Maternal Prenatal Psychological Distress Research Articles

Brain structural and functional outcomes in the offspring of women experiencing psychological distress during pregnancy.

In-utero exposure to maternal psychological distress is increasingly linked with disrupted fetal and neonatal brain development and long-term neurobehavioral dysfunction in children and adults. Elevated maternal psychological distress is associated with changes in fetal brain structure and function, including reduced hippocampal and cerebellar volumes, increased cerebral cortical gyrification and sulcal depth, decreased brain metabolites (e.g., choline and creatine levels), and disrupted functional connectivity. After birth, reduced cerebral and cerebellar gray matter volumes, increased cerebral cortical gyrification, altered amygdala and hippocampal volumes, and disturbed brain microstructure and functional connectivity have been reported in the offspring months or even years after exposure to maternal distress during pregnancy. Additionally, adverse child neurodevelopment outcomes such as cognitive, language, learning, memory, social-emotional problems, and neuropsychiatric dysfunction are being increasingly reported after prenatal exposure to maternal distress. The mechanisms by which prenatal maternal psychological distress influences early brain development include but are not limited to impaired placental function, disrupted fetal epigenetic regulation, altered microbiome and inflammation, dysregulated hypothalamic pituitary adrenal axis, altered distribution of the fetal cardiac output to the brain, and disrupted maternal sleep and appetite. This review will appraise the available literature on the brain structural and functional outcomes and neurodevelopmental outcomes in the offspring of pregnant women experiencing elevated psychological distress. In addition, it will also provide an overview of the mechanistic underpinnings of brain development changes in stress response and discuss current treatments for elevated maternal psychological distress, including pharmacotherapy (e.g., selective serotonin reuptake inhibitors) and non-pharmacotherapy (e.g., cognitive-behavior therapy). Finally, it will end with a consideration of future directions in the field.

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.

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.

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.

Prospective associations between various prenatal exposures to maternal psychological stress and neurodevelopment in children within 24 months after birth

BackgroundThere is increasing evidence that prenatal exposure to maternal psychological distress may be a factor influencing offspring neurodevelopment, but stress type-dependent effects of maternal psychological distress on offspring neurodevelopment in early childhood have yet to be fully elucidated. Additionally, although positive maternal mental health exerts potential effects in protecting against adverse health outcomes, few investigators have considered the effects of positive maternal mental health on offspring neurodevelopment in early childhood. AimsTo determine the associations between various prenatal exposures to maternal psychological distress and positive life-event experiences and offspring neurodevelopment within 24 months of age. MethodsA total of 4412 mother-child dyads were recruited from the Shanghai Maternal-Child Pairs Cohort (Shanghai MCPC). Maternal perceived stress, negative life-event stress, positive life-event experiences around the time of conception (i.e., three months prior to and after conception) were assessed at 12–16 gestational weeks, and maternal anxiety and depressive symptoms were assessed at 32–36 gestational weeks. We measured children's neurodevelopment using the Ages and Stages Questionnaire, Third Edition (ASQ-3) at two, six, 12, and 24 months postnatally. We then exploited generalized linear models to estimate the associations between prenatal maternal psychological distress and positive life-event experiences and children's neurodevelopment at the above periods, and generalized linear mixed models were applied to assess the associations between maternal psychological distress and positive life-event experiences and suspected developmental delay (SDD) in children within 24 months after birth based on a longitudinal design. ResultsMaternal perceived stress and negative life-event stress around the time of conception, and anxiety and depressive symptoms during late pregnancy were negatively associated with scores of children's neurodevelopment at two, six, 12, and 24 months of age; while maternal life-event experiences were positively associated with scores of children's neurodevelopment. Longitudinal analysis revealed that higher levels of maternal negative life-event stress and depressive symptoms augmented the risk of SDD in personal-social (OR = 1.435, 1.681). Mothers who experienced higher levels of positive life-event experiences exhibited a reduced risk of SDD in gross motor and personal-social domains (OR = 0.373, 0.350). ConclusionsPrenatal exposure to maternal psychological distress is negatively associated with children's neurodevelopment in early childhood depending upon the type of distress. Maternal positive life-event experiences around the time of conception appeared to present potential benefits for child neurodevelopment.

Maternal prenatal psychological distress and motor/cognitive development in two-year-old offspring: The Japan Environment and Children's Study.

