Child health

Off-label use in young children suggests that health care professionals and the public underappreciate their risks

Abrar Arbaeen · Nial J Wheate · Jared A Brown · Rose Cairns

SUDI investigations should be led by coroners, supported by experienced paediatric pathologists Jeffery and colleagues examined how sudden unexpected deaths in infancy (SUDI) are investigated in Australia in a questionnaire‐based study,1 reported in this issue of the MJA. They unsurprisingly exposed gaps in the process and unsuitable approaches to investigating these deaths. As Jeffery and colleagues note, the definition of SUDI encompasses all cases in which an infant dies (or suffers a collapse that leads to death) before the age of twelve months, the death could not have been anticipated 24 hours earlier, and no medical cause is apparent. The SUDI definition includes all such deaths, whether they are subsequently explained or not, and thus encompasses sudden infant death syndrome (SIDS), a diagnosis that requires a complete investigation, including history, death scene investigation, and full autopsy. In the absence of generally recognised causes, the investigation of SUDI is a special situation: each case is a subject of research or a problem to be solved. Most cases in Australia fall within the purview of the police and the state coroner. While their questionnaire methodology had inherent limitations, Jeffery and colleagues found that police‐led investigation fell short of evidence‐based standards. Obvious problems are related to inadequate resources and the lack of a national approach to investigating unexpected deaths in infancy, including a national autopsy protocol. In some states, forensic institutions perform autopsies under the jurisdiction of the coroner. Only one employs a paediatric pathologist for this purpose, despite the fact that SUDI autopsy is a specialist procedure. Problems arise when pathologists without relevant specialist expertise overlook key aspects or misinterpret important findings; this can result in unsafe legal outcomes. In 1989, the late SIDS expert forensic pathologist Professor John Hilton discussed the fact that the investigation of SIDS is encumbered by unusual limitations.2 These limitations are pertinent to the study by Jeffery and colleagues, including ethical questions regarding consent for obtaining and retaining tissue, and difficulty in obtaining suitable control material for meaningful research. The specific causes of many cases of SUDI and SIDS remain unknown, despite the resources of 21st century science. Limitations to their investigation may play a role, but there are a number of plausible research hypotheses, especially that centred on the homeostatic control of breathing, arousal, and cardiac function.3 However, it is worrying that few neuropathological or neurotransmitter findings have been linked with SIDS risk factors.4 In contrast, the list of risk factors linked with infection‐based hypotheses (eg, the bacterial toxin hypothesis)5,6 is extensive,7,8 especially strong associations with prone sleeping and the type of sleeping surface.9,10,11 Achieving clarification may require, as demanded by Jeffery and colleagues, the implementation of core components of international standards, such as those recommended by the Kennedy Report,12 including a standardised autopsy protocol. Doing so would maximise the probability that the cause of death is elucidated, and ensure that risk factors are identified, parents and families receive immediate and ongoing support, and the consequences of incorrect diagnosis are avoided. SUDI investigations should be led by coroners, supported by experienced paediatric pathologists playing pivotal roles. A national database of SUDI data could also be helpful for research and monitoring standards, but this will require dedicated financial support.

Paul N Goldwater

The investigation process should be upgraded, as every family has the right to have their child’s death properly investigated

Heather E Jeffery · Angela E Carberry · Adrienne Gordon · Susan Arbuckle

To the Editor: In a recent Editorial,1 Grimwood and Chang cited a review of long COVID in children and adolescents,2 and wrote that symptoms are similar for those with and without evidence of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. But this is an inaccurate description of the review's findings. Cases were more likely to experience persistent symptoms than controls in the majority of studies reviewed.2 The difference in prevalence might be even greater than reported owing to the well documented underdetection of coronavirus disease 2019 (COVID‐19) in children,3 resulting in misclassification of cases as controls. A growing body of evidence indicates children are more affected by COVID‐19 than initially thought. A recent US Centers for Disease Control and Prevention (CDC) analysis of 1.4 million children aged under 12 years and 1.7 million adolescents aged 12–17 years found increased rates of asthma, myocarditis and cardiomyopathy, cardiac dysrhythmias, diabetes, renal failure, venous thromboembolism, and coagulation disorders in children with laboratory‐confirmed COVID‐19 compared with children without COVID‐19. These increased risks (excluding asthma) were also experienced by adolescents with COVID‐19, who were additionally at increased risk of pulmonary embolism.4 Although uncommon or rare, such outcomes suggest children are not spared the cardiovascular and metabolic sequelae of COVID‐19. Recent research using low field magnetic resonance imaging (MRI) revealed persistent pulmonary dysfunction in non‐hospitalised children and adolescents (mean age, 11±3 years) who had recovered from COVID‐19 (n = 29) or had long COVID (n = 25). Despite all children having morphologically normal lungs (except for one recovered child), ventilation and perfusion (V/Q) matching was markedly lower in the recovered group (62±19%) and the long COVID group (60±20%) compared with nine healthy controls (81±6%; mean age, 10±3 years).5 Although the MRI study may be limited by selection bias (ie, children with greater symptomatology being more likely to participate), this and similar research indicate the health impact of paediatric COVID‐19 is greater than generally acknowledged. We do not know what the long term impact of SARS‐CoV‐2 infection might be, but the accumulating data are not encouraging. Reinfection is common and SARS‐CoV‐2 spreads readily in schools in the absence of mitigation measures, such as the use of masks, portable HEPA air cleaners, and improved ventilation. Notably, better ventilation has wider benefits, including improved academic performance. A poorly ventilated classroom can be equivalent to a student skipping breakfast.6 The COVID‐19 pandemic is not over. Ongoing commitment to a public health strategy informed by the precautionary principle is required. This will deliver wide‐ranging social, economic and health benefits.

