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 (v21.0). Buprenorphine transplacental passage was predicted from its physicochemical properties. The maternal-fetal PBPK model integrated reduced transmucosal absorption driven by lower salivary pH and induced metabolism observed during pregnancy. Maternal pharmacokinetics was adequately predicted in the second trimester, third trimester, and postpartum period, with the simulated area under the curve from 0 to 12 h, apparent clearance, and peak concentration falling within the 1.25-fold prediction error range. Following post hoc adjustment of the likely degree of individual maternal sublingual absorption, umbilical cord blood concentrations at delivery (n = 21) were adequately predicted, with a geometric mean ratio between predicted and observed fetal concentrations of 1.15 and with 95.2% falling within the 2-fold prediction error range. The maternal-fetal PBPK model developed in this study can be used to forecast fetal buprenorphine exposure and would be valuable to investigate its correlation to NOWS severity.

Controversies and Conundrums in Newborn Feeding.

Breastfeeding is the biologic norm for newborn feeding, and exclusive breastfeeding for the first 6 months of life is universally endorsed by leading global and national organizations. Despite these recommendations, many people do not meet their breastfeeding goals and controversies surrounding breastfeeding problems exist. Medical issues can present challenges for the clinician and parents to successfully meet desired feeding outcomes. There are studies evaluating these common controversies and medical conundrums, and clinicians should provide evidence-based recommendations when counseling families about newborn feeding.

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. We found that non-Hispanic Black people were four times more likely than non-Hispanic White people to be advised against breastfeeding if using cannabis (adjusted odds ratio 4.1, 95% CI 2.1-8.2). Pregnant non-Hispanic Black people were disproportionately advised not to breastfeed if using cannabis.

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. Rates of positive drug tests for individual and common co-occurring substances measured were reported. RESULTS: 2531 maternal samples were tested (88%) and 33% contained cotinine, 11.3% THC, 7.2% opioids, 3.8% cocaine, and 1.9% methamphetamines. Polysubstance use prevalence was as high as 15%. Among mothers testing positive for methadone or buprenorphine, 93% also tested positive for cotinine and 39% tested positive for a third substance in addition to cotinine. CONCLUSIONS: Substance use at delivery is more prevalent than previously reported. Many mothers testing positive for opioids also test positive for other substances, which may increase overdose risk and exacerbate neonatal opioid withdrawal syndrome (NOWS).

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. To evaluate underlying sources of PK variability, a neonatal physiologically-based pharmacokinetic (PBPK) model of sublingual buprenorphine was developed using Simcyp (version 19.1). The PBPK model included metabolism by cytochrome P450 (CYP) 3A4, CYP2C8, UDP-glucuronosyltransferase (UGT) 1A1, UGT1A3, UGT2B7, and UGT2B17, with additional biliary excretion. Maturation of metabolizing enzymes was incorporated, and default CYP2C8 and UGT2B7 ontogeny profiles were updated according to recent literature. A biliary clearance developmental profile was outlined using clinical data from neonates receiving sublingual buprenorphine as NOWS treatment. Extensive PBPK model validation in adults demonstrated good predictability, with geometric mean (95% confidence interval (CI)) predicted/observed ratios (P/O ratios) of area under the curve from zero to infinity (AUC0-∞ ), peak concentration (Cmax ), and time to reach peak concentration (Tmax ) equaling 1.00 (0.74-1.33), 1.04 (0.84-1.29), and 0.95 (0.72-1.26), respectively. In neonates, the geometric mean (95% CI) P/O ratio of whole blood concentrations was 0.75 (95% CI 0.64-0.87). PBPK modeling and simulation demonstrated that variability in biliary clearance, sublingual absorption, and CYP3A4 abundance are likely important drivers of buprenorphine PK variability in neonates. The PBPK model could be used to guide development of improved buprenorphine starting dose regimens for the treatment of NOWS.

