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Objective: This study was undertaken to determine whether laser thermocoagulation for twin-twin transfusion syndrome (TTTS) causes increased cell-free fetal DNA levels in maternal plasma, potentially as a result of placental injury., Study Design: We enrolled 34 patients with twin pregnancies complicated by severe TTTS who underwent fetoscopic selective laser ablation of placental vascular anastomoses. Blood samples were drawn before and sequentially after the procedure. Fetal DNA in maternal plasma was quantified by polymerase chain reaction amplification of a Y-chromosome sequence., Results: Compared with baseline, median elevations of fetal DNA levels were 0.8% at 30 minutes ( P = .32), 15.8% at 60 minutes ( P = .1), 179.5% at 24 hours ( P = .003), and 172.9% at 48 hours ( P = .003). Factors associated with increased fetal DNA levels at 24 hours after procedure included longer operation time, higher number of vessels ablated, and subsequent in utero fetal death ( P = .01, .04, and .04, respectively)., Conclusions: Persistent elevation of fetal DNA levels in maternal plasma after laser ablation suggests that circulating fetal DNA could derive from placental injury. Plasma fetal DNA analysis may be an additional prognostic marker for fetal outcome after laser therapy.

Introduction: A Mediterranean diet has positive effects on the brain in mid-older adults; however, there is scarce information on pregnant individuals. We aimed to evaluate the effect of a structured Mediterranean diet intervention on the cortical structure of the maternal brain during pregnancy. Methods: This study was a secondary analysis of the IMPACT BCN, a randomized clinical trial with 1221 high-risk pregnant women randomly allocated into three groups at 19–23 weeks of gestation: Mediterranean diet intervention, a mindfulness-based stress reduction program, or usual care. Maternal brain magnetic resonance imaging was performed during the third trimester of pregnancy in a random subgroup of participants. For this study, data from the Mediterranean diet and usual groups were analyzed. Maternal dietary intake, adherence to the Mediterranean diet and metabolite biomarkers were evaluated using a food frequency questionnaire, a 17-item dietary screener and plasma/urine samples, respectively. Results: The cluster-wise analysis showed that the Mediterranean diet group participants (n = 34) had significantly larger surface areas in the right precuneus (90%CI: <0.0001–0.0004, p < 0.001) and left superior parietal (90%CI: 0.026–0.033, p = 0.03) lobules compared to the usual care group participants (n = 37). A larger right precuneus area was associated with high improvements in adherence to the Mediterranean diet, a high intake of walnuts and high concentrations of urinary hydroxytyrosol. A larger left superior parietal area was associated with a high intake of walnuts and high concentrations of urinary hydroxytyrosol. Conclusions: The promotion of a Mediterranean diet during pregnancy has a significant effect on maternal brain structure. [ABSTRACT FROM AUTHOR]

Background: Maternal stress, anxiety, well-being, and sleep quality during pregnancy have been described as influencing factors during pregnancy. Aim: We aimed to describe maternal stress, anxiety, well-being, and sleep quality in pregnant women throughout gestation and their related factors. Methods: A prospective study including pregnant women attending BCNatal, in Barcelona, Spain (n = 630). Maternal stress and anxiety were assessed by the Perceived Stress Scale (PSS) and State-Trait Anxiety Inventory (STAI)-validated questionnaires. Maternal well-being was assessed using the World Health Organization Well-Being Index Questionnaire (WHO-5), and sleep quality was assessed using the Pittsburgh Sleep Quality Index Questionnaire (PSQI). All questionnaires were obtained twice during the second and third trimester of pregnancy. A multivariate analysis was conducted to assess factors related to higher maternal stress and anxiety and worse well-being and sleep quality. Results: High levels of maternal stress were reported in 23.1% of participants at the end of pregnancy, with maternal age <40 years (OR 2.02; 95% CI 1.08–3.81, p = 0.03), non-white ethnicity (OR 2.09; 95% CI 1.19–4.02, p = 0.01), and non-university studies (OR 1.86; 95% CI 1.08–3.19, p = 0.02) being the parameters mostly associated with it. A total of 20.7% of women had high levels of anxiety in the third trimester and the presence of psychiatric disorders (OR 3.62; 95% CI 1.34–9.78, p = 0.01) and non-university studies (OR 1.70; 95% CI 1.11–2.59, p = 0.01) provided a significant contribution to high anxiety at multivariate analysis. Poor maternal well-being was observed in 26.5% of women and a significant contribution was provided by the presence of psychiatric disorders (OR 2.96; 95% CI 1.07–8.25, p = 0.04) and non-university studies (OR 1.74; 95% CI 1.10–2.74, p = 0.02). Finally, less sleep quality was observed at the end of pregnancy (p < 0.001), with 81.1% of women reporting poor sleep quality. Conclusion: Maternal stress and anxiety, compromised maternal well-being, and sleep quality disturbances are prevalent throughout pregnancy. Anxiety and compromised sleep quality may increase over gestation. The screening of these conditions at different stages of pregnancy and awareness of the associated risk factors can help to identify women at potential risk. [ABSTRACT FROM AUTHOR]

