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Context: For children with growth hormone deficiency (GHD), treatment burden with daily somatropin injections [human growth hormone (hGH)] is high, which may lead to poor adherence and suboptimal overall treatment outcomes. Lonapegsomatropin (TransCon hGH) is an investigational long-acting, once-weekly prodrug for the treatment of GHD., Objective: The objective of this study was to evaluate the efficacy and safety of once-weekly lonapegsomatropin vs daily somatropin., Design: The heiGHt trial was a randomized, open-label, active-controlled, 52-week Phase 3 trial (NCT02781727)., Setting: This trial took place at 73 sites across 15 countries., Patients: This trial enrolled and dosed 161 treatment-naïve, prepubertal patients with GHD., Interventions: Patients were randomized 2:1 to receive lonapegsomatropin 0.24 mg hGH/kg/week or an equivalent weekly dose of somatropin delivered daily., Main Outcome Measure: The primary end point was annualized height velocity (AHV) at week 52. Secondary efficacy end points included change from baseline in height SD scores (SDS)., Results: Least squares (LS) mean (SE) AHV at 52 weeks was 11.2 (0.2) cm/year for lonapegsomatropin vs 10.3 (0.3) cm/year for daily somatropin (P = 0.009), with lonapegsomatropin demonstrating both noninferiority and superiority over daily somatropin. LS mean (SE) height SDS increased from baseline to week 52 by 1.10 (0.04) vs 0.96 (0.05) in the weekly lonapegsomatropin vs daily somatropin groups (P = 0.01). Bone age/chronological age ratio, adverse events, tolerability, and immunogenicity were similar between groups., Conclusions: The trial met its primary objective of noninferiority in AHV and further showed superiority of lonapegsomatropin compared to daily somatropin, with similar safety, in treatment-naïve children with GHD., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)

Objective: To identify barriers created and maintained by the health system affecting engagement in a family-based multidisciplinary healthy lifestyle programme for children and adolescents in New Zealand., Methods: We conducted 64 semi-structured interviews with participants of the programme (n = 71) with varying levels of engagement, including those who declined contact after their referral. Half the interviews were with families with Māori children, allowing for appropriate representation. Interviews were analysed using thematic analysis., Results: Five health system factors affecting engagement were identified: the national policy environment, funding constraints, lack of coordination between services, difficulty navigating the health system, and the cost of primary health care., Conclusions: Engaging with a health system that creates and maintains substantial barriers to accessing services is difficult, affecting programme engagement, even where service-level barriers have been minimised. Lack of access remains a crucial barrier to improved health outcomes for children and their families experiencing childhood obesity in New Zealand. There is a need for comprehensive approaches that are accompanied by a clear implementation strategy and coordinated across sectors.

Objective: To determine the incidence of new onset type 1 diabetes in children aged 0-14 years from 1977 to 2019 in Auckland, New Zealand., Research Design and Methods: A cohort study of children with type 1 diabetes aged 0-14 years (n = 1688; 50.4% male) managed by the regional diabetes service between 1977 and 2019. Incidence rates were estimated using census data., Results: The incidence of type 1 diabetes increased by 2.9%/year from 1977 to 2006 (95% confidence interval [CI] 2.13% - 3.48%). Although there was no significant change from 2006 to 2019 (-0.3%/year, 95% CI -1.62% - 1.08%), there was a dramatic fall from 1976 to 2018 in the proportion of New Zealand Europeans, from 69.9 to 33.9%. New Zealand Europeans had the highest incidence (23.3/100,000, 95% CI 20.6-26.1) compared to Māori (8.3/100,000, 95% CI 6.3-10.2), Pasifika (8.6/100,000, 95% CI 6.9-10.4) and other (6.4/100,000, 95% CI 4.7-8.0). All groups showed an overall increase in incidence over time, Māori 4.4%/year, Pasifika 3.7%, compared to New Zealand European 2.7%, and other 2.1%. Incidence increased consistently in 5-9 and 10-14 year olds (2.0% and 2.2%/year, respectively). By contrast, whereas 0-4 year olds showed an increase of 4.6%/year from 1977 to 2003 (p < 0.01), there was no change from 2003 to 2019 (p = 0.2)., Conclusion: There has been a plateau in the incidence of type 1 diabetes in children 0-4 years of age in the Auckland region since 2003, but not older children. The apparent plateau in the overall incidence of new onset type 1 diabetes in children 0-14 years since 2006 was mediated by substantial changes in the ethnic makeup of the Auckland region., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: This study aimed to determine 5-year outcomes from a 12-month, family-based, multidisciplinary lifestyle intervention program for children., Methods: This study was the 5-year follow-up of a randomized clinical trial comparing a low-intensity control group (home-based assessments) with a high-intensity intervention group (assessments plus weekly sessions) in New Zealand. Participants were aged 5 to 16 years with BMI ≥ 98th centile or > 91st centile with weight-related comorbidities. The primary outcome was BMI standard deviation score (BMISDS). Secondary outcomes included various health markers., Results: Of the 199 children included in the study at baseline (47% who identified as Māori, 53% who identified as female, 28% in the most deprived quintile, mean age = 10.7 years, mean BMISDS = 3.12), 86 completed a 5-year assessment (43%). BMISDS reduction at 12 months was not retained (control = 0.00 [95% CI: -0.22 to 0.21] and intervention = 0.17 [95% CI: -0.01 to 0.34]; p = 0.221) but was greater in participants aged <10 years versus >10 years at baseline (-0.15 [95% CI: -0.33 to 0.03] vs. 0.21 [95% CI: 0.03 to 0.40]; p = 0.008). BMISDS trajectory favored participants with high attendance (p = 0.013). There were persistent improvements in water intake and health-related quality of life in both groups as well as reduced sweet drink intake in the intervention group., Conclusions: This intervention, with high engagement from those most affected by obesity, did not achieve long-term efficacy of the primary outcome. Attendance and age remain important considerations for future interventions to achieve long-term BMISDS reduction., (© 2021 The Obesity Society.)

