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The gestational state is a period of particular vulnerability to diseases that affect maternal and fetal health. Stress during gestation may represent a powerful influence on maternal mental health and offspring brain plasticity and development. Here we show that the fetal transcriptome, through microRNA (miRNA) regulation, responds to prenatal stress in association with epigenetic signatures of psychiatric and neurological diseases. Pregnant Long-Evans rats were assigned to stress from gestational days 12 to 18 while others served as handled controls. Gestational stress in the dam disrupted parturient maternal behaviour and was accompanied by characteristic brain miRNA profiles in the mother and her offspring, and altered transcriptomic brain profiles in the offspring. In the offspring brains, prenatal stress upregulated miR-103, which is involved in brain pathologies, and downregulated its potential gene target Ptplb. Prenatal stress downregulated miR-145, a marker of multiple sclerosis in humans. Prenatal stress also upregulated miR-323 and miR-98, which may alter inflammatory responses in the brain. Furthermore, prenatal stress upregulated miR-219, which targets the gene Dazap1. Both miR-219 and Dazap1 are putative markers of schizophrenia and bipolar affective disorder in humans. Offspring transcriptomic changes included genes related to development, axonal guidance and neuropathology. These findings indicate that prenatal stress modifies epigenetic signatures linked to disease during critical periods of fetal brain development. These observations provide a new mechanistic association between environmental and genetic risk factors in psychiatric and neurological disease.

Background Evidence relating maternal history of abuse before pregnancy with pregnancy outcomes is controversial. This study aims to examine the association between maternal histories of abuse before pregnancy and the risk of preterm delivery and low birth weight. Methods We searched Subject Headings and keywords for exposure and the outcomes through MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Psycinfo, CINAHL, Scopus, PILOTS, ProQuest Dissertations & Theses Global and Web of Science Core Collection in April 2017. We selected original studies that reported associations between maternal histories of abuse of any type and either preterm delivery or low birth weight. Studies that included interventions during pregnancy to lower maternal stress but reported no control data were excluded. We utilized the Newcastle-Ottawa Quality Assessment Scales for observational studies to assess the risk of bias in the primary studies. Two independent reviewers performed the selection of pertinent studies, assessment of risk of bias, and data extraction. Unadjusted pooled odds ratios (OR) with 95% Confidence Interval (CI) were calculated for the two outcomes of preterm delivery and low birth weight in 16 included studies. Results Maternal history of abuse before pregnancy was significantly associated with preterm delivery (OR 1.28, 95% CI: 1.12–1.47) and low birth weight (OR 1.35, 95% CI: 1.14–1.59). A substantial level of heterogeneity was detected within the two groups of studies reporting preterm birth and low birth weight (I 2  = 75% and 69% respectively). Subgroup analysis based on the specific time of abuse before pregnancy indicated that childhood abuse increases the risk of low birth weight by 57% (95% CI: 0.99–2.49). When the included studies were categorized based on study design, cohort studies showed the highest effect estimates on preterm delivery and low birth weight (OR: 1.69, 95%CI: 1.19–2.40, OR: 1.56, 95% CI: 1.06–2.3, respectively). Conclusions We recommend that more high quality research studies on this topic are necessary to strengthen the inference. At the practice level, we suggest more attention in detecting maternal history of abuse before pregnancy during antenatal visits and using this information to inform risk assessment for adverse pregnancy outcomes. Trial registration Registration number: PROSPERO ( CRD42016033231 ).

In preparation for delivery, the uterus transitions from actively maintaining quiescence during pregnancy to an active parturient state. This transition occurs as a result of the accumulation of pro-inflammatory signals which are amplified by positive feedback interactions involving paracrine and autocrine signaling at the level of each intrauterine cell and tissue. The amplification events occur in parallel until they reach a certain threshold, ‘tipping the scale’ and contributing to processes of uterine activation and functional progesterone withdrawal. The described signaling interactions all occur upstream from the presentation of clinical labor symptoms. In this review, we will: 1) describe the different physiological processes involved in uterine transition for each intrauterine tissue; 2) compare and contrast the current models of labor initiation; 3) introduce innovative models for measuring paracrine inflammatory interactions; and 4) discuss the therapeutic value in identifying and targeting key players in this crucial event for preterm birth.

