The Impact of the COVID-19 Pandemic on Foreign Body Ingestion Trends in Children: A Comparison of the Pre-Pandemic Period to 2020.

Foreign body ingestion (FBI) among children is associated with morbidity and mortality. We used the National Electronic Injury Surveillance System to compare FBI trends from 2017-2019 to 2020 during the spread of SARS-CoV-2. The pandemic and associated stay-at-home orders were associated with uptrends in button battery and magnet ingestions but unchanged total FBI trends.

Magnet Injuries in Children: An Analysis of the National Poison Data System from 2008 to 2019.

OBJECTIVE: To examine, using the National Poison Data System (the data warehouse for poison control centers in the US), magnet foreign body injuries in pediatric patients. We sought to report demographic data, outcome data, and case trends between 2008 and 2019. STUDY DESIGN: We conducted a retrospective analysis of the National Poison Data System for patients younger than 19 years of age with a magnet "exposure," which poison centers define as an ingestion, inhalation, injection, or dermal exposure to a poison. RESULTS: A total of 5738 magnet exposures were identified. Most were male (3169; 55%), <6 years old (3572; 62%), with an unintentional injury (4828; 84%). There were 222 patients (3.9%) with a confirmed medical "effect," defined as signs, symptoms, and clinical findings not including therapeutic interventions (eg, endoscopy). There was a 33% decrease in cases from 418 (2008-2011) to 281 per year (2012-2017) after high-powered magnet sets were removed from the market. Calls subsequently increased 444% to 1249 per year (2018-2019) after high-powered magnet sets re-entered the market. Cases from 2018 and 2019 increased across all age groups and account for 39% of magnet cases since 2008. CONCLUSIONS: Significant increases in magnet injuries correspond to time periods in which high-powered magnet sets were sold, including a 444% increase since 2018. These results reflect the increased need for preventative or legislative efforts.

Liver involvement in children with SARS-COV-2 infection: Two distinct clinical phenotypes caused by the same virus.

BACKGROUND AND AIMS: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) associated acute liver injury (ALI) has been linked to poor outcomes in adults. Here we compare characteristics in children with elevated ALT (E-ALT) in two distinct manifestations of the infection, multisystem inflammatory syndrome-children (MIS-C) and coronavirus disease 2019 (COVID-19). METHODS: This is a retrospective study of patients ≤21 years of age with positive for SARS-CoV-2 PCR. E-ALT was defined as alanine aminotransferase (ALT) > 40 U/L. Bivariate analysis and multivariable logistic regression were obtained to describe differences in children with and without E-ALT in COVID-19 and MIS-C. RESULTS: E-ALT was detected in 36% of the 291 patients; 31% with COVID-19, and 51% with MIS-C. E-ALT in COVID-19 was associated with obesity (P < .001), immunocompromised status (P = .04), and chronic liver disease (P = .01). In the regression models, E-ALT in COVID-19 was associated with higher c-reactive protein (OR 1.08, P = .01) after adjusting for common independent predictors. Children with E-ALT and MIS-C were more often boys (P = .001), Hispanic (P = .04), or Black (P < .001). In MIS-C, male gender (OR 5.3, P = .02) and Black race (OR 4.4, P = .04) were associated with increased odds of E-ALT. Children with E-ALT in both cohorts had significantly higher multiorgan dysfunction, longer hospitalization, and ICU stay. Children with MIS-C had 2.3-fold increased risk of E-ALT compared to COVID-19. No association was found between E-ALT and mortality. CONCLUSION: E-ALT with SARS-CoV-2 presents as elevated transaminases without hepatic synthetic dysfunction. Patients with either manifestation of SARS-CoV-2 infection and E-ALT experienced more severe disease.

Magnet Ingestions in Children Presenting to Emergency Departments in the United States 2009-2019: A Problem in Flux.