Context: The positive predictive value of newborn screening for congenital adrenal hyperplasia (CAH) in New Zealand is approximately 10%. The use of a second tier liquid chromatography-tandem mass spectrometry bloodspot steroid profile test with birth weight- or gestational age-adjusted screening cutoffs may result in further screening improvements., Methods: Three years of newborn screening data with additional second-tier steroid metabolites was evaluated (n = 167 672 births). Data from babies with a negative screening test and confirmed CAH cases were compared. First- and second-tier steroid measurements were correlated with both birth weight and gestational age. Analysis of variance was used to determine birth weight and gestational age groups. Screening cutoffs were determined and applied retrospectively to model screening performance., Results: First-tier immunoassay data correlated better with gestational age than with birth weight, but there was no difference with second-tier steroid measurements. Four distinct birth weight and gestational age groups were established for 17-hydroxyprogesterone and a steroid ratio measurement. Application of 97.5th percentile second-tier birth weight- or gestational age-adjusted cutoffs would result in 10 positive tests over the period of the study with 8 true-positive screens and 2 false-positive tests. The positive predictive value of screening would be increased from 10.8% to 80%., Conclusions: The use of either birth weight- or gestational age-adjusted cutoffs for second-tier screening tests can significantly reduce the false positive rate of newborn screening for CAH in New Zealand without loss in screening sensitivity., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We describe the approach of an Indigenous-non-Indigenous research partnership in the context of a qualitative study which aimed to understand barriers and facilitators to engagement in a community-based healthy lifestyles program in Aotearoa/New Zealand. Informed by Kaupapa Māori research principles and by "Community-Up" research values, this collaborative approach between the mixed Māori-non-Māori research team effectively engaged with Māori and non-Māori families for in-depth interviews on participant experience, including with non-service users. "Community-Up" research principles allowed for a respectful process which upheld the mana (status, dignity) of the interview participants and the research team. Challenges included maintaining flexibility in our conceptions of ethnicity to reflect the complexity of modern family life in Aotearoa/New Zealand. We were committed to ongoing communication, awareness, and attention to the relationships that formed the basis of our research partnership, which allowed effective navigation of challenges and was critical to the study's success.

Objective: To evaluate the impact of a liquid chromatography-tandem mass spectrometry (LCMSMS) second-tier test on newborn screening for congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH) in New Zealand., Design: In a prospective study, a LCMSMS method to measure 17-hydroxyprogesterone (17OHP) was adapted to measure four additional steroids. Steroid concentrations were collected on all second-tier CAH screening tests while protocols remained unchanged. Steroid ratio parameters with recommended or published screening cuts-offs were evaluated for their impact on newborn screening performance., Measurements: Precision, accuracy, linearity and recovery of the second-tier LCMSMS method were evaluated. Second-tier specimens were divided in 3 groups; newborn screening bloodspots from neonates with confirmed CAH (n = 7) and 2 groups specimens from neonates with a birthweight (BW) ≤1500 g (n = 795) and with a BW > 1500 g (n = 806) with a negative newborn screening test. Six protocols using four steroid ratio parameters were evaluated. The sensitivity, specificity, false positive rate and positive predictive value of screening was calculated for each protocol., Results: The LCMSMS method was sufficiently accurate and precise to be used as a second-tier test for CAH. Screening sensitivity remained at 100% for each protocol apart from (17OHP + androstenedione)/cortisol when the highest cut-off of 3.75 was applied. The false positive rate was significantly improved when (17OHP + androstenedione)/cortisol and (17OHP + 21-deoxycortisol)/cortisol were evaluated with cut-offs of 2.5 and 1.5 respectively (P < .01) and both with a positive predictive value of 64%., Conclusions: A second-tier LCMSMS newborn screening test for CAH offers significant improvements to screening specificity without any other changes to screening protocols., (© 2021 John Wiley & Sons Ltd.)