Maternal prenatal psychological distress, including depression and anxiety, may affect offspring's motor/cognitive development. However, research findings have been inconsistent. We used a dataset from the Japan Environment and Children's Study to evaluate associations between maternal six-item Kessler Psychological Distress Scale (K6) scores and motor/cognitive development among offspring at two years of age. Their offspring's motor/cognitive development was assessed using the Kyoto Scale of Psychological Development 2001. Records for 1859 male and 1817 female offspring were analyzed. The maternal K6 was administered twice during pregnancy: at a median of 14.6 weeks (M-T1) and 27.3 weeks (M-T2) of gestation. Multiple regression analysis was performed with the group with K6 scores ≤4 at both M-T1 and M-T2 as a reference. In the group with K6 scores ≥5 at both M-T1 and M-T2, male offspring had significantly lower developmental quotients (DQ) in the posture-motor area (partial regression coefficient [B]: -3.68, 95% confidence interval [CI]: -5.92 to -1.44) and language-social area (B: -1.93; 95%CI: -3.73 to -0.12), while female offspring had a lower DQ for the language-social area (B: -1.95; 95%CI: -3.73 to -0.17). In those with K6 scores ≥5 only at M-T1 or M-T2, male and female offspring did not differ significantly in DQ for any area. Continuous maternal psychological distress from the first to the second half of pregnancy was associated with lower motor and verbal cognitive development in male offspring and lower verbal cognitive development in female offspring at 2 years compared with the group without persistent maternal prenatal psychological distress.

Maternal distress, DNA methylation, and fetal programing of stress physiology in Brazilian mother-infant pairs.

Maternal prenatal psychosocial stress is associated with adverse hypothalamic-pituitary-adrenal axis (HPAA) function among infants. Although the biological mechanisms influencing this process remain unknown, altered DNA methylation is considered to be one potential mechanism. We investigated associations between maternal prenatal psychological distress, infant salivary DNA methylation, and stress physiology at 12 months. Mother's distress was measured via depression and anxiety in early and late pregnancy in a cohort of 80 pregnant adolescents. Maternal hair cortisol was collected during pregnancy. Saliva samples were collected from infants at 12 months to quantify DNA methylation of three stress-related genes (FKBP5, NR3C1, OXTR) (n=62) and diurnal cortisol (n=29). Multivariable linear regression was used to test for associations between prenatal psychological distress, and infant DNA methylation and cortisol. Hair cortisol concentrations in late pregnancy were negatively associated with two sites of FKBP5 (site 1: B=-22.33, p=.003; site 2: B=-15.60, p=.012). Infants of mothers with elevated anxiety symptoms in late pregnancy had lower levels of OXTR2 CpG2 methylation (B=-2.17, p=.03) and higher evening salivary cortisol (B=0.41, p=.03). Furthermore, OXTR2 methylation was inversely associated with evening cortisol (B=-0.14, p-value≤.001). Our results are, to our knowledge, the first evidence that the methylation of the oxytocin receptor may contribute to the regulation of HPAA during infancy.

Impact of prenatal maternal psychological distress on fetal biometric parameters in household air pollution-exposed Nigerian women.

RationaleStudies identify prenatal household air pollution (HAP) exposure and maternal psychological distress (PMPD) as independent factors contributing to gestational ill-health and adverse birth outcomes.ObjectiveWe investigated the impact of PMPD on fetal biometric parameters (FBP) in HAP-exposed pregnant Nigerian women.MethodsThe randomized controlled trial (RCT; ClinicalTrials.gov NCT02394574) investigated effects of HAP exposure in pregnant Nigerian women (n = 324), who customarily cooked with polluting fuels (firewood or kerosene). Half of the women (intervention group) were given CleanCook ethanol stoves to use for 156 days during the study. Once a month, all women were administered an abridged version of the SF-12v2TM health-related quality of life questionnaire to assess psychological distress. Using mixed effects linear regression models, adjusted for relevant covariates, we analyzed associations between the women’s exposure to PM2·5 (particulate matter with an aerodynamic diameter<2·5 microns) from HAP, their PMPD scores, and FBP (ultrasound estimated fetal weight [UEFW], head circumference [HC], abdominal circumference [AC], femur length [FL], biparietal diameter [BPD], estimated gestational age [GA] and intrauterine growth restriction [IUGR]), and birth anthropometric measures (birth weight [BW] and birth length [BL]).ResultsPMPD negatively impacted UEFW, HC, FL, BPD and BL (p<0·05). Controls (kerosene/firewood users) experienced significantly higher PMPD compared with ethanol-stove users (p<0·05). The mediation analysis revealed that the proportion of the outcome (fetal biometrics, birth anthropometrics, IUGR and GA), which can be explained via PMPD by groups (intervention vs. control) after adjusting for confounding variables was 6·2% (0·062). No significant correlation was observed between levels of PM2.5 exposure and PMPD scores.ConclusionsPMPD was an independent mediator of adverse fetal biometric parameters in pregnant women, who were exposed to HAP from burning of firewood/kerosene. Formulating preventative measures to alleviate maternal distress during pregnancy and reducing exposure to HAP is important from public health perspectives.

