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Purpose: Analyze maternal and infant characteristics by Neonatal Opioid Withdrawal Syndrome (NOWS) status and examine the association between mothers with Hepatitis C Virus (HCV) and infants diagnosed with NOWS. Methods: Hospital discharge diagnoses of low-income women in Tennessee were used to identify NOWS cases (n = 1,369) in 2013 and 2014 and randomly selected controls (n = 1,369) were matched on county of residence and birth year. Maternal and infant characteristics were obtained by linking these data to birth certificate data. Results: Of Tennessee's 683 cases of NOWS in 2013 and 686 in 2014, most (69%) occurred in Eastern Tennessee. Mothers of infants with NOWS were more likely to be older, unmarried, and white than mothers of infants without NOWS. Mothers of infants with NOWS also faced greater health risk: more smoking, HCV, herpes simplex diagnosis, and no or less frequent prenatal care (p <.0001). Infants with NOWS were more likely to present with infection, be admitted into the NICU, have lower birth weight, be enrolled in TennCare, but less likely to be breastfed than infants without NOWS (p <.0001). After adjusting for demographic factors and smoking, compared to mothers of infants without NOWS, mothers of infants with NOWS had an alarmingly increased odds of HCV [OR = 12.97 (95% CI 7.42, 22.66)]. Conclusions: This study emphasizes the complexity of challenges facing families impacted by NOWS, the importance of multifaceted prevention, and the need to conduct HCV testing in NOWS infants. [ABSTRACT FROM AUTHOR]

Background Prescription drug monitoring programs (PDMPs) have been widely adopted as a tool to address the prescription opioid epidemic in the United States. PDMP integration and mandatory use policies are 2 approaches states have implemented to increase use of PDMPs by prescribers. While the effectiveness of these approaches is mixed, it is unclear what factors motivated states to implement them. This study examines whether opioid dispensing, adverse health outcomes, or other non–health-related factors motivated implementation of these PDMP approaches. Methods Time-to-event analysis was performed using lagged state-year covariates to reflect values from the year prior. Extended Cox regression estimated the association of states' rates of opioid dispensing, prescription opioid overdose deaths, and neonatal opioid withdrawal syndrome with implementation of PDMP integration and mandatory use policies from 2009 to 2020, controlling for demographic and economic factors, state government and political factors, and prior opioid policies. Results In our main model, prior opioid dispensing (HR 2.31, 95% CI 1.17, 4.57), neonatal opioid withdrawal syndrome hospitalizations (HR 1.55, 95% CI 1.09, 2.19), and number of prior opioid policies (HR 2.13, 95% CI 1.13, 4.00) were associated with mandatory use policies. Prior prescription opioid overdose deaths (HR 1.21, 95% CI 1.08, 1.35) were also associated with mandatory use policies in a model that did not include opioid dispensing or neonatal opioid withdrawal syndrome. No study variables were associated with implementation of PDMP integration. Conclusion Understanding state-level factors associated with implementing PDMP approaches can provide insights into factors that motivate the adoption of future public health interventions. [ABSTRACT FROM AUTHOR]

Objectives: In 2019, the Council of State and Territorial Epidemiologists ratified a multitiered standardized surveillance case definition (SSCD) for neonatal abstinence syndrome (NAS) to minimize variability in definitions across states. This evaluation of the tier 1 NAS SSCD aimed to identify common challenges and opportunities for enhancement to support consistent implementation of the definition. Methods: This mixed-methods analysis consisted of 3 virtual focus groups in March 2021 with site principal investigators, medical record abstractors, and data analysts (1 focus group each) from 4 jurisdictions piloting the tier 1 NAS SSCD. We analyzed focus group transcripts to create a codebook. We collected written reports in February 2022 from the 4 jurisdictions, conducted thematic analysis of focus group transcripts and written reports to identify themes, and collected surveillance data on infants identified with NAS born from January 2020 through December 2021 from the pilot sites. We analyzed surveillance data to further inform identified themes. We examined agreement among tier 1 classifications assigned independently by each pilot site and the Centers for Disease Control and Prevention to cases of NAS. Results: Three major themes emerged in the data: challenges abstracting data on withdrawal signs from the medical record, difficulty determining the time frame of prenatal substance exposure, and challenges assigning case classifications. In a comparison of tier 1 classifications assigned by the Centers for Disease Control and Prevention and the sites, 82.1% of cases in the dataset were concordant. Conclusions: We identified several opportunities to modify the SSCD to promote consistency and ease implementation across jurisdictions. Promoting consistent implementation supports comparability of NAS incidence estimates across jurisdictions, evaluation of prevention efforts, and allocation of resources to support families. [ABSTRACT FROM AUTHOR]

Aim: To assess inpatient growth parameter trajectories and to identify the type of opioid exposure and treatment characteristics influencing growth parameters of infants admitted to the newborn intensive care unit (NICU) for pharmacological treatment of neonatal opioid withdrawal syndrome (NOWS). Methods: Charts of term infants with NOWS admitted to NICU from 2012 to 2019, who received pharmacologic treatment, were reviewed. Intake (volume: mL/kg/day; calorie: kcal/kg/day) and growth parameter trajectories (weight, head circumference, and length) were analyzed based on the type of prenatal opioid exposure (short‐acting opioids (SAOs), long‐acting opioids (LAOs), and polysubstance), pharmacologic treatment, and sex. Growth measurement patterns over time were compared between groups using longitudinal mixed‐effects models. Results: One hundred nineteen infants were included in the study with median birth weight Z‐score of −0.19 at birth and decreased to a median of −0.72 at discharge. Exposure to SAO was associated with an increase in Z‐scores nearing discharge across all growth parameters (Z‐score for weight p = 0.03). Polysubstance exposure was associated with a decrease in Z‐scores for length and head circumference throughout hospitalization. Infants with adjunct clonidine treatment had an increase in Z‐score for weight trends. Male infants had a decrease in Z‐scores for weight (male −0.96, female −0.59, interaction p = 0.06) and length (male −1.17, female −0.57, interaction p = 0.003) at Day 28. Despite the difference in growth trajectories, intake in terms of amount (mL/kg/day) and calorie intake (kcal/kg/day) was similar based on prenatal exposure, treatment, and sex. Conclusion: Infants with NOWS requiring pharmacologic treatment have a decrease in Z‐scores for weight, length, and head circumference at birth and at hospital discharge. Infants with prenatal polysubstance exposure were at particular risk for poorer inpatient growth relative to infants exposed to SAO and LAO, indicated by lower Z‐scores for length and occipital frontal circumference (OFC). [ABSTRACT FROM AUTHOR]

Purpose: To understand how barriers and facilitators interact over time to support or disrupt breastfeeding among women on opioid maintenance therapy for opioid use disorder. Background: Breastfeeding has additional benefits for newborns with prenatal opioid exposure. Up to 80% of women on opioid maintenance therapy plan to breastfeed, but many do not beyond the first 7 to 10 days. Methods: A qualitative, longitudinal design was used. Semi-structured interviews occurred during the third trimester of pregnancy and again between 1 and 6 weeks postpartum. Thematic analysis was conducted using the Breastfeeding in a Life Course Context model as a framework. The design and methods were informed by a post-positivist, critical realist perspective. Results: Thirteen participants were enrolled, and 19 interviews were completed. Five themes were identified. It Will Work Out was the primary theme that describes participants' sense of self-efficacy, stemming from their experiences of managing addiction recovery. Women considered breastfeeding to support their own health and that of their newborn while in recovery, summarized by Being Healthy. Making the choice to breastfeed, represented by Weighing the Options, was influenced by their perinatal health care providers. During the Sensitive Period, challenges could overwhelm their self-efficacy. Of 9 women, 4 were still breastfeeding when interviewed postpartum, exemplified by Moving On. Conclusions and Implications for Practice: Participants' self-efficacy and motivation to be healthy played a significant role in managing breastfeeding challenges over time. Nursing interventions must empower women's self-efficacy to help them achieve their breastfeeding goals. [ABSTRACT FROM AUTHOR]

