The Epidemic of Neonatal Abstinence Syndrome, Historical References of Its Origins, Assessment, and Management

Neonatal abstinence syndrome (NAS) refers to a constellation of signs that are present in some newborn infants resulting from the abrupt cessation of passive transfer of maternal opioids used during pregnancy. The classic NAS refers to infants born to mothers who used opioids during pregnancy, but the term has broadened to include infants whose mothers have used or abused other psychoactive substances during pregnancy that contribute to the expression of the syndrome. Pregnant women who use opioids do so illicitly, and/or as medically prescribed for pain relief, and/or as medication assisted treatment for opioid dependence. The first case of NAS in infants and the subsequent treatment (or lack thereof) was reported in 1875 and was called Congenital Morphinism. By 2012, the incidence of NAS increased to more than 30 per 1,000 hospital live births, along with an increase in the number of infants being treated pharmacologically for NAS, resulting in an increase in the length of stay and healthcare expenses. We present historical references on NAS, the various factors and events that led to its increasing prevalence and today\u27s current epidemic. We also review the current tools to assess infants with NAS and treatment options in its management

Simplification of the Finnegan Neonatal Abstinence Scoring System: Retrospective Study of Two Institutions in the USA

Objective To develop a simplified Finnegan Neonatal Abstinence Scoring System (sFNAS) that will highly correlate with scores ≥ 8 and ≥12 in infants being assessed with the FNAS. Design, setting and participants This is a retrospective analysis involving 367 patients admitted to two level IV neonatal intensive care units with a total of 40 294 observations. Inclusion criteria included neonates with gestational age ≥ 37 0/7 weeks, who are being assessed for neonatal abstinence syndrome (NAS) using the FNAS. Infants with a gestational age \u3c 37 weeks were excluded. Methods A linear regression model based on the original FNAS data from one institution was developed to determine optimal values for each item in the sFNAS. A backward elimination approach was used, removing the items that contributed least to the Pearson’s correlation. The sFNAS was then cross-validated with data from a second institution. Results Pearson’s correlation between the proposed sFNAS and the FNAS was 0.914. The optimal treatment cut-off values for the sFNAS were 6 and 10 to predict FNAS scores ≥ 8 and ≥ 12, respectively. The sensitivity and specificity of these cut-off values to detect FNAS scores ≥ 8 and ≥ 12 were 0.888 and 0.883 for a cut-off of 6, and 0.637 and 0.992 for a cut-off of 10, respectively. The sFNAS cross-validation resulted in a Pearson’s correlation of 0.908, sensitivity and specificity of 0.860 and 0.873 for a cut-off of 6, and 0.525 and 0.986 for a cut-off of 10, respectively. Conclusion The sFNAS has a high statistical correlation with the FNAS, and it is cross-validated for the assessment of infants with NAS. It has excellent specificity and negative predictive value for identifying infants with FNAS scores ≥ 8 and ≥ 12

Association of a Simplified Finnegan Neonatal Abstinence Scoring Tool With the Need for Pharmacologic Treatment for Neonatal Abstinence Syndrome

Importance: Observer-rated scales, such as the Finnegan Neonatal Abstinence Scoring Tool (FNAST), are used to quantify the severity of neonatal abstinence syndrome (NAS) and guide pharmacologic therapy. The FNAST, a comprehensive 21-item assessment tool, was developed for research and subsequently integrated into clinical practice; a simpler tool, designed to account for clinically meaningful outcomes, is urgently needed to standardize assessment. Objectives: To identify FNAST items independently associated with the decision to use pharmacologic therapy and to simplify the FNAST while minimizing loss of information for the treatment decision. Design, Setting, and Participants: This multisite cohort study included 424 neonates with opioid exposure who had a gestational age of at least 36 weeks with follow-up from birth to hospital discharge in the derivation cohort and 109 neonates with opioid exposure from the Maternal Opioid Treatment: Human Experimental Research Study in the validation cohort. Neonates in the derivation cohort were included in a medical record review at the Universities of Louisville and Kentucky or in a randomized clinical trial and observational study conducted at Tufts University (2014-2018); the Maternal Opioid Treatment: Human Experimental Research was conducted from 2005 to 2008. Data analysis was conducted from May 2017 to August 2019. Exposures: Prenatal opioid exposure. Main Outcomes and Measures: All FNAST items were dichotomized as present or not present, and logistic regression was used to identify binary items independently associated with pharmacologic treatment. The final model was validated with an independent cohort of neonates with opioid exposure. Results: Among 424 neonates (gestational age, ≥36 weeks; 217 [51%] female infants), convulsions were not observed, and high-pitched cry and hyperactive Moro reflex had extremely different frequencies across cohorts. Therefore, these 3 FNAST items were removed from further analysis. The 2 tremor items were combined, and 8 of the remaining 17 items were independently associated with pharmacologic treatment, with an area under the curve of 0.86 (95% CI, 0.82-0.89) compared with 0.90 (95% CI, 0.87-0.94) for the 21-item FNAST. External validation of the 8 items resulted in an area under the curve of 0.86 (95% CI, 0.79-0.93). Thresholds of 4 and 5 on the simplified scale yielded the closest agreement with FNAST thresholds of 8 and 12 (weighted κ = 0.55; 95% CI, 0.48-0.61). Conclusions and Relevance: The findings of this study suggest that 8 signs of NAS may be sufficient to assess whether a neonate meets criteria for pharmacologic therapy. A focus on these signs could simplify the FNAST tool and may enhance its clinical utility

