Background: This study was conducted to assess the efficacy of OM-85 BV (Broncho-Vaxom) in the prevention of pediatric recurrent respiratory tract infections (RTIs). Available evidence suggests that defining recurrent RTIs as ≥3 infections per fall-winter semester is both medically and epidemiologically justified. Therefore, this criterion was chosen as a primary endpoint.

Methods: Trials were identified through consultation of bibliographic databases and other channels. Eleven non-blinded studies plus one dealing with primary prevention were excluded and eight randomized controlled trials were included in the meta-analysis. The data were compared at 6 months, which represented the end of most studies. The complete database was examined according to the guidelines of the Cochrane collaboration.

Results: The mean age of children and the number of RTIs in the preceding year were comparable at admission. Of the patients in the OM-85 BV treated population (n=435), 32% had recurrent RTIs (that is, ≥3 RTIs/6 months) vs. 58.2% in the placebo treated population (n=416; P<0.001). Sensitivity analysis showed that this was not driven by any particular trial. The results of this review were also positive for the active treatment regarding the secondary variables, which were represented by the number of patients with at least one RTI and the mean number of RTIs.

Conclusions: This meta-analysis shows, as observed in several individual trials, that the population treated with OM-85 BV had significantly and consistently fewer cases of recurrent RTIs. The data suggest that the effect is greater in patients at increased risk of recurrent RTIs.

Key words: children; immunostimulant; OM-85 Broncho-Vaxom; recurrent respiratory tract infections

World J Pediatr 2010;6(1):5-12

Background: This article aims to review recent advances in the diagnosis and treatment of pulmonary arterial hypertension in neonates and children with congenital heart disease.

Data sources: Articles on pulmonary arterial hypertension in congenital heart disease were retrieved from PubMed and MEDLINE published after 1958.

Results: A diagnosis of primary (or idiopathic) pulmonary arterial hypertension is made when no known risk factor is identified. Pulmonary arterial hypertension associated with congenital heart disease constitutes a heterogenous group of conditions and has been characterized by congenital systemic-to-pulmonary shunts. Despite the similarities in histologic appearance of pulmonary vascular disease, there are differences between pulmonary arterial hypertension secondary to congenital systemic-to-pulmonary shunts and those with other conditions with respect to pathophysiology, therapeutic strategies, and prognosis. Revision and subclassification within the category of secondary pulmonary arterial hypertension based on pathophysiology were conducted to improve specific treatments. The timing of surgical repair is crucial to prevent and minimize risk of postoperative pulmonary arterial hypertension. Drug therapies including prostacyclin, endothelin-receptor antagonist, phosphodiesterase inhibitor, and nitric oxide have been evolved with promising results in neonates and children.

Conclusions: Among the different forms of congenital heart diseases, an early correction generally prevents subsequent development of pulmonary arterial hypertension. Emerging therapies for treatment of patients with idiopathic pulmonary arterial hypertension also improve quality of life and survival in neonates and children with congenital heart disease associated with pulmonary arterial hypertension. Heart and lung transplantation or lung transplantation in combination with repair of the underlying cardiac defect is a therapeutic option in a minority of patients. Partial repair options are also beneficial in some selected cases. Randomized controlled trials are needed to evaluate the safety and efficacy of these therapies including survival and long-term outcome.

Key words: children; congenital heart disease; endothelin-receptor antagonist; neonate; nitric oxide;

phosphodiesterase inhibitor; prostacyclin; pulmonary arterial hypertension

                   World J Pediatr 2010;6(1):13-31

Background: Clinicians and investigators often do not appreciate the importance of vaginal microbiocoenosis and vaginal cytology in the health of prepubertal and adolescent girls.

Data sources: Based on recent publications in human medicine and our own experience with vaginal cytology and microbiology in children and adolescent girls, we review the principles of vaginal microbiocoenosis and cytology and their roles in disease prevention in prepubertal and adolescent girls.

Results: The main role of vaginal microbiocoenosis and cytology in diagnosing as well as developing vulvovaginitis is demonstrated. Clinicians can identify states of vaginal health and disease by important well-known diagnostic tools, including vaginal cytology. Lactobacilli are infrequently observed in the prepubertal girls, but become more abundant in adolescent girls. Three basic types of vaginal smears are presented in addition to a classification of inflammatory urogenital diseases. Management of common types of vulvovaginitis is also considered.

