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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.

Every 15 minutes in the US, an infant exposed to opioids is born. Approximately 50% of these newborns will develop Neonatal Opioid Withdrawal Syndrome (NOWS) within 5 days of birth. It is not known which infants will develop NOWS, therefore, the current hospital standard-of-care dictates a 96-hour observational hold. Understanding which infants will develop NOWS soon after birth could reduce hospital stays for infants who do not develop NOWS and decrease burdens on hospitals and clinicians. We propose noninvasive clinical indicators of NOWS, including newborn neurobehavior, autonomic biomarkers, prenatal substance exposures, and socioeconomic environments. The goals of this protocol are to use these indicators shortly after birth to differentiate newborns who will be diagnosed with NOWS from those who will have mild/no withdrawal, to determine if the indicators predict development at 6 and 18 months of age, and to increase NOWS diagnostic sensitivity for earlier, more accurate diagnoses. [ABSTRACT FROM AUTHOR]

Background: Neonatal Opioid Withdrawal Syndrome (NOWS) is a consequence of in-utero exposure to prenatal maternal opioids, resulting in the manifestation of symptoms like irritability, feeding problems, tremors, and withdrawal signs. Opioid use disorder (OUD) during pregnancy can profoundly impact both mother and fetus, disrupting fetal brain neurotransmission and potentially leading to long-term neurological, behavioral, and vision issues, and increased infant mortality. Drug resistance complicates OUD and NOWS treatment, with protein kinase regulation of drug transporters not fully understood. Methods: DNA methylation levels of ATP-binding cassette (ABC) and solute carrier (SLC) drug transporters, along with protein kinase C (PKC) genes, were assessed in 96 placental samples using the Illumina Infinium MethylationEPIC array (850K). Samples were collected from three distinct groups: 32 mothers with infants prenatally exposed to opioids who needed pharmacological intervention for NOWS, 32 mothers with prenatally opioid-exposed infants who did not necessitate NOWS treatment, and 32 mothers who were not exposed to opioids during pregnancy. Results: We identified 69 significantly differentially methylated SLCs, with 24 hypermethylated and 34 hypomethylated, and 11 exhibiting both types of methylation changes including SLC13A3, SLC15A2, SLC16A11, SLC16A3, SLC19A2, and SLC26A1. We identified methylation changes in 11 ABC drug transporters (ABCA1, ABCA12, ABCA2, ABCB10, ABCB5, ABCC12, ABCC2, ABCC9, ABCE1, ABCC7, ABCB3): 3 showed hypermethylation, 3 hypomethylation, and 5 exhibited both. Additionally, 7 PKC family genes (PRKCQ, PRKAA1, PRKCA, PRKCB, PRKCH, PRKCI, and PRKCZ) showed methylation changes. These genes are associated with 13 pathways involved in NOWS, including ABC transporters, bile secretion, pancreatic secretion, insulin resistance, glutamatergic synapse, and gastric acid secretion. Conclusion: We report epigenetic changes in PKC-related regulation of drug transporters, which could improve our understanding of clinical outcomes like drug resistance, pharmacokinetics, drug-drug interactions, and drug toxicity, leading to maternal relapse and severe NOWS. Novel drugs targeting PKC pathways and transporters may improve treatment outcomes for OUD in pregnancy and NOWS. [ABSTRACT FROM AUTHOR]

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

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. [ABSTRACT FROM AUTHOR]

