Oscillatory activity in bilateral prefrontal cortices is altered by distractor strength during working memory processing.

Working memory (WM) enables the temporary storage of limited information and is a central component of higher order cognitive function. Irrelevant and/or distracting information can have a negative impact on WM processing and suppressing such incoming stimuli is critical to maintaining adequate performance. However, the neural mechanisms and dynamics underlying such distractor inhibition remain poorly understood. In the current study, we enrolled 46 healthy adults (Mage: 27.92, Nfemale: 28) who completed a Sternberg type WM task with high- and low-distractor conditions during magnetoencephalography (MEG). MEG data were transformed into the time-frequency domain and significant task-related oscillatory responses were imaged to identify the underlying anatomical areas. Whole-brain paired t-tests, with cluster-based permutation testing for multiple comparisons correction, were performed to assess differences between the low- and high-distractor conditions for each oscillatory response. Across conditions, we found strong alpha and beta oscillations (i.e., decreases relative to baseline) and increases in theta power throughout the encoding and maintenance periods. Whole-brain contrasts revealed significantly stronger alpha and beta oscillations in bilateral prefrontal regions during maintenance in high- compared to low-distractor trials, with the stronger beta oscillations being centered on the left dorsolateral prefrontal cortex and right inferior frontal gyrus, while those for alpha being within the right anterior prefrontal cortices and the right middle frontal gyrus. These findings suggest that alpha and beta oscillations in the bilateral prefrontal cortices play a major role in the inhibition of distracting information during WM maintenance. Our results also contribute to prior research on cognitive control and functional inhibition, in which prefrontal regions have been widely implicated.

Extracellular Vesicles heterogeneity through the lens of multiomics.

Extracellular vesicles (EVs) are heterogenous in size, biogenesis, cargo and function. Beside small EVs, aggressive tumor cells release a population of particularly large EVs, namely large oncosomes (LO). This study provides the first resource of label-free quantitative proteomics of LO and small EVs obtained from distinct cancer cell types (prostate, breast, and glioma). This dataset was integrated with a SWATH Proteomic assay on LO, rigorously isolated from the plasma of patients with metastatic prostate cancer (PC). Proteins enriched in LO, which were identified also at the RNA level, and found in plasma LO significantly correlated with PC progression. Single EV RNA-Seq of the PC cell-derived LO confirmed some of the main findings from the bulk RNA-Seq, providing first evidence that single cell technologies can be successfully applied to EVs. This multiomics resource of cancer EVs can be leveraged for developing a multi-analyte approach for liquid biopsy.

Distinct phenotypes induced by acute hypoxia and TGF-ß1 in human adult cardiac fibroblasts.

Myocardial infarction (MI) causes hypoxic injury to downstream myocardial tissue, which initiates a wound healing response that replaces injured myocardial tissue with a scar. Wound healing is a complex process that consists of multiple phases, in which many different stimuli induce cardiac fibroblasts to differentiate into myofibroblasts and deposit new matrix. While this process is necessary to replace necrotic tissue, excessive and unresolved fibrosis is common post-MI and correlated with heart failure. Therefore, defining how cardiac fibroblast phenotypes are distinctly regulated by stimuli that are prevalent in the post-MI microenvironment, such as hypoxia and transforming growth factor-beta (TGF-ß), is essential for understanding and ultimately mitigating pathological fibrosis. In this study, we acutely treated primary human adult cardiac fibroblasts with TGF-ß1 or hypoxia and then characterized their phenotype through immunofluorescence, quantitative RT-PCR, and proteomic analysis. We found that fibroblasts responded to low oxygen with increased localization of hypoxia inducible factor 1 (HIF-1) to the nuclei after 4h, which was followed by increased gene expression of vascular endothelial growth factor A (VEGFA), a known target of HIF-1, by 24h. Both TGF-ß1 and hypoxia inhibited proliferation after 24h. TGF-ß1 treatment also upregulated various fibrotic pathways. In contrast, hypoxia caused a reduction in several protein synthesis pathways, including collagen biosynthesis. Collectively, these data suggest that TGF-ß1, but not acute hypoxia, robustly induces the differentiation of human cardiac fibroblasts into myofibroblasts. Discerning the overlapping and distinctive outcomes of TGF-ß1 and hypoxia treatment is important for elucidating their roles in fibrotic remodeling post-MI and provides insight into potential therapeutic targets.

