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Objective: Intrauterine opioid exposure (IOE) has increased over the last 2 decades and is associated with additional needs after birth. To date, no clinical guidelines address the primary care of children with IOE. We aimed to characterize clinician-reported screening and referral practices, barriers to effective primary care for children with IOE, and clinician- and practice-level characteristics associated with perceived barriers., Methods: We conducted a cross-sectional survey of pediatric residents, pediatricians, and advanced practitioners at 28 primary care clinics affiliated with 7 pediatric residency programs (April-June 2022). We assessed screening and other clinical practices related to IOE and perceived barriers to addressing parental opioid use disorder (OUD). We used descriptive statistics to analyze survey responses, assessed the distribution of reported barriers, and applied a 2-stage cluster analysis to assess response patterns., Results: Of 1004 invited clinicians, 329 (32.8%) responses were returned, and 325 pediatric residents and pediatricians were included in the final analytic sample. Almost all (99.3%) reported parental substance use screening as important, but only 11.6% screened routinely. Half of the respondents routinely refer children with IOE to early intervention services and social work. Lack of standard screening for substance use was the most frequently selected barrier to addressing parental OUD. Participants reporting fewer barriers to addressing parental OUD identified having greater access to OUD treatment programs and home visiting programs., Conclusions: Pediatricians report variations in primary care screenings and referrals for children with IOE. Access to parental OUD treatment programs may mitigate perceived barriers to addressing parental OUD in the pediatric office., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Background and purpose: Conventional measures of withdrawal in newborns with prenatal opioid exposure (POE) rely on nursing assessments, including the subjective judgment of infant irritability. This study investigated limb movement actigraphy as a tool for providing an objective, quantifiable measure of underlying distress. Methods: Correlational analyses compared continuous physiological-detected movement actigraphy and clinical intervallic-scored symptomology (modified Finnegan system) obtained from a control cohort of 37 term neonates with POE studied in their crib in the newborn unit (1-8 days). Results: Infants spent 15% crib time in high movement activity (>100 movements/minute; index irritability) and 38% crib time in low activity (0-5 movements/minute; index calm). There was a significant positive association between actigraphy and Finnegan composite score ( r = .28, p = .001) and between actigraphy and subcomponent scores (i.e., central nervous system, gastrointestinal, and metabolic-vasomotor-respiratory). Conclusion: Movement activity via actigraphy captures underlying distress and calm not measured by conventional assessments. Such objective, quantifiable measures can serve to promote equitable assessment and treatment of hospitalized newborns with POE., (© Copyright 2024 Springer Publishing Company, LLC.)

Background: Traditional approaches to management of neonates prenatally exposed to opioids are based on the use of pharmacotherapy (PT), adjusted to evolution of infant symptoms. Newer approaches focused on non-pharmacological care (NPC) are emerging, but there is little evidence on the active policies to implement to ensure their widespread practice. The primary objective of the study was to assess whether the implementation of a developmental care program in our neonatal medicine department had an impact on the management of these infants during hospitalization, notably exposure to NPC., Method: Observational study in a tertiary perinatal center. Data collected during hospitalization for infants with in utero opioid exposure included admission in the parents-infant unit (PIU) of the maternity ward, exposure to NPC and PT, occurrence of neonatal opioid withdrawal syndrome (NOWS), length of hospital stay (LOS) and feeding type at discharge. The impact of the intervention was measured by comparing three 6-year periods, the first preceding the implementation of a formalized developmental care program (2003-2008); the second following implementation of the program (2009-2014); the third after consolidation of the program (2015-2020)., Results: 258 infants prenatally exposed to opioid were recorded. From the first to the third period, admission rate in the PIU was comparable (68 % to 73 %, p = 0. 95). Exposure to NPC (37 % to 84 %, p < 0.001) increased, whereas exposure to PT (40 % to 15 %, p = 0.002) and LOS (13 [9-18] days to 8 [6-11] days, p = 0.003) decreased. NOWS occurred in 141 (55 %) infants (63 % to 47 %, p = 0.10). In these infants, decrease in PT was also observed (64 % to 34 %, p = 0.02). After adjustment for perinatal confounders, hospitalization in the PIU (OR 3.23 [1.36; 7.66]; p = 0.008), and the 2015-2020 period (OR 5.11 [2.06; 12.64]; p = 0.004) were associated with absence of PT., Conclusions: An active policy, supporting the training and warranting the practice of NPC, is essential to reduce medication usage and length of hospitalization in infants exposed in utero to opioids., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

It is critical that researchers gather evidence of factors that identify infants at risk of out-of-home placement based on types of substance exposures and demographic characteristics. This study applied a validated medical record data extraction tool on data derived from a multi-site ( N = 30) pediatric clinical trials network (ISPCTN) study of Neonatal Opioid Withdrawal (ACT NOW study). Participants included 1808 birthing parent-infant dyads with documented NOWS scoring or prenatal opioid exposure. Non-Hispanic White pregnant persons comprised the largest proportion of the sample (69.8%), followed by Non-Hispanic Black (11.6%), Non-Hispanic Multiracial and Other race (8.5%), and Hispanic (6.2%). Most notably, infant prenatal substance exposure across alcohol, cocaine, meth/amphetamine, and opioids, had the lowest possibility of discharging to parent(s). Additionally, latent class analysis identified distinct classes of substance use during pregnancy that were associated with different probabilities of discharging to parent(s). Specifically, less than half of infants (47%-49%) in the Poly-use and Meth/amphetamine classes were discharged to their parent(s). Severity of infant withdrawal symptoms influenced placement decisions within the Poly-use and Prescription Opioid classes. Findings can inform standard practices for increasing support for pregnant persons and substance-exposed infants including identification, subsequent referrals, communication with Child Protective Services, and plans of safe care., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Babywearing is the practice of carrying an infant in a baby carrier, which may provide an inexpensive, nonpharmacological intervention for the parent-infant dyads to handle mental stressors, such as pain and anxiety, especially among vulnerable infants. This study investigated the influence of babywearing on parent-infant autonomic coregulation based on the changes in the HR of mother-infant and father-infant dyads for infants with neonatal abstinence syndrome (NAS). Guided by the Calming Cycle Theory as the framework, the correlation between parent HR and infant HR and the difference in the mother-infant dyad (n = 17) compared to the father-infant dyad (n = 8) were examined. Although only the mother-infant HRs reached statistical significance during babywearing (r̅ =.52, p = .03), both parent-infant dyads had strong correlations during babywearing (compared to pre- and post-babywearing conditions), indicating that babywearing, for parents and their infants with NAS, may influence autonomic coregulation., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To improve neonatal outcomes through the implementation of an eat, sleep, console (ESC) assessment and change in hospital policy regarding the monitoring requirements for pharmacologic treatment of neonates with neonatal abstinence syndrome (NAS)., Design: Retrospective chart review and descriptive survey design., Setting/local Problem: A hospital in Northwestern Ontario, where an evidence-based practice change was undertaken to improve care for neonates with NAS., Participants: Neonates being screened for NAS during the Modified Finnegan Neonatal Abstinence Syndrome Scoring System (MFNASSS) protocol (n = 75) and ESC protocol (n = 40). Nurses working in the departments after the implementation of ESC were surveyed., Measurements: Length of stay (LOS) and morphine administration by intervention status using unadjusted hazard and risk ratios, respectively. Descriptive statistics are also presented. A one-sample t test was completed for the nurses' perspectives survey questions., Results: Reduced rate of LOS (HR = 1.66, 95% confidence interval [1.1, 2.51]) was observed for participants receiving the ESC intervention (4.53, SD = 1.94), compared to the MFNASSS control (7.45, SD = 6.35). Although the ESC group appeared to have a greater proportion of neonates administered morphine (42.5% ESC vs. 26.7% MFNASSS), the relative risk was not statistically significant (RR = 1.28, 95% confidence interval [0.95, 1.72]). Morphine doses per day were reduced in the ESC group (0.37, SD = 1.50) compared to the MFNASSS group (5.16, SD = 1.02). Overall, the nurses had a positive perspective on the policy change., Conclusion: ESC was successfully implemented in a Northwestern Ontario hospital. The overall LOS of neonates with NAS decreased. Nurses found the policy change to be safe and attainable., (Copyright © 2024 AWHONN. Published by Elsevier Inc. All rights reserved.)

