Iranian Journal of Pediatrics
Volume:29 Issue: 2, Apr 2019

Keyvan Mazda, the famous, world known pediatric orthopedic surgeon passed away on the 3rd of October 2018 at age 59 in Paris. He was born on 1959 in Abadan (Iran) (1, 2) and during his childhood left to France with his family. He studied medicine in France and became a great pediatric orthopedic surgeon, working in Robert Debré Hospital in Paris (3, 4). He worked generously for incapable and disabled children all over the world with Médecins sans Frontiers (Doctors without Borders, the French Medical Non-Governmental Organization) and, La Chaîne de l’Espoir (Chain of Hope, the French Charity Non-Governmental Organization), in Iran and Afghanistan and other countries (3). He invented new methods and devices of pediatric orthopedic surgery and was universally well known for his endeavors and innovations in children’s spinal surgery. During the past 12 years he used to came to Iran frequently and operated many underprivileged patients with scoliosis in Children’s Medical Center, Sina, Shariati. and Noorafshar hospitals. In Tehran his clinic was the host and receptive of ill children from all over the country. Many Balouch, Kurds, Turks, Arabs, and other ethnicities of our colorful and diverse Iran used to come to his clinic. Zanjireyeh-Omid Charity Institute (the Iranian Charity Organization) supported his team and his patients during his visits to Iranian hospitals (5). Dr. Mazda also generously received Iranian physicians in his clinic in France in order to improve their clinical and surgical skills (5, 6). He was Iranian-French, with Zoroastrian roots (2) and maybe that is why he had the feeling to follow the Zoroastrian ancient attitude of “good thoughts, good words and good deeds” of his origin. However these humans are far from being defined by religion and nationality but Iranians and Iranian physicians are proud to be his compatriot. In the era of supremacy and domination of material things he is the example we were searching for, however he mentioned once “I am not an example, I am just trying to be myself”. He had more than one hundred publications in medical journals and developed the Universal Clamp method for spinal scoliosis surgery and invented new methods and instruments in spinal surgery (7, 8). But his great achievement has been the good deeds, charity working and the benevolence in the era of violence of our time. We, doctors of Children’s Medical Center Hospital, had the honor and privilege of working with him in our hospital and we express our sincere condolences to his family, Iranians, the Zoroastrian community and all physicians and humans who wish and try to follow his path.

Infantile nephrotic syndrome (INS) refers to disease that is present after the first three months of life up to one year of age. There is genetic heterogeneity and genotype-phenotype correlation is not clear. The focus of the present study was to analyze genotypic and phenotypic features of both NPHS1 and NPHS2 genes in INS. Clinical data, mutational analysis, histology, treatments, and outcomes of 48 children with NS are evaluated. A direct sequencing of NPHS1 gene and NPHS2 gene was performed. Patients were classified into 3 groups; group 1: cases having only NPHS1 mutation; group 2: cases with only NPHS2 mutation; group 3: cases without any mutation. The mean age at onset of the disease was 8.7 ± 2.3 months, and mean follow-up time was 8.3 years. Seven familial and 41 sporadic cases of INS were found. Kidney biopsy was performed in 45 out of 48 patients and pathological investigations revealed focal segmental glomerulosclerosis in 29 (65%), IgM nephropathy in 6 (13%), and minimal change disease in 10 patients (22%). There were 5 (10.4%) cases in group 1 (patients having only mutations of NPHS1) and 13 cases (27%) in group 2 (patients having only mutations of NPHS2). Thirty cases (62.5%) had neither NPHS1 nor NPHS2 mutation (group 3). The genotypic and phenotypic features of INS were demonstrated. We found that INS with podocin mutation has poor prognosis according to exonal distribution. NPHS1 mutations caused a severe disease but with a more favorable prognosis.

To evaluate fetal cardiac changes in gestational diabetic mothers, compared to healthy ones by means of different indices and to determine which index can first represent the alterations. The study was conducted as an observational cross-sectional study, including 25 pregnant women with gestational diabetes as the cases and 50 healthy pregnant women as the controls. The preload index, left and right side myocardial performance index (MPI), Interventricular septal hypertrophy, the left and right side cardiac output were assessed in all the patients. The gestational ages were 31.65 ± 8.02 and 31.64 ± 5.37 weeks in case and control group respectively, without any significant difference. Both of the left and right ventricular MPI did not differ statistically between the case and controls. The cases had a greater Interventricular septal hypertrophy but the cardiac output was similar. The preload index was higher in the fetuses of the gestational diabetic mothers. In our study, the MPI did not show any difference between the fetuses of the gestational diabetic mothers and non-diabetic ones; but, fetuses of gestational diabetic mothers had a greater value of PLI, representing early diastolic function changes in right heart even before the overt heart failure occurred. This could be a sign of vasculopathy in gestational diabetic mothers.

