Preventing Preterm Birth: Exploring Innovative Solutions.

This review examines the complexities of preterm birth (PTB), emphasizes the pivotal role of inflammation in the pathogenesis of preterm labor, and assesses current available interventions. Antibiotics, progesterone analogs, mechanical approaches, nonsteroidal anti-inflammatory drugs, and nutritional supplementation demonstrate a limited efficacy. Tocolytic agents, targeting uterine activity and contractility, inadequately prevent PTB by neglecting to act on uteroplacental inflammation. Emerging therapies targeting toll-like receptors, chemokines, and interleukin receptors exhibit promise in mitigating inflammation and preventing PTB.

A novel approach to risk exposure and epigenetics-the use of multidimensional context to gain insights into the early origins of cardiometabolic and neurocognitive health.

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.

A systematic review of immune-based interventions for perinatal neuroprotection: closing the gap between animal studies and human trials.

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.

Pharmacological blockade of the interleukin-1 receptor suppressed Escherichia coli lipopolysaccharide-induced neuroinflammation in preterm fetal sheep.

BACKGROUND: Intraamniotic inflammation is associated with preterm birth, especially in cases occurring before 32 weeks' gestation, and is causally linked with an increased risk for neonatal mortality and morbidity. Targeted anti-inflammatory interventions may assist in improving the outcomes for pregnancies impacted by intrauterine inflammation. Interleukin-1 is a central upstream mediator of inflammation. Accordingly, interleukin-1 is a promising candidate target for intervention therapies and has been targeted previously using the interleukin-1 receptor antagonist, anakinra. Recent studies have shown that the novel, noncompetitive, allosteric interleukin-1 receptor inhibitor, rytvela, partially resolved inflammation associated with preterm birth and fetal injury. In this study, we used a preterm sheep model of chorioamnionitis to investigate the anti-inflammatory efficacy of rytvela and anakinra, administered in the amniotic fluid in the setting of intraamniotic Escherichia coli lipopolysaccharide exposure. OBJECTIVE: We hypothesized that both rytvela and anakinra would reduce lipopolysaccharide-induced intrauterine inflammation and protect the fetal brain. STUDY DESIGN: Ewes with a singleton fetus at 105 days of gestation (term is ∼150 days) were randomized to one of the following groups: (1) intraamniotic injections of 2 mL saline at time=0 and time=24 hours as a negative control group (saline group, n=12); (2) intraamniotic injection of 10 mg Escherichia coli lipopolysaccharide in 2 mL saline and intraamniotic injections of 2 mL saline at time=0 hours and time=24 hours as an inflammation positive control group (lipopolysaccharide group, n=11); (3) intraamniotic injection of Escherichia coli lipopolysaccharide in 2 mL saline and intraamniotic injections of 2.5 mg rytvela at time=0 hours and time=24 hours to test the anti-inflammatory efficacy of rytvela (lipopolysaccharide + rytvela group, n=10); or (4) intraamniotic injection of Escherichia coli lipopolysaccharide in 2 mL saline and intraamniotic injections of 100 mg anakinra at time=0 hours and time=24 hours to test the anti-inflammatory efficacy of anakinra (lipopolysaccharide + anakinra group, n=12). Amniotic fluid was sampled at time 0, 24, and 48 hours (ie, at each intervention and at delivery). Fetal umbilical cord blood was collected at delivery for differential blood counts and chemical studies. Inflammation was characterized by the analysis of fetal tissue cytokine and chemokine levels using quantitative polymerase chain reaction, enzyme-linked inmmunosorbent assay, and histology. The primary study outcome of interest was the assessment of anakinra and rytvela brain-protective effects in the setting of Escherichia coli lipopolysaccharide-induced intrauterine inflammation. Secondary outcomes of interest were to assess protection from fetal and intrauterine (ie, amniotic fluid, chorioamnion) inflammation. RESULTS: Intraamniotic administration of lipopolysaccharide caused inflammation of the fetal lung, brain, and chorioamnionitis in preterm fetal sheep. Relative to treatment with saline only in the setting of lipopolysaccharide exposure, intraamniotic administration of both rytvela and anakinra both significantly prevented periventricular white matter injury, microglial activation, and histologic chorioamnionitis. Anakinra showed additional efficacy in inhibiting fetal lung myeloperoxidase activity, but its use was associated with metabolic acidaemia and reduced fetal plasma insulin-like growth factor-1 levels at delivery. CONCLUSION: Intraamniotic administration of rytvela or anakinra significantly inhibited fetal brain inflammation and chorioamnionitis in preterm fetal sheep exposed to intraamniotic lipopolysaccharide. In addition, anakinra treatment was associated with potential negative impacts on the developing fetus.

