Teratological research shows that both prenatal stress and prenatal substance exposure have a significant impact on neurodevelopmental outcomes in children. Using human research, the purpose of this narrative review is to explore the degree to which these exposures may represent complex prenatal and postnatal risks for the development of cognition and behavior in children. An understanding of the HPA axis and its function during pregnancy as well as the types and operationalization of prenatal stress provide a context for understanding the direct and indirect mechanisms by which prenatal stress affects brain and behavior development. In turn, prenatal substance exposure studies are evaluated for their importance in understanding variables that indicate a potential interaction with prenatal stress including reactivity to novelty, arousal, and stress reactivity during early childhood. The similarities and differences between prenatal stress exposure and prenatal substance exposure on neurodevelopmental outcomes including arousal and emotion regulation, cognition, behavior, stress reactivity, and risk for psychopathology are summarized. Further considerations for teratological studies of prenatal stress and/or substance exposure include identifying and addressing methodological challenges, embracing the complexity of pre-and postnatal environments in the research, and the importance of incorporating parenting and resilience into future studies.

Prenatal stress is increasingly recognized as a significant factor impacting an individual\'s life from the beginning. This comprehensive review explores the intricate relationship between prenatal stress and its effects on behaviour, cognition, and psychopathology. Key findings reveal that prenatal stress can lead to a wide range of adverse outcomes in offspring, including neurodevelopmental disorders, emotional dysregulation, cognitive deficits, mood disorders, and an increased risk of psychopathological conditions. These effects\' mechanisms involve epigenetic modifications, hypothalamic-pituitary-adrenal (HPA) axis dysregulation, neurodevelopmental alterations, inflammatory processes, and changes in brain structure and function. Moreover, moderating factors such as maternal stress levels, maternal mental health, socioeconomic status, social support, and early-life adversity can significantly influence the impact of prenatal stress. The review also discusses intervention and prevention strategies, emphasizing the importance of prenatal stress reduction programs, maternal mental health support, nutritional interventions, and targeted early interventions for at-risk populations. These findings have substantial implications for public health and clinical practice, highlighting the need for a holistic approach to prenatal care that prioritizes maternal well-being and mitigates the lasting effects of prenatal stress. Addressing this critical issue promises healthier generations and stronger communities in the future.

Stress during pregnancy can lead to significant adverse outcomes for maternal mental health. Early evaluation of prenatal stress can help identify treatment needs and appropriate interventions. Disparities in the social determinants of health can contribute to stress, but what constitutes stress during pregnancy within the social determinants of health framework is poorly understood.
To scope how prenatal stress is defined and measured among pregnant people exposed to three prominent social stressors in the United States: insecurity pertaining to food, housing, and immigration.
We included all studies that focused on stress during pregnancy in the context of food insecurity, housing instability, and immigration, given their recent policy focus due to the COVID-19 pandemic and ongoing political discourse, in addition to their importance in American College of Obstetricians and Gynecologists (ACOG\'s) social determinants of health screening tool.
We searched PubMed, Scopus, and Web of Science for articles published between January 2012 and January 2022.
Using a piloted charting tool, we extracted relevant study information from the selected articles and analyzed the content pertaining to stress.
An initial search identified 1,023 articles, of which 24 met our inclusion criteria. None of the studies defined prenatal stress, and only one used the Prenatal Distress Questionnaire, a prenatal stress-specific tool to measure it. The Perceived Stress Scale was the most common instrument used in seven studies. Fifteen studies measured over 25 alternative exposures that researchers theorized were associated with stress, and 4 of the 15 studies did not explain the association between the measure and stress.
Our findings demonstrate a fundamental inconsistency in how prenatal stress is defined and measured in the context of social determinants of health, limiting the comparison of results across studies and the potential development of effective interventions to promote better maternal mental health.

Exposure to early life stress (ELS), prenatal or postnatal during childhood and adolescence, can significantly impact mental and physical health. The role of the intestinal microbiome in human health, and particularly mental health, is becoming increasingly evident. This systematic review aims to summarize the clinical data evaluating the effect of ELS on the human intestinal microbiome. The systematic review (CRD42022351092) was performed following PRISMA guidelines, with ELS considered as exposure to psychological stressors prenatally and during early life (childhood and adolescence). Thirteen articles met all inclusion criteria, and all studies reviewed found a link between ELS and the gut microbiome in both prenatal and postnatal periods. However, we failed to find consensus microbiome signatures associated with pre- or postnatal stress, or both. The inconsistency of results is likely attributed to various factors such as different experimental designs, ages examined, questionnaires, timing of sample collection and analysis methods, small population sizes, and the type of stressors. Additional studies using similar stressors and validated stress measures, as well as higher-resolution microbiome analytical approaches, are needed to draw definitive conclusions about the links between stress and the human gut microbiome.

Stress before conception and during pregnancy is associated with less favorable maternal and child health. Alterations in prenatal cortisol levels may serve as a central biological pathway linking stress to adverse maternal and child health. Research examining associations between maternal stress from childhood through pregnancy and prenatal cortisol has not been comprehensively reviewed.
The current scoping review of 48 papers synthesizes studies reporting on associations between stress before conception and during pregnancy with maternal cortisol in pregnancy. Eligible studies measured childhood, the proximal preconception period, pregnancy, or lifetime stress based on stress exposures or appraisals and measured cortisol in saliva or hair during pregnancy.
Higher maternal childhood stress was associated with higher cortisol awakening responses and alterations in typical pregnancy-specific changes in diurnal cortisol patterns across studies. In contrast, most studies of preconception and prenatal stress reported null associations with cortisol and those reporting significant effects were inconsistent in direction. A few studies found that the associations between stress and cortisol during pregnancy varied as a function of several moderators including social support and environmental pollution.
Although many studies have evaluated effects of maternal stress on prenatal cortisol, this scoping review is the first to synthesize existing literature on this topic. The association between stress before conception and during pregnancy and prenatal cortisol may depend on the developmental timing of stress and several moderators. Maternal childhood stress was more consistently associated with prenatal cortisol than proximal preconception or pregnancy stress. We discuss methodological and analytic factors that may contribute to mixed findings.