Conclusions: This essential shift in vaginal bioco-enosis is important to prevent the growth of potentially pathogenic flora in the vagina. The detection of vaginal microbiocoenosis problems and recognition of changing cytology in vaginal development can provide helpful clues to identifying and preventing vaginal diseases in this pediatric population.

Key words: cytology; lactobacilli; vaginal microbiocoenosis; vulvovaginitis             

World J Pediatr 2010;6(1):32-37

Background: Many Kawasaki disease (KD) patients have reached adulthood in Japan. The current status of adult patients who have giant coronary aneurysms with KD is not well understood.

Methods: Medical records of 48 KD patients (33 males and 15 females) with giant coronary aneurysms (maximum coronary artery internal diameter >8 mm) aged 20 years or over were retrospectively reviewed.

Results: The age of the patients at the diagnosis of KD ranged from 0.3 to 12.8 years (median 2.9 years) and the age of the patients in this review ranged from 20.0 to 33.1 years (median 25.2 years). During the follow-up period, the maximum coronary artery internal diameter ranged from 8.2 to 30.0 mm (median 10 mm). Giant coronary aneurysms progressed to coronary artery stenosis and/or complete occlusion in 34 (74%) of 46 patients. Coronary artery bypass graft surgery was performed in 9 (19%) of 48 patients. Myocardial infarction occurred in 14 (31%) of 45 patients. Other complications or problems occurred in 5 patients with angina pectoris, low left ventricular ejection fraction, ventricular tachycardia, hemorrhagic cerebral infarction, or thyroid carcinoma respectively. In the patients followed up, 4 dropped out. In addition, 1 patient succeeded in pregnancy and delivered a baby.

Conclusions: Close attention should be paid to ventricular tachycardia in adult KD patients with giant coronary aneurysms, especially for those who have low left ventricular ejection fraction. To reduce the number of dropped out patients, it is important that the patients should be referred to a new doctor when they change their place of residence.

Key words: giant coronary aneurysm; grown-up patients; Kawasaki disease

                   World J Pediatr 2010;6(1):38-42

Background: Little was known about the therapeutic result of rhabdomyosarcomas (RMSs) and other malignant tumors until the end of the last century in China. Very few prospective clinical research results have been reported. We designed a RS-99 protocol under close cooperation of a multidisciplinary team including surgeons, radiologists, pathologists, and pediatric oncologists at Shanghai Children's Medical Center. This study aimed to improve the prognosis of childhood solid tumors and analyze the results of different tumors with the same protocol, including RMSs, the Ewing sarcoma family of tumors (ESFTs), and ex-cranial germ cell tumors (GCTs).

Methods: Sixty-six patients with malignant solid tumors [RMS (n=30), GCT (n=22), and ESFT (n=14)] were enrolled on the RS-99 protocol from October 1998 to October 2006. They were 34 girls and 32 boys aged 9 to 194 months. The protocol involved surgery, radiotherapy and chemotherapy which included VCP (vincristine, cis-diaminedichloroplatinum, and cyclophosphamide) and IEV (etoposide, vincristine and ifosfamide) for the low-risk group, AVCP (adriamycin, vincristine, cis-diaminedichloroplatinum, and cyclophosphamide) and IEV for the intermediate-risk group and high-risk group. Peripheral blood stem cell transplantation was suggested for the high-risk group. Radiotherapy was only given for RMS and ESFT. Differences in survival between the groups were determined by comparison of entire survival curves and tested by the Kaplan-Meier method and the log-rank tests.

Results: The 5-year event-free survival (EFS) for the whole group (RMS, ESFT and GCT) was 60%. The 5-year EFS for children with RMS was 35% (95% CI 16-54), GCT was 79% (95% CI 70-88) and ESFT was 72% (95% CI 58-86). The 5-year EFS showed that the patients with RMS in the retroperitoneum-pelvis did not have a better result than those with tumors in other sites (P=0.604). The histological classification of RMS exerted prognostic influence on the estimated 5-year EFS (P=0.04). Tumor stage and risk group were also contributive to prognosis (P=0.008). For GCT patients, the primary sites of tumors and their histological classification did not influence the therapeutic result (P=0.814). The 5-year EFS was 100% in stage I and II versus 62% in stage III and IV patients (P=0.02). Because of the small number of patients, we did not analyze the prognostic factors for patients with ESFT. No organ failure or functional impairment occurred in the patients enrolled in the RS-99 protocol. One ESFT patient developed a second cancer.

