More than 50% of newborn infants whose mothers are on methadone maintenance therapy during pregnancy for opiate addiction develop neonatal withdrawal or neonatal abstinence syndrome (NAS). Although a large number of studies have investigated strategies that could predict the occurrence of NAS requiring pharmacological treatment, these studies have had conflicting results and identified no useful strategies. Maternal methadone dosing has been studied as a possible predictive risk factor for occurrence of NAS requiring treatment. Several studies have reported that methadone dosing may influence the onset of NAS. Other studies, however, found no correlation between the amount of methadone and NAS requiring treatment. In one study, the cumulative maternal methadone dose during pregnancy was predictive for the development of NAS. Gestational age and mode of delivery have also been reported to be associated with increased risk of NAS; the interaction between these 2 parameters and the last methadone dose has not been adequately investigated.
This study was a retrospective review designed to investigate and correlate maternal methadone dose and other potential risk factors with the development of NAS requiring pharmacological treatment using clinical parameters easily accessible to clinicians. The study population was 228 methadone-maintained pregnant women who delivered 232 live-born infants between 2001 and 2006. A statistical model based on multiple logistic regression was developed to identify parameters predictive of subsequent need for treatment for NAS. External validation of the prediction model was provided by the use of a separate independent cohort of 188 infants born to methadone-maintained women.
A total of 172 (74%) of the 232 infants were treated for NAS. The risk of withdrawal was associated with a higher last methadone dose and a higher cumulative dose (P < 0.001 for both). Infants delivered at a lower gestational age or by cesarean section were overall less likely to require NAS treatment. Gestational age, mode of delivery, and last methadone dose were identified as risk factors for withdrawal. External validation of the model developed from the original cohort was demonstrated in the validation cohort.
These findings suggest that significant risk factors associated with the development of NAS requiring treatment are timing, mode of delivery, and the last maternal methadone dose. The statistical robustness of the data was demonstrated using internal and external validation methods.
Discipline of Paediatrics, Sydney Medical School—Nepean, The University of Sydney, Penrith, Australia; Department of Psychology, Macquarie University, North Ryde, Australia; and Department of Obstetrics and Gynaecology, Nepean Hospital, Sydney West Area Health Service, Penrith, New South Wales, Australia
Aust N Z J Obstet Gynaecol 2010;50:253–258