Iranian Journal of Pediatrics
Volume:32 Issue: 2, Apr 2022

Glucocorticoid (GC) is a fundamental drug used to treat asthma. GC binds to its corresponding receptor (GR) to formulate a complex that increases the production of anti-inflammatory factors and decreases the amount of pro-inflammatory mediators, covering many cytokines. GR is a nuclear receptor superfamily protein, encoded by NR3C1 gene. Studies suggest that polymorphisms of the NR3C1 gene contribute to a decreased response to GC for the treatment of asthma, even leading to drugresistance. Also, TGF-β1 plays a central role in airway remodeling, GC significantly inhibits the production of TGF-β1, and TGF-β1 can induce GC resistance. Thus, it is possible that the polymorphisms of the NR3C1 gene can affect the expression of TGF-β1 mRNA and tissue remodeling.

This study evaluates the effect of polymorphisms (TthIII1, BclI, ER22/23EK, and N363S) of the NR3C1 GR gene on TGF-β1 mRNA expression in children with asthma.

The samples of this study included 52 outpatients (age range: 6 - 14 years) with asthma referred to Huai’an First People’s Hospital, Nanjing Medical University, from January 2018 to June 2019. Meanwhile, 40 healthy volunteers were included as the control group.

The polymorphisms of the NR3C1 GR gene were identified using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and TGF-β1 mRNA levels were measured by real-time reverse transcription (RT)-PCR. TthIII1 and TGF-β1 mRNA expression levels had significant (P = 0.011) correlations. But BclI showed no e effect on TGF-β 1 mRNA, N363S, and ER22/23EK had not been examined.

According to the results, there was a relationship between single nucleotide polymorphisms (SNPs) of the NR3C1 gene and TGF-β1 mRNA in asthmatic children. TthIII1 CC and CT genotype have the strongest induction effect on the expression of TGF-1. The phenomenon suggests that SNPs may be involved in the asthma pathology

Multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 can involve multiple organs, especially the heart, in some children with prior COVID-19 infection. The World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) guidelines provide valuable case definitions for MIS-C, as utilized in this study. We aimed to identify and summarize the echocardiographic findings of MIS-C based on these case definitions.

We performed a systematic search in PubMed, Embase, Scopus, and Cochrane databases. An additional source was also utilized to extend the identified records. The articles underwent a two-step screening process. Then, eligible articles were included in the qualitative synthesis.

We identified 33 eligible studies, recruiting 1,392 patients with MIS-C. Male patients were the majority, with 791 (56.8%) cases. The mean age of the patients was 8.3 ± 5.9 years, while 28.5% of the children were identified with underlying conditions. The most common echocardiographic findings were left ventricular systolic dysfunction (34.91%), valvular regurgitation (29.08%), pericardial involvement (22.58%), and coronary abnormalities (18.0%).

MIS-C is a rare complication of COVID-19 in children. Early cardiologic investigations, especially echocardiography, can reveal manifestations, including myocardial dysfunction, coronary abnormalities, valvular pathologies, and pericardial involvement

High-mobility group box-1 (HMGB1), a nuclear protein, plays an important role in the pathogenesis of HenochSchönlein purpura (HSP). In a Chinese child population, the correlation between susceptibility to HSP and genetic variation in the HMGB1 gene and also the relationship between HMGB1 gene polymorphism and clinical heterogeneity of HSP were investigated.

We analyzed two HMGB1 tag single nucleotide polymorphisms (SNPs; rs3742305 and rs9508752) in 182 HSP patients and 202 healthy controls using the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry method.

There were no significant differences between HSP patients and controls in the frequency of alleles, genotypes, and haplotypes of HMGB1 SNPs. In addition, there was a slight association betweenHMGB1 gene polymorphisms and the clinicalmanifestations of HSP.

It is suggested that the variation of the HMGB1 gene was not highly correlated with the susceptibility of Chinese children to HSP.

Thiamine is an essential coenzyme, reduced in type I and II diabetes. There has been little research on thiamine levels and their role in children with diabetic ketoacidosis (DKA).

This study aimed to analyze thiamine deficiency in this patient group.

