Neonatal Opioid Withdrawal Syndrome Treatment Guidelines and Birth Hospital Utilization.

BACKGROUND AND OBJECTIVES: In November 2020, the American Academy of Pediatrics published guidelines for management of neonatal opioid withdrawal syndrome (NOWS), recommending nonpharmacologic treatment as the first-line approach, unless pharmacologic treatment is needed for severe NOWS. Using data from tertiary care pediatric hospitals, we examined the impact of the guidelines on use of pharmacotherapy, length of stay, and NICU admission for infants with NOWS. METHODS: We extracted birth hospitalization data for newborns diagnosed with NOWS discharged from 2019 to 2022 from the Pediatric Health Information System. We compared hospital utilization and pharmacologic treatment pre- and postguidelines and used interrupted time series regression to examine trends over time. RESULTS: We included N = 824 newborns (n = 434 pre, n = 390 post) with NOWS from 11 hospitals. The use of pharmacologic treatment was significantly lower in the postguidelines period (59.0% pre versus 50.3% post; P = .01). Median length of stay was similar pre and post (P = .55). NICU admission was significantly lower in the postguidelines period (78.6% pre versus 46.7% post; P < .001), with an immediate decrease (ß = -23.0%; P < .001) and a decrease over time in the postguidelines period (ß = -0.7% per month; P = .03). Most hospitals reduced pharmacologic treatment (8 of 11; 73%) and NICU use (10 of 11; 91%) postguidelines. CONCLUSIONS: There was a reduction in the use of pharmacologic treatment and NICU utilization for infants with NOWS after the release of American Academy of Pediatrics guidelines for NOWS management.

Neonatal and Maternal Ichthyosiform Dermopathy in Association with Kava Use during Pregnancy.

INTRODUCTION: Kava, a substance derived from the Piper methysticum plant, is enjoying a surge in popularity in the United States due to its purported anxiolytic and analgesic effects. Though ichthyosiform dermopathy is a known adverse effect associated with chronic kava exposure in adults, dermopathy in a newborn due to maternal kava use has not yet been described. CASE REPORT: This is a case of a 41-year-old woman who was taking a combination kava/kratom product throughout her pregnancy. She developed an ichthyosiform dermopathy that resolved after she stopped using the product postpartum. Her male infant had a neonatal course complicated by both neonatal opioid withdrawal syndrome, attributed to maternal kratom and buprenorphine use, as well as a diffuse ichthyosiform rash similar to descriptions of kava ichthyosiform dermopathy in adults. His neonatal course was complicated by Group B streptococcus and Serratia marscecens bacteremia (treated with antibiotics) and seizures (treated with lorazepam and phenobarbital). His rash resolved completely by day of life 22. At 9-month outpatient follow-up, he had no dermatologic abnormalities or rash recurrence. DISCUSSION: Maternal kava use during pregnancy may cause fetal dermopathy presenting as an acquired ichthyosis. More public education is needed about the potential consequences of kava use, particularly during pregnancy.

Developmental Outcomes after Opioid Exposure in the Fetus and Neonate.

The overall prevalence of opiate use has been increasing, currently affecting approximately 0.6% of the global population and resulting in a significant proportion of infants being born with prenatal opioid exposure. Animal and human models of prenatal opioid exposure demonstrate detrimental effects on brain anatomy as well as neurodevelopment. Less is known about the neurologic sequelae of postnatal opioid exposure in hospitalized infants. In this review, we summarize our current understanding of the impact of prenatal and postnatal opioid exposure on the brain and on neurodevelopment outcomes. We also identify resources and management strategies that may help mitigate neurodevelopmental delays and deficits associated with opioid exposure in this vulnerable population.

Evaluating a web-based training curriculum for disseminating best practices for the care of newborns with neonatal opioid withdrawal syndrome in a rural hospital, the NOWS-NM Program.

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.

Extended-release versus oral buprenorphine as opioid maintenance treatment during pregnancy-maternal and neonatal outcomes.

