Developmental characteristics and accuracy of autism screening among two-year-old toddlers in the ECHO program.

BACKGROUND: The Modified Checklist for Autism in Toddlers (M-CHAT) is a common pediatric screening tool with mixed accuracy findings. Prior evidence supports M-CHAT screening for developmental concerns, especially in toddlers born preterm. This study examined M-CHAT accuracy in a large, nationwide sample. METHODS: 3393 participants from the Environmental influences on Child Health Outcomes (ECHO) program were included. Harmonized M-CHAT (M-CHAT-H) results were compared with parent-reported autism diagnosis and autism-related characteristics to assess accuracy for term and preterm children, together and separately. Generalized estimating equations, clustering for ECHO cohort and controlling for demographic covariates, were used to examine associations between developmental and behavioral characteristics with M-CHAT-H accuracy. RESULTS: Sensitivity of the M-CHAT-H ranged from 36 to 60%; specificity ranged from 88 to 99%. Positive M-CHAT-H was associated with more developmental delays and behavior problems. Children with severe motor delays and more autism-related problems were more likely to have a false-negative M-CHAT-H. Children with fewer behavior problems and fewer autism-related concerns were more likely to have a false-positive screen. CONCLUSION: The M-CHAT-H accurately detects children at low risk for autism and children at increased risk with moderate accuracy. These findings support use of the M-CHAT-H in assessing autism risk and developmental and behavioral concerns in children. IMPACT: Previous literature regarding accuracy of the Modified Checklist for Autism in Toddlers (M-CHAT) is mixed but this study provides evidence that the M-CHAT performs well in detecting children at low risk for autism and consistently detects children with developmental delays and behavioral problems. The M-CHAT moderately detects children at increased risk for autism and remains a useful screening tool. This study examines M-CHAT accuracy in a large-scale, nationwide sample, examining associations between screening accuracy and developmental outcomes. These findings impact pediatric screening for autism, supporting continued use of the M-CHAT while further elucidating the factors associated with inaccurate screens.

Black-white differences in chronic stress exposures to predict preterm birth: interpretable, race/ethnicity-specific machine learning model.

BACKGROUND: Differential exposure to chronic stressors by race/ethnicity may help explain Black-White inequalities in rates of preterm birth. However, researchers have not investigated the cumulative, interactive, and population-specific nature of chronic stressor exposures and their possible nonlinear associations with preterm birth. Models capable of computing such high-dimensional associations that could differ by race/ethnicity are needed. We developed machine learning models of chronic stressors to both predict preterm birth more accurately and identify chronic stressors and other risk factors driving preterm birth risk among non-Hispanic Black and non-Hispanic White pregnant women. METHODS: Multivariate Adaptive Regression Splines (MARS) models were developed for preterm birth prediction for non-Hispanic Black, non-Hispanic White, and combined study samples derived from the CDC's Pregnancy Risk Assessment Monitoring System data (2012-2017). For each sample population, MARS models were trained and tested using 5-fold cross-validation. For each population, the Area Under the ROC Curve (AUC) was used to evaluate model performance, and variable importance for preterm birth prediction was computed. RESULTS: Among 81,892 non-Hispanic Black and 277,963 non-Hispanic White live births (weighted sample), the best-performing MARS models showed high accuracy (AUC: 0.754-0.765) and similar-or-better performance for race/ethnicity-specific models compared to the combined model. The number of prenatal care visits, premature rupture of membrane, and medical conditions were more important than other variables in predicting preterm birth across the populations. Chronic stressors (e.g., low maternal education and intimate partner violence) and their correlates predicted preterm birth only for non-Hispanic Black women. CONCLUSIONS: Our study findings reinforce that such mid or upstream determinants of health as chronic stressors should be targeted to reduce excess preterm birth risk among non-Hispanic Black women and ultimately narrow the persistent Black-White gap in preterm birth in the U.S.