The application of epiphenotyping approaches to DNA methylation array studies of the human placenta.

Background : Genome-wide DNA methylation (DNAme) profiling of the placenta with Illumina Infinium Methylation bead arrays is often used to explore the connections between in utero exposures, placental pathology, and fetal development. However, many technical and biological factors can lead to signals of DNAme variation between samples and between cohorts, and understanding and accounting for these factors is essential to ensure meaningful and replicable data analysis. Recently, "epiphenotyping" approaches have been developed whereby DNAme data can be used to impute information about phenotypic variables such as gestational age, sex, cell composition, and ancestry. These epiphenotypes offer avenues to compare phenotypic data across cohorts, and to understand how phenotypic variables relate to DNAme variability. However, the relationships between placental epiphenotyping variables and other technical and biological variables, and their application to downstream epigenome analyses, have not been well studied. Results : Using DNAme data from 204 placentas across three cohorts, we applied the PlaNET R package to estimate epiphenotypes gestational age, ancestry, and cell composition in these samples. PlaNET ancestry estimates were highly correlated with independent polymorphic ancestry informative markers, and epigenetic gestational age, on average, was estimated within 4 days of reported gestational age, underscoring the accuracy of these tools. Cell composition estimates varied both within and between cohorts, but reassuringly were robust to placental processing time. Interestingly, the ratio of cytotrophoblast to syncytiotrophoblast proportion decreased with increasing gestational age, and differed slightly by both maternal ethnicity (lower in white vs. non-white) and genetic ancestry (lower in higher probability European ancestry). The cohort of origin and cytotrophoblast proportion were the largest drivers of DNAme variation in this dataset, based on their associations with the first principal component. Conclusions : This work confirms that cohort, array (technical) batch, cell type proportion, self-reported ethnicity, genetic ancestry, and biological sex are important variables to consider in any analyses of Illumina DNAme data. Further, we demonstrate that estimating epiphenotype variables from the DNAme data itself, when possible, provides both an independent check of clinically-obtained data and can provide a robust approach to compare variables across different datasets.

Maternal mental health mediates the effect of prenatal stress on infant temperament: The Harvey Mom Study.

Prenatal maternal stress and mental health problems are known to increase risk for developmental psychopathology in offspring, yet pathways leading to risk or resiliency are poorly understood. In a quasi-experimental design, we prospectively examined associations between disaster-related prenatal stress, maternal mental health symptoms, and infant temperament outcomes. Mothers who were pregnant during Hurricane Harvey (N = 527) reported on objective hardships (e.g., loss of belongings or income, evacuation, home flooding) related to the storm and subsequent mental health symptoms (anxiety/depression, posttraumatic stress) across time. At a postpartum assessment, mothers reported on their infant's temperament (negative affect, positive affect, orienting/regulatory capacity). Greater objective hardship indirectly predicted higher levels of infant orienting/regulatory capacity through its association with increased maternal posttraumatic stress symptoms. Greater objective hardship also indirectly predicted higher levels of infant negative affect through its association with increased maternal anxiety/depression symptoms across time. Our findings suggest a psychological mechanism linking prenatal stress with specific temperamental characteristics via maternal mental health symptoms. Findings point to the importance of high-quality assessment and mental health services for vulnerable women and young children.

Experiencing Trauma During or Before Pregnancy: Qualitative Secondary Analysis After Two Disasters.

