Researching COVID to enhance recovery (RECOVER) pediatric study protocol: Rationale, objectives and design.

IMPORTANCE: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or "Long COVID") in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults. OBSERVATIONS: We describe the protocol for the Pediatric Observational Cohort Study of the NIH's REsearching COVID to Enhance Recovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of four cohorts that comprise RECOVER-Pediatrics: 1) a de novo RECOVER prospective cohort of children and young adults with and without previous or current infection; and 2) an extant cohort derived from the Adolescent Brain Cognitive Development (ABCD) study (n = 10,000). The de novo cohort incorporates three tiers of data collection: 1) remote baseline assessments (Tier 1, n = 6000); 2) longitudinal follow-up for up to 4 years (Tier 2, n = 6000); and 3) a subset of participants, primarily the most severely affected by PASC, who will undergo deep phenotyping to explore PASC pathophysiology (Tier 3, n = 600). Youth enrolled in the ABCD study participate in Tier 1. The pediatric protocol was developed as a collaborative partnership of investigators, patients, researchers, clinicians, community partners, and federal partners, intentionally promoting inclusivity and diversity. The protocol is adaptive to facilitate responses to emerging science. CONCLUSIONS AND RELEVANCE: RECOVER-Pediatrics seeks to characterize the clinical course, underlying mechanisms, and long-term effects of PASC from birth through 25 years old. RECOVER-Pediatrics is designed to elucidate the epidemiology, four-year clinical course, and sociodemographic correlates of pediatric PASC. The data and biosamples will allow examination of mechanistic hypotheses and biomarkers, thus providing insights into potential therapeutic interventions. CLINICAL TRIALS.GOV IDENTIFIER: Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT05172011.

Digital Media and Developing Brains: Concerns and Opportunities.

Purpose of Review: The incorporation of digital technologies and their use in youth's everyday lives has been increasing rapidly over the past several decades with possible impacts on youth development and mental health. This narrative review aimed to consider how the use of digital technologies may be influencing brain development underlying adaptive and maladaptive screen-related behaviors. Recent Findings: To explore and provide direction for further scientific inquiry, an international group of experts considered what is known, important gaps in knowledge, and how a research agenda might be pursued regarding relationships between screen media activity and neurodevelopment from infancy through childhood and adolescence. While an understanding of brain-behavior relationships involving screen media activity has been emerging, significant gaps exist that have important implications for the health of developing youth. Summary: Specific considerations regarding brain-behavior relationships involving screen media activity exist for infancy, toddlerhood, and early childhood; middle childhood; and adolescence. Transdiagnostic frameworks may provide a foundation for guiding future research efforts. Translating knowledge gained into better interventions and policy to promote healthy development is important in a rapidly changing digital technology environment.

Developmental coupling of brain iron and intrinsic activity in infants during the first 150 days.

Brain iron is vital for core neurodevelopmental processes including myelination and neurotransmitter synthesis and, accordingly, iron accumulates in the brain with age. However, little is known about the association between brain iron and neural functioning and how they evolve with age in early infancy. This study investigated brain iron in 48 healthy infants (22 females) aged 64.00 ± 33.28 days by estimating R2 * relaxometry from multi-echo functional MRI (fMRI). Linked independent component analysis was performed to examine the association between iron deposition and spontaneous neural activity, as measured by the amplitude of low frequency fluctuations (ALFF) by interrogating shared component loadings across modalities. Further, findings were validated in an independent dataset (n = 45, 24 females, 77.93 ± 26.18 days). The analysis revealed developmental coupling between the global R2 * and ALFF within the default mode network (DMN). Furthermore, we observed that this coupling effect significantly increased with age (r = 0.78, p = 9.2e-11). Our results highlight the importance of iron-neural coupling during early development and suggest that the neural maturation of the DMN may correspond to growth in distributed brain iron.

Fetal Frontolimbic Connectivity Prospectively Associates With Aggression in Toddlers.

