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Gretchen Kopec, Prem S Shekhawat, Maroun J Mhanna Department of Pediatrics, MetroHealth Medical Centre, Case Western Reserve University, Cleveland, OH, USA Abstract: Intrauterine growth restriction (IUGR) is when fetuses and newborn infants have not reached their true growth potential as genetically defined. Fetuses with IUGR develop in a less than ideal environment that leads to epigenetic changes and marks infants’ metabolism for the rest of their lives. Epigenetic changes affect insulin-like growth factor-1 (IGF-1) levels and lead to insulin resistance and ultimately to a metabolic syndrome. The metabolic syndrome is a constellation of illnesses that raise one’s risk for type 2 diabetes mellitus, coronary artery disease, and ischemic heart disease, including hypertension, dyslipidemia, central obesity, insulin resistance, and inflammation. The association between IUGR or prematurity and long-term insulin resistance, obesity, hypertension, and metabolic syndrome remains unclear. While studies have shown an association, others have not supported such association. If alteration of intrauterine growth can ultimately lead to the development of metabolic derangements in childhood and adulthood, and if such association is true, then early interventions targeting the health of pregnant women will ensure the health of the population to follow. Keywords: diabetes, obesity, low birth weight infants, metabolic syndrome

Background: Subjects with metabolic syndrome and obesity have higher levels of inflammation with depression of the vitamin D (VD) hydroxylase/metabolising genes ( CYP2R1/CYP27A1/CYP27B1/VDR ) required to convert VD consumed in the diet into 25(OH)VD. Compared with total 25(OH)VD levels, measurement of bioavailable 25(OH)VD is a better method to determine the beneficial effect of VD., Objective: This study investigates whether cosupplementation with VD and L-cysteine (LC), which downregulates inflammation and upregulates VD-regulating genes, provides a better therapeutic benefit than supplementation with VD-alone in African Americans (AA)., Methods: AA participants (men/women, aged 18-65 years; n=165) were block randomised into one of four groups and received daily, oral supplementation for 6 months with placebo, LC (1000 mg/day), VD (2000 IU/day) or VD+LC. Fasting blood collected at the baseline and final visits was analysed for total, free and bioavailable 25(OH)VD along with insulin, VD-binding protein (VDBP), sex hormone-binding globulin (SHBG), free and total testosterone, and inflammatory marker levels. Studies were carried out in THP-1 monocytes to elucidate the direct effect of LC and testosterone on VD-regulating genes., Results: Baseline data showed no differences in age, body mass index, calcium, liver or kidney function among the groups. Compared with levels in the group that received VD-alone supplementation, levels of neutrophil-to-lymphocyte ratio, C reactive protein, HOMA-IR, VDBP and HbA1c were significantly lower in the VD+LC group while the VD+LC group showed a significant increase in bioavailable 25(OH)VD in both sexes, total 25(OH)VD levels were significantly elevated in men but not in women treated with VD+LC. Blood levels of SHBG and free/total testosterone were elevated in the VD+LC group but not in the VD-alone group. LC and testosterone treatment significantly upregulated VD-metabolising genes ( CYP2R1/CYP27A1/CYP27B1/VDR ) and SHBG in THP-1 monocytes., Conclusions: VD cosupplemented with LC upregulates circulating bioavailable 25(OH)VD and reduces inflammation. Total 25(OH)VD levels were higher in men but not in women in the VD+LC group. This pilot study suggests that compared with supplementation with VD-alone, VD+LC cosupplementation could be a better approach to raising the total 25(OH)VD in men and the bioavailable 25(OH)VD in both sexes and lowering the inflammatory risk in the AA population., Trial Registration Number: NCT04939792., Competing Interests: None declared., (Copyright © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Objective: Determine screening rates and examine socio-demographic characteristics of metabolic dysfunction-associated steatotic liver disease (MAFLD) screening in a large population of obese children., Methods: We used Explorys (IBM) which contains aggregated population-level electronic health record data from approximately 360 hospitals and 317,000 providers across the United States to determine MAFLD screening rates. In children 10 to 14 years, obesity was determined based on body mass index ≥ 95%, or encounter with an international classification of disease obesity code. We determined screening rates by calculating the percentage of children with obesity who had an alanine aminotransferase tested, further analyzed by gender, race, and insurance., Results: Of 3,558,420 children, 513,170 (14.4%) were obese. Of obese children, only 9.3% were screened for MAFLD. Females were more likely screened than males (odds ratio (OR) 1.09 (95% confidence intervals (CI): 1.07-1.12)); White children were more likely screened than non-White children (OR 1.21 (95% CI: 1.18-1.23)), and children with Medicaid more likely screened than children with non-Medicaid insurance (OR 1.34 (95% CI: 1.32-1.37))., Conclusions: The percentage of obese children receiving screening for MAFLD was low. Female gender, White race, and Medicaid insurance were associated with increased screening rates. These findings highlight the need to increase adherence to MAFLD screening. Reporting screening as a health quality measure may reduce implementation gaps in MAFLD screening., Competing Interests: Declaration of Competing Interest The authors have no example conflicts of interest to disclose., (Copyright © 2024 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Background: Late-onset sepsis is common in extremely low birth weight (ELBW) infants, and it leads to the use of antibiotics to cover resistant organisms, which can be nephrotoxic. Here we have investigated the role of vancomycin plus piperacillin-tazobactam on the rate of acute kidney injury (AKI)., Methods: In a retrospective case-control study, medical records of all ELBW infants who were admitted to our Neonatal Intensive Care Unit (NICU) with late onset sepsis who were prescribed vancomycin plus piperacillin-tazobactam were reviewed for demographics, clinical characteristics, use of potential nephrotoxic medications and outcomes., Results: During the study period, 264 patients were admitted, of whom 28.4%(75/264) received vancomycin plus piperacillin-tazobactam and were matched with 64 controls. There were no differences in gestational age or birth weight between cases and controls [688±160 vs. 689±162 grams (p = 0.99), and 24.7±1.8 vs. 24.7±1.6 weeks (p = 0.99) respectively]. There was no difference in the rate of sepsis between cases and controls [76%(55/72) vs. 64%(41/64) respectively, p = 0.11]. Infants exposed to vancomycin plus piperacillin-tazobactam had a higher percentage of concomitant use of vasopressors and amphotericin. To adjust for confounders, a logistic regression analysis was conducted with AKI as the dependent variable. Use of vasopressors and vancomycin plus piperacillin-tazobactam were the only risk factors associated with AKI with an adjusted OR (95%CI) of 4.08 (1.90-8.74), p < 0.001; and 2.87 (1.26-6.53), p = 0.01 respectively., Conclusion: The use of vancomycin plus piperacillin-tazobactam in ELBW infants is associated with an increased risk for AKI.

