Sydney Children's Hospital Research Articles

Clinical characteristics and in-hospital outcomes associated with RSV-ALRI compared to other viral ALRI in hospitalised children under two years old.

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infections (ALRIs) associated hospitalisations in children. It is unclear if hospitalized RSV-ALRI differs in clinically from other viral ALRIs. We aimed to compare the disease impact of hospitalised RSV with other viral ALRI in children under 2 years. We conducted a retrospective study using electronic medical records of children under 2 hospitalized with ALRIs at Sydney Children's Hospitals Network from 2020-2022. We compared demographics and clinical features between RSV-positive and RSV-negative (positive for other viruses) cases. Poisson quasi-likelihood regression was used to estimate adjusted prevalence ratios (aPRs) for three in-hospital outcomes: length of stay, need for respiratory support and intensive care. We examined 330 children under 2 years hospitalized with RSV-positive ALRIs and 330 with RSV-negative ALRIs (positive for other viruses). RSV-positive cases were older (12 vs. 8 months, p<0.001) and more often presented with cough (99% vs. 92%), fever (80% vs. 58%), crackles (89% vs. 76%), hypoxia (50% vs. 36%), and lethargy (36% vs. 20%). They were also more likely to undergo chest x-rays (74% vs. 49%) and receive antibiotics (65% vs. 35%). Adjusted analysis showed RSV-positive children had a higher likelihood of LOS > 2 days (aPR 1.95, 95% CI 1.14-3.36).). However, there were no differences in the need for intensive care or respiratory support. Children with RSV-ALRI exhibited more severe symptoms, received more antibiotics, and had longer hospital stays compared to those with other viral ALRIs, underscoring the need for effective prevention and treatment strategies for RSV.

'High hopes for treatment': Australian stakeholder perspectives of the clinical translation of advanced neurotherapeutics for rare neurological diseases.

Advanced therapies offer unprecedented opportunities for treating rare neurological disorders (RNDs) in children. However, health literacy, perceptions and understanding of novel therapies need elucidation across the RND community. This study explored healthcare professionals' and carers' perspectives of advanced therapies in childhood-onset RNDs. In this mixed-methodology cross-sectional study, 20 healthcare professionals (clinicians, genetic counsellors and scientists) and 20 carers completed qualitative semistructured interviews and custom-designed surveys. Carers undertook validated psychosocial questionnaires. Thematic and quantitative data analysis followed. Participants described high positive interest in advanced therapies, but low knowledge of, and access to, reliable information. The substantial 'therapeutic gap' and 'therapeutic odyssey' common to RNDs were recognised in five key themes: (i) unmet need and urgency for access; (ii) seeking information; (iii) access, equity and sustainability; (iv) a multidisciplinary and integrated approach to care and supportand (v) difficult decision-making. Participants were motivated to intensify RND clinical trial activity and access to advanced therapies; however, concerns around informed consent, first-in-human trials and clinical trial procedures were evident. There was high-risk tolerance despite substantial uncertainties and knowledge gaps. RNDs with high mortality, increased functional burdens and no alternative therapies were consistently prioritised for the development of advanced therapies. However, little consensus existed on prioritisation to treatment access. This study highlights the need to increase clinician and health system readiness for the clinical translation of advanced therapeutics for RNDs. Co-development and use of educational and psychosocial resources to support clinical decision-making, set therapeutic expectations and promotion of equitable, effective and safe delivery of advanced therapies are essential. Participant insights into the psychosocial burden and information needto enhance the delivery of care in this formative study are informing ongoing partnerships with families, including co-production and dissemination of psychoeducational resources featuring their voices hosted on the Sydney Children's Hospitals Network website SCHNBrain-AidResources.

Genomic multidisciplinary teams: A model for navigating genetic mainstreaming and precision medicine.