OBJECTIVES: Small rare-earth magnet (SREM) ingestions are a dangerous, potentially fatal health hazard in children. The U.S. Consumer Safety Commission removed these products from the market in 2012 until a federal court decision vacated this action in 2016. The present study aims to investigate whether the reintroduction of SREMs is associated with an increase in the national frequency of magnet ingestions in children. PATIENTS AND METHODS: Data from the National Electronic Injury Surveillance System (NEISS) were used to evaluate suspected magnet ingestion (SMI) trends within patients (0-17 years) from 2009 to 2019. SMI cases were stratified (total, small/round, and multiple magnet ingestions) and trend analyses were performed for 2 periods: 2013-2016 (off-market) and 2017-2019 (on-market). National SMI estimates calculated using the NEISS-supplied weights and variance variables. RESULTS: An estimated 23,756 children (59% males, 42% < 5 years old) presented with a SMI from 2009 to 2019 with an average annual case increase of 6.1% (P = 0.01). There was a significant increase in both small/round SMI encounters and multiple magnet ingestion encounters from 2009 to 2019 (P < 0.001 and P < 0.01, respectively). From 2017 to 2019, there was a greater proportion of small/round type SMIs to total SMIs estimated n = 541 (confidence interval [CI], 261-822) and a greater proportion of multiple magnet ingestions to total SMIs estimated n = 797 (CI, 442-1152) (both, P < 0.01). After 2017, there was a 5-fold increase in the escalation of care for multiple magnet ingestions (estimated n = 1094; CI 505-1686). CONCLUSIONS: The significant increase in magnet ingestions by children from 2017 to 2019 indicates that regulatory actions are urgently needed to protect children and reverse these trends.

Detection of graft fibrosis by vibration-controlled transient elastography in pediatric liver transplant recipients.

Pediatric liver transplant recipients are at risk of developing graft fibrosis which can affect patient survival. VCTE is a non-invasive tool that measures LSM and has been shown to correlate with hepatic fibrosis. The aim of this study was to therefore evaluate the ability of LSM to predict fibrosis in pediatric liver transplant recipients with different graft types. We performed a cross-sectional study evaluating LSM of 28 pediatric liver transplant recipients who underwent a total of 20 liver biopsies within 1 month of LSM. LSM was compared to liver histology as well as graft type: WL or PL. The median LSM of all post-transplant patients was 5.6 kPa (range = 2.7-18.3). There was a statistically significant correlation between LSM and METAVIR fibrosis score (P = .001) and LAF score (P < .001). There was no difference in LSM between graft type (P = .088). The AUROC curve for LSM predicting any significant fibrosis (F ≥ 2) was 0.863. A cutoff value of 7.25 had a sensitivity of 71%, specificity of 100%, NPV of 87%, and PPV of 100% for significant fibrosis. LSM by VCTE is feasible in pediatric liver transplant recipients regardless of graft type. We found a significant correlation between LSM and hepatic fibrosis and established a cutoff value that may help determine which patients warrant further evaluation for graft fibrosis.

Liver Stiffness Measurement by Vibration Controlled Transient Elastography Does Not Correlate to Hepatic Iron Overload in Children With Sickle Cell Disease.

BACKGROUND: Children with sickle cell disease (SCD) are at risk of liver injury because of sickle cell hepatopathy and iron overload from chronic transfusions (CT). The authors examine the association between iron overload and liver stiffness measurement (LSM) by vibration controlled transient elastography (VCTE), which has been shown to correlate with fibrosis. METHODS: Patients 21 years of age and less with SCD had VCTE performed; those who received CT underwent magnetic resonance imaging T2* for iron quantification. RESULTS: The authors enrolled 42 patients, 17 (40%) of whom received CT. There was no difference in LSM between patients who underwent CT (5.5±1.5 kPa) and those who did not (5.2±2.3 kPa) (P=0.923). There was no correlation between iron quantification and LSM (r=-0.077, P=0.769). However, children 12 years of age and older had abnormal LSM when compared with a reference range (P=0.013). CONCLUSION: VCTE is a noninvasive technology that is feasible in children with SCD. LSM values were elevated in older children but did not correlate with iron overload, suggesting that fibrosis may not be affected by iron overload alone. Though additional data are needed, LSM may be a useful test for the progression of liver disease in SCD regardless of iron burden.

