To determine age- and sex-specific reference values for serum immunoglobulins (IgA, IgG, and IgM) in a population-based cohort of 6 to 18 years old Danish children and adolescents and investigate if immunoglobulin concentrations vary with body mass index standard deviation score (BMI SDS).

A total of 2171 school children and adolescents (median age 12.0 years) were recruited. BMI SDS was calculated, and health status was assessed by questionnaire and blood samples. Fasting serum concentrations of IgA, IgG, and IgM were determined by immunonephelometry. Sex- and age-specific percentiles were generated and partitioned following the Clinical and Laboratory Standards Institute (CLSI) EP28-A3c guidelines. Multiple linear regression models were used to investigate associations betweenIgA, IgG, IgM, and BMI SDS adjusted for age and sex.

Concentrations of IgA increased with age but did not differ between boys and girls. An age-dependent increase was also detected for concentrations of IgG and IgM, although for IgG it was more pronounced in boys than girls. Girls had higher concentrations of IgG and IgM than boys at all ages. Concentrations of IgM were inversely associated with BMI SDS independent of age and sex.

We generated age- and sex-specific reference intervals for IgA, IgG, and IgM based on children and adolescents from a Danish/North-European Caucasian population-based cohort. The findings can help evaluate alterations seen in primary and secondary immunodeficiencies and autoimmune diseases.

Scarce knowledge about the impact of metabolism-disrupting chemicals (MDCs) on steatotic liver disease limits opportunities for intervention. We evaluated pregnancy MDC-mixture associations with liver outcomes, and effect modification by folic acid (FA) supplementation in mother-child pairs.

We studied ∼200 mother-child pairs from the Mexican PROGRESS cohort, with 43 MDCs measured during pregnancy (estimated air pollutants, blood/urine metals or metalloids, urine high- and low-molecular-weight phthalate [HMWPs, LMWPs] and organophosphate-pesticide metabolites), and serum liver enzymes (ALT, AST) at ∼9 years post-parturition. Outcomes included elevated liver enzymes in children and established clinical scores for steatosis and fibrosis in mothers (i.e.

ALT, FLI, HSI, FIB-4). Bayesian-weighted quantile sum regression assessed MDC-mixture associations with liver outcomes. We further examined chemical-chemical interactions and effect modification by self-reported FA supplementation.

In children, many MDC-mixtures were associated with liver injury. Per quartile HMWP-mixture increase, ALT increased by 10.1% (95% CI 1.67%, 19.4%) and AST by 5.27% (95% CI 0.80%, 10.1%). LMWP-mixtures and air pollutant-mixtures were associated with higher AST and ALT, respectively. Air pollutant and non-essential metal/element associations with liver enzymes were attenuated by maternal cobalt blood concentrations (p-interactions <0.05). In mothers, only the LMWP-mixture was associated with odds for steatosis (odds ratio = 1.53, 95% CI 1.01-2.28 for HSI >36, and odds ratio 1.62, 95% CI 1.05-2.49 for AST:ALT <1). In mothers and children, most associations were attenuated (null) at FA supplementation ≥600 μg/day (p-interactions <0.05).

Pregnancy MDC exposures may increase risk of liver injury and steatosis, particularly in children. Adequate FA supplementation and maternal cobalt levels may attenuate these associations.

The effects of environmental chemical exposures on steatotic liver diseases are not well understood. In a parallel investigation of mothers and children, we found that pregnancy exposures to metabolism-disrupting chemicals may increase the risk of liver injury and steatosis, especially in the child, and that these associations could be attenuated by higher folic acid and/or cobalt levels. These findings can inform policies to decrease environmental chemical pollution and contribute to the design of clinical interventions addressing the metabolic dysfunction-associated steatotic liver disease epidemic.

We aimed to study the prevalence of hypophosphatemia and its associated risk factors in Diabetic Ketoacidosis (DKA) patients in the pediatric population.

We included 65 subjects aged 7 months to 18 years old who were admitted to Hospital Universiti Sains Malaysia (HUSM) for DKA. Patients' socio-demographic and clinical characteristics, and biochemical examinations from their first admission for DKA were analyzed. The diagnosis of DKA was based on the International Society for Pediatric and Adolescent Diabetes (ISPAD) criteria. Multiple logistic regression models examined associations between different variables and hypophosphatemia.

The prevalence of hypophosphatemia in DKA was highest on day 1, at 70.8%, with a mean age of 11 on presentation. Multiple logistic regression analysis showed plasma bicarbonate at day 3 [adjusted odds ratio (OR) 1.2, with a p-value of 0.027] and baseline hemoglobin [adjusted OR 0.62, with p-value 0.009] were significantly associated with hypophosphatemia during DKA.

The prevalence of hypophosphatemia in DKA pediatric patients admitted to our center was highest on day 1 of admission. There were many factors associated with hypophosphatemia from simple logistic regression analysis. However, our final model revealed that plasma bicarbonate on day 3 and baseline Hb were the only significant risk factors for hypophosphatemia in DKA patients in the pediatric population.

Hepatocellular carcinoma (HCC) is a major complication of tyrosinemia type 1 (HT-1), an inborn error of metabolism affecting tyrosine catabolism. The risk of HCC is higher in late diagnoses despite treatment. Alpha-fetoprotein (AFP) is widely used to detect liver cancer but has limitations in early-stage HCC detection. This study aimed to implement a machine-learning (ML) approach to identify the most relevant laboratory variables to predict AFP alteration using constrained multidimensional data from Chilean and Italian HT-1 cohorts. A longitudinal retrospective study analyzed 219 records from 35 HT-1 patients, including 8 with HCC and 5 diagnosed through newborn screening. The dataset contained biochemical and demographic variables that were analyzed using the eXtreme Gradient Boosting algorithm, which was trained to predict abnormal AFP levels (>5 ng/mL). Four key variables emerged as significant predictors: alanine transaminase (ALT), alkaline phosphatase, age at diagnosis, and current age. ALT emerged as the most promising indicator of AFP alteration, potentially preceding AFP level changes and improving HCC detection specificity at a cut-off value of 29 UI/L (AUROC = 0.73). Despite limited data from this rare disease, the ML approach successfully analyzed follow-up biomarkers, identifying ALT as an early predictor of AFP elevation and a potential biomarker for HCC progression.

