Comparison of neonatal outcomes in pregnant women undergoing medication-assisted treatment of opioid use disorder with methadone or buprenorphine/naloxone.

INTRODUCTION: The number of pregnant women with opioid use disorder (OUD) has quadrupled from 1999 to 2014. Current first line treatment for OUD in pregnancy is methadone with increasing support for buprenorphine. Limited data exist on use of buprenorphine/naloxone for OUD in pregnancy despite it being standard therapy in the non-pregnant individuals. The aim of this study was to compare neonatal opioid withdrawal syndrome (NOWS) prevalence and characteristics among neonates born to women prescribed methadone and buprenorphine/naloxone. METHODS: This is a retrospective cohort analysis of mother-neonate dyads treated with either methadone or buprenorphine/naloxone for OUD in pregnancy who received prenatal care in the substance abuse, treatment, education, and prevention program (STEPP) clinic and delivered at OSU. Primary neonatal outcomes included: neonates diagnosed and treated for NOWS, peak scores on Modified Finnegan Neonatal Abstinence Score (FNAS), number of scores ≥9 on FNAS, and duration of treatment for NOWS. Secondary outcomes included: fetal growth restriction, preterm birth (<37 weeks), neonatal head circumference, birth weight, NICU admission, five-minute Apgar score, and length of hospitalization. RESULTS: From 2013 to 2017, we identified 588 mother-neonate dyads: 149 treated with methadone and 439 treated with buprenorphine/naloxone. Ninety-eight neonates (65.8%) in the methadone group were diagnosed with NOWS requiring pharmacological interventions compared with 170 (38.7%) in the buprenorphine/naloxone group (aOR 3.46, 95% confidence interval (CI) 2.31-5.20, p < .01). Methadone-exposed neonates were six times more likely to be treated with >1 medication for NOWS (aOR 6.32, 95% CI 2.20-18.13, p < .01). Fetal growth restriction was diagnosed more often in the methadone group compared to the buprenorphine/naloxone group (aOR 1.73, 95% CI 1.02-2.93, p < .01). Significant maternal findings were that women using methadone for OUD started PNC earlier (15w vs. 17w, p = .04) and were less likely to be taking selective serotonin-reuptake inhibitors (SSRIs) (15% vs. 25%, p = .02) compared to the buprenorphine/naloxone group. CONCLUSIONS: Buprenorphine/naloxone treatment for OUD in pregnancy appears safe and has decreased NOWS and pharmacologic intervention for the neonate.

The Impact of a Prenatal Education Program for Opioid-Dependent Mothers on Breastfeeding Rates of Infants at Risk for Neonatal Abstinence Syndrome.

INTRODUCTION: This study aimed to determine the effect of a prenatal education program for opioid-dependent women on breastfeeding frequency, newborn hospital length of stay, and cost of care for neonates at risk of developing neonatal abstinence syndrome. METHODS: From January 1, 2015 to January 1, 2020, opioid-dependent obstetric patients were educated on non-pharmacological preventative measures for neonatal abstinence syndrome (NAS), with focused counseling on breastfeeding. Data were collected and compared to a control group of opioid-dependent pregnant women who received standard care before initiation of the education program. RESULTS: Sample size calculation revealed that to detect doubling of the breastfeeding rate from 25% to 50% with 80% power and α error of 0.05, 66 participants were required in each group. CONCLUSION: There were 75 women with opioid use disorder who had prenatal NAS education (study group) and 108 women with opioid use disorder who underwent standard care before NAS education (control group). Prenatal NAS education participants significantly increased breastfeeding initiation rates compared to the control group. Newborn length of stay significantly decreased after initiation of prenatal NAS education compared to the 36 months before NAS education program.

A Field Placement Approach to Enhance State and Local Capacity for Opioid-Related Issues Affecting Pregnant and Postpartum People and Infants Prenatally Exposed to Opioids and Other Substances.