Objective: Breastfeeding is the optimal source of nutrition for all infants, but there are limited data on feeding outcomes in infants with neonatal abstinence syndrome (NAS) who are admitted in the neonatal intensive care unit (NICU). Methods: A retrospective cohort study was conducted at a level II/III NICU. Study sample consisted infants with a diagnosis of NAS and those diagnosed with respiratory distress syndrome. The primary outcome was attainment of independent oral feeds, defined as the number of days to transition from full-tube to full oral feeds. Secondary outcomes included length of hospital stay and method (breast or bottle) of oral feeds at the start, at attainment of independent oral feeds, and at hospital discharge. Results: Infants with NAS took significantly longer to attain independent oral feeds than controls (P = .021) and received significantly fewer breastfeeds at the start of oral feeds, at independent oral feeds, and at hospital discharge (P = .000). There was no difference in length of hospital stay between groups. Conclusion: These results suggest that infants with NAS can experience difficulties achieving independent oral feeds and are less likely to receive breastfeeds. Additional support is required to enhance oral feeds in infants with NAS in the NICU. [ABSTRACT FROM AUTHOR]

IntroductionNeonatal abstinence syndrome (NAS) is a complex condition resulting from prenatal substance exposure that has become increasingly prevalent as a result of the opioid epidemic. NAS can lead to long-term developmental challenges. Interdisciplinary teams with experience working with children with disabilities that focus on social determinants of health can be effective at supporting families affected by NAS. Unfortunately, interdisciplinary teams often lack sufficient training, ongoing practice support, and public health policies to support these families. The objective of this project was to determine the feasibility and impact of a National Training Initiative, called Project SCOPE, to improve the capacity of providers to address the needs of children with NAS and their families.MethodsFourteen (14) sites were trained to fidelity in the ECHO model and SCOPE curriculum, and then each team implemented this model for at least one, eight to 12 session series between 2019–2022. The reach, impact, satisfaction, and intention to implement the model were assessed from administrative records, pre/post surveys, and post-session evaluations.ResultsSCOPE state teams delivered the curriculum to 9,392 individuals across 33 US states. Surveys from 2,197 individuals were used for analysis. Most participants (84%) had previous training in trauma informed care, but only 53% had any training on the NAS or the opioid crisis' impact on children. Satisfaction with SCOPE sessions was high (96.4%), and there was a statistically significant increase of self-reported knowledge change from pre- to post-SCOPE. Over 94% reported their skills increased because of participation. Over 97% of participants indicated their motivation to work with this population increased from SCOPE participation and that they could successfully apply what they learned. Almost 70% reported they were “very” or “extremely” likely to use their new skills.DiscussionProject SCOPE is a highly effective and impactful model that can radically improve capacity to support children affected by the opioid epidemic, thereby increasing the capacity of our healthcare system to respond to this epidemic. Moreover, this model can be rapidly deployed and reach a wide geographic region, especially areas that are affected by the opioid crisis and underserved rural communities.

Abstract Background The incidence of neonatal opiate withdrawal syndrome (NOWS) in the US has grown dramatically over the past two decades. Many rural hospitals not equipped to manage these patients transfer them to hospitals in bigger cities. Methods We created a curriculum, the NOWS-NM Program, a web-based curriculum training in best practices. To evaluate the curriculum, we conducted pre- and post-surveys of NOWS knowledge, attitudes, and care practices, plus post-curriculum interviews and focus groups. Results Fourteen participants completed both pre- and post-curriculum surveys. They indicated an increase in knowledge and care practices. A small number of respondents expressed negative attitudes about parents of infants with NOWS at pre-test, the training curriculum appeared to have no impact on such attitudes at post-test. Sixteen participants participated in focus groups or interviews. Qualitative data reinforced the positive quantitative results and contradicted the negative survey results, respondents reported that the program did reduce stigma and improve provider/staff interactions with patients. Conclusions This curriculum demonstrated positive impacts on NOWS knowledge and care practices. Incorporating focus on core concepts of trauma-informed care and self-regulation in future iterations of the curriculum may strengthen the opportunity to change attitudes and address the needs expressed by participants and improve care of families and babies with NOWS.

Objective Infants with neonatal opioid withdrawal syndrome (NOWS) have disrupted neurobehavior that requires hospitalization and treatment. This article aimed to evaluate electroencephalography (EEG) abnormalities using amplitude-integrated EEG (aEEG) in NOWS. Study Design Eighteen term born infants with NOWS were recruited prospectively for an observational pilot study. aEEG monitoring was started within 24 hours of recruitment and twice weekly through discharge. aEEG data were analyzed for background and seizures. Severity of withdrawal was monitored using the modified Finnegan scoring (MFS) system. Results Fifteen neonates had complete datasets. Thirteen (87%) had continuous aEEG background in all recordings. None had sleep–wake cyclicity (SWC) at initial recording. Brief seizures were noted in 9 of 15 (60%) infants. Lack of SWC was associated with higher MFS scores. At discharge, 8 of 15 (53%) had absent or emerging SWC. Conclusion aEEG abnormalities (absent SWC) are frequent and persist despite treatment at the time of discharge in the majority of patients with NOWS. Brief electrographic seizures are common. Neonates with persistent aEEG abnormalities at discharge warrant close follow-up. Key Points EEG abnormalities are common and persist after clinical signs resolve in patients with NOWS. Short subclinical seizures may be seen. aEEG may identify neonates who need follow-up. [ABSTRACT FROM AUTHOR]

Background: The incidence of neonatal opiate withdrawal syndrome (NOWS) in the US has grown dramatically over the past two decades. Many rural hospitals not equipped to manage these patients transfer them to hospitals in bigger cities. Methods: We created a curriculum, the NOWS-NM Program, a web-based curriculum training in best practices. To evaluate the curriculum, we conducted pre- and post-surveys of NOWS knowledge, attitudes, and care practices, plus post-curriculum interviews and focus groups. Results: Fourteen participants completed both pre- and post-curriculum surveys. They indicated an increase in knowledge and care practices. A small number of respondents expressed negative attitudes about parents of infants with NOWS at pre-test, the training curriculum appeared to have no impact on such attitudes at post-test. Sixteen participants participated in focus groups or interviews. Qualitative data reinforced the positive quantitative results and contradicted the negative survey results, respondents reported that the program did reduce stigma and improve provider/staff interactions with patients. Conclusions: This curriculum demonstrated positive impacts on NOWS knowledge and care practices. Incorporating focus on core concepts of trauma-informed care and self-regulation in future iterations of the curriculum may strengthen the opportunity to change attitudes and address the needs expressed by participants and improve care of families and babies with NOWS. Significance: This project evaluates a novel curriculum covering best practices in care of infants with neonatal opiate withdrawal syndrome (NOWS) and is oriented toward supporting care in rural NM hospitals. We evaluated the curriculum with both quantitative and qualitative methods. Results support the effectiveness of the curriculum to increase competence of rural providers in the care of patients with NOWS. The NOWS-NM Program is a novel and effective mobile training tool that can easily be accessed by under-resourced, rural hospital providers using an internet-connected device such as a smart phone, laptop or tablet. [ABSTRACT FROM AUTHOR]

BackgroundThe rising incidence of drug abuse among pregnant women has rendered neonatal opioid withdrawal syndrome a significant global health concern.MethodsDatabases including PubMed, Web of Science, the Cochrane Library, Embase, Elton B. Stephens. Company (EBSCO), China National Knowledge Infrastructure (CNKI), and Wanfang were searched for comparative studies of the Eat, Sleep, Console model vs. traditional assessment tools for neonatal opioid withdrawal syndrome. Two reviewers conducted literature searches, screened according to the inclusion criteria, extracted data, and independently verified accuracy. All meta-analyses were conducted using Review Manager Version 5.4.ResultsIn total, 18 studies involving 4,639 neonates were included in the meta-analysis. The Eat, Sleep, Console model demonstrated superior outcomes in assessing neonatal opioid withdrawal syndrome, significantly reducing the need for pharmacological treatment [risk ratio = 0.44, 95% confidence interval (CI) = 0.34–0.56, P