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

Social touch through infant holding, skin-to-skin contact, and infant carrying (babywearing) decreases infant distress and promotes secure attachment. Unknown is the extent to which these effects are the result of the activation of C-Tactile afferents (CTs), the constellation of nerve fibers associated with affective touch, primarily located in the head and trunk of the body. The purpose of the present study was to compare dynamic touch (CTs activated) to static touch (CTs less activated) during a babywearing procedure among infants experiencing Neonatal Opioid Withdrawal Syndrome (NOWS). NOWS is a spectrum of clinical symptoms, including elevated heart rate (HR), associated with withdrawal from intrauterine opioid exposure. We hypothesized that stroking an infant's head during babywearing would amplify the pleasurable effect of babywearing as measured by changes in infant HR. Twenty-nine infants in a Neonatal Intensive Care Unit (NICU) in the Southwestern USA were worn in an infant carrier starting at five days old (M = 5.4, SD = 2.6; 46.2 % White, 26.9 % Latinx, 11.5 % Native American) and physiological readings were conducted daily; heart rates of infants and caregivers were taken every 15-seconds for 5-minutes, before, during, and after babywearing (30 min per phase). Each day infants alternated (randomly) in a static touch (hands-free babywearing) or dynamic touch condition (stroking the top of the infants' head at a velocity of 3 cm/s while babywearing). On average, infants completed 3 dynamic and 3 static babywearing sessions. Hospital and research staff participated in babywearing when a parent was not available (31.0 % of infants were exclusively worn by volunteers, 27.6 % were exclusively worn by parents). We analyzed the data using Hierarchical Linear Models due to the 3-level nested design (N = 29 infants, N = 191 readings, N = 11,974 heart rates). Compared to baseline (infant calm/asleep and without contact), infant's HRs significantly declined during and after babywearing, controlling for pharmacological treatment. These effects were significantly stronger during the dynamic touch condition (reduction in HR of 11.17 bpm) compared to the static touch condition (reduction in HR of 3.74 bpm). These effects did not significantly vary by wearer (mother, father, volunteer). However, differences between the dynamic and static conditions were significantly stronger in earlier babywearing sessions, potentially indicating a learning effect. There was evidence for a calming effect among caregivers as well, particularly in the dynamic touch condition, when caregivers were engaged in active touch. Activation of CTs appears to be an important mechanism in the physiological benefits of babywearing and in the symbiotic role of caregiver-infant attachment., Competing Interests: Declaration of Competing Interest The authors do not have any conflicts of interest/competing interests. This work is funded as a result of generous financial support from BHHS Legacy Foundation, which is an Arizona charitable organization whose philanthropic mission is to enhance the quality of life and health of those it serves. This work was also funded by a grant from the Ibis Foundation. Ergobaby and Baby K’tan provided the infant carriers used in this study. All aspects of the study received IRB approval and participants actively consented to the study. All authors contributed to the manuscript development., (Published by Elsevier Inc.)

Objective: Evaluate maternal and neonatal outcomes after buprenorphine wean compared to patients maintained on buprenorphine throughout pregnancy., Methods: Prospective cohort study of pregnant patients with opioid use disorder enrolled in a multidisciplinary treatment program between 2015 and 2022. All patients were offered Medications to treat Opioid Use Disorder (MOUD) primarily with buprenorphine. Patients had at least 2 prenatal visits and negative urine drug tests (UDT) prior to weaning. The experimental group underwent a buprenorphine wean greater than 20% of their baseline dose. The control group was maintained on buprenorphine throughout the pregnancy. Relapse was defined as patient reported use or positive UDT during weekly assessments. Mass spectrophotometer was used for detection of drugs in samples. Fisher's exact tests were used to compare outcomes in weaned and control groups., Results: 334 of 456 (73%) patients were treated with buprenorphine during pregnancy, with 39 in the experimental group and 295 in the control group. The mean dose for buprenorphine was similar between the groups (wean: 10.6 mg ± 5.6 vs. control: 10.3 mg ± 4.6, p  = 0.76) but was significantly lower at delivery (wean: 4.4 ± 4.6 mg vs. control: 13.0 ± 4.7, p  < 0.0001). Mean gestational age at initiation of the buprenorphine wean was 22.7 weeks. 10 of 39 (26%) who weaned were able to completely discontinue buprenorphine prior to delivery. Demographic data was similar between the groups, including overdose history. Overdose history at time of enrollment had a higher trend in the non-weaning group. neonatal opioid withdrawal syndrome (NOWS) treatment was significantly lower in the wean group (23 vs. 47%, p  = 0.006), as was highest Finnegan score (9.6 ± 4.5 vs. 12.3 ± 4.0, p  = 0.0003). Birthweight percentile was significantly higher in the wean group (44.3 ± 29.9 vs. 34.8 ± 24.4, p  = 0.03). Gestational age at delivery, mode of delivery, and complications (HTN, DM, preterm labor, or short cervix) at delivery did not significantly differ between the groups., Conclusion: Despite counseling to stay on buprenorphine, there are patients who desire to wean. The NOWS rate in the weaned cohort was significantly lower than the controls with no observed increase in maternal or neonatal morbidity. There were no maternal overdoses or deaths during the pregnancy. Larger studies are needed to evaluate this approach.

