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1.  Transactional relations between caregiving stress, executive functioning, and problem behavior from early childhood to early adolescence 
Development and psychopathology  2016;28(3):743-756.
Developmental psychopathologists face the difficult task of identifying the environmental conditions that may contribute to early childhood behavior problems. Highly stressed caregivers can exacerbate behavior problems, while children with behavior problems may make parenting more difficult and increase caregiver stress. Unknown is: (1) how these transactions originate, (2) whether they persist over time to contribute to the development of problem behavior and (3) what role resilience factors, such as child executive functioning, may play in mitigating the development of problem behavior. In the present study, transactional relations between caregiving stress, executive functioning, and behavior problems were examined in a sample of 1,388 children with prenatal drug exposures at three developmental time points: early childhood (birth-age 5), middle childhood (ages 6 to 9), and early adolescence (ages 10 to 13). Transactional relations differed between caregiving stress and internalizing versus externalizing behavior. Targeting executive functioning in evidence-based interventions for children with prenatal substance exposure who present with internalizing problems and treating caregiving psychopathology, depression, and parenting stress in early childhood may be particularly important for children presenting with internalizing behavior.
doi:10.1017/S0954579416000286
PMCID: PMC4955944  PMID: 27427803
2.  Global motion perception is independent from contrast sensitivity for coherent motion direction discrimination and visual acuity in 4.5-year-old children 
Vision research  2015;115(0 0):83-91.
Global motion processing depends on a network of brain regions that includes extrastriate area V5 in the dorsal visual stream. For this reason, psychophysical measures of global motion perception have been used to provide a behavioural measure of dorsal stream function. This approach assumes that global motion is relatively independent of visual functions that arise earlier in the visual processing hierarchy such as contrast sensitivity and visual acuity. We tested this assumption by assessing the relationships between global motion perception, contrast sensitivity for coherent motion direction discrimination (henceforth referred to as contrast sensitivity) and habitual visual acuity in a large group of 4.5-year-old children (n = 117). The children were born at risk of abnormal neurodevelopment because of prenatal drug exposure or risk factors for neonatal hypoglycaemia. Motion coherence thresholds, a measure of global motion perception, were assessed using random dot kinematograms. The contrast of the stimuli was fixed at 100% and coherence was varied. Contrast sensitivity was measured using the same stimuli by fixing motion coherence at 100% and varying dot contrast. Stereoacuity was also measured. Motion coherence thresholds were not correlated with contrast sensitivity or visual acuity. However, lower (better) motion coherence thresholds were correlated with finer stereoacuity (rho=0.38, p=0.004). Contrast sensitivity and visual acuity were also correlated (rho= −0.26, p=0.004) with each other. These results indicate that global motion perception for high contrast stimuli is independent of contrast sensitivity and visual acuity and can be used to assess motion integration mechanisms in children.
doi:10.1016/j.visres.2015.08.007
PMCID: PMC4587337  PMID: 26318529
Visual development; extrastriate visual cortex; preschool vision assessment; at risk infant
3.  Developmental and behavioral consequences of prenatal methamphetamine exposure: a review of the Infant Development, Environment, and Lifestyle (IDEAL) Study 
This study reviews the findings from the Infant Development, Environment, and Lifestyle Study (IDEAL), a multisite, longitudinal, prospective study designed to determine maternal outcome and child growth and developmental findings following prenatal methamphetamine exposure from birth up to age 7.5 years. These findings are presented in the context of the home environment and caregiver characteristics to determine how the drug and the environment interact to affect the outcome of these children. No neonatal abstinence syndrome requiring pharmacologic intervention was observed but heavy drug exposure was associated with increased stress responses in the neonatal period. Poorer inhibitory control was also observed in heavy methamphetamine exposed children placing them at high risk for impaired executive function. Independent of methamphetamine exposure, children with more responsive home environments to developmental and emotional needs demonstrated lower risks for internalizing and externalizing behavior.
doi:10.1016/j.ntt.2015.07.006
PMCID: PMC4668928  PMID: 26212684
4.  Prenatal Methamphetamine Exposure and Neonatal and Infant Neurobehavioral Outcome: Results from the IDEAL Study 
Background
Methamphetamine (MA) use among pregnant women is an increasing problem in the United States. How MA use during pregnancy affects neonatal and infant neurobehavior is unknown.
