Maternal Prenatal Distress Research Articles

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.

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.

Associations between prenatal distress, mitochondrial health, and gestational age: findings from two pregnancy studies in the USA and Turkey.

Pregnancy outcomes are influenced by maternal distress but the pathways underlying these effects are still unknown. Mitochondria, crucial for stress adaptation and energy production, may link psychosocial stress to its biological effects, especially during pregnancy when energy demands significantly increase. This study explores two mitochondrial markers-circulating cell-free mitochondrial DNA (cf-mtDNA) and Growth Differentiation Factor-15 (GDF15)-as potential mitochondrial health indicators linking maternal distress to pregnancy outcomes in two longitudinal studies from the USA and Turkey. We analyzed biological, demographic, and psychological data from women in two pregnancy studies: EPI (N=187, USA, Mean age=29.6(SD=6.2) and BABIP (N=198, Turkey, Mean age=32.4(SD=4.0)). Data were collected at multiple time points during the perinatal period, including late 2nd and 3rd trimester, with EPI also including additional data at early 2nd trimester and 4-14 months postpartum. Prenatal maternal psychological distress was measured as perceived stress, anxiety, and depressive symptoms. Plasma cf-mtDNA and GDF15 levels were assessed using qPCR and ELISA, respectively. Statistical analyses included Wilcoxon signed-rank tests, Spearman correlations, and Mann-Whitney tests. Plasma cf-mtDNA levels did not change significantly during pregnancy in either study. Plasma GDF15 levels increased from early to late pregnancy in both studies and significantly decreased postpartum in EPI. Perinatal maternal distress in the late 2 nd and 3 rd trimesters was not associated with cf-mtDNA or GDF15 in either study. Metabolic distress, measured as higher pre-pregnancy BMI, was negatively correlated with GDF15 in the late 2 nd trimester in EPI and showed a similar trend in BABIP. Similarly, higher maternal psychological distress in the early 2 nd trimester were associated with lower cf-mtDNA and a trend for lower GDF15 in EPI. Finally, higher pre-pregnancy BMI and maternal distress in late pregnancy were linked to a smaller decline in GDF15 from late pregnancy to postpartum in EPI, suggesting an interaction between metabolic stress, prenatal distress and post-pregnancy physiological recovery. This study identified distinct patterns of plasma cf-mtDNA and GDF15 levels during the perinatal period across studies from two countries, revealing unique associations between maternal characteristics, prenatal distress, and pregnancy outcomes, suggesting that maternal distress can interact with energy mobilization during pregnancy.

Polycyclic aromatic hydrocarbon exposure effects on trajectories of maternal and adolescent mental health

BackgroundParental psychological distress is a well-known risk factor for developmental psychopathology, with longer term parental distress associated with worse youth mental health. Neurotoxicant exposure during pregnancy is a risk factor for both poor maternal and youth mental health. The impact of one class of pollutant, polycyclic aromatic hydrocarbons (PAH), on long-term trajectories of maternal distress and youth self-reported mental health symptoms in adolescence has been understudied.MethodsPAH exposure was measured by DNA adducts in maternal blood sampled during the third trimester of pregnancy. Maternal distress, operationalized as maternal demoralization, was measured at 11 timepoints (prenatal to child age 16). Adolescent mental health symptoms were measured at age 13–15. Follow up analyses examined a subset of measures available at age 15–20 years. Structural equation modeling examined associations between PAH exposure during pregnancy and latent growth metrics of maternal distress, and between maternal distress (intercept and slope) and youth mental health symptoms in a prospective longitudinal birth cohort (N = 564 dyads).ResultsHigher prenatal PAH exposure was associated with higher concurrent maternal distress. Prenatal maternal distress was associated with adolescent’s self-reported anxiety, depression, and externalizing problems. On average, maternal distress declined over time; a slower decline in mother’s distress across the course of the child’s life was associated with greater self-reported anxiety and externalizing problems in youth.ConclusionsOur findings are consistent with an intergenerational framework of environmental effects on mental health: PAH exposure during pregnancy affects maternal mental health, which in turn influences mental health outcomes for youth well into adolescence. Future research is necessary to elucidate the possible social and biological mechanisms (e.g., parenting, epigenetics) underlying the intergenerational transmission of the negative effects of pollution on mental health in caregiver-child dyads.