Recent rapid advances in genomics are revolutionising patient diagnosis and management of genetic conditions. However, this has led to many challenges in service provision, education and upskilling requirements for non-genetics health-care professionals and remuneration for genomic testing. In Australia, Medicare funding with a Paediatric genomic testing item for patients with intellectual disability or syndromic features has attempted to address this latter issue. The Sydney Children's Hospitals Network - Westmead (SCHN-W) Clinical Genetics Department established Paediatric and Neurology genomic multidisciplinary team (MDT) meetings to address the Medicare-specified requirement for discussion with clinical genetics, and increasing genomic testing advice requests. This SCHN-W genomic MDT was evaluated with two implementation science frameworks - the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) and GMIR - Genomic Medicine Integrative Research frameworks. Data from June 2020 to July 2022 were synthesised and evaluated, as well as process mapping of the MDT service. A total of 205 patients were discussed in 34 MDT meetings, facilitating 148 genomic tests, of which 73 were Medicare eligible. This was equivalent to 26% of SCHN-W genetics outpatient activity, and 13% of all Medicare-funded paediatric genomic testing in NSW. 39% of patients received a genetic diagnosis. The genomic MDT facilitated increased genomic testing at a tertiary paediatric centre and is an effective model for mainstreaming and facilitating precision medicine. However, significant implementation issues were identified including cost and sustainability, as well as the high level of resourcing that will be required to scale up this approach to other areas of medicine.

'Integrating Ethics and Equity with Economics and Effectiveness for newborn screening in the genomic age: A qualitative study protocol of stakeholder perspectives.

Newborn bloodspot screening is a well-established population health initiative that detects serious, childhood-onset, treatable conditions to improve health outcomes. With genomic technologies advancing rapidly, many countries are actively discussing the introduction of genomic assays into newborn screening programs. While adding genomic testing to Australia's newborn screening program could improve outcomes for infants and families, it must be considered against potential harms, ethical, legal, equity and social implications, and economic and health system impacts. We must ask not only 'can' we use genomics to screen newborns?' but 'should we'?' and 'how much should health systems invest in genomic newborn screening?'. This study will use qualitative methods to explore understanding, priorities, concerns and expectations of genomic newborn screening among parents/carers, health professionals/scientists, and health policy makers across Australia. In-depth, semi-structured interviews will be held with 30-40 parents/carers recruited via hospital and community settings, 15-20 health professionals/scientists, and 10-15 health policy makers. Data will be analysed using inductive content analysis. The Sydney Children's Hospital Network Human Research Ethics Committee approved this study protocol [2023/ETH02371]. The Standards for Reporting Qualitative Research will guide study planning, conduct and reporting. Few studies have engaged a diverse range of stakeholders to explore the implications of genomics in newborn screening in a culturally and genetically diverse population, nor in a health system underpinned by universal health care. As the first study within a multi-part research program, findings will be used to generate new knowledge on the risks and benefits and importance of ethical, legal, social and equity implications of genomic newborn screening from the perspective of key stakeholders. As such it will be the foundation on which child and family centered criteria can be developed to inform health technology assessments and drive efficient and effective policy decision-making on the implementation of genomics in newborn screening.

Proton pump inhibitors, antibiotics, and atopy increase the risk of eosinophilic esophagitis in children with esophageal atresia.

To determine whether proton pump inhibitor (PPI)exposure is associated with an increased risk of developing eosinophilic esophagitis (EoE) in children with esophageal atresia (EA). A retrospective chart review of children with EA from January 1, 2005 to December31, 2020 was undertaken at Sydney Children's Hospital Randwick. Children with EA and EoE (cases) were matched (1:2) to children with only EA (controls) to compare PPI exposure. Other early-life factors such as infantile antibiotic exposure and personal or family history of atopy were also analyzed using simple and multivariable logistic regression. Of 184 children with EA, 46 (25%) developed EoE during this period. Thirty-eight EoE participants were matched to 76 controls. Children with EoE and EA received PPI for significantly higher durations (p = .018) and at significantly higher cumulative doses (p = .017) than controls. Food allergy (adjusted odds ratio [aOR],7.317; 95% confidence interval [CI],2.244-23.742), family history of atopy (aOR,3.504; 95% CI, 1.268-9.682), and infantile antibiotic exposure (aOR,1.040; 95% CI, 1.006-1.075) were also significantly associated with an increased risk of developing EoE in the EA cohort. Prolonged duration and high cumulative dose of PPI exposure were significantly associated with subsequent EoE development in children with EA. Food allergy, family history of atopy, and infantile antibiotic exposure in EA were also significantly associated with an increased risk of EoE development.