Methods
The Infant Development, Environment, and Lifestyle (IDEAL) study screened 34,833 subjects at 4 clinical centers. 17,961 were eligible and 3,705 were consented, among which 412 were enrolled for longitudinal follow-up. Exposed subjects were identified by self-report and/or GC/MS confirmation of amphetamine and metabolites in meconium. Comparison subjects were matched (race, birth weight, maternal education, insurance), denied amphetamine use and had a negative meconium screen. Both groups included prenatal alcohol, tobacco and marijuana use, but excluded use of opiates, lysergic acid diethylamide, or phencyclidine. The NICU Network Neurobehavioral Scale (NNNS) was administered within the first 5 days of life and again at one month to 380 enrollees (185 exposed, 195 comparison). ANOVA tested exposure effects on NNNS summary scores at birth and one month. GLM repeated measures analysis assessed the effect of MA exposure over time on the NNNS scores with and without covariates.
Results
By one month of age, both groups demonstrated higher quality of movement (P=.029), less lethargy (P=.001), and fewer asymmetric reflexes (P=.012), with no significant differences in NNNS scores between the exposed and comparison groups. Over the first month of life, arousal increased in exposed infants but decreased in comparison infants (p=.031) and total stress was decreased in exposed infants with no change in comparison infants (p=.026).
Conclusions
Improvement in total stress and arousal were observed in MA-exposed newborns by one month of age relative to the newborn period.
doi:10.1080/08897077.2013.814614
PMCID: PMC3942806  PMID: 24588296
5.  Prenatal Cocaine Exposure and Motor Performance at 4 Months 
OBJECTIVE
The relation between prenatal cocaine exposure and quality of movement was studied at 4 mo using the Posture and Fine Motor Assessment of Infants (PFMAI–I).
METHOD
Posture and fine motor scores of 4-month-old infants exposed to cocaine in utero (n = 370) were compared with an unexposed group (n = 533) within the context of gestational age, medical and demographic characteristics, and level of prenatal substance exposure using the PFMAI–I.
RESULTS
Infants prenatally exposed to cocaine had significantly lower posture scores than infants in the unexposed group. There was no main effect of cocaine exposure on fine motor scores; however, there were independent effects of gestational age at birth on both posture and fine motor scores at 4-mo corrected age.
CONCLUSION
These findings demonstrate independent contributions of prenatal cocaine exposure and prematurity to risk of motor delay and support the validity of the PFMAI–I as a measure of motor competence in early infancy.
doi:10.5014/ajot.2011.001263
PMCID: PMC4144172  PMID: 25170184
child development; cocaine-related disorders; motor skills; posture; prenatal exposure delayed effects
6.  Prenatal exposure to recreational drugs affects global motion perception in preschool children 
Scientific Reports  2015;5:16921.
Prenatal exposure to recreational drugs impairs motor and cognitive development; however it is currently unknown whether visual brain areas are affected. To address this question, we investigated the effect of prenatal drug exposure on global motion perception, a behavioural measure of processing within the dorsal extrastriate visual cortex that is thought to be particularly vulnerable to abnormal neurodevelopment. Global motion perception was measured in one hundred and forty-five 4.5-year-old children who had been exposed to different combinations of methamphetamine, alcohol, nicotine and marijuana prior to birth and 25 unexposed children. Self-reported drug use by the mothers was verified by meconium analysis. We found that global motion perception was impaired by prenatal exposure to alcohol and improved significantly by exposure to marijuana. Exposure to both drugs prenatally had no effect. Other visual functions such as habitual visual acuity and stereoacuity were not affected by drug exposure. Prenatal exposure to methamphetamine did not influence visual function. Our results demonstrate that prenatal drug exposure can influence a behavioural measure of visual development, but that the effects are dependent on the specific drugs used during pregnancy.
doi:10.1038/srep16921
PMCID: PMC4652269  PMID: 26581958
7.  Cortisol Reactivity to Social Stress as a Mediator of Early Adversity on Risk and Adaptive Outcomes 
Child development  2014;85(6):2279-2298.
