Forecasting Fetal Buprenorphine Exposure through Maternal-Fetal Physiologically Based Pharmacokinetic Modeling.

Buprenorphine readily crosses the placenta, and with greater prenatal exposure, neonatal opioid withdrawal syndrome (NOWS) likely grows more severe. Current dosing strategies can be further improved by tailoring doses to expected NOWS severity. To allow the conceptualization of fetal buprenorphine exposure, a maternal-fetal physiologically based pharmacokinetic (PBPK) model for sublingual buprenorphine was developed using Simcyp (v21.

Racial Inequities in Breastfeeding Counseling Among Pregnant People Who Use Cannabis.

We examined how breastfeeding advice in the context of cannabis use differed by race and ethnicity. Data from the 2017-2018 PRAMS (Pregnancy Risk Assessment Monitoring System) survey were used to assess differences in breastfeeding guidance related to cannabis use among 1,213 individuals who self-reported cannabis use 3 months before or during pregnancy. A multivariable logistic regression model was specified to examine the extent to which the odds of receiving prenatal advice against breastfeeding if using cannabis differed by self-reported race and ethnicity.

Rates of substance and polysubstance use through universal maternal testing at the time of delivery.

Objective: To report substance and polysubstance use at the time of delivery.

Study Design: A cross-sectional study was performed on mothers consented for universal drug testing (99%) during hospital admission at six delivery hospitals in Cincinnati, Ohio. Mass spectrometry urinalysis detected positivity rates of 46 substances.

A review of pregnancy-induced changes in opioid pharmacokinetics, placental transfer, and fetal exposure: Towards fetomaternal physiologically-based pharmacokinetic modeling to improve the treatment of neonatal opioid withdrawal syndrome.

Physiologically-based pharmacokinetic (PBPK) modeling has emerged as a useful tool to study pharmacokinetics (PK) in special populations, such as pregnant women, fetuses, and newborns, where practical hurdles severely limit the study of drug behavior. PK in pregnant women is variable and everchanging, differing greatly from that in their nonpregnant female and male counterparts typically enrolled in clinical trials. PBPK models can accommodate pregnancy-induced physiological and metabolic changes, thereby providing mechanistic insights into maternal drug disposition and fetal exposure.

Physiologically-Based Pharmacokinetic Modeling to Investigate the Effect of Maturation on Buprenorphine Pharmacokinetics in Newborns with Neonatal Opioid Withdrawal Syndrome.

Neonatal opioid withdrawal syndrome (NOWS) is a major public health concern whose incidence has paralleled the opioid epidemic in the United States. Sublingual buprenorphine is an emerging treatment for NOWS, but given concerns about long-term adverse effects of perinatal opioid exposure, precision dosing of buprenorphine is needed. Buprenorphine pharmacokinetics (PK) in newborns, however, is highly variable.

Regional comparison of self-reported late pregnancy cigarette smoking to mass spectrometry analysis.

Objective: To report a more accurate prevalence estimate of late pregnancy nicotine exposures.

Study Design: A cross-sectional study during a 2-month period in 2019. Participants were women delivering in any of the six county maternity hospitals who consented to universal drug testing at the time of delivery as part of routine hospital admission.

Pharmacotherapy of neonatal opioid withdrawal syndrome: a review of pharmacokinetics and pharmacodynamics.

Introduction: Neonatal opioid withdrawal syndrome (NOWS) often arises in infants born to mothers who used opioids during pregnancy. Morphine, methadone, and buprenorphine are the most common first-line treatments, whereas clonidine and phenobarbital are generally reserved for adjunctive therapy. These drugs exhibit substantial pharmacokinetic (PK) and pharmacodynamic (PD) variability.

Subclinical and Overt Newborn Opioid Exposure: Prevalence and First-Year Healthcare Utilization.

Objectives: To categorize newborn infants in Hamilton County, Ohio by late pregnancy fetal opioid exposure status and to assess their first-year healthcare utilization.

Study Design: We used a population-based cohort of 41 136 live births from 2014-2017 and analyzed healthcare encounters in the first year of life from electronic health records. We prospectively assessed for the presence of opioids in maternal urine collected at delivery and for a diagnosis of newborn neonatal abstinence syndrome (NAS).

Addressing the Disease Burden of Vertically Acquired Hepatitis C Virus Infection Among Opioid-Exposed Infants.

Background: This study aims to estimate the disease burden of vertically acquired hepatitis C virus (HCV) in a large Midwestern hospital and to identify factors associated with HCV diagnostic testing among high-risk infants.

Methods: This is a retrospective analysis of an infant cohort (n = 58 427) born from 2014 to 2016 in the Greater Cincinnati region, where universal maternal urine testing is conducted at delivery to assess for intrauterine drug exposure (IUDE). Demographics and birth characteristics were analyzed among high-risk infants to identify factors associated with receiving HCV testing.

Developmental Disorders and Medical Complications Among Infants with Subclinical Intrauterine Opioid Exposures.

The objective was to compare diagnosis rates representing developmental outcomes and medical complications between infants with intrauterine opioid exposures who did not receive pharmacologic treatment for neonatal abstinence syndrome at the time of birth and infants for whom no exposure to substances of abuse were detected. This retrospective, descriptive study included approximately 95% of Hamilton County, Ohio resident births in 2014 and 2015. Universal maternal drug test results, performed at the time of birth, were documented and linked to electronic health records representing pediatric primary and subspecialty follow-up care as well as urgent care, emergency care, and inpatient services provided by Cincinnati Children's Hospital Medical Center through 2017, when all children were at least 24 months old.