Risk Factors and Clinical Prognosis Associated With RSV-ALRI Intensive Care Unit Admission in Children

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infections (ALRIs) in children <2 years of age. Currently, there are limited data on risk factors for very severe RSV-ALRI requiring intensive care unit (ICU) admission. We conducted a case-control study of children <2 years old admitted with RSV-ALRI to the Sydney Children's Hospital Network, comprising 2 large tertiary pediatric hospitals. Cases were children with laboratory-confirmed RSV-ALRI admitted to ICU, and controls were (1:2, matched on date of admission) children hospitalized with RSV-ALRI but not requiring ICU transfer. Data on risk factors were retrieved from the electronic medical record system. Adjusted odds ratios (aORs) with 95% confidence intervals (95% CI) associated with risk factors for ICU admission and the association with clinical and treatment factors were determined from logistic regression models. A total of 44 (44%) of 100 cases and 90 (48.1%) of 187 controls were male. Age <6 months and preterm births were associated with a 2.10-fold (95% CI: 1.14-3.79) and 2.35-fold (95% CI: 1.26-4.41) increased risk in ICU admissions, respectively. The presence of any chronic health condition was a significant risk factor for ICU admission. The clinical presentations on admission more commonly seen in cases were apnea (aOR: 5.01, 95% CI: 1.50-17.13) and respiratory distress (aOR: 15.91, 95% CI: 4.52-55.97). Cases were more likely to be hospitalized for longer duration and require respiratory support. Our results can be translated into a clinical risk algorithm to identify children at risk of very severe RSV disease.

Reduction of Urinary Tract Infection in Pediatric Surgical Patients Using NSQIP-P and Quality Improvement Methodology.

Hospital-acquired urinary tract infections (UTIs) have a detrimental effect on patients, families, and hospital resources. The Sydney Children's Hospital Network (SCHN) participates in the NSQIP-Pediatric (NSQIP-P) to monitor postoperative complications. NSQIP-P data revealed that the median UTI rate at SCHN was 1.75% in 2019, 3.5 times higher than the NSQIP-P target rate of 0.5%. Over three quarters of the NSQIP-P identified patients with UTI also had a urinary catheterization performed intraoperatively. A quality improvement project was conducted between mid-2018 and 2021 to minimize catheter-associated UTIs (CAUTIs) at SCHN. NSQIP-P samples include pediatric (younger than 18 years) surgical patients from an 8-day cycle operative log. NSQIP-P data are statistically analyzed by the American College of Surgeons and provide biannual internationally benchmarked reports. The project used clinical redesign methodology with a 6-phase process for quality improvement projects. The objectives of the project were to reduce urinary catheter duration of use, educate parents or carers, and improve catheter care and insertion technique by health staff. The duration of a urinary catheter in situ reduced from a median of 4.5 to 3 days from 2017 to 2021. The median NSQIP-P UTI rate at SCHN was reduced by 47.4% from 1.75% in 2019 to 0.9% in 2022. A multifactorial approach in quality improvement has been shown to be an effective strategy to reduce UTI rates at SCHN, and patient outcomes were improved within a 3-year timeframe. Although this project has reduced UTI rates at SCHN, there remain opportunities for further improvement.

Gross motor development in children with epidermolysis bullosa.

Epidermolysis bullosa (EB) is a group of rare, congenital skin disorders, characterized by skin fragility and formation of blisters. The gross motor outcomes of children with EB are not known. The primary objective of the study was to measure the proportion of gross motor delay in children with EB. The secondary objectives were to measure the difference in gross motor outcomes between EB sub-types and change in gross motor outcomes over time. Children with EB, aged between one month and five and a half years of age, attending the Sydney Children's Hospital, Epidermolysis Bullosa Clinic, were eligible. Carers completed Ages and Stages Questionnaires, Third Edition, on behalf of their children. Questionnaires were scored, and outcomes were compared to age-expected norms. There were 24 participants to complete a questionnaire. Eleven participants completed additional questionnaires over the 24 month study duration. The proportion of children with EB with gross motor delay was greater than age-expected norms (29.17% vs. 2.5%). The delay occurred in children with recessive dystrophic (80%) and epidermolysis bullosa simplex (33.33%) sub-types, but not dominant dystrophic (0%). No children with Junctional EB or Kindler EB joined this study. This study demonstrates a difference in gross motor outcomes in children with EB. Children with recessive dystrophic and epidermolysis bullosa simplex should be prioritized for monitoring of, and intervention for, gross motor outcomes through multidisciplinary care. Further research investigating long-term outcomes for children with EB and the effectiveness of interventions would be beneficial.