Association between maternal prenatal psychological distress and autism spectrum disorder among 3-year-old children: The Japan Environment and Children's Study.

Maternal prenatal psychological distress, which includes depression and anxiety, affects the onset of autism spectrum disorder (ASD). However, there is no consistent knowledge regarding at which term during pregnancy psychological distress affects the risk of ASD among children. We used a dataset obtained from the Japan Environment and Children's Study, which is a nationwide prospective birth cohort study, to evaluate the association between the six-item Kessler Psychological Distress Scale (K6) and ASD among 3-year-old children. A total of 78,745 children were analyzed, and 355 of them were diagnosed with ASD (0.45%). The maternal K6 was administered twice during pregnancy: at a median of 15.1 weeks (M-T1) and at that of 27.4 weeks (M-T2) of gestation. Multivariate logistic regression analyses demonstrated that the group with a maternal K6 score of ≥5 at both M-T1 and M-T2 was significantly associated with ASD among the children (adjusted odds ratio, 1.440; 95% confidence interval, 1.104-1.877) compared to the group with a score of ≤4 at both M-T1 and M-T2. There was no significant difference between the group with a score of ≥5 only at M-T1 or M-T2 and that with a score of ≤4 at both M-T1 and M-T2. In conclusion, from the first to the second half of pregnancy, continuous maternal psychological distress was associated with ASD among 3-year-old children. Contrarily, in the group without persistent maternal psychological distress during pregnancy, there was no significant association.

Association of Elevated Maternal Psychological Distress, Altered Fetal Brain, and Offspring Cognitive and Social-Emotional Outcomes at 18 Months

Prenatal maternal psychological distress is associated with disturbances in fetal brain development. However, the association between altered fetal brain development, prenatal maternal psychological distress, and long-term neurodevelopmental outcomes is unknown. To determine the association of fetal brain development using 3-dimensional magnetic resonance imaging (MRI) volumes, cortical folding, and metabolites in the setting of maternal psychological distress with infant 18-month neurodevelopment. Healthy mother-infant dyads were prospectively recruited into a longitudinal observational cohort study from January 2016 to October 2020 at Children's National Hospital in Washington, DC. Data analysis was performed from January 2016 to July 2021. Prenatal maternal stress, anxiety, and depression. Prenatal maternal stress, anxiety, and depression were measured using validated self-report questionnaires. Fetal brain volumes and cortical folding were measured from 3-dimensional, reconstructed T2-weighted MRI scans. Fetal brain creatine and choline were quantified using proton magnetic resonance spectroscopy. Infant neurodevelopment at 18 months was measured using Bayley Scales of Infant and Toddler Development III and Infant-Toddler Social and Emotional Assessment. The parenting stress in the parent-child dyad was measured using the Parenting Stress Index-Short Form at 18-month testing. The cohort consisted of 97 mother-infant dyads (mean [SD] maternal age, 34.79 [5.64] years) who underwent 184 fetal MRI visits (87 participants with 2 fetal studies each) with maternal psychological distress measures between 24 and 40 gestational weeks and completed follow-up infant neurodevelopmental testing. Prenatal maternal stress was negatively associated with infant cognitive performance (β = -0.51; 95% CI, -0.92 to -0.09; P = .01), and this association was mediated by fetal left hippocampal volume. In addition, prenatal maternal anxiety, stress, and depression were positively associated with all parenting stress measures at 18-month testing. Finally, fetal cortical local gyrification index and sulcal depth were negatively associated with infant social-emotional performance (local gyrification index: β = -54.62; 95% CI, -85.05 to -24.19; P < .001; sulcal depth: β = -14.22; 95% CI, -23.59 to -4.85; P = .002) and competence scores (local gyrification index: β = -24.01; 95% CI, -40.34 to -7.69; P = .003; sulcal depth: β = -7.53; 95% CI, -11.73 to -3.32; P < .001). In this cohort study of 97 mother-infant dyads, fetal cortical local gyrification index and sulcal depth were associated with infant 18-month social-emotional and competence outcomes, and fetal left hippocampal volume mediated the association between prenatal maternal stress and infant cognitive outcome. These findings suggest that altered prenatal brain development in the setting of elevated maternal distress has adverse infant sociocognitive outcomes, and identifying early biomarkers associated with long-term neurodevelopment may assist in early targeted interventions.

