnancies. Affected fetuses are exposed to an adverse environment in utero during a critical time of development and may face long-term health consequences such as increased cardiovascular risk in adulthood. Growth restricted fetuses develop remodeled hearts with signs of systolic and diastolic dysfunction. Cardiac adaptations are more evident in early severe cases, but also present in late onset fetal growth restriction. Cardiovascular remodeling persists into postnatal life, from the neonatal period to adolescence, encompassing an increased susceptibility to adult disease. In this review, we summarize the current evidence on cardiovascular programming associated to fetal growth restriction, its postnatal consequences and potential strategies to reduce their cardiovascular risk.

Serological diagnostic of the severe respiratory distress syndrome coronavirus 2 (SARS-CoV-2) is a valuable tool for the determination of immunity and surveillance of exposure to the virus. In the context of an ongoing pandemic, it is essential to externally validate widely used tests to assure correct diagnostics and epidemiological estimations. We evaluated the performance of the COVID-19 ELISA IgG and the COVID-19 ELISA IgM/A (Vircell, S.L.) against a highly specific and sensitive in-house Luminex immunoassay in a set of samples from pregnant women and cord blood. The agreement between both assays was moderate to high for IgG but low for IgM/A. Considering seropositivity by either IgG and/or IgM/A, the technical performance of the ELISA was highly imbalanced, with 96% sensitivity at the expense of 22% specificity. As for the clinical performance, the negative predictive value reached 87% while the positive predictive value was 51%. Our results stress the need for highly specific and sensitive assays and external validation of diagnostic tests with different sets of samples to avoid the clinical, epidemiological and personal disturbances derived from serological misdiagnosis.

Background We performed a population-based study to describe the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on pregnancy outcomes. Methods This prospective, population-based study included pregnant women who consecutively presented at first/second trimester visits or at delivery at 3 hospitals in Barcelona, Spain. SARS-CoV-2 antibodies (immunoglobulin [Ig] G and IgM/IgA) were measured in all participants, and nasopharyngeal real-time polymerase chain reaction (RT-PCR) was performed at delivery. The primary outcome was a composite of pregnancy complications in SARS-CoV-2–positive vs negative women that included miscarriage, preeclampsia, preterm delivery, perinatal death, small-for-gestational-age newborn, or neonatal admission. Secondary outcomes were components of the primary outcome plus abnormal fetal growth, malformation, or intrapartum fetal distress. Outcomes were also compared between positive symptomatic and positive asymptomatic SARS-CoV-2 women. Results Of 2225 pregnant women, 317 (14.2%) were positive for SARS-CoV-2 antibodies (n = 314, 99.1%) and/or RT-PCR (n = 36, 11.4%). Among positive women, 217 (68.5%) were asymptomatic, 93 (29.3%) had mild coronavirus disease 2019 (COVID-19), and 7 (2.2%) had pneumonia, of whom 3 required intensive care unit admission. In women with and without SARS-CoV-2 infection, the primary outcome occurred in 43 (13.6%) and 268 (14%), respectively (risk difference, –0.4%; 95% confidence interval, –4.1% to 4.1). Compared with noninfected women, those with symptomatic COVID-19 had increased rates of preterm delivery (7.2% vs 16.9%, P = .003) and intrapartum fetal distress (9.1% vs 19.2%, P = .004), while asymptomatic women had rates that were similar to those of noninfected cases. Among 143 fetuses from infected mothers, none had anti–SARS-CoV-2 IgM/IgA in cord blood. Conclusions The overall rate of pregnancy complications in women with SARS-CoV-2 infection was similar to that of noninfected women. However, symptomatic COVID-19 was associated with modest increases in preterm delivery and intrapartum fetal distress.

The identification of factors predisposing to severe COVID-19 in young adults remains partially characterized. Low birth weight (LBW) alters cardiovascular and lung development and predisposes to adult disease. We hypothesized that LBW is a risk factor for severe COVID-19 in non-elderly subjects. We analyzed a prospective cohort of 397 patients (18–70 years) with laboratory-confirmed SARS-CoV-2 infection attended in a tertiary hospital, where 15% required admission to Intensive Care Unit (ICU). Perinatal and current potentially predictive variables were obtained from all patients and LBW was defined as birth weight ≤ 2.500 g. Age (adjusted OR (aOR) 1.04 [1–1.07], P = 0.012), male sex (aOR 3.39 [1.72–6.67], P