In this state-of-the-art review, we highlight the major advances over the last 5 years in neonatal acute kidney injury (AKI). Large multicenter studies reveal that neonatal AKI is common and independently associated with increased morbidity and mortality. The natural course of neonatal AKI, along with the risk factors, mitigation strategies, and the role of AKI on short- and long-term outcomes, is becoming clearer. Specific progress has been made in identifying potential preventive strategies for AKI, such as the use of caffeine in premature neonates, theophylline in neonates with hypoxic-ischemic encephalopathy, and nephrotoxic medication monitoring programs. New evidence highlights the importance of the kidney in "crosstalk" between other organs and how AKI likely plays a critical role in other organ development and injury, such as intraventricular hemorrhage and lung disease. New technology has resulted in advancement in prevention and improvements in the current management in neonates with severe AKI. With specific continuous renal replacement therapy machines designed for neonates, this therapy is now available and is being used with increasing frequency in NICUs. Moving forward, biomarkers, such as urinary neutrophil gelatinase-associated lipocalin, and other new technologies, such as monitoring of renal tissue oxygenation and nephron counting, will likely play an increased role in identification of AKI and those most vulnerable for chronic kidney disease. Future research needs to be focused on determining the optimal follow-up strategy for neonates with a history of AKI to detect chronic kidney disease., Competing Interests: POTENTIAL CONFLICT OF INTEREST: For full disclosure, we provide here an additional list of other authors’ commitments and funding sources that are not directly related to this study: Dr Askenazi is a consultant for Baxter, Nuwellis, Medtronic Bioporto, the Acute Kidney Injury Foundation, and Seastar; he receives grant funding for studies not related to this project from Baxter, Nuwellis, Medtronic, and the National Institutes of Health; the other authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Objectives: Inadequate testing (IT) and follow-up in infants with perinatal hepatitis C virus (HCV) exposure are challenging. We sought to identify maternal clinical and demographic risk factors that are associated with inadequate testing (IT) and follow-up of perinatally HCV-exposed infants., Methods: In a retrospective cohort study spanning a period of 23 years, medical records of HCV-infected women and their perinatally exposed infants were reviewed for maternal characteristics that could be associated with their infants' IT and loss to follow-up., Results: A total of 27% (108/407) of HCV-exposed infants were adequately tested (AT) for HCV perinatal transmission. Among AT infants, HCV transmission rate was 11% (12/108). History of maternal intravenous drug use (IVDU) was significantly higher in IT vs. AT infants [88% (193/218) vs. 76% (70/92); p = 0.005]. The percentage of mothers on methadone maintenance treatment during pregnancy was higher in AT vs. IT infants [53% (35/66) vs. 34% (65/186); p = 0.010]. The percentage of mothers with HCV medical care was higher among AT than IT infants [54% (56/102) vs. 41% (106/255); p = 0.022]., Conclusions: Infants born to HCV-infected mothers have suboptimal testing, possibly leading to an underestimation of the rate of HCV vertical transmission. Infants of mothers receiving HCV medical care and methadone treatment have improved testing. Infants of HCV-positive mothers with history of IVDU have lower rates of testing. Screening HCV-infected pregnant women for history of IVDU and linking them to drug treatment programs, and HCV medical care may improve testing and follow-up in their infants.

Objective: This work aimed to study the correlation between invasive blood pressure (IBP) and non-IBP (NIBP) in extremely low gestational age newborns (ELGANs) during their first 72 hours of life., Study Design: In a retrospective cohort study, IBP and simultaneous NIBP measurements during the first 72 hours of life were recorded in ELGANs. Medical records were reviewed for potential risk factors that affect BP. The % difference in mean arterial BP (% Diff-BP) measurements was calculated as (IBP-NIBP)/IBP. Hypotension was defined as mean arterial B p  < gestational age (GA)., Results: In total, 236 infants and 1,340 paired IBP-NIBP measurements were studied. Infants had a (mean ± standard deviation) GA of 25.4 ± 21.6 weeks and a birth weight of 810 ± 249 g. Overall, there was a significant correlation between IBP and NIBP of 0.887 (Spearman Rho; p  < 0.001). However, the agreement between IBP and NIBP was poor, with a mean difference (95% limits of agreement) of 0.20 (-5.48; 5.89). The mean % Diff-BP (±standard deviation) was 0.39 ± 8.25%. In hypotensive infants, NIBP overestimated IBP measurements, with an agreement of -0.67 (-4.17; 2.83)., Conclusion: Mean arterial NIBP correlates with IBP in ELGANs. However, there is a poor agreement between methods. In hypotensive infants, NIBP overestimates IBP measurements., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: To study whether there is an association between nutritional intake during the first week of life and severity of bronchopulmonary dysplasia (BPD) in extremely low birth weight (ELBW) infants., Methods: In a retrospective cohort study, medical records of all ELBW infants admitted to our Neonatal Intensive Care Unit (2010-2017) were reviewed for infants' demographics, clinical characteristics, nutritional intake during their first week of life, and BPD risk factors., Results: During the study period 226 infants were identified of whom 67% (151/226) had moderate-severe BPD and the rest served as controls. Overall infants with moderate-severe BPD were younger, smaller, and spent more time on mechanical ventilation than their controls [(mean±standard deviation) 24.7±1.7 vs. 26.8±2.0 weeks gestational age (p < 0.001); 678±154 vs. 837±129 grams (p < 0.001); and 37.9±23.6 vs. 13.7±15.3 days (p < 0.001) respectively]. During the first week of life, the average caloric, carbohydrate, protein and lipid intakes were significantly lower, and the average fluid intake was significantly higher in the moderate-severe BPD than the control group. After adjustment for confounders, fluid intake, and days on mechanical ventilation were significantly associated with moderate-severe BPD with an odds ratio [OR (95% confidence interval)] of 1.03 (1.01-1.04), and 1.05 (1.03-1.07) respectively. Daily caloric intake was associated with an increased risk for moderate-severe BPD [OR: 0.94 (0.91-0.97)]., Conclusion: Low caloric intake, and high fluid intake during the first week of life are associated with the severity of BPD in ELBW infants.

