Methadone dose and neonatal abstinence syndrome—systematic review and meta-analysis


Brian J. Cleary, Coombe Women and Infants University Hospital, Dublin 8, Ireland. E-mail:


Aim  To determine if there is a relationship between maternal methadone dose in pregnancy and the diagnosis or medical treatment of neonatal abstinence syndrome (NAS).

Methods  PubMed, EMBASE, the Cochrane Library and PsychINFO were searched for studies reporting on methadone use in pregnancy and NAS (1966–2009). The relative risk (RR) of NAS was compared for methadone doses above versus below a range of cut-off points. Summary RRs and 95% confidence intervals (CI) were estimated using random effects meta-analysis. Sensitivity analyses explored the impact of limiting meta-analyses to prospective studies or studies using an objective scoring system to diagnose NAS.

Results  A total of 67 studies met inclusion criteria for the systematic review; 29 were included in the meta-analysis. Any differences in the incidence of NAS in infants of women on higher compared with lower doses were statistically non-significant in analyses restricted to prospective studies or to those using an objective scoring system to diagnose NAS.

Conclusions  Severity of the neonatal abstinence syndrome does not appear to differ according to whether mothers are on high- or low-dose methadone maintenance therapy.