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1.  Protective Factors Can Mitigate Behavior Problems After Prenatal Cocaine and Other Drug Exposures 
Pediatrics  2012;130(6):e1479-e1488.
We determined the role of risk and protective factors on the trajectories of behavior problems associated with high prenatal cocaine exposure (PCE)/polydrug exposure.
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).
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.
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.
PMCID: PMC3507246  PMID: 23184114
behavior problems; cumulative risks; prenatal cocaine exposure; protective factors
2.  Neurobehavioral Disinhibition Predicts Initiation of Substance Use in Children with Prenatal Cocaine Exposure 
Drug and alcohol dependence  2012;126(1-2):80-86.
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 8–16 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.
We studied 386 cocaine exposed and 517 unexposed children followed since birth in a longitudinal study. Five dichotomous variables were computed based on the subject’s report of substance use: alcohol only; tobacco only; marijuana only; illicit substances and any substance.
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.
Prenatal drug exposure appears to be a risk pathway to ND, which by 8/9 years portends substance use initiation.
PMCID: PMC3439586  PMID: 22608010
neurodevelopmental disinhibition; substance use initiation; prenatal cocaine exposure
3.  Long-Term Impact of Maternal Substance Use during Pregnancy and Extrauterine Environmental Adversity: Stress Hormone Levels of Preadolescent Children 
Pediatric research  2011;70(2):213-219.
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. While 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.
PMCID: PMC3686483  PMID: 21546861
4.  Maintaining Participation and Momentum in Longitudinal Research Involving High-Risk Families 
Journal of Nursing Scholarship  2012;44(2):120-126.
The purpose of the current study was to identify and describe strategies available to optimize retention of a high-risk research cohort and assist in the recovery of study participants following participant dropout.
Design and Methods
The Maternal Lifestyle Study (MLS), which investigated the effects of prenatal substance exposure (cocaine or opiates) on child outcome, is a prospective longitudinal follow-up study that extended from birth through 15 years of age. Retention strategies to maximize participation and factors that might negatively impact compliance were examined over the course of five follow-up phases.
At the conclusion of the 15-year visits, MLS had successfully maintained compliance at 76%. Retention rates did not differ by exposure group.
Maintaining ongoing participation of enrolled study subjects is a critical element of any successful longitudinal study. Strategies that can be used to reengage and maintain participants in longitudinal research include persistence, flexibility with scheduling, home visits, long-distance trips, increased incentives, and development of a computerized tracking system. Establishing rapport with families and ensuring confidentiality contributed to overall participant retention. The use of multiple tracking techniques is essential.
Clinical Relevance
Researchers are challenged to maintain participants in longitudinal studies to ensure the integrity of their research.
PMCID: PMC3366028  PMID: 22458928
Longitudinal research; participant retention; tracking; compliance
5.  Psychopathology and Special Education Enrollment in Children with Prenatal Cocaine Exposure 
This study evaluated how enrollment in special education services in 11 year old children relates to prenatal cocaine exposure, psychopathology, and other risk factors.
Participants were 498 children enrolled in The Maternal Lifestyle Study, a prospective, longitudinal, multisite study examining outcomes of children with prenatal cocaine exposure. Logistic regression was used to examine the effect of prenatal cocaine exposure and psychopathology on enrollment in an individualized education plan (a designation specific to children with special education needs), with environmental, maternal, and infant medical variables as covariates.
Prenatal cocaine exposure, an interaction of prenatal cocaine exposure and Oppositional Defiant Disorder, child Attention Deficit Hyperactivity Disorder, parent-reported internalizing behaviors, and teacher-reported externalizing behaviors, predicted enrollment in an individualized education plan. Other statistically significant variables in the model were male gender, low birth weight, being small for gestational age, white race, caregiver change, low socio-economic status, low child intelligence quotient, caregiver depression, and prenatal marijuana exposure.
Prenatal cocaine exposure increased the likelihood of receiving an individualized education plan with adjustment for covariates. Psychopathology also predicted this special education outcome, in combination with and independent of prenatal cocaine exposure.
PMCID: PMC3400535  PMID: 22487696
cocaine; special education; behavior; prenatal substance exposure
6.  Physical Activity And Physical Fitness 
The focus of the PhenX (Phenotypes and eXposures) Toolkit is to provide researchers whose expertise lies outside a particular area with key measures identified by experts for uniform use in large-scale genetic studies and other extensive epidemiologic efforts going forward. The current paper specifically addresses the PhenX Toolkit research domain of physical activity and physical fitness (PA/PF), which are often associated with health outcomes. A Working Group (WG) of content experts completed a 6-month consensus process in which they identified a set of 14 high-priority, low-burden, and scientifically supported measures. During this process the WG considered self-reported and objective measures which included the latest technology (e.g., accelerometers, pedometers, heart-rate monitors). They also sought the input of measurement experts and other members of the research community during their deliberations. A majority of the measures include protocols for children (or adolescents), adults, and older adults or are applicable to all ages.