Opioid use disorder (OUD) poses a significant public health concern impacting maternal and infant outcomes. In 2018, the Centers for Disease Control and Prevention (CDC) partnered with the Association of State and Territorial Health Officials (ASTHO) to develop the Opioid use disorder, Maternal outcomes, and Neonatal abstinence syndrome Initiative Learning Community (OMNI LC) to identify and disseminate best practices and strategies for implementing systems-level changes in state health departments to address OUD affecting pregnant and postpartum persons and infants prenatally exposed to opioids. In 2019, the OMNI LC incorporated a field placement approach that assigned temporary field placement staff in five select OMNI LC states to provide important linkages, facilitate information sharing, and strengthen capacity among state and local health departments and other partners supporting maternal and child health communities affected by the opioid crisis. Using an implementation science framework, the field placement approach was assessed using five implementation outcome measures: appropriateness, acceptability, implementation cost, sustainability, and feasibility. Written responses from the participating OMNI LC states on these implementation outcome measures were analyzed to (1) highlight key strategies used by field placement staff, (2) assess the implementation of the OMNI LC field placement approach within the context of implementation science, and (3) identify implementation barriers. This report describes the implementation of a temporary field placement approach and suggests that this approach could be replicated to enhance state and local capacity to respond to the opioid crisis or other high-consequence events.

Opioid Use Disorder and Perinatal Outcomes.

OBJECTIVES: Evidence on the perinatal health of mother-infant dyads affected by opioids is limited. Elevated risks of opioid-related harms for people with opioid use disorder (OUD) increase the urgency to identify protective factors for mothers and infants. Our objectives were to determine perinatal outcomes after an OUD diagnosis and associations between opioid agonist treatment and birth outcomes. METHODS: We conducted a population-based retrospective study among all women with diagnosed OUD before delivery and within the puerperium period in British Columbia, Canada, between 2000 and 2019 from provincial health administrative data. Controlling for demographic and clinical characteristics, we determined associations of opioid agonist treatment on birth weight, gestational age, infant disorders related to gestational age and birth weight, and neonatal abstinence syndrome via logistic regression. RESULTS: The population included 4574 women and 6720 live births. Incidence of perinatal OUD increased from 166 in 2000 to 513 in 2019. Compared with discontinuing opioid agonist treatment during pregnancy, continuous opioid agonist treatment reduced odds of preterm birth (adjusted odds ratio: 0.6; 95% confidence interval: 0.4-0.8) and low birth weight (adjusted odds ratio: 0.4; 95% confidence interval: 0.2-0.7). Treatment with buprenorphine-naloxone (compared with methadone) reduced odds of each outcome including neonatal abstinence syndrome (adjusted odds ratio: 0.6; 95% confidence interval: 0.4-0.9). CONCLUSIONS: Perinatal OUD in British Columbia tripled in incidence over a 20-year period. Sustained opioid agonist treatment during pregnancy reduced the risk of adverse birth outcomes, highlighting the need for expanded services, including opioid agonist treatment to support mothers and infants.

Prenatal Use of Medication for Opioid Use Disorder and Other Prescription Opioids in Cases of Neonatal Opioid Withdrawal Syndrome: North Carolina Medicaid, 2016-2018.

Objectives. To estimate use of medication for opioid use disorder (MOUD) and prescription opioids in pregnancy among mothers of infants with neonatal opioid withdrawal syndrome (NOWS). Methods. We used linked 2016-2018 North Carolina birth certificate and newborn and maternal Medicaid claims data to identify infants with an NOWS diagnosis and maternal claims for MOUD and prescription opioids in pregnancy (n = 3395). Results. Among mothers of infants with NOWS, 38.6% had a claim for MOUD only, 14.3% had a claim for prescription opioids only, 8.1% had a claim for both MOUD and prescription opioids, and 39.1% did not have a claim for MOUD or prescription opioids in pregnancy. Non-Hispanic Black women were less likely to have a claim for MOUD than non-Hispanic White women. The percentage of infants born full term and normal birth weight was highest among women with MOUD or both MOUD and prescription opioid claims. Conclusions. In the 2016-2018 NC Medicaid population, 60% of mothers of infants with NOWS had MOUD or prescription opioid claims in pregnancy, underscoring the extent to which cases of NOWS may be a result of medically appropriate opioid use in pregnancy.