A cross-sectional study was done in 2019 - 2020 in Children’s Medical Center, a pediatric referral hospital with 350 beds, on children with type I diabetes hospitalized in the PICU for DKA. A blood sample was taken on admission to obtain biochemical laboratory parameters and measure electrolytes and thiamine levels. Blood gases were taken regularly, and the first pH and first bicarbonate level were measured. The time required for pH normalization and recovery from acidosis was recorded. Hospital stay duration was also calculated. Plasma thiamine measurement was done with a Human Vitamin B1 (VB1) ELISA Kit from Bioassay Technology Laboratory. Data were analyzed with SPSS version 22 software.

Of 62 patients, 56.5% were females with a mean age of 63 months. Thiamine level was 1.61 ± 1.17 µg/dL, and 66.1% of the patients were thiamine deficient. Hospitalization duration was 3.52 ± 0.41 days in the thiamine deficient group and 2.47 ± 0.32 days in the normal group (P value < 0.05). The white blood cell (WBC) count was higher in thiamine deficient patients. Thiamine levels were independently and inversely related to age.

Thiamine deficiency is common among children with DKA and could be a prognostic and therapeutic factor.

Octreotide has been used to control bleeding episodes with variceal origin in the pediatric population. To date, there is no clear evidence of octreotide use for non-variceal bleeding in clinical trials.

We aimed to assess the octreotide efficacy as an add-on therapy to the conventional regimen of proton pump inhibitors for controlling upper non-variceal gastrointestinal (GI) bleeding in the pediatric population.

This prospective randomized controlled clinical trial was performed on pediatric patients aged 1 - 15 years and diagnosed with acute non-variceal upper GI bleeding. The participants were allocated to receive octreotide or placebo and pantoprazole concomitantly. The study was conducted in Mofid Children’s Hospital, Tehran, Iran, during February 2019 - December 2019. Patients with hepatic failure, liver stigma, and coagulopathy due to thrombocytopenia were excluded. Demographic, clinical, and preclinical data were recorded in prepared sheets. All the patients were followed until therapy discontinuation. P-value < 0.05 was considered significant.

Forty-three patients with a mean age of 4.98 ± 3.79 years and confirmed non-variceal upper GI bleeding were included in the present study. Most patients had no specific etiology for their bleeding episodes. Patients in the intervention and control groups received pantoprazole in comparable doses. No differences were observed between the two groups in terms of baseline hemoglobin values (P = 0.08), while final hemoglobin values were significantly higher in the intervention group (P = 0.014). The bleeding duration was not significantly different between the two groups (P = 0.99). Moreover, none of the cases showed adverse drug reactions due to octreotide infusion.

Our study demonstrated that octreotide did not alter bleeding duration or need for blood transfusion. However, positive results were observed for hemoglobin, affecting blood loss volume.

Micronutrients, such as vitamin A, vitamin D, iron, and zinc have several useful functions in the body and are necessary for normal growth and development, especially among children. Unfortunately, recent research has showed different levels of deficiency of these two vitamins among children.

This study aimed to compare the prevalence of micronutrient deficiencies, including vitamin A, vitamin D, iron, and zinc, among under-2- and 6-year-old children in Iran in two National Integrated Micronutrient Surveys (NIMS-I, NIMS-II).

In NIMS studies, sampling was done using a single-stage cluster sampling method. The country was divided into 11 study zones. Using simple random sampling, more than 4,400 individuals (about 400 samples in each zone) were included in each study (NIMS-I, NIMS-II). At least 4-mL venous blood samples were taken from all children and transferred to the central laboratory of Tehran University of Medical Sciences (TUMS) with special identification code for further analysis. Then, the levels of vitamin A, vitamin D, iron, and zinc were measured.

In NIMS-I, the prevalence of vitamin A deficiency among under-2-year-old children was 0.5%, which significantly increased to 18.3% in NIMS-II. Regarding vitamin D deficiency, the rate of deficiency was 3.7% in NIMS-I and 23.3% in NIMS-II, which was statistically significant. In none of the NIMS studies (I and II), vitamin A was measured in under-6-year-old children. Also, in the NIMS-I study, vitamin D was not measured among under-6-year-old children, and in NIMS-II study, the prevalence of vitamin D deficiency was 61.8%. Zinc deficiency among under-2-year-old children in both studies was nearly the same (19.1% vs. 19.4%); but in NIMS-II study, zinc deficiency among under-6-year-old children was 13.6%, which significantly decreased compared to the NIMS-I (31%). Iron deficiency status among under-2-year-old children significantly decreased from 37.8% in NIMS-I to 17.1% in NIMS-II. A significant reduction in iron deficiency status was also observed in the NIMS-II study compared to the NIMS-I in under-6-year-old children (9.9% in NIMS-II compared 18.2% in NIMS-I).

