Low-grade Inflammation In Children Research Articles

Inverse association between slow-wave sleep and low-grade inflammation in children and adolescents with major depressive disorder

ObjectiveTo investigate the relationship between both self-reported and objective sleep variables and low-grade inflammation in children and adolescents with major depressive disorder (MDD) of moderate to severe symptom severity. MethodsIn this cross-sectional study, we examined twenty-nine children and adolescents diagnosed with MDD and twenty-nine healthy controls (HC). Following a one-week actigraphy assessment, comprehensive sleep evaluations were conducted, including a one-night sleep EEG measurement and self-reported sleep data. Plasma high-sensitivity C-reactive protein (hsCRP) was employed as a marker to assess low-grade inflammation. ResultsNo significant difference in hsCRP levels was observed between participants with MDD and HC. Furthermore, after adjusting for sleep difficulties, hsCRP exhibited no correlation with the severity of depressive symptoms. In HC, levels of hsCRP were not linked to self-reported and objective sleep variables. In contrast, depressed participants showed a significant correlation between hsCRP levels and increased subjective insomnia severity (Insomnia Severity Index; r = 0.41, p < 0.05), increased time spent in the N2 sleep stage (r = 0.47, p < 0.01), and decreased time spent in slow-wave sleep (r = − 0.61, p < 0.001). Upon additional adjustments for body mass index, tobacco use and depression severity, only the inverse association between hsCRP and time spent in slow-wave sleep retained statistical significance. Moderation analysis indicated that group status (MDD vs. HC) significantly moderates the association between slow-wave sleep and hsCRP. ConclusionOur findings suggest that alterations in the architecture of slow-wave sleep may have a significant influence on modulating low-grade inflammatory processes in children and adolescents with MDD.

Integrated gut metabolome and microbiome fingerprinting reveals that dysbiosis precedes allergic inflammation in IgE-mediated pediatric cow's milk allergy.

IgE-mediated cow's milk allergy (IgE-CMA) is one of the first allergies to arise in early childhood and may result from exposure to various milk allergens, of which β-lactoglobulin (BLG) and casein are the most important. Understanding the underlying mechanisms behind IgE-CMA is imperative for the discovery of novel biomarkers and the design of innovative treatment and prevention strategies. We report a longitudinal invivo murine model, in which two mice strains (BALB/c and C57Bl/6) were sensitized to BLG using either cholera toxin or an oil emulsion (n = 6 per group). After sensitization, mice were challenged orally, their clinical signs monitored, antibody (IgE and IgG1) and cytokine levels (IL-4 and IFN-γ) measured, and fecal samples subjected to metabolomics. The results of the murine models were further extrapolated to fecal microbiome-metabolome data from our population of IgE-CMA (n = 22) and healthy (n = 23) children (Trial: NCT04249973), on which polar metabolomics, lipidomics and 16S rRNA metasequencing were performed. Invitro gastrointestinal digestions and multi-omics corroborated the microbial origin of proposed metabolic changes. During mice sensitization, we observed multiple microbially derived metabolic alterations, most importantly bile acid, energy and tryptophan metabolites, that preceded allergic inflammation. We confirmed microbial dysbiosis, and its associated effect on metabolic alterations in our patient cohort, through invitro digestions and multi-omics, which was accompanied by metabolic signatures of low-grade inflammation. Our results indicate that gut dysbiosis precedes allergic inflammation and nurtures a chronic low-grade inflammation in children on elimination diets, opening important new opportunities for future prevention and treatment strategies.