OBJECTIVE: To get information on subcutaneous extended-release buprenorphine as opioid maintenance treatment during pregnancy, we compared it to orally administered buprenorphine and buprenorphine-naloxone treatments. We hypothesized that maternal and neonatal outcomes do not differ between the treatment groups. Study design In this population-based cohort study, 60 pregnant individuals receiving non-changed opioid maintenance treatment for opioid use disorder with a buprenorphine product from the time before conception to the time after delivery and their newborns were included. They were divided into three groups based on the pharmacotherapy with subcutaneous extended-release buprenorphine, sublingual buprenorphine, or buprenorphine-naloxone. Statistical analyses were conducted using Fischer's exact tests, ANOVA tests, and Kruskal-Wallis tests. All the statistical tests were two-tailed. RESULTS: The frequency of pregnancy or delivery complications did not significantly differ between the group receiving extended-release buprenorphine and the other groups. During pregnancy, 38 % of the women used illicit drugs concomitantly, with equal frequency in the extended-release buprenorphine group and the other groups. Of the neonates, 93 % were born full-term and 90 % got at least eight Apgar points in one minute age, without significant differences between the groups (p = 0.57). The need for pharmacotherapy for neonatal opioid withdrawal syndrome was the lowest in the extended-release buprenorphine group (25 %) and highest in the sublingual buprenorphine group (67 %). Still, the difference between the treatment groups did not reach statistical significance (p = 0.17). Among all neonates, the breastfed infants were less likely to receive pharmacotherapy for withdrawal symptoms than the formula-fed ones (p = 0.048). CONCLUSIONS: Extended-release buprenorphine with steady drug concentration seems to be a promising pharmacotherapy option during pregnancy for mothers. Maternal health during pregnancy may contribute to the well-being of newborns. Larger trials are urgently needed to confirm these results..

Influence of Eat, Sleep, and Console on Infants Pharmacologically Treated for Opioid Withdrawal: A Post Hoc Subgroup Analysis of the ESC-NOW Randomized Clinical Trial.

Importance: The function-based eat, sleep, console (ESC) care approach substantially reduces the proportion of infants who receive pharmacologic treatment for neonatal opioid withdrawal syndrome (NOWS). This reduction has led to concerns for increased postnatal opioid exposure in infants who receive pharmacologic treatment. However, the effect of the ESC care approach on hospital outcomes for infants pharmacologically treated for NOWS is currently unknown. Objective: To evaluate differences in opioid exposure and total length of hospital stay (LOS) for pharmacologically treated infants managed with the ESC care approach vs usual care with the Finnegan tool. Design, Setting, and Participants: This post hoc subgroup analysis involved infants pharmacologically treated in ESC-NOW, a stepped-wedge cluster randomized clinical trial conducted at 26 US hospitals. Hospitals maintained pretrial practices for pharmacologic treatment, including opioid type, scheduled opioid dosing, and use of adjuvant medications. Infants were born at 36 weeks' gestation or later, had evidence of antenatal opioid exposure, and received opioid treatment for NOWS between September 2020 and March 2022. Data were analyzed from November 2022 to January 2024. Exposure: Opioid treatment for NOWS and the ESC care approach. Main Outcomes and Measures: For each outcome (total opioid exposure, peak opioid dose, time from birth to initiation of first opioid dose, length of opioid treatment, and LOS), we used generalized linear mixed models to adjust for the stepped-wedge design and maternal and infant characteristics. Results: In the ESC-NOW trial, 463 of 1305 infants were pharmacologically treated (143/603 [23.7%] in the ESC care approach group and 320/702 [45.6%] in the usual care group). Mean total opioid exposure was lower in the ESC care approach group with an absolute difference of 4.1 morphine milligram equivalents per kilogram (MME/kg) (95% CI, 1.3-7.0) when compared with usual care (4.8 MME/kg vs 8.9 MME/kg, respectively; P = .001). Mean time from birth to initiation of pharmacologic treatment was 22.4 hours (95% CI, 7.1-37.7) longer with the ESC care approach vs usual care (75.4 vs 53.0 hours, respectively; P = .002). No significant difference in mean peak opioid dose was observed between groups (ESC care approach, 0.147 MME/kg, vs usual care, 0.126 MME/kg). The mean length of treatment was 6.3 days shorter (95% CI, 3.0-9.6) in the ESC care approach group vs usual care group (11.8 vs 18.1 days, respectively; P < .001), and mean LOS was 6.2 days shorter (95% CI, 3.0-9.4) with the ESC care approach than with usual care (16.7 vs 22.9 days, respectively; P < .001). Conclusion and Relevance: When compared with usual care, the ESC care approach was associated with less opioid exposure and shorter LOS for infants pharmacologically treated for NOWS. The ESC care approach was not associated with a higher peak opioid dose, although pharmacologic treatment was typically initiated later. Trial Registration: ClinicalTrials.gov Identifier: NCT04057820.

