Drug and Alcohol Dependence 75 (2004) 253–260 Neonatal abstinence syndrome in methadone-exposed infants is altered by level of prenatal tobacco exposure Robin E. Choo a , Marilyn A. Huestis a , Jennifer R. Schroeder b , Angela S. Shin a , Hendrée E. Jones c,d,∗ a Chemistry and Drug Metabolism Section, Clinical Pharmacology and Therapeutics Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institute of Health, 5500 Nathan Shock Drive, Baltimore, MD 21224-6823, USA b Treatment Section, Clinical Pharmacology and Therapeutics Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institute of Health, Baltimore, MD 21224-6823, USA c Center for Addiction and Pregnancy, Johns Hopkins Bayview Medical Center, 4940 Eastern Avenue, D4 East 442, Baltimore, MD 21224-6823, USA d Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21224-6823, USA Received 4 September 2003; received in revised form 10 March 2004; accepted 15 March 2004 Abstract Maternal tobacco consumption during pregnancy has been associated with lower birth weight infants, preterm births, intrauterine growth retardation, smaller head circumference and increase in morbidity, yet few studies have examined the role tobacco has on the opiate neonatal abstinence syndrome (NAS). This study examined the effect of prenatal tobacco exposure on NAS for infants born to mothers maintained on methadone during gestation. Twenty-nine pregnant women and their newborn infants participated in this study. Tobacco exposure was based on maternal self-report with 16 women reporting cigarette consumption of 10 or less per day and 13 reporting smoking 20 cigarettes or more a day. The onset, peak, and duration of NAS were examined. Results showed that infants born to mothers who reported smoking 20 or more cigarettes per day had significantly higher NAS peak scores of 9.8 versus 4.8, and took longer to peak (113.0 h versus 37.8 h), than light smokers of 10 or fewer cigarettes per day. We concluded that tobacco use in conjunction with methadone plays an important role in the timing and severity of NAS in prenatally exposed infants. © 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: Perinatal; Methadone; Nicotine; Withdrawal 1. Introduction Opioid dependence during pregnancy is a growing con- cern in today’s society, especially since the non-medical use of analgesics is rapidly increasing among women in their childbearing years. While methadone remains the rec- ommended treatment for illicit opioid dependence based on its low teratogenic potential and association with improved birth outcome (Kandall et al., 1976; Connaughton et al., 1977; Finnegan, 1991; Kaltenbach and Finnegan, 1986), it is not without disadvantages. Of most concern is the risk that the neonate will undergo neonatal abstinence syndrome (NAS). NAS is characterized by signs and symptoms in- dicated by dysfunction of the autonomic nervous system, ∗ Corresponding author. Tel.: +1-410-550-7684; fax: +1-410-550-7687. E-mail address: hejones@jhmi.edu (H.E. Jones). gastrointestinal tract, and respiratory system (Kaltenbach and Finnegan, 1989; Connaughton et al., 1975; Blinick et al., 1969). While the association between methadone dose and NAS has been examined, the literature is incon- sistent, with eight studies suggesting a relationship between methadone dose and NAS (Dashe et al., 2002; Malpas et al., 1995; Doberczak et al., 1991; Doberczak et al., 1993; Harper et al., 1977; Madden et al., 1977; Strauss et al., 1976; Ostrea et al., 1976) and eight studies suggesting no relationship (Brown et al., 1998; Hagopian et al., 1996; Mack et al., 1991; Stimmel et al., 1982–83; Newman et al., 1975; Rosen and Pippenger, 1976; Rosen and Pippenger, 1975; Blinick et al., 1973). This inability to establish a clear dose–response relationship between methadone dose and NAS severity may be due to other factors, such as tobacco exposure that may contribute to the severity of NAS. As is true for opiates, abrupt cessation of chronic nicotine administration is associated with a withdrawal syndrome 0376-8716/$ – see front matter © 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.drugalcdep.2004.03.012