Neonatal Abstinence Syndrome: Prevention, Recognition, Treatment, and Follow-up.

Neonatal abstinence syndrome (NAS), or neonatal opioid withdrawal syndrome (NOWS) results from acute discontinuation of transplacental opioid exposure following delivery in the setting of maternal opioid use. A rise in the incidence of NAS coincides with the nationwide opioid epidemic. Addressing NAS requires a team approach. First, all pregnant women should be screened for substance use using validated questionnaires. Mothers who screen positive for opioid abuse should be referred to a provider experienced in opioid maintenance therapy. In addition to medical treatment emphasizing stability rather than detoxification, mental and situational health should be addressed. Next, mothers with opioid dependence should be educated regarding NAS. Topics for education include increased length of hospital stay following delivery, neonatal withdrawal symptoms, importance of the mother-baby dyad to treatment, and criteria for pharmacologic intervention. Following delivery, at-risk infants should be evaluated with standardized assessment tool such as Finnegan scoring or the eat-sleep-console tool while simultaneously maximizing nonpharmacologic interventions. Breast-feeding is encouraged in the absence of ongoing illicit or polysubstance use or infectious concerns. Pharmacologic treatment options most commonly include morphine or methadone. Infants without symptoms should be monitored for four to seven days prior to discharge, dependent on type of opioid exposure. Finally, infants with NAS are at risk for long-term mental and physical health problems. Therefore, infants will benefit from connection prior to hospital discharge with a primary care provider as well as entities designed for early childhood intervention and developmental assistance. The importance of well-child exams should be stressed to the family.

Autonomous Care Pathway to Patient Opioid Abstinence: Should All Programs Offer this Approach?

Introduction: The opioid epidemic resulted in vast increase in neonatal opioid withdrawal syndrome (NOWS). To mitigate NOWS and opioid dependency among women, staff established a gender specific, patient driven, autonomy based, outpatient therapeutic substitution program. Methods: Prospective observational study of obstetric patients receiving prenatal care 7/1/2016-12/31/2019. Patients underwent universal urine drug screens to identify illicit drug use with dependency and offered addiction counseling with voluntary outpatient therapeutic substitution in an obstetrical-addictions combined clinic to achieve abstinence with oral Buprenorphine tapering protocol. Urine substance screening and cord blood testing were obtained at delivery. Birth outcomes compared among groups who achieved abstinence at birth, were successful at tapering, or continued opioid use. Results: Of 783 births, 165 (20.9%) demonstrated opioid use with 91 (55.2%) participating at some point in pregnancy in therapeutic substitution program. At birth, 14/94 (14.9%) patients completed the program and achieved opioid abstinence, 22/94 (23.4%) still enrolled and actively tapering. 57/94 (34.5%) patients were lost to follow-up, relapsed, or terminated due to non-compliance. Seventy-four of 67 (44.3%) opioid positive mothers chose not to enroll. Of 14 women who completed the program, 0 babies born with NOWS, compared to 11/22 (50%) still enrolled in program and actively tapering, 29/57 (50.9%) lost to follow-up, relapsed, or terminated due to non-compliance, and 28/74 (37.8%) never enrolled in program. Conclusion/Implications: Outpatient therapeutic substitution with oral Buprenorphine with abstinence is possible in pregnant patients and results zero NOWS. More data are needed to confirm findings and explore methods for enhanced success in obtaining abstinence. Support: Appalachian Regional Commission and Prevention (ARC) 1st through Charleston Area Medical Center in cooperation with Charleston Health Education and Research Institute (CHERI).

Prevalence and Geographic Distribution of Obstetrician-Gynecologists Who Treat Medicaid Enrollees and Are Trained to Prescribe Buprenorphine.