The Environmental Influences on Child Health Outcomes (ECHO)-Wide Cohort.

The Environmental Influences on Child Health Outcomes (ECHO)-Wide Cohort Study (EWC), a collaborative research design comprising 69 cohorts in 31 consortia, was funded by the National Institutes of Health (NIH) in 2016 to improve children's health in the United States. The EWC harmonizes extant data and collects new data using a standardized protocol, the ECHO-Wide Cohort Data Collection Protocol (EWCP). EWCP visits occur at least once per life stage, but the frequency and timing of the visits vary across cohorts. As of March 4, 2022, the EWC cohorts contributed data from 60,553 children and consented 29,622 children for new EWCP data and biospecimen collection. The median (interquartile range) age of EWCP-enrolled children was 7.5 years (3.7-11.1). Surveys, interviews, standardized examinations, laboratory analyses, and medical record abstraction are used to obtain information in 5 main outcome areas: pre-, peri-, and postnatal outcomes; neurodevelopment; obesity; airways; and positive health. Exposures include factors at the level of place (e.g., air pollution, neighborhood socioeconomic status), family (e.g., parental mental health), and individuals (e.g., diet, genomics).

Prenatal and perinatal factors associated with neonatal neurobehavioral profiles in the ECHO Program.

BACKGROUND: Single-cohort studies have identified distinct neurobehavioral profiles that are associated with prenatal and neonatal factors based on the NICU Network Neurobehavioral Scale (NNNS). We examined socioeconomic, medical, and substance use variables as predictors of NNNS profiles in a multi-cohort study of preterm and term-born infants with different perinatal exposures. METHODS: We studied 1112 infants with a neonatal NNNS exam from the Environmental influences on Child Health Outcomes (ECHO) consortium. We used latent profile analysis to characterize infant neurobehavioral profiles and generalized estimating equations to determine predictors of NNNS profiles. RESULTS: Six distinct neonatal neurobehavioral profiles were identified, including two dysregulated profiles: a hypo-aroused profile (16%) characterized by lethargy, hypotonicity, and nonoptimal reflexes; and a hyper-aroused profile (6%) characterized by high arousal, excitability, and stress, with low regulation and poor movement quality. Infants in the hypo-aroused profile were more likely to be male, have younger mothers, and have mothers who were depressed prenatally. Infants in the hyper-aroused profile were more likely to be Hispanic/Latino and have mothers who were depressed or used tobacco prenatally. CONCLUSIONS: We identified two dysregulated neurobehavioral profiles with distinct perinatal antecedents. Further understanding of their etiology could inform targeted interventions to promote positive developmental outcomes. IMPACT: Prior research on predictors of neonatal neurobehavior have included single-cohort studies, which limits generalizability of findings. In a multi-cohort study of preterm and term-born infants, we found six distinct neonatal neurobehavioral profiles, with two profiles being identified as dysregulated. Hypo- and hyper-aroused neurobehavioral profiles had distinct perinatal antecedents. Understanding perinatal factors associated with dysregulated neurobehavior could help promote positive developmental outcomes.

Exposure to phthalate metabolites, bisphenol A, and psychosocial stress mixtures and pregnancy outcomes in the Atlanta African American maternal-child cohort.

