Maternal prenatal lead levels and neonatal brain volumes: Testing moderations by maternal depressive symptoms and family income.

There is considerable evidence that prenatal lead exposure is detrimental to child cognitive and socio-emotional development. Further evidence suggests that the effects of prenatal lead on developmental outcomes may be conditional upon exposure to social stressors, such as maternal depression and low socioeconomic status. However, no studies have examined associations between these co-occurring stressors during pregnancy and neonatal brain volumes. Leveraging a sample of 101 mother-infant dyads followed beginning in mid-pregnancy, we examined the main effects of prenatal urinary lead levels on neonatal lateralized brain volumes (left and right hippocampus, amygdala, cerebellum, frontal lobes) and total gray matter. We additionally tested for moderations between lead and depressive symptoms and between lead and family income relative to the federal poverty level (FPL) on the same neurodevelopmental outcomes. Analyses of main effects indicated that prenatal lead was significantly (ps < 0.05) associated with reduced right and left amygdala volumes (ßs = -0.23- -0.20). The testing and probing of cross-product interaction terms using simple slopes indicated that the negative effect of lead on the left amygdala was conditional upon mothers having low depressive symptoms or high income relative to the FPL. We interpret the results in the context of trajectories of prenatal and postnatal brain development and susceptibility to low levels of prenatal lead in the context of other social stressors.

Autism Prevalence and the Intersectionality of Assigned Sex at Birth, Race, and Ethnicity on Age of Diagnosis.

PURPOSE: An official autism diagnosis is required to access timely intervention and is associated with better long-term wellbeing and mental health. Certain demographic characteristics, such as being female or a racially or ethnically minoritized youth, have been associated with significant diagnostic lag. However, it remains unclear how assigned sex, race, and ethnicity interact with each other in predicting the prevalence and age of autism diagnosis. METHODS: To examine the interactions between assigned sex, race, and ethnicity, we used data from the National Survey of Children's Health (NSCH; 2016 > 2021). RESULTS: One in 38 children had an autism diagnosis and 3.8 males were diagnosed per 1 female. Hierarchical linear regressions yielded diagnostic delays in some females, particularly those who were non-Hispanic white, Black, and Asian. Ethnic and racial minority children had significantly earlier diagnoses than white and non-Hispanic children when not accounting for sex. CONCLUSION: This study demonstrates slight increases in reported autism prevalence, a diagnostic lag in some autistic females that was strongly associated with ethnicity, and earlier diagnoses in racial and ethnic minority youth, a finding that may be explained by factors associated with phenotypic differences. This study has important implications for the diagnosis of minority autistic youth, particularly females and females who are non-Hispanic, who may experience a greater propensity for diagnostic delays.

Racial differences in the associations between adiposity, placental growth hormone and inflammatory cytokines in pregnant women.

Background: The prevalence of obesity among women of child-bearing age has contributed to an increased risk of pregnancy complications with a disproportional impact on women of lower socioeconomic status and among certain racial groups. In particular, socio-demographic and historical factors have resulted in higher rates of premature births and small-for-gestational age infants among Black women, which may be associated with placental function during pregnancy. The current study investigated the influence of maternal pre-pregnancy adiposity and race on the associations between inflammatory proteins, placental growth hormone (PGH), and infant birthweight. This information was collected for a subsample of 109 participants (Black, n = 39 vs. White, n = 70) from the Brain and Early Experiences (BEE) study. Methods: Serum samples were acquired late in the second trimester to assess PGH levels, C-reactive protein (CRP), interleukin 6 (IL-6), interleukin 8 (IL-8), and interleukin-1 receptor antagonist (IL-1Ra). Participant questionnaire responses provided information on pre-pregnancy BMI, health, race, educational attainment, and infant birthweight. Bivariate correlations and multiple linear regression models were utilized to evaluate associations by race between preconception adiposity, inflammatory markers and PGH. Results: After controlling for covariates including maternal age and education, gestational age, and fetal sex, regression models indicated that pre-pregnancy BMI was negatively associated with PGH (ß=-0.42, p<0.05) and IL-8 was positively associated with PGH (ß=0.35, p<0.05) among the Black mothers only; neither were significantly associated with PGH in the White mothers. When extending models to birth outcomes, BMI was positively associated with birthweight corrected for gestational age (BWz) (ß=0.24, p<0.05) and educational attainment was negatively associated with BWz (ß=0.28, p<0.05) for infants of White women. In contrast, neither variable was predictive of BWz for infants of Black mothers. Conclusion: Future work is needed to investigate racial differences in the association between adiposity and placental functioning, which are likely to contribute to differential effects on pregnancy outcomes and fetal growth.

