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1.  Risk for Neurobehavioral Disinhibition in Prenatal Methamphetamine-Exposed Young Children with Positive Hair Toxicology Results 
Therapeutic drug monitoring  2014;36(4):535-543.
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.
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.
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.
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.
PMCID: PMC4101149  PMID: 24518561
methamphetamine; hair; children; prenatal drug exposure; toxicology
2.  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.
PMCID: PMC4476628  PMID: 25033835
Cortisol; Heart rate variability; Adversity; Sex differences; Teenage substance use onset; Behavioral problems; Executive function
3.  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.
PMCID: PMC4451952  PMID: 20407981
Prenatal drug exposure; follow-up; fetal origins
The Journal of pediatrics  2014;164(6):1333-1338.
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).
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.
Prenatal methamphetamine exposure was associated with increased cognitive problems which may impact academic achievement and lead to increased negative behavioral outcomes.
PMCID: PMC4035384  PMID: 24630350
amphetamine; ADHD; Conner’s
5.  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.
PMCID: PMC4447302  PMID: 24909973
6.  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.
PMCID: PMC4337232  PMID: 24583252
cocaine; prenatal exposure; motor activity; reactivity; regulation
7.  Prenatal methamphetamine exposure and neurodevelopmental outcomes in children from 1 to 3 years 
Despite the evidence that women world-wide are using methamphetamine (MA) during pregnancy little is known about the neurodevelopment of their children.
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.
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)
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.
PMCID: PMC3997367  PMID: 24566524
Prenatal exposure; Methamphetamine; Neurodevelopment; Longitudinal
8.  Prenatal Methamphetamine Exposure and Neonatal and Infant Neurobehavioral Outcome: Results from the IDEAL Study 
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.
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.
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).
Improvement in total stress and arousal were observed in MA-exposed newborns by one month of age relative to the newborn period.
PMCID: PMC3942806  PMID: 24588296
9.  Prenatal predictors of infant self-regulation: the contributions of placental DNA methylation of NR3C1 and neuroendocrine activity 
We examined whether placental DNA methylation of the glucocorticoid receptor gene, NR3C1 was associated with self-regulation and neuroendocrine responses to a social stressor in infancy. Placenta samples were obtained at birth and mothers and their infants (n = 128) participated in the still-face paradigm when infants were 5 months old. Infant self-regulation following the still-face episode was coded and pre-stress cortisol and cortisol reactivity was assessed in response to the still-face paradigm. A factor analysis of NR3C1 CpG sites revealed two factors: one for CpG sites 1–4 and the other for sites 5–13. DNA methylation of the factor comprising NR3C1 CpG sites 5–13 was related to greater cortisol reactivity and infant self-regulation, but cortisol reactivity was not associated with infant self-regulation. The results reveal that prenatal epigenetic processes may explain part of the development of infant self-regulation.
PMCID: PMC4448036  PMID: 26074794
DNA methylation; prenatal origins; glucocorticoid receptor gene; self-regulation; infancy
10.  Prenatal Substance Exposure: Neurobiological Organization at One Month 
The Journal of pediatrics  2013;163(4):989-994.e1.
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).
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.
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.
PMCID: PMC3773295  PMID: 23743094
in utero drug exposure; physiology; neurobehavioral
11.  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.
PMCID: PMC3842232  PMID: 23067308
methamphetamine; prenatal; adversity; disinhibition
12.  Prenatal Cocaine Exposure and Motor Performance at 4 Months 
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).
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.
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.
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.
PMCID: PMC4144172  PMID: 25170184
child development; cocaine-related disorders; motor skills; posture; prenatal exposure delayed effects
13.  Risk-Taking Behavior among Adolescents with Prenatal Drug Exposure and Extrauterine Environmental Adversity 
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).
Risk-taking behavior (delinquency, substance use, and sexual activity) was assessed in 963 adolescents (433 cocaine-exposed, 530 nonexposed) at 15 years of age.
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.
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.
PMCID: PMC4139145  PMID: 24220515
prenatal drug exposure; cocaine; adolescence; risk-taking behavior
14.  The Role of Prenatal Substance Exposure and Early Adversity on Parasympathetic Functioning from 3 to 6 Years of Age 
Developmental psychobiology  2013;56(4):821-835.