Background: Aggression is a major public health concern that emerges early in development and lacks optimized treatment, highlighting need for improved mechanistic understanding regarding the etiology of aggression. The present study leveraged fetal resting-state functional magnetic resonance imaging to identify candidate neurocircuitry for the onset of aggressive behaviors before symptom emergence. Methods: Pregnant mothers were recruited during the third trimester of pregnancy to complete a fetal resting-state functional magnetic resonance imaging scan. Mothers subsequently completed the Child Behavior Checklist to assess child aggression at 3 years postpartum (n = 79). Independent component analysis was used to define frontal and limbic regions of interest. Results: Child aggression was not related to within-network connectivity of subcortical limbic regions or within-medial prefrontal network connectivity in fetuses. However, weaker functional coupling between the subcortical limbic network and medial prefrontal network in fetuses was prospectively associated with greater maternal-rated child aggression at 3 years of age even after controlling for maternal emotion dysregulation and toddler language ability. We observed similar, but weaker, associations between fetal frontolimbic functional connectivity and toddler internalizing symptoms. Conclusions: Neural correlates of aggressive behavior may be detectable in utero, well before the onset of aggression symptoms. These preliminary results highlight frontolimbic connections as potential candidate neurocircuitry that should be further investigated in relation to the unfolding of child behavior and psychiatric risk.

Effects of prenatal psychosocial stress and COVID-19 infection on infant attention and socioemotional development.

BACKGROUND: The COVID-19 pandemic dramatically altered the psychosocial environment of pregnant women and new mothers. In addition, prenatal infection is a known risk factor for altered fetal development. Here we examine joint effects of maternal psychosocial stress and COVID-19 infection during pregnancy on infant attention at 6 months postpartum. METHOD: One-hundred and sixty-seven pregnant mothers and infants (40% non-White; n = 71 females) were recruited in New York City (n = 50 COVID+, n = 117 COVID-). Infants' attentional processing was assessed at 6 months, and socioemotional function and neurodevelopmental risk were evaluated at 12 months. RESULTS: Maternal psychosocial stress and COVID-19 infection during pregnancy jointly predicted infant attention at 6 months. In mothers reporting positive COVID-19 infection, higher prenatal psychosocial stress was associated with lower infant attention at 6 months. Exploratory analyses indicated that infant attention in turn predicted socioemotional function and neurodevelopmental risk at 12 months. CONCLUSIONS: These data suggest that maternal psychosocial stress and COVID-19 infection during pregnancy may have joint effects on infant attention at 6 months. This work adds to a growing literature on the effects of the COVID-19 pandemic on infant development, and may point to maternal psychosocial stress as an important target for intervention. IMPACT: This study found that elevated maternal psychosocial stress and COVID-19 infection during pregnancy jointly predicted lower infant attention scores at 6 months, which is a known marker of risk for neurodevelopmental disorder. In turn, infant attention predicted socioemotional function and risk for neurodevelopmental disorder at 12 months. These data suggest that maternal psychosocial stress may modulate the effects of gestational infection on neurodevelopment and highlight malleable targets for intervention.

A comparison of the infant gut microbiome before versus after the start of the covid-19 pandemic.

The COVID-19 pandemic and resulting public health directives led to many changes in families' social and material environments. Prior research suggests that these changes are likely to impact composition of the gut microbiome, particularly during early childhood when the gut microbiome is developing most rapidly. Importantly, disruption to the gut microbiome during this sensitive period can have potentially long-lasting impacts on health and development. In the current study, we compare gut microbiome composition among a socioeconomically and racially diverse group of 12-month old infants living in New York City who provided stool samples before the pandemic (N = 34) to a group who provided samples during the first 9-months of the pandemic (March-December 2020; N = 20). We found that infants sampled during the pandemic had lower alpha diversity of the microbiome, lower abundance of Pasteurellaceae and Haemophilus, and significantly different beta diversity based on unweighted Unifrac distance than infants sampled before the pandemic. Exploratory analyses suggest that gut microbiome changes due to the pandemic occurred relatively quickly after the start of the pandemic and were sustained. Our results provide evidence that pandemic-related environmental disruptions had an impact on community-level taxonomic diversity of the developing gut microbiome, as well as abundance of specific members of the gut bacterial community.

Maternal perceived stress and infant behavior during the COVID-19 pandemic.