Zoë Hyde

A 14-month-old girl was noted to have exfoliation of her peripheries on day 19 after orthotopic liver transplant for end-stage liver disease from extrahepatic biliary atresia

Jessica A Eldredge · Noel E Cranswick · Kathleen H McGrath

Strategies to increase and sustain the COVID-19 vaccination rate among Australian children are needed

Katelyn Barnes · Sally Hall Dykgraaf · Lucas Toca · Michael Wright · Michael Kidd

It is time to reimagine wellbeing and place the future of our children and young people at the centre of public action

Sandro Demaio · Sharon R Goldfeld · Anne Hollonds · George C Patton · Fiona J Stanley · Rosemary Calder · Kate Lycett · Zuleika Arashiro

The Taskforce has made seven specific recommendations on care for pregnant women and those who have recently given birth

for the National COVID‐19 Clinical Evidence Taskforce

During the New South Wales Delta outbreak, social factors caused more hospitalisations than medical reasons

Keith Grimwood · Anne B Chang

To the Editor: We write in response to Reid and colleagues’1 article on congenital cytomegalovirus (CMV). While many countries worldwide have established congenital CMV screening programs, Australia urgently needs to recognise the importance of targeted congenital CMV screening and tracking its outcomes. Our 2019–2020 study tested the feasibility and acceptability of a parent‐completed targeted congenital CMV saliva polymerase chain reaction (PCR) screening program in Victoria.2 Parents of infants who did not pass their newborn hearing screening at four Victorian maternity hospitals completed their infants’ saliva swabs in the hospital or at home. The program was feasible with a 76% participation rate, and all 96 swabs (100%) were completed within the required 21days from birth, despite the majority being completed at home. Furthermore, more than 90% of families found the screen easy to do, thought it was a good idea, and were glad their baby had congenital CMV screening. However, there were challenges: false positive screens due to CMV contamination in breast milk, and excessive time taken from completing the screen to return of results due to reliance on the only laboratory in the state accredited to process saliva CMV PCR. We now have the means to overcome these challenges, determine whether universal congenital CMV screening in Australia is warranted, and systematically track outcomes of targeted congenital CMV screening. For 2years from October 2021, Murdoch Children’s Research Institute’s Generation Victoria (GenV) is recruiting a whole‐of‐state infant–parent cohort, collecting over 110000 saliva swabs from newborns to test for CMV using novel CRISPR technology at the Walter and Eliza Hall Institute of Medical Research.3 Our study, funded by the National Health and Medical Research Council, will determine the population prevalence of congenital CMV, develop a rapid bedside point‐of‐care test for congenital CMV screening, and establish whether universal congenital CMV screening is cost‐effective. In addition, the Australasian Congenital CMV Registry has been recently established to track outcomes of congenital CMV.4 These initiatives will pave the way for Australia to emerge as a leader in congenital CMV screening, better recognise this undetected condition of public health importance, and provide personalised care to affected children.