Evaluation of cardiac autonomic function and low-grade inflammation in children with obesity living in the Northeast Brazilian region

ObjectiveEvaluate autonomic function and low-grade inflammation and characterize the correlation between these variables in schoolchildren with obesity living in the Brazilian northeast region. Methods84 children with obesity and 41 with normal weight were included in this cross-sectional study. Anthropometry, body composition, blood pressure (BP), inflammatory biomarkers, and heart rate variability (HRV) indexes were analyzed in children aged 7 to 11 years. Resultschildren with obesity had increased systolic (p = 0.0017) and diastolic (p = 0.0131) BP and heart rate (p = 0.0022). The children with obesity displayed significantly lower SDNN, RMSSD, NN50, HF (ms), HF (nu), SD1, SD2, and higher LF (ms), LF (nu), LF/HF, SD1/SD2, DFA-α1, and DFA-α2, compared to normal weight. A lower and higher capacity for producing IL-10 (p = 0.039) and IL-2 (p = 0.009), respectively, were found in children with obesity compared to children with normal weight. Although IL-2, IL-4 and IL17A did not correlate with HRV parameters, IL-6 was positively correlated with SDNN, LF (ms) and SD2, TNF-α was positively correlated with LF/HF and SD1/SD2 ratio, and IFN-γ was positively correlated with SDNN, RMMSSD, NN50, LF (ms), HF (ms), SD1, and SD2. ConclusionsThe findings suggest that children with obesity have impaired autonomic function and systemic low-grade inflammation compared to children within the normal weight range, the inflammatory biomarkers were correlated with HRV parameters in schoolchildren living in the northeastern region of Brazil.

Autonomic nervous function and low-grade inflammation in children with sleep-disordered breathing.

The objective of the study was to assess the relationship between autonomic nervous function and low-grade inflammation in children with sleep-disordered breathing. We enrolled habitually snoring children aged 3-14 years for overnight polysomnography (PSG) and high-sensitivity C-reactive protein (hsCRP) measurement. Low-grade inflammation was defined as hsCRP >1.0 mg/L to <10.0 mg/L. An electrocardiogram recording was extracted from PSG. Heart rate variability was analyzed using time and frequency domain methods. In total, 190 children were included, with 61 having primary snoring (PS), 39 mild obstructive sleep apnea (OSA), and 90 moderate-to-severe OSA. The average RR interval displayed a significant decline, whereas the low frequency/high frequency (LF/HF) ratio showed an increasing tendency in children with PS, mild OSA, and moderate-to-severe OSA. Mean RR was mainly influenced by age and the apnea hypopnea index (AHI) (all P < 0.01). AHI was an independent risk factor for the altered LF/HF ratio at all sleep stages except N3 stage (all P < 0.05). In the wake stage, low-grade inflammation was an independent risk factor of altered LF/HF ratio (P = 0.014). Autonomic nervous function was impaired in children with OSA. The sympathetic-vagal balance was influenced by low-grade inflammation in the wake stage, whereas it was only affected by AHI when falling asleep. We found that autonomic nervous function was impaired in children with OSA. We found that there was a negative correlation between systemic inflammation and autonomic nervous function in children with SDB only at wake stage. A negative association between systemic inflammation and autonomic nervous function was demonstrated in children in this study. Furthermore, altered LF/HF ratio maybe a good indicator of autonomic nervous dysfunction in children as it only correlated with the SDB severity, not with age.

Role of Procalcitonin As an Inflammatory Marker in a Sample of Egyptian Children with Simple Obesity.

BACKGROUND:Obesity is a multifactorial disease, associated with metabolic disorders and chronic low-grade inflammation. Procalcitonin (PCT) is well known as a biomarker of infection, and systemic inflammation. Recently, it has potential as a marker for chronic low-grade inflammation.AIM:This study aims to evaluate the role of serum PCT as an inflammatory biomarker in the diagnosis of obesity-related low-grade inflammation.METHOD:In this case-control study, 50 obese and 35 normal weight children and adolescents aged 5–15 years were enrolled. Anthropometric parameters were measured in all subjects. Blood samples were collected for measurement of lipid profile, blood glucose, insulin, high sensitivity-CRP (Hs-CRP) and serum procalcitonin. Serum (PCT) levels were assessed using enzyme-linked immunosorbent assay.RESULTS:Obese participants had higher concentrations of serum PCT, total cholesterol, triglycerides, LDL-c, glucose and Hs-CRP than control group. On correlation analysis, procalcitonin had significant positive correlation with (BMI) z-score (P = 0.02), insulin (P = 0.00), insulin resistance (HOMA-IR) (P = 0.006), Hs-CRP (P = 0.02), total cholesterol (P = 0.04) and triglycerides (P = 0.00) in obese group.CONCLUSION:The increased serum procalcitonin concentrations were closely related to measures of adiposity, Hs-CRP and insulin resistance, suggesting that PCT may be an excellent biomarker for obesity-related chronic low-grade inflammation in children and adolescents.

