No abstract

Objective To examine opioid replacement therapy in pregnancy and maternal effects on neonatal outcomes including length of hospital stay for neonatal abstinence syndrome. Design Retrospective descriptive study. Setting Labor and Delivery Unit and Neonatal Intensive Care Unit (NICU), Eastern Maine Medical Center, Bangor, Maine. Participants One hundred fifty two opioid dependent pregnant women on methadone maintenance therapy (MMT) (n = 136) or buprenorphine maintenance therapy (BMT) (n =16) during pregnancy and their neonates. The neonates were born between January 1, 2005 and December 31, 2007. Methods A review of the electronic medical records (EMR) was conducted of all opioid dependent women who were maintained on MMT or BMT at the time of admission for labor and delivery and their neonates. Results Maternal methadone dose and concomitant in-utero exposure to benzodiazepines prolonged the length of hospital stay for neonates. Length of stay was shorter in breastfed neonates as compared to formula fed neonates or neonates who received formula and breast milk. Neonates with a prenatal exposure to MMT as compared to BMT spent more days in the hospital (21 vs. 14 days) for treatment of neonatal abstinence syndrome (NAS). Conclusion These findings are consistent with previous research on the simultaneous use of methadone and benzodiazepines during pregnancy and provide further direction for the treatment of opioid dependency during pregnancy. Harm reduction strategies for opioid dependent pregnant women in substance abuse treatment with MMT may one day include guidance on daily treatment doses and recommendations to avoid the concomitant use of benzodiazepines to lessen NAS. Breastfeeding should be recommended to shorten LOS. Understanding perinatal and neonatal outcomes of pregnant women on methadone or buprenorphine will help to identify optimal treatment for opioid dependency in pregnancy.

No abstract

Objective Neonatal abstinence syndrome (NAS) from in utero opioid exposure is highly variable with genetic factors appearing to play an important role. Epigenetic changes in cytosine:guanine (CpG) dinucleotide methylation can occur after drug exposure and may help to explain NAS variability. We correlated DNA methylation levels in the mu-opioid receptor (OPRM1) promoter in opioid-exposed infants and correlate them with NAS outcomes. Study design DNA samples from cord blood or saliva were analyzed for 86 infants being treated for NAS according to institutional protocol. Methylation levels at 16 OPRM1 CpG sites were determined and correlated with NAS outcome measures, including need for treatment, treatment with >2 medications, and length of hospital stay. We adjusted for co-variates and multiple genetic testing. Results Sixty-five percent of infants required treatment for NAS, and 24% required ≥2 medications. Hypermethylation of the OPRM1 promoter was measured at the −10 CpG in treated versus non-treated infants [adjusted difference δ=3.2% (95% CI 0.3–6.0%), p=0.03; NS after multiple testing correction]. There was hypermethylation at the −14 [δ=4.9% (95% CI 1.8–8.1%), p=0.003], −10 [δ=5.0% (95% CI 2.3–7.7%), p=0.0005)], and +84 [δ=3.5% (95% CI 0.6 – 6.4), p=0.02] CpG sites in infants requiring ≥2 medications which remained significant for −14 and −10 after multiple testing correction. Conclusions Increased methylation within the OPRM1 promoter is associated with worse NAS outcomes, consistent with gene silencing.

No abstract