We aimed to analyze the nasopharyngeal microbiota profiles in pregnant women with and without SARS-CoV-2 infection, considered a vulnerable population during COVID-19 pandemic. Pregnant women were enrolled from a multicenter prospective population-based cohort during the first SARS-CoV-2 wave in Spain (March-June 2020 in Barcelona, Spain) in which the status of SARS-CoV-2 infection was determined by nasopharyngeal RT–PCR and antibodies in peripheral blood. Women were randomly selected for this cross-sectional study on microbiota. DNA was extracted from nasopharyngeal swab samples, and the V3-V4 region of the 16S rRNA of bacteria was amplified using region-specific primers. The differential abundance of taxa was tested, and alpha/beta diversity was evaluated. Among 76 women, 38 were classified as positive and 38 as negative for SARS-CoV-2 infection. All positive women were diagnosed by SARS-CoV-2 IgG and IgM/IgA antibodies, and 14 (37%) also had a positive RT–PCR. The overall composition of the nasopharyngeal microbiota differ in pregnant women with SARS-CoV-2 infection (positive SARS-CoV-2 antibodies), compared to those without the infection (negative SARS-CoV-2 antibodies) (p = 0.001), with a higher relative abundance of the Tenericutes and Bacteroidetes phyla and a higher abundance of the Prevotellaceae family. Infected women presented a different pattern of microbiota profiling due to beta diversity and higher richness (observed ASV, This study was partially funded by the KidsCorona Child and Mother COVID-19 OpenData and Biobank Initiative from Hospital Sant Joan de Déu (Stavros Niarchos Foundation, Santander Foundation and others), “LaCaixa” Foundation, Sant Pau Research Institute, ISGlobal and Fundació Privada Daniel Bravo Andreu, Barcelona, Spain. All funders had no role in the study design, data collection, data analysis, data interpretation or writing the manuscript.

Preeclampsia is a pregnancy-specific multisystem disorder and a leading cause of maternal and perinatal morbidity and mortality. The exact pathogenesis of this multifactorial disease remains poorly defined. We applied proteomics analysis on maternal blood samples collected from 14 singleton pregnancies with early-onset severe preeclampsia and 6 uncomplicated pregnancies to investigate the pathophysiological pathways involved in this specific subgroup of preeclampsia. Maternal blood was drawn at diagnosis for cases and at matched gestational age for controls. LC–MS/MS proteomics analysis was conducted, and data were analyzed by multivariate and univariate statistical approaches with the identification of differential pathways by exploring the global human protein–protein interaction network. The unsupervised multivariate analysis (the principal component analysis) showed a clear difference between preeclamptic and uncomplicated pregnancies. The supervised multivariate analysis using orthogonal partial least square discriminant analysis resulted in a model with goodness of fit (R2X = 0.99, p < 0.001) and a strong predictive ability (Q2Y = 0.8, p < 0.001). By univariate analysis, we found 17 proteins statistically different after 5% FDR correction (q-value < 0.05). Pathway enrichment analysis revealed 5 significantly enriched pathways whereby the activation of the complement and coagulation cascades was on top (p = 3.17e−07). To validate these results, we assessed the deposits of C5b-9 complement complex and on endothelial cells that were exposed to activated plasma from an independent set of 4 cases of early-onset severe preeclampsia and 4 uncomplicated pregnancies. C5b-9 and Von Willbrand factor deposits were significantly higher in early-onset severe preeclampsia. Future studies are warranted to investigate potential therapeutic targets for early-onset severe preeclampsia within the complement and coagulation pathway.

Purpose: To identify obstetric risk factors of delivering a neonate with poor neonatal adaptation at birth.Material and methods: Nested case-control study. Poor neonatal adaptation was defined for presence of at least: umbilical cord artery pH

