Comparison of chest radiograph and lung ultrasound in children with acute respiratory failure.

PURPOSE: Chest x-ray (CXR) is the standard imaging used to evaluate children in acute respiratory distress and failure. Our objective was to compare the lung-imaging techniques of CXR and lung ultrasound (LUS) in the evaluation of children with acute respiratory failure (ARF) to quantify agreement and to determine which technique identified a higher frequency of pulmonary abnormalities. METHODS: This was a secondary analysis of a prospective observational study evaluating the sensitivity and specificity of LUS in children with ARF from 12/2018 to 02/2020 completed at the University of Wisconsin-Madison (USA). Children > 37.0 weeks corrected gestational age and ≤ 18 years of age admitted to the PICU with ARF were evaluated with LUS. We compared CXR and LUS completed within 6 h of each other. Kappa statistics (k) adjusted for maximum attainable agreement (k/kmax) were used to quantify agreement between imaging techniques and descriptive statistics were used to describe the frequency of abnormalities. RESULTS: Eighty-eight children had LUS completed, 32 with concomitant imaging completed within 6 h are included. There was fair agreement between LUS and CXR derived diagnoses with 58% agreement (k/kmax = 0.36). Evaluation of imaging patterns included: normal, 57% agreement (k = 0.032); interstitial pattern, 47% agreement (k = 0.003); and consolidation, 65% agreement (k = 0.29). CXR identified more imaging abnormalities than LUS. CONCLUSIONS: There is fair agreement between CXR and LUS-derived diagnoses in children with ARF. Given this, clinicians should consider the benefits and limitations of specific imaging modalities when evaluating children with ARF. Additional studies are necessary to further define the role of LUS in pediatric ARF given the small sample size of our study.

Rank and Tenure Amongst Faculty at Academic Medical Centers: A Study of More Than 50 Years of Gender Disparities.

PURPOSE: To investigate progress toward gender equality in academic medicine through a longitudinal analysis of gender parity among faculty at medical schools. METHOD: The authors conducted a retrospective analysis of Association of American Medical Colleges Faculty Roster data on gender, tenure status, and academic rank of faculty in basic science (BSc) and clinical science (CSc) departments from 1966 to 2019. They expressed data as whole numbers and percent female. A trend analysis projected time to gender parity across rank and tenure categories, and cross-tabulation analysis revealed the relative odds of females being in a rank and tenure position relative to males. RESULTS: A 12-fold increase in the number of faculty occurred from 1966 to 2019, driven largely by increases in non-tenure track faculty. Female tenured and tenure track numbers increased at consistent rates (121 and 174 per year; P < .001). Female non-tenure track rates mirrored those for males, both changing in 2000. Odds ratios in 2019 for BSc and CSc females to be in tenure track versus non-tenure track positions compared with males were 0.83/0.98 and to be tenured were 0.63/0.44. Odds ratios in 2019 for BSc and CSc females to be full professors versus assistant or associate professors compared with males were 0.55/0.42. BSc assistant and associate professor percent female rates increased linearly from 1966 to 2019, while full professor rates increased in 1986. Transition points between periods of linear change were seen later in CSc departments (1977, 1980, 1985, 1994). Best fit line models indicated gender parity will be reached for BSc/CSc faculty in 2034/2023, 2047/2033, and 2065/2053 for assistant, associate, and full professors, respectively. CONCLUSIONS: These findings suggest large historical changes in medical school expansion, medical education, and economics have shifted gender curves at all academic ranks. To achieve gender parity, additional national changes are needed.

Lung Ultrasound Artifact Findings in Pediatric Patients Admitted to the Intensive Care Unit for Acute Respiratory Failure.

