Maternal continuous oral oxycodone self-administration alters pup affective/social communication but not spatial learning or sensory-motor function.

BACKGROUND: The broad use/misuse of prescription opioids during pregnancy has resulted in a surge of infants with Neonatal Opioid Withdrawal Syndrome (NOWS). Short-term irritability and neurological complications are its hallmarks, but the long-term consequences are unknown. METHODS: A newly-developed preclinical model of oxycodone self-administration enables adult female rats to drink oxycodone (∼10/mg/kg/day) before and during pregnancy, and after delivery, and to maintain normal liquid intake, titrate dosing, and avoid withdrawal. RESULTS: Oxycodone was detected in the serum of mothers and pups. Growth parameters in dams and pups and litter mass and size were similar to controls. There were no differences in paw retraction latency to a thermal stimulus between Oxycodone and Control pups at postnatal (PN) 2 or PN14. Oxycodone and Control pups had similar motor coordination, cliff avoidance, righting time, pivoting, and olfactory spatial learning from PN3 through PN13. Separation-induced ultrasonic vocalizations at PN8 revealed higher call frequency in Oxycodone pups relative to Control pups (p<0.031; Cohen's d=1.026). Finally, Oxycodone pups displayed withdrawal behaviors (p's<0.029; Cohen's d's>0.806), and Oxycodone males only vocalized more than Control pups in the first minute of testing (p's<0.050; Cohen's d's>.866). Significant effects were corroborated by estimation plots. CONCLUSIONS: Our rat model of oral oxycodone self-administration in pregnancy shows exacerbated affect/social communication in pups in a sex-dependent manner but spared cognition and sensory-motor behaviors. This preclinical model reproduces selective aspects of human opioid use during pregnancy, enabling longitudinal analysis of how maternal oxycodone changes emotional behavior in the offspring.

Automated quantification of opioid withdrawal in neonatal rat pups using Ethovision® XT software.

Chronic prenatal exposure to opioids often causes fetal opioid dependence that leads to neonatal opioid withdrawal syndrome (NOWS) shortly after delivery. Rat models of NOWS often require quantifying neonatal withdrawal behaviors using time-consuming, labor-intensive manual scoring methods. The goal of this study was to automate quantification of opioid withdrawal in neonatal rat pups. Accordingly, we used the animal behavior software Ethovision® XT to analyze archived videos of rat pups subjected to precipitated opioid withdrawal testing on postnatal day 0. We compared results obtained from Ethovision® XT with those previously obtained from manual scoring. Two endpoints reported by Ethovision® XT, Distance Moved (cm) and Movement Duration (s), had strong positive linear relationships with manually derived global withdrawal scores (GWS; R2 > 0.73). Sensitivity and specificity of each endpoint to discriminate presence and absence of low-grade withdrawal were assessed by receiver operator characteristic curve analysis, which indicated that Distance Moved and Movement Duration had excellent accuracy (AUC > 0.90). Finally, we analyzed main and interaction effects of prenatal treatment (with vehicle or mu opioid receptor full agonists) and postnatal challenge (with saline or an opioid receptor antagonist) on each endpoint and determined they were similar for the manual and automated methods. These results show that Ethovision® XT software can reliably quantify opioid withdrawal in neonatal rat pups with non-inferiority to manual scoring even in videos that were not originally purposed and optimized for Ethovision® XT analysis. This faster and less labor-intensive method of analysis is expected to accelerate progress in preclinical studies of NOWS.

Do Maternal Pharmacogenetics Impact the Neonatal Abstinence Syndrome Following In Utero Exposure to Antidepressant Medications?

