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Background: Pregnant women with sickle cell disease (SCD) are at increased risk of maternal and fetal complications. There are limited data on the outcome of the treatment of VOCs with opioids in relation to neonatal complications during pregnancy., Methods: This is a retrospective cohort study of women with SCD from January 1999 to December 2008. Women with SCD were identified by ICD-9 codes and matched 2:1 to a control group of women on methadone for opioid dependence. The primary outcome was the rate of neonatal abstinence syndrome (NAS). Secondary outcomes included the mean NAS score prior to treatment and the length of treatment. Statistical analysis was performed using SPSS., Results: Twenty-one women with SCD who delivered a total of 23 neonates were included. The rate of NAS among infants born to women with SCD who were treated with opioids at any time was 22% compared to 54% in the methadone controls (p = .010). The rate of NAS was 27% among infants born to women taking opioids daily compared to 54% in the methadone control group (p = .062)., Conclusions: Neonates born to women with SCD who are treated with daily opioids are at a similar risk for developing NAS as those born to mothers on methadone for opioid dependence. Neonates born to women with SCD treated with episodic opioids are at a significantly lower risk for developing NAS than those born to women on methadone for opioid dependence., (Copyright © 2018 National Medical Association. Published by Elsevier Inc. All rights reserved.)