PURPOSE: To describe point-of-care lung ultrasound (POC-LUS) artifact findings in children admitted to the pediatric intensive care unit (PICU) for acute respiratory failure (ARF). METHODS: This is a secondary analysis of a prospective observational study completed in a 21-bed PICU. Children > 37 weeks gestational age and ≤ 18 years were enrolled from December 2018 to February 2020. POC-LUS was completed and interpreted by separate physicians blinded to all clinical information. POC-LUS was evaluated for the presence of lung sliding, pleural line characteristics, ultrasound artifacts, and the ultrasound diagnosis. RESULTS: Eighty-seven subjects were included. A-lines were the most frequent artifact, occurring in 58% of lung zones (163/281) in those with bronchiolitis, 39% of lung zones (64/164) in those with pneumonia, and 81% of lung zones (48/59) in those with status asthmaticus. Sub-pleural consolidation was second most common, occurring in 28% (80/281), 30% (50/164), and 12% (7/59) of those with bronchiolitis, pneumonia, and status asthmaticus, respectively. The pattern a priori defined as bronchiolitis, pneumonia, and status asthmaticus was demonstrated in 31% (15/48), 10% (3/29), and 40% (4/10) of subjects with bronchiolitis, pneumonia, and status asthmaticus, respectively. CONCLUSION: We found significant heterogeneity and overlap of POC-LUS artifacts across the most common etiologies of ARF in children admitted to the PICU. We have described the POC-LUS artifact findings in pediatric ARF to support clinicians using POC-LUS and to guide future pediatric POC-LUS studies. Determining the optimal role of POC-LUS as an adjunct in the care of pediatric patients requires further study.

A New Normal: Assessment Outcomes and Recommendations for Virtual Versus In-Person Curricula in Post-COVID-19 Times.

Introduction: COVID-19 response efforts that began in March 2020 prompted an urgent need to transition medical education from an in-person to a virtual format. Our aim is to provide evaluation of a virtual platform for a fully integrated curriculum to provide future guidance in teaching methods. Materials and Methods: We used summative assessments and course evaluations from pre- and post-transition from in-person to virtual delivery of educational content to measure the impacts of this transition on student performance and perceptions. Additionally, we surveyed students about their in-person versus online educational preferences. Results: There were no statistically significant differences in student knowledge acquisition as assessed by weighted averages of summative assessments when comparing an in-person to a virtual educational platform. While the transition to virtual learning was initially well-received by students, our studied cohorts gave lower scores for the overall learning experience after prolonged virtual learning (p < 0.001). Students had a strong preference that anatomy and other group sessions should be delivered in-person. There was no strong preference whether other learning modalities should be given in-person or virtually. Conclusions: Although student knowledge acquisition remained stable on a virtual platform, the student learning experience varied. We recommend that when returning to a new normal after COVID-19 restrictions are lifted, sessions that require 3-dimensional or group learning should remain in-person, while other educational activities may be offered on a virtual platform and that, whenever virtual learning is employed, attention be paid to ensuring ongoing social and academic engagement between learners and faculty.

The Inter-Rater Reliability of Pediatric Point-of-Care Lung Ultrasound Interpretation in Children With Acute Respiratory Failure.

OBJECTIVES: Use of point-of-care lung ultrasound (POC-LUS) has increased significantly in pediatrics yet it remains under-studied in the pediatric intensive care unit (PICU). No studies explicitly evaluate the reliability of POC-LUS artifact interpretation among critically ill children with acute respiratory failure (ARF) in the PICU. We thus designed this study to determine the inter-rater reliability of POC-LUS interpretation in pediatric ARF among pediatric intensivists trained in POC-LUS and an expert intensivist. METHODS: We compared the interpretation of lung sliding, pleural line characteristics, ultrasound artifacts, and POC-LUS diagnoses among pediatric intensivists and an expert intensivist in a cohort of children admitted to the PICU for ARF. Kappa statistics (k) adjusted for maximum attainable agreement (k/kmax ) were used to quantify chance-correct agreement between the pediatric intensivist and expert physician. RESULTS: We enrolled 88 patients, evaluating 3 zones per hemithorax (anterior, lateral, and posterior) for lung sliding, pleural line characteristics, ultrasound artifacts, and diagnosis. There was moderate agreement between the PICU intensivist and expert-derived diagnoses with 56% observed agreement (k/kmax  = 0.46, 95% confidence interval [CI] 0.31-0.65). Agreement in identification of lung sliding (k = 0.19, 95% CI -0.17 to 0.56) and pleural line characteristics (k = 0.24, 95% CI 0.08-0.40) was slight and fair, respectively, while agreement in the interpretation of ultrasound artifacts ranged from moderate to substantial. CONCLUSIONS: Evidence supporting the evaluation of neonatal and adult patients with POC-LUS should not be extrapolated to critically ill pediatric patients. This study adds to the evidence supporting use of POC-LUS in the PICU by demonstrating moderate agreement between PICU intensivist and expert-derived POC-LUS diagnoses.

