Design and methods of a randomized telehealth-based intervention to improve fitness in survivors of childhood cancer with exercise intolerance.

BACKGROUND: Exercise intolerance among childhood cancer survivors substantially increases risk for early mortality, reduced cognitive function, poor quality of life, emotional distress, and sub-optimal participation in social roles. Fortunately, exercise intolerance is modifiable, even among individuals with impaired cardiopulmonary and neuromuscular health. This study aims to evaluate the impact of tailored exercise intervention remotely supervised by fitness professionals in survivors with exercise intolerance. Telehealth-based delivery of the intervention aims to enhance uptake by removing the burden of travel and allowing participants to gain confidence with exercise and physical activity at home. METHODS: This is an ongoing single-blind, two-arm, prospective, clinical trial that will randomize 160 participants 1:1 to intervention (n = 80) and attention control (n = 80) groups. The intervention group receives an individually tailored exercise prescription based on results from baseline assessments performed remotely via a Health Insurance Portability and Accountability Act-compliant virtual platform and personal preferences for aerobic exercise. Each prescription includes aerobic and strengthening components designed to progress gradually to 150-300-min of moderate aerobic activity and twice weekly strengthening exercises over 20-weeks. The first two weeks are supervised for 6 sessions, tapering to twice/week for weeks 3-4, once/week for weeks 5-8, every other week for weeks 9-16 and once midway between weeks 17-20. The schedule is modifiable depending on participant need, adherence, and response to exercise. Each session is approximately one hour. CONCLUSION: This study tests the efficacy of an individually prescribed, virtually supervised exercise intervention on exercise intolerant childhood cancer survivors. CLINICALTRIALS: gov registration: NCT04714840.

Design and methods of a randomized web-based physical activity intervention among children with cancer: A report from the Children's Oncology Group.

BACKGROUND: Promoting physical activity soon after treatment for childhood cancer may benefit health because sedentary lifestyle during curative therapy may perpetuate physical and emotional complications. The primary goals of this study are to evaluate the effects of a 6-month web-based, rewards-based physical activity intervention on fitness, biomarkers of cardiometabolic health, inflammation, adipokine status, quality of life and school attendance, and determine if effect of intervention on markers of cardiometabolic health is mediated by changes in fitness. The primary outcome of interest is fitness (physiological cost index, six-minute walk test) measured at end of intervention. METHODS: This ongoing study is a two-arm, prospective, randomized design with accrual goals of 192 children for intervention and control groups. Children ≥8 years and < 16 years of age, not meeting recommended levels of physical activity, who completed therapy within the past 12 months are eligible. Both groups receive: 1) educational materials encouraging physical activity, 2) activity monitor, 3) access to web-based interface designed to motivate physical activity, 4) rewards based on physical activity levels, and 5) access to their activity data on the web-interface. Those randomized to intervention: 1) can view others' activity and interact with other participants, and 2) receive rewards based on physical activity levels throughout the intervention (vs. at the end of the intervention for control group). CONCLUSION: Unique, scalable, and portable physical activity interventions that motivate young survivors are needed. This study will inform future web-based physical activity interventions for children with cancer by demonstrating effects of rewards and social interaction. CLINICAL TRIALS: ClinicalTrials.gov Identifier: NCT03223753; COG Identifier: ALTE1631.

Parent-child relationship quality and adolescent health: Testing the differential susceptibility and diathesis-stress hypotheses in African American youths.

This study tested two competing models of differential susceptibility and diathesis-stress in a prospective longitudinal study of African American youths (N = 935). It examined whether individual variations in the functioning of the hypothalamic-pituitary-adrenocortical axis at age 11 interact with middle childhood parent-child relationship quality to predict mental and physical health problems in adolescence (ages 11-15 years old). Adolescent boys with lower levels of cortisol reactivity to laboratory challenges had the highest levels of internalizing problems if they experienced a high conflictual relationship with their parents. Equally low-reactive boys, however, reported the lowest number of physical illnesses if their relationship with their parents was characterized by high levels of intimacy and support.

Developmental changes in external and internal performance monitoring across middle childhood: An ERP study.