The increase in both vitamin A and vitamin D deficiency rates in NIMS study is alarming. Due to the special roles of these two vitamins in health, special considerations and effective actions are needed in this respect. Data from two national studies indicated a decrease in the prevalence of iron deficiency in both age groups, which could be due to the successful implementation of nutritional intervention programs in Iran, such as iron supplementation and iron fortification.

Respiratory distress syndrome (RDS) is considered one of the most common causes of morbidity in neonates. None of the interventions made in the last three decades to manage this disease has been able to affect the development of RDS as much as surfactant replacement.

Although the standard approach is intubation during surfactant administration, the development of alternative methods in surfactant administration, such as surfactant administration using nebulizers, has been considered that is the aim of the current study.

This randomized controlled trial was conducted on neonates with a gestational age of 28 - 32 weeks with RDS under nasal continuous positive airway pressure (nCPAP) in Beheshti Medical Center in Isfahan, Iran, within March 2018 to August 2020. The neonates requiring the fraction of inspired oxygen ≥ 0.4 for periods longer than 30 minutes to maintain oxygen saturation in the right hand within the range of 89 - 95% while being supported under continuous distending pressure ≥ 5 cm H2O were randomly divided into a control group and an intervention group. Survanta was administered in the control group through INSURE method and aerosolization using mesh nebulizers in the intervention group.

This study showed no significant difference in the arterial/alveolar oxygen ratio gradient after Survanta administration (P-value: 0.10), need for subsequent doses of surfactant (P-value: 0.771) and mechanical ventilation (P-value: 0.145), prevalence of pneumothorax (P-value: 0.50), chronic lung disease (P-value: 0.269), and high-grade intraventricular hemorrhage (P-value: 0.221), duration of nCPAP support (P-value: 0.089), or prevalence of death between the two groups (P-value: 1.00).

Since aerosolization is considered to be a noninvasive method, it is required to perform further studies to improve this approach.

Lymphadenitis is the most common complication following BCG vaccination observed in 0.1% to 1% of children.

The presence of immunodeficiency can increase the probability of lymphadenitis or contribute to its exacerbation, so the early detection of immunodeficiency in those developing lymphadenitis can help prevent its many catastrophic complications.

This study was performed on patients referred to Taleghani Hospital of Gorgan city in 1396. Forty children with lymphadenitis and 40 healthy children entered the study. Serum samples were taken to measure white blood cell counts and the antibodies, including IgE, IgG, IgM, and IgA. Purified protein derivative (PPD) test was done in both groups.

In this study, there were 40 patients with lymphadenitis, of whom 24 were boys (60%), and 16 were girls (40%), and in the control group were 22 boys (55%) and 18 girls (45%). There was no statistically significant difference between the two groups. Lymphadenitis was ipsilateral to the vaccine injection site in all 40 cases, and it was in the anterior axillary region in 82%. Abscess at the lymphadenitis site occurred in 25% of cases. The mean size of induration following PPD in the lymphadenitis group was larger than the control group (5.86 mm and 3.04 mm, respectively) (P = 0.004). There were five patients (12.5%) under one year of age with lymphopenia (lymphocyte count > 3,000), but no lymphopenia was observed in the control group. The mean average IgA and IgM levels were different between the case and control groups (P = 0.001), (P = 0.016), respectively. There was no statistical difference in IgG and IgE levels between both groups (P = 0.92 and P = 0.762, respectively).

This study shows that the size of indurations following PPD injection is higher in those with post-vaccination lymphadenitis. Although the probability of a primary immunodeficiency disorder in the cases of our study was low considering the normal immunoglobulin levels and CBC report, further studies with a larger sample size and more specific investigations, such as flow cytometry and specific antibody response, are needed.

Glutamine (Gln), as a precursor of glutathione and attenuation of pro-inflammatory cytokines, has a vital role in the antioxidant and anti-inflammatory defense of the body. Oxidative stress and inflammatory cytokines increase in respiratory diseases.

