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1.  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
2.  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
3.  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
4.  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
5.  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
6.  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
7.  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
8.  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
9.  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
10.  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
11.  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
12.  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
13.  Prenatal Methamphetamine Exposure and Inhibitory Control among Young School-Age Children 
The Journal of pediatrics  2012;161(3):452-459.
Objective
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.
Results
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.
Conclusions
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.
doi:10.1016/j.jpeds.2012.02.002
PMCID: PMC3392459  PMID: 22424953
Prenatal exposure; Amphetamines; Children; Neuropsychology; Executive Function
14.  MATERNAL DEPRESSION AND PRENATAL EXPOSURE TO METHAMPHETAMINE: NEURODEVELOPMENTAL FINDINGS FROM THE INFANT DEVELOPMENT, ENVIRONMENT, AND LIFESTYLE (IDEAL) STUDY 
Depression and anxiety  2012;29(6):515-522.
Background
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).
Methods
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.
Results
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.
Conclusions
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.
doi:10.1002/da.21956
PMCID: PMC3717341  PMID: 22555777
amphetamine; drug; antenatal
15.  Prenatal Methamphetamine Exposure and Short-Term Maternal and Infant Medical Outcomes 
American journal of perinatology  2012;29(5):391-400.
Objective
Examine maternal and infant medical outcomes of prenatal exposure to methamphetamine (MA).
Study Design
Four hundred and twelve mother-infant pairs (204 MA-exposed and 208 unexposed matched comparisons) were enrolled in the Infant Development, Environment and Lifestyle (IDEAL) study. Exposure was determined by maternal self-report during this pregnancy and/or positive meconium toxicology. Maternal interviews assessed prenatal drug use, pregnancy course, and sociodemographic information. Medical chart reviews provided medical history, obstetric complications, infant outcomes, and discharge placement.
Results
MA-using mothers were more likely to be poor, to have a psychiatric disorder/emotional illness and less prenatal care, and to be less likely to breast-feed their infant than comparison mothers. After adjusting for covariates, MA-exposed infants were more likely to exhibit poor suck, to have smaller head circumferences and length, to require neonatal intensive care unit (NICU) admission, and to be referred to child protective services (CPS). Several outcomes previously reported from studies that lacked adequate control groups or adjustment for covariates were not significantly different in this study.
Conclusion
Prenatal MA exposure is associated with maternal psychiatric disorder/emotional illness, poor suck, NICU admission, and CPS involvement, and MA-exposed infants were less likely to be breast-fed; however, the absence of many serious complications, such as fetal distress, chronic hypertension, preeclampsia, placenta previa, abruptio placentae, and cardiac defects, suggests confounding variables influenced prior studies.
doi:10.1055/s-0032-1304818
PMCID: PMC3717348  PMID: 22399214
amphetamine; methamphetamine; drug; antenatal; neonate
16.  The Effects of Prenatal Methamphetamine Exposure on Childhood Growth Patterns from Birth to 3 Years of Age 
American journal of perinatology  2011;29(3):203-210.
We examined the effects of prenatal methamphetamine (MA) exposure on growth parameters from birth to age 3 years. The 412 subjects included (n = 204 exposed) were enrolled at birth in the Infant Development, Environment and Lifestyle study, a longitudinal study assessing the effects of prenatal MA exposure on childhood outcomes. Individual models were used to examine the effects of prenatal MA exposure on weight, head circumference, height, and weight-for-length growth trajectories. After adjusting for covariates, height trajectory was lower in the exposed versus the comparison children (p = 0.021) over the first 3 years of life. Both groups increased height on average by 2.27 cm per month by age 3 years. In term subjects, MA exposure was also associated with a lower height trajectory (p = 0.034), with both the exposed and comparison groups gaining 2.25 cm per month by age 3 years. There was no difference in weight, head circumference, or weight-for-length growth trajectories between the comparison and the exposed groups. Children exposed prenatally to MA have a modest decrease in height growth trajectory during the first 3 years of life with no observed difference in weight, head circumference, or weight-for-length trajectories.
doi:10.1055/s-0031-1285094
PMCID: PMC3717349  PMID: 21818727
height; antenatal; drug; amphetamine
17.  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.
doi:10.1203/PDR.0b013e3182291b13
PMCID: PMC3686483  PMID: 21546861
18.  Prenatal Methamphetamine Exposure and Childhood Behavior Problems at 3 and 5 Years of Age 
Pediatrics  2012;129(4):681-688.