OBJECTIVE: Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are the most commonly used medications for mood and anxiety disorders in women. Many women need to continue or initiate these medications during pregnancy, but there is concern about potential withdrawal effects in the newborn, referred to as neonatal abstinence syndrome (NAS). The reason why some infants remain asymptomatic while others are affected has not been elucidated. The objective of this study was to examine whether genetic differences in maternal drug metabolism influence the incidence of NAS. METHODS: Women who took Selective serotonin reuptake inhibitors s/SNRIs during pregnancy were recruited from obstetrical clinics. DNA was extracted from saliva samples for genetic analyses of cytochrome P450 (CYP) enzyme polymorphisms. Delivery and NAS data were collected from electronic medical records. RESULTS: Ninety-five women participated. The overall NAS rate was 16.2%. Mild NAS was seen in 13.8% of neonates and severe NAS, in 2%. One-quarter (25%) of the neonates with mild withdrawal symptoms were born to mothers with polymorphisms associated with slower metabolism of their particular antidepressant, but this association was not statistically significant. CONCLUSION: Importantly, the overall rate of NAS in our study was lower than previously reported. Maternal CYP polymorphisms did not affect the rate of NAS in neonates exposed to SSRIs/SNRIs in utero. This study lends added assurance to patients requiring SSRIs or SNRIs during pregnancy.

A Mixed-Methods Study to Investigate Barriers and Enablers to Nurses' Implementation of Nonpharmacological Interventions for Infants With Neonatal Abstinence Syndrome.

BACKGROUND: The incidence of neonatal abstinence syndrome has increased significantly as a result of the opioid epidemic. A lengthy hospitalization is often required to treat the infant's withdrawal symptoms. A comprehensive understanding of factors that influence nurses' implementation of nonpharmacological interventions for infants with neonatal abstinence syndrome is needed. PURPOSE: To investigate barriers and enablers to nurses' implementation of nonpharmacological interventions for infants with neonatal abstinence syndrome through the lens of the Theoretical Domains Framework, which provides a structure to examine factors that influence healthcare providers' behavior related to the implementation of evidence-based practice and interventions in clinical practice. METHODS: A convergent parallel mixed-methods study was conducted. Qualitative data were collected using semistructured interviews and quantitative data were collected using a tailored Determinants of Implementation Behavior Questionnaire with neonatal nurses. Findings from the interviews and surveys were merged through joint review to compare and contrast themes. RESULTS: Enablers and barriers to nurses' implementation of nonpharmacological interventions included education, experience, ability to implement nonpharmacological interventions, parental participation, stigmatization, lack of managerial/organizational support, staffing ratios, internal and external resources, and stress. Knowledge, Skills, Beliefs About Capabilities, Social/Professional Role and Identity, Organization, and Emotion of the Theoretical Domains Framework aligned with these themes. IMPLICATIONS FOR PRACTICE AND RESEARCH: Findings from this study will inform the development of programs to improve nurses' implementation of nonpharmacological interventions and health and utilization outcomes in infants with neonatal abstinence syndrome. Furthermore, future work should focus on the development of programs to improve nurses' implementation of nonpharmacological interventions, with specific strategies aimed to mitigate marginalization of vulnerable patient populations.

Engaging Mothers to Implement Nonpharmacological Care for Infants With Neonatal Abstinence Syndrome: Perceptions of Perinatal and Pediatric Nurses.

BACKGROUND: Little is known about nurse perceptions regarding engagement of mothers in implementation of nonpharmacological care for opioid-exposed infants. PURPOSE: This study was designed to describe perinatal and pediatric nurse perceptions of (1) engaging mothers in the care of opioid-exposed infants and (2) facilitators and barriers to maternal engagement. METHODS: This study used a qualitative descriptive design to interview perinatal and pediatric nurses in one Midwest United States hospital. Interviews were conducted via telephone using a semistructured interview guide and audio recorded. Audio files were transcribed verbatim and thematically analyzed using the constant comparative method. RESULTS: Twenty-one nurses participated in the study, representing a family birth center, neonatal intensive care unit, and pediatric unit. Five major themes resulted from analysis: (1) vulnerability and bias; (2) mother-infant care: tasks versus model of care; (3) maternal factors affecting engagement and implementation; (4) nurse factors affecting engagement and implementation; and (5) recommendations and examples of nursing approaches to barriers. Minor themes supported each of the major themes. IMPLICATIONS FOR PRACTICE: Nurses must engage mothers with substance use histories with empathy and nonjudgment, identify and promote maternal agency to care for their infants, and engage and activate mothers to deliver nonpharmacological care during the hospital stay and following discharge. IMPLICATIONS FOR RESEARCH: Findings suggest interventions are needed to improve (1) nursing education regarding maternal substance use and recovery, (2) empathy for substance-using mothers and mothers in treatment, and (3) identification and support of maternal agency to provide nonpharmacological care to withdrawing infants.