BACKGROUND: Maternal stress has negative consequences on infant behavioral development, and COVID-19 presented uniquely stressful situations to mothers of infants born during the pandemic. We hypothesized that mothers with higher levels of perceived stress during the pandemic would report higher levels of infant regulatory problems including crying and interrupted sleep patterns. METHODS: As part 6 sites of a longitudinal study, mothers of infants born during the pandemic completed the Perceived Stress Scale, the Brief Infant Sleep Questionnaire, and an Infant Crying survey at 6 (n = 433) and 12 (n = 344) months of infant age. RESULTS: Maternal perceived stress, which remained consistent at 6 and 12 months of infant age, was significantly positively correlated with time taken to settle infants. Although maternal perceived stress was not correlated with uninterrupted sleep length, time taken to put the infant to sleep was correlated. Perceived stress was also correlated with the amount of infant crying and fussiness reported at 6 months. CONCLUSIONS: Mothers who reported higher levels of perceived stress during the pandemic reported higher levels of regulatory problems, specifically at 6 months. Examining how varying levels of maternal stress and infant behaviors relate to overall infant developmental status over time is an important next step. IMPACT: Women giving birth during the COVID-19 pandemic who reported higher levels of stress on the Perceived Stress Scale also reported higher levels of infant fussiness and crying at 6 months old, and more disruptive sleep patterns in their infants at 6 months and 12 months old. Sleeping problems and excessive crying in infancy are two regulatory problems that are known risk factors for emotional and behavioral issues in later childhood. This paper is one of the first studies highlighting the associations between maternal stress and infant behaviors during the COVID-19 pandemic.

Intergenerational Transmission of Maternal Childhood Maltreatment Prior to Birth: Effects on Human Fetal Amygdala Functional Connectivity.

OBJECTIVE: Childhood maltreatment (CM) is a potent risk factor for developing psychopathology later in life. Accumulating research suggests that the influence is not limited to the exposed individual but may also be transmitted across generations. In this study, we examine the effect of CM in pregnant women on fetal amygdala-cortical function, prior to postnatal influences. METHOD: Healthy pregnant women (N = 89) completed fetal resting-state functional magnetic resonance imaging (rsfMRI) scans between the late second trimester and birth. Women were primarily from low socioeconomic status households with relatively high CM. Mothers completed questionnaires prospectively evaluating prenatal psychosocial health and retrospectively evaluating trauma from their own childhood. Voxelwise functional connectivity was calculated from bilateral amygdala masks. RESULTS: Connectivity of the amygdala network was relatively higher to left frontal areas (prefrontal cortex and premotor) and relatively lower to right premotor area and brainstem areas in fetuses of mothers exposed to higher CM. These associations persisted after controlling for maternal socioeconomic status, maternal prenatal distress, measures of fetal motion, and gestational age at the time of scan and at birth. CONCLUSION: Pregnant women's experiences of CM are associated with offspring brain development in utero. The strongest effects were found in the left hemisphere, potentially indicating lateralization of the effects of maternal CM on the fetal brain. This study suggests that the time frame of the Developmental Origins of Health and Disease research should be extended to exposures from mothers' childhood, and indicates that the intergenerational transmission of trauma may occur prior to birth.

Researching COVID to enhance recovery (RECOVER) pediatric study protocol: Rationale, objectives and design.

Importance: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or "Long COVID") in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults. Observations: We describe the protocol for the Pediatric Observational Cohort Study of the NIH's RE searching COV ID to E nhance R ecovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of five cohorts that comprise RECOVER-Pediatrics: 1) a de novo RECOVER prospective cohort of children and young adults with and without previous or current infection; and 2) an extant cohort derived from the Adolescent Brain Cognitive Development (ABCD) study ( n =10,000). The de novo cohort incorporates three tiers of data collection: 1) remote baseline assessments (Tier 1, n=6000); 2) longitudinal follow-up for up to 4 years (Tier 2, n=6000); and 3) a subset of participants, primarily the most severely affected by PASC, who will undergo deep phenotyping to explore PASC pathophysiology (Tier 3, n=600). Youth enrolled in the ABCD study participate in Tier 1. The pediatric protocol was developed as a collaborative partnership of investigators, patients, researchers, clinicians, community partners, and federal partners, intentionally promoting inclusivity and diversity. The protocol is adaptive to facilitate responses to emerging science. Conclusions and Relevance: RECOVER-Pediatrics seeks to characterize the clinical course, underlying mechanisms, and long-term effects of PASC from birth through 25 years old. RECOVER-Pediatrics is designed to elucidate the epidemiology, four-year clinical course, and sociodemographic correlates of pediatric PASC. The data and biosamples will allow examination of mechanistic hypotheses and biomarkers, thus providing insights into potential therapeutic interventions. Clinical Trialsgov Identifier: Clinical Trial Registration: http://www.clinicaltrials.gov . Unique identifier: NCT05172011.