OBJECTIVE:
We evaluated behavior problems in children who were prenatally exposed to methamphetamine (MA) at ages 3 and 5 years.
METHODS:
The Infant Development, Environment, and Lifestyle study, a prospective, longitudinal study of prenatal MA exposure and child outcome, enrolled subjects postpartum in Los Angeles, California; Honolulu, Hawaii; Des Moines, Iowa; and Tulsa, Oklahoma. Prenatal exposure was determined by maternal self-report and/or meconium results. Exposed and comparison groups were matched on race, birth weight, public health insurance, and education. Mothers in the comparison group denied use and had a negative meconium screen for amphetamines. Prenatal exposures to tobacco, alcohol, or marijuana occurred in both groups. At ages 3 and 5 years, 330 children (166 exposed and 164 comparison) were assessed for behavior problems by using the caregiver report on the Child Behavior Checklist. General linear mixed models were used to determine the effects of prenatal MA exposure, including heavy exposure (≥3 days per week), age, and the interaction of exposure and age on behavior problems with adjustment for other drugs of abuse and environmental risk factors.
RESULTS:
MA exposure was associated with increased emotional reactivity and anxious/depressed problems at both ages and externalizing and attention-deficit/hyperactivity disorder problems by age 5 years. Heavy exposure was related to attention problems and withdrawn behavior at both ages. There were no effects of MA on the internalizing or total behavior problems scales.
CONCLUSIONS:
This first report of behavior problems in patients as young as 3 years associated with MA exposure identifies an important public health problem. Continued follow-up can inform the development of preventive intervention programs.
doi:10.1542/peds.2011-2209
PMCID: PMC3313637  PMID: 22430455
amphetamines; behavior disorders/problems; children; methamphetamine; prenatal exposure
19.  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.
doi:10.1017/S0954579411000290
PMCID: PMC3335443  PMID: 21756431
20.  Motor and Cognitive Outcomes Through Three Years Of Age In Children Exposed To Prenatal Methamphetamine 
Neurotoxicology and teratology  2011;33(1):176-184.
Background
Methamphetamine (MA) use among pregnant women is an increasing problem in the United States. The impact of prenatal MA exposure on development in childhood is unknown.
Objective
To examine the effects of prenatal MA exposure on motor and cognitive development in children at 1, 2, and 3 years of age.
Design/Methods
IDEAL enrolled 412 mother-infant pairs at four sites (Tulsa OK, Des Moines IA, Los Angeles CA, and Honolulu HI). MA subjects (n=204) were identified by self-report or GC/MS confirmation of amphetamine and metabolites in infant meconium. Comparison subjects (n=208) were matched (race, birth weight, maternal education, type of 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, phencyclidine or cocaine only. The Peabody Developmental Motor Scales (PDMS-2) were administered to the infants at the 1 and 3 year visits. This analysis includes a subsample (n=350) of the IDEAL study with completed 1 and/or 3 year visits (n= 330 and 281, respectively). At each annual visit we also conducted the Bayley Scales of Infant Development (BSID-II) as a general evaluation of mental and motor development. The BSID-II analysis includes a subsample (n=356) of the IDEAL study with completed 1, 2, and/or 3 year visits (n= 331, 288, and 278 respectively). GLM analysis conducted on the PDMS-2 and BSID-II examined the effects of MA exposure and heavy MA exposure (≥3 days of use/week), with and without covariates. Longitudinal analyses were used to examine the effects of MA exposure on changes in motor and cognitive performance over time.
Results
Heavy MA exposure was associated with significantly lower grasping scores than some and no use at 1 year (P = 0.018). In longitudinal analysis, lower grasping scores associated with any MA exposure and heavy exposure persisted to 3 years. There were no effects of MA exposure, including heavy exposure, on the Bayley Mental Development Index (MDI) or Psychomotor Development Index (PDI) at any or across age.