This retrospective cohort study included 77 mother-infant dyads that delivered term pregnancies at a single tertiary care institution. The primary objective was to investigate whether maternal dose of opioid maintenance therapy during pregnancy affects infant outcomes. All infants had prenatal exposure to opioid maintenance therapies. Maternal dose was converted into morphine milligram equivalents (MMEs) and stratified into high- (MME >1000 mg) and low-dose groups (MME ≤1000 mg). Associations between infant outcomes and MME dosage were examined using Wilcoxon rank-sum and Fisher's Exact tests. Days to symptom control were significantly higher in the high MME group (5 days vs 2.8 days, P = .016). Rates of developmental delay at 24 months were higher in the high MME group (21.2% vs 4.5%, P = .0335). Maternal MME did not predict need for NOWS treatment. Higher MME-exposed infants should have optimized nonpharmacologic interventions for consolation and be increasingly observed for signs of developmental delay., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Data from birth registries can be studied to assess the prevalence of prenatal alcohol use and associated maternal and neonatal outcomes., Methods: Linked maternal and neonatal data (2015-2018) for alcohol-exposed pregnancies were obtained from the Better Outcomes Registry and Network (BORN) Ontario. Descriptive statistics were generated for maternal demographics, prenatal substance use, mental health/substance use history, and neonatal outcomes. Logistic regression models were performed to assess the odds of prenatal heavy (binge or weekly) alcohol and other substance use based on mental health/substance use history and other maternal demographics, and the impacts of heavy alcohol use and other prenatal substance exposures on neonatal outcomes., Results: A total of 10,172 (2.4%) women reported alcohol use during pregnancy. One-third had pre-existing or current mental health and/or substance use problems, which was associated with significantly higher odds of heavy alcohol use during pregnancy. Prenatal exposure to heavy alcohol use was associated with increased odds of neonatal abstinence syndrome (2.5 times); respiratory distress syndrome (2.3 times); neonatal intensive care unit (NICU) admission (58%); and hyperbilirubinemia (57%). Prenatal exposure to one or more substances in addition to alcohol was associated with significantly higher odds of fetal/maternal/placental pregnancy complications; preterm birth; NICU admission; low APGAR scores; one or more confirmed congenital anomalies at birth; respiratory distress syndrome; and intrauterine growth restriction., Conclusions: It is crucial to routinely screen childbearing-age and pregnant women for alcohol and other substance use as well as mental health problems in order to prevent adverse maternal and neonatal outcomes.

Introduction: Neonatal opioid withdrawal syndrome (NOWS) is caused by sudden cessation from in utero exposure to opioids. The indications for opioid use during pregnancy are diverse including medication for opioid use disorder and analgesia. The opioid dose typically depends on the indication, with higher doses used for medication for opioid use disorder and lower doses used for analgesia. The aim of this study was to investigate the relationship between maternal opioid dose during pregnancy and the risk of NOWS., Material and Methods: We conducted a historical multicenter cohort study of neonates prenatally exposed to opioids in Eastern Denmark during a six-year period from 2013 to 2018. The data was extracted from reviewing the individual's medical record(s), which were identified through a search of the Danish National Patient Register. Four groups (quartiles) according to maternal opioid dose during the last four weeks prior to delivery were compared. Unadjusted and adjusted logistic regression analyses were conducted to examine the risk of NOWS while controlling for relevant covariates., Results: A total of 130 in utero opioid exposed neonates were included. The majority of the pregnant patients (88%) were treated with opioids for analgesic purposes. Overall, 52% of neonates developed NOWS. The cumulative incidence of NOWS was 21%, 28%, 67% and 91% at maternal average daily dose of morphine milligram equivalent during the last four weeks prior to delivery of 0.7-14 (group I), 14.3-38.6 (group II), 40-90 (group III) and 90.9-1440 (group IV), respectively. Compared to group I the adjusted odds (aOR) of NOWS increased significantly in group III (aOR 10.6 [2.9-39.1]) and group IV (aOR 37.8 [7.6-188.2]) but not in group II (aOR 1.5 [0.4-5.2]). No cases of NOWS were reported at maternal dose less than an average daily dose of five morphine milligram equivalent during the last four weeks prior to delivery. No significant changes in the incidence of NOWS were observed between 2013 and 2018., Conclusions: The odds of neonatal opioid withdrawal syndrome increased significantly as the maternal average daily dose of morphine milligram equivalent during the last four weeks prior to delivery surpassed 40., (© 2024 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Objective: Neonatal Opioid Withdrawal Syndrome (NOWS) has been associated with the development of necrotizing enterocolitis (NEC) in term and late-preterm neonates. In this study, we used stool gene expression to determine if an increase in baseline inflammation in the intestine of infants with NOWS is associated with these findings., Study Design: Stool samples were prospectively collected between days 1-3 and days 4-9 after delivery for opioid-exposed ( n = 9) or non-exposed neonates (n = 8). Stool gene expression for TLR4 and HMGB1 was determined via real-time PCR., Results: TLR4 expression was higher in the stool of the non-exposed group in both time periods, between days 1-3 (P < 0.0001) and days 4-9 (P < 0.05) after delivery. No significant difference in HMGB1 expression was found at either time point (P > 0.05)., Conclusion: These findings point to an important interplay between opioid exposure and/or NOWS and the inflammatory milieu of the neonatal intestine., (© 2023. The Author(s).)

Objective: To evaluate factors associated with borderline/clinical range Child Behavior Checklist (CBCL) scores in opioid-exposed children., Study Design: Retrospective study of 94 children with prenatal opioid exposure evaluated with the CBCL at age 2 years., Results: Twenty-eight children (30%) had borderline/clinical findings on the CBCL, with 27% scoring borderline/clinical for Externalizing Problems. In the multivariable model, lower Bayley-III motor scores and discharge home with mother with safety plan were associated with borderline/clinical Externalizing Problems. Medication treatment for neonatal opioid withdrawal syndrome (NOWS) was associated with normal Externalizing Problems scores. Treatment with clonidine or phenobarbital was associated with scores in the normal range in all broadband CBCL measures., Conclusion: Specific factors are associated with behavioral and emotional challenges measured by borderline/clinical CBCL scores among opioid-exposed children., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Infant health among newborns with neonatal abstinence syndrome (NAS) has been understudied. We examined infant mortality and hospitalizations among infants diagnosed with NAS after birth., Methods: All live births in British Columbia (BC), Canada, for fiscal years from 2004-2005 to 2019-2020, were included ( N  = 696,900). NAS was identified based on International Classification of Diseases, version 10, Canadian modification (ICD-10-CA) codes; the outcomes included infant death and hospitalizations during the first year of life, ascertained from BC linked administrative data. Generalized estimating equation models were used to adjust for maternal factors., Results: There were 2,439 infants with NAS (3.50 per 1,000 live births). Unadjusted for other factors, infant mortality was 2.5-fold higher in infants with vs. without NAS (7.79 vs. 3.08 per 1,000 live births, respectively) due to increased post-discharge mortality NAS (5.76 vs. 1.34 per 1,000 surviving infants, respectively). These differences diminished after adjustment: adjusted odds ratio (AOR) for infant death was 0.85 [95% confidence interval (CI): 0.52-1.39]; AOR for post-discharge death was 1.75 (95% CI 1.00-3.06). Overall, 22.3% infants with NAS had at least one hospitalization after post-neonatal discharge, this proportion was 10.7% in those without NAS. During the study period, discharge to foster care declined from 49.5% to 20.3% in infants with NAS., Conclusion: Unadjusted for other factors, infants with NAS had increased post-discharge infant mortality and hospitalizations during the first year of life. This association diminished after adjustment for adverse maternal and socio-medical conditions. Infants with NAS had a disproportionately higher rate of placement in foster care after birth, although this proportion declined dramatically between 2004/2005 and 2019/2020. These results highlight the importance of implementing integrated care services to support infants born with NAS and their mothers during the first year of life and beyond, even though NAS itself is not independently associated with increased infant mortality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Lisonkova, Wen, Richter, Ting, Lyons, Mitchell-Foster, Oviedo-Joekes, Muraca, Bayrampour, Cattoni and Abrahams.)