Digital psychosocial assessment of youth in Australian hospitals: From aspiration to implementation

Abstract Background Some of the leading causes of morbidity and mortality for Australian youth arise from modifiable psychosocial concerns. Psychosocial assessment can help identify young people at risk and support actions that protect wellbeing. The gold standard assessment for youth is the HEEADSSS interview. Australian governments recommend the HEEADSSS interview for young people in health settings, but adoption is still in its early stages. Recently, a digital self-assessment version of the HEEADSSS (the e-HEEADSSS) was piloted at the Sydney Children's Hospital Network. A program of research has been established to evaluate outcomes and consider broader implementation. Methods Study 1 involved a retrospective analysis to compare the HEEADSSS interview and the e-HEEADSSS. Documentation from 146 matched records collected at the Sydney Children's Hospital Network were analysed to compare approaches. Study 2 utilised a qualitative design to evaluate patient and staff barriers and facilitators to implementation and scale-up of the e-HEEADSSS. Patients (n = 8) and staff (n = 8) participated in online semi-structured interviews. Results Study 1 found the e-HEEADSSS improves assessment uptake and sensitivity compared to face-to-face interviews and takes less time. Disclosure rates were higher for all psychosocial categories especially in sensitive areas of emotions, drug use, sex, and safety. Study 2 found strong support for the e-HEEADSSS from patients and staff. Key benefits included design, functionality, reduced time, convenience, improved disclosure, perceived privacy, improved fidelity, and reduced stigma. Key challenges were available resources, continuity of staff training, clinical pathways, and risks of off-site completions. Conclusions The e-HEEADSSS shows promise as a psychosocial screening tool to support intervention for young people. More work is required to appropriately scale and sustain implementation of the e-HEEADSSS within the Australian health system. Key messages • Digital psychosocial assessments show promise for supporting the mental and physical health of adolescents and young adults. • Implementation of digital psychosocial assessments within the Australian health system requires considered support.

Asthma and Susceptibility to COVID-19 in Australian Children During Alpha, Delta and Omicron Waves of the COVID-19 Pandemic.

Earlier coronavirus-19 (COVID-19) pandemic reports did not implicate increased disease burden in asthmatics while subsequent findings have been inconsistent. To date, the impact of COVID-19 on childhood asthma remains undetermined and is further complicated with ongoing emergence of new variants. This study aimed to investigate association between asthma and COVID-19 for children in New South Wales (NSW), Australia and compare its differences across four major outbreaks from alpha, delta and omicron variants/subvariants. This is a retrospective cross-sectional study of all children aged ≤17 years old who sought care for COVID-19 at Sydney Children's Hospitals Network (SCHN) between 1 January 2020 and 31 May 2022. Of the 18,932 children with polymerase chain reaction (PCR) confirmed COVID-19 who attended SCHN, 60% received their care during delta wave, and 5.41% (n = 913) had prior diagnosis of asthma. Among children with COVID-19, the odds of having asthma were lower during alpha (aOR = 0.43; 95% CI, 0.19-0.83) and delta wave (aOR = 0.84; 95% CI, 0.73-0.96), but were higher during omicron wave (aOR = 1.56; 95% CI, 1.23-1.95). Length of hospital stay (LOS) for asthmatic children were increased by 0.55 days and 1.17 days during delta and the second omicron wave, respectively. Intensive care and mechanical ventilation requirements were not significantly different between asthmatic and non-asthmatic children. Eleven deaths were reported but none had asthma. Although children with asthma were more susceptible to COVID-19 infections during omicron waves compared to that of alpha or delta waves, they were not at greater risk of COVID-19 severity at any stage of the outbreak regardless of the predominant SARS-CoV-2 variants/subvariants.

Genotyping in patients with congenital adrenal hyperplasia by sequencing of newborn bloodspot samples.

