Toni M. Whitaker

The Combined Effects of Prenatal Drug Exposure and Early Adversity on Neurobehavioral Disinhibition in Childhood and Adolescence

The negative effects of prenatal substance exposure on neurobiological and psychological development and of early adversity are clear, but little is known about their combined effects. In this study, multilevel analyses of the effects of prenatal substance exposure and early adversity on the emergence of neurobehavioral disinhibition in adolescence were conducted. Neurobehavioral disinhibition has previously been observed to occur frequently in multiproblem youth from high-risk backgrounds. In the present study, neurobehavioral disinhibition was assessed via behavioral dysregulation and poor executive function composite measures. Data were drawn from a prospective longitudinal investigation of prenatal substance exposure that included 1,073 participants followed from birth through adolescence. The results from latent growth modeling analyses showed mean stability but significant individual differences in behavioral dysregulation and mean decline with individual differences in executive function difficulties. Prior behavioral dysregulation predicted increased executive function difficulties. Prenatal drug use predicted the emergence and growth in neurobehavioral disinhibition across adolescence (directly for behavioral dysregulation and indirectly for executive function difficulties via early adversity and behavioral dysregulation). Prenatal drug use and early adversity exhibited unique effects on growth in behavioral dysregulation; early adversity uniquely predicted executive function difficulties. These results are discussed in terms of implications for theory development, social policy, and prevention science.

Neurobehavioral Disinhibition Predicts Initiation of Substance Use in Children with Prenatal Cocaine Exposure

BACKGROUND In previous work we (Fisher et al., 2011) examined the emergence of neurobehavioral disinhibition (ND) in adolescents with prenatal substance exposure. We computed ND factor scores at three age points (8/9, 11 and 13/14 years) and found that both prenatal substance exposure and early adversity predicted ND. The purpose of the current study was to determine the association between these ND scores and initiation of substance use between ages 8 and 16 in this cohort as early initiation of substance use has been related to later substance use disorders. Our hypothesis was that prenatal cocaine exposure predisposes the child to ND, which, in turn, is associated with initiation of substance use by age 16. METHODS We studied 386 cocaine exposed and 517 unexposed children followed since birth in a longitudinal study. Five dichotomous variables were computed based on the subjects report of substance use: alcohol only; tobacco only; marijuana only; illicit substances and any substance. RESULTS Cox proportional hazard regression showed that the 8/9 year ND score was related to initiation of alcohol, tobacco, illicit and any substance use but not marijuana use. The trajectory of ND across the three age periods was related to substance use initiation in all five substance use categories. Prenatal cocaine exposure, although initially related to tobacco, marijuana and illicit substance initiation, was no longer significant with ND scores in the models. CONCLUSION Prenatal drug exposure appears to be a risk pathway to ND, which by 8/9 years portends substance use initiation.

Protective factors can mitigate behavior problems after prenatal cocaine and other drug exposures

BACKGROUND: We determined the role of risk and protective factors on the trajectories of behavior problems associated with high prenatal cocaine exposure (PCE)/polydrug exposure. METHODS: The Maternal Lifestyle Study enrolled 1388 children with or without PCE, assessed through age 15 years. Because most women using cocaine during pregnancy also used other substances, we analyzed for the effects of 4 categories of prenatal drug exposure: high PCE/other drugs (OD), some PCE/OD, OD/no PCE, and no PCE/no OD. Risks and protective factors at individual, family, and community levels that may be associated with behavior outcomes were entered stepwise into latent growth curve models, then replaced by cumulative risk and protective indexes, and finally by a combination of levels of risk and protective indexes. Main outcome measures were the trajectories of externalizing, internalizing, total behavior, and attention problems scores from the Child Behavior Checklist (parent). RESULTS: A total of 1022 (73.6%) children had known outcomes. High PCE/OD significantly predicted externalizing, total, and attention problems when considering the balance between risk and protective indexes. Some PCE/OD predicted externalizing and attention problems. OD/no PCE also predicted behavior outcomes except for internalizing behavior. High level of protective factors was associated with declining trajectories of problem behavior scores over time, independent of drug exposure and risk index scores. CONCLUSIONS: High PCE/OD is a significant risk for behavior problems in adolescence; protective factors may attenuate its detrimental effects. Clinical practice and public health policies should consider enhancing protective factors while minimizing risks to improve outcomes of drug-exposed children.