Objective: Child and adolescent obesity continues to be a major health issue internationally. This study aims to understand the views and experiences of caregivers and participants in a child and adolescent multidisciplinary programme for healthy lifestyle change., Design: Qualitative focus group study., Setting: Community-based healthy lifestyle intervention programme in a mixed urban-rural region of Aotearoa/New Zealand., Participants: Parents/caregivers (n=6) and children/adolescents (n=8) who participated in at least 6 months of an assessment and weekly session, family-based community intervention programme for children and adolescents affected by obesity., Results: Findings covered participant experiences, healthy lifestyle changes due to participating in the programme, the delivery team, barriers to engagement and improvements. Across these domains, four key themes emerged from the focus groups for participants and their caregivers relating to their experience: knowledge-sharing, enabling a family to become self-determining in their process to achieve healthy lifestyle change; the importance of connectedness and a family-based programme; the sense of a collective journey and the importance of a nonjudgemental, respectful welcoming environment. Logistical challenges and recommendations for improvement were also identified., Conclusions: Policymakers need to consider the experiences of participants alongside quantitative outcomes when informing multidisciplinary intervention programmes for children and adolescents affected by obesity. Trial registration number Australian New Zealand Clinical Trials Registry (ANZCTR):12611000862943; Post-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: To explore the perceptions and experiences of caregivers of preschool children with weight issues referred from New Zealand's preschool check (the B4 School Check) to a healthy lifestyle programme. Second, to understand determinants of engagement with the programme for families post referral., Methods: Semi-structured focus groups and interviews were conducted with caregivers of preschool children referred from the national preschool check (the B4 School Check) to the Whānau Pakari healthy lifestyle programme. A purposeful sampling approach ensured the opinions of Māori (New Zealand's indigenous population) and non-Māori caregivers were included. Those who engaged and did not engage with the programme were included from across Taranaki (a semi-rural region of New Zealand). Focus groups and interviews were run separately for Māori and non-Māori participants., Results: Thematic analysis yielded one sub-theme related to caregiver perceptions of weight: societal beliefs about childhood weight, and three sub-themes related to determinants of engagement: referral experience, competing life demands, and caregiver resistance to and motivation for accepting external support. A negative referral experience to Whānau Pakari often resulted in caregivers declining to engage with the programme. Themes were similar across both Māori and non-Māori caregivers., Conclusions: This study confirmed that caregiver perceptions influence their acceptance and management of their child's weight issues. The experience of the referral to a healthy lifestyle programme is important for determining future engagement, and is likely to be facilitated by providing improved training and support to health professionals around discussing childhood weight issues with caregivers of young children., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: The objective of the current study was to identify challenges of making and sustaining healthy lifestyle changes for families with children/adolescents affected by obesity, who were referred to a multicomponent healthy lifestyle assessment and intervention programme in Aotearoa/New Zealand (NZ)., Design: Secondary qualitative analysis of semi-structured interviews., Setting: Taranaki region of Aotearoa/NZ., Participants: Thirty-eight interviews with parents/caregivers (n 42) of children/adolescents who had previously been referred to a family-focused multidisciplinary programme for childhood obesity intervention, who identified challenges of making healthy lifestyle changes. Participants had varying levels of engagement, including those who declined contact after their referral., Results: Participant-identified challenges included financial cost, impact of the food environment, time pressures, stress, maintaining consistency across households, independence in adolescence, concern for mental health and frustration when not seeing changes in weight status., Conclusions: Participants recognised a range of factors that contributed towards their ability to make and sustain change, including factors at the wider socio-environmental level beyond their immediate control. Even with the support of a multidisciplinary healthy lifestyle programme, participants found it difficult to make sustained changes within an obesogenic environment. Healthy lifestyle intervention programmes and families' abilities to make and sustain changes require alignment of prevention efforts, focusing on policy changes to improve the food environment and eliminate structural inequities.