Stress and anxiety are frequent occurrences among pregnant women. We aimed to evaluate the effects of a Mediterranean diet intervention during pregnancy on maternal stress, well-being, and sleep quality throughout gestation. In a randomized clinical trial, 1221 high-risk pregnant women were randomly allocated into three groups at 19–23 weeks' gestation: a Mediterranean diet intervention, a Mindfulness-Based Stress Reduction program, or usual care. All women who provided self-reported life-style questionnaires to measure their anxiety (State Trait Anxiety Inventory (STAI), Perceived Stress Scale (PSS)), well-being (WHO Five Well Being Index (WHO-5)), and sleep quality (Pittsburgh sleep quality index (PSQI)) at enrollment and at the end of the intervention (34–36 weeks) were included. In a random subgroup of 106 women, the levels of cortisol and related metabolites were also measured. At the end of the intervention (34–36 weeks), participants in the Mediterranean diet group had significantly lower perceived stress and anxiety scores (PSS mean (SE) 15.9 (0.4) vs. 17.0 (0.4), p = 0.035; STAI-anxiety mean (SE) 13.6 (0.4) vs. 15.8 (0.5), p = 0.004) and better sleep quality (PSQI mean 7.0 ± 0.2 SE vs. 7.9 ± 0.2 SE, p = 0.001) compared to usual care. As compared to usual care, women in the Mediterranean diet group also had a more significant increase in their 24 h urinary cortisone/cortisol ratio during gestation (mean 1.7 ± SE 0.1 vs. 1.3 ± SE 0.1, p < 0.001). A Mediterranean diet intervention during pregnancy is associated with a significant reduction in maternal anxiety and stress, and improvements in sleep quality throughout gestation. [ABSTRACT FROM AUTHOR]

The outbreak of a pandemic has negative psychological effects. We aimed to determine the impact of the SARS-CoV-2 pandemic during pregnancy and identify the risk factors for maternal well-being. A multicenter, prospective, population-based study was carried out that included women (n = 1320) who were pregnant during the SARS-CoV-2 pandemic in Barcelona (Spain) compared against a pre-pandemic cohort (n = 345). Maternal well-being was assessed using the validated World Health Organization Well-Being Index Questionnaire (WHO-5 Index). Pregnant women attended during the COVID-19 pandemic showed worst WHO-5 well-being scores (median (IQR) of 56 (36–72) for the pandemic cohort vs. 64 (52–76) for the pre-pandemic cohort p < 0.001), with 42.8% of women presenting a poor well-being score vs. 28% for the pre-pandemic cohort (p < 0.001). Presence of a previous psychiatric disorder (OR 7.1; 95% CI 2.6–19, p < 0.001), being in the third trimester of pregnancy (OR 1.7; 95% CI 1.5–2, p < 0.001), or requiring hospital admission for COVID-19 (OR 4.7; 95% CI 1.4–16.7, p = 0.014), significantly contributed to low maternal well-being during the COVID-19 pandemic (multivariate analysis). Being infected by SARS-CoV-2 was not associated with a lower well-being score. We conclude that, during the COVID-19 pandemic, there were higher rates of poor maternal well-being; the infection of SARS-CoV-2 itself did not worsen maternal well-being, but other factors as psychiatric disorders, being in the third trimester of pregnancy or hospital admission for COVID-19 disease did. [ABSTRACT FROM AUTHOR]

