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Vol 15, No 3
Vol 15, No 3 June 2019 ISSN 1708-8569
 
Review articles
Meta-analysis
Original articles
Clinical image
Letter to the Editors
   
Review articles:
Sleep and prematurity: sleep outcomes in preterm children and influencing factors
  Maria Gogou, Katerina Haidopoulou, Evangelos Pavlou
 
Background: Sleep undergoes changes from birth to adulthood, while sleep disorders are associated with various cognitive deficiencies in childhood. In parallel, prematurity is known to predispose to poor neurodevelopmental outcomes. Our aim is to provide literature data about factors influencing sleep in the premature infants and sleep outcomes in this population.
Methods: A systematic review was conducted using a variety of health-related databases. Original research papers were considered and no year-of-publication restriction was placed.
Results: In total, 22 articles fulfilled our selection criteria. Available studies present remarkable heterogeneity in terms of methodological design. Compared to full term, premature infants exhibit significant differences in sleep structure, which mainly include differences in electroencephalographic spectral values, in total sleep time and in arousal threshold. Furthermore, prematurity seems to be a risk factor of sleep breathing disorders in childhood and adolescence. Data about the effect of methylxanthines and the environment of neonatal intensive care unit is controversial. With regard to the impact of prematurity-related sleep disorders on future neurodevelopment, available research papers are generally few.
Conclusions: The alterations in sleep patterns are an outcome of prematurity (immaturity of nervous system) as well as of postnatal factors and comorbidities. Sleep problems in this population of infants seems to be a missing piece of the puzzle of impaired neurodevelopment. Future studies should focus on interventions to improve sleep hygiene and limit neurodevelopmental problems.
  [Abstract] [Full Text] [PDF]  
Progress in treatment and newborn screening for Duchenne muscular dystrophy and spinal muscular atrophy
  Qing Ke, Zheng-Yan Zhao, Jerry R. Mendell, Mei Baker, Veronica Wiley, Jennifer M. Kwon, Lindsay N. Alfano, Anne M. Connolly, Catherine Jay, Hanna Polari, Emma Ciafaloni, Ming Qi, Robert C. Griggs, Michele A. Gatheridge
 
Background: Advances in treatment for Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA) hold promise for children with these disorders. Accurate genetic diagnosis, early in the disease process, will allow these treatments to be most effective. Newborn screening (NBS) for SMA has been recommended in the United States, and a pilot DMD NBS program is underway in Hangzhou, China.
Data sources: A PubMed search, limited to the past 5 years, was conducted to identify: (1) therapeutic advancements for DMD/SMA approved by the United States Food and Drug Administration or the European Medicine Agency and (2) The status of NBS for DMD/SMA.
Results: We review the current state of approved treatments for DMD/SMA. We present recommendations regarding the future of NBS for these diseases, with a focus on the outcomes and challenges of SMA NBS in New York, USA, and the DMD NBS pilot program in Hangzhou, China.
Conclusions: Approved treatments for DMD and SMA may change the natural history of these diseases. Long-term studies of these treatments are underway. To avoid the known diagnostic delay associated with these disorders and provide optimal effectiveness of these treatments, early identification of patients through NBS will be necessary. Establishing comprehensive follow-up plans for positively identified patients will need to be in place for NBS programs to be successful.
  [Abstract] [Full Text] [PDF]  
Management and outcomes of gastric volvulus in children: a systematic review
  Karina Miura da Costa, Amulya K. Saxena
 
