Developmental Impact of Prenatal Exposure to Methamphetamine and Early Adversity on Children

The rapidly escalating abuse of methamphetamine (METH) in the United States places a sense of urgency on understanding the consequences of METH use during pregnancy for the developing child. To our knowledge, our IDEAL (Infant Development Environment and Lifestyle) study is the only prospective longitudinal NIH study of prenatal METH exposure and child outcome.  204 exposed and 208 matched comparison children were recruited at birth from diverse populations in Iowa, Oklahoma, California and Hawaii where METH use is prevalent.  Children were evaluated at birth to age 7 years for infant neurobehavioral deficits (NNNS) and acoustic cry parameters, mother-infant attachment, cortisol reactivity, cognitive and motor development, behavior problems, school readiness and executive function.  Also measured were psychosocial risk factors (e. g, poverty, out of home placement, maternal psychiatric status, continued substance abuse in the home) to determine how the effects of prenatal METH exposure are affected for early adversity. There are over 30 publications from the IDEAL study.  Primary Investigators: Barry Lester PhD, Linda LaGasse PhD. 

Epigenetics and Infant Stress Reactivity Related to Variations in Parenting

Merging the fields of epigenetics and human behavior is potentially “game changing” and provides an unprecedented opportunity to discover the molecular basis of human behavior.  Here, we are interested in the role of parenting in altering epigenetic mechanisms that could affect the infants physiological stress reactivity (cortisol) which has been shown to be related to later childhood mental and behavioral disorders. The sample includes infants followed from birth to 4 months of age. DNA of the infant from the placenta and infant neurobehavior (NNNS and cry) were collected at birth. At 4 months, DNA was collected from the infant and the quality of mother infant interaction and infant cortisol stress reactivity were measured.  We expect that results will also inform caregiving-induced signatures on the epigenome that influence infant physiological stress reactivity. Primary Investigators: Barry Lester PhD, Elizabeth Conradt PhD, Carmen Marsit PhD.

Maternal Lifestyle Study

The Maternal Lifestyle Study (MLS) is the largest of the NIH longitudinal studies of children with prenatal cocaine exposure.  MLS is a multi-site observational study of the long term effects of in-utero exposure to cocaine on child development.  The study included 25 data collection visits (birth to age 16 years) in the birth hospital, study clinic, home, and school. Neurobehavior evaluation (NNNS) and acoustic cry analysis were conducted at the 1-month visit.  Quality of attachment was conducted at 18 and 36 months. Heart rate recording occurred during child activity in the study clinic. Cortisol reactivity during the stressful Trier Task and diurnal cortisol pattern both showed a blunted response in cocaine exposed children, suggesting chronic stress in these children’s lives.  Cocaine exposed children are likely to live in adverse circumstances that may increase the likelihood of behavior problems leading to poor executive function and school achievement, psychopathology, delinquency, early sex and drug use.  MLS has published over 75 publications. Primary Investigators: Barry Lester PhD, Linda LaGasse PhD.

The MLS data set has been submitted for public access to the National Addiction and HIV Data Archive Program, Inter-University Consortium for Political and Social Research (University of Michigan). The URL is http://dx.doi.org/10.3886/ICPSR34312.v1

The Impact of Prenatal Methamphetamine Exposure on Children in New Zealand (NZ)

Does the impact of prenatal exposure to methamphetamine on children differ with cultural and resource differences?  The IDEAL (Infant Development Environment and Lifestyle) study in the US was replicated in NZ to compare whether differences between the societies may influence outcome in children with prenatal METH exposure.  Unlike the US, NZ has a harm reduction approach toward drug use, no mandatory reporting statutes for prenatal illicit drug use hence rare child removal, free universal health care and generous financial resources. Drug-using NZ mothers are far more likely to have prenatal care than US mothers and their infants were born  heavier and longer than US infants.  However, exposed infants in both US and NZ had a similar neurobehavioral pattern (NNNS) including under arousal, poorer quality of movement and increased stress and similar mild motor deficits from 1 to 3 years of age.  On the other hand, NZ mothers were 5 times more likely to have comorbidity between psychopathology and substance use disorder than US mothers. Ongoing analyses of academic achievement, social-emotional development and behavioral problems from 5 -7 years may be more sensitive to culture and resources as well as early adversity. Primary Investigators: Linda LaGasse PhD, Barry Lester, PhD.

The Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI)

Infants born less than 30 weeks gestational age are at high risk for developing severe impairment including cognitive, language, and behavior disorders and autism. Unfortunately, there is no method to identify which of these infants will become impaired and which will not. The purpose of the NOVI study is to follow approximately 900 infants across six sites from hospital discharge to two years of age and to determine if our neurobehavioral exam (NNNS) , medical factors and epigenetic marks, can identify infants that will be impaired by age 2.  Acoustic cry measures will also be used to help identify infants at risk for autism. Early identification can lead to interventions that can ameliorate or prevent later deficits. Primary Investigator: Barry Lester PhD.   

Treatment of Withdrawal from Opiates in Newborn Infants

Heroine addicted pregnant women are often treated with methadone, a synthetic opiate that crosses the placenta and the fetus becomes addicted. Following delivery these babies undergo severe withdrawal (Neonatal Abstinence Syndrome or NAS).  The two most common drugs used to treat these babies are methadone and morphine, gradually titrating the dose in the hospital until the baby is asymptomatic.  This is a randomized, multi-site clinical trial comparing the efficacy and long term (2 year) effects of these drugs on medical, neurobehavioral (NNNS), genetic and epigenetic measures. Primary Investigator: Barry Lester PhD.

Walking Reduces Stress in Pregnant Women with Depression

Depressive symptoms are prevalent among pregnant women and consistently linked with adverse outcomes for both women and infants.  Few interventions have been developed to reduce prenatal depressive symptoms.  Because pregnant women are often reluctant to take antidepressants, a pressing need exists to evaluate interventions that are efficacious in reducing symptoms and more acceptable and accessible to pregnant women.  The American College of Obstetricians and Gynecologists strongly recommends regular physical activity throughout pregnancy, yet, in practice, many pregnant women are unsure of how to safely adhere to this recommendation.  Findings from our research indicate that a tailored, supported physical activity intervention would be acceptable to depressed pregnant women and would be preferable over pharmacotherapy.  No study to date, however, has evaluated physical activity as an intervention for depressed pregnant women. Our team recently developed a gentle, 10-week, pedometer-based walking intervention designed for pregnant women, the Prenatal Walking Program (PWP), including detailed intervention manuals, interventionist training programs, and adherence scales. The current study is a RCT to evaluate PWP in comparison with a perinatal-focused Health Education Control (HEC) condition. The primary aim is to examine whether the PWP group has greater reductions in depressive symptoms relative to healthy controls.  In addition, infant neurobehavioral exams (NNNS) will evaluate possible benefits from the intervention.  Potential mechanisms will also be tested, including behavioral factors (behavioral activation, decreased avoidance), psychological factors (increased self-efficacy), and physiological factors (decreased inflammation, improved sleep).  Primary Investigators: Cynthia Battle PhD, Amy Salisbury PhD.