Prenatal Stress Research Articles

Prenatal Stress Modulates Placental and Fetal Serotonin Levels and Determines Behavior Patterns in Offspring of Mice

Available evidence from animal studies suggests that placental serotonin plays an important role in proper fetal development and programming by altering brain circuit formation, which later translates into altered abnormal adult behaviors. Several environmental stimuli, including stress and maternal inflammation, affect placental and, hence, fetal serotonin levels and thus may disturb fetal brain development. We investigated the effect of prenatal stress of varying intensities on the formation of adaptive behaviors in mouse offspring and the role of placental serotonin in these processes. Mild prenatal stress increased placental serotonin synthesis, whereas exposure to moderate stress decreased it. Prenatal stress of varying intensities also resulted in multidirectional changes in animal behavior in progeny, consistent with changes in serotonin levels in the placenta and fetal tissues. Mice exposed to mild prenatal stress showed higher sociality and exploratory activity, whereas, after moderate stress, in contrast, they avoided contact with other individuals of their species and had reduced exploratory activity, with no effect on locomotor activity. Thus, in mice, stressors of varying intensities during the critical period of intrauterine development can affect the synthesis of serotonin by the placenta and lead to multidirectional changes in animal behavior in postnatal life.

The effect of nursing care during pregnancy termination on women's prenatal grief, depression, anxiety, stress and coping levels: A randomized controlled study.

The termination of pregnancy is considered an emotionally devastating experience. Early intervention and counseling are essential to prevent adverse complications following pregnancy loss. This study aimed to determine the effect of nursing care based on Swanson's Theory of Caring on women's prenatal grief, depression, anxiety, stress, and coping levels during pregnancy termination. The training and counseling program, based on Swanson's Theory of Caring, included hospital care, a mobile application, and telephone follow-ups. We conducted this prospective randomized controlled experimental study in the gynecology and obstetrics clinic of a tertiary university hospital in Türkiye between September 2021 and May 2022. The study sample consisted of 50 women (intervention group: 25, control group: 25) whose pregnancy was terminated in the second trimester. The women were assigned to groups according to a randomization list created by a statistician. Data collection tools included a Personal Information Form, the Perinatal Grief Scale, the Depression, Anxiety, and Stress Scale, the Coping and Adaptation Process Scale, and the Numerical Rating Scale. We collected the data during hospitalization, between the 6th and 8thweeks after discharge, and at the 12thweek. We performed a chi-square test, a paired samples t-test, and an independent samples t-test on the IBM Statistical Package for the Social Sciences Statistics 26. The intervention group had lower mean perinatal grief (54.76 ± 19.49), depression (2.56 ± 2.39), anxiety (2.08 ± 2.10), and stress (3.52 ± 1.78) scores and higher mean coping and adjustment scores (140.48 ± 11.47) than the control group(p < .05). The intervention group also had a lower perception of labor pain, shorter discharge time, and a higher level of readiness for a new pregnancy (p < .05). The program that we applied in the study was effective in managing the pregnancy termination and post-discharge period in the population we studied.

Reduce Prenatal Maternal Stress to Improve Pregnancy and Birth Outcomes: Recommendations for U.S. Policy

Reduce Prenatal Maternal Stress to Improve Pregnancy and Birth Outcomes: Recommendations for U.S. Policy

Prenatal Maternal Psychological Stress (PMPS) and Its Effect on the Maternal and Neonatal Outcome: A Retrospective Cohort Study.