Performance monitoring is critical for learning and behavioral adaption and is supported by both externally and internally sourced information. Cross-sectional studies indicate an increase in internal error processing across childhood, suggesting a potential developmental transition from reliance on external information to reliance on internally developed models. However, little research has examined the association between these constructs longitudinally. Data from 339 children assessed annually from kindergarten to 2nd grade were examined to determine the developmental trajectory of ERP indices of performance monitoring, and whether the association between these indices changes across time. EEG data were recorded during an incentivized Go/No-Go task and ERP component amplitudes were extracted as peak measures at Fz. Despite small increases in magnitude, no significant changes were observed in any of the ERPs. Multi-level regression analyses indicated that in kindergarten a more negative feedback-related negativity (FRN) was associated with a more negative error-related negativity (ERN) and a more negative error positivity (Pe). Further, the association between the FRN and Pe changed over time, such that in 2nd grade the FRN and Pe decoupled from one another and were no longer associated. These results suggest that the development of performance monitoring through middle childhood may be a phasic process. More specifically, matured external feedback monitoring processes may first facilitate the development of conscious error recognition, and then the development of internal error monitoring processes. Once internal models of error monitoring are well-established, children may then reduce their utilization of external feedback.

Influences of adversity across the lifespan on respiratory sinus arrhythmia during pregnancy.

There is limited understanding of factors across the lifespan that influence pregnant women's respiratory sinus arrhythmia (RSA), which could have implications for their health and offspring development. We examined associations among 162 English- and Spanish-speaking pregnant women's childhood maltreatment history, emotion dysregulation, recent life stress, and resting RSA during the third trimester. Moderated mediation analyses indicated that more severe childhood maltreatment history (95% confidence interval (CI) [0.26, 0.63]) and higher emotion dysregulation (95% CI [0.001, 0.006]) predicted more stress during pregnancy, and childhood maltreatment history interacted with emotion dysregulation to predict resting RSA (95% CI [-0.04, -0.0003]). Exploratory analyses revealed that women's health-related stress during pregnancy mediated the relation between emotion dysregulation and RSA regardless of childhood maltreatment severity (95% CI [-0.007, -0.002]). These findings suggest that women's resting RSA during pregnancy may reflect physical and emotional stress accumulation across the lifespan and that relations between early life adversity and prenatal psychophysiology may be buffered by protective factors, such as emotion regulation. In addition, these findings underscore the importance of distinguishing between types of prenatal stress. Given the implications for women's health and offspring development, we urge researchers to continue exploring factors associated with pregnant women's psychophysiology.

Prenatal maternal transdiagnostic, RDoC-informed predictors of newborn neurobehavior: Differences by sex.

We examined whether Research Domain Criteria (RDoC)-informed measures of prenatal stress predicted newborn neurobehavior and whether these effects differed by newborn sex. Multilevel, prenatal markers of prenatal stress were obtained from 162 pregnant women. Markers of the Negative Valence System included physiological functioning (respiratory sinus arrhythmia [RSA] and electrodermal [EDA] reactivity to a speech task, hair cortisol), self-reported stress (state anxiety, pregnancy-specific anxiety, daily stress, childhood trauma, economic hardship, and family resources), and interviewer-rated stress (episodic stress, chronic stress). Markers of the Arousal/Regulatory System included physiological functioning (baseline RSA, RSA, and EDA responses to infant cries) and self-reported affect intensity, urgency, emotion regulation strategies, and dispositional mindfulness. Newborns' arousal and attention were assessed via the Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scale. Path analyses showed that high maternal episodic and daily stress, low economic hardship, few emotion regulation strategies, and high baseline RSA predicted female newborns' low attention; maternal mindfulness predicted female newborns' high arousal. As for male newborns, high episodic stress predicted low arousal, and high pregnancy-specific anxiety predicted high attention. Findings suggest that RDoC-informed markers of prenatal stress could aid detection of variance in newborn neurobehavioral outcomes within hours after birth. Implications for intergenerational transmission of risk for psychopathology are discussed.

Behavioral and physiological stress responses: Within-person concordance during pregnancy.

