Research

Prenatal Substance Exposure

Infant Developmental Environment and Lifestyle Study (IDEAL-II, School Age)

The rapidly escalating abuse of methamphetamine in the United States, places a sense of urgency on understanding the consequences of methamphetamine use during pregnancy for the developing child. In 2002 we began the Infant Development, Environment and Lifestyle Study (IDEAL) which is the only prospective, longitudinal NIH study of prenatal methamphetamine exposure and child outcome. IDEAL was designed as a community research network with scientific leadership, management, and data analysis conducted by the Brown Center for Children and recruitment and data collection in Iowa, Oklahoma, California, and Hawaii where methamphetamine use by pregnant women is prevalent. We are now following these 408 children into school to age 7 years. During the early school years, the neural networks develop in the brain that relate to executive functioning, such as motivation, attention, memory, inhibitory control, visual motor integration, and motor control memory. These abilities are building blocks for the academic skills needed for school success. Early identification of deficits in executive function processes enhances our ability to provide appropriate interventions for these children before they experience school failure. For more information contact: Sheri DellaGrotta at sdellagrotta@wihri.org.

Maternal Lifestyle Study (MLS)

In the mid 1980’s cocaine use by pregnant women was identified as a major public health problem.  Yet, little is known about the long-term developmental outcome of cocaine-exposed children.  MLS is the largest prospective study of cocaine-exposed children.  Approximately 1400 children were enrolled in the study at birth in Detroit, Memphis, Miami, and Providence.  These children are now turning 13 and we are studying how prenatal cocaine exposure by itself and in combination with other drug and environmental factors affects their cognitive, school, psychological, behavioral and emotional outcomes.  For more information contact: Linda Lagasse at Linda_Lagasse@brown.edu.

Neuroimaging

We are conducting two types of neuroimaging research in collaboration with on-campus departments at Brown University as well as collaborators at other institutions.  First, a series of studies is investigating the potential long term impact of prenatal cocaine exposure on brain development.  This research has included an initial investigation of brain function in 8 – 9 year old children with prenatal exposure to cocaine.  Using fMRI, we have identified preliminary evidence for the effects of prenatal cocaine on frontal brain functioning during a simple response inhibition task.  This research has been conducted in collaboration with Dr. Jerome Sanes in the Department of Neuroscience, as well as Dr. B.J. Casey at Cornell Medical School.  Morphological studies of the brains of these children are being conducted in collaboration with Dr. Barry Kosofsky, also at Cornell.  In addition, in a related effort, and also in collaboration with Dr. Kosofsky, we are working to implement multi-site MRI scanning procedures for use in pediatric populations, interfacing with the Biomedical Informatics Research Network (BIRN).  A second set of MRI studies involves understanding the response of individuals with Autism Spectrum Disorders to social information using fMRI.  These studies are in collaboration with the Pessoa and Tarr labs at Brown University (see Autism Research).  For more information contact: Stephen Sheinkopf at Stephen_Sheinkopf@brown.edu.

Sleep in adolescents: Implications for development

Research suggests that sleeping difficulties predict negative short- and long-term outcomes, whether they occur during infancy or adolescence. The association between sleep problems and negative developmental outcomes, however, has not been widely assessed in adolescents and we do not know how prenatal vulnerabilities, such as drug exposure, might influence the negative effects of sleep problems on normal development. The purpose of this study is to investigate in MLS children 1) whether sleep problems during childhood predict adolescent sleep problems, 2) whether increased sleep problems predict increased problems in other areas of functioning, and 3) whether that relationship is affected by other pre- and postnatal adversity. For more information contact: Kristen Stone at kstone@wihri.org.

Methamphetamine Exposure and Child Development in New Zealand and USA

An increasing drug of choice for pregnant women in the US and around the world including New Zealand (NZ) is methamphetamine. Methamphetamine is a potent, addictive drug that can be manufactured from ingredients available in drug and hardware stores. Due to the naturally occurring social conditions in NZ, we can isolate the effects of prenatal methamphetamine exposure from co-occurring conditions in the USA that also impact development including poverty and the removal of children from their biological mother. We anticipate 240 NZ mothers and children with methamphetamine exposure and matched comparisons. We will examine neurobehavior at birth, 1 month, 12 months, 24 months, and 36, replicating our USA IDEAL study. Exposed and non-exposed infants in NZ will be compared to their counterparts in the USA. The study increases our understanding of the role of culture, social policy, child rearing, and nonmaternal care on the outcome of methamphetamine exposed children. For more information contact: Sheri DellaGrotta at sdellagrotta@wihri.org.