First, do no harm: impact of the transition to an integrated curriculum on medical knowledge acquisition of the transitional cohort.

INTRODUCTION: Many medical schools are moving toward integrated curricula in response to the 2010 Carnegie report. However, there is often apprehension that student performance on standard assessment metrics of medical knowledge acquisition could suffer during the transition period. Therefore, we sought to analyze the impact of curriculum redesign on the medical knowledge acquisition of the transitional cohort, as measured by NBME subject exam scores. METHODS: The University of Wisconsin School of Medicine and Public Health Legacy curriculum followed a standard 2 + 2 medical school educational model, including traditional, department-based, third-year clinical clerkships. In the new ForWard curriculum, students enter clinical rotations one semester earlier, and those core clinical experiences are organized within four integrated blocks combining traditional clerkship specialties. This retrospective program evaluation compares NBME subject exam scores between the final cohort of Legacy third-year students (2016-17) and first cohort of ForWard students (2018) for the Adult Ambulatory Medicine, Medicine, Neurology, Obstetrics and Gynecology, Pediatrics, Psychiatry, and Surgery exams. RESULTS: NBME subject exam mean scores ranged from 75.5-79.4 for the Legacy cohort and 74.9-78.7 for the ForWard cohort, with no statistically significant differences in scores identified for each individual exam analyzed. Results remained constant when controlled for student demographic variables. DISCUSSION: Faculty and students may worry about impacts to the transitional cohort during curriculum redesign, however our results suggest no substantive negative effects to acquisition of medical knowledge during transition to an integrated curriculum. Further monitoring is necessary to examine whether medical knowledge acquisition remains stable or changes after the integrated curriculum is established.

Point-of-Care Lung Ultrasound to Diagnose the Etiology of Acute Respiratory Failure at Admission to the PICU.

OBJECTIVES: Determine the sensitivity and specificity of point-of-care lung ultrasound in identifying the etiology of acute respiratory failure at admission to the PICU. DESIGN: Prospective observational study. SETTING: Tertiary PICU. PATIENTS: Children older than 37 weeks gestational age and less than or equal to 18 years old admitted to the PICU with acute respiratory failure from December 2018 to February 2020. INTERVENTION: Point-of-care lung ultrasound performed within 14 hours of admission to the PICU by physicians blinded to patient history and clinical course. Two physicians, blinded to all clinical information, independently interpreted the point-of-care lung ultrasound and then established a consensus diagnosis (ultrasound diagnosis). The ultrasound diagnosis was compared with an independent, standardized review of the medical record following hospital discharge (final diagnosis). MEASUREMENTS AND RESULTS: Eighty-eight patients were enrolled in the study. Forty-eight patients had a final diagnosis of bronchiolitis/viral pneumonitis (55%), 29 had pneumonia (33%), 10 had status asthmaticus (11%), and one was excluded because of an inability to differentiate the final diagnosis. Point-of-care lung ultrasound correctly identified the etiology of acute respiratory failure in 56% of patients (49/87; 95% CI, 46-66%). It identified bronchiolitis/viral pneumonitis with 44% sensitivity (95% CI, 0.31-0.58) and 74% specificity (95% CI, 0.59-0.85), pneumonia with 76% sensitivity (95% CI, 0.58-0.88) and 67% specificity (95% CI 0.54-0.78), and status asthmaticus with 60% sensitivity (95% CI, 0.31-0.83) and 88% specificity (95% CI, 0.79-0.94). CONCLUSIONS: In contrast to literature demonstrating high utility differentiating the cause of acute respiratory failure in adults, blinded point-of-care lung ultrasound demonstrates moderate sensitivity and specificity in identifying the etiology of pediatric acute respiratory failure at admission to the PICU among children with bronchiolitis, pneumonia, and status asthmaticus.