Compared with the Finnegan Neonatal Abstinence Scoring System (FNASS), the Eat, Sleep, Console (ESC) approach reduces pharmacotherapy and length of stay (LOS) for neonatal opioid withdrawal syndrome (NOWS) infants. The independent outcome contribution of ESC is unknown as the approach combines ESC assessment with additional management changes. Our objective was to evaluate ESC assessment's independent impact on outcomes compared with FNASS. We conducted a retrospective cohort study of in utero opioid-exposed infants ≥35 weeks gestation managed with FNASS versus ESC. Outcomes included pharmacotherapy initiation, LOS, length of pharmacotherapy, and emergency department visit/readmissions. Among 151 FNASS and 100 ESC managed infants, pharmacotherapy initiation (P =.47), LOS for all infants (P =.49), and LOS for pharmacologically treated infants (P =.68) were similar. Length of pharmacotherapy did not differ (P =.84). Emergency department evaluation/NOWS readmission was equally rare (P =.65). Using equivalent models of care, comparison of ESC and FNASS assessment tools showed no difference in NOWS outcomes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective This study aimed to describe our experience with universal urine drug screening (UDS) with rapid confirmation (RC) via liquid chromatography mass spectrometry (LC-MS) before infant's discharge, in efforts to increase detection of neonates at risk of neonatal opioid withdrawal syndrome (NOWS) while reducing patient burden related to false positive results. Study Design Two-phase retrospective study of all pregnant women admitted to our labor and delivery (L&D) unit before (phase 1, April 2018–March 2019) and after (phase 2, October 2019–September 2020) RC of UDS was initiated. Urine samples were obtained on admission and screened for drugs using an enzyme immunoassay with positive results reflexed to confirmation via LC-MS. The turnaround time for LC-MS was 1 week in phase 1 and 24 hours in phase 2. For mothers with positive LC-MS confirmation, the infant's meconium was sent for drug screening. Positive results were determined to be true or false positive based on urinary LC-MS results. The primary outcome was the rate of opioid-positive mothers who were unanticipated. The secondary outcome was the difference in rate of neonates who were observed for NOWS, before and after implementation of RC with LC-MS. Results In phase 2, a total of 2,395 deliveries occurred of which 2,122 (88.6%) had available UDS results. Fifty-two (2.5%) women had a positive UDS for at least one drug with LC-MS confirmation. Of those, 25 were true positive and 27 were false positive. Twenty-one (84%) true positive mothers were taking opioids and 8 (37%) of them were unanticipated positives. Among mothers with positive UDS for opioids, the neonatal observation rate for development of NOWS was 100% (22/22) and 48% (21/44) before and after implementation of LC-MS RC, respectively. Conclusion Universal UDS and LC-MS RC in L&D may improve detection of unanticipated positive mothers whose infants are at risk of NOWS. RC of positive results allows intervention only for confirmed cases. Key Points Universal UDS can detect more infants at risk of NOWS. Rapid confirmation of positive UDS reduces burden. Only confirmed infants should be observed in the neonatal intensive care unit. Child Protective Services should only be notified of confirmed opioid-positive results. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 5 824 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 (β = -23.0%; P < .001) and a decrease over time in the postguidelines period (β = -0.7% per month; P 5 .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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim: How maternal opioid maintenance treatment (OMT) affects children is under‐researched. This population‐based registry study investigated child growth and somatic health following intrauterine exposure to this treatment. Methods: Children born between 1 March 2011 and 30 May 2021 to mothers who used buprenorphine, buprenorphine‐naloxone, or methadone throughout their pregnancies were followed for 2 years at the Helsinki University Hospital, Finland. Appropriate statistical tests were used to compare the treatment groups. Results: Of the 67 neonates, 52% were male, 96% were born full‐term and 63% were treated for neonatal opioid withdrawal syndrome. Otherwise, the children were predominantly healthy, although relatively small: 22% were small for gestational age, the methadone group children being the smallest. Foetal exposure to maternal methadone treatment, illicit drugs, hepatitis C and smoking were associated with small for gestational age; the former two were also associated with later slower growth, especially head growth and weight gain (p < 0.001). However, 29% were overweight at 2 years. Conclusion: Using child growth as the outcome, we found that buprenorphine‐naloxone and buprenorphine‐monotherapy had equal effects as forms of maternal OMT. Exposure to multiple risk factors may harm foetal and subsequent growth. We recommend long‐term follow‐up of children exposed to maternal OMT. [ABSTRACT FROM AUTHOR]

