Glucocorticoid Therapy In Children Research Articles

Primary nephrotic syndrome relapse within 1year after glucocorticoid therapy in children is associated with gut microbiota composition at syndrome onset.

Children with primary nephrotic syndrome (PNS) who relapse after glucocorticoid therapy are shown to have a decreased total proportion of butyrate-producing bacteria in the gut at onset. Glucocorticoid treatment changes the gut microbiota composition. It is unclear whether gut microbiota at remission right after therapy and gut bacteria other than butyrate-producing bacteria are associated with PNS relapse. PNS relapse of paediatric patients within 1year after glucocorticoid therapy was recorded. The gut microbiota composition, profiled with 16S rRNA gene V3-V4 region sequencing, was compared between relapsing and non-relapsing PNS children at onset before glucocorticoid treatment (preT group) and in PNS children at remission right after treatment (postT group), respectively. The gut microbiota composition of postT children significantly differed from that of preT children by having lower levels of Bacteroides, Lachnoclostridium, Flavonifractor, Ruminococcaceae UBA1819, Oscillibacter, Hungatella and Coprobacillus and higher levels of Ruminococcaceae UCG-013 and Clostridium sensu stricto 1 group. In the preT group, compared with non-relapsing patients, relapsing patients showed decreased Blautia, Dialister and total proportion of butyrate-producing bacteria and increased Oscillibacter, Anaerotruncus and Ruminococcaceae UBA1819. However, relapsing and non-relapsing postT children showed no difference in gut microbiota composition. PNS relapse-associated gut microbiota dysbiosis at onset, which includes alterations of both butyrate-producing and non-butyrate-producing bacteria, disappeared right after glucocorticoid therapy. It is necessary to study the association of the longitudinal changes in the complete profiles of gut microbiota after glucocorticoid treatment with later PNS relapse.

2.76 Too Much Too Soon, and Too Little Known: A Systematic Review of Glucocorticoid-Induced Psychosis in Children and Adolescents

Knowledge is limited regarding the adverse effects of therapeutic glucocorticoids on pediatric mental health outcomes. Glucocorticoid-induced psychosis (GIP) is a rare but severe side effect of high-dose glucocorticoid therapy in children and adolescents. This study identified all reported pediatric cases of true GIP, based on DSM-5 criteria, and defined the presentation, treatments, and outcomes of this condition.

A clinical investigation into the usefulness of fractional exhaled nitric oxide in guiding glucocorticoid therapy in children with bronchial asthma.

The present study aims to investigate the value of fractional exhaled nitric oxide (FeNO) combined with pulmonary function in guiding the dose adjustment of inhaled glucocorticosteroids (ICSs) in children with asthma. A total of 133 children aged 6-12 years with newly diagnosed asthma were enrolled as the study subjects and randomly divided into the experimental group (n=68) and the control group (n=65). After three months of ICS treatment, in the experimental group, the dose of ICSs was adjusted based on the control status of the children and the results of the pulmonary function tests and FeNO assays, and in the control group, the dose was adjusted based on the control status of the children and the results of the pulmonary function tests. After another three months of treatment, the number of acute asthma attacks and the Childhood Asthma Control Test (C-ACT) scores were compared between the two groups, and the outcome of pulmonary function tests and FeNO assays during treatment were analyzed. When examining pulmonary function and FeNO levels, when compared with before treatment, there were no statistically significant differences in either group or between the groups after three months of ICS treatment (P>0.05). After dose adjustment and another three months of treatment, when compared with the control group, the improvement in pulmonary function in the experimental group was greater, the reduction in FeNO levels was greater, the incidence of acute asthma attacks was lower, and the C-ACT score was higher (P<0.05). We concluded that the combination of FeNO assays and pulmonary function tests to guide the ICS dose adjustment in children with asthma could improve asthma control and reduce the risk of acute asthma attacks.