The Role of Stigma in the Nursing Care of Families Impacted by Neonatal Abstinence Syndrome.

BACKGROUND: The current US opioid crisis has resulted in a significant increase in opioid use disorder among pregnant and parenting women. Substance use disorders, in general, are highly stigmatized conditions. Stigma serves as a well-documented global barrier to health-seeking behaviors and engagement in healthcare. While extensive research exists on the stigma of mental illness, few studies have explored the stigma experienced by families impacted by neonatal abstinence syndrome (NAS). PURPOSE: Therefore, the purpose of this article is to explore the role of stigma in the care of families impacted by NAS. METHODS: In this article, we present a discussion about the effects of stigma on this patient population and provide exemplars of stigma experiences from our previous research and the existing literature. FINDINGS/RESULTS: Mothers of infants with NAS faced the challenges of overcoming stigma as they were often ostracized, excluded, and shamed. Nurses who provide care for these women and their infants have reported experiencing ethical distress, moral distress, and compassion fatigue. IMPLICATIONS FOR PRACTICE: Greater awareness of the impact of opioid use on the maternal-child population has resulted in numerous educational offerings for healthcare providers; however, this alone is not adequate to end stigma. Fortunately, promising tools and methods have been developed for assisting nurses with addressing stigma in a manner that can be both nonconfrontational and highly effective. IMPLICATIONS FOR RESEARCH: Future research is needed to explore and evaluate the efficacy of various existing strategies for counteracting harmful stigma in this patient population.

A Review of Feeding Practices in Infants With Neonatal Abstinence Syndrome.

BACKGROUND: There has been an increase in infants with neonatal abstinence syndrome (NAS) in neonatal intensive care units (NICUs) over the past several decades. Infants with NAS experience withdrawal as a result of the sudden termination at birth of substance exposure during pregnancy. A serious sign related to infants diagnosed with NAS is poor feeding. The prevalence of NAS urges researchers and clinicians to develop effective strategies and techniques to treat and manage the poor feeding of infants exposed to substances in utero. PURPOSE: To synthesize current feeding methods and practices used for infants diagnosed with NAS. METHODS/SEARCH STRATEGY: PubMed, CINAHL, and Scopus were searched for articles published within the last 20 years that focused on feeding practices or feeding schedules, were written in English, were peer-reviewed, and described human studies. The search terms utilized were "neonatal abstinence syndrome" OR "neonatal opioid withdrawal syndrome" AND "feeding." FINDINGS/RESULTS: Three findings emerged regarding techniques and management of poor feeding in the NAS population. The findings included infants who received mother's own milk had decreased severity and later onset of clinical signs of withdrawal, demand feeding is recommended, and the infant's cues may be helpful to follow when feeding. IMPLICATIONS FOR PRACTICE: Clinicians should encourage mother's own milk in this population unless contraindications are present. Caregivers and clinicians must be receptive to cues when feeding infants with NAS. IMPLICATIONS FOR RESEARCH: Even with the clinical knowledge and experience that infants with NAS are difficult to feed, there is limited research assessing techniques and schedules that are effective in managing successful feeding. Future research should compare feeding schedules such as on-demand feeding versus regimented feeding schedules, as well as investigate techniques that mothers and nurses can utilize to encourage oral intake in this population.Video abstract available at https://journals.lww.com/advancesinneonatalcare/Pages/videogallery.aspx?autoPlay=false&videoId=37.

Childhood Health and Educational Outcomes After Neonatal Abstinence Syndrome: A Systematic Review and Meta-analysis.