Objective: Preterm birth is a significant cause of infant morbidity and mortality, which are primarily the result of respiratory and neurodevelopmental complications. However, no objective biomarker is currently available to predict at birth the risk and severity of such complications. Thus, we sought to determine whether serum neurotrophins concentrations measured at birth correlate with risk for later development of bronchopulmonary dysplasia (BPD) and long-term neurodevelopmental outcomes., Methods: This study prospectively included 223 newborns admitted to neonatal intensive care units (NICU) and divided into three groups: (i) preterm infants who developed BPD; (ii) preterm infants who did not develop BPD; (iii) term infants. An exploratory cohort was enrolled in West Virginia, followed by a validation cohort recruited in four NICUs in Ohio. Specimens for serum and tracheal neurotrophins concentrations were collected within 48 h of admission. Infants requiring a fraction of inspired oxygen >0.21 for at least 28 days were diagnosed with BPD. Neurodevelopmental outcomes were extrapolated from Bayley Scales of Infant Development-Third Edition (BSID-III) administered at the 24-month follow-up visit., Results: Serum brain-derived neurotrophic factor (BDNF) concentration at birth had significant negative correlation with later diagnosis of BPD (P = 0.011) and with duration of invasive ventilation and oxygen supplementation (P = 0.009 and 0.015, respectively). Serum nerve growth factor (NGF) concentration at birth had significant positive correlation with BSID-III cognitive and language composite scores at 24 months (P < 0.001 and 0.010, respectively)., Conclusions: These data suggest that serum neurotrophins concentrations measured at birth provide prognostic information on subsequent respiratory and neurodevelopmental outcomes., (© 2018 Wiley Periodicals, Inc.)

Objective: Assessment of adrenal function in a sick neonate remains a challenge in spite of major advances in neonatal care. We used 2D ultrasound of adrenal glands to assess maturity of adrenal glands in extremely preterm infants and sick term and near term infants., Study Design: We collected demographics details of 99 mother-infants pairs (24-41 weeks) and obtained 2D ultrasound scans of adrenal glands in first week of life to measure adrenal volume, fetal zone size, and adrenal to kidney ratios. Relationship between adrenal measurements, antenatal factors, and postnatal outcomes were studied., Results: We reported normative adrenal gland volume data during gestation from 80 appropriate for gestational age (AGA) infants. In a binary analysis, adrenal size was significantly related to gender, race, intrauterine growth restriction (IUGR), maternal chorioamnionitis, and maternal hypertension. Linear regression analysis showed that fetal zone is significantly related to not only gestational age but also chorioamnionitis and later development of intraventricular hemorrhage (IVH). Adrenal volume likewise is also related to gestational age, preeclampsia, and IVH., Conclusions: Antenatal maternal factors and uterine environment affects adrenal growth and development thus postnatal high resolution 2D US scan of adrenal glands can provide useful information to predict outcomes. This information can complement hormone and adrenocorticotrophic hormone (ACTH) stimulation assays.

Objective: To analyze safety, tolerance and efficacy of enteral omega-3 fatty acids (FAs) in the resolution of Parenteral Nutrition Associated Cholestasis (PNAC) and postnatal growth among preterm neonates., Study Design: This is a single center retrospective case-control study of all neonates born less than 32 weeks of gestation and developed PNAC (Direct bilirubin >2 mg/dl). Infants who received enteral omega-3 FAs supplementation (1 g/Kg/d) served as cases and were compared with gestational age, gender and direct bilirubin level matched controls who did not receive enteral omega-3 FAs supplementation., Results: A total of 48 infants were analyzed, 24 who received enteral omega-3 fatty acids were matched with 24 controls. The omega-3 FAs and control groups were similar in gestational age (weeks) and birth weight (gram). Overall there were no differences between the two groups in infants' demographics or clinical characteristics including risk factors for the development of PNAC. Infants who received enteral omega-3 FAs had significantly fewer days of cholestasis (p = 0.025) and a higher average daily weight gain (grams/day) (p = 0.011) than their controls. In a linear regression analysis with days of cholestasis as the dependent variable and Ursodeoxycholic acid (UDCA) and Omega-3 FAs as independent variables, enteral omega-3 FAs remained associated with a shorter duration of cholestasis, p < 0.001., Conclusion: Enteral fish oil is inexpensive, safe & well tolerated in preterm neonates with no contraindications to enteral feeding. Enteral omega-3 FAs are easy to administer and help in rapid resolution of PNAC while promoting postnatal weight gain in preterm infants.

Objectives: We investigated the association of fluid overload and oxygenation in critically sick children, and their correlation with various outcomes (duration of ventilation, ICU stay, and mortality). We also assessed whether renal angina index (RAI) at admission can predict mortality or acute kidney injury (AKI) on day 3 after admission. Design and setting: Prospective study, pediatric intensive care in a tertiary hospital. Duration: June 2013-June 2014. Patients: Patients were included if they needed invasive mechanical ventilation for >24 h and had an indwelling arterial catheter. Patients with congenital heart disease or those who received renal replacement therapy (RRT) were excluded. Methods: Oxygenation index, fluid overload percent (daily, cumulative), RAI at admission and pediatric logistic organ dysfunction (PELOD) score were obtained in all critically ill children. KDIGO classification was used to define AKI, using both creatinine and urine output criteria. Admission data for determination of RAI included the use of vasopressors, invasive mechanical ventilation, percent fluid overload, and change in kidney function (estimated creatinine clearance). Univariable and multivariable approaches were used to assess the relations between fluid overload, oxygenation index and clinical outcomes. An RAI cutoff >8 was used to predict AKI on day 3 of admission and mortality. Results: One hundred and two patients were recruited. Fluid overload predicted oxygenation index in all patients, independent of age, gender and PELOD score ( p < 0.05). Fluid overload was associated with longer duration of ventilation ( p < 0.05), controlled for age, gender, and PELOD score. Day-3 AKI rates were higher in patients with a RAI of 8 or more, and higher areas under the RAI curve had better prediction rates for Day-3 AKI. An RAI <8 had high negative predictive values (80-95%) for Day-3 AKI. RAI was better than traditional markers of pediatric severity of illness (PELOD) score for prediction of AKI on day 3. Conclusions: This study emphasizes that positive fluid balance adversely affects intensive care in critically ill children. Further, the RAI prediction model may help optimize treatment and improve clinical prediction of AKI.

Purpose: Rome criteria are considered the gold standard for diagnosing functional constipation. The modified Bristol stool form scale (m-BSFS) was validated to measure stool form in children. However, neither the potential use of the m-BSFS as a tool to facilitate the diagnosis of potential constipation, nor the agreement between m-BSFS and stool consistency by Rome has been studied. Our objective is to determine if m-BSFS is a reliable tool to facilitat detection of constipation; and the agreement between stool form by m-BSFS and hard stool criteria in Rome., Methods: A survey tool with the Rome III criteria and the m-BSFS was developed. A Likert-scale addressed frequency of each stool form on the m-BSFS. Responses to Rome III and m-BSFS were compared., Results: The sensitivity and specificity of the m-BSFS was 79.2% and 66.0% respectively; and in children <4 years. improved to 81.2% and 75.0% respectively. There was poor agreement between hard stools by m-BSFS and the painful or hard bowel movement question of Rome Criteria., Conclusion: The potential utility of m-BSFS as a reasonably good tool to facilitate the diagnosis of potential constipation in children is shown. The poor agreement between painful or hard stool question in Rome III, and ratings for hard stool on the m-BSFS illustrates that one's perception may differ between a question and a picture. A useful pictorial tool to appraise stool form may, thus, be a favorable complement in the process of enquiry about bowel habits in well-child care.