Comparison of the effect of phenobarbital & levetiracetam in the treatment of neonatal abstinence syndrome (NAS) as adjuvant treatment in neonates admitted to the neonatal intensive care unit: a randomized clinical trial.

BACKGROUND: Infants who are born from mothers with substance use disorder might suffer from neonatal abstinence syndrome (NAS) and need treatment with medicines. One of these medicines is phenobarbital, which may cause side effects in long-term consumption. Alternative drugs can be used to reduce these side effects. This study seeks the comparison of the effects of phenobarbital & levetiracetam as adjuvant therapy in neonatal abstinence syndrome. METHODS: This randomized clinical trial was performed in one year from May 2021 until May 2022. The neonates who were born from mothers with substance use disorder and had neonatal abstinence syndrome in Afzalipoor Hospital of Kerman were studied. The treatment started with morphine initially and every four hours the infants were checked. The infants who were diagnosed with uncontrolled symptoms After obtaining informed consent from the parents were randomly divided into two groups and treated with secondary drugs, either phenobarbital or levetiracetam. RESULTS: Based on the obtained results, it was clear that there was no significant difference between the hospitalization time of the two infant groups under therapy (phenobarbital: 18.59 days versus Levetiracetam 18.24 days) (P-value = 0.512). Also, there was no significant difference between both groups in terms of the frequency of re-hospitalization during the first week after discharge, the occurrence of complications, and third treatment line prescription (P-value = 0.644). CONCLUSIONS: Based on the obtained results, like hospitalization duration time (P-value = 0.512) it seems that levetiracetam can be used to substitute phenobarbital in treating neonatal abstinence syndrome. TRIAL REGISTRATION: The current study has been registered in the Iran registry of clinical trials website (fa.irct.ir) on the date 25/2/2022 with registration no. IRCT20211218053444N2.

Neonatal Abstinence Syndrome and Corresponding Pharmacotherapy Approaches from 2 University-affiliated Neonatal Intensive Care Units in Puerto Rico (2018-2020).

OBJECTIVE: Neonatal abstinence syndrome (NAS) is a set of drug withdrawal symptoms suffered by neonates exposed to drugs in utero. Several studies have widely described NAS incidence and treatment approach; however, little is known regarding the incidence and manifestations of this disease in Puerto Rico (PR). The principal aim of this study was to describe NAS incidence in the neonatal units of hospitals affiliated with the University of PR in terms of occurrence, clinical manifestations, and treatment approaches. METHODS: Our study evaluated the medical records of NAS babies diagnosed from 2018 through 2020 at 2 hospitals affiliated with the University of PR Medical Sciences Campus. Descriptive and inferential statistics were employed to analyze trends. RESULTS: We identified 12 neonates diagnosed with NAS, 5 with low birthweights (<2500 g); for a NAS incidence of 2 cases per 1000 admitted for the 3 years of recollected data. The urine toxicology results revealed that 9 had experienced intrauterine polydrug exposure. Phenobarbital loading dose were determined on the day of diagnosis (indicated by Finnegan score). The first manifestation of NAS symptoms varied: 8 neonates showed symptoms within 48 hours after birth, whereas 4 had withdrawal symptoms within 72-120 hours of their births. Differences between dosing practices and guidelines were observed, ranging from a 0.69% to a 25% difference during treatment initiation. CONCLUSION: Further research on the incidence of NAS in PR (national level) is needed for a deeper understanding that we hope will lead to the development of enhanced treatment protocols in PR.

COVID-19 Pandemic-Related Changes in Rates of Neonatal Abstinence Syndrome.

This cross-sectional study examines COVID-19 pandemic­related changes in rates of neonatal abstinence syndrome (NAS) and whether infants in urban or rural areas and those with low socioeconomic status were disproportionately affected.

