Iranian Journal of Pediatrics
Volume:24 Issue: 1, Feb 2014

Periodic fever syndromes are a group of diseases characterized by episodes of fever with healthy intervals between febrile episodes. The first manifestation of these disorders are present in childhood and adolescence, but an infrequently it may be presented in young and middle ages. Genetics base has been known for all type of periodic fever syndromes except periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA). Common periodic fever disorders are Familial Mediterranean fever (FMF) and PFAPA. In each patient with periodic fever, acquired infection with chronic and periodic nature should be ruled out. It is depend on epidemiology of infectious diseases. Some of them are common in Iran such as Familial Mediterranean fever and PFAPA. In Iran and other Middle East countries, brucellosis, Malaria and infectious mononucleosis should be considered in differential diagnosis of periodic fever disorders especially with fever and arthritis manifestation. In children, urinary tract infection may be presented as periodic disorder, urine analysis and culture is necessary in each child with periodic symptoms. Some malignancies such as leukemia and tumoral lesion should be excluded in each patient with periodic syndromes and weight loss in each age. After exclude infection, malignancy and cyclic neutropenia, FMF and PFAPA are the most common periodic fever disorders. Similar other countries, Hyper IgD, Chronic Infantile Neurologic Cutaneous and Articular, TRAPS and other authoinflamatory syndromes are rare causes of periodic fever disorders in our system registry of periodic fever in Iran. In the part 1 of this paper we reviewed FMF and PFAPA regarding to the prevalence of them in Iran. In the second part, some uncommon auto-inflammatory disorders such as TRAPS, Hyper IgD sydroms and cryopyrin associated periodic syndromes will be reviewed.

To identify and compare risk factors for recurrent respiratory infections in preschool children between resident and floating population in Yiwu, China. Investigations was conducted in resident and floating population in Yiwu city, Zhejiang province. A structured questionnaire was used to collect information on influence factors. Univariate and multivariate analyses were carried out using the Binary logistic regression. The study was conducted in Yiwu from June 2009 to September 2010. We recruited 844 participants，resident population 639（75.7%） and floating population 205（24.3%） who were preschool children. Multivariate analysis showed that Childbearing age (OR=0.93, 95%CI: 0.88-0.99), Asthma (OR=3.20, 95%CI: 1.60-6.45), Rickets (OR=5.30, 95%CI: 1.99-14.09), Food preference (OR=1.57, 95%CI: 1.02-2.43), Snack (OR=1.50, 95%CI: 1.07-2.07) were the influence factors for recurrent respiratory infections in resident preschool children. Infant feeding (OR=2.24, 95%CI: 1.31-3.81), Snack (OR=2.06, 95%CI: 1.07-3.98,), Trip mode (OR=2.77, 95%CI: 1.11-6.94) were the influence factors for recurrent respiratory infections in floating preschool children. Public health measures against risk factors should be taken to protect against recurrent respiratory infections in resident and floating preschool children respectively.

Most of phenylketonuria (PKU) develops bone turnover impairment and low bone mineral density (BMD). Measurements of BMD reflect only bone mineral status but not the dynamics of bone turnover. Bone markers are a noninvasive tool useful for the assessment of bone formation and bone resorption processes. Our study was to assess the levels of bone markers in PKU in order to select a screen marker and detect the most specific marker which can be combined with BMD for appropriate follow up. Thirty three classic PKU patients were studied. BMD and bone mineral content (BMC) were measured. Total alkaline phosphatase (ALP), osteocalcin (OC) and carboxy-terminal propeptide of type I collagen (CICP), osteoprotegerin (OPG), receptor activator of nuclear factor κβ ligand (RANKL) and Deoxypyridinoline (DPD) were measured. Nineteen (57.6%) male and fourteen (42.4 %) female PKU patients were involved in the current study. Their mean age was 8.4±4.6 yrs and the age range 3-19 yrs. The control group consisted of twenty two (52.4%) males and twenty (47.6%) females. Their mean age was 8.5±3.3 yrs and th age range 2-17 yrs. Using the Z score values, there was a significant decrease of total BMC (TBMC-Z), BMD of the femoral neck BMD-FN-Z, BMD of lumbar vertebrae (BMD-L-Z), BMD-FN and DPD while RANKL increased. There was a negative correlation between CICP and TBMC and between CICP and BMD-L in these patients. Also, a negative correlation between ALP and TBMC and between ALP and BMD-L was observed. It was concluded that the ALP provides a good impression of the new bone formation in the PKU patients and it has a highly significant negative correlation with the many parameters of the bone mineral status beside the wide availability of inexpensive and simple methods. So a screening test and/or follow up for the PKU patients using ALP would be available. Once the level of ALP decrease is detected, one can combine it with BMD to explore the bone mineral status and with specific bone markers (OC, RANKL and DBD), to verify the dynamics of bone turnover. This schedule will reduce the risk of exposure of these patients to the risk hazards of DXA and limit its use only to a limited number of the highly suspected cases.

