Biomarkers In Children Research Articles

The Association between Gut Microbiota and Serum Biomarkers in Children with Atopic Dermatitis.

Background. Currently, it is known that the gut microbiota plays an important role in the functioning of the immune system, and a rebalancing of the bacterial community can arouse complex immune reactions and lead to immune-mediated responses in an organism, in particular, the development of atopic dermatitis (AD). Cytokines and chemokines are regulators of the innate and adaptive immune response and represent the most important biomarkers of the immune system. It is known that changes in cytokine profiles are a hallmark of many diseases, including atopy. However, it remains unclear how the bacterial imbalance disrupts the function of the immune response in AD. Objectives. We attempted to determine the role of gut bacteria in modulating cytokine pathways and their role in atopic inflammation. Methods. We sequenced the 16S rRNA gene from 50 stool samples of children aged 3-12 years who had confirmed atopic dermatitis, and 50 samples from healthy children to serve as a control group. To evaluate the immune status, we conducted a multiplex immunofluorescence assay and measured the levels of 41 cytokines and chemokines in the serum of all participants. Results. To find out whether changes in the composition of the gut microbiota were significantly associated with changes in the level of inflammatory cytokines, a correlation was calculated between each pair of bacterial family and cytokine. In the AD group, 191 correlations were significant (Spearman's correlation coefficient, p ≤ 0.05), 85 of which were positive and 106 which were negative. Conclusions. It has been demonstrated that intestinal dysbiosis is associated with alterations in cytokine profiles, specifically an increase in proinflammatory cytokine concentrations. This may indicate a systemic impact of these conditions, leading to an imbalance in the immune system's response to the Th2 type. As a result, atopic conditions may develop. Additionally, a correlation between known AD biomarkers (IL-5, IL-8, IL-13, CCL22, IFN-γ, TNF-α) and alterations in the abundance of bacterial families (Pasteurellaceae, Barnesiellaceae, Eubacteriaceae) was observed.

Immune Status Assessment using mRNA gene Expression of New Biomarkers in Children with Sepsis and Septic Shock: Role of G-CSF in Improving the Outcome

Immune Status Assessment using mRNA gene Expression of New Biomarkers in Children with Sepsis and Septic Shock: Role of G-CSF in Improving the Outcome

Transmethylation and Oxidative Biomarkers in Children with Autism Spectrum Disorder: A Cross Sectional Study.

We aimed to investigate the potential role of biomarkers of transmethylation, oxidative stress, and mitochondrial dysfunction in children with Autism Spectrum Disorder (ASD) by comparing them with that of typically developing children (TDC) controls. We also tried to correlate them with severity of autism, sensory issues, behavioural comorbidities and developmental quotients 119 with ASD and 52 age and sex matched typically developing children (TDC) controls were enrolled excluding those with chronic-illness or on any antioxidant therapy/multivitamins/anti-epileptic drugs. Median levels of biomarkers- serum homocysteine, cysteine, methionine, urine uric acid-to-creatinine ratio, arterial lactate, serum vitamin E, vitamin B12, folate, Nε-carboxymethyllysine, Nω- carboxymethylarginine (CMA), dityrosine and MTHFR C677T polymorphism were calculated. Children with ASD were further characterised using Childhood Autism Rating Scale-2, Childhood behavioural checklist, child sensory profile 2 caregiver questionnaire, Developmental Profile 3 for any correlation with the various biomarker levels. The median level of serum homocysteine in ASD group was 9 μmol/L(Range, 7- 16μmol/L), which was significantly higher than controls 7 μmol/L(Range, 4- 11μmol/L)(p=0.01). The prevalence of hyper-homocystinemia(>15μmol/L) was 13.4% in ASD as compared to 3.8% in controls with a significant difference(p=0.04). Dityrosine level was higher among ASD children when compared to TDC (9.8 vs 2.2 counts per second(cps), p<0.001). No significant correlation was found between prevalence of hyperhomocysteinemia and severity of autism/DQ/behavioural issues. No significant difference was found between the median levels of other biomarkers. Results support possible role of transmethylation defects and oxidative stress in ASD pathogenesis. Further studies are warranted for a better understanding of ASD pathogenesis.

