Deep learning identifies cardiac coupling between mother and fetus during gestation

In the last two decades, stillbirth has caused around 2 million fetal deaths worldwide. Although current ultrasound tools are reliably used for the assessment of fetal growth during pregnancy, it still raises safety issues on the fetus, requires skilled providers, and has economic concerns in less developed countries. Here, we propose deep coherence, a novel artificial intelligence (AI) approach that relies on 1 min non-invasive electrocardiography (ECG) to explain the association between maternal and fetal heartbeats during pregnancy. We validated the performance of this approach using a trained deep learning tool on a total of 941 one minute maternal-fetal R-peaks segments collected from 172 pregnant women (20–40 weeks). The high accuracy achieved by the tool (90%) in identifying coupling scenarios demonstrated the potential of using AI as a monitoring tool for frequent evaluation of fetal development. The interpretability of deep learning was significant in explaining synchronization mechanisms between the maternal and fetal heartbeats. This study could potentially pave the way toward the integration of automated deep learning tools in clinical practice to provide timely and continuous fetal monitoring while reducing triage, side-effects, and costs associated with current clinical devices

Prenatal exposure to maternal anxiety affects neurocognition in the first year of life

status: publishe

Discovery and Characterization of Novel Selective NKCC1 Inhibitors for Down Syndrome and Brain Disorders with Depolarizing GABAergic Transmission

Proper GABAergic transmission through Cl-permeable GABAA receptors is fundamental for physiological brain development and function. Indeed, defective GABAergic signaling -due to a high ratio of expression of the Cl importer NKCC1 and Cl exporter KCC2- has been implicated in several neurodevelopmental disorders (e.g., Down syndrome, DS). Interestingly, NKCC1 inhibition by the FDAapproved diuretic bumetanide reverts cognitive deficits in the TS65Dn mouse models of DS and core symptoms in a number of models of other brain disorders. However, the required chronic treatment with bumetanide is burdened by its diuretic side effects caused by the antagonism of the kidney Cl- importer NKCC2, which leads to hypokalemia and jeopardizes drug compliance. Crucially, these issues would be solved by selective NKCC1 inhibitors, thus devoid of the diuretic effect. Starting from bumetanide\u2019s structure, we applied a computational ligand-based approach to design new molecular entities that we tested in vitro for their capacity to selectively block NKCC1. Among the 3 newly-identified and highly promising NKCC1 inhibitors, one showed excellent solubility and metabolic stability in vitro. Moreover, analysis of WT and Ts65Dn mice systemically treated with this NKCC1 inhibitor revealed no diuretic effect. Finally, chronic treatment with our novel, selective NKCC1 inhibitor was able to rescue cognitive deficits in Ts65Dn mice in four different memory tasks, with no major signs of toxicity. Thus, our selective NKCC1 inhibitor devoid of the diuretic effect could represent a suitable and solid therapeutic strategy for the treatment of Down syndrome and all the brain disorders with depolarizing GABAergic transmission

The biology of the first 1000 days

The first 1,000 days, from conception to 2 years of age, is a critical window of growth and development. Exposures to dietary, environmental, hormonal, and other stressors during this period have been associated with an increased risk of adverse health outcomes. Researchers using cell culture, animal models, and humans have identified this time as a period of rapid physiological change and plasticity with significant potential for lasting effects. As such, interventions during the first 1,000 days will have the greatest impact on outcomes, particularly in low- and middle-income countries where the need is greatest. To date, there is no single resource that compiles our knowledge of the biology of the first 1,000 days. Our knowledge and understanding of the biology behind the first 1,000 days is still limited. This greater understanding is helping us inform effective nutrition policy and programming. The strength of this book lies in its cross- disciplinary nature that encompasses the full range of human biology, providing a more holistic perspective during this critical time frame. Moreover, we have broadened the scope and included important periods before and after the 1,000 days. We have designed this book as a comprehensive resource for those involved in global health and nutrition policy, strategy, programming, or research. This book will also be a resource for students learning about nutrition and health across the 1,000 days. The book includes an exceptional group of contributors who are experts in their given fields. As biology underlies the core of each discussion, it allows the readers to answer the what and why, and, we hope, the how for new discovery research and more effective interventions. Each chapter in this volume provides insight into a specific life stage, disease state, nutrient, and stressor in the first 1,000 days. As such, each chapter can be read independently, providing a comprehensive overview of that subject. However, there is continuity between chapters allowing this collection of chapters to be read cover to cover. The first chapters set the stage, providing a succinct resource to understand the well-established biological mechanisms that underlie growth regulation and nutrient recommendations throughout the first 1,000 days. The next chapters move on to the evidence behind nutrition-specific and nutrition-sensitive interventions to combat adverse outcomes and disease states in the first 1,000 days. This book also features emerging research areas, such as the gut microbiome, environmental enteric dysfunction, and the role of epigenetics in health and development. The final chapter pushes the boundaries of discovery research, exploring novel areas such as proteomics and metabolomics, and how insults such as environmental enteric dysfunction affect metabolism in the first 1,000 days. We approached this book with the ambition to shed more light on the biology during 1,000 days, but there was also a need to put the biology into a broader context of nutrition and health. There are still many gaps in our understanding of the biology of the first 1,000 days. It is only by bridging this knowledge gap through research that we can inform effective interventions to improve outcomes during the first 1,000 days

