Maximizing cardiovascular benefits of fish consumption within the One Health approach: Should current recommendations be revised?

AIMS: Current dietary recommendations on fish consumption for cardiovascular disease (CVD) prevention put somewhat vague emphasis on fatty fish, mainly driven by evidence on the cardioprotective effects of n-3 PUFAs. Recent data on the consumption of different types of fish in relation to hard cardiovascular endpoints suggests that fatty but not lean fish can contribute to CVD prevention. This considered, we aimed at evaluating, by an environmental perspective, fish consumption limited to the fatty type - in appropriate amounts for optimizing CVD prevention - within the European context. DATA SYNTHESIS: Starting from the current average intake of total fish by the European population (i.e., 2 servings/week of fatty plus lean fish), we show that the shift towards the consumption of 2 servings/week of solely fatty fish - appropriate for optimizing CVD prevention - would allow a 32% saving of greenhouse gas (GHG) emissions related to fish consumption. This is due to the lower environmental impact of fatty fish globally considered, compared to lean fish. However, since the carbon footprint of different fatty fish species can vary significantly - with small blue fish (e.g., anchovies, sardines, herrings) in the lowest range, we estimated that GHG emissions due to fish consumption in Europe could be reduced by 82% by focusing on small blue fish consumption. CONCLUSIONS: Consumption of 2 servings/week of small blue fish could represent a feasible and effective choice among the functional dietary strategies available to achieve the maximal benefits for human and environmental health.

Modelling food policies in Italian urban agendas in the time of Covid-19: Experiences, challenges and opportunities.

Global food systems are broken and in need of profound change. These imbalances and vulnerabilities are particularly strong in cities, where most of the global population lives and that are at the core of the major challenges linked with food production and consumption. The food system transition needs cities as key game-changers towards more sustainable, equitable, healthier and fairer food systems. Against this backdrop, the present article analyses the role of food policies within urban policies, with a focus on Italian cities. In particular, the article discusses data collected from representatives of 100 municipalities across Northern, Central and Southern Italy. Moreover, it addresses the types of policies and initiatives adopted at the local level, the main obstacles encountered, the role of national and international city networks and the impact of Covid-19 on urban food security, with the aim to identify potential models of urban food policies as a structural component of a broader urban agenda. By doing this, the article aims at filling a research gap in current literature, as it is the first large-scale survey on urban food policies in Italy, identifying models of urban food policies that are already being developed within broader urban development agendas.

Good for the heart, good for the Earth: proposal of a dietary pattern able to optimize cardiovascular disease prevention and mitigate climate change.

BACKGROUND AND AIMS: Human and planetary health are inextricably interconnected through food systems. Food choices account for 50% of all deaths for cardiovascular diseases (CVD) - the leading cause of death in Europe - and food systems generate up to 37% of total greenhouse gas (GHG) emissions. METHODS AND RESULTS: Based on a systematic revision of meta-analyses of prospective studies exploring the association between individual foods/food groups and the incidence of CVD, we identified a dietary pattern able to optimize CVD prevention.. This dietary pattern was compared to the current diet of the European population. The nutritional adequacy of both diets was evaluated according to the European Food Safety Authority (EFSA) recommended nutrient intake for the adult population, and their environmental impact was evaluated in terms of carbon footprint (CF). As compared to the current diet, the desirable diet includes higher intakes of fruit, vegetables, wholegrains, low glycemic index (GI) cereals, nuts, legumes and fish, and lower amounts of beef, butter, high GI cereals or potatoes and sugar. The diet here identified provides appropriate intakes of all nutrients and matches better than the current Europeans' one the EFSA requirements. Furthermore, the CF of the proposed diet is 48.6% lower than that of the current Europeans' diet. CONCLUSION: The transition toward a dietary pattern designed to optimize CVD prevention would improve the nutritional profile of the habitual diet in Europe and, at the same time, contribute to mitigate climate change by reducing the GHG emissions linked to food consumption almost by half.

Prenatal Stress and Neurodevelopmental Plasticity: Relevance to Psychopathology.

