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).

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.

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.

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.

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.

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.

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.

Addressing the impact of opioids on women and children.

Women and children bear a substantial part of the burden of opioid overuse in the United States. Opioid use during pregnancy can lead to neonatal opioid withdrawal syndrome, and both the mothers and babies may be at higher risk of opioid use and its consequences later in the life course, setting up intergenerational cycles of opioid overuse. As part of the HEAL (Helping to End Addiction Long-term) Initiative of the National Institutes of Health, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the Environmental influences on Child Health Outcomes program are together launching observational and intervention research programs to interrupt these cycles, beginning with opportunities in pregnancy and the newborn period. The Eunice Kennedy Shriver National Institute of Child Health and Human Development has also launched programs to find alternatives to opioids for painful conditions in women of reproductive age, including a range of gynecologic conditions. These coordinated efforts promise to help turn the tide against the opioid crisis by providing the necessary evidence to improve care for women and children affected by these substances.

Opioid Use in Pregnancy.

PURPOSE OF REVIEW: Perinatal opioid use is a major public health problem and is associated with a number of deleterious maternal and fetal effects. We review recent evidence of perinatal outcomes and treatment of opioid use disorder (OUD) during pregnancy. RECENT FINDINGS: Opioid exposure in pregnancy is associated with multiple obstetric and neonatal adverse outcomes, with the most common being neonatal opioid withdrawal syndrome (NOWS). Treatment with buprenorphine or methadone is associated with NOWS, but neither medication appears to have significant adverse effects on early childhood development. Buprenorphine appears to be superior to methadone in terms of incidence and severity of NOWS in exposed infants. The long-term effects of opioid exposure in utero have been inconclusive, but recent longitudinal studies point to potential differences in brain morphology that may increase vulnerability to future stressors. Maintenance therapy with methadone or buprenorphine remains the standard of care for pregnant women with OUD given its consistent superiority to placebo in terms of rates of illicit drug use and pregnancy outcomes. New non-pharmacologic management options for NOWS appear promising. Future research is needed to further evaluate the effects of opioid exposure in utero and determine the optimal delivery model for maintenance therapy.

A state-level study of opioid use disorder treatment access and neonatal abstinence syndrome.

BACKGROUND: Adult opioid use and neonatal abstinence syndrome (NAS) are growing public health problems in the United States (U.S.). Our objective was to determine how opioid use disorder treatment access impacts the relationship between adult opioid use and NAS. METHODS: We conducted a cross-sectional state-level ecologic study using 36 states with available Healthcare Cost and Utilization Project State Inpatient Databases in 2014. Opioid use disorder treatment access was determined by the: 1) proportion of people needing but not receiving substance use treatment, 2) density of buprenorphine-waivered physicians, and 3) proportion of individuals in outpatient treatment programs (OTPs). The incidence of NAS was defined as ICD-9 code 779.5 (drug withdrawal syndrome in newborn) from any discharge diagnosis field per 1000 live births in that state. RESULTS: Unmet need for substance use disorder treatment correlated with NAS (r = 0.54, 95% CI: 0.26-0.73). The correlation between adult illicit drug use/dependence and NAS was higher in states with a lower density of buprenorphine-waivered physicians and individuals in OTPs. CONCLUSIONS: Measures of opioid use disorder treatment access dampened the correlation between illicit drug use/dependence and NAS. Future studies using community- or individual-level data may be better poised to answer the question of whether or not opioid use disorder treatment access improves NAS relative to adult opioid use.

Opioid Detoxification in Pregnancy: Systematic Review and Meta-Analysis of Perinatal Outcomes.

OBJECTIVE: We sought to compare the efficacy and safety of detoxification from opioids compared with opioid replacement therapy (ORT) during pregnancy. STUDY DESIGN: We searched PubMed, Embase, Cochrane Library, and ClinicalTrials.gov from inception to June 2017 for English-language randomized-controlled trials or cohort studies that compared detoxification with ORT. We sought studies with outcomes data on maternal abstinence at the time of delivery, neonatal abstinence syndrome (NAS), stillbirth, and preterm birth (PTB). We calculated pooled relative risks (RRs) with a random-effects model, assessed heterogeneity using the chi-square test for heterogeneity, and quantified heterogeneity using the I 2 test. We assessed publication bias using funnel plots and the Harbord test. RESULTS: Three cohort studies met the inclusion criteria; eligible studies included 235 women with opioid use disorder in pregnancy. Maternal detoxification was associated with increased risk of relapse (RR = 1.91; 95% confidence interval [CI] = 1.14-3.21); however, no treatment differences were observed for the rates of NAS (RR = 0.99; 95% CI = 0.38-2.53) or PTB (RR = 0.39; 95% CI = 0.10-1.60). CONCLUSION: Our findings suggest an increased risk of relapse with detoxification treatment compared with ORT; however, detoxification does not alter the risk of PTB or NAS. Further studies should confirm our findings and explore mechanisms to fight the current opioid epidemic.