This study aimed to evaluate parasitic infections in children with allergic rhinitis (AR) referring to a tertiary center in Egypt. A case-control study was conducted on 139 children (78 males) with allergic rhinitis aged from 6 to 14 years attending Assiut University Hospitals, as well as 70 healthy children as controls. All participants underwent stool analysis, serology for IgG antibodies to Toxocara canis, IgE antibodies to Ascaris lumbricoides, serum IL-5 levels, and urinary leukotriene E4. AR patients showed significantly higher values of absolute eosinophilic count (AEC), IL-5, urinary leukotriene E4, and total IgE than controls. Anti-Ascaris IgE and IgG anti- Toxocara canis were positive in 18.7% and 18% of patients respectively. Giardia infection was detected in stools of 20.1% of patients. Patients with parasitic infections showed significantly higher AEC, serum IL-5, and urinary leukotriene E4 values than those with negative infection and controls. Our study revealed that infections with Ascaris, Toxocara, and Giardia were more common among AR children compared to healthy children and they were significantly associated with disease severity so the infection with these parasites may be a risk factor for AR among Upper Egyptian children.

The aim of this study was to evaluate the importance of abdominal pain in children with paroxysmal supraventricular tachycardia (PSVT). The authors reviewed the medical records of patients aged between three and 18 years old, who were diagnosed and treated for PSVT between March, 2011 and February, 2016. According to the presence of abdominal pain, they were grouped and analyzed for the difference of patient’s age, gender, interval between symptom onset and diagnosis, response to adenosine infusion, and the relationship with levels of N-terminal fragments of pro-brain natriuretic peptide (NT-proBNP). A total of 43 patients (24 males and 19 females) were registered and the mean age at diagnosis of PSVT was 10.65 ± 4.81 years old. Although palpitation was the most common symptom (n = 29, 67.4 %), abdominal pain was also common (n = 18, 41.9%) with more frequent symptoms under 10 years old (n = 15/16, 93.8% versus n = 3/27, 11.1% in older than 10 years old). The PSVT patients with abdominal pain (group 1) were younger, had more frequent vomiting, less palpitation, and longer time to diagnosis of PSVT than subjects without this complication (group 2). In group 1, the level of NT-proBNP was shown significantly higher than group 2 (776.07 ± 913.57 versus 93.72 ± 51.25 pg/mL, P < 0.001). Abdominal pain may be an initial presentation of PSVT in children, especially under 10 years old.

Russell-Silver syndrome is a rare heterogeneous genetic disorder that is mostly known because of its prenatal and postnatal growth retardation. Patients with Russell-Silver syndrome have syndromic facial appearance, as well as some other common clinical features. Disrupted methylation of 11p15 is the most common genetic abnormality that is seen in these patients, called as one of the tire molecular studies in diagnostic guidelines. In the present study, the methylation status of 11p15 was evaluated in a group of children with clinical diagnosis of Russell-Silver syndrome in Iran. A total number of 15 children with a clinical diagnosis of Russell-Silver syndrome were enrolled in this descriptive study. Children’s DNA was extracted by the salting-out method and the 11p15 region was assessed by the methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) method. The correlation of molecular results was then evaluated with clinical features. The mean age of children was 4.5 years and most of them were male. Among 15 children, four children had a confirmed molecular diagnosis of Russell-Silver syndrome according to the MS-MLPA results. All of these four patients had low set ears, high peach voice, micrognathia, failure to gain weight, growth failure, and triangular face. Less than one-third (26.6 %) of our patients had confirmed Russell-Silver syndrome by the MLPA analysis. This experiment showed that Russell-Silver syndrome with abnormal 11p15 methylation was less frequent in our population and showed similar clinical findings in comparison with other studies.