Twice Daily Compared to Three Times Daily Hydrocortisone in Prepubertal Children with Congenital Adrenal Hyperplasia

Introduction: Glucocorticoid therapy in children with congenital adrenal hyperplasia (CAH) must be finely balanced between optimizing adrenal control and minimizing side effects. Twice (BID) rather than three times daily (TID) hydrocortisone may provide similar adrenal control and reduce metabolic risk. We compared BID and TID regimens with respect to adrenal control, growth, and metabolic effects. Methods: A retrospective chart review (n = 128 visits, 36 individual patients) of prepubertal children with classical CAH was conducted at a tertiary care center between March 2007 and February 2020. Adrenal control, growth, and metabolic data were extracted in those taking hydrocortisone BID versus TID. Univariate generalized estimating equations models were performed to analyze the effect of dose frequency on outcomes of interest. Results: Overall, we found no difference in adrenal control (8% vs. 18% poor control) or testosterone levels (9.65 ng/dL vs. 7.62 ng/dL) between the BID versus TID groups. We detected no difference in growth velocity (6.86 vs. 6.32 cm/year) or bone age advancement (11.3 vs. 5.91 months) between the groups. There was no difference in daily steroid dose (12.1 vs. 11.7 mg/m²/day), BMI Z-score (0.43 vs. 0.31), or systolic blood pressure percentile (65.5 vs. 61.7). Conclusion: BID dosing provides similar adrenal control and does not appear to impact growth or bone age advancement. On the other hand, TID dosing does not appear to increase the metabolic side effect profile in this age-group. Dosing should be patient-centered with individualized consideration.

Linear growth and systemic glucocorticoid therapy in children with systemic lupus erythematosus

Background The use of long-term oral glucocorticoid therapy, specifically in the treatment of systemic lupus erythematosus (SLE), has increased in the past two decades. Chronic glucocorticoid use may lead to a linear growth disturbances.&#x0D; Objective To determine the association between linear growth and systemic glucocorticoid therapy in pediatric SLE patients.&#x0D; Methods This retrospective cohort study used medical record data of pediatric SLE patients. All subjects received systemic glucocorticoids. The linear growth parameters recorded in this study were height-for-age z-score (HAZ) and height velocity at 0, 6, and 12 months of treatment. We recorded potential risk factors of linear growth disturbance, such as pubertal status, sex, SLE severity, pulse methylprednisolone use, daily glucocorticoid dose, and nutritional status.&#x0D; Results Of 42 patients with SLE, 83.3% were female, with a mean age of 13 years at diagnosis. Eighteen subjects (42.9%) experienced abnormal height velocity. There was a significant reduction in HAZ between 0, 6, and 12 months of treatment (P=0.016). Between 0 and 6 months of treatment, there was a mean HAZ decrease of 0.11 (P=0.015). There was a trend towards a risk for decreased HAZ at 6 and 12 months of treatment with pulse methylprednisolone (RR 1.25 and 1.27, respectively), as well as for abnormal height velocity (RR 1.73), but they did not reach statistical significance.&#x0D; Conclusion There is a reduction in linear growth in the first 12 months of systemic glucocorticoid therapy in children with SLE. Administration of systemic glucocorticoid significantly reduced HAZ in the first six months of therapy.

Does transitory steroid-induced central hypothyroidism in children treated for haematological malignancies warrant clinical intervention?

Steroid-induced central hypothyroidism (CH) is a frequent but under-diagnosed hormonal disturbance in children treated for acute lymphoblastic leukaemia (ALL) and lymphoma. To determine the occurrence, frequency of symptoms, replacement therapy administration, and association of CH with glucocorticoid therapy in children treated for haematological malignancies. A prospective clinical survey was conducted on 21 patients (61.9% male, mean age 9.1 years) treated in the Children's Hospital Zagreb during 2019, of whom 12 were treated for for ALL and 6 for Hodgkin lymphoma (HL), based on clinical (signs and symptoms) and laboratory data (hormonal status). Overt CH was verified in 15 (71.4%) and mild CH in 3 patients (14.2%). The most common symptoms and signs were fatigue, apathy, and electrolyte imbalance, observed in 50% of CH cases. Hormonal substitutional therapy was initiated in 44.4% of affected patients, during a mean of 2.08 months, with significant clinical improvement. Overt CH was more prevalent in patients with ALL than in those with HL (p = 0.025). Among children with ALL there was no difference in CH occurrence between the prednisone and dexamethasone groups; however, dexamethasone-induced CH was more frequently symptomatic (p = 0.03). The prednisone dosage played no role in CH incidence in patients with HL. Further studies are needed to determine the real incidence of thyroid dysfunction during intensive chemotherapy treatment in children with ALL and lymphoma. Recommendations for optimal hormonal replacement therapy and a follow-up plan for paediatric oncology patients with CH are also urgently required.