Cow`s milk protein allergy usually occurs in infants within the first months of life. It can affect several organs, but gastrointestinal symptoms are the most clinical symptoms observed. The most effective treatment is restricting the cow `s milk protein in mother and infant`s diet. Lactobacillus GG supplementation in infant could be effective through modulation of the immune system and the gut microflora. Thirty two breastfed infants with cow`s milk protein allergy were enrolled in a double-blinded randomized controlled trial in which they received Synbiotic (n=16) or placebo (n=16) once a day for one month, simultaneously with cow`s milk protein restriction in mother and infant`s diet. Clinical gastrointestinal symptoms (vomiting, colic, rectal bleeding and diarrhea), head circumference, body length and weight were recorded at the beginning, the end of the first and third month of study. Percentage of increment in head circumference and weight were statistically more in synbiotic group compared with placebo group at the end of the first and third month of study. There was no significant difference in resolution of clinical gastrointestinal symptoms (vomiting, colic, rectal bleeding or diarrhea) and percentage of increment in body length. Synbiotic supplementation in infants may improve increment of head circumference and weight gain, but has no effect on resolution of clinical symptoms.

Thalassemia along with hematopoietic stem cell transplantation (HSCT) can lead to major oxidative stress. Vitamins A and E are antioxidants which protect membrane from lipid peroxidation. We sought to determine for the first time, whether vitamins A and E supplementation is efficacious in maintaining or increasing plasma level of these vitamins in thalassemic children undergoing HSCT. A cross-sectional study was performed on 50 children with β-thalassemia major hospitalized for HSCT. Patients took a daily multivitamin. Plasma vitamins A and E levels were measured at four different times: on admission, HSCT day (day 0), day 7 and day 14 after HSCT. Plasma vitamin A and E were abnormal on admission in most patients (62.0% and 60.0% respectively). Ratio of patient with normal to abnormal plasma level of the vitamins improved from baseline to a peak on day 7 then deteriorated afterward until day 14. There was an increasingly positive correlation between daily oral intake and plasma vitamin A at different times, but plasma vitamin E showed inverse correlation at first which tended towards no correlation subsequently. In multivariate analysis, supplementation significantly changed plasma level of vitamin A at different measurement times (P=0.001) within study subjects. But, plasma level of vitamin E showed no significant difference (P=0.2). Our findings suggest that oral supplementation could have beneficial effects due to increasing plasma vitamin A level and preventing plasma vitamin E depletion.

Patent ductus arteriosus (PDA) is an extremely common in very premature infants. Untreated symptomatic PDA may be associated with chronic lung disease. PDA has a major role in neonatal mortality and morbidity. To compare the efficacy and safety of oral versus intravenous ibuprofen for the pharmacological closure of PDA in low birth weight (LBW) preterm infants. A randomized, single-blinded, controlled study was performed on premature neonates at the neonatal unit, University Hospital for Obstetrics and Gynecology “Koço Gliozheni”, Tirana, Albania from January 2010 to December 2012. The study enrolled 68 preterm infants with a confirmed and significant PDA. The preterm infants received either intravenous or oral ibuprofen randomly as an initial dose of 10 mg/kg, followed by 5 mg/kg at 24 and 48 h. 36 patients were treated with oral ibuprofen and 32 with intravenous ibuprofen during this period. After the first course of the treatment, the PDA closed in 30 (83.3%) of the patients assigned to the oral ibuprofen group versus 23 (71.8%) of those enrolled in the intravenous ibuprofen group (p= 0.355). 15 patiens needed a second treatment course and they were all (100%) with clinical signs of infection and positive bloodculture. There was no reopening of the ductus after the closure. Our data indicate that, for LBW infants, the rate of early ductal closure was comparable and the adverse effects were fewer with oral ibuprofen in comparison to the intravenous route. Association of PDA with perinatal infection has a negative impact in pharmacological closure of the ductus, increasing the need for a second course or for surgery.