Implications of Tennessee's Opioid Legislation for Neonatal Abstinence Syndrome.

Opioid use during pregnancy is on the rise in the United States. Neonatal abstinence syndrome (NAS), also known as newborn drug withdrawal, is a public health epidemic. Between 2004 and 2014, Tennessee experienced a fivefold increase in NAS hospitalizations, from 1.5 to 8.0 per 1,000 live births. Soaring increases in the number of newborns with NAS nationwide have caught the attention of many federal and state lawmakers, especially given the unknown burdens associated with medical and social services needed by those affected over time. Tennessee opioid-related regulations and laws enacted between 2000 and 2018 were systematically reviewed and analyzed to identify each law's purpose; effects on families and individuals; pros and cons in terms of social, practical, and legal factors; and implications for nursing practice. Our findings were that Tennessee's laws are intended to decrease the number of opioids prescribed, ensure access to continued prenatal care and substance abuse management for mothers with substance use disorders, and reduce the ease of obtaining opioids. We also found that Tennessee lawmakers have enacted laws and regulations aimed at decreasing the abuse of opioids, but not reducing the incidence of NAS. As new laws are considered, it is critical that health care providers and lawmakers work together to ensure that the developed and enacted laws strike a balance between safely managing the care of both pregnant women and their newborns without producing negative outcomes.

Conceptualizing Neonatal Abstinence Syndrome as a Cascade of Care: A Qualitative Study With Healthcare Providers in Ohio.

BACKGROUND: The opioid epidemic remains a serious issue in the United States and presents additional challenges for women of childbearing age. An increasingly common complication of opioid use is neonatal abstinence syndrome (NAS), or infant withdrawal from in utero exposure to opioids. PURPOSE: The objective of our qualitative study was to identify service needs and barriers to care in the NAS epidemic in Ohio, which has among the highest rates of opioid use and NAS in the nation. METHODS: Drawing on interviews with 18 healthcare providers, we investigated the challenges, opportunities, and service gaps in treating NAS. Open-ended questions covered opioid misuse and drug treatment, provision of and barriers to healthcare, and suggestions to improve prevention and programming. Content analysis identified major themes. FINDINGS: Providers were primarily women (67%) and included individuals working in healthcare administrative positions, hospital settings, clinics, and social support positions for pregnant women or new mothers. Our results suggest that rather than an acute diagnosis, NAS is better conceptualized as a "cascade of care" including (1) prevention, (2) prenatal care, including drug treatment, (3) labor and delivery, and (4) aftercare. Providers identified challenges and opportunities at each stage of the cascade that could influence NAS outcomes. IMPLICATIONS FOR PRACTICE: Our results suggest that greater resources, coordination, and cross-disciplinary education are urgently needed across the cascade of care to effectively address NAS. IMPLICATIONS FOR RESEARCH: Framing NAS as a cascade of care allows researchers to identify points along a cascade where mothers and infants require enhanced care and access to social and health services.

Transitioning from methadone to buprenorphine maintenance in management of opioid use disorder during pregnancy.

BACKGROUND: Opioid use disorder during pregnancy is a growing health concern. Methadone maintenance is the treatment of choice but emerging data indicate buprenorphine is a viable alternative. Due to costs and limited accessibility of methadone, pregnant women may require transition from methadone to buprenorphine for maintenance treatment. OBJECTIVES: To assess safety and effectiveness of transitioning from methadone to buprenorphine when necessary during pregnancy. METHODS: A standardized protocol using low buprenorphine doses to minimize emergent withdrawal symptoms under careful obstetric and psychiatric monitoring was implemented in 20 pregnant women. Outpatient maternal and neonatal outcomes were assessed. RESULTS: Women maintained on an average methadone dose of 44 ± 4.77 (20-100) mg/day (mean±standard error mean (SEM); range) were successfully transitioned to 12.60 ± 0.8 (8-16) mg/day (mean±SEM; range) of buprenorphine. Within 4 weeks of transition, 15% had illicit drugs detected in urine drug screens. Ninety percent of women maintained outpatient follow-up until delivery. At delivery, 38.9% of mothers were exclusively adherent to buprenorphine (without use of illicit substances and/or other psychotropic medications); this resulted in significantly lower rates of neonatal abstinence syndrome (NAS) and shorter hospital stays. DISCUSSION: Pregnant women transitioned from methadone to buprenorphine maintenance showed maternal and neonatal outcomes comparable to studies of women on buprenorphine throughout pregnancy. Infants born to buprenorphine-maintained women who abstained from illicit substances and other prescribed psychotropic medications experienced less severe NAS and shorter hospitalizations compared with women with illicit substance use and other psychotropic medications. These findings suggest women can safely be transitioned from methadone to buprenorphine during pregnancy.