BACKGROUND: Despite the existing knowledge about stress, trauma and pregnancy and maternal stress during natural disasters, little is known about what types of trauma pregnant or preconception women experience during these disasters. In May 2016, the worst natural disaster in modern Canadian history required the evacuation of nearly 90,000 residents of the Fort McMurray Wood Buffalo (FMWB) area of northern Alberta. Among the thousands of evacuees were an estimated 1850 women who were pregnant or soon to conceive. In August 2017, Hurricane Harvey devastated areas of the United States including Texas, with 30,000 people forced to flee their homes due to the intense flooding. OBJECTIVE: To explore immediate and past traumatic experiences of pregnant or preconception women who experienced one of two natural disasters (a wildfire and a hurricane) as captured in their expressive writing. Research questions were: (1) What trauma did pregnant or preconception women experience during the fire and the hurricane? (2) What past traumatic experiences, apart from the disasters, did the women discuss in their expressive writing? METHODS: A qualitative secondary analysis of expressive writing using thematic content analysis was conducted on the expressive writing of 50 pregnant or preconception women who experienced the 2016 Fort McMurray Wood Buffalo Wildfire (n = 25) and the 2017 Houston Hurricane Harvey (n = 25) Narrative data in the form of expressive writing entries from participants of two primary studies were thematically analyzed. One of the expressive writing questions was used in this analysis: "What is the most traumatic, upsetting experience of your entire life, especially that you have never discussed in great detail with others?" NVivo 12 supported thematic content analysis. RESULTS: For some women, the disasters elicited immense fear and anxiety that surpassed previous traumatic life events. Others, however, disclosed significant past traumas that continue to impact them, including betrayal by a loved one, abuse, maternal health complications, and illness. CONCLUSION: We recommend a strengths-based and trauma-informed care approach in both maternal health and post-disaster relief care.

Environmental Enrichment Promotes Transgenerational Programming of Uterine Inflammatory and Stress Markers Comparable to Gestational Chronic Variable Stress.

Prenatal maternal stress is linked to adverse pregnancy and infant outcomes, including shortened gestation lengths, low birth weights, cardio-metabolic dysfunction, and cognitive and behavioural problems. Stress disrupts the homeostatic milieu of pregnancy by altering inflammatory and neuroendocrine mediators. These stress-induced phenotypic changes can be passed on to the offspring epigenetically. We investigated the effects of gestational chronic variable stress (CVS) in rats using restraint and social isolation stress in the parental F0 generation and its transgenerational transmission across three generations of female offspring (F1-F3). A subset of F1 rats was housed in an enriched environment (EE) to mitigate the adverse effects of CVS. We found that CVS is transmitted across generations and induces inflammatory changes in the uterus. CVS did not alter any gestational lengths or birth weights. However, inflammatory and endocrine markers changed in the uterine tissues of stressed mothers and their offspring, suggesting that stress is transgenerationally transmitted. The F2 offspring reared in EE had increased birth weights, but their uterine gene expression patterns remained comparable to those of stressed animals. Thus, ancestral CVS induced changes transgenerationally in fetal programming of uterine stress markers over three generations of offspring, and EE housing did not mitigate these effects.

Pharmacodynamic characterization of rytvela, a novel allosteric anti-inflammatory therapeutic, to prevent preterm birth and improve fetal and neonatal outcomes.