Background: The definition of acute kidney injury (AKI) has evolved over the years, and three definitions have been adapted including pediatric risk injury failure, loss of kidney function (pRIFLE), Acute Kidney Injury Network (AKIN), and Neonatal Modified Kidney Disease Improving Global Outcomes (KDIGO). We sought to report the prevalence and outcome of (AKI) according to the three existing definitions in extremely low birth weight (ELBW) infants., Methods: In a retrospective cohort study, medical records of all ELBW infants (<1000 g) admitted to our neonatal intensive care unit (NICU) between Jan 2002 and Dec 2011 were reviewed. Infants' demographics, anthropometric measurements, and clinical characteristics were collected at the time of birth and at discharge from the NICU. Infants were staged according to the three different definitions., Results: During the study period, 483 ELBW infants met our inclusion criteria. The incidence of AKI was 56, 59, and 60% according to pRIFLE, AKIN, and KDIGO, respectively. Mortality, NICU length of stay, and serum creatinine (SCr) at NICU discharge were higher in infants with advanced AKI stages regardless of the definition. In addition, discharge NICU weight and length z scores were lower in infants with advanced AKI stages. SCr at 72 h of life and SCr peak were predictable of NICU mortality [AUC 0.667 (95% CI 0.604-0.731), p < 0.001 and AUC 0.747 (95% CI 0.693-0.801), p < 0.001, respectively]., Conclusion: Regardless of the definition, advanced AKI is associated with increased mortality, prolonged NICU length of stay, and poor growth in ELBW infants. SCr at 72 h of life and SCr peak may be predictable of NICU mortality.

Background: The respiratory severity score (RSS) is a byproduct of mean airway pressure (MAP) and fraction of inspired oxygen (FiO 2 ). We sought to determine whether RSS could be used as a screening tool to predict extubation readiness in very low birth weight (VLBW) infants., Methods: In a retrospective cohort study, medical records of all VLBW infants admitted to our unit (6/1/09-2/28/12) were reviewed for infants' demographics, prenatal characteristics, and medication use. Also, records were reviewed for unplanned vs. planned extubation, blood gas, ventilator parameters and signs of severe respiratory failure [RF, defined as partial pressure of carbon dioxide (pCO 2 ) > 65, pH < 7.20, FiO 2  > 50%, and MAP > 10 cm] on the day of extubation., Results: During the study period 31% (45/147) failed extubation. Overall, infants who failed extubation had a lower birth weight (BW) and gestational age (GA), and on the day of extubation had a higher RSS and percentage of having one or more signs of severe RF. In a logistic regression model, adjusting for BW, GA, RSS and RF, RSS remained the only risk factor associated with extubation failure [adjusted OR 1.63 (95% CI: 1.10-2.40); p = 0.01]. RSS had a sensitivity of 0.86 (95% CI: 0.72-0.94) at a cutoff of 1.26 and a specificity of 0.88 (95% CI: 0.80-0.94) at a cutoff of 2.5. There was no difference in extubation failure between unplanned vs. planned extubation [41% (9/22) vs. 29% (36/125); p = 0.25]., Conclusion: An elevated RSS is associated with extubation failure. Successful unplanned extubation is common in VLBW infants., (Copyright © 2017. Published by Elsevier B.V.)

Objective: To study the outcome of extremely low birth weight (ELBW) infants with a history of acute kidney injury (AKI)., Method: In a retrospective, case control study, medical records of all ELBW infants admitted to the neonatal intensive care unit (NICU) between Jan 2002 and Dec 2011 were reviewed. Medical records were reviewed for infants' demographics, blood pressure (BP) at NICU discharge and at ≥3 years, and estimated glomerular filtration rate (eGFR) at ≥2 years., Results: During the study period, 222 patients met the inclusion criteria, of whom 10% (23 out of 222) had AKI stage 2 and 3, 39% (87 out of 222) had AKI stage 1, and the rest did not have AKI. At NICU discharge, there was a difference in diastolic BP (DBP) among infants who had AKI stages 2 and 3, those who had stage 1, and those who did not have AKI (53 ± 12 vs 46 ± 9 vs 46 ± 11 mmHg respectively; p = 0.007), and 11% (23 out of 209) had hypertension (HTN). Although there was a significant correlation between the rise in SCr and DBP at NICU discharge in infants with AKI (R = 0.304; p = 0.004), there was no difference in HTN between infants with and those without AKI. At ≥2 years of age, 4% (5 out of 120) across all groups had an eGFR < 90 ml/min/1.73m 2 or chronic kidney disease (CKD). At ≥3 years of age, 5% (11 out of 222) had HTN., Conclusion: At NICU discharge, infants with AKI stages 2 and 3 have a higher DBP than infants with stage 1 AKI and those who did not have AKI. However, there is no difference in the rate of HTN between the two groups. At ≥2 years ELBW infants are at risk for CKD independently of whether or not they develop neonatal AKI.

Background: To investigate strategies used for the management of respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD) in extremely low birth weight (ELBW) infants., Methods: A survey of neonatal specialists working in US academic institutions with fellowship training programs., Results: Eighty percent (72/89) of the identified academic institutions had at least one physician who responded to the survey. Among respondents, 85% (171/201) agreed or strongly agreed to use continuous positive airway pressure (CPAP) initially for the management of RDS, and the majority agreed or strongly agreed to use a fraction of inspired oxygen (FiO2) ≥0.4 and a mean airway pressure (MAP) ≥10 cm H2O as a criteria for surfactant therapy; and 73% (146/200) sometimes or always used caffeine to prevent BPD. Only 25% (50/202) sometimes or almost always used steroids to prevent or treat BPD. Identified indications to use steroids were 3 or more extubation failures or inability to extubate beyond 8 weeks of age., Conclusions: Variability in treatment strategies of ELBW is common among neonatal specialists. However, the majority of the respondents agreed or strongly agreed to use early CPAP for the management of RDS, consider a FiO2 ≥0.4 and a MAP ≥10 cm H2O as criteria for surfactant therapy, and sometimes or almost always used caffeine to prevent BPD. Steroids continue to have a role in the management of BPD in infants who are difficult to extubate.