During pregnancy, a woman's emotions can have longstanding implications for both her own and her child's health. Within-person emotional concordance refers to the simultaneous measurement of emotional responses across multiple levels of analysis. This method may provide insight into how pregnant women experience emotions in response to stress. We enrolled 162 pregnant women and assessed concordance through autonomic physiology (electrodermal activity [EDA], respiratory sinus arrhythmia [RSA]), and coded behavior (Prosocial, Flight, Displacement) during the Trier Social Stress Test-Speech. We used multilevel models to examine behavioral-physiological concordance and whether self-reported emotion dysregulation moderated these effects. Participants exhibited EDA-Prosocial concordance, suggesting that prosocial behavior may be a marker of stress. Emotion dysregulation did not moderate concordance. These findings provide novel information about behavioral coping to stress in pregnancy. Given the importance of observed behavior in the maintenance and treatment of psychopathology, these findings may provide a launchpad for future perinatal intervention research.

Prenatal substance exposure and maternal hostility from pregnancy to toddlerhood: Associations with temperament profiles at 16 months of age.

We investigated whether infant temperament was predicted by level of and change in maternal hostility, a putative transdiagnostic vulnerability for psychopathology, substance use, and insensitive parenting. A sample of women (N = 247) who were primarily young, low-income, and had varying levels of substance use prenatally (69 nonsmokers, 81 tobacco-only smokers, and 97 tobacco and marijuana smokers) reported their hostility in the third trimester of pregnancy and at 2, 9, and 16 months postpartum, and their toddler's temperament and behavior problems at 16 months. Maternal hostility decreased from late pregnancy to 16 months postpartum. Relative to pregnant women who did not use substances, women who used both marijuana and tobacco prenatally reported higher levels of hostility while pregnant and exhibited less change in hostility over time. Toddlers who were exposed to higher levels of prenatal maternal hostility were more likely to be classified in temperament profiles that resemble either irritability or inhibition, identified via latent profile analysis. These two profiles were each associated with more behavior problems concurrently, though differed in their association with competence. Our results underscore the utility of transdiagnostic vulnerabilities in understanding the intergenerational transmission of psychopathology risk and are discussed in regards to the Research Domain Criteria (RDoC) framework.

Prenatal maternal hair cortisol concentrations are related to maternal prenatal emotion dysregulation but not neurodevelopmental or birth outcomes.

Hair cortisol concentrations measured during pregnancy have emerged as a novel biomarker for prenatal stress exposure. However, associations between prenatal stress and distress, broadly defined, and hair cortisol concentrations during pregnancy are inconsistent. We examined relations among hair cortisol concentrations during the third trimester with (a) emotion dysregulation and (b) detailed measures of maternal prenatal stress. We also examined the predictive validity of maternal hair cortisol during pregnancy for adverse newborn health outcomes. Cortisol concentrations were derived from 6 cm of hair during the third trimester of pregnancy. Mothers reported on their emotion dysregulation and stress at this time. A standardized newborn neurobehavioral exam was conducted shortly after birth and newborn birth weight and gestational age were assessed from medical records. All hypotheses were preregistered on the Open Science Framework (osf.io/279ng). High levels of emotion dysregulation, but not stress, were predictive of high hair cortisol concentrations. Maternal prenatal BMI mediated the relation between maternal prenatal emotion dysregulation and hair cortisol concentrations. There was no association between hair cortisol and infant birth outcomes. This research supports the notion that transdiagnostic markers of psychopathology are important correlates of hair cortisol concentrations during pregnancy.

Intergenerational transmission of emotion dysregulation: Part I. Psychopathology, self-injury, and parasympathetic responsivity among pregnant women.

The World Health Organization recently reported that maternal mental health is a major public health concern. As many as one in four women suffer from psychiatric disorders at some point during pregnancy or the first postpartum year. Furthermore, self-injurious thoughts and behaviors (SITBs) represent one of the leading causes of death among women during this time. Thus, efforts to identify women at risk for serious forms of psychopathology and especially for SITBs are of utmost importance. Despite this urgency, current single-diagnostic approaches fail to recognize a significant subset of women who are vulnerable to perinatal stress and distress. The current study was among the first to investigate emotion dysregulation-a multilevel, transdiagnostic risk factor for psychopathology-and its associations with stress, distress, and SITBs in a sample of pregnant women (26-40 weeks gestation) recruited to reflect a range of emotion dysregulation. Both self-reported emotion dysregulation and respiratory sinus arrhythmia, a biomarker of emotion dysregulation, demonstrated expected associations with measures of mental health, including depression, anxiety, borderline personality pathology, and SITBs. In addition, self-reported emotion dysregulation was associated with blunted respiratory sinus arrhythmia responsivity to an ecologically valid infant cry task. Findings add to the literature considering transdiagnostic risk during pregnancy using a multiple-levels-of-analysis approach.