BACKGROUND: Consumer products are common sources of exposure for phthalates and bisphenol A (BPA), which disrupt the endocrine system. Psychosocial stressors have been shown to amplify the toxic effects of endocrine disruptors but, information is limited among African Americans (AAs), who experience the highest rates of adverse pregnancy outcomes and are often exposed to the highest levels of chemical and non-chemical stressors. We examined the association between an exposure mixture of phthalate metabolites, BPA, and psychosocial stressors with gestational age at delivery and birthweight for gestational age z-scores in pregnant AA women. STUDY DESIGN: Participants were enrolled in the Atlanta African American Maternal-Child Cohort (N = 247). Concentrations of eight phthalate metabolites and BPA were measured in urine samples collected at up to two timepoints during pregnancy (8-14 weeks gestation and 20-32 weeks gestation) and were averaged. Psychosocial stressors were measured using self-reported, validated questionnaires that assessed experiences of discrimination, gendered racial stress, depression, and anxiety. Linear regression was used to estimate individual associations between stress exposures (chemical and psychosocial) and birth outcomes. We leveraged quantile g-computation was used to examine joint effects of chemical and stress exposures on gestational age at delivery (in weeks) and birthweight for gestational age z-scores. RESULTS: A simultaneous increase in all phthalate metabolites and BPA was associated with a moderate reduction in birthweight z-scores (mean change per quartile increase = -0.22, 95% CI = -0.45, 0.0). The association between our exposure mixture and birthweight z-scores became stronger when including psychosocial stressors as additional exposures (mean change per quantile increase = -0.35, 95% CI = -0.61, -0.08). Overall, we found null associations between exposure to chemical and non-chemical stressors with gestational age at delivery. CONCLUSIONS: In a prospective cohort of AA mother-newborn dyads, we observed that increased prenatal exposure to phthalates, BPA, and psychosocial stressors were associated with adverse pregnancy outcomes.

Infant epigenetic aging moderates the link between Black maternal childhood trauma and offspring symptoms of psychopathology.

Although offspring of women exposed to childhood trauma exhibit elevated rates of psychopathology, many children demonstrate resilience to these intergenerational impacts. Among the variety of factors that likely contribute to resilience, epigenetic processes have been suggested to play an important role. The current study used a prospective design to test the novel hypothesis that offspring epigenetic aging - a measure of methylation differences that are associated with infant health outcomes - moderates the relationship between maternal exposure to childhood adversity and offspring symptomatology. Maternal childhood adversity was self-reported during pregnancy via the ACEs survey and the CTQ, which assessed total childhood trauma as well as maltreatment subtypes (i.e., emotional, physical, and sexual abuse). Offspring blood samples were collected at or shortly after birth and assayed on a DNA methylation microarray, and offspring symptomatology was assessed with the CBCL/1.5-5 when offspring were 2-4 years old. Results indicated that maternal childhood trauma, particularly sexual abuse, was predictive of offspring symptoms (ps = 0.003-0.03). However, the associations between maternal sexual abuse and offspring symptomatology were significantly attenuated in offspring with accelerated epigenetic aging. These findings further our understanding of how epigenetic processes may contribute to and attenuate the intergenerational link between stress and psychopathology.

Connectivity at the origins of domain specificity in the cortical face and place networks.

It is well established that the adult brain contains a mosaic of domain-specific networks. But how do these domain-specific networks develop? Here we tested the hypothesis that the brain comes prewired with connections that precede the development of domain-specific function. Using resting-state fMRI in the youngest sample of newborn humans tested to date, we indeed found that cortical networks that will later develop strong face selectivity (including the "proto" occipital face area and fusiform face area) and scene selectivity (including the "proto" parahippocampal place area and retrosplenial complex) by adulthood, already show domain-specific patterns of functional connectivity as early as 27 d of age (beginning as early as 6 d of age). Furthermore, we asked how these networks are functionally connected to early visual cortex and found that the proto face network shows biased functional connectivity with foveal V1, while the proto scene network shows biased functional connectivity with peripheral V1. Given that faces are almost always experienced at the fovea, while scenes always extend across the entire periphery, these differential inputs may serve to facilitate domain-specific processing in each network after that function develops, or even guide the development of domain-specific function in each network in the first place. Taken together, these findings reveal domain-specific and eccentricity-biased connectivity in the earliest days of life, placing new constraints on our understanding of the origins of domain-specific cortical networks.

Perinatal Outcomes during versus Prior to the COVID-19 Pandemic and the Role of Maternal Depression and Perceived Stress: A Report from the ECHO Program.