Associations of Insulin Resistance and Glycemia With Liver Enzymes in Hispanic/Latino Youths: Results From the Hispanic Community Children's Health Study/Study of Latino Youth (SOL Youth).

BACKGROUND: Associations of insulin resistance and hyperglycemia with a panel of liver enzymes have not been well studied in a young, heterogenous Hispanic/Latino population. We aimed to assess the associations of insulin resistance and glycemia with nonalcoholic fatty liver disease (NAFLD), as measured by liver enzymes and the pediatric NAFLD fibrosis index (PNFI), and whether these associations are modified by body mass index and mediated by inflammation or endothelial dysfunction. MATERIALS AND METHODS: We conducted a cross-sectional study of 1317 boys and girls aged 8 to 16 years from the Hispanic Community Children's Health Study/Study of Latino Youth. We used Poisson regression to assess the associations of fasting glucose, hemoglobin A1c, and homeostasis model assessment of insulin resistance (HOMA-IR) with elevated alanine aminotransferase (ALT) (>25 U/L in boys, >22 U/L in girls), aspartate aminotransferase (AST) (≥37 U/L), gamma-glutamyl transpeptidase (GGT) (≥17 U/L), and PNFI (≥9; a function of age, waist circumference, and triglyceride level). RESULTS: HOMA-IR was associated with elevated ALT, AST, GGT, and PNFI [prevalence ratios (95% confidence intervals) for each 1-unit increase in the natural log of HOMA-IR: 1.99 (1.40-2.81), 2.15 (1.12-4.12), 1.70 (1.26-2.30), and 1.98 (1.43-2.74), respectively]. Associations were observed in overweight/obese children, but not in normal weight children (P-interaction=0.04 for AST and P-interaction=0.07 for GGT). After further adjustment for adiponectin, high-sensitivity C-reactive protein, e-selectin, and PAI-1, associations of HOMA-IR with liver enzymes and PNFI were attenuated, but remained statistically significant for AST and PNFI. CONCLUSION: Insulin resistance was associated with NAFLD in overweight/obese Hispanic/Latino youth, and this association may be partially mediated by inflammation and endothelial dysfunction.

Clinical Practice Approach to Nonalcoholic Fatty Liver Disease by Pediatric Gastroenterologists in the United States.

OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is common; however, no information is available on how pediatric gastroenterologists in the United States manage NAFLD. Therefore, study objectives were to understand how pediatric gastroenterologists in the US approach the management of NAFLD, and to identify barriers to care for children with NAFLD. METHODS: We performed structured one-on-one interviews to ascertain each individual pediatric gastroenterologist's approach to the management of NAFLD in children. Responses were recorded from open-ended questions regarding screening for comorbidities, recommendations regarding nutrition, physical activity, medications, and perceived barriers to care. RESULTS: Response rate was 72.0% (486/675). Mean number of patients examined per week was 3 (standard deviation [SD] 3.5). Dietary intervention was recommended by 98.4% of pediatric gastroenterologists. Notably, 18 different dietary recommendations were reported. A majority of physicians provided targets for exercise frequency (72.6%, mean 5.6 days/wk, SD 1.6) and duration (69.9%, mean 40.2 minutes/session, SD 16.4). Medications were prescribed by 50.6%. Almost one-half of physicians (47.5%) screened for type 2 diabetes, dyslipidemia, and hypertension. Providers who spent more than 25 minutes at the initial visit were more likely to screen for comorbidities (P = 0.003). Barriers to care were reported by 92.8% with 29.0% reporting ≥3 barriers. CONCLUSIONS: The majority of US pediatric gastroenterologists regularly encounter children with NAFLD. Varied recommendations regarding diet and exercise highlight the need for prospective clinical trials. NAFLD requires a multidimensional approach with adequate resources in the home, community, and clinical setting.

Yield of diagnostic tests in obese children with an elevated alanine aminotransferase.