We employed latent growth curve analysis to examine trajectories of respiratory sinus arrhythmia (RSA) from 3 to 6 years among children with varying levels of prenatal substance exposure and early adversity. Data were drawn from a prospective longitudinal study of prenatal substance exposure that included 1,121 participants. Baseline RSA and RSA reactivity to an attention-demanding task were assessed at 3, 4, 5, and 6 years. Overall, there were significant individual differences in the trajectories of RSA reactivity, but not baseline RSA, across development. Greater levels of prenatal substance exposure, and less exposure to early adversity, were associated with increased RSA reactivity at 3 years, but by 6 years, both were associated with greater RSA reactivity. Prenatal substance exposure had an indirect influence through early adversity on growth in RSA reactivity. Results are in support of and contribute to the framework of allostatic load.
PMCID: PMC4132658  PMID: 24002807
allostatic load; prenatal substance exposure; early adversity; respiratory sinus arrhythmia
15.  Importance of Stability of Early Living Arrangements on Behavior Outcomes of Children With and Without Prenatal Drug Exposure 
We evaluated whether living arrangements of children with or without prenatal drug exposure would be associated with their behavior outcomes and adaptive functioning.
1388 children with or without prenatal cocaine or opiate exposure were enrolled in a longitudinal cohort study at one month of age, were seen at intervals, tracked over time for their living situation, and evaluated for behavior problems and adaptive functioning at three years of age. Child Behavior Check List and Vineland Adaptive Behavior Scales (VABS) were administered. Using multiple regression models, we determined the factors that would predict behavior problems and adaptive functioning.
1,092 children were evaluated. Total and externalizing behavior problems T scores of children in relative care were lower (better) than those in parental; externalizing behavior scores were lower than those in non-relative care (p<0.05). Total behavior problem scores increased 2.3 and 1.3 points respectively with each move/year and each year of Child Protective Services’ involvement. Compared to children in non-relative care, those in parental or relative care had higher (better) scores in the VABS total composite (p<0.023), communication (p<0.045), and daily living (p<0.001). Each caretaker change was associated with a decrease of 2.65 and 2.19 points respectively in communication and daily living scores.
Children’s living arrangements were significantly associated with childhood behavior problems and adaptive functioning. The instability of living situation was also a significant predictor of these outcomes. While family preservation continues to be the goal of the child welfare system, expediting decision toward permanency remains paramount once children are placed in foster care.
PMCID: PMC3984541  PMID: 18349707
Prenatal cocaine; prenatal opiate; out-of-home-care; child behavior
16.  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.
PMCID: PMC3717345  PMID: 22588827
Methamphetamine; Adequate prenatal care; New Zealand; Kessner Index; Child protective services
17.  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.
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.
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.
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.
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.
PMCID: PMC3498544  PMID: 22789630
Methamphetamine; Maternal Drug Use; Comorbidity; Substance Use Disorder; Psychiatric Disorder
18.  Prenatal Methamphetamine Exposure, Home Environment, and Primary Caregiver Risk Factors Predict Child Behavioral Problems at 5 Years 
This study investigated the prospective association between prenatal methamphetamine (MA) exposure and child behavioral problems at 5 years while also examining the home environment at 30 months and several primary caregiver (PC) risk factors. Participants were 97 MA-exposed and 117 comparison children and their PCs enrolled in the Infant Development, Environment and Lifestyle Study. Hypotheses were that child behaviors would be adversely impacted by (a) prenatal MA exposure, (b) home environments that provided less developmental stimulation and emotional responsiveness to the child, and (c) the presence of PC psychological symptoms and other risk factors. Prenatal MA exposure was associated with child externalizing behavioral problems at 5 years. Home environments that were more conducive to meeting children’s developmental and emotional needs were associated with fewer internalizing and externalizing behavioral problems. Independent of prenatal MA exposure, PC parenting stress and psychological symptoms were associated with increased child behavioral problems. Findings suggest prenatal MA exposure may contribute to externalizing behavioral problems in early childhood and the importance of considering possible vulnerabilities related to prenatal MA exposure in the context of the child’s caregiving environment.
PMCID: PMC3721329  PMID: 23330624
infants; children; pregnant women; methamphetamine use; prenatal substance exposure; primary caregiver; caregiving environment; parenting stress
19.  The Effect of Prenatal Methamphetamine Exposure on Attention as Assessed by Continuous Performance Tests: Results from the Infant Development, Environment, and Lifestyle (IDEAL) Study 
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.
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%.
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).
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.
PMCID: PMC3800474  PMID: 23275056
20.  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
21.  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.