Implementing point of care ultrasound in the neonatal intensive care unit: a safety study.

OBJECTIVE: Point of care ultrasound (POCUS) use is increasing in pediatrics and has been demonstrated to be superior in identifying central catheter tip location in neonatal intensive care units. However, limited data exist regarding cardiorespiratory changes secondary to POCUS in neonates. STUDY DESIGN: A prospective observational equivalence study was performed on 50 POCUS assessments of central catheter tip location in 46 patients ≥23 weeks gestation. Heart rate (HR), respiratory rate (RR), and percent oxygen saturation (SpO2) levels were collected before and after POCUS. Limits of equivalence were set in advance. RESULT: Equivalence was demonstrated in HR, RR, and SpO2 before and after POCUS. HR decreased by 3.24 beats per minute (90% CI: -5.36, -1.14). RR increased by 0.71 breath/min (90% CI: -1.84, +3.27). SpO2 increased by 0.54 percentage points (90% CI: -0.23, +1.31). CONCLUSION: Identifying central catheter tip location using POCUS in neonates appears safe without affecting cardiorespiratory stability.

Point-of-care ultrasound use in umbilical line placement: a review.

Point-of-care ultrasound (POCUS) has become a novel tool for assessing umbilical catheter tip location in the neonate. This review analyzes the current evidence on the efficacy and utility of POCUS for identifying umbilical catheter positioning. Medline, EMBASE, and Cochrane searches were performed until October 2018. Eight studies were identified comparing POCUS to x-ray in assessing umbilical catheter tip location in the last 10 years. POCUS was shown to be feasible and appears to be a superior imagining modality to x-rays in assessing umbilical line tip location. POCUS is more accurate in determining umbilical catheter positioning, allows for more rapid line umbilical catheter placement, and reduces the time to treatment as well as radiation exposure to the neonate when compared with x-ray. The available studies support further education in training neonatal providers to become proficient in POCUS for assessing umbilical lines.

A Diet With Docosahexaenoic and Arachidonic Acids as the Sole Source of Polyunsaturated Fatty Acids Is Sufficient to Support Visual, Cognitive, Motor, and Social Development in Mice.

Polyunsaturated fatty acids serve multiple functions in neurodevelopment and neurocognitive function. Intravenous lipid emulsions are administered to children that are dependent on parenteral nutrition to provide the essential fatty acids needed to sustain growth and development. One of these emulsions, derived from fish-oil, is particularly poor in the traditional essential fatty acids, linoleic and alpha-linolenic acids. However, it does contain adequate amounts of its main derivatives, arachidonic acid (ARA) and docosahexaenoic acid (DHA), respectively. This skewed composition has raised concern about the sole use of fish-oil based lipid emulsions in children and how its administration can be detrimental to their neurodevelopment. Using a custom-made diet that contains ARA and DHA as a sole source of polyunsaturated fatty acids, we bred and fed mice for multiple generations. Compared to adult, chow-fed mice, animals maintained on this special diet showed similar outcomes in a battery of neurocognitive tests performed under controlled conditions. Chow-fed mice did perform better in the rotarod test for ataxia and balance, although both experimental groups showed a conserved motor learning capacity. Conversely, mice fed the custom diet rich in DHA and ARA showed less neophobia than the chow-fed animals. Results from these experiments suggest that providing a diet where ARA and DHA are the sole source of polyunsaturated fatty acids is sufficient to support gross visual, cognitive, motor, and social development in mice.

Effects of dietary omega-3 fatty acids on bones of healthy mice.