OBJECTIVE: We sought to evaluate the impact of the coronavirus disease 2019 (COVID-19) pandemic on perinatal outcomes while accounting for maternal depression or perceived stress and to describe COVID-specific stressors, including changes in prenatal care, across specific time periods of the pandemic. STUDY DESIGN: Data of dyads from 41 cohorts from the National Institutes of Health Environmental influences on Child Health Outcomes Program (N = 2,983) were used to compare birth outcomes before and during the pandemic (n = 2,355), and a partially overlapping sample (n = 1,490) responded to a COVID-19 questionnaire. Psychosocial stress was defined using prenatal screening for depression and perceived stress. Propensity-score matching and general estimating equations with robust variance estimation were used to estimate the pandemic's effect on birth outcomes. RESULTS: Symptoms of depression and perceived stress during pregnancy were similar prior to and during the pandemic, with nearly 40% of participants reporting mild to severe stress, and 24% reporting mild depression to severe depression. Gestations were shorter during the pandemic (B = - 0.33 weeks, p = 0.025), and depression was significantly associated with shortened gestation (B = - 0.02 weeks, p = 0.015) after adjustment. Birth weights were similar (B = - 28.14 g, p = 0.568), but infants born during the pandemic had slightly larger birth weights for gestational age at delivery than those born before the pandemic (B = 0.15 z-score units, p = 0.041). More women who gave birth early in the pandemic reported being moderately or extremely distressed about changes to their prenatal care and delivery (45%) compared with those who delivered later in the pandemic. A majority (72%) reported somewhat to extremely negative views of the impact of COVID-19 on their life. CONCLUSION: In this national cohort, we detected no effect of COVID-19 on prenatal depression or perceived stress. However, experiencing the COVID-19 pandemic in pregnancy was associated with decreases in gestational age at birth, as well as distress about changes in prenatal care early in the pandemic. KEY POINTS: · COVID-19 was associated with shortened gestations.. · Depression was associated with shortened gestations.. · However, stress during the pandemic remained unchanged.. · Most women reported negative impacts of the pandemic..

Prenatal Maternal Stress and Pediatric Asthma Across Development: Adolescent Female-Specific Vulnerability.

Prenatal maternal stress (PNMS) is linked to physical sequelae in offspring, including childhood asthma. This study sought to examine the roles of objective and subjective PNMS in the development of asthma at offspring ages 5 and 15. The sample included 815 mother-child dyads from the Mater Misericordiae Mothers' Hospital-University of Queensland Study of Pregnancy. PNMS was measured via retrospective self-report during pregnancy and 3-5 days after birth. Postnatal maternal stress was measured at offspring age 5. Objective PNMS was associated with elevated asthma risk at age 5 (OR 1.21, 95% CI 1.00, 1.45, p = 0.05), albeit not above concurrent postnatal stress. Sex moderated the association between PNMS and asthma at age 15, controlling for postnatal stress. Sex stratified analyses revealed a positive association between objective PNMS and age 15 asthma in females, but not males. Results provide evidence that PNMS may impact asthma outcomes in adolescence.

Psychological Distress Prospectively Predicts Later Sleep Quality in a Sample of Black American Postpartum Mothers.

Objective: Previous longitudinal studies have demonstrated prospective relationships between maternal sleep quality and subsequent psychological distress in the postpartum period. Despite evidence for prospective relationships between mood and subsequent sleep quality in adult populations, this direction has not been examined in postpartum women. We aimed to test prospective relationships between sleep quality and subsequent psychological distress, as well as the plausible reverse possibility, in a sample of Black American postpartum mothers (n = 146).Participants: Mothers were recruited prenatally from two hospitals in a Southeastern city of the United States. Eligible and interested mothers enrolled in a follow-up study on infant development. Data from the current study were obtained during the follow-up study.Method: Mothers reported on their psychological distress (i.e., anxiety, depression, stress) and sleep quality at 3- and 6-months postpartum. We performed hierarchical linear regressions to explore whether 1) maternal sleep quality at 3-months postpartum would predict maternal psychological distress at 6-months postpartum, after adjustment for mothers' earlier psychological distress, and 2) whether psychological distress at 3-months postpartum would predict maternal sleep quality at 6-months postpartum, after adjustment for mothers' earlier sleep quality.Results: Maternal sleep quality at 3-months postpartum was not a significant predictor of psychological distress at 6-months postpartum. However, maternal psychological distress at 3-months postpartum was a significant predictor of sleep quality at 6-months postpartum.Conclusions: Mothers' psychological distress earlier in the postpartum was a significant predictor of their later sleep quality. Replication is needed in large, prospective studies, with results stratified by race/ethnicity.

