Updated diagnosis and treatment of childhood tuberculosis

Shou-Chien Chen, Kwo-Liang Chen, Kou-Huang Chen, Shun-Tien Chien, Kow-Tong Chen

Taiwan, China

Author Affiliations: Department of Family Medicine, Da-Chien General Hospital, Taiwan, China (Chen SC); General Education Center, Ta Tung University, Taiwan, China (Chen SC); Department of Industrial Engineering and Management, China University of Science and Technology, Taiwan, China (Chen KL, Chen KH); Chest Hospital, Department of Health, Executive Yuan, Taiwan, China (Chien ST); Department of Public Health, College of Medicine, National Cheng Kung University, China (Chen KT)

Corresponding Author: Kow-Tong Chen, Department of Public Health, College of Medicine, National Cheng-Kung University, No. 1, University Road, Taiwan, China (Tel: 886-6-2353535 ext 5563; Fax: 886-6-2359033; Email: ktchen@mail.ncku.edu.tw)

doi: 10.1007/s12519-013-0404-6

Background: Childhood tuberculosis (TB) accounts for a significant proportion of the global tuberculosis disease burden. However, current and previous efforts to develop better diagnostic, therapeutic, and preventive interventions have focused on TB in adults, and childhood TB has been relatively neglected. The purpose of this review is to provide an update on the diagnostic and therapeutic recommendations for childhood TB with an emphasis on intrathoracic disease.

Data sources: The literature from a range of sources was reviewed and synthesized to provide an overview of the contemporary approaches for the diagnosis and treatment of childhood TB.

Results: This review summarizes the clinical, radiological, bacteriological, and immunological approaches to diagnose TB infection and disease in children. In addition, we summarize the updated guidelines for the treatment of TB in children.

Conclusions: The development of better diagnostic and therapeutic methods for childhood TB remains a significant challenge. As the strategies for diagnosis and treatment of childhood TB continue to improve and the knowledge base increases, the implementation of these strategies will be crucial.

Key words: childhood; diagnosis; treatment; tuberculosis

World J Pediatr 2013;9(1):9-16

Incidence of brain injuries in premature infants with gestational age ≤34 weeks in ten urban hospitals in China 

Hui-Jin Chen, Ke-Lun Wei, Cong-Le Zhou, Yu-Jia Yao, Yu-Jia Yang, Xiu-Fang Fan, Xi-Rong Gao, Xiao-Hong Liu, Ji-Hong Qian, Ben-Qing Wu, Gao-Qiang Wu, Qing-Mei Zhang, Xiao-Lan Zhang

Shanghai, China

Author Affiliations: Shanghai Institute for Pediatric Research, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China (Chen HJ); The Second Affiliated Hospital of China Medical University, Shenyang 110004, Liaoning Province, China (Wei KL); Peking University First Hospital, Beijing 100034, China (Zhou CL); West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China (Yao YJ); Xiangya Hospital of Central South University, Changsha 410008, Hunan Province, China (Yang YJ); Jinan Women & Children Hospital, Jinan 250012, Shandong Province, China (Fan XF); Hunan Children's Hospital, Changsha 410007, Hunan Province, China (Gao XR); Shenzhen Children's Hospital, Shenzhen 518026, Guangdong Province, China (Liu XH); Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China (Qian JH); Shenzhen City People's Hospital, the Second Affiliated Hospital of Jinan University Medical College, Shenzhen 518020, Guangdong Province, China (Wu BQ); Ulumuqi Women & Children Hospital, Ulumuqi 830000, Xinjiang Uyghur Autonomous Region, China (Wu GQ); Shenyang Women Hospital, Shenyang 110014, Liaoning Province, China (Zhang QM); Shenzhen Maternity and Child Healthcare Hospital, Shenzhen 518028, Guangdong Province, China (Zhang XL)

Corresponding Author: Hui-Jin Chen, MD, Professor of Pediatrics, Shanghai Institute for Pediatric Research, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China (Tel: +86-21-65790000-6471; Fax: +86-21-65791316; Email: hjchenk@163.com)

doi: 10.1007/s12519-012-0395-8

Background: There is a large number (1.5 million per year) of premature births in China. It is necessary to obtain the authentic incidences of intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL), the common brain injuries, in Chinese premature infants. The present multicenter study aimed to investigate the incidence of brain injuries in premature infants in ten urban hospitals in China.