Surveillance of Intrauterine Opioid Exposures Using Electronic Health Records.

The objective was to use population-based electronic health records for surveillance of intrauterine exposures to substances of abuse, including opioids, and to monitor changes in exposure rates over time. This retrospective, descriptive analysis utilized geocoded neonatal physician billing records representing intrauterine exposures to substances of abuse detected through universal maternal drug testing. Census tract-level exposure rates were identified among the newborn population of Hamilton County, Ohio between 2014 and 2016.

Torticollis in Infants with a History of Neonatal Abstinence Syndrome.

In this retrospective cohort study, we assessed the incidence of torticollis in infants with a history of neonatal abstinence syndrome. Understanding the elevated risk of torticollis in this population is important for early identification and treatment.

Opioid Neonatal Abstinence Syndrome: An Overview.

Opioid neonatal abstinence syndrome (NAS) refers to signs of withdrawal observed in infants experiencing intrauterine opioid exposures. Early identification of at-risk infants allows for the prompt initiation of nonpharmacologic supportive care. When withdrawal symptoms are severe despite these interventions, pharmacologic therapy including opioid weaning is initiated.

Comparison of Neonatal Abstinence Syndrome Treatment with Sublingual Buprenorphine versus Conventional Opioids.

Objective:  The objective of this study was to compare duration of opioid treatment and length of stay outcomes for neonatal abstinence syndrome (NAS) using sublingual buprenorphine versus traditional weaning with methadone or morphine.

Study Design:  This retrospective cohort analysis evaluated infants treated for NAS at a single community hospital from July 2013 through June 2017. A standardized weaning protocol was introduced in June 2015, allowing for treatment with sublingual buprenorphine regardless of type of intrauterine opioid exposure.

Care Coordination Associated with Improved Timing of Newborn Primary Care Visits.

Objective Despite practice recommendations that all newborns be examined within 3-5 days after discharge, many are not seen within this timeframe. Our objective was to determine the association between care coordination and timing of newborn follow-up. Methods This retrospective study evaluated 6251 newborns from eight maternity hospitals who scheduled a primary care appointment at one of two academic pediatric practices over 3.

Cohort Analysis of a Pharmacokinetic-Modeled Methadone Weaning Optimization for Neonatal Abstinence Syndrome.

Objective: To evaluate neonatal abstinence syndrome (NAS) treatment outcomes achieved using an optimized methadone weaning protocol developed using pharmacokinetic (PK) modeling compared with standard methadone weaning.

Study Design: This pre-post cohort study evaluated 360 infants who completed pharmacologic treatment for NAS with methadone as inpatients at 1 of 6 nurseries in southwest Ohio between January 2012 and March 2015. Infants were initially treated with a standard methadone weaning protocol (n = 267).

Implementation of a Neonatal Abstinence Syndrome Weaning Protocol: A Multicenter Cohort Study.

Objectives: To evaluate the generalizability of stringent protocol-driven weaning in improving total duration of opioid treatment and length of inpatient hospital stay after treatment of neonatal abstinence syndrome (NAS).

Methods: We conducted a retrospective cohort analysis of 981 infants who completed pharmacologic treatment of NAS with methadone or morphine from January 2012 through August 2014. Before July 2013, 3 of 6 neonatology provider groups (representing Ohio's 6 children's hospitals) directed NAS nursery care by using group-specific treatment protocols containing explicit weaning guidelines.

Universal maternal drug testing in a high-prevalence region of prescription opiate abuse.

Objective: To evaluate the efficacy of a universal maternal drug testing protocol for all mothers in a community hospital setting that experienced a 3-fold increase in neonatal abstinence syndrome (NAS) over the previous 5 years.

Study Design: We conducted a retrospective cohort study between May 2012 and November 2013 after the implementation of universal maternal urine drug testing. All subjects with positive urine tests were reviewed to identify a history or suspicion of drug use, insufficient prenatal care, placental abruption, sexually transmitted disease, or admission from a justice center, which would have prompted urine testing using our previous risk-based screening guidelines.

Factors associated with readmission in late-preterm infants: a matched case-control study.

Objective: The goal of this study was to evaluate risk factors for readmission among late-preterm (34-36 weeks' gestation) infants in clinical practice.

Methods: This was a retrospective, matched case-control study of late-preterm infants receiving care across 8 regional hospitals in 2009 in the United States. Those readmitted within 28 days of birth were matched to non-readmitted infants at a ratio of 1:3 according to birth hospital, birth month, and gestational age.

Design considerations for point-of-care clinical trials comparing methadone and buprenorphine treatment for opioid dependence in pregnancy and for neonatal abstinence syndrome.

Rationale: In recent years, the U.S. has experienced a significant increase in the prevalence of pregnant opioid-dependent women and of neonatal abstinence syndrome (NAS), which is caused by withdrawal from in-utero drug exposure.

A multicenter cohort study of treatments and hospital outcomes in neonatal abstinence syndrome.

Objectives: To compare pharmacologic treatment strategies for neonatal abstinence syndrome (NAS) with respect to total duration of opioid treatment and length of inpatient hospital stay.

Methods: We conducted a cohort analysis of late preterm and term neonates who received inpatient pharmacologic treatment of NAS at one of 20 hospitals throughout 6 Ohio regions from January 2012 through July 2013. Physicians managed NAS using 1 of 6 regionally based strategies.