Chris Derauf

The Infant Development, Environment, and Lifestyle Study: Effects of Prenatal Methamphetamine Exposure, Polydrug Exposure, and Poverty on Intrauterine Growth

OBJECTIVE. Methamphetamine use among pregnant women is an increasing problem in the United States. Effects of methamphetamine use during pregnancy on fetal growth have not been reported in large, prospective studies. We examined the neonatal growth effects of prenatal methamphetamine exposure in the multicenter, longitudinal Infant Development, Environment and Lifestyle study. DESIGN/METHOD. The Infant Development, Environment and Lifestyle study screened 13808 subjects at 4 clinical centers: 1618 were eligible and consented, among which 84 were methamphetamine exposed, and 1534 were unexposed. Those who were methamphetamine exposed were identified by self-report and/or gas chromatography-mass spectrometry confirmation of amphetamine and metabolites in infant meconium. Those who were unexposed denied amphetamine use and had a negative meconium screen. Both groups included prenatal alcohol, tobacco, or marijuana use, but excluded use of opiates, LSD, PCP or cocaine only. Neonatal parameters included birth weight and gestational age in weeks. One-way analysis of variance and linear-regression analyses were conducted on birth weight by exposure. The relationship of methamphetamine exposure and the incidence of small for gestational age was analyzed using multivariate logistic-regression analyses. RESULTS. The methamphetamine exposed group was 3.5 times more likely to be small for gestational age than the unexposed group. Mothers who used tobacco during pregnancy were nearly 2 times more likely to have small-for-gestational-age infants. In addition, less maternal weight gain during pregnancy was more likely to result in a small-for-gestational-age infant. Birthweight in the methamphetamine exposed group was lower than the unexposed group. CONCLUSIONS. These findings suggest that prenatal methamphetamine use is associated with fetal growth restriction after adjusting for covariates. Continued follow-up will determine if these infants are at increased risk for growth abnormalities in the future.

Methamphetamine and Other Substance Use During Pregnancy: Preliminary Estimates From the Infant Development, Environment, and Lifestyle (IDEAL) Study

Objectives: Methamphetamine use is a continuing problem in several regions of the United States and yet few studies have focused on prenatal methamphetamine exposure. The purpose of this study was to estimate the prevalence and correlates of alcohol, tobacco, and other substance use—including methamphetamine—during pregnancy. Methods: The sample consisted of the first 1632 eligible mothers who consented to participate in a large-scale multisite study focused on prenatal methamphetamine exposure. This unselected screening sample included both users and nonusers of alcohol, tobacco, methamphetamine, and other drugs. Substance use was determined by maternal self-report and/or GC/MS confirmation of a positive meconium screen. Results: Overall, 5.2% of women used methamphetamine at some point during their pregnancy. One quarter of the sample smoked tobacco, 22.8% drank alcohol, 6.0% used marijuana, and 1.3% used barbiturates prenatally. Less than 1% of the sample used heroin, benzodiazapenes, and hallucinogens. Multivariate modeling results showed that tobacco smokers and illicit drug users were more likely to be single and less educated, have attended less than 11 prenatal visits, and utilize public financial assistance. Conclusions: This is the first large-scale investigation to report the prevalence of methamphetamine use during pregnancy in areas of the United States where methamphetamine is a notable concern. Follow-up research is ongoing to investigate the outcomes associated with prenatal methamphetamine exposure. Given that this research extends and confirms previous findings showing that high-risk groups of pregnant women can be identified on the basis of basic demographic characteristics, targeted interventions are greatly needed to reduce serious adverse outcomes associated with prenatal alcohol and tobacco use.

Neuroimaging of Children Following Prenatal Drug Exposure

Recent advances in MR-based brain imaging methods have provided unprecedented capabilities to visualize the brain. Application of these methods has allowed identification of brain structures and patterns of functional activation altered in offspring of mothers who used licit (e.g., alcohol and tobacco) and illicit (e.g., cocaine, methamphetamine, and marijuana) drugs during pregnancy. Here we review that literature, which though somewhat limited by the complexities of separating the specific effects of each drug from other confounding variables, points to sets of interconnected brain structures as being altered following prenatal exposure to drugs of abuse. In particular, dopamine-rich cortical (e.g., frontal cortex) and subcortical (e.g., basal ganglia) fetal brain structures show evidence of vulnerability to intrauterine drug exposure suggesting that during brain development drugs of abuse share a specific profile of developmental neurotoxicity. Such brain malformations may shed light on mechanisms underlying prenatal drug-induced brain injury, may serve as bio-markers of significant intrauterine drug exposure, and may additionally be predictors of subsequent neuro-developmental compromise. Wider clinical use of these research-based non-invasive methods will allow for improved diagnosis and allocation of therapeutic resources for affected infants, children, and young adults.

Prenatal methamphetamine exposure and neonatal neurobehavioral outcome in the USA and New Zealand.