Associations between fatty acids and low-grade inflammation in children from the LISAplus birth cohort study.

Assessing fatty acid (FA) composition in relation to inflammatory markers can shed light on the role of different FA and their metabolism in low-grade inflammation. Existing exploratory studies in children are scarce, and findings inconsistent. We hence aim to analyse associations of FA with common inflammatory markers, high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6), in 10-year-old children. Complete data were available for 958 participants from the 10-year follow-up of the LISAplus (Influence of Lifestyle-Related Factors on the Immune System and the Development of Allergies in Childhood plus the Influence of Traffic Emissions and Genetics) birth cohort study. FA composition was assessed in serum glycerophospholipids. Hs-CRP and IL-6 were categorised into three levels. Associations of FA with inflammatory markers were assessed using multinomial logistic regression, adjusting for potential confounders. Additionally, sex-stratified analyses were carried out. FA exposures associated with significantly higher low-grade inflammation, as indicated by higher hs-CRP or IL-6 levels, included: palmitic acid (PA) (IL-6: P<0.001, 95% confidence interval: 1.30; 2.43), arachidonic acid (AA) (hs-CRP: P=0.002, 1.07; 1.31), n-6 highly unsaturated FA (HUFA) (hs-CRP: P=0.002, 1.06; 1.27), ratio of AA to linoleic acid (AA/LA) (hs-CRP: P<0.001, 1.16; 1.62) and total saturated FA (SFA) (IL-6: P<0.001, 1.77; 3.15). FA exposures associated with reduced levels of inflammatory markers included LA (hs-CRP: P=0.001, 0.84; 0.96; IL-6: P<0.001, 0.69; 0.90) and total polyunsaturated FA (PUFA) (IL-6: P<0.001, 0.57; 0.78). These findings suggest that higher SFA and minor n-6 HUFA, namely PA and AA, are associated with increased low-grade inflammation in children, whereas the major dietary n-6 PUFA and total PUFA are associated with reduced inflammation. Elevated desaturase activity, estimated by the ratio AA/LA, may be associated with higher inflammation, particularly in boys.

The Presence and Duration of Overweight Are Associated with Low-Grade Inflammation in Prepubertal Chilean Children.

Overweight is associated with low-grade inflammation, but it is under debate whether the effect of fat mass accumulation is acute or chronic. We aimed to study the association of overweight duration with low-grade inflammation in children in whom overweight initiation can be established. Observational longitudinal study, including a subsample of 250 Chilean children from the Growth and Obesity Cohort Study followed-up yearly since preschool age (n = 1195). At 4 years, 324 children provided blood. From those, 272 participants were evaluated at 7 years. The current analysis includes 250 children with a blood sample at 4 and 7 years of age and C-reactive protein (CRP) <5 mg/L. Anthropometric data (0-4 years) were obtained from health records and measured thereafter; sex- and age-specific body mass index Z-scores (BAZ) were computed. Among overweight (BAZ ≥ 1) participants at 7 years, the duration of overweight (time since diagnosis) was computed and categorized according to tertiles: <36, 36-<72, or ≥72 months. The independent association between overweight (diagnosis and duration) and low-grade inflammation (CRP ≥ 1 mg/L) was studied (logistic regression models). Overweight was associated with CRP ≥ 1 mg/L at 7 years [odds ratio (OR) = 2.93 confidence interval (95% CI = 1.60-5.38)], but not at 4 years [OR = 1.26 (95% CI = 0.71-2.26)]. An overweight duration <36 m was independently associated with CRP ≥ 1 mg/L [OR = 3.53 (95% CI = 1.21-10.28)] (reference = normal weight), whereas longer overweight durations (36-<72 or ≥72 m) were not associated with CRP ≥ 1 mg/L [OR = 1.35 (95% CI = 0.41-4.40) and OR = 1.21 (95% CI = 0.35-4.18), respectively]. Overweight at 7 years of age was associated with low-grade inflammation only in the case of recent onset. Inflammatory disturbances may be associated with the early phases of excess weight.

