Turner syndrome in diverse populations.

Turner syndrome (TS) is a common multiple congenital anomaly syndrome resulting from complete or partial absence of the second X chromosome. In this study, we explore the phenotype of TS in diverse populations using clinical examination and facial analysis technology. Clinical data from 78 individuals and images from 108 individuals with TS from 19 different countries were analyzed. Individuals were grouped into categories of African descent (African), Asian, Latin American, Caucasian (European descent), and Middle Eastern. The most common phenotype features across all population groups were short stature (86%), cubitus valgus (76%), and low posterior hairline 70%. Two facial analysis technology experiments were conducted: TS versus general population and TS versus Noonan syndrome. Across all ethnicities, facial analysis was accurate in diagnosing TS from frontal facial images as measured by the area under the curve (AUC). An AUC of 0.903 (p < .001) was found for TS versus general population controls and 0.925 (p < .001) for TS versus individuals with Noonan syndrome. In summary, we present consistent clinical findings from global populations with TS and additionally demonstrate that facial analysis technology can accurately distinguish TS from the general population and Noonan syndrome.

A Narrative Review on Diabetic Ketoacidosis in Children.

BACKGROUND: Diabetic ketoacidosis (DKA) is a life-threatening complication in children with diabetes mellitus. There are considerable differences in the management approaches for DKA between different countries. One of the main areas of differences between guidelines is the administration of fluid, with most guidelines adopting a restrictive approach. This is based on the concern over cerebral oedema, a lethal sequela allegedly to be caused by excessive fluid administration. However, in recent years, new clinical studies suggest that there is no causal relationship between intravenous fluid therapy and DKA-related cerebral injury. The British Society of Paediatric Endocrinology updated its guideline in 2020 to adopt a more permissive approach to fluid administration, which has sparked controversy among some paediatricians. OBJECTIVES: The purpose of this article is to provide a narrative review on the management of DKA. METHODS: A PubMed search was performed with clinical queries using the key term "diabetic ketoacidosis". The search strategy included randomized controlled trials, clinical trials, meta-analyses, observational studies, guidelines, and reviews. The search was restricted to English literature and the age range of 18 years and younger. Moreover, we reviewed and compared major guidelines. CONCLUSION: The management of DKA involves early recognition, accurate diagnosis, meticulous fluid and insulin treatment with close monitoring of blood glucose, ketones, electrolytes, renal function, and neurological status. There is still limited clinical evidence to support either a restrictive or permissive approach in the fluid management of paediatric DKA patients. Clinicians should exercise caution when applying different guidelines in their clinical practice, considering the specific circumstances of individual paediatric patients.

Association of vitamin D-binding protein polymorphisms and serum 25(OH)D concentration varies among Chinese healthy infants of different VDR-FokI genotypes: A multi-centre cross-sectional study.

Hypovitaminosis D during infancy is associated with the development of chronic diseases and poor health later in life. While the effect of environmental factors on vitamin D concentration has been extensively explored, this study aimed to explore the effect of genetic factors on vitamin D concentration among Chinese infants. We conducted a multi-centre cross-sectional study in Hong Kong from July 2019 to May 2021. A candidate genetic approach was adopted to study four selected genetic variants of the vitamin D-binding protein (DBP) and vitamin D receptor (VDR) (rs4588, rs7041, rs2282679 and rs2228570) to examine their associations with measured serum 25(OH)D concentration. A total of 378 Chinese infants aged 2-12 months were recruited in this study. Peripheral blood samples were collected from the infants to measure serum 25(OH)D concentration and extract DNA. Results showed that rs7041T and rs2282679C were significantly associated with lower serum 25(OH)D concentration. Further analysis of the DBP variants revealed that the GC1F allele was significantly associated with lower 25(OH)D concentration and identified as the risk DBP isoform in infants. While our results revealed that there is no direct association between VDR-FokI genotype and serum 25(OH)D concentration, a VDR-FokI genotype-specific pattern was observed in the association between DBP isoforms and serum 25(OH)D concentration. Specifically, significant associations were observed in the DBP genotypes GC1F/F, GC1F/2 and GC1S/2 among VDR-FokI TT/TC carriers, but not in VDR-FokI CC carriers. Our findings lay down the basis for the potential of genetic screening to identify high risk of hypovitaminosis D in Chinese infants.

Obesity in children and adolescents: Overview of the diagnosis and management.