Methods: The research proposal was designed by the Subspecialty Group of Neonatology of Pediatric Society of the Chinese Medical Association. Ten large-scale urban hospitals voluntarily joined the multicenter investigation. All premature infants with a gestational age ≤34 weeks in the ten hospitals were subjected to routine cranial ultrasound within three days after birth, and then to repeated ultrasound every 3-7 days till their discharge from the hospital from January 2005 to August 2006. A uniform data collection sheet was designed to record cases of brain injuries.

Results: The incidences of overall IVH and severe IVH were 19.7% (305/1551) and 4.6% (72/1551), respectively with 18.4% (56/305) for grade 1, 58.0% (177/305) for grade 2, 17.7% (54/305) for grade 3 and 5.9% (18/305) for grade 4 in nine hospitals. The incidences of overall PVL and cystic PVL were 5.0% (89/1792) and 0.8% (14/1792) respectively, with 84.3% (75/89) for grade 1, 13.5% (12/89) for grade 2, and 2.2% (2/89) for grade 3 in the ten hospitals. The statistically significant risk factors that might aggravate the severity of IVH were vaginal delivery (OR=1.883, 95% CI: 1.099-3.228, P=0.020) and mechanical ventilation (OR=4.150, 95% CI: 2.384-7.223, P=0.000). The risk factors that might result in the development of cystic PVL was vaginal delivery (OR=21.094, 95% CI: 2.650-167.895, P=0.000).

Conclusions: The investigative report can basically reflect the incidence of brain injuries in premature infants in major big cities of China. Since more than 60% of the Chinese population live in the rural areas of China, it is expected to undertake a further multicenter investigation covering the rural areas in the future.

Key words: incidence; intraventricular hemorrhage; multicenter investigation; periventricular leukomalacia; premature infants

World J Pediatr 2013;9(1):17-24

Solid tumors in Turkish children: a multicenter study

Ayper Kacar, Irem Paker, Zuhal Akcoren, Safak Gucer, Gulsev Kale, Diclehan Orhan, Beril Talim, Aylar Poyraz, Omer Uluoglu, Aylin Okcu Heper, Sema Apaydin, Nilufer Arda, Esin Boduroglu, Aynur Albayrak, Murat Alper, Ata Turker Arikok

Ankara, Turkey

Author Affiliations: Pathology Department, Ankara Child Diseases Hematology Oncology Research and Training Hospital, Turkey (Kacar A); 2nd Pathology Department, Diskapi Yildirim Beyazit Research and Training Hospital, Turkey (Paker I, Albayrak A, Alper M, Arikok AT); Pediatric Pathology Unit, Child Health and Diseases Department, Faculty of Medicine, Hacettepe University, Turkey (Akcoren Z, Gucer S, Kale G, Orhan D, Talim B); Pathology Department, Faculty of Medicine, Gazi University, Turkey (Poyraz A, Uluoglu O); Pathology Department, Faculty of Medicine, Ankara University, Turkey (Heper AO); Pathology Department, Dr. Sami Ulus Child Diseases Research and Training Hospital, Turkey (Apaydin S, Arda N, Boduroglu E)

Corresponding Author: Ayper Kacar, Ankara Child Diseases Hematology Oncology Research and Training Hospital, Pediatric Pathology Department, Altindag, Ankara, Turkey, Konutkent 2 A2 Blok No: 3 Cayyolu, Yeni Mahalle, Ankara, Turkey (Tel: 0533 655 76 57; Fax: 0312 347 23 30; Email: ayperkacar@yahoo.com)

doi: 10.1007/s12519-011-0323-3

Background: This paper presents a detailed incidence study on childhood solid tumors comprising a histopathology-based documentation of benign and malignant lesions.

Methods: The Ankara Pediatric Pathology Working Group collected databases of pediatric solid tumors from six pediatric reference centers in order to analyze the incidence, distribution and some epidemiologic characteristics of the tumors and to establish a multicenter database for further studies. A five-year retrospective archive search was carried out. Excluding epithelial tumors of the skin, leukemia, lymphoreticular system neoplasias, metastatic tumors, and hamartomas, 1362 solid tumors in 1358 patients were classified according to age, sex, localization, histopathology and clinical behavior.

Results: The male/female ratio was 0.9; 14.8% (201) of the patients belonged to 0-1 year age group, 20.7% (281) to 2-4 years, 25.9% (352) to 5-10 years, 22.2% (301) to 11-14 years, and 16.4% (223) to 15-18 years. Among all tumors, 708 (52.0%) were malignant, 645 (47.4%) benign tumors, 2 (0.1%) borderline tumors, and 2 (0.1%) unknown behavioral tumors. Malignant tumors were found in 50.2% (357) of female patients and in 54.0% (349) of male patients. A balanced distribution between benign and malignant entities among children under 18 years was observed. Comparison between the age groups revealed malignant cases outnumbered benign cases under 4 years of age while benign tumor numbers increased after 10 years of age. The most common entities in the malignant group were of sympathetic nervous system origin, while soft tissue tumors far outnumbered the others in the benign group.