Maternal prenatal psychological distress and vitamin intake with children's neurocognitive development.

Maternal prenatal psychological distress (PPD) is increasingly linked to sub-optimal child neurodevelopment. Daily intake of prenatal vitamin during pre-conception and early pregnancy may ameliorate the effects of PPD on cognition in the offspring. PPD was assessed in early (12-16 weeks) and late (28-32 weeks) gestation in the Ontario Birth Study. Prenatal vitamin supplement intake information was collected in early gestation. Child cognition at 4 years was assessed using the NIH Toolbox. Poisson regression was used to investigate associations between PPD and/or prenatal vitamin intake and child cognition. Four hundred and eighteen mother-child dyads were assessed. Moderate-severe PPD experienced during early gestation was associated with reduced cognition (adjusted incidence rate ratio (IRRadj) = 3.71, 95% confidence interval (CI): 1.57-8.77, P = 0.003). Daily intake of prenatal vitamins was not associated with cognition (IRRadj = 1.34, 95% CI: 0.73-2.46, P = 0.34). Upon stratification, the experience of mild-severe PPD with daily intake of prenatal vitamins was associated with higher incident rates of suboptimal cognition compared to children of women with daily prenatal vitamin intake without any episode of PPD (IRRadj = 2.88, 95% CI: 1.1-7.4). Moderate-severe PPD in early pregnancy is associated with poor cognition in children and daily intake of prenatal vitamin did not ameliorate this association. Our findings expand on existing literature by highlighting that exposure to prenatal psychological distress (PPD), in moderate-to-severe form, in the early stages of pregnancy, can have detrimental effects on the offspring's cognitive development at 4 years. Overall, prenatal vitamin intake did not ameliorate the effects of PPD. Early screening and treatment of prenatal maternal mental illness is crucial.

Maternal prenatal psychological distress associates with offspring early-life wheezing - FinnBrain Birth Cohort.

BackgroundExposure to prenatal maternal psychological distress may contribute to the development of childhood atopic disorders. Little is known about the importance of distress severity and its duration for the risk. Our aim was to investigate how chronic maternal depressive and anxiety symptoms across gestation influence the risk of wheezing and eczema at child age 24 months.MethodsThe study population was drawn from the FinnBrain Birth Cohort Study, including 1305 mother‐infant dyads followed across gestation until the child age of 24 months when the outcomes were mother‐reported wheezing ever and doctor‐diagnosed eczema. To investigate the risk of wheezing phenotypes, wheezing with and without eczema was separated. Maternal distress was assessed with the Edinburgh Postnatal Depression Scale for depressive and the Symptom Checklist‐90 for anxiety symptoms three times during pregnancy, and the chronicity was demonstrated using symptom trajectories composed by latent growth mixture modeling.ResultsOf the children, 219/1305 (17%) had wheezing ever and 285/1276 (22%) had eczema. Risk of wheezing ever was elevated with maternal consistently high depressive symptoms (adjusted odds ratio 2.74; 95% confidence interval 1.37–5.50) or moderate and increasing anxiety symptoms (1.94; 1.06–3.54, respectively). Similarly, wheezing without eczema was associated with consistently high depressive (3.60; 1.63–7.94, respectively) and moderate and increasing anxiety symptoms (2.43; 1.21–4.91, respectively).ConclusionsMaternal chronic psychological distress across gestation was associated with toddler wheezing and especially wheezing without other atopic features (eczema). This finding supports the theory of intrauterine programming effect by maternal psychological distress on offspring immune system and respiratory morbidity.