Children chronically exposed to stress early in life are at increased risk for maladaptive outcomes, though the physiological mechanisms driving these effects are unknown. Cortisol reactivity was tested as a mediator of the relation between prenatal substance exposure and/or early adversity on adaptive and maladaptive outcomes. Data were drawn from a prospective longitudinal study of prenatal substance exposure (N = 860). Cortisol reactivity was assessed at age 11. Among African-Americans, prenatal substance exposure exerted an indirect effect through early adversity and cortisol reactivity to predict externalizing behavior, delinquency, and a positive student-teacher relationship at age 11. Decreased cortisol reactivity was related to maladaptive outcomes, and increased cortisol reactivity predicted better executive functioning and a more positive student-teacher relationship.
doi:10.1111/cdev.12316
PMCID: PMC4236260  PMID: 25376131
Prenatal Substance Exposure; Early Adversity; cortisol; problem behavior; delinquency
8.  Cross-national comparison of prenatal methamphetamine exposure on infant and early child physical growth: A natural experiment 
The current study seeks to compare the effects of prenatal methamphetamine exposure (PME) on infant and child physical growth between the United States (US) and New Zealand (NZ). This cross-national comparison provides a unique opportunity to examine the potential impact of services provided to drug using mothers on child health.
Methods
The longitudinal Infant Development, Environment and Lifestyle (IDEAL) study of PME from birth to 36 months was conducted in the US and NZ. The US cohort included 204 children with PME and 212 non-PME matched comparisons (NPME); the NZ cohort included 108 children with PME and 115 NPME matched comparisons. Latent growth curve models were used to examine effects of PME, country of origin, and the country × PME interaction on growth in length/height and weight.
Results
In regard to length/height, PME and country of origin were associated with initial length and growth over time. There was also a significant interaction effect, such that children with PME in the US were shorter at birth than children with PME in NZ after controlling for other prenatal exposures, infant set, socioeconomic status, and maternal height. In regard to weight, there was only an effect of country of origin.
Conclusions
Effects of PME on infant and child growth were shown to differ across countries, with exposed children in NZ faring better than exposed children in the US. Implications for prevention programs and public policy are discussed.
doi:10.1007/s11121-013-0431-5
PMCID: PMC3947752  PMID: 23943149
prenatal methamphetamine exposure; length/height; weight; cross-national research
9.  Risk for Neurobehavioral Disinhibition in Prenatal Methamphetamine-Exposed Young Children with Positive Hair Toxicology Results 
Therapeutic drug monitoring  2014;36(4):535-543.
Background
The objective was to evaluate effects of prenatal methamphetamine exposure (PME) and postnatal drug exposures identified by child hair analysis on neurobehavioral disinhibition at 6.5 years of age.
Methods
Mother-infant pairs were enrolled in the Infant Development, Environment, and Lifestyle (IDEAL) Study in Los Angeles, Honolulu, Tulsa and Des Moines. PME was determined by maternal self-report and/or positive meconium results. At the 6.5-year follow-up visit, hair was collected and analyzed for methamphetamine, tobacco, cocaine, and cannabinoid markers. Child behavioral and executive function test scores were aggregated to evaluate child neurobehavioral disinhibition. Hierarchical linear regression models assessed the impact of PME, postnatal substances, and combined PME with postnatal drug exposures on the child’s neurobehavioral disinhibition aggregate score. Past year caregiver substance use was compared to child hair results.
Results
A total of 264 children were evaluated. Significantly more PME children (n=133) had hair positive for methamphetamine/amphetamine (27.1% versus 8.4%) and nicotine/cotinine (38.3% versus 25.2%) than children without PME (n=131). Overall, no significant differences in analyte hair concentrations were noted between groups. Significant differences in behavioral and executive function were observed between children with and without PME. No independent effects of postnatal methamphetamine or tobacco exposure, identified by positive hair test, were noted and no additional neurobehavioral disinhibition was observed in PME children with postnatal drug exposures, as compared to PME children without postnatal exposure.
Conclusions
Child hair testing offered a non-invasive means to evaluate postnatal environmental drug exposure, although no effects from postnatal drug exposure alone were seen. PME, alone and in combination with postnatal drug exposures, was associated with behavioral and executive function deficits at 6.5 years.
doi:10.1097/FTD.0000000000000049
PMCID: PMC4101149  PMID: 24518561
methamphetamine; hair; children; prenatal drug exposure; toxicology
10.  Physiological Correlates of Neurobehavioral Disinhibition that Relate to Drug Use and Risky Sexual Behavior in Adolescents with Prenatal Substance Exposure 
Developmental neuroscience  2014;36(0):306-315.