Prenatal psychology studies show that stress, depression, and psychological stress during pregnancy can have a significant impact on maternal and fetal health and are highly prevalent. The aim of the study was to compare maternal and neonatal short-term outcomes in pregnant women* (the asterisk (*) is used at the appropriate places in this text to indicate that all genders are included) with a history of prenatal maternal psychological stress (PMPS) with those of pregnant women* not exposed to PMPS to determine differences and identify risk factors. Statistical tests for differences and relative risks between the groups were carried out with the perinatal data of University Hospital Tübingen from 2022 using IBM SPSS. The study shows that PMPS has significant negative effects on various parameters, including the rate of premature births, preeclampsia, induction of birth, birth duration, and fetal asphyxia, as well as the birth weight of the children and their Apgar values (an assessment of newborn health scored shortly after birth). In addition, the risk of PMPS increases in women* with stillbirths and two or more previous miscarriages. However, the practical relevance must be critically scrutinized and confirmed by bigger studies. PMPS has a significant impact on the maternal and neonatal birth outcomes and must be identified as a risk factor in pregnancy. There is still a need for further research with larger samples, more balanced groups, and multivariate regression models to generate detailed, more transferable results and a deeper insight into the significant effects of PMPS and the role midwives can play in helping it.

Multifactorial effects of probiotic Parasutterella excrementihominis on gestational inflammation, offspring behaviour and prenatal-stress induced disruptions in tryptophan metabolism.

Prenatal stress (PNS) has widespread effects on offspring, including aberrant immune development and behavioural deficits. The microbiome is a mediator of the dissemination of stress effects to the offspring through immunomodulation and metabolite production. Metabolites derived from the mother and their gut microbiota pass to the foetus and can affect immune and nervous development. Stress affects the abundance of such metabolites, including the tryptophan (Trp) pathway, which are involved in immune and nervous system function. We hypothesized that the PNS is associated with dysregulation of Trp metabolism. We further posited that treatment with a Trp-metaboliser Parasutterella excrementihominis would abrogate PNS-associated deleterious effects on offspring development. To test this hypothesis, pregnant mice were exposed to restraint stress and administered P. excrementihominis (Dam n= 3-9; Offspring n= 5-10). PNS increased maternal gut Trp and both maternal and offspring inflammation. P. excrementihominis treatment reduced the PNS-induced excess pool of maternal gut Trp. Some PNS effects on foetal neuroinflammation were reduced in severity due to handling effects from bacterial gavage. However, P. excrementihominis was anti-inflammatory in dam and offspring and anxiolytic in offspring of Pe-treated dams. These data illustrate that elevated Trp levels are associated PNS and its downstream deleterious offspring inflammatory and behavioural outcomes while P. excrementihominis, a Trp-metabolizer, can ameliorate these effects and improve offspring outcomes.

Stress in pregnancy alters hepatic unfolded protein responses in male adult offspring

Stress is considered an independent risk factor for the development of cardiometabolic disorders, especially when it occurs during pregnancy, and it may play an important role in stress-induced fetal programming on the protein-folding homeostasis in hepatic endoplasmic reticulum. The study aimed to determine the effects of prenatal stress on the unfolded protein responses in the liver of male and female offspring of Wistar rats. Pregnant Wistar rats at 90 days old were divided into control and stress groups. The unpredictable stress protocol was performed from the 14th to the 21st day of pregnancy. The offspring of each group were divided into four groups according to sex and intervention. After the lactation period, the dams were anesthetized and euthanized for blood collection to determine plasma corticosterone levels. At 90 days old, the offspring were anesthetized and euthanized for liver tissue collection to measure protein expression of the endoplasmic reticulum stress. Dams submitted to prenatal stress showed an increase in corticosterone levels when compared to the control group. In the male offspring, prenatal stress induced lower body mass at birth and at 90 days compared to control, while females presented lower body mass only at birth. Prenatal stress reduced eIF2α expression in males, while increased p-eIF2α expression similarly in both sexes. Furthermore, only males had a greater p-eIF2α/eIF2α ratio and androgen receptor expression when compared to its respective control group and females. Prenatal stress induced a hepatic programming in the reticulum endoplasmic responses only in males at 90 days old by increasing androgen receptor, eIF2α phosphorylation and activity, while in females stress during pregnancy reduced cHDL and had little impact on hepatic unfolded protein response.