Conclusions: The RS-99 protocol is well tolerated and is reasonable for the 3 different tumors. Risk-based grouping protocol design is needed and the protocol for high risk RMS should be revised.

Key words: children; Ewing sarcoma; germ cell tumor; rhabdomyosarcoma

World J Pediatr 2010;6(1):43-49

Background: Open colectomy has been preferred for intestinal neuronal dysplasia type B (IND) due to its low morbidity rate and good functional results. The aim of this study was to investigate the feasibility and results of laparoscopic colectomy with transanal Soave pull-through for the treatment of IND in children.

Methods: Seventeen infants and children suffering from IND were treated by laparoscopic extensive colectomy with transanal Soave pull-through. The diagnosis of IND was made via anorectal manometry, X-ray contrast enema, suction biopsies, and laparoscopic full-thickness biopsies with hematoxylin-eosin staining. The technique used four or five abdominal ports. The sigmoid, transverse, and right colon up to the last ileal cove were mobilized laparoscopically in the extended form of IND. A modified Soave's anastomosis was performed. The patients' data, surgical procedures, operative data, postoperative complications and clinical outcomes were analyzed.

Results: Five patients underwent laparoscopic left colectomy with modified transanal Soave procedures, and the other 12 were treated by laparoscopic subtotal colectomy and required a Deloyers' maneuver for the Soave pull-through. The proximal margin of barium stagnation in patients with left colectomy was restricted to the distal end of the descending colon, sigmoid colon, and that in patients with subtotal colectomy was restricted to the proximal end of the descending colon, transverse colon, hepatic flexure, and ascending colon. Postoperative complications included anastomotic leakage, severe perianal erosions, postoperative enterocolitis, and soiling. During a mean follow-up of 4 years, bowel frequency was 4-10 times per day in 3 months postoperatively in patients with subtotal colectomy. The clinical results were good, with no stool incontinence or constipation.

Conclusions: Laparoscopic procedure for left colectomy and subtotal colectomy with transanal Soave pull-through in infants and children with IND is safe, feasible, and effective. The location of barium stagnation in proximal margin may be used as a method to predict initially the proximal margin of the resected bowel segment.

Key words: intestinal neuronal dysplasia; laparoscopy; subtotal colectomy

                  World J Pediatr 2010;6(1):50-54

Background: The diagnosis and treatment of intussusception is often confusing in infants aged younger than 3 months. This study aimed to discuss the particularity of diagnosis and treatment of intussusception in this age group.

Methods: From April 1983 to June 2008, 39 infants aged 3 months or younger who had been diagnosed with intussusception were treated and their clinical data were analyzed retrospectively.

Results: Of the 39 infants (29 boys and 10 girls), ages ranged from 12 hours to 3 months, with a mean age of 52.6 days. The duration from onset to admission ranged from 7 to 142 hours (mean 39.6 hours). Three infants had intrauterine intussusception and 36 postnatal intussusception. The 3 infants with intrauterine intussusception had typical presentations of complete ileus after birth. Gap type ileal atresia was found in surgery in 2 of the 3 infants and primary anatomosis was performed therapeutically. The other infant was found to have ileal separation and a patent proximal end with diffused meconium peritonitis. The patient died 2 days after primary anastomosis. Most infants with postnatal intussusception had two or more manifestations of the tetralogy, namely intermittent screaming, vomiting, bloody stool, and abdominal mass. In 23 infants who underwent pneumatic reduction, 17 had a successful reduction and 6 converted to open surgery. Surgery was indicated for 19 infants, with maneuver procedure in 14. Meckel's diverticulum was noted as a leading cause  in 2 infants, ileal duplication in 1 with necrosis of intussusceptum, and primary intussusception with lead point necrosis in 2. The 5 infants, on whom segmental resection was performed, underwent primary anastomosis. All infants with postnatal intussusception had a smooth recovery.