Prevalence of developmental and behavioral disorders in a pediatric hospital

OBJECTIVE. The objective of this study was to estimate the prevalence of developmental and behavioral disorders in a convenience sample of children in an acute care pediatric hospital setting. We hypothesized that hospitalized children would have a higher prevalence of developmental and behavioral disorders than the general population. METHODS. Data for this cross-sectional study were collected during interviews with primary caregivers of 325 children from infancy throughout childhood who were admitted to a general pediatric service. Screening tests included the Child Development Inventory (3 months to 6 years), Parents’ Evaluation of Developmental Status (0–8 years), Pediatric Symptom Checklist (4–18 years), and Vanderbilt Attention-Deficit/Hyperactivity Disorder Parent Rating Scale (6–18 years). Children were classified as having a known developmental and behavioral disorder, a suspected developmental and behavioral disorder, or no developmental and behavioral disorder. RESULTS. The prevalence of developmental and behavioral disorders among the hospitalized children 6 months to 17 years of age was 33.5%. A total of 72 children (22.1%) had known developmental and behavioral disorders and 37 (11.4%) had suspected developmental and behavioral disorders. This high prevalence of developmental and behavioral disorders included high rates of cerebral palsy (6.1%) and mental retardation or developmental delay (8.6%). CONCLUSION. Hospitalization for treatment of acute conditions provides another opportunity for developmental surveillance. This higher prevalence of developmental and behavioral disorders in hospitalized children emphasizes the need to screen for developmental disabilities at every opportunity. Strategies to implement systematic screening of hospitalized children should be examined.

Risk-Taking Behavior Among Adolescents with Prenatal Drug Exposure and Extrauterine Environmental Adversity

Objective: High-risk environments characterized by familial substance use, poverty, inadequate parental monitoring, and violence exposure are associated with an increased propensity for adolescents to engage in risk-taking behaviors (e.g., substance use, sexual behavior, and delinquency). However, additional factors such as drug exposure in utero and deficits in inhibitory control among drug-exposed youth may further influence the likelihood that adolescents in high-risk environments will engage in risk-taking behavior. This study examined the influence of prenatal substance exposure, inhibitory control, and sociodemographic/environmental risk factors on risk-taking behaviors in a large cohort of adolescents with and without prenatal cocaine exposure (PCE). Method: Risk-taking behavior (delinquency, substance use, and sexual activity) was assessed in 963 adolescents (433 cocaine-exposed, 530 nonexposed) at 15 years of age. Results: Prenatal cocaine exposure predicted later arrests and early onset of sexual behavior in controlled analyses. Associations were partially mediated, however, by adolescent inhibitory control problems. PCE was not associated with substance use at this age. In addition, male gender, low parental involvement, and violence exposure were associated with greater odds of engaging in risk-taking behavior across the observed domains. Conclusions: Study findings substantiate concern regarding the association between prenatal substance exposure and related risk factors and the long-term outcomes of exposed youth. Access to the appropriate social, educational, and medical services is essential in preventing and intervening with risk-taking behaviors and the potential consequences (e.g., adverse health outcomes and incarceration), especially among high-risk adolescent youth and their families.

Long-term impact of maternal substance use during pregnancy and extrauterine environmental adversity: stress hormone levels of preadolescent children.

Prenatal cocaine exposure (PCE) is associated with blunted stress responsivity within the extrauterine environment. This study investigated the association between PCE and diurnal salivary cortisol levels in preadolescent children characterized by high biological and/or social risk (n = 725). Saliva samples were collected at their home. Analyses revealed no group differences in basal evening or morning cortisol levels; however, children with higher degrees of PCE exhibited blunted overnight increases in cortisol, controlling for additional risk factors. Race and caregiver depression were also associated with diurnal cortisol patterns. Although repeated PCE may contribute to alterations in the normal or expected stress response later in life, sociodemographic and environmental factors are likewise important in understanding hormone physiology, especially as more time elapses from the PCE. Anticipating the potential long-term medical, developmental, or behavioral effects of an altered ability to mount a normal protective cortisol stress response is essential in optimizing the outcomes of children with PCE.

Prenatal Substance Exposure: Neurobiologic Organization at 1 Month

OBJECTIVE To examine the autonomic nervous system and neurobehavioral response to a sustained visual attention challenge in 1-month-old infants with prenatal substance exposure. STUDY DESIGN We measured heart rate, respiratory sinus arrhythmia, and neurobehavior during sustained visual orientation tasks included in the Neonatal Intensive Care Unit Network Neurobehavioral Scale in 1129 1-month-old infants with prenatal substance exposure. Four groups were compared: infants with prenatal cocaine and opiate exposure, infants with cocaine exposure, infants with opiate exposure, and infants with exposure to other substances (ie, alcohol, marijuana, and tobacco). RESULTS The infants with prenatal exposure to both cocaine and opiates had the highest heart rates and lowest levels of respiratory sinus arrhythmia during a sustained visual attention challenge compared with the other 3 groups. Infants with prenatal cocaine and opiate exposure had poorer quality of movement and more hypertonicity during the Neonatal Intensive Care Unit Network Neurobehavioral Scale examination. They also had more nonoptimal reflexes and stress/abstinence signs compared with infants with prenatal exposure to cocaine only and those with prenatal exposure to alcohol, tobacco, and marijuana. CONCLUSION Problems with arousal regulation were identified in infants with prenatal substance exposure. Autonomic dysregulation has been implicated as a mechanism by which these difficulties occur. Our results suggest that infants with prenatal exposure to both cocaine and opiates have the greatest autonomic response to the challenge of a sustained visual attention task, possibly putting these infants at risk for problems associated with physiologic and behavioral regulation, a necessary prerequisite for early learning.

