Pharmacokinetic Modeling and Model-Based Hypothesis Generation for Dose Optimization of Clonidine in Neonates With Neonatal Opioid Withdrawal Syndrome.

The No-POPPY study (NCT03396588), a double-blind, randomized trial compared morphine with clonidine therapy for neonatal opioid withdrawal syndrome (NOWS) and found that the duration of treatment was similar across groups. This is significant because perinatal use of morphine has the potential for neurodevelopmental consequences. Still, the clonidine group reached symptom stabilization (Finnegan score (FS) < 8) later than the morphine group and had a more significant number of patients who required adjunct therapy.

Clonidine as Monotherapy for Neonatal Opioid Withdrawal Syndrome: A Randomized Trial.

Objective: We sought to determine whether clonidine, a non-opioid α-2-adrenergic agonist, would effectively treat neonatal opioid withdrawal syndrome (NOWS).

Methods: This was an intention-to-treat randomized clinical trial. Enrollment criteria included prenatal opioid exposure, age ≤7 days, gestational age ≥35 weeks, no other medical condition, and need for pharmacotherapy.

The impact of intermittent hypoxemia on type 1 retinopathy of prematurity in preterm infants.

Background: Intermittent hypoxemia (IH) may influence retinopathy of prematurity (ROP) development in preterm infants, however, previous studies had mixed results. This study tests the hypothesis that increased IH is associated with Type 1 ROP; a stage beyond which treatment is indicated.

Methods: IH was quantified by continuously monitoring oxygen saturation (SpO) using high-resolution pulse oximeters during the first 10 weeks of life.

Predicting Extubation Readiness in Preterm Infants Utilizing Machine Learning: A Diagnostic Utility Study.

Objective: The objective of this study was to predict extubation readiness in preterm infants using machine learning analysis of bedside pulse oximeter and ventilator data.

Study Design: This is an observational study with prospective recordings of oxygen saturation (SpO) and ventilator data from infants <30 weeks of gestation age. Research pulse oximeters collected SpO (1 Hz sampling rate) to quantify intermittent hypoxemia (IH).

Wearable fiber-free optical sensor for continuous monitoring of neonatal cerebral blood flow and oxygenation.

Background: Unstable cerebral hemodynamics places preterm infants at high risk of brain injury. We adapted an innovative, fiber-free, wearable diffuse speckle contrast flow-oximetry (DSCFO) device for continuous monitoring of both cerebral blood flow (CBF) and oxygenation in neonatal piglets and preterm infants.

Methods: DSCFO uses two small laser diodes as focused-point and a tiny CMOS camera as a high-density two-dimensional detector to detect spontaneous spatial fluctuation of diffuse laser speckles for CBF measurement, and light intensity attenuations for cerebral oxygenation measurement.

Neonatal Abstinence Signs during Treatment: Trajectory, Resurgence and Heterogeneity.

Neonatal abstinence syndrome (NAS) presents with a varying severity of withdrawal signs and length of treatment (LOT). We examined the course and relevance of each of the NAS withdrawal signs during treatment in a sample of 182 infants with any prenatal opioid exposure, gestational age ≥ 35 weeks, without other medical conditions, and meeting the criteria for pharmacological treatment. Infants were monitored using the Finnegan Neonatal Abstinence Scoring Tool.

The Impact of Intermittent Hypoxemia on Type 1 Retinopathy of Prematurity in Preterm Infants.

Background: Intermittent hypoxemia (IH) may influence retinopathy of prematurity (ROP) development in preterm infants, however, previous studies had mixed results. This study aims to assess the influence and evaluate the predictive ability of IH measures on Type 1 ROP, a stage beyond which ROP treatment is indicated.

Methods: IH was quantified by continuously monitoring oxygen saturation (SpO) using high-resolution pulse oximeters during the first 10 weeks of life.

A Wearable Fiber-Free Optical Sensor for Continuous Monitoring of Neonatal Cerebral Blood Flow and Oxygenation.

Impact: The innovative DSCFO technology may serve as a low-cost wearable sensor for continuous bedside monitoring of multiple cerebral hemodynamic parameters in neonatal intensive care units.Concurrent DSCFO and DCS measurements of CBF variations in neonatal piglet models generated consistent results.No consistent correlation patterns were observed among peripheral and cerebral monitoring parameters in preterm neonates, suggesting the importance of multi-parameter measurements for understanding deep insights of peripheral and cerebral regulations during IH events.

Recent and lifetime maternal substance use: Rurality and economic distress.

Research on opioid use disorder (OUD) in pregnancy has mainly considered women in urban areas receiving treatment, with less known about women in rural areas. We sought to describe demographics and substance use characteristics of pregnant women with OUD and to compare the women based on urbanicity, in a state (Kentucky) with unfavorable economic conditions in many rural counties; we hypothesized that pregnant women in rural areas would have greater adversity, broadly defined, related to substance use. Using data collected from a larger project between 2017 and 2020, we analyzed characteristics of 93 pregnant women (59 rural and 34 urban) with OUD; we examined data in medical, employment, substance use, legal, family history, relationship, and psychiatric health domains, both overall and within rural (population <50,000) and urban (population ≥50,000) strata.

A case-control study comparing rates and diagnoses of hospital readmission in infants affected by neonatal abstinence syndrome.

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.

Understanding the effects of opioids vs non-opioids in the treatment of neonatal abstinence syndrome, an in vitro model.

Neonatal abstinence syndrome (NAS) refers to cadre of withdrawal manifestations in infants born to mothers who used illicit and licit substances during pregnancy. The increasing prevalence of NAS has been largely due to the maternal use of opioids during pregnancy. NAS contributes to increased morbidity and long-term disability in surviving infants.

Assessment of the relative clinical utility of shortened Finnegan neonatal abstinence scoring tools.