Environmental Toxicants and the Developing Brain.

Early life represents the most rapid and foundational period of brain development and a time of vulnerability to environmental insults. Evidence indicates that greater exposure to ubiquitous toxicants like fine particulate matter (PM2.5), manganese, and many phthalates is associated with altered developmental, physical health, and mental health trajectories across the lifespan. Whereas animal models offer evidence of their mechanistic effects on neurological development, there is little research that evaluates how these environmental toxicants are associated with human neurodevelopment using neuroimaging measures in infant and pediatric populations. This review provides an overview of 3 environmental toxicants of interest in neurodevelopment that are prevalent worldwide in the air, soil, food, water, and/or products of everyday life: fine particulate matter (PM2.5), manganese, and phthalates. We summarize mechanistic evidence from animal models for their roles in neurodevelopment, highlight prior research that has examined these toxicants with pediatric developmental and psychiatric outcomes, and provide a narrative review of the limited number of studies that have examined these toxicants using neuroimaging with pediatric populations. We conclude with a discussion of suggested directions that will move this field forward, including the incorporation of environmental toxicant assessment in large, longitudinal, multimodal neuroimaging studies; the use of multidimensional data analysis strategies; and the importance of studying the combined effects of environmental and psychosocial stressors and buffers on neurodevelopment. Collectively, these strategies will improve ecological validity and our understanding of how environmental toxicants affect long-term sequelae via alterations to brain structure and function.

Testing a cascade model linking prenatal inflammation to child executive function.

Inflammation during pregnancy is beginning to be understood as a risk factor predicting poor infant health and neurodevelopmental outcomes. The long-term sequelae associated with exposure to prenatal inflammation are less well established. The current study examined associations between maternal inflammation during pregnancy, markers of infant neurodevelopment (general cognitive ability, negative affect, and sleep quality), and preschool executive function (EF) in a longitudinal sample of 40 African American mother-infant dyads. Mothers completed a blood draw in the third trimester of pregnancy to measure plasma levels of C-reactive protein (CRP) and pro-inflammatory cytokines (e.g., interleukin 6 [IL-6], tumor necrosis factor-alpha [TNF-α]). When infants were 6 months of age, we assessed general cognitive ability via the Bayley-III, negative affect via the Still-Face Paradigm, and sleep quality via actigraphy monitoring. When children were 4 years of age, we assessed their EF ability using four tasks from the EF Touch battery. Elevated levels of maternal CRP, IL-6, and TNF-α were associated with poorer infant general cognitive ability. Although there were no direct effects of prenatal inflammation on preschool EF, we observed an indirect relationship between IL-6 and preschool EF ability via infant general cognitive ability. Our findings suggest that prenatal inflammation may have long-lasting, cascading implications for child neurodevelopment. Implications of these findings for health disparities in women and children of color are discussed.

Improvements in motor competence skills are associated with improvements in executive function and math problem-solving skills in early childhood.

Efforts to increase moderate-to-vigorous physical activity (MVPA) in school-age children are associated with improved health, cognitive, and academic outcomes. However, questions remain about whether similar benefits are observed in early childhood. We hypothesized that motor competence, not MVPA, would be related to improved cognitive and academic skill development in early childhood. For this study, 283 children were recruited from 13 community-based preschools (55% female; M = 4.2 years old, SD = .6; 41% non-Hispanic White, 37% non-Hispanic Black; 10% Hispanic, 10% mixed race, 2% Asian, 1% American Indian). Children's physical activity, motor competence, executive function (EF), and math problem-solving skills were measured using the same protocol in three assessments in a single academic year (i.e., fall, winter, spring). Although motor competence was strongly correlated with contemporaneous measures of EF and math problem-solving skills (rs = .51-.63), MVPA was weakly correlated with EF and math problem-solving skills (rs = .03-.18). Mixed linear models demonstrated that improvements in children's motor competence were related to improvements in their EF and math problem-solving skills (ps < .001), their improvements in MVPA were not statistically significant related to any of the outcomes. These within-child associations provide a stronger basis of inference by controlling for all time-invariant confounders. The results of this study suggest that efforts to improve motor competence skills in young children may improve EF and math problem-solving skills, though experimental studies are required to rigorously test this idea. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Between- and within-person contributions of simple reaction time to executive function skills in early childhood.