AIM: Nonalcoholic fatty liver disease (NAFLD) is associated with obesity and affects roughly 10% of children. However, NAFLD is often diagnosed by exclusion - that is, obese children with an elevated alanine aminotransferase (ALT) are screened for other liver diseases in the absence of a biopsy. This testing is nonstandardized, and professional society recommendations differ. This study examines the yield of testing for disorders other than NAFLD in this patient population. METHODS: A retrospective study was performed in 120 obese, asymptomatic, noncholestatic children with an ALT ≥40 U/L and additional diagnostic testing. RESULTS: No patients were found to have Wilson's, hepatitis A, hepatitis B, hepatitis C, cytomegalovirus, alpha-1 antitrypsin deficiency, autoimmune hepatitis, celiac disease or Epstein-Barr virus. Only one patient (1/120) was identified with definite disease other than NAFLD, which was muscular dystrophy. The positive predictive value of a screening test was 5%, and the specificity was 97%. Of 70 children with an abdominal ultrasound, no significant abnormalities were identified. CONCLUSION: Extensive testing in asymptomatic, noncholestatic, obese children with an elevated ALT may be of limited diagnostic value and false-positive tests are likely. Large, prospective studies are needed to help focus the work up in this patient population.

Nonalcoholic fatty liver disease.

On the basis of strong research and consensus, nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in children and is soon to be the most common indication for liver transplantation in adults. Although the disease begins as simple steatosis, some patients may progress to nonalcoholic steatohepatitis (NASH) and cirrhosis, making early identification and treatment critical.• The diagnosis of NAFLD can be challenging because patients are typically asymptomatic, with no major clinical symptoms of liver disease. Overweight and obese children are at the highest risk for disease. (1)(2)• On the basis of moderate research and consensus, serum ALT is usually mildly elevated but is an imperfect test with a low sensitivity for detecting NAFLD at commonly used thresholds.(10) Liver biopsy is still considered the gold standard for diagnosis but is too invasive for population-level screening and is often used selectively. Novel, noninvasive diagnostic modalities and serum biomarkers are currently being studied but warrant further validation, especially in children.• On the basis of moderate research and consensus, assessing serum liver tests in any overweight or obese child is reasonable.Liver disease should be suspected if the serum ALT is ‡22 U/L(0.37 mkat/L) in girls and ‡25 U/L (0.42 mkat/L) in boys. (10)Subspecialist referral should be considered for those with a normal BMI, persistent ALT elevation longer than 6 months,specific symptoms of advanced liver disease such as splenomegaly, or concerning laboratory findings on selected screening tests.• On the basis of strong research evidence, weight loss is the most efficacious treatment for NAFLD.• On the basis of some research and consensus, initiation of vitamin E therapy (400 IU BID) may be started, although its use probably should be restricted to those children with biopsy-proven disease. (12)• On the basis of some research and consensus, novel elastography-based imaging modalities are being studied in children and several drugs show promise in treating NAFLD.

Variation in Alanine Aminotransferase in Children with Non-Alcoholic Fatty Liver Disease.

Background: Pediatric non-alcoholic fatty liver disease (NAFLD) is a major public health concern. Aminotransferase (ALT) is frequently used for screening and monitoring, but few studies have reported typical patterns of ALT elevation in children. Methods: TARGET-NASH is a real-world longitudinal observational cohort of patients with NAFLD receiving care across the United States. Analyses included children enrolled between 1 August 2016, and 12 October 2020, with at least one ALT measurement after enrollment. Peak ALT was based on the first and last available record and categorized into clinical cut points: <70 IU/L, >70−<250 IU/L, and >250 IU/L. A chi-squared test was used to compare differences in proportions, and a Kruskal−Wallis test was used to compare the medians and distributions of continuous responses. Results: Analyses included 660 children with a median age of 13 years. Of the 660, a total of 187 had undergone a biopsy and were more likely to be Hispanic or Latino (67% vs. 57%, p = 0.02) and to have cirrhosis (10% vs. 1%, p < 0.001). The highest ALT scores ranged from 28 U/L to 929 U/L; however, these scores varied across time. The prevalence of cirrhosis or any liver fibrosis stage was most common among children with a peak ALT > 70 U/L. Conclusions: Large variability was seen in ALT among children, including many values > 250 U/L. Higher levels of ALT were associated with increased prevalence of comorbidities and more advanced stages of NAFLD. These findings support an increased need for therapeutics and disease severity assessment in children with peak ALT > 70 U/L.