Socioeconomic status inequalities in low-grade inflammation during childhood

BackgroundFamily socioeconomic status (SES) is an important source of child health disparities in the USA. Chronic stress is one way SES may impact children's physiology with implications for later health...

Whole-blood fatty acids and inflammation in European children: the IDEFICS Study.

Fatty acids are hypothesized to influence cardiovascular disease risk because of their effect on inflammation. The aim of this study is to assess the relationship between whole-blood fatty acids (WBFAs) and high-sensitivity C-reactive protein (hs-CRP) in European children. A total of 1401 subjects (697 boys and 704 girls) aged between 2 and 9 years from the IDEFICS (Identification and prevention of Dietary- and lifestyle-induced health EFfects in Children and infantS) study were measured in this cross-sectional analysis. The sample was divided into three categories of hs-CRP. Associations between WBFA and hs-CRP were assessed by logistic regression models adjusting for body mass index (BMI), country, age, breastfeeding, mother's education and hours of physical activity. Linoleic acid (LA) (P=0.013, 95% confidence interval (CI): 0.822-0.977) and sum of n-6 WBFA (P=0.029, 95% CI: 0.866-0.992) concentrations were associated with lower concentrations of hs-CRP in boys. In girls, a high ratio of eicosapentaenoic acid (EPA)/arachidonic acid (AA) was associated (P=0.018, 95% CI: 0.892-0.989) with lower hs-CRP concentrations. In contrast, sum of blood n-6 highly unsaturated fatty acids (P=0.012, 95% CI: 1.031-1.284), AA (P=0.007, 95% CI: 1.053-1.395) and AA/LA ratio (P=0.005, 95% CI: 1.102-1.703) were associated (P<0.05) with higher concentrations of hs-CRP in girls. The n-6 WBFAs (sum of n-6 FA and LA) were associated with lower hs-CRP in boys and with higher hs-CRP in girls (AA, sum of n-6 highly unsaturated and AA/LA ratio). More studies are needed to identify the optimal levels of WBFAs to avoid low-grade inflammation in children considering the differences by sex and BMI.

Relationship between serum γ-glutamyltransferase level and leukocyte count in Korean children and adolescents

Background. Elevated γ-glutamyltransferase (GGT) is an important risk factor for cardiometabolic diseases, which may result from chronic low-grade inflammation. Leukocyte count is widely considered a marker of inflammation and is also an independent predictor of cardiometabolic diseases. This study aimed to determine the relationship between GGT and leukocyte count in a representative sample of Korean children and adolescents. Methods. A nationwide cross-sectional study was conducted to examine the relationship between GGT and leukocyte count in 830 boys and 714 girls (aged 10–18 years), using data from the 2010–2012 Korean National Health and Nutrition Examination Survey. The odds ratios (ORs) and 95% confidence intervals (CIs) for high leukocyte count (≥ 75th percentile) were calculated across GGT quartiles using multiple logistic regression analyses. Results. Leukocyte count gradually increased in accordance with serum GGT quartiles in both boys and girls (all p-values < 0.001). The OR (95% CI) for high leukocyte of the highest GGT quartile was 2.19 (1.05–4.58) for boys and 2.36 (1.13–4.93) for girls after adjusting for age, BMI, blood pressure, total cholesterol, triglyceride, physical activity, household income, and residential area. Similarly, these positive associations were observed in multiple logistic regression analysis using log2-transformed serum GGT as a continuous variable. Conclusions. The present study demonstrates a positive relationship between serum GGT and leukocyte count. These findings indicate that serum GGT may be closely related with subclinical low-grade inflammation in children and adolescents.