Biological and social cascades of prenatal contextual risk and maternal psychological distress to early-childhood adjustment.

In the peripartum, putative mechanisms in the transmission of prenatal contextual risk and maternal psychological distress include biological and social processes. In this study, path analyses were used to test unique, cascading pathways of prenatal contextual risk and pre- and postnatal maternal psychological distress through social mediators (parenting) and biological mediators (infant stress physiology) on infant temperament and toddler adjustment. The sample is comprised of racially and ethnically diverse first-time mothers (N = 200) living in low-income contexts (< 200% poverty) who were followed from pregnancy to 18-36 months postpartum. In pregnancy, mothers reported contextual risk and psychological distress (anxiety, depression). In the postpartum, mothers reported their psychological distress. At 2-4 months postpartum, observed mother-infant interactions were coded for sensitive responsiveness. Infant cortisol baseline and reactivity to a lab stressor were collected when infants were 4-6 months old. Mothers reported on infant's temperament (negative affect, effortful control) at 10-12 months and on child adjustment (internalizing, externalizing symptoms) at 18-36 months. Prenatal contextual risk predicted infant cortisol reactivity. Prenatal psychological distress predicted postnatal distress but, when accounting for postnatal distress, did not predict putative mediators or indicators of child adjustment. In contrast, maternal postnatal depression predicted subsequent maternal sensitive responsiveness, which in turn predicted later infant baseline cortisol and cortisol reactivity. Baseline cortisol predicted infant negative affectivity, which predicted toddler internalizing and externalizing symptoms. There was no evidence of mediated effects of prenatal variables on child adjustment outcomes, whereas contextual risk, postnatal psychological distress, and parenting were more salient predictors of child adjustment. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Supplemental Material for Biological and Social Cascades of Prenatal Contextual Risk and Maternal Psychological Distress to Early-Childhood Adjustment

Supplemental Material for Biological and Social Cascades of Prenatal Contextual Risk and Maternal Psychological Distress to Early-Childhood Adjustment

Prenatal Maternal Psychological Distress During the COVID-19 Pandemic and Newborn Brain Development

Elevated maternal psychological distress during pregnancy is associated with altered fetal brain development. During the COVID-19 pandemic, prenatal maternal psychological distress more than doubled. To examine the association of the pandemic and rising maternal psychological distress with brain growth in newborns using quantitative 3-dimensional volumetric magnetic resonance imaging (MRI). This prospective cross-sectional study recruited mother-infant dyads at Children's National Hospital, Washington, DC, during the COVID-19 pandemic (June 1, 2020, to June 30, 2022) into a longitudinal infant brain development study and compared them with an existing normative healthy cohort (recruited March 1, 2014, to December 31, 2019). Exclusion criteria included multiple gestation pregnancy, known or suspected congenital infection, documented chromosomal abnormalities, or any maternal contraindication to MRI, as well as prenatal COVID-19 exposure. Infants with structural brain abnormalities or a postnatal confirmation of a genetic syndrome were excluded. Psychological distress during COVID-19 pandemic. Prenatal maternal mental health was evaluated using the Spielberger State-Trait Anxiety Inventory and the Perceived Stress Scale. Neonates underwent nonsedated brain MRI. An ordinary least squares linear regression model was used to measure the differences in regional brain volumes of neonates born before vs during the pandemic with and without exposure to elevated prenatal maternal psychological distress after adjustment for neonatal sex and gestational age at MRI and maternal age and educational level. A total of 159 mother-infant dyads were included in the analysis: 103 before and 56 during the pandemic (median gestational age of infants, 39.6 [IQR, 38.4-40.4] weeks; median maternal age, 34.5 [IQR, 31.0-37.0] years). Eighty-three infants (52.2%) were female. Among the mothers, 130 (81.8%) had a college degree and 87 (54.7%) had a graduate degree. Forty-four mothers (27.7%) identified as Asian, Hispanic, or multiracial; 27 (17.0%), as Black; and 88 (55.3%), as White. Scores on anxiety and stress measures were significantly increased in the pandemic cohort. Infants of mothers with elevated maternal distress showed median reductions in white matter (-0.36 [95% CI, -0.61 to -0.11] cm3; Q < .001), right hippocampal (-0.35 [95% CI, -0.65 to -0.06] cm3; Q = .04), and left amygdala (-0.49 [95% CI, -0.84 to -0.13] cm3; Q = .03) volumes compared with infants of mothers with low distress levels. After adjusting for the cohort effect of the pandemic, elevated trait anxiety remained significantly associated with decreased left amygdalar volumes (-0.71 [95% CI, -1.12 to -0.29]; Q < .001). In this cross-sectional study of maternal-infant dyads prior to and during the COVID-19 pandemic, regional neonatal brain volumes were associated with elevated maternal psychological distress.