The role of prenatal perceived stress and hair cortisol as they relate to toddler socioemotional outcomes over the first three years

Prenatal maternal psychological distress and physiological stress (hypothalamic-pituitary-adrenal [HPA] activity) can negative impact early child development. Research rarely examines the combined or interactive role of prenatal perceived stress and HPA activity on child outcomes. The current longitudinal study examined how prenatal distress and HPA activity impacted child socioemotional functioning from age 1–3. This sample (n=148) was followed from pregnancy, 15-, 24- and 35-months postpartum. During pregnancy, mothers reported their levels of perceived stress and hair samples were collected, reflecting cortisol secretion in the past 3 months. At each postpartum timepoint, mothers reported toddler socioemotional functioning using the Brief Infant–Toddler Social and Emotional Assessment. Multivariate regression results indicated that higher maternal perceived stress interacted with higher hair cortisol levels in association with greater socioemotional problems at 15 and 24 months. In addition, there was a main effect of higher prenatal perceived stress in relation to greater socioemotional problems at 36 months. Exploratory sex-specific moderation analyses indicated that sex interacted with hair cortisol, such that higher levels of prenatal cortisol were associated greater behaviour problems and lower socioemotional competence for females compared to males at 24-months. Findings indicated the importance of examining both physiological stress and psychological stress in pregnancy, as they interact to impact child socioemotional development. Findings also highlight sex-specific prenatal effects.

The Interaction of Second Trimester Prenatal Maternal Inflammation and Psychosocial Stress on Offspring Depressive Symptoms in Adolescence

BackgroundHigher second trimester (T2) prenatal maternal inflammation (PNMI) and prenatal maternal psychosocial stress have been shown to independently contribute to offspring depression risk. Similarly, interactions between sources of inflammation and maternal daily life stress in T2, previously have been associated with increased offspring adolescent depressive symptoms. We aimed to extend previous findings by examining the potential interaction between exposure to higher T2 PNMI and maternal daily life stress on offspring depressive symptoms in adolescence. Methods614 mother-offspring dyads from the Child Health and Development Studies (CHDS) had data available for T2 maternal serum interleukin (IL)-6, IL-8, IL-1 receptor antagonist (IL-1ra), and soluble TNF receptor-II (sTNF-RII), presence/absence of maternal reported daily life stress coded from interviews primarily conducted in T2, and adolescent offspring (ages 15-18 years) depressive symptoms assessed via self-report. Interactions were evaluated using hierarchical multiple regressions, controlling for maternal education. ResultsMaternal daily life stress interacted with higher serum levels of maternal T2 IL-6 and T2 IL-8 to predict adolescent offspring depressive symptoms. Higher IL-6 and higher IL-8 were only associated with offspring depression in the presence of daily life stress. Maternal T2 IL-1ra and sTNF-RII were not associated with offspring adolescent depressive symptoms. ConclusionThe interaction of the adverse impacts of maternal daily life stress and higher maternal IL-6 and/or IL-8 levels during the second trimester may contribute significantly to exacerbate depression risk in adolescent offspring. These results have potential implications for multiple targets of future early intervention and prevention research.

Prenatal glucocorticoid exposure and congenital abdominal wall defects: Involvement of CXCR4 – SDF-1 signaling

Developmental defects of the ventral abdominal wall, such as gastroschisis, have been associated with prenatal stress exposure. To investigate this further, dexamethasone (DEX), a synthetic glucocorticoid, was administered to fertilized chicken eggs on day 1 of incubation to simulate stress, and embryonic development was subsequently analyzed through in-situ hybridization, immunohistochemistry, and histological methods. Significant developmental abnormalities were displayed by DEX-treated embryos, including open abdomens, reduced MYOG expression in the abdominal wall, and disrupted muscle fiber formation, as indicated by altered Myosin heavy chain patterns. Additionally, early markers of muscle development, such as Pax3, and the CXCR4-SDF-1 signaling axis, crucial for the migration of myogenic precursors of the dermomyotome, were markedly affected. Significant alterations in the expression of mesenchymal markers, including Vimentin and Fibronectin in the lateral plate mesoderm, were observed, alongside alterations in Pitx2, BMP4 and TFAP2A expression. Importantly, a downregulation of Glucocorticoid Receptors was identified, emphasizing the chronic stress exposure. These results provide critical insights into how DEX interferes with key developmental pathways, particularly those involving chemokines like CXCR4 and SDF-1, and other markers of mesodermal differentiation. An advancement in the understanding of the mechanisms underlying ventral abdominal wall defects in the context of prenatal stress is provided by this research, with potential implications for preventing these congenital anomalies.