Genotype-phenotype correlation in congenital adrenal hyperplasia (CAH) caused by 21-hydroxylase deficiency ranges from 45 to 97 %. We performed massively parallel sequencing of CYP21A2 on stored newborn bloodspot samples to catalogue the genotypes present in our patients with CAH and enable genotype-phenotype comparison. Participants≤15 years old with clinically diagnosed CAH were recruited from The Sydney Children's Hospitals Network. Phenotype was classified from clinical and biochemical details in the medical record as salt wasting (SW), simple virilising (SV), non-classic (NC) or an intermediate phenotype (SW/SV; SV/NC). Amplicon-based sequencing for CYP21A2 was performed on stored newborn bloodspot samples by the New South Wales Newborn Bloodspot Screening Laboratory on MiSeq™Dx (Illumina, California). Available genetic test results were also obtained from the medical records. Samples from 67 participants (43 % female, age 0.3-15 years) were sequenced, including 9 sibships. SW phenotype was present in 33/67 participants (49 %), SV in 9 (13 %) and NC in 16 (24 %). Intermediate phenotypes included SW/SV in seven participants (10 %) and SV/NC in two (3 %). Variants were identified in 90/116 alleles (78 %). A complete genotype was available in 47/67 participants (70 %). The most common genotype was homozygous c.293-13A/C>G (I2G) in 7/47 participants (15 %). Genotype correlated with the mostcommonly reported phenotype in 36/44 cases (82 %). Correlation was higher in SW and NC phenotypes. This study uses genetic testing of newborn bloodspots to identify and characterise the genotypes present in an ethnically diverse Australian population with CAH. It further strengthens our knowledge of genotype-phenotype correlations in CAH.

Prevalence, Predictive Factors, and Clinical Manifestations of Fungal Esophagitis in Children.

Fungal esophagitis (FE) is the most common cause of esophageal infection and its prevalence in immunocompetent adults is rising. However, there is minimal data on FE in children without human immunodeficiency virus. Therefore, the objective of this study was to determine the prevalence, symptoms, endoscopic appearances, and predictive factors of FE in children, regardless of immune status. A 2010-2020 retrospective case-control study was conducted on 1823 children presenting to Sydney Children's Hospital for elective endoscopy with esophageal biopsy. Histopathology reports were reviewed to identify FE cases and determine prevalence rates. Thirty-two patients with FE were age- and sex-matched (1:2) to 64 controls. Significant symptoms and risk factors of FE were identified via univariate and multivariate logistic regression analysis. The prevalence of FE in children was 1.76%. Common symptoms included dysphagia (25%), heartburn (25%), poor oral intake (21.9%), vomiting (18.8%), cough (15.6%), nausea (12.5%), and weight loss (9.4%). No significant differences in symptoms were found between cases and controls. On endoscopy, although white plaques were associated with FE ( P < 0.001), visually normal findings were reported in 28.1% of cases. Topical swallowed corticosteroids were a significant independent risk factor for FE (adjusted odds ratio = 10.740, 95% confidence interval: 1.213-95.101, P = 0.033). The prevalence of FE in this pediatric cohort reflects rates among immunocompetent adults. Given that many of these children presented with a wide range of gastrointestinal symptoms, esophageal biopsy is required to accurately diagnose FE. Pediatricians should consider the risk of FE when prescribing topical swallowed corticosteroids.

The Carrier Frequency of Two SMN1 Genes in Parents of Symptomatic Children with SMA and the Significance of SMN1 Exon 8 in Carriers.

Current carrier screening methods do not identify a proportion of carriers that may have children affected by spinal muscular atrophy (SMA). Additional genetic data is essential to inform accurate risk assessment and genetic counselling of SMA carriers. This study aims to quantify the various genotypes among parents of children with SMA. A retrospective cohort study was undertaken at Sydney Children's Hospital Network, the major SMA referral centre for New South Wales, Australia. Participants included children with genetically confirmed SMA born between 2005 and 2021. Data was collected on parent genotype inclusive of copy number of SMN1 exons 7 and 8. The number of SMN2 exon 7 copies were recorded for the affected children. Descriptive statistics were used to determine the proportion of carriers of 2+0 genotype classified as silent carriers. Chi-square test was used to correlate the association between parents with a heterozygous SMN1 exon 7 deletion and two copies of exon 8 and ≥3 SMN2 copy number in the proband. SMA carrier testing was performed in 118/154 (76.6%) parents, incorporating 59 probands with homozygous SMN1 deletions and one proband with compound heterozygote pathogenic variants. Among parents with a child with SMA, 7.6% had two copies of SMN1 exon 7. When only probands with a homozygous SMN1 exon 7 deletion were included, 6.9% of parents had two copies of SMN1 exon 7. An association was observed between heterozygous deletion of SMN1 exon 7 with two copies of exon 8 in a parent and ≥3 SMN2 copy number in the affected proband (p = 0.07). This study confirmed a small but substantial proportion of silent carriers not identified by conventional screening within an Australian context. Accordingly, the effectiveness of carrier screening for SMA is linked with genetic counselling to enable health literacy regarding high and low risk results and is complemented by new-born screening and maintaining clinical awareness for SMA. Gene conversion events may underpin the associations between parent carrier status and proband SMN2 copy number.