Fetal body organ T2* relaxometry at low field strength (FOREST).

Fetal Magnetic Resonance Imaging (MRI) at low field strengths is an exciting new field in both clinical and research settings. Clinical low field (0.55T) scanners are beneficial for fetal imaging due to their reduced susceptibility-induced artifacts, increased T2* values, and wider bore (widening access for the increasingly obese pregnant population). However, the lack of standard automated image processing tools such as segmentation and reconstruction hampers wider clinical use. In this study, we present the Fetal body Organ T2* RElaxometry at low field STrength (FOREST) pipeline that analyzes ten major fetal body organs. Dynamic multi-echo multi-gradient sequences were acquired and automatically reoriented to a standard plane, reconstructed into a high-resolution volume using deformable slice-to-volume reconstruction, and then automatically segmented into ten major fetal organs. We extensively validated FOREST using an inter-rater quality analysis. We then present fetal T2* body organ growth curves made from 100 control subjects from a wide gestational age range (17-40 gestational weeks) in order to investigate the relationship of T2* with gestational age. The T2* values for all organs except the stomach and spleen were found to have a relationship with gestational age (p<0.05). FOREST is robust to fetal motion, and can be used for both normal and fetuses with pathologies. Low field fetal MRI can be used to perform advanced MRI analysis, and is a viable option for clinical scanning.

Structural and functional fetal cardiac imaging using low field (0.55†T) MRI.

Purpose: This study aims to investigate the feasibility of using a commercially available clinical 0.55 T MRI scanner for comprehensive structural and functional fetal cardiac imaging. Methods: Balanced steady-state free precession (bSSFP) and phase contrast (PC) sequences were optimized by in utero studies consisting of 14 subjects for bSSFP optimization and 9 subjects for PC optimization. The signal-to-noise ratio (SNR) of the optimized sequences were investigated. Flow measurements were performed in three vessels, umbilical vein (UV), descending aorta (DAo), and superior vena cava (SVC) using the PC sequences and retrospective gating. The optimized bSSFP, PC and half-Fourier single shot turbo spin-echo (HASTE) sequences were acquired in a cohort of 21 late gestation-age fetuses (>36 weeks) to demonstrate the feasibility of a fetal cardiac exam at 0.55 T. The HASTE stacks were reconstructed to create an isotropic reconstruction of the fetal thorax, followed by automatic great vessel segmentations. The intra-abdominal UV blood flow measurements acquired with MRI were compared to ultrasound UV free-loop flow measurements. Results: Using the parameters from 1.5 T as a starting point, the bSSFP sequences were optimized at 0.55 T, resulting in a 1.6-fold SNR increase and improved image contrast compared to starting parameters, as well as good visibility of most cardiac structures as rated by two experienced fetal cardiologists. The PC sequence resulted in increased SNR and reduced scan time, subsequent retrospective gating enabled successful blood flow measurements. The reconstructions and automatic great vessel segmentations showed good quality, with 18/21 segmentations requiring no or minor refinements. Blood flow measurements were within the expected range. A comparison of the UV measurements performed with ultrasound and MRI showed agreement between the two sets of measurements, with better correlation observed at lower flows. Conclusion: We demonstrated the feasibility of low-field (0.55 T) MRI for fetal cardiac imaging. The reduced SNR at low field strength can be effectively compensated for by strategically optimizing sequence parameters. Major fetal cardiac structures and vessels were consistently visualized, and flow measurements were successfully obtained. The late gestation study demonstrated the robustness and reproducibility at low field strength. MRI performed at 0.55 T is a viable option for fetal cardiac examination.

Placental multimodal MRI prior to spontaneous preterm birth <32 weeks' gestation: An observational study.