Maternal Depression

Screening for Depression at Developmental Follow-Up Visits in Mothers of Preterm Infants

This study screens for maternal depression at infant follow-up visits to determine whether mothers of children born prematurely experience ongoing depressive symptoms following their infants discharge.  The focus of the study is to provide pilot data for a larger parenting intervention grant designed to support mothers of preterm infants who are experiencing postpartum depression.  Under the larger parenting intervention grant, parents will be instructed in specific strategies shown to be beneficial to the development of preterm infants’ social regulation skills.  Parents in the intervention group would also be provided with supports related to their depressive symptoms.  This work is being done in collaboration with Dr. Betty Vohr, Director of the Neonatal Follow-up program at Women & Infants Hospital.  For more information contact: Cynthia Loncar, at Cynthia_Loncar@brown.edu.

F.I.R.S.T. Study – 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. 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. For more information, contact Beth Hott at 401-453-7960 or fetalstudy@wihri.org.

Depression in Pregnancy

Approximately 600,000 infants born each year are exposed to maternal depression.  At least 40% 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.  We do not currently know if treatment of the disorder is better or worse for the developing fetus.  This study directly addresses this question by examining the effects of maternal antidepressant use and maternal depression on fetal and newborn neurobehavioral development.  Fetal neurobehavior measures are obtained by ultrasound and fetal heart rate evaluation at 26-28 and 36-38 weeks gestational age.  After delivery, we observe the infants motor patterns, reflexes, behavior, sleep, and attention.  The study has enrolled over 160 participants and is actively recruiting new participants.  For more information, contact Beth Hott at 401-453-7960 or bhott@wihri.org.

Autism

Autism Spectrum Disorders

Research on autism spectrum disorders (ASD) seeks to understand how children with ASD’s respond to social information and explores individual differences in social functioning in ASD.  We are particularly interested in joint attention and other social communication behaviors and on understanding biobehavioral determinants of individual differences in such social pragmatic skills.  Our research methods include observation of behavioral and physiologic reactions to behavioral assays (well controlled sequences of social interactions and events), with special attention to cardiorespiratory reactivity and regulation.  In addition, we investigate group and individual differences in brain functioning during the processing of social information using fMRI.  The lead investigator for autism studies at the Center is Stephen Sheinkopf, Ph.D.  Collaborators at the Center include Dr. Loncar and Dr. Salisbury.  In addition, these studies are conducted in collaboration with investigators at E. P. Bradley Hospital (Dr. Rowland Barrett & Dr. Chris Borden) and Brown University Department of Psychology (Dr. Luiz Pessoa) and Cognitive & Linguistic Sciences (Dr. Michael Tarr).  For more information contact: Stephen Sheinkopf at Stephen_Sheinkopf@brown.edu.

Study of Social Anxiety in Asperger's Disorder

The goal of this pilot study is to determine if social anxiety manifests itself differently in children with Asperger's Disorder compared to children with social anxiety alone. We will examine heart rate, stress hormone response (cortisol), galvanic skin response, as well as parent and child reports of anxiety during a mild social stressor (The Trier Social Stress Test). We will compare these data between the two groups and determine if neurobiological differences do exist which can help elucidate differential response to stress and social anxiety.  For more information contact: Todd Levine at tlevine@wihri.org.

Preterm Infant Development

Adolescent Development Study

This prospective longitudinal investigation is one of a few in which the course of competence outcomes have been examined in children born at various degrees of perinatal morbidity.  With rising number of preterm infant survivors, it serves as a model to understand how preterm infants born today will do when they reach late adolescence.  This study, inclusive from birth to age 17, will provide a comprehensive understanding of specific developmental trajectories, and risk and protective processes that exacerbate or ameliorate the impact of cumulative risk on competency outcomes in full term and preterm children.  The ultimate reason to understand the trajectories of long term outcomes is identification of possibilities for preventative interventions.  Formulating a science of prevention requires attention to complex interactions between children and their contexts across periods of time.  For more information contact:  Mary Sullivan at MCSullivan@uri.edu.

