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Methadone dose and neonatal abstinence syndrome-systematic review and meta-analysis.Cleary, Brian J; Donnelly, Jean; Strawbridge, Judith; Gallagher, Paul J; Fahey, Tom; Clarke, Mike; Murphy, Deirdre J; Coombe Women and Infants University Hospital, Dublin 8, Ireland School of, Pharmacy, Royal College of Surgeons in Ireland, Dublin 2, Ireland., email@example.com (2012-02-01)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.