Body composition and body mass index measures from 8 to 18 years old in children with cystic fibrosis

BackgroundHistorically, body mass index (BMI) >50th percentile has represented optimal nutritional status in children with cystic fibrosis (CF) due to its positive association with lung function. Body composition parameters including fat-free mass index (FFMI) have been suggested as a more physiological nutrition benchmark. Aims: (1) describe changes in body composition with age and gender; (2) assess the correlation between measures of nutritional status (FFMI-z, FMI-z, BMI-z) and lung function (forced expiratory volume in one second predicted; FEV1pp). MethodsThis retrospective, mixed cross-sectional and serial measures study consisted of children with CF (8 to 18 years) attending Sydney Children's Hospital (2007–2020). FFMI and fat mass index (FMI) were taken from biennial dual energy x-ray absorptiometry (DXA) scans. Z-scores were derived using Well's reference population [1]. Repeated measures correlation analyses assessed correlations between FFMI-z, FMI-z, and BMI-z with FEV1pp. Results339 DXA reports were analysed from 137 patients. There were slight downwards trends in BMI-z and FMI-z, and an upwards trend in FFMI-z with increasing age and across both genders. Females had higher FMI-z and FFMI-z than males from 12.5 years. There was a weak, positive correlation between FEV1pp and BMI-z (r = 0.14, p = 0.04), and FFMI-z (r = 0.25, p<0.001). FMI-z had no correlation with FEV1pp (r=-0.06, p = 0.41). ConclusionDeficits in FFMI exist despite increasing trends with age. FFMI-z and BMI-z had a weak, positive correlation with FEV1pp. In contemporary cohorts, nutritional status (reflected by surrogate markers such as FFMI and BMI) may be less influential upon lung function than in previous decades.[1]: Wells, J.C., et al. Body-composition reference data for simple and reference techniques and a 4-component model: a new UK reference child. Am. J. Clin. Nutr.96, 1316–1326 (2012).

National surveillance of severe microcephaly in Australia.

Acta PaediatricaAccepted Articles BRIEF REPORT National surveillance of severe microcephaly in Australia Carlos Nunez, Corresponding Author Carlos Nunez [email protected] orcid.org/0000-0002-5417-9582 The University of Sydney. Faculty of Medicine and Health, Discipline of Child and Adolescent Health, Sydney, NSW, Australia The Australian Paediatric Surveillance Unit (APSU). Sydney, NSW, Australia Correspondence Dr Carlos Nunez, the Australian Paediatric Surveillance (APSU), Level 2, Kids Research, The Children's Hospital at Westmead, Locked Bag 4001, Westmead NSW 2145, Australia. Email: [email protected]Search for more papers by this authorAnne Morris, Anne Morris The University of Sydney. Faculty of Medicine and Health, Discipline of Child and Adolescent Health, Sydney, NSW, Australia The Australian Paediatric Surveillance Unit (APSU). Sydney, NSW, Australia Kids Research, The Sydney Children's Hospitals Network (Westmead), Sydney, NSW, AustraliaSearch for more papers by this authorElizabeth J. Elliott, Elizabeth J. Elliott The University of Sydney. Faculty of Medicine and Health, Discipline of Child and Adolescent Health, Sydney, NSW, Australia The Australian Paediatric Surveillance Unit (APSU). Sydney, NSW, Australia Kids Research, The Sydney Children's Hospitals Network (Westmead), Sydney, NSW, AustraliaSearch for more papers by this author Carlos Nunez, Corresponding Author Carlos Nunez [email protected] orcid.org/0000-0002-5417-9582 The University of Sydney. Faculty of Medicine and Health, Discipline of Child and Adolescent Health, Sydney, NSW, Australia The Australian Paediatric Surveillance Unit (APSU). Sydney, NSW, Australia Correspondence Dr Carlos Nunez, the Australian Paediatric Surveillance (APSU), Level 2, Kids Research, The Children's Hospital at Westmead, Locked Bag 4001, Westmead NSW 2145, Australia. Email: [email protected]Search for more papers by this authorAnne Morris, Anne Morris The University of Sydney. Faculty of Medicine and Health, Discipline of Child and Adolescent Health, Sydney, NSW, Australia The Australian Paediatric Surveillance Unit (APSU). Sydney, NSW, Australia Kids Research, The Sydney Children's Hospitals Network (Westmead), Sydney, NSW, AustraliaSearch for more papers by this authorElizabeth J. Elliott, Elizabeth J. Elliott The University of Sydney. Faculty of Medicine and Health, Discipline of Child and Adolescent Health, Sydney, NSW, Australia The Australian Paediatric Surveillance Unit (APSU). Sydney, NSW, Australia Kids Research, The Sydney Children's Hospitals Network (Westmead), Sydney, NSW, AustraliaSearch for more papers by this author First published: 14 May 2023 https://doi.org/10.1111/apa.16846 This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi:10.1111/apa.16846. AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Accepted ArticlesAccepted, unedited articles published online and citable. The final edited and typeset version of record will appear in the future. RelatedInformation

