Winnie Tso

The Clinical Impact of Chromosomal Microarray on Paediatric Care in Hong Kong

Objective To evaluate the clinical impact of chromosomal microarray (CMA) on the management of paediatric patients in Hong Kong. Methods We performed NimbleGen 135k oligonucleotide array on 327 children with intellectual disability (ID)/developmental delay (DD), autism spectrum disorders (ASD), and/or multiple congenital anomalies (MCAs) in a university-affiliated paediatric unit from January 2011 to May 2013. The medical records of patients were reviewed in September 2013, focusing on the pathogenic/likely pathogenic CMA findings and their “clinical actionability” based on established criteria. Results Thirty-seven patients were reported to have pathogenic/likely pathogenic results, while 40 had findings of unknown significance. This gives a detection rate of 11% for clinically significant (pathogenic/likely pathogenic) findings. The significant findings have prompted clinical actions in 28 out of 37 patients (75.7%), while the findings with unknown significance have led to further management recommendation in only 1 patient (p<0.001). Nineteen out of the 28 management recommendations are “evidence-based” on either practice guidelines endorsed by a professional society (n = 9, Level 1) or peer-reviewed publications making medical management recommendation (n = 10, Level 2). CMA results impact medical management by precipitating referral to a specialist (n = 24); diagnostic testing (n = 25), surveillance of complications (n = 19), interventional procedure (n = 7), medication (n = 15) or lifestyle modification (n = 12). Conclusion The application of CMA in children with ID/DD, ASD, and/or MCAs in Hong Kong results in a diagnostic yield of ∼11% for pathogenic/likely pathogenic results. Importantly the yield for clinically actionable results is 8.6%. We advocate using diagnostic yield of clinically actionable results to evaluate CMA as it provides information of both clinical validity and clinical utility. Furthermore, it incorporates evidence-based medicine into the practice of genomic medicine. The same framework can be applied to other genomic testing strategies enabled by next-generation sequencing.

Folinic Acid Responsive Epilepsy in Ohtahara Syndrome Caused by STXBP1 Mutation

BACKGROUND Ohtahara syndrome is a severe condition with early onset of recurrent unprovoked seizures associated with abnormal electroencephalography and global developmental delay. Folinic acid-responsive seizures are treatable causes of Ohtahara syndrome, which is thought to be due to recessive mutations in the ALDH7A1 gene, resulting in deficiency of antiquitin. METHOD Here we report a girl with Ohtahara syndrome who exhibited transient folinic acid responsiveness but without evidence of antiquitin dysfunction. RESULTS She was later found to have a known missense mutation (c.1439 C > T, p.P480 L) in exon 16 of the STXBP1 gene. CONCLUSION For infants presenting with Ohtahara syndrome with responsiveness to folinic acid and negative antiquitin deficiency analyses, genetic testing for other possible causative genes such as STXBP1 mutation is recommended.

Socioeconomic Gradient in Childhood Obesity and Hypertension: A Multilevel Population-Based Study in a Chinese Community

Background This study aims to assess evidence for any socioeconomic gradients in childhood obesity and hypertension in a population-representative sample in Hong Kong, China. Methods The data of a stratified random sampled growth survey collected in 2005–2006 was matched with a population by-census. Obesity was defined using the International Obesity Task Force standard and hypertension was defined using the Hong Kong norm table. Family socioeconomic status (SES) was measured by maternal education level. Neighbourhood SES was measured by median household income of the neighbourhood. Multilevel Poisson regression models with robust standard error were used to test the association. Body mass indices of children’s parents were included as potential confounders. Intra-school/neighbourhood correlations were adjusted using random factors. Results Totally 14842 children (age 6–19 years) included in the analysis, in which 16.6% of them were overweight or obese. Children whose mother only completed secondary school or below had higher risk of childhood obesity (RR 1.41, 95% CI 1.13–1.76, p = 0.003) and hypertension (RR 1.18, 95% CI 1.01–1.36, p = 0.03). Meanwhile, children in the lowest neighbourhood SES group had higher risk of childhood underweight (RR 1.61, 95% CI 1.04–2.49, p = 0.03), overweight (RR 1.35, 95% CI 1.05–1.72, p = 0.02), and obesity (RR 2.07, 95% CI 1.11–3.88, p = 0.02). Conclusions Socioeconomic gradient in childhood obesity and hypertension existed in Hong Kong, one of the most developed cities in China. These results have implications for policymakers and public health experts and highlight the need to monitor trends in other parts of China.