Physiological correlates of behavioral and emotional problems, substance use onset and initiation of risky sexual behavior have not been studied in adolescents with prenatal drug exposure. We studied the concordance between baseline respiratory sinus arrhythmia (RSA) at age 3 and baseline Cortisol levels at age 11. We hypothesized that children who showed concordance between RSA and Cortisol would have lower neurobehavioral disinhibition scores which would in turn predict age of substance use onset and first sexual intercourse. The sample included 860 children aged 16 years participating in the Maternal Lifestyle Study, a multisite longitudinal study of children with prenatal exposure to cocaine and other substances. Structural equation modeling was used to test pathways between prenatal substance exposure, early adversity, baseline RSA, baseline Cortisol, neurobehavioral disinhibition, drug use, and sexual behavior outcomes. Concordance was studied by examining separate male and female models in which there were statistically significant interactions between baseline RSA and Cortisol. Prenatal substance exposure was operationalized as the number of substances to which the child was exposed. An adversity score was computed based on caregiver postnatal substance use, depression and psychological distress, number of caregiver changes, socioeconomic and poverty status, quality of the home environment, and child history of protective service involvement, abuse and neglect. RSA and Cortisol were measured during a baseline period prior to the beginning of a task. Neurobehavioral disinhibition, based on composite scores of behavioral dysregulation and executive dysfunction, substance use and sexual behavior were derived from questionnaires and cognitive tests administered to the child. Findings were sex specific. In females, those with discordance between RSA and Cortisol (high RSA and low Cortisol or low RSA and high Cortisol) had the most executive dysfunction which, in turn, predicted earlier initiation of alcohol by age 16. Among boys, there also existed a significant baseline RSA by baseline Cortisol interaction. Boys with low baseline RSA and high baseline Cortisol had the highest levels of behavioral dysregulation. This increase in behavioral dysregulation was in turn related to initiation of alcohol use by age 16 and lower age of first sexual intercourse. We found sex-specific pathways to the initiation of alcohol use and risky sexual behavior through the combined activity of parasympathetic and neuroendocrine functioning. The study of multiple physiological systems may suggest new pathways to the study of age of onset of substance use and engagement in risky sexual behavior in adolescents.
doi:10.1159/000365004
PMCID: PMC4476628  PMID: 25033835
Cortisol; Heart rate variability; Adversity; Sex differences; Teenage substance use onset; Behavioral problems; Executive function
11.  Children of Addicted Women 
Journal of addictive diseases  2010;29(2):259-276.
The purpose of this article was to review follow up studies of children with prenatal drug exposure from preschool through adolescence. Specifically, the authors focus on the effects of prenatal exposure to cocaine, methamphetamine, and opiates on behavior and development. The largest number of studies have examined cocaine-exposed children. The authors identified 42 studies that suggest that there are unique effects of prenatal cocaine exposure on 4- to 13-year-old children, particularly in the areas of behavior problems, attention, language, and cognition. In addition, studies make reasonable attempts to control for possible confounding factors. Systematic research on the long-term effects of prenatal methamphetamine exposure is just beginning but seems to be showing similar effects to that of cocaine. The literature on the on the long-term effects of children with prenatal opiate exposure is more substantial than the methamphetamine literature but it is still relatively sparse and surprising in that there is little recent work. Thus, there are no studies on the current concerns with opiates used for prescription mediation. There is a growing literature using neuroimaging techniques to study the effects of prenatal drug exposure that holds promise for understanding brain/behavior relationships. In addition to pharmacological and teratogenic effects, drugs can also be viewed from a prenatal stressor model. The author discuss this “fetal origins” approach that involves fetal programming and the neuroendocrine system and the potential implications for adolescent brain and behavioral development.
doi:10.1080/10550881003684921
PMCID: PMC4451952  PMID: 20407981
Prenatal drug exposure; follow-up; fetal origins
12.  EFFECTS OF PRENATAL METHAMPHETAMINE EXPOSURE ON BEHAVIORAL AND COGNITIVE FINDINGS AT 7.5 YEARS 
The Journal of pediatrics  2014;164(6):1333-1338.
Objective
To examine child behavioral and cognitive outcomes after prenatal exposure to methamphetamine.
Study design
412 mother-infant pairs (204 methamphetamine-exposed and 208 unexposed matched comparisons) were enrolled in the Infant Development, Environment and Lifestyle (IDEAL) study. The 151 children exposed to methamphetamine and 147 comparisons who attended the 7.5 year visit were included. Exposure was determined by maternal self-report and/or positive meconium toxicology. Maternal interviews assessed behavioral and cognitive outcomes using the Conner’s Parent Rating Scale – Revised: Short Form (CPRS-R:S).