Perinatal Psychoneuroimmunology of Prenatal Stress and Its Effects on Fetal and Postnatal Brain Development.

Prenatal stress (PS) impacts early behavioral, neuroimmune, and cognitive development. Pregnant rat models have been very valuable in examining the mechanisms of such fetal programming. A pregnant sheep model of maternal stress offers the unique advantages of chronic in utero monitoring and manipulation. This chapter presents the techniques used to model single and multigenerational stress exposures and their pleiotropic effects on the offspring.

Enduring effects of acute prenatal ischemia in rat soleus muscle, and protective role of erythropoietin.

Motor disorders are considered to originate mainly from brain lesions. Placental dysfunction or maternal exposure to a persistently hypoxic environment is a major cause of further motor disorders such as cerebral palsy. Our main goal was to determine the long-term effects of mild intrauterine acute ischemic stress on rat soleus myofibres and whether erythropoietin treatment could prevent these changes. Rat embryos were subjected to ischemic stress at embryonic day E17. They then received an intraperitoneal erythropoietin injection at postnatal days 1-5. Soleus muscles were collected at postnatal day 28. Prenatal ischemic stress durably affected muscle structure, as indicated by the greater fiber cross-sectional area (+ 18%) and the greater number of mature vessels (i.e. vessels with mature endothelial cells) per myofibres (+ 43%), and muscle biochemistry, as shown by changes in signaling pathways involved in protein synthesis/degradation balance (-81% for 4EBP1; -58% for AKT) and Hif1α expression levels (+ 95%). Erythropoietin injection in ischemic pups had a weak protective effect: it increased muscle mass (+ 25% with respect to ischemic pups) and partially prevented the increase in muscle degradation pathways and mature vascularization, whereas it exacerbated the decrease in synthesis pathways. Hence, erythropoietin treatment after acute ischemic stress contributes to muscle adaptation to ischemic conditions.

The Effect of Prenatal Stress on the Level of NO-Metabolites in the Central Nervous System

Nitric oxide performs a number of essential functions in the central nervous system. This neurotransmitter regulates apoptotic processes, differentiation and proliferation of neurons, synaptic activity, plasticity. Prenatal stress may be a factor affecting the NO level in different parts of the central nervous system (CNS). The aim of the work was to study the level of NO metabolites in phylogenetically different parts of the central nervous system in prenatally stressed mature male and female rats, depending on the stage of the estrous cycle. Pregnant female rats (n = 12) were subjected to stress from the 16th to the 19th days of pregnancy for 3 hours in the morning. The NO level was assessed in adult (4-month-old) offspring of both sexes. In males, there was a decrease in the level of NO metabolites in the cerebellum and hypothalamus and an increase in the spinal cord. The level of NO metabolites within the studied parts of the CNS of females in the control was higher, after undergoing prenatal stress it changed less compared to males: significant changes were noted in the spinal cord regardless of the estrus cycle stage and in the cerebellum at the stage of estrus. Thus, regardless of gender, the phylogenetically younger structure, the cerebral cortex, turned out to be the most resistant to prenatal stress; the most pronounced changes were noted in the phylogenetically ancient part of the CNS, the spinal cord. Given the importance of NO in the CNS as a key signaling molecule, any changes in its level under the influence of prenatal stress can both have a significant adaptive value and have negative consequences for the functional state of the tissue.

Assessment of Prenatal Transportation Stress and Sex on Gene Expression Within the Amygdala of Brahman Calves.