Exposure to stress during early development may lead to altered neurobiological functions, thus increasing the risk for psychiatric illnesses later in life. One potential mechanism associated with those outcomes is the disruption of glial density and morphology, despite results from rodent studies have been conflicting. To address that we performed a systematic review and meta-analysis of rodent studies that investigated the effects of prenatal stress (PNS) and early life stress (ELS) on microglia, astrocyte, and oligodendrocyte density and morphology within the offspring. Our meta-analysis demonstrates that animals exposed to PNS or ELS showed significant increase in microglia density, as well as decreased oligodendrocyte density. Moreover, ELS exposure induced an increase in microglia soma size. However, we were unable to identify significant effects on astrocytes. Meta-regression indicated that experimental stress protocol, sex, age, and type of tissue analyzed are important covariates that impact those results. Importantly, PNS microglia showed higher estimates in young animals, while the ELS effects were stronger in adult animals. This set of data reinforces that alterations in glial cells could play a role in stress-induced dysfunctions throughout development.

Animals vary on intrinsic characteristics such as temperament and stress responsiveness, and this information can be useful to experimentalists for identifying more homogeneous subsets of animals that show consistency in risk for a particular research outcome. Such information can also be useful for balancing experimental groups, ensuring animals within an experiment have similar characteristics. In this review, we describe the BioBehavioral Assessment Program at the California National Primate Research Center, which, since its inception in 2001, has been providing quantitative information on intrinsic characteristics to scientists for subject selection and balancing, and to colony management staff for management purposes. We describe the program and review studies relating to asthma, autism, behavioral inhibition, etc., where the BBA Program was used to select animals. We also review our work, showing that factors such as rearing, ketamine exposure, and prenatal experience can affect biobehavioral organization in ways that some investigators might want to control for in their studies. Attention to intrinsic characteristics of subject populations is consistent with the growing interest in precision medicine and can lead to a reduction in animal numbers, savings in time and money for investigators, and reduced distress for the animals.

Exposure to prenatal stress (PNS) can lead to long-lasting neurobiological and behavioral consequences for the offspring, which may enhance the susceptibility for mental disorders. The hypothalamus-pituitary-adrenal (HPA) axis and the immune system are two major factors involved in the stress response. Here, we performed a systematic review and meta-analysis of rodent studies that investigated the effects of PNS exposure on the HPA axis and inflammatory cytokines in adult offspring. Our analysis shows that animals exposed to PNS display a consistent increase in peripheral corticosterone (CORT) levels and central corticotrophin-releasing hormone (CRH), while decreased levels of its receptor 2 (CRHR2). Meta-regression revealed that sex and duration of PNS protocol are covariates that moderate these results. There was no significant effect of PNS in glucocorticoid receptor (GR), CRH receptor 1 (CRHR1), pro- and anti-inflammatory cytokines. Our findings suggest that PNS exposure elicits long-lasting effects on the HPA axis function, providing an important tool to investigate in preclinical settings key pathological aspects related to early-life stress exposure. Furthermore, researchers should be aware of the mixed outcomes of PNS on inflammatory markers in the adult brain.

The present study systematically reviewed 56 articles that assessed hair cortisol concentrations during pregnancy collected from PubMed, Scopus, and Web of Science on 8/9/19 and updated on 6/29/20. Our goals were to establish reference ranges by trimester based on published studies. The majority of any given sample (e.g., 70 %, the range of -1SD to +1SD) is expected to fall between 0 and 34.15 pg/mg in trimester 1 and 2, and between 8.59 and 44 pg/mg in trimester 3, with very wide ranges (e.g., values of >250 pg/mg) and substantially higher values (e.g., averages of 200\'s-300\'s reaching as high as 768 pg/mg) coming out of one specific lab. Delineating a reference range for hair cortisol concentrations across pregnancy is challenging because of known factors like differences in values returned by different laboratories and assay types. We observed inconsistency in descriptions of the data and data preparation steps post-assay. Key findings include that only half of the studies examining all three trimesters showed a constant increase in mean levels (most retrospectively assessed via segmenting), with considerable variability in patterns of change. None of the studies reported individual patterns of change. Examining within-person changes are an important next step for the field. We conclude that researchers should more clearly report decisions around outliers, units, and specifics of data transformations in the future in order to improve our ability to compare findings across studies, to understand differences in HCC values reported, and potentially to understand differences in reported associations of HCC with other phenotypes in the literature.

Gestational period plays critical role in neuropsychological development. One of the genes that undergoes changes by prenatal stress (PNS) exposure, is the gene coding brain derived neurotrophic factor (BDNF). Studies have reported different patterns of change following PNS in BDNF, which emphasizes the complexity of the issue. In this review, systematic search of PubMed, Scopus, Web of Science and Cochrane CENTRAL databases was performed. Primary searches resulted in 2132 studies and finally 43 studies were found to meet the inclusion criteria. Transcriptional and epigenetic changes of BDNF gene in the brain were recorded. Decreased or unchanged BDNF total mRNA and BDNF mature protein, with hypermethylation of the coding exons were the most reported changes. However, stress paradigm, gender of the fetus and the day of sacrifice were found to significantly affect the results. Hippocampus and prefrontal cortex are the most vulnerable regions. They can show long lasting and persistent transcriptional and epigenetics changes of BDNF gene following PNS. Further studies evaluating the importance of these findings in humans are essential.