Neonatal jaundice resulting from raised blood bilirubin levels is one of the most common clinical conditions that needs medical attention. To initiate appropriate management that can both prevent and treat severe neonatal jaundice, screening methods that measure bilirubin level are warranted. In this study, we present an Android OS-based application for detecting neonatal jaundice. We used the application to detect jaundice in 113 neonates. Our smartphone-based estimation of bilirubin levels depends on a smartphone, a color calibration card, and a 100X zoom microscope clip. Our application was designed to acquire images of the newborn’s forehead skin in a standardized manner, estimate the average R, G, B scores of the images that have been taken from the forehead skin and calibration card, and then convert them to hue, saturation, intensity (HSI) parameters. All these are performed offline; in this application, we used offline machine learning and regression techniques for analysis Our smartphone-based estimation of bilirubin levels had a sensitivity of 68% and specificity of 92.3% for estimating the bilirubin levels of less than 10 mg/dL and sensitivity of 82.1% and specificity of 100% for estimating the bilirubin levels of less than 15 mg/dL. Our application-based estimation of bilirubin levels had the correlation of 0.479 with the total serum bilirubin values. Our results suggest that our smartphone-based application can serve as a promising screening tool for neonatal jaundice, and it can aid in determining neonates requiring a blood draw for measuring total serum bilirubin level.

The incidence of gallstones in children has increased in recent years. Risk factors that increase the formation of bile duct stones have been described in children, and discussions are ongoing about surgical indications of uncomplicated gallstones. This study aimed to investigate the impact of risk factors on gallstone-induced complications and identify surgical indications for uncomplicated gallstones in children. Patients who had a cholecystectomy in the pediatric surgery clinic between October 2011 and January 2018 were evaluated. Data including age and sex, body mass index (BMI), associated risk factors, gallstone-induced complications, postoperative complications, postoperative complaints, and pathological results were recorded. Seventy-two patients were included in the study. The mean age was 13.2 years with a female-to-male ratio of 2.27:1. Obesity was the most common risk factor (25%). A total of 44% of the patients experienced a complication on admission. The risk factors had no effect on the development of complications. The patients underwent cholecystectomy, but some symptoms persisted in thirteen patients postoperatively (18.1%). Ten of these patients did not have any risk factors; however, chronic cholecystitis findings were not identified in six specimens of those with uncomplicated gallstones. The risk factors have no influence on the development of gallstone-induced complications in children. Gallstones were cured with cholecystectomy; however, some complaints persisted in risk-free and uncomplicated gallstones. We think that if there are no risk factors in patients with uncomplicated gallstones, the patients should not receive surgery but be closely monitored.

To determine the factors affecting the development of pneumothorax in critically ill children admitted to pediatric intensive care unit (PICU). This was a single-centered retrospective case control study comparing the clinical features of mechanically ventilated patients, who developed pneumothorax with matched control cases. The study screened 2850 patients admitted to the PICU over a 3 year period. Among 1140 patients who were mechanically ventilated, 4.4% (n = 50) developed pneumothorax. Median age was 24 months. Patients with pneumothorax were found to have median pediatric risk of mortality (PRISM):26, Pediatric logistic organ dysfunction (PELOD):22 and multiorgan disfuction (MODS):3 whereas in the control group they were 15.5, 12, and 3, respectively. PRISM and PELOD were significantly higher in pneumothorax group. Pneumothorax was observed on the 11.6th day of mechanical ventilation (MV). Pneumothorax was mainly secondary to pneumonia (n = 18, 36%) and MV-related reasons (n = 13, 26%). The risk of pneumothorax was higher when P-mean was > 14 cmH2O and tidal volume (TV) was > 10 mL/kg (P < 0.05). The mean albumin level was 2.7 g/dL in the pneumothorax group compared with 3.6 g/dL in the control group (P < 0.001). The number of days on mechanical ventilator and the duration of hospital stay were statistically significant in pneumothorax group (P < 0.05). The mortality outcome was 44% (n = 22) in the pneumothorax group compared with 6.7% (n = 2) in the control group (P < 0.001). Pneumothorax in critically ill children was related to increased morbidity, mortality and prolonged length of stay in hospital. Higher pediatric risk of mortality (PRISM) and Pediatric logistic organ dysfunction (PELOD) scores were associated with increased risk of pneumothorax. Hypoalbuminemia as a reflection of malnutrition status of patients might be a risk factor.

