Neonatal Abstinence Syndrome Symptoms Research Articles

Gut Microbiota and Symptom Expression and Severity in Neonatal Abstinence Syndrome.

Problem: Neonatal abstinence syndrome (NAS) affecting neonates with fetal exposure to opioids, is defined by expression and severity of symptoms. The pathophysiology behind symptoms variability is lacking. The study aims were to examine (a) differences in gut microbiota of neonates with and without NAS, (b) the relationships between gut microbiota and symptom expression and NAS severity, and (c) the changes in the neonate gut microbiota diversity during the course of NAS treatment. Methods: A cross-sectional observational design was used to examine differences in microbiota and a longitudinal, repeated measures approach was used to determine relationships between gut microbiota and NAS symptoms. Symptom data were collected using the Finnegan Neonatal Abstinence Scoring Tool and the Neonatal Pain Agitation and Sedation Scale. Stool samples were collected for microbiome analyses with 16S rRNA microbiome sequencing. Results: Differences in alpha and beta diversity between neonates with and without NAS were seen. Relative abundance results revealed 18 taxa were different in neonates with NAS compared to neonates without NAS. No differences were found in alpha or beta diversity in neonates with NAS between enrollment and hospital discharge. There was increased abundance of Escherichia-Shigella and Bacteriodes genera related to higher symptom scores. Discussion: Differences in alpha and beta diversity between neonates with and without NAS may be due to differences in birth mode and type of feeding. The findings of specific increased bacteria related to increased symptoms in the neonates with NAS may also be influenced by birth mode and type of feeding.

Neonatal Abstinence Syndrome: Non-pharmacologic Interventions for the Maternal-Infant Dyad

Neonatal Abstinence Syndrome (NAS) remains a concern for health care providers. The incidence of NAS has increased globally, and it has emerged as a worldwide health concern. In our previous article, we explored the efficacy of current pharmacologic treatment for NAS symptoms. Our purpose now is to focus on non-pharmacologic interventions for NAS symptoms and the involvement of caregivers, specifically the mother. We will discuss breastfeeding, rooming in, babywearing, the eat, sleep, console approach, and laser acupuncture. We intend to describe the involvement of the interdisciplinary team and all who care for these infants, including parents.

Do small for gestational age infants have less severe neonatal abstinence syndrome?

Small for gestational age (SGA) infants are likely to have decreased placental transfer of opioids and other substances and lower amounts of fat deposition, hence less severe neonatal abstinence syndrome (NAS). The goal of this study is to correlate SGA status and severity of NAS in infants admitted to the neonatal intensive care unit (NICU). This is a retrospective analysis of term and late-preterm infants (≥35 weeks gestation) exposed to in-utero substances, born between September 2006 and May 2021, and admitted to an inner-city NICU for medical therapy for NAS. Indicators of the severity of NAS (duration of medical treatment, duration of hospitalization, use of phenobarbital, and use of clonidine) were compared between infants characterized as SGA (birth weight <10th percentile for gestational age) to those not categorized as SGA (non-SGA). A total of 992 infants met the study criteria; 205 (20.7%) in the SGA group and 787 (79.3%) in the non-SGA group. The median duration of medical treatment was significantly lower in infants in the SGA group (22 days vs. 26 days, p = 0.04) and they were less likely to be treated with phenobarbital (19% vs. 26.8%, p = 0.02). SGA infants displayed less severe NAS symptoms as indicated by shorter a duration of medical treatment and decreased need for phenobarbital. Our findings may impact decisions around identifying the optimum treatment protocols catered to SGA infants with NAS.

Mechanisms of opioid-induced respiratory depression.