BACKGROUND: Preterm birth is the leading cause of neonatal morbidity and mortality. Studies have shown that interleukin 1 plays a major role in the pathophysiology of preterm birth by inducing the production of proinflammatory mediators and uterine activation proteins leading to labor. More importantly, uteroplacental inflammation, associated with preterm birth parturition pathways, is detrimental to fetal tissues and leads to long-term sequelae. Our group has developed an allosteric antagonist of the interleukin 1 receptor, rytvela, found to be potent and safe in preventing preterm birth by suppressing inflammation via the inhibition of the mitogen-activated protein kinase pathway while preserving the Nuclear factor kappa B pathway (important in immune vigilance). Rytvela has been shown to inhibit inflammatory up-regulation and uterine activation while preserving fetal development. OBJECTIVE: This study aimed to further the preclinical development of rytvela by evaluating its optimal dose and minimal duration of treatment to inhibit the inflammatory cascade, prolong gestation, and promote neonatal outcomes. STUDY DESIGN: Pregnant CD-1 mice were administered with lipopolysaccharide (10 µg, intraperitoneal administration) or interleukin 1 (1 µg/kg, intrauterine administration) on gestational day 16 to induce preterm labor. Rytvela was administered at different doses (0.1, 0.5, 1.0, 2.0, 4.0 mg/kg/d subcutaneously) from gestational days 16 to 18.5. To evaluate the minimal duration of treatment, the mice were administered with rytvela (2 mg/kg/d subcutaneously) for 24, 36, or 48 hours. The rate of prematurity (gestational day <18.5) and neonate survival and weight were evaluated. Gestational tissues were collected at gestational day 17.5 to quantify cytokines, proinflammatory mediators, and uterine activating proteins by real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. The neonatal lungs and intestines were collected from postnatal days 5 to 7 and analyzed by histology. RESULTS: Rytvela exhibited a dose-response profile and achieved maximum efficacy at a dose of 2 mg/kg/d by reducing 70% of lipopolysaccharide-induced preterm births and 60% of interleukin 1ß-induced preterm births. In addition, rytvela attained maximum efficacy at a dose of 1 mg/kg/d by increasing neonate survival by up to 65% in both models of preterm birth. Rytvela protected fetuses from inflammatory insult as of 24 hours, preserving lung and intestinal integrity, and prevented preterm birth and fetal mortality by 60% and 50%, respectively, as of 36 hours of treatment. CONCLUSION: The maximum efficacy of rytvela was achieved at 2 mg/kg/d with improved birth outcomes and prevented inflammatory up-regulation upon 36 hours (only) of treatment. Rytvela exhibited desirable properties for the safe prevention of preterm birth and fetal protection.

Sex-specific stress and biobehavioral responses to human experimenters in rats.

Important factors influencing the outcome of animal experiments in preclinical research are often overlooked. In the current study, the reaction of female and male rats toward the biological sex of a human experimenter was investigated in terms of anxiety-like behaviors and physiological stress responses, as measured by infrared (IR) thermography, circulating corticosterone (CORT) and oxytocin levels. Female rats displayed consistently exacerbated anxiety-related behaviors along with elevated body surface temperature during repeated exposure to male experimenters. Experimental stress further intensified thermal responses to a male experimenter, especially in female rats. The behavioral responses to a male experimenter in females were associated with higher circulating CORT and lower oxytocin levels. Similar responses were induced by a T-shirt worn by a human male. The findings suggest that psychophysiological responses of female rats to a male experimenter are influenced by both visual and olfactory cues. The results emphasize the need to not only consider sex differences in experimental animals, but also standardize and report the experimenter's biological sex to avoid ambiguity in the generation and interpretation of results.

New Life Through Disaster: A Thematic Analysis of Women's Experiences of Pregnancy and the 2016 Fort McMurray Wildfire.

Background: On May 3, 2016, residents of Fort McMurray Wood Buffalo, Alberta were evacuated due to an uncontrolled wildfire. The short-notice evacuation had destabilizing consequences for residents, including changes in routines, loss of control, and increased uncertainty. These consequences were especially detrimental to women who were pregnant or pre-conception during the evacuation. Pregnant and pre-conception women are particularly susceptible to a vast range of negative consequences during and post natural disasters, including elevated stress and higher incidence of pregnancy complications including gestational diabetes mellitus, pregnancy induced hypertension and C-section. The aim of this study was to understand the experiences, perceived stress and resilience of women who were pregnant during the wildfire. As well as to explore potential interventions to promote the health and enhance resilience of pregnant women and to assist in recovery after exposure to a natural disaster or other traumatic events. Methods: A qualitative thematic analysis of 16 narratives penned by pregnant women and recounted in Ashley Tobin's compilations 93/88,000 and 159 More/ 88,000: Stories of Evacuation, Re-Entry and the In-Between was conducted. Results: Analysis revealed five key themes: (1) experience of stress responses due to personal and external factors, (2) social connectedness and support as a facilitator of resilience, (3) performance of resilience-enhancing activities, (4) the roles of pregnancy and motherhood in the experiences of loss and resilience, and (5) the importance of home. Conclusion: Pregnant women have unique barriers that may negatively impact them during a natural disaster or other form of stressful event. They may benefit from assistance with navigating role transition during pregnancy, training in stress management strategies, and writing interventions to build resiliency and begin the process of recovery from trauma.