The climate crisis is the existential threat of our times and for generations to come. This is no longer a threat but a reality affecting us, our children, and the generations that follow. Pregnant mothers, their fetuses, and their children are among those at greatest risk in every population and every jurisdiction. A timely consideration is the health of racialized groups who are particularly vulnerable owing to the confluence of several risk factors that are compounded by climate change. Included among these are Indigenous communities that are the most directly threatened by climate change. This review discusses the main health challenges faced by mothers, fathers, and their children during the climate crisis, focusing on mental health as a causal factor. Exploration of this topic includes the role of prenatal maternal and paternal stresses, allostatic load, and the effect of degradation of the environment and ecosystems on individuals. These will be examined in relation to adverse pregnancy outcomes and altered developmental trajectories of children. The climate crisis is a health threat multiplier that amplifies the health inequities of the most at-risk populations and individuals. It accelerates the increase in allostatic load of those at risk. The path of tragedy begins with an accumulating allostatic load that overwhelms both individual and socio-ecological resilience. This can lead to worse mental health including depression and anxiety and, in the case of pregnant women and their children, more adverse pregnancy outcomes and impaired developmental trajectories for their newborn children. We argue that there is an urgent need to develop new (or re-discover or re-purpose existing) tools that will predict communities and individuals who are experiencing the highest levels of climate-related hazards and intervene to reduce stress and increase resilience in pre-conceptual women and men, pregnant and post-partum women, and their young children.

Background Each mother–child dyad represents a unique combination of genetic and environmental factors. This constellation of variables impacts the expression of countless genes. Numerous studies have uncovered changes in DNA methylation (DNAm), a form of epigenetic regulation, in offspring related to maternal risk factors. How these changes work together to link maternal-child risks to childhood cardiometabolic and neurocognitive traits remains unknown. This question is a key research priority as such traits predispose to future non-communicable diseases (NCDs). We propose viewing risk and the genome through a multidimensional lens to identify common DNAm patterns shared among diverse risk profiles. Methods We identified multifactorial Maternal Risk Profiles (MRPs) generated from population-based data ( n  = 15,454, Avon Longitudinal Study of Parents and Children (ALSPAC)). Using cord blood HumanMethylation450 BeadChip data, we identified genome-wide patterns of DNAm that co-vary with these MRPs. We tested the prospective relation of these DNAm patterns ( n  = 914) to future outcomes using decision tree analysis. We then tested the reproducibility of these patterns in (1) DNAm data at age 7 and 17 years within the same cohort ( n  = 973 and 974, respectively) and (2) cord DNAm in an independent cohort, the Generation R Study ( n  = 686). Results We identified twenty MRP-related DNAm patterns at birth in ALSPAC. Four were prospectively related to cardiometabolic and/or neurocognitive childhood outcomes. These patterns were replicated in DNAm data from blood collected at later ages. Three of these patterns were externally validated in cord DNAm data in Generation R. Compared to previous literature, DNAm patterns exhibited novel spatial distribution across the genome that intersects with chromatin functional and tissue-specific signatures. Conclusions To our knowledge, we are the first to leverage multifactorial population-wide data to detect patterns of variability in DNAm. This context-based approach decreases biases stemming from overreliance on specific samples or variables. We discovered molecular patterns demonstrating prospective and replicable relations to complex traits. Moreover, results suggest that patterns harbour a genome-wide organisation specific to chromatin regulation and target tissues. These preliminary findings warrant further investigation to better reflect the reality of human context in molecular studies of NCDs. Graphical Abstract

The heterogeneity of spontaneous preterm birth (SPTB) requires an interdisciplinary approach to determine potential predictive risk factors of early delivery. The aim of this study was to investigate maternal whole blood gene expression profiles associated with spontaneous preterm birth (SPTB, <37 weeks) in asymptomatic pregnant women. The study population was a matched subgroup of women (51 SPTBs, 114 term delivery controls) who participated in the All Our Babies community based cohort in Calgary (n = 1878). Maternal blood at 17-23 (sampling time point 1, T1) and 27-33 weeks of gestation (T2) were collected. Total RNA was extracted and microarray was performed on 326 samples (165 women). Univariate analyses determined significant clinical factors and differential gene expression associated with SPTB. Thirteen genes were validated using qRT-PCR. Three multivariate logistic models were constructed to identify gene expression at T1 (Model A), T2 (Model B), and gene expression fold change from T1 to T2 (Model C) associated with SPTB. All models were adjusted for clinical factors. Model C can predict SPTB with 65% sensitivity and 88% specificity in asymptomatic women after adjusting for history of abortion and anaemia (occurring before T2). Clinical data enhanced the sensitivity of the Models to predict SPTB. In conclusion, clinical factors and whole blood gene expression are associated with SPTB in asymptomatic women. An effective screening tool for SPTB during pregnancy would enable targeted preventive approaches and personalised antenatal care.

