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Tension pneumothorax is a rare and life-threatening situation in neonates requiring immediate intervention through thoracentesis. Significant complications can arise while performing thoracentesis in the case of inadequate skill level or exposure to the condition. Although simulation-based training (SBT) has proven to be effective in learning surgical skills, training sessions are long, subjective, and expensive, because of which they cannot be held regularly. This article attempts to improve traditional SBT for neonatal thoracentesis through an autonomous simulator that can provide real-time objective feedback during surgical training and assessment.The simulator incorporates a custom manikin and virtual reality software interfaced through electromagnetic sensors that track the motion of surgical instruments. The software application reads and stores instrument motion information to replicate physical actions in the virtual environment, play back previously stored surgical performances and analyze data through a pretrained neural network. The simulator encapsulates the experience of SBT by allowing trainees to watch and replicate an ideal method of conducting the procedure, providing simplified, real-time autonomous guidance during practice and an objective taskwise assessment of the performance during testing.The preliminary trial held at the University of Illinois Hospital in the presence of 1 neonatologist and 4 fellows revealed that all the participants used the autonomous guidance more than once, and all found simulation experience to be accurate and overall effective in learning thoracentesis.Although the sample size is small, the simulator shows potential in being a viable alternative approach for training and assessment for thoracentesis.

Infants born extremely preterm (28 weeks' gestation) are at high risk of neurodevelopmental impairment (NDI) with 50% of survivors showing moderate or severe NDI when at 2 years of age. We sought to develop novel models by which to predict neurodevelopmental outcomes, hypothesizing that combining baseline characteristics at birth with medical care and environmental exposures would produce the most accurate model.Using a prospective database of 692 infants from the Preterm Epo Neuroprotection (PENUT) Trial, which was carried out between December 2013 and September 2016, we developed three predictive algorithms of increasing complexity using a Bayesian Additive Regression Trees (BART) machine learning approach to predict both NDI and continuous Bayley Scales of Infant and Toddler Development 3rd ed subscales at 2 year follow-up using: 1) the 5 variables used in the National Institute of Child Health and Human Development (NICHD) Extremely Preterm Birth Outcomes Tool, 2) 21 variables associated with outcomes in extremely preterm (EP) infants, and 3) a hypothesis-free approach using 133 potential variables available for infants in the PENUT database.The NICHD 5-variable model predicted 3-4% of the variance in the Bayley subscale scores, and predicted NDI with an area under the receiver operator curve (AUROC, 95% CI) of 0.62 (0.56-0.69). Accuracy increased to 12-20% of variance explained and an AUROC of 0.77 (0.72-0.83) when using the 21 pre-selected clinical variables. Hypothesis-free variable selection using BART resulted in models that explained 20-31% of Bayley subscale scores and AUROC of 0.87 (0.83-0.91) for severe NDI, with good calibration across the range of outcome predictions. However, even with the most accurate models, the average prediction error for the Bayley subscale predictions was around 14-15 points, leading to wide prediction intervals. Higher total transfusion volume was the most important predictor of severe NDI and lower Bayley scores across all subscales.While the machine learning BART approach meaningfully improved predictive accuracy above a widely used prediction tool (NICHD) as well as a model utilizing NDI-associated clinical characteristics, the average error remained approximately 1 standard deviation on either side of the true value. Although dichotomous NDI prediction using BART was more accurate than has been previously reported, and certain clinical variables such as transfusion exposure were meaningfully predictive of outcomes, our results emphasize the fact that the field is still not able to accurately predict the results of complex long-term assessments such as Bayley subscales in infants born EP even when using rich datasets and advanced analytic methods. This highlights the ongoing need for long-term follow-up of all EP infants.Supported by the National Institute of Neurological Disorders and StrokeU01NS077953 and U01NS077955.

