Maternal symptoms of depression and anxiety as modifiers of the relationship between prenatal phthalate exposure and infant neurodevelopment in the Atlanta African American maternal-child cohort.

Background: Prenatal exposure to phthalates, a group of synthetic chemicals widely used in consumer products, has previously been associated with adverse infant and child development. Studies also suggest that maternal depression and anxiety, may amplify the harmful effects of phthalates on infant and child neurodevelopment. Study design: Our analysis included a subset of dyads enrolled in the Atlanta African American Maternal-Child Cohort (N = 81). We measured eight phthalate metabolites in first and second trimester (8-14 weeks and 24-32 weeks gestation) maternal urine samples to estimate prenatal exposures. Phthalate metabolite concentrations were averaged across visits and natural log-transformed for analysis. Maternal symptoms of depression and anxiety were assessed using validated questionnaires (Edinberg Postnatal Depression Scale and State Trait Anxiety Inventory, respectively) and the total score on each scale was averaged across study visits. The NICU Network Neurobehavioral Scale (NNNS) was administered at two weeks of age. Our primary outcomes included two composite NNNS scores reflecting newborn attention and arousal. Linear regression was used to estimate associations between individual phthalate exposures and newborn attention and arousal. We assessed effect modification by maternal depression and anxiety. Results: Higher levels of urinary phthalate metabolites were not associated with higher levels of infant attention and arousal, but true associations may still exist given the limited power of this analysis. In models examining effect modification by maternal depression, we observed that an interquartile range increase in mono (2-ethlyhexyl) phthalate (MEHP), mono (2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) was associated with a significant increase in newborn arousal only among those with high depressive symptoms (MEHP: ß = 0.71, 95% confidence interval [CI] = 0.10, 1.32 for high, ß = -0.30, 95% CI = -0.73, 0.12 for low; MEOHP: ß = 0.60, 95% CI = -0.03, 1.23 for high, ß = -0.12, 95% CI = -0.58, 0.33 for low; MEHHP: ß = 0.54, 95% CI = -0.04, 1.11 for high, ß = -0.11, 95% CI = -0.54, 0.32 for low). Similar patterns were observed in models stratified by maternal anxiety, although CIs were wide. Conclusion: Our results suggest maternal anxiety and depression symptoms may exacerbate the effect of phthalates on infant neurodevelopment. Future studies are needed to determine the optimal levels of attention and arousal in early infancy.

Longitudinal Changes in Youth Mental Health From Before to During the COVID-19 Pandemic.

Importance: Robust longitudinal studies of within-child changes in mental health associated with the COVID-19 pandemic are lacking, as are studies examining sources of heterogeneity in such changes. Objective: To investigate within-child changes, overall and between subgroups, in youth mental health from prepandemic to midpandemic. Design, Setting, and Participants: This cohort study used longitudinal prepandemic and midpandemic data from the Environmental influences on Child Health Outcomes (ECHO) Program, collected between January 1, 2015, and March 12, 2020 (prepandemic), and between March 13, 2020, and August 31, 2022 (midpandemic). Data were analyzed between December 1, 2022, and June 1, 2024. The sample included 9 US-based observational longitudinal pediatric ECHO cohorts. Cohorts were included if they collected the Child Behavior Checklist (CBCL) School Age version before and during the pandemic on more than 20 participants of normal birth weight aged 6 to 17 years. Exposure: The COVID-19 pandemic. Main Outcomes and Measures: Prepandemic to midpandemic changes in CBCL internalizing, externalizing, depression, anxiety, and attention-deficit/hyperactivity disorder (ADHD) scores were estimated, and differences in outcome trajectories by child sociodemographic characteristics (age, sex, race, ethnicity, and poverty level) and prepandemic mental health problems were examined using established CBCL clinical score thresholds. Results: A total of 1229 participants (mean [SD] age during the pandemic, 10.68 [2.29] years; 625 girls [50.9%]) were included. The sample was socioeconomically diverse (197 of 1056 children [18.7%] lived at ≤130% of the Federal Poverty Level; 635 (51.7%) identified as White, 388 (31.6%) as Black, 147 (12.0%) as multiracial, 40 (3.3%) as another race, and 118 (9.6%) as Hispanic). Generalized linear mixed-effects models revealed minor decreases in externalizing problems (ß = -0.88; 95% CI, -1.16 to -0.60), anxiety (ß = -0.18; 95% CI, -0.31 to -0.05), and ADHD (ß = -0.36; 95% CI, -0.50 to -0.22), but a minor increase in depression (ß = 0.22; 95% CI, 0.10 to 0.35). Youth with borderline or clinically meaningful prepandemic scores experienced decreases across all outcomes, particularly externalizing problems (borderline, ß = -2.85; 95% CI, -3.92 to -1.78; clinical, ß = -4.88; 95% CI, -5.84 to -3.92). Low-income (ß = -0.76; 95% CI, -1.14 to -0.37) and Black (ß = -0.52; 95% CI, -0.83 to -0.20) youth experienced small decreases in ADHD compared with higher income and White youth, respectively. Conclusions and Relevance: In this longitudinal cohort study of economically and racially diverse US youth, there was evidence of differential susceptibility and resilience for mental health problems during the pandemic that was associated with prepandemic mental health and sociodemographic characteristics.