To fully take advantage of blood test results, comparative data are required. Today, the reference interval is a commonly used concept. This review aims to summarise the current state of reference intervals, focusing on infants.

Literature on reference percentiles (birth to 12 months of age) published from January 1950 until November 2024 was reviewed. Search terms comprised paediatric, infant, or neonatal reference intervals and similar terminology. Furthermore, reference interval data in current clinical use were investigated by searching 7 Nordic laboratory websites for three routinely used biomarkers.

During infancy, the levels of several biomarkers change rapidly with development and growth. Conventionally used techniques for deriving reference intervals have limitations and require extensive blood samplings. New approaches basing reference limits on mathematically trimmed data from laboratory systems have emerged. Due to the risk of modelling pathological data, the results of these studies need verification. Recently published Nordic reference interval data, based on healthy infants and defined on specified time points, could present new opportunities.

Infant reference interval methodology requires particular consideration. The currently observed heterogeneity in this area calls for further methodological investigations, improved concepts, harmonisation activities, and software development.

New 2023 CF liver disease (CFLD) guidelines advocate for additional screening in people with cystic fibrosis (PwCF), including biennial abdominal ultrasound. As a first step towards effective and equitable guidelines implementation, we examined our current practice of CFLD screening and hepatobiliary involvement (HBI) evaluation. We identified characteristics of PwCF at-risk for incomplete screening and factors affecting evaluation.

We retrospectively reviewed medical records of PwCF aged 0-21 years, with native liver and ≥ 2 outpatient CF clinic visits 2017-2023. Logistic regression was used to identify characteristics associated with incomplete screening and with HBI.

Amongst 112 PwCF at our center: 37% (n = 42) self-reported as mixed race, 27% (n = 30) as Hispanic; 53% (n = 59) had public insurance. Incomplete lab screening was identified in 19% of our cohort. GGT was the most frequently missed component (14%, n = 16). Hispanics and publicly insured people were more likely to have incomplete screening. Of the 112, 45 met criteria for HBI. Demographics did not predict HBI. Five with CF and HBI had the full hepatitis workup recommended by the new guidelines. Those with HBI documented (42%, n = 19) were more likely to receive additional workup. PwCF who were seen by a gastroenterologist were more likely to have additional diagnostic work-up for HBI.

One in five PwCF at our center were incompletely screened for CFLD, with Hispanics and publicly insured at higher risk. Accurate diagnosis and adequate documentation are the first steps to identifying HBI in PwCF. A dedicated CF gastroenterologist is key to completing CFLD screening and liver diagnosis.

Venous thromboembolism is a common cause of morbidity and mortality in children with renal disease. To properly treat and prevent thromboembolism in this patient population, it is important to be familiar with the multitude of anticoagulant agents currently available. Many anticoagulant drugs undergo some extent of renal elimination. There are important considerations for the selection, dosing, and monitoring of anticoagulant drugs for patients with renal impairment due to various pharmacokinetic alterations that may occur. While there are data to help guide dosing and monitoring in adults, evidence regarding renal dose adjustment of many anticoagulant drugs in children are limited. For the clinician, anticoagulation management in children with renal impairment presents unique challenges. In addition to considering overall bleeding risk, the extent of renal impairment may vary by patient, making a one-size-fits-all approach to managing these patients difficult. These factors, combined with limited data, can make managing anticoagulation in children with renal impairment a challenge. Therefore, the focus of this review will be to describe the pharmacokinetics of the following anticoagulants in children with impaired renal function: unfractionated heparin, enoxaparin, dalteparin, rivaroxaban, apixaban, edoxaban, fondaparinux, bivalirudin, argatroban, dabigatran, and warfarin.

Adolescent primary hyperparathyroidism (PHPT) is a rare endocrine disorder bearing distinctions from the adult form. This review examines its unique aspects, focusing on clinical presentation, genetic etiologies, genotype-phenotype correlations, and therapeutic management. Adolescent PHPT often has a genetic basis, whether familial, syndromic, or apparently sporadic, and identifying the underlying genetic cause is important for patient care. The clinical presentation is predominantly symptomatic worldwide. Unique manifestations in this age group include rickets, short stature, and slipped capital femoral epiphysis. Genotype-specific differences are evident in the adolescent PHPT characteristics. Diagnostic evaluation requires careful interpretation of biochemical and dual-energy X-ray absorptiometry findings using age and gender-specific reference ranges, with targeted screening for syndrome-associated neoplasms. Surgery remains the cornerstone of management. Current knowledge gaps in their management include treatment protocols for multiple endocrine neoplasia type 1-associated PHPT, the efficacy and safety of nonsurgical options, and long-term post-surgical outcomes.

To assess foetal circulating free foetal haemoglobin (fHbF) levels and heme defences, correlated to foetal circulatory biometry and foetal sex in severe early-onset foetal growth restriction (FGR).

A prospective study severe early-onset foetal growth restriction pregnancies with close clinical management (estimated foetal weight (EFW) < 3rd centile and < 600 g at 20-26 + 6 weeks; N = 20).

