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Ineffective morphine treatment regimen for the control of Neonatal Abstinence Syndrome in buprenorphine- and methadone-exposed infants

Published online by Cambridge University Press:  02 April 2012

A. L. Gordon ,
O. V. Lopatko ,
R. R. Haslam ,
H. Stacey ,
V. Pearson ,
A. Woods ,
A. Fisk  and
J. M. White
A. L. Gordon*
Affiliation:
School of Nursing and Midwifery, Sansom Institute for Health Research, University of South Australia, Adelaide, Australia Discipline of Pharmacology, University of Adelaide, Adelaide, Australia
O. V. Lopatko
Affiliation:
Discipline of Pharmacology, University of Adelaide, Adelaide, Australia
R. R. Haslam
Affiliation:
Women's and Children's Hospital, Adelaide, Australia
H. Stacey
Affiliation:
Women's and Children's Hospital, Adelaide, Australia
V. Pearson
Affiliation:
Drug and Alcohol Services South Australia, Adelaide, Australia
A. Woods
Affiliation:
Drug and Alcohol Services South Australia, Adelaide, Australia
A. Fisk
Affiliation:
Drug and Alcohol Services South Australia, Adelaide, Australia
J. M. White
Affiliation:
Discipline of Pharmacology, University of Adelaide, Adelaide, Australia School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, Australia
*
*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
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Abstract

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 = 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 14+: 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 ± 3.95 mg) compared with buprenorphine infants (22.77 ± 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.

Keywords

buprenorphinemethadonemorphine treatmentneonatal abstinence syndromenon-opioid-exposed controls
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 3 , Issue 4 , August 2012 , pp. 262 - 270
Copyright
Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2012