Twin-to-twin transfusion syndrome (TTTS) is characterized by an unbalanced blood transfer through placental abnormal vascular connections. Prenatal ultrasound (US) is the imaging technique to monitor monochorionic pregnancies and diagnose TTTS. Fetoscopic laser photocoagulation is an elective treatment to coagulate placental communications between both twins. To locate the anomalous connections ahead of surgery, preoperative planning is crucial. In this context, we propose a novel multi-task stacked generative adversarial framework to jointly learn synthetic fetal US generation, multi-class segmentation of the placenta, its inner acoustic shadows and peripheral vasculature, and placenta shadowing removal. Specifically, the designed architecture is able to learn anatomical relationships and global US image characteristics. In addition, we also extract for the first time the umbilical cord insertion on the placenta surface from 3D HD-flow US images. The database consisted of 70 US volumes including singleton, mono- and dichorionic twins at 17-37 gestational weeks. Our experiments show that 71.8% of the synthesized US slices were categorized as realistic by clinicians, and that the multi-class segmentation achieved Dice scores of 0.82 ± 0.13, 0.71 ± 0.09, and 0.72 ± 0.09, for placenta, acoustic shadows, and vasculature, respectively. Moreover, fetal surgeons classified 70.2% of our completed placenta shadows as satisfactory texture reconstructions. The umbilical cord was successfully detected on 85.45% of the volumes. The framework developed could be implemented in a TTTS fetal surgery planning software to improve the intrauterine scene understanding and facilitate the location of the optimum fetoscope entry point. [ABSTRACT FROM AUTHOR]

Introduction: Placenta-derived exosomes may represent an additional pathway by which the placenta communicates with the maternal system to induce maternal vascular adaptations to pregnancy and it may be affected during Fetal growth restriction (FGR). The objective of this study was to quantify the concentration of total and placenta-derived exosomes in maternal and fetal circulation in small fetuses classified as FGR or small for gestational age (SGA).Methods: Prospective cohort study in singleton term gestations including 10 normally grown fetuses and 20 small fetuses, sub-classified into SGA and FGR accordingly to birth weight (BW) percentile and fetoplacental Doppler. Exosomes were isolated from maternal and fetal plasma and characterized by morphology, enrichment of exosomal proteins, and size distribution by electron microscopy, western blot, and nanoparticle tracking analysis, respectively. Total and specific placenta-derived exosomes were determined using quantum dots coupled with CD63+ve and placental-type alkaline phosphatase (PLAP)+ve antibodies, respectively.Results: Maternal concentrations of CD63+ve and PLAP+ve exosomes were similar between the groups (all p > 0.05). However, there was a significant positive correlation between the ratio of placental-derived to total exosomes (PLAP+ve ratio) and BW percentile, [rho = 0.77 (95% CI: 0.57 to 0.89); p = 0.0001]. The contribution of placental exosomes to the total exosome concentration in maternal and fetal circulation showed a significant decrease among cases, with lower PLAP+ve ratios in FGR compared to controls and SGA cases.Discussion: Quantification of placental exosomes in maternal plasma reflects fetal growth and it may be a useful indicator of placental function. [ABSTRACT FROM AUTHOR]

Aim: To compare intra-amniotic versus fetal subcutaneous injections for selective fetal labeling in multifetal rat pregnancies.Methods: A total of 14 pregnant rats were randomized to receive intra-amniotic injections of dyes (including Fluorescein, Indigo Carmine, or Evans Blue) or fetal subcutaneous injections (of commercial tattoo ink) both guided by ultrasound at 15-17 days of gestation. Survival, injection, and labeling success rates of both techniques were compared.Results: Survival rates (84.4% for intra-amniotic injections vs. 90.9% for fetal subcutaneous injections) and injection success rates (94% for intra-amniotic injections vs. 100% for fetal subcutaneous injections) were similar among both groups. None of the neonates from the intra-amniotic injections group were labeled at birth, while 93% of the neonates from fetal subcutaneous injections group were tagged, showing a visible spot in the skin at birth.Conclusion: Our results suggest that ultrasound-guided fetal subcutaneous injections might be an adequate strategy for selectively labeling fetuses in multifetal pregnant animals. [ABSTRACT FROM AUTHOR]