Early risk for child externalising symptoms: Examining genetic, prenatal, temperamental and parental influences.

This study utilized the Early Growth and Development Study (N = 561 adoptive children; 57.2% male, 55.3% White), a study of children adopted at birth, to examine heritable (birth parent psychopathology) and prenatal risk (prenatal maternal distress and smoking during pregnancy), infant negative affectivity, adoptive parent over-reactivity and warmth as independent predictors of childhood externalizing symptoms. The current study evaluated if: (1) infant negative affectivity and over-reactive parenting are candidate mediators for the effects of heritable and prenatal risk on externalizing symptoms and (2) parental warmth weakens the influence of heritable risk, prenatal risk, negative affectivity, and over-reactive parenting on externalizing symptoms. There were main effects of heritable risk, infant negative affectivity, and over-reactive parenting on child externalizing symptoms. The study found no support for the hypothesized mediation and moderation effects, suggesting that targeting parental over-reactivity rather than warmth would be more effective in reducing risk for childhood externalizing symptoms.

Stress during pregnancy and fetal serum BDNF in cord blood at birth

IntroductionAdverse environments during pregnancy impact neurodevelopment including cognitive abilities of the developing children. The mediating biological alterations are not fully understood. Maternal stress may impact the neurotrophic regulation of the offspring as early as in utero and at birth. Brain-derived neurotrophic factor (BDNF) is essential for neurodevelopment. Short-term higher levels of BDNF in mice upon stressors associate with lower BDNF later in life, which itself associates with depression in animals and humans. Stress including glucocorticoids may impact BDNF, but there is a lack of data at birth. This study investigated if stress near term associates with fetal BDNF at birth in humans. MethodsPregnant women near term who underwent primary cesarean sections (at 38.80±0.64 weeks), were included in this study (n=41). Stress at the end of pregnancy was assessed before the cesarean section by determining maternal depressive symptoms (EDPS), maternal state and trait anxiety (STAI-S and STAI-T), maternal prenatal distress (PDQ), stress over the past month (PSS), prenatal attachment to the offspring (PAI), maternal social support (F-Sozu), maternal early life stress (CTQ), socioeconomic status, and the glucocorticoids cortisol and cortisone (n=40) in amniotic fluid at birth. The association with fetal BDNF was analyzed. Cord blood serum of n=34 newborns at birth was analyzed for BDNF and newborn anthropometrics (weight, length and head circumference per gestational age at birth) were assessed. The association of fetal BDNF with anthropometrics at birth was analyzed. ResultsAfter a BDNF-outlier (>3 SD) was removed, higher fetal BDNF associated significantly with maternal depressive symptoms (r=0.398, p=0.022), with lower socioeconomic status as assessed by the average number of people per room in the household (r=0.526, p=0.002) and with borderline significance with net income per person in the household (r=-0.313, p=0.087) in the bivariate analyses. In multivariable analysis, BDNF stayed positively associated with maternal depressive symptoms (β=0.404, 95% CI [7.057, 306.041], p=0.041) and lower net income per person in the household (β=-0.562, 95% CI [-914.511, −60.523], p=0.027) when controlling for maternal age, maternal pre-pregnancy BMI, fetal sex and gestational age. Fetal BDNF did not associate with newborn anthropometrics with the outlier removed in bivariate analyses or in multivariable analyses when controlling for maternal BMI and fetal sex. ConclusionMaternal depressive symptoms and lower socioeconomic status associated with higher fetal BDNF when controlling for confounders. Fetal BDNF did not associate with newborn anthropometrics with the outlier removed. Further studies should investigate how early altered BDNF associate with the development and possibly psychopathology of the offspring.