Social Isolation Stress Modulates Pregnancy Outcomes and the Inflammatory Profile of Rat Uterus.

Prenatal stressors have been linked to adverse pregnancy outcomes; including preterm birth (PTB). Recent work demonstrates that social isolation in mothers represents a silent stressor contributing to PTB risk. Here; we investigate the association of inflammatory and stress markers with PTB risk in Long-Evans rats exposed to social isolation stress (SIS) during preconception and pregnancy across four generations (F0-F3). Gestational length; blood glucose; corticosterone levels; and maternal and offspring weights were assessed in two SIS paradigms: transgenerational (TG) and multigenerational (MG) exposure. Maternal uterine tissues were collected 21 days after the dams gave birth. Exposure to SIS reduced pregnancy lengths in the parental generation and neonatal birth weights in the F1 and F2 generations. Interleukin (IL)-1ß (Il1b) mRNA levels increased in F0 animals but decreased in the offspring of both stress lineages. Protein levels of IL-1ß decreased in the TG lineage. Corticotrophin-releasing hormone receptor 1 (Crhr1) expression decreased in SIS-exposed F0 animals and increased in the TG-F2 and MG-F1 offspring. Expression of enzyme 11-ß hydroxysteroid dehydrogenase-2 (11bHSD2) was enhanced in F1 animals. These findings suggest SIS has adverse consequences on the F0 mothers; but their F1-F3 progeny may adapt to this chronic stress; thus supporting the fetal programming hypothesis.

Inflammatory Amplification: A Central Tenet of Uterine Transition for Labor.

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.

Resilient Parents Resilient Communities: A Pilot Study Trialing the Bounce Back and Thrive! Resilience-Training Program With Military Families.

INTRODUCTION: The resilience of Canadian military families (CMFs) - the main support of the Canadian Armed Forces service members (SMs) - is imperative. The Canadian Armed Forces aims to ensure that SMs and their families are resilient and SMs ready to respond when called upon for combat, peacekeeping or pandemic/disaster-response. Family concerns, however, can realistically distract SMs from the mission, potentially compromising themselves, their unit and the mission. Resilience-training programs such as Bounce Back and Thrive! (BBT) can help families manage the realities of military life. OBJECTIVE: This pilot study aimed to evaluate suitability of BBT implementation by Military Family Resource Centers (MFRCs), including whether BBT: (1) fosters resilience-building among parents, (2) facilitates CMF resilience-building, (3) can be contextualized for CMFs, and (4) supports MFRCs in cultivating a culture of resilience. METHODS: An exploratory qualitative design was used. BBT was offered to parents face-to-face. Participants completed focus groups after the first 6 sessions, final 4 sessions, and one-year post-intervention. Data was thematically analyzed. RESULTS: Nine military parents participated. Four major themes resulted: (1) military parent resilience-building, (2) CMF resilience-building, (3) BBT program feedback and contextualization, and (4) MFRCs as community resilience hubs. DISCUSSION: BBT enabled parents to gain a new perspective on resilience, engage in dialogue and intentionally role model resilience skills. Military-specific BBT contextualization and online-delivery formats would increase suitability and access for CMFs. Access to resilience programs delivered through MFRCs would support CMFs. Further research is warranted.

The Fort McMurray Mommy Baby Study: A Protocol to Reduce Maternal Stress Due to the 2016 Fort McMurray Wood Buffalo, Alberta, Canada Wildfire.