Predictive factors for glucocorticoid therapy in children with eosinophilic gastroenteritis.

To study the predictive factors for glucocorticoid therapy by analyzing the association between the clinical features and treatment regimens in children with eosinophilic gastroenteritis. A retrospective analysis was performed on the medical data of 182 children with eosinophilic gastroenteritis who were admitted to Guangzhou Women and Children's Medical Center from January 2012 to December 2020. According to whether glucocorticoids were used, these children were divided into a glucocorticoid treatment group and a control group. The two groups were compared in terms of age, history of allergy, clinical symptoms, laboratory examination results, endoscopic findings, and pathological results of gastrointestinal mucosa. A multivariate logistic regression analysis was performed for the results with statistical significance. Of the 182 children, 36 (19.8%) received glucocorticoid therapy. The rates of hematochezia, anemia, and mucosal ulceration/luminal stenosis under endoscopy and the mucosal eosinophil infiltration count were significantly higher in the glucocorticoid treatment group than those in the control group (P<0.05). The serum albumin level in the glucocorticoid treatment group was significantly lower than that in the control group (P<0.05). The multivariate logistic regression analysis showed that mucosal ulceration/luminal stenosis under endoscopy (OR=10.830, 95%CI: 3.090-37.961, P<0.001) and the increased mucosal eosinophil infiltration count (OR=0.967, 95%CI: 0.941-0.993, P=0.015) were predictive factors for glucocorticoid therapy in children with eosinophil gastroenteritis. Mucosal ulceration/luminal stenosis under endoscopy or a significant increase in the mucosal eosinophil infiltration count based on pathology suggests that glucocorticoid therapy can be considered in children with eosinophil gastroenteritis.

The therapeutic effect of glucocorticoids on children with sepsis: A Meta-analysis

Objective To evaluate the effect of glucocorticoid therapy in children with sepsis. Methods Databases including PubMed, EMbase, The Cochrane Library, Wanfang Data, VIP and CNKI were searched from inception to July 2019 to collect randomized controlled trials(RCTs)about glucocorticoid for children with sepsis.Two independent researchers screened the literature, extracted data, and assessed the risk of bias in the included studies.Data results were analyzed by RevMan5.3 software for Meta-analysis. Results A total of 7 RCTs, involving 1 359 patients were included.The results of Meta-analysis showed that, compared with the control group, the corticosteroid treatment group did not improve mortality(OR=1.09, 95%CI 0.61, 1.97, P=0.76), length of stay(MD=-3.13, 95%CI -8.29, 2.03, P=0.23), PICU stay time(MD=-2.33, 95%CI -5.03, 0.37, P=0.09), mechanical ventilation time(MD=-2.01, 95%CI -4.66, 0.65, P=0.14), in hospital infection rate(OR=1.58, 95%CI 0.27, 9.21, P=0.61). Conclusion The existing evidence shows that glucocorticoid adjuvant therapy can not effectively reduce the mortality, hospital stay, PICU stay time, mechanical ventilation time, hospital infection rate of children with sepsis, but it is limited by the number and quality of the included studies, which needs further large-scale, multicenter, double-blind, randomized controlled trials to verify. Key words: Glucocorticoid; Sepsis; Children; Meta-analysis

Relationship between serum ferritin level and the severity of community acquired pneumonia in children

