Sheri DellaGrotta

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 Heavy exposure was related to attention problems and withdrawn behavior at both ages.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.

Prenatal Methamphetamine Exposure and Inhibitory Control among Young School-Age Children

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 of prenatal methamphetamine exposure (heavy, some, or none) 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-like task. Caregiver psychological symptoms and Child Protective Services report of physical or sexual abuse were associated with reduced accuracy in the incongruent and mixed consitions and in the incongruent conditions, respectively. CONCLUSION Heavy prenatal methamphetamine exposure, along with caregiver psychological distress and child maltreatment, are related to subtle deficits in inhibitory control during the early school-age years.

Co-morbidity of substance use disorder and psychopathology in women who use methamphetamine during pregnancy in the US and New Zealand

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 (BSI) was used to measure the likelihood of a positive diagnosis of a psychiatric disorder. RESULTS In the US and NZ, MA groups had lower SES, increased single parenting, delayed prenatal care, and 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 BSI criteria for a diagnosable psychiatric disorder. In NZ, but not the US, MA users were five times more likely to 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.

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 childrens 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 childs caregiving environment.

Prenatal methamphetamine exposure and neurodevelopmental outcomes in children from 1 to 3 years.

BACKGROUND Despite the evidence that women world-wide are using methamphetamine (MA) during pregnancy little is known about the neurodevelopment of their children. DESIGN The controlled, prospective longitudinal New Zealand (NZ) Infant Development, Environment and Lifestyle (IDEAL) study was carried out in Auckland, NZ. Participants were 103 children exposed to MA prenatally and 107 who were 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 performances at ages 1, 2 and 3, and the Peabody Developmental Motor Scale, Second Edition (PDMS-II) measured gross and fine motor performances at 1 and 3. Measures of the childs environment included the Home Observation of Measurement of the Environment and the Maternal Lifestyle Interview. The Substance Use Inventory measured maternal drug use. RESULTS After controlling for other drug use and contextual factors, prenatal MA exposure was associated with poorer motor performance at 1 and 2 years on the BSID-II. No differences were observed for cognitive development (MDI). Relative to non-MA exposed children, longitudinal scores on the PDI and the gross motor scale of the PDMS-2 were 4.3 and 3.2 points lower, respectively. Being male and of Maori descent predicted lower cognitive scores (MDI) and being male predicted lower fine motor scores (PDMS-2). CONCLUSIONS Prenatal exposure to MA was associated with delayed gross motor development over the first 3 years, but not with 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.

The effect of prenatal methamphetamine exposure on attention as assessed by continuous performance tests: results from the Infant Development, Environment, and Lifestyle study.

Objective: To assess for the increased risk of attention-deficit hyperactivity disorder (ADHD) in young children with prenatal methamphetamine exposure from the multicenter, longitudinal Infant Development, Environment, and Lifestyle (IDEAL) study. Methods: The IDEAL study enrolled 412 mother-infant pairs at 4 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 included a subsample of 301 subjects who were administered the Conners’ Kiddie Continuous Performance Test (K-CPT) at 5.5 years of age (153 exposed and 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 < .001), increased variability in reaction time with longer interstimulus intervals (p < .01), and increased likelihood of greater than 50% on the ADHD confidence index (odds ratio, 3.1; 95% confidence interval, 1.2–7.8; p = .02). Conclusion: Prenatal methamphetamine exposure was associated with subtle differences in K-CPT scores at 5.5 years of age. Even at this relatively young age, these children exhibit indicators of risk for ADHD and warrant monitoring.

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. Of the subjects, 17,961 were eligible and 3705 were consented, among which 412 were enrolled for longitudinal follow-up. Exposed subjects were identified by self-report and/or gas chromatography/mass spectroscopy (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 Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scale (NNNS) was administered within the first 5 days of life and again at 1 month to 380 enrollees (185 exposed, 195 comparison). Analysis of variance (ANOVA) tested exposure effects on NNNS summary scores at birth and 1 month. General linear model (GLM) repeated-measures analysis assessed the effect of MA exposure over time on the NNNS scores with and without covariates. RESULTS By 1 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 1 month of age relative to the newborn period.

Epigenome-wide Analysis Identifies Genes and Pathways Linked to Neurobehavioral Variation in Preterm Infants

Background & Objectives Neonatal neurobehavioral performance measures, such as the NICU Network Neurobehavioral Scale (NNNS), have been developed to assess the neurobehavioral characteristics of infants and provide insights into future developmental trajectories. The identification of molecular biomarkers of very early life neurobehavioral experiences could lead to better predictions of the long-term developmental outcomes of high-risk infants including preterm infants. To this end, we aimed to examine whether variability in DNA methylation (DNAm) or epigenetic age from surrogate tissues are associated with NNNS profiles in a cohort of infants born less than 30 weeks postmenstrual age (PMA). Methods This study was performed within the Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) Study and included those infants with complete NNNS assessment data and DNAm measured from buccal cells, collected at near term-equivalent age using the Illumina EPIC array (N=536). We tested whether epigenetic age and age acceleration differed between infants based on their NNNS profile classifications. Then we performed an epigenome-wide association study, to test whether DNAm at individual epigenetic loci varied between these NNNS profile groupings. Models were adjusted for recruitment site, infant sex, postmenstrual age, and estimated tissue heterogeneity. Results We found that infants with an optimal NNNS profile had slightly older epigenetic age than other NOVI infants (β1 = 0.201, p-value = 0.026), and that infants with an atypical NNNS profile had differential methylation at 29 CpG sites (FDR < 10%). The genes annotated to these differentially methylated CpGs included PLA2G4E, TRIM9, GRIK3, and MACROD2, which have previously been associated with neurological structure and function, or with neurobehavioral disorders. Conclusions Greater epigenetic age is associated with optimal NNNS responses while altered DNAm of multiple genes are associated with an atypical neurobehavioral profile at near-term equivalent age. These findings build upon the existing evidence that epigenetic variations in buccal cells may serve as markers of neonatal neurobehavior and might facilitate early identification of children at risk for abnormal developmental outcome.