Introduction: Data show that maternal stress triggered by exposure to a natural disaster before, during or just after pregnancy is associated with adverse pregnancy and newborn outcomes. In this paper, the first aim is to describe our efforts to test a simple, low-cost intervention to large numbers of women following a major natural disaster. The second aim is to outline the challenges faced and lessons learned during the execution of this natural disaster study. Methods: The setting was the May 2016 Fort McMurray Wood Buffalo wildfire in northern Alberta, Canada. Women who were pregnant or preconception at the time of the disaster were invited to participate via social media. This prospective cohort study included a randomized controlled trial to test the effectiveness of an expressive writing intervention on the levels of prenatal maternal stress and maternal, birth, and early childhood outcomes. At recruitment and at multiple timepoints postpartum, a battery of questionnaires was administered to evaluate objective and subjective stress exposure to the fire as well as maternal mental health, resilience and its contributing factors as well as infant developmental milestones. Qualitative content analysis of the expressive writing was conducted. Discussion: There is an increasing need to develop effective, wide-spread, rapid, and low-cost interventions to reduce prenatal maternal stress, increase resilience, and improve pregnancy outcomes following a natural disaster. Though analysis of data is ongoing, we highlight the strengths of this study which include strong community participation, rapid recruitment of eligible participants, low-cost intervention and data acquisition, and successful testing of the intervention. We acknowledge the challenges we encountered including the high rate of participant disqualifications or losses due to incomplete collection of online data; evacuation, dispersal, and inconsistent return to homes; and the high levels of stress accumulated post-disaster which led to inability to complete the study. Despite potential challenges, there remains a need for such research amid natural disasters.

Enhancing Resilience in Canadian Military Families and Communities: A Qualitative Analysis of the Reaching In Reaching Out and Bounce Back and Thrive! Resiliency Skills Training Programs.

Introduction: A new vision of resilience and well-being for Canadian military service members (SMs), Veterans and their families has been championed by the Canadian Armed Forces (CAF) and Veterans Affairs Canada (VAC). Operationalizing this vision, which aims to support those who serve/have served and their families as they navigate life during and post-service, requires the support of service providers (SPs). Training SPs to deliver complementary resilience-training programs Reaching In… Reaching Out (RIRO; for adults working with parents of young children) and Bounce Back and Thrive! (BBT; for parents of children aged 0-8 years of age) may support this vision. Objective: To assess the appropriateness of RIRO/BBT trainer training for SPs, and RIRO and BBT resilience-training for military populations and families. Methods: This qualitative descriptive study involved the delivery of RIRO/BBT trainer training to SPs (n = 20), followed by focus groups (n = 6) with SPs and organisational leaders (n = 4). Focus groups were recorded, and data were transcribed and thematically-analysed. Results: Several themes emerged: (1) RIRO/BBT trainer training enabled SPs to model resilience and deliver the resilience-training programs, (2) training was appropriate and adaptable for the CAF and SMs/CMFs, and (3) training could support the development of resilient communities. Discussion: RIRO/BBT trainer training and RIRO and BBT resilience-training programs use a holistic, integrated, experiential, and community approach to resilience-building and align with CAF and VAC initiatives. Once contextualised, such programs could support resilience-building in the military context.

A Strategic Program for Risk Assessment and Intervention to Mitigate Environmental Stressor-Related Adverse Pregnancy Outcomes in the Indian Population.