Conclusions: We conclude that the cancer patterns of children in the Ankara region mostly resemble with those of the western population. This study provides useful information on the diagnosis of solid tumors in children and highlights variations in cancer incidence in different age groups.

Key words: cancer; childhood; epidemiology; incidence; solid tumor

World J Pediatr 2013;9(1):25-31

Effect of proton pump inhibition on acid, weakly acid and weakly alkaline gastro-esophageal reflux in children

Helena Turk, Bruno Hauser, Jernej Brecelj, Yvan Vandenplas, Rok Orel

Ljubljana, Slovenia; Brussels, Belgium

Author Affiliations: University Children's Hospital, University Medical Centre Ljubljana, Slovenia (Turk H, Brecelj J, Orel R) and UZ Brussel Kinderen, Vrije Universiteit Brussel, Brussels, Belgium (Hauser B, Vandenplas Y)

Corresponding Author: Rok Orel, MD, PhD, University Children's Hospital, University Medical Centre Ljubljana, Slovenia (Tel: +386 1 522 9254; Fax: +386 1 522 9357; Email: rok.orel@kclj.si)

doi: 10.1007/s12519-013-0405-5

Background: The effect of proton pump inhibitors on the characteristics of gastroesophageal reflux (GER) in children and adolescents was evaluated.

Methods: Twenty-one children and adolescents with symptoms suggesting GER disease (GERD) underwent upper endoscopy and a 24-hour multichannel intraluminal impedance/pH (MII-pH) monitoring before and at the end of 2 months of therapy with proton pump inhibitors (PPIs).

Results: Fourteen (67%) patients reported clinically relevant symptom improvement after 2 months of PPIs intake. At the first endoscopy, 8 (38%) patients had macroscopic signs of reflux esophagitis; after two months of therapy, 6/8 (75%) patients had a complete mucosal recovery. There was a significant reduction in the total percentage of mean acid reflux time (from 13.1% to 3.8%), and the De Meester score dropped to normal (from 46.4 to 13.1). The mean number of acid refluxes decreased significantly from 48 to 15 per 24 hours, while inversely, the mean number of weakly acid refluxes increased significantly from 26 to 64 per 24 hours. PPI therapy did not affect the total number of reflux episodes, the number of liquid and mixed refluxes, the duration of esophageal bolus exposure and proximal extent of the reflux.

Conclusions: In children and adolescents with GERD, PPIs do not affect the total number of reflux episodes. PPIs only decrease the acidity of refluxate. Nevertheless, the majority of patients with typical reflux symptoms may report symptom improvement. Esophagitis can be healed after PPI treatment. The treatment of weakly acid and weakly alkaline reflux remains a challenge for physicians in the future.

Key words: acid reflux; gastro-esophageal reflux (disease); multichannel intraluminal impedance; pH monitoring; proton pump inhibitor

World J Pediatr 2013;9(1):36-41

Common WU polyomavirus infection in a Beijing population indicated by surveillance for serum IgG antibody against capsid protein VP2

Ni-Na Zhang, Lin-Qing Zhao, Yuan Qian, Ru-Nan Zhu, Jie Deng, Fang Wang, Yu Sun, Li-Ying Liu

Beijing, China

Author Affiliations: Laboratory of Virology, Capital Institute of Pediatrics, 2 Yabao Road, Beijing 100020, China (Zhang NN, Zhao LQ, Qian Y, Zhu RN, Deng J, Wang F, Sun Y, Liu LY)

Corresponding Author: Yuan Qian, MD, Director of the Laboratory of Virology, Capital Institute of Pediatrics, 2 Yabao Road, Beijing 100020, China (Tel: 86-10-85610550; Fax: 86-10-85610550; Email: yqianbjc@263.net)

doi: 10.1007/s12519-013-0397-1

Background: WU polyomavirus (WU virus) was identified as a novel polyomavirus in 2007 from specimens of pediatric patients with acute respiratory infection (ARI). A lack of permissive cell lines has limited investigations into WU virus pathogenesis and prevalence.