OBJECTIVE: To systematically review and meta-analyze the association between neonatal abstinence syndrome (NAS) and adverse health or educational childhood outcomes. STUDY DESIGN: An all-language search was conducted across 11 databases between January 1, 1975, and September 3, 2019; 5865 titles were identified. Observational studies of children between 28 days and 16 years of age, in whom a diagnosis of NAS was documented, were included. Outcomes included reasons for hospital admissions, childhood diagnoses, developmental outcomes, and academic attainment scores. All studies underwent independent review by 2 trained reviewers, who extracted study data and assessed risk of bias using the Newcastle Ottawa Tool. RESULTS: Fifteen studies were identified that included 10 907 children with previous NAS and 1 730 213 children without previous NAS, aged 0-16 years. There was a strong association between NAS and subsequent child maltreatment (aOR, 6.49; 95% CI, 4.46-9.45; I2 = 52%), injuries and poisoning (aOR, 1.34; 95% CI, 1.21-1.49; I2 = 0%), and a variety of mental health conditions. Studies consistently demonstrated an increased incidence of strabismus and nystagmus among those with previous NAS. Children with NAS also had lower mean academic scores than the control group in every domain of testing across age groups. CONCLUSIONS: NAS is significantly associated with future child maltreatment, mental health diagnoses, visual problems, and poor school performance. Owing to the necessary inclusion of nonrandomized studies, incomplete reporting among studies, and likely unadjusted confounding, this review does not suggest causation. However, we highlight associations requiring further investigation and targeted intervention, to positively impact the life course trajectories of this growing population of children.

Engagement in Early Intervention Services Among Mothers in Recovery From Opioid Use Disorders.

BACKGROUND AND OBJECTIVES: Opioid-exposed infants frequently qualify for early intervention (EI). However, many eligible families choose not to enroll in this voluntary service. This study aims to understand the perceptions and experiences that may impact engagement with, and the potential benefits of, EI services among mothers in recovery from opioid use disorders (OUDs). METHODS: We conducted semistructured qualitative interviews (n = 22) and 1 focus group (n = 6) with mothers in recovery from OUDs in western Massachusetts. Transcripts were coded and analyzed by using a descriptive approach. RESULTS: The mean participant age was 32 years, and 13 had a high school degree or less. Five major themes emerged revealing mothers' development through stages of engagement in EI services: (1) fear, guilt, and shame related to drug use (emotions acting as barriers to enrollment); (2) the question of whether it is "needed" (deciding whether there is value in EI for opioid-exposed infants); (3) starting with "judgment" (baseline level of perceived stigma that parents in recovery associate with EI); (4) breaking down the "wall" (how parents overcome the fear and perceived judgment to build partnerships with providers); and (5) "above and beyond" (need for a personal connection with mothers and concrete supports through EI in addition to the child-focused services provided). CONCLUSIONS: Barriers to engagement in EI among mothers in recovery from OUDs include a range of emotions, perceived stigma, and ambivalence. An effort to purposefully listen to and care for mothers through a strengths-based, bigenerational approach may help establish greater connections and foster stronger EI engagement among families affected by OUDs.

One-Year Postpartum Mental Health Outcomes of Mothers of Infants with Neonatal Abstinence Syndrome.

INTRODUCTION: Women with substance use disorders have high incidences of psychiatric and mood disorders, which may affect their ability to cope with an infant with neonatal abstinence syndrome (NAS), particularly one with a protracted NICU course, exacerbating symptoms of mental health disorders. We examined the incidence of mental health diagnoses in the first 12 postpartum months in mothers of an NAS infant compared to mothers of an infant without NAS. METHODS: In this retrospective, cohort study, data were extracted from MarketScan® database (2005-2013). NAS newborns were identified using ICD-9 codes. Each mother of an NAS newborn was matched to a mother of a newborn without NAS on age at delivery, birth year, gestational age, NICU stay and maternal mental health diagnoses in the 9 months prior to delivery. Primary outcomes were claims for major depression, postpartum depression, anxiety, adjustment reaction, post-traumatic stress disorder, and suicidal ideation. RESULTS: 338 mother-infant pairs met all inclusion/exclusion criteria and were matched 1-to-1 with controls. 245 (73%) of the NAS infants had a NICU admission. Median length of stay for these infants was 10 days compared to 3 days for infants with no NICU admission (p < 0.001). Mothers of NAS infants were more likely to have claims for major depression (33% vs. 15%, p < 0.01), postpartum depression (7% vs. 3%, p = 0.04), and anxiety (27% vs. 13%, p < 0.01). CONCLUSION: Mothers of infants with NAS have a higher incidence of mental health diagnoses in the first 12 months postpartum compared to mothers of infants without NAS.