Objectives To compare the term equivalent brain magnetic resonance imaging (MRI) findings between erythropoietin (Epo) treated and placebo control groups in infants 240/7-276/7 weeks of gestational age and to assess the associations between MRI findings and neurodevelopmental outcomes at 2 years corrected age. Study design The association between brain abnormality scores and Bayley Scales of Infant Development, Third Edition at 2 years corrected age was explored in a subset of infants enrolled in the Preterm Erythropoietin Neuroprotection Trial. Potential risk factors for neurodevelopmental outcomes such as treatment assignment, recruitment site, gestational age, inpatient complications, and treatments were examined using generalized estimating equation models. Results One hundred ten infants were assigned to Epo and 110 to placebo groups. 27% of MRI scans were rated as normal, and 60%, 10%, and 2% were rated as having mild, moderate, or severe abnormality. Brain abnormality scores did not significantly differ between the treatment groups. Factors that increased the risk of higher brain injury scores included intubation; bronchopulmonary dysplasia; retinopathy of prematurity; opioid, benzodiazepine, or antibiotic treatment >7 days; and periventricular leukomalacia or severe intraventricular hemorrhage diagnosed on cranial ultrasound. Increased global brain abnormality and white matter injury scores at term equivalent were associated with reductions in cognitive, motor, and language abilities at 2 years of corrected age. Conclusions Evidence of brain injury on brain MRIs obtained at term equivalent correlated with adverse neurodevelopmental outcomes as assessed by the Bayley Scales of Infant and Toddler Development, Third Edition at 2 years corrected age. Early Epo treatment had no effect on the MRI brain injury scores compared with the placebo group.

BACKGROUND Our understanding of the normative concentrations of urine biomarkers in premature neonates is limited. METHODS We evaluated urine from 750 extremely low gestational age (GA) neonates without severe acute kidney injury (AKI) to determine how GA affects ten different urine biomarkers at birth and over the first 30 postnatal days. Then, we investigated if the urine biomarkers changed over time at 27, 30, and 34 weeks postmenstrual age (PMA). Next, we evaluated the impact of sex on urine biomarker concentrations at birth and over time. Finally, we evaluated if urine biomarkers were impacted by treatment with erythropoietin (Epo). RESULTS We found that all ten biomarker concentrations differ at birth by GA and that some urine biomarker concentrations increase, while others decrease over time. At 27 weeks PMA, 7/10 urine biomarkers differed by GA. By 30 weeks PMA, 5/10 differed, and by 34 weeks PMA, only osteopontin differed by GA. About half of the biomarker concentrations differed by sex, and 4/10 showed different rates of change over time between males vs. females. We found no differences in urine biomarkers by treatment group. CONCLUSIONS The temporal patterns, GA, and sex differences need to be considered in urine AKI biomarker analyses. IMPACT Urine biomarker concentrations differ by GA at birth. Some urine biomarkers increase, while others decrease, over the first 30 postnatal days. Most urine biomarkers differ by GA at 27 weeks PMA, but are similar by 34 weeks PMA. Some urine biomarkers vary by sex in premature neonates. Urine biomarkers did not differ between neonates randomized to placebo vs. Epo.

Background: Ductal response to indomethacin in extremely-low-birth-weight (ELBW) infants is not well studied. Objective: The purpose of this study was to identify predictors of ductal closure in ELBW infants treated with indomethacin. Methods: A single-center, retrospective cohort of ELBW infants treated with indomethacin for patent ductus arteriosus (PDA) were included. Predictors of PDA closure were identified using multivariable adjusted logistic regression. Results: One hundred and five infants with a PDA were treated with indomethacin. Primary PDA closure with one course of indomethacin occurred in 61.9%. The rate of primary PDA closure was lower in infants with gestational age (GA) < 28 weeks compared to infants ≥ 28 weeks (58.1% vs 91.7%, p =0.03). Multivariable logistic regression model identified PDA size (OR 0.29, 95% CI 0.11-0.74, p =0.009) and exposure to antenatal indomethacin (OR 0.28, 95% CI 0.08–0.99, p =0.048) and magnesium (OR 0.31, 95% CI 0.12–0.82, p =0.019) as significant predictors for failure of ductal closure in infants treated with indomethacin. Infants with failed PDA closure were more likely to have moderate/severe bronchopulmonary dysplasia, severe intraventricular hemorrhage, and longer duration of hospitalization (p Conclusions: Large PDA and antenatal indomethacin and magnesium were predictors for failure of ductal closure with indomethacin. The negative association between antenatal indomethacin and magnesium on ductal closure with postnatal indomethacin warrants further investigation regarding routine use in mothers at risk for preterm delivery. Future studies focusing on developing predictive models to identify ideal candidates for indomethacin within the ELBW population could reduce the burden of the disease and improve overall outcomes.