Aim: It is important that intervention programmes are accessible and acceptable for groups most affected by excess weight. This study aimed to understand the barriers to and facilitators of engagement for Māori in a community-based, assessment-and-intervention healthy lifestyle programme (Whānau Pakari)., Methods: Sixty-four in-depth, home-based interviews were conducted with past service users. Half of these were with families with Māori children and half with non-Māori families. The interviews were thematically analysed with peer debriefing for validity., Results: Māori families experienced barriers due to racism throughout the health system and society, which then affected their ability to engage with the programme. Key barriers included the institutionalised racism evident through substantial structural barriers and socio-economic challenges, the experience of interpersonal racism and its cumulative impact with weight stigma, and internalised racism and beliefs of biological determinism. Responses to these barriers were distrust of health services, followed by renewed engagement or complete disengagement. Participants identified culturally appropriate care as that which was compassionate, respectful, and focused on relationship building., Conclusions: While Whānau Pakari is considered appropriate due to the approach of the delivery team, this is insufficient to retain some Māori families who face increased socio-economic and structural barriers. Past instances of weight stigma and racism have enduring effects when re-engaging with future health services, and inequities are likely to persist until these issues are addressed within the health system and wider society., (© 2020 The Authors Journal of Paediatrics and Child Health published by John Wiley & Sons Australia, Ltd on behalf of Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Physical activity (PA) is an important part of lifestyle management for adolescents with Type 1 diabetes (T1D). Opportunities for PA were reduced by COVID-19 restrictions. Therefore, the purpose of this cross-sectional study was to compare PA among adolescents with and without T1D during the first New Zealand (NZ) COVID-19 lockdown. PA levels of adolescents aged 11-18 years with T1D ( n = 33) and healthy controls ( n = 34) were assessed through self-reported and parent proxy-reported questionnaires. Overall, PA levels during lockdown were below recommended levels. PA levels did not differ between T1D and control participants ( p = 0.212) nor between genders ( p = 0.149). Younger adolescents tended to be more active than older adolescents ( p = 0.079). PA level was negatively associated with BMI z-score ( r = -0.29, p = 0.026) but was not associated with socioeconomic status (SES) or T1D-related parameters. In the T1D group, higher HbA1c was associated with lower school decile ( r = -0.58, p < 0.001) and higher BMI z-score ( r = 0.68, p < 0.001). Overall, young people were insufficiently active during lockdown, and some sub-groups were more affected than others by the restrictions. Pandemics are likely to be part of our future, and further studies are needed to understand their impact on the health and wellbeing of adolescents.

Background: Duchenne muscular dystrophy is caused by mutations in the DMD gene, resulting in cardiomyopathy in all affected children by 18 years. Although cardiomyopathy is now the leading cause of mortality in these children, there is ongoing debate regarding timely diagnosis, secondary prevention, and treatment of this condition. The purpose of this study was to use exercise cardiac magnetic resonance imaging in asymptomatic young boys with Duchenne muscular dystrophy to describe their heart function and compare this with healthy controls., Methods: We studied 11 boys with Duchenne muscular dystrophy aged 8.6 to 13.9 years and 11 healthy age- and sex-matched controls., Results: Compared with the controls, boys with Duchenne muscular dystrophy had lower ejection fraction at rest (57% versus 63%; P = 0.004). During submaximal exercise, they reached similar peak tachycardia but increased their heart rate and cardiac output only half as much as controls (P = 0.003 and P = 0.014, respectively). End-systolic volume remained higher in boys with Duchenne muscular dystrophy both at rest and during exercise. When transthoracic echocardiography was compared with cardiac magnetic resonance imaging, 45% of the echocardiograms had suboptimal or poor views in the Duchenne muscular dystrophy group., Conclusions: Boys with Duchenne muscular dystrophy had abnormalities in left ventricular systolic function that were exaggerated by exercise stress. Exercise cardiac magnetic resonance imaging is feasible in a select population of children with Duchenne muscular dystrophy, and it has the potential to unmask early signs of cardiomyopathy., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The first report of children born very preterm (<32 weeks of gestation) having insulin resistance was made 16 years ago. However, neonatal care has improved since. Thus, we aimed to assess whether children born very preterm still have lower insulin sensitivity than term controls., Methods: Participants were prepubertal children aged 5 to 11 years born very preterm (<32 weeks of gestation; n = 51; 61% boys) or at term (37-41 weeks; n = 50; 62% boys). Frequently sampled intravenous glucose tolerance tests were performed, and insulin sensitivity was calculated using Bergman's minimal model. Additional clinical assessments included anthropometry, body composition using whole-body dual-energy X-ray absorptiometry scans, clinic blood pressure, and 24-hour ambulatory blood pressure monitoring., Results: Children born very preterm were 0.69 standard deviation score (SDS) lighter (P < .001), 0.53 SDS shorter (P = .003), and had body mass index 0.57 SDS lower (P = .003) than children born at term. Notably, children born very preterm had insulin sensitivity that was 25% lower than term controls (9.4 vs 12.6 × 10 -4 minutes -1 ·[mU/L]; P = .001). Other parameters of glucose metabolism, including fasting insulin levels, were similar in the two groups. The awake systolic blood pressure (from 24-hour monitoring) tended to be 3.1 mm Hg higher on average in children born very preterm (P = .054), while the clinic systolic blood pressure was 5.4 mm Hg higher (P = .002)., Conclusions: Lower insulin sensitivity remains a feature of children born very preterm, despite improvements in neonatal intensive care. As reported in our original study, our findings suggest the defect in insulin action in prepubertal children born very pretermis primarily peripheral and not hepatic., (© 2020 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)