A longitudinal study examining the associations between prenatal and postnatal maternal distress and toddler socioemotional developmental during the COVID-19 pandemic.

Elevated psychological distress, experienced by pregnant women and parents, has been well-documented during the COVID-19 pandemic. Most research focuses on the first 6-months postpartum, with single or limited repeated measures of perinatal distress. The present longitudinal study examined how perinatal distress, experienced over nearly 2years of the COVID-19 pandemic, impacted toddler socioemotional development. A sample of 304 participants participated during pregnancy, 6-weeks, 6-months, and 15-months postpartum. Mothers reported their depressive, anxiety, and stress symptoms, at each timepoint. Mother-reported toddler socioemotional functioning (using the Brief Infant-Toddler Social and Emotional Assessment) was measured at 15-months. Results of structural equation mediation models indicated that (1) higher prenatal distress was associated with elevated postpartum distress, from 6-weeks to 15-months postpartum; (2) associations between prenatal distress and toddler socioemotional problems became nonsignificant after accounting for postpartum distress; and (3) higher prenatal distress was indirectly associated with greater socioemotional problems, and specifically elevated externalizing problems, through higher maternal distress at 6weeks and 15months postpartum. Findings suggest that the continued experience of distress during the postpartum period plays an important role in child socioemotional development during the COVID-19 pandemic.

Negative associations between maternal prenatal hair cortisol and child socioemotional problems

Maternal prenatal distress can participate in the programming of offspring development, in which exposure to altered maternal long-term cortisol levels as measured by hair cortisol concentrations (HCC) may contribute. Yet, studies investigating whether and how maternal prenatal HCC associates with problems in child socioemotional development are scarce. Furthermore, questions remain regarding the timing and potential sex-specificity of fetal exposure to altered cortisol levels and whether there are interactions with maternal prenatal distress, such as depressive symptoms. The subjects were drawn from those FinnBrain Birth Cohort families that had maternal reports of child socioemotional problems (the Brief Infant-Toddler Social and Emotional Assessment [BITSEA] at 2 years and/or the Strengths and Difficulties Questionnaire [SDQ] at 5 years) as follows: HCC1 population: maternal mid-pregnancy HCC measured at gestational week 24 with 5 cm segments to depict cortisol levels from the previous five months (n = 321); and HCC2 population: end-of-pregnancy HCC measured 1–3 days after childbirth (5 cm segment; n = 121). Stepwise regression models were utilized in the main analyses and a sensitivity analysis was performed to detect potential biases. Negative associations were observed between maternal HCC2 and child BITSEA Total Problems at 2 years but not with SDQ Total difficulties at 5 years, and neither problem score was associated with HCC1. In descriptive analyses, HCC2 was negatively associated with Internalizing problems at 2 years and SDQ Emotional problems at 5 years. A negative association was observed among 5-year-old girls between maternal HCC1 and SDQ Total Difficulties and the subscales of Conduct and Hyperactivity/inattentive problems. When interactions were also considered, inverse associations between HCC2 and BITSEA Internalizing and Dysregulation Problems were observed in subjects with elevated prenatal depressive symptoms. It was somewhat surprising that only negative associations were observed between maternal HCC and child socioemotional problems. However, there are previous observations of elevated end-of-pregnancy cortisol levels associating with better developmental outcomes. The magnitudes of the observed associations were, as expected, mainly modest. Future studies with a focus on the individual changes of maternal cortisol levels throughout pregnancy as well as studies assessing both maternal and child HPA axis functioning together with child socioemotional development are indicated.