OBJECTIVE: To utilise combined diffusion-relaxation MRI techniques to interrogate antenatal changes in the placenta prior to extreme preterm birth among both women with PPROM and membranes intact, and compare this to a control group who subsequently delivered at term. DESIGN: Observational study. SETTING: Tertiary Obstetric Unit, London, UK. POPULATION: Cases: pregnant women who subsequently spontaneously delivered a singleton pregnancy prior to 32 weeks' gestation without any other obstetric complications. CONTROLS: pregnant women who delivered an uncomplicated pregnancy at term. METHODS: All women consented to an MRI examination. A combined diffusion-relaxation MRI of the placenta was undertaken and analysed using fractional anisotropy, a combined T2*-apparent diffusion coefficient model and a combined T2*-intravoxel incoherent motion model, in order to provide a detailed placental phenotype associated with preterm birth. Subgroup analyses based on whether women in the case group had PPROM or intact membranes at time of scan, and on latency to delivery were performed. MAIN OUTCOME MEASURES: Fractional anisotropy, apparent diffusion coefficients and T2* placental values, from two models including a combined T2*-IVIM model separating fast- and slow-flowing (perfusing and diffusing) compartments. RESULTS: This study included 23 women who delivered preterm and 52 women who delivered at term. Placental T2* was lower in the T2*-apparent diffusion coefficient model (p < 0.001) and in the fast- and slow-flowing compartments (p = 0.001 and p < 0.001) of the T2*-IVIM model. This reached a higher level of significance in the preterm prelabour rupture of the membranes group than in the membranes intact group. There was a reduced perfusion fraction among the cases with impending delivery. CONCLUSIONS: Placental diffusion-relaxation reveals significant changes in the placenta prior to preterm birth with greater effect noted in cases of preterm prelabour rupture of the membranes. Application of this technique may allow clinically valuable interrogation of histopathological changes before preterm birth. In turn, this could facilitate more accurate antenatal prediction of preterm chorioamnionitis and so aid decisions around the safest time of delivery. Furthermore, this technique provides a research tool to improve understanding of the pathological mechanisms associated with preterm birth in vivo.

Hypoxic-Normoxic Crosstalk Activates Pro-Inflammatory Signaling in Human Cardiac Fibroblasts and Myocytes in a Post-Infarct Myocardium on a Chip.

Myocardial infarctions locally deprive myocardium of oxygenated blood and cause immediate cardiac myocyte necrosis. Irreparable myocardium is then replaced with a scar through a dynamic repair process that is an interplay between hypoxic cells of the infarct zone and normoxic cells of adjacent healthy myocardium. In many cases, unresolved inflammation or fibrosis occurs for reasons that are incompletely understood, increasing the risk of heart failure. Crosstalk between hypoxic and normoxic cardiac cells is hypothesized to regulate mechanisms of repair after a myocardial infarction. To test this hypothesis, microfluidic devices are fabricated on 3D printed templates for co-culturing hypoxic and normoxic cardiac cells. This system demonstrates that hypoxia drives human cardiac fibroblasts toward glycolysis and a pro-fibrotic phenotype, similar to the anti-inflammatory phase of wound healing. Co-culture with normoxic fibroblasts uniquely upregulates pro-inflammatory signaling in hypoxic fibroblasts, including increased secretion of tumor necrosis factor alpha (TNF-α). In co-culture with hypoxic fibroblasts, normoxic human induced pluripotent stem cell (hiPSC)-derived cardiac myocytes also increase pro-inflammatory signaling, including upregulation of interleukin 6 (IL-6) family signaling pathway and increased expression of IL-6 receptor. Together, these data suggest that crosstalk between hypoxic fibroblasts and normoxic cardiac cells uniquely activates phenotypes that resemble the initial pro-inflammatory phase of post-infarct wound healing.

Correlation of fetal lung area with MRI derived pulmonary volume.