Maternal transmission of dysmenorrhea includes substantial genetic influence.

aDepartment of Pain Medicine, Sydney Children's Hospital, Bright Alliance Building, Randwick, Australia bSchool of Clinical Medicine, University of NSW, Kensington, Australia *E-mail address: [email protected] (G. D. Champion) Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Respiratory and sleep outcomes in children with SMA treated with nusinersen - real world experience

It is unclear how improvements in peripheral motor function in children with spinal muscular atrophy (SMA), treated with nusinersen, translate into clinically significant respiratory/sleep outcomes. A retrospective chart review of SMA children at the Sydney Children's Hospital Network was undertaken looking at 2 years before and after receiving their first dose of nusinersen. Polysomnography (PSG), spirometry and clinical data were collected and analysed using paired and unpaired t-tests for PSG parameters and generalised estimating equations for longitudinal lung function data. Forty-eight children (10 Type 1, 23 Type 2, 15 Type 3) at mean age 6.98 yrs (SD 5.25) for nusinersen initiation were included. There was a statistically significant improvement in oxygen nadir during sleep in individuals post nusinersen (mean of 87.9% to 92.3% (95%CI 1.24 – 7.63, p = 0.01)). Based on clinical and PSG findings, 6/21 patients (5 Type 2, 1 Type 3) ceased nocturnal NIV post nusinersen. Non-significant improvements were demonstrated in mean slope for FVC% predicted, FVC Z-score and mean FVC% predicted. Within 2 years of commencing nusinersen, stabilisation of respiratory outcomes occurred. Whilst some of the SMA type 2/3 cohort ceased NIV, there were no statistically significant improvements lung function and most PSG parameters.

The Fentanyl System Shock - Are There Lessons to Learn From the COVID-19 System Shock Framework? Comment on "The COVID-19 System Shock Framework: Capturing Health System Innovation During the COVID-19 Pandemic".

The Sydney Children's Hospitals Network (SCHN) addressed the challenges of the COVID-19 pandemic by implementing innovative changes which made their health system resilient and responsive. For other healthcare systems, there are important takeaways. In the United States and Canada, an urgent widespread response is needed to address the overdose crisis, driven by potent synthetic opioids (ie, fentanyl and its derivates). We project the COVID-19 System Shock Framework (CSSF) on to the North American healthcare systems and suggest a Fentanyl System Shock Framework, which provides a framework for necessary changes and innovations to address the overdose crisis. To become resilient to the fentanyl system shock, core components as well as overarching values, health policy, and online technologies need to be adapted to reduce the death count and meet the evolving needs of marginalised individuals who use opioid. Future research should focus on scientifically assessing such implementations to guide evidence-based decision making.

Impact and recovery of the COVID-19 pandemic on weight status of children and adolescents.