A major cause of preterm labor in pregnant women is intra-amniotic infection, which is mediated by an inflammatory process. Hydrogen sulfide (H2S), a gaseous transmitter, has been implicated to be involved in inflammatory responses. We sought to investigate whether H2S affects infectious preterm birth using the mouse model of lipopolysaccharides (LPS)-induced preterm birth. Administration of LPS at 0.4 mg/kg with two injections intraperitoneally (i.p.) on gestational day 14.5 induced preterm labor. LPS significantly increased leukocyte infiltration in uterus, stimulated the expression of pro-inflammatory cytokines interleukin 1β (IL-1β), IL-6, tumor necrosis factor α (TNF-α), CCL2 and CXCL15 in myometrium. Administration of NaHS (i.p.) delayed the onset of labor induced by LPS in a dose-dependent manner. NaHS prevented leukocyte infiltration into intrauterine tissues and inhibited the production of pro-inflammatory cytokines in myometrium and decreased the levels of these cytokines in maternal circulation. H2S also decreased LPS-activated extracellular signal-regulated kinase (ERK) 1/2/ nuclear factor (NF)-κB signaling pathways in myometrium. This study provides new in vivo evidence for the roles of H2S in attenuating inflammation, and a potential novel therapeutic strategy for infection-related preterm labor.

Background Perinatal infection/inflammation is associated with a high risk for neurological injury and neurodevelopmental impairment after birth. Despite a growing preclinical evidence base, anti-inflammatory interventions have not been established in clinical practice, partly because of the range of potential targets. We therefore systematically reviewed preclinical studies of immunomodulation to improve neurological outcomes in the perinatal brain and assessed their therapeutic potential. Methods We reviewed relevant studies published from January 2012 to July 2023 using PubMed, Medline (OvidSP) and EMBASE databases. Studies were assessed for risk of bias using the SYRCLE risk of bias assessment tool (PROSPERO; registration number CRD42023395690). Results Forty preclinical publications using 12 models of perinatal neuroinflammation were identified and divided into 59 individual studies. Twenty-seven anti-inflammatory agents in 19 categories were investigated. Forty-five (76%) of 59 studies reported neuroprotection, from all 19 categories of therapeutics. Notably, 10/10 (100%) studies investigating anti-interleukin (IL)-1 therapies reported improved outcome, whereas half of the studies using corticosteroids (5/10; 50%) reported no improvement or worse outcomes with treatment. Most studies (49/59, 83%) did not control core body temperature (a known potential confounder), and 25 of 59 studies (42%) did not report the sex of subjects. Many studies did not clearly state whether they controlled for potential study bias. Conclusion Anti-inflammatory therapies are promising candidates for treatment or even prevention of perinatal brain injury. Our analysis highlights key knowledge gaps and opportunities to improve preclinical study design that must be addressed to support clinical translation.

Understanding patterns of biodiversity distribution is essential to conservation strategies 1 , but severe data constraints make surrogate measures necessary 2 , 3 , 4 . For this reason, many studies have tested the performance of terrestrial vertebrates as surrogates for overall species diversity, but these tests have typically been limited to a single taxon or region 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 . Here we show that global patterns of richness are highly correlated among amphibians, reptiles, birds and mammals, as are endemism patterns. Furthermore, we demonstrate that although the correlation between global richness and endemism is low, aggregate regions selected for high levels of endemism capture significantly more species than expected by chance. Although areas high in endemism have long been targeted for the protection of narrow-ranging species 11 , 12 , our findings provide evidence that endemism is also a useful surrogate for the conservation of all terrestrial vertebrates.

Funding for conservation action to preserve vanishing species is limited, so finances have to be targeted at areas that are richest in biodiversity. The representation approach to biodiversity conservation, in which examples of all ecosystem and habitat types are preserved, is promoted. The Global 200 ecoregions represent terrestrial, freshwater, and marine major habitat types in each biogeographic realm. A detailed list of these regions summarized their approximate location and current conservation status. The boundaries of these regions are derived from intensive regional analyses of biodiversity patterns. Each ecoregion is rated in one of four categories of biological distinctiveness as well. Island ecoregions are projected to experience a wave of extinctions in the next 20 yr because of their fragility, sensitivity to competition from introduced species, and endemicity. The Global 200 list is an effective strategy for targeting biodiversity units and promoting ecosystem-level representation on a global scale, because it broadens the focus from species diversity to habitat diversity, ecological processes, evolutionary phenomena, and adaptations.