Temporal foetal vascular obstetric biometry was recorded. Cord blood fHbF and key heme-scavenger defences were measured and compared with normal term births (N = 26) and births with late-onset FGR (N = 12).

fHbF was elevated in early-onset FGR compared with normal pregnancy: 0.437(0.337/0.753) mg/mL; and 0.098 (0.045/0.264) mg/mL, respectively (p < 0.0001); whilst hemopexin was downregulated in early- (p < 0.001) and late-onset FGR (p < 0.0001), compared to normal pregnancy: 36(14/81) μg/mL, 25(19/40) μg/mL, and 155(132/219) μg/mL, respectively; median (interquartile ranges). Early-onset FGR male foetuses had higher HbF compared with the normal males: 0.710(0.433/0.857) mg/mL; (p < 0.001); 0.099(0.043/0.246) mg/mL, respectively; median (interquartile ranges). In early-onset FGR, ratios of mid-cerebral artery and umbilical artery pulsatility indices correlated positively with heme-scavenger levels (hemopexin and a heme-handling composite measure: p < 0.05, r = 0.672; and p < 0.01, r = 0.620; respectively), indicating lower levels are associated with cerebral vascular redistribution. These heme handling measures also positively correlated with gestational age at delivery (r = 0.713 and r = 0.642, respectively, p < 0.01, both) and birthweight (r = 0.742, p < 0.001; and r = 0.523, p < 0.05; respectively).

Overproduction of fHbF and an inadequate heme defence may contribute to foetal distress and poor umbilical arterial Dopplers in early onset FGR due to elevated placental vascular resistance and vascular inflammation.

Hypophosphatasia is a rare inherited systemic metabolic disorder, with an estimated prevalence in the severe forms of the disease of 1/100.000-1/300.000, that affects the typical architecture of bone, leading to defective mineralization during growth and remodeling. It is characterized by loss-of-function variants in the ALPL gene, resulting in low activity of tissue-nonspecific alkaline phosphatase. In severe cases, it can be fatal.

To generate recommendations on the diagnosis, treatment, and follow-up of patients with hypophosphatasia based on available evidence.

A search for evidence published between 2012 and 2024 was carried out in Medline and Embase. The search was expanded with information from various sources, including official sites of development groups, consensuses, technology evaluations, Google Scholar, clinical experts, and reference lists. The quality of the evidence was evaluated according to the type of document type. A modified Delphi consensus process was carried out with external experts, apart from the development group, it was established an 80% agreement threshold to define the final recommendations.

Sixty-one papers were found in the evidence search. The global quality of the evidence was low. In addition, a consensus was reached on 94 recommendations regarding diagnosis, treatment, and follow-up. Those recommendations were approved by external clinical experts from Colombia, Argentina, Spain, and Mexico.

The recommendations proposed in this document are based on the evidence available to the date the search was carried out, and the judgment of clinical experts. The recommendations on diagnosis, treatment, and follow-up are expected to guide the daily clinical practice for patients with HPP.

Chronic nonbacterial osteomyelitis (CNO) is a rare autoinflammatory disease of unknown cause, predominantly affecting teens and young adults. The early diagnosis and management are challenging due to the lack of reliable diagnostic markers and the occasional intractable cases despite conventional anti-inflammatory treatments. Janus kinase (JAK) inhibitors have recently shown potential utility; however, reports on their use for pediatric patients with CNO remain limited, and no established biomarkers exist to monitor disease activity. We aimed to investigate the pathophysiology of CNO and explore the rapid testing methods for accurate diagnosis and also assessing the disease activity.

We assessed intracellular phosphorylation of signal transducer and activator of transcription 1 (pSTAT1) in peripheral blood monocytes or T cells following interferon-gamma (IFNγ) stimulation, using flow cytometry in 9 patients under 15 years old with CNO. The pSTAT1 expression levels were compared with those in patients with STAT1-gain of function (STAT1-GOF) mutations (n = 5), other autoinflammatory diseases (n = 7), and healthy controls. Clinical and immunological data were monitored in 4 patients with intractable CNO treated with adjunctive JAK inhibitors, focusing on scoring scales, imaging data, lymphocyte subsets, cytokine profiles, and pSTAT1 levels.

Monocyte pSTAT1 expression after IFNγ stimulation was elevated at diagnosis or during active CNO, similar to levels observed in STAT1-GOF cases. The pSTAT1 levels in CNO patients were significantly higher than those in other autoinflammatory diseases (p = 0.024) or controls (p < 0.001). Notably, pSTAT1 levels in CNO monocytes fluctuated with disease activity, decreasing in 5 patients during clinical remission following conventional therapies (p = 0.016). In four intractable cases, pSTAT1 levels remained high despite conventional treatments but significantly decreased after initiating JAK inhibitors (p = 0.036). This reduction correlated with improved patient pain visual analog scale (p = 0.008), CNO clinical disease activity score (p = 0.029), and better bone and joint imaging, though cytokine levels remained unchanged.

The monocyte pSTAT1 levels after IFNγ stimulation reflect the activity of CNO, indicating the diagnostic utility as well as the monitoring effect of disease control. Adjunctive JAK inhibitors successfully controlled inflammation in treatment-resistant cases. Rapid pSTAT1 testing may help reduce osteo-articular complications, although the long-term adverse effects and resistance should be further investigated.

Interpretation of alkaline phosphatase (ALP) activity is essential for the diagnosis of certain diseases. ALP changes during life and may vary between different populations.

To establish reference intervals (RIs) and percentile charts for ALP activity in the Spanish population through a multicentric observational study and to compare the RIs to those defined in other countries.

A total of 662 350 ALP measurements from individuals ages 0 to 99 years from 9 Spanish tertiary care centers collected between 2020 and 2022 were analyzed. This study is the largest published on this topic in the literature to date.

Continuous percentile charts for ALP according to sex and age were established which can be used as RIs. Higher levels are reached during the first weeks of life. In puberty, a differential evolution is observed in both sexes, reaching a peak at 10 to 13 years of age in boys and remaining stable in girls at this age. Significant differences were also observed in adults, higher in men between ages 20 and 49 years and between ages 50 and 79 years in women, as reported in some countries.

ALP activity follows an age- and sex-dependent fluctuation with geographic differences. It is important to have appropriate reference values for each population in order to allow for a correct diagnostic interpretation and early diagnosis of diseases related to ALP abnormalities.