Pharmacokinetic assessment of alprazolam-induced neonatal abstinence syndrome using physiologically based pharmacokinetic model.

Sustained benzodiazepine use during pregnancy can induce neonatal abstinence syndrome (NAS). In this study, the association between NAS and plasma alprazolam concentration was examined using the measured neonatal concentrations in the time series as well as simulated plasma concentrations of pregnant woman and neonate by physiologically based pharmacokinetic (PBPK) modeling. A neonate born to a mother taking alprazolam daily throughout pregnancy exhibited symptoms such as apnea and vomiting from 9 h to 4 days after birth. Finnegan score was 7 at birth and decreased to 0 by day 4. Apnea improved by 24 h post-delivery and gastrointestinal symptoms disappeared by day 4. The plasma alprazolam concentration in the neonate was 15.2 ng/mL immediately after birth and gradually decreased over 3 days. Measured neonate and estimated maternal plasma alprazolam concentrations were within the 90% prediction intervals of each concentration by PBPK simulation using "pregnancy" and "pediatrics" population parameters including in Simcyp population-based ADME simulator. In conclusion, NAS symptoms such as apnea and digestive events disappeared in parallel with the decrease of the neonate's plasma alprazolam concentrations. Moreover, PBPK modeling and simulation is a useful methodology for toxicological assessment in special characteristics populations lacking specific experimental data.

Moral distress of nurses surrounding neonatal abstinence syndrome: Application of a theoretical framework.

TOPIC: Neonatal nurses who care for infants with symptoms of neonatal abstinence syndrome (NAS) may experience moral distress through conflicting professional ethics. The nurse may find it difficult to simultaneously exemplify beneficence and nonmaleficence. OBJECTIVE: The purpose of this paper is to explore the moral distress of nurses in the context of infants experiencing symptoms of NAS and apply a new conceptual model to this phenomenon. Understanding how nurses navigate moral dilemmas may provide insight into strategies to better support them to address moral conflict. METHODS: Moral distress was explored in the context of nurses who care for infants with symptoms of NAS. A literature review was completed, followed by the application of the model onto the derived themes. RESULTS: The theoretical application resulted in a framework that exemplifies the experience of caring for infants with symptoms of NAS and their families described by many nurses within the literature. If moral distress is not resolved, negative outcomes may be experienced by the nurse, with additional negative outcomes experienced by the family. CONCLUSION: This theoretical model provided insight into the experience of moral distress surrounding nursing care for infants with symptoms of NAS. Additional research is needed to investigate moral residue and moral resilience in this particular caregiving dynamic.

Trying to Do What Is Best: A Qualitative Study of Maternal-Infant Bonding and Neonatal Abstinence Syndrome.

BACKGROUND: The maternal experience of caring for and bonding with infants affected by neonatal abstinence syndrome (NAS) has not been adequately characterized. PURPOSE: This study was designed to describe mothers' experiences of, supports for, and barriers to bonding with infants with NAS. METHODS: Semistructured interviews were coded using computer-assisted thematic content analysis. A code co-occurrence model was used to visualize the relationships between themes. RESULTS: Thirteen mothers of infants with NAS participated. Trying to Do What Is Best emerged as the overarching theme with which several subthemes co-occurred. Subthemes that captured mothers loving their infants and bonding, feeling supported by the infants' fathers, feeling supported in the community, and receiving information from hospital staff were associated with mothers' trying to do what is best. Barriers to trying to do what is best included feeling unsupported in the community, guilt about taking medications or substances during pregnancy, feeling judged, and infant withdrawal. IMPLICATIONS FOR PRACTICE: Specific implications for practice may be derived from the mothers' criticisms of NAS assessment tools. Mothers highlighted the value of reassurance and education from providers and the uniquely nonjudgmental support received from peers and male coparents. IMPLICATIONS FOR RESEARCH: There is a lack of information about maternal-infant bonding in dyads affected by NAS and factors that contribute to parental loss of custody. Qualitative, quantitative, and mixed-methods studies in diverse populations might help researchers better understand the long-term outcomes of NAS and develop interventions that decrease family separation.