Recent interest in the use of oil-soluble contrast media (OSCM) for hysterosalpingography (HSG) and other tubal flushing procedures is largely the result of publication of the large, multicentre, randomized controlled H2Oil trial in the New England Journal of Medicine in 2017, addressing the long-held suspicion that pregnancy rates following HSG with OSCM are higher than if a water-soluble contrast media (WSCM) is used. However, the findings of this trial have been compromised by the WSCM selected for comparison with OSCM. The chosen WSCM belongs to a superceded class of ionic media, with an iodine concentration, osmolality and viscosity all lying at the extreme end of the range for water-soluble radiographic contrast. The requirement for safe, cheap, versatile WSCM for intravascular use during computerized tomography, angiography and interventional procedures has resulted in considerable refinement of WSCM, with current widespread use of non-ionic, low osmolality or iso-osmolar WSCM in radiology, including for HSG. However, the use of the earlier ionic, high osmolality agents such as that selected for the H2Oil trial persists for HSG in some centres, despite potential adverse effects on the endometrium and fallopian tubal epithelium compared with more modern, less toxic WSCM. Knowledge of the variety of physical and chemical characteristics of the available WSCM is essential for interpretation of the current literature and establishing the most effective and safe water-soluble agent to use for HSG. Design of future clinical trials to establish the potential superiority of OSCM over WSCM for fertility enhancement must include the use of the readily available, inexpensive modern WSCM. While the fertility rates following OSCM HSG have been shown to be high in women with idiopathic infertility, more robust trials are required before the widespread use of OSCM for HSG or other modalities such as ultrasound and laparoscopy should be adopted., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Iodine is a vital micronutrient and its importance in thyroid function is well established. However, abnormalities in iodine intake may also have other effects. In particular, iodine is taken up avidly by the ovary and endometrium. Iodine deficiency is associated with reduced fertility. The use of high iodine concentration contrast media has recently been shown to improve conception rates in couples with unexplained infertility (UI). We hypothesize that this improvement could be related to the iodine excess and mechanisms independent of its action on thyroid. In this article, the metabolism of iodine and its potential role in fertility will be discussed, including the impact of both iodine deficiency and excess states and the importance of iodine in normal fetal development. This will include insights from animal studies on the effect of iodine in the uterine and ovarian structural environment, hormonal milieu and immunological factors affecting implantation. We speculate that iodine may well have a role as a potential therapy for UI., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: To determine whether 12-month BMI SDS reductions persisted at 24 months in a multi-disciplinary assessment and intervention program for children and adolescents with obesity, and whether secondary outcomes improved., Methods: This was a community-based 12-month RCT in Aotearoa/New Zealand. Eligible participants were aged 5 to 16 years with BMI ≥98th centile or BMI >91st centile with weight-related comorbidities. The low-intensity control received comprehensive home-based baseline assessments and advice, and 6-monthly follow-up. The high-intensity intervention received the same assessments and advice, but also weekly multidisciplinary sessions. Primary outcome was BMI SDS at 12 months. Secondary outcomes included cardiovascular and metabolic markers., Results: 121 participants (60% of participants at baseline) were assessed at 24 months. BMI SDS reduction at 12 months was lost at 24 months in the modified intention-to-treat analysis [Control -0.03 (95%CI -0.14, 0.09) and Intervention -0.02 (-0.12, 0.08); P = .93]. However, sweet drink intake was reduced, water intake increased, and there were improvements in cardiovascular fitness in the high-intensity intervention. ≥70% attendance in the high-intensity intervention resulted in a persistent BMI SDS reduction of -0.22 after 24 months (95%CI -0.38, -0.06)., Conclusions: This trial was negative in terms of primary outcome at 24 months. However, high engagement led to sustained treatment effect, and there were multiple improvements in health measures., (© 2020 World Obesity Federation.)