Background: Gastric volvulus (GV) in children is a rare condition. This study reviewed management and outcomes of GV in the pediatric population.
Methods: MEDLINE/PubMed, Embase, and Google Scholar databases were searched for studies in English regarding GV in patients < 18 years old between 2008 and 2017, selected by two reviewers. Results were presented as percentages and medians. Fisher*s exact test was used to evaluate categorical variables, and Bonferroni correction was applied for multiple comparisons.
Results: Ninety-seven papers with 125 patients were included. The median age was 24 months, with slightly female preponderance. Vomiting was the most common symptom and acute presentation occurred in the majority of cases. History of previous surgery/abdominal trauma was described in 12 and 3 children, respectively. Radiology was diagnostic for GV in most cases. The initial management was surgical in the majority of cases, with most of them including gastropexy, gastrostomy, or gastric resection. Mesenteroaxial GV was associated with acute presentation (P = 0.004) and the latter with ischemia (P < 0.01). Complications occurred in 23 (18.9%) children, esophageal stenosis being the most common. There were eight (6.4%) deaths, and only one recurrence 6 months after endoscopic management. The median follow-up period was 12 months. The inclusion of only case reports/case series, the incomplete reporting from papers, and the short followup were limitations of the study.
Conclusions: GV occurs at a median age of 24 months and requires high suspicion and prompt management, as mortality is considerable. The preferred surgical approach for GV includes variations of gastropexy. Esophageal stenosis is the most common morbidity post-GV management.
  [Abstract] [Full Text] [PDF]  
Meta-analysis:
Efficacy of different analgesic or sedative drug therapies in pediatric patients with congenital heart disease undergoing surgery: a network meta-analysis
  Rui-Zhu Liu, Bing-Tong Li, Guo-Qing Zhao
 
Background: Surgery is an effective therapy for congenital heart disease (CHD) and the management after surgery poses challenges for the clinical workers. We performed this network meta-analysis to enhance the corresponding evidence with respect to the relative efficacy of different drug treatments applied after the CHD surgery.
Methods: Embase and PubMed were systematically retrieved to identify all published controlled trials investigating the effectiveness of drugs for patients up to 25 August, 2018. Mean differences (MD), odds ratios and their 95% credible intervals (CrIs) were used to evaluate multi-aspect comparisons. Surface under cumulative ranking curve (SUCRA) was used to analyze the relative ranking of different treatments in each endpoint.
Results: Compared to saline, all the drugs achieved better preference under the effi cacy endpoints except fentanyl in JET. As for ventilator time, all drugs were more effective than saline while only the difference of dexmedetomidine was statistically obvious (MD = 6.92, 95% CrIs 1.77每12.54). Under the endpoint of ICU time, dexmedetomidine was superior to saline as well (MD = 1.26, 95% CrIs 0.11每2.45). When all the endpoints were taken into consideration and with the help of ranking probabilities and SUCRA values, fentanyl combined with dexmedetomidine was one of the recommended drugs due to its shorter time on ventilator and stay in hospital as well as lower mortality.
Conclusions: Overall, based on the comprehensive consideration of all the endpoints, fentanyl combined with dexmedetomidine was considered to be the best-recommended clinical interventions among all the methods.
  [Abstract] [Full Text] [PDF]  
Original articles:
Patient-specific three-dimensional printed heart models benefit preoperative planning for complex congenital heart disease
  Jia-Jun Xu, Yu-Jia Luo, Jin-Hua Wang,, Wei-Ze Xu, Zhuo Shi, Jian-Zhong Fu, Qiang Shu
 
Background: Preoperative planning for children with congenital heart diseases remains crucial and challenging. This study aimed to investigate the roles of three-dimensional printed patient-specific heart models in the presurgical planning for complex congenital heart disease.
Methods: From May 2017 to January 2018, 15 children diagnosed with complex congenital heart disease were included in this study. Heart models were printed based on computed tomography (CT) imaging reconstruction by a 3D printer with photosensitive resin using the stereolithography apparatus technology. Surgery options were first evaluated by a sophisticated cardiac surgery group using CT images only, and then surgical plans were also set up based on heart models.
Results: Fifteen 3D printed heart models were successfully generated. According to the decisions based on CT, 13 cases were consistent with real options, while the other 2 were not. According to 3D printed heart models, all the 15 cases were consistent with real options. Unfortunately, one child diagnosed with complete transposition of great arteries combined with interruption of aortic arch (type A) died 5 days after operation due to postoperative low cardiac output syndrome. The cardiologists, especially the younger ones, considered that these 3D printed heart models with tangible, physical and comprehensive illustrations were beneficial for preoperative planning of complex congenital heart diseases.
Conclusion: 3D printed heart models are beneficial and promising in preoperative planning for complex congenital heart diseases, and are able to help conform or even improve the surgery options.
  [Abstract] [Full Text] [PDF]  
Alterations of intestinal flora and the effects of probiotics in children with recurrent respiratory tract infection
  Ke-Liang Li, Ben-Zhen Wang, Zi-Pu Li, Yi-Lei Li, Jing-Jing Liang
 