Case Series of Individuals Treated With Naltrexone During Pregnancy for Opioid and/or Alcohol Use Disorder.

OBJECTIVE: There is a lack of knowledge about the relative safety and efficacy of naltrexone for the treatment of pregnant individuals with opioid and/or alcohol use disorder, including the range of outcomes, in both the pregnant individual and the infant, over the course of peripartum period. Our objective was to describe these outcomes in a cohort of pregnant individuals on naltrexone. METHODS: In this prospective case series, 7 pregnant individuals with opioid use disorder (OUD) or alcohol use disorder (AUD) treated with naltrexone were followed from pregnancy through 12 months after delivery. Clinical treatment protocols and outcomes related to safety and efficacy during pregnancy, delivery, and the postpartum period are described. RESULTS: There were 4 pregnant individuals with OUD and 3 with AUD, of which 3 were managed with oral and 4 with extended-release naltrexone. The mean gestational age at study enrollment was 21.7 (SD, 12) weeks. Of the 7 participants, there was no return to nonprescribed opioid use and 2 who experienced a return to alcohol use over the course of the study. All individuals delivered vaginally at a mean of 37 weeks gestation without any peripartum pain difficulties. Five of the individuals (71.4%) remained on naltrexone 12 months after delivery. There were no reported fetal anomalies and one preterm delivery. None of the infants developed neonatal opioid withdrawal syndrome. CONCLUSIONS: For pregnant individuals with OUD or AUD treated with naltrexone, there were low rates of return to nonprescribed use and reassuring pregnant person and infant outcomes to 12 months postpartum.

Salivary Therapeutic Monitoring of Buprenorphine in Neonates After Maternal Sublingual Dosing Guided by Physiologically Based Pharmacokinetic Modeling.

BACKGROUND: Opioid use disorder (OUD) during pregnancy is associated with high mortality rates and neonatal opioid withdrawal syndrome (NOWS). Buprenorphine, an opioid, is used to treat OUD and NOWS. Buprenorphine active metabolite (norbuprenorphine) can cross the placenta and cause neonatal respiratory depression (EC 50 = 35 ng/mL) at high brain extracellular fluid (bECF) levels. Neonatal therapeutic drug monitoring using saliva decreases the likelihood of distress and infections associated with frequent blood sampling. METHODS: An adult physiologically based pharmacokinetic model for buprenorphine and norbuprenorphine after intravenous and sublingual administration was constructed, vetted, and scaled to newborn and pregnant populations. The pregnancy model predicted that buprenorphine and norbuprenorphine doses would be transplacentally transferred to the newborns. The newborn physiologically based pharmacokinetic model was used to estimate the buprenorphine and norbuprenorphine levels in newborn plasma, bECF, and saliva after these doses. RESULTS: After maternal sublingual administration of buprenorphine (4 mg/d), the estimated plasma concentrations of buprenorphine and norbuprenorphine in newborns exceeded the toxicity thresholds for 8 and 24 hours, respectively. However, the norbuprenorphine bECF levels were lower than the respiratory depression threshold. Furthermore, the salivary buprenorphine threshold levels in newborns for buprenorphine analgesia, norbuprenorphine analgesia, and norbuprenorphine hypoventilation were observed to be 22, 2, and 162 ng/mL. CONCLUSIONS: Using neonatal saliva for buprenorphine therapeutic drug monitoring can facilitate newborn safety during the maternal treatment of OUD using sublingual buprenorphine. Nevertheless, the suitability of using adult values of respiratory depression EC 50 for newborns must be confirmed.

Impaired vision in children prenatally exposed to methadone: an observational cohort study.