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. Fueled by the soaring opioid epidemic in the United States, opioid use during pregnancy continues to rise, leading to an increased incidence of neonatal opioid withdrawal syndrome (NOWS). The severity of NOWS is influenced by a complex interplay of extrinsic and intrinsic factors, and varies substantially between newborns, but the extent of prenatal opioid exposure is likely the primary driver. Fetomaternal PBPK modeling is an attractive approach to predict in utero opioid exposure. To facilitate the development of fetomaternal PBPK models of opioids, this review provides a detailed overview of pregnancy-induced changes affecting the PK of commonly used opioids during gestation. Moreover, the placental transfer of these opioids is described, along with their disposition in the fetus. Lastly, the implementation of these factors into PBPK models is discussed. Fetomaternal PBPK modeling of opioids is expected to provide improved insights in fetal opioid exposure, which allows for prediction of postnatal NOWS severity, thereby opening the way for precision postnatal treatment of these vulnerable infants.

Quality Improvement Initiative to Improve Healthcare Providers' Attitudes towards Mothers with Opioid Use Disorder.

INTRODUCTION: Individuals with opioid use disorder often report feelings of shame and describe feeling judged negatively. These feelings are especially true for pregnant women with opioid use disorder. The Ohio Perinatal Quality Collaborative conducted a multimodal quality improvement initiative for infants born with Neonatal Abstinence Syndrome (NAS). An important component of the project was focused on improving staff attitudes toward mothers of infants with NAS. METHODS: The Ohio Perinatal Quality Collaborative implemented an education program for healthcare providers at 39 participating hospital units regarding opioid use as a chronic disease and principles of nonjudgmental, trauma-informed care. Healthcare providers partnered with the mother of infants with NAS in the care of the infant and connected with local community resources. This work was a subcomponent of an overall multimodal quality improvement project. Healthcare provider attitudes were measured with the "Attitude Measurement: Brief Scales" questionnaire anonymously, at 3 different time points throughout the project. Attitude change was measured by pretraining and posttraining scores. ANOVA methods were used to compare individual items and a summary score across the 3 surveys. RESULTS: Summary scores improved significantly from 18.99 at baseline (January-March 2014) to 19.94 (P < 0.0001) in February 2015 and were maintained at 20.05 in July 2016. CONCLUSIONS: A nonjudgmental attitude toward mothers of infants with NAS is an important component of compassionate care. Improving healthcare provider attitudes can benefit a mother of an infant with NAS and help preserve the mother-infant dyad.

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. RESULTS: Of 2531 tested samples, 18.7% tested positive for high levels of cotinine indicating primary smoking or other primary use of tobacco products. Together, 33.0% of the study population tested positive for nicotine exposure during late pregnancy compared to vital records which reported 8.2% cigarette smoking during the third trimester of pregnancy and 10.5% cigarette smoking at any time during pregnancy through maternal self-report. CONCLUSION: Captured vital birth smoking measures vastly underreport actual primary exposures to nicotine products. Vital birth data also fail to capture secondhand exposures which constitute a significant proportion of the population.

Physiologic Indirect Response Modeling to Describe Buprenorphine Pharmacodynamics in Newborns Treated for Neonatal Opioid Withdrawal Syndrome.

BACKGROUND AND OBJECTIVE: Buprenorphine has been shown to be effective in treating infants with neonatal opioid withdrawal syndrome. However, an evidence-based buprenorphine dosing strategy has not been established in the treatment of neonatal opioid withdrawal syndrome because of a lack of exposure-response data. The aim of this study was to develop an integrated pharmacokinetic and pharmacodynamic model to predict buprenorphine treatment outcomes in newborns with neonatal opioid withdrawal syndrome. METHODS: Clinical data were obtained from 19 newborns with a median (range) gestational age of 37 (34-41) weeks enrolled in a pilot pharmacokinetic study of buprenorphine. Sparse blood sampling, comprising three specimens obtained around the second dose of buprenorphine, was performed using heel sticks with dried blood spot technology. Standardized neonatal opioid withdrawal syndrome severity scores (Finnegan scores) were collected every 3-4 h based on symptoms by bedside nursing staff. Mean Finnegan scores were used as a pharmacodynamic marker in the exposure-response modeling. The blood concentration-Finnegan score relationship was described using a physiologic indirect response model with inclusion of natural disease remission. RESULTS: A total of 52 buprenorphine blood concentrations and 780 mean Finnegan scores were available for the pharmacokinetic/pharmacodynamic modeling and exposure-response analysis. A one-compartment model with first-order absorption adequately described the pharmacokinetic data. The buprenorphine blood concentration at 50% of maximum effect for the inhibition of disease progression was 0.77 ng/mL (95% confidence interval 0.32-1.2). The inclusion of natural disease remission described as a function of postnatal age significantly improved the model fit. CONCLUSIONS: A buprenorphine pharmacokinetic/pharmacodynamic model was successfully developed. The model could facilitate model-informed optimization of the buprenorphine dosing regimen in the treatment of neonatal opioid withdrawal syndrome.