Conclusions
There were no differences in cognition as assessed by the BSID-II between the groups. There was a subtle MA exposure effect on fine motor performance at 1 year with the poorest performance observed in the most heavily exposed children. By 3 years, no differences in fine motor performance were observed. These findings suggest MA exposure has modest motor effects at 1 year that are mostly resolved by 3 years.
doi:10.1016/j.ntt.2010.10.004
PMCID: PMC3033584  PMID: 21256431
prenatal exposure; neurodevelopment; Bayley; Peabody
21.  Intrauterine Growth of Infants Exposed to Prenatal Methamphetamine: Results from the Infant Development, Environment, and Lifestyle (IDEAL) Study 
The Journal of pediatrics  2010;157(2):337-339.
Previous studies suggest prenatal methamphetamine (MA) exposure inhibits fetal growth. We examined neonatal growth effects of prenatal MA exposure in a prospective cohort study. After adjusting for covariates, exposed neonates had a higher incidence of being small for gestational age (SGA) than unexposed neonates.
doi:10.1016/j.jpeds.2010.04.024
PMCID: PMC3018351  PMID: 20570284
drug; amphetamine; antenatal; small for gestational age
22.  Prenatal Cocaine Exposure Alters Cortisol Stress Reactivity in 11 Year Old Children 
The Journal of pediatrics  2010;157(2):288-295.e1.
Objective
Determine the association between prenatal cocaine exposure and postnatal environmental adversity on salivary cortisol stress reactivity in school aged children.
Study design
Subjects included 743 11 year old children (n=320 cocaine exposed; 423 comparison) followed since birth in a longitudinal prospective multisite study. Saliva samples were collected to measure cortisol at baseline and after a standardized procedure to induce psychological stress. Children were divided into those who showed an increase in cortisol from baseline to post stress and those who showed a decrease or blunted cortisol response. Covariates measured included site, birthweight, maternal pre and postnatal use of alcohol, tobacco or marijuana, social class, changes in caretakers, maternal depression and psychological symptoms, domestic and community violence, child abuse and quality of the home.
Results
With adjustment for confounding variables, cortisol reactivity to stress was more likely to be blunted in children with prenatal cocaine exposure. Cocaine exposed children exposed to domestic violence showed the strongest effects.
Conclusion
The combination of prenatal cocaine exposure and an adverse postnatal environment could down regulate the hypothalamic-pituitary-adrenal axis (HPA) resulting in the blunted cortisol response to stress possibly increasing risk for later psychopathology and adult disease.
doi:10.1016/j.jpeds.2010.02.039
PMCID: PMC3121327  PMID: 20400094
prenatal cocaine exposure; cortisol reactivity; environmental adversity
23.  Patterns of Methamphetamine Use During Pregnancy: Results from the Infant Development, Environment, and Lifestyle (IDEAL) Study 
Maternal and child health journal  2009;14(4):519-527.
The objectives of this study are to characterize methamphetamine (MA) usage patterns during pregnancy, examine whether patterns of MA use are associated with sociodemographic characteristics and prenatal care, and test the hypothesis that persistent or increasing MA use during pregnancy is associated with greater use of other illicit drugs. The sample consisted of 191 MA-using mothers who participated in a large-scale multi-site study of prenatal MA exposure. Patterns of substance use were assessed by maternal self-report via the Substance Use Inventory (SUI), which included detailed information about MA use, including frequency, quantity, and maximum use during each trimester of pregnancy. The study demostrated that on average, the prevalence of MA use decreased over the three trimesters of pregnancy (84.3% vs. 56.0% vs. 42.4%), and decreased frequency was observed among users from the first trimester to the third (3.1 vs. 2.4 vs. 1.5 days/week). Closer examination of the individual patterns revealed that 29.3% of women maintained consistently high frequency, 9.4% increased frequency, 25.7% had a stable low/moderate pattern, and 35.6% decreased their frequency of MA over the course of pregnancy. These four groups did not differ in sociodemographic characteristics; women who decreased their use of MA had significantly more prenatal visits compared to the consistently high-use group, but were the most likely to use alcohol during their pregnancy. In conclusion, this article elucidated the different patterns of MA use in this community sample. Approximately, one third of MA-using mothers could be classified as consistently high users with a profile of use with the greatest risk to themselves and potentially to their infants including high levels of MA use throughout pregnancy and fewer prenatal care visits. Overall, we found that MA use declined across pregnancy; however, a substantial proportion of users had consistently high or increasing MA use, while those who decreased their MA frequency had a higher prevalence of polydrug use. Future research will investigate the association of these patterns with neonatal outcomes.