Intergenerational Impacts of Maternal Stress on Early Childhood Atopy in Black Americans.

OBJECTIVE: Black children are disproportionately affected by atopic diseases (i.e., atopic dermatitis, allergic rhinitis, asthma, and food allergies), with health disparities present in early life. Studies in White samples suggest that maternal stress confers risk for offspring atopy, yet little is known about these relationships in Black populations. This study seeks to (a) examine the relationship between self-reported and physiological indicators of maternal stress and offspring atopy and (b) explore warm and responsive caregiving as a potential protective factor in Black Americans. METHODS: A sample of 179 Black mother-child dyads of varying socioeconomic status participated in a prospective longitudinal study. Mothers completed self-reports of childhood trauma, prenatal stress, postnatal stress, and physician diagnosis of offspring atopy; provided blood samples to assess physiological responses to chronic stress exposure; and participated in a behavioral task with their infant. RESULTS: Maternal self-reports of childhood trauma, prenatal stress, and postnatal stress were not associated with offspring diagnosis of atopy by 2-3 years of age. Mothers who produced a smaller inflammatory response during pregnancy were more likely to have an offspring with atopy by 2-3 years of age. Warm and responsive parenting demonstrated a protective effect; the positive association between maternal stress and offspring atopy was less apparent in cases of mother-child interactions characterized by high levels warm and responsive parenting. CONCLUSION: Failure to replicate previous findings suggests that the maternal stress-offspring atopy relationship is complex. Future studies must examine the unique stressors in Black Americans, as well as caregiving as a potential protective factor.

HPA-axis multilocus genetic profile score moderates the association between maternal prenatal perceived stress and offspring depression in early adulthood.

Maternal stress during pregnancy can cause alterations to the fetal hypothalamus-pituitary-adrenal (HPA) axis, a phenomenon known as fetal programming that may have lasting effects on offspring outcomes, including depression. Evidence suggests that these effects may vary with respect to the offspring's genetic risk. Nonetheless, few studies have examined these effects into adulthood, when risk for depression onset is highest. The present study builds upon the extant literature by examining the interaction of maternal prenatal perceived stress (MPPS) and offspring HPA-axis polygenic risk to predict offspring depression in early adulthood. A total of 381 mother-child dyads participated in a prospective, longitudinal study that spanned from pregnancy until offspring were 20 years of age. Polygenic risk was defined by a multilocus genetic profile score (MGPS) that reflected the additive risk of three HPA-axis candidate genes. The results indicated that the interaction of MPPS and HPA-axis MGPS confers risk for offspring depression at age 20, in line with the differential susceptibility model. This interaction may be specific to prenatal stress, as maternal stress during early childhood did not interact with genetic risk to predict depression. These findings provide the first evidence that genetic variants that are associated with the HPA axis may act in a polygenic, additive fashion to moderate the association between fetal programming and adult depression.

School-age social behavior and pragmatic language ability in children with prenatal serotonin reuptake inhibitor exposure.