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. Current pharmacological treatments for NOWS are based on institutional protocols and largely rely on empirical treatment of patient symptoms. AREAS COVERED: This article reviews the PK/PD of NOWS pharmacotherapies with a focus on the implication of physiological development and maturation. Body size-standardized clearance is consistently low in neonates, except for methadone. This can be ascribed to underdeveloped metabolic and elimination pathways. The effects of pharmacogenetics have been clarified especially for morphine. The PK/PD relationship of medications used in the treatment of NOWS is generally understudied. EXPERT OPINION: Providing an appropriate opioid dose in neonates is challenging. Advancements in quantitative pharmacology and PK/PD modeling approaches facilitate identification of key factors driving PK/PD variability and characterization of exposure-response relationships. PK/PD model-informed simulations have been widely employed to define age-appropriate pediatric dosing regimens. The model-informed approach holds promise to aid more rational use of medications in the treatment of NOWS.

Orchestrated Testing of Formula Type to Reduce Length of Stay in Neonatal Abstinence Syndrome.

BACKGROUND: Despite the standardization of care, formula feeding varied across sites of the Ohio Perinatal Quality Collaborative (OPQC). We used orchestrated testing (OT) to learn from this variation and improve nonpharmacologic care of infants with neonatal abstinence syndrome (NAS) requiring pharmacologic treatment in Ohio. METHODS: To test the impact of formula on length of stay (LOS), treatment failure, and weight loss among infants hospitalized with NAS, we compared caloric content (high versus standard) and lactose content (low versus standard) using a 22 factorial design. During October 2015 to June 2016, OPQC sites joined 1 of 4 OT groups. We used response plots to examine the effect of each factor and control charts to track formula use and LOS. We used the OT results to revise the nonpharmacologic bundle and implemented it during 2017. RESULTS: Forty-seven sites caring for 546 NAS infants self-selected into the 4 OT groups. Response plots revealed the benefit of high-calorie formula (HCF) on weight loss, treatment failure, and LOS. The nonpharmacologic treatment bundle was updated to recommend HCF when breastfeeding was not possible. During implementation, HCF use increased, and LOS decreased from 17.1 to 16.4 days across the OPQC. CONCLUSIONS: OT revealed that HCF was associated with shorter LOS in OPQC sites. Implementation of a revised nonpharmacologic care bundle was followed by additional LOS improvement in Ohio. Despite some challenges in the implementation of OT, our findings support its usefulness for learning in improvement networks.

Medication treatment for opioid use disorder in expectant mothers (MOMs): Design considerations for a pragmatic randomized trial comparing extended-release and daily buprenorphine formulations.

Opioid use disorder (OUD) in pregnant women has increased significantly in recent years. Maintaining these women on sublingual (SL) buprenorphine (BUP) is an evidence-based practice but BUP-SL is associated with several disadvantages that an extended-release (XR) BUP formulation could eliminate. The National Drug Abuse Treatment Clinical Trials Network (CTN) is conducting an intent-to-treat, two-arm, open-label, pragmatic randomized controlled trial, Medication treatment for Opioid-dependent expectant Mothers (MOMs), to compare mother and infant outcomes of pregnant women with OUD treated with BUP-XR, relative to BUP-SL. A second aim is to determine the relative economic value of utilizing BUP-XR. Approximately 300 pregnant women with an estimated gestational age (EGA) of 6-30 weeks, recruited from 12 sites, will be randomized in a 1:1 ratio to BUP-XR or BUP-SL, balancing on site, EGA, and BUP-SL status (taking/not taking) at the time of randomization. Participants will be provided with study medication and attend weekly medication visits through 12 months postpartum. Participants will be invited to participate in two sub-studies to evaluate the: 1) mechanisms by which BUP-XR may improve mother and infant outcomes; and 2) effects of prenatal exposure to BUP-XR versus BUP-SL on infant neurodevelopment. This paper describes the key design decisions for the main trial made during protocol development. This Investigational New Drug (IND) trial uniquely uses pragmatic features where feasible in order to maximize external validity, hence increasing the potential to inform clinical practice guidelines and address multiple knowledge gaps for treatment of this patient population.

