Restricción de crecimiento intrauterino

ResumenLa restricción del crecimiento intrauterino es una importante causa de morbilidad y mortalidad perinatal, con consecuencias que pueden tener implicancias hasta en la vida adulta. No existen estrategias terapéuticas a la fecha por lo que, su manejo consiste principalmente en su diagnóstico y seguimiento para definir el momento de finalizar el embarazo, equilibrando los riesgos de prematurez con la morbimortalidad esperada para cada condición fetal. En el presente artículo se describen las claves del diagnóstico, clasificación y seguimiento de acuerdo a estándares actuales que permitan el adecuado manejo clínico.SummaryIntrauterine growth restriction is a major cause of perinatal morbidity and mortality with consequences that may have implications even in adulthood. No treatment have currently available, so, management is mainly based in diagnosis and monitoring in order to choose the right time to delivery, balancing the risks of prematurity with the expected morbidity and mortality. A precise diagnosis, classification and fetal surveillance according to current standards is discussed

Heart morphology differences induced by intrauterine growth restriction and premature birth measured on the ECG in pre-adolescents

Pre-adolescents who had suffered from intrauterine growth restriction (IUGR) during their mothers'' pregnancy usually present more spherical hearts (smaller relation between base to apex measure and basal diameter), measured using echocardiograms, which has been associated with long-term cardiac disfunction. The present work aims to analyse these heart morphology changes by means of the surface ECG so as to have an early diagnostic tool of this pathology. The dataset is conformed by 148 pre-adolescents with either preterm or term births, and with or without IUGR. Once QRS and T-wave loops were obtained from the vectorcardiogram, the angles between the dominant vector of the QRS loop and -XY or -YZ planes(FR-XY, FR-YZ) and the difference between FR-XY and the angle between the dominant vector of T-wave loop (FT-XY) and the XY-plane showed different values for pre-adolescents who suffered from premature birth and IUGR than for control subjects (p < 0.05). These characteristics can open the door for a much easier diagnosis and follow-up of candidates for these disfunctions

Feasibility of 4D-Spatio Temporal Image Correlation (STIC) in the Comprehensive Assessment of the Fetal Heart Using FetalHQ®.

Fetal Heart Quantification (FetalHQ®) is a novel speckle tracking software that permits the study of global and regional ventricular shape and function from a 2D four-chamber-view loop. The 4D-Spatio Temporal Image Correlation (STIC) modality enables the offline analysis of optimized and perfectly aligned cardiac planes. We aimed to evaluate the feasibility and reproducibility of 4D-STIC speckle tracking echocardiography (STE) using FetalHQ® and to compare it to 2D STE. We conducted a prospective study including 31 low-risk singleton pregnancies between 20 and 40 weeks of gestation. Four-chamber view volumes and 2D clips were acquired with an apex pointing at 45° and with a frame rate higher than 60 Hz. Morphometric and functional echocardiography was performed by FetalHQ®. Intra- and interobserver reproducibility were evaluated by the intraclass correlation coefficient (ICC). Our results showed excellent reproducibility (ICC > 0.900) for morphometric evaluation (biventricular area, longitudinal and transverse diameters). Reproducibility was also good (ICC > 0.800) for functional evaluation (biventricular strain, Fractional Area Change, left ventricle volumes, ejection fraction and cardiac output). On the contrary, the study of the sphericity index and shortening fraction of the different ventricular segments showed lower reproducibility (ICC < 0.800). To conclude, 4D-STIC is feasible, reproducible and comparable to 2D echocardiography for the assessment of cardiac morphometry and function

SARS-CoV-2 RNA and antibody detection in breast milk from a prospective multicentre study in Spain

This study has been supported by a research grant from Fundacion La Marato-TV3 (MilkCORONA, ref 202106).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.Fundacion La Marato-TV3 20210