doi:10.1007/s10995-009-0491-0
PMCID: PMC2895902  PMID: 19565330
Methamphetamine; Pregnancy; Alcohol and other drug use; Women; Epidemiology
24.  New Meconium Biomarkers of Prenatal Methamphetamine Exposure Increase Identification of Affected Neonates 
Clinical chemistry  2010;56(5):856-860.
BACKGROUND
Prenatal methamphetamine (MAMP) exposure is poorly reflected in neonatal meconium. Often, maternal self-reported MAMP use is not corroborated by positive results in amphetamines immunoassays of meconium, and even if initial test results are positive, they frequently are not confirmed for MAMP or amphetamine (AMP) by chromatographic analysis. The presence of the MAMP metabolites p-hydroxymethamphetamine (pOHMAMP), p-hydroxyamphetamine (pOHAMP), and norephedrine (NOREPH) in meconium may improve the identification of MAMP- and AMP-exposed neonates.
METHODS
Immunoassay-positive and -negative meconium samples were subjected to liquid chromatography–tandem mass spectrometric reanalysis for these recently identified metabolites.
RESULTS
pOHAMP and NOREPH were detected only when MAMP and/or AMP were present and thus do not appear to be promising biomarkers of prenatal MAMP exposure. pOHMAMP, in contrast, identified 6 additional neonates whose mothers reported MAMP exposure, yet had a meconium sample screened as negative; pOHMAMP was more likely to be present if maternal MAMP use continued into the third trimester. Although the pOHMAMP results for meconium samples corroborated the maternal self-reports, the confirmation rate for positive meconium screening results did not improve with the inclusion of these new biomarkers.
CONCLUSIONS
pOHMAMP identified additional MAMP-exposed neonates; therefore, MAMP, AMP, and pOHMAMP should be included in meconium chromatographic analyses. To maximize the identification of MAMP-exposed children requires improvement in immunoassay screening tests to reduce false-negative and false-positive results. Additional research will help clarify which AMP-related compounds, if any, contribute to unconfirmed positive results in screening tests. Furthermore, nonamphetamine compounds endogenous to the complex meconium matrix also may cross-react, making chromatographic confirmation of screening results essential.
doi:10.1373/clinchem.2009.139055
PMCID: PMC2883877  PMID: 20185623
25.  The Maternal Lifestyle Study: Sleep Problems in Children with Prenatal Substance Exposure 
Objective
To examine the relationships between sleep problems and prenatal exposure to cocaine, opiates, marijuana, alcohol, and nicotine in children 1 month to 12 years of age.
Design
Sleep data was collected by maternal report in a prospective longitudinal follow-up of children participating in the Maternal Lifestyle multisite study.
Setting
Hospital based research centers in Providence, RI, Miami, FL, Detroit, MI, and Memphis, TN
Participants
There were 808 participants: 374 exposed to cocaine and/or opiates; 434 comparison.
Main exposure
Prenatal cocaine, opiate, marijuana, alcohol, and nicotine exposure.
Outcome measure
Sleep problems in early, middle, and late childhood, assessed as composites of maternal report items.
Results
Of the five substances, prenatal nicotine exposure was the only unique predictor of sleep problems (B = .074, R2 Δ = .008, p = .012) with adjustment for covariates including SES, marital status, physical abuse, prenatal medical care, and postnatal cigarette smoke exposure.
Conclusion
Prenatal exposure to nicotine was positively associated with children's sleep problems persisting throughout the first 12 years of life. Targeting this group of children for educational and behavioral efforts to prevent and treat sleep problems is merited given that good sleep may serve as a protective factor for other developmental outcomes.
doi:10.1001/archpediatrics.2010.52
PMCID: PMC2917192  PMID: 20439796

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