Assessing Neonatal Opioid Withdrawal Syndrome Severity as a Function of Maternal Buprenorphine Dose and Umbilical Cord Tissue Concentrations.

BACKGROUND: Infants born to mothers with opioid use disorder (OUD) and prenatally treated with buprenorphine have a significantly lower incidence of neonatal opioid withdrawal syndrome (NOWS), its treatment duration, and hospital length of stay compared with methadone. However, risk of NOWS remains and clinicians continue to lack an objective methodology to predict NOWS severity among these infants. OBJECTIVE: The purpose of this study was to assess the relationship between buprenorphine exposure, umbilical cord tissue (UCT) concentrations, and NOWS development and severity. METHODS: A single-center retrospective observational cohort study from March 2018 through June 2020 of newborns exposed to buprenorphine in utero. Associations between quantified buprenorphine exposure, neonatal UCT concentrations, NOWS diagnosis, and severity were made using regression analyses. RESULTS: A total of 24 mothers and 25 neonates were included. Length of maternal buprenorphine therapy (months) positively correlated to norbuprenorphine (r2 = 0.234, P = 0.019) and buprenorphine + norbuprenorphine UCT concentrations (r2 = 0.203, P = 0.031). A positive relationship was seen between active metabolite concentrations and cumulative morphine dose (mg/kg) for treatment of severe NOWS (r2 = 0.471, P = 0.007). A 0.36 ng/g buprenorphine + norbuprenorphine UCT (CI = 0.002-0.72, P = 0.049) equated in a 1-point increase in modified peak Finnegan score. CONCLUSION AND RELEVANCE: Buprenorphine and norbuprenorphine UCT concentrations can allow for quantification of in utero fetal exposure and demonstrate an association with a longer duration of exposure with the severity and treatment of NOWS in exposed infants.

Increased unfractionated heparin requirements with decreasing body mass index in pregnancy.

BACKGROUND: Pregnant women receiving low-molecular-weight heparin for therapeutic anticoagulation are often converted to unfractionated heparin in anticipation of labor. We aim to characterize the impact of maternal body mass index on attainment of target anticoagulation during the conversion process. METHODS: We conducted a five-year retrospective study of a pregnancy cohort converted from low-molecular-weight heparin to unfractionated heparin in the third trimester. Patient demographics, anticoagulation regimens, and clinical outcomes were extracted from the medical record. Nonparametric statistical methods were used for analysis by body mass index (<30, 30-35, and >35). RESULTS: Thirty-one subjects were evenly distributed by body mass index (p = 0.97). Linear regression revealed an inverse correlation between patient body mass index and unfractionated heparin dose needed to achieve therapeutic anticoagulation (p = 0.04). Subjects with body mass index > 35 attained therapeutic activated partial thromboplastin time levels at 18 U (Units)/kg/h, while subjects with body mass index < 30 required 25 U/kg/h (p = 0.02). CONCLUSION: Higher doses of unfractionated heparin are needed to achieve anticoagulation in patients with body mass index < 30 during pregnancy. This paradoxical relationship may be explained by physiologic characteristics that increase unfractionated heparin elimination, including diminished adiposity and increased renal clearance.