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: Linda LaGasse PhD.

Environmental Influences on Neurodevelopmental Outcome in Infants Born Very Preterm (ECHO-NOVI)

The Environmental influences on Child Health Outcomes (ECHO) program is part of a National Institutes of Health (NIH)'s seven-year initiative to support multiple, synergistic, longitudinal studies using existing study populations, called cohorts, to investigate environmental exposures — including physical, chemical, biological, social, behavioral, natural and built environments — on child health and development. ECHO plans to enroll over 50,000 children from across the United States in an attempt to collect a broad amount of data that helps determine the trajectory of health development, prediction of disease development and new tools and approaches for both environmental and pediatric monitoring.

We are focusing on the neurodevelopmental outcomes related to the ECHO initiative, through our study, "The Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI)." We are calling this integration of NOVI into the ECHO initiative, "ECHO-NOVI".

About one-third of infants born less than 30 weeks suffer long-term developmental challenges. We hope to identify which infants are more likely to become developmentally impaired and determine whether special types of care in the neonatal intensive care unit (NICU) and early developmental intervention services after discharge could improve the developmental outcomes for premature infants and their families. To date in the NOVI study, we have collected data on these infant's early behavioral development up to the age of two. In ECHO-NOVI, we plan to follow these children through age seven to further determine potential mechanisms that lead to developmental and child health outcomes. Primary Investigator: Barry Lester 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.

Epigenetics in Children with Prenatal Exposure to Methamphetamine 

Children with prenatal exposure to methamphetamine are at risk for poor developmental outcome due to the combination of the drug effects and environmental adversity.  In this 10-year follow up of a birth cohort from the Infant Development and Lifestyle Study (IDEAL), we are studying how prenatal methamphetamine exposure and environmental adversity result in epigenetic changes that in turn affect cognitive and behavioral outcome Primary Investigators: Barry Lester PhD, Linda LaGasse PhD.   

Fetal and Infant Response to SRI Treatment 

Approximately 600,000 infants born each year are exposed to maternal depression. At least 30% of those infants will also be exposed to psychotropic medication. Fetal exposure during pregnancy to maternal depression and the medications to treat the disorder have been associated with neurobehavioral differences in infants. It has been suggested that these differences are transient and it is not known if they are related to the mother's depression or the medication used to treat the depression. The F.I.R.S.T. is studying the clinical course of newborns' symptoms directly after birth and for the infants' first 30 days after birth. Fetal neurobehavior measures are obtained by ultrasound and fetal heart rate evaluation at 28-30 and 32-34 weeks gestational age. After delivery, we observe the infants motor patterns, reflexes, behavior, sleep, and attention. Primary Investigator: Amy Salisbury PhD. 

Kinematics Analysis in Children with Prenatal Exposure to SSRIs

Kinematic analysis of fine motor control in 3- and 5-year olds is part of the longitudinal study of prenatal serotonin reuptake inhibitors (SRIs) and postnatal development. Kinematic analysis measures how well the reach was executed including movement time, smoothness, velocity peak, and acceleration. We manipulate visual information to examine the components of motor control in two ways: the child can see the target object but cannot see their hand; the child cannot see either the object or the hand (reaching in the dark), which requires using memory to organize the reach and grasp. New evidence has shown that prenatal SRI exposure may compromise fine motor control. We have developed an innovative protocol and are currently evaluating participants.Primary Investigators: Linda LaGasse PhD, Amy Salisbury 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

Preschool Neurobehavior and Prenatal Antidepressant Exposure

Over 400,000 pregnant women and their fetuses experience Major Depressive Disorder (MDD) every year in the United States.   Serotonin/Norepinephrine Reuptake Inhibitors (SRIs) are the most commonly chosen antidepressant medications for MDD during pregnancy.  The original prenatal project focused on prenatal and postnatal development of infants whose mothers had MDD during pregnancy, with and without SRI treatment, compared to non-depressed mothers.  Our early findings suggest that prenatal MDD and SRI exposure are both associated with alterations in sensory-motor development in the fetal period and early infancy. We are now following these children and their families through the preschool years. We hypothesize that the early motor effects of prenatal SRI exposure are related to alterations in fetal serotonin development and that these effects will diminish in exposed children by preschool age.  By comparison, effects attributed to maternal MDD will be longer-lasting.  We are currently examining the role of maternal MDD and prenatal SRI exposure on child sensory-motor integration, gross and fine motor control (kinematics), temperament, behavioral and emotional development, and sleep state with circadian biomarkers (urinary melatonin sulfate levels) related to psychiatric symptoms.  We are also identifying potential epigenetic markers associated with these effects.  The rationale for the proposed research is that once we know how early SRI exposure affects these key areas related to serotonin function, we will be able to identify specific mechanistic pathways, including epigenetic targets and biomarkers, for psychopathology.  The expected outcomes will have a positive impact because they will lead to informed risk-benefit decision-making for pregnant women with MDD and provide new preventive and therapeutic targets for psychopathology in children.  This will further translate into enormous reductions in overall costs due to the social and functional disability that may result from such conditions. Primary Investigators:  Amy Salisbury PhD.  

Preterm Infant outcome in the Single Family Room Model of Care 

Preterm infants are often cared for in “open bay” Neonatal Intensive Care Units (NICU) that can be crowded, noisy and overstimulating and with little privacy for families to provide and interact with their babies.  A new model of care, the Single Family Room NICU, in which each infant has their own room, has been proposed as a way to improve infant medical and developmental outcome.  Women and Infants Hospital transitioned from an open bay to a Single Family Room NICU enabling us to compare a group of babies who cared for in the open bay NICU with a group of babies cared for in the single family room NICU.  We are comparing them at hospital discharge on medical and developmental outcome and at 18 months follow-up. We are also studying “mediators” or factors that may explain the how and why of improved outcome in the single family room model.  Primary Investigators: Barry Lester PhD, James Padbury MD.

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.