Maternal prenatal and postnatal psychological distress trajectories and impact on cognitive development in 4-year-old children: the Japan Environment and Children's Study.

Maternal prenatal and postnatal psychological distress, including depression and anxiety, may affect children's cognitive development. However, the findings have been inconsistent. We aimed to use the dataset from the Japan Environment and Children's Study, a nationwide prospective birth cohort study, to examine this association. We evaluated the relationship between the maternal six-item version of the Kessler Psychological Distress Scale (K6) scores and cognitive development among children aged 4 years. K6 was administered twice during pregnancy (M-T1; first half of pregnancy, M-T2; second half of pregnancy) and 1 year postpartum (C-1y). Cognitive development was assessed by trained testers, using the Kyoto Scale of Psychological Development 2001. Multiple regression analysis was performed with the group with a K6 score ≤ 4 for both M-T1 and M-T2 and C-1y as a reference. Records from 1,630 boys and 1,657 girls were analyzed. In the group with K6 scores ≥ 5 in both M-T1 and M-T2 and C-1Y groups, boys had significantly lower developmental quotients (DQ) in the language-social developmental (L-S) area (partial regression coefficient: -4.09, 95% confidence interval: -6.88 - -1.31), while girls did not differ significantly in DQ for the L-S area. Among boys and girls, those with K6 scores ≤ 4 at any one or two periods during M-T1, M-T2, or C-1y did not have significantly lower DQ for the L-S area. Persistent maternal psychological distress from the first half of pregnancy to 1 year postpartum had a disadvantageous association with verbal cognitive development in boys, but not in girls aged 4 years.

Antidepressants use during pregnancy and child psychomotor, cognitive and language development at 2years of age-Results from the 3D Cohort Study.

Introduction: Approximately 5.5% of pregnant women take antidepressants. Studies on prenatal exposure to antidepressants reported no association with child cognition, and inconsistent results with motor function and language development. A limitation has been the failure to adjust for prenatal maternal distress. Objectives: Assess the associations between prenatal exposure to antidepressants and child development at age two, while adjusting for maternal depressive symptoms and stress during pregnancy. Explore indirect effects through birth complications and consider sex-specific associations. Methods: This is an ancillary study of the 3D (Design Develop, Discover) Study initiated during pregnancy. Data on antidepressants were collected through medication logs spanning the entire pregnancy. Depressive symptoms and stress were assessed during pregnancy by self-reported questionnaires, motor and cognitive development with the Bayley Scales of Infant and Toddler Development (BSID-III), and language development with the MacArthur Communicative Development Inventories at age 2. Multiple linear regressions were used to assess the associations between exposure and developmental outcomes. Mediation models were used to assess indirect effects. Interaction terms were introduced to assess sex-specific associations. Results: 1,489 mother-child dyads were included, of whom 61 (4.1%) reported prenatal antidepressant use. Prenatal exposure was negatively associated with motor development (B = -0.91, 95% CI -1.73, -0.09 for fine motor, B = -0.89, 95% CI -1.81, 0.02 for gross motor), but not with cognitive (B = -0.53, 95% CI -1.82, 0.72) and language (B = 4.13, 95% CI -3.72, 11.89) development. Adjusting for maternal prenatal distress only slightly modified these associations. No indirect effect or differential effect according to child sex were found. Conclusion: This study supports evidence of a negative association between prenatal exposure to antidepressants and motor development at age two, after adjusting for maternal distress, but the effect size remains very small, with about only one BSID-III point lower in average.