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). At birth, infants were classified as unexposed to opioids, exposed to opioids and diagnosed with NAS, or subclinically exposed to opioids (exposure that did not result in NAS). RESULTS: The prevalence of newborn opioid exposure was 37 per 1000 births. The duration of the hospital birth encounter was significantly longer for infants with subclinical exposure compared with unexposed infants (10% increase; 95% CI, 7%-13%). However, duration for infants with subclinical exposure was shorter compared to those with NAS. Neither subclinical exposure nor NAS was associated with total emergency department visits. Subclinical exposure was associated with increased odds of having at least 1 hospitalization in the first year. However, the total length of stay for hospitalizations was 82% that of the unexposed group (95% CI, 75%-89%). Infants with NAS had a 213% longer total length of stay compared with the unexposed group (95% CI, 191%-237%). CONCLUSIONS: Subclinical and overt opioid exposure among newborn infants was associated with increased first-year healthcare utilization. From 2014 to 2017, this cost the Hamilton County healthcare system an estimated $1 109 452 for longer birth encounters alone.

Reported Prevalence of Maternal Hepatitis C Virus Infection in the United States.

OBJECTIVE: To quantify the reported prevalence and trend of maternal hepatitis C virus (HCV) infection in the United States (2009-2017) and identify maternal characteristics and obstetric outcomes associated with HCV infection during pregnancy. METHODS: We conducted a population-based retrospective cohort study of all live births in the United States for the period 2009 through 2017 using National Center for Health Statistics birth records. We estimated reported prevalence and trends over this time period for the United States. We also evaluated demographic factors and pregnancy outcomes associated with maternal HCV infection for a contemporary U.S. cohort (2014-2017). RESULTS: During the 9-year study period, there were 94,824 reported cases of maternal HCV infection among 31,207,898 (0.30%) live births in the United States. The rate of maternal HCV infection increased from 1.8 cases per 1,000 live births to 4.7 cases per 1,000 live births (relative risk [RR] 2.7, 95% CI 2.6-2.8) in the United States. After adjusting for various confounders in the contemporary U.S. cohort (2014-2017), demographic characteristics associated with HCV infection included non-Hispanic white race (adjusted RR 2.8, 95% CI 2.7-2.8), Medicaid insurance (adjusted RR 3.3, CI 3.2-3.3), and cigarette smoking (adjusted RR 11.1, CI 10.9-11.3). Co-infection during pregnancy with hepatitis B (adjusted RR 19.2, CI 18.1-20.3), gonorrhea, chlamydia, or syphilis were also associated with maternal HCV infection. Obstetric and neonatal outcomes associated with maternal HCV infection included cesarean delivery, preterm birth, maternal intensive care unit admission, blood transfusion, having small-for-gestational-age neonates (less than the 10th percentile) birth weight, neonatal intensive care unit admission, need for assisted neonatal ventilation, and neonatal death. CONCLUSION: The reported prevalence of maternal HCV infection has increased 161% from 2009 to 2017.

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. Diagnosis rates were compared between drug exposure groups using chi-square tests. Among infants born at >34 weeks gestation and without other complex clinical conditions, infants with subclinical opioid exposures (N = 473) were more likely than infants with no drug exposures (N = 14,933) to be diagnosed with behavioral or emotional disorders (3.0% vs 1.1%, P = 0.0008), developmental delay (15.6% vs 7.6%, P < 0.0001), speech disorder (10.1% vs 6.5%, P = 0.001), or strabismus (3.4% vs 1.0%, P < 0.0001), and more likely to be exposed to the hepatitis C virus (6.8% vs 0.1%, P < 0.0001). Increased diagnosis rates among all opioid exposed infants, regardless of withdrawal severity, may warrant the additional allocation of resources for screening and follow-up. Awareness of the increased risk for certain developmental delays and medical conditions is critical to early intervention and treatment supporting improved outcomes.