As the amygdala is associated with fear and anxiety, it is important to determine the potential effects of gestational stressors on behavior and stress responses in offspring. The objective of this study was to investigate the effects of prenatal transportation stress on amygdala gene expression in 25-day-old Brahman calves, focusing on sex-specific differences. Amygdala tissue samples from prenatally stressed (PNS) and control bull and heifer calves were analyzed using RNA sequencing. A thorough outlier detection process, utilizing visual inspection of multidimensional scaling plots, robust principal component analysis, and PCAGrid methods, led to the exclusion of 5 of 32 samples from subsequent analyses. Differential expression analysis revealed no significant treatment differences between the control and PNS groups within either sex. However, sex-specific differences in gene expression were identified in both the control and PNS groups. The control group showed seven differentially expressed genes between sexes, while ten were identified between PNS males and females, with seven located on the X chromosome. Among these was the ubiquitin-specific peptidase 9 X-linked gene, which plays a role in neurodevelopmental pathways. When comparing males to females, regardless of treatment, a total of 58 genes were differentially expressed, with 45 showing increased expression in females. Gene enrichment analysis indicated that many differentially expressed genes are associated with infectious disease-related pathways. Future research should explore amygdala size and functional responses to various postnatal stimuli.

Prenatal Maternal Stress Suppresses Embryonic Neurogenesis via Elevated Glucocorticoid Levels.

Although it is known that prenatal maternal stress (PNMS) has negative influence on nervous system development in offspring, there has been no solid evidence showing the effect of PNMS on early neurogenesis during development. In this study, we established a chick embryo model to investigate how PNMS affects early neurogenesis by mimicking an intrauterine environment with high dexamethasone (Dex) levels. The results showed that Dex-mimicked PNMS significantly suppressed the development of gastrula embryos and increased the risks of neural tube defects and cranial deformity. Using immunofluorescence staining and Western blots to determine the expression levels of pHIS3, PCNA/Sox2, we found that PNMS significantly inhibited the proliferation of neural progenitor cells, and the downregulation of TGFβ signaling pathway might be responsible for the inhibition. Furthermore, immunofluorescence staining and Western blots manifested that PNMS could suppress the differentiation of neural progenitor cells to neuronal lineages, but promote them to transform into neuroglial cells, which might be due to the restriction of expressions of key genes (BMP4, SHH, Wnt3a, Slug, and Msx1) related to neural differentiation. In summary, our data reveal that PNMS dramatically impacts the earliest stages of neural development, thereby greatly increasing the risk of physical and mental health problems in childhood or adulthood.

S-ketamine alleviates depression-like behavior and hippocampal neuroplasticity in the offspring of mice that experience prenatal stress

Prenatal stress exerts long-term impact on neurodevelopment in the offspring, with consequences such as increasing the offspring’s risk of depression in adolescence and early adulthood. S-ketamine can produce rapid and robust antidepressant effects, but it is not clear yet whether and how S-ketamine alleviates depression in prenatally stressed offspring. The current study incestigated the preliminary anti-depression mechanism of S-ketamine in prenatally stressed offspring, particularly with regard to neuroplasticity. The pregnant females were given chronic unpredictable mild stress on the 7th-20th day of pregnancy and their male offspring were intraperitoneally injected with a single dose of S-ketamine (10 mg/kg) on postnatal day 42. Our findings showed that S-ketamine treatment counteracted the development of depression-like behaviors in prenatally stressed offspring. At the cellular level, S-ketamine markedly enhanced neuroplasticity in the CA1 hippocampus: Golgi-Cox staining showed that S-ketamine alleviated the reduction of neuronal complexity and dendritic spine density; Transmission electron microscopy indicated that S-ketamine reversed synaptic morphology alterations. At the molecular level, by western blot and RT-PCR we detected that S-ketamine significantly upregulated the expression of BDNF and PSD95 and activated AKT and mTOR in the hippocampus. In conclusion, prenatal stress induced by chronic unpredictable mild stress leads to depressive-like behaviors and hippocampal neuroplasticity impairments in male offspring. S-ketamine can produce antidepressant effects by enhancing hippocampal neuroplasticity via the BDNF/AKT/mTOR signaling pathway.