Effect of Oral Nutritional Supplementation on Health-Related Outcomes and Nutritional Biomarkers in Children and Adolescents with Undernutrition: A Systematic Review and Meta-Analysis.

This systematic review aims to synthesize scientific evidence on the effects of oral nutritional supplementation (ONS) on health-related outcomes and nutritional biomarkers among children and adolescents with undernutrition. The review protocol was reported following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines. A comprehensive keyword and reference search was conducted in seven electronic bibliographic databases: PubMed, Academic Search Complete, Academic Search Premier, CINAHL, Global Health, Web of Science, and Scopus. We identified 14 peer-reviewed articles reporting results from 13 unique studies (eight randomized controlled trials, four pre-post studies, and one observational study). Study participants were recruited from 14 countries/regions, with ages ranging from 1 to 14 years. Outcomes of interest include health-related outcomes (acute diseases and infections) and nutritional biomarkers (e.g., serum iron and zinc). Six of the eight studies examining acute diseases/infections and five of the seven examining nutritional biomarkers reported statistically significant improvement in some, but not all, outcomes. A meta-analysis of three studies found that ONS interventions reduce the incidence of upper respiratory tract infection (URTI) by 39% (95% CI, 0.42-0.91) in children at nutritional risk when compared to dietary counseling (DC) alone. This systematic review suggests that ONS interventions can improve certain health-related outcomes and nutritional biomarkers in undernourished children and adolescents. Specifically, the use of ONS significantly reduces the risk of URTI, highlighting its potential to enhance immune function and break the cycle of undernutrition and infection.

Preclinical Detection of Early Glomerular Injury in Children with Kidney Diseases-Independently of Usual Markers of Kidney Impairment and Inflammation.

Glomerular kidney diseases typically begin insidiously and can progress to end stage kidney failure. Early onset of therapy can slow down disease progression. Early diagnosis is required to ensure such timely therapy. The goal of our study was to evaluate protein biomarkers (BMs) for common nephropathies that have been described for children with Alport syndrome. Nineteen candidate BMs were determined by commercial ELISA in children with congenital anomalies of the kidneys and urogenital tract, inflammatory kidney injury, or diabetes mellitus. It is particularly essential to search for kidney disease BMs in children because they are a crucial target group that likely exhibits early disease stages and in which misleading diseases unrelated to the kidney are rare. Only minor differences in blood between affected individuals and controls were found. However, in urine, several biomarker candidates alone or in combination seemed to be promising indicators of renal injury in early disease stages. The BMs of highest sensitivity and specificity were collagen type XIII, hyaluronan-binding protein 2, and complement C4-binding protein. These proteins are unrelated to inflammation markers or to risk factors for and signs of renal failure. In conclusion, our study evaluated several strong candidates for screening for early stages of kidney diseases and can help to establish early nephroprotective regimens.