MRI/fMRI and Kinematics in Preterm Infants

We use Magnetic Resonance Imaging (MRI) and Functional Magnetic Resonance Imaging (fMRI) to detect structural abnormalities in brain motor areas and differences in neuroactivation during motor tasks in children with poor motor performance and suspected brain pathology due to perinatal.  The research protocol is designed to acclimate children of a wide age range to the Magnetic Resonance system in a developmentally appealing paradigm adjusted for complexity by using nearly identical visual motor and kinematic assessment in a pre-MR session that are repeated in the magnet in an expanded visual-spatial task.  Kinematic analysis provides a precise measure of the position of the moving limb in 3-dimensional space at all points during the reach, generating parameters that relate to the efficiency of the reaching process.  This is a new application of kinematic analysis which is particularly relevant to this project because it is sensitive to perinatal insult or residual brain damage in children and adolescents, particularly those with subsequent motor diagnoses; and, kinematic parameters are sensitive to cognitive load, which may be more compromised in children with deficits in visual-motor integration.  Motor planning and execution of a directed reach includes processing information (e.g., attention, discrimination), localization of target, and implementation of the reach by muscles and joints.  The kinematic assessment is being done in collaboration with Dr. LaGasse at the Center.  This project also includes collaboration with the University of Rhode Island and the Brown University MR Facility.  For more information contact: Mary Sullivan at MCSullivan@uri.edu .

Effects of Open-Bay vs. Single Room NICU on Infant Outcomes at Discharge

Prematurity is an increasing public health concern as the rate of prematurity in the U.S. is on the rise. Efforts to improve preterm infant outcomes include environmental stimulation (sound and light), psychosocial factors, developmental care, family centered care and staff behavior and attitudes. Women and Infants Hospital is building a new NICU with 70 individual single rooms. The “single family room” model of care is one of the environments thought to enhance medical and developmental outcomes. The single room concept is attractive because factors that adversely affect the infant can be better controlled, patient care can be individualized and parent satisfaction can be improved. However, nearly all of the evidence is anecdotal. This study aims to compare the medical and neurodevelopmental course from birth through discharge from the NICU between infants in the current open bay nursery with infants in the new single room nursery. This provides an exciting one-time opportunity to conduct a naturalistic study and compare infant outcome in the current open bay nursery with the outcome of infants in the coming single room nursery. Our plan is to study virtually all infants in the NICU, with birthweight <1500 gms, for four consecutive years, two years before and two years after the move to the new NICU. We hypothesize that infants in the single room NICU will have better medical and neurobehavioral outcomes at discharge than infants in the open bay NICU. Medical outcomes include length of stay, gestational age at discharge, weight, weight gain, illness severity and resource utilization, gestational age at enteral feeding, sepsis and necrotizing enterocolitis. Neurobehavioral outcomes include better NICU Network Neurobehavioral Scale (NNNS) profiles, better sleep state organization and sleep physiology, better infant mother feeding interaction scores and lower pain scores. We also hypothesize that the positive effects of the new NICU will be explained in part by other mediating factors that can be expected to co-occur with the transition to the new NICU. These factors include changes in family centered care, developmental care, parenting and family factors, staff behavior and attitudes and changes in medical practice. These factors will be measured repeatedly before and after the move to the new NICU and used as mediators in the statistical analysis. Findings from this study will likely influence the future quality of NICU design and model of care throughout the Nation. For more information contact: Katheleen Hawes at 453-7635 or khawes@wihri.org.

Intervention

Evaluation of the Vulnerable Infants Program

The purpose of this project is to evaluate the Vulnerable Infants Program of Rhode Island (VIP-RI).  VIP is a statewide model of coordinated care and support for drug-exposed infants and their families and has been expanded to include the needs of biological and foster parents, siblings and families.  This unique hospital based program is designed to improve the community’s ability to manage cases of drug-exposed children at-risk for compromised development, and to provide the earliest and best intervention for vulnerable infants and their families.  The program now includes the Family Treatment Drug Court with the goal of permanent placement and reunification with the biological mother, where feasible, based on a treatment model.  In addition, VIP will track and screen infants and their siblings thus assisting the state in complying with CAPTA law.  This work is being done in collaboration with Chief Judge Jeremiah at the Rhode Island Court and the National Perinatal Information Center.  For more information contact: Lynne Andreozzi Fontaine at landreozzi@wihri.org.