Opioid-induced respiratory depression (OIRD), the primary cause of opioid-induced death, is the neural depression of respiratory drive which, together with a decreased level of consciousness and obstructive sleep apnea, cause ventilatory insufficiency. Variability of responses to opioids and individual differences in physiological and neurological states (e.g., anesthesia, sleep-disordered breathing, concurrent drug administration) add to the risk. Multiple sites can independently exert a depressive effect on breathing, making it unclear which sites are necessary for the induction of OIRD. The generatorof inspiratoryrhythm is the preBötzinger complex (preBötC) in the ventrolateral medulla. Other important brainstem respiratory centres includethe pontine Kölliker-Fuse and adjacent parabrachial nuclei (KF/PBN) in the dorsal lateral pons, and the dorsal respiratory group in the medulla. Deletion of μ opioid receptors from neurons showed that the preBötC and KF/PBN contribute to OIRD with the KF as a respiratory modulator and the preBötC as inspiratory rhythm generator. Glutamatergic neurons expressing NK-1R and somatostatin involved in the autonomic function of breathing, and modulatory signal pathways involvingGIRK and KCNQ potassium channels, remain poorly understood. Reversal of OIRD has relied heavily on naloxone which also reverses analgesia but mismatches between the half-lives of naloxone and opioids can make it difficult to clinically safely avoid OIRD. Maternal opioid use, which is rising, increases apneas and destabilizes neonatal breathing but opioid effects on maternal and neonatal respiratory circuits in neonatal abstinence syndrome (NAS) are not well understood. Methadone, administered to alleviate symptoms of NAS in humans, desensitizes rats to RD.

Comparison of Two Morphine Dosing Strategies in the Management of Neonatal Abstinence Syndrome.

The incidence of neonatal abstinence syndrome (NAS) has increased in recent years. Treatment approaches usually involve opioid replacement; however, the optimal treatment strategy is unknown. This study sought to determine the impact of weight- and symptom-based morphine dosing strategies on LOS and medication exposure in patients with NAS. A retrospective review was conducted from May 2015 to June 2017 at 2 NICUs within a health-system using different dosing approaches for NAS. Data were compared using Fisher exact tests for categorical data and t tests and Wilcoxon ranked sums for continuous data. Baseline demographics were well-matched except for postmenstrual age at morphine initiation (p = 0.04). The weight-based group had a larger initial morphine dose (p < 0.001) and fewer number of steps to maximum morphine dose (p = 0.009). There were no differences between groups in LOS, number of dose adjustments, doses administered, weaning steps, maximum dose, or need to re-escalate dosing. There was also no difference between the first 3 modified Finnegan scores (MFS) after transferring patients to a neonatology service. Neonates with symptom-based dosing had a higher maximum MFS (p = 0.024). Neonates in the symptom-based group required adjunct therapy more often (p < 0.0001). Data indicate the dosing strategy impacts number of steps to reach maximum dose and need for adjunctive therapy. Weight-based dosing may decrease the number of steps required to reach the morphine maximum dose and the need for adjunctive therapy by controlling NAS symptoms earlier.

A Meta-Analysis of Breastfeeding Effects for Infants With Neonatal Abstinence Syndrome.

Neonatal abstinence syndrome (NAS) rates have dramatically increased. Breastfeeding is a nonpharmacological intervention that may be beneficial, reducing NAS symptom severity and thus the need for and duration of pharmacological treatment and length of hospital stay. Conduct meta-analysis to determine whether breastfeeding results in better outcomes for NAS infants. Variables included symptom severity, need for and duration of pharmacological treatment, and length of hospital stay. PubMed, Scopus, Embase, and Cochrane Library were searched from 2000 to 2020, and comparative studies examining breastfeeding for NAS infants were extracted. Randomized trials and cohort studies were included. Data were extracted and evaluated with Review Manager Version 5.3. A random-effects model was used to pool discontinuous outcomes using risk ratio and 95% confidence intervals. Continuous outcomes were evaluated by mean differences and 95% confidence intervals. Across 11 studies, 6,375 neonates were included in the meta-analysis. Using a random-effects analysis, breastfeeding reduced initiation of pharmacological treatment, reduced duration of pharmacological treatment, and reduced length of stay. No differences were detected for severity of NAS symptoms. Most studies only reported one to two variables of interest. For most studies, these variables were not the primary study outcomes. All studies were found to be of low risk and good quality based on the Cochrane Risk Assessment Tools. Varying breastfeeding definitions limit generalizability. Breastfeeding is associated with decreased initiation and duration of pharmacological treatment and length of stay.