Age and sex differences in the cortisol stress reactivity and recovery among infants exposed to prenatal psychological distress

BackgroundAltered hypothalamic-pituitary-adrenal axis (HPA) functioning is one of the potential mechanisms bridging exposure to maternal prenatal psychological distress (PPD) and later risk for offspring psychiatric illness. Research on infant cortisol stress reactivity, on scarcely studied recovery and their associations with maternal PPD is needed to clarify these mechanisms. Knowledge on sex differences in prospective settings is largely lacking. We aimed at filling these gaps by building upon our previous report showing that exposure to maternal prenatal depressive and anxiety symptoms associates with slower cortisol recovery among 10-week-old female infants. MethodsIn all, 363, 205 and 263 infants at 10 weeks, six and 14 months of age from the FinnBrain Birth Cohort Study participated in a stress test comprising of venipuncture and nasopharynx sampling. Five saliva cortisol samples were collected during each visit to measure cortisol reactivity and recovery. PPD was assessed from maternal self-reports for depressive, anxiety and pregnancy-related anxiety symptoms at gestational weeks 14, 24 and 34. ResultsAn 11% enhanced recovery among 14-month-old females was associated with higher depressive and anxiety symptoms (95% CI=1–23%) and pregnancy-related anxiety symptoms (2–21%). No alterations in the female cortisol reactivity or male cortisol stress responses were observed. ConclusionsThe opposite directions in the associations between the PPD exposure and infant cortisol recovery among 10-week-old and 14-month-old females suggest sex- and age-dependent associations between HPA axis functioning and PPD exposure among healthy infants. Follow-up is needed to characterize the impact of this altered negative feedback mechanism on later health.

Maternal caregiving ameliorates the consequences of prenatal maternal psychological distress on child development.

Children exposed to prenatal maternal psychological distress are at elevated risk for a range of adverse outcomes; however, it remains poorly understood whether postnatal influences can ameliorate impairments related to prenatal distress. The current study evaluated if sensitivematernal care during the first postnatal year could mitigate child cognitive and emotional impairments associated with prenatal psychological distress. Prenatal maternal psychological distress was assessed via self-reports of anxiety, depression, and perceived stress for 136 mothers at five prenatal and four postpartum time points. Quality of maternal care (sensitivity to nondistress, positive regard, and intrusiveness reverse-scored) were assessed during a mother-child play interaction at 6 and 12 months. Child cognitive function and negative emotionality were assessed at 2 years, using The Bayley Scales and the Early Childhood Behavior Questionnaire. Elevated prenatal distress was associated with poorer child cognitive function and elevated negative emotionality. Children exposed to elevated prenatal maternal distress did not, however, display these outcomes if they received high-quality caregiving. Specifically, maternal care moderated the relation between prenatal psychological distress and child cognitive function and negative emotionality. This association remained after consideration of postnatal maternal psychological distress and relevant covariates. Sensitive maternal care was associated with altered offspring developmental trajectories, supporting child resilience following prenatal distress exposure.

Prenatal maternal psychological distress and fetal developmental trajectories: associations with infant temperament.

Associations between prenatal maternal psychological distress and offspring developmental outcomes are well documented, yet relatively little research has examined links between maternal distress and development in utero, prior to postpartum influences. Fetal heart rate (FHR) parameters are established indices of central and autonomic nervous system maturation and function which demonstrate continuity with postnatal outcomes. This prospective, longitudinal study of 149 maternal-fetal pairs evaluated associations between prenatal maternal distress, FHR parameters, and dimensions of infant temperament. Women reported their symptoms of psychological distress at five prenatal visits, and FHR monitoring was conducted at the last three visits. Maternal report of infant temperament was collected at 3 and 6 months of age. Exposure to elevated prenatal maternal psychological distress was associated with higher late-gestation resting mean FHR (FHRM) among female but not male fetuses. Higher late-gestation FHRM was associated with lower infant orienting/regulation and with higher infant negative affectivity, and these associations did not differ by infant sex. A path analysis identified higher FHRM as one pathway by which elevated prenatal maternal distress was associated with lower orienting/regulation among female infants. Findings suggest that, for females, elevated maternal distress alters fetal development, with implications for postnatal function. Results also support the notion that, for both sexes, individual differences in regulation emerge prenatally and are maintained into infancy. Collectively, these findings underscore the utility of direct assessment of development in utero when examining if prenatal experiences are carried forward into postnatal life.