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., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Buprenorphine-naloxone treatment may confer substantial benefits for the treatment of opioid use disorder (OUD) during pregnancy including lower risk for overdose/death, less diversion potential and reduced use of other substances. Treatment may also result in less severe Neonatal Abstinence Syndrome (NAS), but little is known about the effects of this medication on fetal neurodevelopment., Methods: The purpose of the current study is to evaluate neurobehaviors among fetuses exposed to buprenorphine-naloxone at four time points over the second and third trimesters of gestation in pregnant women with OUD on buprenorphine-naloxone therapy. Sixty minutes of continuous fetal monitoring via fetal actocardiograph with a single wide array abdominal transducer took place at times of peak and trough buprenorphine-naloxone levels in 24 pregnant women. Data collection, which included measures of fetal heart rate and motor activity, was conducted between 24 and 36 weeks gestation, with the majority (84.6%) monitored at two or more gestational ages. Medication dose and other substance use was monitored throughout the study and infant NAS severity was assessed., Results: Fetal heart rate (FHR), FHR variability, accelerations in FHR, and motor activity were suppressed when buprenorphine-naloxone levels were at pharmacologic peak as compared to trough concentrations at 36 weeks, but not earlier in gestation. Maternal medication dose was unrelated to infant NAS severity., Conclusions: Conclusions: There were evident subclinical fetal neurophysiological responses at times of peak maternal buprenorphine/naloxone levels in later gestation, similar to those previously described for buprenorphine only. Further studies evaluating the effects of these changes in fetal neurobehaviors on the longer-term infant development are needed., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Lauren Jansson reports financial support was provided by National Institute on Drug Abuse. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Breastfeeding is the optimal source of nutrition for all infants, but there are limited data on feeding outcomes in infants with neonatal abstinence syndrome (NAS) who are admitted in the neonatal intensive care unit (NICU)., Methods: A retrospective cohort study was conducted at a level II/III NICU. Study sample consisted infants with a diagnosis of NAS and those diagnosed with respiratory distress syndrome. The primary outcome was attainment of independent oral feeds, defined as the number of days to transition from full-tube to full oral feeds. Secondary outcomes included length of hospital stay and method (breast or bottle) of oral feeds at the start, at attainment of independent oral feeds, and at hospital discharge., Results: Infants with NAS took significantly longer to attain independent oral feeds than controls ( P = .021) and received significantly fewer breastfeeds at the start of oral feeds, at independent oral feeds, and at hospital discharge ( P = .000). There was no difference in length of hospital stay between groups., Conclusion: These results suggest that infants with NAS can experience difficulties achieving independent oral feeds and are less likely to receive breastfeeds. Additional support is required to enhance oral feeds in infants with NAS in the NICU., Competing Interests: The authors have no conflict of interest to declare and have not received funding for this study., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To elicit expert consensus on quality indicators for the hospital-based care of opioid-exposed infants., Methods: We used the ExpertLens online platform to conduct a 3-round modified Delphi panel. Expert panelists included health care providers, parents in recovery, quality experts, and public health experts. We identified 49 candidate quality indicators from a literature review and environmental scan. A total of 32 experts rated the importance and feasibility of the indicators using a 9-point Likert scale (Round 1), reviewed and discussed the initial ratings (round 2), and revised their original ratings (Round 3). Numeric scores corresponded with descriptive ratings of "low" (1-3), "uncertain" (4-6), or "high" (7-9). We measured consensus using the RAND/UCLA Appropriateness Method., Results: Candidate quality indicators assessed structures, processes, and outcomes in multiple domains of clinical care. After the final round, 36 indicators were rated "high" on importance and feasibility. Experts had strong consensus on the importance of quality indicators to assess universal screening of pregnant people for substance use disorder, hospital staff training, standardized assessment for neonatal opioid withdrawal syndrome, nonpharmacologic interventions, and transitions of care. For indicators focused on processes and outcomes, experts saw feasibility as dependent on the information routinely documented in electronic medical records or billing records. To present a more complete picture of hospital quality, experts suggested development of composite measures that summarize quality across multiple indicators., Conclusions: A panel of experts reached consensus on a range of quality indicators for hospital-based care of opioid-exposed infants, with potential for use in national benchmarking, intervention studies, or hospital performance measurement., (Copyright © 2024 by the American Academy of Pediatrics.)

The increase in substance use during pregnancy results in a higher incidence of neonatal abstinence syndrome/neonatal opioid withdrawal syndrome (NAS/NOWS), straining health care and social systems and creating an economic burden. There is a paradigm shift in transitioning the care approach for NAS/NOWS from a medical model of care to a family-centered individualized non-pharmacological care approach with non-pharmacological interventions as the first line of treatment. Supporting families after birth with a nurturing environment and providing them with a toolbox of non-pharmacological interventions prepares them for the transition from hospital to home., Competing Interests: Disclosure The author has no commercial or financial conflicts of interest and did not receive funding for this article., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: An increased incidence of maternal opioid use disorder (OUD) and neonatal abstinence syndrome (NAS) has prompted recommendations supporting a dyadic approach to care for birthing persons and their infants. However, there are no consensus guidelines outlining how the dyad is clinically defined., Methods: To examine how the opioid-exposed birthing person-infant dyad has been defined for purposes of data collection and research, a literature review applying the RAND/UCLA Appropriateness Method was conducted., Results: The search yielded 320 abstracts, with 110 articles identified as having a dyadic focus. While no articles included a specific definition for the dyad, 33 (30%) contained a descriptive reference to the birthing person-infant dyad. Thematic analysis revealed eight recurring elements characteristic of the dyad: (1) engagement, (2) communication, (3) bonding, (4) attachment, (5) mutual responsiveness, (6) reciprocity, (7) synchrony, and (8) attunement. Integrating these elements revealed the interactional relationship between the opioid-exposed birthing person and infant as the foundational principle that defines the dyad., Discussion: This definition shifts the focus of the opioid-exposed dyad from two individual patient populations to an interactional relationship that has broad applicability for clinical use, public health data collection, and research considerations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Jilani, Davis, Goldstein, Grossman, Jansson, Terplan and Jones.)

Neonatal opioid withdrawal syndrome (NOWS) is a growing public health concern. The complexity of in utero opioid exposure in clinical studies makes it difficult to investigate underlying mechanisms that could ultimately inform early diagnosis and treatments. Clinical studies are unable to dissociate the influence of maternal polypharmacy or the environment from direct effects of in utero opioid exposure, highlighting the need for effective animal models. Early animal models of prenatal opioid exposure primarily used the prototypical opioid, morphine, and opioid exposure that was often limited to a narrow period during gestation. In recent years, the number of preclinical studies has grown rapidly. Newer models utilize both prescription and nonprescription opioids and vary the onset and duration of opioid exposure. In this review, we summarize novel prenatal opioid exposure models developed in recent years and attempt to reconcile results between studies while critically identifying gaps within the current literature., Competing Interests: Declaration of interests The authors declare no competing interests in relation this work., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Individual patient-level measures of adverse social determinants of health are associated with neonatal opioid withdrawal syndrome (NOWS), but the relative impact of community-level adverse social determinants of health remains to be defined. We examined the association between community-level social vulnerability and NOWS among pregnant individuals receiving buprenorphine for opioid use disorder., Study Design: We conducted a secondary analysis of an established cohort of pregnant individuals and their infants participating in a multidisciplinary prenatal/addiction care program from 2013 to 2021. Addresses were geocoded using ArcGIS and linked at the census tract to the Centers for Disease Control and Prevention 2018 Social Vulnerability Index (SVI), incorporating 15 census variables. The primary exposure was the SVI as a composite measure of community-level social vulnerability, and secondarily, individual scores for four thematic domains (socioeconomic status, household composition and disability, minority status and language, and housing type and transportation). The primary outcome was a clinical diagnosis of NOWS defined as withdrawal requiring pharmacological treatment following buprenorphine exposure., Results: Among 703 pregnant individuals receiving buprenorphine, 39.8% (280/703) of infants were diagnosed with NOWS. Among our patinets, those who were nulliparous, had post-traumatic stress disorder, a term birth (≥ 37 weeks) and had a male infant were more likely to have an infant diagnosed with NOWS. Individuals with and without an infant diagnosed with NOWS had similarly high community-level social vulnerability per composite SVI scores (mean [standard deviation]: 0.6 [0.4-0.7] vs. 0.6 [0.4-0.7], p  = 0.2]. In adjusted analyses, SVI, as a composite measure as well as the four domains, was not associated with NOWS diagnosis., Conclusion: Among pregnant persons receiving buprenorphine enrolled in a multidisciplinary prenatal and addition care program, while individual risk factors that measure adverse social determinants of health were associated with an NOWS diagnosis in the infant, community-level social vulnerability as measured by the SVI was not associated with the outcome., Key Points: · Community-level SVI was not associated with neonatal opioid use disorder.. · Certain individual risk factors were identified as being associated with NOWS.. · Homogeneity of composite SVI scores may have led to lack of significant findings.., Competing Interests: None declared., (Thieme. All rights reserved.)