PMCID: PMC3717339  PMID: 22552952
Parenting stress; Prenatal drug exposure; Methamphetamine; Child behavior problems; Maternal depression
22.  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
23.  Prenatal Methamphetamine Exposure and Inhibitory Control among Young School-Age Children 
The Journal of pediatrics  2012;161(3):452-459.
To examine the association between prenatal methamphetamine exposure and inhibitory control in 66 month old children followed since birth in the multicenter, longitudinal Infant Development, Environment and Lifestyle Study.
Study design
The sample included 137 children with prenatal methamphetamine exposure and 130 comparison children, matched for race, birth weight, maternal education and type of insurance. Inhibitory control, an executive function related to emotional and cognitive control, was assessed using a computerized Stroop-like task developed for young children. Hierarchical linear modeling tested the relationship between the extent (heavy, some and no use) of prenatal methamphetamine exposure and accuracy and reaction time outcomes, adjusting for prenatal exposure to alcohol, tobacco and marijuana, age, sex, socioeconomic status, caregiver IQ and psychological symptoms, child protective services report of physical or sexual abuse, and site.
In adjusted analyses, heavy prenatal methamphetamine exposure was related to reduced accuracy in both the incongruent and mixed conditions on the Stroop task. Caregiver psychological symptoms and Child Protective Services (CPS) report of physical or sexual abuse were associated with reduced accuracy in the incongruent and mixed, and incongruent conditions, respectively.
Heavy prenatal methamphetamine exposure, along with caregiver psychological distress and child maltreatment, is related to subtle deficits in inhibitory control during the early school-aged years.
PMCID: PMC3392459  PMID: 22424953
Prenatal exposure; Amphetamines; Children; Neuropsychology; Executive Function
24.  Impact of maternal substance use during pregnancy on childhood outcome 
The impact of maternal substance abuse is reflected in the 2002–2003 National Survey on Drug Use and Health. Among pregnant women in the 15–44 age group, 4.3%, 18% and 9.8% used illicit drugs, tobacco and alcohol, respectively. Maternal pregnancy complications following substance use include increases in sexually transmitted disorders, placental abruption and HIV-positive status. Effects on the neonate include a decrease in growth parameters and increases in central nervous system and autonomic nervous system signs and in referrals to child protective agencies. In childhood, behavioral and cognitive effects are seen after prenatal cocaine exposure; tobacco and alcohol have separate and specific effects. The ongoing use of alcohol and tobacco by the caretaker affects childhood behavior. Therefore, efforts should be made to prevent and treat behavioral problems as well as to limit the onset of drug use by adolescent children born to women who use drugs during pregnancy.
PMCID: PMC3717561  PMID: 17317350
Alcohol; Child medicine; Cocaine; Neonatal; Neurobehavioral outcome; Polydrug use; Tobacco
Depression and anxiety  2012;29(6):515-522.
Maternal depression is associated with a higher incidence of behavioral problems in infants, but the effects of maternal depression as early as 1 month are not well characterized. The objective of this study is to determine the neurobehavioral effects of maternal depression on infants exposed and not exposed to methamphetamine (MA) using the NICU Network Neurobehavioral Scale (NNNS).
Four hundred twelve mother–infant pairs were enrolled (MA = 204) and only biological mothers with custody of their child were included in the current analysis. At the 1-month visit (n = 126 MA-exposed; n = 193 MA-unexposed), the Beck Depression Inventory-II (BDI-II) was administered, and the NNNS was administered to the infant. Exposure was identified by self-report and/or gas chromatography/mass spectroscopy confirmation of amphetamine and metabolites in newborn meconium. Unexposed subjects were matched, denied amphetamine use, and had negative meconium screens. General Linear Models tested the effects of maternal depression and prenatal MA exposure on NNNS, with significance accepted at P < .05.
The MA group had an increased incidence of depression-positive diagnosis and increased depression scores on the BDI-II. After adjusting for covariates, MA exposure was associated with increased arousal and handling scores, and a decreased ability to self-regulate. Maternal depression was associated with higher autonomic stress and poorer quality of movement. No additional differences were observed in infants whose mothers were both depressed and used MA during pregnancy.
Maternal depression is associated with neurodevelopmental patterns of increased stress and decreased quality of movement, suggesting maternal depression influences neurodevelopment in infants as young as 1 month.
PMCID: PMC3717341  PMID: 22555777
amphetamine; drug; antenatal

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