Fetal behavior during MRI changes with age and relates to network dynamics.

Fetal motor behavior is an important clinical indicator of healthy development. However, our understanding of associations between fetal behavior and fetal brain development is limited. To fill this gap, this study introduced an approach to automatically and objectively classify long durations of fetal movement from a continuous four-dimensional functional magnetic resonance imaging (fMRI) data set, and paired behavior features with brain activity indicated by the fMRI time series. Twelve-minute fMRI scans were conducted in 120 normal fetuses. Postnatal motor function was evaluated at 7 and 36 months age. Fetal motor behavior was quantified by calculating the frame-wise displacement (FD) of fetal brains extracted by a deep-learning model along the whole time series. Analyzing only low motion data, we characterized the recurring coactivation patterns (CAPs) of the supplementary motor area (SMA). Results showed reduced motor activity with advancing gestational age (GA), likely due in part to loss of space (r = -.51, p < .001). Evaluation of individual variation in motor movement revealed a negative association between movement and the occurrence of coactivations within the left parietotemporal network, controlling for age and sex (p = .003). Further, we found that the occurrence of coactivations between the SMA to posterior brain regions, including visual cortex, was prospectively associated with postnatal motor function at 7 months (r = .43, p = .03). This is the first study to pair fetal movement and fMRI, highlighting potential for comparisons of fetal behavior and neural network development to enhance our understanding of fetal brain organization.

OWLET: An automated, open-source method for infant gaze tracking using smartphone and webcam recordings.

Groundbreaking insights into the origins of the human mind have been garnered through the study of eye movements in preverbal subjects who are unable to explain their thought processes. Developmental research has largely relied on in-lab testing with trained experimenters. This constraint provides a narrow window into infant cognition and impedes large-scale data collection in families from diverse socioeconomic, geographic, and cultural backgrounds. Here we introduce a new open-source methodology for automatically analyzing infant eye-tracking data collected on personal devices in the home. Using algorithms from computer vision, machine learning, and ecological psychology, we develop an online webcam-linked eye tracker (OWLET) that provides robust estimation of infants' point of gaze from smartphone and webcam recordings of infant assessments in the home. We validate OWLET in a large sample of 7-month-old infants (N = 127) tested remotely, using an established visual attention task. We show that this new method reliably estimates infants' point-of-gaze across a variety of contexts, including testing on both computers and mobile devices, and exhibits excellent external validity with parental-report measures of attention. Our platform fills a significant gap in current tools available for rapid online data collection and large-scale assessments of cognitive processes in infants. Remote assessment addresses the need for greater diversity and accessibility in human studies and may support the ecological validity of behavioral experiments. This constitutes a critical and timely advance in a core domain of developmental research and in psychological science more broadly.

Increasing diversity in developmental cognitive neuroscience: A roadmap for increasing representation in pediatric neuroimaging research.

Understanding of human brain development has advanced rapidly as the field of developmental cognitive neuroscience (DCN) has matured into an established scientific discipline. Despite substantial progress, DCN lags behind other related disciplines in terms of diverse representation, standardized reporting requirements for socio-demographic characteristics of participants in pediatric neuroimaging studies, and use of intentional sampling strategies to more accurately represent the socio-demographic, ethnic, and racial composition of the populations from which participants are sampled. Additional efforts are needed to shift DCN towards a more inclusive field that facilitates the study of individual differences across a variety of cultural and contextual experiences. In this commentary, we outline and discuss barriers within our current scientific practice (e.g., research methods) and beliefs (i.e., what constitutes good science, good scientists, and good research questions) that contribute to under-representation and limited diversity within pediatric neuroimaging studies and propose strategies to overcome those barriers. We discuss strategies to address barriers at intrapersonal, interpersonal, community, systemic, and structural levels. Highlighting strength-based models of inclusion and recognition of the value of diversity in DCN research, along with acknowledgement of the support needed to diversify the field is critical for advancing understanding of neurodevelopment and reducing health inequities.