STUDY OBJECTIVE Little guidance exists on the treatment duration of culture-negative early-onset sepsis (CN-EOS) in neonates, which may lead to prolonged antimicrobial therapy and adverse outcomes. Our objective was to identify risk factors associated with prolonged antibiotic therapy in CN-EOS in neonates. DESIGN This was a retrospective, matched cohort study of neonates treated with empiric antibiotic therapy for EOS. Infants were sampled with matching of gestational age (GA) into short (≤3 days) and prolonged (>3 days) antibiotic course. Primary outcomes were to identify predictive factors that may be associated with prolonged therapy and compare rates of late-onset sepsis (LOS) and mortality. Secondary outcomes included necrotizing enterocolitis, feeding intolerance, and early development assessment. Predictors associated with prolonged antibiotic therapy were identified using multivariable-adjusted logistic regression. MEASUREMENTS AND MAIN RESULTS Three hundred infants were included with 150 infants in each group. Mean GA and birthweights were 34.2 ± 4.7 weeks and 2293 ± 991 g, respectively. Male gender, 5-min Apgar

Extremely preterm infants are among the populations receiving the highest levels of transfusions. Erythropoietin has not been recommended for premature infants because most studies have not demonstrated a decrease in donor exposure.To determine whether high-dose erythropoietin given within 24 hours of birth through postmenstrual age of 32 completed weeks will decrease the need for blood transfusions.The Preterm Erythropoietin Neuroprotection Trial (PENUT) is a randomized, double-masked clinical trial with participants enrolled at 19 sites consisting of 30 neonatal intensive care units across the United States. Participants were born at a gestational age of 24 weeks (0-6 days) to 27 weeks (6-7 days). Exclusion criteria included conditions known to affect neurodevelopmental outcomes. Of 3266 patients screened, 2325 were excluded, and 941 were enrolled and randomized to erythropoietin (n = 477) or placebo (n = 464). Data were collected from December 12, 2013, to February 25, 2019, and analyzed from March 1 to June 15, 2019.In this post hoc analysis, erythropoietin, 1000 U/kg, or placebo was given every 48 hours for 6 doses, followed by 400 U/kg or sham injections 3 times a week through postmenstrual age of 32 weeks.Need for transfusion, transfusion numbers and volume, number of donor exposures, and lowest daily hematocrit level are presented herein.A total of 936 patients (488 male [52.1%]) were included in the analysis, with a mean (SD) gestational age of 25.6 (1.2) weeks and mean (SD) birth weight of 799 (189) g. Erythropoietin treatment (vs placebo) decreased the number of transfusions (unadjusted mean [SD], 3.5 [4.0] vs 5.2 [4.4]), with a relative rate (RR) of 0.66 (95% CI, 0.59-0.75); the cumulative transfused volume (mean [SD], 47.6 [60.4] vs 76.3 [68.2] mL), with a mean difference of -25.7 (95% CI, 18.1-33.3) mL; and donor exposure (mean [SD], 1.6 [1.7] vs 2.4 [2.0]), with an RR of 0.67 (95% CI, 0.58-0.77). Despite fewer transfusions, erythropoietin-treated infants tended to have higher hematocrit levels than placebo-treated infants, most noticeable at gestational week 33 in infants with a gestational age of 27 weeks (mean [SD] hematocrit level in erythropoietin-treated vs placebo-treated cohorts, 36.9% [5.5%] vs 30.4% [4.6%] (P .001). Of 936 infants, 160 (17.1%) remained transfusion free at the end of 12 postnatal weeks, including 43 in the placebo group and 117 in the erythropoietin group (P .001).These findings suggest that high-dose erythropoietin as used in the PENUT protocol was effective in reducing transfusion needs in this population of extremely preterm infants.ClinicalTrials.gov Identifier: NCT01378273.