Background: HIV infection and HAART trigger genetic and functional mitochondrial alterations leading to cell death and adverse clinical manifestations. Mitochondrial dynamics enable mitochondrial turnover and degradation of damaged mitochondria, which may lead to apoptosis.Objectives: To evaluate markers of mitochondrial dynamics and apoptosis in pregnancies among HIV-infected women on HAART and determine their potential association with obstetric complications.Methods: This controlled, single-site, observational study without intervention included 26 HIV-infected pregnant women on HAART and 18 control pregnancies and their newborns. Maternal PBMCs and neonatal cord blood mononuclear cells (CBMCs) were isolated at the first trimester of gestation and at delivery. The placenta was homogenized at 5% w/v. Mitochondrial dynamics, fusion events [mitofusin 2 (Mfn2)/β-actin] and fission events [dynamin-related protein 1 (Drp1/β-actin)] and apoptosis (caspase 3/β-actin) were assessed by western blot analysis.Results: Obstetric complications were significantly more frequent in pregnancies among HIV-infected women [OR 5.00 (95% CI 1.21-20.70)]. Mfn2/β-actin levels in PBMCs from controls significantly decreased during pregnancy (202.13 ± 57.45%), whereas cases maintained reduced levels from the first trimester of pregnancy and no differences were observed in CBMCs. Mfn2/β-actin and Drp1/β-actin contents significantly decreased in the placenta of cases. Caspase 3/β-actin levels significantly increased during pregnancy in PBMCs of cases (50.00 ± 7.89%), remaining significantly higher than in controls. No significant differences in caspase 3/β-actin content of neonatal CBMCs were observed, but there was a slight increased trend in placenta from cases.Conclusions: HIV- and HAART-mediated mitochondrial damage may be enhanced by decreased mitochondrial dynamics and increased apoptosis in maternal and placental compartments but not in the uninfected fetus. However, direct effects on mitochondrial dynamics and implication of apoptosis were not demonstrated in adverse obstetric outcomes. [ABSTRACT FROM AUTHOR]

Background--Fetal growth restriction (FGR) affects 5% to 10% of newborns and is associated with increased cardiovascular mortality in adulthood. We evaluated whether prenatal cardiovascular changes previously demonstrated in FGR persist into preadolescence. Methods and Results--A cohort study of 58 FGR (defined as birth weight below 10th centile) and 94 normally grown fetuses identified in utero and followed-up into preadolescence (8-12 years of age) by echocardiography and 3-dimensional shape computational analysis. Compared with controls, FGR preadolescents had a different cardiac shape, with more spherical and smaller hearts. Left ventricular ejection fraction was similar among groups, whereas FGR had decreased longitudinal motion (decreased mitral annular systolic peak velocities: control median, 0.11 m/s [interquartile range, 0.09-0.12] versus FGR median 0.09 m/s [interquartile range, 0.09-0.10]; P<0.01) and impaired relaxation (isovolumic relaxation time: control, 0.21 ms [interquartile range, 0.12-0.35] versus FGR, 0.35 ms [interquartile range, 0.20-0.46]; P=0.04). Global longitudinal strain was decreased (control mean, -22.4% [SD, 1.37] versus FGR mean, -21.5% [SD, 1.16]; P<0.001) compensated by an increased circumferential strain and with a higher prevalence of postsystolic shortening in FGR as compared with controls. These differences persisted after adjustment for parental ethnicity and smoking, prenatal glucocorticoid administration, preeclampsia, gestational age at delivery, days in intensive care unit, sex, age, and body surface area at evaluation. Conclusions--This study provides evidence that cardiac remodeling induced by FGR persists until preadolescence with findings similar to those reported in their prenatal life and childhood. The findings support the hypothesis of primary cardiac programming in FGR for explaining the association between low birth weight and cardiovascular risk in adulthood. [ABSTRACT FROM AUTHOR]