Importance: The incidence of opioid use during pregnancy is increasing, and drug overdoses are a leading cause of postpartum mortality. Most women who are pregnant do not receive medications for treatment of opioid use disorder, despite the mortality benefit that these agents confer. Furthermore, buprenorphine is associated with milder symptoms of neonatal abstinence syndrome (NAS) compared with methadone. Objective: To describe the prevalence and geographic distribution across the US of obstetrician-gynecologists who can prescribe buprenorphine (henceforth described as X-waivered) in 2019. Design, Setting, and Participants: A cross-sectional, nationwide study linking physician-specific data to county- and state-level data was conducted from September 1, 2019, to March 31, 2020. Data were obtained on 31 211 obstetrician-gynecologists who accept Medicaid insurance through the Centers for Medicare & Medicaid Services Physician Compare data set and linked to the Drug Addiction Treatment Act buprenorphine-waived clinician list. Exposures: State-level NAS incidence and county-level uninsured rates and rurality. Main Outcomes and Measures: Prevalence and geographic distribution of obstetrician-gynecologists who are trained to prescribe buprenorphine. Results: Among the 31 211 identified obstetrician-gynecologists, 18 710 (59.9%) were women. Most had hospital privileges (23 236 [74.4%]) and worked in metropolitan counties (28 613 [91.7%]). Only 560 of the identified obstetrician-gynecologists (1.8%) were X-waivered. Obstetrician-gynecologists in counties with fewer than 5% uninsured residents had nearly twice the odds of being X-waivered (adjusted odds ratio [aOR], 1.59; 95% CI, 1.04-2.44; P = .04) compared with those in counties with greater than 15% uninsured residents. Compared with those located in metropolitan counties, obstetrician-gynecologists in suburban counties (eg, urban population of ≥20 000 and adjacent to a metropolitan area) were more likely to be X-waivered (aOR, 1.85; 95% CI, 1.26-2.71; P = .002). Compared with states with an NAS rate of 5 per 1000 births or less, obstetrician-gynecologists in states with an NAS rate of 15 per 1000 births or greater had nearly 5 times the odds of being X-waivered (aOR, 4.94; 95% CI, 3.60-6.77; P < .001). Obstetrician-gynecologists without hospital privileges were more likely to be X-waivered (aOR, 1.32; 95% CI, 1.08-1.61; P = .007). Conclusions and Relevance: Fewer than 2% of obstetrician-gynecologists who accept Medicaid are able to prescribe buprenorphine, and their geographic distribution appears to be skewed in favor of suburban counties. This finding suggests that there is an opportunity for health systems and professional societies to incentivize X-waiver trainings among obstetrician-gynecologists to increase patients' access to buprenorphine, especially during pregnancy.

Prevention of Neonatal Abstinence Syndrome in an Outpatient Prenatal Buprenorphine Tapering Program.

OBJECTIVES: Many addicted pregnant patients receiving buprenorphine medication-assisted therapy (MAT) wish to discontinue this medication while pregnant. This study was undertaken to determine whether outpatient detoxification from buprenorphine during pregnancy is safe and effective when confirmed with postdetoxification urine drug screens (UDSs). METHODS: This case series reports the maternal and neonatal outcomes for 21 patients who ended MAT with buprenorphine while pregnant. A retrospective chart review of both maternal and newborn electronic medical records was performed to obtain results. Newborn neonatal abstinence syndrome (NAS) diagnosis, need for morphine, maternal safety and fetal/newborn complications were assessed. Maternal sobriety was documented with UDSs at the time of admission for delivery. Umbilical cord blood also was assessed for substances of abuse. An additional 182 pregnant women who lowered their buprenorphine doses but did not decide to end MAT were assessed via routine quality assurance methods. RESULTS: None of the women who stopped buprenorphine during their pregnancy as confirmed by UDSs and umbilical cord sampling delivered neonates who had NAS. Eleven patients ended MAT with medical assistance and 10 ended MAT without medical assistance. No overdoses were reported for the 182 additional pregnant patients who indicated an intention to taper buprenorphine dosage while pregnant but who did not decide to end MAT; the neonatal benefits were obtained without any identified maternal harm. CONCLUSIONS: The neonates of pregnant women enrolled in an outpatient buprenorphine MAT tapering program who are able to completely stop taking buprenorphine (as documented by negative urinary drug screen) are very unlikely to have NAS. Further research will be important.

OB/GYN perceptions of prescription drug monitoring programs as a primary prevention tool for neonatal abstinence syndrome.