Measures from the PA/PF domain and 20 other domains are publicly available and found at the PhenX Toolkit website, The use of common measures and protocols across large studies enhances the capacity to combine or compare data across studies, benefitting both PA/PF experts and non-experts. Use of these common measures by the research community should increase statistical power and enhance the ability to answer scientific questions that might have previously gone unanswered.
PMCID: PMC3331998  PMID: 22516489
7.  Childhood Outcomes after Hypothermia for Neonatal Encephalopathy 
The New England journal of medicine  2012;366(22):2085-2092.
We previously reported early results of a randomized trial of whole-body hypothermia for neonatal hypoxic–ischemic encephalopathy showing a significant reduction in the rate of death or moderate or severe disability at 18 to 22 months of age. Long-term outcomes are now available.
In the original trial, we assigned infants with moderate or severe encephalopathy to usual care (the control group) or whole-body cooling to an esophageal temperature of 33.5°C for 72 hours, followed by slow rewarming (the hypothermia group). We evaluated cognitive, attention and executive, and visuospatial function; neurologic outcomes; and physical and psychosocial health among participants at 6 to 7 years of age. The primary outcome of the present analyses was death or an IQ score below 70.
Of the 208 trial participants, primary outcome data were available for 190. Of the 97 children in the hypothermia group and the 93 children in the control group, death or an IQ score below 70 occurred in 46 (47%) and 58 (62%), respectively (P = 0.06); death occurred in 27 (28%) and 41 (44%) (P = 0.04); and death or severe disability occurred in 38 (41%) and 53 (60%) (P = 0.03). Other outcome data were available for the 122 surviving children, 70 in the hypothermia group and 52 in the control group. Moderate or severe disability occurred in 24 of 69 children (35%) and 19 of 50 children (38%), respectively (P = 0.87). Attention–executive dysfunction occurred in 4% and 13%, respectively, of children receiving hypothermia and those receiving usual care (P = 0.19), and visuospatial dysfunction occurred in 4% and 3% (P = 0.80).
The rate of the combined end point of death or an IQ score of less than 70 at 6 to 7 years of age was lower among children undergoing whole-body hypothermia than among those undergoing usual care, but the differences were not significant. However, hypothermia resulted in lower death rates and did not increase rates of severe disability among survivors. (Funded by the National Institutes of Health and the Eunice Kennedy Shriver NICHD Neonatal Research Network; number, NCT00005772.)
PMCID: PMC3459579  PMID: 22646631
8.  The Combined Effects of Prenatal Drug Exposure and Early Adversity on Neurobehavioral Disinhibition in Childhood and Adolescence 
Development and Psychopathology  2011;23(3):777-788.
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 1073 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.
PMCID: PMC3335443  PMID: 21756431
9.  The Mediating Effect of Depressive Symptoms on the Relationship between Traumatic Childhood Experiences and Drug Use Initiation 
Addictive behaviors  2011;36(5):527-531.
Stressful experiences such as childhood trauma and depressive symptoms have both been implicated in the initiation of drug use; however, longitudinal designs have not yet been used to elucidate their respective roles to better understand the causal sequence. In the present study, a sensitivity analysis was conducted using two mediation strategies to examine how this sequence may differ by various levels of statistical control, including (1) the standard mediational model in which the effect of lifetime traumatic stressors (Year 1) on the onset of drug use (Years 3 and 4) is mediated by levels of depressive symptoms (Year 2); and (2) a stronger test of causality such that the effect of lifetime traumatic stressors (Year 1) on the onset of drug use (Years 3 and 4) was mediated by changes in depressive symptoms (Year 1 to 2), measured by a residualized change score that controlled for levels in Year 1. Two types of trauma were studied in a community-based study of 489 Hispanic preadolescents (aged 10–12): (a) the number of lifetime traumatic stressors and (b) seven specific lifetime stressors. We also controlled for new onset traumatic stressors occurring between Years 1 and 2. Primary findings indicate that drug use initiation during early adolescence (e.g., ages 14–16) may not be tied to immediate proximal perturbations in risk factors, such as traumatic experiences and depressive symptoms. Rather, the effects of trauma on depression in this sample appear to be established earlier in childhood (ages 10–14 or younger) and persist in a relatively stable manner into middle adolescence when the risk for drug use may be heightened.
PMCID: PMC3046237  PMID: 21296505
drug use; youth; childhood trauma; depression; mediation; prevention
10.  Serial Pediatric Symptom Checklist Screening in Children with Prenatal Drug Exposure 
To examine screening results obtained by serial annual behavioral assessment of children with prenatal drug exposure.
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 to an established broad-based behavioral measure at 9, 11, and 13 years. PSC results were analyzed for 1,081 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.
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 pre- and post-natally 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.
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.
PMCID: PMC3069136  PMID: 21200328
Behavior disorder; child behavior; mental health; screening; prenatal cocaine exposure; Pediatric Symptom Checklist

Results 1-10 (10)