Psychological stress during pregnancy is known to have a range of long-lasting negative consequences on the development and health of offspring. Here, we tested whether a measure of prenatal early-life stress was associated with a biomarker of physiological development at birth, namely epigenetic gestational age, using foetal cord-blood DNA-methylation data. Longitudinal cohorts from the Netherlands (Generation R Study [Generation R], n = 1,396), the UK (British Avon Longitudinal Study of Parents and Children [ALSPAC], n = 642), and Norway (Mother, Father and Child Cohort Study [MoBa], n1 = 1,212 and n2 = 678) provided data on prenatal maternal stress and genome-wide DNA methylation from cord blood and were meta-analysed (pooled n = 3,928). Measures of epigenetic age acceleration were calculated using three different gestational epigenetic clocks: \"Bohlin\", \"EPIC overlap\" and \"Knight\". Prenatal stress exposure, examined as an overall cumulative score, was not significantly associated with epigenetically-estimated gestational age acceleration or deceleration in any of the clocks, based on the results of the pooled meta-analysis or those of the individual cohorts. No significant associations were identified with specific domains of prenatal stress exposure, including negative life events, contextual (socio-economic) stressors, parental risks (e.g., maternal psychopathology) and interpersonal risks (e.g., family conflict). Further, no significant associations were identified when analyses were stratified by sex. Overall, we find little support that prenatal psychosocial stress is associated with variation in epigenetic age at birth within the general paediatric population.

OBJECTIVE: There is emerging evidence for an increased prevalence of autism in children of mothers with a migration background. To date, the mechanisms underlying this relationship are poorly understood. We investigated whether prenatal stress exposure mediates the association between maternal migration and child autistic traits, assessing first- and second-generation migrant mothers in the Netherlands and their children.
METHODS: The study was embedded in the prospective population-based Generation R cohort. Of the 4,727 participants, 1,773 mothers (38%) had a migration background. Prenatal stress was assessed using questionnaires related to stressful life events, family functioning, self-esteem, long-lasting difficulties, symptoms of psychopathology, social support, and perceived discrimination. Autistic traits were measured at age 6 years with the parent-reported Social Responsiveness Scale exclusively. Longitudinal multiple mediation analyses were performed. Analyses were stratified by migration origin (Europe and outside Europe) because of differences in migration characteristics.
RESULTS: Maternal migration background was associated with more experienced stress and with higher child autistic trait scores (Europe: mean = 0.42, SD = 0.25; outside Europe: mean = 0.50, SD = 0.24) compared to no migration background (Netherlands: mean = 0.38, SD = 0.23; both p < .01). Prenatal stress, especially perceived discrimination and maternal psychopathology, accounted for up to half of the total effect of maternal migration, which remained after adjusting for sociodemographic factors (Bindirect = 0.035, 95% CI = 0.027, 0.043, Btotal = 0.074).
CONCLUSIONS: Stress during pregnancy mediated the association between maternal migration status and child autistic traits. Future research should focus on early interventions to assess whether reducing prenatal stress exposure among women with a migration background can result in lower offspring autistic traits.
UNASSIGNED: We worked to ensure that the study questionnaires were prepared in an inclusive way. We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We actively worked to promote sex and gender balance in our author group. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.

Prenatal environment has long-lasting effects on offspring development and health. Research on prenatal stress identified various mechanisms of these effects, from changes in epigenetic and gene expression profiles to Maternal-Placental-Fetal (MPF) stress biology. There is also evidence for the role of additional risk and protective factors influencing the impact of prenatal stress on maternal and infant outcomes. Considering these findings, we present the study protocol of BABIP, a prospective birth cohort from Turkey. The aim of the project is to investigate the effect of prenatal stress on MPF stress biology (i.e. neuroendocrine, immune and metabolic systems), differential DNA methylation and gene expression patterns, and infant birth and developmental outcomes. We are recruiting 150 pregnant women and their babies for a longitudinal project with 4 time points: 20-24 (T1) and 30-34 (T2) weeks of pregnancy, and 1-month (T3) and 4-months (T4) after giving birth. Maternal early and prenatal environment (prenatal stress, early life stress, psychosocial resources, and health-related behaviors) are assessed during pregnancy with MPF stress biology, DNA methylation and gene expression measures. Infant birth outcomes, DNA methylation and development are assessed postpartum. BABIP is the first prospective birth cohort from Turkey with extensive measures on prenatal environment and health. Through investigating the multilevel impact of prenatal stress and related risk and protective factors during and after pregnancy, BABIP will contribute to our understanding of the mechanisms by which prenatal environment influences infant development and health. Being the first such cohort from Turkey, it may also allow identification of prenatal risk and protective factors specific to the context and population in Turkey.

