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 (SpO2) and ventilator data from infants <30 weeks of gestation age. Research pulse oximeters collected SpO2 (1 Hz sampling rate) to quantify intermittent hypoxemia (IH). Continuous ventilator metrics were collected (4-5-minute sampling) from bedside ventilators. Data modeling was completed using unbiased machine learning algorithms. Three model sets were created using the following data source combinations: (1) IH and ventilator (IH + SIMV), (2) IH, and (3) ventilator (SIMV). Infants were also analyzed separated by postnatal age (infants <2 or ≥2 weeks of age). Models were compared by area under the receiver operating characteristic curve (AUC). RESULTS: A total of 110 extubation events from 110 preterm infants were analyzed. Infants had a median gestation age and birth weight of 26 weeks and 825 g, respectively. Of the 3 models presented, the IH + SIMV model achieved the highest AUC of 0.77 for all infants. Separating infants by postnatal age increased accuracy further achieving AUC of 0.94 for <2 weeks of age group and AUC of 0.83 for ≥2 weeks group. CONCLUSIONS: Machine learning analysis has the potential to enhance prediction accuracy of extubation readiness in preterm infants while utilizing readily available data streams from bedside pulse oximeters and ventilators.

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 (SpO2) using high-resolution pulse oximeters during the first 10 weeks of life. Statistical analyses assessed the relationship and predictive ability of weekly and cumulative IH for Type 1 ROP development. RESULTS: Most analyses showed no association between IH and Type 1 ROP adjusting for gestational age (GA) and birth weight (BW). However, cumulative IH of longer duration during weeks 5-10, 6-10, and 7-10 were significantly associated with Type 1 ROP adjusting for GA and BW, e.g., the adjusted odds ratio of Type 1 ROP was 2.01 (p = 0.03) for every 3.8 seconds increase in IH duration from week 6-10. IH did not provide statistically significant added predictive ability above GA and BW. CONCLUSIONS: For most analyses there was no significant association between IH and Type 1 ROP adjusting for GA and BW. However, infants with longer IH duration during the second month of life had higher risk for Type 1 ROP. IMPACT: The relationship and predictive ability of intermittent hypoxemia (IH) on retinopathy of prematurity (ROP) is controversial. This study shows no significant association between IH events and Type 1 ROP after adjusting for gestational age (GA) and birth weight (BW), except for cumulative IH of longer duration in the second month of life. In this cohort, IH does not provide a statistically significant improvement in ROP prediction over GA and BW. This study is the first to assess the cumulative impact of IH measures on Type 1 ROP. Interventions for reducing IH duration during critical postnatal periods may improve ROP outcomes.

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. The DSCFO was first validated against the established diffuse correlation spectroscopy (DCS) in neonatal piglets and then utilized for continuous CBF and oxygenation monitoring in preterm infants during intermittent hypoxemia (IH) events. RESULTS: Significant correlations between the DSCFO and DCS measurements of CBF variations in neonatal piglets were observed. IH events induced fluctuations in CBF, cerebral oxygenation, and peripheral cardiorespiratory vitals in preterm infants. However, no consistent correlation patterns were observed among peripheral and cerebral monitoring parameters. CONCLUSIONS: This pilot study demonstrated the feasibility of DSCFO technology to serve as a low-cost wearable sensor for continuous monitoring of multiple cerebral hemodynamic parameters. The results suggested the importance of multi-parameter measurements for understanding deep insights of peripheral and cerebral regulations. 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. Integrating and correlating multiple cerebral functional parameters with clinical outcomes may identify biomarkers for prediction and management of IH associated brain injury.

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. Daily mean Finnegan scores were estimated using linear mixed models with random subject effects to account for repeated withdrawal scores from the same subject. Daily item prevalence was estimated using generalized estimating equations with a within-subject exchangeable correlation structure. The median LOT was 12.86 days. The prevalence of withdrawal signs decreased from day one to day three of treatment. However, certain central nervous system (CNS) and gastrointestinal (GI) signs showed sporadic increases in prevalence notable around two weeks of treatment, accounting for increases in Finnegan scores that guided pharmacotherapy. We question whether the resurgence of signs with a prolonged LOT is mainly a consequence of opioid tolerance or withdrawal. Monitoring CNS and GI signs throughout treatment is crucial. Future studies directed to better understand this clinical phenomenon may lead to the refining of NAS pharmacotherapy and perhaps the discovery of treatment alternatives.