With Industry 4.0, big data and artificial intelligence have become paramount in the field of medicine. Electronic health records, the primary source of medical data, are not collected for research purposes but represent real-world data; therefore, they have various constraints. Although structured, laboratory data often contain unstandardized terminology or missing information. The major challenge lies in the lack of standardization of test results in terms of metrology, which complicates comparisons across laboratories. In this review, we delve into the essential components necessary for integrating real-world laboratory data into high-quality big data, including the standardization of terminology, data formats, equations, and the harmonization and standardization of results. Moreover, we address the transference and adjustment of laboratory results, along with the certification for quality of laboratory data. By discussing these critical aspects, we seek to shed light on the challenges and opportunities inherent to utilizing real-world laboratory data within the framework of healthcare big data and artificial intelligence.

This study aimed to develop machine learning (ML) prediction models for identifying bloodstream infection (BSI) and septic shock (SS) in pediatric patients with cancer who presenting febrile neutropenia (FN) at emergency department (ED) visit.

A retrospective study was conducted on patients, younger than 18 years of age, who visited a tertiary university-affiliated hospital ED due to FN between January 2004 and August 2022. ML models, based on XGBoost, were developed for BSI and SS prediction.

After applying the exclusion criteria, we identified 4423 FN events during the study period. We identified 195 (4.4%) BSI and 107 (2.4%) SS events. The BSI and SS models demonstrated promising performance, with area under the receiver operating characteristic curve values of 0.87 and 0.88, respectively, which were superior to those of the logistic regression models. Clinical features, including body temperature, some laboratory results, vital signs, and diagnosis of acute myeloblastic leukemia were identified as significant predictors.

The ML-based prediction models, which use data obtainable at ED visits may be valuable tools for ED physicians to predict BSI or SS.

Bone turnover markers (BTMs) can provide information on the bone growth of apparently healthy children and adolescents or useful results in the diagnosis and monitoring of the disease condition, comparing them with appropriate reference intervals (RIs). The aim of this study was to establish the RI for the BTM [specific bone alkaline phosphatase (BALP), carboxy-terminal cross-linked collagen type I telopeptide (CTX), N-terminal propeptide pro-collagen type I (PINP), osteocalcin (OC), resistant to acid tartrate phosphatase isoform 5b (TRAcP-5b)] on serum samples from children and adolescents.

202 samples from children and adolescents (ages 1-18 years) (51.48% male), considered apparently healthy. The biomarker was analyzed on automatic immunometric equipment (TGSTA Technogenetics) and the IDS-iSYS automated system kits The RI of the studied parameters was calculated according to CLSI Guideline C28-A3 with stratification by age and sex. Evaluation of the distribution of values and the meaning of the biomarker concentrations were used to calculate general and specific RI for an age group.

BTM concentrations vary with pubertal growth. The pattern of change differs for each bone marker. General and age-specific RI were calculated: 1-14 years, 15-18 years for BALP and CTX; 1-13 years, 14-18 years for Oc and PINP and 1-12 years, 13-18 years for TRAcP.

Concentrations for biomarker studied vary with age and gender. The proof of concentrations with insignificant changes until puberty led to identification of two groups of RI relating to the covariables (age and sex) for each biomarker.

To compare postnatal outcomes of anterior urethral valves (AUV) and posterior urethral valves (PUV) patients to evaluate for potential differences between these conditions, given that AUV with or without concomitant PUV is a rare congenital anomaly leading to lower urinary tract obstruction (LUTO).

We reviewed our LUTO database and included patients with AUV or concomitant AUV+PUV, managed at our institution between 2003 and 2023 matching them to comparable PUV cases. Assessed variables included prenatal diagnosis, gestational age (GA) at birth, initial management, kidney function, presence and degree of hydronephrosis (HN), and need for renal replacement therapy (RRT).

The AUV ± PUV group (AUV: n = 11, concomitant PUV: n = 2) and PUV group (n = 26) had similar presenting ages and follow-up times (P >.05). Only 15.4% of AUV cases presented prenatally compared to 72.0% of PUV cases (P = .0016), leading to delayed postnatal management in AUV patients (P = .0260). Findings at presentation included UTI, weak stream or a palpable penile mass. PUV patients demonstrated significantly higher creatinine levels at the initial visit and at last follow-up (P = .0120 and P = .0302) than the AUV ± PUV group, with only 1 patient requiring RRT (P >.05). At the last follow-up, no patient in the AUV ± PUV group required clean intermittent catheterization compared to 37.5% in the PUV group (P = .0331) which also demonstrated more patients with persistent HN (P = .0039).

AUV with or without concomitant PUV is a rare finding that should be considered in patients presenting with weak stream, UTI, and penile swelling. Our data suggest potential differences in presentation and less severe postnatal outcomes in AUV compared to PUV patients.

Blood plasma storage is a crucial element of pediatric biobanking. Improperly stored or handled specimens (e.g., at > -30°C) can result in altered biomolecular compositions that no longer reflects in vivo reality. We report application of a previously developed assay in adults-the ΔS-Cys-Albumin assay, which facilitates estimation of plasma and serum exposure to thawed conditions-to a population of pediatric EDTA plasma samples from patients aged 3-18 years to determine the assay's applicability, estimate its reference range for pediatric samples, and assess the impact of pre-centrifugation delay at 0°C. In addition, the effect of plasma thawed-state exposure to a range of times at 23°C, 4°C, and -20°C on ΔS-Cys-Albumin was evaluated. Using 98 precollected and processed pediatric EDTA plasma specimens, no difference was found in ΔS-Cys-Albumin under conditions of pre-centrifugation delay for up to 10 hours at 0°C. This lack of change allowed us to estimate a pediatric reference range for ΔS-Cys-Albumin of 7.0%-22.5% (mean of 12.8%) with a modest Pearson correlation between ΔS-Cys-Albumin and age (p = 0.0037, R2 = 0.29). ΔS-Cys-Albumin stability in six specimens at 23°C, 4°C, and -20°C was also evaluated. Plateaus in the decay curves were reached by 1 day, 7 days, and 14-28 days at these respective temperatures. The estimated pediatric reference range observed in children was lower than that previously observed in 180 adults of 12.3%-30.6% (mean of 20.0%), and the slope of the age correlation in children was twice as steep as that from adults. ΔS-Cys-Albumin decay curves at 23°C, 4°C, and -20°C were similar to those previously observed in adults. The data reported here support the use of ΔS-Cys-Albumin in evaluating the integrity and overall exposure of pediatric EDTA plasma specimens to thawed conditions. In doing so, they add an important quality control tool to the biobanker's arsenal.