Effectiveness of a Culturally Attuned Internet-based Depression Prevention Program for Chinese Adolescents: A Randomized Controlled Trial

Depression prevention among adolescents is crucial for reducing the global disease burden. Internet‐based depression prevention approaches are found to be effective but they were mostly evaluated in a Western context. Grasping the Opportunity is a Chinese Internet intervention, which was translated and modified from CATCH‐IT developed in the West. We aimed to evaluate the effectiveness of Grasp the Opportunity in reducing depressive symptoms in Chinese adolescents.

Implementation of an interprofessional team-based learning program involving seven undergraduate health and social care programs from two universities, and students' evaluation of their readiness for interprofessional learning

BackgroundInterprofessional learning is gaining momentum in revolutionizing healthcare education. During the academic year 2015/16, seven undergraduate-entry health and social care programs from two universities in Hong Kong took part in an interprofessional education program. Based on considerations such as the large number of students involved and the need to incorporate adult learning principles, team-based learning was adopted as the pedagogy for the program, which was therefore called the interprofessional team-based learning program (IPTBL). The authors describe the development and implementation of the IPTBL program and evaluate the effectiveness of the program implementation.MethodsEight hundred and one students, who are predominantly Chinese, participated in the IPTBL. The quantitative design (a pretest-posttest experimental design) was utilized to examine the students’ gains on their readiness to engage in interprofessional education (IPE).ResultsThree instructional units (IUs) were implemented, each around a clinical area which could engage students from complementary health and social care disciplines. Each IU followed a team-based learning (TBL) process: pre-class study, individual readiness assurance test, team readiness assurance test, appeal, feedback, and application exercise. An electronic platform was developed and was progressively introduced in the three IUs. The students’ self-perceived attainment of the IPE learning outcomes was high. Across all four subscales of RIPLS, there was significant improvement in student’s readiness to engage in interprofessional learning after the IPTBL. A number of challenges were identified: significant time involvement of the teachers, difficulty in matching students from different programs, difficulty in making IPTBL count towards a summative assessment score, difficulty in developing the LAMS platform, logistics difficulty in managing paper TBL, and inappropriateness of the venue.ConclusionsDespite some challenges in developing and implementing the IPTBL program, our experience showed that TBL is a viable pedagogy to be used in interprofessional education involving hundreds of students. The significant improvement in all four subscales of RIPLS showed the effects of the IPTBL program in preparing students for collaborative practice. Factors that contributed to the success of the use of TBL for IPE are discussed.

Expanded Prader–Willi syndrome due to chromosome 15q11.2–14 deletion: Report and a review of literature†

We report on a male infant with de novo unbalanced t(5;15) translocation resulting in a 17.23 Mb deletion within 15q11.2–q14 and a 25.12 kb deletion in 5pter. The 15q11.2–q14 deletion encompassed the 15q11.2–q13 Prader–Willi syndrome (PWS) critical region and the recently described 15q13.3 microdeletion syndrome region while the 5pter deletion contained no RefSeq genes. From our literature review, patients with similar deletions in chromosome 15q exhibit expanded phenotype of severe developmental delay, protracted feeding problem, absent speech, central visual impairment, congenital malformations and epilepsy in addition to those typical of PWS. The patient reported herein had previously unreported anomalies of mega cisterna magna, horseshoe kidney and the rare neonatal interstitial lung disease known as pulmonary interstitial glycogenosis. Precise breakpoint delineation by microarray is useful in patients with atypical PWS deletions to guide investigation and prognostication.