Limited research has examined a comprehensive set of predictors when evaluating discharge placement decisions for infants exposed to substances prenatally. Using a previously validated medical record data extraction tool, the current study examined prenatal substance exposure, infant intervention (i.e., pharmacologic, or non-pharmacologic), and demographic factors (e.g., race and ethnicity and rurality) as predictors of associations with discharge placement in a sample from a resource-poor state ( N = 136; 69.9% Non-Hispanic White). Latent class analysis (LCA) was used to examine whether different classes emerged and how classes were differentially related to discharge placement decisions. Logistic regressions were used to determine whether each predictor was uniquely associated with placement decisions. Results of the LCA yielded a two-class solution comprised of (1) a Low Withdrawal Risk class, characterized by prenatal exposure to substances with low risk for neonatal abstinence syndrome (NAS) and non-pharmacologic intervention, and (2) a High Withdrawal Risk class, characterized by a high risk of NAS and pharmacologic intervention. Classes were not related to discharge placement decisions. Logistic regressions demonstrated that meth/amphetamine use during pregnancy was associated with greater odds of out of home placement above other substance types. Future research should replicate and continue examining the clinical utility of these classes., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

This pilot and acceptability study sought to report provider acceptability and developmental concerns expressed by caregivers of children with prenatal opioid exposure using the Shared Decision-Making Tool (SDMT), an instrument created by study authors. Data were collected from five health care and early intervention providers and 83 caregivers from a medical clinic and early intervention service center. Descriptive statistics were used to identify frequency, mean level, and prioritization of developmental concerns using the SDMT, and to summarize provider acceptability about integrating the SDMT into their workflow. Communication was the most frequently cited concern in four consecutive age categories, followed by Inattention/impulsivity and Problem behavior. All providers "strongly agreed" or "agreed" with all statements on the provider feedback survey, except two instances. Results of this study support the SDMT as a potential tool to help engage caregivers and providers of children with prenatal opioid exposure in the shared decision-making process by standardizing communication related to areas of developmental concern and caregivers' priority needs. Findings from this pilot study will inform modifications to the SDMT and administration instructions before our next study, which will examine psychometric properties and caregiver acceptability of the scale., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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., (© 2024. The Author(s).)

Objective: An increase in maternal use of licit or illicit substances, alcohol, and tobacco has resulted in an increased incidence of neonatal abstinence syndrome (NAS). In recent years, NAS management has shifted to initiating an Eat, Sleep, Console (ESC) approach prior to pharmacologic treatment. The objective of this study was to evaluate the impact of ESC in combination with pharmacologic treatment in the management of NAS for infants exposed to substance use in utero ., Methods: This single system, multisite, retrospective cohort study evaluated infants with known exposure to substance or polysubstance use in utero or those who had signs and symptoms of withdrawal with a positive toxicology screen. The primary outcome of rate of pharmacologic therapy initiated was evaluated pre and post implementation of ESC. Secondary outcomes included hospital length of stay, day of life that pharmacologic therapy was initiated, and an evaluation of the ESC guideline. A subgroup analysis with similar outcomes was also performed for patients with maternal polysubstance use., Results: A total of 2843 patients were screened, and 50 patients were randomly selected for -inclusion in both pre- and post-groups. The rate of pharmacologic therapy initiated post implementation of ESC decreased from 58% to 30% (p < 0.01). In the post-group, there was a decrease in the number of -patients requiring scheduled morphine (33%, p < 0.01) and duration of pharmacologic therapy (14.6 days vs 6.47 days, p < 0.01)., Conclusions: Implementing an ESC guideline decreased the length of stay and rate of pharmacologic intervention needed for infants with NAS at our institution., Competing Interests: Disclosure. The authors declare no conflicts or financial interest in any product or service mentioned in the manuscript, including grants, equipment, medications, employment, gifts, and honoraria. The authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis., (Copyright. Pediatric Pharmacy Association. All rights reserved. For permissions, email: membership@pediatricpharmacy.org.)

Objective: The difference in infant health outcomes by maternal opioid use disorder (OUD) status is understudied. We measured the association between maternal OUD during pregnancy and infant mortality and investigated whether this association differs by infant neonatal opioid withdrawal syndrome (NOWS) or maternal receipt of medication for OUD (MOUD) during pregnancy., Methods: We sampled 204,543 Medicaid-paid births from Wisconsin, United States (2010-2018). The primary exposure was any maternal OUD during pregnancy. We also stratified this exposure on NOWS diagnosis (no OUD; OUD without NOWS; OUD with NOWS) and on maternal MOUD receipt (no OUD; OUD without MOUD; OUD with <90 consecutive days of MOUD; OUD with 90+ consecutive days of MOUD). Our outcome was infant mortality (death at age <365 days). Demographic-adjusted logistic regressions measured associations with odds ratios (OR) and 95% confidence intervals (CI)., Results: Maternal OUD was associated with increased odds of infant mortality (OR 1.43; 95% CI 1.02-2.02). After excluding infants who died <5 days post-birth (i.e., before the clinical presentation of NOWS), regression estimates of infant mortality did not significantly differ by NOWS diagnosis. Likewise, regression estimates did not significantly differ by maternal MOUD receipt in the full sample., Conclusions: Maternal OUD is associated with an elevated risk of infant mortality without evidence of modification by NOWS nor by maternal MOUD treatment. Future research should investigate potential mechanisms linking maternal OUD, NOWS, MOUD treatment, and infant mortality to better inform clinical intervention., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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.