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

Opioid use disorder (OUD) is highly prevalent, affecting up to 1% of pregnancies. The current standard of care for the management of OUD during pregnancy has been maintained with opioid agonist treatment (OAT), using either methadone or buprenorphine. OAT use has been associated with a risk of neonatal abstinence syndrome (NAS), which requires a longer neonatal length of stay for monitoring and possible pharmacological treatment. As a result, opioid medical detoxification (OMD) was proposed as an alternative strategy to reduce the stigma associated with OAT and to eliminate the risk of NAS by detoxifying or tapering pregnant persons during their pregnancy before delivery; however, the safety and effectiveness of OMD during pregnancy have not been established. This scoping review aims to summarize recent evidence related to maternal, obstetrical, and neonatal outcomes of OMD in comparison to OAT maintenance. This review also provides recommendations for future research initiatives to fill gaps in managing this patient population. [ABSTRACT FROM AUTHOR]

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

Background: A challenge in addressing neonatal opioid withdrawal syndrome (NOWS) is knowing who has been exposed and needs monitoring for withdrawal. Women do not always get asked about or disclose opioid use, and biologic testing is neither universal nor infallible. We investigate the prevalence and effectiveness of methods for identifying prenatal opioid exposure. Methods: A review of medical charts at five delivery hospitals identified newborns with known exposure (i.e., NOWS diagnosis) for study inclusion. Results: Over 95% of the mothers had 1+ urine drug screening (UDS) during pregnancy, 38% had UDS at delivery, 94% had documentation of self-report inquiry, and 81% of the newborns had biologic testing of meconium and/or cord tissue. Pregnancy UDS detected opioid use for 17% of the sample, UDS at delivery detected for 32%. A self-report of the use prenatally/at delivery identified 85%. Cord tissue testing was positive for 78%, meconium for 61%, and infant UDS 15%. 96% of the newborns were positive on 1+ exposure variable. Conclusions: With drug testing only when indicated, almost all exposed pregnancies included inquiry about and biologic testing for opioid use/exposure. Reliance on any one assessment method may miss exposed newborns, but consideration of all information may identify most if not all newborns needing monitoring for NOWS. [ABSTRACT FROM AUTHOR]

Abstract 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.

Introduction Design Methods Results Conclusions Clinical Relevance Prenatal opioid exposure (POE) is a major public health consequence of the opioid epidemic. Long‐term health outcomes associated with POE remain unclear, especially for children with POE without a diagnosis of neonatal abstinence syndrome (NAS). Here, we aimed to describe the health outcomes of children with POE and with POE and NAS compared to unexposed children during the first 7 years of life.In this retrospective observational cohort study, children born between 2015 and 2022 were identified from the Maternal and Infant Data Hub (MIDH), a data repository that continuously integrates maternal, neonatal, and pediatric records from two academic medical centers and one pediatric hospital system in the Midwest, USA.International Classification of Diseases, 10th Revision, Clinical Modification (ICD‐10 CM) chapters A00‐N99 served as outcomes of interest. Annual incidence and crude incidence rate ratios were calculated to explore descriptive differences between the exposed and unexposed groups.The study included 22,002 children, 20,130 (91.5%) of whom were unexposed and 1872 (8.5%) were exposed. Of the 1872 exposed children, 371 (19.8%) received a diagnosis of NAS (POE + NAS) and 1501 were in the POE‐NAS group. Across all 7 years, exposed children had a higher incidence of diagnoses in most ICD‐10 CM chapters compared to unexposed children. A consistently higher incidence rate ratio of diagnosis was observed in both POE‐NAS and POE + NAS groups (vs. unexposed) related to mental and behavioral disorders, eye diagnoses, and diseases of the musculoskeletal system and gastrointestinal systems.POE is associated with an increased risk of diagnoses in a number of ICD‐10 CM chapters throughout childhood. These findings underscore the need for early screening and targeted interventions to support exposed children and improve their well‐being. Further research is required to explore underlying mechanisms and develop preventive measures for at‐risk populations.Understanding the conditions more often diagnosed in children with prenatal opioid exposure will help to improve care provided to this population. As a result of study findings, nurses who provide care to children with prenatal opioid exposure can prioritize their assessments and allocate time, resources, and education toward areas more likely to be affected. [ABSTRACT FROM AUTHOR]