BACKGROUND: Neonatal chest-Xray (CXR)s are commonly performed as a first line investigation for the evaluation of respiratory complications. Although lung area derived from CXRs correlates well with functional assessments of the neonatal lung, it is not currently utilised in clinical practice, partly due to the lack of reference ranges for CXR-derived lung area in healthy neonates. Advanced MR techniques now enable direct evaluation of both fetal pulmonary volume and area. This study therefore aims to generate reference ranges for pulmonary volume and area in uncomplicated pregnancies, evaluate the correlation between prenatal pulmonary volume and area, as well as to assess the agreement between antenatal MRI-derived and neonatal CXR-derived pulmonary area in a cohort of fetuses that delivered shortly after the antenatal MRI investigation. METHODS: Fetal MRI datasets were retrospectively analysed from uncomplicated term pregnancies and a preterm cohort that delivered within 72 h of the fetal MRI. All examinations included T2 weighted single-shot turbo spin echo images in multiple planes. In-house pipelines were applied to correct for fetal motion using deformable slice-to-volume reconstruction. An MRI-derived lung area was manually segmented from the average intensity projection (AIP) images generated. Postnatal lung area in the preterm cohort was measured from neonatal CXRs within 24 h of delivery. Pearson correlation coefficient was used to correlate MRI-derived lung volume and area. A two-way absolute agreement was performed between the MRI-derived AIP lung area and CXR-derived lung area. RESULTS: Datasets from 180 controls and 10 preterm fetuses were suitable for analysis. Mean gestational age at MRI was 28.6 ± 4.2 weeks for controls and 28.7 ± 2.7 weeks for preterm neonates. MRI-derived lung area correlated strongly with lung volumes (p < 0.001). MRI-derived lung area had good agreement with the neonatal CXR-derived lung area in the preterm cohort [both lungs = 0.982]. CONCLUSION: MRI-derived pulmonary area correlates well with absolute pulmonary volume and there is good correlation between MRI-derived pulmonary area and postnatal CXR-derived lung area when delivery occurs within a few days of the MRI examination. This may indicate that fetal MRI derived lung area may prove to be useful reference ranges for pulmonary areas derived from CXRs obtained in the perinatal period.

The Fetal Spleen in Low-Risk Pregnancies and prior to Preterm Birth: Observational Study of the Role of Anatomical and Functional Magnetic Resonance Imaging.

INTRODUCTION: Spontaneous preterm birth complicates ∼7% of pregnancies and causes morbidity and mortality. Although infection is a common etiology, our understanding of the fetal immune system in vivo is limited. This study aimed to utilize T2-weighted imaging and T2* relaxometry (which is a proxy of tissue oxygenation) of the fetal spleen in uncomplicated pregnancies and in fetuses that were subsequently delivered spontaneously prior to 32 weeks. METHODS: Women underwent imaging including T2-weighted fetal body images and multi-eco gradient echo single-shot echo planar sequences on a Phillips Achieva 3T system. Previously described postprocessing techniques were applied to obtain T2- and T2*-weighted imaging of the fetal spleen and T2-weighted fetal body volumes. RESULTS: Among 55 women with uncomplicated pregnancies, an increase in fetal splenic volume, splenic:body volume, and a decrease in splenic T2* signal intensity was demonstrated across gestation. Compared to controls, fetuses who were subsequently delivered prior to 32 weeks' gestation (n = 19) had a larger spleen when controlled for the overall size of the fetus (p = 0.027), but T2* was consistent (p = 0.76). CONCLUSION: These findings provide evidence of a replicable method of studying the fetal immune system and give novel results on the impact of impending preterm birth on the spleen. While T2* decreases prior to preterm birth in other organs, preservation demonstrated here suggests preferential sparing of the spleen.

Advanced magnetic resonance imaging detects altered placental development in pregnancies affected by congenital heart disease.

Congenital heart disease (CHD) is the most common congenital malformation and is associated with adverse neurodevelopmental outcomes. The placenta is crucial for healthy fetal development and placental development is altered in pregnancy when the fetus has CHD. This study utilized advanced combined diffusion-relaxation MRI and a data-driven analysis technique to test the hypothesis that placental microstructure and perfusion are altered in CHD-affected pregnancies. 48 participants (36 controls, 12 CHD) underwent 67 MRI scans (50 control, 17 CHD). Significant differences in the weighting of two independent placental and uterine-wall tissue components were identified between the CHD and control groups (both pFDR < 0.001), with changes most evident after 30 weeks gestation. A significant trend over gestation in weighting for a third independent tissue component was also observed in the CHD cohort (R = 0.50, pFDR = 0.04), but not in controls. These findings add to existing evidence that placental development is altered in CHD. The results may reflect alterations in placental perfusion or the changes in fetal-placental flow, villous structure and maturation that occur in CHD. Further research is needed to validate and better understand these findings and to understand the relationship between placental development, CHD, and its neurodevelopmental implications.

Fully automated planning for anatomical fetal brain MRI on 0.55T.