This study tested whether the bivariate association between simple reaction time (SRT) and executive function (EF) performance that has been observed in early childhood represented a between- and/or within-person association. Up to three repeated assessments (i.e., fall, winter, and spring assessments from September to May) were available for 282 preschool-aged children (Mage = 4.2 years; 54% female) who participated in the Kids Activity and Learning Study. A series of three-level hierarchical linear models (repeated measures nested in child; child nested in classroom) was used to disaggregate the observed variation in EF and SRT into between-classroom, between-person, and within-person components. EF composite scores were regressed on two indicators of SRT, which reflected between- and within-child sources of variation, along with demographic covariates (child age, gender, and parental education). Both between-person (b = -21.2, p < 0.001) and within-person (b = -13.2, p < 0.001) sources of SRT variation were uniquely related to EF performance. These results are discussed with respect to interest in using SRT as a proxy for foundational cognitive processes that contribute to EF task performance in early childhood, including the appropriateness of using SRT to refine EF task scores.

Decisional Capacity for Informed Consent in Males and Females with Fragile X Syndrome.

Although informed consent is critical for all research, there is increased ethical responsibility as individuals with intellectual or developmental disabilities (IDD) become the focus of more clinical trials. This study examined decisional capacity for informed consent to clinical trials in individuals with fragile X syndrome (FXS). Participants were 152 adolescents and adults (80 males, 72 females) with FXS who completed a measure of decisional capacity and a comprehensive battery of neurocognitive and psychiatric measures. Females outperformed males on all aspects of decisional capacity. The ability to understand aspects of the clinical trial had the strongest association with the ability to appreciate and reason about the decision. Scaffolding improved understanding, suggesting researchers can take steps to improve decisional capacity and the informed consent process.

Supporting informed clinical trial decisions: Results from a randomized controlled trial evaluating a digital decision support tool for those with intellectual disability.

BACKGROUND: Informed consent requires that individuals understand the nature of the study, risks and benefits of participation. Individuals with intellectual disabilities (ID) have cognitive and adaptive impairments that may affect their ability to provide informed consent. New treatments and clinical trials for fragile X syndrome, the most commonly known inherited cause of ID, necessitate the development of methods to improve the informed consent process. The goal of this study was to compare the efficacy of a digital decision support tool with that of standard practice for informed consent and to examine whether the tool can improve decisional capacity for higher functioning individuals. METHODS: Participants (N = 89; mean age = 21.2 years) were allocated to the experimental group (consenting information provided via the digital decision support tool), or the comparison group (information provided via standard practice). Participants were assessed on four aspects of decisional capacity (Understanding, Appreciating, Reasoning, and Expressing a choice). We used regression analyses to test the impact of the tool on each outcome, repeating the analyses on the higher functioning subsample. RESULTS: No differences existed in any domain of decisional capacity for the sample in full. However, participants in the higher IQ subsample who used the tool scored better on Understanding after adjustment (ß = 0.25, p = 0.04), but not on Appreciating or Reasoning. No differences by experimental group existed in the decision to join the hypothetical trial for the full sample or higher functioning subsample. CONCLUSIONS: A decision support tool shows promise for individuals with fragile X syndrome with higher cognitive abilities. Future studies should examine the level of cognitive ability needed for sufficient understanding, whether these findings can be translated to other clinical populations, and the impact of the tool in larger trials and on trial retention.

Using Repeated-Measures Data to Make Stronger Tests of the Association between Executive Function Skills and Attention Deficit/Hyperactivity Disorder Symptomatology in Early Childhood.