The ideal nourishment for newborns with low birth-weight is breast milk. The purpose of the study was to determine the effect of natural-feeding education given to mothers of low-birth-weight infants, on the mothers’ breast-feeding self-efficacy level, breast-feeding success, and the growth of the infants. The study was conducted in a quasi-experimental way. The study group consisted of a total of 85 low-birth-weight infants and their mothers who had been treated in the neonatal clinics of two hospitals. The mothers included in the test group were given breast-feeding education for half an hour per day, during the first 5 days of their hospitalization. Home visits were carried out at the homes of the participants from both the test and control groups, until the infants reached 6 months of age. For collecting data, the following forms were used: Personal Information Form, Breast-feeding Self-Efficacy Form, LATCH Breast-feeding Assessment Tool, and Anthropometric Measurements Form. For analyzing the collected data, percentage, arithmetic mean, standard deviation, and chi-square we used, and, in independent groups, t-tests were employed. It was determined that natural-feeding education given to the mothers increases their breast-feeding self-efficacy levels and success in breast-feeding (P<0.05). It was found that in the test group, the rate of feeding the infants exclusively with breast milk is higher in comparison with the control group (P<0.001). Results of the study indicate that natural-feeding education increases breast-feeding self-efficacy levels, breast-feeding success, and the breast-feeding duration.

Respiratory distress syndrome (RDS) is a common cause of respiratory distress in premature infants. This study was designed to evaluate two different RDS treatment protocols by comparing the outcomes. This study was a double center cross sectional study performed from June to December 2012. During that period, 386 neonates with RDS were hospitalized and treated according to two different therapeutic protocols so-called Acute Care of at-Risk Newborns (ACoRN) respiratory sequence protocol (group I) and Early Nasal Continuous Positive Airway Pressure (E-NCPAP) protocol (group II). The variables and main outcomes of this study were gestational age, birth weight, bronchopulmonary dysplasia (BPD), pulmonary hemorrhage (PH), intraventricular hemorrhage (IVH), air leak and mortality rate (MR). Out of 386 infants, 202 infants were in group I (male 60.4%, female 39.6%, mean gestational age 316/7 weeks, mean birth weight=1688 grams) and group II included 184 infants (male 61.4%, female 38.6%, mean gestational age 32 weeks, mean birth weight 1787 grams), P= 0.07. The ratios of BPD of group I to group II and PH of group I to group two were not significant (P=0.63 and P=0.84, respectively). Air leak ratio in group I was higher than in group II (P=0.001). Although IVH ratio in group II was higher than in group I (P=0.01), grade III and IV IVH was higher in group I (30% vs. 4.6%). In case of MR, it was higher in group I than in group II (P=0.001). According to the findings the incidence of air leak, grade III and IV IVH and MR was less common in E-NCPAP protocol, so it may show the effectiveness of this protocol. The authors suggest that more researches are needed for more accurate results.

Marshall Syndrome or PFAPA is an inflammatory periodic disease characterized by periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis. Although PFAPA is an auto inflammatory disease, it doesn''t have genetic basis such as other periodic fevers. This study evaluates the 12 common MEFV gene mutations in patients with PFAPA syndrome. 21 patients with PFAPA syndrome who had diagnostic criteria were enrolled in this study and 12 common MEFV gene mutations were evaluated in them. The 12 most common MEFV gene mutations (P369S, F479L, M680I (G / C), M680I (G / A), I692del, M694V, M680I, K695R, V726A, A744S, R761H, E148Q) were analyzed by using amplification refractory mutation system for 11 of the first and the PCR was performed for E148Q.The age of patients was between 6 months to 14 years old, and 15 were male. Seven patients had heterozygote and one had compound heterozygote (K695R, V725A) mutation. There were 4 alleles M694V, 3 alleles V726A, 1 allele E148Q and 1 allele K694R. No significant difference between mutated patients with non-mutated in symptoms like aphthous and stomatitis, duration of attacks, episodes of fever and response to treatment. Gaslini score test was not helpful to predict the probability of gene mutations.About 30 percent of patients had MEFV gene mutations but these mutations don''t play a main role in presentation of PFAPA symptoms.

To determine epidemiologic and metabolic characteristics of renal stone in the northern Iran. We prospectively analyzed demographic, clinical and metabolic findings in children less than 16 years old with renal stone revealed by ultrasonography from September 2003 to May 2012. Evaluations included serum and urine measurement of main elements predisposing patients to stone formation. 271 children (160 males) aged 2 months to 16-years (mean 30 months) were evaluated. 91 (33.6%) had a positive family history, abdominal discomfort (18.8%), UTI (11.8%) and hematuria (11.4%) were main presenting features. 45 children were diagnosed accidentally without any specific compliant. Nearly all (99%) stones lay in kidney., 35.1% had metabolic, 10% infective and 4.1% obstructive trends, 110 children had no definable etiology. Hypercalciuria (25.5%) hyperoxaluria (18.4%) and hypocitraturia (18.1%) were more frequent than uricosuria (8.5%) and cystinuria (3.1%) Metabolic derangement plays significant role in stone formation in our area. Patients should be carefully evaluated considering this point of view.