Sex differences in the associations between maternal prenatal distress and infant cortisol reactivity and recovery

Previous research suggests that maternal prenatal psychological distress (PPD) is related to altered cortisol reactivity in the exposed child. There are indications for the sex differences in vulnerability for prenatal adversities that depend on the exposure and child outcome. Still, it is not known whether the association between maternal PPD and infant cortisol stress response is moderated by sex. In addition, the recovery phase of the cortisol stress response has not been given as much attention as reactivity. Our aim was to study the sex differences in the associations between self-reported maternal prenatal depressive-, anxiety- and pregnancy-related anxiety symptoms through gestational weeks 14, 24 and 34 and the saliva cortisol reactivity to and recovery from the acute stress among 10-week-old infants. The study population comprised of 363 mother-infant pairs from the FinnBrain Birth Cohort Study. We found evidence for sex-dependent associations between PPD exposure and infant cortisol response. A less steep recovery slope (-10 % per one SD increase in PPD [95 % CI = -18 to -2 %] and -8 % [-16 to 0 %] depending on the exposure) and a possibly less steep reactivity slope (-14 % [95 % CI = -25 to 0 %] and -10 % [-21 to 3 %]) were associated with higher PPD exposure in females. Of the PPD measures, the strongly intercorrelated, and thus combined, depressive and anxiety symptom score provided the most robust prediction of infant cortisol recovery. Our results demonstrate sexually dimorphic alterations in the functioning of the infant hypothalamus-pituitary-adrenal axis and especially in the functioning of the negative feedback loop of the axis after prenatal PPD exposure among healthy babies.

Maternal prenatal psychological distress and hair cortisol levels associate with infant fecal microbiota composition at 2.5 months of age

BackgroundMaternal prenatal stress associates with infant developmental outcomes, but the mechanisms underlying this association are not fully understood. Alterations in the composition and function of infant intestinal microbiota may mediate some of the observed health effects, a viewpoint that is supported by animal studies along with a small human study showing that exposure to prenatal stress modifies the offspring’s intestinal microbiota. In the current study, we aim to investigate the associations between maternal prenatal psychological distress (PPD) and hair cortisol concentration (HCC) with infant fecal microbiota composition in a large prospective human cohort. MethodsThe study population was drawn from FinnBrain Birth Cohort Study. Maternal PPD was measured with standardized questionnaires (EPDS, SCL, PRAQ-R2, Daily Hassles) three times during pregnancy (n = 398). A measure addressing the chronicity of PPD was composed separately for each questionnaire. HCC was measured from a five cm segment at gestational week 24 (n = 115), thus covering the early and mid-pregnancy. Infant fecal samples were collected at the age of 2.5 months and analyzed with 16S rRNA amplicon sequencing. ResultsMaternal chronic PPD (all symptom measures) showed positive associations (FDR < 0.01) with bacterial genera from phylum Proteobacteria, with potential pathogens, in infants. Further, chronic PPD (SCL, PRAQ-R2, and Daily Hassles negative scale) associated negatively with Akkermansia. HCC associated negatively with Lactobacillus. Neither maternal chronic PPD nor HCC associated with infant fecal microbiota diversity. ConclusionChronic maternal PPD symptoms and elevated HCC associate with alterations in infant intestinal microbiota composition. In keeping with the earlier literature, maternal PPD symptoms were associated with increases in genera fromProteobacteria phylum. Further research is needed to understand how these microbiota changes are linked with later child health outcomes.

Maternal psychological distress and child weight at 24 months: investigating indirect effects through breastfeeding in the All Our Families cohort.