Black-White Differences in Chronic Stress Exposures to Predict Preterm Birth: Interpretable, Race/Ethnicity-Specific Machine Learning Models.

We developed Multivariate Adaptive Regression Splines (MARS) machine learning models of chronic stressors using the Pregnancy Risk Assessment Monitoring System data (2012-2017) to predict preterm birth (PTB) more accurately and identify chronic stressors driving PTB among non-Hispanic (N-H) Black and N-H White pregnant women in the U.S. We trained the MARS models using 5-fold cross-validation, whose performance was evaluated with AUC. We computed variable importance for PTB prediction. Our models showed high accuracy (AUC: 0.754-0.765). The number of prenatal care visits, premature rupture of membrane, and medical conditions were the most important variables in predicting PTB across the populations. Chronic stressors (e.g., low maternal education and violence) and their correlates were pivotal for PTB prediction only for N-H Black women. Interpretable, race/ethnicity-specific MARS models can predict PTB accurately and explain the most impactful life stressors and their magnitude of effect on PTB risk among N-H Black and N-H White women.

Examining the association between prenatal cannabis exposure and child autism traits: A multi-cohort investigation in the environmental influences on child health outcome program.

This study examined the association between prenatal cannabis exposure and autism spectrum disorder (ASD) diagnoses and traits. A total sample of 11,570 children (ages 1-18; 53% male; 25% Hispanic; 60% White) from 34 cohorts of the National Institutes of Health-funded environmental influences on child health outcomes consortium were included in analyses. Results from generalized linear mixed models replicated previous studies showing that associations between prenatal cannabis exposure and ASD traits in children are not significant when controlling for relevant covariates, particularly tobacco exposure. Child biological sex did not moderate the association between prenatal cannabis exposure and ASD. In a large sample and measuring ASD traits continuously, there was no evidence that prenatal cannabis exposure increases the risk for ASD. This work helps to clarify previous mixed findings by addressing concerns about statistical power and ASD measurement.

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.

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.

Assessing the usability of an immersive virtual reality grocery store in healthy controls.

BACKGROUND: Immersive virtual reality (IVR) as a research platform to study human behaviors is an emerging field and may be useful for studying self-care management, especially in the gap between formal healthcare recommendations and day-to-day living. Self-care activities, such as grocery shopping, can be challenging for people with chronic illness. We developed an IVR environment that simulates a real-life grocery store and conducted a usability study to demonstrate the safety and acceptability of IVR as an experimental environment. METHODS: This study was a three-arm randomized control trial involving 24 participants, conducted as a usability study to evaluate aspects of the experimental condition including the effectiveness of a training exposure, the occurrence of undesirable effects associated with IVR, and participants' experiences of realism, immersion, and spatial presence. The experiment, using a head mounted device and handheld controllers, included a 10-minute training exposure, followed by one of three unique 30-minute experimental conditions which exposed participants to different combinations of tasks and stimuli, and a post-experience interview. We measured controller errors, undesirable symptoms associated with IVR, and the perception of realism, immersion, and spatial presence. RESULTS: Participants used controllers effectively to interact within the IVR environment. Hand controller use errors were fewer during the experimental conditions compared to the training exposure. Minimal undesirable IVR symptoms were reported. Presence was rated in the middle range with no significant differences based on experimental condition. Overall, user experience feedback was positive. CONCLUSIONS: We demonstrated that participants could engage in our IVR environment without excessive error or experiencing undesirable effects and confirmed that the virtual experience attained a level of presence necessary to effectively engage in the study. These findings give us confidence that this IVR intervention designed to explore instrumental activities of daily living is safe, effective and provides a credible, controlled simulated community-like setting.