This study aimed to evaluate the feasibility of pegaspargase taking place of L-asparaginase to treat children with advanced-stage LBL on the Non-Hodgkin’s Lymphoma-Berlin-Frankfurt- Munster 95 regimen. 54 newly diagnosed patients with stage Ⅲ or Ⅳ LBL and without any treatment before were enrolled in this study. pegaspargase took place of L-asparaginase in NHL-BFM95. The complications and treatment responses of patients treated on the modified NHL-BFM-95 protocol and BFM-95 protocol were then evaluated respectively. For patients with LBL, compared NHL-BFM 95 protocol with modified NHL-BFM 95 protocol, the CR rate, EFS, OS were similar. Stage 4 myelosuppression was the most common complication in two groups. Besides that, among 31 patients receiving pegaspargase, coagulation defects was the most common complication. The other 23 patients had receivied BFM-95 protocol. Allergic reaction was the most common complication.Although a few patients receiving pegaspargase experienced some complications, all of them were well tolerated and recovered soon after associated symptomatic treatment. Obviouslly, our study showed that L-asparaginase could be replaced by pegaspargase safely without affecting the OS and EFS.

Congenital cyanotic heart diseases (CCHDs) are a series of cardiac anomalies that have long been recognized as a potential cause of nephropathy. There have been few reports on renal impairment in patients with CCHD before and after corrective cardiac surgery. The aim of this study was to evaluate the prevalence of renal dysfunction before and after cardiac surgery and the impact of some risk factors on final renal outcome. Thirty children with CCHD who had done corrective cardiac surgery in the previous 6 months were enrolled in this study. All data prior to surgery were collected from the charts. Post-operation data including blood and spot urine samples were taken simultaneously for CBC, Cr, and uric acid and 24 hour urine was collected for microalbumin and Cr during the follow up visits. Pre- and post-operation parameters were compared to study the impact of cardiac surgery on renal function. Pre- and post-operative GFRs were not significantly different. Final GFR was significantly and inversely associated with pre- and post-operation age (P=0.008 r=-0.48, P=0.03 r=-0.38). Three (10%) patients had microalbuminuria. The prevalence of microalbuminuria in children older than 10 years was 30%. There was no link between microalbuminuria and age, GFR, and hematocrit (P=0.1, P=0.3, P=0.3, respectively). Patients with preoperation hematocrit >45 had a significantly lower final GFR compared to children with HCT <45 (83.7±6.5 vs 111.10.2, P=0.001). The mean uric acid fraction (FEua) excretion was 8.21±4.75. Pre-operative HCT was inversely associated to FEua (P=0.01, r=-0.44). There was no relationship between FEua and age, serum uric acid, and GFR (P=0.7, P=0.4, P=0.2). Children with CCHD are at increased risk of renal injury which is related more to the duration of cyanosis and higher degree of hematocrit level. To lower the risk, corrective cardiac surgery is recommended to be done as soon as possible to improve renal function and stop more renal impairment.

Physicians’ awareness of pediatric health problems is very important in health system. This has not been investigated in Iran as yet. Therefore this study was conducted to characterize the knowledge of the Iranian physicians which has direct association with health status of children. One hundred and four physicians, mainly pediatric specialists (58.6%) working in the state hospitals (45.1%) were enrolled. They filled a valid and reliable questionnaire, containing 26 questions about pediatric issues. Thirty nine (37.5%) physicians answered correctly more than 2/3 of all questions (passed the examination) before educational pediatric program (EPP), which increased to 42.3% after EEP. Subgroup analysis showed that the total scores of general practitioners (P=0.007) was significantly increased after the EPP. Moreover, physicians with shorter practicing time (P=0.006) and those with shorter time past graduation (P=0.01) had a significant improvement in their total scores after the program. The best scores of education issues were documented in growth and development (16.0%; P=0.04), followed by dermatology (9.2%, P=0.04), urology (9.1%; P=0.04), and asthma and allergy (9.0%, P=0.04). This study revealed that there are gaps in the knowledge of professionals about the pediatric issues.