Mediterranean Diet and Cardiometabolic Biomarkers in Children and Adolescents

No prior systematic review and meta-analysis has specifically verified the association of Mediterranean diet (MedDiet)-based interventions with biomarkers of cardiometabolic health in children and adolescents. To review and analyze the randomized clinical trials (RCTs) that assessed the effects of MedDiet-based interventions on biomarkers of cardiometabolic health among children and adolescents. Four electronic databases were searched (PubMed, Cochrane Library, Web of Science, and Scopus) from database inception to April 25, 2024. Only RCTs investigating the effect of interventions promoting the MedDiet on cardiometabolic biomarkers (ie, systolic blood pressure [SBP], diastolic blood pressure [DBP], triglycerides [TGs], total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], glucose, insulin, and homeostatic model assessment for insulin resistance [HOMA-IR]) among children and adolescents (aged ≤18 years) were included. A systematic review and meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Data were extracted from the studies by 2 independent reviewers. Results across studies were summarized using random-effects meta-analysis. The effect size of each trial was computed by unstandardized mean differences (MDs) of changes in biomarker levels (ie, SBP, DBP, TGs, TC, HDL-C, LDL-C, glucose, insulin, HOMA-IR) between the intervention and the control groups. The quality of the evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations approach. Nine RCTs were included (mean study duration, 17 weeks; range, 8-40 weeks). These studies involved 577 participants (mean age, 11 years [range, 3-18 years]; 344 girls [59.6%]). Compared with the control group, the MedDiet-based interventions showed a significant association with reductions in SBP (mean difference, -4.75 mm Hg; 95% CI, -8.97 to -0.52 mm Hg), TGs (mean difference, -16.42 mg/dL; 95% CI, -27.57 to -5.27 mg/dL), TC (mean difference, -9.06 mg/dL; 95% CI, -15.65 to -2.48 mg/dL), and LDL-C (mean difference, -10.48 mg/dL; 95% CI, -17.77 to -3.19 mg/dL) and increases in HDL-C (mean difference, 2.24 mg/dL; 95% CI, 0.34-4.14 mg/dL). No significant associations were observed with the other biomarkers studied (ie, DBP, glucose, insulin, and HOMA-IR). These findings suggest that MedDiet-based interventions may be useful tools to optimize cardiometabolic health among children and adolescents.

The Neutrophil-to-Lymphocyte Ratio (NLR) as a Prognostic Biomarker in Children with Guillain-Barre Syndrome (GBS): A Systematic Review (P9-11.003)

The Neutrophil-to-Lymphocyte Ratio (NLR) as a Prognostic Biomarker in Children with Guillain-Barre Syndrome (GBS): A Systematic Review (P9-11.003)

Blood Adhesion Molecules as Biomarkers in Children with Chronic Urticaria.

The prevailing etiological model of both acute and chronic urticaria implicates specific allergen exposure that triggers the local release of vasoactive factors and inflammatory adhesion molecules, including vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), endothelial leukocyte adhesion molecule 1 (ELAM-1), P-selectin and E-selectin in the superficial dermis. This study focused on the possible role of VCAM-1 and ICAM-1 as biomarkers in children with acute and chronic urticaria. This study involved 184 children, 40 with acute urticaria, 71 with chronic urticaria, and 73 matched comparison subjects. The serum levels of ICAM-1 and VCAM-1 were determined in venous blood in all the participants on enrollment. Antihistamine treatment was administered to all the patients. In the children with chronic urticaria, the Urticaria Activity Score Questionnaire (UAS7) was completed daily by the parents. In 16 of the patients with acute urticaria and 43 with chronic urticaria, the serum levels of ICAM-1 and VCAM-1 were determined at follow-up after 6-8 weeks of treatment. The mean serum levels of both VCAM-1 and ICAM-1 were higher in both groups of children with urticaria than in the comparison subjects at the start of the study. In the chronic urticaria group, the levels decreased significantly (p = 0.03 and p = 0.01, respectively) following treatment. Similarly, the acute urticaria group exhibited significant reduction in the mean levels of VCAM and ICAM (p < 0.001). In both groups, the mean level of ICAM after treatment was comparable with that of the comparison group. VCAM-1 and ICAM-1 are suggested as promising biomarkers for monitoring both acute and chronic urticaria in children. Future research should explore their utility in larger cohorts and investigate their role in personalized treatment strategies.

The Soluble Urokinase Plasminogen Activator Receptor as a Severity Biomarker in Children With Acute COVID-19 or Multisystem Inflammatory Syndrome.