Intra-horn insemination in the alpaca Vicugna pacos: Copulatory wounding and deep sperm deposition.

Alpacas (Vicugna pacos) are reported to be the rare mammal in which the penis enters the uterus in mating. To date, however, only circumstantial evidence supports this assertion. Using female alpacas culled for meat, we determined that the alpaca penis penetrates to the very tips of the uterine horns, abrading the tract and breaking fine blood vessels. All female alpacas sacrificed one hour or 24 hours after mating showed conspicuous bleeding in the epithelium of some region of their reproductive tract, including the hymen, cervix and the tips of each uterine horn, but typically not in the vagina. Unmated females showed no evidence of conspicuous bleeding. Histological examination of mated females revealed widespread abrasion of the cervical and endometrial epithelium, injuries absent in unmated females. Within one hour of mating, sperm were already present in the oviduct. The male alpaca's cartilaginous penis tip with a hardened urethral process is likely responsible for the copulatory abrasion. The entire female reproductive tract interacts with the penis, functioning like a vagina. Alpacas are induced ovulators, and wounding may hasten delivery of the seminal ovulation-inducing factor beta-NGF into the female's blood stream. There is no evidence of sexual conflict in copulation in alpaca, and thus wounding may also be one of a variety of mechanisms devised by mammals to induce a beneficial, short-term inflammatory response that stimulates blastocyst implantation, the uterine remodeling associated with placental development, and thus the success of early pregnancy.

Measurement bias in caregiver-report of early childhood behavior problems across demographic factors in an ECHO-wide diverse sample.

Background: Research and clinical practice rely heavily on caregiver-report measures, such as the Child Behavior Checklist 1.5-5 (CBCL/1.5-5), to gather information about early childhood behavior problems and to screen for child psychopathology. While studies have shown that demographic variables influence caregiver ratings of behavior problems, the extent to which the CBCL/1.5-5 functions equivalently at the item level across diverse samples is unknown. Methods: Item-level data of CBCL/1.5-5 from a large sample of young children (N = 9087) were drawn from 26 cohorts in the Environmental influences on Child Health Outcomes program. Factor analyses and the alignment method were applied to examine measurement invariance (MI) and differential item functioning (DIF) across child (age, sex, bilingual status, and neurodevelopmental disorders), and caregiver (sex, education level, household income level, depression, and language version administered) characteristics. Child race was examined in sensitivity analyses. Results: Items with the most impactful DIF across child and caregiver groupings were identified for Internalizing, Externalizing, and Total Problems. The robust item sets, excluding the high DIF items, showed good reliability and high correlation with the original Internalizing and Total Problems scales, with lower reliability for Externalizing. Language version of CBCL administration, education level and sex of the caregiver respondent showed the most significant impact on MI, followed by child age. Sensitivity analyses revealed that child race has a unique impact on DIF over and above socioeconomic status. Conclusions: The CBCL/1.5-5, a caregiver-report measure of early childhood behavior problems, showed bias across demographic groups. Robust item sets with less DIF can measure Internalizing and Total Problems equally as well as the full item sets, with slightly lower reliability for Externalizing, and can be crosswalked to the metric of the full item set, enabling calculation of normed T scores based on more robust item sets.

Visualization of health information within immersive virtual reality environments.

The Advanced Visualization Branch of the National Institute of Nursing Research uses computer technologies to study information visualization in support of self-care management. Advanced technologies, such as immersive virtual reality (IVR), afford researchers the opportunity to study health information visualization where user-initiated information search in visually dense settings precedes acquisition, interpretation, and use. While IVR has broad applicability in healthcare, we chose to target lay people managing chronic disease because of the growing unmet need to translate clinical recommendations into everyday behaviors. To explore how lay people seek, acquire, and interpret health information in everyday settings, we developed an IVR grocery store. In this environment, a person can locate food products, read and compare nutrition labels, and use information to make food selections. The goal of this perspective is to introduce the opportunities afforded by IVR to both present and study health information visualization and to highlight critical design considerations.