Methods: The encoding region of the capsid protein VP2 gene was amplified from a WU virus DNA-positive clinical specimen and expressed as a recombinant His-tagged protein in Escherichia coli BL21 (DE3). The expressed VP2 was identified by expected molecular weight and immunoreactivity with anti-His monoclonal antibody in Western blotting assay. Serum samples collected from 455 individuals of all ages in Beijing without symptoms of ARI were tested for IgG antibodies against the affinity-purified recombinant VP2 protein by Western blotting to investigate the prevalence of natural WU virus infection. In addition, serum samples from four ARI pediatric patients, whose nasopharyngeal aspirates were positive for WU virus DNA and negative for all other respiratory-related viruses, were tested for IgM antibody against the recombinant VP2.

Results: Of the 455 serum samples, 238 reacted with the recombinant VP2, yielding an overall positive rate of 52.3% for IgG against VP2 of WU virus. The positive rate was the highest in serum samples from infants and children between 1 to 4 years of age. One of four ARI pediatric patients was positive for IgM against WU virus VP2, implicating WU virus as the causative disease agent.

Conclusions: The high prevalence of IgG against WU polyomavirus in Beijing-based study population indicates that WU virus infection is common in Beijing. WU virus may be responsible for some pediatric ARI cases, and primary infection of this virus may occur mostly in childhood.

Key words: antibody; infection; virus; WU polyomavirus

World J Pediatr 2013;9(1):48-52

Novel OCRL mutations in Chinese children with Lowe syndrome

Yan-Qin Zhang, Fang Wang, Jie Ding, Hui Yan, Yan-Ling Yang

Beijing, China

Author Affiliations: Department of Pediatrics, Peking University First Hospital, Beijing, China (Zhang YQ, Wang F, Ding J, Yan H, Yang YL)

Corresponding Author: Ding J, MD, PhD, Department of Pediatrics, Peking University First Hospital, 100034 Beijing, China (Tel: 86-010 -83572168; Fax: 86-010-66530532; Email: djnc_5855@126.com)

doi: 10.1007/s12519-013-0406-4

Background: Lowe syndrome is a rare X-linked recessive hereditary disease caused by mutations of the OCRL gene, which encodes an inositol polyphosphate-5-phosphatase. The disease is clinically characterized by congenital cataracts, psychomotor retardation, and proximal tubulopathy.

Methods: We retrospectively reviewed three unrelated Chinese patients with Lowe syndrome, clinically diagnosed by the abnormalities of eyes, nervous system, and kidneys. Genetic analysis of the OCRL gene was done for the three patients as well as their family members.

Results: Three OCRL gene mutations were detected in our study. Two of the mutations, g.1897delT in exon 18 (patient 1) and g.1470delG in exon 15 (patient 2), were novel. A missense mutation (p.Y513C) in exon 15, which had been reported previously, was found in patient 3. The mothers of all patients were heterozygous carriers of the respective mutations.

Conclusions: Three Chinese children were diagnosed with Lowe syndrome through clinical and genetic analyses. And two novel mutations in the OCRL gene were identified.

Key words: cataract; Dent disease 2; Lowe syndrome; mutations; OCRL

World J Pediatr 2013;9(1):53-57

Assessment of nutrient intakes of picky-eating Chinese preschoolers using a modified food frequency questionnaire

Flora Yin-Ying Kwok, Yvonne Yi-Fong Ho, Chung-Mo Chow, Christabella Yat-Nam So, Ting-Fan Leung

Hong Kong, China

Author Affiliations: Department of Pediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong (Kwok FY, Ho YY, Chow CM, Leung TF); University of Western Ontario, London, Ontario, Canada (So CY)

Corresponding Author: Ting Fan Leung, MD, Department of Pediatrics, 6/F, Clinical Sciences Building, Prince of Wales Hospital, Shatin, N.T., Hong Kong (Tel: 852-2632 2981; Fax: 852-2636 0020; Email: tfleung@cuhk.edu.hk))

doi: 10.1007/s12519-012-0386-9

Background: Dietary assessment is crucial for monitoring nutritional status of young children. This study applied a modified Chinese food frequency questionnaire (FFQ) to assess nutrient intakes of young picky-eating Hong Kong children.

Methods: Nutrient intakes were obtained by FFQ and 3-day food record (3DFR) in 29 picky-eating children aged 44.8±9.2 months who participated in a randomised controlled trial of a new milk formula.

Results: When compared with 3DFR, FFQ over-reported energy intake by 283 kcal (26.5%) at baseline and 237 kcal (21.4%) at end-of-study, and also over-estimated intakes of carbohydrates, proteins and fats. At baseline, FFQ and 3DFR classified 34.4%-65.5% of subjects into the same tertiles for most nutrients. These methods showed weak-to-moderate agreement in measuring most nutrients, with 3DFR showing a trend towards a systematic increase in the differences with increasing nutrient intake.