Introduction: Acute kidney injury (AKI) affects ~30% of hospitalized neonates. Critical to advancing our understanding of neonatal AKI is collaborative research among neonatologists and nephrologists. The Neonatal Kidney Collaborative (NKC) is an international, multidisciplinary group dedicated to investigating neonatal AKI. The AWAKEN study (Assessment of Worldwide Acute Kidney injury Epidemiology in Neonates) was designed to describe the epidemiology of neonatal AKI, validate the definition of neonatal AKI, identify primary risk factors for neonatal AKI, and investigate the contribution of fluid management to AKI events and short-term outcomes., Methods and Analysis: The NKC was established with at least one pediatric nephrologist and neonatologist from 24 institutions in 4 countries (USA, Canada, Australia, and India). A Steering Committee and four subcommittees were created. The database subcommittee oversaw the development of the web-based database (MediData Rave™) that captured all NICU admissions from 1/1/14 to 3/31/14. Inclusion and exclusion criteria were applied to eliminate neonates with a low likelihood of AKI. Data collection included: (1) baseline demographic information; (2) daily physiologic parameters and care received during the first week of life; (3) weekly "snapshots"; (4) discharge information including growth parameters, final diagnoses, discharge medications, and need for renal replacement therapy; and (5) all serum creatinine values., Ethics and Dissemination: AWAKEN was proposed as human subjects research. The study design allowed for a waiver of informed consent/parental permission. NKC investigators will disseminate data through peer-reviewed publications and educational conferences., Discussion: The purpose of this publication is to describe the formation of the NKC, the establishment of the AWAKEN cohort and database, future directions, and a few "lessons learned." The AWAKEN database includes ~325 unique variables and >4 million discrete data points. AWAKEN will be the largest, most inclusive neonatal AKI study to date. In addition to validating the neonatal AKI definition and identifying risk factors for AKI, this study will uncover variations in practice patterns related to fluid provision, renal function monitoring, and involvement of pediatric nephrologists during hospitalization. The AWAKEN study will position the NKC to achieve the long-term goal of improving the lives, health, and well-being of newborns at risk for kidney disease.

Our journal covers a broad range of research and scholarly topics related to children's respiratory disorders. For updated perspectives on the rapidly expanding knowledge in our field, we will summarize the past year's publications in our major topic areas, as well as selected publications in these areas from the core clinical journal literature outside our own pages. The current review (Part 3) covers articles on asthma, diagnostic testing/endoscopy, respiratory complications of neuromuscular disorders, and rare lung diseases. Pediatr Pulmonol. 2016;51:747-753. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background: High-flow nasal cannula (HFNC) is commonly being used to provide noninvasive respiratory support in newborn infants. Continuous distending pressure generated by these devices in preterm infants has not been elucidated. The aim of this work was to determine the association between HFNC flow in L/min and end-expiratory esophageal pressure in cm H2O in premature infants., Methods: In a prospective observational study, end-expiratory esophageal pressure measurements were conducted in clinically stable premature infants who required HFNC. The end-expiratory esophageal pressure generated by the HFNC was measured by a regular feeding tube overlying the lower esophagus and connected to a pressure transducer. Each infant had different end-expiratory esophageal pressure measurements at different high flows ranging from 2 to 8 L/min., Results: Nineteen premature infants were studied. Their birthweight (mean ± SD) was 904 ± 574 g, and gestational age was 26.6 ± 3.1 weeks. Overall, 93 end-expiratory esophageal pressure measurements were conducted. At the time of the end-expiratory esophageal pressure measurements, infants were 1,458 ± 828 g and 7.2 ± 4.8 weeks old. At HFNC flows ranging from 2 to 8 L/min, the corresponding esophageal pressures ranged from 2 to 15 cm H2O. There was a statistically significant association between esophageal pressures and flows. In a linear regression model with the end-expiratory esophageal pressure as the dependent variable and HFNC flow as the independent variable, there was a significant correlation between the 2 variables: end-expiratory esophageal pressure (cm H2O) = 1.18 × HFNC (L/min) (r(2) = 0.95, P < .001)., Conclusions: HFNC-associated end-expiratory esophageal pressure is measurable in premature infants. There is a significant association between flows and generated esophageal pressures. There is also variability in the amount of end-expiratory esophageal pressure generated. These observations should be kept in mind when using high HFNC flows in preterm infants., (Copyright © 2016 by Daedalus Enterprises.)

Objective: To identify determinants of survival by comparing cardiopulmonary function in two patient groups: prolonged survivors of Duchenne muscular dystrophy (DMD) versus DMD patients who experienced early death (ED)., Methods: Retrospective chart review of our DMD patients from 1999 to 2013. Prolonged Survival (PS) was defined as alive and ≥30 years old. Early death (ED) was defined as death at < 30 years old., Exclusion Criteria: steroid therapy., Results: Eleven patients met criteria for PS and 14 patients for ED (mean age ± SD: 34.3 ± 4.3 years vs. 21.7 ± 3.8 years, respectively; P < 0.001). Pulmonary function was better in the ED patients: all PS patients had a vital capacity of 0 ml (n = 11) versus 23% (3/13) of the ED patients (P < 0.001). Thirteen of 14 ED patients and all PS patients received assisted ventilation. Heart function was worse in the ED patients: ejection fraction (EF) was 42.2 ± 14.2% in the PS patients (n = 11) versus 29.2 ± 14.1% in the ED patients (n = 13; P = 0.035). Dilated cardiomyopathy was present in 36% (4/11) of PS patients versus 78% (11/14) of ED patients (P =0.048). Among ED patients, 57% (8/14) died from progressive cardiomyopathy., Conclusion: In our study group, good heart function was a pre-condition for PS and poor heart function was the primary cause of early death. Our results suggest that, when DMD patients are treated with assisted ventilation, heart function is the main determinant of their survival., (© 2015 Wiley Periodicals, Inc.)

OBJECT Decompressive craniectomy (DC) for the management of severe traumatic brain injury (TBI) is controversial. The authors sought to determine if DC improves the outcome of children with severe TBI. METHODS In a retrospective, case-control study, medical records of all patients admitted to the pediatric ICU between May 1998 and May 2008 with severe TBI and treated with DC were identified and matched to patients who were treated medically without DC. Medical records were reviewed for patients' demographic data and baseline characteristics. RESULTS During the study period, 17 patients with severe TBI treated with DC at a median of 2 hours (interquartile range [IQR] 1-14 hours) after admission were identified and matched to 17 contemporary controls. On admission, there were no differences between DC and control patients regarding age (10.2 ± 5.9 years vs 12.4 ± 5.4 years, respectively [mean ± SD]), sex, weight, Glasgow Coma Scale score (median 5 [IQR 3-7] vs 4 [IQR 3-6], respectively; p = 0.14), or the highest intracranial pressure (median 42 [IQR 22-54] vs 30 [IQR 21-36], respectively; p = 0.77). However, CT findings were significant for a higher rate of herniation and cerebral edema among patients with DC versus controls (7/17 vs 2/17, respectively, had herniation [p = 0.05] and 14/17 vs 6/17, respectively, had cerebral edema [p = 0.006]). Overall there were no significant differences in survival between patients with DC and controls (71% [12/17] vs 82% [14/17], respectively; p = 0.34). However, among survivors, at 4 years (IQR 1-6 years) after the TBI, 42% (5/12) of the DC patients had mild disability or a Glasgow Outcome Scale score of 5 vs none (0/14) of the controls (p = 0.012). CONCLUSIONS In this retrospective, small case-control study, the authors have shown that early DC in pediatric patients with severe TBI improves outcome in survivors. Future prospective randomized controlled studies are needed to confirm these findings.