Emma Webb · Cheryl A Jones · Valerie Sung

Community support for children with special care needs could reduce the number of COVID-19-related hospitalisations

Phoebe Williams · Archana Koirala · Gemma L Saravanos · Laura K Lopez · Catherine Glover · Ketaki Sharma · Tracey Williams · Emma Carey · Nadine Shaw · Emma Dickens · Neela Sitaram · Joanne Ging · Paula Bray · Nigel W Crawford · Brendan McMullan · Kristine Macartney · Nicholas Wood · Elizabeth L Fulton · Christine Lau · Philip N Britton

To the Editor: We read with interest the article by Kelly and colleagues,1 In our opinion, the authors’ statement “Access to timely gender‐affirming care is associated with improved mental health outcomes and overall wellbeing” is not well supported by the two citations provided. The first citation is a systematic review by Rew and colleagues.2 A critique of this review was recently published.3 Rew et al, in response, clarified that they did not make any causal statements about puberty blockers and reported improved mental health outcomes, but believe their findings warrant more rigorous longitudinal studies.4 Kelly and colleagues’ second citation is a systematic review by Mahfouda et al.5 This review concluded there is only scarce and preliminary evidence that hormonal and surgical gender‐affirming treatments in adolescents are associated with mental health benefit and improved quality of life. The available evidence was described as having multiple methodological limitations and being at medium to high risk of bias. The authors called for further urgent research to clarify long term outcomes on psychological functioning and safety. Importantly, two recent systematic reviews by the United Kingdom’s National Institute for Health and Care Excellence found that the results of the studies investigating the benefits or adverse effects of puberty blockers and gender‐affirming hormones are of very low certainty and, as the studies themselves may not be reliable, any identified changes could be due to confounding, bias or chance.6,7 The recently published interim report of the UK’s Cass Review also noted that there are different views on the benefits versus harms of early social transition and more information about outcomes is required.8 In conclusion, the literature does not support there being a robust evidence base for the gender‐affirming social, medical and surgical interventions for children and adolescents. Rather, the literature highlights the scarce and low quality evidence and the urgent need for more high quality evidence. In any consideration of the processes of informed consent and/or court consent it would seem imperative that there is acknowledgement of the uncertain evidence base underpinning these interventions. Thus, it is of concern that Kelly and colleagues fail to do this.

Alison Clayton · Roberto D’Angelo · Patrick Clarke

Timely introduction of allergens did not reduce breastfeeding or increase extremely early introduction to solid foods

Jennifer Koplin · Victoria Soriano · Merryn Netting · Rachel Peters

The current lack of a national strategy for Indigenous adolescent health in Australia is a glaring gap

Seth Westhead · Quinton Appleby · Brittney Andrews · Tina Brodie · Alex Brown · Karla Canuto · Josh Cooke · Mahlia Garay · Thomas Harrington · Djai Hunter · Corey Kennedy · Jaeda Lenoy · Olivia Lester · Hannah McCleary · Odette Pearson · Lorraine Randall · Rachel Reilly · Hamish Rose · Daniel Rosendale · Jakirah Telfer · Peter Azzopardi

The prevalence of SARS-CoV-2 antibodies in children and adolescents in early 2021 was very low

the PAEDS Serosurvey Group

The COVID-19 pandemic has revealed that social connection and social factors are critical for the mental health of young people

Fiona Shand · Michelle Torok

A previously well 4-month-old boy was admitted to a tertiary Victorian paediatric hospital in February 2022 following a febrile convulsion

Andrea Zhu · Nikki Petrakis · Mohamed Gaber · Daniel Mason · Vanessa Clifford · Julian Kelly

About two in three of participating urban Aboriginal infants had mild or moderate hearing loss at twelve months of age

Tamara Veselinović · Sharon A Weeks · Valerie M Swift · Deborah Lehmann · Christopher G Brennan‐Jones