PURPOSE: Widening the availability of fetal MRI with fully automatic real-time planning of radiological brain planes on 0.55T MRI. METHODS: Deep learning-based detection of key brain landmarks on a whole-uterus echo planar imaging scan enables the subsequent fully automatic planning of the radiological single-shot Turbo Spin Echo acquisitions. The landmark detection pipeline was trained on over 120 datasets from varying field strength, echo times, and resolutions and quantitatively evaluated. The entire automatic planning solution was tested prospectively in nine fetal subjects between 20 and 37 weeks. A comprehensive evaluation of all steps, the distance between manual and automatic landmarks, the planning quality, and the resulting image quality was conducted. RESULTS: Prospective automatic planning was performed in real-time without latency in all subjects. The landmark detection accuracy was 4.2 ± $$ \pm $$ 2.6 mm for the fetal eyes and 6.5 ± $$ \pm $$ 3.2 for the cerebellum, planning quality was 2.4/3 (compared to 2.6/3 for manual planning) and diagnostic image quality was 2.2 compared to 2.1 for manual planning. CONCLUSIONS: Real-time automatic planning of all three key fetal brain planes was successfully achieved and will pave the way toward simplifying the acquisition of fetal MRI thereby widening the availability of this modality in nonspecialist centers.

Effect of the Communities that HEAL intervention on receipt of behavioral therapies for opioid use disorder: A cluster randomized wait-list controlled trial.

BACKGROUND: The U.S. opioid overdose crisis persists. Outpatient behavioral health services (BHS) are essential components of a comprehensive response to opioid use disorder and overdose fatalities. The Helping to End Addiction Long-Term® (HEALing) Communities Study developed the Communities That HEAL (CTH) intervention to reduce opioid overdose deaths in 67 communities in Kentucky, Ohio, New York, and Massachusetts through the implementation of evidence-based practices (EBPs), including BHS. This paper compares the rate of individuals receiving outpatient BHS in Wave 1 intervention communities (n = 34) to waitlisted Wave 2 communities (n = 33). METHODS: Medicaid data included individuals ≥18 years of age receiving any of five BHS categories: intensive outpatient, outpatient, case management, peer support, and case management or peer support. Negative binomial regression models estimated the rate of receiving each BHS for Wave 1 and Wave 2. Effect modification analyses evaluated changes in the effect of the CTH intervention between Wave 1 and Wave 2 by research site, rurality, age, sex, and race/ethnicity. RESULTS: No significant differences were detected between intervention and waitlisted communities in the rate of individuals receiving any of the five BHS categories. None of the interaction effects used to test the effect modification were significant. CONCLUSIONS: Several factors should be considered when interpreting results-no significant intervention effects were observed through Medicaid claims data, the best available data source but limited in terms of capturing individuals reached by the intervention. Also, the 12-month evaluation window may have been too brief to see improved outcomes considering the time required to stand-up BHS. TRIAL REGISTRATION: Clinical Trials.gov http://www. CLINICALTRIALS: gov: Identifier: NCT04111939.

Automated body organ segmentation, volumetry and population-averaged atlas for 3D motion-corrected T2-weighted fetal body MRI.

Structural fetal body MRI provides true 3D information required for volumetry of fetal organs. However, current clinical and research practice primarily relies on manual slice-wise segmentation of raw T2-weighted stacks, which is time consuming, subject to inter- and intra-observer bias and affected by motion-corruption. Furthermore, there are no existing standard guidelines defining a universal approach to parcellation of fetal organs. This work produces the first parcellation protocol of the fetal body organs for motion-corrected 3D fetal body MRI. It includes 10 organ ROIs relevant to fetal quantitative volumetry studies. We also introduce the first population-averaged T2w MRI atlas of the fetal body. The protocol was used as a basis for training of a neural network for automated organ segmentation. It showed robust performance for different gestational ages. This solution minimises the need for manual editing and significantly reduces time. The general feasibility of the proposed pipeline was also assessed by analysis of organ growth charts created from automated parcellations of 91 normal control 3T MRI datasets that showed expected increase in volumetry during 22-38 weeks gestational age range.

Advanced magnetic resonance imaging detects altered placental development in pregnancies affected by congenital heart disease.

Congenital heart disease (CHD) is the most common congenital malformation and is associated with adverse neurodevelopmental outcomes. The placenta is crucial for healthy fetal development and placental development is altered in pregnancy when the fetus has CHD. This study utilized advanced combined diffusion-relaxation MRI and a data-driven analysis technique to test the hypothesis that placental microstructure and perfusion are altered in CHD-affected pregnancies. 48 participants (36 controls, 12 CHD) underwent 67 MRI scans (50 control, 17 CHD). Significant differences in the weighting of two independent placental and uterine-wall tissue components were identified between the CHD and control groups (both pFDR<0.001), with changes most evident after 30 weeks gestation. A Significant trend over gestation in weighting for a third independent tissue component was also observed in the CHD cohort (R = 0.50, pFDR=0.04), but not in controls. These findings add to existing evidence that placental development is altered in CHD. The results may reflect alterations in placental perfusion or the changes in fetal-placental flow, villous structure and maturation that occur in CHD. Further research is needed to validate and better understand these findings and to understand the relationship between placental development, CHD, and its neurodevelopmental implications.