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. [ABSTRACT FROM AUTHOR]

Objective: The opioid epidemic has led to a surge in diagnoses of neonatal opioid withdrawal syndrome (NOWS). Many states track the incidence of NOWS by using the P96.1 International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) code for "neonatal withdrawal symptoms from maternal use of drugs of addiction." In October 2018, an ICD-10-CM code for neonatal opioid exposure (P04.14) was introduced. This code can be used when an infant is exposed to opioids in utero but does not have clinically significant withdrawal symptoms. We analyzed the effect of the P04.14 code on the incidence rate of NOWS (P96.1) and "other" neonatal drug exposure diagnoses (P04.49). Methods: We used private health insurance data collected for infants in the United States from the first quarter of 2016 through the third quarter of 2021 to describe incidence rates for each code over time and examine absolute and percentage changes before and after the introduction of code P04.14. Results: The exclusive use of code P96.1 declined from an incidence rate per 1000 births of 1.08 in 2016-2018 to 0.70 in 2019-2021, a −35.7% (95% CI, −47.6% to −23.8%) reduction. Use of code P04.49 only declined from an incidence rate of 2.34 in 2016-2018 to 1.64 in 2019-2021, a −30.0% (95% CI, −36.4% to −23.7%) reduction. Use of multiple codes during the course of treatment increased from an average incidence per 1000 births of 0.56 in 2016-2018 to 0.79 in 2019-2021, a 45.5% (95% CI, 24.8%-66.1%) increase. Conclusion: The introduction of ICD-10-CM code P04.14 altered the use of other neonatal opioid exposure codes. The use of multiple codes increased, indicating that some ambiguity may exist about which ICD-10-CM code is most appropriate for a given set of symptoms. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study is to explore the early parenting experiences among a cohort of postpartum individuals with opioid use disorder (OUD) both during and after the delivery hospitalization to identify areas of intervention to strengthen bonding and attachment. Methods: Semistructured qualitative interviews with recently pregnant people with OUD assessed parenting needs, supports, and goals in the context of the demands of addiction treatment and early motherhood. Probes explored the relationship between early parenting experiences, addiction, and recovery, as well as enabling factors and barriers to mother-infant bonding. Interviews were completed between 2019 to 2020. A constant comparative methods approach was used for codebook development and analysis. Results: Twenty-sixwomen completed interviews amean of 10.1 months postpartum. Twenty-four women were receiving methadone or buprenorphine treatment at delivery for OUD. Four interrelated themes emerged. Women experienced the following: (1) increased surveillance from healthcare workerswho doubted their parenting ability; (2) a desire for a "normal" early parenting experience that was not disrupted by increased medical monitoring and surveillance; (3) complex and intersecting identities of being both a mother and a person in recovery; and (4) the importance of support from and advocacy by clinicians and peers to developing maternal confidence and connection. Conclusions: Interventions are needed to improve the early parenting experiences of opioid-exposed mother-infant dyads, to address the mutual mistrust between health care providers and parents, and to provide additional supports to families. Promotion of positive attachment and parental self-efficacy should be prioritized over increased surveillance and scrutiny to sustain maternal recovery trajectories into early childhood and foster family well-being. [ABSTRACT FROM AUTHOR]

Background and Objectives: Parenting women in treatment for opioid use disorder (OUD) report a lack of family centeredness and anticipatory guidancewithin well child care (WCC), andWCC utilization is low among affected children. We explore priorities for WCC visit content to inform primary care recommendations for this population. Methods: This study is a qualitative study of parenting women from one urban, academic OUD treatment program and pediatric primary care clinicians from a nearby affiliated pediatric practice. Eligible parent participants had a child =2 years old and were English speaking. Semistructured interviews elicited perspectives on WCC, with questions and prompts related to visit content. Inductive thematic analysis was led by 2 investigators using open coding procedures. Results:Among 30 parent participants, the majority were White (83%) and unmarried (90%). Approximately 60% reported their child received pharmacotherapy for neonatal opioid withdrawal syndrome. Of 13 participating clinicians, 9 were attending pediatricians. Five themes emerged from parental and clinician interviews: (1) improving knowledge and confidence related to child development, behavior, and nutrition; (2) mitigating safety concerns; (3) addressing complex health and subspecialty needs through care coordination; (4) acknowledging parental health and wellbeing in the pediatric encounter; and (5) supporting health education and care related to neonatal opioid withdrawal syndrome. Parents and clinicians expressed difficulty comprehensively addressing such issues due to time constraints, social determinants of health, and significant informational needs. Conclusions: Parenting women in treatment for OUD and pediatric clinicians share multiple priorities for anticipatory guidance withinWCC visits and barriers to addressing them comprehensively. [ABSTRACT FROM AUTHOR]

Abstract Background Growing research points to potential long-term developmental implications of prenatal opioid exposure for children. Yet, polysubstance use and adverse childhood experiences are raised as potential confounders. Further, there is a lack of data on school-age children and the children’s strengths. Methods Parents and caregivers of children with prenatal opioid exposure worked with the study team to design, collect, and descriptively analyze mixed method data. Data were collected through survey (n = 148) and two focus groups (n = 15) from a convenience sample in mostly West Virginia and Massachusetts. Results Nearly half of the children in the sample were diagnosed with multiple developmental delays, behavioral health conditions, and specific learning disorders. Roughly 85% of children have behavioral challenges. Associations between prenatal opioid exposure and negative developmental outcomes did not vary by type of opioid nor by polysubstance use, while controlling for adverse childhood experiences. Importantly, over 80% of families also reported their child’s strengths, including empathy, social magnetism, and their resilience. Conclusions The challenges for children born with prenatal opioid exposure may extend into school-age. The results are consistent with prior research on younger children, suggesting a need for best practices for caring for these children beyond the neonatal stage.

The impact of the opioid epidemic on pregnant people and children is a growing public health crisis. Understanding how opioids affect the developing brain during pregnancy and postnatally remains a critical area of investigation. Biological sex plays a crucial role in all physiologic processes, with the potential for a significant impact on neonatal outcomes, including those infants with opioid exposure. Here, we aim to explore current literature on the effect of sex on neonatal outcomes following prenatal opioid exposure. Sex differences in adults with opioid use disorder have been well studied, including increased mortality among males and higher rates of psychiatric comorbidities and likelihood of relapse in females. However, such differences are not yet well understood in neonates. Emerging clinical data suggest sex-specific effects in infants with prenatal opioid exposure on the expression of genes related to feeding regulation and reward signaling pathways. Increased susceptibility to white matter injury has also been noted in female infants following prenatal opioid exposure. Understanding the impact of sex as a biological variable on neonatal outcomes following prenatal opioid exposure is paramount to improving the health and well-being of infants, children, and adults impacted by the opioid epidemic.