Mothers’ prenatal distress accelerates adrenal pubertal development in daughters

Human life history schedules vary, partly, because of adaptive, plastic responses to early-life conditions. Little is known about how prenatal conditions relate to puberty timing. We hypothesized that fetal exposure to adversity may induce an adaptive response in offspring maturational tempo. In a longitudinal study of 253 mother-child dyads followed for 15 years, we investigated if fetal exposure to maternal psychological distress related to children’s adrenarche and gonadarche schedules, assessed by maternal and child report and by dehydroepiandrosterone sulfate (DHEA-S), testosterone, and estradiol levels. We found fetal exposure to elevated maternal prenatal psychological distress predicted earlier adrenarche and higher DHEA-S levels in girls, especially first-born girls, and that associations remained after covarying indices of postnatal adversity. No associations were observed for boys or for gonadarche in girls. Adrenarche orchestrates the social-behavioral transition from juvenility to adulthood; therefore, significant findings for adrenarche, but not gonadarche, suggest that prenatal maternal distress instigates an adaptive strategy in which daughters have earlier social-behavioral maturation. The stronger effect in first-borns suggests that, in adverse conditions, it is in the mother’s adaptive interest for her daughter to hasten social maturation, but not necessarily sexual maturation, because it would prolong the duration of the daughter allomothering younger siblings. We postulate a novel evolutionary framework that human mothers may calibrate the timing of first-born daughters’ maturation in a way that optimizes their own reproductive success.

Maternal prenatal distress exposure negatively associates with the stability of neonatal frontoparietal network

Maternal prenatal distress (PD), frequently defined as in utero prenatal stress exposure (PSE) to the developing fetus, influences the developing brain and numerous associations between PSE and brain structure have been described both in neonates and in older children. Previous studies addressing PSE-linked alterations in neonates’ brain activity have focused on connectivity analyses from predefined seed regions, but the effects of PSE at the level of distributed functional networks remains unclear. In this study, we investigated the impact of prenatal distress on the spatial and temporal properties of functional networks detected in functional MRI data from 20 naturally sleeping, term-born (age 25.85 ± 7.72 days, 11 males), healthy neonates. First, we performed group level independent component analysis (GICA) to evaluate an association between PD and the identified functional networks. Second, we searched for an association with PD at the level of the stability of functional networks over time using leading eigenvector dynamics analysis (LEiDA). No statistically significant associations were detected at the spatial level for the GICA-derived networks. However, at the dynamic level, LEiDA revealed that maternal PD negatively associated with the stability of a frontoparietal network. These results imply that maternal PD may influence the stability of frontoparietal connections in neonatal brain network dynamics and adds to the cumulating evidence that frontal areas are especially sensitive to PSE. We advocate for early preventive intervention strategies regarding pregnant mothers. Nevertheless, future research venues are required to assess optimal intervention timing and methods for maximum benefit.

Examining the relationship between fetal cortical thickness, gestational age, and maternal psychological distress

In utero exposure to maternal stress, anxiety, and depression has been associated with reduced cortical thickness (CT), and CT changes, in turn, to adverse neuropsychiatric outcomes. Here, we investigated global and regional (G/RCT) changes associated with fetal exposure to maternal psychological distress in 265 brain MRI studies from 177 healthy fetuses of low-risk pregnant women. GCT was measured from cortical gray matter (CGM) voxels; RCT was estimated from 82 cortical regions. GCT and RCT in 87% of regions strongly correlated with GA. Fetal exposure was most strongly associated with RCT in the parahippocampal region, ventromedial prefrontal cortex, and supramarginal gyrus suggesting that cortical alterations commonly associated with prenatal exposure could emerge in-utero. However, we note that while regional fetal brain involvement conformed to patterns observed in newborns and children exposed to prenatal maternal psychological distress, the reported associations did not survive multiple comparisons correction. This could be because the effects are more subtle in this early developmental window or because majority of the pregnant women in our study did not experience high levels of maternal distress. It is our hope that the current findings will spur future hypothesis-driven studies that include a full spectrum of maternal mental health scores.

Exploring the differentiation of behavioural and emotional problems across childhood: A prospective longitudinal cohort study.