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References

1.Kaltenbach, K, Berghella, V, Finnegan, L. Opioid dependence during pregnancy. Effects and management. Obstet Gynecol Clin North Am. 1998; 25, 139–151.CrossRefGoogle ScholarPubMed
2.Finnegan, LP, Kandall, SR. Maternal and neonatal effects of alcohol and drugs. In Substance Abuse (eds. Lowinson JH, Ruiz P, Millman RB, Langrod JG), 3rd edn, 1997; pp. 513–534. Williams and Wilkins: Baltimore.Google Scholar
3.Colombini, N, Elias, R, Busuttil, M, et al. . Hospital morphine preparation for abstinence syndrome in newborns exposed to buprenorphine or methadone. Pharm World Sci. 2008; 30, 227–234.CrossRefGoogle ScholarPubMed
4.Ebner, N, Rohrmeister, K, Winklbaur, B, et al. . Management of neonatal abstinence syndrome in neonates born to opioid maintained women. Drug Alcohol Depend. 2007; 87, 131–138.CrossRefGoogle ScholarPubMed
5.Fischer, G, Ortner, R, Rohrmeister, K, et al. . Methadone versus buprenorphine in pregnant addicts: a double-blind, double-dummy comparison study. Addiction. 2006; 101, 275–281.CrossRefGoogle ScholarPubMed
6.Jones, HE, Kaltenbach, K, Heil, SH, et al. . Neonatal abstinence syndrome after methadone or buprenorphine exposure. N Engl J Med. 2010; 363, 2320–2331.CrossRefGoogle ScholarPubMed
7.Lejeune, C, Simmat-Durand, L, Gourarier, L, Aubisson, S. Prospective multicenter observational study of 260 infants born to 259 opiate-dependent mothers on methadone or high-dose buprenorphine substitution. Drug Alcohol Depend. 2006; 82, 250–257.Google Scholar
8.Jackson, L, Ting, A, McKay, S, Galea, P, Skeoch, C. A randomised controlled trial of morphine versus phenobarbitone for neonatal abstinence syndrome. Arch Dis Child Fetal Neonatal Ed. 2004; 89, F300–F304.Google Scholar
9.Kraft, WK, Gibson, E, Dysart, K, et al. . Sublingual buprenorphine for treatment of neonatal abstinence syndrome: a randomized trial. Pediatrics. 2008; 122, e601–e607.Google Scholar
10.Langenfeld, S, Birkenfeld, L, Herkenrath, P, et al. . Therapy of the neonatal abstinence syndrome with tincture of opium or morphine drops. Drug Alcohol Depend. 2005; 77, 31–36.CrossRefGoogle ScholarPubMed
11.Johnson, K, Gerada, C, Greenough, A. Treatment of neonatal abstinence syndrome. Arch Dis Child Fetal Neonatal Ed. 2003; 88, F2–F5.Google Scholar
12.Kuschel, C. Managing drug withdrawal in the newborn infant. Semin Fetal Neonatal Med. 2007; 12, 127–133.Google Scholar
13.Osborn, DA, Jeffery, HE, Cole, M. Opiate treatment for opiate withdrawal in newborn infants. Cochrane Database Syst Rev. 2005, CD002059.Google Scholar
14.Winklbaur, B, Jung, E, Fischer, G. Opioid dependence and pregnancy. Curr Opin Psychiatry. 2008; 21, 255–259.CrossRefGoogle ScholarPubMed
15.Winklbaur, B, Kopf, N, Ebner, N, et al. . Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence: a knowledge synthesis for better treatment for women and neonates. Addiction. 2008; 103, 1429–1440.CrossRefGoogle ScholarPubMed
16.Crane, E, Morris, JK. Changes in maternal age in England and Wales – implications for Down syndrome. DSRP. 2006; 10, 41–43.Google ScholarPubMed
17.Godding, V, Bonnier, C, Fiasse, L, et al. . Does in utero exposure to heavy maternal smoking induce nicotine withdrawal symptoms in neonates? Pediatr Res. 2004; 55, 645–651.CrossRefGoogle ScholarPubMed
18.Llewellyn-Jones, D. Fundamentals of Obstetrics and Gynecology, 7th edn, 1999. Mosby: Barcelona.Google Scholar
19.Merrick, J, Merrick, E, Morad, M, Kandel, I. Fetal alcohol syndrome and its long-term effects. Minerva Pediatr. 2006; 58, 211–218.Google ScholarPubMed
20.Kraft, WK, Dysart, K, Greenspan, JS, et al. . Revised dose schema of sublingual buprenorphine in the treatment of the neonatal opioid abstinence syndrome. Addiction. 2011; 106, 574–580.Google Scholar
21.Fischer, G, Johnson, RE, Eder, H, et al. . Treatment of opioid-dependent pregnant women with buprenorphine. Addiction. 2000; 95, 239–244.CrossRefGoogle ScholarPubMed
22.Blinick, G, Jerez, E, Wallach, RC. Methadone maintenance, pregnancy, and progeny. JAMA. 1973; 225, 477–479.Google Scholar
23.Kaltenbach, K, Finnegan, LP. Perinatal and developmental outcome of infants exposed to methadone in-utero. Neurotoxicol Teratol. 1987; 9, 311–313.Google Scholar
24.Kandall, SR, Albin, S, Lowinson, J, et al. . Differential effects of maternal heroin and methadone use on birthweight. Pediatrics. 1976; 58, 681–685.Google Scholar
25.Wouldes, TA, Roberts, AB, Pryor, JE, Bagnall, C, Gunn, TR. The effect of methadone treatment on the quantity and quality of human fetal movement. Neurotoxicol Teratol. 2004; 26, 23–34.CrossRefGoogle ScholarPubMed
26.Wen, SW, Kramer, MS, Usher, RH. Comparison of birth weight distributions between Chinese and Caucasian infants. Am J Epidemiol. 1995; 141, 1177–1187.Google Scholar
27.Singh, GK, Yu, SM. Birthweight differentials among Asian Americans. Am J Public Health. 1994; 84, 1444–1449.CrossRefGoogle ScholarPubMed
28.Humphrey, MD, Holzheimer, DJ. Differing influences on Aboriginal and non-Aboriginal neonatal phenotypes: a prospective study. Med J Aust. 2001; 174, 503–506.CrossRefGoogle ScholarPubMed
29.Doberczak, TM, Kandall, SR, Wilets, I. Neonatal opiate abstinence syndrome in term and preterm infants. J Pediatr. 1991; 118, 933–937.Google Scholar
30.Ballard, JL. Treatment of neonatal abstinence syndrome with breast milk containing methadone. J Perinatol Neonat Nurs. 2002; 15, 76–85.Google Scholar
31.Begg, EJ, Malpas, TJ, Hackett, LP, Ilett, KF. Distribution of R- and S-methadone into human milk during multiple, medium to high oral dosing. Br J Clin Pharmacol. 2001; 52, 681–685.Google Scholar
32.Johnson, RE, Jones, HE, Jasinski, DR, et al. . Buprenorphine treatment of pregnant opioid-dependent women: maternal and neonatal outcomes. Drug Alcohol Depend. 2001; 63, 97–103.CrossRefGoogle ScholarPubMed
33.Marquet, P, Chevrel, J, Lavignasse, P, Merle, L, Lachatre, G. Buprenorphine withdrawal syndrome in a newborn. Clin Pharmacol Ther. 1997; 62, 569–571.CrossRefGoogle ScholarPubMed
34.McCarthy, JJ, Posey, BL. Methadone levels in human milk. J Hum Lact. 2000; 16, 115–120.Google Scholar
35.Schindler, SD, Eder, H, Ortner, R, et al. . Neonatal outcome following buprenorphine maintenance during conception and throughout pregnancy. Addiction. 2003; 98, 103–110.Google Scholar
36.McGlone, L, Mactier, H, Hamilton, R, et al. . Visual evoked potentials in infants exposed to methadone in utero. Arch Dis Child. 2008; 93, 784–786.Google Scholar
37.van Baar, AL, de Graaff, BM. Cognitive development at preschool-age of infants of drug-dependent mothers. Dev Med Child Neurol. 1994; 36, 1063–1075.Google Scholar
38.van Baar, AL, Soepatmi, S, Gunning, WB, Akkerhuis, GW. Development after prenatal exposure to cocaine, heroin and methadone. Acta Paediatr Suppl. 1994; 404, 40–46.CrossRefGoogle ScholarPubMed
39.Whitham, JN, Spurrier, NJ, Sawyer, MG, et al. . The effects of prenatal exposure to buprenorphine or methadone on infant visual evoked potentials. Neurotoxicol Teratol. 2010; 32, 280–288.Google Scholar
40.Voepel-Lewis, T, Marinkovic, A, Kostrzewa, A, Tait, AR, Malviya, S. The prevalence of and risk factors for adverse events in children receiving patient-controlled analgesia by proxy or patient-controlled analgesia after surgery. Anesth Analg. 2008; 107, 70–75.CrossRefGoogle ScholarPubMed
41.Jasinski, DR, Pevnick, JS, Griffith, JD. Human pharmacology and abuse potential of the analgesic buprenorphine: a potential agent for treating narcotic addiction. Arch Gen Psychiatry. 1978; 35, 501–516.Google Scholar
42.Walsh, SL, Preston, KL, Stitzer, ML, Cone, EJ, Bigelow, GE. Clinical pharmacology of buprenorphine: ceiling effects at high doses. Clin Pharmacol Ther. 1994; 55, 569–580.CrossRefGoogle ScholarPubMed
43.Ward, J, Mattick, RP, Hall, W (eds) Methadone Maintenance Treatment and Other Opioid Replacement Therapies, 1998. Hardwood Academic Publishers: Amsterdam.Google Scholar