Empirical evaluation of human fetal fMRI preprocessing steps.

Increased study and methodological innovation have led to growth in the field of fetal brain fMRI. An important gap yet to be addressed is optimization of fetal fMRI preprocessing. Rapid developmental changes, imaged within the maternal compartment using an abdominal coil, introduce novel constraints that challenge established methods used in adult fMRI. This study evaluates the impact of (1) normalization to a group mean-age template versus normalization to an age-matched template; (2) independent components analysis (ICA) denoising at two criterion thresholds; and (3) smoothing using three kernel sizes. Data were collected from 121 fetuses (25-39 weeks, 43.8% female). Results indicate that the mean age template is superior in older fetuses, but less optimal in younger fetuses. ICA denoising at a more stringent threshold is superior to less stringent denoising. A larger smoothing kernel can enhance cross-hemisphere functional connectivity. Overall, this study provides improved understanding of the impact of specific steps on fetal image quality. Findings can be used to inform a common set of best practices for fetal fMRI preprocessing.

Perceived medical care quality during COVID-19 illness links socioeconomic disadvantage to vaccine hesitancy.

Maximizing vaccine uptake is critical for the optimal implementation of COVID-19 immunization programs. Indicators of socioeconomic status (SES) have been associated with variations in COVID-19 vaccine uptake in the United States. The present study investigates COVID-19 vaccination behavior in individuals with history of COVID-19 infection, with the specific goal of understanding whether experiences during illness explain socioeconomic disproportionalities in vaccine uptake. We leveraged a large sample of adults (n = 1584) infected with COVID-19 in NYC to examine this question, investigating whether specific experiences during illness explained the association between socioeconomic status and COVID-19 vaccine hesitancy. Data from this study were collected during February and March 2021. Principal component analysis was used to create three composite variables that measure distinct COVID-19 related experiences: infection-related health impacts, pandemic-related psychosocial disruption, and perceived quality of medical care during COVID-19 illness. Neither infection-related impacts nor psychosocial disruption were related to vaccine hesitancy after adjusting for related sociodemographic covariates. However, perceptions of higher quality care received during COVID-19 illness predicted decreased COVID-19 vaccine hesitancy. Furthermore, mediation analysis revealed that perceived care quality during COVID-19 illness mediate the relationship between objective socioeconomic risk and COVID-19 vaccine hesitancy. These findings highlight patient-reported care quality during illness as a novel target that may increase vaccine uptake among socioeconomically vulnerable populations.

Maternal-fetal attachment, parenting stress during infancy, and child outcomes at age 3 years.

Maternal-fetal attachment (MFA), a woman's relationship with and affiliative behaviors toward her unborn child, has been linked to near-term infant physical and developmental outcomes. However, further longitudinal research is needed to understand whether the impact of MFA extends past the earliest years of life. The current study explored relationships between MFA and child socioemotional competence and behavior problems at age 3 and whether parenting stress mediated the association between MFA and child outcomes. Data were collected from 221 primarily Black/African-American mothers who completed a scale of MFA during pregnancy. Mothers reported on parenting stress at infant age 7 months and reported on child socioemotional competence and problem behaviors at child age 3 years. In path analyses, MFA was directly associated with child socioemotional competence at age 3 years, but an indirect association between MFA and socioemotional competence via parenting stress was not significant. We also observed a significant indirect association between lower MFA and child internalizing behavior problems via parenting stress that was related to maternal dissatisfaction regarding interactions with her child. Findings suggest that assessing MFA may serve as a means to identify dyads who would benefit from support to promote individual health outcomes.