Background: As the overdose crisis unfolded, narratives mischaracterizing neonatal abstinence syndrome (NAS) as "addicted babies" with echoes to the "crack babies" panic proliferated in mainstream media. his study examines NAS misinformation dynamics and characteristics over a seven-year period., Methods: Based on a comprehensive query, Media Cloud was used to compile mainstream media content relating to NAS between 2015 and 2021. Articles were redundantly coded on key parameters such as speakers represented, publication source, and scientific accuracy., Results: Of the 348 articles meeting search criteria, 264 (76 %) featured misinformed narratives, 70 (20 %) featured informed narratives, and 14 (4 %) featured both informed and misinformed content. Most frequent misinformation elements related to misrepresentation of babies as "addicted" at birth and exaggeration of NAS symptomatology and long-term harms. Least represented voices were people most affected, with just 11 (2 %) featuring mothers who used opioids prepartum., Discussion: Since misinformation contributes to punitive legal responses and harms patient care, efforts to prevent, monitor, and address inaccurate and stigmatizing narratives are essential to improving policy and practice., Competing Interests: Declaration of competing interest The authors declare no conflicts of interests., (Copyright © 2024. Published by Elsevier B.V.)

Objective: To develop a dyadic-centered framework focused on clinical care, surveillance, and research for birthing persons with opioid use disorder (OUD) and their infants and children., Study Design: Between February and March 2023, an analysis was conducted within the US Department of Health and Human Services (HHS) of activities directed at opioid-exposed birthing persons and their infants and children (the dyad) to identify: 1) number of activities, stratified by type and 2) characteristics across health and supportive activities that serve the dyad vs birthing persons or infants and children individually. Descriptive and thematic analyses were used to assess quantity and characteristics of fiscal year 2023-2024 activities aggregated across eleven HHS agencies., Results: Of 181 activities examined, 75 met inclusion criteria specific to serving birthing persons with OUD and opioid-exposed infants and children. Sixty-two percent of activities were dyad focused. Five categories of dyadic activities were identified: research (45%), education and training (28%), health and supportive services (21%), surveillance (4%), and quality improvement (2%). Eight specific characteristics were key to dyadic activities: a life course and generational approach, emphasis on relationship, dyadic outcomes, service wraparound, payment structures supporting dyadic care, data linkage, and social determinants of health., Conclusions: This analysis of HHS activities directed at birthing persons with OUD and opioid-exposed infants and children showed that most programs had a dyadic focus. Synthesizing elements identified from activities serving the dyad facilitated the development of a dyadic framework integrating clinical care, public health surveillance, and research., Competing Interests: Declaration of Competing Interest Funding sources: None. The views expressed in this article are those of the authors and not necessarily those of the Department of Health and Human Services or its divisions. The authors declare no conflicts of interest., (Published by Elsevier Inc.)

Objective: Infants with prenatal substance exposure or neonatal abstinence syndrome (NAS) use health services more often than other children; however, little is known about their use of mental health services and psychotropic medication., Methods: The sample (N=1,004,085) consisted of infants born in 2016 in 38 states who were followed through the fifth year of life and enrolled each year in Medicaid or the Children's Health Insurance Program. Infants with prenatal substance exposure or NAS were identified with ICD-10 diagnosis codes; procedure and revenue codes documented their service use., Results: Rates of any mental health visit and of psychotropic medication use were higher among infants with prenatal substance exposure or NAS compared with infants without either condition; these patterns persisted during most years of the 5-year study., Conclusions: Infants' elevated mental health services use through their first 5 years of life highlights the importance of early screening and subsequent engagement in school-based mental health interventions., Competing Interests: The authors report no financial relationships with commercial interests.

Background: The severity of neonatal abstinence syndrome (NAS) may be assessed with the Finnegan score (FS). Since the FS is laborious and subjective, alternative ways of assessment may improve quality of care., Objective: In this pilot study, we examined associations between the FS and routine monitoring data obtained from the electronic health record system., Methods: The study included 205 neonates with NAS after intrauterine (n=23) or postnatal opioid exposure (n=182). Routine monitoring data were analyzed at 60±10 minutes (t-1) and 120±10 minutes (t-2) before each FS assessment. Within each time period, the mean for each variable was calculated. Readings were also normalized to individual baseline data for each patient and parameter. Mixed effects models were used to assess the effect of different variables., Results: Plots of vital parameters against the FS showed heavily scattered data. When controlling for several variables, the best-performing mixed effects model displayed significant effects of individual baseline-controlled mean heart rate (estimate 0.04, 95% CI 0.02-0.07) and arterial blood pressure (estimate 0.05, 95% CI 0.01-0.08) at t-1 with a goodness of fit (R2m) of 0.11., Conclusions: Routine electronic data can be extracted and analyzed for their correlation with FS data. Mixed effects models show small but significant effects after normalizing vital parameters to individual baselines., (© Till Rech, Kerstin Rubarth, Christoph Bührer, Felix Balzer, Christof Dame. Originally published in JMIR Pediatrics and Parenting (https://pediatrics.jmir.org).)

Objective: The opioid epidemic has led to a surge in diagnoses of neonatal opioid withdrawal syndrome (NOWS). Many states track the incidence of NOWS by using the P96.1 International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) code for "neonatal withdrawal symptoms from maternal use of drugs of addiction." In October 2018, an ICD-10-CM code for neonatal opioid exposure (P04.14) was introduced. This code can be used when an infant is exposed to opioids in utero but does not have clinically significant withdrawal symptoms. We analyzed the effect of the P04.14 code on the incidence rate of NOWS (P96.1) and "other" neonatal drug exposure diagnoses (P04.49)., Methods: We used private health insurance data collected for infants in the United States from the first quarter of 2016 through the third quarter of 2021 to describe incidence rates for each code over time and examine absolute and percentage changes before and after the introduction of code P04.14., Results: The exclusive use of code P96.1 declined from an incidence rate per 1000 births of 1.08 in 2016-2018 to 0.70 in 2019-2021, a -35.7% (95% CI, -47.6% to -23.8%) reduction. Use of code P04.49 only declined from an incidence rate of 2.34 in 2016-2018 to 1.64 in 2019-2021, a -30.0% (95% CI, -36.4% to -23.7%) reduction. Use of multiple codes during the course of treatment increased from an average incidence per 1000 births of 0.56 in 2016-2018 to 0.79 in 2019-2021, a 45.5% (95% CI, 24.8%-66.1%) increase., Conclusion: The introduction of ICD-10-CM code P04.14 altered the use of other neonatal opioid exposure codes. The use of multiple codes increased, indicating that some ambiguity may exist about which ICD-10-CM code is most appropriate for a given set of symptoms., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Rates of neonatal abstinence syndrome (NAS) resulting from opioid misuse are rising. However, policies to treat opioid misuse during pregnancy are unclear. We apply a difference-in-differences design to national pediatric discharge records to examine the effects of state Medicaid policies on NAS. Among states in which Medicaid covered two clinically-recommended medications for treating opioid misuse (buprenorphine, methadone), the Affordable Care Act's Medicaid expansion reduced Medicaid-covered NAS hospitalizations. Medicaid expansion did not affect NAS hospitalizations in other expansion states. These findings imply a nuanced relationship between Medicaid policy and NAS that should be considered in addressing opioid misuse among pregnant women., Competing Interests: Conflict of Interest Statement: The authors have no known conflict of interest regarding the subject of this paper.