After NAS.

Mothers have used opioids for thousands of years but neonatal abstinence syndrome (NAS) or rather, survivors of NAS, is a modern phenomenon. Unrecognized and/or untreated opioid withdrawal was almost always fatal but with greater awareness and standardization of treatment, NAS is now an uncommon direct cause of infant death. However, opioids are now increasingly accessible and potent and the outcomes of children after the neonatal period are of great concern, especially when coupled with multiple other social and health risks. Complex individual, environmental and genetic factors need to be considered when assessing outcomes or future research for babies with NAS. Any intervention or research efforts must address these multifactorial complexities. This review will discuss pertinent post neonatal outcomes, including mortality, physical and mental health and social functioning of children with a history of NAS.

Parent's experiences of their child's withdrawal syndrome: a driver for reciprocal nurse-parent partnership in withdrawal assessment.

Withdrawal assessment in critically ill children is complicated by the reliance on non-specific behaviours and compounded when the child's typical behaviours are unknown. The existing approach to withdrawal assessment assumes that nurses elicit the parents' view of the child's behaviours. OBJECTIVE AND RESEARCH METHODOLOGY: This qualitative study explored parents' perspectives of their child's withdrawal and preferences for involvement and participation in withdrawal assessment. Parents of eleven children were interviewed after their child had completed sedation weaning during recovery from critical illness. Data were analysed using thematic analysis. SETTING: A large children's hospital in the Northwest of England. FINDINGS: Parents experienced varying degrees of partnership in the context of withdrawal assessment and identified information deficits which contributed to their distress of parenting a child with withdrawal syndrome. Most parents were eager to participate in withdrawal assessment and reported instances where their knowledge enabled a personalised interpretation of their child's behaviours. Reflecting on the reciprocal nature of the information deficits resulted in the development of a model for nurse-parent collaboration in withdrawal assessment. CONCLUSION: Facilitating nurse-parent collaboration in withdrawal assessment may have reciprocal benefits by moderating parental stress and aiding the assessment and management of withdrawal syndrome.

Problematisation and regulation: Bodies, risk, and recovery within the context of Neonatal Abstinence Syndrome.

BACKGROUND: Neonatal Abstinence Syndrome (NAS) is an anticipated effect of maternal drug use during pregnancy. Yet it remains a contested area of policy and practice. In this paper, we contribute to ongoing debates about the way NAS is understood and responded to, through different treatment regimes, or logics of care. Our analysis examines the role of risk and recovery discourses, and the way in which the bodies of women and babies are conceptualised within these. METHODS: Qualitative interviews with 16 parents (9 mothers, 7 fathers) and four focus groups with 27 health and social care professionals based in Scotland. All the mothers were prescribed opioid replacement therapy and parents were interviewed after their baby was born. Data collection explored understandings about the causes and consequences of NAS and experiences of preparing for, and caring for, a baby with NAS. Data were analysed using a narrative and discursive approach. RESULTS: Parent and professional accounts simultaneously upheld and subverted logics of care which govern maternal drug use and the assessment and care of mother and baby. Despite acknowledging the unpredictability of NAS symptoms and the inability of the women who are opioid-dependent to prevent NAS, logics of care centred on 'proving' risk and recovery. Strategies appealed to the need for caution, intervening and control, and obscured alternative logics of care that focus on improving support for mother-infant dyads and the family as a whole. CONCLUSION: Differing notions of risk and recovery that govern maternal drug use, child welfare and family life both compel and trouble all logics of care. The contentious nature of NAS reflects wider socio-political and moral agendas that ultimately have little to do with meeting the needs of mothers and babies. Fundamental changes in the principles, quality and delivery of care could improve outcomes for families affected by NAS.