Tiffany Rudzitis

 Introduction. Opioid abuse in pregnant women has become a prevalent public health concern as reported cases have increased 333% from 1.5 per 1000 deliveries in 1999 to 6.5 per 1000 deliveries in 2014.² One of many consequences of opioid abuse during pregnancy is Neonatal Abstinence Syndrome (NAS). NAS is the result of separation of the blood supply from mother and fetus during birth resulting in sudden discontinuation of fetal exposure to the drug used by the mother during pregnancy.¹ The original treatment for opioid use disorder in pregnant women was Methadone, a synthetic complete m-opioid receptor agonist.^1,4  Buprenorphine has been suggested as a new potential treatment. Neither Methadone nor Buprenorphine are approved for pregnancy, and still impact the fetus, but both have shown to improve NAS symptoms in the fetus.¹ Many studies have reported that Buprenorphine treatment is superior to Methadone in terms of improved NAS symptoms.¹ Buprenorphine is a semisynthetic opioid that is a partial agonist at the m-opioid receptor and agonist at the nociceptin/orphanin FQ (NOP) receptor.⁶ The hypothesized mechanism is suggested that due to the binding of Buprenorphine to NOP receptors, it reduces its efficacy on the m-opioid receptor leading to decrease activity. This is suggested as one of many reasons that Buprenorphine is more ideal than Methadone.⁶ Methods. Female rats were implanted with mini osmotic pumps of Methadone and Buprenorphine 5 days before mating. Blood and brain concentrations in dams and pups were measured on gestation day 22.⁵ Results. Methadone fetal brain concentration (1.89 ± 0.35 nmol/g) was double that of the mother (0.84 ± 0.10 nmol/g), whereas the Buprenorphine fetal brain concentration (20.02 ± 4.97 pmol/g) was one-third of maternal levels (60.22 ± 8.21 pmol/g). In those same offspring, fetal Methadone blood concentration (0.48 ± 0.08 mM) was 1.6 times higher than maternal blood levels (0.30 ± 0.04 mM) compared to Buprenorphine where maternal (5.65 ± 0.16 nM) and pup blood concentrations were relatively equal (4.56 ± 00.93 nM).⁵ Conclusion. Buprenorphine proved to be a more superior drug to Methadone due to lower or equal blood and brain concentrations in pups compared to their mothers.⁵ It is important that more work be done in this area not only to decrease the incidence of NAS, but also to address the opioid epidemic, especially as it pertains to opioid abuse in pregnant women.³ Improvement in this area could improve the lives of infants born with NAS.

1. Kocherlakota P. Neonatal abstinence syndrome. 2014 Aug;134(2):e547-61. doi: 10.1542/peds.2013-3524. Review. PubMed PMID: 25070299.
2. Haight SC, Ko JY, Tong VT, Bohm MK, Callaghan WM. Opioid Use Disorder Documented at Delivery Hospitalization – United States, 1999-2014. MMWR Morb Mortal Wkly Rep. 2018 Aug 10;67(31):845-849. doi: 10.15585/mmwr.mm6731a1. PubMed PMID: 30091969; PubMed Central PMCID: PMC6089335.
3. New Studies Clarify Risk Factors for Neonatal Abstinence Syndrome. National Institute on Drug Abuse website. https://www.drugabuse.gov/news-events/nida-notes/2019/1/new-studies-clarify-risk-factors-neonatal-abstinence-syndrome. January 8, 2019. Accessed February 24, 2020.
4. Wang S-C, Chen Y-C, Lee C-H, Cheng C-M. Opioid Addiction, Genetic Susceptibility, and Medical Treatments: A Review. International Journal of Molecular Sciences. 2019;20(17):4294. doi:10.3390/ijms20174294
5. Kongstorp M, Bogen IL, Stiris T, Andersen JM. High Accumulation of Methadone Compared with Buprenorphine in Fetal Rat Brain after Maternal Exposure. Journal of Pharmacology and Experimental Therapeutics. 2019;371(1):130-137. doi:10.1124/jpet.119.259531.
6. Khroyan TV, Wu J, Polgar WE, et al. BU08073 a buprenorphine analogue with partial agonist activity at μ-receptors in vitro but long-lasting opioid antagonist activity in vivo in mice. Br J Pharmacol. 2015;172(2):668–680. doi:10.1111/bph.12796