BACKGROUND/OBJECTIVES: To examine prevalence of failed visual assessment at 8-10 years in children born to methadone-maintained opioid dependent (MMOD) mothers and relate this to known in utero substance exposure. SUBJECTS/METHODS: Follow up of observational cohort study of methadone-exposed and comparison children matched for birthweight, gestation and postcode of residence at birth. Participants were 144 children (98 exposed, 46 comparison). Prenatal drug exposure was previously established via comprehensive maternal and neonatal toxicology. Children were invited to attend for visual assessment and casenotes were reviewed. Presence of acuity poorer than 0.2 logMAR, strabismus, nystagmus and/or impaired stereovision constituted a 'fail'. Fail rates were compared between methadone-exposed and comparison children after adjusting for known confounding variables. RESULTS: 33 children attended in person: data were also derived from casenote review for all children. After controlling for maternal reported tobacco use, methadone-exposed children were more likely to have a visual 'fail' outcome, adjusted odds ratio 2.6, 95% CI 1.1-6.2; adjusted relative risk 1.8 (95% CI 1.1-3.4). Visual 'fail' outcome rates did not differ between methadone-exposed children who had (n = 47) or had not (n = 51) received pharmacological treatment for neonatal abstinence/opioid withdrawal syndrome (NAS/NOWS); fail rate 62% vs 53% (95% CI of difference-11-27%). CONCLUSIONS: Children born to MMOD mothers are almost twice as likely as unexposed peers to have significant visual abnormalities at primary school age. Prenatal methadone exposure should be considered in the differential diagnosis of nystagmus. Findings support visual assessment prior to school entry for children with any history of prenatal opioid exposure. TRIAL REGISTRATION: The study was prospectively registered on ClinicalTrials.gov (NCT03603301), https://clinicaltrials.gov/ct2/show/NCT03603301 .

Transplacental methadone exposure and risk of Neonatal Opioid Withdrawal Syndrome.

STUDY OBJECTIVE: Neonatal opioid withdrawal syndrome (NOWS) is a condition that often occurs in neonates born to mothers who received methadone treatment for opioid use disorder during pregnancy. Early identification and treatment of infants at risk of NOWS may improve clinical outcomes. The purpose of this study was to evaluate whether maternal and umbilical cord plasma concentrations of methadone and its metabolite, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), could predict the need for NOWS treatment. DESIGN: Single-center prospective study. SETTING: University of Michigan Neonatal Intensive Care Unit. PATIENTS: The study included 11 opioid-dependent mother-infant dyads, where the mothers were treated with methadone at 34 weeks' gestation or later. INTERVENTION: Maternal and cord blood samples were collected from the study participants. MEASUREMENTS AND MAIN RESULTS: Maternal and cord plasma concentrations of methadone and EDDP were determined. Six out of the 11 infants required treatment for NOWS. Maternal methadone plasma concentrations were comparable between infants requiring and not requiring NOWS treatment (329.1 ± 229.7 ng/mL vs. 413.2 ± 329.8 ng/mL). However, the average cord plasma methadone concentration in infants who did not require NOWS treatment was 2.9-fold higher than in those who required the treatment (120.0 ± 88.6 ng/mL vs. 40.9 ± 24.4 ng/mL), although the difference was not statistically significant. The ratios of maternal-to-cord methadone plasma concentrations were significantly higher in patients who required treatment for NOWS compared with those who did not (7.7 ± 1.9 vs. 3.5 ± 1.6, p = 0.003). Maternal and cord plasma EDDP concentrations and the maternal-to-cord plasma EDDP concentration ratios did not differ between patients who required and did not require treatment for NOWS. CONCLUSIONS: The results suggest that methadone permeability across the blood-placental barrier may affect in utero exposure to methadone, and the maternal-to-cord methadone plasma concentration ratio could be a potential biomarker for predicting the need for NOWS treatment.

Rise in Neonatal Abstinence Syndrome Rate Is Associated with Increase in Buprenorphine Prescription Numbers.