Conclusions: Infants aged 3 months or younger may suffer from intussusception and most of them present with typical symptoms. Early diagnosis and treatment are needed for a good prognosis. Intrauterine intussusception may be an etiological factor for ileal atresia.

Key words: diagnosis; infant; intussusception; neonate; pneumatic reduction; treatment

                 World J Pediatr 2010;6(1):55-59

Background: Celiac disease (CD) may cause changes throughout the gastrointestinal tract. Patchy distribution of duodenal mucosal lesions has been described in adults as well as in children. This study aimed to verify the concept and to evaluate the frequency of histologic lesion variability of the duodenal mucosa in Indian children with CD.

Methods: We enrolled 67 children prospectively who underwent upper gastrointestinal endoscopy because of positive tissue transglutaminase antibodies and biopsy as the final evaluation for suspected CD. Four biopsies were taken from the descending duodenum distal to the papilla, and duodenal bulb. The histologic lesions were classified according to the Oberhuber classification with modification proposed by our group.

Results: Forty-three CD children (64.2%) had a "mixed" type 3 lesion characterized by a different degree of villous atrophy at different biopsy sites. Eight children (11.9%) showed two different types of histologic lesions in the same patient at different biopsy sites. The overall variability of histologic lesion (variability in the grade of villous atrophy [type 3a, 3b, or 3c], and coexistence of villous atrophy and type 2 lesion) was seen in 51 (76.1%) of the CD patients.

Conclusions: Children with CD show a high frequency of variability of histologic lesions. Therefore, multiple endoscopic biopsy specimens should be obtained not only from the distal duodenum but also from the bulb.

Key words: celiac disease; duodenum; histologic lesion; villous atrophy

       World J Pediatr 2010;6(1):60-64

Background: Human bocavirus (HBoV) was first reported in 2005. The worldwide presence of HBoV in children with acute respiratory tract infection (ARTI) has been confirmed. This study aimed to understand the prevalence and clinical features of HBoV in children with ARTI in Shanghai and explore the causative implication of HBoV in ARTI.

Methods: We retrospectively reviewed the medical records of 349 hospitalized children with ARTI between November 2006 and January 2007. From these children, 351 nasopharyngeal aspirate samples were collected; 325 of the samples were obtained from those with community-acquired ARTI and 26 from those with hospital-acquired ARTI. All samples were routinely screened for seven common respiratory viruses by immunofluorescence and further tested for HBoV by polymerase chain reaction.

Results: HBoV was detected in 16 (4.6%) of the 351 samples, and it was the second most commonly detected virus after respiratory syncytial virus. Three (19%) HBoV-positive samples were dual infection with respiratory syncytial virus or parainfluenza virus type 3. Of the 325 children with community-acquired ARTI, HBoV was identified to be positive in 11 (3.4%), of whom 6 were diagnosed with pneumonia with patchy or interstitial infiltrates in the lung indicated by chest radiography, 3 with bronchitis, and 2 with bronchial asthma exacerbation with attendant lung infection. Out of the 26 children with nosocomial ARTI, 5 (19.2%) had bronchitis which was found to be HBoV positive without co-detection of other viruses. The HBoV-positive children were aged 1.7 months to 43 months and their mean age was 13.7 months. Sixteen (100%) children had cough, 11 (68.8%) had wheezing, and 10 (62.5%) had fever.

Conclusions: HBoV was circulating in Shanghai during the study period, and which was detected frequently in children with ARTI. HBoV was found to be associated with community-acquired ARTI and may play a pathogenic role in nosocomial ARTI.

Key words: acute respiratory tract infection; children; community-acquired infection; hospital-acquired infection; human bocavirus

World J Pediatr 2010;6(1):65-70

Background: Neonatal tetanus (NNT) is a major cause of newborn deaths especially in the developing world. While efforts aimed at eradicating NNT should be sustained, it is equally imperative to reduce death among affected infants. Therefore, the factors associated with mortality rate in this condition need to be studied.

Methods: The records of infants with NNT over a 15-year period (1991-2005) were reviewed. A statistical comparison of the survivors and fatalities for relevant clinical characteristics was done, and the determinants of fatality rate were also determined using logistic regression.