Elevated soluble urokinase plasminogen activator receptor (suPAR) has been associated with a poor prognosis in serious infections. The aim of this study was to evaluate the clinical value of suPAR in children with acute coronavirus disease 2019 (COVID-19) or multisystem inflammatory syndrome (MIS-C). Serum suPAR was measured using the suPARnostic AUTO Flex enzyme-linked immunosorbent assay in hospitalized children with COVID-19, MIS-C, bacterial pneumonia, and healthy controls. A total of 211 children with a mean (±SD) age of 6.9 ± 4.96 years were tested; with COVID-19: 59 (28%), MIS-C: 36 (17%), pneumonia: 78 (37%) and healthy controls: 38 (18%). In the acute phase, the levels of suPAR (mean ± SD) were: MIS-C: 8.11 ± 2.80 ng/mL, COVID-19: 4.91 ± 1.90 ng/mL, pneumonia: 4.25 ± 1.44 ng/mL and controls: 2.09 ± 0.47 ng/mL ( P < 0.001). Children with acute COVID-19 and a severe or moderate clinical presentation had higher values than those with mild symptoms: 5.79 ± 1.58 versus 5.40 ± 1.94 versus 3.19 ± 0.73 ng/mL, respectively ( P < 0.001). In the MIS-C group, children hospitalized in the intensive care unit and in need of mechanical ventilation had higher suPAR than those who were not admitted to an intensive care unit: 9.32 ± 3.06 versus 7.13 ± 2.19 ng/mL, respectively ( P = 0.023). In children with COVID-19 or MIS-C, a correlation was detected between suPAR values and length of hospitalization ( rs = 0.418, P < 0.001). The findings suggest that suPAR may be a valuable biomarker of disease severity in children with COVID-19 or MIS-C. This could facilitate the identification of children in need of intensive anti-inflammatory treatment, as it has been shown in adults with severe COVID-19.

CMR 3-118 - Myocardial and Liver T1 Mapping and Circulating Fibrosis Biomarkers in Children with Fontan Circulation

CMR 3-118 - Myocardial and Liver T1 Mapping and Circulating Fibrosis Biomarkers in Children with Fontan Circulation

Comparison of Oral Health and Salivary Biomarkers in Children with Juvenile Idiopathic Arthritis and Healthy Individuals.

This study examines the effects of juvenile idiopathic arthritis (JIA) on the oral health and detectability of inflammatory biomarkers IL-17, tumour necrosis factor-alpha (TNF-α) and total antioxidant status (TAS) in the saliva of children with JIA. This study included 117 participants (39 patients with JIA and 78 systemically healthy subjects aged 8-12 years). Demographic data, responses to an oral health-related questionnaire, saliva samples, periodontal parameters [plaque index (PI), gingival index (GI) and bleeding on probing (BOP)] and dental recordings [facial profile (FP) and dental occlusion relationship (DOR)] were obtained. Enzyme-linked immunosorbent assays were used to determine the levels of salivary IL-17, TNF-α and TAS. The Caries Assessment Spectrum and Treatment (CAST) index, FP and DOR distributions did not change between groups (P > 0.05). JIA patients had more temporomandibular joint (TMJ) discomfort than gingivitis patients and healthy subjects (P < 0.05). JIA patients had greater salivary IL-17 levels than healthy subjects (P < 0.05). The healthy group's TAS was higher than that of the JIA and gingivitis groups (P < 0.05). Saliva TNF-α levels were similar between groups (P > 0.05). PI, GI, BOP and TNF-α were positively associated with salivary IL-17 (P < 0.001). Elevated salivary IL-17 and TAS levels could be used as biological markers for discriminating the clinical health status of children with JIA and gingivitis.

Diagnostic Value of Immunological Biomarkers in Children with Asthmatic Bronchitis and Asthma.