Malnutrition is a significant concern in paediatric populations, particularly among children with neurodevelopmental disorders such as foetal alcohol spectrum disorder (FASD). This study aimed to examine macronutrient and micronutrient imbalances and assess the nutritional status of a group of patients with FASD.

This study involved an analysis of the serum levels of key nutrients in a group of children diagnosed with FASD. Macronutrients and micronutrients were measured to identify any imbalances, including vitamin D, B12, E, A, albumin, and serum protein, among others.

The study found a high prevalence of vitamin D deficiency among the patients. Additionally, elevated serum concentrations of micronutrients such as vitamin B12, E, and A were observed in 8%, 7%, and 19% of patients, respectively. Macronutrient imbalances were noted, including high levels of albumin and serum protein, indicating a possible metabolic disturbance. Unexpectedly, high rates of hypercholesterolemia were observed, raising concerns about an increased risk of metabolic syndrome in this population.

These findings suggest that the principal issue among patients with FASD is an altered metabolism rather than nutritional deficiencies. Potential causes of these abnormalities could include oxidative stress and changes in body composition. The results underline the need for further research to better understand the unique nutritional challenges in children with FASD and to guide the development of targeted therapeutic strategies.

Ventricular assist devices (VADs) are used to bridge pediatric patients to heart transplantation. Paracorporeal VADs require the placement of cannulas, which can create an environment for infections. We examined cannula infections in pediatric VAD patients and the role of nutritional status.

This retrospective study (2005-2021) included patients <20 years old on VAD support using Berlin Heart EXCOR® cannulas. Cannula infections were defined by a positive culture and need for antibiotic therapy. Malnutrition was defined using the American Society of Parenteral and Enteral Nutrition guidelines as well as the Michigan MTool.

There were 76 patients with a median age at implant of 0.9 years (IQR 0.4, 3.6), 50% male, with 73.7% having non-congenital heart disease. More than one-quarter (26.3%) of patients developed a cannula infection. Higher pre-implant weight (OR = 1.93, p = 0.05), creatinine (OR = 1.02, p = 0.044), and pre-albumin (OR = 15.79, p = 0.025), as well as duration of VAD support (OR = 1.01; p = 0.003) were associated with increased odds of developing a cannula infection. There was no difference in the malnutrition parameters between those with and without an infection.

Further exploration in a larger cohort is needed to see whether these associations remain and if the incorporation of objective measures of nutritional status at the time of infection are predictive.

Acute kidney injury (AKI) is an acute condition of impaired kidney function with decreased glomerular filtration rate, which results in dysregulation in volume, electrolyte, and acid-base equilibrium. AKI can be a life-threatening condition and can also lead to chronic kidney disease. It is important to diagnose AKI early in the course of the disease or to predict its development, as this can influence therapeutic decisions, outcome, and, consequently, the prognosis. In clinical practice, an elevated serum creatinine concentration remains the most common laboratory indicator for diagnosing AKI. However, due to the delay in its rise, creatinine levels are often insensitive and inaccurate for early diagnosis. Novel biomarkers of kidney tubular injury and the renal angina index have shown promise in predicting AKI earlier and more accurately. Contrast-enhanced ultrasonography (CEUS) and ultra-microangiography (UMA) are radiological methods that can quantify renal microperfusion and may be able to predict the development of AKI. They have not yet been used for quantifying renal perfusion in children with risk factors for developing AKI. Further research is needed to compare these sonographic techniques with the renal angina index and emerging kidney injury biomarkers for predicting acute kidney injury (AKI) in both children and adults.

In the past thirty years, childhood obesity rates have risen significantly worldwide, affecting over 340 million children in affluent nations. This surge is intricately tied to metabolic disorders, notably insulin resistance, type 2 diabetes mellitus (T2DM), and the continually evolving spectrum of metabolic-associated (dysfunction) steatotic liver disease (MASLD). This review underscores the alarming escalation of childhood obesity and delves comprehensively into the evolving and dynamic changes of nomenclature surrounding diverse conditions of hepatic steatosis, from the initial recognition of non-alcoholic fatty liver disease (NAFLD) to the progressive evolution into MASLD. Moreover, it emphasizes the crucial role of pediatric endocrinologists in thoroughly and accurately investigating MASLD onset in children with T2DM, where each condition influences and exacerbates the progression of the other. This review critically highlights the inadequacies of current screening strategies and diagnosis, stressing the need for a paradigm shift. A proposed solution involves the integration of hepatic magnetic resonance imaging assessment into the diagnostic arsenal for children showing insufficient glycemic control and weight loss post-T2DM diagnosis, thereby complementing conventional liver enzyme testing. This holistic approach aims to significantly enhance diagnostic precision, fostering improved outcomes in this vulnerable high-risk pediatric population.

To determine reference intervals (RI) for fasting blood insulin (FBI) in Brazilian adolescents, 12 to 17 years old, by direct and indirect approaches, and to validate indirectly determined RI.

Two databases were used for RI determination. Database 1 (DB1), used to obtain RI through a posteriori direct method, consisted of prospectively selected healthy individuals. Database 2 (DB2) was retrospectively mined from an outpatient laboratory information system (LIS) used for the indirect method (Bhattacharya method).