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

STUDY QUESTION Do fetuses from frozen embryo transfer (FET) present signs of cardiac remodeling and suboptimal function similar to those observed in fetuses from fresh embryo transfer (ET)? SUMMARY ANSWER Fetuses from both fresh ET and FET present signs of fetal cardiac remodeling and suboptimal function, with more pronounced changes after fresh ET as compared to FET. WHAT IS KNOWN ALREADY Our group and others have previously demonstrated that fetuses and children conceived by ARTs present cardiac remodeling and suboptimal function. These fetuses show dilated atria, more globular and thicker ventricles, reduced longitudinal motion, and impaired relaxation. Cardiac changes were already present in utero and persisted after birth. Most of the ART fetuses included in previous publications were from fresh ET. However, singletons from FET have different perinatal outcomes compared to those from fresh ET. There are no previous studies comparing cardiac morphology and function between fetuses following fresh and FET. STUDY DESIGN, SIZE, DURATION This is a prospective cohort study of 300 singleton pregnancies recruited from 2017 to 2020, including 100 spontaneously conceived (SC) pregnancies, 100 fetuses conceived by IVF with FET, and 100 fetuses conceived by IVF with fresh ET. Fetal structural and functional echocardiography was performed in all pregnancies. PARTICIPANTS/MATERIALS, SETTING, METHODS Pregnancies conceived by IVF were recruited from a single assisted reproduction center, ensuring homogeneity in IVF stimulation protocols, endometrial preparation for FET, laboratory procedures, and embryo culture conditions. SC pregnancies from fertile couples were selected from the general population and matched to IVF pregnancies by maternal age. Epidemiological and perinatal outcomes were collected in all cases. Fetal echocardiography was performed at 28–33 weeks of pregnancy to assess cardiac structure and function in all pregnancies. All echocardiographic comparisons were adjusted by maternal age, nulliparity, birthweight centile, preeclampsia, and prematurity. MAIN RESULTS AND THE ROLE OF CHANCE Parental age, ethnicity, body mass index and smoking were similar among the study groups. Median gestational age at echocardiography and estimated fetal weight were similar in all study groups. Both fresh ET and FET groups showed similar fetal echocardiographic changes, with more pronounced features in the fresh ET as compared to FET pregnancies. Fetuses conceived by IVF showed larger atria (right atria-to-heart ratio: fresh ET mean 18.1% (SD 3.2) vs FET 18.0% (3.9) vs SC 17.3% (3.2); linear tendency P-value LIMITATIONS, REASONS FOR CAUTION The cardiac changes reported here are subclinical, with most cardiovascular indexes lying within normal ranges. Although echocardiographic changes are recognized as potential cardiovascular risk factors, their association with the long-term cardiovascular disease remains to be proven. The observed milder fetal cardiac features in FET fetuses cannot condition the choice of this technique and must be considered together with the global perinatal results related to these gestations. WIDER IMPLICATIONS OF THE FINDINGS The identification of cardiac remodeling in fetuses conceived by IVF with fresh ET and FET represents an opportunity for early detection. Future studies are warranted to study the potential long-term consequences of these findings. STUDY FUNDING/COMPETING INTEREST(S) This project has been partially funded with support from the Erasmus + Programme of the European Union (Framework Agreement number: 2013-0040). This publication reflects the views only of the author, and the Commission cannot be held responsible for any use, which may be made of the information contained therein. Additionally, the research leading to these results has received funding from ‘la Caixa’ Foundation under grant agreement LCF/PR/GN18/10310003, the Instituto de Salud Carlos III (PI15/00130, PI17/00675, PI18/00073) integrated into the Plan Nacional de I + D+I and cofinanced by ISCIII-Subdirección General de Evaluación and Fondo Europeo de Desarrollo Regional (FEDER) ‘Una manera de hacer Europa’, Cerebra Foundation for the Brain Injured Child (Carmarthen, Wales, UK) and AGAUR 2017 SGR grant n° 1531. The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER N/A

Objectives This study examined family dynamics as a moderator of the association between discrimination and both depression and life satisfaction for Latino youth. Specifically, we hypothesized that discrimination would have a negative impact on depression and life satisfaction. We also hypothesized that negative family dynamics would compound the negative impact of discrimination, whereas positive family dynamics would buffer against the impact of discrimination on depression and life satisfaction. Method Participants were 229 Latino youth (Mage = 22.40, SD = 2.46, % female = 81.7) from a diverse region who completed measures of perceived discrimination, depressive symptoms, life satisfaction, and family relationship dynamics. Regression models were used to test both direct associations and moderation (i.e., interaction effects) between these variables. Results Findings indicated that negative aspects of family dynamics marginally exacerbated the link between discrimination and depression and life satisfaction, and were also directly associated with these outcomes. Family positivity significantly moderated the association between discrimination and both depression and life satisfaction. However, positive aspects of family dynamics were only associated with more positive outcomes when discrimination was minimal to absent. Conclusions Family dynamics moderated the association between discrimination and both depression and life satisfaction in Latino youth. However, family dynamics did not appear sufficient to buffer against the negative impact of discrimination, suggesting that even positive and cohesive families cannot buffer youth from discrimination. Marginal findings suggest that negative family dynamics compound the negative impact of discrimination. Implications for improving the mental health of Latino youth through targeting both discrimination and family dynamics are discussed. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