The correlation of right 2D:4D finger length ratio to the low-grade inflammation marker IL-6 in children. The Healthy Growth Study

BackgroundSecond to fourth digit ratio (2D:4D) is associated with cardiometabolic risk in adults. AimTo examine the association of right 2D:4D with cardiovascular disease risk factors in children. Study designCross-sectional study. SubjectsA sample of 301 children (53.5% girls) aged 9–13 in Greece and their parents. Children who were sick during the previous week of examination (n=44) were excluded from the analyses. Outcome measuresSocio-demographic (gestational age, birth weight, age, gender, maternal education level), anthropometric (body weight and height, finger length), clinical (pubertal stage, sickness during the previous week of the examination), blood [serum high sensitivity C-reactive protein (CRP), serum high sensitivity interleukin-6 (IL-6), serum leptin], lifestyle (dietary intake, maternal smoking during pregnancy) and physical fitness (handgrip strength) data were collected. CRP, IL-6 and leptin were measured with ELISA, using standard equipment and procedures, in accordance with manufacturers' instructions. ResultsFull data were available for 257 children (52.1% girls). The rank values of right 2D:4D and IL-6 were included in the analyses. Right 2D:4D was correlated only with IL-6 at a bivariate level (r=0.216, p=0.012) in girls. At a linear multivariate level, this association remained significant, even after adjusting for several potential confounders such as age, Tanner stage, maternal education level, body mass index, maternal smoking during pregnancy, duration of pregnancy, protein-, carbohydrate-, fat-intake and physical fitness (β±SE=0.220±0.066, p=0.001). ConclusionsRight 2D:4D was found to be associated with IL-6 in girls. Right 2D:4D may be a valuable, simple screening tool of low-grade inflammation in children.

Nocturnal activity of 11β-hydroxy steroid dehydrogenase type 1 is increased in type 1 diabetic children

AimThe objective of this study was to investigate low-grade inflammation in children with type 1 diabetes (T1D) and its association with cortisol levels as well as its bioavailability through 11β-hydroxy steroid dehydrogenase type 1 (11β-HSD1) activity. MethodsChildren with T1D (n=45) and their non-diabetic siblings (n=28) participated in the study. Interleukin-6 (IL-6) and high-sensitivity C-reactive protein (CRPhs) were measured between 1400 and 1800h. Glucocorticoid metabolites were measured in the first morning urine on clinic day and 11β-HSD1 activity was estimated by tetrahydrocortisol/tetrahydrocortisone (THF/THE) ratio. ResultsDiabetic patients presented with an increased THF/THE ratio compared with controls (median: 0.68 [range: 0.45–1.18] vs 0.45 [0.27–0.98], respectively; P<10–3). There was no difference between diabetic patients and controls for IL-6 (0.6ng/mL [0.6–6.8] vs 0.6 [0.6–2.2], respectively; P=0.43) and CRPhs (0.4mg/L [0–7.4] vs 0.3 [0–8.2]; P=0.26, respectively). When adjusted for age, gender and BMI, the THF/THE ratio was significantly associated with CRPhs (β=0.32, P=0.02) in diabetic patients, but not in controls. ConclusionLow-grade inflammation assessed by plasma CRPhs and IL-6 concentrations was not detectable in our cohort of T1D children. Nocturnal 11β-HSD1 activity was increased and associated with plasma CRPhs concentration in diabetic patients. These results may be explained by either a direct or inflammation-mediated effect of the relative hepatic lack of insulin due to subcutaneous insulin therapy.