BACKGROUND & AIMS: Altering the lipid component in diets may affect the incidence of metabolic bone disease in patients dependent on parenteral nutrition. Consumption of polyunsaturated fatty acids (PUFA) can impact bone health by modulating calcium metabolism, prostaglandin synthesis, lipid oxidation, osteoblast formation, and osteoclastogenesis. The aim of this study was to evaluate the dietary effects of PUFA on murine bone health. METHODS: Three-weeks-old male (n = 30) and female (n = 30) C57BL/6J mice were randomized into one of three dietary groups. The diets differed only in fat composition: soybean oil (SOY), rich in ω-6 PUFA; docosahexaenoic acid alone (DHA), an ω-3 PUFA; and DHA with arachidonic acid, an ω-6 PUFA, at a 20:1 ratio (DHA/ARA). After 9 weeks of dietary treatment, femurs were harvested for micro-computed tomographic analysis and mechanical testing via 3-point bending. Separate mice from each group were used solely for serial blood draws for measurement of biomarkers of bone formation and resorption. RESULTS: At the microstructural level, although some parameters in cortical bone reached differences that were statistically significant in female mice, these were too small to be considered biologically relevant. Similarly, trabecular bone parameters in male mice were statistically different in some dietary groups, although the biological interpretation of such subtle changes translate into a lack of effect in favor of any of the experimental diets. No differences were noted at the mechanical level and in blood-based biomarkers of bone metabolism across dietary groups within gender. CONCLUSIONS: Subtle differences were noted at the bones' microstructural level, however these are likely the result of random effects that do not translate into changes that are biologically relevant. Similarly, differences were not seen at the mechanical level, nor were they reflected in blood-based biomarkers of bone metabolism. Altogether, dietary consumption of PUFA do not seem to affect bone structure or metabolism in a healthy model of growing mice.

Challenging the 48-Hour Rule-Out for Central Line-Associated Bloodstream Infections in the Pediatric Intestinal Failure Population: A Retrospective Pilot Study.

INTRODUCTION: While parenteral nutrition (PN) has revolutionized the management of patients with intestinal failure (IF), central line-associated bloodstream infections (CLABSIs) remain a leading cause of mortality and morbidity in this population. The objective of this study is to characterize the presentation of CLABSIs in pediatric IF and to determine the time to positivity of blood cultures. METHODS: A retrospective cohort study of children with IF who presented to our institution for evaluation of a possible CLABSI from January 1, 2012, to December 31, 2012, was performed. RESULTS: Sixty patients with IF were identified. There were 33 cases of CLABSI in 16 patients, with a rate of 1.5 infections per 1000 catheter days. There were no significant differences in age, growth parameters, or catheter days between patients with or without CLABSI. Fever was documented in 85% of patients with CLABSI. These patients demonstrated an increased percentage of neutrophils and higher C-reactive protein levels compared with patients without CLABSI. The mean time to culture positivity was 13.2 hours, and 97% of cultures were positive within 24 hours. CONCLUSION: Our data suggest that most pediatric patients with IF who have CLABSI develop positive cultures within 24 hours, and the absence of fever and leukocytosis does not necessarily indicate the absence of infection. These findings may support clinical practice guidelines in favor of shorter hospital stay when CLABSI is suspected; however, a prospective analysis of CLABSI in this population is recommended to determine the safety and appropriate setting prior to any practice change.

The addition of medium-chain triglycerides to a purified fish oil-based diet alters inflammatory profiles in mice.

OBJECTIVE: Parenteral nutrition associated liver disease (PNALD) is a deadly complication of long term parenteral nutrition (PN) use in infants. Fish oil-based lipid emulsion has been shown in recent years to effectively treat PNALD. Alternative fat sources free of essential fatty acids have recently been investigated for health benefits related to decreased inflammatory response. We hypothesized that the addition of medium-chain triglycerides (MCT) to a purified fish oil-based diet would decrease the response to inflammatory challenge in mice, while allowing for sufficient growth and development. MATERIALS/METHODS: Six groups of ten adult male C57/Bl6 mice were pair-fed different dietary treatments for a period of twelve weeks, varying only in fat source (percent calories by weight): 10.84% soybean oil (SOY), 10% coconut oil (HCO), 10% medium-chain triglycerides (MCT), 3% purified fish oil (PFO), 3% purified fish oil with 3% medium-chain triglycerides (50:50 MCT:PFO) and 3% purified fish oil with 7.59% medium-chain triglycerides (70:30 MCT:PFO). An endotoxin challenge was administered to half of the animals in each group at the completion of dietary treatment. RESULTS: All groups demonstrated normal growth throughout the study period. Groups fed MCT and HCO diets demonstrated biochemical essential fatty acid deficiency and decreased IL-6 and TNF-α response to endotoxin challenge. Groups containing PFO had increased inflammatory response to endotoxin challenge, and the addition of MCT to PFO mitigated this inflammatory response. CONCLUSION: These results suggest that the addition of MCT to PFO formulations may decrease the host response to inflammatory challenge, which may pose potential for optimized PN formulations. Inclusion of MCT in lipid emulsions given with PN formulations may be of use in therapeutic interventions for disease states resulting from chronic inflammation.