The increasing use of opioids in pregnant women has led to an alarming rise in the number of cases of neonates with drug-induced withdrawal symptoms known as neonatal opioid withdrawal syndrome (NOWS). NOWS is a toxic heterogeneous condition with many neurologic, autonomic, and gastrointestinal symptoms including poor feeding, irritability, tachycardia, hypertension, respiratory defects, tremors, hyperthermia, and weight loss. Paradoxically, for the management of NOWS, low doses of morphine, methadone, or buprenorphine are administered. NOWS is a polygenic disorder supported by studies of genomic variation in opioid-related genes. Single-nucleotide polymorphisms (SNPs) in CYP2B6 are associated with variations in NOWS infant responses to methadone and SNPs in the OPRM1, ABCB1, and COMT genes are associated with need for treatment and length of hospital stay. Epigenetic gene changes showing higher methylation levels in infants and mothers have been associated with more pharmacologic treatment in the case of newborns, and for mothers, longer infant hospital stays. Respiratory disturbances associated with NOWS are not well characterized. Little is known about the effects of opioids on developing neonatal respiratory control and respiratory distress (RD), a potential problem for survival of the neonate. In a rat model to test the effect of maternal opioids on the developing respiratory network and neonatal breathing, maternal-derived methadone increased apneas and lessened RD in neonates at postnatal (P) days P0 and P1. From P3, breathing normalized with age suggesting reorganization of respiratory rhythm-generating circuits at a time when the preBötC becomes the dominant inspiratory rhythm generator. In medullary slices containing the preBötC, maternal opioid treatment plus exposure to exogenous opioids showed respiratory activity was maintained in younger but not older neonates. Thus, maternal opioids blunt centrally controlled respiratory frequency responses to exogenous opioids in an age-dependent manner. In the absence of maternal opioid treatment, exogenous opioids abolished burst frequencies at all ages. Prenatal opioid exposure in children stunts growth rate and development while studies of behavior and cognitive ability reveal poor performances. In adults, high rates of attention deficit disorder, hyperactivity, substance abuse, and poor performances in intelligence and memory tests have been reported. [ABSTRACT FROM AUTHOR]

Background: The prevalence of neonatal abstinence syndrome is increasing, but the number and quality of clinical practice guidelines available are unknown. This systematic review aimed to identify, appraise and evaluate clinical practice guidelines for neonatal abstinence syndrome. Methods: A systematic search of databases and the grey literature was conducted between 1 June and 1 July 2022. Full-text guidelines published by national or state-wide institutions were included. The recommendations from each guideline were extracted. The AGREE-II instrument was used to assess guideline quality. Sufficient-quality scores were defined as >60 and good-quality scores were >80 for each domain of AGREE-II. Results: A total of 1703 records were identified, and 22 guidelines from the United States, Australia, Canada and the United Kingdom, published between 2012 to 2021, were included. The quality scores were low, with median scores of 37/100 for stakeholder involvement, 33/100 for methodology, 34/100 for applicability and 0 for editorial independence. Scope and purpose scored 72/100, and presentation scored 85/100. Sixteen (73%) guidelines did not meet the cut-offs for clinical use. Conclusion: Many guidelines were of insufficient quality to guide clinical practice for neonatal abstinence syndrome. This emphasises the need for high-quality studies to inform clinical practice guidelines, improve care and reduce the risk of poor outcomes in these high-risk infants. [ABSTRACT FROM AUTHOR]

Maternal opioid use poses a significant health concern not just to the expectant mother but also to the fetus. Notably, increasing numbers of children born suffering from neonatal opioid withdrawal syndrome (NOWS) further compounds the crisis. While epidemiological research has shown the heightened risk factors associated with NOWS, little research has investigated what molecular mechanisms underly the vulnerabilities these children carry throughout development and into later life. To understand the implications of in utero and post-natal opioid exposure on the developing brain, we sought to assess the response to one of the most common pediatric injuries: minor traumatic brain injury (mTBI). Using a rat model of in utero and post-natal oxycodone (IUO) exposure and a low force weight drop model of mTBI, we show that not only neonatal opioid exposure significantly affects neuroinflammation, brain metabolites, synaptic proteome, mitochondrial function, and altered behavior in juvenile rats, but also, in conjunction with mTBI these aberrations are further exacerbated. Specifically, we observed long term metabolic dysregulation, neuroinflammation, alterations in synaptic mitochondria, and impaired behavior were impacted severely by mTBI. Our research highlights the specific vulnerability caused by IUO exposure to a secondary stressor such as later life brain injury. In summary, we present a comprehensive study to highlight the damaging effects of prenatal opioid abuse in conjunction with mild brain injury on the developing brain.

Background: Growing research points to potential long-term developmental implications of prenatal opioid exposure for children. Yet, polysubstance use and adverse childhood experiences are raised as potential confounders. Further, there is a lack of data on school-age children and the children's strengths. Methods: Parents and caregivers of children with prenatal opioid exposure worked with the study team to design, collect, and descriptively analyze mixed method data. Data were collected through survey (n = 148) and two focus groups (n = 15) from a convenience sample in mostly West Virginia and Massachusetts. Results: Nearly half of the children in the sample were diagnosed with multiple developmental delays, behavioral health conditions, and specific learning disorders. Roughly 85% of children have behavioral challenges. Associations between prenatal opioid exposure and negative developmental outcomes did not vary by type of opioid nor by polysubstance use, while controlling for adverse childhood experiences. Importantly, over 80% of families also reported their child's strengths, including empathy, social magnetism, and their resilience. Conclusions: The challenges for children born with prenatal opioid exposure may extend into school-age. The results are consistent with prior research on younger children, suggesting a need for best practices for caring for these children beyond the neonatal stage. [ABSTRACT FROM AUTHOR]

Objective: Although medications for opioid use disorder improve both maternal and neonatal outcomes, little is known about opioid-exposed infants born during episodes of incarceration. The study sought to ex- amine birth outcomes for infants born with opioid exposure during perinatal incarceration. Methods: Participants were identified from clinic rosters in a South- eastern women’s prison (2016–2019). Included infants born to preg- nant people with opioid use disorder incarcerated in the study facility at the time of delivery. We abstracted hospital length of stay, neonatal opioid withdrawal syndrome (NOWS) severity, and discharge plan from hospital records and report descriptive statistics, analysis of vari- ance F tests, and chi-square tests to compare outcomes by opioid expo- sure type. Results: There were 125 infants born after exposure to methadone (n = 34), buprenorphine (n = 15), oxycodone (n = 22), or no opioid medication (n = 54) during prenatal incarceration. Most infants ex- posed to methadone or buprenorphine had difficulty with eating, sleeping, or consoling (97% and 80%), and 59% and 47% were treated with medication for NOWS, respectively. The majority with prenatal opioid exposure required intervention for NOWS symptoms after their birthing parent was discharged to the prison. The average hospital length of stay was different for infants with no opioid, methadone, buprenorphine, and oxycodone exposure during incarceration (4, 15, 12, and 9 days, respectively, P < 0.001). Conclusions: Neonatal hospitalization experiences of infants with peri- natal opioid exposures during maternal incarceration mirror those of sim- ilarly exposed infants born outside the context of incarceration, except for hospital length of stay. Consideration of avoiding separation of the parent-infant dyad may be needed to improve outcomes for these infants. [ABSTRACT FROM AUTHOR]

OBJeCTiVe We describe a single center experience with gabapentin as adjunctive therapy in infants with neonatal opioid withdrawal syndrome (NOWS). MeTHODS We performed a retrospective chart review of infants receiving gabapentin for NOWS. Data points collected included patient's sex, gestational age, maternal opioid exposure, NOWS medication dosing and length of therapy, number of failed wean attempts, time to successful morphine wean and duration of morphine wean, length of stay in the neonatal intensive care unit (NICU), and NOWS medications at discharge. ReSUlTS Six infants received gabapentin as adjunctive treatment for NOWS. All infants failed 2-4 morphine weans before initiation of gabapentin despite the addition of clonidine. All infants that received gabapentin were successfully weaned off morphine. The time to wean off morphine after gabapentin initiation varied from 4-35 days. Maximum gabapentin doses ranged from 15 - 42.7 mg/kg/day. Five infants were discharged from the NICU on gabapentin. COnClUSiOnS Gabapentin appeared to facilitate successful morphine weans in six patients with NOWS who were previously unable to wean despite the initiation of clonidine. [ABSTRACT FROM AUTHOR]