Pregnancy is one of the most complex periods in a woman\'s life, not only because of the biological changes involved but also because of the psychological aspects. Stress during pregnancy refers to the concerns and distress that arise during pregnancy and that can be assessed by means of psychological and physiological scales. The aim of this study was to analyse prenatal stress and to evaluate its consequences on the health of both the mother and the foetus. A descriptive longitudinal study was carried out on a sample of 398 pregnant women being followed up during their entire pregnancy, who gave birth at the Punta de Europa University Hospital in Algeciras (Spain) between September 2021 and August 2023. The Prenatal Distress Questionnaire (PDQ) was used, as well as serum cortisol levels in each trimester of pregnancy and birth experience using the Childbirth Experience Questionnaire in its validated Spanish version, CEQ-E. Demographic and obstetric variables were included. One of the main findings was that experiencing more stress in late pregnancy had a negative impact on obstetric outcomes. Women who had higher levels of prenatal distress had higher blood cortisol levels and increased risk of having a caesarean section at delivery. A significant negative correlation was also found between stress and Apgar test values in the first minute of life. It is concluded that interventions promoted by the health system that provide comprehensive prenatal care contribute to decreased stress as perceived by these pregnant women, thus reducing the risk of maternal and foetal morbidity.

There is increasing evidence that prenatal stress elevates the risk of children\'s social-emotional development, but the mechanisms underlying this association are unclear. Home environment provides learning opportunities and stimulation required for children\'s early development and can be influenced by prenatal maternal stress. This study aimed to examine whether home environment can mediate the association between prenatal stress during the pandemic of coronavirus disease 2019 (COVID-19) and their offspring\'s social-emotional problems thereafter. A pilot sample was derived from 2020 to 2021 Maternal and Child Health Cohort study (N = 82) with the pregnant women recruited during the COVID-19 lockdown period in 2020. Prenatal stress was assessed using the Perceived Stress Scale. Home environment was measured using the Child Home Nurture Environment Scales. Mother-reported toddler social-emotional problems were assessed at 12 months of age. The mediation model was used for data analysis. The mean scores of social-emotional problems, which include externalizing, internalizing, dysregulation, and competence, were 10.98 (5.08), 14.72 (6.49), 15.15 (6.31), and 36.73 (10.26), respectively. Prenatal stress, home environment, and social-emotional problems were significantly related (P < 0.05). Home environment significantly mediated the association between prenatal stress and social-emotional problems with the indirect effect [95% CI] of 0.06 [0.01, 0.14] for externalizing behaviors, 0.10 [0.00, 0.24] for internalizing behaviors, - 0.15 [- 0.31, - 0.01] for competence, 0.08 [0.01, 0.17] and 0.08 [0.01, 0.21] for dysregulation. These findings suggest that prenatal stress may affect offspring\'s social-emotional problems through the home environment. Screening for prenatal stress and promoting supportive home environment may be potential strategies for social-emotional problems interventions in children.

Early life stress is robustly associated with poor sleep across life. Preliminary studies suggest that these associations may begin already in utero. Here, we study the longitudinal associations of prenatal psychosocial stress with sleep across childhood, and assess whether prenatal stress interacts with genetic liability for poor sleep.The study is embedded in the Generation R population-based birth cohort. Caregivers reported on prenatal psychosocial stress (life events, contextual, parental or interpersonal stressors) and on children\'s sleep at ages 2 months, 1.5, 2, 3 and 6 years. The study sample consisted of 4,930 children; polygenic risk scores for sleep traits were available in 2,063.Prenatal stress was consistently associated with more sleep problems across assessments. Effect sizes ranged from small (B = 0.21, 95%CI: 0.14;0.27) at 2 months to medium (B = 0.45, 95%CI: 0.38;0.53) at 2 years. Prenatal stress was moreover associated with shorter sleep duration at 2 months (Bhrs = -0.22, 95%CI: -0.32;-0.12) and at 2 years (Bhrs = -0.04, 95%CI -0.07; -0.001), but not at 3 years (Bhrs = 0.02, 95%CI: -0.02;0.06). Prenatal negative life events interacted with polygenic risk for insomnia to exacerbate sleep problems at 6 years (Binteraction = 0.07, 95%CI: 0.02;0.13).Psychosocial stress during pregnancy has negative associations with children\'s sleep that persist across childhood, and are exacerbated by genetic liability for insomnia. Associations with sleep duration were more pronounced in infancy and seem to attenuate with age. These findings highlight the role of the prenatal environment for developing sleep regulation, and could inform early intervention programs targeting sleep in children from high-risk pregnancies.