The natural history of cirrhosis from parenteral nutrition-associated liver disease after resolution of cholestasis with parenteral fish oil therapy.

OBJECTIVE: To determine the natural history of cirrhosis from parenteral nutrition-associated liver disease (PNALD) after resolution of cholestasis with fish oil (FO) therapy. BACKGROUND: Historically, cirrhosis from PNALD resulted in end-stage liver disease, often requiring transplantation for survival. With FO therapy, most children now experience resolution of cholestasis and rarely progress to end-stage liver disease. However, outcomes for cirrhosis after resolution of cholestasis are unknown and patients continue to be considered for liver/multivisceral transplantation. METHODS: Prospectively collected data were reviewed for children with cirrhosis because of PNALD who had resolution of cholestasis after treatment with FO from 2004 to 2012. Outcomes evaluated included need for liver/multivisceral transplantation, mortality, and the clinical progression of liver disease. RESULTS: Fifty-one patients with cirrhosis from PNALD were identified, with 76% demonstrating resolution of cholestasis after FO therapy. The mean direct bilirubin decreased from 6.4 ± 4 mg/dL to 0.2 ± 0.1 mg/dL (P < 0.001) 12 months after resolution of cholestasis, with a mean time to resolution of 74 days. None of the patients required transplantation or died from end-stage liver disease. Pediatric End-Stage Liver Disease scores decreased from 16 ± 4.6 to -1.2 ± 4.6, 12 months after resolution of cholestasis (P < 0.001). In children who remained PN-dependent, the Pediatric End-Stage Liver Disease score remained normal throughout the follow-up period. CONCLUSIONS: Cirrhosis from PNALD may be stable rather than progressive once cholestasis resolves with FO therapy. Furthermore, these patients may not require transplantation and show no clinical evidence of liver disease progression, even when persistently PN-dependent.

Elevated Alkaline Phosphatase in Infants With Parenteral Nutrition-Associated Liver Disease Reflects Bone Rather Than Liver Disease.

BACKGROUND: Elevated serum alkaline phosphatase (ALP) in infants with intestinal failure (IF) can be due to parenteral nutrition-associated liver disease (PNALD) or metabolic bone disease (MBD). The purpose of the study was to determine the utility of serum ALP in the diagnostic criteria for PNALD by measuring tissue-specific levels in infants with IF and PNALD. METHODS: A retrospective review of patient data for 15 infants diagnosed with PNALD between December 2012 and August 2013 was performed. PNALD was defined as the presence of 2 consecutive direct bilirubin (DB) levels >2 mg/dL. Fractionated serum alkaline phosphatase was measured in each patient, while the DB was >2 mg/dL. Parathyroid hormone (PTH), vitamin D3, calcium, and phosphate levels were recorded where available. RESULTS: In 15 infants with PNALD, elevation in total ALP was due to marked elevations in bone-specific ALP. The median liver-specific ALP remained within the normal range. PTH, vitamin D3, calcium, and phosphate levels were within normal limits. CONCLUSION: While elevated ALP can reflect biliary stasis, the ALP elevation observed in infants with IF and PNALD is predominantly of bone rather than hepatic origin. An elevated unfractionated ALP in infants with PNALD should therefore raise suspicion of underlying bone disease, rather than being attributed to liver disease alone.

Neonatal intestinal physiology and failure.