Maternal psychological distress in pregnancy has been associated with both breastfeeding duration and child weight at 24months; however, the potential that breastfeeding duration partially mediates the risk of maternal mental health problems during pregnancy on child weight classification has not been examined. The current study investigated this proposed relationship. Data was taken from the All Our Families (AOF) cohort, an ongoing prospective pregnancy cohort located in Calgary, Canada. Psychological distress, defined as clinically significant symptoms of anxiety and depression, was assessed via self-report and measured between 34 and 36weeks of gestation. Breastfeeding duration was assessed in the postpartum by self-report. Child overweight classification was defined as a weight-for-length/height z-score at or above the 97th percentile as per World Health Organization's child growth guidelines. In this sample of 1582 mother-child pairs, there was no direct relationship between psychological distress and child overweight status. Both anxiety (B = - 5.40, p = 0.001) and depression (B = - 6.54, p = 0.008) were associated with decreased weeks breastfeeding. Breastfeeding duration mediated the association between maternal prenatal psychological distress and child overweight status at 24months, for both anxiety (B(SE) = 0.10(0.05), CI 0.03-0.21) and depression (B(SE) = 0.11(0.07), CI 0.01-0.27). Covariates included maternal age, education, ethnicity, income, pre-pregnancy BMI, gestational weight gain, and infant birth weight. The results of this longitudinal cohort analysis support an indirect relationship between maternal psychological distress in pregnancy and the childhood overweight/obesity at 24months old, mediated through breastfeeding duration.

Association of Prenatal Maternal Psychological Distress With Fetal Brain Growth, Metabolism, and Cortical Maturation

Prenatal maternal stress is increasingly associated with adverse outcomes in pregnant women and their offspring. However, the association between maternal stress and human fetal brain growth and metabolism is unknown. To identify the association between prenatal maternal psychological distress and fetal brain growth, cortical maturation, and biochemical development using advanced 3-dimensional volumetric magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (1H-MRS). This cohort study prospectively recruited pregnant women from low-risk obstetric clinics in Washington, DC, from January 1, 2016, to April 17, 2019. Participants were healthy volunteers with a normal prenatal medical history, no chronic or pregnancy-induced physical or mental illnesses, and normal results on fetal ultrasonography and biometry studies. Fetal brain MRI studies were performed at 2 time points between 24 and 40 weeks' gestation. Prenatal maternal stress, anxiety, and depression. Volumes of fetal total brain, cortical gray matter, white matter, deep gray matter, cerebellum, brainstem, and hippocampus were measured from 3-dimensional reconstructed T2-weighted MRI scans. Cortical folding measurements included local gyrification index, sulcal depth, and curvedness. Fetal brain N-acetylaspartate, creatine, and choline levels were quantified using 1H-MRS. Maternal stress, depression, and anxiety were measured with the Perceived Stress Scale (PSS), Edinburgh Postnatal Depression Scale (EPDS), Spielberger State Anxiety Inventory (SSAI), and Spielberger Trait Anxiety Inventory (STAI). A total of 193 MRI studies were performed in 119 pregnant women (67 [56%] carrying male fetuses and 52 [44%], female fetuses; maternal mean [SD] age, 34.46 [5.95] years) between 24 and 40 gestational weeks. All women were high school graduates, 99 (83%) were college graduates, and 100 (84%) reported professional employment. Thirty-two women (27%) had positive scores for stress, 31 (26%) for anxiety, and 13 (11%) for depression. Maternal trait anxiety was associated with smaller fetal left hippocampal volume (STAI score: -0.002 cm3; 95% CI, -0.003 to -0.0008 cm3; P = .004). Maternal anxiety and stress were associated with increased fetal cortical gyrification in the frontal lobe (β for SSAI score: 0.004 [95% CI, 0.001-0.006; P = .002]; β for STAI score: 0.004 [95% CI, 0.002-0.006; P < .001]; β for PSS score: 0.005 [95% CI, 0.001-0.008; P = .005]) and temporal lobe (β for SSAI score: 0.004 [95% CI, 0.001-0.007; P = .004]; β for STAI score: 0.004 [95% CI, 0.0008-0.006; P = .01]). Elevated maternal depression was associated with decreased creatine (EPDS score: -0.04; 95% CI, -0.06 to -0.02; P = .005) and choline (EPDS score: -0.03; 95% CI, -0.05 to -0.01; P = .02) levels in the fetal brain. This study found that the prevalence of maternal psychological distress in healthy, well-educated, and employed pregnant women was high, underappreciated, and associated with impaired fetal brain biochemistry and hippocampal growth as well as accelerated cortical folding. These findings appear to support the need for routine mental health surveillance for all pregnant women and targeted interventions in women with elevated psychological distress.