Prevalence and treatment of obstructive sleep apnoea/hypopnoea syndrome in adults with Down syndrome

Obstructive sleep apnoea/hypopnoea syndrome (OSAHS) is characterised by repeated cycles of upper airway obstruction during sleep, leading to diurnal symptoms. Individuals with Down syndrome (DS) are predisposed to this as the DS phenotype overlaps with OSAHS risk factors. Around 2-4% of the general adult population and 55% of children with DS have OSAHS but, to date, no large-scale study has assessed OSAHS prevalence or efficacy of treatment in DS adults. This study aimed to: 1) Systematically assess subjective and objective OSAHS prevalence; 2) Assess the effectiveness of continuous positive airway pressure (CPAP) in an adult DS population. Standard questionnaires including pictorial Epworth Sleepiness Scale (pESS) and Developmental Behaviour Checklist for Adults (DBC-A) were sent to UK adults aged ≥16yr with DS and their caregivers. All questionnaire responders were invited to undergo home polygraphy. Symptomatic adults with DS with ≥10 apnoeas/hypopnoeas per hour in bed (AH) on home polygraphy were invited to participate in a prospective randomised controlled trial (RCT) of CPAP v. lifestyle advice, with review at 1, 3, 6 and 12m. Participants in the lifestyle arm were offered CPAP at 1m. Standard measurements of sleepiness, behaviour, cognitive function and general health were undertaken. Standard statistical analyses were conducted, with significance set at p<0.001 to control for multiple testing. Of 5270 questionnaires sent, 1105 responses were valid (21%). Responders (55% males) were overweight/obese young adults: mean BMI 29.0±6.8kg/m2; mean age 28±9 years. Women had a higher BMI (p<0.0001), but collar size was greater in men (p<0.0001). Mean pESS scores were broadly within the normal range (7±5/24). No significant gender differences in OSAHS symptoms were noted. Individuals with probable OSAHS had higher pESS and DBC-A scores, and significantly more symptoms of OSAHS. Subjective OSAHS prevalence was estimated at 35%. Of the 790 individuals invited, 149 underwent polygraphy, with 134 valid studies obtained: mean AH 21.8(10.9-42.7); mean oximetry desaturation index (ODI) 6.6(2.3-20.0). No significant gender differences were observed. Forty-two percent of participants met standard clinical diagnostic criteria for OSAHS. Twenty-eight eligible adults with DS (19 male) were randomised: age 28±9yr; BMI 31.5±7.9kg/m2; AH 28.6(14.8-47.9); ODI 7.3(1.8-21.9); pESS 11±6/24. Groups did not differ significantly at baseline. By 12m, 4 participants had withdrawn (all remaining participants on CPAP). The pESS (p=0.001), DBC-A Disruptive (p<0.0001) and Kaufmann Brief Intelligence Test verbal subscale (p=0.001) scores improved significantly. This first large study of OSAHS prevalence in the adult DS population estimates a prevalence of 35-42% - around 10 times higher than in the general adult population. Sustained, significant improvements in sleepiness, cognitive function and behavioural/emotional outcomes with CPAP use over a 12m period were demonstrated during this first RCT of CPAP in adults with DS. A larger trial of CPAP in this population is warranted