Introduction: Evidence of opioid use at hospital delivery has increased over the past two decades, increasing risk of neonatal withdrawal. Breastfeeding may improve infant outcomes, but little is known about breastfeeding experiences of women who have a history of opioid use prior to or during pregnancy. This study aimed to determine if self-reported opioid use prior to or during pregnancy impacted breastfeeding, specifically attempt to breastfeed, duration of breastfeeding, assessment of prenatal breastfeeding intention, source of breastfeeding information, and early hospital experiences. Methods: Data from ten states (n = 10,550) that evaluated opioid use in the 2016 Pregnancy Risk Assessment Monitoring System survey were included. Weighted univariate and multivariate linear and logistic regression were calculated. The multivariate regression also included adjustment for covariates. Results: Among the overall sample, 939 participants reported opioid exposure before or during pregnancy. We found no significant difference in breastfeeding attempt. Breastfeeding for at least 6, 10, or 20 weeks was significantly less likely in participants reporting opioid exposure. Exposure correlated with lower odds of skin-to-skin contact, infant being fed in the first hour, exclusive breastfeeding in the hospital, and feeding on demand. Hospital pacifier use was associated with opioid exposure. Conclusion: While we found no difference in breastfeeding attempt, we did observe significant differences in breastfeeding duration and early hospital experiences which may represent modifiable gaps in clinical practice. Future work should focus on optimizing early hospital experiences and support when breastfeeding is clinically indicated. [ABSTRACT FROM AUTHOR]

In recent years, there has been a sixfold increase in the number of pregnant people with opioid use disorder (OUD). Rates of neonatal opioid withdrawal syndrome (NOWS), previously known as neonatal abstinence syndrome (NAS), have significantly increased in virtually every state and demographic group (Healthcare Cost Utilization Project, HCUP, 2010). NOWS is a condition resulting from chronic exposure to either therapeutic opioid use (e.g., medication for OUD, chronic pain conditions) or nonprescribed opioid use. To date, there is no known prenatal treatment to help decrease the risk of infants developing NOWS and subsequent neurodevelopmental outcomes. Given the increasing support for how placental signaling, or placental programming, may play a role in downstream pathology, prospective research investigating how the placenta is affected by chronic opioid exposure morphologically, histologically, and at the cellular level may open up potential treatment opportunities in this field. In this review, we discuss literature exploring the physiological roles of nitric oxide and dopamine not only in the vascular development of the placenta, but also in fetal cerebral blood flow, neurogenesis, neuronal differentiation, and neuronal activity. We also discuss histological preclinical studies that suggest chronic opioid exposure to induce some combination of placental dysfunction and hypoxia in a manner similar to other well‐known placental pathologies, as denoted by the compensatory neovascularization and increased utilization of the placenta's supply of trophoblast cells, which play an essential role in placental angiogenesis. Overall, we found that the current literature, while limited, suggests chronic opioid exposure negatively impacts placental function and fetal brain development on a cellular and histopathological level. We conclude that it is worthwhile to consider the placenta as a therapeutic target with the ultimate goal of decreasing the incidence of NOWS and the long‐term impacts of prenatal opioid exposure. [ABSTRACT FROM AUTHOR]

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.

Introduction: Current WHO guidelines recommend using methadone or buprenorphine as maintenance treatments for maternal opioid use disorder. However, buprenorphine‐naloxone, with a lower abuse risk than buprenorphine monotherapy or methadone, offers a potentially beneficial alternative, but scientific evidence on its effects on pregnancies, fetuses, and newborns is scarce. This paper compares the outcomes of the pregnancies, deliveries, and newborns of women on buprenorphine‐naloxone, buprenorphine, or methadone maintenance treatments. According to the hypothesis, as a maintenance treatment, buprenorphine‐naloxone does not have more adverse effects than buprenorphine, whereas methadone is more complicated. Material and methods: In this population‐based study, 172 pregnant women on medical‐assisted treatments were followed‐up at Helsinki University Women's Hospital (Finland). Women receiving the same opioid maintenance treatment from conception to delivery and their newborns were included. Consequently, 67 mother–child dyads met the final inclusion criteria. They were divided into three groups based on their opioid pharmacotherapy. The outcomes were compared among the groups and, where applicable, with the Finnish population. Results: The buprenorphine‐naloxone and buprenorphine groups showed similar outcomes and did not significantly differ from each other in terms of maternal health during pregnancies, deliveries, or newborns. Illicit drug use during the pregnancy was common in all groups, but in the methadone group it was most common (p = 0.001). Most neonates (96%) were born full‐term with good Apgar scores. They were of relatively small birth size, with those in the methadone group tending to be the smallest. Of the neonates 63% needed pharmacological treatment for neonatal opioid withdrawal syndrome. The need was lower in the buprenorphine‐based groups than in the methadone group (p = 0.029). Conclusions: Buprenorphine‐naloxone seems to be as safe for pharmacotherapy for maternal opioid use disorder as buprenorphine monotherapy for both mother and newborn. Hence it could be a choice for oral opioid maintenance treatment during pregnancy, but larger studies are needed before changing the official recommendations. Women on methadone treatment carry multifactorial risks and require particularly cautious follow up. Furthermore, illicit drug use is common in all treatment groups and needs to be considered for all patients with opioid use disorder. [ABSTRACT FROM AUTHOR]

Background: Infants, children, and youth in foster care have frequently experienced prenatal substance exposure (PSE), neglect, and maltreatment as well as disruptions in their relationships with families. They also have great capacity for overcoming early adversities. In this synthesis of two previously conducted scoping reviews, we aimed to identify and describe literature that identifies a range of interventions that support the health and development of this population. Methods: This review integrates and extends two previously conducted scoping reviews, one focusing on infants and one focusing on children and youth, to synthesize themes across these developmental stages. The Joanna Briggs Institute scoping review methodology was employed for the current and previous reviews. A three-step search strategy identified published studies in the English language from January 2006 to February 2020. Results: One-hundred and fifty-three sources were included in this review. Four themes were identified: (1) early screening, diagnosis, and intervention; (2) providing theoretically grounded care; (3) supporting parents and foster care providers; and (4) intersectoral collaboration. Conclusion:Infants, children, and youth with PSE are overrepresented in foster care. Child welfare system planning should take a multi-sectoral approach to addressing the cumulative needs of this population and their care providers over developmental ages and stages. Although research remains limited, early screening, diagnosis, and developmentally and fetal alcohol spectrum disorder-informed intersectoral interventions are critical for optimizing outcomes. [ABSTRACT FROM AUTHOR]

Birthing people with opioid use disorder (OUD) face unique stressors during the transition from pregnancy to postpartum that can negatively impact the maternal–infant dyad. This study aimed to describe the development of a family-centered, technology-delivered intervention tailored to help pregnant people receiving medication for OUD (MOUD) prepare for this transition. Formative data from patients and providers identified intervention content: (1) recovery-oriented strategies for the pregnancy-to-postpartum transition; (2) guidance around caring for an infant with opioid withdrawal symptoms; and (3) preparation for child welfare interactions. The content was reviewed in successive rounds by an expert panel and modified. Pregnant and postpartum people receiving MOUD pre-tested the intervention modules and provided feedback in semi-structured interviews. The multidisciplinary expert panel members (n = 15) identified strengths and areas for improvement. Primary areas for improvement included adding content, providing more structure to help participants navigate the intervention more easily, and revising language. Pre-testing participants (n = 9) highlighted four themes: reactions to intervention content, navigability of the intervention, feasibility of the intervention, and recommendation of the intervention. All iterative feedback was incorporated into the final intervention modules for the prospective randomized clinical trial. Family-centered interventions tailored for pregnant people receiving MOUD should be informed by patient-reported needs and multidisciplinary perspectives. [ABSTRACT FROM AUTHOR]

