Does Higher Maternal Methadone Dose Increase Risk for Neonatal Abstinence Syndrome?

To determine whether there is a dose-response relationship between maternal methadone dose in pregnancy and neonatal abstinence syndrome (NAS), researchers conducted a systematic review and meta-analysis of the literature published between 1966–2009. Of the 212 studies reporting maternal receipt of methadone and NAS, 67 met inclusion criteria (28 retrospective cohort studies, 37 prospective cohort studies, and 2 randomized controlled trials).

• Nineteen studies found an association between methadone dose and incidence, severity, or duration of NAS; 18 did not. The remaining 30 studies did not report an association.

• Of the 29 studies included in the meta-analysis (those that provided data on NAS incidence across a range of methadone dosage cut-off points), no statistically significant differences were found in incidence of NAS between lower and higher methadone dosage groups except among those comparing ≤20 mg with >20 mg (relative risk [RR], 0.52) or those comparing ≤40 mg with >40 mg (RR, 0.69).

• These differences disappeared when analyses were limited to prospective studies or studies with an objective scoring system to diagnose NAS.

Comments:

Further research is needed to determine if maternal methadone dose is an important determinant of NAS. Although NAS is only one of the risks to consider when monitoring methadone during pregnancy, the evidence from this well-designed systematic review coupled with the equally (if not more) important goals of maternal withdrawal-symptom control, maintenance, and stability suggest lowering methadone dose to decrease NAS risk cannot be justified by the available literature.

Nicolas Bertholet, MD, MSc

Reference:

Cleary BJ, Donnelly J, Strawbridge J, et al. Methadone dose and neonatal abstinence syndrome—systematic review and meta-analysis. Addiction. 2010;105(12):2071–2084.