Objective To analyze the relationship between the level of serum ferritin (SF)and the severity of community acquired pneumonia (CAP)in children, and to explore the timing of glucocorticoid therapy for children with CAP. Methods Retrospective analysis was performed on the clinical data of 738 children with CAP who were hospita-lized at the Department of Respiratory, Beijing Children′s Hospital, Capital Medical University from January 2014 to December 2015.All patients were divided into a mild group and a severe group based on the severity of CAP, and the levels of SF, C-reactive protein(CRP), erythrocyte sedimentation rate(ESR), white blood cell(WBC) and D-dimer were compared between the 2 groups.In addition, the analysis of receiver operating characteristic(ROC) curve was performed to study the usefulness of SF as severity indicators for CAP, and to learn the relationship between the level of SF and the glucocorticoid therapy in children with CAP.Simultaneous analysis of SF and CRP, WBC, ESR, D-dimer was made at the same time. Results (1) There were all 738 children enrolled into this study.There were 442 children in the mild group and 296 children in the severe group.There was no significant difference in age and sex between the mild group and the severe group(all P>0.05). (2)Comparisons between the mild group and the severe group were as follows: days of hospitalization [10.0(9.0, 13.0) days], duration of fever [10.0(7.0, 10.0)days] and heat peak[39.9 ℃(39.1 ℃, 40.1 ℃)]in the severe group, which had significant differences than those in the mild group [days of hospitalization 7.0(6.0, 9.0) days, duration of fever 7.0(5.0, 10.0) days and heat peak 39.3 ℃(39.0 ℃, 39.8 ℃)](all P<0.05). The levels of SF[ 229.0(150.0, 436.2) μg/L], CRP [30.00(9.84, 78.20) mg/L], WBC [8.44(5.91, 12.6)×109/L], ESR [30.5(16.0, 49.0) mm/1 h ]and D-dimer [0.871(0.317, 2.532) μg/L] in the severe group were significantly higher than those in the mild group [SF: 98.0(68.2, 136.1) μg/L, CRP: 11.50(5.77, 11.50) mg/L, WBC: 7.59(5.87, 10.1)×109/L, ESR: 23.0(13.0, 36.3) mm/1 h and D-dimer 0.232(0.159, 0.407) μg/L], and the differences were statistically significant (all P<0.05). (3)The le-vels of SF [258.5(177.8, 404.9) μg/L] and CRP [8.0(8.0, 16.5) mg/L]in CAP children in the recovery phase were significantly lower than those in the acute phase [SF: 912.1(418.7, 1 380.3) μg/L, CRP: 47.4(18.8, 105.8) mg/L]. (4)The level of SF had significantly positive correlations with CRP, ESR, D-dimer (r=0.485, 0.286, 0.611, all P<0.05). (5) The cutoff value for SF, D-dimer for diagnosing severe pneumonia was 168.0 μg/L (sensitivity 70.6%, specificity 86.2%), and 0.616 μg/L (sensitivity 58.1%, specificity 87.1%). (6) There were 17.2% cases (76/442 cases) in the mild group and 52.7% cases (159/296 cases) in the severe group who received systemic glucocorticoid therapy. Conclusion The level of SF was correlated with the severity of CAP in children, and the level of SF in patients in recovery phase was significantly lower than that in the acute phase.When SF ≥168.0 μg/L, D-dimer ≥0.616 μg/L, attention should be paid to the possibility of severe CAP, regarding the indication for systemic steroid therapy for CAP in children. Key words: Serum ferritin; Community acquired pneumonia; Glucocorticoid; Child

Frequency and Duration of Adrenal Suppression Following Glucocorticoid Therapy in Children With Rheumatic Diseases.

Adrenal suppression (AS), a glucocorticoid (GC) side effect with potentially significant morbidity, is poorly understood. The purpose of our study was to determine frequency, duration, and predictors of AS following a gradual taper of GC in children with rheumatic conditions. A prospective, observational cohort study was conducted. All patients ages ≤16 years ready to discontinue GC after >4 weeks of therapy were included. Morning cortisol was tested 4 weeks after GC taper to physiologic doses and then repeatedly until normalization. GCs were subsequently discontinued and a low-dose adrenocorticotropic hormone stimulation test was performed. The study was completed by 31 of 39 patients. The median age was 12.9 years and median duration of GC therapy was 39.6 weeks. Seventeen patients (54.8%) had AS. Of the patients with AS, 50% showed recovery by 7 months. Two patients had persistent AS at 12 months and 1 patient at 2 years. A higher maximum GC dose was a significant predictor for the development of AS. More than 50% of our patients had AS after GC discontinuation, despite a gradual taper of GC. Stress steroids should be considered in children treated with long-term GC, even after steroid discontinuation, to prevent possible adrenal crisis.