From DB1, 29345 individuals were enrolled (57.65 % female) and seven age ranges and sex partitions were statistically determined according to mean FBI values: females: 12 and 13 years-old, 14 years-old, 15 years-old, 16 and 17 years-old; and males: 12, 13 and 14 years-old, 15 years-old, 16 and 17 years-old. From DB2, 5465 adolescents (67.5 % female) were selected and grouped according to DB1 partitions. The mean FBI level was significantly higher in DB2, on all groups. The RI upper limit (URL) determined by Bhattacharya method was slightly lower than the 90 % CI URL directly obtained on DB1, except for group female 12 and 13 years old. High agreement rates for diagnosing elevated FBI in all groups on DB1 validated indirect RI presented.

The present study demonstrates that Bhattacharya indirect method to determine FBI RI in adolescents can overcome some of the difficulties and challenges of the direct approach.

Establishing direct reference intervals (RIs) for paediatric patients is a very challenging endeavour. Indirect RIs can address this problem, using existing clinical laboratory databases from real-world data research. Compared to the traditional direct method, the indirect approach is highly practical, widely applicable, and low-cost. Considering the relevance of dyslipidemia in the paediatric age, to provide better laboratory services to the local paediatric population, we established population-specific lipid RIs via data mining.

Our laboratory information system was searched for cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) of patients aged less than 18 years, performed from January 2009 until December 2022. RIs were estimated using RefineR algorithm.

Values from 215,594 patients were initially collected. After refining data on the basis of specific exclusion criteria that left 17,933 patients, we determined the RIs for each analyte, including corresponding 95% confidence interval (95% CI). Age and sex partitions were required for proper stratification of the heterogenous subpopulations. Age-related variations in TC and TG values were observed mainly in children until 5 years. RIs were defined for children less than 3 years and for those of 3-18 years. In our population, the obtained RIs were comparable with those of the literature, but the upper TG limit in subjects under the age of 3 (2.03 mmol/L with 95% CI: 1.45-2.86) was lower than that previously reported.

Our RIs, necessary for paediatric lipid monitoring, are tailored to the serviced patient population as should be done whenever possible.

Acute kidney injury (AKI) is a common and important complication of burn injury. Although there are numerous adult studies, data regarding AKI in pediatric burn patients are scarce. Here, we aimed to evaluate the frequency, clinical features, and prognosis of AKI among pediatric burn injury patients.

This is a retrospective cohort study. Patients aged between 1 month and 18 years who had been followed up between the years 2011 and 2017 were included, and patients with previous kidney disease were excluded. Demographic data, laboratory and clinical variables, management strategies, and outcome data were obtained from the hospital records. Factors associated with AKI were determined by logistic regression analysis.

A total of 697 patients had been followed up, and 87 (12.5%) had AKI. Older age, refugee status, prolonged duration between the incident and time of hospitalization, presence of sepsis, severity and type of burn, volume of fluid administration, intubation status, and accompanying organ failure were all associated with the development of AKI. According to multivariate logistic regression analysis, the most statistically significant factors associated with the development of AKI were older age and increased serum hemoglobin values. In terms of outcomes, length of stay and mortality increased in patients with AKI when compared with patients without AKI.

Similar to adults, AKI is an important and common complication of burn injury in pediatric burn patients and is associated with increased length of stay, morbidity, and mortality. Early recognition and prompt and appropriate management are crucial to avoid morbidity and mortality.

Detecting dyslipidemia early is important because atherosclerosis originates in childhood and early treatment can improve outcomes. In 2022, the Canadian Cardiovascular Society (CCS) and Canadian Pediatric Cardiology Association (CPCA) published a clinical practice update to detect, evaluate, and manage pediatric dyslipidemia. However, guidance on its translation into clinical laboratories is lacking. The Canadian Society of Clinical Chemists Working Group on Reference Interval Harmonization Lipid Team aims to assist guideline implementation and promote harmonized pediatric lipid reporting across Canada. The 2022 CCS/CPCA clinical practice update, 2011 National Heart, Lung, and Blood Institute integrated guidelines, and new data analysis (Canadian pediatric reference values from the Canadian Laboratory Initiative on Pediatric Reference Intervals [CALIPER] and retrospective patient data from large community laboratories) were incorporated to develop 5 key recommendations. These include recommendations to: (1) offer nonfasting and fasting lipid testing; (2) offer a lipid panel including total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, and triglycerides, with apolipoprotein B and lipoprotein(a) available as individually orderable tests; (3) flag total cholesterol, LDL-C, and non-HDL-C results ≥ 95th percentile, and HDL-C results < 10th percentile, as recommended by CCS/CPCA/National Heart, Lung, and Blood Institute and validated by CALIPER, and flag apolipoprotein B and nonfasting triglyceride results ≥ 95th percentile on the basis of CALIPER, and do not flag Lp(a) results but mention the adult cutoff in the interpretive comments; (4) implement interpretive comments listed in the current report; and (5) implement the National Institutes of Health LDL-C equation. The Canadian Society of Clinical Chemists Working Group on Reference Interval Harmonization Lipid Team will support clinical laboratories to implement these recommendations using knowledge translation strategies. Harmonizing pediatric lipid reporting across Canadian clinical laboratories will optimize clinical decision-making and improve cardiovascular risk management in youth.

Scarce knowledge about the impact of metabolism-disrupting chemicals (MDCs) on liver injury limits opportunities for intervention. We evaluated pregnancy MDC-mixture associations with liver injury and effect modification by folic acid (FA) supplementation in mother-child pairs.

We studied ∼200 mother-child pairs from the Mexican PROGRESS cohort, with measured 43 MDCs during pregnancy (estimated air pollutants, blood/urine metals or metalloids, urine high- and low-molecular-weight phthalate [HMWPs, LMWPs] and organophosphate-pesticide [OP] metabolites), and serum liver enzymes (ALT, AST) at ∼9 years post-parturition. We defined liver injury as elevated liver enzymes in children, and using established clinical scores for steatosis and fibrosis in mothers (i.e., AST:ALT, FLI, HSI, FIB-4). Bayesian Weighted Quantile Sum regression assessed MDC-mixture associations with liver injury outcomes. We further examined chemical-chemical interactions and effect modification by self-reported FA supplementation.