We sought to investigate the effect of Gln supplementation on serum levels of some inflammatory and oxidative stress indices in hospitalized children with ARI.

We conducted a 5-day parallel-group, randomized controlled trial. This clinical trial was held for 5 days to assess the efficacy of the 0.5 g/kg body weight Gln, along with medical therapy, in hospitalized children with ARI.

The difference in the high-sensitivity C-reactive protein (hs-CRP) between the Gln and placebo groups was significant after the intervention (analyzed by analysis of covariance [ANCOVA] after adjusting for the duration of cough and biochemical baseline values, 10.67 [7.77] vs 14.04 [6.57], respectively; P = 0.005). Moreover, at the end of the trial, there was no significant difference regarding the duration of hospitalization between the Gln and placebo groups (3.25 [1.37] vs 3.35 [0.8], respectively; P = 0.70).

The effect of Gln supplementation on the reduction of hs-CRP in children with ARI was demonstrated in this study. Further research is needed to determine the exact effect of Gln on inflammatory and oxidative stress biomarkers in children with ARI.

Mortality among children under 5 years is an important health indicator. Therefore, determining the most common causes and manners of death according to the postmortem data is necessary for designing intervention programs to reduce mortality.

This study aimed to evaluate the causes and manners of death in children aged under 5 years old in Tehran, Iran using autopsy findings.

This descriptive cross-sectional study was conducted on the data of all deaths among children aged under 5 years who were referred to the Legal Medicine Organization of Tehran, Iran, during January 2009-December 2019. The data were collected using the checklists of demographic characteristics, autopsy, toxicological findings, pathological findings, hospital records, and judicial documents, which were then analyzed.

Among 1750 children aged under 5 years old included in this study, 898 (51.3%) cases were male, and 997 (56.9%) were hospitalized. Most of the mortality cases occurred about two months after birth. The most common causes of death were found as congenital cardiovascular anomalies (14.7%), pneumonia (11.7%), and preterm labor (11%). Moreover, natural death (77.7%), accidental death (17.7%), homicide (2.7%), and unknown death (2%) were the major manners of death in these children.

Postmortem examination to determine the causes of unnatural death could help clinicians and policymakers to propose a suitable intervention for reducing the mortality rate in children under 5 years.

Nephrotic syndrome (NS), like any other chronic illness, may affect the health-related quality of life (HRQoL) of children, so do the complications related to the disease, and its treatment. A better understanding of the (HRQoL) of people with nephrotic syndrome may help to better guide their treatment.

Sixty children with nephrotic syndrome were assigned as the first case group, besides 81 healthy children as the first control group and 98 children with other chronic illnesses as the second control cohort. The participant and his or her caregiver were asked to fill in the standard HRQoL questionnaire. The patient’s demographic data were also collected and analyzed using SPSS version 26 software.

60 patients with nephrotic syndrome (mean age 9.8±3.7) scored lower grades in physical, social, educational fields as well as total scores than the healthy controls (mean age 9.5 ± 2.7) and higher than the controls with other chronic diseases (mean age 9.7±3.9) (P < 0.05). The emotional QOL score was close to that of the non-healthy control group. No correlation was found between the clinical phenotype of disease regarding the response to steroids and HRQOL (P > 0.05).

The study shows that nephrotic syndrome can affect all aspects of the quality of life of patients. We suggest that comprehensive care of patients with NS be routinely managed in a multidisciplinary clinic with filling HRQOL questionnaires integrated as a common practice.

Tall stature is defined as length or height more than two standard deviations above the mean for age of the reference population. There are different causes of tall stature from a familial trait or a transient anticipation of growth with no major consequences to growth disorders, such as endocrine disorder and syndromic conditions like overgrowth syndromes.

In this study, we reported the case of a 7-year-old girl with tall stature from birth. The patient showed a generalized overgrowth, associated with extremely advanced bone age, dysmorphic features such as a broad forehead and large extremities, and a slight neurodevelopmental delay. Laboratory tests were normal, and the main hormonal disorders were ruled out. The diagnosis of overgrowth syndrome was suspected according to the clinical presentation, and the diagnosis of Weaver syndrome was confirmed by the finding of the pathogenic mutation c.2050C > T p.(Arg684Cys) in EZH2 gene through next generation sequencing (NGS).