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.Integrating and correlating multiple cerebral functional parameters with clinical outcomes may identify biomarkers for prediction and management of IH associated brain injury. 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. The DSCFO was first validated against the established diffuse correlation spectroscopy (DCS) in neonatal piglets and then utilized for continuous CBF and oxygenation monitoring in preterm infants during intermittent hypoxemia (IH) events. Results: Consistent results between the DSCFO and DCS measurements of CBF variations in neonatal piglets were observed. IH events induced fluctuations in CBF, cerebral oxygenation, and peripheral cardiorespiratory vitals in preterm infants. However, no consistent correlation patterns were observed among peripheral and cerebral monitoring parameters. Conclusions: This pilot study demonstrated the feasibility of DSCFO technology to serve as a low-cost wearable sensor for continuous monitoring of multiple cerebral hemodynamic parameters. The results suggested the importance of multi-parameter measurements for understanding deep insights of peripheral and cerebral regulations.

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 (SpO2) using high-resolution pulse oximeters during the first 10 weeks of life. Statistical analyses assessed the relationship and predictive ability of weekly and cumulative IH variables for Type 1 ROP development. Results: Univariate analyses suggested that IH measures are greater in infants with Type 1 ROP and are predictive of Type 1 ROP development. Multivariable logistic regression analyses revealed that cumulative IH of longer duration during certain postnatal periods are associated with Type 1 ROP development after adjusting for gestational age (GA) or birth weight (BW). Although area under the curve (AUC) analyses revealed added predictivity of cumulative IH variables above GA or BW, these increments in AUC were not statistically significant. Conclusions: The duration of IH events was associated with Type 1 ROP development. Interventions for reducing the duration of IH events may potentially improve ROP outcomes.

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. Pregnant women with OUD from rural and urban areas were similar on almost all attributes. Among the few significant differences, 30% from urban areas perceived inadequate prenatal care versus 11% from rural areas (p = 0.024); 21% of urban women used amphetamines/methamphetamines in the month before delivery versus 0% of rural women (p < 0.001); and rural women had longer most recent abstinence from substance use than their urban counterparts (medians 7.0 and 2.8 months, p = 0.049). The few significant differences that were discovered favored rural women. These findings, contrary to our hypothesis, suggest that tailoring interventions may require more than focusing on geography. The participants in this study were pregnant women being treated for OUD, and as such there is patient contribution of data.

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. 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.

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. Clinically, oral opioid therapies for opioid exposure have been a standard treatment with morphine (MO) being the most commonly used medication. Recently, a non-opioid agent, clonidine (CD) has also been used with potentially favorable short- and long-term outcomes in infants. However, data regarding the cellular and molecular effects of these treatments on the developing brain is still lacking due to a lack of a reliable animal model that targets the neonatal brain. To address this gap in knowledge we determined the effects of MO or CD on the cell death of neonatal cortical explant cultures that were exposed to oxycodone (OXY) in utero. Sprague Dawley rats were randomized and implanted with programmable infusion pumps before mating to receive either the OXY (dose increasing from 1.21-1.90 mg/kg/day to a maximum dose of 2.86-3.49 mg/kg/day) or normal saline (NS) throughout pregnancy and until one week after delivery. Male and female rat pups were sacrificed on postnatal day 4, and the prefrontal cortex (PFC) and hippocampus (HC) were dissected and treated with MO (0.10-1.00 µM) or CD (1.20-120.00 µM) in culture media. After 5 days of treatment the explants were labeled with propidium iodide to detect cell death. Dead cells were analyzed and counted under fluorescence microscopy. In explants from the PFC, cell death was greater in those prenatally exposed to OXY and postnatally treated with MO (OXY/MO) (736.8 ± 76.5) compared to OXY/CD (620.9 ± 75.0; p = 0.005). In the HC explants, mean cell death counts were not significantly different between groups regardless of prenatal exposure or postnatal treatment (p = 0.19). The PFC is vital in controlling higher-order executive functions such as behavioral flexibility, learning and working memory. Therefore, our finding is consistent with executive function problems in children with prenatal opioid exposure.