In children, many MDC-mixtures were associated with liver injury outcomes. Per quartile HMWP-mixture increase, ALT increased by 10.1% (95%CI: 1.67%, 19.4%) and AST by 5.27% (95% CI: 0.80%, 10.1%). LMWP-mixtures and air pollutant-mixtures were associated with higher AST and ALT, respectively. Air pollutant and non-essential metal/element associations with liver enzymes were attenuated by maternal cobalt blood concentrations ( p -interactions<0.05). In mothers, only the LMWP-mixture was associated with liver injury [OR=1.53 (95%CI: 1.01, 2.28) for HSI>36, and OR=1.62 (95%CI: 1.05, 2.49) for AST:ALT<1]. In mothers and children, most associations were attenuated (null) at FA supplementation≥600mcg/day ( p -interactions<0.05).

Pregnancy MDC exposures may increase liver injury risk, particularly in children. These associations may be attenuated by higher FA supplementation and maternal cobalt levels.

Acute kidney injury (AKI) is associated with long-term consequences and poor outcomes in the neonatal intensive care unit. Its precocious diagnosis represents one of the hardest challenges in clinical practice due to the lack of sensitive and specific biomarkers. Currently, neonatal AKI is defined with urinary markers and serum creatinine (sCr), with limitations in early detection and individual treatment. Biomarkers and risk factor scores were studied to predict neonatal AKI, to early identify the stage of injury and not the damage and to anticipate late increases in sCr levels, which occurred when the renal function already began to decline. Sepsis is the leading cause of AKI, and sepsis-related AKI is one of the main causes of high mortality. Moreover, preterm neonates, as well as patients with post-neonatal asphyxia or after cardiac surgery, are at a high risk for AKI. Critical patients are frequently exposed to nephrotoxic medications, representing a potentially preventable cause of AKI. This review highlights the definition of neonatal AKI, its diagnosis and new biomarkers available in clinical practice and in the near future. We analyze the risk factors involving patients with AKI, their outcomes and the risk for the transition from acute damage to chronic kidney disease.

We aimed to develop a tool for predicting HNF1B mutations in children with congenital abnormalities of the kidneys and urinary tract (CAKUT).

The clinical and laboratory data from 234 children and young adults with known HNF1B mutation status were collected and analyzed retrospectively. All subjects were randomly divided into a training (70%) and a validation set (30%). A random forest model was constructed to predict HNF1B mutations. The recursive feature elimination algorithm was used for feature selection for the model, and receiver operating characteristic curve statistics was used to verify its predictive effect.

A total of 213 patients were analyzed, including HNF1B-positive (mut + , n = 109) and HNF1B-negative (mut - , n = 104) subjects. The majority of patients had mild chronic kidney disease. Kidney phenotype was similar between groups, but bilateral kidney anomalies were more frequent in the mut + group. Hypomagnesemia and hypermagnesuria were the most common abnormalities in mut + patients and were highly selective of HNF1B. Hypomagnesemia based on age-appropriate norms had a better discriminatory value than the age-independent cutoff of 0.7 mmol/l. Pancreatic anomalies were almost exclusively found in mut + patients. No subjects had hypokalemia; the mean serum potassium level was lower in the HNF1B cohort. The abovementioned, discriminative parameters were selected for the model, which showed a good performance (area under the curve: 0.85; sensitivity of 93.67%, specificity of 73.57%). A corresponding calculator was developed for use and validation.

This study developed a simple tool for predicting HNF1B mutations in children and young adults with CAKUT.

After natalizumab discontinuation severe relapses can occur despite pregnancy, but third trimester exposure is associated with neonatal haematological abnormalities (HA). The best time point for stopping natalizumab during pregnancy is unclear.

Prospective, observational cohort with 350 natalizumab exposed pregnancies from the German Multiple Sclerosis and Pregnancy Registry. Clinical disease activity and neonatal outcomes are compared between women with natalizumab discontinuation during (1st Trim-group) versus after the first trimester (maintaining-group) and for subgroup analysis before (<30-subgroup) or after (≥30-subgroup) the 30th gestational week (gw).

Baseline characteristics did not significantly differ between the 1st Trim-group (n=179; median exposure duration: 2.60 gw, IQR 1.30-3.60) and the maintaining-group (n=171; median exposure duration: 30.9 gw, IQR 26.9-33.3). Fewer relapses occurred during pregnancy and the postpartum year in the maintaining-group (25.7%) compared with the 1st Trim-group (62.6%; p<0.001). Women in ≥30-subgroup had a significantly lower relapse risk in the first 6 months postpartum (relapse rate ratio: 0.36, 95% CI: 0.15 to 0.84). In total, 7.5% retained meaningful disability 12 months postpartum. No significant effect on neonatal outcomes were observed, but anaemia (OR: 2.62, 95% CI: 1.12 to 6.52) and thrombocytopaenia (OR: 2.64, 95% CI: 1.15 to 6.46) were significantly more common in the ≥30-subgroup. 21.8% of all neonates were born small for gestational age, independent of the timing of natalizumab discontinuation.

Continuing natalizumab during pregnancy after gw 30 decreases the relapse risk postpartum going along with a higher risk for HA in the newborns. These results add relevant knowledge as a basis for informed risk-benefit discussion.

To determine the reference intervals (RI) for serum levels of IgG, IgM, and IgE in healthy children aged 1-10 years living in central Brazil.

A sample of 1743 healthy children was randomly selected from kindergartens and public schools. Reference intervals were defined by non-parametric rank (Clinical Laboratory Standards Institute, USA), bootstrapping, and Horn's robust methods.