Theoretical models of Attention deficit/hyperactivity disorder (ADHD) have long implicated executive function (EF) skills as contributing to the etiology, maintenance, and changes in ADHD symptomatology over time. Although there is interest making within-person inferences (i.e., deficits in EF skills give rise to ADHD behaviors), most of the evidence has been derived from studies that conflated between- and within-person sources of variance. Here, we use repeated-measures data to test within-person association between EF skills and ADHD behaviors. Participants included 1160 children from the Family Life Project, an ongoing prospective longitudinal study of child development in low-income, nonmetropolitan communities. We tested the magnitude of the association between EF skills and ADHD behaviors when children were 3, 4, and 5 years old. Consistent with meta-analyses, unadjusted bivariate associations between EF and ADHD (which reflect combined between- and within-person variation) were of moderate magnitude (rs = -0.20 to -0.30). However, after controlling for all time-invariant, between-person sources of variation, the within-person associations between EF skills and ADHD behaviors were weak (ßs - 0.04 to -0.05, ps = 0.01). These results suggest that EF skills may contribute less prominently to ADHD behaviors in early childhood than is commonly assumed and provoke broader questions about developmental models of ADHD.

Clinical models of telehealth in genetics: A regional telegenetics landscape.

The use of live video consultations in genetics has been shown to improve patient access with high satisfaction; however, little is known about the current landscape of clinical telehealth models in the field of genetics (i.e., telegenetics). This survey aimed to address that gap across seven states and the District of Columbia. Among 51 self-defined telegenetics programs responding to an online survey, 32 currently utilized live videoconferencing as at least one of their technologies (i.e., were "video-capable"). Analysis of this subgroup revealed that medical institutions were the most common program setting, and prenatal and cancer services were the most common sub-specialty. Forty-seven percent of these programs reported billing insurance for patient care. When exploring measures of patient access among these programs, 56% had a wait time of under 2 weeks, 25% saw more than 50 patients per month, 50% estimated their geographic reach at over 200 miles, and 59% were able to provide remote telegenetics consultations to patients' homes. Professional licensure was reported as the biggest barrier, and patient access and convenience were reported as the largest benefit and success. Among the 19 remaining programs, eight currently active programs exclusively used telephone technology; these were less likely to have a geneticist (p = 0.01), had a shorter wait time (p = 0.04), and had been established for a longer time (p = 0.02) when compared to video-capable programs. Further, two currently active programs indicated the use of store-and-forward telehealth. Finally, nine programs were currently planning their programs, with a focus on video-capable technologies and more varied patient specialties. We observed a diverse landscape of telehealth models being utilized to provide genetic services, and the data demonstrated that these programs are focused on enhancing patient access. Our query about telegenetics drew responses from programs that were not using live videoconferencing technology models, which prompts further exploration, and challenges us to develop consensus around the meaning of "telegenetics." Similarly, our data suggest a need for continued research to assess the equivalency, accessibility, and role of telephone consultations across genetic services. While a multitude of policy factors influence which service delivery models are utilized, further research on these varied approaches, and their associated patient outcomes, is also needed to inform program development.

Health care for individuals with fragile X Syndrome: Understanding access and quality.

BACKGROUND: Previous research suggests that individuals with intellectual or developmental disabilities (IDD) may experience challenges accessing quality health care. OBJECTIVE/HYPOTHESIS: This study explored parent perceptions of access and quality of health care services for children with fragile X syndrome (FXS), the leading hereditary cause of intellectual/developmental disabilities. METHODS: Nearly 600 primary caregivers of at least one child with FXS completed an online survey on access, barriers, and quality of health care for their family member with FXS (N = 731). RESULTS: In a convenience sample of well-educated and affluent caregivers, the majority did not report experiencing difficulties with access to services. Caregivers of younger children and those with lower family incomes reported greater challenges with health care access. Nearly 40% of caregivers indicated that their child's PCP was not as knowledgeable about FXS-related needs as they would prefer, indicating a possible knowledge gap on the part of providers. CONCLUSIONS: These factors represent potential barriers to quality health care for individuals with FXS, with potential lifelong effects ranging from delayed age of diagnosis to difficulty accessing a PCP in adulthood.

Testing longitudinal associations between executive function and academic achievement.