La afectividad materno-fetal (MFA), la relación y comportamientos de afiliación de una mujer hacia su niño en el vientre, ha sido conectada a los resultados físicos y de desarrollo del infante cuya gestación está cerca al término. Sin embargo, se necesita investigación longitudinal adicional para comprender si el impacto de MFA se extiende más allá de los más tempranos años de vida. El presente estudio exploró las relaciones entre MFA y la competencia socioemocional y problemas de comportamiento del niño a la edad de 3 años y si el estrés de crianza medió la asociación entre MFA y los resultados en el niño. Se recogió información de 221 madres, primariamente negras/afroamericanas, que completaron una escala de MFA durante el embarazo. Las madres reportaron sobre el estrés de crianza cuando el infante tenía 7 meses y reportaron sobre la competencia socioemocional y los problemas de comportamiento del niño cuando éste tenía 3 años. En análisis de trayectoria, se asoció MFA directamente con la competencia socioemocional del niño a la edad de 3 años, pero una asociación indirecta entre MFA y la competencia socioemocional por medio del estrés de crianza no fue significativa. También observamos una significativa asociación indirecta entre MFA y la internalización de problemas del comportamiento por parte del niño vía el estrés de crianza que se relacionó con la insatisfacción materna en cuanto a las interacciones con su niño. Los resultados indican que evaluar MFA pudiera servir como un medio de identificar díadas que se beneficiarían del apoyo para promover resultados de salud individuales.

L'attachement maternel foetal (Maternal-fetal attachment, soit MFA), une relation de la femme avec son enfant à naître et des comportements affiliatifs envers l'enfant à naître, a été lié à des résultats physiques et développementaux du bébé quasiment à terme. Cependant des recherches longitudinales plus approfondies sont nécessaires afin de comprendre si l'impact du MFA dépasse les premières années de la vie. Cette étude a exploré les relations entre le MFA et la compétence socio-émotionnelle de l'enfant et les problèmes de comportement à l'âge de trois ans et si le stress de parentage affectait l'association entre le MFA et les résultats sur l'enfant. Les données ont été recueillies à partir de 221 mères américaines majoritairement noires/afro-américaines qui ont rempli l'échelle du MFA durant la grossesse. Les mères ont fait état de stress de parentage à l'âge de 7 mois pour le bébé et répondu à des questions sur la compétence socio-émotionnelle de l'enfant et les problèmes de comportement à l'âge de 3 ans. Dans les analyses de trajectoire le MFA était directement lié à la compétence socio-émotionnelle de l'enfant à l'âge de 3 ans, mais un lien indirect entre le MFA et la compétence socio-émotionnelle à travers le stress de parentage n'était pas important. Nous avons aussi observé un lien indirect important entre le MFA et les problèmes de comportement d'internalisation de l'enfant au travers du stress de parentage qui était lié à l'insatisfaction maternelle concernant les interactions avec son enfant. Les résultats suggèrent que l'évaluation du MFA peut servir de moyen d'identifier des dyades qui bénéficierait d'un soutien pour promouvoir des résultats de santé individuels.

Geotemporal analysis of perinatal care changes and maternal mental health: an example from the COVID-19 pandemic.

Our primary objective was to document COVID-19 induced changes to perinatal care across the USA and examine the implication of these changes for maternal mental health. We performed an observational cross-sectional study with convenience sampling using direct patient reports from 1918 postpartum and 3868 pregnant individuals collected between April 2020 and December 2020 from 10 states across the USA. We leverage a subgroup of these participants who gave birth prior to March 2020 to estimate the pre-pandemic prevalence of specific birthing practices as a comparison. Our primary analyses describe the prevalence and timing of perinatal care changes, compare perinatal care changes depending on when and where individuals gave birth, and assess the linkage between perinatal care alterations and maternal anxiety and depressive symptoms. Seventy-eight percent of pregnant participants and 63% of postpartum participants reported at least one change to their perinatal care between March and August 2020. However, the prevalence and nature of specific perinatal care changes occurred unevenly over time and across geographic locations. The separation of infants and mothers immediately after birth and the cancelation of prenatal visits were associated with worsened depression and anxiety symptoms in mothers after controlling for sociodemographic factors, mental health history, number of pregnancy complications, and general stress about the COVID-19 pandemic. Our analyses reveal widespread changes to perinatal care across the US that fluctuated depending on where and when individuals gave birth. Disruptions to perinatal care may also exacerbate mental health concerns, so focused treatments that can mitigate the negative psychiatric sequelae of interrupted care are warranted.

Fetal Hippocampal Connectivity Shows Dissociable Associations with Maternal Cortisol and Self-Reported Distress during Pregnancy.