Recent evidence suggests the immediate effects of the COVID-19 lockdowns and restrictions have resulted in increased weight in children and adolescents. However, the longer-term effects have not been assessed. The aim of this study was to examine the impact and longer-term effects of the COVID-19 pandemic on BMI and weight status of children and adolescents. This study used routinely collected clinical data from the Sydney Children's Hospitals Network, comprising two socio-demographically diverse children's hospitals in New South Wales, Australia from 2018 to 2021. Of 245 836 individuals ≤18-years assessed, mean BMI percentile increased from 58.7 (SD 31.6) pre-COVID-19 to 59.8 (SD 31.7) (p < .05) post-restrictions and overweight/obesity increased by 5.5% (obesity alone 6.3%), predominantly in children <12-years and from lower socioeconomic backgrounds. The trend in BMI percentile was steady pre-COVID-19 (β=-0.03 [95% CI -0.07, 0.01]), peaked immediately following COVID-19 restrictions (β=1.28 [95% CI 0.24, 2.32]) and returned to pre-pandemic levels over ensuing 21 months (β=-0.04 [95% CI -0.13, 0.04]). Routine anthropometric measurement facilitates ongoing monitoring and evaluation of the weight status of children and adolescents, helping to identify those at-risk. Despite initial BMI and weight increases among children and adolescents, longer-term follow-up highlighted a return to pre-pandemic rates, possibly attributed to state-wide policies aimed at reducing childhood obesity.

Newborn screening for spinal muscular atrophy in Australia: a non-randomised cohort study

In light of a new therapeutic era for spinal muscular atrophy (SMA), newborn screening has been proposed as a gateway to facilitate expedient diagnosis and access to therapeutics. However, there is paucity of evidence on health outcomes outside the homogenous populations in clinical trials to justify broader implementation of newborn screening for SMA. In this real-world study, we aimed to investigate the effectiveness of newborn screening coupled with access to disease-modifying therapeutics, as an intervention for SMA. In this prospective, non-randomised cohort study done at Sydney Children's Hospital Network (NSW, Australia), we included children younger than 16 years with homozygous exon 7 deletions of survival motor neuron 1 gene (SMN1) mutations, non-selectively assigned to a screening group (incident population diagnosed by newborn screening) from Aug 1, 2018, to Aug 1, 2020, or a comparator group (incident population diagnosed by clinical referral) from Aug 1, 2016, to July 31, 2018. We excluded infants with compound heterozygous SMN1 mutations and those participating in ongoing and unpublished clinical trials. Effectiveness of newborn screening for SMA was compared using motor development milestone attainment defined by WHO Multicentre Growth Reference Study at 2 years post diagnosis. Secondary outcome measures included mortality and change in Hammersmith Infant Neurological Examination-2 (HINE-2) score, ventilation requirements, and enteral requirements 2 years from the time of diagnosis. 34 children met the study inclusion criteria, but 33 children were included in the study population after one neonate was excluded due to participation in an ongoing unpublished clinical trial. 15 children were included in the screening group (seven [47%] male and eight [53%] female; median age 2·1 weeks [IQR 1·9-2·7]) and 18 children (nine [50%] male and nine [50%] female) were included in the comparator group (median age 47·8 weeks [13·0-99·9]). The 2-year survival rate was 93% (14 of 15 children) in the screening group and 89% (16 of 18) in the comparator group. Among survivors, 11 (79%) of 14 walked independently or with assistance in the screening group, compared with one (6%) of 16 children in the comparator group (χ2=16·27; p<0·0001). A significantly greater change in motor function was observed in the screening group compared with the comparator group over 2 years (HINE-2 score group difference, 12·32; p<0·0001). The requirement for non-intensive ventilation or feeding support at follow-up was higher in the comparator group than in the screening group (odds ratio 7·1 [95% CI 0·7-70·2]). Significant predictors of functional motor outcomes as determined by HINE-2 score at 2 years post diagnosis were HINE-2 score (p=0·0022), CHOP-INTEND (p=0·0001), compound muscle action potential (CMAP; p=0·0006), and disease status (p=0·023) at diagnosis. Newborn screening for SMA, coupled with early access to disease-modifying therapies, effectively ameliorates the functional burden and associated comorbidities for affected children. For children diagnosed through newborn screening, motor score, CMAP, and disease status at diagnosis has clinical utility to determine functional independence. Brain Foundation and National Health and Medical Research Council.