Children with higher levels of executive function (EF) skills consistently demonstrate higher levels of academic achievement. Despite the consistency of these associations, fundamental questions remain about whether efforts to improve an individual child's EF skills result in corresponding improvements in his or her academic performance. In the absence of experimental evidence, developmentalists have used repeated measures designs to test the nature, magnitude, and direction of the associations between EF skills and academic achievement. In contrast to previous studies, this study described how between- and within-person associations between EF and achievement address different questions. Using data from a subsample of participants (N = 6,040) from the Early Childhood Longitudinal Study-Kindergarten, 2010-2011 (ECLS-K:2011) cohort, we estimated a series of latent growth curve models with structured residuals to test the between and within-person associations between 2 dimensions of EF (working memory, cognitive flexibility) and 2 domains of academic achievement (math, reading). Whereas between-person associations between EF and achievement were large (φ = .55-.91), the within-person associations were small (ßs = -.10-.25). Within-person effects of earlier reading achievement on later EF skills was the most consistent finding. Results were unchanged when analyses were repeated using the subset of children who were eligible for free and reduced-price lunch, a proxy for low socioeconomic households. Results are discussed with respect to interest in improving EF skills as a means for facilitating school outcomes. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Mindfulness and Acceptance as Potential Protective Factors for Mothers of Children With Fragile X Syndrome.

Women with an FMR1 premutation may be at increased genetic risk for stress vulnerability. This increased vulnerability, when combined with stressful parenting that can result from raising children with fragile X syndrome (FXS), may result in negative physical and emotional outcomes. Mindfulness and acceptance have been found to be protective factors for parents of children with similar behavioral challenges, but these traits have not previously been explored among mothers with a child with FXS. This study explored the associations of child disability severity with maternal stress, anxiety, depression, and physical health symptoms in 155 biological mothers of children with FXS. Women completed an online survey using standardized measures of stress, mindfulness, and acceptance. General mindfulness, mindfulness in the parenting role, and general acceptance were explored as potential protective factors between the child disability severity and maternal outcomes. Trait mindfulness and acceptance were significant predictors of lower stress, anxiety, depression, and daily health symptoms, while mindful parenting was associated with lower stress, anxiety, and depression. Acceptance was found to attenuate the effects of child severity on maternal stress and depression. These findings suggest that interventions focused on improving mindfulness and acceptance may promote health and well-being for mothers of children with FXS and have important health implications for all individuals with an FMR1 premutation.

Sensory Difficulties in Children With an FMR1 Premutation.

Abnormal sensory processing is one of the core characteristics of the fragile X phenotype. Studies of young children with fragile X syndrome (FXS) and the FMR1 premutation have shown sensory challenges as early as infancy and into early childhood. This study sought to examine differences in sensory difficulties in children with an FMR1 premutation compared with children with FXS and typically developing children. We conducted an online survey of 176 parents of affected children (FXS or FMR1 premutation). Most respondents were mothers who are Caucasian (86%), have a 4-year college or graduate degree (68%), and are married (92%). Children ranged in age from 5 to 18, with a mean age of 13.0 years (3.3 SD). Participants completed the BBC Sensory Scales, a 50-item Likert-type scale (1 = Almost Always, 4 = Almost Never) comprised of 8 subscales that assessed auditory processing, visual processing, tactile processing, and eating and feeding behaviors. Mean scores were calculated for the items and each of the subscales. Non-parametric tests examined differences in child and family-level variables. Across all BBCSS subscales, children with an FMR1 premutation displayed more sensory challenges than typically developing children. For six out of the eight subscales, children with the full mutation had the lowest scores indicating more sensory challenges, but this was closely followed by children with an FMR1 premutation. Fragile X status was associated with seven of the eight subscales; children with an FMR1 premutation did not differ from children with FXS on any of the subscales but had more digestive problems than children with no fragile X. Gender, autism status, and family income were also related to sensory sensitivities. In conclusion, these data provide further evidence that some children with an FMR1 premutation experience sensory difficulties that are similar to children with FXS but different than typically developing children.

A comparison of functional academic and daily living skills in males with fragile X syndrome with and without autism.