Maternal stress can shape long-term child neurodevelopment beginning in utero. One mechanism by which stress is transmitted from mothers to their offspring is via alterations in maternal cortisol, which can cross the placenta and bind to glucocorticoid receptor-rich regions in the fetal brain, such as the hippocampus. Although prior studies have demonstrated associations between maternal prenatal stress and cortisol levels with child brain development, we lack information about the extent to which these associations originate prior to birth and prior to confounding postnatal influences. Pregnant mothers (n = 77) completed questionnaires about current perceived stress, depressive symptoms, and anxiety symptoms, provided three to four salivary cortisol samples, and completed a fetal resting-state functional MRI scan during their second or third trimester of pregnancy (mean gestational age = 32.8 weeks). Voxelwise seed-based connectivity analyses revealed that higher prenatal self-reported distress and higher maternal cortisol levels corresponded to dissociable differences in fetal hippocampal functional connectivity. Specifically, self-reported distress was correlated with increased positive functional coupling between the hippocampus and right posterior parietal association cortex, while higher maternal cortisol was associated with stronger positive hippocampal coupling with the dorsal anterior cingulate cortex and left medial prefrontal cortex. Moreover, the association between maternal distress, but not maternal cortisol, on fetal hippocampal connectivity was moderated by fetal sex. These results suggest that prenatal stress and peripheral cortisol levels may shape fetal hippocampal development through unique mechanisms.

Perceived discrimination as a modifier of health, disease, and medicine: empirical data from the COVID-19 pandemic.

Increasing reports of long-term symptoms following COVID-19 infection, even among mild cases, necessitate systematic investigation into the prevalence and type of lasting illness. Notably, there is limited data regarding the influence of social determinants of health, like perceived discrimination and economic stress, that may exacerbate COVID-19 health risks. Here, 1,584 recovered COVID-19 patients that experienced mild to severe forms of disease provided detailed medical and psychosocial information. Path analyses examined hypothesized associations between discrimination, illness severity, and lasting symptoms. Secondary analyses evaluated sex differences, timing of infection, and impact of prior mental health problems. Post hoc logistic regressions tested social determinants hypothesized to predict neurological, cognitive, or mood symptoms. 70.6% of patients reported presence of one or more lasting symptom after recovery. 19.4% and 25.1% of patients reported lasting mood or cognitive/memory problems. Perceived discrimination predicted increased illness severity and increased lasting symptom count, even when adjusting for sociodemographic factors and mental/physical health comorbidities. This effect was specific to stress related to discrimination, not to general stress levels. Further, patient perceptions regarding quality of medical care influenced these relationships. Finally, illness early in the pandemic is associated with more severe illness and more frequent lasting complaints. Lasting symptoms after recovery from COVID-19 are highly prevalent and neural systems are significantly impacted. Importantly, psychosocial factors (perceived discrimination and perceived SES) can exacerbate individual health risk. This study provides actionable directions for improved health outcomes by establishing that sociodemographic risk and medical care influence near and long-ranging health outcomes. All data from this study have been made publicly available.

Frontal Alpha Asymmetry in Response to Stressor Moderates the Relation Between Parenting Hassles and Child Externalizing Problems.

Inequitable urban environments are associated with toxic stress and altered neural social stress processing that threatens the development of self-regulation. Some children in these environments struggle with early onset externalizing problems that are associated with a variety of negative long-term outcomes. While previous research has linked parenting daily hassles to child externalizing problems, the role of frontal alpha asymmetry (FAA) as a potential modifier of this relationship has scarcely been explored. The present study examined mother-child dyads, most of whom were living in low socioeconomic status households in an urban environment and self-identified as members of racial minority groups. Analyses focused on frustration task electroencephalography (EEG) data from 67 children (mean age = 59.0 months, SD = 2.6). Mothers reported the frequency of their daily parenting hassles and their child's externalizing problems. Frustration task FAA moderated the relationship between parenting daily hassles and child externalizing problems, but resting FAA did not. More specifically, children with left frontal asymmetry had more externalizing problems as their mothers perceived more hassles in their parenting role, but parenting hassles and externalizing problems were not associated among children with right frontal asymmetry. These findings lend support to the motivational direction hypothesis and capability model of FAA. More generally, this study reveals how individual differences in lateralization of cortical activity in response to a stressor may confer differential susceptibility to child behavioral problems with approach motivation (i.e., left frontal asymmetry) predicting externalizing problems under conditions of parental stress.