Objective: To assess the proposed shortened tools based on the Finnegan neonatal abstinence scoring tool (FNAS) for relative clinical utility.

Study Design: Retrospective study comparing shortened tools with FNAS on need for treatment, medication initiation cutoff score agreement, and length of treatment in 369 infants with prenatal opioid exposure using estimated areas under the receiver operating characteristic curves, Pearson and Spearman correlations, and proportion correctly classified, sensitivity, and specificity.

Results: The tools by Gomez et al.

The Trend of Urinary N Terminal Probrain Natriuretic Peptide in Extremely Low Birth Weight Infants during the Neonatal Period.

Objective: N-terminal probrain natriuretic peptide (NT-proBNP) is a biomarker of interest in many cardiopulmonary diseases in extremely low birth weight (ELBW) Infants. However, there is a gap in knowledge about the trend of ELBW infant's urinary NT-proBNP during the neonatal period.

Aim: To determine the trend of urinary NT-proBNP during the first 4 weeks of life of an ELBW infant.

Stratification by obesity class, rather than age, can identify a higher percent of children at risk for non-alcoholic fatty liver disease and metabolic dysfunction.

Background: An increasing number of clinical practice guidelines recommend screening children with obesity for non-alcoholic fatty liver disease (NAFLD). However, there is limited evidence regarding what parameters should be used to initiate the screening.

Objective: The objective of this study was to determine whether obesity class rather than age group can identify a higher percent of children at risk of NAFLD as assessed by abnormal alanine aminotransferase (ALT).

Response to first dose of inhaled albuterol in mechanically ventilated preterm infants.

Background: Bronchodilator responses among preterm infants are heterogeneous. Bedside measurements may identify responders.

Study Design: Respiratory measurements (Resistance, Compliance, FiO) and pulse oximetry (SpO) patterns were downloaded from infants <30 weeks gestational age during the first 2 months of life.

Objective Assessment of Physiologic Alterations Associated With Hemodynamically Significant Patent Ductus Arteriosus in Extremely Premature Neonates.

Delay in closure of ductus arteriosus in postnatal life may lead to serious consequences and complications in an extremely premature neonate secondary to hemodynamic alterations in regional blood flow pattern in various organs. Despite the widespread recognition amongst neonatologists to identify a hemodynamically significant patent ductus arteriosus (hsPDA) early in the postnatal course, there is lack of consensus in its definition and thus the threshold to initiate treatment. Echocardiographic assessment of PDA shunt size and volume combined with neonatologists' impression of clinical significance is most frequently used to determine the need for treatment of PDA.

Clinical pharmacology and dosing regimen optimization of neonatal opioid withdrawal syndrome treatments.

In this paper, we review the management of neonatal opioid withdrawal syndrome (NOWS) and clinical pharmacology of primary treatment agents in NOWS, including morphine, methadone, buprenorphine, clonidine, and phenobarbital. Pharmacologic treatment strategies in NOWS have been mostly empirical, and heterogeneity in dosing regimens adds to the difficulty of extrapolating study results to broader patient populations. As population pharmacokinetics (PKs) of pharmacologic agents in NOWS become more well-defined and knowledge of patient-specific factors affecting treatment outcomes continue to accumulate, PK/pharmacodynamic modeling and simulation will be powerful tools to aid the design of optimal dosing regimens at the patient level.

Simultaneous measurements of tissue blood flow and oxygenation using a wearable fiber-free optical sensor.

Significance: There is an essential need to develop wearable multimodality technologies that can continuously measure both blood flow and oxygenation in deep tissues to investigate and manage various vascular/cellular diseases.

Aim: To develop a wearable dual-wavelength diffuse speckle contrast flow oximetry (DSCFO) for simultaneous measurements of blood flow and oxygenation variations in deep tissues.

Approach: A wearable fiber-free DSCFO probe was fabricated using 3D printing to confine two small near-infrared laser diodes and a tiny CMOS camera in positions for DSCFO measurements.

Noncontact optical imaging of brain hemodynamics in preterm infants: a preliminary study.

Extremely preterm infants' hemodynamic instability places them at high risk of brain injury. Currently there is no reliable bedside method to continuously monitor cerebral hemodynamics in the neonatal intensive care unit (NICU). This paper reports a feasibility study to adapt and test an innovative speckle contrast diffuse correlation tomography (scDCT) device for noncontact, high-density, 3D imaging of cerebral blood flow (CBF) in preterm infants.

Intermittent Hypoxemia in Preterm Infants: A Potential Proinflammatory Process.

Objective: A major consequence of prematurity is intermittent hypoxemia (IH). Data from both adult studies and neonatal animal models suggest that IH is proinflammatory; however, there is limited data in preterm infants. Here, we assess the relationship between IH and systemic inflammation, namely, serum C-reactive protein (CRP) in preterm infants.

Association of prenatal opiate exposure with youth outcomes assessed from infancy through adolescence.

Objective: This study examined acute findings and long-term outcome trajectories between birth and adolescence in children with prenatal opiate exposure.

Study Design: Ninety children (45 opiate-exposed, 45 non-exposed) completed assessments between 1 month and 15 years of age. Outcome variables (medical, anthropomorphic, developmental, and behavioral) were analyzed at individual time points and using longitudinal statistical modeling.

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.

Role of NT-proBNP in the prediction of moderate to severe Bronchopulmonary Dysplasia in preterm infants.

Objective: The objective of the study was to determine the clinical utility of brain natriuretic peptide (NT-proBNP) for prediction of moderate to severe bronchopulmonary dysplasia (BPD). We hypothesized that elevated NT-proBNP levels at 4 weeks of postnatal age may predict the severity of BPD in preterm infants.

Study Design: The study design was a prospective observational study.