Intergenerational transmission of emotion dysregulation: Part II. Developmental origins of newborn neurobehavior.

We investigated whether neurobehavioral markers of risk for emotion dysregulation were evident among newborns, as well as whether the identified markers were associated with prenatal exposure to maternal emotion dysregulation. Pregnant women (N = 162) reported on their emotion dysregulation prior to a laboratory assessment. The women were then invited to the laboratory to assess baseline respiratory sinus arrhythmia (RSA) and RSA in response to an infant cry. Newborns were assessed after birth via the NICU Network Neurobehavioral Scale. We identified two newborn neurobehavioral factors-arousal and attention-via exploratory factor analysis. Low arousal was characterized by less irritability, excitability, and motor agitation, while low attention was related to a lower threshold for auditory and visual stimulation, less sustained attention, and poorer visual tracking abilities. Pregnant women who reported higher levels of emotion dysregulation had newborns with low arousal levels and less attention. Larger decreases in maternal RSA in response to cry were also related to lower newborn arousal. We provide the first evidence that a woman's emotion dysregulation while pregnant is associated with risks for dysregulation in her newborn. Implications for intergenerational transmission of emotion dysregulation are discussed.

A developmental origins perspective on the emergence of violent behavior in males with prenatal substance exposure.

Children with prenatal substance exposure are at increased risk for externalizing behavior problems and violence. However, the contribution of early life experiences for placing these individuals at risk is not well understood. Utilizing a sample of 1,388 children with prenatal substance exposure from the Maternal Lifestyle Study, we attempt to shed light on these contributing factors by examining the impact of infant temperament, maternal sensitivity, and early life stress on the expression of violent behavior at ages 12 through 14 years. Males may be more at risk for increases in violent behavior in early adolescence through a number of early life experiences, such as variability in responses to maternal flexibility and engagement related to individual differences in temperament, as well as exposure to early adversity. Comparing two prevailing developmental theoretical frameworks, deficit models and differential susceptibility, we aim to understand the developmental origins of violent behavior in males by identifying children who may be most susceptible to early caregiving experiences.

The Recruitment Experience of a Randomized Clinical Trial to Aid Young Adult Smokers to Stop Smoking without Weight Gain with Interactive Technology.

Multiple recruitment strategies are often needed to recruit an adequate number of participants, especially hard to reach groups. Technology-based recruitment methods hold promise as a more robust form of reaching and enrolling historically hard to reach young adults. The TARGIT study is a randomized two-arm clinical trial in young adults using interactive technology testing an efficacious proactive telephone Quitline versus the Quitline plus a behavioral weight management intervention focusing on smoking cessation and weight change. All randomized participants in the TARGIT study were required to be a young adult smoker (18-35 years), who reported smoking at least 10 cigarettes per day, had a BMI < 40 kg/m2, and were willing to stop smoking and not gain weight. Traditional recruitment methods were compared to technology-based strategies using standard descriptive statistics based on counts and proportions to describe the recruitment process from initial pre-screening (PS) to randomization into TARGIT. Participants at PS were majority Black (59.80%), female (52.66%), normal or over weight (combined 62.42%), 29.5 years old, and smoked 18.4 cigarettes per day. There were differences in men and women with respect to reasons for ineligibility during PS (p < 0.001; ignoring gender specific pregnancy-related ineligibility). TARGIT experienced a disproportionate loss of minorities during recruitment as well as a prolonged recruitment period due to either study ineligibility or not completing screening activities. Recruitment into longer term behavioral change intervention trials can be challenging and multiple methods are often required to recruit hard to reach groups.

Calcium intake and body composition in African-American children and adolescents at risk for overweight and obesity.

This study examined the role of calcium intake on body composition in 186 African-American adolescents at risk for overweight and obesity. The average weight of 89.8 kg ± 23.6 (SD) had a mean BMI z score of 2.2. Females with a calcium intake of <314 mg/day had higher percent fat mass compared to those with the highest calcium intakes that were ≥634 mg/day. Compared to those with a low calcium intake (<365 mg/day), those with the highest calcium intake of >701 mg/day had higher intake of thiamin, folate, cobalamin, vitamin D, phosphorus, iron, zinc.