Prenatal development constitutes a critical time for shaping adult behaviour and may set the stage for vulnerability to disease later in life. A wealth of information from humans as well as from animal research has revealed that exposure to hostile conditions during gestation may result in a series of coordinated biological responses aimed at enhancing the probability of survival, but could also increase the susceptibility to mental illness. Prenatal stress has been linked to abnormal cognitive, behavioural and psychosocial outcomes both in animals and in humans, but the underlying molecular and physiological mechanisms remain largely unknown. In this chapter, we shall review experimental data from studies reported for rats, since more information is available for them than for other species. The major focus of the present chapter is to update and discuss data on behavioural, functional and morphological effects of prenatal stress in rats that may have counterparts in prospective and/or retrospective studies of gestational stress in humans. This work contributes to understanding the role of neuronal plasticity in the long-term effects of developmental adversity on brain function and its implications for vulnerability to disease.

In Search of Concomitant Alterations of Dopaminergic and Neurotensinergic Systems in Stress Conditions.

The aim of the present article is to review experimental evidence which suggest joint involvement of both the dopaminergic and neurotensinergic systems in stress conditions. At present, the concept of stress refers to an environmental demand exceeding the normal regulatory ability of an organism, particularly during unpredictable and uncontrollable situations. Chronic stress yields devastating effects including cognitive and working memory dysfunctions, for which neurotransmission mediated by the catecholamines dopamine and noradrenaline is crucial. Catecholamine synthesis depends on the rate-limiting enzyme, tyrosine hydroxylase, whose expression is associated with working memory and the response to chronic stress. Neurotensin is a tridecapeptide widely distributed in the nervous system, at both central and peripheral levels, which behaves as a neurotransmitter or neuromodulator. It mediates diverse biological actions including reward, locomotion, pain modulation and stress. Neurotensin and its high affinity NTS1 receptor are densely localized in areas that process emotion (amygdala nucleus), cognition (such as hippocampal nuclei and cortical areas) and the response to stress (hypothalamic nucleus). Experimental evidence indicates a crosstalk between the dopaminergic and the neurotensinergic systems either from an anatomical or a biochemical point of view. It is suggested that a concomitant alteration of dopaminergic and neurotensinergic systems takes place in diverse stress conditions.

Prenatal restraint stress decreases the expression of alpha-7 nicotinic receptor in the brain of adult rat offspring.

Prenatal stress (PS) strongly impacts fetal brain development and function in adulthood. In normal aging and Alzheimer's disease, there is hypothalamic-pituitary-adrenal axis dysfunction and loss of cholinergic neurons and neuronal nicotinic acetylcholine receptors (nAChRs). This study investigated whether prenatal restraint stress affects nAChR expression in the brain of adult offspring. For PS, pregnant dams were placed in a plastic restrainer for 45 min, three times daily during the last week of pregnancy; controls were undisturbed. Male offspring were analyzed at postnatal day (PND) 60 (n = 4 rats per group). Western blot (WB) and fluorescence microscopy showed that PS decreased α7-AChR subunit expression (∼50%) in the frontal cortex in the adult offspring. PS decreased significantly the number of α7-AChR-expressing cells in the medial prefrontal cortex (by ∼25%) and in the sensory-motor cortex (by ∼20%) without affecting the total cell number in those areas. No alterations were found in the hippocampus by quantitative polymerase chain reaction (qPCR), or WB analysis, but a detailed fluorescence microscopy analysis showed that PS affected α7-AChR mainly in the CA3 and dentate gyrus subfields: PS decreased α7-AChR subunit expression by ∼25 and ∼30%, respectively. Importantly, PS decreased the number of α7-AChR-expressing cells and the total cell number (by ∼15 and 20%, respectively) in the dentate gyrus. PS differently affected α4-AChR: PS impaired its mRNA expression in the frontal cortex (by ∼50%), without affecting protein levels. These results demonstrate that disturbances during gestation produce long-term alterations in the expression pattern of α7-AChR in rat brain.

Current perspectives on perinatal mental health and neurobehavioral development: focus on regulation, coregulation and self-regulation.