The Complexities Associated with Caring for Hospitalised Infants with Neonatal Abstinence Syndrome: The Perspectives of Nurses and Midwives.

The global incidence of Neonatal Abstinence Syndrome (NAS) has increased significantly in the last decade. Symptoms of NAS manifest from the central and autonomic nervous systems as well as the gastrointestinal system and vary in severity and duration. The clinical management of infants experiencing NAS is dependent on symptoms and may include both pharmacological and non-pharmacological measures. In cases where symptoms are severe, infants may be admitted to special care nurseries or neonatal intensive care units. Existing research on nurses’ involvement in caring for infants with NAS focuses on pharmacological and non-pharmacological interventions to treat physical symptoms associated with NAS. This research sought to add to the body of knowledge around NAS and conveys nurses’ and midwives’ experiences of delivering care for infants with NAS. Semi-structured interviews were held with nine nurses/midwives. Interviews were audio-recorded, transcribed verbatim and thematically analysed. Five themes emerged from the data. These themes are: Complex care needs; Prioritising physiological care; Experiencing compassion fatigue; Lacking continuity of care; and Stigma. The findings demonstrated the complex nature of care provision for infants with NAS. Competing priorities and the stigmatising nature of NAS threaten optimal care being delivered to these vulnerable infants and their parents.

Neonatal abstinence syndrome in babies of opioid-addicted mothers and follow-up in the neonatal intensive care unit: A single center experience

Aim: Neonatal abstinence syndrome (NAS) is a clinical condition characterized by findings that develop after intrauterine exposure to addictive substances, especially opioids, and is characterized by signs related to the absence of the addictive substance in the postpartum period. Typically, NAS manifests in the first few days of life in the form of hypertonia, autonomic instability, irritability, poor absorption reflex, weight loss and, rarely, seizures. The present study was performed the clinical features of mothers who used addictive substances during pregnancy.Materials and Methods: Neonates born between September 2016 and December 2019 to opioid-addicted mothers and admitted to the neonatal intensive care unit (NICU) after birth for findings consistent with NAS were included in this study. The patients' files were analyzed retrospectively. Maternal age, drug used/duration of use, smoking/alcohol use, the last time the substance was taken, gestational week of neonates, mode of delivery, birth weight, onset of NAS symptoms, highest Finnegan score, nutritional status, length of hospitalization, treatment duration and NICU follow-up data were recorded.Results: Nine babies were admitted to the NICU of follow-up for NAS symptoms. All mothers had heroin addiction. The median gestational week of the neonates was 37 (31-40) weeks and median birth weight was 2740(1530-3860) g. Median onset of symptoms was 2(1-4) days and the median Finnegan score of the patients was 10(3-17). Six (66.7%) neonates who did not recover with nonpharmacological treatment received phenobarbital therapy. Conclusions: For patients with NAS, phenobarbital therapy can be used as the first option when symptoms cannot be controlled by nonpharmacological methods in settings such as Turkey where oral morphine solution is not available. In our study, the symptoms were successfully controlled by phenobarbital therapy. However, more comprehensive studies are needed as there are insufficient data on long-term results.

Non-pharmacological care for opioid withdrawal in newborns.

Non-pharmacological care for opioid withdrawal in newborns.

Recovering Together: Mothers' Experiences Providing Skin-to-Skin Care for Their Infants With NAS.

Over the past 2 decades, the prevalence of neonatal abstinence syndrome (NAS) has increased almost 5-fold. Skin-to-skin care (SSC), a method of parent-infant holding, is a recommended nonpharmacologic intervention for managing NAS symptoms. SSC has the potential to reduce withdrawal symptoms while positively influencing parent-infant attachment. Yet, little is known about the SSC experiences of mothers of infants with NAS. The purpose of this study was to explore the SSC experiences of mothers of infants with NAS, including perceived barriers to SSC in the hospital and following discharge home. A qualitative descriptive design was used to obtain new knowledge regarding the experience of SSC of mothers of infants with NAS. Purposive sampling was used to recruit participants eligible for the study. We conducted semistructured individual interviews with postpartum mothers of infants with NAS. Data were analyzed using thematic analysis. Thirteen mothers participated in the study. Four themes emerged from the data analysis: "a little nerve racking"; "she needed me, and I needed her"; dealing with the "hard times"; and "a piece of my puzzle is missing." SSC was described as a conduit for healing and bonding; in addition, several barriers to SSC were reported. These findings highlight the inherent benefits of SSC for infants with NAS and demonstrate the unique challenges of these mother-infant dyads. Critical changes in hospital practices are needed to create an environment supportive of SSC for this patient population. In addition, research regarding implementation of interventions to increase SSC usage in this population is warranted.