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

Detecting and quantifying the possible association between tegmen tympani (TT) status and superior semicircular canal (SSC) pattern.Observational study.Study conducted in three tertiary Spanish hospitals.Nonselected consecutive patients of all ages (607 temporal bones).Thin-section multidetector row computed axial tomography (CAT scan) of the temporal bones.Thickness of SSC bone coverture adjacent to the middle fossa, and TT status as a dichotomous variable: dehiscence (TTD) or integrity (TTI).The observed SSC patterns were dehiscence (3.79%), papyraceous or thin (11.20%), normal (76.77%), thick (4.94%), and pneumatized (3.29%). The observed TT statuses were TTD (10.87%) and TTI (89.13%). TTD was associated with SSCD and papyraceous patterns, and TTI percentages were higher in normal and thick patterns (χ2 = 11.102; p = 0.001). The TTD probability was estimated as a function of SSC pattern and age by a multivariate binary logistics regression model (χ2 = 45.939; p 0.001).SSC pattern was significantly associated with TT status. Age influenced this association. The risk for TTD increased by 4.1% per each year of increasing age, did not differ significantly for normal and thick patterns, and increased 12 times and 20 times for papyraceous and SSCD patterns, respectively.

OBJECTIVES: To describe placental histopathological findings in a large cohort of pregnancies complicated by pre-eclampsia (PE) and/or small-for-gestational age (SGA), and to investigate their association with fetoplacental Doppler parameters. METHODS: This was a prospective observational study of normotensive pregnancies with SGA (defined as birth weight < 10(th) centile) (n = 184), PE pregnancies with a normally grown fetus (n = 102), pregnancies with both PE and SGA (n = 120) and uncomplicated pregnancies (n = 202). Uterine (UtA), umbilical (UA) and fetal middle cerebral (MCA) artery pulsatility indices (PI) were assessed. The cerebroplacental ratio (CPR) was calculated by dividing MCA-PI by UA-PI. Doppler parameters were considered abnormal when UtA-PI or UA-PI was > 95(th) centile or MCA-PI or CPR was < 5(th) centile. Placental lesions were categorized as vascular (maternal or fetal side), immunoinflammatory or other, according to the 2014 Amsterdam Placental Workshop Group Consensus Statement. Comparison between the study groups was performed using univariate and multiple regression analysis, and logistic regression was used to determine the relationship between abnormal Doppler parameters and placental lesions. RESULTS: Maternal-side vascular lesions were significantly more common in PE pregnancies with SGA than in the other groups (PE + SGA, 73% vs PE, 46% vs SGA, 38% vs controls, 31%; P = 0.01) and included mainly two types of lesion: developmental (PE + SGA, 13% vs PE, 5% vs SGA, 3% vs controls, 1.5%; P < 0.001) and malperfusion (PE + SGA, 70% vs PE, 39% vs SGA, 32% vs controls, 25%; P = 0.001). In contrast, the incidence of fetal-side developmental lesions was significantly higher in normotensive SGA pregnancies than in controls and PE pregnancies (PE + SGA, 0% vs PE, 3% vs SGA, 8% vs controls, 2%; P = 0.001). All cases displayed a lower prevalence of infectious lesions than did controls, with the highest prevalence of immune lesions observed in pregnancies with both PE and SGA (PE + SGA, 18% vs PE, 8% vs SGA, 10% vs controls, 9%; P = 0.001). All fetoplacental Doppler parameters evaluated were associated with maternal-side vascular lesions, mainly malperfusion (mean UtA-PI: odds ratio (OR), 2.45 (95% CI, 1.51-3.97); UA-PI: OR, 2.05 (95% CI, 1.02-4.47); MCA-PI: OR, 2.75 (95% CI, 1.40-5.42); CPR: OR, 1.75 (95% CI, 1.04-2.95)). This association was evident mainly in the normotensive SGA group, being non-significant in controls or PE pregnancies without SGA. No significant associations were observed between fetoplacental Doppler parameters and other placental lesions in any of the study groups. CONCLUSIONS: PE and SGA are associated with different patterns of placental histopathological lesions in accordance with the clinical manifestation of the placental disorder (maternal vs fetal). Fetoplacental Doppler findings show an association with placental malperfusion lesions on the maternal side, supporting the use of abnormal Doppler as a surrogate for placental insufficiency. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Background Evaluation of the efficacy and safety of a mandibular advancement device (MAD) (KlearwayTM) in the treatment of mild-to-moderate obstructive sleep apnea and chronic roncopathy. Material and Methods A randomized, placebo-controlled, double blinded, and crossover clinical trial was conducted. Placebo device (PD) defined as a splint in the centric occlusion that did not induce a mandibular advancement served as a control. The mandible was advanced to the maximum tolerable distance or to a minimum of 65% of the maximum protrusion. After each sequence of treatment, patients were assessed by questionnaires, conventional polysomnography, and objective measurement of snoring at the patient’s own home. Results Forty two patients participated in the study and 38 completed the study. Patients mean age was 46 ±9 years and the 79% were males. The mean mandibular advancement was 8.6 ±2.8 mm. Patients used the MAD and the PD for 6.4 +2.4 hours and 6.2 +2.0 hours, respectively. Secondary effects (mostly mild) occurred in the 85.7% and the 86.8% of the users of MAD and PD, respectively. The MAD induced a decrease in the apnea-hypopnea index (AHI) from 15.3 +10.2 to 11.9 +15.5. The 50% reduction in the AHI was achieved in the 46.2% and the 18.4% of the patients treated with MAD and PD, respectively. The use of the MAD induced a reduction in the AHI by 3.4 +15.9 while the PD induced an increase by 10.6 +26.1. The subjective evaluation of the roncopathy indicated an improvement by the MAD and an increase in the perceptive quality of sleep. However, the objective evaluation of the roncopathy did not show significant improvements. Conclusions The use of MAD is efficient to reduce the AHI and improve subjectively the roncopathy. MAD could be considered in the treatment of mild-to-moderate OSA and chronic roncopathy. Key words:Obstructive sleep apnea (OSA), mandibular advance device, treatment, efficacy, clinical assay.