A core outcome set for neonatal abstinence syndrome: Study protocol for a systematic review, parent interviews and a Delphi survey

Background: The prevalence of neonatal abstinence syndrome (NAS) is increasing globally resulting in an increased incidence of adverse neonatal outcomes and health system costs. Evidence regarding the effectiveness of NAS prevention and management strategies is very weak and further research initiatives are critically needed to support meta-analysis and clinical practice guidelines. In NAS research, the choice of outcomes and the use of valid, responsive and feasible measurement instruments are crucial. There is currently no consensus and evidence-based core outcome set (COS) for NAS. Methods/design: The development of the NAS-COS will include five stages led by an international Multidisciplinary Steering Committee: (1) qualitative interviews with parents/families and a systematic review (SR) to identify items for inclusion in a COS. The SR will also identify participants for the Delphi survey, (2) a three-round Delphi survey to gain expert opinion on the importance of health outcomes influencing NAS management decisions, (3), a consensus meeting to finalize the items and definitions with experts and COS users, (4) feasibility and pilot testing, development of the COS and explanatory document and (5) implementation planning. Discussion: Since standardized outcome measurement and reporting will improve NAS clinical research consistency, efficacy and impact, this COS will reflect the minimum set of health outcomes which should be measured in trials evaluating interventions for preventing or treating NAS

Fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin with gemtuzumab ozogamicin improves event-free survival in younger patients with newly diagnosed aml and overall survival in patients with npm1 and flt3 mutations

Purpose To determine the optimal induction chemotherapy regimen for younger adults with newly diagnosed AML without known adverse risk cytogenetics. Patients and Methods One thousand thirty-three patients were randomly assigned to intensified (fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin [FLAG-Ida]) or standard (daunorubicin and Ara-C [DA]) induction chemotherapy, with one or two doses of gemtuzumab ozogamicin (GO). The primary end point was overall survival (OS). Results There was no difference in remission rate after two courses between FLAG-Ida + GO and DA + GO (complete remission [CR] + CR with incomplete hematologic recovery 93% v 91%) or in day 60 mortality (4.3% v 4.6%). There was no difference in OS (66% v 63%; P = .41); however, the risk of relapse was lower with FLAG-Ida + GO (24% v 41%; P < .001) and 3-year event-free survival was higher (57% v 45%; P < .001). In patients with an NPM1 mutation (30%), 3-year OS was significantly higher with FLAG-Ida + GO (82% v 64%; P = .005). NPM1 measurable residual disease (MRD) clearance was also greater, with 88% versus 77% becoming MRD-negative in peripheral blood after cycle 2 (P = .02). Three-year OS was also higher in patients with a FLT3 mutation (64% v 54%; P = .047). Fewer transplants were performed in patients receiving FLAG-Ida + GO (238 v 278; P = .02). There was no difference in outcome according to the number of GO doses, although NPM1 MRD clearance was higher with two doses in the DA arm. Patients with core binding factor AML treated with DA and one dose of GO had a 3-year OS of 96% with no survival benefit from FLAG-Ida + GO. Conclusion Overall, FLAG-Ida + GO significantly reduced relapse without improving OS. However, exploratory analyses show that patients with NPM1 and FLT3 mutations had substantial improvements in OS. By contrast, in patients with core binding factor AML, outcomes were excellent with DA + GO with no FLAG-Ida benefit

The Epidemic of Neonatal Abstinence Syndrome, Historical References of Its’ Origins, Assessment, and Management

Neonatal abstinence syndrome (NAS) refers to a constellation of signs that are present in some newborn infants resulting from the abrupt cessation of passive transfer of maternal opioids used during pregnancy. The classic NAS refers to infants born to mothers who used opioids during pregnancy, but the term has broadened to include infants whose mothers have used or abused other psychoactive substances during pregnancy that contribute to the expression of the syndrome. Pregnant women who use opioids do so illicitly, and/or as medically prescribed for pain relief, and/or as medication assisted treatment for opioid dependence. The first case of NAS in infants and the subsequent treatment (or lack thereof) was reported in 1875 and was called Congenital Morphinism. By 2012, the incidence of NAS increased to more than 30 per 1,000 hospital live births, along with an increase in the number of infants being treated pharmacologically for NAS, resulting in an increase in the length of stay and healthcare expenses. We present historical references on NAS, the various factors and events that led to its increasing prevalence and today’s current epidemic. We also review the current tools to assess infants with NAS and treatment options in its management