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. and Chervoneva et al. are most predictive of the FNAS cut-off values to initiate treatment, have cutoff values that best align with the FNAS cutoff values, and strongly correlate with the FNAS (r ≥ 0.88 corresponding to treatment initiation, r ≥ 0.83 during first 10 days of treatment). CONCLUSION: The tools of Gomez and Chervoneva demonstrated potential clinical usefulness by strongly associating with the need for treatment and monitoring the course of NAS therapy.

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. STUDY DESIGN: We analyzed prospectively enrolled 87 ELBW infants. Urinary NT-proBNP to creatinine ratios were measured on days 1 to 7, 14, and 28 of life. We plotted each study point's means to determine the trend of urinary NT-proBNP over the entire neonatal period. Data were analyzed using the Friedman analysis of variance for comparative analysis of study points. RESULTS: Urinary NT-proBNP/creatinine ratios were significantly elevated on days 1 to 7 (mean 2,452, ± 1,518) than day 14 (mean 747, ± 176), and day 28 (mean 149, ± 54), p = 0.001. Overall, urinary NT-proBNP levels were highest during days 1 to 3 (mean 3,232, ± 1,255) and lowest on day 28 (mean 149, ± 54). CONCLUSION: Urinary NT-proBNP levels are higher during the first week in ELBW infants with a downward trend during the neonatal period, the lowest values at 4 weeks postnatal age. More studies are required to determine the clinical utility of this trend during and beyond the neonatal period. KEY POINTS: · NT-proBNP is a biomarker for monitoring cardiac disease in premature infants.. · The trend of urinary NT-proBNP is unknown in premature infants.. · A trend of urinary NT-proBNP was determined during the first 4 weeks in premature infants..

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). METHODS: This is a cross-sectional study in a regional referral clinic for evaluation of obesity. Children were stratified by age group or by obesity class, and data obtained at first visit were analysed. RESULTS: Of the 784 children, 482 were ≥10, 209 were 6 to 9 and 93 were 2 to 5 years of age. Abnormal ALT was observed in 32.1%, 46.9% and 61.0% of children with class I, II or III obesity, respectively (p < 0.001), while the risk of abnormal ALT did not differ in very young (2-5), young (6-9), or children older than 10 years. A multivariable analysis showed that class II and class III obesity were associated with 2.1-fold (1.27-3.72) and 4-fold (2.41-6.96) greater odds of abnormal ALT compared with class I obesity. African-American children had lower risk of abnormal ALT (0.27), whereas Hispanic children had higher risk (2.37). Obesity class was a better predictor of abnormal ALT than age, especially in girls. Furthermore, 66.7% of boys (p = 0.009) and 69% of girls (p < 0.001) with abnormal ALT exhibited additional signs of metabolic dysfunction. CONCLUSION: Obesity class is more strongly associated with abnormal ALT than age.

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, FiO2) and pulse oximetry (SpO2) patterns were downloaded from infants <30 weeks gestational age during the first 2 months of life. Mechanically ventilated infants who received albuterol were included (n = 33). Measurements were compared before and after first albuterol. Secondary analyses assessed subsequent doses. RESULTS: Median gestation and birthweight were 25 3/7 weeks and 730 g, respectively. Mean Resistance decreased post-albuterol (p = 0.007). Sixty-eight percent of infants were responders based on decreased Resistance. Compliance and FiO2 did not significantly differ. Percent time in hypoxemia (SpO2 < 85%) decreased post albuterol (p < 0.02). In responders, Resistance changes diminished with subsequent administration (all p = 0.01). CONCLUSIONS: Ventilator resistance decreased in two-thirds of preterm infants, consistent with studies that utilized formal pulmonary function testing. Albuterol had a variable effect on delivered FiO2; however, hypoxemia may be useful in evaluating albuterol response.

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. Common clinical signs of hsPDA utilized as surrogate for decreased tissue perfusion may lag behind early echocardiographic signs. Although echocardiogram allows direct assessment of PDA shunt and hemodynamic alterations in the heart, it is limited by dependence on pediatric cardiologist availability, interobserver variation and isolated time point assessment. Electrical cardiometry (EC) is a non-invasive continuous real time measurement of cardiac output by applying changes in thoracic electrical impedance. EC has been validated in preterm newborns by concomitant transthoracic echocardiogram assessments and may be beneficial in studying changes in cardiac output in premature newborns with hsPDA. Alterations in perfusion index derived from continuous pulse oximetry monitoring has been used to study changes in cardiac performance and tissue perfusion in infants with PDA. Near infrared spectroscopy (NIRS) has been used to objectively and continuously assess variations in renal, mesenteric, and cerebral oxygen saturation and thus perfusion changes due to diastolic vascular steal from hsPDA in preterm neonates. Doppler ultrasound studies measuring resistive indices in cerebral circulation indicate disturbance in cerebral perfusion secondary to ductal steal. With recent trends of change in practice toward less intervention in care of preterm newborn, treatment strategy needs to be targeted for select preterm population most vulnerable to adverse hemodynamic effects of PDA. Integration of these novel ways of hemodynamic and tissue perfusion assessment in routine clinical care may help mitigate the challenges in defining and targeting treatment of hsPDA thereby improving outcomes in extremely premature neonates.