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. A nested, matched, case-control analysis examined the association of pediatric HCV infection and IUDE. RESULTS: The HCV prevalence rate among high-risk infants who received testing was 3.6%-5.2% of births. Approximately 66.7% of maternally acquired HCV infections may be missed using current testing recommendations. Prenatal care had no significant effect (adjusted odds ratio [aOR], 1.2; 95% confidence interval [CI], 0.4-3.5) on the odds of a high-risk infant receiving HCV testing. Opioid-exposed cases had a more than 6-fold increase in the odds of HCV infection (aOR, 6.2; 95% CI, 2.3-16.6]) compared with nonopioid exposed infants. CONCLUSIONS: The IUDE was significantly associated with increased odds of pediatric HCV infection in this population. The gaps in pediatric HCV testing identified in this study, despite known risk level and maternal infection, suggest the need for increased focus on HCV identification in the pediatric population.

Ohio Perinatal Quality Collaborative Improves Care of Neonatal Narcotic Abstinence Syndrome.

OBJECTIVES: Neonatal abstinence syndrome (NAS) after an infant's in-utero exposure to opioids has increased dramatically in incidence. No treatment standards exist, leading to substantial variations in practice, degree of opioid exposure, and hospital length of stay. METHODS: The Ohio Perinatal Quality Collaborative conducted an extensive multi-modal quality improvement initiative with the goal to (1) standardize identification, nonpharmacologic and pharmacologic treatment in level-2 and 3 NICUs in Ohio, (2) reduce the use of and length of treatment with opioids, and (3) reduce hospital length of stay in pharmacologically treated newborns with NAS. RESULTS: Fifty-two of 54 (96%) Ohio NICUs participated in the collaborative. Compliance with the nonpharmacologic bundle improved from 37% to 59%, and the pharmacologic bundle improved from 59% to 68%. Forty-eight percent of the 3266 opioid-exposed infants received pharmacologic treatment of symptoms of NAS, and this rate did not change significantly across the time period. Regardless of the opioid used to pharmacologically treat infants with NAS, the length of treatment decreased from 13.4 to 12.0 days, and length of stay decreased from 18.3 to 17 days. CONCLUSIONS: Standardized approaches to the identification and nonpharmacologic and pharmacologic care were associated with a reduced length of opioid exposure and hospital stay in a large statewide collaborative. Other states and institutions treating opioid-exposed infants may benefit from the adoption of these practices.

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.

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. Among 27,896 newborns, the authors detected an intrauterine opioid exposure rate of 37.9 per 1000 infants, with 10.5 per 1000 experiencing severe opioid withdrawal (neonatal abstinence syndrome). Individual data were mapped to 222 US census tracts. Tract-level opioid exposure rates ranged from 0.0 to 607.1 (median: 32.9) per 1000 live births. Secondary use of electronic health record data has potential to aid in intrauterine opioid exposure and other public health surveillance efforts without disrupting clinical workflows or placing an additional burden on limited resources. Surveillance of intrauterine opioid exposures may inform stakeholders and enable targeting of interventions and prevention strategies toward the highest risk populations.

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. General linear models were used to calculate adjusted mean duration of opioid treatment and length of hospitalization with 95% confidence intervals for infants treated with buprenorphine compared with traditional weaning with either methadone or morphine. RESULTS: A total of 360 infants were treated with either buprenorphine (n = 174) or a traditional opioid (n = 186). Infants treated with buprenorphine experienced a 3.0-day reduction in opioid treatment duration of 7.4 (6.3-8.5) versus 10.4 (9.3-11.5) days (p < 0.001) and a 2.8-day reduction in length of stay of 12.4 (11.3-13.6) versus 15.2 (14.1-16.4) days (p < 0.001). CONCLUSION: Our study provides an independent confirmation that among infants experiencing NAS following a wide array of intrauterine opioid exposures, buprenorphine weaning supports a shortened treatment duration compared with conventional weaning agents.