Hospital morphine preparation for abstinence syndrome in newborns exposed to buprenorphine or methadone

Objective This study was undertaken to evaluate the adequacy of a hospital formulated oral morphinepreparation for management of neonatal abstinence syndrome (NAS) and to compare clinical features in infants exposed to methadoneor buprenorphinein utero. Method Between October 1998 and October 2004 all infants born to mothers treated with buprenorphineor methadoneduring pregnancy were enrolled into this prospective study. Morphine hydrochloridesolution (0.2 mg/ml) was prepared without preservatives under a flow laminar air box (class 100). Mean outcome measure Morphinesolution: quantitative and qualitative HPLC analysis and microbiological study at regular intervals during storage at 4°C for 6 months. Maternal characteristics: age, opiate dose during pregnancy. Neonatal characteristics: gestational age at delivery, birth weight, Lipsitz scores. Morphinedose: daily morphinedose, maximum morphinedose, duration of NAS, and duration of treatment required to achieve stable Lipsitz scores below 4. Statistics: Kruskal–Wallis test for comparison of median values. Results Microbiological and HPLC analysis showed that the morphinepreparation remained stable for 6 months at 4°C. Nine methadone-exposed infants and 13 buprenorphine-exposed infants were included in the study. All infants presented NAS requiring treatment with the morphinesolution. Lipsitz scores at birth were significantly different in the methadoneand buprenorphinegroups (P < 0.05). The methadonegroup required significantly higher doses of morphinepreparation than the buprenorphinegroup during the first 38 days of treatment (P < 0.05): 0.435 ± 0.150 mg/kg/day vs. 0.257 ± 0.083 mg/kg/day. Conclusion This hospital morphinesolution is adequate for management of NAS. Preparations showed good stability and doses could be adjusted with a margin of 0.02 mg. The onset of NAS occurred within 24 h after birth in methadone-exposed infants (range 6–24 h) and within 48 h after birth in buprenorphine-exposed infants (range 24–168 h). Due to the possibility of delayed onset of NAS up to 7 days, infants born to mothers treated with buprenorphineshould be kept in the hospital for an appropriate surveillance period. Treatment time was significantly longer (45 vs. 28 days) and the mean morphinedoses were higher (1.7 fold) in methadone-exposed than buprenorphine-exposed infants.