PURPOSE OF REVIEW: Perinatal mental health research provides an important perspective on neurobehavioral development. Here, we aim to review the association of maternal perinatal health with offspring neurodevelopment, providing an update on (self-)regulation problems, hypothesized mechanistic pathways, progress and challenges, and implications for mental health. RECENT FINDINGS: (1) Meta-analyses confirm that maternal perinatal mental distress is associated with (self-)regulation problems which constitute cognitive, behavioral, and affective social-emotional problems, while exposure to positive parental mental health has a positive impact. However, effect sizes are small. (2) Hypothesized mechanistic pathways underlying this association are complex. Interactive and compensatory mechanisms across developmental time are neglected topics. (3) Progress has been made in multiexposure studies. However, challenges remain and these are shared by clinical, translational and public health sciences. (4) From a mental healthcare perspective, a multidisciplinary and system level approach employing developmentally-sensitive measures and timely treatment of (self-)regulation and coregulation problems in a dyadic caregiver-child and family level approach seems needed. The existing evidence-base is sparse. SUMMARY: During the perinatal period, addressing vulnerable contexts and building resilient systems may promote neurobehavioral development. A pluralistic approach to research, taking a multidisciplinary approach to theoretical models and empirical investigation needs to be fostered.

Prenatal maternal restraint stress exposure alters the reproductive hormone profile and testis development of the rat male offspring.

Several studies have demonstrated that the presence of stressors during pregnancy induces adverse effects on the neuroendocrine system of the offspring later in life. In the present work, we investigated the effects of early programming on the male reproductive system, employing a prenatal stress (PS) paradigm. This study found that when pregnant dams were placed in a plastic restrainer three times a day during the last week of pregnancy, the offspring showed reduced anogenital distance and delayed testicular descent. Serum luteinising hormone (LH) and follicle-stimulating hormone (FSH) levels were decreased at postnatal day (PND) 28 and testosterone was decreased at PND 75. Increased testosterone plus dihydrotestosterone (T + DHT) concentrations correlated with increased testicular 5α Reductase-1 (5αR-1) mRNA expression at PND 28. Moreover, PS accelerated spermatogenesis at PND 35 and 60, and increased mean seminiferous tubule diameter in pubertal offspring and reduced Leydig cell number was observed at PND 35 and 60. PS offspring had increased androgen receptor (AR) mRNA level at PND 28, and at PND 35 had increased the numbers of Sertoli cells immunopositive for AR. Overall, the results confirm that stress during gestation can induce long-term effects on the male offspring reproductive system. Of particular interest is the pre-pubertal imbalance of circulating hormones that probably trigger accelerated testicular development, followed by an increase in total androgens and a decrease in testosterone concentration during adulthood. Exposure to an unfavourable intrauterine environment might prepare for harsh external conditions by triggering early puberty, increasing reproductive potential.

Age-dependent effects of prenatal stress on the corticolimbic dopaminergic system development in the rat male offspring.

We have previously demonstrated that prenatal stress (PS) exerts an impairment of midbrain dopaminergic (DA) system metabolism especially after puberty, suggesting a particular sensitivity of DA development to variations in gonadal hormonal peaks. Furthermore we demonstrated that PS alters the long term androgens profile of the rat male offspring from prepubertal to adult stages. In this work we evaluated the sexual hormones activational effects on the DA system by analysing PS effects on the dopaminergic D2-like (D2R) and on the gonadal hormones receptor levels on cortical and hippocampal areas of prepubertal and adult male offspring. We further evaluated the dendritic arborization in the same areas by quantifying MAP2 immunoexpresion. Our results show that PS affected oestrogen receptor alpha (ERα) expression: mRNA er1s and ERα protein levels were decreased on prefrontal cortex and hippocampus of adult offspring. Moreover, PS reduced D2R protein levels in hippocampus of prepubertal rats. Morphological studies revealed that prepubertal PS rats presented decreased MAP2 immunoexpression in both areas suggesting that PS reduces the number of dendritic arborizations. Our findings suggest that PS exerts long-term effects on the DA system by altering the normal connectivity in the areas, and by modulating the expression of D2R and ERα in an age-related pattern. Since the developing forebrain DA system was shown to be influenced by androgen exposure, and PS was shown to disrupt perinatal testosterone surges, our results suggest that prenatal insults might be affecting the organizational role of androgens and differentially modulating their activational role on the DA development.

