There is reduced immunohistochemical staining of placental aromatase in severe neonatal opioid withdrawal syndrome.

BACKGROUND: Placental cytochrome p450 (CYP450) enzymes and efflux transporters, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), are critical for transfer of drugs from the placenta to maternal circulation. CYP19A1 (aromatase) is the enzyme responsible for metabolizing methadone and buprenorphine in the human placenta. OBJECTIVE: We sought to determine if differences exist in CYP19A1 and efflux transporter immunostaining intensity and density within the syncytiotrophoblast in opioid-exposed and unexposed pregnancies. Additionally, we sought to investigate whether CYP19A1 and efflux transporter expression was different in placentas of infants who developed severe neonatal opioid withdrawal syndrome (NOWS) and those who did not. STUDY DESIGN: This was a retrospective nested case control study from 2014 to 2019 at a single tertiary care center. The opioid-exposed cohort included pregnant women aged ≥18 years on maintenance methadone or buprenorphine with non-anomalous singleton fetuses and gestational age ≥33 weeks. Controls included pregnant women with no medication exposure delivering at ≥37 weeks. De-paraffinized placental sections, inclusive of the apical syncytiotrophoblast membrane, were labeled with monoclonal antibodies for aromatase, P-gp, and BCRP. Placentas were scored for the presence and intensity of staining using the Allred scoring schema. Data were analyzed using descriptive, parametric, and nonparametric statistics. p < .05 was considered significant. RESULTS: One hundred and ten opioid-exposed neonates were included in this analysis (51 opioid-exposed cases and 59 opioid-exposed controls), with 68/110 delivering at term. Ten unexposed controls delivering at term were also included. The median placental Allred scores for aromatase were significantly lower in the opioid-exposed cohort compared with the unexposed controls (exposed 6.8 ± 1.4 vs. unexposed 7.5 ± 0.7, p = .03). The median placental Allred scores for aromatase were significantly lower in opioid-exposed cases that developed severe NOWS compared to opioid-exposed controls (p = .03) that did not develop severe NOWS. There were no differences in P-gp and BCRP scores between groups. CONCLUSIONS: Syncytiotrophoblast aromatase immunostaining scores were reduced in opioid-exposed cases compared to unexposed controls. Additionally, infants who developed severe NOWS had significantly lower placental aromatase in the apical syncytiotrophoblast compared with those without severe NOWS.

Outpatient Management of Heavy Menstrual Bleeding in Adolescent and Young Women with Inherited Platelet Function Disorders.

STUDY OBJECTIVE: To assess the treatment patterns and efficacy of hormonal (HM) and non-HM (NHM) management of heavy menstrual bleeding (HMB) in young women with inherited platelet function disorders (IPFDs). DESIGN, SETTING, AND PARTICIPANTS: A retrospective chart review was performed of outpatient treatment of HMB in female patients age 9-25 years who were diagnosed with IPFDs and referred to gynecology and/or hematology at a tertiary care hospital between 2006 and 2018. INTERVENTIONS: The study sample was identified using billing codes for IPFDs. Data on HM and NHM treatments and outcomes over a one- to two-year period were collected. Initial treatment was defined as the first treatment prescribed after referral. Descriptive statistics, Pearson χ2, and t tests were used for analysis. MAIN OUTCOME MEASURES: Treatment failure was defined as a change in treatment method because of continued bleeding. RESULTS: Thirty-four girls met inclusion criteria. After their initial visit, 19/34 (56%) were treated with HM, 12/34 (35%) with NHM, 2/34 (6%) with a combination of methods, and 1/34 (3%) were untreated. Initial treatment failed in 19/34 (56%) and those patients subsequently required a mean of 2 additional treatments during follow-up. Of the 34 included, 6/34 (18%) remained uncontrolled despite numerous treatment changes and 2/34 (6%) because of noncompliance. When control was achieved, 7/26 (27%) of patients were receiving combined oral contraceptives and 6/26 (23%) desmopressin acetate. CONCLUSION: HMB in girls with IPFDs can be difficult to control despite ongoing follow-up and treatment changes. Although the most effective treatment for HMB in young women with IPFDs was not identified, these findings will help providers and patients with setting expectations. Prospective studies are needed to develop recommendations on best practices.