Abstract Background Neonatal Opioid Withdrawal Syndrome (NOWS) is a significant public health issue and while millions of neonates are affected each year, an optimal pharmacologic weaning protocol has yet to be demonstrated. In this study, we compare hospital length of stay (LOS) and length of treatment (LOT) for treatment of neonatal opioid withdrawal (NOWS) with morphine versus methadone. Methods This was a single-site, open-label, randomized controlled pilot study conducted from October 2016-September 2018. Infants were eligible if their primary in-utero drug exposure was heroin, oral opioids, or methadone and they were born at greater than or equal to 34 weeks gestation. Infants were excluded for serious medical comorbidities and primary in-utero exposure to buprenorphine. Results Sixty-one infants were enrolled; 30 were randomized to methadone treatment, and 31 to morphine treatment. Overall 46% of infants required treatment for NOWS. LOS and LOT for infants treated with morphine was 17.9 days and 14.7 days respectively, compared to 16.1 days and 12.8 days for babies treated with methadone (p = 0.5, p = 0.54). Infants treated with morphine received lower total morphine equivalents than those treated with methadone (9.7 vs. 33, p

Neonatal Opioid Withdrawal Syndrome (NOWS) requires advanced and often prolonged medical care in the neonatal intensive care unit (NICU). We examined the effect of NICU design on treatment and NICU length of stay (NICU-LOS) for infants with NOWS.A retrospective chart review of eligible infants with NOWS was conducted from 2013 to 2018. We collected and analyzed data on demographics, medication, and NICU-LOS characteristics. A multivariable linear regression on log-transformed NICU-LOS was performed for comparison between the open-bay design (OBD) for 2013–2015 (August) and the new single-family-room (SFR) NICU for September 2015–2018.There were 118 neonates analyzed in OBD and 138 neonates in the SFR. Among infants in the SFR NICU, 86% received pharmacotherapy, compared to 76% of infants in the OBD (p = 0.059). The breastfeeding rate was 26% in the SFR and 6% in the OBD (p =< 0.001 ). Infants in the SFR NICU had 1.3 times longer mean NICU-LOS (p = 0.0163) than infants in OBD after adjusting for covariates including small for gestational age. The median (1Q, 3Q) cumulative doses of morphine (mg/kg) among the SFR and OBD groups were 6.4 (2.3,17.3) and 8.7 (3.2,19.3) p: NS, respectively.The SFR NICU was associated with longer NICU-LOS for infants with NOWS despite higher rates of breastfeeding and no difference in morphine dosage. While providing more privacy and possible improved patient satisfaction, there may be unintended consequences of the SFR design. [ABSTRACT FROM AUTHOR]

Background: The prevalence of neonatal abstinence syndrome is increasing, but the number and quality of clinical practice guidelines available are unknown. This systematic review aimed to identify, appraise and evaluate clinical practice guidelines for neonatal abstinence syndrome. Methods: A systematic search of databases and the grey literature was conducted between 1 June and 1 July 2022. Full-text guidelines published by national or state-wide institutions were included. The recommendations from each guideline were extracted. The AGREE-II instrument was used to assess guideline quality. Sufficient-quality scores were defined as >60 and good-quality scores were >80 for each domain of AGREE-II. Results: A total of 1703 records were identified, and 22 guidelines from the United States, Australia, Canada and the United Kingdom, published between 2012 to 2021, were included. The quality scores were low, with median scores of 37/100 for stakeholder involvement, 33/100 for methodology, 34/100 for applicability and 0 for editorial independence. Scope and purpose scored 72/100, and presentation scored 85/100. Sixteen (73%) guidelines did not meet the cut-offs for clinical use. Conclusion: Many guidelines were of insufficient quality to guide clinical practice for neonatal abstinence syndrome. This emphasises the need for high-quality studies to inform clinical practice guidelines, improve care and reduce the risk of poor outcomes in these high-risk infants.

Neonatal abstinence syndrome (NAS) due to maternal opioid use affects both term and preterm infants; however, the relationship between gestational age and clinical symptomatology is still poorly understood. In this study, we compared the clinical features and outcomes of NAS in infants admitted to a neonatal intensive care unit (NICU) based on gestational age groups: preterm (32–36 6/7 weeks) and term (37 weeks or older). A retrospective data analysis was conducted using the medical records of infants with a diagnosis of NAS admitted to a regional perinatal center between 2014 and 2020. A modified Finnegan scoring system was used based on three different symptom categories, including Central Nervous System (CNS), Gastrointestinal (GI) and Other. In total, 166 infants with a diagnosis of NAS were included, with 52 (31%) who were preterm and 114 (69%) who were term. The highest NAS score was significantly lower for the preterm group than for the term group. Preterm infants were less likely to require first-line pharmacotherapy with morphine (52% versus 75%) and to experience GI symptoms during their hospitalization. Newer NAS assessment modalities, such as eat, sleep, console (ESC), may overcome the existing challenges of traditional scoring systems, but will require validation in preterm infants.

Background: Placental cytochrome p450 (CYP450) enzymes and efflux transporters, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), are critical for transfer of drugs from the placenta to maternal circulation. CYP19A1 (aromatase) is the enzyme responsible for metabolizing methadone and buprenorphine in the human placenta. Objective: We sought to determine if differences exist in CYP19A1 and efflux transporter immunostaining intensity and density within the syncytiotrophoblast in opioid-exposed and unexposed pregnancies. Additionally, we sought to investigate whether CYP19A1 and efflux transporter expression was different in placentas of infants who developed severe neonatal opioid withdrawal syndrome (NOWS) and those who did not. Study design: This was a retrospective nested case control study from 2014 to 2019 at a single tertiary care center. The opioid-exposed cohort included pregnant women aged ≥18 years on maintenance methadone or buprenorphine with non-anomalous singleton fetuses and gestational age ≥33 weeks. Controls included pregnant women with no medication exposure delivering at ≥37 weeks. De-paraffinized placental sections, inclusive of the apical syncytiotrophoblast membrane, were labeled with monoclonal antibodies for aromatase, P-gp, and BCRP. Placentas were scored for the presence and intensity of staining using the Allred scoring schema. Data were analyzed using descriptive, parametric, and nonparametric statistics. p < .05 was considered significant. Results: One hundred and ten opioid-exposed neonates were included in this analysis (51 opioid-exposed cases and 59 opioid-exposed controls), with 68/110 delivering at term. Ten unexposed controls delivering at term were also included. The median placental Allred scores for aromatase were significantly lower in the opioid-exposed cohort compared with the unexposed controls (exposed 6.8 ± 1.4 vs. unexposed 7.5 ± 0.7, p = .03). The median placental Allred scores for aromatase were significantly lower in opioid-exposed cases that developed severe NOWS compared to opioid-exposed controls (p = .03) that did not develop severe NOWS. There were no differences in P-gp and BCRP scores between groups. Conclusions: Syncytiotrophoblast aromatase immunostaining scores were reduced in opioidexposed cases compared to unexposed controls. Additionally, infants who developed severe NOWS had significantly lower placental aromatase in the apical syncytiotrophoblast compared with those without severe NOWS. [ABSTRACT FROM AUTHOR]

Objective Neonatal opioid withdrawal syndrome (NOWS) can occur in newborns exposed to opioids in pregnancy. Opioids delay gastric emptying and inhibit gastric motility in adults, but little is known about their effect in the fetus. We sought to assess gastric area ratio (GAR) in opioid-exposed fetuses. Study Design Retrospective cohort study including opioid-exposed maternal-neonatal dyads between 2007–2017. Primary outcome: severe NOWS (three consecutive Finnegan scores ≥8 or three scores totaling ≥24 within 96 h of life). GAR: (gastric area)/(transverse abdominal area) × 100. Data analysis was by descriptive, parametric, and non-parametric tests. Results Forty-nine maternal-neonatal dyads were included, 67% (n = 33) with severe NOWS. GAR <95th percentile for gestational age was seen in 80% of neonates (n = 39). However, GAR was not different between groups (p = .90) and did not predict severe NOWS. Conclusion Fetal GAR was <95th percentile in 80% of opioid-exposed neonates. However, fetal GAR may not predict NOWS treatment. [ABSTRACT FROM AUTHOR]