Warning Labels and High-Powered Magnet Exposures.

BACKGROUND AND OBJECTIVES: High-powered magnets are among the most dangerous childhood foreign bodies. Consumer advocates and physicians have called for these products to be effectively banned, but manufacturers assert warning labels would sufficiently mitigate risk. METHODS: Subjects from Injuries, Morbidity, and Parental Attitudes Concerning Tiny High-powered Magnets (IMPACT of Magnets), a retrospective, multicenter study of children with high-powered magnet exposures (ie, ingestion or bodily insertion), were contacted. Consenting participants responded to a standardized questionnaire regarding the presence and utility of warning labels, magnet product manufacturer, and attitudes around risk. RESULTS: Of 596 patients in the IMPACT study, 173 parents and 1 adult patient were reached and consented to participate. The median age was 7.5 years. Subjects reported not knowing if a warning label was present in 60 (53.6%) cases, whereas 25 (22.3%) stated warnings were absent. Warnings were present in 28 (24.1%) cases but only 13 (46.4%) reported reading them. A manufacturer was identified by families in 28 (16.1%) exposures; 25 of these were domestic and 27 had warnings. Subjects reported knowing magnets were dangerous in 58% of the cases, although 44.3% believed they were children's toys and only 6.9% knew high-powered magnets were previously removed from the United States market. CONCLUSIONS: Over 90% of subjects from the IMPACT study didn't know if warning labels were present or failed to read them if they were, whereas almost half believed high-powered magnets were children's toys. Warning labels on high-powered magnet products are, therefore, unlikely to prevent injuries in children.

High-Powered Magnet Exposures in Children: A Multi-Center Cohort Study.

BACKGROUND AND OBJECTIVES: High-powered magnets were effectively removed from the US market by the Consumer Product Safety Commission (CPSC) in 2012 but returned in 2016 after federal court decisions. The United States Court of Appeals for the 10th Circuit cited imprecise data among other reasons as justification for overturning CPSC protections. Since then, incidence of high-powered magnet exposure has increased markedly, but outcome data are limited. In this study, we aim to describe the epidemiology and outcomes in children seeking medical care for high-powered magnets after reintroduction to market. METHODS: This is a multicenter, retrospective cohort study of patients aged 0 to 21 years with a confirmed high-powered magnet exposure (ie, ingestion or insertion) at 25 children's hospitals in the United States between 2017 and 2019. RESULTS: Of 596 patients with high-powered magnet exposures identified, 362 (60.7%) were male and 566 (95%) were <14 years of age. Nearly all sought care for magnet ingestion (n = 574, 96.3%), whereas 17 patients (2.9%) presented for management of nasal or aural magnet foreign bodies, 4 (0.7%) for magnets in their genitourinary tract, and 1 patient (0.2%) had magnets in their respiratory tract. A total of 57 children (9.6%) had a life-threatening morbidity; 276 (46.3%) required an endoscopy, surgery, or both; and 332 (55.7%) required hospitalization. There was no reported mortality. CONCLUSIONS: Despite being intended for use by those >14 years of age, high-powered magnets frequently cause morbidity and lead to high need for invasive intervention and hospitalization in children of all ages.

Relationship of Vitamin D Deficiency and Fatty Liver in Children as Defined by Multiple Imaging and Histologic Endpoints.