An individual's overall burden of behavioural and emotional problems across childhood is associated with increased likelihood of later mental health conditions. However, the relative extent of behavioural versus emotional problems - that is, the extent to which the domains are differentiated from one another - may provide additional information about who is at risk of developing a mental health condition. Here, we seek to validate differentiation as an independent predictor of later mental health conditions, and to explore its aetiology. We analysed data from ~79,000 children in the population-based Norwegian Mother, Father, and Child Cohort Study, and linked health-care registries. In preregistered analyses, we modelled the extent and rate of differentiation of behavioural and emotional problems between ages 1.5-5years, and estimated associations with later symptoms (age 8) and diagnoses (after age 8). We also explored the aetiology of differentiation by estimating associations with early life exposures and, in a subset of 23,945 full siblings, assessing the impact of accounting for unobserved familial confounding. Differentiation of behavioural and emotional problems was associated with later symptoms and diagnoses of mental health conditions, independent of total problems. Maternal at-risk drinking (β=0.04 [0.02, 0.06]) and parental relationship problems (β=0.04 [0.02, 0.05]) were associated with higher behavioural relative to emotional problems at age 5. Maternal prenatal distress (|β|=0.04 [0.03, 0.06]), concurrent distress (|β|=0.04 [0.02, 0.06]) and parental education (|β|=0.05 [0.04, 0.07]) predicted higher emotional relative to behavioural problems at age 5. Estimates for maternal prenatal distress and at-risk drinking were consistent across both unadjusted and adjusted analyses accounting for unobserved familial risk. Differentiation of behavioural and emotional problems in early childhood represents a valid source of inter-individual variability linked to the later emergence of psychopathology and may be relevant for early detection and prevention strategies for mental health.

Social Disparities Increase Risk of SUDs

Back to table of contents Previous article Next article Annual MeetingFull AccessSocial Disparities Increase Risk of SUDsNick ZagorskiNick ZagorskiSearch for more papers by this authorPublished Online:16 Jun 2023https://doi.org/10.1176/appi.pn.2023.07.7.53AbstractAt APA’s 2023 Annual Meeting, National Institute on Drug Abuse Director Nora Volkow, M.D., highlighted the relationship between early stress and brain development.The COVID-19 pandemic made many hidden truths more abundantly clear, National Institute on Drug Abuse (NIDA) Director Nora Volkow, M.D., said during a presentation at APA’s Annual Meeting in May. Among them was the power of social determinants of health—as racial and ethnic minorities, those with less income, and people with psychiatric illness bore the brunt of negative health outcomes.Social determinants of health are also strong risk factors for substance use disorders, Volkow continued.She noted that brain imaging data indicate that the environment plays a stronger role than genetics in guiding brain development between the ages of 5 and 8 years. In households with dysfunction, stress, and/or financial difficulties, children tend to receive more negative environmental stimulation and less positive stimulation.Making use of new imaging data from over 7,500 9- and 10-year-old children enrolled in NIDA’s Adolescent Brain and Cognitive Development (ABCD) Study, Volkow together with Dardo Tomasi, Ph.D., a staff scientist at the National Institute on Alcohol Abuse and Alcoholism, evaluated the relationship between family income and brain structure. Their analysis revealed that children from higher-income families appeared to have larger and thicker frontal cortices as well as higher cognitive test scores compared with children from lower-income families.Another brain imaging study of babies born during the COVID-19 pandemic uncovered a similar pattern: Greater levels of maternal stress and anxiety were associated with worse connectivity between the amygdala and frontal cortex in the infants. Lower social support was a significant predictor of clinically elevated prenatal maternal distress, the study found.Such early changes in brain structure may increase the risk of later problems with substance use, Volkow noted, as data show that people who are more sensitive to negative conditioning (for example, learning quickly not to touch a hot stove after getting burned) and/or have blunted reward conditioning are at higher risk of addiction.Showing a correlation is one thing, but is there evidence that correlation can be changed?Well, yes, Volkow noted. She pointed to one controlled intervention in which 1,000 low-income mothers from several U.S. cities were randomly allocated either a $333 or $20 monthly stipend after the birth of their child. About 400 of the babies were selected for EEG scans at one year of age, and the EEG data found that babies of mothers with the high-cash stipend had more robust and active brain activity than the babies of mothers who received the low-cash stipend.“This simple monetary intervention probably reduced the mother’s stress [related to] how she would support her child and maybe let them spend more time together,” Volkow said. There was a clear positive neurodevelopmental outcome.Volkow acknowledged that the United States may not have the resources right now to implement some of these early-life interventions on a large scale, but building up the infrastructure is one of NIDA’s priorities. Just attenuating the impact of poverty can boost childhood development and prevent susceptibility to substance use down the road, she said. ■Resources“Associations of Family Income with Cognition and Brain Structure in USA Children: Prevention Implications”“Prenatal Maternal Distress During the COVID-19 Pandemic and Associations With Infant Brain Connectivity” ISSUES NewArchived