OBJECTIVES: Southern Appalachia is a region of the United States that is disproportionately affected by the opioid epidemic and by increasing rates of neonatal abstinence syndrome (NAS). NAS rates increased approximately 400% between 1999 and 2012. Buprenorphine prescriptions written to treat opioid use disorder also increased dramatically. The present study was undertaken to ascertain any relationship between the number of buprenorphine prescriptions compared with NAS rates in southern Appalachia. METHODS: A total of 250 southern Appalachian counties across seven states, including all of West Virginia and portions of Virginia, Kentucky, Maryland, North Carolina, Ohio, and Tennessee were identified. A retrospective cohort analysis of these counties was conducted for the years 2005-2018. All of the data were obtained from publicly accessible sources or direct communication with government offices. Measures from each county in southern Appalachia included annual NAS rates, buprenorphine prescription rates, drug-induced death rates, and opioid prescribing rates. Associations among these variables were examined using a generalized linear regression. RESULTS: Significant linear associations exist between the rising rate of NAS diagnoses and the rising rate of buprenorphine prescriptions (r = 0.977, R2 = 95.53%, P < 0.001) and between the rising rate of buprenorphine prescriptions and the increase in drug-induced deaths (r = 0.712, R2 = 50.82%, P = 0.031). CONCLUSIONS: This is the first report that documents an association between rising NAS rates and increasing buprenorphine prescribing. Between the years 2010 and 2018, the NAS rate in southern Appalachia rose by 335%, and the number of buprenorphine prescriptions rose by 413%. Discussions regarding the current policies for buprenorphine management during pregnancy are warranted. We suggest a reevaluation of buprenorphine prescribing recommendations during pregnancy and further research on establishing the lowest effective buprenorphine dose for each pregnant patient.

Guideline No. 443b: Opioid Use Throughout Women's Lifespan: Opioid Use in Pregnancy and Breastfeeding.

OBJECTIVE: To provide health care providers the best evidence on opioid use and women's health. Areas of focus include pregnancy and postpartum care. TARGET POPULATION: The target population includes all women currently using or contemplating using opioids. OUTCOMES: Open, evidence-informed dialogue about opioid use will improve patient care. BENEFITS, HARMS, AND COSTS: Exploring opioid use through a trauma-informed approach provides the health care provider and patient with an opportunity to build a strong, collaborative, and therapeutic alliance. This alliance empowers women to make informed choices about their own care. It also allows for the diagnosis and possible treatment of opioid use disorders. Opioid use should not be stigmatized, as stigma leads to poor "partnered care" (i.e., the partnership between the patient and care provider). Health care providers need to understand the effect opioids can have on pregnant women and support them to make knowledgeable decisions about their health. EVIDENCE: A literature search was designed and carried out in PubMed and the Cochrane Library databases from August 2018 until March 2023 using following MeSH terms and keywords (and variants): opioids, opioid agonist therapy, illicit drugs, fertility, pregnancy, fetal development, neonatal abstinence syndrome, and breastfeeding. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and conditional [weak] recommendations). INTENDED AUDIENCE: All health care providers who care for pregnant and/or post-partum women and their newborns. TWEETABLE ABSTRACT: Opioid use during pregnancy often co-occurs with mental health issues and is associated with adverse maternal, fetal, and neonatal outcomes; treatment of opioid use disorder with agonist therapy for pregnant women can be safe during pregnancy where the risks outnumber the benefits. SUMMARY STATEMENTS: RECOMMENDATIONS.

Implementation of the Eat, Sleep, and Console Model of Care: A Quality Improvement Project.

A Southeastern, 741-bed acute care, Magnet designated teaching hospital and level III B NICU identified assessment and treatment concerns for Neonatal Opioid Withdrawal Syndrome (NOWS). In March 2020, a quality improvement project led to a multidisciplinary team formation to determine the effectiveness of the Eat, Sleep, Console (ESC) model of care in reducing the length of treatment (LOT) and length of stay (LOS) for neonates experiencing NOWS rather than use of the Finnegan Neonatal Abstinence Syndrome Scoring tool. The results concluded a decrease in the average LOT from 19.2 to 2.5 days and the average LOS from 23.9 to 9.3 days for those admitted directly into the ESC model of care on postpartum vs previous direct admission to the NICU. A group samples t-test showed there was a statistically significant decrease in LOS for ESC patients (p < .001) and LOT for ESC patients (p <001).

Distribution of morphine and methadone to the brain in a developmental chicken embryo model.