Aims: To evaluate the effects of side-alternating vibration therapy on physical function and body composition in adolescents with Down syndrome., Methods: Fourteen adolescents (8 males) with Down syndrome (mean ± SD age: 15.5 ± 2.3 years) performed vibration treatment nine minutes daily, four times per week, for 20 weeks on a Galileo vibration platform. Data were collected at baseline and after 20 weeks of intervention. Assessments included six-minute walk test, muscle function (force plate), whole-body dual-energy X-ray absorptiometry and peripheral quantitative computed tomography of the non-dominant tibia., Results: After 20 weeks, participants increased their distance walked in the six-minute walk test ( p  = 0.009), 2-leg single jump efficiency ( p  = 0.024) and jump velocity ( p  = 0.046). Participants also increased their power ( p  = 0.034) and reduced the time taken during the chair rise test ( p  < 0.001). At the total body level, increases were seen in bone mineral density ( p  = 0.004), bone mineral content ( p  = 0.043), fat free mass ( p  = 0.013) and lean mass ( p  = 0.021)., Conclusion: Side-alternating vibration therapy was associated with increases in physical function and muscle mass with no effects on bone health in adolescents with Down syndrome., Clinical Trial Registration Number: Australian New Zealand Clinical Trial Registry (ACTRN12615000092594) - registered on 4 th February 2015.

Background: Cerebral palsy (CP) is the most common cause of physical disability in early childhood. Vibration therapy (VT) is a promising rehabilitation approach for children with CP with potential to impact mobility, bone and muscle health as demonstrated by extant research. However, it is still unclear how long therapy must be conducted for and what the optimal vibration frequency is in order to gain health benefits., Methods/design: The study is a randomized clinical trial evaluating and comparing the effects of two vibration frequency (20 Hz vs 25 Hz) and duration protocols (12 weeks vs 20 weeks) of side-alternating VT on mobility and other health parameters in children with CP. Children aged 5-12 years old with CP and GMFCS level I-III who are able to understand instruction and safely stand are eligible for the study. Exclusion criteria include bone fracture within 12 weeks of enrolment; acute conditions; the history of significant organic disease; the history of taking anabolic agents, glucocorticoids, growth hormone, and botulinum toxin injection into lower limbs within 3 months of enrolment. All participants will act as their own control with a 12-week lead-in period prior to intervention. The intervention period will consist of 20 weeks of home- or school-based VT 9 min per day, 4 times a week. After the baseline assessment, participants will be randomized to either a 20 Hz or 25 Hz vibration-frequency group. The primary outcome is mobility measured by a 6-min walking test, with analysis performed on the principle of intention to treat. Secondary outcomes include body composition, muscle strength, physical activity level, balance, gross motor function, respiratory function, and quality of life. Participants will undergo four assessment visits over the study period: baseline, at weeks 12, 24, and 32., Discussion: The results of the study will provide evidence-based insights into the health benefits of side-alternating VT as a therapeutic tool in young children with cerebral palsy. The investigation of different vibration training protocols will help define the optimal parameters of intervention protocols (duration, frequency) of side-alternating VT to maximize outcomes on the health of 5-12-year-old children with CP., Trial Registration: Australian New Zealand Clinical Trials Registry (ANZCTR): 12618002026202 (Registration date 18/12/2018).

Aim: To examine the feasibility and acceptability of a brief self-compassion intervention for adolescents with type 1 diabetes and disordered eating behaviour., Methods: Twenty-seven adolescents with type 1 diabetes were recruited and randomized to receive the brief (two 2.5-h sessions) self-compassion intervention, either in the intervention group (n=11) or in a waitlist control group (n=8). The intervention was adapted from the standardized eight-session 'Making Friends with Yourself' programme, and sessions were delivered 1 week apart. Acceptability was assessed through qualitative questionnaires and feasibility was assessed based on session attendance and recruitment metrics. Possible changes to disordered eating behaviour, self-care behaviours, diabetes-related distress, self-compassion, stress and glycaemic control were also assessed., Results: Nineteen participants completed the study, and they reported an increased sense of common humanity (acknowledging that we are not alone), mindfulness, and coping resources. In terms of feasibility, recruitment took longer than expected (8 months) and not all participants were able to attend both sessions (nine could only attend one of the two sessions)., Conclusions: While self-compassion is a strong conceptual fit for the issues of type 1 diabetes and disordered eating behaviour in adolescence, and the intervention content appears acceptable, feasibility issues were such that brief self-compassion programmes will probably need to be adapted into digital interventions for future research. (Trial registration number: ANZCTR 12619000541101)., (© 2020 Diabetes UK.)