Results
After adjusting for covariates, children exposed to methamphetamine had significantly higher cognitive problems subscale scores than comparisons and were 2.8 times more likely to have cognitive problems scores that were above average on the CPRS-R:S No association between prenatal methamphetamine exposure and behavioral problems, measured by the oppositional, hyperactivity and ADHD Index subscales, were found.
Conclusion
Prenatal methamphetamine exposure was associated with increased cognitive problems which may impact academic achievement and lead to increased negative behavioral outcomes.
doi:10.1016/j.jpeds.2014.01.053
PMCID: PMC4035384  PMID: 24630350
amphetamine; ADHD; Conner’s
13.  The contributions of early adverse experiences and trajectories of respiratory sinus arrhythmia on the development of neurobehavioral disinhibition among children with prenatal substance exposure 
Development and psychopathology  2014;26(4 0 1):901-916.
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.
doi:10.1017/S095457941400056X
PMCID: PMC4447302  PMID: 24909973
14.  Prenatal Cocaine Exposure and Childhood Obesity at Nine Years 
Neurotoxicology and teratology  2010;33(2):188-197.
Little is known about the association between prenatal cocaine exposure and obesity. We tested whether prenatal cocaine exposure increases the likelihood of obesity in 561 9-year-old term children from the Maternal Lifestyle Study (MLS). Overall, 21.6% of children met criterion for obesity (body mass index [BMI] ≥ 95th percentile, age and sex-specific). While there was no overall cocaine effect on obesity, multivariate logistic analysis revealed that children exposed to cocaine but not alcohol were 4 times more likely to be obese (OR 4.11, CI 2.04–9.76) than children not exposed to either drug. No increase in obesity prevalence was found in children exposed to alcohol but not cocaine (OR 1.08, CI .59–1.93) or both (OR 1.21, CI 0.66–2.22). Alcohol exposure may attenuate the effect of cocaine exposure on obesity. Increased obesity associated with cocaine but not alcohol exposure was first observed at 7 years. BMI was also elevated from 3 to 9 years in children exposed to cocaine but not alcohol, due to increasing weight but normal height. Prenatal exposure to cocaine may alter the neuroendocrine system and metabolic processes resulting in increased weight gain and childhood obesity.
doi:10.1016/j.ntt.2010.11.002
PMCID: PMC3058125  PMID: 21109003
Prenatal cocaine exposure; prenatal alcohol exposure; childhood obesity; growth; fetal origins
15.  Prenatal methamphetamine exposure and neonatal neurobehavioral outcome in the USA and New Zealand 
Neurotoxicology and teratology  2010;33(1):166-175.
Background
Methamphetamine (MA) use among pregnant women is a world-wide problem, but little is known of its impact on exposed infants.
Design
The prospective, controlled longitudinal Infant Development, Environment and Lifestyle (IDEAL) study of prenatal MA exposure from birth to 36 months was conducted in the US and NZ. The US cohort has 183 exposed and 196 comparison infants; the NZ cohort has 85 exposed and 95 comparison infants. Exposure was determined by self-report and meconium assay with alcohol, marijuana, and tobacco exposures present in both groups. The NICU Neurobehavior Scale (NNNS) was administered within 5 days of life. NNNS summary scores were analyzed for exposure including heavy exposure and frequency of use by trimester and dose-response relationship with the amphetamine analyte.
Results
MA Exposure was associated with poorer quality of movement, more total stress/abstinence, physiological stress, and CNS stress with more nonoptimal reflexes in NZ but not in the USA. Heavy MA exposure was associated with lower arousal and excitability. First trimester MA use predicted more stress and third trimester use more lethargy and hypotonicity. Dose-response effects were observed between amphetamine concentration in meconium and CNS stress.
Conclusion
Across cultures, prenatal MA exposure was associated with a similar neurobehavioral pattern of under arousal, low tone, poorer quality of movement and increased stress.