The Problem: Global environmental stressors of human health include, but are not limited to, conflict, migration, war, natural disasters, climate change, pollution, trauma, and pandemics. In combination with other factors, these stressors influence physical and mental as well as reproductive health. Maternal stress is a known factor for adverse pregnancy outcomes such as preterm birth (PTB); however, environmental stressors are less well-understood in this context and the problem is relatively under-researched. According to the WHO, major Indian cities including New Delhi are among the world's 20 most polluted cities. It is known that maternal exposure to environmental pollution increases the risk of premature births and other adverse pregnancy outcomes which is evident in this population. Response to the Problem: Considering the seriousness of this problem, an international and interdisciplinary group of researchers, physicians, and organizations dedicated to the welfare of women at risk of adverse pregnancy outcomes launched an international program named Optimal Pregnancy Environment Risk Assessment (OPERA). The program aims to discover and disseminate inexpensive, accessible tools to diagnose women at risk for PTB and other adverse pregnancy outcomes due to risky environmental factors as early as possible and to promote effective interventions to mitigate these risks. OPERA has been supported by the Worldwide Universities Network, World Health Organization (WHO) and March of Dimes USA. Addressing the Problem: This review article addresses the influence of environmental stressors on maternal-fetal health focusing on India as a model population and describes the role of OPERA in helping local practitioners by sharing with them the latest risk prediction and mitigation tools. The consequences of these environmental stressors can be partially mitigated by experience-based interventions that build resilience and break the cycle of inter- and-transgenerational transmission. The shared knowledge and experience from this collaboration are intended to guide and facilitate efforts at the local level in India and other LMIC to develop strategies appropriate for the jurisdiction for improving pregnancy outcomes in vulnerable populations.

Maternal Mental Health after a Wildfire: Effects of Social Support in the Fort McMurray Wood Buffalo Study.

OBJECTIVE: Following disasters, perinatal women are vulnerable to developing post-traumatic stress disorder (PTSD)-like symptoms. Little is known about protective factors. We hypothesized that peritraumatic stress would predict PTSD-like symptoms in pregnant and postpartum women and would be moderated by social support and resilience. METHOD: Women (n = 200) who experienced the 2016 Fort McMurray Wood Buffalo wildfire during or shortly before pregnancy completed the Peritraumatic Distress Inventory (PDI), Peritraumatic Dissociative Experiences Questionnaire, and the Impact of Event Scale-Revised for current PTSD-like symptoms. They also completed scales of social support (Social Support Questionnaire-Short Form) and resilience (Connor-Davidson Resilience Scale). RESULTS: Greater peritraumatic distress (r = 0.56) and dissociative experiences (r = 0.56) correlated with more severe PTSD-like symptoms. Greater social support satisfaction was associated with less severe post-traumatic stress symptoms but only when peritraumatic distress was below average; at more severe levels of PDI, this psychosocial variable was not protective. CONCLUSIONS: Maternal PTSD-like symptoms after a wildfire depend on peritraumatic distress and dissociation. Higher social support satisfaction buffers the association with peritraumatic distress, although not when peritraumatic reactions are severe. Early psychosocial interventions may protect perinatal women from PTSD-like symptoms after a wildfire.

Climate change is a major stressor causing poor pregnancy outcomes and child development.

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.

Targeting Toll-like receptor-4 to tackle preterm birth and fetal inflammatory injury.

Every year, 15 million pregnancies end prematurely, resulting in more than 1 million infant deaths and long-term health consequences for many children. The physiological processes of labour and birth involve essential roles for immune cells and pro-inflammatory cytokines in gestational tissues. There is compelling evidence that the mechanisms underlying spontaneous preterm birth are initiated when a premature and excessive inflammatory response is triggered by infection or other causes. Exposure to pro-inflammatory mediators is emerging as a major factor in the 'fetal inflammatory response syndrome' that often accompanies preterm birth, where unscheduled effects in fetal tissues interfere with normal development and predispose to neonatal morbidity. Toll-like receptors (TLRs) are critical upstream gatekeepers of inflammatory activation. TLR4 is prominently involved through its ability to sense and integrate signals from a range of microbial and endogenous triggers to provoke and perpetuate inflammation. Preclinical studies have identified TLR4 as an attractive pharmacological target to promote uterine quiescence and protect the fetus from inflammatory injury. Novel small-molecule inhibitors of TLR4 signalling, specifically the non-opioid receptor antagonists (+)-naloxone and (+)-naltrexone, are proving highly effective in animal models for preventing preterm birth induced by bacterial mimetic LPS, heat-killed Escherichia coli, or the TLR4-dependent pro-inflammatory lipid, platelet-activating factor (PAF). Here, we summarise the rationale for targeting TLR4 as a master regulator of inflammation in fetal and gestational tissues, and the potential utility of TLR4 antagonists as candidates for preventative and therapeutic application in preterm delivery and fetal inflammatory injury.