High-dose methadone in pregnant women and its effect on duration of neonatal abstinence syndrome

Published:November 03, 2008DOI:


      The purpose of this study was to examine high-dose methadone in pregnant women and its effect on the duration of neonatal abstinence syndrome.

      Study Design

      This was a retrospective chart review of 68 neonates and their mothers who received methadone therapy during pregnancy. The last dosage of maternal methadone just before delivery and the length of treatment for neonatal abstinence syndrome were examined with an analysis of variance model.


      When the data were analyzed for methadone dosages as a continuous variable, each 1-mg increase in the last maternal methadone dosage before delivery was associated with an additional 0.18 days of infant treatment for neonatal abstinence syndrome (P < .001; 95% CI, 0.112-0.255). In other words, every increase of 5.5 mg of methadone in the mother was associated statistically with 1 additional day of neonatal abstinence syndrome treatment for the infant. Gestational age at delivery and birthweight were not statistically significant.


      Higher doses of maternal methadone were associated with an increase in diagnosis and longer duration of neonatal abstinence syndrome.

      Key words

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        • Allen M.H.
        Detoxification Considerations in the medical management of substance abuse in pregnancy.
        Bull NY Acad Med. 1991; 67: 270-276
        • Kaltenbach K.
        • Berghella V.
        • Finnegan L.
        Opioid dependence during pregnancy.
        Obstet Gynecol Clin N Am. 1998; 25: 139-151
        • Finnegan L.P.
        • Karon R.E.
        • Connaughton J.F.
        • Emich J.P.
        Assessment and treatment of abstinence in the infant of the drug-dependent mother.
        Int J Clin Pharmacol. 1975; 12: 19-32
        • Dashe J.S.
        • Sheffield J.S.
        • Olscher D.A.
        • Todd S.J.
        • Jackson G.L.
        • Wendel G.D.
        Relationship between maternal methadone dosage and neonatal withdrawal.
        Obstet Gynecol. 2002; 200: 1244-1249
        • Berghella V.
        • Lim P.J.
        • Hill M.K.
        • Cerpes J.
        • Chennat J.
        • Kaltenbach K.
        Maternal methadone dose and neonatal withdrawal.
        Am J Obstet Gynecol. 2003; 189: 312-317
        • Abdel-Latif M.E.
        • Pinner J.
        • Clews S.
        • Cooke F.
        • Lui K.
        • Oei J.
        Effects of breast milk on the severity and outcome of neonatal abstinence syndrome among infants of drug-dependent mothers.
        Pediatrics. 2006; 117: e1163-e1169
        • Ostrea E.M.
        • Chavez C.J.
        • Strauss M.E.
        A study of factors that influence the severity of neonatal narcotic withdrawal.
        J Pediatr. 1976; 88: 642-645
        • McCarthy J.J.
        • Leamon M.H.
        • Parr M.S.
        • Anania B.
        High-dose methadone maintenance in pregnancy: maternal and neonatal outcomes.
        Am J Obstet Gynecol. 2005; 193: 606-610
        • Dashe J.S.
        Letter to the editor.
        Am J Obstet Gynecol. 2004; 190: 1807
        • Harper R.G.
        • Solish G.
        • Feingold E.
        • Gersten-Woolf N.B.
        • Sokal M.M.
        Maternal ingested methadone, body fluid methadone, and the neonatal withdrawal syndrome.
        Am J Obstet Gynecol. 1977; 129: 417-424
        • Sanz E.J.
        • De-las-Cuevas C.
        • Kiuru A.
        • Bate A.
        • Edwards R.
        Selective serotonin reuptake inhibitors in pregnant women and neonatal withdrawal syndrome: a database analysis.
        Lancet. 2005; 365: 482-487
        • Jansson L.
        • Choo R.
        • Velez M.L.
        • et al.
        Methadone maintenance and breastfeeding in the neonatal period.
        Pediatrics. 2008; 121: 106-114
        • McCarthy J.J.
        • Posey B.L.
        Methadone levels in human milk.
        J Hum Lact. 2000; 16: 115-120
        • Begg E.J.
        • Malpas T.J.
        • Hackett L.P.
        • Ilett K.F.
        Distribution of R- and S-methadone into human milk during multiple, medium, and high oral dosing.
        Br J Clin Pharmacol. 2001; 52: 681-685
        • Liu A.J.W.
        • Ralph N.
        Letter to the editor: methadone maintenance and breastfeeding in the neonatal period.
        Pediatrics. 2008; 121: 869
        • American Academy of Pediatrics
        • Committee on Drugs
        The transfer of drugs and other chemicals into human breast milk.
        Pediatrics. 2001; 108: 776-789
        • Farrel M.
        • Ward J.
        • Mattick R.
        • et al.
        Fortnightly review: methadone maintenance treatment in opiate dependence.
        BMJ. 1994; 309: 997-1001
        • Pond S.M.
        • Kreek M.J.
        • Tong T.G.
        • Raghunath J.
        • Benowitz N.L.
        Altered methadone pharmacokinetics in methadone-maintained pregnant women.
        J Pharmacol Exp Ther. 1985; 233: 1-6

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        American Journal of Obstetrics & GynecologyVol. 201Issue 3
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          The article by Lim et al1 adds important data to the question of how maternal methadone dose affects both the rate of neonatal abstinence syndrome (NAS) and length of pharmacologic treatment for NAS. In 2007, Dysart et al2 noted that there were 19 studies, including 1951 neonates, on the relationship between maternal methadone dose and NAS, with the results equally divided for and against. Determining the true answer is difficult because of different methodologies that have been used.
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