In recent years, there have been significant advancements in our understanding of acute kidney injury (AKI) and its impact on outcomes across medicine. Research based on single-center cohorts suggests that neonatal AKI is very common and associated with poor outcomes. In this state-of-the-art review on neonatal AKI, we highlight the unique aspects of neonatal renal physiology, definition, risk factors, epidemiology, outcomes, evaluation, and management of AKI in neonates. The changes in renal function with gestational and chronologic age are described. We put forth and describe the neonatal modified Kidney Diseases: Improving Global Outcomes AKI criteria and provide the rationale for its use as the standardized definition of neonatal AKI. We discuss risk factors for neonatal AKI and suggest which patient populations may warrant closer surveillance, including neonates <1500 g, infants who experience perinatal asphyxia, near term/ term infants with low Apgar scores, those treated with extracorporeal membrane oxygenation, and those requiring cardiac surgery. We provide recommendations for the evaluation and treatment of these patients, including medications and renal replacement therapies. We discuss the need for long-term follow-up of neonates with AKI to identify those children who will go on to develop chronic kidney disease. This review highlights the deficits in our understanding of neonatal AKI that require further investigation. In an effort to begin to address these needs, the Neonatal Kidney Collaborative was formed in 2014 with the goal of better understanding neonatal AKI, beginning to answer critical questions, and improving outcomes in these vulnerable populations., (Copyright © 2015 by the American Academy of Pediatrics.)

Objective: To determine the prevalence and weight gain as a risk factor of hypertension (HTN) at three years of age and older among extremely low birth weight (ELBW) infants., Study Design: Retrospective cohort study of all ELBW infants born and followed up at our institution over 15 years., Results: 204 infants were followed up for [median (inter-quartile range)] 10.2 years (6.9-13.0). Their birth weight and gestational age were (mean±standard deviation) 758±149 g and 26.4±2.1 weeks respectively. At 3 years of age and older, the prevalence of HTN was 7.3% (15/204), and the prevalence of obesity was 13.2% (27/204). Obesity was more prevalent in children with than without HTN [33% (5/15) vs. 12% (22/189); p = 0.01]. In a regression analysis, body mass index (BMI) percentile at 3 years of age and older (p = 0.04) and increase in weight Z scores since birth (p = 0.008) were associated with a higher systolic blood pressure (SBP; R = 0.386, p <  0.001)., Conclusion: Obesity is prevalent in ELBW infants at three years of age and older, and it is significantly associated with hypertension. An increase in BMI percentile at ≥3 years of age, and the rate of weight gain since birth among ELBW infants are associated with an increase in SBP.

Objectives: We sought to compare the value of HCV universal screening versus risk-based selective screening in pregnant women., Study Design: In a prospective observational study (Jan 2012 - March 2012), pregnant women, in a high risk inner city clinic, who were at "low risk" for HCV infection were tested for HCV antibodies (universal screening) and their medical records were compared to the medical records of pregnant women who were at "high risk" (risk based selective screening as assessed by their obstetricians' screening questionnaire)., Results: During the study period, 419 women delivered at our institution with 8.8% (37/419) at high risk for HCV. In 95% (183/193) of available and consenting low risk women, HCV antibody testing was done. The prevalence of HCV was 3.18% (7/220; 95% CI: 1.36-6.50) in all tested women versus 0.95% (4/419; 95% CI: 0.31-2.59) in risk-based selectively tested women. Overall the screening questionnaire had a sensitivity of 0.85 (0.42-0.99) and a specificity of 0.52 (0.45-0.58) in all women who had HCV antibody testing and questionnaire screening., Conclusions: Using a screening questionnaire to identify women at risk for HCV infection during pregnancy under-estimates the real prevalence of HCV. A universal screening should be considered in high risk cities.

Background: Surfactant replacement therapy has been used for few decades for the treatment of respiratory distress syndrome (RDS) and has significantly improved morbidity and mortality in premature infants. Non-invasive respiratory support has recently emerged as a strategy in the early management of RDS. In this review, we discuss the different strategies of early management of RDS., Data Sources: A literature search of PubMed database was conducted to review the subject. The quality of evidence of key clinical studies was graded according to a modified grading system of the international GRADE group., Results: Continuous positive airway pressure (CPAP) with selective surfactant is a safe alternative to routine intubation, surfactant and mechanical ventilation in preterm infants with spontaneous breathing, and such an approach has been associated with decreased risk of death and bronchopulmonary dysplasia. There is a risk of pneumothorax when using a high pressure of CPAP (≥8 cm of H2O), a high partial pressure of carbon dioxide (PCO2 >75 mm of Hg), and a high fraction of inspired oxygen (FiO2 >0.6) as a threshold for intubation while on CPAP., Conclusion: Not all preterm infants need surfactant treatment, and non-invasive respiratory support is a safe and effective approach.

Background: The American Academy of Pediatrics recommends hepatitis C virus (HCV) antibody testing for all HCV- exposed infants at age ≥ 18 months. However, many of these infants are not appropriately tested. In 2006, the pediatric infectious disease service (PIDS) at our institution implemented interventions using electronic medical records (EMR) to improve appropriate HCV testing for HCV-exposed infants., Methods: Two-part study: During the first period (January 1, 1993, to December 31, 2005), medical records of all infants born to mothers with HCV were retrospectively reviewed for patient's demographics and infant's HCV testing. PIDS interventions included contacting the primary care physician through EMR requesting HCV testing for children without proper testing. During the second period (January 1, 2006, to December 31, 2011), interventions using EMR were implemented prospectively, including PIDS consultations during birth hospitalization for all HCV-exposed infants, addition of HCV exposure to the EMR problem list and communication with PCPs via the EMR to assure appropriate HCV testing., Results: About 67,112 infants were born during the study period; 280 had maternal HCV infection and 193 continued to receive medical care at our institution. PIDS interventions using EMR resulted in a significant improvement of appropriate HCV testing among HCV-exposed infants from 8% (10/121) to 50% (36/72); P <0.0001. It also resulted in the identification of 5 new HCV-infected children; 3 of them were born before 2006 and previously undiagnosed., Conclusions: Interventions using EMR improved the identification and appropriate HCV follow up of infants born to HCV-infected mothers.