Since the first use of methadone to treat OUD in pregnancy in the 1970s, there has been a long, controversial, and confusing history of studies, regulatory actions, and practice changes that have clouded an accurate perception of methadone's use in pregnancy. This review will trace this history with a focus on the effect of methadone exposure during pregnancy on neonatal abstinence syndrome (NAS). A new laboratory measure, the serum methadone/metabolite ratio (MMR), has provided a tool for documenting the profoundly dynamic nature of perinatal metabolism. Continuous induction of metabolic enzymes during pregnancy requires dose adjustments and dose frequency changes. The concept of "fetal methadone dosing" emphasizes that relative stability of methadone levels in the fetus is an important consideration for methadone dosing in pregnancy. Finally, the effects of the societal "war on drugs" on pediatric management of neonatal withdrawal risks will be discussed, as well as the importance of comprehensive services for mother and child including the "rooming-in" approach of neonatal care which has considerably replaced the older NICU care model of maternal/infant separation., Competing Interests: Author LF was employed by Finnegan Consulting LLC. Dr. Finnegan declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2023 McCarthy and Finnegan.)

Objectives: Studies have shown significant increases in the prevalence of maternal opioid use. Most prevalence estimates are based on unverified ICD-10-CM diagnoses. This study determined the accuracy of ICD-10-CM opioid-related diagnosis codes documented during delivery and examined potential associations between maternal/hospital characteristics and diagnosis with an opioid-related code., Methods: To identify people with prenatal opioid use, we identified a sample of infants born during 2017-2018 in Florida with a NAS related diagnosis code (P96.1) and confirmatory NAS characteristics (N = 460). Delivery records were scanned for opioid-related diagnoses and prenatal opioid use was confirmed through record review. The accuracy of each opioid-related code was measured using positive predictive value (PPV) and sensitivity. Modified Poisson regression was used to calculate adjusted relative risks (aRR) and 95% confidence intervals (CI)., Results: We found the PPV was nearly 100% for all ICD-10-CM opioid-related codes (98.5-100%) and the sensitivity was 65.9%. Non-Hispanic Black mothers were 1.8 times more likely than non-Hispanic white mothers to have a missed opioid-related diagnosis at delivery (aRR:1.80, CI 1.14-2.84). Mothers who delivered at a teaching status hospital were less likely to have a missed opioid-related diagnosis (p < 0.05)., Conclusions for Practice: We observed high accuracy of maternal opioid-related diagnosis codes at delivery. However, our findings suggest that over 30% of mothers with opioid use may not be diagnosed with an opioid-related code at delivery, although their infant had a confirmed NAS diagnosis. This study provides information on the utility and accuracy of ICD-10-CM opioid-related codes at delivery among mothers of infants with NAS., (© 2023. The Author(s).)

Introduction: Estimating Neonatal Abstinence Syndrome (NAS) and prenatal substance exposure rates in Medicaid can help target program efforts to improve access to services., Methods: The data for this study was extracted from the 2016-2020 Transformed Medicaid Statistical Information System (T-MSIS) Analytic Files (TAF) Research Identifiable Files (RIF) and included infants born between January 1, 2016 and December 31, 2020 with a either a NAS diagnosis or prenatal substance exposure., Results: Between 2016 and 2020, the estimated national rate of NAS experienced a 18% decline, while the estimated national rate of prenatal substance exposure experienced a 3.6% increase. At the state level in 2020, the NAS rate ranged from 3.2 per 1000 births (Hawaii) to 68.0 per 1000 births (West Virginia). Between 2016 and 2020, 28 states experienced a decline in NAS births and 20 states had an increase in NAS rates. In 2020, the lowest prenatal substance exposure rate was observed in New Jersey (9.9 per 1000 births) and the highest in West Virginia (88.1 per 1000 births). Between 2016 and 2020, 38 states experienced an increase in the rate of prenatal substance exposure and 10 states experienced a decline., Discussion: Estimated rate of NAS has declined nationally, but rate of prenatal substance exposure has increased, with considerable state-level variation. The reported increase in prenatal substance exposure in the majority of US states (38) suggest that substances other than opioids are influencing this trend. Medicaid-led initiatives can be used to identify women with substance use and connect them to services., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objective: Rates of neonatal abstinence syndrome/neonatal opioid withdrawal syndrome (NAS/NOWS), a withdrawal syndrome from opioids and other substances resulting from intrauterine exposure, have been increasing exponentially in the U.S. To improve health outcomes, it is important to understand population health risks, including rehospitalization and related diagnoses, using current data. This study will compare and describe the rates of rehospitalization, the demographic characteristics and the rehospitalization diagnoses and age at diagnosis between the infants affected by NAS/NOWS to those sampled who were unaffected. This study will also describe the frequency of NAS/NOWS births per year along with a yearly comparison of readmissions in those affected by NAS/NOWS to those who were not (2016-2020)., Methods: Health claims data were used to conduct a case/control study. Diagnosis codes for neonatal withdrawal syndrome/NAS/NOWS (P04.49 or P96.1 and P96.1 alone) from 1 October 2015 to 1 June 2021 were extracted, and controls were case-matched based on month/year of birth. Rehospitalizations following birth and the related diagnoses were described and grouped using the Agency of Healthcare Research Quality Clinical Classifications Software Refined Frequency distribution. The chi-square test of association and generalized estimating equation modeling were used for data analysis., Results: Infants affected by NAS/NOWS are 2.7 times more likely to have a rehospitalization. White, non-Hispanic neonates (OR = 1.5; p  = .007) and those infants residing in rural areas (OR = 1.9; p  < .001) were disproportionately affected. We identified a host of admission diagnoses with increased prevalence in infants affected by NAS/NOWS when compared to those who were not affected (e.g. infectious diseases, feeding disorders)., Conclusions: Infants with NAS/NOWS are at increased risk of rehospitalization with a host of diagnoses, and specific demographic groups (White, rural) are more highly affected.

Objectives: To characterize demographics, birth parameters, and social determinants of health among mother-infant dyads affected by neonatal abstinence syndrome (NAS) in Pennsylvania., Methods: We linked 2018-2019 NAS surveillance data to birth record data using probabilistic methods and then geospatially linked to local social determinants of health data based on residential address. We generated descriptive statistics and used multivariable mixed-effects logistic regression to model the association between maternal characteristics, birth parameters, social determinants of health, and NAS., Results: In adjusted models maternal age > 24, non-Hispanic white race/ethnicity, low educational attainment, Medicaid as payor at delivery, inadequate or no prenatal care, smoking during pregnancy, and low median household income were associated with NAS. We found no significant associations between NAS and county-level measures of clinician supply, number of substance use treatment facilities, or urban/rural designation., Conclusions for Practice: This study characterizes mother-infant dyads affected by NAS using linked non-administrative, population data for Pennsylvania. Results demonstrate a social gradient in NAS and inequity in prenatal care receipt among mothers of infants with NAS. Findings may inform implementation of state-based public health interventions., (© 2023. The Author(s).)