Studies examining associations between fetal serotonin reuptake inhibitor (SRI) exposure and child autism spectrum disorder (ASD) diagnoses or delayed language remain mixed and rarely prospectively follow children or employ gold-standard assessments. We prospectively followed a cohort of mother-child dyads from pregnancy through early elementary school (N = 178), and obtained maternal and alternate-caregiver ratings of behaviors related to ASD (N = 137), as well as direct, gold-standard assessments of child ASD symptoms and pragmatic language among dyads who experienced prenatal depression and either took SRIs or were medication free during pregnancy (N = 44). Prenatal SRI exposure was related to maternal ratings of ASD-related behaviors (ß = 0.24 95% confidence interval; CI [0.07, 0.48]), and, among boys, alternative caregiver ratings (males-only ß = 0.28 95% CI [0.02, 0.55], females-only ß = -0.21 95% CI [-0.63, 0.08]). However, results of our direct assessments suggest an association between SRI exposure and reduced pragmatic language scores (ß = -0.27, 95% CI [-0.53, -0.01], but not ASD (Autism Diagnostic Observation Schedule ß = 0.14 95% CI [-0.15, 0.41]; Social Responsiveness Scale ß = 0.08 95% CI [-0.25, 0.40]). These discrepancies point to issues regarding how ASD is assessed, and the possibility that SRIs may be more strongly associated with language or other broader behaviors that coincide with ASD. Larger prospective studies that incorporate thorough, gold-standard assessments of ASD, language, and other ASD-related behaviors are needed.

Prenatal antidepressant exposures and gastrointestinal complaints in childhood: A gut-brain axis connection?

Selective serotonin/norepinephrine reuptake inhibitors (collectively, SRIs) are the most commonly prescribed antidepressant agents for the treatment of depression in pregnancy. SRIs affect maternal and placental serotonin signaling, which might impact fetal brain development. Alterations in serotonin signaling might also impact the developing gut-brain axis (GBA) via alterations in the fetal enteric nervous system (ENS). Emerging evidence suggests that gestational SRI exposure may be associated with offspring gastrointestinal problems. However, prospective human studies of the effects of fetal SRI exposure on the ENS and function are absent in the literature. In this paper we present data demonstrating significant associations between prenatal SRI exposure and children's gastrointestinal (GI) problems in two well-characterized, prospective cohorts of preschool and later childhood individuals. The results support the hypothesis that prenatal SRI exposure can increase the risk for childhood GI difficulties. Further research is warranted on the potential SRI-induced changes to the child gut including the role of the microbiome and the GBA in the development of GI problems.

Protocol for the Emory University African American maternal stress and infant gut microbiome cohort study.

BACKGROUND: The microbial population of the human gut (the gut microbiome) is an integral cog in the bidirectional communication axis that exists between the gastrointestinal tract and the central nervous system. African American infants disproportionately experience multiple, overlapping vulnerabilities such as preterm birth and formula rather than breast feeding that may disrupt the development of the infant microbiome. African American infants also are more likely to have mothers affected by chronic stress both pre- and post-natally. Perhaps relatedly, African American offspring are disproportionately affected by neurodevelopmental delays. Taken together, these findings suggest that one important mechanism that may link prenatal and postnatal stress and African American infant brain development is the composition of the infant microbiome. METHODS: In our ongoing longitudinal study, Maternal Stress and the Gut-Brain Axis in African American Infants (R01MD009746), we investigate associations between maternal prenatal and postnatal stress and the composition of the infant gut microbiome, in relation to cognitive and social-emotional development. We aim to recruit 300 African American mother-infant dyads, contingent on the mother's previous participation in an associated prenatal cohort study: Biobehavioral Determinants of the Microbiome and Preterm Birth in Black Women (R01NR014800). Following enrollment, we assess infants at 1-week, and 3-, 6-, 12-and 18-months to collect: standardized assessments of infant neurocognitive and social-emotional development; questionnaire measures of infant feeding and health; observational data on maternal-infant interactions; maternal reports of postnatal stress; blood and saliva samples to evaluate maternal and infant psychoneuroimmunologic (PNI) function; and infant stool samples to characterize acquisition and trajectory of gut microbiome composition. Genetic variants of the major histocompatibility complex that may influence gut microbiome composition are also being evaluated. DISCUSSION: This rich data set will allow future consideration of risk and protective factors that influence neurodevelopment in African American infants who are exposed to varying levels of prenatal and early life stress. Evidence for a mechanistic role of the microbiome would provide a framework for future clinical evaluations of preventative interventions (e.g., probiotics, culturally-appropriate breastfeeding campaigns) that could potentially improve the health and development of African American children in infancy and across the lifespan.