Massage for Methadone Study

The purpose of this study is to determine the utility of infant massage for neonates of methadone-maintained mothers who require medication treatment due to opiate withdrawal. According to the 1996 report by the National Pregnancy & Health Survey, 34,000 women used methadone during pregnancy. Infant massage has been shown to be beneficial for many populations of infants including preterm, cocaine-exposed preterm and infants of depressed mothers, showing improvements in weight gain and behavior. Infants in The Massage for Methadone Study is randomized into two groups, those receiving massage, and those receiving standard care. We hypothesize that infants who receive massage will show lower peak daily withdrawal scores, require less total amount of anti-withdrawal medications, have shorter neonatal length of stay in the hospital and display better neurobehavioral scores. If the result of this study concurs with the hypothesis, we can teach these mothers massage which will help babies as well as mothers, especially in bonding, neurobehavioral adjustments and mother's depression. This study is funded by NIDA and is currently being conducted at two hospitals, Women and Infants' Hospital and Charlton Memorial Hospital in Fall River, MA with plans for Kent Hospital to be added as a third site. The lead investigator for this study is Dr. Yun Joo Lee, M.D. For more information contact: Kate Halloran at (401) 276-7835 or khalloran@wihri.org.

Maternal Opioid Treatment: Human Experimental Research

Though clearly beneficial, the use of methadone during pregnancy remains controversial in part due to the large percentage of newborns having signs of opioid withdrawal requiring medical intervention and extended hospitalization.  A new medication, Buprenorphine, is approved by the Food and Drug Administration (FDA) for the treatment of non-pregnant opioid dependent patients and produces only a mild abstinence syndrome following abrupt withdrawal.  This randomized, parallel group study is the first multi-site trial to assess in opioid-dependent pregnant women the efficacy of buprenorphine for reducing withdrawal relative to methadone. Johns Hopkins School of Medicine (Dr. Hendree Jones) is the Lead Site for this study involving six United States and two international sites study. Opioid-dependent pregnant women at the Brown site in New Bedford will be randomized to optimal doses of methadone or buprenorphine and followed throughout pregnancy. Treatment groups will be compared on the primary outcome measures related to severity of withdrawal.  This study will provide pivotal data to the FDA to support an indication for the use of buprenorphine during pregnancy and potentially optimize strategies for safe and effective treatment of pregnant opioid-dependent women. The study is directed by Dr. Mara Coyle at Women and Infants Hospital and St. Lukes Hospital. For more information contact: Lee Breault at lbreault@wihri.org.

Outcome of the Rhode Island Family Treatment Drug Court-After ASFA

After ASFA: Outcome of the Rhode Island Family Treatment Drug Court (FTDC), examines the long-term trajectories of parents who participate in FTDC, the developmental outcomes of their substance-exposed infants, and the success of the FTDC in complying with the Adoption and Safe Families Act (ASFA) guidelines for permanent placement.  Parenting and child assessments are done at 6 month intervals between infant ages of 12 to 30 months.  This project will provide the first longitudinal preliminary descriptive data on participants of a FTDC specifically designed for perinatal substance users.  The outcome measures from this study includes data on parent and child strengths and vulnerabilities.  Factors that affect substance-using parents’ ability to successfully become the permanent placement for their infant, including home environments, substance use, mental health, parenting attitudes, social support and child abuse potential are examined.  Study results can be applied to developing more efficacious services for perinatal substance users and their children and to better inform public policy decisions related to families affected by perinatal substance use.  This work is being done in collaboration with Chief Judge Jeremiah at the Rhode Island Court and the National Perinatal Information Center.  For more information contact: Jean Twomey, at jtwomey@wihri.org.

PATCH (Parents Active in Treatment with Children)

The prevalence of behavior problems in children born premature is substantially higher than children born full-term. Early intervention for behavior problems in young preterm children is critical due to the stability of these behaviors and poor prognosis without treatment. The purpose of this study is to examine the efficacy of a parent-training intervention, Parent-Child Interaction Therapy (PCIT), for 18-month to 5-year-old children who were born prematue (less than 37 weeks gestation) and currently have behaviors that are difficult to manage. We are also examining the role of physiology, including heart rate variability and salivary cortisol, as potential mediators of treatment outcome. Parents participate in our program at no cost and will learn specific techniques to reduce their child's behavior problems. We coach parents in the use these techniques with their child through our one-way mirror using a wireless headset. This work is being done in collaboration with Dr. Betty Vohr, Director of the Neonatal Follow-up program at Women & Infants Hospital. For more information contact: Dr. Daniel Bagner at (401) 276-7856 or dbagner@wihri.org.

Epigenetics