Perinatal risk factors for the neonatal abstinence syndrome in infants born to women on methadone maintenance therapy

Background: Neonatal abstinence syndrome (NAS) occurs in more than 50% of infants exposed to intrauterine opiates. Maternal opiate dosing has been investigated with conflicting results. Aims: The aims of this study were to correlate maternal methadone dose and other risk factors with the development of NAS requiring pharmacological treatment by using easily accessible clinical parameters. Methods: Retrospective medical record review of data from 228 opioid dependent pregnant women who delivered 232 live-born infants. Logistic regression analysis was performed on maternal, perinatal and neonatal parameters to identify risk factors for NAS requiring treatment. A prediction model was developed and validated on a separate independent cohort of 188 infants. Results: Of the 232 infants, 172 (74%) infants were treated for NAS. The risk of withdrawal increased by 17% per 5 mg increment of the last maternal methadone dose. The risk was lower for younger gestational ages and for those delivered by Caesarean section compared to those delivered by normal vaginal delivery. Through predictive modeling, gestational age, mode of delivery and last methadone dose were established as risk factors for withdrawal. The model was validated by other statistical measures and its diagnostic performance confirmed on the separate independent cohort. Conclusions: Our data suggests that timing and mode of delivery as well as last maternal methadone dose are significant risk factors for the development of NAS requiring treatment. Based on these clinical parameters, risk stratification for perinatal management of pregnancies associated with opioid dependency and risk prediction for the neonate might now be possible.