BACKGROUND: Adaptive behaviors, such as functional academic and daily living skills, are critical for independence in adults with intellectual and developmental disabilities. However, little is known about these skills in fragile X syndrome (FXS), the most common form of inherited intellectual disability. AIMS: The purposes of this study were to describe the functional academic and daily living skills of males diagnosed with FXS across different age groups and compare skill attainment by autism status and other common co-occurring conditions. METHODS AND PROCEDURES: We used survey methods to assess parent-reported functional academic and daily living skills in 534 males with FXS. Functional academic skills included time and schedules, money, math, reading, and writing skills. Daily living skills included hygiene, cooking, laundry and housekeeping, transportation, and safety skills. OUTCOMES AND RESULTS: Analyses examined functional academic and daily living skills in a cross-sectional sample of males between ages 5 and 67. Differences in skill attainment were found by child age, co-morbid autism status, total number of co-occurring conditions, and respondent education. Functional academic and daily living skills were predictive of community employment and independent living. CONCLUSIONS AND IMPLICATIONS: These data provide important information on the mastery of both foundational and more complex adaptive skills in males with FXS. Both functional academic and daily living skills were predictive of measures of independence above and beyond other child and family characteristics. These findings point to the need to focus interventions to support the attainment of independence in males with FXS.

Attendance at Fragile X Specialty Clinics: Facilitators and Barriers.

The objectives were to describe the demographic characteristics of children with Fragile X syndrome (FXS) and to determine predictors of attendance at Fragile X (FX) clinics. Findings from the Community Support Network (CSN) and Our Fragile X World (OFXW) samples showed that children who attended FX Clinics were mostly male, high-school aged or younger, and white, non-Hispanic. Using logistic regression models, awareness about FX Clinic services, guardian education, and income (CSN), and child age, family income, and total number of co-occurring conditions (OFXW) were predictors of clinic attendance. Demographic and child characteristics accounted for a large portion of the explained variance. Importantly, symptom severity and parent knowledge about services were independent predictors beyond the demographic characteristics of families.

Efficacy of a family-focused intervention for young drivers with attention-deficit hyperactivity disorder.

OBJECTIVE: Teenage drivers diagnosed with attention-deficit/hyperactivity disorder (ADHD) are at significant risk for negative driving outcomes related to morbidity and mortality. However, there are few viable psychosocial treatments for teens with ADHD and none focus on the key functional area of driving. The Supporting the Effective Entry to the Roadway (STEER) program was evaluated in a clinical trial to investigate whether it improved family functioning as a proximal outcome and driving behavior as a distal outcome. METHOD: One hundred seventy-two teenagers with ADHD, combined type, were randomly assigned to STEER or a driver education driver practice program (DEDP). RESULTS: Relative to parents in the DEDP condition, parents in STEER were observed to be less negative at posttreatment and 6-month follow-up but not at 12-month follow-up, and there were no significant differences for observed positive parenting. Relative to teens in the DEDP condition, teens in STEER reported lower levels of risky driving behaviors at posttreatment and 6-month follow-up, but not at 12-month follow-up. Groups did not differ on objective observations of risky driving or citations/accidents. CONCLUSIONS: The STEER program for novice drivers with ADHD was effective in reducing observations of negative parenting behavior and teen self-reports of risky driving relative to DEDP; groups did not significantly differ on observations of positive parenting or driving behaviors. (PsycINFO Database Record

Maternal medical conditions during pregnancy and gross motor development up to age 24 months in the Upstate KIDS study.

AIM: We examined whether children of mothers with a medical condition diagnosed before or during pregnancy took longer to achieve gross motor milestones up to age 24 months. METHOD: We obtained information on medical conditions using self-reports, birth certificates, and hospital records in 4909 mothers participating in Upstate KIDS, a population-based birth cohort. Mothers reported on their children's motor milestone achievement at 4, 8, 12, 18, and 24 months of age. RESULTS: After adjustment for covariates (including pre-pregnancy body mass index), children of mothers with gestational diabetes took longer to achieve sitting without support (hazard ratio [HR]=0.84, 95% confidence interval [CI] 0.75-0.93), walking with assistance (HR=0.88, 95% CI 0.77-0.98), and walking alone (HR=0.88, 95% CI 0.77-0.99) than children of females with no gestational diabetes. Similar findings emerged for maternal diabetes. Gestational hypertension was associated with a longer time to achieve walking with assistance. These associations did not change after adjustment for gestational age or birthweight. Severe hypertensive disorders of pregnancy were related to a longer time to achieve milestones, but not after adjustment for perinatal factors. INTERPRETATION: Children exposed to maternal diabetes, gestational or pre-gestational, may take longer to achieve motor milestones than non-exposed children, independent of maternal obesity.