The neonatal intestine is a complex organ that regulates the absorption of nutrients essential for growth and development. Intestinal failure results from insufficient or functionally inadequate bowel and can lead to failure of neonatal growth and development. Current literature on neonatal intestinal physiology and failure was reviewed and summarized. A homeostatic interplay of electrolytes, enzymes, and hormonal regulators is essential to achieve the physiologic balance needed for adequate intestinal performance. Physiologic consequences of intestinal failure are dependent on the length and anatomic location of the diseased or surgically resected bowel. Intestinal failure leads to disruption of normal intestinal physiology and may have long-term consequences for growth and development if inadequately treated. Parenteral nutrition remains the mainstay of treatment for neonatal intestinal failure.

Treatment of parenteral nutrition-associated liver disease: the role of lipid emulsions.

Parenteral nutrition is a life-saving therapy for infants with intestinal failure. However, long-term parenteral nutrition carries the risk of progressive liver disease. Substantial data has implicated components of parenteral soybean oil in the pathogenesis of parenteral nutrition-associated liver disease (PNALD). Elevated serum concentrations of phytosterols, an abundance of omega-6 polyunsaturated fatty acids, and a relative paucity of α-tocopherol have been associated with the risk of cholestasis and hepatic injury observed in PNALD. Currently available treatment strategies include the reduction of the dose of administered parenteral soybean oil and/or the replacement of parenteral soybean oil with alternative parenteral lipid emulsions. The purpose of this review is to provide an overview of the pathogenetic mechanisms associated with the development of PNALD and the data evaluating currently available treatment strategies.

Role of parenteral lipid emulsions in the preterm infant.

Parenteral nutrition (PN) is necessary for infants unable to receive adequate calories enterally due to prematurity, decreased bowel length, or functional intestinal disorders. While PN can be life saving, its use is associated with significant risks of sepsis from catheter-associated infections and progressive liver dysfunction from prolonged use. The preterm infant population is at highest risk for these complications due to the presence of multiple comorbidities and immaturity of the biliary system. Strong data has implicated parenteral lipids in the multifactorial pathogenesis of PN-associated liver disease (PNALD). However, lipids are essential in early infant development, particularly in the neurocognitive development of preterm infants. Substitution of the lipid source from soybean oil to fish oil has emerged as a safe and efficacious treatment of PNALD, with marked improvements in morbidity and mortality. Knowledge of the developmental needs and physiologic limitations of preterm infants is crucial to optimizing parenteral lipid administration to nurture growth, and minimize and treat associated complications. The purpose of this review is to provide an overview of lipid requirements of the preterm infant and discuss the role of parenteral lipid emulsions in the management of PNALD and other diseases of prematurity.

Fish oil-based lipid emulsion in the treatment of parenteral nutrition-associated liver disease.

PURPOSE OF REVIEW: Parenteral nutrition-associated liver disease (PNALD) is a major cause of morbidity and mortality in the parenteral nutrition-dependent population. Here, we review the most recent literature involving a fish oil-based lipid emulsion (FOLE) and its effects on PNALD. RECENT FINDINGS: Vegetable oil-based lipid emulsions (VBLEs) contribute to PNALD. This may be due to parenteral phytosterols and/or the presence of pro-inflammatory mediators. Whereas a small reduction in the dose of VBLE does not appear to prevent PNALD, a significant reduction in the dose may reverse PNALD; however, it carries the risk of essential fatty acid deficiency. Furthermore, the impact of extreme lipid restriction on subsequent neurodevelopment is unknown. Combination lipid emulsions containing fish oil are associated with decreased bilirubin levels, though no studies compare these emulsions with the outcomes with FOLE alone. The utility of FOLE in the reversal of PNALD has been demonstrated and its administration does not lead to essential fatty acid deficiency. Furthermore, there is evidence that FOLE may prevent PNALD. CONCLUSION: FOLE appears to be an efficacious treatment to reverse PNALD. However, more studies are necessary to determine if FOLE might also be beneficial in the prevention of PNALD. Future studies should additionally focus on the preterm infant population, as they represent a major population requiring parenteral nutrition support for survival.