Natural Disasters as a Maternal Prenatal Stressor and Children's Neurodevelopment: A Systematic Review.

The intrauterine period is a time of high sensitivity in the development of the embryo and the fetus. Therefore, low levels of maternal stress are closely associated with healthy brain development in the neonatal and early childhood periods. There is increasing evidence linking natural disasters as prenatal maternal stress (PNMS) to neurodevelopmental disorders (including subclinical manifestations). Natural disasters involve many factors in addition to the trauma they cause, including loss and the physical and psychosocial difficulties that result from that trauma. This review article aims to bring together research findings on the neurodevelopmental effects of natural disasters on children as PNMS. It also looks at how factors such as gestational age and gender contribute to these effects. We conducted a systematic review on PubMed, Web of Science, and Scopus, with 30 studies meting the inclusion criteria. This systematic review was conducted in accordance with the PRISMA guidelines. A total of 1,327,886 mother-child dyads participated in the included studies. The results of the studies indicate that natural disasters have a negative impact on children's outcomes in terms of cognitive development, language development, autism/autism-like features, motor skills, performance in mathematics, mental development, sleep, attention, behavioral and emotional problems, and various psychiatric comorbidities.

Perinatal running training reversed postnatal anxiety and depressive-like behavior and cognitive impairment in mice following prenatal subchronic variable stress

BackgroundPregnancy is a very complex and highly stressful time in women. Despite the high prevalence of postpartum depression, more than 50 % of mothers are undiagnosed or untreated, showing an urgent need to explore an effective preventive strategy. Regular physical activity has been suggested to be associated with an increased quality of life in pregnant and postpartum women. The purpose of this study was to determine whether perinatal running training can affect maternal care stress-related anxiety, depressive-like behavior, and cognitive changes in postpartum dams and to explore the possible underlying mechanism. Methods40 female C57BL/6J mice were divided into four groups: prenatal control (NC) and running training (EX) group (NC+EX), prenatal control and nonrunning training (RE) group (NC+RE), prenatal subchronic variable stress (SCVS) and running training group (SCVS+EX) and prenatal SCVS and non-running training group (SCVS+RE). Mice in prenatal stress groups were subjected to SCVS after pregnancy confirmed. Mice in running training groups subjected to running training throughout pregnancy and lactation. Then after the delivery, maternal behavior, cognitive changes, anxiety and depressive-like behaviors were tested. Then we measured the serum prolactin (PRL), hypothalamic–pituitary adrenal (HPA) axis activity, and adult hippocampus neurogenesis (AHN) in dams. ResultsCompared to NC+RE, prenatal SCVS caused cognitive impairments, the decrease in maternal behavior, and anxiety and depressive-like behavior in SCVS+RE dams, accompanying increase in HPA axis activity and decreased the PRL levels and AHN in postpartum period. Then compared to SCVS+RE, perinatal running training mitigates cognitive impairments, increased maternal behavior, and alleviates anxiety and depressive-like behavior in SCVS+EX dams, accompanying the decreased HPA axis activity, and the increased PRL levels and AHN in postpartum period. ConclusionOverall, this study suggests that perinatal running training might improve maternal care and reverse prenatal stress-related cognitive impairment and anxiety and depressive-like behavior in postpartum dams.

Long-Term Implicit Epigenetic Stress Information in the Enteric Nervous System and its Contribution to Developing and Perpetuating IBS.