Objective To assess the cost effectiveness of buprenorphine versus methadone in the management of opioid use disorder (OUD) during pregnancy. Methods We designed a decision-analytic model to evaluate the costs and outcomes associated with buprenorphine compared to methadone for pregnant people with OUD. We used a theoretical cohort of 22,400 pregnant people, which is an estimation of pregnancies affected by OUD per year in the United States. Outcomes included maternal retention in maintenance treatment, neonatal opioid withdrawal syndrome, preterm birth, fetal growth restriction, cerebral palsy, and maternal overdose in addition to cost and quality-adjusted life-years (QALYs). We used a willingness-to-pay threshold of $100,000/QALY. All model inputs were derived from the literature and varied in sensitivity analyses to assess the robustness of our baseline inputs. Results In our theoretical cohort, treatment of OUD with buprenorphine during pregnancy resulted in 2413 fewer cases of neonatal opioid withdrawal syndrome, 1089 fewer preterm births, 299 fewer cases of fetal growth restriction, 32 fewer stillbirths, and 13 fewer cases of cerebral palsy compared to methadone treatment. Despite lower rates of retention, buprenorphine treatment saved nearly 123 million healthcare dollars and resulted in 558 additional QALYs, making it the dominant strategy compared to methadone treatment. Our findings were robust over a wide range of assumptions. Conclusion Our data suggest that buprenorphine should be considered a cost effective treatment option for OUD in pregnancy, as it is associated with improved neonatal outcomes compared to methadone despite the risk of treatment discontinuation. [ABSTRACT FROM AUTHOR]

OBJECTIVE Lack of a standardized opioid wean guideline for the treatment of neonatal abstinence syndrome (NAS) has the potential to increase the length of the wean and subsequently the length of stay for neonates in the neonatal intensive care unit (NICU). The purpose of this study was to assess the effect of a pharmacist-driven methadone stewardship program for NAS treatment. METHODS The NAS stewardship program consisted of provider, pharmacist, and nursing education, a pharmacy surveillance system rule, and an updated clinical practice guideline. The pre- and postintervention period were defined as patients admitted to the NICU from July 2019-October 2019 and August 2020--November 2020, respectively. The primary objective was to assess the effect of the stewardship program on the duration of opioid treatment in days. Secondary outcomes included number of dose titrations and length of hospital stay. RESULTS A total of 21 patients were included in this study. Neonates treated following the adoption of the stewardship program (n = 8) experienced a 34% decreased median duration of treatment (29 days vs 19 days; p = 0.84). Secondary endpoints of median number of titrations and length of stay were decreased by 15% (1.5 titrations; p = 0.52) and 24% (8 days; p = 0.85), respectively, leading to an average cost savings of $60,020 per patient. CONCLUSIONS Implementation of a standardized stewardship guideline for treatment of NAS resulted in a favorable decrease in all considered endpoints. Implications of the study further support the need for more evidence-based standardized guidelines for optimal treatment of patients with NAS. [ABSTRACT FROM AUTHOR]

Policy PointsOver the past several decades, states have adopted policies intended to address prenatal drug use. Many of these policies have utilized existing child welfare mechanisms despite potential adverse effects. Recent federal policy changes were intended to facilitate care for substance‐exposed infants and their families, but state uptake has been incomplete.Using legal mapping and qualitative interviews, we examine the development of state child welfare laws related to substance use in pregnancy from 1974 to 2019, with a particular focus on laws adopted between 2009 and 2019. Our findings reveal policies that may disincentivize treatment‐seeking and widespread implementation challenges, suggesting a need for new treatment‐oriented policies and refined state and federal guidance. Context: Amid increasing drug use among pregnant individuals, legislators have pursued policies intended to reduce substance use during pregnancy. Many states have utilized child welfare mechanisms despite evidence that these policies might disincentivize treatment‐seeking. Recent federal changes were intended to facilitate care for substance‐exposed infants and their families, but implementation of these changes at the state level has been slowed and complicated by existing state policies. We seek to provide a timeline of state child welfare laws related to prenatal drug use and describe stakeholder perceptions of implementation. Methods: We catalogued child welfare laws related to prenatal drug use, including laws that defined child abuse and neglect and established child welfare reporting standards, for all 50 states and the District of Columbia (DC), from 1974 to 2019. In the 19 states that changed relevant laws between 2009 and 2019, qualitative interviews were conducted with stakeholders to capture state‐level perspectives on policy implementation. Findings: Twenty‐four states and DC have passed laws classifying prenatal drug use as child abuse or neglect. Thirty‐seven states and DC mandate reporting of suspected prenatal drug use to the state. Qualitative findings suggested variation in implementation within and across states between 2009 and 2019 and revealed that implementation of changes to federal law during that decade, intended to encourage states to provide comprehensive social services and linkages to evidence‐based care to drug‐exposed infants and their families, has been complicated by existing policies and a lack of guidance for practitioners. Conclusions: Many states have enacted laws that may disincentivize treatment‐seeking among pregnant people who use drugs and lead to family separation. To craft effective state laws and support their implementation, state policymakers and practitioners could benefit from a treatment‐oriented approach to prenatal substance use and additional state and federal guidance. [ABSTRACT FROM AUTHOR]

Rationale: In utero opioid exposure is associated with lower weight and a neonatal opioid withdrawal syndrome (NOWS) at birth, along with longer-term adverse neurodevelopmental outcomes and mood disorders. While NOWS is sometimes treated with continued opioids, clinical studies have not addressed if long-term neurobehavioral outcomes are worsened with continued postnatal exposure to opioids. In addition, pre-clinical studies comparing in utero only opioid exposure to continued post-natal opioid administration for withdrawal mitigation are lacking. Objectives: Here, we sought to understand the impact of continued postnatal opioid exposure on long term behavioral consequences. Methods: We implemented a rodent perinatal opioid exposure model of oxycodone (Oxy) exposure that included Oxy exposure until birth (short Oxy) and continued postnatal opioid exposure (long Oxy) spanning gestation through birth and lactation. Results: Short Oxy exposure was associated with a sex-specific increase in weight gain trajectory in adult male mice. Long Oxy exposure caused an increased weight gain trajectory in adult males and alterations in nociceptive processing in females. Importantly, there was no evidence of long-term social behavioral deficits, anxiety, hyperactivity, or memory deficits following short or long Oxy exposure. Conclusions: Our findings suggest that offspring with prolonged opioid exposure experienced some long-term sequelae compared to pups with opioid cessation at birth. These results highlight the potential long-term consequences of opioid administration as a mitigation strategy for clinical NOWS symptomology and suggest alternatives should be explored. [ABSTRACT FROM AUTHOR]

Hospital and community healthcare providers have expressed concerns around the continuity and quality of care for infants with neonatal abstinence syndrome (NAS) during hospitalization and transition home. This qualitative study explored the experiences of hospital and community-based healthcare providers and identified themes related to the management of NAS for mothers and infants. Healthcare providers that cared for women with substance use disorders and/or cared for newborns with NAS in a large urban setting in Canada met inclusion criteria for this study and were interviewed in groups or as individuals. Interview transcripts were reviewed iteratively using inductive thematic analysis to identify an overarching theme linked with primary themes. In total, 45 healthcare providers were interviewed. Qualitative analysis of their experiences derived the overarching theme of hope with five primary themes being: mother/infant, mental health, system, judgement, and knowledge. The study identified gaps in NAS care including fear, stigma, and language. This research demonstrates that programs and interventions that work with mothers and newborns with NAS must foster hope in mothers, families, and in the extended care provider team and improve communication between hospital and community networks. [ABSTRACT FROM AUTHOR]