The contributions of early adverse experiences and trajectories of respiratory sinus arrhythmia on the development of neurobehavioral disinhibition among children with prenatal substance exposure.

Neurobehavioral disinhibition (ND) is a complex condition reflecting a wide range of problems involving difficulties with emotion regulation and behavior control. Respiratory sinus arrhythmia (RSA) is a physiological correlate of emotion regulation that has been studied in a variety of at-risk populations; however, there are no studies of RSA in children with ND. Data were drawn from a prospective longitudinal study of prenatal substance exposure that included 1,073 participants. Baseline RSA and RSA reactivity to an attention-demanding task were assessed at 3, 4, 5, and 6 years. ND was assessed at ages 8/9, 11, and 13/14 years via behavioral dysregulation and executive dysfunction composite measures. Greater exposure to early adversity was related to less RSA reactivity at 3 years, increases in RSA reactivity from ages 3 to 6 years, and increased behavioral dysregulation from ages 8/9 to 13/14. RSA reactivity was examined as a moderator of the association between early adversity and changes in ND. A significant Early Adversity × RSA Reactivity quadratic interaction revealed that children with decelerations in RSA reactivity exhibited increases in behavioral dysregulation, regardless of their exposure to early adversity. However, greater exposure to early adversity was related to greater increases in behavioral dysregulation, but only if children exhibited accelerations in RSA reactivity from ages 3 to 6 years. The results contribute to our understanding of how interactions across multiple levels of analysis contribute to the development of ND.

Early caregiving stress exposure moderates the relation between respiratory sinus arrhythmia reactivity at 1 month and biobehavioral outcomes at age 3

There is a growing scientific interest in the psychophysiological functioning of children living in low-socioeconomic status (SES) contexts, though this research is complicated by knowledge that physiology-behavior relations often operate differently in these environments among adults. Importantly, such research is made more difficult because SES may be a proxy for a wide range of risk factors including poor caregiving and exposure to parental substance use. We used factor analysis to organize risk-exposure data collected from 827 children-many of whom were raised in low-SES contexts and exposed to substances prenatally-into dissociable components including economic stress, caregiving stress (e.g., stress the caregiver may experience, including parental psychopathology), and postnatal substance exposure. These factors, along with respiratory sinus arrhythmia (RSA) reactivity at age 1 month, were used to predict behavior dysregulation and resting RSA at age 3 years. A significant RSA Reactivity × Caregiving Stress interaction indicated that infants who exhibited high RSA reactivity at 1 month experienced the greatest behavior dysregulation at 3 years, but only when they were exposed to high levels of caregiving stress. Among African Americans, the highest resting RSA at 3 years was found in infants with less RSA reactivity, but only if they also experienced less caregiving stress. Our work is consistent with biological sensitivity to context, adaptive calibration, and allostatic load models, and highlights the importance of studying Physiology × Environment interactions in low-SES contexts for predicting behavior and resting RSA.

Serial pediatric symptom checklist screening in children with prenatal drug exposure

Objective: To examine screening results obtained by serial annual behavioral assessment of children with prenatal drug exposure. Method: The Maternal Lifestyle Study enrolled children with prenatal cocaine exposure (PCE) at birth for longitudinal assessments of developmental, behavioral, and health outcomes. At 8, 9, 10, 11, and 12 years of age, caregivers rated participants on the Pediatric Symptom Checklist (PSC). Serial PSC results were compared with an established broad-based behavioral measure at 9, 11, and 13 years. PSC results were analyzed for 1081 children who had at least 2 annual screens during the 5-year time span. Most subjects (87%) had 4 or more annual screens rated by the same caregiver (80%). PSC scores (and Positive screens) over time were compared at different time points for those with and without PCE. Covariates, including demographic factors and exposures to certain other substances, were controlled. Results: Children with PCE had significantly higher scores overall, with more Positive screens for behavior problems than children without PCE. Children with PCE had more externalizing behavior problems. Children exposed to tobacco prenatally and postnatally also showed higher PSC scores. Over time, PSC scores differed slightly from the 8-year scores, without clear directional trend. Earlier PSC results predicted later behavioral outcomes. Conclusion: Findings of increased total PSC scores and Positive PSC screens for behavioral concerns in this group of children with prenatal substance exposure support the growing body of evidence that additional attention to identification of mental health problems may be warranted in this high-risk group.