doi:10.1016/j.ntt.2010.06.009
PMCID: PMC2974956  PMID: 20615464
Prenatal exposure; Methamphetamine; Neurodevelopment; Meconium
16.  Reactivity and Regulation of Motor Responses in Cocaine-Exposed Infants 
Effects of prenatal exposure to cocaine on the reactivity and regulation of the motor system of 825 four-month-old infants enrolled in the Maternal Lifestyle Study were examined. Videotaped assessments of 338 cocaine-exposed (CE) infants and 487 non-exposed comparison infants were coded by examiners masked to exposure status. Exposure status was determined by meconium assay and maternal self-report of prenatal cocaine use. Infants were presented with a series of 17 visual, auditory and tactile stimuli for 30-second each. Intensity and latency of limb movement responses on a subset of items were analyzed to test the following hypotheses: CE infants are more active in general; CE infants exhibit increased movement levels for a larger proportion of time in response to stimulation; the motor systems of CE infants are more reactive to stimulation (e.g., shorter latencies to respond); and CE infants are poorer regulators of the motor system. Results CE infants were not more active in general and data do not indicate a more highly reactive motor system. However, CE infants exhibited increased movement levels for a larger proportion of time in response to stimulation. Additional analysis of movement exhibited during three tactile items found increased movement lability in CE infants and different patterns of responding, suggesting that the effects of prenatal cocaine exposure on the motor system may vary by context. Covariate effects for tobacco, alcohol, and marijuana are also reported.
doi:10.1016/j.ntt.2014.02.005
PMCID: PMC4337232  PMID: 24583252
cocaine; prenatal exposure; motor activity; reactivity; regulation
17.  Prenatal methamphetamine exposure and neurodevelopmental outcomes in children from 1 to 3 years 
Background:
Despite the evidence that women world-wide are using methamphetamine (MA) during pregnancy little is known about the neurodevelopment of their children.
Design:
The controlled, prospective longitudinal New Zealand (NZ) Infant Development, Environment and Lifestyle (IDEAL) study was carried out in Auckland, NZ. Participants were 103 children exposed to MA prenatally and 107 not exposed. The Mental Developmental Index (MDI) and the Psychomotor Developmental Index (PDI) of the Bayley Scales of Infant Development, Second Edition (BSID-II) measured cognitive and motor performance at ages 1, 2 and 3, and the Peabody Developmental Motor Scale, Second Edition (PDMS-II) measured gross and fine motor performance at 1 and 3. Measures of the child’s environment included the Home Observation of Measurement of the Environment and the Maternal Lifestyle Interview. The Substance Use Inventory measured maternal drug use.
Results:
After controlling for other drug use and contextual factors, prenatal MA exposure was associated with poorer motor performance at 1 and 2 years on the BSID-II. No differences were observed for cognitive development (MDI). Relative to non-MA exposed children, longitudinal scores on the PDI and the gross motor scale of the PDMS-2 were 4.3 and 3.2 points lower, respectively. Being male and of Maori descent predicted lower cognitive scores (MDI) and being male predicted lower fine motor scores (PDMS-2)
Conclusions:
Prenatal exposure to MA was associated with delayed gross motor development over the first 3 years, but not cognitive development. However, being male and of Maori descent were both associated with poorer cognitive outcomes. Males in general did more poorly on tasks related to fine motor development.
doi:10.1016/j.ntt.2014.02.004
PMCID: PMC3997367  PMID: 24566524
Prenatal exposure; Methamphetamine; Neurodevelopment; Longitudinal
18.  Prenatal Substance Exposure: Neurobiological Organization at One Month 
The Journal of pediatrics  2013;163(4):989-994.e1.
Objective
To examine the autonomic nervous system and neurobehavioral response to a sustained visual attention challenge among 1-month old infants with prenatal substance exposure.
Study design
We measured heart rate (HR), respiratory sinus arrhythmia (RSA), and neurobehavior during sustained visual orientation tasks included in the NICU Network Neurobehavioral Scale (NNNS) in 1,129, 1-month 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 (i.e. alcohol, marijuana, and tobacco).
Results
Infants with prenatal cocaine and opiate exposure had the highest HRs and lowest levels of RSA during a sustained visual attention procedure compared with the other three groups. Infants with prenatal cocaine and opiate exposure had poorer quality of movement and more hypertonicity during the NNNS exam compared with the other three exposure groups. Infants with prenatal cocaine and opiate exposure had more nonoptimal reflexes and stress/abstinence signs compared with infants with prenatal cocaine exposure only and infants with prenatal exposure to alcohol, tobacco, and marijuana.