KID-PROTEKT is a child-centred psychosocial healthcare intervention which aims at improving the identification of psychosocial needs and navigation in the outpatient gynaecologic and paediatric setting. In this cluster randomized-controlled trail we examined the effect of KID-PROTEKT on the referrals (to support services) in comparison to the regular gynaecologic and paediatric outpatient healthcare . A variant based on the qualification of the healthcare providers (qualified treatment, QT) and a variant with social worker (supported treatment, ST) were compared to the regular healthcare (treatment as usual, TAU). Twenty-four gynaecologic and paediatric practices were randomized to one of three study arms. Therefore 8,458 pregnant women and families recruited in one of these practices were enrolled in the study. Participating patients reported on average 1.73 (SD = 1.34) psychosocial risks. In total 522 patients were linked to a support service. Compared to TAU, the probability of a referral was significantly higher in QT (OR = 10.70) and ST (OR = 11.28). Also, a higher number of psychosocial risks were linked to a referral (OR = 2.72). These findings support the importance of a psychosocial assessment in the gynaecologic and paediatric setting.
KID-PROTEKT es una intervención en asistencia sanitaria psicosocial centrada en el niño, cuyo objetivo es mejorar la detección de las necesidades psicosociales y la navegación en un entorno ambulatorio ginecológico y pediátrico. En este ensayo clínico aleatorizado por conglomerados analizamos el efecto de KID-PROTEKT en las derivaciones (a los servicios de apoyo) en comparación con la asistencia ginecológica y pediátrica externa periódica. Se comparó una variante basada en la cualificación de los proveedores de asistencia sanitaria (tratamiento cualificado, TC) y otra variante con trabajador social (tratamiento de apoyo, TA) con la asistencia sanitaria periódica (tratamiento habitual, TH). Se aleatorizaron 24 servicios ginecológicos y pediátricos en una de las tres ramas del estudio. De este modo participaron en el estudio 8,458 mujeres gestantes y familias reclutadas en una de estas prácticas. Los pacientes participantes notificaron una media de 1.73 (DT = 1.34) riesgos psicosociales. En total se vinculó a 522 pacientes a un servicio de apoyo. En comparación con el tratamiento habitual, la probabilidad de una derivación fue significativamente elevada en el tratamiento cualificado (OR = 10.70) y de apoyo (OR = 11.28). Igualmente se vinculó un elevado número de riesgos psicosociales a una derivación (OR = 2.72). Los resultados confirman la importancia de la evaluación psicosocial en el tratamiento ginecológico y pediátrico.

Few studies have examined how parenting influences the associations between prenatal maternal stress and children\'s mental health. The objectives of this study were to examine the sex-specific associations between prenatal maternal stress and child internalizing and externalizing symptoms, and to assess the moderating effects of parenting behaviors on these associations.
This study is based on 15 963 mother-child dyads from the Norwegian Mother, Father, and Child Cohort Study (MoBa). A broad measure of prenatal maternal stress was constructed using 41 self-reported items measured during pregnancy. Three parenting behaviors (positive parenting, inconsistent discipline, and positive involvement) were assessed by maternal report at child age 5 years. Child symptoms of internalizing and externalizing disorders (depression, anxiety, attention-deficit hyperactivity disorder, conduct disorder, and oppositional-defiant disorder) were assessed by maternal report at age 8. Analyses were conducted using structural equation modeling techniques.
Prenatal maternal stress was associated with child internalizing and externalizing symptoms at age 8; associations with externalizing symptoms differed by sex. Associations between prenatal maternal stress and child depression, and conduct disorder and oppositional-defiant disorder in males, became stronger as levels of inconsistent discipline increased. Associations between prenatal maternal stress and symptoms of attention-deficit hyperactivity disorder in females were attenuated as levels of parental involvement increased.
This study confirms associations between prenatal maternal stress and children\'s mental health outcomes, and demonstrates that these associations may be modified by parenting behaviors. Parenting may represent an important intervention target for improving mental health outcomes in children exposed to prenatal stress.

BACKGROUND: Early-life adverse experiences can elevate the magnitude of the risk of developmental psychopathology, but the potential synergistic effects of multiple factors have not been well studied.
OBJECTIVE: To determine whether prenatal exposures to maternal stress (Superstorm Sandy) and maternal cannabis use synergistically alter the risk of developmental psychopathology.
METHODS: The study included 163 children (53.4% girls), longitudinally tracked (ages 2-5 years) in relation to the effects of two early-life adverse exposures (Superstorm Sandy and maternal cannabis use). Offspring were grouped by exposure status (neither, only maternal cannabis use, only Superstorm Sandy or both). DSM-IV disorders for offspring were derived from structured clinical interviews; caregiver-reported ratings of family stress and social support were also assessed.
RESULTS: A total of 40.5% had been exposed to Superstorm Sandy and 24.5% to maternal cannabis use. Offspring exposed to both (n = 13, 8.0%), relative to those exposed to neither, had a 31-fold increased risk of disruptive behavioural disorders (DBDs) and a seven-fold increased risk of anxiety disorders. The synergy index demonstrated that offspring with two exposures had synergistic elevation in risk of DBDs (synergy index, 2.06, P = 0.03) and anxiety disorders (synergy index, 2.60, P = 0.004), compared with the sum of single risks. Offspring with two exposures had the highest parenting stress and lowest social support.
CONCLUSIONS: Our findings are consistent with the double-hit model suggesting that offspring with multiple early-life adverse exposures (Superstorm Sandy and maternal cannabis use) have synergistically increased risks of mental health problems. Given the increasing frequency of major natural disasters and cannabis use, especially among women under stress, these findings have significant public health implications.

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.