Accuracy of dietary assessment instruments such as food frequency questionnaire (FFQ) is crucial in the evaluation of diet–disease relationships. Test–retest reliability and concurrent and construct validity of a FFQ were evaluated in 150 pregnant women at high risk to develop fetal growth restriction randomly selected from those included in the improving mothers for better prenatal care trial Barcelona (IMPACT BCN). The FFQ and dietary records were performed at baseline and 34–36 weeks of gestation. Test–retest reliability of the FFQ for 12 food groups and 17 nutrients was moderate (ICC = 0.55) and good (ICC = 0.60), respectively. Concurrent validity between food, nutrients and a composite Mediterranean diet score (MedDiet score) and food records was fair for foods and nutrients (ρ average = 0.38 and 0.32, respectively) and moderate (r = 0.46) for the MedDiet score. Validation with biological markers ranged from poor (r = 0.07) for olives to moderate (r = 0.41) for nuts. A fair concordance between methods were found for nutrients (weighted κ = 0.22) and foods (weighted κ = 0.27). The FFQ-derived MedDiet score correlated in anticipated directions with intakes of nutrients and foods derived by food records. The FFQ showed a moderate test–retest reliability and reasonable validity to rank women according to their food and nutrient consumption and adherence to the Mediterranean diet.

Objectives Dehiscence of the superior semicircular canal (SSC) has been associated with alteration of the temporomandibular joint, although data explaining this association are lacking. The present study examined the correlations between the presence of dehiscences and thickness of the bone covering the SSC and the roof of the glenoid fossa (RGF). Study Design Computed tomography was used in a cross-sectional analysis of the presence of dehiscences and thickness of the bone overlying the SCC and RGF in 156 temporal bones of 78 patients. The correlations of the presence of dehiscences in the SSC and ipsilateral RGF and the thickness of bone covering the SSC and RGF were analyzed by using the χ2 or Fisher's exact test. The relationship between the thickness of the bone overlying the SCC and RGF was analyzed by using the Spearman correlation coefficient and the Kruskal-Wallis test. The relationship between the thickness of the RGF and the covering of the SCC and patient age and gender was analyzed with the general linear model. Results Significant correlations were found between the presence of dehiscences and thickness of the bone overlying the SSC and RGF (P Conclusions There is a morphologic relationship between the structure of the SSC and RGF.

Objective: The aim of this study is to determine whether sex and age influence posterior semicircular canal (PSC) thickness. Methods: This observational study was conducted in 3 tertiary hospitals. The minimal distance between the PSC and the posterior cranial fossa (PSC thickness) was estimated by thin-section multidetector row computed axial tomography (CAT) scan of the temporal bones. Nonselected consecutive patients of all ages (607 temporal bones) were considered. Results: A significant effect was only detected for sex (F = 5.418, p = 0.020); PSC thickness showed a higher mean value in women (mean difference ± SE: 0.224 ± 0.096 mm). A significant and negative r value was detected for males aged >45 years (-0.173, p = 0.026); in that group of patients, PSC thickness decreased as age increased (0.018 ± 0.008 mm/year). For females aged ≤45 years, a significant and positive r value was found (0.198, p = 0.022); in that group, PSC thickness increased as age increased (0.020 ± 0.008 mm/year). Conclusions: PSC thickness did not significantly evolve with age in young males (≤45 years) but it decreased from age 45 years onwards. On the other hand, PCS thickness increased with age in women until the age of 45 years and it did not significantly change in older females.