Childhood obesity is one of the biggest public health challenges globally. It is associated with various adverse health consequences throughout life. Prevention and early intervention represent the most reasonable and cost-effective approaches. Considerable progress has been achieved in the management of obesity in children and adolescents; yet, implementation in the real world remains a challenge. This article aimed to present an overview of the diagnosis and management of obesity in children and adolescents.

Incidence and Predictors for Oncologic Etiologies in Chinese Children with Pituitary Stalk Thickening.

BACKGROUND: With the increasing use of magnetic resonance imaging (MRI) in the evaluation of children with endocrine disorders, pituitary stalk thickening (PST) poses a clinical conundrum due to the potential for underlying neoplasms and challenges in obtaining a tissue biopsy. The existing literature suggests Langerhans cell histiocytosis (LCH) to be the commonest (16%) oncologic cause for PST, followed by germ cell tumors (GCTs, 13%) (CCLG 2021). As the cancer epidemiology varies according to ethnicity, we present herein the incidence and predictors for oncologic etiologies in Hong Kong Chinese children with PST. METHODS: Based on a territory-wide electronic database, we reviewed patients aged < 19 years who presented to three referral centers with endocrinopathies between 2010 and 2022. Records for patients who underwent at least one MRI brain/pituitary were examined (n = 1670): those with PST (stalk thickness ≥ 3 mm) were included, while patients with pre-existing cancer, other CNS and extra-CNS disease foci that were diagnostic of the underlying condition were excluded. RESULTS: Twenty-eight patients (M:F = 10:18) were identified. The median age at diagnosis of PST was 10.9 years (range: 3.8-16.5), with central diabetes insipidus (CDI) and growth hormone deficiency (GHD) being the most frequent presenting endocrine disorders. At a median follow-up of 4.8 years, oncologic diagnoses were made in 14 patients (50%), including 13 GCTs (46%; germinoma = 11, non-germinoma = 2) and one LCH (4%). Among patients with GCTs, 10 were diagnosed based on histology, two by abnormal tumor markers and one by a combination of histology and tumor markers. Three patients with germinoma were initially misdiagnosed as hypophysitis/LCH. The cumulative incidence of oncologic diagnoses was significantly higher in boys and patients with PST at presentation ≥6.5 mm, CDI or ≥2 pituitary hormone deficiencies at presentation and evolving hypopituitarism (all p < 0.05 by log-rank). CONCLUSIONS: A higher rate of GCTs was observed in Chinese children with endocrinopathy and isolated PST. The predictors identified in this study may guide healthcare providers in Asia in clinical decision making. Serial measurement of tumor markers is essential in management.

An Assessment of Risk Factors for Insufficient Levels of Vitamin D during Early Infancy.

Recent evidence suggests that breastfeeding may increase the risk of vitamin D deficiency in offspring. However, it is unclear whether increased risk results from breastfeeding alone, or whether it is associated together with other risk factors. This study surveyed 208 infant-mother dyads recruited by stratified random sampling in different districts of Hong Kong. Mothers were asked to complete a questionnaire on their demographics, history of risk behavior, and feeding practices. Peripheral blood samples were collected from infants to determine their vitamin D status. Among all infant participants, 70 were vitamin D insufficient or deficient. Being breastfed, being a girl, having a multiparous mother, and the use of sun cream were found to be the strongest risk factors for vitamin D insufficiency during infancy (all p < 0.05), after mutual adjustment. The cumulative risk model displayed a dose-response pattern between the number of risk factors and the risk of vitamin D insufficiency during this period. Our findings indicate the risk profile of infants with insufficient vitamin D. Guidelines and recommendations on healthy diet and lifestyle should be provided to mothers during the early stage of pregnancy to increase the likelihood of adequate levels of vitamin D in their offspring.

Association of Early Nutritional Status With Child Development in the Asia Pacific Region.