OBJECTIVES: The relationship between vitamin D deficiency (VDD) and pediatric nonalcoholic fatty liver disease (NAFLD) remains uncertain due to conflicting results and few studies with histologic endpoints. We therefore used multiple imaging and histologic NAFLD endpoints to more comprehensively assess the association between VDD and NAFLD in a large pediatric population. METHODS: Data were obtained from an ongoing pediatric NAFLD study in Bronx, NY. Briefly, overweight and obese children aged 2-18 years with alanine aminotransferase (ALT) levels ≥ 35 U/L were serially enrolled. Liver biopsy was obtained in accordance with clinical guidelines. All participants had liver imaging, namely, controlled attenuation parameter (CAP; Echosens, France) to assess steatosis and, to assess fibrosis, vibration controlled transient elastography (VCTE; FibroScan™, Echosens, France) and acoustic radiation force impulse (ARFI; Philips, Netherlands) imaging. Levels of 25-hydroxyvitamin D were measured serologically. RESULTS: N=276 (88%) of 315 participants had 25-OH vitamin D results, of whom 241 (87%) were Hispanic, 199 (72%) were male, and 92 (33%) underwent liver biopsy. VDD was univariately associated with high waist circumference (p=0.004), high-density lipoprotein level (p=0.01), season (p=0.009), and CAP score (p=0.01). In multivariate analysis, only waist circumference (p=0.0002) and biopsy inflammation grade (p=0.03) were associated with VDD, though the latter had not approximated statistical significance in univariate analysis (p=0.56). There was no association between VDD and hepatic steatosis, ballooning, NAFLD Activity Score, ARFI or VCTE elasticity scores. CONCLUSIONS: VDD was not associated with NAFLD defined by imaging and histologic endpoints, except for a possible relation with histologic inflammation grade.

Differential Diagnosis of a Patient with Lysosomal Acid Lipase Deficiency: A Case Report.

BACKGROUND: We describe the differential diagnosis of an obese 12-year-old boy of Mexican origin who presented with a 6-year history of abnormal lipid profile and elevated liver transaminase levels. METHODS: The patient underwent routine clinical testing, an abdominal ultrasound and, ultimately, a liver biopsy. Based on the histologic findings, a serum leukocyte lysosomal acid lipase (LAL) assay and DNA sequencing of the lipase A (LIPA) gene were performed. RESULTS: Liver biopsy revealed diffuse microvesicular steatosis with clusters of foamy histiocytes in the lobules and portal areas. Our differential diagnosis included nonalcoholic fatty liver disease; medication-induced hepatotoxicity; glycogenic hepatopathy; medium-chain acyl coenzyme A dehydrogenase or long-chain acyl coenzyme A dehydrogenase deficiency; and lysosomal storage disorders, including Niemann-Pick disease and lysosomal acid lipase deficiency (LAL-D). Serum LAL activity was absent, and DNA sequencing confirmed homozygous mutation in LIPA. CONCLUSIONS: Although it occurs rarely, LAL-D should be considered in the differential diagnosis of microvesicular steatosis for a timely diagnosis.

Methods to improve the noninvasive diagnosis and assessment of disease severity in children with suspected nonalcoholic fatty liver disease (NAFLD): Study design.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is strongly associated with obesity and is the most common liver disease in the developed world. In children with suspected NAFLD, present guidelines suggest consideration of alternative diagnoses via extensive blood testing, though the yield of this work up is unknown. Furthermore, the gold standard diagnostic test for NAFLD remains liver biopsy, making the development of non-invasive tests critically important. OBJECTIVES: Our objectives are: 1) to determine the accuracy of elastography and multiple serum biomarkers - each assessed individually and as algorithms (including those previously tested in adults) - for the diagnosis of nonalcoholic steatohepatitis (NASH) and early fibrosis in children and (2) to examine the utility of extensive testing for rare alternative diagnoses in overweight or obese children with elevated alanine aminotransferase (ALT) suspected to have NAFLD. DESIGN: This is an ongoing, cross-sectional study in children 2-18 years of age with up to 2 years of prospective follow up. Eligible patients are asymptomatic, overweight or obese, and have an ALT ≥35 U/L upon enrollment. Two forms of elastography are obtained serially along with anthropometric data and routine laboratory tests. Elastography and serum biomarkers are also performed immediately prior to any clinically-indicated biopsy. METHODS: Between April 2015 and April 2018, 193 children have been enrolled in this ongoing study and 71 have undergone liver biopsy. Here we carefully report the rationale, methodology, and preliminary data for this study.