By the rank method, the IgG RI was 792-1771 mg/dL for children of both sexes aged 1-10 years. IgM RI were different for gender and age groups, being 45-196 mg/dL and 34-190 mg/dL for boys aged 1-2 years and 3-10 years, respectively. For girls, the IgM RI were 50-212 mg/dL and 39-212 mg/dL, for ages 1-4 and 5-10 years, respectively. The IgE RI for both sexes and ages 1-10 years was 6-1005 mg/dL. The bootstrap method showed RI similar to the rank method but with slightly different confidence intervals. Horn's robust method determined RI different from those obtained by previous methods.

RI for serum concentrations of IgG, IgM, and IgE were established for Brazilian children aged 1-10 years. This definition will be useful for Brazilian physicians, who will have more adequate parameters for their clinical decision-making.

Cystic fibrosis (CF) may cause a spectrum of hepatobiliary complications, including portal hypertension, multilobular cirrhosis, and liver failure. Current guidelines on the detection and monitoring of hepatobiliary complications in CF were published in 1999. The CF Foundation assembled a committee to evaluate research advances and formulate revised guidelines for CF-associated liver disease. A committee of hepatologists, gastroenterologists, pulmonologists, pharmacists, nurses, dietitians, individuals with CF, and the parents of a child with CF devised "population, intervention, comparison, and outcome" questions regarding hepatobiliary disease in CF. PubMed literature searches were performed for each population, intervention, comparison, and outcome question. Recommendations were voted on with 80% agreement required to approve a recommendation. Public comment on initial recommendations was solicited prior to the formulation of final recommendations. Thirty-one population, intervention, comparison, and outcome questions were assembled, 6401 manuscripts were title screened for relevance, with 1053 manuscripts undergoing detailed full-text review. Seven recommendations were approved for screening, 13 for monitoring of existing disease, and 14 for treatment of CF-associated hepatobiliary involvement or advanced liver disease. One recommendation on liver biopsy did not meet the 80% threshold. One recommendation on screening ultrasound was revised and re-voted on. Through a multidisciplinary committee and public engagement, we have assembled updated recommendations and guidance on screening, monitoring, and treatment of CF-associated hepatobiliary involvement and advanced liver disease. While research gaps remain, we anticipate that these recommendations will lead to improvements in CF outcomes through earlier detection and increased evidence-based approaches to monitoring and treatment.

Chronic kidney disease (CKD) represents one of today's main public health problems. Serum creatinine measurement and estimation of the glomerular filtration rate (GFR) are the main tools for evaluating renal function. There are several equations to estimate GFR, and CKD-EPI equation (Chronic Kidney Disease - Epidemiology) is the most recommended one. There are still some controversies regarding serum creatinine measurement and GFR estimation, since several factors can interfere in this process. An important recent change was the removal of the correction for race from the equations for estimating GFR, which overestimated kidney function, and consequently delayed the implementation of treatments such as dialysis and kidney transplantation. In this consensus document from the Brazilian Societies of Nephrology and Clinical Pathology and Laboratory Medicine, the main concepts related to the assessment of renal function are reviewed, as well as possible existing controversies and recommendations for estimating GFR in clinical practice.

To investigate the relationship between body mass index (BMI) and blood biochemical indicators in early adolescence, and to provide ideas for early prevention of diseases and explore possible disease-related predictors.

3125 participants aged 10 ∼ 14 years were selected from China from the survey of "China Nutrition and Health Surveillance ( 2016 ∼ 2017 ) ". Employing advanced statistical methods, including generalized linear models, heatmaps, hierarchical clustering, and generalized additive models, the study delved into the associations between BMI and various biochemical indicators.

In early adolescence, indicators including systolic pressure, diastolic pressure, weight, height, BMI, hemoglobin, blood uric acid, serum creatinine, albumin, vitamin A presented increasing trends with the increase of age ( P < 0.05 ), whereas LDL-C, vitamin D, and ferritin showed decreasing trends with the increase of age ( P < 0.05 ). The increase in hemoglobin and blood uric acid levels with age was more pronounced in males compared to females ( P < 0.05 ). BMI was positively correlated with blood glucose, hemoglobin, triglyceride, LDL-C, blood uric acid, serum creatinine, ferritin, transferrin receptor, hs-CRP, total protein, vitamin A ( P < 0.05 ). There was a significant BMI × age interaction in the correlation analysis with LDL-C, transferrin receptor, serum creatinine, and hs-CRP ( P < 0.05 ). BMI was a risk factor for hypertension, hypertriglyceridemia, low high density lipoprotein cholesterolemia, and metabolic syndrome in all age groups ( OR > 1, P < 0.05 ).

High BMI was a risk factor for hypertension, hypertriglyceridemia, low high density lipoprotein cholesterolemia, and MetS in early adolescents. With the focus on energy intake beginning in early adolescence, the maintenance of a healthy weight warrants greater attention.

Plasma calprotectin is a promising new biomarker of inflammatory activity and has been found to correlate well with clinical and endoscopic activity in children and adolescents with inflammatory bowel disease. A pediatric reference interval for plasma calprotectin has not been established for the Phadia 250 EliA™ Calprotectin fluoroenzyme immunoassay. In studies regarding pre-analytical properties, excellent precision and stability was found. However, sensitivity to hemolysis was demonstrated. We identified pediatric blood samples from apparently healthy children who were referred by their general practitioner for blood sampling including measurement of hemoglobin (Hb) and C-reactive protein (CRP). We excluded samples from children who had undergone additional blood sampling within 2 months before or after the index sample, if Hb was outside of local reference ranges or CRP levels were above the lower limit of the measuring interval (LLM), and any samples with a hemolysis above 0.02 mmol/L. Using this algorithm, we identified 141 blood samples. No outliers were identified. We established the following reference intervals according to CLSI C28-A3 using non-parametric statistics: 1-17 years: 16-246 µg/L. Our results may prove useful for further utilization of plasma calprotectin as a marker of inflammation in children and adolescents with inflammatory disorders.