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., Competing Interests: Declaration of competing interest This work was supported by U01DA050243. We have no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Neonatal abstinence syndrome (NAS) highlights the intricate interplay between maternal substance use during pregnancy and the challenges neonates face from the distressing global opioid crisis. This comprehensive review captures the multilayered landscape of NAS, encircling its underlying mechanisms, epidemiology, diagnostic intricacies, clinical manifestations, continuing developmental impacts, treatment paradigms, and the crucial role of multidisciplinary care. The core pathophysiology of NAS involves the transplacental passage of addictive substances, activating chemical dependence in the maturing fetus, which is characterized by neurotransmitter dysregulation, neuroadaptations, and receptor sensitization. A diverse clinical presentation ranges from central nervous system hyperactivity and autonomic dysregulation to gastrointestinal manifestations, necessitating homogenous assessment tools such as the Finnegan Neonatal Abstinence Scoring System. The demand for a multilayered approach is essential for comprehensive management, involving pharmacological interventions like morphine or methadone and non-pharmacological strategies such as swaddling. The complications of NAS are not only limited to but are also well beyond infancy, leading to behavioral, longstanding cognitive, and socioemotional consequences. Addressing these developmental arcs demands decisive longitudinal monitoring and early interventions. NAS management is fundamentally multidisciplinary, requiring the teamwork of nurses, social workers, psychologists, pediatricians, and neonatologists. Apart from the clinical realm, managing the psychosocial needs of families traversing NAS requires resources and empathy. A crucial comprehensive approach is essential to confront the challenges and limitations of NAS. From early identification and prevention to longstanding support through pharmacological, non-pharmacological, and psychological channels, it creates a holistic structure that emerges as the basis for understanding the complicated relationship between maternal substance use and its impact on neonates. An amalgamation of community engagement, society, policy initiatives, and medical expertise is essential to mitigate the repercussions of NAS and adopt healthier outcomes for affected infants., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Dumbhare et al.)

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

Background: An infant's cognitive development is highly dependent on early interactions with its primary caregiver, often its mother. Feeding, a frequent and early exchange between mothers and infants, is an important time for maternal-infant bonding. Mothers with opioid use disorder have been found to be more physically and verbally stimulating and more active during feeds than mothers with no opioid use., Purpose: The purpose of this study was to describe the characteristics of verbal interactions mothers with opioid use disorder expressed while engaged in a feeding encounter with their infant undergoing treatment for neonatal opioid withdrawal syndrome to offer insight into maternal experiences and potential challenges of feeding infants experiencing withdrawal., Methods: A qualitative descriptive analysis of maternal verbalizations during the feeding was used in a secondary analysis using the Barnard Model as the theoretical framework for maternal-infant interaction., Results: A theory-driven deductive approach was assumed to organize the identified subthemes within the concepts of the Barnard Model. Mothers frequently commented on hunger, satiation, and stress cues, while providing consolation, praise, and encouragement. Mothers expressed concerns regarding feeding volume and pace, and consequences related to feeding., Implications for Practice and Research: It is crucial that clinicians remember that feeding is an important time for maternal-infant bonding. Further research into the feeding interactions of mother-infant dyads with opioid exposure is warranted. As infants may present with subacute signs of withdrawal, including persistent feeding difficulties for months, further investigation into feeding challenges dyads experience after discharge from the hospital is needed., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 by The National Association of Neonatal Nurses.)

Objective: To determine if a policy change that limited the ability of parental caregivers to leave the postpartum unit during the COVID-19 pandemic influenced neonatal abstinence syndrome (NAS) scores, admissions to the NICU for NAS treatment, and length of stay (LOS) on the nursing unit., Design: Retrospective chart review., Setting/local Problem: During the pandemic, a change in policy limited parental caregivers from leaving the nursing unit., Participants: Neonates being screened for NAS during the period before the policy change from April 2, 2019, through April 1, 2020 (n = 44), and the period after the policy change (n = 23) from April 2, 2020, to April 1, 2021., Measurements: Levene's test was used to determine homogeneity of variance before independent t tests on mean NAS scores and LOS across groups. A linear mixed-effects model tested differences in NAS scores, accounting for time and group. Chi-square tests determined differences in the number of neonates transferred to the NICU across groups., Results: No differences between group variables were found, with the exception of feeding type and cocaine/cannabinoid use (p < .05). No significant differences were found in mean NAS scores (p = .96), LOS (p = .77) or NAS scores accounting for time and between groups (p = .069). Transfers to the NICU in the pre-policy change group were significantly greater (p = .05)., Conclusion: Although no decrease was observed for mean NAS scores and LOS of the neonates, a decrease in transfers to the NICU for pharmacologic treatment for NAS was observed. Further research is required to determine casual relationships for the decrease in NICU transfers., (Copyright © 2023 AWHONN. Published by Elsevier Inc. All rights reserved.)

Buprenorphine (BUP) is the preferred treatment for opioid use disorder during pregnancy but can cause neonatal opioid withdrawal syndrome (NOWS). Norbuprenorphine (NorBUP), an active metabolite of BUP, is implicated in BUP-associated NOWS. We hypothesized that BUP, a low-efficacy agonist of mu opioid receptors, will not antagonize NorBUP, a high-efficacy agonist of mu opioid receptors, in producing NOWS. To test this hypothesis, we treated pregnant Long-Evans rats with BUP (0, 0.01, 0.1 or 1mg/kg/day) ± NorBUP (1mg/kg/day) from gestation day 9 until pup delivery, and tested pups for opioid dependence using our established NOWS model. We used LC-MS-MS to quantify brain concentrations of BUP, NorBUP, and their glucuronide conjugates. BUP had little effect on NorBUP-induced NOWS, with the exception of 1mg/kg/day BUP significantly increasing NorBUP-induced NOWS by 58% in females. BUP and NorBUP brain concentrations predicted NOWS in multiple linear regression models. Interestingly, NorBUP contributed more to NOWS in females (β NorBUP = 51.34, p = 0.0001) than in males (β NorBUP = 19.21, P = 0.093), while BUP was similar for females (β BUP = 10.62, P = 0.0017) and males (β BUP = 11.38, P = 0.009). We are the first to report that NorBUP induces NOWS in the presence of BUP and it is more influential in females than males in the contribution of NorBUP to BUP-associated NOWS. These findings suggest that females are more susceptible to NorBUP-induced NOWS, and that treatment strategies that reduce prenatal NorBUP exposure may be more effective for females than males., Competing Interests: Declaration of Competing Interest No conflict declared., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Neonatal abstinence syndrome (NAS) is a collection of symptoms that neonates may experience following antenatal exposure to substances that induce withdrawal. Optimal management remains unknown, and there is variation in management and outcomes., Objectives: To describe the management, length of hospitalization, and adverse events in near-term and full-term neonates with NAS for whom treatment (pharmacotherapy and/or supportive care) was initiated in the neonatal intensive care unit (NICU)., Methods: A chart review was conducted of neonates admitted to the NICU of Surrey Memorial Hospital, Surrey, British Columbia, who received treatment for NAS between September 1, 2016, and September 1, 2021., Results: A total of 48 neonates met the inclusion criteria. Opioids represented the most frequent type of antenatal exposure. Polysubstance exposures occurred in 45 (94%) of the neonates. Morphine was given to 29 (60%) of the neonates, and phenobarbital to 6 (13%); 5 of these neonates received both medications. The average duration of morphine treatment was 14 days, and the average length of hospitalization (all patients) was 16 days. All of the neonates experienced adverse events; in particular, 9 (30%) of the 30 who received pharmacotherapy were too sedated to feed, compared with 0% of the 18 with no pharmacotherapy., Conclusions: The common finding of polysubstance antenatal exposure, involving predominantly opioids, was associated with scheduled morphine pharmacotherapy for the majority of patients, prolonged hospitalization, and frequent adverse events. Pharmacotherapy for NAS was associated with levels of sedation that interfered with feeding in neonates., Competing Interests: Competing interests: None declared., (2023 Canadian Society of Hospital Pharmacists. All content in the Canadian Journal of Hospital Pharmacy is copyrighted by the Canadian Society of Hospital Pharmacy. In submitting their manuscripts, the authors transfer, assign, and otherwise convey all copyright ownership to CSHP.)