Conclusion: Our FFQ shows promising results for assessing nutrient intakes in picky-eating Chinese preschoolers.

Key words: Chinese; food frequency questionnaire; nutrition; preschooler

World J Pediatr 2013;9(1):58-63

Asthma management by medical practitioners: the situation in a developing country

Osarogiagbon Wilson Osaretin, Nwaneri Damian Uchechukwu, Oviawe Osawaru

Benin City, Nigeria

Author Affiliations: Department of Child Health, University of Benin Teaching Hospital, PMB 1111, Benin City, Nigeria (Osarogiagbon WO, Nwaneri DU, Oviawe O)

Corresponding Author: Oviawe O, Department of Child Health, University of Benin Teaching Hospital, PMB 1111, Benin City, Edo State, Nigeria (Tel: +2348037275398; Email: sonofeto@yahoo.com).

doi: 10.1007/s12519-012-0389-6

Background: Asthma is a common chronic disease worldwide and is responsible for considerable morbidity, socioeconomic burden, and depletion of health resources. Clinically, diagnosis of asthma is based on information obtained from symptom questionnaires, physical examination and demonstration of variable airflow obstruction. Proper diagnosis of asthma is mandatory in clinical practice in order to avoid undue use of potentially toxic asthma medications and prevent unwarranted social stigmatization. This study aimed to determine how medical practitioners in Nigeria diagnose asthma and use asthma medications during asthma exacerbation and the follow-up period.

Methods: A semi-structured self-administered questionnaire on asthma management was distributed to medical practitioners attending the annual scientific meeting/update course in August, 2009. Forty-nine practice centers in the 6 geopolitical zones in Nigeria were included in this survey.

Results: Totally 131 medical practitioners (80 males, 51 females) completed the questionnaire. Post National Youth Service Corp practice (mean ± SD) was 9.95±7.78 years, ranging from 2 to 39 years. The practice centers of respondents included university teaching hospitals (65.6%), state specialist hospitals (17.6%), private hospitals (10.7%), and missionary hospitals (6.l%). Respondents' assessment of burden of asthma was high (30.5%), moderate (63.4%) and low (6.1%). Asthma diagnosis was made by various methods including: symptoms only (35.9%), health personnels (32.3%), mother/self evaluation (20.3%), and use of spirometry/peak expiratory flow rate (11.5%). Thus inappropriate asthma diagnosis could have been practiced by 116 (88.5%) medical practitioners.

Conclusion: The study revealed inadequate knowledge of asthma diagnosis and drug management of asthma by medical practitioners in Nigeria.

Key words: airflow obstruction; asthma; medical practitioner; peak expiratory flow rate

World J Pediatr 2013;9(1):64-67

Liver steatosis in Polish children assessed by medico-legal autopsies

Marta Rorat, Tomasz Jurek, Ernest Kuchar, Leszek Szenborn, Wojciech Golema, Agnieszka Halon

Wroclaw, Poland

Author Affiliations: Department of Forensic Medicine (Rorat M, Jurek T, Golema W), Department of Pediatrics and Infectious Diseases (Kuchar E, Szenborn L), Department of Pathological Anatomy (Halon A), Wroclaw Medical University, Poland

Corresponding Author: Marta Rorat, Department of Forensic Medicine, Medical University of Wroclaw, Mikulicza Radeckiego 4, Wroclaw 50-368, Poland (Tel: +48-71-784-14-74; Fax: + 48-71-784-00-95; Email: marta.rorat@gmail.com)

doi: 10.1007/s12519-012-0387-8

Background: Cases of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are increasing in the pediatric population. Their growing prevalence coincides with the obesity epidemic. Assessment of the incidence requires liver biopsies on a representative population sample, which are hampered by the absence of indications for invasive examination on children without clinical symptoms. The aim of the current study was to assess the incidence of liver steatosis in the population of children up to 18 years old from Lower Silesia.

Methods: We retrospectively reviewed 342 medico-legal autopsy reports from 2000 to 2009. We separated a group of 256 children whose death was caused by trauma. Liver steatosis was diagnosed according to the results of histopathological examinations and typical macroscopic imaging.

Results: In the 265 children who died from trauma, liver steatosis was reported in 11 (4.2%) children (6 boys) aged between 6 months and 18 years old. Six of the 11 children (54.5%) were found to be overweight. In all 342 children, steatosis was found in 18 (5.3%) children (13 boys), while NASH was diagnosed in 1 (0.3%). Excess body weight was observed in 55.6% (10/18) of children with steatosis.