Substance use during pregnancy is associated with poor neonatal outcomes. Women incarcerated during pregnancy may have a history of substance use, and their babies may be at risk of neonatal abstinence syndrome (NAS). This study examines the incidence of NAS and other outcomes in infants born to currently or formerly incarcerated women. Infants born between 1985 and 2011 in Western Australia were divided into three mutually exclusive groups: born to women incarcerated during pregnancy (n = 708); born within 9–24 months of the mother's release from prison (n = 651); and born to women who were never incarcerated (n = 17,712). The impact of the timing of incarceration during pregnancy was also examined. Neonatal outcomes (NAS, preterm birth, low birthweight, infant mortality and admission to special care nursery) were compared using logistic regression. Infants born to currently or recently incarcerated women had higher odds of all adverse outcomes than infants in the nonexposed group. Infants born to women incarcerated during the second or third trimester (but not the month of birth) had poorer outcomes than infants born to women incarcerated during the month of birth. The findings show that babies born to currently or formerly incarcerated women are equally likely to experience adverse neonatal outcomes. Enhanced maternal healthcare must be provided during incarceration and after release. [ABSTRACT FROM AUTHOR]

Introduction: There are limited and conflicting data regarding the impact of hepatitis C in pregnancy on adverse birth outcomes. Methods: Using the Surveillance for Emerging Threats to Pregnant People and Infants Network (SET-NET), a large surveillance cohort, we describe birth outcomes among a cohort of people with HCV in pregnancy in total and by reported substance use. Results: Among 1418 infants, 89% were born to people with reported substance use during pregnancy. The proportion born preterm was 20%, 13% were small-for-gestational age and 34% of term infants required intensive care. Conclusions: Assessments of recent changes to recommendations for HCV screening in pregnancy should evaluate the impact on maternal access to care for both HCV treatment as well as comorbidities such as substance use disorder which may contribute to adverse birth outcomes. Significance: Incidence of hepatitis C in pregnancy is increasing. Prematurity, small-for-gestational age, and intensive care unit admission were common among this surveillance cohort of infants born to people with hepatitis C in pregnancy with high frequency of substance use. Assessments of recent changes to recommendations for HCV screening in pregnancy should evaluate the impact on maternal access to care for both HCV treatment as well as comorbidities such as substance use disorder which may contribute to adverse birth outcomes. [ABSTRACT FROM AUTHOR]

• This is a preliminary work of pregnancy-long treatment with extended-release buprenorphine. • Extended-release buprenorphine appeared well tolerated in pregnancy and delivery. • Neonates with prenatal extended-release buprenorphine exposure were born in good condition. • The birth sizes were relatively small but within the normal limits. • Extended-release buprenorphine might reduce neonatal opioid withdrawal symptoms. 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. 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). 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.. [ABSTRACT FROM AUTHOR]

Background: The Chandler Regional Medical Center (CRMC) neonatal intensive care unit (NICU) began a phased implementation of Eat-Sleep-Console (ESC) for the management of those at risk for neonatal opioid withdrawal syndrome (NOWS). Purpose: The purpose of this initiative is to track short-term outcomes as well as the program's effect on nursing workflow and job performance rating/satisfaction. Methods: A retrospective review of the ESC implementation process at CRMC from the years 2018-2020. The study consisted of 3 epochs: (1) traditional pharmacologic management; (2) parent-led ESC management; and (3) parent/nurse-led ESC management. Length of stay (LOS), treatment pathway assignment, and proportion of infants treated with pharmacologic agents were compared between epochs. In addition, a survey of NICU nursing staff was distributed to measure nurses' perceptions and attitudes towards the ESC program and the management of infants with NOWS. Results: The proportion of infants treated via ESC increased (0%, 53%, and 100%), with an associated decrease in LOS (18.4, 10.5, and 9.3 days) during each epoch of the study period. Thirty-seven nurses completed the survey, with 94% of nurses reporting being comfortable caring for ESC patients and 89% feeling supported in their ESC nursing assignments, with only 11% stating that caring for ESC patients significantly alters their other nursing care processes. Implications for Practice and Research: Implementation of an ESC treatment program for infants with NOWS significantly decreased LOS and the proportion of infants treated pharmacologically. This phased implementation process was not associated with self-reported negative nursing perceptions of the program and its treatment goals/outcomes. [ABSTRACT FROM AUTHOR]