OBJECTIVE: To evaluate whether extremely low gestational age neonates (ELGANs) randomized to erythropoietin have better or worse kidney-related outcomes during hospitalization and at 22–26 months corrected gestational age (cGA) compared with those randomized to placebo. STUDY DESIGN: We performed an ancillary study to a multicenter double-blind, placebo-controlled randomized clinical trial of erythropoietin in ELGANs. RESULTS: The prevalence of severe (stage 2 or 3) acute kidney injury (AKI) was 18.2%. We did not find a statistically significant difference between those randomized to erythropoietin vs. placebo for in-hospital primary (severe AKI) or secondary outcomes (any AKI and serum creatinine [SCr]/ cystatin C values at days 0, 7, 9 and 14). At 22–26 months cGA, 16% of the cohort had an estimated glomerular filtration rate (eGFR) 30 mg/g, 23% had a systolic blood pressure (SBP) >95(th) percentile for age, and 40% had a diastolic blood pressure (DBP) >95(th) percentile for age. SBP >90(th) percentile occurred less often among recipients of erythropoietin (p95(th) percentile or DBP >90(th) or >95(th) percentiles. CONCLUSIONS: ELGANs have high rates of in-hospital AKI and kidney-related problems at 22–26 months cGA. Recombinant erythropoietin (rhEpo) may protect ELGANs against long-term elevated SBP, but does not appear to protect from AKI, low eGFR, albuminuria or elevated DBP at 22–26 months cGA.

BACKGROUND: High-dose erythropoietin has been shown to have a neuroprotective effect in preclinical models of neonatal brain injury, and phase 2 trials have suggested possible efficacy; however, the benefits and safety of this therapy in extremely preterm infants have not been established. METHODS: In this multicenter, randomized, double-blind trial of high-dose erythropoietin, we assigned 941 infants who were born at 24 weeks 0 days to 27 weeks 6 days of gestation to receive erythropoietin or placebo within 24 hours after birth. Erythropoietin was administered intravenously at a dose of 1000 U per kilogram of body weight every 48 hours for a total of six doses, followed by a maintenance dose of 400 U per kilogram three times per week by subcutaneous injection through 32 completed weeks of postmenstrual age. Placebo was administered as intravenous saline followed by sham injections. The primary outcome was death or severe neurodevelopmental impairment at 22 to 26 months of postmenstrual age. Severe neurodevelopmental impairment was defined as severe cerebral palsy or a composite motor or composite cognitive score of less than 70 (which corresponds to 2 SD below the mean, with higher scores indicating better performance) on the Bayley Scales of Infant and Toddler Development, third edition. RESULTS: A total of 741 infants were included in the per-protocol efficacy analysis: 376 received erythropoietin and 365 received placebo. There was no significant difference between the erythropoietin group and the placebo group in the incidence of death or severe neurodevelopmental impairment at 2 years of age (97 children [26%] vs. 94 children [26%]; relative risk, 1.03; 95% confidence interval, 0.81 to 1.32; P = 0.80). There were no significant differences between the groups in the rates of retinopathy of prematurity, intracranial hemorrhage, sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, or death or in the frequency of serious adverse events. CONCLUSIONS: High-dose erythropoietin treatment administered to extremely preterm infants from 24 hours after birth through 32 weeks of postmenstrual age did not result in a lower risk of severe neurodevelopmental impairment or death at 2 years of age. (Funded by the National Institute of Neurological Disorders and Stroke; PENUT ClinicalTrials.gov number, NCT01378273.)