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

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

Integrative Review of Gut Microbiota and Expression of Symptoms Associated With Neonatal Abstinence Syndrome.

Neonatal exposure and subsequent withdrawal from maternal substance use disorder are a growing problem and consequence of the current opioid epidemic. Neonatal abstinence syndrome (NAS) is defined by a specified cluster of symptoms with treatment guided by the expression and severity of these symptoms. The mechanisms or pathophysiology contributing to the development of NAS symptoms are not well known, but one factor that may influence NAS symptoms is the gut microbiota. The purpose of this integrative review was to examine evidence that might show if and how the gut microbiota influence expression and severity of symptoms similar to those seen in NAS. Using published guidelines, a review of research studies that focused on the gut microbiome and symptoms similar to those seen in NAS was conducted, using the Cochrane, EMBASE, and Scopus databases, from 2009 through 2019. The review results included findings of aberrant microbial diversity, differences in microbial communities between study groups, and associations between specific taxa and symptoms. In studies involving interventions, there were reports of improved microbial diversity, community structure, and symptoms. The review findings provide evidence that the gut microbiota may play a role in modifying variability in the expression and severity of symptoms associated with NAS. Future research should focus on examining the gut microbiota in infants with and without the syndrome as well as exploring the relationship between symptom expression and aberrant gut microbiota colonization in infants with NAS.

Evaluation and analysis of the Modified Finnegan Scoring System for assessment of neonatal abstinence syndrome.

The Finnegan Neonatal Abstinence Scoring System (FNASS) is the most commonly used scoring system for neonatal abstinence syndrome (NAS) both in its original and modified versions, despite challenges related to tool length and observer bias. The purpose of this study was to determine the most frequent symptoms of NAS that led to score elevation and prompted initiation of drug therapy on the Modified Finnegan (MF). We also sought to identify vital sign changes associated with score elevation. We conducted a retrospective study of neonates diagnosed with NAS, based on ICD-9 codes and charge data for methadone administration. The study setting was in a Level III Neonatal Intensive Care Unit. Ninety patients with a total of 286 MF scores recorded from 2011 to 2015 met inclusion criteria. The primary outcome was overall occurrence for each specific component of the MF scoring tool during symptomatic periods. Secondary outcomes were vital sign changes. Among the MF elements, there were 13 components that were scored more often than others in symptomatic infants. Respiratory rate (RR) was elevated in infants with NAS, but other vital signs did not differ from age-specific norms. Of the various signs of NAS used to score the MF, few are frequently observed. Our study reinforces literature that proposes a shortened MF assessment tool. Experimental research will be needed to determine the efficacy of a shortened MF tool for diagnosing NAS.

Geographic Distribution of Medicaid-Claimant OB-GYNs Approved to Prescribe Buprenorphine for Opioid Use Disorder [15E