Factors influencing cardiovascular risk following termination of glucocorticoid therapy for nephrotic syndrome

This study attempted to identify the cardiovascular risk factors associated with retention of excess weight following termination of glucocorticoid therapy in children with nephrotic syndrome. We performed a retrospective study of 30 Japanese children (18 males, 12 females, aged 1-14years) who had been treated with glucocorticoids for steroid-sensitive nephrotic syndrome and 32 control children (17 males, 15 females, aged 1-15years). The subjects receiving glucocorticoid therapy were divided into a retention group (n=14) or a reduction group (n=16) on the basis of the presence or absence of a maintained body mass index (BMI) following glucocorticoid termination. BMI z-scores, age, gender, blood pressure, serum total cholesterol levels (T-cho), and the dose and duration of glucocorticoid exposure were evaluated in each group during the study period. The retention group had a significantly (P<0.05) increased dose and duration of glucocorticoid exposure, and of T-cho at the time of last visit compared with the control or reduction group. Moreover, logistic regression analysis showed that the adjusted odds ratio for T-cho at the time of last visit in the retention group was significantly higher (P<0.05) relative to the reduction group. Retention of excess weight during the period of remission from nephrotic syndrome following cessation of glucocorticoid therapy was related to the dose and duration of glucocorticoid exposure and was associated with hyperlipidemia, which might enhance cardiovascular risk.

Behavioural abnormalities in children with nephrotic syndrome

Glucocorticoid therapy in children with nephrotic syndrome can lead to many adverse effects including behavioural problems. The present study was undertaken to assess the changes in individual behaviour among different sub-groups of patients with idiopathic nephrotic syndrome (INS) and also to find out the relationship, if any, between different behavioural problems with cumulative dose of steroid therapy. This was a prospective hospital-based study. We assessed behavioural patterns in 131 children and adolescents with steroid-responsive INS aged 1.5-15 years. Fifty healthy children matched for age and gender were included to serve as controls. The Achenbach Child Behaviour Checklist was used to assess individual behaviour. Patients were sub-grouped according to age (1.5-5 and 6-15 years) and disease status (first attack before and after 12-week prednisolone, infrequent relapser, frequent relapser/steroid-dependent). All groups had significantly elevated mean behavioural abnormality scores for dimensions assessed in both age groups, except rule-breaking behaviour. Besides sleep problems, frequent relapsers/steroid-dependent patients exhibited maximum scores in comparison to first attack and infrequent relapsers in the 1.5- to 5-year age group. Total and individual behavioural scores showed close associations with cumulative prednisolone dose in both groups. It is evident that nephrotic syndrome patients should be given due consideration in clinical practice for behavioural abnormalities especially after steroid therapy.

New means to monitor the effect of glucocorticoid therapy in children

To study the individual effects of glucocorticoid (GC) therapy on the state of immune activation in patient serum. We developed a novel assay in which the effect of corticosteroid-treated patient serum on healthy donor peripheral blood mononuclear cells (target cells) was studied, with a panel of markers for effector [interferon (IFN)gamma and interleukin (IL)-5] and regulatory T cells (FOXP3 and glucocorticoid-induced tumor necrosis factor receptor, GITR). The study group comprised 19 children with inflammatory bowel disease. The individual effect of patient serum on target cells was analyzed prior to GC therapy and 2 wk later. The effect of GC therapy mediated by patient serum was seen as a decrease in the target cells expression of regulatory T-cell-related markers GITR (median suppression 24%, range of suppression 1%-63%, in 2 cases increase of 6% and 77%, P < 0.01 for mitogen-activated target cells) and FOXP3 (median suppression 33%, range of suppression 0%-79%, in one case an increase of 173%, P < 0.05 for resting cells), and secretion of IFNgamma [from a mean of 87 700 pg/mL (SD 33 900 pg/mL) to 60 900 pg/mL (SD 44 200 pg/mL) in mitogen-activated target cells, 13 of the cases showed a decrease, P < 0.01]. The total or weight-related prednisolone dose did not correlate with the patient-serum-induced changes in the target cell markers. GC response could be monitored at an individual level by studying the effect of patient serum on signaling pathways of target immune cells.