Conclusions: Liver steatosis can occur at any age, even in infancy. Being overweight is a very important risk factor. Gross examination of the liver is insufficient for the diagnosis of steatosis because of its lower sensitivity and specificity. Verification of liver steatosis requires reference histopathological examination.

Key words: autopsy; liver steotosis; non-alcoholic fatty liver disease; obesity

World J Pediatr 2013;9(1):68-72

Clinical features of benign convulsions with mild gastroenteritis in Chinese infants

Yun-Feng Wang, Zhong-Shu Zhou

Beijing, China

Author Affiliations: Department of Pediatrics, China-Japan Friendship Hospital, Beijing, China (Wang YF, Zhou ZS)

Corresponding Author: Zhong-Shu Zhou, Department of Pediatrics, China-Japan Friendship Hospital, Beijing, China (Tel: +86-10-84206180; Email: wangyf252@126.com)

doi: 10.1007/s12519-012-0393-x

Background: Benign convulsions occur in infants during the course of mild gastroenteritis. It is now recognized as a distinct clinical entity in many countries. However, its occurrence in China has not yet been widely recognized by Chinese pediatricians.

Methods: A retrospective study was conducted in 48 patients with convulsions between January 1, 2004 and December 31, 2009.

Results: The age of onset of gastroenteritis was between 13 months and 24 months in 34 patients (70.83%). The episodes occurred at a distinct autumn/winter peak (75%). The seizures mostly occurred within the first 5 days of gastroenteritis, especially within the first 3 days, peaking on day 2 (39.58%). Thirty-five patients (72.92%) had clustered seizures in their episodes. Most episodes were symmetric, generalized tonic–clonic (83.33%) and brief (93.75%). The seizures were induced by pain and/or crying in 19 (39.58%) patients. Stool culture was positive for rotavirus in 21 (53.85%) of the 39 patients. Twenty patients (20/41, 48.78%) still had clustered seizures after the administration of a single anticonvulsant. The seizures persisted even after the administration of two combined anticonvulsants in 5 (26.32%) of 19 episodes. All patients exhibited normal psychomotor development.

Conclusions: Benign convulsions with mild gastroenteritis are not rare in China, and rotavirus infection is a major cause.

Key words: gastroenteritis; infant; seizure

World J Pediatr 2013;9(1):73-75

Clinical and pathological features of a neonate with autosomal recessive polycystic kidney disease caused by a nonsense PKHD1 mutation

Xi-Hui Zhou, Zhi-Yan Hui, Yuan Li

Xi'an, China

Author Affiliations: Department of Neonatology, the First Affiliated Hospital, Medical School of Xi an Jiaotong University/Ion Channel Disease Laboratory, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an 710061, China (Zhou XH, Hui ZY, Li Y)

Corresponding Author: Xi-Hui Zhou, MD, Department of Neonatology, First Affiliated Hospital, Medical College of Xi'an Jiaotong University, Xi'an 710061, China (Email: zhouxih@mail.xjtu.edu.cn)

doi: 10.1007/s12519-013-0407-3

Background: Autosomal recessive polycystic kidney disease (ARPKD) is one of the most common hereditary nephropathies in childhood. We report a neonate with ARPKD presenting with oligohydramnios, enlargement and increased echogenicity of both kidneys shown by antenatal sonograms after a 29-week gestation and died within the first few hours of life.

Methods: The neonate was investigated pathologically post-mortem. PCR-DNA direct sequencing was performed to detect the exons of the PKHD1 gene for mutation analysis.

Results: Autopsy findings of the kidney and liver confirmed the diagnostic hypothesis. PKHD1 mutation analysis revealed that there was a homozygous nonsense mutation c.9319C>T (p.R3107X), which was found to be pathogenic, in exon 58 in the neonate.

Conclusions: The recurrence of PKHD1 mutation c.9319C>T (p.R3107X) in the ARPKD population might be a good evidence that it is disease associated. Given the limitations of antenatal ultrasound, PKHD1 mutation analysis is helpful for accurate genetic counseling and early prenatal diagnosis.