INTRODUCTION: High incidences of opioid use disorder (OUD) during pregnancy and neonatal abstinence syndrome (NAS) are manifestations of the U.S. opioid epidemic. Buprenorphine is an effective treatment for OUD, but with restricted access due to prescribing barriers. Neonates with in-utero buprenorphine exposure have milder NAS symptoms and shorter hospital stays. We sought to describe the geographic distribution of buprenorphine-approved obstetrician-gynecologists (ob-gyns). METHODS: To identify buprenorphine-waiver status and geographic location, we linked the Drug Addiction Treatment Act buprenorphine-waived provider list to the Centers for Medicare &amp; Medicaid Services Physician Compare dataset, and extracted all physicians of the specialty “obstetrics and gynecology.” We obtained state NAS data from state agencies' reports, and classified counties based on rural-urban continuum codes. RESULTS: Out of 31,211 obgyns who treat patients with Medicaid insurance, only 1.8% (560) can prescribe buprenorphine. Only 292 out of 3220 counties have at least 1 buprenorphine-approved ob-gyn. Among the 292, 76.4% (223) are metropolitan, 23.6% (69) are non-metropolitan. All 10 states with the highest opioid overdose deaths rates have at least 1 buprenorphine-approved ob-gyn (2 to 48). West-Virginia and Maine, however, have the highest NAS rates (50.6 and 80 per 1000 births respectively, compared to 8 nationally), but each have only 4 buprenorphine-approved ob-gyns. CONCLUSION: Buprenorphine is a mainstay and guideline-recommended treatment for OUD in pregnancy. The geographic distribution of buprenorphine-approved ob-gyns in the US is variable and does not reflect the incidence of NAS. Policy and educational interventions could improve buprenorphine access during pregnancy to limit the opioid epidemic's impact on maternal-fetal outcomes.

Safety, Feasibility, and Effectiveness of Weighted Blankets in the Care of Infants With Neonatal Abstinence Syndrome: A Crossover Randomized Controlled Trial.

Nurses are caring for increasing numbers of infants diagnosed with neonatal abstinence syndrome (NAS). The recommended initial line of treatment to alleviate NAS symptoms includes nonpharmacologic interventions; however, there is little rigorous evidence on the effectiveness of nonpharmacologic interventions. The purpose of this study was to assess the safety, feasibility, and effectiveness of weighted blankets in the care of NAS infants. This pilot study was a crossover randomized nonblinded controlled trial conducted at a level III neonatal intensive care unit. Infants' care included 30-minute sessions utilizing either a nonweighted or weighted blanket, with infants serving as their own controls. A total of 16 patients were enrolled for a total of 67 weighted blanket sessions. To address safety, no adverse events were observed, the weighted blankets were never removed due to infant distress, and infants experienced no significant temperature change. To address feasibility, 94% of approached mothers were receptive to the use of weighted blankets and staff reported no obstacles to using the blanket. Finally, to assess effectiveness, there was a significant decrease in the infant's heart rate and Finnegan score when a weighted blanket was used. There was no significant change in respiratory rate with the use of a weighted blanket. Weighted blankets may be safe, feasible, and effective in decreasing NAS symptoms. Larger studies are needed to thoroughly study the use of weighted blankets in this population and examine additional outcomes, such as need for pharmacologic intervention, length of hospital stay, and cost of hospital stay.

The Parental Experience of Newborns With Neonatal Abstinence Syndrome Across Inpatient Care Settings: A Qualitative Study.

Understanding the experience of parents with newborns hospitalized with neonatal abstinence syndrome (NAS) across all inpatient settings is important in optimizing their involvement as part of the care team. A descriptive qualitative study design was utilized to understand the parental experience and identify barriers to parent involvement in care of newborns with NAS care. Semistructured one-on-one interviews were conducted with parents of a convenience sample of fifteen infants admitted for NAS in the newborn nursery and level II/III neonatal intensive care unit within a tertiary care center in Northern New England. Interviews were analyzed using thematic content analysis. Sixty percent of mothers were treated with buprenorphine during pregnancy, and 60% of infants required pharmacological treatment for NAS symptoms. The predominant themes of parental experience included preparation/education for hospitalization, communication with providers, NAS management, family resources, physical hospital environment, and maternal guilt. The parental experience of care for NAS is negatively affected by lack of standardized NAS education in the prenatal and postnatal settings, inconsistent communication with providers, the Finnegan scoring system, lack of provider sensitivity to parental substance use disorder, and maternal guilt. This study also highlights the parental desire to be more involved in the care of newborns with NAS.

Transition Home: Safe Plan of Care for Infants With a History of Neonatal Abstinence Syndrome.