Fecal calprotectin remains high during glucocorticoid therapy in children with inflammatory bowel disease

Objective. Fecal calprotectin is a promising marker for the assessment of gastrointestinal inflammation. Fecal calprotectin levels were followed-up in children with inflammatory bowel disease (IBD) who were introduced to glucocorticoid therapy. The aim of this study was to assess whether the changes in fecal calprotectin levels reflect therapeutic responses. Material and methods. Fecal calprotectin was measured by enzyme immunoassay in 57 children (mean age 9.8 years, range 0.9–18 years) who underwent colonoscopies (IBD n=31, non-IBD disease n=13, normal n=13) and followed-up in 15 children (mean age 13 years, range 3.6–18 years) who were introduced to glucocorticoid therapy because of active IBD at 0, 2, and 4 weeks and at 4-week intervals until one month after discontinuation of the therapy. Results. Fecal calprotectin was <100 µg/g in 70% of the children with normal findings on colonoscopy or a non-IBD disease. Fecal calprotectin was >100 µg/g in all but one child with active IBD and in 13/15 of those children who were introduced to glucocorticoids by the clinicians. Fecal calprotectin values decreased within 4 weeks in line with clinical improvement in 7 children and normalized in 4/15 children during the follow-up. Fecal calprotectin increased in 5/8 of the non-steroid-dependent children after discontinuation of glucocorticoids. Conclusions. Fecal calprotectin is a sensitive marker for chronic colitis. In active disease treated with glucocorticoids, fecal calprotectin levels declined in line with the clinical improvement but seldom fell within the normal range, which suggests ongoing inflammation in a clinically silent disease. The measurement of fecal calprotectin may provide new tools for the assessment of the level of gut inflammation in children with chronic colitis in the follow-up of clinical responses.

Impaired adrenal function after glucocorticoid therapy in children with acute lymphoblastic leukemia.

Glucocorticoids are commonly used in the treatment of childhood acute lymphoblastic leukemia (ALL). The purpose of this study was to assess the incidence of adrenal insufficiency and the time for children with ALL to recover after treatment with the glucorticoids prednisolone or dexamethasone. Seventeen children, 2-15 years, with ALL were studied after receiving prednisolone (60 mg/m(2)/day, n = 10) for 5 weeks during remission induction therapy or dexamethasone (10 mg/m(2)/day, n = 7) for 3 weeks during reinduction therapy. Both drugs were tapered over 9 days. The adrenal function was assessed by an ACTH stimulation test within 2 weeks after discontinuing glucocorticoid therapy. In case of adrenal insufficiency, the ACTH test was repeated at 3-5 weeks interval, and patients were put on hydrocortisone substitution therapy. Three out of ten patients had a normal adrenal function within the first 2 weeks after prednisolone therapy. Another three patients recovered within 7 weeks, whereas the remaining four patients still showed adrenal insufficiency at the end of follow-up after 2.5-4 months. For dexamethasone, two out of seven patients showed a normal adrenal function within the first 2 weeks. Of the remaining patients, two recovered within 7 weeks, whereas three patients still had a demonstrated adrenal insufficiency at the end of follow-up after 4-8 months. Adrenal insufficiency occurs and may persist for several months in children with ALL after treatment with high doses of prednisolone or dexamethasone.

Hypothalamic-pituitary-adrenal axis suppression after short-term, high-dose glucocorticoid therapy in children with asthma

Short-term, high-dose oral glucocorticoid therapy is often required for control of acute asthma episodes in children. To evaluate possible hypothalamic-pituitary-adrenal (HPA) axis suppression after such therapy, we studied 11 children with just asymptomatic asthma before and at 3 and 10 days after completion of a five-day course of prednisone (up to 2 mg/kg/day in divided doses, maximum dose = 60 mg/day). HPA axis responsiveness was tested by measuring plasma corticosteroid levels before and after insulin-induced hypoglycemia. When these levels were compared to pretreatment levels, there was a statistically significant blunting of the peak corticosteroid responses to hypoglycemia 3 days after completion of the course of prednisone ( p < 0.001). However, corticosteroid responses were normal in all children 10 days after completion of the course of prednisone. We concluded that a single course of short-term, high-dose glucocorticoid therapy in children with asymptomatic asthma produces only transient (<10 days) HPA axis suppression.