Background and Objectives: This study aimed to investigate the diagnostic value of immunological biomarkers in children with asthmatic bronchitis and asthma and to develop a machine learning (ML) model for rapid differential diagnosis of these two diseases. Materials and Methods: Immunological biomarkers in peripheral blood were detected using flow cytometry and immunoturbidimetry. The importance of characteristic variables was ranked and screened using random forest and extra trees algorithms. Models were constructed and tested using the Scikit-learn ML library. K-fold cross-validation and Brier scores were used to evaluate and screen models. Results: Children with asthmatic bronchitis and asthma exhibit distinct degrees of immune dysregulation characterized by divergent patterns of humoral and cellular immune responses. CD8+ T cells and B cells were more dominant in differentiating the two diseases among many immunological biomarkers. Random forest showed a comprehensive high performance compared with other models in learning and training the dataset of immunological biomarkers. Conclusions: This study developed a prediction model for early differential diagnosis of asthmatic bronchitis and asthma using immunological biomarkers. Evaluation of the immune status of patients may provide additional clinical information for those children transforming from asthmatic bronchitis to asthma under recurrent attacks.

Urinary Protein-Biomarkers Reliably Indicate Very Early Kidney Damage in Children With Alport Syndrome Independently of Albuminuria and Inflammation

Alport syndrome (AS) is a hereditary type IV collagen disease. It starts shortly after birth, without clinical symptoms, and progresses to end-stage kidney disease early in life. The earlier therapy starts, the more effectively end-stage kidney disease can be delayed. Clearly then, to ensure preemptive therapy, early diagnosis is an essential prerequisite. To provide early diagnosis, we searched for protein biomarkers (BMs) by mass spectrometry in dogs with AS stage 0. At this very early stage, we identified 74 candidate BMs. Of these, using commercial enzyme-linked immunosorbent assays (ELISAs), we evaluated 27 in dogs and 28 in children, 50 with AS and 104 healthy controls. Most BMs from blood appeared as fractions of multiple variants of the same protein, as shown by their chromatographic distribution before mass spectrometry. Blood samples showed only minor differences because ELISAs rarely detect disease-specific variants. However, in urine , several proteins, individually or in combination, were promising indicators of very early and preclinical kidney injury. The BMs with the highest sensitivity and specificity were collagen type XIII, hyaluronan binding protein 2 (HABP2), and complement C4 binding protein (C4BP). We generated very strong candidate BMs by our approach of first examining preclinical AS in dogs and then validating these BMs in children at early stages of disease. These BMs might serve for screening purposes for AS before the onset of kidney damage and therefore allow preemptive therapy.

Symptoms, Physical Activity, and Biomarkers in Children at the End of Leukemia Maintenance Therapy.

Background: Symptoms in children with acute lymphocytic leukemia (ALL) change over the trajectory of treatment but little is known about their symptoms as treatment ends. Physical activity may help decrease symptom distress and is vital for ongoing development. The role of biomarkers in symptom science is emerging. The purpose of the study was to explore relationships between self-report of symptoms and physical activity, actigraphy measures, and cerebrospinal fluid (CSF) biomarkers. Methods: Participants were children who were ages 3 to 18 years at the time of ALL diagnosis and were now in the last 12-week cycle of ALL maintenance. Self-reports of fatigue, sleep disturbance, depressive symptoms, and physical activity were completed by participants and parents of younger children. Participants wore a wrist actigraph continuously for the 7 days before other measurements. F2-isoprostanes and interleukin-8 were evaluated in CSF samples. Results: Among the 15 participants, self-report of symptoms and physical activity indicated levels similar to healthy peers. F2-isoprostane had a strong positive correlation with fatigue levels and with depressive symptoms. Fatigue, sleep disturbance, and depressive symptoms positively correlated with each other. Actigraph measures showed children met the CDC guidelines for 60 min of daily moderate to vigorous activity; sleep time was slightly less than healthy norms. Discussion: During maintenance therapy, most children return to healthy norms in symptom burden and physical activity. F2-isoprostane in the CSF is a biomarker for fatigue and depressive symptoms. Children who had persistent symptoms experienced them as a cluster, which confirms previous symptom cluster research.