Background: Recurrent respiratory tract infection (RRTI) is a disease occurred frequently in preschool children.
Methods: A total of 120 RRTI children were randomly divided into active group, remission group, intervention group and control group, meanwhile 30 healthy children were selected as the healthy group. Children in the intervention group were given oral Bifidobaeterium tetravaccine tablets (Live) for 2 months, while the control group received routine treatment. Stool sample were detected to analyze the bacterial strains. The occurrence of respiratory tract infection (RTI) was compared between different groups during 1 year follow-up.
Results: Compared with the healthy group, the number of Bifidobacteria and Lactobacilli in the active group, remission group, intervention group and control group was significantly decreased (P < 0.05). The number of Bifidobacteria and Lactobacilli in the intervention group was significantly higher compared to other RRTI groups (P < 0.05). During the follow-up period, the average annual frequency of different acute RTI and use of antibiotics were significantly reduced (P < 0.05), the average duration of cough, fever and use of antibiotics at each episode were also significantly shortened (P < 0.05) in the intervention group compared to the control group.
Conclusions: Children with RRTI are susceptible to intestinal flora imbalance. Oral probiotics can effectively improve the RRTI intestinal microecological balance in children and reduce the frequency of RTI.
  [Abstract] [Full Text] [PDF]  
Usefulness of mizoribine administration in children with frequently relapsing nephrotic syndrome, and the relationship between pharmacokinetic parameters and efficacy: a multicenter prospective cohort study in China
  Zheng-Kun Xia, Yuan-Fu Gao, Li-Ping Rong, Xi-Qiang Dang, Qian Shen, Xiao-Yun Jiang, Zhu-Wen Yi, Hong Xu
 
Background: Mizoribine (MZR) is an immunosuppressant used to treat adult nephropathy. There is little experience with the drug in treating Chinese children with frequently relapsing nephrotic syndrome (FRNS). We investigated the efficacy and safety for treating MZR with FRNS. Furthermore, the relationship between efficacy and serum concentration was investigated.
Methods: A prospective multicenter observational 12-month study was performed for evaluating the usefulness of MZR with FRNS. Serum MZR concentration was measured, and the relationships between pharmacokinetic parameters (Cmax, AUC), number of relapses, and urinary protein were evaluated.
Results: Eighty-two pediatric patients from four hospitals were treated with MZR and prednisone. MZR treatment significantly reduced the number of relapses and steroid doses. A correlation between pharmacokinetic parameters and relapses was observed, which fits well with the sigmoidal Emax model. Even in the relationship between pharmacokinetic parameters and urinary proteins, it was recognized that there was a threshold in the pharmacokinetic parameters for the therapeutic effect similar to the results obtained with the sigmoidal Emax model. Eleven patients (13.4%) experienced mild adverse events.
Conclusions: MZR therapy was effective in reducing the number of relapses and steroid doses. No severe adverse reactions were observed. Therapeutically effective serum concentrations were estimated to be Cmax ≡ about 2 米g/mL or AUC ≡ about 10 米g h/mL. MZR and steroid treatment were eff ective and safe for pediatric FRNS.
  [Abstract] [Full Text] [PDF]  
Clinical features in proven and probable invasive fungal disease in children and adolescents at a pediatric referral center: a 5-year experience
  Kenji Kishimoto, Masashi Kasai, Noriko Kawamura, Yusuke Ito, Makiko Yoshida, Daiichiro Hasegawa, Keiichiro Kawasaki, Yoshiyuki Kosaka
 