Objectives: Pregnancy complicated by cancer is one of the most serious challenges of modern perinatology. The increasing number of cancers diagnosed and treated during pregnancy requires a multidisciplinary approach to optimize the treatment of the person who is pregnant and deliver a healthy child. The aim of the study is to analyze the course of the neonatal period in children of mothers suffering from cancer during pregnancy, treated in a specialist hospital for women and children for ten years. Material and methods: Retrospective observational study. Being diagnosed with cancer during pregnancy significantly increases the risk of premature delivery, prematurity and intrauterine growth restriction. Results: Our own observations show no significant differences in the course of the neonatal period in children of mothers suffering from a malignant tumor during pregnancy compared to children of healthy mothers. This applies to both full-term and premature babies. Conclusions: Modern treatment of malignant tumors during pregnancy seems to be safe for the fetus and newborn. It is optimal to conduct oncological, obstetric and neonatological treatment in one center. It seems advisable to conduct long-term follow-up observations in children of pregnant people with cancer. Since the described groups of patients and their newborns are small and heterogeneous, in order to develop appropriate standards, it is recommended to report these cases to central registers. [ABSTRACT FROM AUTHOR]

Prenatal opioid exposure is an established public health problem, in particular among Medicaid-covered births. Yet, existing prevalence rates are plausibly underestimated. We leverage extensive linked longitudinal administrative data for all Medicaid-covered live births in Wisconsin from 2010 to 2019 to estimate a range of prevalence rates using an innovative strategy that jointly accounts for both likelihood of exposure and potential risk to prenatal development. We find that 20.8% of infants may have been prenatally exposed to opioids, with 1.7% diagnosed with neonatal abstinence syndrome and an additional 1.2% having a high combined likelihood of exposure and potential risk to prenatal development, 2.6% a moderate combined likelihood and risk, and 15.3% a low or uncertain combined likelihood and risk. We assess improvements in prevalence estimates based on our nuanced classification relative to those of prior studies. Our strategy could be broadly used to quantify the scope of the opioid crisis for pregnant populations, target interventions, and promote child health and development. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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

Rates of neonatal opioid withdrawal syndrome (NOWS) have been increasing. Acute withdrawal symptoms are well characterized in NOWS infants, but environmental confounds and difficulties in conducting longitudinal studies make it challenging to elucidate potential long-term clinical effects. Preclinical animal models have great utility for studying the persisting consequences of perinatal opioid exposure and to address the mechanistic basis of these effects. Several preclinical perinatal opioid exposure models have been developed. Whereas early animal models primarily used the prototypical opioid, morphine, and a limited opioid exposure period, more recent models have been using various opioid types and different durations of perinatal opioid exposure. Behavioral phenotypes vary across models, reaffirming the importance of dosage, type of opioid, and duration of exposure for the development of specific phenotypes. 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. [ABSTRACT FROM AUTHOR]

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

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. [ABSTRACT FROM AUTHOR]