Key words: infants; pyelonephritis; vesicoureteral reflux

World J Pediatr 2013;9(1):76-79

Acute cerebellitis associated with rotavirus infection

Zenichiro Kato, Hideo Sasai, Michinori Funato, Takahiko Asano, Naomi Kondo

Gifu, Japan

Author Affiliations: Department of Pediatrics, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu, Japan (Kato Z, Sasai H, Funato M, Kondo N); Department of Radiology, Gifu University Hospital, 1-1 Yanagido, Gifu 501-1194, Japan (Asano T)

Corresponding Author: Zenichiro Kato, MD, PhD, Department of Pediatrics, Graduate School of Medicine, Gifu University, 1-1 Yanagido, 501-1194 Gifu , Japan (Tel: +81 58 230 6386, Fax: +81 58 230 6387, Email: zen-k@gifu-u.ac.jp)

doi: 10.1007/s12519-011-0298-0

Background: Rotavirus infection is occasionally associated with central nervous system involvement, including cerebellitis. However, the precise clinical sequelae of central nervous system disorders and the usefulness of neuroradiological examination for clinical therapies, such as steroid pulse therapy, have not been clarified.

Methods: We present a case of rotavirus cerebellitis examined by magnetic resonance imaging (MRI), magnetic resonance spectroscopy, and single photon emission computed tomography.

Results: MRI demonstrated abnormal intensities in the right cerebellum on fluid attenuated inversion recovery images and, much more obviously, on diffusion-weighted images, but not on T1- or T2-weighted images. Single photon emission computed tomography showed only mild hypoperfusion in the right cerebellum on the 15th day, while 4 weeks later the image showed remarkably low perfusion in the right cerebellum.

Conclusion: The findings of the reported case suggest the importance of performing radiological examinations at early phases of the disease, especially by new modalities such as diffusion weighted imaging, to make timely and appropriate therapeutic decisions.

Key words: cerebellar ataxia; cerebellitis; magnetic resonance imaging; rotavirus; single photon emission computed tomography

World J Pediatr 2013;9(1):87-89

Correspondence

Issues concerning psychomotor development of children after preimplanntation genetic diagnosis and parental stress evaluation

Loretta Thomaidis and colleagues^[1] describe a significant study of assessing the psychomotor development of children born after preimplantation genetic diagnosis (PGD) and parental stress. Their results showed that PGD children have poorer cognitive and motor skills and lower parental stress compared with naturally conceived children. But there are several confounding factors that may bias the conclusion.

First, the high prevalence of twin and triplet pregnancies (33.3%) in PGD children may contribute greatly to the lower cognitive and motor ability, other than PGD itself. As we know, multiple pregnancies and deliveries have long been considered as risk factors, and the likelihood of adverse outcomes for subsequent development is usually elevated.^[2,3] There is considerable possibility that multiple pregnancies give rise to the poor developmental ability of PGD children. In addition, there are 41.7% of all pregnancies with complications. Both of the conditions result in a higher rate of premature delivery and children small for gestational age. Therefore, for the factors of technology of PGD, multiple pregnancies and peri-neonatal complications, it is really difficult to determine the key factors leading to the developmental adverse outcomes. We should control these factors if we try to reach a conclusion on any adverse consequences of PGD per se.

Second, there is no detailed information about the parents of PGD children and controls in evaluating the parent stress levels. The authors recruited a control group of 35 parents (19 mothers and 16 fathers), but did not clarify if the interviewee was the caregiver or not. Although mothers are the primary caregivers in the daily care for children, fathers are increasingly involved in family life. But in the present study, the authors did not specifically address whether the persons who provided the information were the caregivers; this would affect the reliability of the evaluation of parent stress because growing researches showed that different roles of mothers and fathers who experienced different aspects of their child's behavior as especially stressful.^[4,5] Moreover, the parity number of children in the control group was not noted. It is well known that parent experience would bias the results of parent stress levels. Hence, it is difficult to draw a reasonable conclusion regarding the parent stress levels because information resources were not provided in detail.

Based on these issues, we should be careful when interpreting the results.

Jian Shen, Shu-Jiong Mao

Department of Pediatrics

Hangzhou First People's Hospital

Hangzhou, China

Email: maoshujiong@126.com

References

1       Thomaidis L, Kitsiou-Tzeli S, Critselis E, Drandakis H, Touliatou V, Mantoudis S, et al. Psychomotor development of children born after preimplantation genetic diagnosis and parental stress evaluation. World J Pediatr 2012;8:309-316.

2       Akerman BA, Thomassen PA. The fate of "small twins": a four-year follow-up study of low birthweight and prematurely born twins. Acta Genet Med Gemellol (Roma) 1992;41:97-104.

3       Machin GA, Keith LG. Can twin-to-twin transfusion syndrome be explained, and how is it treated? Clin Obstet Gynecol 1998;41:104-113.

4       Keller D, Honig AS. Maternal and paternal stress in families with school-aged children with disabilities. Am J Orthopsychiatry 2004;74:337-348.