Impact of nutritional supplements on cognitive development of children in developing countries: A meta-analysis

Nutritional supplements may be important on cognition but the evidence is heterogeneous. This meta-analysis aimed (1) to determine whether nutritional supplements provided to pregnant women or young children could improve cognitive development of children in developing countries, and (2) to explore how supplementation characteristics could improve children’s cognitive outcomes. This meta-analysis examined nutritional supplementation studies in 9 electronic databases and 13 specialist websites. Experimental studies were included if they were published from 1992 to 2016, were conducted in developing countries, had nutritional supplementation for pregnant women or children aged ≤8, and reported effect sizes on cognitive outcomes. Interventions with confounded components, such as stimulation and parenting, were excluded. 67 interventions (48 studies) for 29814 children from 20 developing countries were evaluated. Childhood nutritional supplementation could improve children’s cognitive development (d 0.08, 95% CI 0.03–0.13) and those with ≥5 nutrients was particularly beneficial (0.15, 0.08–0.22). Antenatal supplementation did not improve cognitive development (0.02, -0.01 to 0.06) except for those implemented in the first trimester (0.15, 0.03–0.28). In conclusion, childhood nutritional supplementation was beneficial to cognitive development but could be optimised by providing multiple nutrients; antenatal supplementation should target pregnancy women in the first trimester for better cognitive benefits.

Risk factors for child physical abuse and neglect among Chinese young mothers

Although studies have reported a linkage between young pregnancy and child maltreatment risk, it is still unclear about what factors place young mothers at greater risk of maltreating their child in Chinese context. Based on the socio-ecological model, risk factors in 4 domains: family background/structure, maternal stressors, mother-child interaction, and child behavioral issue in relation to physical assault, neglect, both physical assault and neglect, and either physical assault or neglect among Chinese young mothers in Hong Kong were assessed. 392 young mothers were recruited from an integrated supportive program for young mothers. The mean age of mothers at delivery was 21.8 (SD=3.0) and 52.3% were married. Individual risk factors and cumulative risk domains related to different child maltreatment groups were examined. Our results show both overlapping and unique risk factors across the domains associated with physical assault and neglect. Further, young families exposed to higher number of risk domains show higher rates for physical assault and neglect, co-occurrence of physical assault and neglect, and either form of maltreatment. In addition, various risk domains were found to be particularly important for different forms of maltreatment: family background/structure domain was found to be an important risk domain for neglect; mother-child interaction domain for both physical assault and neglect; family background/structure and maternal stressors domains for either physical assault or neglect. Closer examination of a subgroup of adolescent mothers aged 18 and below shows that family background/structure was an important risk domain for this group.

Linking Healthcare and Social Service Databases to Study the Epidemiology of Child Maltreatment and Associated Health Problems: Hong Kong's Experience

Objective To examine the incidence and trend of child maltreatment and its associated health problems in Hong Kong by linking healthcare and social service databases. Study design Data on 4816 children under the age of 18 years registered with the Child Protection Registry and matching health records in public hospitals in Hong Kong from 2003 to 2010 were extracted. Associations were examined between different types of child maltreatment and childs medical diagnosis according to the International Statistical Classification of Diseases and Related Health Problems, 10th Revision codes including suicidal attempt (X60‐X84), nonchild maltreatment related injuries (S00‐S99; T00‐T98, excluding T74 and T76 that are maltreatment related injuries), mental health problems (F00‐F99), and congenital malformations/chromosomal abnormalities (Q00‐Q99). Results Significant rising trends were found for child physical abuse, neglect, and sexual abuse during the period from 2003 to 2010. Psychological abuse remained stable. Risk of suicide attempt was higher among children suffering from sexual abuse, psychological abuse, and children experiencing multiple abuses; mental health diagnoses were more common in victims of psychological and multiple abuses. Congenital malformations and chromosomal abnormalities were more commonly found among neglected children. Conclusions In contrast to the decreasing trend observed in the West during the study period, there has been an escalating trend in child maltreatment in Hong Kong and child maltreatment is strongly associated with major health problems. This is one of the first studies to demonstrate the power of linking healthcare and social service databases, which allows for both a better understanding of the impact of child maltreatment and as a guide future policy and service planning.