Background: There is limited information concerning the overall epidemiology of invasive fungal disease (IFD) in children. The aim of this study was to clarify the clinical features of IFD in a tertiary pediatric care hospital.
Methods: Patients diagnosed with proven or probable IFD at our hospital between 2011 and 2015 were retrospectively reviewed. Proven and probable IFD were defined according to the European Organization for Research and Treatment of Cancer/Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group consensus. Patients with possible IFD were excluded.
Results: The incidence of proven or probable IFD was 26 of 20,079 hospitalized patients (0.13%). The predominant underlying disease was malignancy (54%) and congenital anomaly (27%). The most common diagnosis was candidemia among the patients with proven IFD (8 of 13, 62%). All the isolated pathogens in the candidemia patients were non-albicans Candida spp. The most common site of infection was the lungs in patients with probable IFD (11 of 13 patients, 85%). In probable IFD episodes, positive 汕-D-glucan and galactomannan were found in 12 of 13 (92%) and 5 of 13 (38%) patients, respectively. All but one patient (96%) received empirical antifungal therapy. No patients underwent surgical resection of residual lesions. The overall mortality was 23% and the attributable mortality of IFD was 12%.
Conclusion: Our results suggest the emergence of non-albicans Candida species as important pathogens in childhood IFD.
  [Abstract] [Full Text] [PDF]  
Prevalence and classification of equinus foot in bilateral spastic cerebral palsy
  Axel Horsch, Marco Götze, Andreas Geisb邦sch, Nicholas Beckmann, Stefanos Tsitlakidis, Gregor Berrsche, Matthias Klotz
 
Background: Equinus is a common deformity in children with bilateral spastic cerebral palsy (BSCP). While dynamic equinus usually is treated by conservative therapy, fixed contractures need surgical correction. To choose the appropriate surgical method, it is important to discriminate between isolated gastrocnemius shortening and combined gastrosoleus complex contracture.
Methods: In a retrospective study 938 patients with BSCP were studied. Patients underwent gait analysis and clinical examination. 248 patients (496 limbs) met the inclusion criteria. Data from motion analysis and clinical examination were used to calculate the prevalence and to further classify fixed equinus foot.
Results: The prevalence of equinus was 83.3%. During clinical exam 246 (59.6%) limbs showed combined gastrosoleus complex contracture and 167 (40.4%) isolated gastrocnemius contracture. Max. DF at stance and mean DF at initial contact were significantly reduced in combined contracture, while max. ROM was increased (P < 0.05).
Conclusions: Corroborating the results of previous studies, in this study there was a high prevalence of fixed equinus in patients with BSCP. The prevalence of equinus correlated with increasing age. As half of the patients with fixed equinus show a different involvement of gastrocnemius and soleus muscle, we recommend to apply Silfver skiöld*s test to discriminate between those two types to choose the appropriate surgical therapy.
  [Abstract] [Full Text] [PDF]  
Impact of preterm birth and low birth weight on medical conditions, medication use and mortality among neonates: a prospective observational cohort study
  Krishna Undela, Bashar Talal Saad Mohammed, Parthasarathi Gurumurthy, Srinivasa Murthy Doreswamy
 
Background: There is a paucity of studies conducted in India on neonatal outcomes of preterm birth and low birth weight. Hence, we aimed to assess the impact of preterm birth and low birth weight on medical conditions, medication use and mortality among neonates.
Methods: A prospective observational cohort study was conducted at the neonatal intensive care unit (NICU) over a period of 9 months. Neonates of either sex, admitted to NICU and who received at least one medication were enrolled in the study. Perinatal and demographic data, reason(s) for NICU admission, diagnoses, medications prescribed, medication-related problems, discharge status and the direct medical cost were documented and analyzed.
Results: Four hundred and fi ve neonates were included in the study: 60.5% were boys, 32.7% were preterm and 44.2% were born underweight. Neonatal sepsis (n = 125, 16.7%), unconjugated hyperbilirubinemia (n = 83, 11.1%) and respiratory distress syndrome (n = 62, 8.3%) were the most common medical conditions and were significantly more common among preterm and underweight neonates. Nearly half of the medications prescribed were anti-infectives for systemic use (n = 1310, 47.4%). The mean number of medications received by neonates increased from term to extremely preterm (5.2每15.0) and normal birth weight to extremely low birth weight (5.0每14.9). Mortality rate was significantly higher among extremely preterm (66.7%), and very preterm (15.2%) neonates compared to term (2.9%) neonates. The median direct medical cost for NICU admission was INR 21,430 (USD 331).
Conclusion: Medical conditions, medications prescribed and mortality rate were significantly higher among preterm and underweight neonates admitted to NICU.
  [Abstract] [Full Text] [PDF]  
Risk factors for recurrent macrosomia and child outcomes
  Fang Fang, Qing-Ying Zhang, Jun Zhang, Xiao-Ping Lei, Zhong-Cheng Luo, Hai-Dong Cheng
 