Purpose: Infants prenatally exposed to opioids exhibit withdrawal symptomology that introduce physiological noise and can impact newborn hearing screening results. This study compared the referral rate and physiological noise interpreted by number of trials rejected due to artifact on initial newborn hearing screenings of infants with prenatal opioid exposure (POE) and infants with no opioid exposure (NOE). Furthermore, within the POE group, it examined the relationship of referral rates with severity of withdrawal symptomology, and with maternal and infant risk factors. Method: This study used a retrospective cohort design of electronic medical records from six delivery hospitals in South-Central Appalachia. Newborn hearing screenings were conducted using automated auditory brainstem response (ABR) for 334 infants with POE and 226 infants with NOE. Severity of withdrawal symptomology was measured using the Modified Finnegan Neonatal Abstinence Scoring Tool, which includes observation of behaviors that introduce physiological noise. Results: There was no significant difference in newborn hearing screening referral rate between infants with POE and infants with NOE. Referral rate was not affected by maternal or infant risk factors. Infants with POE had statistically significant higher artifact (defined as rejected ABR sweeps) than infants with NOE. There was a strong positive correlation between Finnegan scores and artifact but not referral rates. Sensitivity and specificity analysis indicated artifact decreased substantially after Day 4 of life. Conclusions: Referral rates of infants with POE were similar to those of infants with NOE. Nevertheless, the withdrawal symptomology of infants with POE introduces physiological noise reflected as artifact on ABR, which can affect efficiency of newborn hearing screenings. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this proof-of-concept pilot study was to test the initial feasibility and limited efficacy of ArtSpective™ for perinatal substance use (PSU), a novel, arts-based intervention designed to decrease stigmatizing attitudes toward PSU. Methods: Using a pre-post mixed methods quasiexperimental design, ArtSpective™for PSU was pilot tested for proof of concept among a convenience sample of 11 undergraduate and graduate students with experience in maternal-infant nursing from a Midwestern U.S. nursing school. As a proof-of-concept pilot study, we evaluated feasibility (acceptability, demand, and implementation) and limited efficacy. Participants completed presurveys and postsurveys that included satisfaction items, demographic items, and an adapted version of the Attitudes About Drug Use in Pregnancy Scale and participated in a focus group. Focus group data were analyzed using constant comparative methods, and survey data were analyzed using descriptive statistics and Wilcoxon signed rank tests. Results: Participants reported high demand and satisfaction with the intervention and provided recommendations to improve scalability. ArtSpective™demonstrated significant improvement in stigma toward PSU (pre vs. post: p = .003; d = .633). Conclusion: ArtSpective™ for PSU demonstrated initial feasibility and limited efficacy for improving nurse attitudes toward PSU. Efforts are needed to further test this novel intervention, adapt it to augment existing educational interventions, and improve its scalability. [ABSTRACT FROM AUTHOR]

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Prescription opioid use among women of reproductive age and pregnant women is relatively common, and increased prescription opioid use is associated with a commensurate increase in opioid use disorder (OUD) among pregnant women and neonatal abstinence syndrome (NAS) among infants. In this article, we examine whether state opioid control policies affected prescription opioid use and, in turn, infant health and maternal behaviors. Results from our analysis suggest that reductions in prescription opioid use because of state prescription opioid control policies have improved infant health marginally at the population level with larger implied effects at the individual level. [ABSTRACT FROM AUTHOR]

BackgroundInfant health among newborns with neonatal abstinence syndrome (NAS) has been understudied. We examined infant mortality and hospitalizations among infants diagnosed with NAS after birth.MethodsAll 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.ResultsThere 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.ConclusionUnadjusted 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.

Background: Cor triatriatum dexter (CTD) is an extremely rare pathology, with an incidence of < 0.4%. Its main characteristic is a partitioning of the right atrium by the persistence of the embryonic valve of the right sinus venosus. Clinical case: In this report, we describe the case of a 7-day-old newborn who presented with persistent cyanosis associated with feeding and crying. The diagnosis of CTD was made after an echocardiogram and confirmed using cardiac magnetic resonance imaging. The patient underwent successful surgery on day 14 with a favorable outcome and without complications. Conclusion: The importance of our case lies in the identification of rare heart disease as a cause of cyanosis and desaturation in a neonatal patient in the first days of life who did not present signs of heart failure and whose condition improved with supplemental oxygen. We also demonstrate that early diagnosis with echocardiography and surgical resolution resulted in clear clinical improvement and avoided future complications. [ABSTRACT FROM AUTHOR]