Rapid determination of polycyclic aromatic hydrocarbons in rainwater by liquid-liquid microextraction and LC with core-shell particles column and fluorescence detection.

Liquid-liquid microextraction coupled to LC with fluorescence detection for the determination of Environmental Protection Agency's 16 priority pollutant polycyclic aromatic hydrocarbons in rainwater has been developed. The optimization of the extraction method has involved several parameters, including the comparison between an ultrasonic bath and a magnetic stirrer as extractant apparatus, the choice of the extractant solvent, and the optimization of the extraction time. Liquid-liquid microextraction gave good results in terms of recoveries (from 73.6 to 102.8% in rainwater) and repeatability, with a very simple procedure and low solvent consumption. The reported chromatographic method uses a Core-Shell technology column, with particle size <3 µm instead of classical 5-µm particles column. The resulting backpressure was below 300 bar, allowing the use of a conventional HPLC system rather than the more expensive ultrahigh performance LC (UHPLC). An average decrease of 59% in run time and 75% in eluent consumption has been obtained, compared to classical HPLC methods, keeping good separation, sensitivity, and repeatability. The proposed conditions were successfully applied to the determinations of polycyclic aromatic hydrocarbons in genuine rainwater samples.

Autism Spectrum Disorder: A Neuro-Immunometabolic Hypothesis of the Developmental Origins.

Fetal neuroinflammation and prenatal stress (PS) may contribute to lifelong neurological disabilities. Astrocytes and microglia, among the brain's non-neuronal "glia" cell populations, play a pivotal role in neurodevelopment and predisposition to and initiation of disease throughout lifespan. One of the most common neurodevelopmental disorders manifesting between 1-4 years of age is the autism spectrum disorder (ASD). A pathological glial-neuronal interplay is thought to increase the risk for clinical manifestation of ASD in at-risk children, but the mechanisms remain poorly understood, and integrative, multi-scale models are needed. We propose a model that integrates the data across the scales of physiological organization, from genome to phenotype, and provides a foundation to explain the disparate findings on the genomic level. We hypothesize that via gene-environment interactions, fetal neuroinflammation and PS may reprogram glial immunometabolic phenotypes that impact neurodevelopment and neurobehavior. Drawing on genomic data from the recently published series of ovine and rodent glial transcriptome analyses with fetuses exposed to neuroinflammation or PS, we conducted an analysis on the Simons Foundation Autism Research Initiative (SFARI) Gene database. We confirmed 21 gene hits. Using unsupervised statistical network analysis, we then identified six clusters of probable protein-protein interactions mapping onto the immunometabolic and stress response networks and epigenetic memory. These findings support our hypothesis. We discuss the implications for ASD etiology, early detection, and novel therapeutic approaches. We conclude with delineation of the next steps to verify our model on the individual gene level in an assumption-free manner. The proposed model is of interest for the multidisciplinary community of stakeholders engaged in ASD research, the development of novel pharmacological and non-pharmacological treatments, early prevention, and detection as well as for policy makers.

EU-27 ecological footprint was primarily driven by food consumption and exceeded regional biocapacity from 2004 to 2014.

The European Union (EU) plans to decarbonize the region by 2050. As highlighted by the Green Deal and Farm to Fork Strategy, food systems are essential for this transition. Here we investigate the resource dependence and carbon emissions of the EU-27's food systems from 2004 to 2014 via an ecological footprint (EF)-extended multi-regional input-output approach, accounting for demand and supply (including trade), and considering multiple externalities. Food contributes towards almost a third of the region's EF, and appropriates over half of its biocapacity. Average reliance on biocapacity within national borders decreased, while reliance on intra-EU biocapacity increased; yet a quarter of the biocapacity for food consumption originates from non-EU countries. Despite a reduction in both total EF and food EF over the study period, EU-27 residents demand more from nature than the region's ecosystems can regenerate-highlighting the need for new or strengthened food and trade policies to enable a transformation to sustainable EU food systems.

Complex drought patterns robustly explain global yield loss for major crops.