Nasopharyngeal microbiota profiling of pregnant women with SARS-CoV-2 infection

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 < 0.001) and evenness (Shannon index < 0.001) at alpha diversity. These changes were also present in women after acute infection, as revealed by negative RT–PCR but positive SARS-CoV-2 antibodies, suggesting a potential association between SARS-CoV-2 infection and long-lasting shift in the nasopharyngeal microbiota. No significant differences were reported in mild vs. severe cases. This is the first study on nasopharyngeal microbiota during pregnancy. Pregnant women with SARS-CoV-2 infection had a different nasopharyngeal microbiota profile compared to negative cases.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.Peer reviewe

Breastfeeding during the COVID-19 pandemic: analysis of the breastmilk antibodies, neutralization capacity and microbiota profile from infected and vaccinated wome

Resumen del póster presentado a las III Jornadas Científicas PTI+ Salud Global, celebradas en el Centro de Ciencias Humanas y Sociales (CCHS), CSIC (Madrid) del 20 al 22 de noviembre de 2023.[Background] Breastmilk is considered the gold standard in infant nutrition and provides bioactive compounds to the neonate, among them antibodies and microbiota. In the context of the COVID- 19 pandemics, there were great concerns about a possible mother-to-infant transfer of SARS-CoV-2, since limited knowledge about the safety of breastfeeding after natural infection or vaccination, as well as the transfer of protective antibodies and their neutralization capacity, was available. Additionally, there are concerns about potential short- and long-term adverse effects of SARS-CoV-2 infection and vaccine-induced changes to the breastmilk microbiome composition, which contributes in shaping the early-life microbiome.[Methods] This study included 60 mothers which had a confirmed SARS-CoV-2 infection and also, 86 mothers vaccinated with mRNA-based (Comirnaty, mRNA-1273) and adenoviral-vectored vaccines (ChAdOx1 nCoV-19) were recruited and breastmilk samples were collected longitudinally from baseline up to 30 days after the second dose at seven or eight time points (depending on vaccine type). In COVID-19 lactating mothers, the presence of SARS-CoV-2 was assessed by RT-qPCR targeting the N1 region of the nucleocapsid gene and the envelope (E) gene. In both studies, the levels of SARS-CoV-2 RBD-specific IgA, IgM and IgG were determined by ELISA. The neutralization capacity was tested using pseudotyped vesicular stomatitis virus carrying either the Wuhan-Hu-1, Delta, or BA.1 Omicron spike proteins. To assess the microbiome composition, DNA from breastmilk samples was extracted and the V3-V4 region of the 16S rRNA gene was sequenced using the MiSeq system of Illumina.[Results] After SARS-CoV-2 infection, no virus-specific RNA was detected in breastmilk samples. Determination of antibody levels in mothers with confirmed SARS-CoV-2 infection showed that 82.9% (58 of 70) of milk samples were positive for at least one of the three tested antibody isotypes. Vaccination elicited also a strong induction of SARS-CoV-2-specific antibodies, which was higher in IgG when compared to COVID-19 convalescent women and was strongly increased after the 2nd dose. mRNA-based vaccines induced higher IgG and IgA levels when compared to the adenovirus- vectored vaccine, and women with previous virus exposure increased their IgG antibodies levels after the first dose to a similar level observed in vaccinated women after the second dose. When assessing the neutralization capacity, natural infection resulted in higher neutralizing titers that correlated positively with levels of SARS-CoV-2-specific immunoglobulin A in breastmilk. Breastmilk samples from COVID-19 convalescent mothers infected during the first wave (Wuhan-Hu-1 strain) neutralized less effectively Omicron BA.1 than the Wuhan-Hu-1 variant. In addition, significant differences in the capacity to produce neutralizing antibodies were observed between both mRNA- based vaccines and the adenovirus-vectored ChAdOx1 COVID-19 vaccine. First results of the analysis of the breastmilk microbiome found no significant differences in the mean diversity of species (alpha-diversity) after natural SARS-CoV-2 infection, whereas some specific bacterial groups were increased (e.g. Enterobacteriaceae).[Conclusions] Overall, our results indicate that breastmilk from naturally infected women or those vaccinated with mRNA-based vaccines contain SARS-CoV-2 neutralizing antibodies that could potentially provide protection to breastfed infants from infection.Peer reviewe