To the Editor: Fraile Navarro and colleagues1 recently published 20 recommendations for the treatment of coronavirus disease 2019 (COVID‐19) in children and adolescents from the National COVID‐19 Clinical Evidence Taskforce. For the paediatric inflammatory multisystem syndrome (PIMS‐TS) recommendations, the Taskforce convened an expert advisory group.1 In the absence of clinical trials, the panel considered peer‐reviewed guidelines and cohort studies to formulate consensus recommendations.1 However, they deferred providing any guidance to help clinicians prevent thromboembolism. We suggest the Taskforce consider the same approach for paediatric anticoagulation guidance. COVID‐19 is associated with marked coagulation activation and hypercoagulability in children.2,3 Life‐threatening pulmonary embolus requiring thrombolysis has been encountered in Australian adolescents hospitalised with COVID‐19. A retrospective cohort study published in 2021 found that 2.1% of children hospitalised with symptomatic COVID‐19 infection and 6.5% of those with PIMS‐TS developed thrombosis.4 Thrombosis occurred more frequently in children aged 12years and over who had central lines, PIMS‐TS, or an underlying oncological diagnosis. A D‐dimer of more than five times the upper limit of normal was significantly associated with thrombosis.4 The authors refer to “paediatric guidelines published in the US”, which are published on behalf of the Pediatric/Neonatal Hemostasis and Thrombosis Subcommittee of the International Society of Thrombosis and Haemostasis; these adapt current consensus prophylaxis guidelines to include COVID‐19‐specific features.5 In deferring making specific recommendations, the authors suggested using existing local thromboprophylaxis guidelines. The Royal Children’s Hospital, Melbourne and the Sydney Children’s Hospital, Randwick have both independently developed COVID‐19‐specific thromboprophylaxis guidelines (that are very closely aligned),6,7 as have many other centres globally because previous local thromboprophylaxis guidelines are inadequate for COVID‐19‐associated thrombotic coagulopathy. The Melbourne/Sydney guidelines advise baseline coagulation testing in hospitalised children with COVID‐19, incorporating D‐dimer to assist risk assessment, twice‐daily enoxaparin and anti‐Xa monitoring/dose titration.6,7 These could be provided as supplemental material in these living guidelines. The COVID‐19 anticoagulation in Children–Thromboprophylaxis (COVAC‐TP) trial — a phase 2 single‐arm study looking at 40 children who will receive monitored, low dose, twice‐daily enoxaparin (ClinicalTrials.gov Identifier NCT04354155) — will not change the level of evidence, so waiting for completion of this trial does not seem appropriate.

Gemma L Crighton · Anthea Greenway · Susan Russell

Recommendations are based on evidence-based knowledge of safety, immunogenicity and efficacy of the vaccines in the general population, plus emerging data regarding COVID-19 vaccination in immunocompromised individuals

Eliska Furlong · Rishi S Kotecha · Rachel Conyers · Tracey A O'Brien · Jordan R Hansford · Leanne Super · Peter Downie · David D Eisenstat · Gabrielle Haeusler · Brendan McMullan · Marianne B Phillips · Bhavna Padhye · Luciano Dalla‐Pozza · Frank Alvaro · Christopher J Fraser · Wayne Nicholls · Julia E Clark · Matthew O'Connor · Benjamin R Saxon · Heather Tapp · John Heath · Sarah E Hunter · Karen Tsui · Mark Winstanley · Amanda Lyver · Emma J Best · Ushma Wadia · Daniel Yeoh · Christopher C Blyth · Nicholas G Gottardo

Recent legal changes are negatively affecting provision of timely medical care to Australian transgender youth

Fiona Kelly · Simona Giordano · Michelle M Telfer · Ken C Pang

To the Editor: We must clarify that the findings of Iorfino and colleagues1 do not apply to headspace clients. This understandable misperception comes from the article’s title, “early intervention mental health services”, and participants coming from “clinics” that “provide both primary care services (headspace) and more specialised services”. Quotes from an InSight+ article2 and the accompanying editorial3 infer that the findings generalise to headspace, but they do not. Although some participants in the Iorfino study came from two headspace‐branded centres, they also included young people accessing specialised services. This is evident in the limitations: “our sample was restricted to young people who remained in contact with the service for at least two years … biasing our sample towards people who required ongoing care and were accordingly more likely to have poorer outcomes”. Generally, headspace does not provide care over a period of two years or more; centres typically provide brief episodes of care, befitting young people with mild to moderate presentations for common mental health problems. The average number of sessions is 4.4 (standard deviation [SD], 6.2); 98% of clients receive 20 sessions or fewer. A negligible 0.4% of clients are still receiving care at two years. Average time between the first and last session is 73.7 days (SD, 120), about 2.5 months (headspace 2015–2021, national unpublished data). Clarification that the findings are not representative of, nor generalisable to, headspace clients is essential; the headspace initiative is not targeted at young people who need more sustained mental health care. The results are inconsistent with reported outcomes for 24 034 headspace clients from 55 fully established centres.4 Significant improvement in the Social and Occupational Functioning Assessment Scale (SOFAS) scores was evident for 37.1% of headspace clients, 43.4% had no significant change, and 19.5% significantly deteriorated. Updated outcomes are forthcoming. Importantly, multiple outcomes must be considered for headspace clients; these are young people with diverse early intervention needs — the single‐item, clinician‐rated SOFAS is insufficient to ascertain meaningful outcomes. Despite the inability to generalise from Iorfino’s study to the national headspace centre network, we agree that young people with complex and persisting mental health conditions require more resource‐intensive responses than headspace primary care services were designed for.

Debra J Rickwood · Jason Trethowan · Annette Carruthers