Objectives: Recruitment and retention in child and adolescent healthy lifestyle intervention services for childhood obesity is challenging, and inequalities across social groups are persistent. This study aimed to understand the barriers and facilitators to engagement in a multicomponent assessment-and-intervention healthy lifestyle programme for children and their families, based in the home and community., Design: Qualitative interview-based study of past users (n=76) of a family-based multicomponent healthy lifestyle programme in a mixed urban-rural region of New Zealand. Semistructured, home-based interviews were conducted and thematically analysed with peer debriefing for validity., Participants: Families were selected through stratified random sampling to include a range of levels of engagement, including those who declined their referral, with equal numbers of interviews with Indigenous and non-Indigenous families., Results: Three interactive and compounding determinants were identified as influencing engagement in Whānau Pakari: acute and chronic life stressors, societal norms of weight and body size and historical experiences of healthcare. These determinants were present across societal, system and healthcare service levels. A negative referral experience to Whānau Pakari often resulted in participants declining further input or disengaging from the programme. A fourth domain, respectful and compassionate healthcare, was identified as a mitigator of these three themes, facilitating participant engagement despite previous negative experiences., Conclusions: While participant engagement in healthy lifestyle programmes is affected by determinants which appear to operate outside immediate service provision, the programme is an opportunity to acknowledge past instances of stigma and the wider challenges of healthy lifestyle change. The experience of the referral to Whānau Pakari is important for setting the scene for future engagement in the programme. Respectful, compassionate care is critical to enhanced retention in multidisciplinary healthy lifestyle programmes and ongoing engagement in healthcare services overall., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: We aimed to assess the role of adipose tissue distribution in cardiometabolic risk (in particular insulin sensitivity) in a population of children and adolescents with obesity. Methods: In this cross-sectional study, participants were 479 children and adolescents with obesity (322 boys and 157 girls) aged 3 to 18 years attending the Children's Hospital at Zhejiang University School of Medicine (Hangzhou, China). Clinical assessments included anthropometry, body composition (DXA scans), carotid artery ultrasounds, and OGTT. Insulin sensitivity was assessed using the Matsuda index. Participants were stratified into groups by sex and pubertal stage. Key predictors were DXA-derived android-to-gynoid-fat ratio (A/G) and total body fat percentage (TBF%). Results: Irrespective of sex and pubertal stage, there was a strong association between increasing A/G (i.e., greater abdominal adiposity) and lower insulin sensitivity. In multivariable models, every 0.1 increase in A/G was associated with a reduction in insulin sensitivity in prepubertal boys [-29% (95% CI -36%, -20%); p < 0.0001], pubertal boys [-13% (95% CI -21%, -6%); p = 0.001], and pubertal girls [-16% (95% CI -24%, -6%); p = 0.002]. In contrast, TBF% was not associated with insulin sensitivity when A/G was adjusted for, irrespective of pubertal stage or sex. In addition, every 0.1 increase in A/G was associated with increased likelihood of dyslipidemia in prepubertal boys [adjusted odds ratio (aOR) 1.62 (95% CI 1.05, 2.49)], impaired glucose tolerance in pubertal boys [aOR 1.64 (95% CI 1.07, 2.51)] and pubertal girls [aOR 1.81 (95% CI 1.10, 2.98)], and odds of NAFLD in both prepubertal [aOR 2.57 (95% CI 1.56, 4.21)] and pubertal [aOR 1.69 (95% CI 1.18, 2.40)] boys. In contrast, higher TBF% was only associated with higher fasting insulin and ALT in pubertal boys, being also predictive of NAFLD in this group [aOR 1.15 per percentage point (95% CI 1.06, 1.26)], but was not associated with the likelihood of other cardiometabolic outcomes assessed in any group. Conclusions: A/G is a much stronger independent predictor of cardiometabolic risk factors in children and adolescents with obesity in China, particularly glucose metabolism., (Copyright © 2020 Jin, Lin, Yuan, Dong, Huang, Wu, Chen, Zhang, Wang, Liang, Dai, Xu, Zhou, Zhu, Li, Cutfield, Hofman, Derraik and Fu.)