The role of placental insufficiency in spontaneous preterm birth: A literature review.

Preterm Birth (delivery before 37 weeks of gestation) is the leading cause of childhood mortality and is also associated with significant morbidity both in the neonatal period and beyond. The aetiology of spontaneous preterm birth is unclear and likely multifactorial incorporating factors such as infection/inflammation and cervical injury. Placental insufficiency is emerging as an additional contributor to spontaneous preterm delivery; however, the mechanisms by which this occurs are not fully understood. Serum biomarkers and imaging techniques have been investigated as potential predictors of placental insufficiency, however none have yet been found to have a sufficient predictive value. This review examines the evidence for the role of the placenta in preterm birth, preterm prelabour rupture of the membranes and abruption as well as highlighting areas where further research is required.

Preterm premature rupture of the membranes (PPROM): a study of patient experiences and support needs.

BACKGROUND: Preterm prelabour rupture of membranes (PPROM) is a common obstetric condition but outcomes can vary depending on gestation. Significant maternal and foetal complications occur including preterm birth, infection, abruption, cord prolapse, pulmonary hypoplasia and even death. Although the need for psychological support is recognised it is unclear how much is actually offered to women and their families. This study aimed to survey the views of women and their families who have undergone PPROM in order to understand the care and psychological burden these families face. METHODS: An online survey was conducted, recruiting women via social media with collaboration from the patient advocacy support group Little Heartbeats. Responses were collated where fields were binary or mean and standard deviations calculated. Framework analysis was used to identify and analyse themes in free text responses. RESULTS: 180PPROM pregnancies were described from 177 respondents. Although carewas variable and respondents were from across the world there werecommon themes. Five themes were highlighted which were: a lack ofbalanced information regarding the condition, support in decisionmaking and support with the process, specific psychological supportand ongoing psychological consequences of PPROM. CONCLUSION: This survey highlights areas in which care needs to be improved for women with PPROM. Previous studies have shown that providing good care during the antenatal period reduces long-term psychological morbidity for the whole family. The need for support, with regard both to information provided to women and their families and their psychological support needs to be addressed urgently.

Preeclampsia Associated Differences in the Placenta, Fetal Brain, and Maternal Heart Can Be Demonstrated Antenatally: An Observational Cohort Study Using MRI.

BACKGROUND: Preeclampsia is a multiorgan disease of pregnancy that has short- and long-term implications for the woman and fetus, whose immediate impact is poorly understood. We present a novel multiorgan approach to magnetic resonance imaging (MRI) investigation of preeclampsia, with the acquisition of maternal cardiac, placental, and fetal brain anatomic and functional imaging. METHODS: An observational study was performed recruiting 3 groups of pregnant women: those with preeclampsia, chronic hypertension, or no medical complications. All women underwent a cardiac MRI, and pregnant women underwent a placental-fetal MRI. Cardiac analysis for structural, morphological, and flow data were undertaken; placenta and fetal brain volumetric and T2* (which describes relative tissue oxygenation) data were obtained. All results were corrected for gestational age. A nonpregnant cohort was identified for inclusion in the statistical shape analysis. RESULTS: Seventy-eight MRIs were obtained during pregnancy. Cardiac MRI analysis demonstrated higher left ventricular mass in preeclampsia with 3-dimensional modeling revealing additional specific characteristics of eccentricity and outflow track remodeling. Pregnancies affected by preeclampsia demonstrated lower placental and fetal brain T2*. Within the preeclampsia group, 23% placental T2* results were consistent with controls, these were the only cases with normal placental histopathology. Fetal brain T2* results were consistent with normal controls in 31% of cases. CONCLUSIONS: We present the first holistic assessment of the immediate implications of preeclampsia on maternal heart, placenta, and fetal brain. As well as having potential clinical implications for the risk stratification and management of women with preeclampsia, this gives an insight into the disease mechanism.