Early Life Adversity alters Maternal-Fetal-Placental Biology and may Propagate Population Health Disparities

Research findings dating back decades indicate that prenatal maternal psychological distress can predict poor child health outcomes, with potentially lasting effects. These results have been extensively replicated and have encouraged longitudinal cohort studies to begin before birth; many clinical interventions to promote maternal health in pregnancy are underway. Studies of prenatal maternal distress emphasize in utero effects, likely arising from multiple biological changes. Alternatively, developmental and life history models suggest that prenatal distress likely has pre-pregnancy developmental origins. Studies linking pre-pregnancy adversity to prenatal maternal distress and maternal-fetal-placental biology are underway, but are typically limited in scope. The ECHO-UPSIDE cohort is well-positioned to contribute novel data to this area; it is a prospective pregnancy cohort study of a socio-economically and racially/ethnically diverse sample at elevated psychosocial risk but normal medical risk status (Rochester, NY; n=326). Clinical, socio-demographic, health data and extensive biological samples were collected at each trimester and placentae were collected at birth. Women who experienced higher adversity in early childhood (using Adverse Childhood Experiences [ACE] scale) reported wide-spread differences in prenatal health, with moderate effect sizes (Cohen’s d>.5) for depressive and anxiety symptoms, stress, body mass index (BMI), sleep disturbance, and diet. Higher ACE scores predicted altered (flatter) diurnal cortisol pattern throughout pregnancy (p<.01). There was also limited but significant impact on maternal immune activation from specific immune markers and measures of placenta structure and function. The studies demonstrate potential pathways through which pre-pregnancy adversity may propagate persisting health disparities.

The role of m6A methylation in prenatal maternal psychological distress and birth outcome

BackgroundPrenatal maternal psychological distress (PMPD) is a known risk factor for adverse birth outcomes. N6-methyladenosine RNA (m6A) methylation is crucial in moderating RNA biology. This study aimed to evaluate the relationships between PMPD, birth outcomes, and placental m6A methylation. MethodsThis was a prospective cohort study. PMPD exposure was assessed by questionnaires about prenatal stress, depression, and anxiety. Placental m6A methylation was measured using a colorimetric assay. The relationships between PMPD, m6A methylation, gestational age (GA), and birth weight (BW) were analyzed using structural equation models (SEMs). Maternal weight gain during pregnancy and infant sex were included as covariables. ResultsThe study included 209 mother-infant dyads. In an adjusted SEM, PMPD was associated with BW (B = −26.034; 95 % CI: −47.123, −4.868) and GA (B = −0.603; 95 % CI: −1.102, −0.154). M6A methylation was associated with PMPD (B = 0.055; 95 % CI: 0.040,0.073) and BW (B = −305.799; 95 % CI: −520.164, −86.460) but not GA. The effect of PMPD on BW was partially mediated by m6A methylation (B = −16.817; 95 % CI: −31.348, −4.638) and GA (B = −12.280; 95 % CI: −23.612, −3.079). Maternal weight gain was associated with BW (B = 5.113; 95 % CI: 0.229,10.438). LimitationsThe study sample size was small, and the specific mechanism of m6A methylation on birth outcomes needs to be further explored. ConclusionsIn this study, PMPD exposure negatively affected BW and GA. Placental m6A methylation was associated with PMPD and BW and partially mediated the effect of PMPD on BW. Our findings highlight the importance of perinatal psychological evaluation and intervention.