BACKGROUND: The U.S. Centers for Disease Control and Prevention recommend clinicians use Prescription Drug Monitoring Program (PDMPs) as a risk assessment tool for opioid-related harms. This survey assessed perceptions of PDMPs for the purpose of Neonatal Abstinence Syndrome (NAS) prevention among a national sample of obstetricians-gynecologists (OB/GYNs) who are the primary care providers for most pregnancies. METHODS: A survey was emailed to a random sample of active American College of Obstetricians and Gynecologists (ACOG) members. Proxy data for the intensity of the opioid epidemic and state policies related to NAS were added to respondents survey answers. Chi-squared analyses were used to compare response frequencies. RESULTS: Among 397 submitted responses, nearly 70% identified PDMPs having a role in preventing diversion and opioid use disorders but only 25.1% identified PDMPs as a tool to prevent NAS. States with stricter NAS policies (e.g. child abuse, mandatory testing) generally had higher positive responses for PDMPs' role in preventing NAS. States with voluntary PDMP use versus mandatory reported higher positive responses for PDMPs with NAS but differences were not statistically significant (30.6% vs. 23.8%, p = 0.374). State-specific measures of the overall intensity of the opioid epidemic were not associated with perceptions of PDMP. CONCLUSIONS: OB/GYNs do not associate PDMPs as a primary prevention tool against NAS despite endorsements. Tailored educational interventions to this practice environment are needed. Pharmacist engagement with pregnant patients and as champions of PDMP usage may help fill these gaps.

Avoiding NICU Transfers for Newborns With Neonatal Opioid Withdrawal Syndrome (NOWS): A Quality Improvement Initiative to Manage NOWS on the Mother-baby Unit.

OBJECTIVES: To reduce transfers to the neonatal intensive care unit (NICU) for neonates with opioid withdrawal while also reducing length of stay and pharmacologic intervention, and maintaining standards of safety. PATIENTS AND METHODS: This was a single-center quality-improvement (QI) initiative in a free-standing maternity hospital comparing outcomes for neonatal opioid withdrawal syndrome (NOWS) before and after a series of QI bundles in infants >36 weeks' gestation age (GA). We compared outcomes to our preintervention period (January, 2013 to December, 2013; n = 42) with outcomes postintervention cycle 1 (October, 2016 to September, 2017; n = 126), and postintervention cycle 2 (November, 2017 to October, 2018; n = 160). Cycle 1 included organizing a multidisciplinary task force who focused on emphasis on nonpharmacologic and dyad-centered care, and also standardized pharmacologic management. Cycle 2 reflects the transition to a functional assessment tool and as-needed morphine administration on the postpartum floor. RESULTS: Transfer to the NICU for management of NOWS dropped from 71.4% before the quality improvement project down to 5.6% (P < 0.001), with the remainder managed on the mother-baby unit. Length of stay decreased from 17.8 days to 7.2 days, and opioid replacement dropped from 60% down to 16% (P < 0.001 for both). There were no adverse events from morphine administration for any of the infants in this series. CONCLUSIONS: Our study demonstrates how care can be safely provided to most infants with neonatal opioid withdrawal on a postpartum unit without needing transfer to another unit or a higher level of care facility.

Care-by-parent model as a tool for reduction of neonatal opioid withdrawal syndrome in neonates exposed to buprenorphine maintenance therapy in-utero.

Objective: To determine if a structured care-by-parent (CBP) protocol is associated with a reduction in diagnosis of treatment-requiring Neonatal Opioid Withdrawal Syndrome (NOWS).Study design: We performed a pilot retrospective, case control study of pregnant women enrolled in a comprehensive prenatal care program for opioid-dependent patients during which they received buprenorphine for Medication Assisted Treatment (MAT) for Opioid Use Disorder (OUD). Patients who participated in the CBP program actively roomed-in with their infants even after maternal hospital discharge while infants continued to be monitored for development of treatment-requiring NOWS. The primary outcome was the rate of treatment-requiring NOWS in the CBP grouping.Results: Thirty-two (32) cases that were enrolled in the CBP model were compared with 32 matched controls that were not enrolled in this model. There was a significant reduction in the rate of treatment-requiring NOWS among cases compared to the controls (OR = 0.10; p = .001). Neonates undergoing CBP had a decreased length of stay and lower Finnegan scores compared to those who did not undergo CBPConclusion: Among infants born to mothers with OUD in pregnancy, CBP significantly reduces the rate of treatment-requiring NOWS.