Multi-purpose crops as maize, rice, soybean, and wheat are key in the debate concerning food, land, water and energy security and sustainability. While strong evidence exists on the effects of climate variability on the production of these crops, so far multifaceted attributes of droughts-magnitude, frequency, duration, and timing-have been tackled mainly separately, for a limited part of the cropping season, or over small regions. Here, a more comprehensive assessment is provided on how droughts with their complex patterns-given by their compound attributes-are consistently related to negative impacts on crop yield on a global scale. Magnitude and frequency of both climate and yield variability are jointly analysed from 1981 to 2016 considering multiscale droughts, i.e., dry conditions occurring with different durations and timings along the whole farming season, through two analogous and standardized indicators enabling comparison among crops, countries, and years. Mainly winter wheat and then spring wheat, soybean and the main maize's season reveal high susceptibility of yield under more complex drought patterns than previously assessed. The second maize's season and rice present less marked and more uncertain results, respectively. Overall, southern and eastern Europe, the Americas and sub-Saharan Africa presents multi-crop susceptibility, with eastern Europe, Middle East and Central Asia appearing critical regions for the most vulnerable crop, which is wheat. Finally, yield losses for wheat and soybean clearly worsen when moving from moderate to extreme multiscale droughts.

The positive climate impact of the Mediterranean diet and current divergence of Mediterranean countries towards less climate sustainable food consumption patterns.

The Mediterranean diet (MD) is a world-renowned healthy dietary pattern. In the present study we analyse the climate sustainability of the MD and the greenhouse gas emissions (EGHG) associated with current dietary patterns in Mediterranean and non-Mediterranean EU countries, focusing on the major deviations from the MD health and environmental targets in Mediterranean countries. The EGHG associated with dietary patterns were calculated for seven Mediterranean countries (Cyprus, Croatia, Greece, Italy, Portugal, Spain and Malta, referred to as 7MED) and the other 21 countries in the EU 28 (referred to as 21OTHER), using 2017 as the reference year. A new harmonised compilation of 3449 carbon footprint values of food commodities, based on a standardised methodology to extract information and assign optimal footprint values and uncertainties to food items, was used to estimate EGHG of food consumption. Our findings show that the EGHG associated with the ideal MD pattern, 2.3 kg CO2equivalents (CO2eq) capita-1 d-1, are in line with planetary GHG climate targets, though GHG emissions associated with food consumption in Mediterranean countries strongly diverged from the ideal MD. Both MED and 21OTHER countries were found to have comparable dietary associated EGHG (4.46 and 4.03 kg CO2eq capita-1 d-1 respectively), almost double that expected from a sustainable dietary pattern. The primary factor of dietary divergence in 7MED countries was found to be meat overconsumption, which contributed to 60% of the EGHG daily excess (1.8 kg of CO2eq capita-1 d-1).

Early Biomarkers and Intervention Programs for the Infant Exposed to Prenatal Stress.

Functional development of affective and reward circuits, cognition and response inhibition later in life exhibits vulnerability periods during gestation and early childhood. Extensive evidence supports the model that exposure to stressors in the gestational period and early postnatal life increases an individual's susceptibility to future impairments of functional development. Recent versions of this model integrate epigenetic mechanisms of the developmental response. Their understanding will guide the future treatment of the associated neuropsychiatric disorders. A combination of non-invasively obtainable physiological signals and epigenetic biomarkers related to the principal systems of the stress response, the Hypothalamic-Pituitary axis (HPA) and the Autonomic Nervous System (ANS), are emerging as the key predictors of neurodevelopmental outcomes. Such electrophysiological and epigenetic biomarkers can prove to timely identify children benefiting most from early intervention programs. Such programs should ameliorate future disorders in otherwise healthy children. The recently developed Early Family-Centered Intervention Programs aim to influence the care and stimuli provided daily by the family and improving parent/child attachment, a key element for healthy socio-emotional adult life. Although frequently underestimated, such biomarker-guided early intervention strategy represents a crucial first step in the prevention of future neuropsychiatric problems and in reducing their personal and societal impact.

True Cost Accounting of a healthy and sustainable diet in Italy.