Objective This study aims to estimate the impact of acute kidney injury (AKI) on postnatal renal adaptation, morbidity, and mortality in very low-birth-weight (VLBW) infants. Design We conducted a retrospective study of 457 VLBW infants admitted to a tertiary level neonatal intensive care unit (NICU) between July 2009 and April 2015. We compared patient characteristics, risk factors, serum creatinine trends, and adverse outcomes in infants with and without AKI using multivariate logistic regression analysis. Results Incidence of AKI was 19.5%. On multivariate analysis, postnatal risk factors such as patent ductus arteriosus and vancomycin use were significantly associated with AKI. Infants with AKI had significantly higher mortality; 25/89 (28%) versus 15/368 (4%) (p Conclusion Presence of AKI was associated with impaired postnatal renal adaptation, BPD, significantly longer stay in the NICU and higher mortality.

Aims Atrioventricular junction ablation (AVJA) combined with biventricular (BiV) pacing (AVJA/BiV) is an effective treatment for refractory atrial fibrillation (AF) and rapid ventricular response (RVR) associated with heart failure (HF). This study compared the outcomes between patients with non-ischaemic (DCM) and ischaemic cardiomyopathy (ICM) following AVJA/BiV for AF/RVR. Methods and results This was a retrospective study of 45 patients, comparing the response to AVJA/BiV in patients with ICM to those with DCM. The study compared (a) the change in echocardiographic parameters of HF (ejection fraction (EF) and left ventricular dimensions) prior to, and at least 6 months post AVJA/BiV; and (b) HF hospitalizations (HFH) and appropriate implantable cardioverter defibrillator (ICD) therapies occurring post-procedure. Ejection fraction improved significantly in the DCM group (ΔEF 11.2% ± 11.9; P < 0.01); however, EF remained unchanged (ΔEF 0.5% ± 9.9; P = NS) in the ICM group post-AVJA/BiV. Post-procedurely, HFH were significantly more common (15/18 vs. 4/25; P < 0.0001), and there were significantly more appropriate ICD therapies (9.4 ± 12.3 vs. 2.3 ± 6.1; P = 0.01) in the ICM compared with the DCM group. Conclusion After AVJA/BiV, there was significantly less post-procedural echocardiographic reverse remodelling, and more HFH in the ICM compared with the DCM group. In addition, significantly more appropriate ICD therapies occurred in ICM patients post-procedure. These differences may be due to the presence of more extensive discrete myocardial scar in patients with ICM. Furthermore, it is possible that tachycardia-induced cardiomyopathy plays more of a causative role in HF in patients with AF and DCM than those with ICM.

To follow the natural progression of fetal renal pyelectasis detected in the mid second trimester ultrasound in an unselected obstetric population.Single-centered, retrospective study that included all level II ultrasounds done from Jan 2008 to Dec 2009. The initial level II ultrasound was done in the mid second trimester. The renal pyelectasis detected on the antenatal ultrasound (AUS) was classified as mild (5-7 mm), moderate (7.1-9 mm), or severe (9.1 mm). Postnatal outcomes were classified as "Resolved", "Improving", or "Worsened".Ninety-eight cases of fetal renal pyelectasis were detected. Sixteen patients were excluded. Of the remaining 82 cases of fetal pyelectasis, 32 (39%) were mild, 21 (25.6%) moderate, and 29 (35.4%) severe. In 74 (90.2%) infants, pyelectasis resolved, remained stable, or improved in the postnatal ultrasound. In eight (9.8%) infants, pyelectasis worsened.Totally, 90.2% of pyelectasis detected on AUS resolved spontaneously, remained stable or improved. The magnitude of fetal renal pyelectasis did not correlate with postnatal outcome. All fetal renal pyelectasis ≥ 5 mm detected on the mid second trimester ultrasound should be followed antenatally. Those fetuses with persistent pyelectasis should be evaluated after birth and followed until resolution of pyelectasis or until a diagnosis is obtained.