Acoustic Cry Analyzer for the Diagnosis of Infants Suffering Withdrawal Due To Prenatal Opioid Exposure

The current national opioid epidemic has called for more objective measures of Neonatal Abstinence Syndrome (NAS), the withdrawal that occurs in newborn infants due to the abrupt discontinuation of prenatal exposure to opiates such as prescription pain medication. Current methods to diagnose NAS rely heavily on cry characteristics (e.g. pitch, amount of crying) but are highly subjective and could lead to the misdiagnosis of NAS and poor or inappropriate treatment. We have developed an automated, computerized Infant Cry Analyzer (ICA) that quantifies the acoustic characteristics of infant cries. This system provides a reliable, objective measure of the acoustical properties of the cry necessary for the accurate diagnosis and clinical management of NAS. Our objective is to quantify the acoustic characteristics of cries of infants with NAS. This proof-of-concept project will enable us to collect data that would attract potential investors in the development of an automated, hand held "iPhone-like" device. Such a device would provide a digital readout indicative of whether or not the infant's cry is symptomatic of NAS. This information can then be used to provide a more accurate diagnosis of NAS, thereby reducing the likelihood of misdiagnosis, and improve the treatment and management of these infants. Primary Investigators: Barry Lester PhD, Stephen Sheinkopf PhD, Harvey Silverman PhD. 

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.

Infant Cry Acoustics:  Measurement Tools and Relation to Developmental Outcomes

The acoustic features of infant cries contains information about the neurodevelopmental health of infants. We have investigated the relation between the acoustic features of cries from infants at risk for autism in relation to later childhood diagnoses.  In a recent study, we found that 6 month old infants at risk for autism had higher pitched cries than low risk infants, and those infants with later diagnoses of autism produced cries that were both high in pitch (fundamental frequency) and poorly voiced (dysphonation).  In order to follow up on these initial observations, we have developed an improved, modern and well validated measurement tool for acoustic analyses of infant cries. This cry analyzer is available as a research tool for qualified investigators. Primary Investigators: Stephen Sheinkopf, PhD, Barry Lester PhD, Harvey Silverman 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

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 were 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. NZ has a harm reduction approach toward drug use compared to the more punitive approach in the US, especially with pregnant women. NZ has no mandatory reporting statutes hence very little child removal for prenatal illicit drug use and offers free universal health care and generous financial resources. In recent findings, drug-using NZ mothers are far more likely to have prenatal care than US mothers. Further, NZ infants are 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. Ongoing analyses of academic achievement 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