Our patient showed phenotypical features related to different overgrowth syndrome characteristics. We underlined the difficulties in reaching a clinical diagnosis in presence of tall stature. The role of molecular biology, particularly genetic analysis by NGS approach, should be considered in cases of tall stature with phenotypic overlap.

Triosephosphate isomerase (TPI) deficiency is an autosomal recessive disease and the most severe form of glycolytic enzymopathies, characterized by hemolytic anemia, neurological disorders, infections, and muscle weakness that can affect breathing and heart function. Signs and symptoms include anemia, pallor, jaundice, fatigue, shortness of breath, muscle weakness, atrophy, movement problems, dystonia, tremors, seizures, cardiomyopathy, and diaphragm weakness.

A three-day female newborn was admitted because of hemolytic anemia. All usual assessments for hemolysis, G6PD, osmotic fragility, RBC morphology and cell panel, minor blood groups, antibody screening, and echocardiography were normal. Neurological manifestations appeared after six months of age, including some seizure-like movements, dystonia, and opisthotonus. Whole exome sequencing confirmed the diagnosis of TPI deficiency with the variant NM-000365.5:c.315G>C chr12- 6978338(hg19) which revealed the mutation of p.Glu105Asp. By the age of two years, in addition to some drugs for neurologic manifestations and folic acid, the patient was hospitalized every 30 - 45 days for blood transfusion or because of pneumonia. The episodes of pneumonia increased after 24 months of age, and finally, the child expired at the age of 34 months due to pneumonia and respiratory failure.

Triosephosphate isomerase deficiency should be considered in all neonates with hemolytic anemia without usual causes.

Cystic fibrosis (CF) is a genetic disorder characterized by CF transmembrane conductance regulator (CFTR) gene defects and chronic inflammation. Management of CF patients is challenging, and no definitive treatment is available. Although evidence suggests that curcumin is effective against inflammation and can regulate ion channels, its effect on CF patients is not well established.

This systematic review evaluated the available evidence for the application of curcumin in experimental models of CF.

The data in this study were selected from articles published in PubMed, ScienceDirect, ProQuest, and Springer until July 2021. Articles on the use of curcumin in CF patients were included based on the purpose of the study. In this review, 11 articles were found in the final search. Then, a quality assessment was performed using SYRCLE’s RoB tool.

Eleven out of 2188 screened studies were eligible for this systematic review. Most in vitro studies (7 out of 8) reported that curcumin influences channel function through a variety of mechanisms, while only 1 study provided comparable results. Regarding anti-inflammatory function, 1 study showed that curcumin could suppress the toll-like receptor 2 (TLR2) gene and protein expression in the CF bronchial epithelial cell line. Two of 3 in vivo studies reported channel correction with curcumin.

The available evidence in this systematic study demonstrates the usefulness of curcumin via different mechanisms among different study models. Given that few studies have been conducted in this field, this systematic review suggests more investigations be undertaken to facilitate generalization to human studies.

Coronavirus disease 2019 (COVID-19) has been infecting children since December 2019 and has caused a severe epidemic and millions of deaths worldwide. COVID-19 has severe clinical effects and is more complicated to manage in patients with underlying diseases, such as congenital heart disease (CHD), past surgical operations, arrhythmia, and end-organ damage.

This study aimed to evaluate the clinical course, follow-up, and treatment process of patients with CHD and COVID-19 in Inonu University Faculty of Medicine, Department of Pediatrics, Turkey during March 2020-February 2021.

This retrospective study was performed on patients with CHD and COVID-19 in the Department of Pediatrics at Inonu University Faculty of Medicine during March 2020-February 2021, selected by making full count sampling. Admission complaints, clinical findings, biochemical parameters, echocardiography results, hospitalization times, treatments, and clinical follow-up findings were retrieved from patients' files.

11 patients with underlying CHD and COVID-19 were evaluated retrospectively during the study. Ten patients were hospitalized and treated due to COVID-19. Treatment of seven of these patients continued in the intensive care unit (ICU), and five were followed up under a mechanical ventilator. Two patients died during follow-up in the ICU.

The clinical course of COVID-19 is severe, and the mortality rate is high in patients with serious diseases, such as underlying CHD. Therefore, COVID-19 in patients with CHD requires more serious and careful follow-up.