Transforming Growth Factor Beta 1 as a Potential Biomarker in Children With Sickle Cell Disease.

Ilonze, Chibuzo MD, MPH*; Anderson, Michael PhD†; Stubblefield, Alex MS‡; McNall-Knapp, René MD§; Braly, Emily CRNP§; Journeycake, Janna MD§; Sinha, Arpan A. MBBS, MD§ Author Information

Endothelial and Glycocalyx Biomarkers in Children With Sepsis After One Bolus of Unbalanced or Balanced Crystalloids.

To assess the disruption of endothelial glycocalyx integrity in children with sepsis receiving fluid resuscitation with either balanced or unbalanced crystalloids. The primary outcome was endothelial glycocalyx disruption (using perfused boundary region >2 µm on sublingual video microscopy and syndecan-1 greater than 80 mg/dL) according to the type of crystalloid. The secondary outcomes were increased vascular permeability (using angiopoietin-2 level), apoptosis (using annexin A5 level), and associated clinical changes. A single-center prospective cohort study from January to December 2021. Twelve medical-surgical PICU beds at a university hospital. Children with sepsis/septic shock before and after receiving fluid resuscitation with crystalloids for hemodynamic instability. None. We included 106 patients (3.9 yr [interquartile range, 0.60-13.10 yr]); 58 of 106 (55%) received boluses of unbalanced crystalloid. This group had greater odds of endothelial glycocalyx degradation (84.5% vs 60.4%; adjusted odds ratio, 3.78; 95% CI, 1.49-9.58; p < 0.01) 6 hours after fluid administration, which correlated with increased angiopoietin-2 (rho = 0.4; p < 0.05) and elevated annexin A5 ( p = 0.04). This group also had greater odds of metabolic acidosis associated with elevated syndecan-1 (odds ratio [OR], 4.88; 95% CI, 1.23-28.08) and acute kidney injury (OR, 1.7; 95% CI, 1.12-3.18) associated with endothelial glycocalyx damage. The perfused boundary region returned to baseline 24 hours after receiving the crystalloid boluses. Children with sepsis, particularly those who receive unbalanced crystalloid solutions during resuscitation, show loss and worsening of endothelial glycocalyx. The abnormality peaks at around 6 hours after fluid administration and is associated with greater odds of metabolic acidosis and acute kidney injury.

Impact of IV-line Insertion on Salivary Cortisol Levels as a Stress Biomarker in Children

BACKGROUND: Children with leukemia will be treated for a quite long period of time that they will be subjected to multiple invasive procedures, one of which is IV-line insertion. This procedure can cause stress, which increases cortisol levels in the body. AIM: This study aimed to investigate how IV-line insertion affected cortisol levels as a stress biomarker in children. METHODS: This is a single-group pre-test and post-test design pre-experimental study. The study enrolled 30 children undergoing IV line insertion, aged from 6 to 18 years, who had not been eating or drinking for 30 min before the saliva sampling was scheduled to get IV-line insertion. The ELISA test was used to measure the salivary cortisol. If the difference in the cortisol levels is &gt; 0.05 ng/ml, it is clinically significant. Furthermore, the Wilcoxon test was used to analyze the data. Cortisol changes were considered statistically significant if the p-value was &lt;0.05. RESULTS: The cortisol levels were 3.43 (0.19–16.67) ng/ml and 4.14 (0.19–16.67) ng/ml before and after IV-Line insertion, respectively. The difference in the median was 0.71 ng/ml. The &gt; 0.05 ng/ml difference indicates that IV-line insertion affects cortisol elevation. The Wilcoxon test showed a value of p = 0.34 (p &gt; 0.05) indicating that IV-line insertion had no statistically significant effect on cortisol. CONCLUSION: Although an IV-line insertion does not have a statistically significant effect on cortisol, it clinically influences the increase of cortisol in children with leukemia.