CDC Grand Rounds: Public Health Strategies to Prevent Neonatal Abstinence Syndrome.

Neonatal abstinence syndrome (NAS) is a drug withdrawal syndrome that most commonly occurs in infants after in utero exposure to opioids, although other substances have also been associated with the syndrome (1). NAS usually appears within 48-72 hours of birth with a constellation of clinical signs, including central nervous system irritability (e.g., tremors), gastrointestinal dysfunction (e.g., feeding difficulties), and temperature instability (1) (Box 1). Opioid exposure during pregnancy might result from clinician-approved use of prescription opioids for pain relief; misuse or abuse of prescription opioids; illicit use (e.g., heroin); or medication-assisted treatment (MAT) of opioid use disorder (2) (Box 2).

Pain Management in the Opioid-Dependent Pregnant Woman.

Opioid dependence is an epidemic in the United States, and the percentage of pregnant women who are opioid dependent has increased dramatically in the last decade. Pain management, already a concern for intrapartum and postpartum care, is complicated in the context of opioid dependence. This clinical review surveys the literature on pain management in opioid-dependent pregnant women to summarize current consensus and evidence to guide clinical practice. Points of consensus for pain management in opioid-dependent pregnant women include continual opioid maintenance therapy throughout the pregnancy and the postpartum period; adequate management of acute pain; the contraindication of opioid agonist-antagonists for pain management; and the need for interdisciplinary teams using a multimodal approach to provide optimal care to opioid-dependent pregnant women.

A Population Health Driver Diagram to Address Neonatal Abstinence Syndrome.

This article describes the process for developing a population health driver diagram to address a priority health issue in East Tennessee: neonatal abstinence syndrome (NAS). Population health driver diagrams are used in quality improvement processes for determining and aligning actions that a community can take to achieve a specified outcome. The Tennessee Department of Health contracted with the University of Tennessee's Department of Public Health to conduct a community participatory process to contribute to a statewide health improvement plan. Colleagues in local public health practice identified NAS as the leading perinatal health issue, and community engagement was achieved by involving community health councils. Qualitative and quantitative data were collected, analyzed, and provided to these councils. A region-wide stakeholders' meeting resulted in the development of a population health driver diagram to address NAS. We describe this process and provide lessons learned that can be valuable in other settings. Population health diagrams have important implications for practice because of their use as a framework for community action, especially in the context of a community health assessment.

Buprenorphine Versus Methadone for Opioid Dependence in Pregnancy.

OBJECTIVE: To evaluate maternal and neonatal safety outcomes for methadone and buprenorphine in the obstetric population. DATA SOURCES: A literature search of PubMed (1966 to March 2016) and EMBASE (1973 to March 2016) was completed using the search terms buprenorphine, methadone, pregnancy, opioid, and neonatal abstinence syndrome Priority was given to randomized controlled trials and trials directly comparing buprenorphine and methadone during pregnancy. The bibliographies were reviewed for other relevant articles. STUDY SELECTION AND DATA EXTRACTION: All human studies published in English, that compared methadone and buprenorphine use in pregnancy were evaluated. Because of the limited number of obstetric studies, only 5 critical studies were found. DATA SYNTHESIS: Buprenorphine significantly improved or had similar outcomes to methadone for development of neonatal abstinence syndrome (NAS), percentage of infants requiring treatment for NAS (20%-47% vs 45.5%-57%, respectively), total amount of morphine used to treat NAS (0.472-3.4 vs 1.862-10.4 mg, respectively), duration of NAS (4.1-5.6 vs 5.3-9.9 days, respectively), peak NAS (3.9-11 vs 4.9-12.8 score, respectively), infant hospital stay (6.8-10.6 vs 8.1-17.5 days, respectively), and gestational age at delivery (38.8-39.7 vs 37.9-38.8 weeks, respectively). No difference was found with other neonatal or maternal outcomes. CONCLUSIONS: Both methadone and buprenorphine are effective agents, with improved safety compared with continued nonmedical opioid use during pregnancy. There is evidence to suggest that buprenorphine should be considered as an equivalent option to methadone for use in pregnancy; however, larger studies are still needed to fully evaluate buprenorphine safety and advantages over methadone in the obstetric population.