Background: Women who had delivered a macrosomic newborn will have a higher risk to deliver another macrosomia. We aimed to examine the recurrence risk of macrosomia in the subsequent pregnancy and the implications in long-term child health.
Methods: Data from the Collaborative Perinatal Project, a longitudinal birth cohort with 54,371 singleton births, were used. 401 recurrent macrosomic infants (macro-macro) and 1327 normal weight babies with a macrosomia in the last pregnancy (macro-normal) were selected to explore risk factors for recurrent macrosomia. Furthermore, 768 newly onset macrosomia with normal birthweight infant in previous pregnancies (normal-macro) were identified to examine long-term health effects of recurrent macrosomia.
Results: The recurrent rate of macrosomia was 23.2% [95% confidence interval (CI) 21.2%, 25.2%]. White race, higher pre-pregnant body mass index (BMI), more gestational weight gain, male infant and more prior macrosomic infants were significant risk factors for recurrent macrosomia. At 4 years of age, recurrent macrosomic infants had a higher BMI (16.7 vs. 16.1 kg/m2, adjusted 汕: 0.36, 95% CI: 0.12, 0.60) and a higher risk of overweight and obesity (adjusted OR: 1.56, 95% CI: 1.10, 2.23) than infants with normal birthweight after a previous macrosomic sibling. There was no significant difference between recurrent macrosomia and newly onset macrosomia in child outcomes after adjustment for covariates.
Conclusions: Fetal macrosomia has a high recurrence rate in the following pregnancy. Higher maternal pre-pregnant BMI and gestational weight gain are still important risk factors for recurrence of macrosomia, which in turn increases the risk for childhood obesity.
  [Abstract] [Full Text] [PDF]  
Auxo-endocrinological features in a cohort of internationally adopted children in Italy
  Barbara Bortone, Camilla Totaro, Pasqua Putignano, Sara Sollai, Luisa Galli, Maurizio de Martino, Elena Chiappini
 
Background: Internationally adopted children (IAC) can present growth impairment at arrival, which usually recovers over time. Moreover, a major prevalence of precocious puberty has been reported in this group.
Methods: All IAC referred to a tertiary level hospital in Italy from January 2016 to June 2017, underwent a standardized screening protocol and were prospectively enrolled in the study. The analyses of possible risk factors for growth impairment and precocious puberty were performed.
Results: Overall, 422 children were included (males 59.5%), with median age of 6.5 years (IQR 9.4每3.9), 29.9% adopted from Europe, 26.8% from Asia, 23.9% from Africa and 19.4% from Latin America. Children were in Italy from a median of 75 days (IQR 137.0每38.7). Stunting was observed in 12.9% of children, wasting in 4.3%, underweight in 12.9%. Precocious puberty was diagnosed in 2.2% of children. 17.1% IAC had diagnosis of special needs. Fetal alcohol spectrum disorders represented the 41.7% of children with special needs and 48.1% of Russian children. Independent predictive factors for stunting were age < 5 years, a diagnosis of special need and having been living in Italy for < 60 days since the arrival.
Conclusion: Stunting among IAC is a frequent fi nding especially in children < 5 years and in those with special needs, independently from their geographical origin.
  [Abstract] [Full Text] [PDF]  
Clinical image:
Magnetic resonance spectroscopy in Leigh-MELAS overlap syndrome
  Ara Ko, Young-Mock Lee
 
  [Abstract] [Full Text] [PDF]  
Letter to the Editors:
A patient with DAX1 mutation presenting with elevated testosterone in early infancy
  Juan Ge, Tang Li
 
  [Abstract] [Full Text] [PDF]  
   
 
 
 
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