Transdiagnostic pathways from early social stress to psychopathology: a 20-year prospective study.

BACKGROUND: Adverse family environments confer susceptibility to virtually all psychiatric problems. This study evaluated two possible models to explain this diversity of associations. Stressful family circumstances during childhood could either activate general, transdiagnostic liabilities to mental disorder or promote numerous disorder-specific liabilities. METHODS: We recruited a high-risk sample of 815 mother-offspring pairs and assessed social stressors in the family context prospectively from the perinatal period through offspring age 5. We factor analyzed offspring mental disorder diagnoses at age 20 to parse transdiagnostic and disorder-specific dimensions of psychopathology. RESULTS: Structural analyses revealed nearly equivalent prospective effects of early family stress on overarching Internalizing (ß = .30) and Externalizing (ß = .29) dimensions. In contrast, there was no evidence of disorder-specific effects. CONCLUSIONS: Social stressors early in life activate transdiagnostic, and not disorder-specific, liabilities to psychopathology. A focus on higher-order dimensions of psychopathology could accelerate etiological research and intervention efforts for stress-linked mental disorders.

Physiological attunement in mother-infant dyads at clinical high risk: The influence of maternal depression and positive parenting.

A growing number of research studies have examined the intradyadic coregulation (or attunement) of hypothalamus-pituitary-adrenal axis functioning in mothers and their children. However, it is unclear how early this coregulation may be present in dyads at clinical high risk and whether certain factors, such as maternal depression or positive parenting, are associated with the strength of this coregulation. The present study examined cortisol attunement within mother-infant dyads in a high-risk sample of 233 mothers who received treatment for psychiatric illness during pregnancy and whose infants were 6 months old at the study visit. Results showed that maternal and infant cortisol covaried across four time points that included a stressor paradigm and a mother-infant interaction task. Greater maternal positive affect, but not depression, predicted stronger cortisol attunement. In addition, infants' cortisol level following separation from the mother predicted mothers' cortisol level at the next time point. Mothers' cortisol level following the separation and the laboratory stress paradigm predicted infants' cortisol levels at each successive time point, over and above infants' own cortisol at the previous time point. These findings suggest that maternal and infant cortisol levels influence one another in a bidirectional fashion that may be temporally and context dependent.

Maternal depression and cortisol in pregnancy predict offspring emotional reactivity in the preschool period.

Prenatal exposures to higher levels of maternal cortisol and depression have been linked to a variety of adverse physiological, neurological, and behavioral outcomes, such as dysregulated cortisol production, structural and functional differences in limbic areas of the brain, and greater negative emotionality. This study investigated prospective associations between maternal prepartum depression/cortisol levels and offspring emotional reactivity in 163 mother-child pairs. Women were assessed repeatedly during pregnancy, and later participated in a laboratory visit with their preschool-aged children. Mothers self-reported on depressive symptomatology during pregnancy and provided saliva samples for cortisol assay. Offspring emotional reactivity was assessed through multiple measures, including caregiver reports, cortisol response following a stressor, and laboratory observations of behavior. The findings suggest potential prenatal timing effects, with depression and maternal cortisol measured in the first and second trimesters being more strongly associated with child emotional reactivity. Sex was found to moderate associations between maternal prepartum depression/cortisol and child emotional reactivity, with the general pattern reflecting positive associations in girls, and negative associations in boys.