5       Krauss MW. Child-related and parenting stress: similarities and differences between mothers and fathers of children with disabilities. Am J Ment Retard 1993;97:393-404.

doi: 10.1007/s12519-013-0408-2

Author reply

We have read very carefully all your comments regarding the results of our study and the way they should be interpreted. Several confounders and methodological issues may also affect the final results of our study, but we would like to make some clarifications.

Firstly, we decided not to exclude prematures, intra-uterine growth retardation and multliples although these factors could contribute to the adverse outcome of our study population. However, we are of the opinion supported elsewhere^[1] that developmental studies in in vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) children must be designed in such a way to include parameters as multiparity, prematurity, and low birth weight.

As far as the pregnancy complications are concerned, we must clarify that in most cases they were the usual complications reported in preimplantation genetic diagnosis or preimplantation genetic screening (PGD/PGS) pregnancies,^[2] such as diabetes mellitus, hypertension and placental bleeding. In our study population, most of these maternal problems have been treated with medication at home, and they did not lead to an eventful perinatal period.

 We should point out that PGD psychomotor development was evaluated using Bayley and Griffith's scales. As these tests do not measure intelligence quotients but general developmental quotients, their results can be useful for early intervention in children with lower scores. Bowen et al^[3] have commented on psychomotor assessment with Bayley scale that low developmental scores, especially if used in ages <12 months, are not implicating a poor developmental outcome but support the need of a close follow-up of the child. Future studies with long-term follow-up of PGD/PGS children to older ages could be useful to estimate permanent intelligent quotient scores. 

We should inform that we are continuing our study by expanding our sample population, so far, to 51 PGD children. Psychomotor evaluation by the same team, using again Bayley and Griffith's scales, showed a lower incidence of severely low mental quotients, while motor and general quotients remained unchanged (Table). In the same study, the percentage of PGD children with normal quotients was consistent with the current literature.^[4] Furthermore, a significant percentage of PGD children showed advanced developmental skills (Table). 

Regarding your second comment, in both parent-groups we asked the main caregiver of the child to complete PSI-SF questionnaire. As far as parity of the control group is concerned, all children of the control group were singletons. Our finding that PGD parents do not experience high levels of total parental stress compared with parents of naturally conceived children, it is consistent with the current literature^[4] while it was argued in studies of IVF parents as well.^[5,6]

Thank you for your arguments. Multi-centre, long-term and carefully-designed studies are needed to further elucidate the exact impact of confounders such as prematurity, multiparity, low birth weight, perinatal complications in PGD children.

Eleni Leze, Loretta Thomaidis

Developmental Assessment Unit

Second Department of Pediatrics

"P. & A. Kyriakou" Children's Hospital

National and Kapodistrian University of Athens

School of Medicine;

Sophia Kitsiou-Tzeli, Emmanouel Kanavakis

Department of Medical Genetics

National and Kapodistrian University of Athens School of Medicine

Athens, Greece

Email: lenaezel@yahoo.gr, dr_thomaidis@yahoo.gr

References

1       Middelburg KJ, Heineman MJ, Bos AF, Hadders-Algra M. Neuromotor, cognitive, language and behavioural outcome in children born following IVF or ICSI- a systematic review. Hum Reprod Update 2008;14:219-231.

2       Desmyttere S, De Schepper J, Nekkebroeck J, De Vos A, De Rycke M, Staessen C, et al. Two-year auxological and medical outcome of singletons born after embryo biopsy applied in preimplantation genetic diagnosis or preimplantation genetic screening. Hum Reprod 2009;24:470-476.

3       Bowen J, Gibson F, Leslie G, Saundres D. Medical and developmental outcome at 1 year for children conceived by intracytoplasmic sperm injection. Lancet 1998;351:1529-1533.

4       Nekkebroeck J, Bonduelle M, Desmyttere S, Van den Broeck W, Ponjaert-Kristoffersen I. Socio-emotional and language development of 2-year-old children born after PGD/PGS, and parental well-being. Hum Reprod 2008;23:1849-1857.

5       McMahon CA, Gibson F, Leslie G, Cohen J, Tennant C. Parents of 5-year-old in vitro fertilization children: psychological adjustment, parenting stress, and the influence of subsequent in vitro fertilization treatment. J Fam Psychol 2003;17:361-369.

6       Papaligoura Z, Panopoulou-Maratou O, Solman M, Arvaniti K, Sarafidou J. Cognitive development of 12 month old Greek infants conceived after ICSI and the effects of the method on their parents. Hum Reprod 2004;19:1488-1493.

doi: 10.1007/s12519-013-0409-1