Fetal growth restriction results in remodeled and less efficient hearts in children

BACKGROUND-: Fetal growth restriction (FGR) affects 5% to 10% of newborns and is associated with increased cardiovascular mortality in adulthood. The most commonly accepted hypothesis is that fetal metabolic programming leads secondarily to diseases associated with cardiovascular disease, such as obesity, diabetes mellitus, and hypertension. Our main objective was to evaluate the alternative hypothesis that FGR induces primary cardiac changes that persist into childhood. METHODS AND RESULTS-: Within a cohort of fetuses with growth restriction identified in fetal life and followed up into childhood, we randomly selected 80 subjects with FGR and compared them with 120 normally grown fetuses, matched for gender, birth date, and gestational age at birth. Cardiovascular assessment was performed in childhood (mean age of 5 years). Compared with control subjects, children with FGR had a different cardiac shape, with increased transversal diameters and more globular cardiac ventricles. Although left ejection fraction was similar among the study groups, stroke volume was reduced significantly, which was compensated for by an increased heart rate to maintain output in severe FGR. This was associated with subclinical longitudinal systolic dysfunction (decreased myocardial peak velocities) and diastolic changes (increased E/E′ ratio and E deceleration time). Children with FGR also had higher blood pressure and increased intima-media thickness. For all parameters evaluated, there was a linear increase with the severity of growth restriction. CONCLUSIONS-: These findings suggest that FGR induces primary cardiac and vascular changes that could explain the increased predisposition to cardiovascular disease in adult life. If these results are confirmed, the impact of strategies with beneficial effects on cardiac remodeling should be explored in children with FGR. © 2010 American Heart Association, Inc.This study was supported by grants from the Fondo de Investigación Sanitaria (PI/060347; Spain), Ministerio de Ciencia e Innovación (SAF2009-08815; Spain), Centro para el Desarrollo Técnico Industrial (CENIT 20092012, apoyado por el Ministerio de Ciencia e Innovación, y Fondo de inversión local para el empleo; Spain), Cerebra Foundation for the Brain Injured Child (Carmarthen, Wales, United Kingdom), Thrasher Research Fund (Salt Lake City, Utah), Medical Research Council (GO601295 and MRC G0700288), and British Heart Foundation support (BHF Programme Grant RG/09/001/25940). Dr Crispi (CM07/00076) and Dr Eixarch (CM08/00105) are supported by a grant from the Carlos III Institute of Health (Spain).Peer Reviewe

Main Patterns of Fetal Cardiac Remodeling

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.European Union (EU) 2013-0040 La Caixa Foundation LCF/PR/GN14/10270005 Instituto de Salud Carlos III PI15/00130 PI15/00263 PI17/00675 PI18/00073 Centro de Investigacion Biomedica en Red de Enfermedades Raras ERPR04G719/2016 Cerebra Foundation for the Brain Injured Child (Carmarthen, Wales, UK) AGAUR 2017 SGR grant 153

Restricción de crecimiento intrauterino

La restricción del crecimiento intrauterino es una importante causa de morbilidad y mortalidad perinatal, con consecuencias que pueden tener implicancias hasta en la vida adulta. No existen estrategias terapéuticas a la fecha por lo que, su manejo consiste principalmente en su diagnóstico y seguimiento para definir el momento de finalizar el embarazo, equilibrando los riesgos de prematurez con la morbimortalidad esperada para cada condición fetal. En el presente artículo se describen las claves del diagnóstico, clasificación y seguimiento de acuerdo a estándares actuales que permitan el adecuado manejo clínico