Development and psychometric validation of the Pandemic-Related Traumatic Stress Scale for children and adults.

To assess the public health impact of the COVID-19 pandemic on mental health, investigators from the National Institutes of Health Environmental influences on Child Health Outcomes (ECHO) research program developed the Pandemic-Related Traumatic Stress Scale (PTSS). Based on the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) acute stress disorder symptom criteria, the PTSS is designed for adolescent (13-21 years) and adult self-report and caregiver-report on 3-12-year-olds. To evaluate psychometric properties, we used PTSS data collected between April 2020 and August 2021 from non-pregnant adult caregivers (n = 11,483), pregnant/postpartum individuals (n = 1,656), adolescents (n = 1,795), and caregivers reporting on 3-12-year-olds (n = 2,896). We used Mokken scale analysis to examine unidimensionality and reliability, Pearson correlations to evaluate relationships with other relevant variables, and analyses of variance to identify regional, age, and sex differences. Mokken analysis resulted in a moderately strong, unidimensional scale that retained nine of the original 10 items. We detected small to moderate positive associations with depression, anxiety, and general stress, and negative associations with life satisfaction. Adult caregivers had the highest PTSS scores, followed by adolescents, pregnant/postpartum individuals, and children. Caregivers of younger children, females, and older youth had higher PTSS scores compared to caregivers of older children, males, and younger youth, respectively. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Is BMI a Useful Indicator of Prenatal Health Among Black American Women?

OBJECTIVE: BMI is commonly used to measure risk to prenatal health but may not be sensitive to adiposity-associated health problems for Black women. The aim of the present study was to test associations between indices of prenatal health and BMI in Black women. METHODS: Data were from 652 women enrolled in two studies. Height and weight were used to calculate BMI. Depression and perceived stress were measured via maternal report, systemic inflammation via C-reactive protein (CRP), and nutrition by the ratio of omega-3 docosahexaenoic acid to omega-6 arachidonic acid fatty acids. RESULTS: Neither perceived stress, depression, nor fatty acids were associated with prenatal BMI. CRP levels were positively associated with BMI (beta = 6.56, t = 13.30, p < .001). The prevalence of high-risk levels of CRP (> 3 mg/L) was below 10% for all weight classes except for BMI ≥ 40. CONCLUSIONS: Results suggest that BMI may not be a sensitive index of adiposity related risk to prenatal health for Black women.

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.

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.

COVID-19 Stress and Child Behavior: Examining Discrimination and Social Support in Racially Diverse ECHO Cohorts.

OBJECTIVE: To examine the additive or moderating influences of caregiver COVID-19-related stress, social support, and discrimination on children's behavior problems across racially diverse populations. METHOD: In this Environmental influences on Child Health Outcomes (ECHO) cohort study (N = 1,999 caregiver/child pairs), we operationalized caregiver COVID-19-related stress in 2 ways: first, as the number of stressors (eg, financial concerns, social distancing); and second, as the level of pandemic-related traumatic stress symptoms reported via questionnaires administered between April 2020 and August 2022. At the same assessment visit, caregivers also reported their current levels of discrimination, and a subsample (n = 968) reported their emotional and instrumental support. Either concurrently or at a later assessment visit, caregivers reported on their children's internalizing and externalizing behavior problems using the Child Behavior Checklist for Ages 6-18 (CBCL/6-18). RESULTS: Multivariable analyses controlling for maternal education, marital status, child age, and child sex revealed that COVID-19-related stress (caregiver stressors and symptoms) and discrimination were positively associated, and that perceived support was negatively associated with child internalizing and externalizing behavior problems. Unexpectedly, neither emotional nor instrumental support attenuated the relationship between caregiver COVID-19-related stressors nor traumatic stress symptoms and child behavior problems. In the subset of Black American participants, caregiver perceived discrimination moderated the relationship between caregiver COVID-19 traumatic stress symptoms and child internalizing problems, such that the association was stronger at higher levels of discrimination. CONCLUSION: Our findings highlight the potential importance of relieving caregiver stress and increasing caregiver social support to optimize children's behavioral outcomes.