Is duration of breastfeeding in infancy associated with serum uric acid levels and markers of low-grade inflammation in children

Is duration of breastfeeding in infancy associated with serum uric acid levels and markers of low-grade inflammation in children

Is duration of breastfeeding in infancy associated with serum uric acid levels and markers of low-grade inflammation in children

Is duration of breastfeeding in infancy associated with serum uric acid levels and markers of low-grade inflammation in children

Absence of insulin resistance and low-grade inflammation despite early metabolic syndrome manifestations in children born after in vitro fertilization

To investigate the metabolic profile, traditional adipokines, and indices of insulin resistance and low-grade inflammation in children born as a result of IVF compared with spontaneously conceived controls. Cross-sectional, case-control study. IVF Section of the First Department of Obstetrics and Gynecology and the First Department of Pediatrics of the University of Athens. One hundred six children conceived after classic IVF and 68 age-matched spontaneously conceived controls, aged 4-14 years. Children underwent physical examination and morning fasting samples were collected. Lipid profile, circulating fasting glucose, insulin, leptin, adiponectin, high-sensitivity interleukin-6, and high-sensitivity C-reactive protein were determined and the fasting glucose-to-insulin ratio was calculated. Children born as a result of classic IVF had significantly higher systolic and diastolic blood pressures (BP) and triglycerides than controls. These BP differences remained significant even after correction for birth size and multiple births. No significant differences in biochemical indices of insulin resistance, circulating adipokines, and inflammatory markers were detected before or after these same corrections. Despite an increase of BP, children born as a result of IVF have no biochemical evidence of insulin resistance, including fasting glucose-to-insulin ratio and circulating adipokines, or low-grade chronic inflammation. However, the long-term impact of periconceptual manipulations should be closely monitored.

Early Life Origins of Low-Grade Inflammation and Atherosclerosis Risk in Children and Adolescents

To examine the relationship between birth weight and later low-grade inflammation in children and adolescents. We selected 166 children (49.4% boys; aged, 9.5 +/- 0.3 years) and 126 adolescents (43.7% males; aged, 15.5 +/- 0.4 years) from the Swedish part of the European Youth Heart Study. Birth weight data were collected from parental recall. Low-grade inflammatory markers include C-reactive protein, fibrinogen, and complement factors C3 and C4. Fatness was measured by the sum of 5 skinfold thicknesses. Cardiorespiratory fitness was measured with a maximal ergometer bike test. The association between birth weight and low-grade inflammatory markers was examined with multiple regression analyses. Birth weight was negatively associated with fibrinogen (beta = -0.059; P = .036), C3 (beta = -0.019; P = .010), and C4 (beta = -0.024; P = .031), after controlling for sex, pubertal status, mother's body mass index and socioeconomic status, fatness and fitness. Birth weight was not associated to later C-reactive protein level (all P > .1). Our results showed that smaller birth weight is associated with chronic low-grade inflammation in children and adolescents. Because of the implication of complement factors on atherosclerosis process, these results contribute to explain the increased cardiovascular risk associated with low birth weight.

C-reactive protein and body mass index in children: Findings from the Third National Health and Nutrition Examination Survey, 1988-1994

Objectives: To examine the relationship between C-reactive protein (CRP) concentration and body mass index (BMI) in children. Study design: With the use of data from 5305 children aged 6 to 18 years in the Third National Health and Nutrition Examination Survey (1988 to 1994), a cross-sectional health survey, we examined whether CRP concentrations were elevated among overweight children. Results: Among children whose BMI was below the age- and sex-specific 15th percentile, 6.6% of boys and 10.7% of girls had an elevated CRP concentration (>2.1 mg/L) compared with 24.2% of boys and 31.9% of girls whose BMI was ≥95th percentile. After adjustment was done for age, sex, race or ethnicity, poverty income ratio, high-density lipoprotein cholesterol concentration, white blood cell count, and history of chronic bronchitis, the adjusted odds of having an elevated CRP concentration were 2.20 (95% CI 1.30, 3.75) for children with a BMI of 85th to <95th percentile and 4.92 (95% CI 3.39, 7.15) for children with a BMI of ≥95th percentile compared with children who had a BMI of 15th to <85th percentile. The associations did not differ significantly by age, sex, or race or ethnicity. Conclusions: In a large representative sample of US children, CRP concentration was significantly elevated among children with a BMI ≥85th percentile, thus confirming previous findings of this association in children and extending previous research in adults to children. Excess body weight may be associated with a state of chronic low-grade inflammation in children. (J Pediatr 2001;138:486-92)