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

Neonatal Neurobehavior and Diffusion MRI Changes in Brain Reorganization Due to Intrauterine Growth Restriction in a Rabbit Model

Background: Intrauterine growth restriction (IUGR) affects 5–10 % of all newborns and is associated with a high risk of abnormal neurodevelopment. The timing and patterns of brain reorganization underlying IUGR are poorly documented. We developed a rabbit model of IUGR allowing neonatal neurobehavioral assessment and high resolution brain diffusion magnetic resonance imaging (MRI). The aim of the study was to describe the pattern and functional correlates of fetal brain reorganization induced by IUGR. Methodology/Principal Findings: IUGR was induced in 10 New Zealand fetal rabbits by ligation of 40–50 % of uteroplacental vessels in one horn at 25 days of gestation. Ten contralateral horn fetuses were used as controls. Cesarean section was performed at 30 days (term 31 days). At postnatal day +1, neonates were assessed by validated neurobehavioral tests including evaluation of tone, spontaneous locomotion, reflex motor activity, motor responses to olfactory stimuli, and coordination of suck and swallow. Subsequently, brains were collected and fixed and MRI was performed using a high resolution acquisition scheme. Global and regional (manual delineation and voxel based analysis) diffusion tensor imaging parameters were analyzed. IUGR was associated with significantly poorer neurobehavioral performance in most domains. Voxel based analysis revealed fractional anisotropy (FA) differences in multiple brain regions of gray and white matter, including frontal, insular, occipital and temporal cortex, hippocampus, putamen, thalamus, claustrum, medial septa

Pulmonary hypertension in congenital diaphragmatic hernia: Antenatal prediction and impact on neonatal mortality

Objective: To determine the prevalence of pulmonary hypertension (PAH) in left-sided congenital diaphragmatic hernia (CDH); how we could predict it; and how PAH contributed to the model for mortality prediction. Study Design: Retrospective analysis in three European centers. The primary outcome was the presence of PAH on postnatal day (d) 1, 7, and at discharge. Studied predictors of PAH were: observed/expected-lung/head-ratio (o/e LHR), liver-herniation, fetoscopic endoluminal tracheal occlusion (FETO), and gestational age (GA) at delivery. The combined effect of pre- and postnatal variables on mortality was modeled by Cox regression. Results: Of the 197 neonates, 56 (28.4%) died. At d1, 67.5% (133/197) had PAH and 61.9% (101/163) by d7. Overall, 6.4% (9/141) had PAH at discharge. At d1, o/e LHR (odds ratio (OR) 0.96) and FETO (OR 2.99) independently correlated to PAH (areas under the curve [AUC]: 0.74). At d7, PAH significantly correlated only with the use of FETO (OR 3.9; AUC: 0.65). None were significant for PAH at discharge. Combining the occurrence of PAH with antenatal biomarkers improved mortality prediction (p = 0.02), in a model including o/e LHR (HR: 0.94), FETO (HR: 0.35), liver herniation (HR: 16.78), and PAH (HR: 15.95). Conclusions: Antenatal prediction of PAH was only moderate. The postnatal occurrence of PAH further increases the risk of death. Whereas this may be used to counsel parents in the postnatal period, our study demonstrates there is a need to find more accurate antenatal predictors for PAH

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

We aimed to analyze the nasopharyngeal microbiota profles 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 frst SARS-CoV-2 wave in Spain (March-June 2020 in Barcelona, Spain) in which the status of SARSCoV-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 amplifed using region-specifc primers. The diferential abundance of taxa was tested, and alpha/beta diversity was evaluated. Among 76 women, 38 were classifed 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 difer 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 diferent pattern of microbiota profling 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 signifcant diferences were reported inmild vs. severe cases. This is the frst study on nasopharyngeal microbiota during pregnancy. Pregnant women with SARS-CoV-2 infection had a diferent nasopharyngeal microbiota profle compared to negative cases

Guidelines for the management of spontaneous preterm labor: identification of spontaneous preterm labor, diagnosis of preterm premature rupture of membranes, and preventive tools for preterm birth

Preterm premature rupture of the membranes (preterm PROM) is a common and significant cause of preterm birth and perinatal morbidity and mortality. The obstetric caregiver has the opportunity significantly to alter pregnancy and perinatal outcome for women suffering from this complication. Although management is often predetermined by the presence of clinical infection, vaginal bleeding, labor, or nonreassuring fetal heart-rate pattern on admission, a gestational age-based approach to the management of the stable patient with preterm PROM offers the potential to reduc

Complement and coagulation cascades activation is the main pathophysiological pathway in early-onset severe preeclampsia revealed by maternal proteomics

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

Hypoxia induces dilated cardiomyopathy in the chick embryo: mechanism, intervention, and long-term consequences