Background: The pediatric literature addressing extubation readiness parameters and strategies to wean from mechanical ventilation is limited., Methods: We designed a survey to assess the use of extubation readiness parameters among pediatric critical care physicians at academic centers in the United States., Results: The overall response rate was 44.1% (417/945). The majority of respondents check for air leak and the amount of tracheal secretions. Fewer respondents use sedation score, the rapid shallow breathing index, or the airway-occlusion pressure 0.1 s after the start of inspiratory flow prior to extubation. The majority perform a spontaneous breathing trial with pressure support. The majority consider 30 cm H2O as the upper limit of an air leak test, and the need for endotracheal suctioning once every 2-4 hours as acceptable for extubation. In preparation for termination of mechanical ventilation the majority daily wean the ventilator rate and/or the pressure support instead of conducting a spontaneous breathing trial., Conclusions: Most pediatric critical care physicians reported assessing extubation readiness by checking air leak and suctioning need, and less often consider or perform sedation score or the rapid shallow breathing index.

Background: To determine the characteristics and outcomes of pulmonary arterial hypertension (PAH) in extremely low birth weight (ELBW) infants., Methods: A retrospective case-control study of all ELBW infants admitted to a level III neonatal intensive care unit (NICU) between January 1, 2003 and December 31, 2010., Results: During the study period, 450 ELBW infants were admitted. 6.4% (29/450) were diagnosed with PAH and were matched to 26 controls. The mean gestational age of infants with PAH and their controls were similar [24.5 ± 1.3 vs. 24.9 ± 1.8 weeks (P=0.26)]; however the cases were smaller at birth than were controls [640.7 ± 119.5 vs. 727.0 ± 184.5 g (P=0.04)]. The diagnosis of PAH was made at a mean postnatal age of 131.8 ± 53.7 days. Infants with PAH had a higher rate of intrauterine exposure to illicit maternal drug use [12/29 (41%) vs. 1/25 (4%); P=0.001], a longer duration of initial mechanical ventilation [74.9 ± 28.3 vs. 59.1 ± 27.8 days; P=0.04)], a higher incidence of severe BPD [23/29 (79%) vs. 13/26 (50%); P=0.02], and a greater NICU mortality rate [12/29 (41%) vs. 4/26 (15%); P=0.04]., Conclusion: PAH in ELBW infants is associated with maternal illicit drug use in pregnancy, longer exposure to mechanical ventilation, severe bronchopulmonary dysplasia and a significant increase in early mortality.

Persistent Pulmonary Hypertension of the Newborn (PPHN) results from the failure of relaxation of the pulmonary vasculature at birth, leading to shunting of non-oxygenated blood from the pulmonary to the systemic circulation. More often, full term and near-term infants are affected, however it is not uncommon to see PPHN in preterm infants who have respiratory distress syndrome. In some infants pulmonary vascular remodeling is present at birth, pointing toward the prenatal onset of the disease process. Regardless of the etiology, PPHN should be diagnosed and treated as soon as possible to avoid hypoxia related short term and long-term morbidities. The mainstay therapy is the treatment of the underlying condition along with several promising therapeutic modalities such as oxygen supplementation, mechanical ventilation, nitric oxide, phosphodiesterase inhibitors, prostaglandins analogs, endothelin receptor antagonists, and extracorporeal membrane oxygenation. The optimal approach to the management of PPHN remains controversial. After discharge from the NICU, infants with PPHN warrant long-term follow up since they are at risk for neurodevelopmental disabilities and chronic health conditions.

Background: Extremely low birth weight (ELBW <1000 g) infants may have increased sensitivity to radiation exposure. Our objective was to estimate the radiation exposure in survivors of ELBW infants during their neonatal intensive care unit (NICU) stay., Methods: In this retrospective cohort study, medical records of all ELBW infants who had been admitted to our NICU between May 1999 and October 2009 were reviewed. The infants' total entrance skin exposure [ESE in micro-Gray (μGy)] was estimated., Results: Among 450 survivors, the mean gestational age (GA) was 26.3±2.1 weeks, and the mean birth weight (BW) was 774.2±144.4 g. Infants received a median of 32 (range: 1-159) X-rays, with an estimated ESE of 1471 μGy (range: 28-9264). Total ESE was inversely proportional to GA (r=-0.34; P<0.01), and BW (r=-0.39; P=0.01) and proportional to the severity of illness [score for neonatal acute physiology-perinatal extension (SNAPPE), r=0.39; P=0.01]. In a linear regression analysis, GA, SNAPPE and necrotizing enterocolitis were associated with radiation exposure (ESE) in ELBW infants (r2=0.133; P<0.001)., Conclusions: During their NICU stay, ELBW infants were subjected to a significant number of diagnostic X-ray procedures. Our data highlight the need to closely monitor the number of X-ray procedures ordered to ELBW infants to avoid unnecessary radiation exposure.

Objective: To evaluate the association between the respiratory severity score (RSS) and oxygenation index (OI) in intubated, mechanically ventilated, newborn infants., Study Design: In a retrospective cohort study (December 2006 to June 2010) medical records of all infants who were admitted to our neonatal intensive care unit (NICU) and required invasive mechanical ventilation were reviewed for patients' demographics, ventilator settings, and arterial blood gas (ABG)., Results: During the study period 2,332 infants were admitted to our NICU, and 425 infants were intubated and had an ABG with a gestational age of 30.5 ± 4.9 weeks and a birth weight of 1,635 ± 923 g (mean ± standard deviation). There was a strong association between RSS and OI in infants with oxygen saturation (SaO2 ) between 88% and 94% (R2  = 0.982, n = 101; P < 0.001)., Conclusion: In intubated newborn infants, there is a strong association between RSS and OI at SaO2 between 88% and 94%., (Copyright © 2013 Wiley Periodicals, Inc.)

We sought to investigate the risk factors and outcome of Ventilator Associated Tracheitis (VAT) according to the Center for Disease Control (CDC) definition in pediatric trauma patients who were ventilated for ≥48 hr. In a retrospective cohort study, medical records of all pediatric trauma patients admitted to our Pediatric Intensive Care Unit (PICU) between April 2002 and April 2007 were reviewed. Medical records were reviewed for patients' demographics, Trauma Injury Severity Score (TISS), Glasgow Coma Scale (GCS), type of trauma, and other potential risk factors prior to the development of VAT (such as hyperglycemia, rate of re-intubation and tracheotomy, presence of chest tubes and central lines, urinary tract infection, seizures, need for cardiopulmonary resuscitation, use of total parental nutrition, transfusion, use of H(2) blockers, steroids, and pressors/inotropes). Medical records were also reviewed for days of mechanical ventilation, PICU length of stay, and PICU mortality. During the study period, 217 trauma patients were admitted to the PICU, 113 patients met our inclusion criteria and 21.2% (24/113) developed VAT. On average patients with VAT (in comparison to patients without VAT), had a higher TISS score on admission [38.6 ± 16.9 vs. 24.2 ± 10.6; respectively (P < 0.01)], longer days of ventilation and PICU length of stay [11.5 ± 6.2 vs. 3.7 ± 2.3 days (P < 0.001) and 16.4 ± 8.3 vs. 5.4 ± 2.8 days (P < 0.001), respectively]. There was no difference in mortality between the two groups. In a logistic regression model adjusting for possible confounders, the TISS score (adjusted OR 7.53; CI: 2.01-28.14; P = 0.03 and use of pressors/inotropes (adjusted OR 4.64; CI: 1.28-16.86; P = 0.01) were the only independent risk factors associated with VAT. We conclude that the severity of illness and use of pressors/inotropes are associated with VAT in pediatric trauma patients. We also conclude that VAT is associated with an increase in days of mechanical ventilation and PICU length of stay in pediatric trauma patients., (Copyright © 2012 Wiley Periodicals, Inc.)