It is widely upheld that global food systems are unsustainable. Sustainable diets are gaining prominence as key components to entangle global food system challenges, as well as to transition towards the pathway of the 2030 Agenda and the Sustainable Development Goals (SDGs). Hence, sustainable and healthy diets are at the core of much research with the aim to bring together nutritional adequacy, cultural acceptability, environmental sustainability, economic affordability, and shape future consumption patterns. This article contributes to advancing knowledge on sustainable diets by proposing a True Cost Accounting method to assess the cost and impact of the adoption of a more sustainable and healthier diet, using Italy as an illustration. The research analyses the complexity of a diet from an environmental, health, and socioeconomic point of view and defines a new assessment framework that can be replicated and adapted to other contexts. Results show that in Italy, the adoption of a sustainable and healthy diet has a 47% lower carbon footprint and 25% lower water footprint than the current diet, while impacting 13% less on the average income and food monthly expenditure. Also, the desirable diet has a 21% lower impact on the sanitary costs related to cardiovascular disease. This study corroborates that the consumption of the desirable diet would provide a total cost saving of 741 EUR per year per capita, if we consider its impact on the environment, health, and socio-economic costs.

Prenatal stress perturbs fetal iron homeostasis in a sex specific manner.

The adverse effects of maternal prenatal stress (PS) on child's neurodevelopment warrant the establishment of biomarkers that enable early interventional therapeutic strategies. We performed a prospective matched double cohort study screening 2000 pregnant women in third trimester with Cohen Perceived Stress Scale-10 (PSS-10) questionnaire; 164 participants were recruited and classified as stressed and control group (SG, CG). Fetal cord blood iron parameters of 107 patients were measured at birth. Transabdominal electrocardiograms-based Fetal Stress Index (FSI) was derived. We investigated sex contribution to group differences and conducted causal inference analyses to assess the total effect of PS exposure on iron homeostasis using a directed acyclic graph (DAG) approach. Differences are reported for p < 0.05 unless noted otherwise. Transferrin saturation was lower in male stressed neonates. The minimum adjustment set of the DAG to estimate the total effect of PS exposure on fetal ferritin iron biomarkers consisted of maternal age and socioeconomic status: SG revealed a 15% decrease in fetal ferritin compared with CG. Mean FSI was higher among SG than among CG. FSI-based timely detection of fetuses affected by PS can support early individualized iron supplementation and neurodevelopmental follow-up to prevent long-term sequelae due to PS-exacerbated impairment of the iron homeostasis.

Maternal-fetal stress and DNA methylation signatures in neonatal saliva: an epigenome-wide association study.

BACKGROUND: Maternal stress before, during and after pregnancy has profound effects on the development and lifelong function of the infant's neurocognitive development. We hypothesized that the programming of the central nervous system (CNS), hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS) induced by prenatal stress (PS) is reflected in electrophysiological and epigenetic biomarkers. In this study, we aimed to find noninvasive epigenetic biomarkers of PS in the newborn salivary DNA. RESULTS: A total of 728 pregnant women were screened for stress exposure using Cohen Perceived Stress Scale (PSS), 164 women were enrolled, and 114 dyads were analyzed. Prenatal Distress Questionnaire (PDQ) was also administered to assess specific pregnancy worries. Transabdominal fetal electrocardiograms (taECG) were recorded to derive coupling between maternal and fetal heart rates resulting in a 'Fetal Stress Index' (FSI). Upon delivery, we collected maternal hair strands for cortisol measurements and newborn's saliva for epigenetic analyses. DNA was extracted from saliva samples, and DNA methylation was measured using EPIC BeadChip array (850 k CpG sites). Linear regression was used to identify associations between PSS/PDQ/FSI/Cortisol and DNA methylation. We found epigenome-wide significant associations for 5 CpG with PDQ and cortisol at FDR < 5%. Three CpGs were annotated to genes (Illumina Gene annotation file): YAP1, TOMM20 and CSMD1, and two CpGs were located approximately lay at 50 kb from SSBP4 and SCAMP1. In addition, two differentiated methylation regions (DMR) related to maternal stress measures PDQ and cortisol were found: DAXX and ARL4D. CONCLUSIONS: Genes annotated to these CpGs were found to be involved in secretion and transportation, nuclear signaling, Hippo signaling pathways, apoptosis, intracellular trafficking and neuronal signaling. Moreover, some CpGs are annotated to genes related to autism, post-traumatic stress disorder (PTSD) and schizophrenia. However, our results should be viewed as hypothesis generating until replicated in a larger sample. Early assessment of such noninvasive PS biomarkers will allow timelier detection of babies at risk and a more effective allocation of resources for early intervention programs to improve child development. A biomarker-guided early intervention strategy is the first step in the prevention of future health problems, reducing their personal and societal impact.