Background: Intrauterine growth restriction is associated with an increased future risk for developing cardiovascular diseases. Hypoxia in utero is a common clinical cause of fetal growth restriction. We have previously shown that chronic hypoxia alters cardiovascular development in chick embryos. The aim of this study was to further characterize cardiac disease in hypoxic chick embryos. Methods: Chick embryos were exposed to hypoxia and cardiac structure was examined by histological methods one day prior to hatching (E20) and at adulthood. Cardiac function was assessed in vivo by echocardiography and ex vivo by contractility measurements in isolated heart muscle bundles and isolated cardiomyocytes. Chick embryos were exposed to vascular endothelial growth factor (VEGF) and its scavenger soluble VEGF receptor-1 (sFlt-1) to investigate the potential role of this hypoxia-regulated cytokine. Principal Findings: Growth restricted hypoxic chick embryos showed cardiomyopathy as evidenced by left ventricular (LV) dilatation, reduced ventricular wall mass and increased apoptosis. Hypoxic hearts displayed pump dysfunction with decreased LV ejection fractions, accompanied by signs of diastolic dysfunction. Cardiomyopathy caused by hypoxia persisted into adulthood. Hypoxic embryonic hearts showed increases in VEGF expression. Systemic administration of rhVEGF165 to normoxic chick embryos resulted in LV dilatation and a dose-dependent loss of LV wall mass. Lowering VEGF levels in hypoxic embryonic chick hearts by systemic administration of sFlt-1 yielded an almost complete normalization of the phenotype. Conclusions/Significance: Our data show that hypoxia causes a decreased cardiac performance and cardiomyopathy in chick embryos, involving a significant VEGF-mediated component. This cardiomyopathy persists into adulthood

Viruses

In this multicentre cohort study, we evaluated the risks of maternal ZIKV infections and adverse pregnancy outcomes among exposed travellers compared to women living in areas with ZIKV circulation (residents). The risk of maternal infection was lower among travellers compared to residents: 25.0% (n = 36/144) versus 42.9% (n = 309/721); aRR 0.6; 95% CI 0.5-0.8. Risk factors associated with maternal infection among travellers were travelling during the epidemic period (i.e., June 2015 to December 2016) (aOR 29.4; 95% CI 3.7-228.1), travelling to the Caribbean Islands (aOR 3.2; 95% CI 1.2-8.7) and stay duration \textbackslashtextgreater2 weeks (aOR 8.7; 95% CI 1.1-71.5). Adverse pregnancy outcomes were observed in 8.3% (n = 3/36) of infected travellers and 12.7% (n = 39/309) of infected residents. Overall, the risk of maternal infections is lower among travellers compared to residents and related to the presence of ongoing outbreaks and stay duration, with stays \textbackslashtextless2 weeks associated with minimal risk in the absence of ongoing outbreaks

Limited Relationship between Cervico-Vaginal Fluid Cytokine Profiles and Cervical Shortening in Women at High Risk of Spontaneous Preterm Birth

Objective: to determine the relationship between high vaginal pro-inflammatory cytokines and cervical shortening in women at high risk of spontaneous preterm labor and to assess the influence of cervical cerclage and vaginal progesterone on this relationship. Methods: this prospective longitudinal observational study assessed 112 women with at least one previous preterm delivery between 16 and 34 weeks’ gestation. Transvaginal cervical length was measured and cervico-vaginal fluid sampled every two weeks until 28 weeks. If the cervix shortened (<25 mm) before 24 weeks’ gestation, women (cases) were randomly assigned to cerclage or progesterone and sampled weekly. Cytokine concentrations were measured in a subset of cervico-vaginal fluid samples (n = 477 from 78 women) by 11-plex fluid-phase immunoassay. Results: all 11 inflammatory cytokines investigated were detected in cervico-vaginal fluid from women at high risk of preterm birth, irrespective of later cervical shortening. At less than 24 weeks’ gestation and prior to intervention, women destined to develop a short cervix (n = 36) exhibited higher cervico-vaginal concentrations than controls (n = 42) of granulocyte-macrophage colony-stimulating factor [(GM-CSF) 16.2 fold increase, confidence interval (CI) 1.8–147; p = 0.01] and monocyte chemotactic protein-1 [(MCP-1) 4.8, CI 1.0–23.0; p = 0.05]. Other cytokines were similar between cases and controls. Progesterone treatment did not suppress cytokine concentrations. Interleukin (IL)-6, IL-8, granulocyte colony-stimulating factor (G-CSF), interferon (IFN)-γ and tumour necrosis factor (TNF)-α concentrations were higher following randomization to cerclage versus progesterone (p<0.05). Cerclage, but not progesterone treatment, was followed by a significant increase in cervical length [mean 11.4 mm, CI 5.0–17.7; p<0.001]. Conclusions: although GM-CSF and MCP-1 cervico-vaginal fluid concentrations were raised, the majority of cervico-vaginal cytokines did not increase in association with cervical shortening. Progesterone treatment showed no significant anti-inflammation action on cytokine concentrations. Cerclage insertion was associated with an increase in the majority of inflammatory markers and cervical length