Importance: Stunting was used as a proxy for underdevelopment in early childhood in previous studies, but the associations between child development and other growth and body composition parameters were rarely studied. Objective: To estimate the association between malnutrition and early child development (ECD) at an individual level. Design, Setting, and Participants: This population-based, cross-sectional study used data from the East Asia Pacific Early Child Development Scales, a population-representative survey of children aged 3 to 5 years old, conducted in 2012 to 2014 in communities in Cambodia, China, Mongolia, Papua New Guinea, and Vanuatu. Data analysis was performed from November 2019 to April 2021. Exposures: Stunting (height-for-age [HFA] z score less than -2), wasting (weight-for-height z score less than -2), overweight (weight-for-height z score greater than 2), body mass index (BMI)-for-age z score, and body fat proportion based on existing growth standard and formula. Main Outcomes and Measures: ECD directly assessed using the validated East Asia-Pacific ECD Scales. Results: A total of 7108 children (3547 girls; mean [SD], age 4.48 [0.84] years) were included in this study. The prevalence of stunting was 27.1% (range across countries, 1.2%-55.0%), that of wasting was 13.7% (range, 5.4%-35.9%), and that of overweight was 15.9% (range, 2.2%-53.7%). Adjusted for country variations, age, sex, urbanicity, family socioeconomic status, and body fat proportion, ECD was linearly associated with HFA (ß, 1.57; 95% CI, 1.35-1.80) and BMI-for-age (ß, 0.64; 95% CI, 0.45-0.82). After adjustment for BMI and height, better ECD was associated with low body fat proportion (ß, 0.93; 95% CI, 0.45-1.42). The association of HFA was more pronounced in Southeast Asia and the Pacific region than in East Asia, and the association of fat proportion was specific to children living in urban environments. Conclusions and Relevance: HFA, BMI-for-age, and body fat proportion were independently associated with ECD, and these findings suggest that future studies should consider using these parameters to estimate the prevalence of child underdevelopment; nutritional trials should examine to what extent the associations are causal.

Impact of COVID-19 Pandemic on Serum Vitamin D Level among Infants and Toddlers: An Interrupted Time Series Analysis and before-and-after Comparison.

Background: During the coronavirus disease 2019 (COVID-19) pandemic, the implementation of social distancing and home confinement measures may elevate the risk of vitamin D deficiency particularly for infants. This study aimed to quantify changes in vitamin D level among infants and toddlers in Hong Kong after the COVID-19 outbreak. Methods: We recruited 303 infants and toddlers aged 2-24 months by stratified random sampling from 1 June 2019 to November 30, 2020. Regression models were used to estimate the effect of time on infants' serum 25-hydroxyvitamin D (25(OH)D) level overall and by age groups before and after the outbreak. Interrupted time series (ITS) analysis was performed to examine the sustained effect of COVID-19 on their serum 25(OH)D level. Results: The ITS results showed no immediate reduction in serum 25(OH)D level among infants, but a decreasing trend was observed in the subsequent months post-outbreak at a monthly decline rate of -6.32 nmol/L. When analyzed by age group, the magnitude of post-outbreak reduction in 25(OH)D was stronger among younger infants (aged 2-6 months). Conclusion: Guidelines and recommendations should be given to pregnant women and mothers to ensure sufficient vitamin D level in their infants during the COVID-19 period.

Rapid whole-exome sequencing facilitates precision medicine in paediatric rare disease patients and reduces healthcare costs.

BACKGROUND: Rapid whole-exome sequencing (rWES) offers the potential for early diagnosis-predicated precision medicine. Previous evidence focused predominantly on infants from the intensive care unit (ICU). This study sought to examine the diagnostic and clinical utility, and the economic impact on clinical management of rWES in patients beyond infancy and ICU setting. METHODS: rWES was performed on a prospective cohort of patients with suspected monogenic disorder referred from territory-wide paediatric ICUs and non-ICUs in Hong Kong urging for rapid genetic diagnosis. All eligible families were invited. We aimed to achieve a rapid turnaround time (TAT) of 14 days. Clinical utility and costs associated with clinical management were assessed in diagnosed cases. Actual quantitative changes in healthcare utilisation were compared with a counterfactual diagnostic trajectory and/or with matched historical control whenever possible. FINDINGS: rWES were offered to 102 families and 32/102 (31%) patients received a molecular diagnosis, with a median TAT of 11 days. Clinical management changed in 28 of 32 diagnosed patients (88%), including but not limited to modifications in treatment, avoidance of surgeries, and informing decisions on redirection of care. Cost analysis was performed in eight patients. rWES was estimated to reduce hospital length of stay by 566 days and decrease healthcare costs by HKD$8,044,250 (GBP£796,460) for these eight patients. The net cost-savings after inclusion of rWES costs were estimated to be HKD$5,325,187 (GBP£527,246). INTERPRETATION: This study replicates the diagnostic capacity and rapid TAT of rWES in predominantly Chinese patients, and demonstrates diagnosis-predicated precision medicine and net healthcare savings. Findings were corroborated by evidence from multinational cohorts, combined as part of a meta-analysis. rWES merits consideration as a first-tier diagnostic tool for patients with urgent needs in the clinical setting. FUNDING: Health and Medical Research Fund, HKU Seed Fund for Basic Research, The Society for the Relief of Disabled Children, and Edward and Yolanda Wong Fund.