Preeclampsia and fetal growth restriction share some pathophysiologic features and are both associated with placental insufficiency. Fetal cardiac remodeling has been described extensively in fetal growth restriction, whereas little is known about preeclampsia with a normally grown fetus.To describe fetal cardiac structure and function in pregnancies complicated by preeclampsia and/or fetal growth restriction as compared with uncomplicated pregnancies.This was a prospective, observational study including pregnancies complicated by normotensive fetal growth restriction (n=36), preeclampsia with a normally grown fetus (n=35), preeclampsia with fetal growth restriction (preeclampsia with a normally grown fetus-fetal growth restriction, n=42), and 111 uncomplicated pregnancies matched by gestational age at ultrasound. Fetal echocardiography was performed at diagnosis for cases and recruitment for uncomplicated pregnancies. Cord blood concentrations of B-type natriuretic peptide and troponin I were measured at delivery. Univariate and multiple regression analysis were conducted.Pregnancies complicated by preeclampsia and/or fetal growth restriction showed similar patterns of fetal cardiac remodeling with larger hearts (cardiothoracic ratio, median [interquartile range]: uncomplicated pregnancies 0.27 [0.23-0.29], fetal growth restriction 0.31 [0.26-0.34], preeclampsia with a normally grown fetus 0.31 [0.29-0.33), and preeclampsia with fetal growth restriction 0.28 [0.26-0.33]; P.001) and more spherical right ventricles (right ventricular sphericity index: uncomplicated pregnancies 1.42 [1.25-1.72], fetal growth restriction 1.29 [1.22-1.72], preeclampsia with a normally grown fetus 1.30 [1.33-1.51], and preeclampsia with fetal growth restriction 1.35 [1.27-1.46]; P=.04) and hypertrophic ventricles (relative wall thickness: uncomplicated pregnancies 0.55 [0.48-0.61], fetal growth restriction 0.67 [0.58-0.8], preeclampsia with a normally grown fetus 0.68 [0.61-0.76], and preeclampsia with fetal growth restriction 0.66 [0.58-0.77]; P.001). Signs of myocardial dysfunction also were observed, with increased myocardial performance index (uncomplicated pregnancies 0.78 z scores [0.32-1.41], fetal growth restriction 1.48 [0.97-2.08], preeclampsia with a normally grown fetus 1.15 [0.75-2.17], and preeclampsia with fetal growth restriction 0.45 [0.54-1.94]; P.001) and greater cord blood B-type natriuretic peptide (uncomplicated pregnancies 14.2 [8.4-30.9] pg/mL, fetal growth restriction 20.8 [13.1-33.5] pg/mL, preeclampsia with a normally grown fetus 31.8 [16.4-45.8] pg/mL and preeclampsia with fetal growth restriction 37.9 [15.7-105.4] pg/mL; P.001) and troponin I as compared with uncomplicated pregnancies.Fetuses of preeclamptic mothers, independently of their growth patterns, presented cardiovascular remodeling and dysfunction in a similar fashion to what has been previously described for fetal growth restriction. Future research is warranted to better elucidate the mechanism(s) underlying fetal cardiac adaptation in these conditions.

Fetal growth may be impaired by poor placental function or maternal conditions, each of which can influence the transfer of nutrients and oxygen from the mother to the developing fetus. Large-scale studies of metabolites (metabolomics) are key to understand cellular metabolism and pathophysiology of human conditions. Herein, maternal and cord blood plasma samples were used for NMR-based metabolic fingerprinting and profiling, including analysis of the enrichment of circulating lipid classes and subclasses, as well as the number of sub-fraction particles and their size. Changes in phosphatidylcholines and glycoproteins were prominent in growth-restricted fetuses indicating significant alterations in their abundance and biophysical properties. Lipoprotein profiles showed significantly lower plasma concentrations of cholesterol-intermediate density lipoprotein (IDL), triglycerides-IDL and high-density lipoprotein (HDL) in mothers of growth-restricted fetuses compared to controls (p