Results: Ninety-six of 151 newborns with NNT died, giving a mortality rate of 63.6%. The case fatality rate during the study period varied between 33.3% and 100%. More deaths occurred in the infants with low birth weight (P=0.004) within 1 day at the onset of symptoms (P<0.001), whose mothers aged 18 years or less (P=0.001) belonged to socio-economic class V (P=0.001). Determinants of mortality in these infants with NNT included low socio-economic class (P=0.002), no anti-tetanus vaccination (P=0.006), presentation with spasms (P<0.001), and non-administration of anti-tetanus serum during treatment (P=0.013).

Conclusions: The mortality rate in infants with NNT remains significantly high in Nigeria. Improved maternal anti-tetanus vaccination and timely recognition and treatment of affected infants may jointly reduce the incidence and fatality rate of NNT.

Key words: mortality rate; neonatal tetanus; Nigeria; risk factors

World J Pediatr 2010;6(1):71-75

Background: Congenital Morgagni-Larrey's hernia (CMLH) is rare and known to be associated with a high incidence of bilaterality and associated anomalies. This study aimed to review our patients with bilateral CMLH and evaluate their presentation, associated anomalies, diagnostic difficulties and therapy.

Methods: From January 1989 to December 2007, we treated 8 children with bilateral CMLH at our hospital. Their medical records were retrospectively reviewed for age, sex, symptoms, associated anomalies, diagnosis, operative findings, treatment and outcome.

Results: Among the 8 children, 4 were male and 4 female, with a mean age of 22.74 months (range: 0.93-108 months). Six of them sustained repeated attacks of pneumonia. In 5 children, bilaterality was diagnosed at surgery. Associated anomalies were observed in all children, including congenital heart disease in 5, Down's syndrome in 4, malrotation in 3, inguinal hernia in 2, umbilical hernia in 1, and pyloric stenosis in 1. All of these children were operated on transabdominally. All of them did well postoperatively and on follow-up ranging from 1.5 years to 5 years (mean: 3 years), one had recurrence of the hernia as well as an incisional hernia.

Conclusions: The diagnosis of bilateral CMLH may be difficult preoperatively, especially if one of the hernial sacs is empty. CT scan is valuable to diagnose bilateral hernias. To repair these hernias, we advocate a transabdominal approach, which allows easy reduction and inspection of contents, access and repair of bilateral hernias, and correction of associated malrotation if present.

Key words: bilateral Morgagni-Larrey's hernia; congenital diaphragmatic hernia; diagnosis

                  World J Pediatr 2010;6(1):76-80

Background: Vitamin A deficiency may increase the responsiveness of the respiratory tract and increase the risk of respiratory tract infection, resulting in airway obstruction and wheezing. This study aimed to investigate the relation between vitamin A deficiency and infant wheezing.

Methods: Three ml venous blood samples were collected from 331 hospitalized children who suffered from wheezing to determine the serum vitamin A concentration and the relationship between vitamin A and some causative factors of wheezing.

Results: The severity of vitamin A deficiency was related to the course of wheezing. In the persistent wheezing group, 14 patients (34.1%) were diagnosed as having severe vitamin A deficiency and 16 patients (39%) having moderate vitamin A deficiency; among the acute wheezing group, 18 patients (16.4%) were diagnosed as having severe vitamin A deficiency and 32 patients (29%) having moderate vitamin A deficiency. Comparison of the two groups revealed that there was a significantly higher rate of moderate and severe vitamin A deficiency in the persistent wheezing group than in the acute wheezing group (P<0.01). The severity of vitamin A deficiency was related to the infants' wheezing severity. Severe vitamin A deficiency was found in 24 patients (47%) in the severe wheezing group and 8 (8%) in the mild and moderate wheezing groups. The rate of severe vitamin A deficiency was significantly higher in patients with severe wheezing than in those with mild and moderate wheezing (P<0.01).

Conclusions: Serum vitamin A deficiency could be commonly found in infants with wheezing. The severity of vitamin A deficiency might be related to the course of wheezing and the infants' wheezing severity.

Key words: infant; vitamin A deficiency;  wheezing

                  World J Pediatr 2010;6(1):81-84