Opioid use disorder is an ever-expanding health epidemic affecting populations across the lifespan. Infants diagnosed with neonatal abstinence syndrome (NAS) often require additional resources while inpatient and after discharge to support ongoing NAS symptoms and improve outcomes. The purpose of this article is to highlight the need for a "safe plan of care" for infants with a history of NAS and provide evidence-based recommendations for providers. In response to the opioid crisis, legislative efforts were passed to enhance access to care and provide valuable resources for families and clinical providers. These efforts require the development of comprehensive plans of care that include assessment of the home environment along with specialized care and services. Despite active legislation, infants and families continue to lack adequate access to resources such as therapy, specialized nutritional support, developmental specialists, and financial support. An effective safe plan of care ensures that infants with a history of NAS are discharged to caregivers who are prepared, devoted, and responsive to the infants' needs. These essential components include responsive caregiving, safe and secure environments, appropriate nutrition, and health-promoting behaviors. A review of current practice and evidence-based recommendations reveals essential components of a safe plan of care for infants with a history of NAS. By embracing the need for a comprehensive plan, providers can empathize with family needs and activate resources to promote healthy families and improve long-term outcomes of these infants.

Buprenorphine compared with methadone in opioid-dependent pregnant women: How does it affect neonatal abstinence syndrome?

The growing opioid epidemic in the United States has led to increasingly high rates of neonatal abstinence syndrome (NAS). Preliminary studies have shown that buprenorphine maintenance treatment (BMT) may lead to better outcomes for infants than methadone maintenance treatment (MMT). The authors gathered recent evidence to answer the following PICO (population, intervention, comparison, and outcome) question: In opioid-dependent pregnant women, how does buprenorphine compared with methadone administration affect NAS? A literature search was completed in PubMed, Scopus, Embase, and Web of Science databases and limited to the past 5 years. The following parameters were analyzed in the articles: NAS occurrence, length of hospital stay in days, NAS treatment length, and amount of pharmacotherapy administered to treat NAS. In comparison to methadone, buprenorphine exposure in utero is associated with significantly shorter hospital stays for the infant after delivery, shorter length of NAS treatment, and decreased frequency/duration of pharmacotherapy for NAS symptoms in the infant. Based on the findings, a weak recommendation can be made for the use of BMT over MMT in opioid-dependent pregnant women. However, further research is necessary to definitively recommend buprenorphine over methadone use in this population, especially regarding the effect of maternal severity of addiction on adherence to BMT, and long-term effects of in utero buprenorphine exposure.

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.

Reduction in Length of Stay and Morphine Use for NAS With the "Eat, Sleep, Console" Method.

To reduce average length of stay (ALOS) in infants with neonatal abstinence syndrome (NAS) transferred to the inpatient floor from the mother-infant unit. Secondarily, we aimed to reduce morphine exposure in these infants. Using quality improvement methodology, we redesigned our approach to NAS on the inpatient floor. Key interventions included transitioning from a modified Finnegan Neonatal Abstinence Scoring System to the "Eat, Sleep, Console" method for withdrawal assessment, reeducation on nonpharmacologic interventions, and adding as-needed morphine as initial pharmacotherapy. Data for infants ≥35 weeks' gestation with confirmed in utero opioid exposure and worsening symptoms of NAS requiring transfer to the inpatient floor were obtained, including ALOS, number of morphine doses, and total morphine amount administered. Infants with conditions requiring nothing by mouth for >12 hours or morphine initiation in the ICU were excluded. ALOS for infants (baseline n = 40; intervention n = 36) with NAS transferred to the inpatient floor decreased from 10.3 to 4.9 days. Average morphine administered decreased from 38 to 0.3 doses per infant. No infant in the intervention period required scheduled morphine. The percent of all infants transferred to the floor for NAS requiring any morphine decreased from 92% at baseline to 19% postimplementation. There were no observed adverse events or NAS-related readmissions in the intervention period. Transitioning to the Eat, Sleep, Console assessment with re-enforcement of nonpharmacologic care and use of as-needed morphine as initial pharmacotherapy resulted in a notably decreased ALOS and near elimination of postnatal opioid treatment of infants with NAS managed on our inpatient floor.