To assess the impact of HIV-infection and highly active anti-retroviral treatment in mitochondria and apoptotic activation of caspases during pregnancy and their association with adverse perinatal outcome. Changes of mitochondrial parameters and apoptotic caspase activation in maternal peripheral blood mononuclear cells were compared at first trimester of pregnancy and delivery in 27 HIV-infected and -treated pregnant women versus 24 uninfected pregnant controls. We correlated immunovirological, therapeutic and perinatal outcome with experimental findings: mitochondrial DNA (mt DNA) content, mitochondrial protein synthesis, mitochondrial function and apoptotic caspase activation. The HIV pregnancies showed increased adverse perinatal outcome ( OR: 4.81 [1.14-20.16]; P < 0.05) and decreased mt DNA content (42.66 ± 5.94%, P < 0.01) compared to controls, even higher in naïve participants. This depletion caused a correlated decrease in mitochondrial protein synthesis (12.82 ± 5.73%, P < 0.01) and function (20.50 ± 10.14%, P < 0.001), not observed in controls. Along pregnancy, apoptotic caspase-3 activation increased 63.64 ± 45.45% in controls ( P < 0.001) and 100.00 ± 47.37% in HIV-pregnancies ( P < 0.001), in correlation with longer exposure to nucleoside analogues. HIV-infected women showed increased obstetric problems and declined genetic and functional mitochondrial parameters during pregnancy, especially those firstly exposed to anti-retrovirals. The apoptotic activation of caspases along pregnancy is emphasized in HIV pregnancies promoted by nucleoside analogues. However, we could not demonstrate direct mitochondrial or apoptotic implication in adverse obstetric outcome probably because of the reduced sample size. [ABSTRACT FROM AUTHOR]

Background: We tested the hypothesis whether texture analysis (TA) from MR images could identify patterns associated with an abnormal neurobehavior in small for gestational age (SGA) neonates. Methods: Ultrasound and MRI were performed on 91 SGA fetuses at 37 weeks of GA. Frontal lobe, basal ganglia, mesencephalon and cerebellum were delineated from fetal MRIs. SGA neonates underwent NBAS test and were classified as abnormal if ≥1 area was <5th centile and as normal if all areas were >5th centile. Textural features associated with neurodevelopment were selected and machine learning was used to model a predictive algorithm. Results: Of the 91 SGA neonates, 49 were classified as normal and 42 as abnormal. The accuracies to predict an abnormal neurobehavior based on TA were 95.12% for frontal lobe, 95.56% for basal ganglia, 93.18% for mesencephalon and 83.33% for cerebellum. Conclusions: Fetal brain MRI textural patterns were associated with neonatal neurodevelopment. Brain MRI TA could be a useful tool to predict abnormal neurodevelopment in SGA. [ABSTRACT FROM AUTHOR]

