Journal of Developmental Origins of Health and Disease (2012), 3(4), 262–270. & Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2012 doi:10.1017/S2040174412000190 ORIGINAL ARTICLE Ineffective morphine treatment regimen for the control of Neonatal Abstinence Syndrome in buprenorphine- and methadone-exposed infants A. L. Gordon 1,2 *, O. V. Lopatko 2 , R. R. Haslam 3 , H. Stacey 3 , V. Pearson 4 , A. Woods 4 , A. Fisk 4 and J. M. White 2,5 1 School of Nursing and Midwifery, Sansom Institute for Health Research, University of South Australia, Adelaide, Australia 2 Discipline of Pharmacology, University of Adelaide, Adelaide, Australia 3 Women’s and Children’s Hospital, Adelaide, Australia 4 Drug and Alcohol Services South Australia, Adelaide, Australia 5 School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, Australia This study aimed to determine if morphine is effective in ameliorating Neonatal Abstinence Syndrome (NAS) symptoms to non-opioid- exposed control levels in methadone- and buprenorphine-exposed infants. A prospective, non-randomized comparison study with flexible dosing was undertaken in a large teaching maternity hospital in Australia. Twenty-five infants in the groups of buprenorphine-, methadone- and control non-opioid-exposed infants were compared (total n 5 75 infants). Oral morphine sulphate (1 mg/ml) was administered every 4 h to opioid agonist-exposed infants. Modified Finnegan Withdrawal Scale (MFWS) scores determined dosing: score of 8–10: 0.5 mg/kg/day, 11–13: 0.7 mg/kg/day and 141: 0.9 mg/kg/day. Withdrawal score, amount of morphine administered and length of hospital stay, were used to assess NAS over a 4-week follow-up period. No controls achieved a score higher than 7 on the MFWS. There was no significant difference in the percentage of infants requiring treatment between methadone (60%) and buprenorphine (48%) infants. For treated infants, significantly (P , 0.01) more morphine was administered to methadone (40.07 6 3.95 mg) compared with buprenorphine infants (22.77 6 4.29 mg) to attempt to control NAS. Following treatment initiation, significantly more (P , 0.01) methadone (87%) compared with buprenorphine infants (42%) continued to exceed scoring thresholds for morphine treatment requirement, and non-opioid-exposed control infant scores. For treated infants, there was no significant difference in length of hospital stay between methadone and buprenorphine infants. Morphine treatment was not entirely effective in ameliorating NAS to non-opioid-exposed control symptom levels in methadone or buprenorphine infants. The regimen may be less effective in methadone compared with buprenorphine infants. Received 30 November 2011; Revised 27 February 2012; Accepted 5 March 2012; First published online 2 April 2012 Key words: buprenorphine, methadone, morphine treatment, neonatal abstinence syndrome, non-opioid-exposed controls Introduction Neonatal Abstinence Syndrome (NAS) results from the sud- den cut-off from supply of drug that the mother used during pregnancy. NAS is defined as ‘a generalised disorder char- acterised by signs and symptoms of central nervous system hyperirritability, gastrointestinal dysfunction, respiratory distress and vague autonomic symptoms that include yawning, sneezing, mottling and fever’ 1 (p. 147). NAS as a result of opioid exposure is typically measured using a Finnegan Withdrawal Scale or modified version of this scale 2 and often requires treatment resulting in long infant hospital stays. Although large case series and smaller randomized controlled trials have observed less severe NAS in buprenorphine- compared with methadone-exposed infants 3–7 , there is a lack of strong evidence to suggest which is the most effective pharmacological interven- tion to reduce NAS for both buprenorphine- and methadone- exposed infants. Importantly, there are no studies that explore the ability of pharmacological interventions to ameliorate NAS symptoms in buprenorphine- and methadone-exposed infants to levels experienced by non-opioid-exposed control infants. Multiple studies have been undertaken to assess the effec- tiveness of different pharmacological interventions to control NAS as a result of different maternal opioid exposures. From these studies it is apparent that the use of opioids is effective for the management of opioid-related NAS in opioid-exposed infants, and in particular is superior to that of sedative medications alone. 3,4,8–10 However, interpretation and forthright comparisons of currently available literature to determine the most appropriate opioid replacement therapy for the opioid-exposed infant are confounded by non- standardized methodological approaches. 11–15 Most importantly, no research has been undertaken to assess the effectiveness of a pharmacological intervention in the management of NAS *Address for correspondence: A. L. Gordon, School of Nursing and Midwifery, Sansom Institute for Health Research, University of South Australia, GPO Box 2471, Adelaide, South Australia 5001, Australia. (Email andrea.gordon@unisa.edu.au)