Speckle tracking echocardiography has great value in evaluation of regional and global myocardial function. The goal of this study was an assessment of cardiac function and remodeling in children with thalassemia major after infusion of a high dose of deferoxamine during a short course by speckle echocardiography and evaluate the efficacy of this imaging modalities in the early recognition of recovering of myocardial dysfunction. In a prospective study between Feb 2014 till 2017 conventional 2 dimensional and speckle tracking echocardiography were done consecutively on 21 patients with beta-thalassemia major before intravenous infusion of high dose of deferoxamine (50 mg/kg) for 5 days and then after 3 months echocardiographic measurements repeated for assessment of efficacy of deferoxamine infusion on ventricular function and cardiac remodeling of our study population. Serum ferritin of all patients reduced significantly (P < 0.001). Ejection fraction was improved after the therapy (P < 0.001). Mitral E/A velocity ratio after therapy increased significantly (P < 0.001). Strain imaging measures showed an increase in apical lateral, mid-lateral, basal lateral, mid-septal, basal septal left ventricular longitudinal wall strain three months after the use of high dose deferoxamine (P < 0.001). Apico-septal wall strain measurements of the left ventricle did not change significantly after high dose deferoxamine (P = 0.144). Intravenous infusion of high dose of deferoxamine after chelating of iron results in reduction of serum ferritin which may cause washout of cardiac deposit of iron with consequent improvement of cardiac function and remodeling.

Cystitis is very common in children and the diagnosis is usually made based on clinical findings with laboratory examinations including urinalysis and urine culture. Bladder wall thickening and presence of fine nodule shaped echoes within the bladder are the suggested sonographic findings of cystitis. In this study we aimed to compare diagnostic value of bladder wall thickening and presence of fine nodule shaped echoes within the bladder and also perivesical fluid collection for cystitis in infants by correlating urinalysis results. Urinary tract ultrasound and urinalysis results of a total 1094 infants were retrospectively screened. Patients were classified as groups according to presence of internal echoes in bladder lumen and/or bladder wall thickening and/or perivesical fluid collection. Control group was constituted of the patients who had normal ultrasound results. Also three subgroups of group 2 (the patients with only bladder wall thkening, P2) were classified according to the size of the thickening. Comparison of pathological urinalysis rate of each group with control group was made with statistical analysis. Also subgroups of group 2 (P2) were compared with each other. When compared with control group, all the groups except perivesical fluid group (P1), had statistically significantly higher pathological urinalysis rates (P < 0.05). The pathological urinalysis rates are highest in the thickened wall and echoes in the lumen and perivesical fluid group (P8) and in the thickened wall and echoes in the lumen without perivesical fluid group (P7) (60% and 54.5%, respectively). Also among subgroups of group 2, pathological urinalysis rate was highest in subgroup 3 in which the patients had most thickened bladder wall and the difference was found to be statistically significant (P < 0.005). We suggest that when thickened wall or echoes in the lumen or perivesical fluid collection accompany each other, pathological urinalysis rates increase. Also pathological urinalysis rates increase as the size of thickness of bladder wall increases.

Due to high incidence of sepsis as the main cause of neonatal mortality, early detection and proper treatment are important in reducing of neonatal mortality. Therefore, researchers are looking for a way of early diagnosis and treatment of sepsis. Platelet indices are one of these ways. But, can they determine different causing germs of neonatal sepsis? In this study, the septic neonates with positive blood culture were studied. Neonates with positive blood culture were divided into three groups; Gram-positive, Gram-negative and fungal infections. Platelet count and other parameters of platelets including PDW (platelet distribution width), and MPV (mean platelet volume) were evaluated, and compared with respect to different germs of septic neonates. In this study 99 newborns with positive blood cultures were evaluated. Of these 13 neonates were excluded because of contaminated culture. In the remaining 86 cases thrombocytopenia, thrombocytosis, PDW, and MPV in different types of neonatal sepsis were evaluated and compared. Although thrombocytosis may be a laboratory finding for sepsis but it is not common in early onset sepsis. Elevated PDW is more common in Gram-negative infections and may be helpful in determining different germs of neonatal sepsis but mean values of PDW in Gram-negative infections are not more than that caused by other germs.

Mutations in LPS-responsive and beige-like anchor (LRBA) gene in patients were firstly described to associate with a syndrome of immune deficiency and autoimmunity in 2012. However, there was still no LRBA deficient patient reported in China. We present a Chinese patient with heterozygous LRBA gene mutations with his clinical, immunological and genetic features. Patient’s clinical data was collected and analyzed. Laboratory results included lymphocyte subsets analysis and immunoglobulin quantification. Targeted gene capture followed by next-generation sequencing was used to identify the gene mutations, and flow cytometry assay was used to analyze B cell immunophenotyping of this patient. The patient mainly suffered from recurrent respiratory tract infections, EBV-associated lymphoproliferative disease and systemic vasculitis. Heterozygous LRBA gene mutations were identified in the patient, which were inherited from his parents, respectively. B cell immunophenotyping revealed that he had decreased total B cells, bone marrow progenitor B cell subsets (HSC, CLP, Pro-B and Pre-B cells), immature B cells, non-switched memory B cells, switched memory B cells and B1 cell subsets. Besides, he had extremely high level of IgE. Herein, we firstly report a patient with heterozygous LRBA gene mutations in China. LRBA might play an important role in B cell development.