Assessment of Liver Dysfunction Using Combination Biomarkers in Children Living with HIV Infection

Assessment of Liver Dysfunction Using Combination Biomarkers in Children Living with HIV Infection

Prenatal Metal Exposures and Associations with Kidney Injury Biomarkers in Children.

Prenatal exposure to arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) may be nephrotoxic, yet limited studies have examined subclinical kidney injury biomarkers in children. We assessed whether metal exposure in the second trimester (2T), a crucial time of kidney development, is associated with altered urine kidney injury and function biomarkers in preadolescent children. Analyses included 494 children participating in a birth cohort study in Mexico City. Concentrations of As, Cd, and Pb were measured from pregnant women in 2T blood and urine, and Hg in urine only. Kidney biomarkers were measured from children in urine at age 8-12 years. We assessed the associations between individual metals and (1) kidney biomarkers using linear regression and (2) a multi-protein kidney mixture using weighted quantile sum (WQS) regression. Associations of separate urine and blood metal mixtures with individual kidney biomarkers were assessed via WQS. Within the multi-protein mixture, the association with increased urinary As was predominated by urine alpha-1-microglobulin (A1M), interferon gamma-induced protein 10 (IP10), and fatty acid binding protein 1; the association with increased urinary Cd was predominated by A1M, clusterin, and albumin. The urine metal mixture was associated with increased albumin (0.23 ng/mL; 95% confidence interval (CI): 0.10, 0.37), IP10 (0.15 ng/mL; 95% CI: 0.02, 0.28), and cystatin C (0.17 ng/mL; 95% CI: 0.04, 0.31); these associations were mainly driven by urinary As and Cd. We observed null associations between prenatal blood or urine metal mixtures and estimated glomerular filtration rate. Higher prenatal urinary metals, individually and as a mixture were associated with altered kidney injury biomarkers in children. Further research and longer participant follow-up are required to ascertain the risk of kidney disease later in life.

Associations of Prenatal Metals Exposure with Kidney Injury Biomarkers in Children

Background and Aim: Prenatal exposure to toxic metal(loid)s, including arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) during development may have nephrotoxic effects in children. We assessed associations between prenatal metal exposure and urinary kidney injury biomarkers in children. Methods: Analyses included 418 children participating in the PROGRESS birth cohort study in Mexico City. Concentrations of As, Cd, Pb, and Hg (urine only) were quantified in maternal second trimester (2T) blood and urine. Kidney parameters were assessed at 8-10 years of age. We examined associations between individual metals and 1) kidney injury biomarkers using linear regression and 2) a multi-protein kidney index using weighted quantile sum (WQS) regression. Associations of separate urine and blood metal mixtures with individual kidney injury biomarkers were assessed via WQS. Covariates included child’s age, sex, body mass index z-score, urine creatinine, 2T socioeconomic status, and 2T smoking exposure. Results: In single metal analyses, doubling of urine Cd was associated with higher urinary TIMP metallopeptidase inhibitor 1 (TIMP1), alpha-1-microglobulin (A1M), clusterin, and cystatin C. Within the multi-protein index, the association with increased urinary As was predominated by albumin, fatty acid binding protein 1 (FABP1), and interferon gamma-induced protein 10 (IP10), and the association with increased urinary Cd was predominated by albumin, A1M, TIMP1, lipocalin, and FABP1. Decile increases in urine metal mixture was associated with increased urinary albumin, IP10, and cystatin C. Urinary As and Cd comprised 60-96% of the metal mixture weights contributing to the associations. Conclusions: Prenatal urinary metals, individually and as a mixture were associated with increased urinary kidney injury biomarkers in healthy children. Prenatal metals exposure may lead to subclinical glomerular or tubular injury in school age children. Further research is required to ascertain resolution or worsening of subclinical kidney injury at later life stages. Keywords: Heavy metals; Renal health; Mixtures