Infant Neurobehavior Following Prenatal Exposure to Methadone or Buprenorphine: Results From the Neonatal Intensive Care Unit Network Neurobehavioral Scale

Abstract

This study examined the neurobehavioral functioning of neonates prenatally exposed to methadone (n = 11) or buprenorphine (n = 10), who underwent the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) examinations on days 3, 5, 7, 10, and 14 post-delivery. Linear mixed model analyses revealed that NNNS scores of arousal and excitability showed significant differences between medications over time. Compared to neonates who did not require medication to treat neonatal abstinence syndrome (NAS), neonates receiving pharmacotherapy for NAS showed differences over time in quality of movement, excitability, and lethargy. Results suggest the NNNS may detect subtle differences over time between both neonates prenatally exposed to methadone or buprenorphine and neonates pharmacologically treated or untreated for NAS.

RÉSUMÉ

Neurocomportement infantile suite à une exposition prénatale à la méthadone ou la buprénorphine: Les résultats de l’Unité néonatale de soins intensifs neuro-réseau à grande échelle

Cette étude a observé le fonctionnement neuro-comportemental des nouveau-nés exposés avant la naissance à la méthadone (n = 11) ou à la buprénorphine (n = 10), qui ont bénéficié des tests NNNS Neonatal Intensive Care Unit Network Neurobehavioral Scale à J3, J5, J7, J10 et J14 de vie. Les analyses selon un modèle linéaire mixte ont révélé que les scores NNNS d’éveil et de l’excitabilité montrent des différences significatives entre les médicaments en fonction du temps. En comparaison aux nouveaux nés qui n’ont pas eu besoin de médicaments pour traiter le syndrome de sevrage néonatal (NAS), les nouveau-nés traités pour les NAS montrent des différences en fonction du temps pour la qualité du mouvement, l’excitabilité, et la léthargie. Les résultats suggèrent que les tests NNNS peuvent détecter des différences subtiles dans le temps entre les nouveau-nés exposés avant la naissance à la méthadone ou la buprénorphine, et également pour les nouveau-nés traités ou non traités pour un NAS.

RESUMEN

Neuroconductuales infantil después de la exposición prenatal a la metadona o la buprenorfina: Los resultados de la Unidad de Cuidados Intensivos Neonatales Red Neurocomportamentales Escala

En este estudio se examinó el neurocomportamiento de neonatos expuestos a metadona (n = 11) o buprenorfina (n = 10) durante el periodo prenatal, usando el Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) los días 3, 5, 7, 10 y 14 después del nacimiento. Los análisis estadísticos usando modelos lineares mixtos revelaron que las puntuaciones del NNNS en las categorías de “arousal” y excitabilidad, mostraron diferencias significativas entre los medicamentos y en el tiempo. En comparación con los recién nacidos que no requirieron medicamentos para tratar el síndrome de abstinencia neonatal (SAN), recién nacidos que recibieron tratamiento farmacológico para el SAN mostraron diferencias a través del tiempo en la calidad del movimiento, excitabilidad, y el nivel de letargia. Los resultados sugieren que el NNNS puede detectar diferencias sutiles a través del tiempo tanto entre recién nacidos expuestos durante el periodo prenatal a la metadona o la buprenorfina, como entre recién nacidos tratados o no farmacologicamente para el SAN.

Keywords :

• Pregnancy
• substance abuse
• methadone
• buprenorphine
• developmental neurobehavior
• neonatal abstinence syndrome

THE AUTHORS

Martha Velez is a pediatrician working with substance-dependent pregnant women and their children for more than 15 years at the Center for Addiction and Pregnancy in Baltimore, Maryland. She has directed grant funded projects for the development of a parent training program for substance abusing mothers and for the development of screening, assessment and interventions measures for drug dependent women exposed to trauma. Other research interests include substance exposure and fetal and infant neurobehavior.

Kevin E. O’Grady received his PhD in clinical psychology from the University of Connecticut in 1980. He is now an Associate Professor in the Department of Psychology at the University of Maryland, College Park. His research interests have focused on (1) the etiology of substance abuse, particularly individual, familial, and social factors that place an individual at increased risk for the development of a drug-abusing lifestyle; (2) the development of intervention programs that seek to impact at-risk individuals, where these programs are guided by the risk-factor information available from participants; and (3) the development of conceptual models that explain differential responsiveness to substance abuse treatment.

Hendrée E. Jones, PhD, received her doctorate in psychology from the Virginia Commonwealth University in 1997 and then completed a post-doctoral fellowship at the Behavioral Pharmacology Research Unit at the Johns Hopkins University (JHU) School of Medicine, Baltimore, MD. Dr. Jones, a licensed psychologist in the state of Maryland, is currently a full professor in both the Department of Psychiatry and Behavioral Sciences, and the Department of Obstetrics and Gynecology, at the JHU School of Medicine. As part of her duties, Dr. Jones is the Director of Research for the Center for Addiction and Pregnancy, and the Executive Program Director of Cornerstone, an aftercare program for detoxified heroin-dependent patients. Dr. Jones is currently on sabbatical from JHU and working as a senior research psychologist at Research Triangle Institute International. Since 1994, Dr. Jones has been continuously funded by NIDA as a principal investigator designing and leading studies that focus on the in utero exposure to abused substances. Among her many research interests, she is best known for her work development of both behavioral and pharmacologic treatments for drug-dependent pregnant women.

Rolley E. Johnson, PharmD, received his bachelor of pharmacy from the University Kentucky College of Pharmacy in 1971 and his doctorate in 1979. He entered the US Public Health Service in 1971 following graduation and retired in 1991 at the rank of Navy Captain after completing 3 years with the Indian Health Services on the Navajo Indian reservation and 17 years with the National Institute on Drug Abuse intramural research program, where his primary area of study with buprenorphine lead to the first pivotal clinical trial of buprenorphine for the treatment of opioid dependence. He served as consultant medical reviewer for the Center for Drug Evaluation and Research, FDA from 1989 through 1990. In 1991 he joined Department of Psychiatry and Behavioral Sciences, the Johns Hopkins University School of Medicine as assistant professor and rose through the academic ranks to professor in 2003. Dr. Johnson joined Reckitt Benckiser Pharmaceuticals as Vice President clinical, scientific and regulatory affairs with the launch of Suboxone in 2003.

Lauren M. Jansson, MD, is an Associate Professor of pediatrics at the Johns Hopkins University School of Medicine. She is a developmental pediatrician and has provided pediatric care exclusively to drug-exposed infants and children to age 21 for the past 19 years at the Center for Addiction and Pregnancy, a treatment facility for drug-dependent pregnant and post-partum women and their children in Baltimore, MD. Her research interests include breastmilk and methadone and fetal and infant neurodevelopment in opioid-exposed preganancies.