Fetal Outcomes with Detoxification from Opioid Drugs during Pregnancy: A Systematic Review.

OBJECTIVE: This study aimed to perform a systematic review of all studies reporting fetal outcomes following detoxification or tapering of opioid drugs during pregnancy. STUDY DESIGN: PubMed, Scopus, Medline, and Google Scholar were searched, and only manuscripts clearly reporting pregnancy/fetal outcomes involving tapering or detoxification from opioid drugs were included. Only pregnancies managed after 1980 were included (when antenatal fetal surveillance became more routine). Collected data included study design, location, years patients were managed, number of patients who were tapered or detoxified, method of tapering, and pregnancy outcome. RESULTS: A total of 14 publications met the criteria for review after evaluating more than 2,000 abstracts and 153 published manuscripts. In 1,097 pregnancies, based on mortality rate analyses and forest plots, no increased fetal risks due to tapering or detoxification from opioid drugs were identified. No increased risk of preterm delivery was found. CONCLUSION: Pregnant women with opioid use disorder who are stable in a medication-assisted treatment program with behavioral health can be informed that tapering or full detoxification from opioid drugs does not increase the fetal risk of poor pregnancy outcome. Future research needs to answer the questions on maternal and long-term newborn consequences of tapering or detoxification versus long-term newborn consequences of continued chronic in utero opioid exposure.

Management and monitoring of opioid use in pregnancy.

Opioid use during pregnancy has serious consequences for mother and baby. The true extent of the problem is unknown and there is a need for better screening. Existing guidelines with respect to the management of pregnant women with opioid use are based on limited evidence. To improve recommendations for optimal identification, management, and treatment, publications on opioids in pregnancy were reviewed. Published literature from 2007 to 2017 was searched in PubMed, Cochrane and Embase databases. The review employed 60 publications from 210 studies identified, that were of varying quality and included randomized controlled trials, systematic reviews, meta-analyses, and Cochrane reviews. The prevalence of opioid use in pregnancy is underestimated. Screening by urine testing and self-reporting is acceptable to identify fetal exposure. To minimize risk, opioid agonist pharmacotherapy should replace the continued use of opioids or detoxification. Current guidelines recommend methadone and buprenorphine equally. However, recent studies indicate that buprenorphine has advantages over methadone. Accordingly, we suggest buprenorphine as first-line therapy. Future studies should elaborate on better objective screening methods to prevent the consequences of fetomaternal opioid exposure.

Effects of Partially Hydrolyzed Formula on Severity and Outcomes of Neonatal Abstinence Syndrome.

OBJECTIVE: This study compares the effect of partially hydrolyzed formula (PHF) and standard formula (SF) on the severity and short-term outcomes of neonatal abstinence syndrome (NAS). STUDY DESIGN: We performed a retrospective chart review of 124 opioid-dependent mothers and their term or near-term infants. Infants were categorized according to the predominant type of formula consumed during the hospital stay. Finnegan's scale was used to assess symptoms of withdrawal. RESULTS: A total of 110 infants met our inclusion criteria. Thirty-four (31%) infants were fed predominantly PHF, 60 (54%) infants were fed SF, and 16 (15%) infants were fed maternal breast milk. There was no difference between the infants in the PHF and SF groups with respect to requirement of morphine (MSO4) therapy, maximum dose of MSO4 used, duration of MSO4 treatment or length of hospital stay after performing multivariate analyses to control for type of drug used by the mother, maternal smoking, regular prenatal care, inborn status, and maximum Finnegan score prior to MSO4 treatment. CONCLUSION: Use of PHF failed to impact short-term outcomes in infants treated for NAS including maximum MSO4 dose, duration of MSO4 treatment, and length of hospital stay. A prospective randomized controlled trial may be indicated to confirm this finding.