Conclusions
Problems with arousal regulation were identified among infants with prenatal substance exposure. Autonomic dysregulation has been implicated as a mechanism by which these difficulties occur. Our results suggest that infants with both prenatal cocaine and opiate exposure have the greatest autonomic response to the challenge of a sustained visual attention task, which may place these infants at risk for developing problems associated with physiological and behavioral regulation, a necessary prerequisite for early learning.
doi:10.1016/j.jpeds.2013.04.033
PMCID: PMC3773295  PMID: 23743094
in utero drug exposure; physiology; neurobehavioral
19.  Examining the Relationships Between Prenatal Methamphetamine Exposure, Early Adversity, and Child Neurobehavioral Disinhibition 
Methamphetamine use is a growing problem among pregnant women in the United States. Many negative consequences of methamphetamine use have been documented for the users, but little research has examined the long-term association between prenatal methamphetamine exposure (PME) and childhood outcomes. The current study examined the extent to which PME was predictive of childhood neurobehavioral disinhibition (ND), as well as the extent to which early adversity mediated this relationship. A sample of 320 mother–infant dyads (162 PME) was followed from birth through 6.5 years of age. ND was conceptualized as a two factor model consisting of deficits in (a) behavioral and emotional control, and (b) executive function. PME was associated with behavioral and emotional control at 5 years, which was associated with executive function deficits at 6.5 years. Early adversity (birth through year 3) significantly mediated the relationship between PME and ND. Associations with previous research and implications for prevention are discussed.
doi:10.1037/a0030157
PMCID: PMC3842232  PMID: 23067308
methamphetamine; prenatal; adversity; disinhibition
20.  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
PCE 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 are essential in preventing and intervening with risk-taking behaviors and the potential consequences (e.g., adverse health outcomes, incarceration), especially among high-risk adolescent youth and their families.
doi:10.1097/01.DBP.0000437726.16588.e2
PMCID: PMC4139145  PMID: 24220515
prenatal drug exposure; cocaine; adolescence; risk-taking behavior
21.  Predictors of Inadequate Prenatal Care in Methamphetamine-Using Mothers in New Zealand and the United States 
Maternal and child health journal  2013;17(3):566-575.
This study compared patterns of prenatal care among mothers who used methamphetamine (MA) during pregnancy and non-using mothers in the US and New Zealand (NZ), and evaluated associations among maternal drug use, child protective services (CPS) referral, and inadequate prenatal care in both countries. The sample consisted of 182 mothers in the MA-Exposed and 196 in the Comparison groups in the US, and 107 mothers in the MA-Exposed and 112 in the Comparison groups in NZ. Positive toxicology results and/or maternal report of MA use during pregnancy were used to identify MA use. Information about sociodemographics, prenatal care and prenatal substance use was collected by maternal interview. MA-use during pregnancy is associated with lower socio-economic status, single marital status, and CPS referral in both NZ and the US. Compared to their non-using counterparts, MA-using mothers in the US had significantly higher rates of inadequate prenatal care. No association was found between inadequate care and MA-use in NZ. In the US, inadequate prenatal care was associated with CPS referral, but not in NZ. Referral to CPS for drug use only composed 40 % of all referrals in the US, but only 15 % of referrals in NZ. In our study population, prenatal MA-use and CPS referral eclipse maternal sociodemographics in explanatory power for inadequate prenatal care. The predominant effect of CPS referral in the US is especially interesting, and should encourage further research on whether the US policy of mandatory reporting discourages drug-using mothers from seeking antenatal care.
doi:10.1007/s10995-012-1033-8
PMCID: PMC3717345  PMID: 22588827
Methamphetamine; Adequate prenatal care; New Zealand; Kessner Index; Child protective services
22.  Co-morbidity of substance use disorder and psychopathology in women who use methamphetamine during pregnancy in the US and New Zealand 
Drug and alcohol dependence  2012;127(1-3):101-107.
BACKGROUND
Methamphetamine (MA) abuse is a worldwide problem. Little is known about the co-morbidity of substance use disorders (SUD) and other psychiatric disorders of mothers who use MA prenatally. The Infant Development, Environment and Lifestyle (IDEAL) Study is a prospective, investigation of prenatal MA use and child outcome in the United States (US) and New Zealand (NZ). This study examined prenatal MA use and the co-morbidity of SUD and psychiatric disorders at 1-month postpartum.
METHOD
Mothers who used MA (US = 127, NZ = 97) were compared to a matched comparison group (US = 193, NZ = 110). The Substance Abuse Subtle Screening Inventory-3 was used to measure the probability of a SUD. The Brief Symptom Inventory was used to measure the likelihood of a positive diagnosis of a psychiatric disorder.