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. Although there is an increasing number of clinical trials on the comparative efficacy of treatment agents in NOWS, here, we also draw attention to the importance of optimizing the dosing regimen, which can be arguably equally important at identifying the optimal treatment agent.

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. The spatial diffuse speckle contrast and light intensity measurements at the two different wavelengths enable quantification of tissue blood flow and oxygenation, respectively. The DSCFO was first calibrated using tissue phantoms and then tested in adult forearms during artery cuff occlusion. RESULTS: Phantom tests determined the largest effective source-detector distance (15 mm) and optimal camera exposure time (10 ms) and verified the accuracy of DSCFO in measuring absorption coefficient variations. The DSCFO detected substantial changes in forearm blood flow and oxygenation resulting from the artery occlusion, which meet physiological expectations and are consistent with previous study results. CONCLUSIONS: The wearable DSCFO may be used for continuous and simultaneous monitoring of blood flow and oxygenation variations in freely behaving subjects.

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. STUDY DESIGN: Serum CRP was measured at 30 days of life, at the time of peak IH frequency. IH measures (e.g., per cent time in hypoxemia, frequency, duration) were calculated the week prior to CRP collection. Statistical analyses were based on Spearman's correlation. RESULTS: A total of 26 infants were included. Median gestational age and birth weight were 274/7 weeks and 980 g, respectively. There were positive correlations between primary IH measures and CRP levels, especially for events longer than 1-minute duration (r range: 0.56-0.74, all p < 0.01). CONCLUSION: We demonstrate that IH is associated with increased CRP for the first time in preterm infants. Our findings are consistent with studies from adults and neonatal animal models suggesting that IH is a proinflammatory process. KEY POINTS: · IH events are common.. · IH is associated with elevated C-reactive protein.. · Longer IH events (>1 min) are of most significance..

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. The scDCT scans a focused point near-infrared illumination to multiple source positions for deep tissue penetration, and controls an electron multiplying charge-coupled-device camera with thousands of pixels to achieve a high-density sampling. The optimized scDCT for use in preterm infants was first evaluated against an established diffuse correlation spectroscopy in an infant-head-simulating phantom with known properties. The observed significant correlation between the two measurements verified the capability of scDCT for transcranial brain imaging. The insignificant influence of transparent incubator wall on scDCT measurements was then confirmed by comparing adult forearm blood flow responses to artery cuff occlusions measured inside and outside the incubator. Finally, the scDCT device was moved to the NICU to image CBF variations in two preterm infants. Infant #1 with no major organ deficits showed little CBF fluctuation over the first 3 weeks of life. Infant #2 showed a significant CBF increase after the 2 h pharmacotherapy for patent ductus arteriosus closure. While these CBF variations meet physiological expectations, the fact that no significant changes are noted with peripheral monitoring of blood oxygen saturation suggests necessity of direct cerebral monitoring. This feasibility study with timely technology development is an important and necessary step towards larger clinical studies with more subjects to further validate it for continuous monitoring and instant management of cerebral pathologies and interventions in the NICU.

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. RESULTS: Opiate-exposed infants displayed transient neurologic findings, but no substantial signs or symptoms long term. There were no group differences in growth, cognitive functioning, or behavior at individual time periods; however, the trajectories of outcomes using longitudinal analyses adjusting for variables known to impact outcome demonstrated increased deficits among opiate-exposed children over time with regards to weight, head circumference, cognitive functioning, and behavior. CONCLUSIONS: Findings support concerns that maternal opiate use during pregnancy may negatively impact a child's developmental trajectory, which in turn may impose concerns to society (e.g., increased need for social, medical, and/or educational services).