OBJECTIVE: To perform a comprehensive assessment of the placental aging process in small term fetuses classified as being small-for-gestational age (SGA) or having fetal growth restriction (FGR) through analysis of senescence and apoptosis markers. METHODS: This was a prospective nested case-control study of singleton pregnancies delivered at term, including 21 control pregnancies with normally grown fetuses and 36 with a small fetus classified as SGA (birth weight between the 3(rd) and 9(th) percentiles and normal fetoplacental Doppler; n = 18) or FGR (birth weight < 3(rd) percentile and/or abnormal cerebroplacental ratio and/or uterine artery Doppler; n = 18). Telomerase activity, telomere length (quantified by comparing the amount of amplification product for the telomere sequence (T) to that of a single copy of the gene 36B4 (S)) and RNA expression of senescence (Sirtuins 1, 3 and 6) and apoptosis (p53, p21, BAX and Caspases 3 and 9) markers (analyzed using the 2(- Ct) method) were determined in placental samples collected at birth and compared between the three groups. RESULTS: Compared to pregnancies with a normally grown fetus, both SGA and FGR pregnancies presented signs of accelerated placental aging, including lower telomerase activity (mean ± SD, 12.8 ± 6.6% in controls vs 7.98 ± 4.2% in SGA vs 7.79 ± 4.6% in FGR; P = 0.008), shorter telomeres (mean ± SD T/S ratio, 1.20 ± 0.6 in controls vs 1.08 ± 0.9 in SGA vs 0.66 ± 0.5 in FGR; P = 0.047) and reduced Sirtuin-1 RNA expression (mean ± SD 2(- Ct) , 1.55 ± 0.8 in controls vs 0.91 ± 0.8 in SGA vs 0.63 ± 0.5 in FGR; P = 0.001) together with increased p53 RNA expression (median (interquartile range) 2(- Ct) , 1.07 (0.3-3.3) in controls vs 5.39 (0.6-15) in SGA vs 3.75 (0.9-7.8) in FGR; P = 0.040). FGR cases presented signs of apoptosis, with increased Caspase-3 RNA levels (median (interquartile range) 2(- Ct) , 0.94 (0.7-1.7) in controls vs 3.98 (0.9-31) in FGR; P = 0.031) and Caspase-9 RNA levels (median (interquartile range) 2(- Ct) , 1.21 (0.6-4.0) in controls vs 3.87 (1.5-9.0) in FGR; P = 0.037) compared with controls. In addition, Sirtuin-1 RNA expression, telomerase activity, telomere length and Caspase-3 activity showed significant linear trends across groups as severity of the condition increased. CONCLUSIONS: Accelerated placental aging was observed in both clinical forms of late-onset fetal smallness (SGA and FGR), supporting a common pathophysiology and challenging the concept of SGA fetuses being constitutionally small. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Background Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage ≥3 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage ≥3 CKD in a large cohort of patients affected by T1DM. Methods A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage ≥3 CKD (eGFR 30% from baseline was evaluated. Results The mean estimated GFR was 98 ± 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions Albuminuria and eGFR reduction represent independent risk factors for incident stage ≥3 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening. Electronic supplementary material The online version of this article (10.1186/s12882-018-1136-6) contains supplementary material, which is available to authorized users.

Objective To develop an integrated model with the best performing criteria for predicting adverse outcome in small-for-gestational-age (SGA) pregnancies. Methods A cohort of 509 pregnancies with a suspected SGA fetus, eligible for trial of labor, was recruited prospectively and data on perinatal outcome were recorded. A predictive model for emergency Cesarean delivery because of non-reassuring fetal status or neonatal acidosis was constructed using a decision tree analysis algorithm, with predictors: maternal age, body mass index, smoking, nulliparity, gestational age at delivery, onset of labor (induced vs spontaneous), estimated fetal weight (EFW), umbilical artery pulsatility index (PI), mean uterine artery (UtA) PI, fetal middle cerebral artery PI and cerebroplacental ratio (CPR). Results An adverse outcome occurred in 134 (26.3%) cases. The best performing predictors for defining a high risk for adverse outcome in SGA fetuses was the presence of a CPR 95th centile or an EFW

Objective: To explore the value of circulating luteinizing human chorionic gonadotropin receptor (LHCGR) forms for the prediction of preeclampsia (PE) in the first trimester of pregnancy. Methods: Case-control study, based on a cohort of 5,759 pregnancies, including 20 early PE, 20 late PE, and 300 controls. We recorded/measured maternal characteristics, mean arterial pressure (MAP), uterine artery (UtA) Doppler, placental growth factor (PlGF), soluble Fms-like tyrosine kinase-1 (sFtl-1), and LHCGR forms (hCG-LHCGR and soluble LHCGR), and their independent predictive values were analyzed by logistic regression. Results: For early PE, the model included black ethnicity, chronic hypertension, previous PE, MAP, UtA Doppler, PlGF, sFlt-1, and LHCGR forms, achieving detection rates (DR) of 83% at 10% of false-positive rates (FPR) [AUC: 0.961 (95% CI: 0.921-1)]. For late PE, the model included body mass index, previous PE, UtA Doppler, PlGF, sFlt-1, and LHCGR forms, with DR of 75% at 10% of FPR [AUC: 0.923 (95% CI: 0.871-0.976)]. In both early and late PE, LHCGR forms improved DR by 6-15%. Conclusions: LHCGR forms improved the prediction for early and late PE. These results should be confirmed in larger prospective studies.