Introduction: Neonatal abstinence syndrome (NAS) is a complex condition resulting from prenatal substance exposure that has become increasingly prevalent as a result of the opioid epidemic. NAS can lead to long-term developmental challenges. Interdisciplinary teams with experience working with children with disabilities that focus on social determinants of health can be effective at supporting families affected by NAS. Unfortunately, interdisciplinary teams often lack sufficient training, ongoing practice support, and public health policies to support these families. The objective of this project was to determine the feasibility and impact of a National Training Initiative, called Project SCOPE, to improve the capacity of providers to address the needs of children with NAS and their families., Methods: Fourteen (14) sites were trained to fidelity in the ECHO model and SCOPE curriculum, and then each team implemented this model for at least one, eight to 12 session series between 2019-2022. The reach, impact, satisfaction, and intention to implement the model were assessed from administrative records, pre/post surveys, and post-session evaluations., Results: SCOPE state teams delivered the curriculum to 9,392 individuals across 33 US states. Surveys from 2,197 individuals were used for analysis. Most participants (84%) had previous training in trauma informed care, but only 53% had any training on the NAS or the opioid crisis' impact on children. Satisfaction with SCOPE sessions was high (96.4%), and there was a statistically significant increase of self-reported knowledge change from pre- to post-SCOPE. Over 94% reported their skills increased because of participation. Over 97% of participants indicated their motivation to work with this population increased from SCOPE participation and that they could successfully apply what they learned. Almost 70% reported they were "very" or "extremely" likely to use their new skills., Discussion: Project SCOPE is a highly effective and impactful model that can radically improve capacity to support children affected by the opioid epidemic, thereby increasing the capacity of our healthcare system to respond to this epidemic. Moreover, this model can be rapidly deployed and reach a wide geographic region, especially areas that are affected by the opioid crisis and underserved rural communities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Weber, Hardesty, Witwer, Dahl, Bush, Thomas, Baker, Dudley and Moody.)

Concomitant with the opioid epidemic, there has been a rise in pregnant women diagnosed with opioid use disorder and cases of infants born with neonatal opioid withdrawal syndrome (NOWS). NOWS refers to signs and symptoms following cessation of prenatal opioid exposure that comprise neurological, gastrointestinal, and autonomic system dysfunction. A critical indicator of NOWS severity is excessive, high-pitched crying. However, NOWS evaluation is, in large part, subjective, and additional cry features may not be easily recognized during clinical assessment. Thus, there is a need for more objective measures to determine NOWS severity. We used a third trimester-approximate opioid exposure paradigm to model NOWS traits in genetically similar inbred substrains of FVB/N mice (NJ, NCrl, NHsd, and NTac). Pups were injected twice daily from postnatal day 1 (P1) to P14 with morphine (10 mg/kg, s.c.) or saline (20 ml/g, s.c.). Because there were only very minor substrain differences in spontaneous withdrawal-induced ultrasonic vocalization (USV) profiles, we collapsed across substrains to evaluate the effects of morphine withdrawal on additional USV properties. We identified syllable sequences unique to morphine-withdrawn and saline-control FVB/N pups on P7 and P14. We also observed an effect of spontaneous morphine withdrawal on the acoustic properties of USVs and specific syllables on P7 and P14. Multiple withdrawal traits correlated with some acoustic properties of USVs and syllable type emission in morphine-withdrawn FVB/N pups on P7 and P14. These data provide an in-depth investigation of mouse USV syllable profiles and acoustic features during spontaneous neonatal opioid withdrawal in mice., Competing Interests: Competing Interests The authors have nothing to disclose.

Objective: To increase nurses' awareness and use of a human milk feeding (HMF) and opioid use disorder (OUD) standardized care pathway to improve rates of HMF at discharge in opioid-exposed neonates (OENs)., Design: Quality improvement project., Setting/local Problem: Underutilizing an HMF and OUD standardized care pathway in an academic medical center led to declining HMF rates at discharge., Participants: Staff nurses in the women and infants department (N = 311)., Intervention/measurements: Nurses completed an asynchronous online educational module regarding awareness and use of the HMF and OUD standardized care pathway for supporting HMF in OENs. Monthly infographics were placed in each nursing unit to reinforce content. Nurses completed pre- and posteducation surveys to evaluate their knowledge and use of the pathway. After the education, rates of OENs receiving human milk at discharge were collected from the electronic health record., Results: A total of 240 (77.2%) nurses participated in the educational module; awareness of the pathway increased from 91.5% to 97.3%. HMF rate at discharge significantly increased from 29.8% to 59.4% (p = .03)., Conclusion: Improved awareness among nurses of a standardized HMF and OUD care pathway was associated with a doubling of HMF rates at discharge in OENs., (Copyright © 2024 AWHONN. Published by Elsevier Inc. All rights reserved.)

Abstract Background Up to 95% of neonates exposed to opioids in utero experience neonatal opioid withdrawal syndrome at birth. Nonpharmacologic approaches (e.g., breastfeeding; rooming-in; skin-to-skin care) are evidence-based and should be implemented. These approaches, especially breastfeeding, rely on engagement of the neonates’ mothers to help deliver them. However, little is known about the structural and social dynamic context barriers and facilitators to implementing maternal-delivered nonpharmacologic care. Methods Using a qualitative descriptive design, perinatal nurses from a Midwest United States hospital family birthing center, neonatal intensive care unit, and inpatient pediatric unit were interviewed. These units were involved in caring for mothers and neonates affected by opioid use. Telephone interviews followed a semi-structured interview guide developed for this study, were audio-recorded, and lasted about 30–60 min. Interviews were transcribed verbatim and independently analyzed by five investigators using the constant comparative method. Themes were discussed until reaching consensus and subsequently mapped to a conceptual model adapted for this study. Results Twenty-one nurses participated in this study (family birth center, n = 9; neonatal intensive care, n = 6; pediatrics, n = 6). Analysis resulted in four major themes: 1) Lack of education and resources provided to staff and mothers; 2) Importance of interdisciplinary and intradisciplinary care coordination; 3) Flexibility in nurse staffing models for neonatal opioid withdrawal syndrome; and 4) Unit architecture and layout affects maternal involvement. Minor themes supported each of the four major themes. All themes mapped to the conceptual model. Conclusions This study provides a more comprehensive understanding of the barriers and facilitators affecting implementation of maternal involvement in nonpharmacologic care of newborns with neonatal opioid withdrawal syndrome. Future efforts implementing nonpharmacologic approaches must consider the context factors affecting implementation, including structural and social factors within the units, hospital, and broader community.

BACKGROUND: Infants with in-utero exposure to opioids are at risk Neonatal Opioid Withdrawal Syndrome (NOWS) and non-pharmacological methods of care, like swaddling, quiet ambient environment are routinely recommended but are not systematically studied. We hypothesized that opioid exposed infants can tolerate whole body massage while hospitalized. METHODS: This is a prospective observational study (August 2017 to January 2019) and infants of mothers having a history of opioids use (OUD) were included. Infants received whole body massage for 30 minutes from birth till discharge home. Infants heart rate (HR), respiratory rate (RR), systolic (sBP) and diastolic blood pressure (dBP) were recorded prior to and at the end of massage session. RESULTS: The pilot study enrolled 30 infants. The mean birth weight and gestational age were 38±1 weeks and 2868±523 grams, respectively. All massage sessions were well tolerated. There was marked decrease in HR, systolic and diastolic BP and RR, (p < 0.01) in all study infants post massage, more profound among infants with NOWS (p < 0.01) than without NOWS. CONCLUSIONS: Whole body massage is very well tolerated by infants with in-utero opioid exposure. Infants with NOWS had marked decrease in their HR and BP from their baseline after massage. [ABSTRACT FROM AUTHOR]