Background: Intrauterine Growth Restriction (IUGR) due to placental insufficiency occurs in 5–10% of pregnancies and is a major risk factor for abnormal neurodevelopment. The perinatal diagnosis of IUGR related abnormal neurodevelopment represents a major challenge in fetal medicine. The development of clinical biomarkers is considered a promising approach, but requires the identification of biochemical/molecular alterations by IUGR in the fetal brain. This targeted metabolomics study in a rabbit IUGR model aimed to obtain mechanistic insight into the effects of IUGR on the fetal brain and identify metabolite candidates for biomarker development. Methodology/Principal Findings: At gestation day 25, IUGR was induced in two New Zealand rabbits by 40–50% uteroplacental vessel ligation in one horn and the contralateral horn was used as control. At day 30, fetuses were delivered by Cesarian section, weighed and brains collected for metabolomics analysis. Results showed that IUGR fetuses had a significantly lower birth and brain weight compared to controls. Metabolomics analysis using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) and database matching identified 78 metabolites. Comparison of metabolite intensities using a t-test demonstrated that 18 metabolites were significantly different between control and IUGR brain tissue, including neurotransmitters/peptides, amino acids, fatty acids, energy metabolism intermediates and oxidative stress metabolites. Principle component and hierarchical cluster analysis showed cluster formations that clearly separated control from IUGR brain tissue samples, revealing the potential to develop predictive biomarkers. Moreover birth weight and metabolite intensity correlations indicated that the extent of alterations was dependent on the severity of IUGR. Conclusions: IUGR leads to metabolic alterations in the fetal rabbit brain, involving neuronal viability, energy metabolism, amino acid levels, fatty acid profiles and oxidative stress mechanisms. Overall findings identified aspargine, ornithine, N-acetylaspartylglutamic acid, N-acetylaspartate and palmitoleic acid as potential metabolite candidates to develop clinical biomarkers for the perinatal diagnosis of IUGR related abnormal neurodevelopment. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to evaluate the feasibility of fetoscopic surgery in complicated monochorionic and dichorionic triplet pregnancies. Study design: This was a case series of fetoscopic surgery in 12 cases of monochorionic (n = 5) or dichorionic (n = 7) triamniotic triplets complicated by severe feto-fetal transfusion (n = 8), twin reversed arterial perfusion sequence (n = 3), or discordant for an anomaly (n = 1). Six underwent cord occlusion, and 6 had laser coagulation of the vascular anastomoses. Results: All procedures were successfully completed, and the outcome was comparable to that reported for similar procedures in twins. Eighty-three percent of fetuses survived, and 13% had long-term problems. Conclusion: Fetoscopic surgery may be considered as a therapeutic option in complicated triplet pregnancies, with results similar to those found in twins. [ABSTRACT FROM AUTHOR]

Evaluates the effectiveness of various plugging techniques in sealing the fetal membrane defect created by fetoscopy in the rabbit at mid-gestation. Fetal survival, amniotic integrity and amniotic fluid presence in study groups; Exposure of the uterus by a midline abdominal incision; Comparison of fetal lung/body weight ratio according to integrity of amnion.

Reports on a study which sought to evaluate the circulating levels of lipid peroxides and vitamin E and the placental levels of of lipid peroxides in pregnant women suffering different forms of hypertension. Details on the design of the study; What methods of research were used in the study; Details on tests conducted during the research; Results of the tests; Conclusion reached at the end of the study.

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 >2 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 <2 weeks associated with minimal risk in the absence of ongoing outbreaks. [ABSTRACT FROM AUTHOR]

Characterization of brain changes produced by intrauterine growth restriction (IUGR) is among the main challenges of modern fetal medicine and pediatrics. This condition affects 5–10% of all pregnancies and is associated with a wide range of neurodevelopmental disorders. Better understanding of the brain reorganization produced by IUGR opens a window of opportunity to find potential imaging biomarkers in order to identify the infants with a high risk of having neurodevelopmental problems and apply therapies to improve their outcomes. Structural brain networks obtained from diffusion magnetic resonance imaging (MRI) is a promising tool to study brain reorganization and to be used as a biomarker of neurodevelopmental alterations. In the present study this technique is applied to a rabbit animal model of IUGR, which presents some advantages including a controlled environment and the possibility to obtain high quality MRI with long acquisition times. Using a Q-Ball diffusion model, and a previously published rabbit brain MRI atlas, structural brain networks of 15 IUGR and 14 control rabbits at 70 days of age (equivalent to pre-adolescence human age) were obtained. The analysis of graph theory features showed a decreased network infrastructure (degree and binary global efficiency) associated with IUGR condition and a set of generalized fractional anisotropy (GFA) weighted measures associated with abnormal neurobehavior. Interestingly, when assessing the brain network organization independently of network infrastructure by means of normalized networks, IUGR showed increased global and local efficiencies. We hypothesize that this effect could reflect a compensatory response to reduced infrastructure in IUGR. These results present new evidence on the long-term persistence of the brain reorganization produced by IUGR that could underlie behavioral and developmental alterations previously described. The described changes in network organization have the potential to be used as biomarkers to monitor brain changes produced by experimental therapies in IUGR animal model. [ABSTRACT FROM AUTHOR]