697 Exploring sex differences in syncytiotrophoblast aromatase and placental efflux transporter expression in opioid exposed pregnancies

Abstract

Male sex is associated with the development of severe neonatal opioid withdrawal syndrome (NOWS) in opioid exposed pregnancies. Placental efflux transporters, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), are critical for transfer of drugs from the placenta to maternal circulation. Aromatase is responsible for metabolizing Methadone and Buprenorphine in the human placenta. We sought to determine whether sex differences exist in placental aromatase and efflux transporter density within the apical syncytiotrophoblast. This was a retrospective cohort study from 2014-2019 at a single tertiary site. Pregnant women ≥ age 18 with non-anomalous fetuses on maintenance Methadone or Buprenorphine with gestational age ≥33 weeks were included. De-paraffinized placental sections, including the apical syncytiotrophoblast membrane, were labeled with monoclonal antibodies for aromatase, P-gp and BCRP. Placentas were scored for presence and intensity of staining using the Allred scoring schema. Severe NOWS requiring opioid treatment was defined by 3 consecutive Finnegan scores ≥8 or the sum of 3 consecutive Finnegan scores ≥24 within 72 hours of birth. Data was analyzed using descriptive, parametric and non-parametric statistics. A p-value of <0.05 was considered significant. There were 110 opioid exposed neonates included in this analysis with a mean gestational age of 37 weeks. Of the 46% (51/110) of infants with severe NOWS, 69% (35/51) were Methadone exposed and 31% (16/51) were Buprenorphine exposed (p =0.01). There were significantly more males in the group with severe NOWS (non-severe 24 (41%) vs severe 34 (67%), p<0.01). There were no differences in median placental Allred scores for aromatase, P-gp or BCRP between groups (p>0.05). Aromatase and placental efflux transporters had weak, but significant correlation (rho=0.22). P-gp and BCRP exhibited strong correlation (rho=0.59). Male infants within our cohort were significantly more likely to develop severe NOWS. We found no sex differences in aromatase, P-gp and BCRP within apical syncytiotrophoblasts.View Large Image Figure ViewerDownload Hi-res image Download (PPT)