To study the radiological patterns of the bony roof of the superior semicircular canal with a view for obtaining readily applicable conclusions.84 patients (163 petrous bones) have been studied by Multi-slice Helical Computed tomography (Philips Brilliance 6). We have determined the distribution of the different types of bone cover of the superior semicircular canal, taking some previously notified, standardised measurements of normality as reference.During the analysis of the roof of the superior semicircular canal, we have distinguished five different types, depending on their thickness and tomodensitometric aspect. Normal pattern in 121 cases (74.2 %), with a thickness of between 0.6 and 1.7 mm, papyraceous pattern or fine thickness ≤0.5 mm that appears in 23 of our cases (14.1 %), thick pattern ≥1.8 mm that we have observed in 11 cases (6.7 %), and pneumatised pattern in 5 cases (3.1 %), which is characterised by having supralabyerinthine cells. Finally, a dehiscent pattern was observed in three cases (1.8 %).We describe five patterns of superior semicircular canal roofs: normal, thick, papyraceous, pneumatised and dehiscent. The papyraceous type and the dehiscent type would be subject to producing pathology, and in some cases the latter could be a consequence of the former.

Our aim was to characterize and compare eating patterns of university students in Chile, by sex and body weight, body mass index, and nutritional status.This was a cross-sectional study. University students (n = 1454) of Chile were evaluated. A self-assessment survey was used to evaluate healthy eating habits using a questionnaire with values between 1 (do not consume) and 5 (consume) for a total of 9 to 45 points (higher values represent better eating habits). Unhealthy habits were assessed with six questions, including consumption of sugary soft drinks, alcohol, fried foods, fast food, and snacks and adding salt to foods without tasting first.Obese students had a lower consumption of healthy foods (P 0.05) compared with normal weight participants. Underweight male participants had higher unhealthy food consumption (P 0.05) and obese women had the lowest score (P 0.05). Protective factors for being overweight/obese were included (odds ratio [OR] = 0.5; 95% confidence interval [CI] 0.3-0.8), consumption of ≥2 servings of vegetables (OR = 0.5; 95% CI 0.4-0.7). Risk factors included consumption (more than 1 cup a day) of sugary soft drinks (OR = 1.5; 95% CI 1.0-2.1) and male sex (OR = 1.8; 95% CI 1.3-2.4).The consumption of vegetables and belonging to an undergraduate program in health sciences at a university contributed to protection against for obesity. On the other hand, male sex and consumption of sugary drinks were found to be risk factors for obesity.

OBJECTIVE: To assess the relationship between longitudinal changes in placental Doppler indices and maternal circulating angiogenic factors in the first half of pregnancy and delivery of a small-for-gestational-age (SGA) neonate, and ascertain whether longitudinal evaluation of these variables improves the prediction achieved by second-trimester cross-sectional evaluation. METHODS: From a prospective cohort of unselected singleton pregnancies undergoing first-trimester screening for aneuploidy, 138 were included in this study. Of these, 46 were complicated by SGA (delivering after 34 weeks' gestation with a birth weight < 10(th) centile) and 92 were appropriate-for-gestational-age (AGA) pregnancies, which were included as controls (ratio 1:2). First-to-second trimester longitudinal changes in uterine artery (UtA) Doppler indices and maternal circulating levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were analyzed. RESULTS: Compared with the AGA group, SGA pregnancies had significantly higher UtA impedance in the first (Z-score: 0.46 vs -0.57; P < 0.001) and second (Z-score: 1.71 vs -0.75; P < 0.001) trimesters. Likewise, the sFlt-1/PlGF ratio was significantly higher in SGA than in AGA pregnancies in the first (98.0 vs 67.9; P = 0.01) and early second (22.4 vs 8.8; P < 0.001) trimesters. The predictive performance of the longitudinal changes in UtA Doppler indices for SGA was significantly lower than that of second-trimester cross-sectional values (area under receiver-operating characteristics curve (AUC), 60.8% vs 84.3%; P = 0.0035). The detection rate of SGA, at a 10% false-positive rate (FPR), was 17.7% by longitudinal changes in UtA Doppler and 56.2% by second-trimester cross-sectional UtA Doppler values. Similarly, the predictive performance of the longitudinal changes in PlGF was significantly lower than that of early second-trimester cross-sectional values (AUC, 71.4% vs 76.5%; P = 0.008). The detection rate of SGA at a 10% FPR was 40.6% when screening by longitudinal changes in PlGF and 52.1% when screening by early second-trimester cross-sectional values. CONCLUSIONS: First- and second-trimester UtA Doppler velocimetry and maternal circulating angiogenic markers have clinical utility as a cross-sectional assessment for the identification of pregnancies at high risk of delivering a SGA neonate, however, they do not improve prediction when their longitudinal changes are used. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.