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.

Prenatal Methamphetamine Exposure and Childhood Behavior Problems at 3 and 5 Years of Age

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.

Intrauterine growth of infants exposed to prenatal methamphetamine: results from the infant development, environment, and lifestyle study.

Previous studies suggest that prenatal methamphetamine exposure inhibits fetal growth. We examined neonatal growth effects of prenatal methamphetamine exposure in a prospective cohort study. After adjusting for covariates, exposed neonates had a higher incidence of being small for gestational age than unexposed neonates.

Demographic and Psychosocial Characteristics of Mothers Using Methamphetamine During Pregnancy: Preliminary Results of the Infant Development, Environment, and Lifestyle Study (IDEAL)

This study describes the psychological characteristics and caretaking environments of 131 women enrolled in the first longitudinal study of prenatal methamphetamine (MA) exposure and child development. Prenatal MA use was associated with lower maternal perceptions on quality of life, greater likelihood of substance use among family and friends, increased risk for ongoing legal difficulties, and a markedly increased likelihood of developing a substance abuse disorder. Our preliminary findings suggest that MA using women are more likely to have multiple, intertwined psychosocial risks that may result in maladaptive parenting and caregiving. These factors may impact the developmental outcomes of affected children.

Motor and cognitive outcomes through three years of age in children exposed to prenatal methamphetamine

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, and 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.

Subcortical and Cortical Structural Central Nervous System Changes and Attention Processing Deficits in Preschool-Aged Children with Prenatal Methamphetamine and Tobacco Exposure

Objective: To examine the independent contributions of prenatal methamphetamine exposure (PME) and prenatal tobacco exposure (PTE) on brain morphology among a sample of nonalcohol-exposed 3- to 5-year-old children followed prospectively since birth. Study Design: The sample included 20 children with PME (19 with PTE) and 15 comparison children (7 with PTE), matched on race, birth weight, maternal education and type of insurance. Subcortical and cortical volumes and cortical thickness measures were derived through an automated segmentation procedure from T1-weighted structural magnetic resonance images obtained on unsedated children. Attention was assessed using the computerized Conners’ Kiddie Continuous Performance Test Version 5 (K-CPT™ V.5). PME effects on subcortical and cortical brain volumes and cortical thickness were tested by general linear model with type III sum of squares, adjusting for PTE, prenatal marijuana exposure, age at time of scan, gender, handedness, pulse sequence and total intracranial volume (for volumetric outcomes). A similar analysis was done for PTE effects on subcortical and cortical brain volumes and thickness, adjusting for PME and the above covariates. Results: Children with PME had significantly reduced caudate nucleus volumes and cortical thickness increases in perisylvian and orbital-frontal cortices. In contrast, children with PTE showed cortical thinning in perisylvian and lateral occipital cortices and volumetric increases in frontal regions and decreases in anterior cingulate. PME was positively related and caudate volume was inversely related to K-CPT reaction time by inter-stimulus interval, a measure of the ability to adjust to changing task demands, suggesting that children with PME may have subtle attentional deficits mediated by caudate volume reductions. Conclusions: Our results suggest that PME and PTE may have distinct differential cortical effects on the developing central nervous system. Additionally, PME may be associated with subtle deficits in attention mediated by caudate volume reductions.

Infant temperament and high-risk environment relate to behavior problems and language in toddlers.

Objective: This study examined the role that easy infant temperament and cumulative environmental risk play in predicting cognitive, language, and behavioral outcomes in 3-year-old children at high social risk. Methods: Subjects were 412 mother-infant dyads, recruited at birth, participating in a longitudinal study examining the effects of prenatal methamphetamine on child development. This analysis includes a subsample (n = 290) of the study with a completed 3-year visit. Temperament was assessed by the Infant Behavior Questionnaire at 12 months. Factor analysis from well-validated measures generated “easy” and “difficult” temperament profiles and a profile for high-risk environment. Caretaker receptive vocabulary served as a proxy for intelligence quotient. Outcomes at 3 years included motor and mental development, behavior problems, and language. Linear regression and hierarchical linear modeling examined the effects of temperament, high-risk environment, and caregiver receptive language on outcomes adjusting for maternal drug use and demographic and socioeconomic covariates. Results: Internalizing and externalizing behaviors were lower in children with easy temperament and higher with increased environmental risk. Easy temperament attenuated behavioral problems only in the setting of lower environmental risk. Caregiver receptive language was associated with lower internalizing scores. High-risk environment and temperament factors were not related to cognitive or motor outcomes. Prenatal methamphetamine exposure was not associated with 3-year-old outcomes, nor did it alter the protective effects of an easier temperament on child behavior. Conclusions: Children growing up in adverse social environments had increased behavioral problems and compromised language development. Conversely, an easy temperament acts as a protective factor for social-emotional development and could be related to resilience.