In this multicenter, randomized trial involving extremely preterm infants, high-dose erythropoietin administered 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.
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.
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.
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.
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%) (
< 0.001). Among survivors with AKI, bronchopulmonary dysplasia (BPD) was more prevalent (52.8 vs. 23.9%,
< 0.001), serum creatinine remained elevated for a longer duration and median length of stay extended by 38 days.
Presence of AKI was associated with impaired postnatal renal adaptation, BPD, significantly longer stay in the NICU and higher mortality.
Purpose: Acute Kidney Injury (AKI) in Very Low Birth Weight (VLBW) infants can cause interruptions to nephrogenesis and result in functional renal loss. Serum Creatinine (S.Cr), although a useful ...marker for the diagnosis of AKI, is not reliable in monitoring ongoing renal dysfunction due to the lack of normal baseline values. On the other hand, glomerular filtration rate (GFR) is a better measure of ongoing renal dysfunction as it represents S.Cr values in relation to height and age dependent constant values. Effect of early injury to the developing kidneys can be estimated by tracking GFR in these patients over time. In this study, we intend to examine the impact of early AKI on GFR in VLBW infants during the first month of life. Methods: We conducted a retrospective chart analysis of VLBW infants admitted to a single-center tertiary level NICU between August 2012 and April 2015. We identified infants with AKI based on the Acute Kidney Injury Network (AKIN) criteria and compared them at a 1:2 ratio with gestational age (GA)-, birth-weight (BW)- and gender-matched controls without AKI. Average GFR computed using weekly S.Cr and height using equation GFR (ml/min/1.73 sq.m) = 0.33*Height (cm)/S.Cr (mg/dl) was compared between these two groups during weeks 1, 2, 3 and 4. Contributions of other co-morbid conditions and nephrotoxic drugs to poor GFR were also analyzed using a regression model. Results: o Fifty-five infants with AKI were identified during the 2.5-year time-period and compared to 110 matched controls. o Median age at onset of AKI was 6 days. o Average GA and BW of infants in the AKI and non-AKI groups were 25.47 vs 27.12 weeks and 759.05 vs 943.71 grams, respectively. o Presence of AKI was the single most predictive factor for poor GFR in the first month of life. o Average weekly GFR was significantly lower during weeks 1, 2, 3 and 4 in infants with AKI compared to controls (Table 1). o In addition to AKI, other significant predictors of poor GFR in this population included: o Week 1: Lower GA and BW o Week 2: Lower GA and presence of PDA o Week 3: Indomethacin use o Week 4: Higher percentage of weight loss since birth Conclusion: VLBW infants with early onset AKI had persistently poor renal function during the first month of life compared to infants without AKI. GFR remained low in these patients despite stabilizing creatinine values following the initial surge. GFR should therefore be monitored in all patients with AKI. Infants with persistently low or worsening GFR should be appropriately referred and evaluated for chronic kidney disease.
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.
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.
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 <7, immature-to-total neutrophil ratio ≥0.2, C-reactive protein (CRP) ≥10 mg/L, need for vasopressors, and mechanical ventilation were identified as significant predictors for prolonged antibiotics in all infants. Independent of GA, elevated CRP (OR 40.84, 95% CI 15.28-109.15, p < 0.001), need for vasopressors (OR 13.48, 95% CI 3.86-47.15, p < 0.001), and mechanical ventilation (OR 12.98, 95% CI 4.91-34.35, p < 0.001) remained significant predictors of prolonged antibiotic use. Infants in the prolonged courses experienced significant delays in achieving independent oral feeding compared with infants receiving short-course antibiotics (median 17.5 vs. 8 days, p = 0.002, respectively). There were no significant differences in LOS, mortality, or other neonatal comorbidities.
Elevated CRP levels, need for vasopressors, and mechanical ventilation were associated with prolonged antibiotic use in neonates presumptively treated for CN-EOS. Further research is warranted in identifying selective biomarkers for EOS and evaluating whether early antibiotic discontinuation for CN-EOS, despite abnormal laboratory tests/illness severity, is safe and justified.
IMPORTANCE: 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. OBJECTIVES: 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. DESIGN, SETTING, AND PARTICIPANTS: 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. INTERVENTIONS: 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. MAIN OUTCOMES AND MEASURES: Need for transfusion, transfusion numbers and volume, number of donor exposures, and lowest daily hematocrit level are presented herein. RESULTS: 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). CONCLUSIONS AND RELEVANCE: 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. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01378273
Outcomes of extremely low gestational age neonates (ELGANs) may be adversely impacted by packed red blood cell (pRBC) transfusions. We investigated the impact of transfusions on neurodevelopmental ...outcome in the Preterm Erythropoietin (Epo) Neuroprotection (PENUT) Trial population.
This is a post hoc analysis of 936 infants 24-0/6 to 27-6/7 weeks' gestation enrolled in the PENUT Trial. Epo 1000 U/kg or placebo was given every 48 h × 6 doses, followed by 400 U/kg or sham injections 3 times a week through 32 weeks postmenstrual age. Six hundred and twenty-eight (315 placebo, 313 Epo) survived and were assessed at 2 years of age. We evaluated associations between BSID-III scores and the number and volume of pRBC transfusions.
Each transfusion was associated with a decrease in mean cognitive score of 0.96 (95% CI of -1.34, -0.57), a decrease in mean motor score of 1.51 (-1.91, -1.12), and a decrease in mean language score of 1.10 (-1.54, -0.66). Significant negative associations between BSID-III score and transfusion volume and donor exposure were observed in the placebo group but not in the Epo group.
Transfusions in ELGANs were associated with worse outcomes. We speculate that strategies to minimize the need for transfusions may improve outcomes.
Transfusion number, volume, and donor exposure in the neonatal period are associated with worse neurodevelopmental (ND) outcome at 2 years of age, as assessed by the Bayley Infant Scales of Development, Third Edition (BSID-III). The impact of neonatal packed red blood cell transfusions on the neurodevelopmental outcome of preterm infants is unknown. We speculate that strategies to minimize the need for transfusions may improve neurodevelopmental outcomes.
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 of corrected ...gestational age (cGA) compared with those randomized to placebo.
We performed an ancillary study to a multicenter double-blind, placebo-controlled randomized clinical trial of erythropoietin in ELGANs.
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/cystatin C values at days 0, 7, 9, and 14). At 22-26 months of cGA, 16% of the cohort had an estimated glomerular filtration rate (eGFR) <90 mL/min/1.73 m2, 35.8% had urine albumin/creatinine ratio >30 mg/g, 23% had a systolic blood pressure (SBP) >95th percentile for age, and 40% had a diastolic blood pressure (DBP) >95th percentile for age. SBP >90th percentile occurred less often among recipients of erythropoietin (P < .04). This association remained even after controlling for gestational age, site, and sibship (aOR 0.6; 95% CI 0.39-0.92). We did not find statistically significant differences between treatment groups in eGFR, albumin/creatinine ratio, rates of SBP >95th percentile, or DBP >90th or >95th percentiles at the 2 year follow-up visit.
ELGANs have high rates of in-hospital AKI and kidney-related problems at 22-26 months of cGA. Recombinant erythropoietin 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 of cGA.
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.
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.
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.
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.
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