RESULTS
In US and NZ, the MA groups had lower SES, increased single parenting, delayed prenatal care, increased polydrug use. In the US only, MA mothers had lower income than the comparison group. MA users were 10 times more likely to have a SUD and twice as likely to meet Brief Symptom Inventory criteria for a diagnosable psychiatric disorder. In NZ, but not the US, MA users were five times more likely have co-morbidity of both. This disparity may be due to higher quantities of prenatal alcohol use associated with increased psychiatric symptoms.
CONCLUSION
These findings suggest that addressing both substance abuse and psychiatric disorders in mothers who use MA may be required to effectively treat maternal MA use.
doi:10.1016/j.drugalcdep.2012.06.016
PMCID: PMC3498544  PMID: 22789630
Methamphetamine; Maternal Drug Use; Comorbidity; Substance Use Disorder; Psychiatric Disorder
23.  The Effect of Prenatal Methamphetamine Exposure on Attention as Assessed by Continuous Performance Tests: Results from the Infant Development, Environment, and Lifestyle (IDEAL) Study 
Objective
The purpose of this study is to assess for increased risk of attention deficit hyperactivity problem in young children with prenatal methamphetamine exposure from the multicenter, longitudinal Infant Development, Environment, and Lifestyle (IDEAL) study.
Methods
IDEAL enrolled 412 mother-infant pairs at four sites (Tulsa, OK; Des Moines, IA; Los Angeles, CA; and Honolulu, HI). Methamphetamine exposed subjects (n=204) were identified by self-report and/or gas chromatography/mass spectrometry confirmation of amphetamine and metabolites in infant meconium. Matched subjects (n=208) denied methamphetamine use and had a negative meconium screen. This analysis includes a subsample of 301 subjects that were administered the Conners’ Kiddie Continuous Performance Test (K-CPT) at age 5.5 years (153 exposed, 148 comparison). Hierarchical linear models adjusted for covariates tested exposure effects on K-CPT measures. Using the same covariates, logistic regression was used to determine the effect of exposure on the incidence of a positive ADHD confidence index score, defined as greater than 50%.
Results
There were no differences between the groups in omission or commission errors or reaction time for correct trials. However, methamphetamine exposure was associated with subtle differences in other outcomes predictive of ADHD, including increased slope of reaction time across blocks (p<0.001), increased variability in reaction time with longer interstimulus intervals (p<0.01), and increased likelihood of greater than 50% on the ADHD confidence index (OR 3.1, 95% CI 1.2–7.8; p=0.02).
Conclusion
Prenatal methamphetamine exposure was associated with subtle differences in K-CPT scores at age 5.5 years. Even at this relatively young age, these children exhibit indicators of risk for ADHD and warrant monitoring.
doi:10.1097/DBP.0b013e318277a1c5
PMCID: PMC3800474  PMID: 23275056
24.  Perceived Child Behavior Problems, Parenting Stress, and Maternal Depressive Symptoms Among Prenatal Methamphetamine Users 
The present study was designed to examine parenting stress, maternal depressive symptoms, and perceived child behavior problems among mothers who used methamphetamine (MA) during pregnancy. Participants were a subsample (n = 212; 75 exposed, 137 comparison) of biological mothers who had continuous custody of their child from birth to 36 months. The subsample was drawn from a larger, ongoing longitudinal study on the effects of prenatal methamphetamine exposure (n = 412; 204 exposed, 208 comparison) (Arria et al in Matern Child Health J 10:293–302 2006). Mothers who used MA during pregnancy reported more parenting stress and more depressive symptoms than a matched comparison group. There were no differences between groups on perceived child behavior problems. In a hierarchical linear model, depressive symptoms, and perceived child behavior problems, but not MA exposure, were statistically significant predictors of parenting stress. Screening for potential parenting problems among mothers with a history of substance abuse is warranted. Parenting interventions targeting depressive symptoms, parenting stress, and child behavior problems are needed for this population.
doi:10.1007/s10578-012-0305-2
PMCID: PMC3717339  PMID: 22552952
Parenting stress; Prenatal drug exposure; Methamphetamine; Child behavior problems; Maternal depression
25.  Neurobehavioral Disinhibition Predicts Initiation of Substance Use in Children with Prenatal Cocaine Exposure 
Drug and alcohol dependence  2012;126(1-2):80-86.
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 8–16 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 subject’s 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.
doi:10.1016/j.drugalcdep.2012.04.014
PMCID: PMC3439586  PMID: 22608010
neurodevelopmental disinhibition; substance use initiation; prenatal cocaine exposure

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