In an attempt to determine the risk factors associated with the need for a tracheostomy in extremely low birth weight (ELBW) infants, a retrospective, case control study was conducted (each infant with a tracheostomy [case] was matched to two controls). Medical records were reviewed for patients' characteristics, risk factors for tracheostomy and outcome. During the study period (June 1996 to Dec 2010), 934 ELBW infants were admitted to our institution and nine infants had a tracheostomy and were matched to 18 controls. There were no differences in birth weight (BW) and gestation age (GA) between cases and controls (828.1 ± 136.2 g vs. 822.0 ± 140.9 g [P = 0.91] and 26.6 ± 1.8 weeks vs. 26.5 ± 1.6 weeks [P = 0.88], respectively). In comparison to their controls, infants with a tracheostomy had a higher rate of intubation (median 13 [11-15] vs. 3 [2-5], P ≤ 0.001), a higher rate of total intubation attempts (median 18 [13-21] vs. 5.5 [3-7], P = 0.001), and more days of mechanical ventilation prior to their tracheostomy (mean 100.7 ± 27.7 vs. 29.2 ± 19.8 days [P < 0.001]). Also infants with a tracheostomy had a higher rate of non-congenital upper airway obstruction (55% [5/9] vs. 0% [0/18]; P = 0.001), a higher rate of chronic lung disease (100% [9/9] vs. 5% [1/18]; P < 0.001) and a higher mortality (44% [4/9] vs. 0% [0/18]; P = 0.007) than their controls. In conclusion, chronic lung disease, multiple intubations and intubation attempts, duration of mechanical ventilation, and non-congenital upper airway obstruction are risk factors associated with tracheostomies in ELBW infants., (Copyright © 2012 Wiley Periodicals, Inc.)

The aim of this study was to determine the incidence, risk factors, and outcome of acute kidney injury (AKI) in extremely low birth weight (ELBW) infants. In a case-control study, medical records of all ELBW infants who were admitted to our Neonatal Intensive Care Unit (NICU) between 1 January 2000 and 31 January 2008 were reviewed. During the study period, 12.5% (59/472) of all ELBW infants developed AKI. Forty-six infants with available medical records were matched to 46 controls. The mean gestational age and birth weight of infants with AKI and their controls were 24.7 ± 1.8 vs. 24.9 ± 1.9 weeks (p = 0.61) and 614 ± 128 vs. 616 ± 127 g (p = 0.93), respectively. Infants with AKI had a higher mean airway pressure, a lower mean arterial blood pressure, and higher exposure to cefotaxime than their controls. Infants with AKI also had an increased mortality in comparison to their controls [33/46 (70%) vs. 10/46 (22%), respectively; p < 0.0001), and oliguric patients had a higher mortality than nonoliguric patients [31/38 (81%) vs. 2/8 (25%), respectively, p = 0.003]. Based on our results, we conclude that a high mean airway pressure, low blood pressure, and the use of cefotaxime are associated with renal failure in ELBW infants. AKI in ELBW infants is also associated with an increased mortality, especially in the presence of oliguria.

Objective: Increased intrathoracic pressures during airway pressure release ventilation (APRV) may compromise systemic venous return resulting in decreased cardiac output and renal perfusion. We sought to study the short-term effect of APRV on blood pressure (BP) and urine output (UO) in children with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS)., Design: Retrospective cohort study., Patients: All patients with ALI/ARDS who were admitted to our Pediatric Intensive Care Unit (PICU) between 1/00 and 06/04, and who were ventilated with APRV (for at least 12 hr) for worsening oxygenation while on conventional ventilation (CV)., Measurements and Results: Medical records were reviewed for patients' demographics, Pediatric Risk of Mortality (PRISM III) score, admitting diagnosis, ventilator settings, gas exchange data, heart rate (HR), central venous pressure (CVP), blood pressure (BP), UO, and use of other therapies [sedatives, pressors, inotropes, and intravenous fluid (IVF)]. Eleven patients met our inclusion and exclusion criteria with a mean age of 6.2 +/- 4.8 years (range: 1-15 years), a weight of 35.5 +/- 29.5 kg (range: 12-90 kg), and a PRISM score of 18.4 +/- 9.6 (range: 2-36). Within 10 hrs of APRV, patients' mean airway pressure (Paw) increased from 16.1 +/- 6.6 to 21.1 +/- 5.5 cm of H(2)O (P = 0.04). Despite a higher Paw there were no differences in HR, CVP, BP, UO, IVF and use of other therapies while on CV or APRV (P > 0.10)., Conclusion: In children with ALI/ARDS, despite a higher Paw, APRV does not affect BP or UO., ((c) 2009 Wiley-Liss, Inc.)

Bronchodilators have been used in premature infants. Levalbuterol (LEV) an R-isomer of Albuterol has fewer hemodynamic side effects than Racemic Albuterol (RAC) in adults and children. In a retrospective study we sought to investigate the effects of LEV (0.31 mg) versus RAC (1.25 mg) in very low-birth weight infants (VLBW) who were treated with a beta-2 agonist for > or =2 weeks. Medical records (between January 2001 and December 2006) were reviewed for patients' demographics, medications use, hemodynamic and respiratory parameters, hypokalemia and hyperglycemia. Among 811 VLBW infants who were admitted to our NICU, 16 infants received RAC and 31 infants received LEV for > or =2 weeks. Infants who received RAC were younger, smaller, and received less Ipratropium Bromide (IB) than infants who received LEV [26.1 +/- 1.2 weeks vs. 28.1 +/- 3.7 weeks (P = 0.01), 817 +/- 211 g vs. 1,127 +/- 589 g (P = 0.01) and 2/16 (12%) vs. 15/31 (48%; P = 0.01); respectively]. In infants treated exclusively with RAC or LEV without IB, mean arterial blood pressures were lower in the RAC (n = 14) than the LEV group (n = 16, P = 0.05 by general linear model with repeated measures); however there were no differences in daily heart rates, oxygen supplementations, oxygen saturations, or respiratory rates. Also there were no differences between the two groups in hypokalemia or hyperglycemia. We conclude that LEV at a dose of 0.31 mg might have an indication in VLBW infants who are at risk for hemodynamic instability.