Detection of maternal and fetal stress from the electrocardiogram with self-supervised representation learning.

In the pregnant mother and her fetus, chronic prenatal stress results in entrainment of the fetal heartbeat by the maternal heartbeat, quantified by the fetal stress index (FSI). Deep learning (DL) is capable of pattern detection in complex medical data with high accuracy in noisy real-life environments, but little is known about DL's utility in non-invasive biometric monitoring during pregnancy. A recently established self-supervised learning (SSL) approach to DL provides emotional recognition from electrocardiogram (ECG). We hypothesized that SSL will identify chronically stressed mother-fetus dyads from the raw maternal abdominal electrocardiograms (aECG), containing fetal and maternal ECG. Chronically stressed mothers and controls matched at enrolment at 32 weeks of gestation were studied. We validated the chronic stress exposure by psychological inventory, maternal hair cortisol and FSI. We tested two variants of SSL architecture, one trained on the generic ECG features for emotional recognition obtained from public datasets and another transfer-learned on a subset of our data. Our DL models accurately detect the chronic stress exposure group (AUROC = 0.982 ± 0.002), the individual psychological stress score (R2 = 0.943 ± 0.009) and FSI at 34 weeks of gestation (R2 = 0.946 ± 0.013), as well as the maternal hair cortisol at birth reflecting chronic stress exposure (0.931 ± 0.006). The best performance was achieved with the DL model trained on the public dataset and using maternal ECG alone. The present DL approach provides a novel source of physiological insights into complex multi-modal relationships between different regulatory systems exposed to chronic stress. The final DL model can be deployed in low-cost regular ECG biosensors as a simple, ubiquitous early stress detection and monitoring tool during pregnancy. This discovery should enable early behavioral interventions.

A Review on the Vagus Nerve and Autonomic Nervous System During Fetal Development: Searching for Critical Windows.

The autonomic nervous system (ANS) is one of the main biological systems that regulates the body's physiology. Autonomic nervous system regulatory capacity begins before birth as the sympathetic and parasympathetic activity contributes significantly to the fetus' development. In particular, several studies have shown how vagus nerve is involved in many vital processes during fetal, perinatal, and postnatal life: from the regulation of inflammation through the anti-inflammatory cholinergic pathway, which may affect the functioning of each organ, to the production of hormones involved in bioenergetic metabolism. In addition, the vagus nerve has been recognized as the primary afferent pathway capable of transmitting information to the brain from every organ of the body. Therefore, this hypothesis paper aims to review the development of ANS during fetal and perinatal life, focusing particularly on the vagus nerve, to identify possible "critical windows" that could impact its maturation. These "critical windows" could help clinicians know when to monitor fetuses to effectively assess the developmental status of both ANS and specifically the vagus nerve. In addition, this paper will focus on which factors-i.e., fetal characteristics and behaviors, maternal lifestyle and pathologies, placental health and dysfunction, labor, incubator conditions, and drug exposure-may have an impact on the development of the vagus during the above-mentioned "critical window" and how. This analysis could help clinicians and stakeholders define precise guidelines for improving the management of fetuses and newborns, particularly to reduce the potential adverse environmental impacts on ANS development that may lead to persistent long-term consequences. Since the development of ANS and the vagus influence have been shown to be reflected in cardiac variability, this paper will rely in particular on studies using fetal heart rate variability (fHRV) to monitor the continued growth and health of both animal and human fetuses. In fact, fHRV is a non-invasive marker whose changes have been associated with ANS development, vagal modulation, systemic and neurological inflammatory reactions, and even fetal distress during labor.