Effective and simple interventions to improve outcomes for preterm infants worldwide: The FIGO PremPrep-5 initiative.

Preterm birth remains the leading cause of mortality among under-5's and is a major contributor to the reduction in quality-of-life adjusted years and reduction in human capital. Globally, there are many interventions and care bundles that aim to reduce the impact of preterm birth once preterm labor has ensued and into the neonatal period; not all of these are applicable in all settings. Here, we introduce the FIGO PremPrep-5 initiative, which aims to disseminate key information on the most simple and effective interventions with the aim of increasing implementation globally. Before delivery, we recommend a course of antenatal corticosteroids, and intrapartum magnesium sulfate. At delivery, we recommend delayed cord clamping. Postnatally, we recommend early feeding with breast milk and immediate kangaroo care. While there are many other interventions that may improve outcomes at the time of labor and after preterm birth, these are clinically effective and relatively inexpensive options that can be practiced in most settings and supplemented with more advanced care. We include examples of a training video and infographics that will be used for dissemination.

Fetal growth restriction: How reliable is information available to patients on Google? A systematic review.

OBJECTIVES: To review systematically the quality, readability and credibility of English language webpages offering patient information on fetal growth restriction. STUDY DESIGN: A systematic review of patient information was undertaken on Google with location services and browser history disabled. Websites from the first page were included providing they gave at least 300 words of health information on fetal growth restriction aimed at patients. Validated assessment of readability, credibility and quality were undertaken. An accuracy assessment was performed based on international guidance. Characteristics were tabulated. RESULTS: Thirty-one websites including 30 different texts were included. No pages had a reading age of 11 years or less, none were credible, and only one was of high quality. Median accuracy rating was 9/24. CONCLUSION: Patients cannot rely on Google as a source of information on fetal growth restriction. As well as being difficult to read, information tends to be low quality, low accuracy and not credible. Healthcare professionals must consider how to enable access to high-quality patient information and give time for discussion of information patients have found: failure to do so may disenfranchise patients.

Adrenal volumes in fetuses delivering prior to 32 weeks' gestation: An MRI pilot study.

INTRODUCTION: Spontaneous preterm birth prior to 32 weeks' gestation accounts for 1% of all deliveries and is associated with high rates of morbidity and mortality. A total of 70% are associated with chorioamnionitis which increases the incidence of morbidity, but for which there is no noninvasive antenatal test. Fetal adrenal glands produce cortisol and dehydroepiandosterone-sulphate which upregulate prior to spontaneous preterm birth. Ultrasound suggests that adrenal volumes may increase prior to preterm birth, but studies are limited. This study aimed to: (i) demonstrate reproducibility of magnetic resonance imaging (MRI) derived adrenal volumetry; (ii) derive normal ranges of total adrenal volumes, and adrenal: body volume for normal; (iii) compare with those who have spontaneous very preterm birth; and (iv) correlate with histopathological chorioamnionitis. MATERIAL AND METHODS: Patients at high risk of preterm birth prior to 32 weeks were prospectively recruited, and included if they did deliver prior to 32 weeks; a control group who delivered an uncomplicated pregnancy at term was also recruited. T2 weighted images of the entire uterus were obtained, and a deformable slice-to-volume method was used to reconstruct the fetal abdomen. Adrenal and body volumes were obtained via manual segmentation, and adrenal: body volume ratios generated. Normal ranges were created using control data. Differences between groups were investigated accounting for the effect of gestation by use of regression analysis. Placental histopathology was reviewed for pregnancies delivering preterm. RESULTS: A total of 56 controls and 26 cases were included in the analysis. Volumetry was consistent between observers. Adrenal volumes were not higher in the case group (p = 0.2); adrenal: body volume ratios were higher (p = 0.011), persisting in the presence of chorioamnionitis (p = 0.017). A cluster of three pairs of adrenal glands below the fifth centile were noted among the cases all of whom had a protracted period at risk of preterm birth prior to MRI. CONCLUSIONS: Adrenal: body volume ratios are significantly larger in fetuses who go on to deliver preterm than those delivering at term. Adrenal volumes were not significantly larger, we hypothesize that this could be due to an adrenal atrophy in fetuses with fulminating chorioamnionitis. A straightforward relationship of adrenal size being increased prior to preterm birth should not be assumed.