The association of low birth weight (LBW) with adult onset diseases like hypertension is suggested to be partially mediated by a low number of nephrons at birth. Studies have established a relation between LBW and renal volume as the latter is a surrogate marker of total nephron number. Most such studies have considered birth weight or gestational age as separate independent predictors, without taking into consideration the baby’s weight with respect to its gestational age. This study aims to investigate the influence of weight for gestational age on kidney volume in newborns. Consecutive newborns delivered in the department of neonatology in a tertiary care medical college and hospital, were included in a cross-sectional study. The subjects were classified as appropriate for gestational age (AGA) and small for gestational age (SGA) as per Lubchenco’s charts of weight for gestational age (WGA). Bilateral kidney dimensions were measured by a single observer and combined kidney volumes were calculated and compared between the groups. Four hundred and seventeen newborns (SGA 159; AGA 258) were included. The mean combined kidney volume (CKV) was significantly lower among SGA newborns (13.85±4.02 cm3) compared to that of AGA (16.88±4.53 cm3) (P<.001). Univariable and multivariable analyses were done for assessing the effect of demographic, anthropometric and maternal parameters on CKV. WGA, crown heel length, gestational age and postnatal age (hours of life) were independent predictors of mean CKV. An SGA newborn was expected to have a mean CKV 1.57 cm less (95% CI -2.49 cm to -0.65 cm) than that of its AGA counterpart. Considering the future implications of being SGA and having low kidney volumes at birth, it is essential to have an objective depiction of the relationship between these two vital parameters. This study from the Indian subcontinent brings forth such an association.

About one third of partial seizures are refractory to treatment. Several anticonvulsant drugs have entered the market in recent decades but concerns about intolerance, drug interactions, and the safety of the drug are notable. One of these new anticonvulsants is pregabalin, a safe drug with almost no interaction with other antiepileptic drugs. In this open label clinical trial study, pregabalin was used for evaluation of its efficacy on reducing seizure frequency in 29 children suffering from refractory partial seizures.Average daily and weekly seizure frequency of the patients was recorded during a 6-week period (baseline period). Then, during a period of 2 weeks (titration period), pregabalin was started with a dose of 25-75 mg/d, using method of flexible dose, and was brought to maximum dose of drug that was intended in this study (450 mg/d) based on clinical response of the patients and seizure frequency. Then the patients were given the drug for 12 weeks and the average frequency of daily and weekly seizures were recorded again (treatment period). Reduction in seizure frequency in this study was 36% and the responder rate or number of patients who gained more than 50% reduction in seizure frequency was 51.7%. This study showed that pregabalin can be used with safety and an acceptable efficacy in treatment of childhood refractory partial seizures.

The goal of this study is to evaluate some structural changes in muscular, collagenous and neural components as well as expression of Cajal-like cells and apoptosis of smooth muscle cells in congenital ureteropelvic junction obstruction (UPJO). Tissue specimens were obtained from 25 patients with UPJO and compared with normal ureteropelvic junction regions of 19 autopsies. In paraffin embedded sections the amount of Cajal-like cells, density of nerve fibers and smooth muscle cell apoptosis (using immunohistochemical staining) were determined. Collagen deposition and muscular components were stained by Trichrome-Masson staining and evaluated by image analysis techniques. Arrangement of muscular bundles was also evaluated qualitatively. The number of Cajal-like cells was significantly lower in patients than in controls. The apoptotic score and mean number of nerve fibers were not statistically different for the two groups. Arrangement of muscular fibers was more irregular in patients than in controls (P<0.001). Collagen deposition was significantly higher in patients than in controls (P<0.001). The mean amount of muscular component was lower in patients than in normal ones. (P= 0.09) We found significant pathologic changes in congenital ureteropelvic junction obstruction such as decrease in Cajal-like cells, increase in collagen deposition and irregular arrangement of muscle fibers.

Recently application of complementary and alternative medicine (CAM) is increasing in children worldwide. The present study was conducted to determine the prevalence, related factors, types, the sources of information and knowledge of mothers for the possible side effects. This descriptive and analytical study carried out within three months from April-June 2012 through oral interviews and questionnaires with 300 mothers of children referred to pediatric clinic in Vali-Asr Hospital, Birjand (center of South Khorasan province: East of Iran). 35.6% of mothers had used CAM as medication at least once for their children during the last year. There was a significant and direct correlation between using CAM for children with increased maternal age, decreased level of mother’s education, mother being as a housewife and having more than two children. Most (93.3%) common treatments included medicinal herbs, oil rub (26.6 %) and prayer therapy (25.7%). Relative (72%) and neighbors (50%) were the most sources for mother’s information while physicians consist only 2% of the information source. Only 1.3% of mothers knew that CAM may also exert some side effects. Considering the fact that about one third of mothers used CAM modalities, physicians were the least maternal source of CAM information, nearly all mothers were unaware of the side effects of CAM It is recommended that physicians should learn about the CAM to enable them for providing information to parents regarding its benefits and disadvantages. It is also highly recommended to enhance community knowledge about the proper use of different kinds of CAM.