Psychiatric and mood disorders may play an important role in the development and persistence of irritable bowel syndrome (IBS). Previously, we hypothesized that stress-induced implicit memories may persist throughout life via epigenetic processes in the enteric nervous system (ENS), independent of the central nervous system (CNS). These epigenetic memories in the ENS may contribute to developing and perpetuating IBS. Here, we further elaborate on our earlier hypothesis. That is, during pregnancy, maternal prenatal stresses perturb the HPA axis and increase circulating cortisol levels, which can affect the maternal gut microbiota. Maternal cortisol can cross the placental barrier and increase cortisol-circulating levels in the fetus. This leads to dysregulation of the HPA axis, affecting the gut microbiota, microbial metabolites, and intestinal permeability in the fetus. Microbial metabolites, such as short-chain fatty acids (which also regulate the development of fetal ENS), can modulate a range of diseases by inducing epigenetic changes. These mentioned processes suggest that stress-related, implicit, long-term epigenetic memories may be programmed into the fetal ENS during pregnancy. Subsequently, this implicit epigenetic stress information from the fetal ENS could be conveyed to the CNS through the bidirectional microbiota-gut-brain axis (MGBA), leading to perturbed functional connectivity among various brain networks and the dysregulation of affective and pain processes.

Prenatal maternal subjective distress predicts higher autistic-like traits in offspring: The Iowa Flood Study.

Autism spectrum disorder prevalence more than quadrupled in the United States between 2000 and 2020. Ice storm-related prenatal maternal stress (PNMS) predicts autistic-like trait severity in children exposed early in gestation. The objective was to determine the extent to which PNMS influences the severity and trajectory of autistic-like traits in prenatally flood-exposed children at ages 4-7 years and to test moderation by sex and gestational timing. Soon after the June 2008 floods in Iowa, USA, 268 women pregnant during the disaster were assessed for objective hardship, subjective distress, and cognitive appraisal of the experience. When their children were 4, 5½, and 7 years old, mothers completed the Social Communication Questionnaire (SCQ) to assess their children's autistic-like traits; 137 mothers completed the SCQ for at least one age. The final longitudinal multilevel model showed that the greater the maternal subjective distress, the more severe the child's autistic-like traits, controlling for objective hardship. The effect of PNMS on rate of change was not significant, and there were no significant main effects or interactions involving sex or timing. Prenatal maternal subjective distress, but not objective hardship or cognitive appraisal, predicted more severe autistic-like traits at age 4, and this effect remained stable through age 7.

Association between maternal perinatal stress and depression and infant DNA methylation in the first year of life

Maternal stress and depression during pregnancy and the first year of the infant’s life affect a large percentage of mothers. Maternal stress and depression have been associated with adverse fetal and childhood outcomes as well as differential child DNA methylation (DNAm). However, the biological mechanisms connecting maternal stress and depression to poor health outcomes in children are still largely unknown. Here we aim to determine whether prenatal stress and depression are associated with differences in cord blood mononuclear cell DNAm (CBMC-DNAm) in newborns (n = 119) and whether postnatal stress and depression are associated with differences in peripheral blood mononuclear cell DNAm (PBMC-DNAm) in children of 12 months of age (n = 113) from the Canadian Healthy Infant Longitudinal Development (CHILD) cohort. Stress was measured using the 10-item Perceived Stress Scale (PSS) and depression was measured using the 20-item Center for Epidemiologic Studies Depression Questionnaire (CESD). Both stress and depression were measured longitudinally at 18 weeks and 36 weeks of pregnancy and six months and 12 months postpartum. We conducted epigenome-wide association studies (EWAS) using robust linear regression followed by a sensitivity analysis in which we bias-adjusted for inflation and unmeasured confounding using the bacon and cate methods. To quantify the cumulative effect of maternal stress and depression, we created composite prenatal and postnatal adversity scores. We identified a significant association between prenatal stress and differential CBMC-DNAm at 8 CpG sites and between prenatal depression and differential CBMC-DNAm at 2 CpG sites. Additionally, we identified a significant association between postnatal stress and differential PBMC-DNAm at 8 CpG sites and between postnatal depression and differential PBMC-DNAm at 11 CpG sites. Using our composite scores, we further identified 2 CpG sites significantly associated with prenatal adversity and 7 CpG sites significantly associated with postnatal adversity. Several of the associated genes, including PLAGL1, HYMAI, BRD2, and ERC2 have been implicated in adverse fetal outcomes and neuropsychiatric disorders. These data further support the finding that differential DNAm may play a role in the relationship between maternal mental health and child health.