The use and/or misuse of opioids by pregnant women would expose the fetuses to these drugs during critical stages of development with serious effects for the newborn, like the neonatal abstinence syndrome (NAS). We have revisited an established chicken model for NAS to describe the distribution of morphine and methadone to the brain and explore its validity as a valuable alternative to rodent models. For this purpose, chicken eggs were injected with a single dose of 10 mg/kg or 20 mg/kg morphine or 20 mg/kg methadone onto the chorioallantoic membrane (CAM) on embryonal day 13. Whole brains and lungs were harvested and the concentrations of morphine, methadone and their subsequent metabolites (morphine-3-glucuronide and EDDP, respectively) determined in the brain and lungs at different time points using LC-MS/MS. Morphine and methadone, as well as their metabolites, were detected both in the brain and lungs, with significantly higher concentrations in the lungs. Pharmacokinetic modelling showed that the distribution of morphine to the brain followed a first-order absorption with transit compartments and linear elimination, with concentrations linearly dependent on dose. Moreover, methadone, but not morphine, reduced µ receptor (the main morphine receptor) binding, which can be of relevance for opioid tolerance. The present study is the first to report the brain distribution of morphine, which can be described by standard pharmacokinetic processes, and methadone in the developing chicken embryo. The present findings supplement the already established model and support the use of this chicken model to study NAS.

Neonatal Outcomes after Medications for Opioid Use Disorder during Pregnancy in a State Women's Prison Facility, 2016-2019.

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 examine birth outcomes for infants born with opioid exposure during perinatal incarceration. METHODS: Participants were identified from clinic rosters in a Southeastern women's prison (2016-2019). Included infants born to pregnant 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 variance F tests, and chi-square tests to compare outcomes by opioid exposure 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 exposed 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 perinatal opioid exposures during maternal incarceration mirror those of similarly 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.

[Neonatal abstinence syndrome due to kratom]. / Neonataal abstinentiesyndroom door kratom.

BACKGROUND: Kratom (Mitragyna speciosa) is a herbal product obtained from the tropical tree family 'Rubiaceae'. Kratom is available without prescription in several formulations. The active component mitragynine acts in high dose as a mu-opioid agonist. It is misconceived to be a safe alternative to conventional opioid drugs for the treatment of chronic pain. Therefore, maternal use of Kratom is not without risks as opioid use during pregnancy is associated with Neonatal Abstinence Syndrome (NAS). CASE DESCRIPTION: In this case report we describe a term neonate with severe NAS as a result of daily Kratom ingestion by the mother during pregnancy. Presence of mitragynine was confirmed in serum of the neonate. NAS was successfully treated with oral phenobarbital. CONCLUSION: Maternal Kratom use during pregnancy can cause severe NAS via in utero exposure. Physicians should be aware of the possible maternal use of Kratom in the case of a neonate with NAS. NAS as a result of maternal Kratom use can be effectively treated with oral phenobarbital.

Decreased myelin-related gene expression in the nucleus accumbens during spontaneous neonatal opioid withdrawal in the absence of long-term behavioral effects in adult outbred CFW mice.

Prenatal opioid exposure is a major health concern in the United States, with the incidence of neonatal opioid withdrawal syndrome (NOWS) escalating in recent years. NOWS occurs upon cessation of in utero opioid exposure and is characterized by increased irritability, disrupted sleep patterns, high-pitched crying, and dysregulated feeding. The main pharmacological strategy for alleviating symptoms is treatment with replacement opioids. The neural mechanisms mediating NOWS and the long-term neurobehavioral effects are poorly understood. We used a third trimester-approximate model in which neonatal outbred pups (Carworth Farms White; CFW) were administered once-daily morphine (15 mg/kg, s.c.) from postnatal day (P) day 1 through P14 and were then assessed for behavioral and transcriptomic adaptations within the nucleus accumbens (NAc) on P15. We also investigated the long-term effects of perinatal morphine exposure on adult learning and reward sensitivity. We observed significant weight deficits, spontaneous thermal hyperalgesia, and altered ultrasonic vocalization (USV) profiles following repeated morphine and during spontaneous withdrawal. Transcriptome analysis of NAc from opioid-withdrawn P15 neonates via bulk mRNA sequencing identified an enrichment profile consistent with downregulation of myelin-associated transcripts. Despite the neonatal behavioral and molecular effects, there were no significant long-term effects of perinatal morphine exposure on adult spatial memory function in the Barnes Maze, emotional learning in fear conditioning, or in baseline or methamphetamine-potentiated reward sensitivity as measured via intracranial self-stimulation. Thus, the once daily third trimester-approximate exposure regimen, while inducing NOWS model traits and significant transcriptomic effects in neonates, had no significant long-term effects on adult behaviors.