There are some evidences suggesting functional constipation-related growth retardation in children, especially in early childhood. Considering high prevalence of constipation, early diagnosis and treatment of constipated patients may improve the quality of life in these children. In this study, weight and height of Iranian children aged 2 to 12 years with functional constipation was evaluated compared to healthy children. A total of 130 Iranian children aged 2 - 12 years, 65 with functional constipation and 65 as healthy children referred to pediatric gastroenterology clinic during Jan to Dec of 2016, were enrolled in this case-control study. Functional constipation was defined as Rome III criteria. The growth status was evaluated using the growth charts, and Z scores of weight and height for age were recorded, with the consent of parents and child willingness. 65 constipated patients (44 boys, 21 girls) with the mean age of 8.28 ± 3.24 years and 65 healthy children (25 boys, 40 girls) with the mean age of 8.32 ± 3.42 years were evaluated. The mean weight of case group was 23.69 ± 4.14 kg and mean height 126.49 ± 10.34 cm. The mean weight of control group with 31.62 ± 4.85 kg and mean height 153.47 ± 13.88 cm, demonstrated significant difference with the case group. The observed mean weight and height were significantly lower in constipated group and the differences of height-for-age and weight-for-age Z scores were statistically meaningful in constipated and healthy children. Functional constipation in children aged 2 to 12 years may retard their weight and height growth, so early diagnosis and treatment of children with constipation is beneficial in their adequate growth status.

Neurologic dysfunctions, specifically hearing impairments due to hyperbilirubinemia are ranked among the main concerns in medicine. This study evaluates the prevalence of acute auditory neuropathy (AN) disorders in term neonates with mild to moderate hyperbilirubinemia and low bilirubin-induced neurological dysfunction (BIND) score and the roll of early treatment on reducing their incidence. Fifty one term jaundice neonates with normal newborn exam and total serum bilirubin (TSB) ≥ 15 mg/dL after the third day of birth with normal otoacoustic emission (OAE) test were enrolled. The BIND score assessment for severity of neurologic dysfunction was done. Neonates with low BIND score were divided into two groups based on their TSB levels at the time of admission (15 - 18 mg/dL: Mild-moderate hyperbilirubinemia and ≥ 19 mg/dL: Severe hyperbilirubinemia). ABR was performed within the first 12 hours of their admission and the second ABR was performed before discharge. The 30.60% of neonates with TSB < 19 mg/dl had abnormal ABR. Latency of V, III waves and interpeak interval latency of I-III, I-V waves were detected. Mean latency of wave V and I-V interpeak latency after phototherapy were significantly decreased compared to pre-treatment (P < 0.001). With the prevalence of auditory neuropathy (AN) at lower TSB concentrations (that have traditionally been considered safe) it can be concluded that more attention should be given to this group despite the absence of neurologic signs, and it also shows the sensitivity of early phototherapy to lower bilirubin level.

Pyruvate dehydrogenase complex deficiency (PDHD) is a rare genetic mitochondrial disorder that is characterized by the broad clinical manifestations from lactic acidosis in neonate to chronic neurodegenerative conditions. Incidence and prevalence of PDHD are unknown because of early lethality and difficulty of diagnosis. We report a case of preterm male infant born at 31 + 3/7 weeks gestation with a birth weight of 1,310 g by cesarean section. He presented with scoliosis, polydactyly and severe metabolic acidosis at birth. Corpus callosum agenesis and increased parenchymal echogenicity were detected by cranial ultrasound. Pyruvate and lactate in blood and CSF were elevated, and lactate-pyruvate ratio was normal. Next-generation sequencing (NGS) technique identified a novel PDHA1 mutation, c.1157-1162del (p.Phe386Lys387del) on X chromosome in him and his mother. PDHD is a rare and fatal disease in case of neonatal onset. This case demonstrates early diagnosis of PDHD in preterm infant using NGS technique.