The Association of Concomitant Maternal Marijuana Use on Health Outcomes for Opioid Exposed Newborns in Massachusetts, 2003-2009.

This population-based study showed that maternal opioid plus marijuana use during pregnancy was associated with increased odds of prematurity and low birth weight but lower odds of neonatal abstinence syndrome and prolonged hospitalization compared with opioid exposure without marijuana use. Further research should evaluate the biologic mechanisms responsible for these outcomes.

Buprenorphine and Naloxone Versus Buprenorphine for Opioid Use Disorder in Pregnancy: A Cohort Study.

OBJECTIVE: To compare maternal and fetal outcomes among dyads prescribed buprenorphine and naloxone or buprenorphine during pregnancy. METHODS: Retrospective cohort study of patients with opioid use disorder obtaining care in a comprehensive, perinatal program. Patients utilized medication for opioid use disorder: a buprenorphine and naloxone combination product or buprenorphine monotherapy. The primary outcome was neonatal abstinence syndrome requiring treatment. Maternal secondary outcomes included: negative urine drug screen at delivery, obstetrical care attendance, primary cesarean delivery, and preterm delivery. Neonatal secondary outcomes included neonatal biometry, admission to neonatal intensive care, appropriate findings on cord toxicology, and length of stay. Univariate analyses included Chi square, Fisher exact, t-, or Mann-Whitney tests, as appropriate. Multivariate binary logistic regressions examined the association of type of buprenorphine product with diagnosis of neonatal abstinence syndrome requiring treatment and adjusted for variables significantly different in between-group comparisons and correlates of treatments and the primary outcome. RESULTS: The rate of neonatal abstinence syndrome was significantly higher (P = 0.007) among infants exposed in utero to buprenorphine versus buprenorphine and naloxone: 59/108 (54.6%) versus 30/85 (35.3%), respectively. The combined product, relative to the monoproduct, was associated with lower odds of neonatal abstinence syndrome: odds ratio (OR) = 0.453 (95% confidence interval [CI] 0.253-0.813; P = 0.008). Adjusting for dose of buprenorphine product at delivery, year of expected delivery, type of prescriber, diagnosis of hepatitis C, and preterm delivery negated these results: adjusted OR = 0.627 (95% CI 0.309-1.275). Secondary outcomes were similar. CONCLUSION: Compared with buprenorphine monotherapy, the combined buprenorphine and naloxone product was an acceptable alternative pharmacologic treatment for opioid use disorder during pregnancy.

Identifying Co-Exposure to Opiates and Gabapentin During Pregnancy.

Neonatal withdrawal can be difficult to treat in infants with co-exposure to opiates and gabapentin. Because maternal self-report can underestimate exposures, we evaluated the effect of universal toxicology screening for gabapentin. Identification of co-exposure to opiates and gabapentin increased after implementation of toxicology screening, with implications for improved neonatal care.

Complications in pregnant women with sickle cell disease.

Pregnancy in women with sickle cell disease (SCD) is associated with increased maternal and fetal morbidity and mortality. Outcomes vary widely owing to methodological limitations of clinical studies, but overall, hypertensive disorders of pregnancy, venothromboembolism, poor fetal growth, and maternal and perinatal mortality are increased globally. Few therapeutic interventions have been explored other than prophylactic and selective transfusion therapy. Unfortunately, existing data are limited, and it remains unclear whether prophylactic use of chronic transfusions will improve pregnancy outcomes. Management of pregnant women with SCD is best accomplished with a multidisciplinary team that includes a sickle cell expert and an obstetrician familiar with high-risk pregnancies. Women with SCD should have individualized care plans that outline management of acute pain and guidelines for transfusion therapy. Neonates require close monitoring for neonatal abstinence syndrome and hemolytic disease of the newborn. Ideally all young women with SCD will have a "reproductive life plan" developed as a component of preconception counseling and health promotion. Research leading to improved pregnancy management focused on diminishing adverse maternal and neonatal outcomes is overdue. International collaborations should be considered to improve subject recruitment and foster timely completion of clinical trials. Additional therapeutic interventions outside of transfusion therapy should be explored.