Background: It is unclear whether newborns with mild thyrotropin elevation (mTSHe) are at risk of neurocognitive impairment. We assessed whether mTSHe at birth persists during childhood and compared neurocognitive functioning to siblings., Methods: This study encompassed children born in the Auckland region (New Zealand) with a newborn screen TSH level of 8 to 14 mIU/L blood, age 6.9 to 12.6 years at assessment, and their siblings. Thyroid function tests (serum TSH and free thyroxine) and neurocognitive assessments were performed, including IQ via the Wechsler Intelligence Scale for Children, fourth edition., Results: Ninety-six mTSHe individuals were studied, including 67 children recruited with 75 sibling controls. Mean mTSHe newborn TSH level was 10.1 mIU/L blood and 2.4 mIU/L at assessment (range, 0.8-7.0 mIU/L, serum). Although higher newborn TSH levels in the mTSHe group correlated with lower full-scale IQ scores (r = 0.25; P = .040), they were not associated with the magnitude of the IQ difference within sibling pairs (P = .56). Cognitive scores were similar for mTSHe and controls (full-scale IQ 107 vs 109; P = .36), with a minor isolated difference in motor coordination scores., Conclusions: Our data do not suggest long-term negative effects of neonatal mild TSH elevation. TSH elevation below the screen threshold appears largely transient, and midchildhood neurocognitive performance of these children was similar to their siblings. We propose that associations between neonatal mild TSH elevation and IQ are due to familial confounders. We caution against the practice of reducing screening CH cutoffs to levels at which the diagnosis may not offer long-term benefit for those detected., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives Based on the ellipse trial, liraglutide was recently approved for use in pediatric patients with type 2 diabetes. We report the comparative exposure of liraglutide in pediatric vs. adult patients. Methods In this pharmacokinetic (PK) and exposure-response meta-analysis, data from two pediatric trials (including ellipse) and two adult trials of liraglutide were compiled (1,137 PK observations from 116 patients) to determine the impact of body weight, age and sex on liraglutide exposure. The exposure-response relationship for glycated hemoglobin (HbA1c) and body weight was compared between pediatric and adult patients. Additionally, the relationships between exposure and change from baseline in body mass index (BMI) and BMI standard deviation score (SDS) were assessed. Results The same liraglutide dose showed comparable exposure levels in pediatric and adult patients. Body weight and sex were the most important covariates for liraglutide exposure. There was an increasing response with higher liraglutide concentrations, and greater reductions were observed from baseline in HbA1c at 26 weeks vs. placebo. A trend toward lower body weight, BMI and BMI SDS was observed at 26 weeks. Conclusions These results support use of the same liraglutide dosing regimen in children and adolescents, aged ≥10 years, as that used in adults.

Aim: Cost-effective psychosocial interventions that can feasibly be implemented into busy clinical settings are needed to improve psychological and physical health outcomes in adolescents with Type 1 diabetes. We examined the efficacy of a gratitude journalling intervention to improve psychological well-being and glycaemic control in adolescents aged 10-16 years with Type 1 diabetes., Methods: Eighty adolescents were randomized to the 8-week gratitude intervention (N = 40) or standard care (N = 40). Self-reported measures of stress, quality of life, self-care, depression and gratitude were assessed at baseline and 8 weeks after baseline. Glycaemic control (HbA 1c ) was assessed at baseline and 12 weeks after baseline. A per-protocol analysis was conducted with the adolescents who completed all questionnaires (N = 60). Analysis of covariance (ANCOVA) was used to examine differences between treatment arms at follow-up adjusting for baseline scores., Results: There was no evidence of any between-group differences in the psychological or behavioural measures at follow-up (all P-values > 0.05). Glycaemic control slightly increased in the control group while remaining stable in the gratitude group, with a between-group difference of 6.1 mmol/mol [95% confidence interval (CI) -2.6 to 14.7; 0.6%, 95% CI -0.2 to 1.3] at 12 weeks after baseline. After adjusting for baseline HbA 1c , this between-group difference was significant (P = 0.048)., Conclusions: This is the first randomized trial of a gratitude journalling intervention for adolescents with Type 1 diabetes. Gratitude journalling interventions represent a clinically usable approach. If and how it helps to stabilise glycaemic control in adolescents with Type 1 diabetes remains to be confirmed in future research., (© 2019 Diabetes UK.)

Aims: A pilot study was performed to establish the safety, feasibility and efficacy of vibration therapy (VT) on bone and muscle health in children and adolescents with a range of musculoskeletal disorders., Methods: Seventeen participants (15.7 years ± 2.9 years), with conditions that impacted on their musculoskeletal health, completed 20 weeks of side-alternating VT for 9 min/session, 4 times/week at 20 Hz. Data were collected at baseline and after 20 weeks of intervention. Assessments included whole-body dual-energyX-ray absorptiometry, muscle function (force plate) and 6-min walk test., Results: Compliance with the prescribed VT training protocol was relatively high overall at 78% and there were no adverse events reported. After 20 weeks intervention, functional assessments showed time taken to perform the chair test was reduced by 15% (P = 0.018), leg balance improved with standard ellipse area decreasing by 88% (P = 0.006) and distance walked in the 6-min walk test improved by 9% (P = 0.002). Participants displayed increased total body mass (1.94 kg; P = 0.018) with increased lean mass (1.20 kg; P = 0.019) but not fat mass (P = 0.19). There was no change in total body bone mineral density (P = 0.44) or bone mineral content (P = 0.07)., Conclusions: Twenty weeks of side-alternating VT was a feasible protocol that was associated with improvements in physical function and no detrimental effects on lean mass, bone mass or density in children and adolescents with musculoskeletal disorders., (© 2020 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Objective: Gratitude interventions are easy-to-deliver, offering promise for use in clinical-care. Although gratitude interventions have consistently shown benefits to psychological wellbeing, the effects on physical health outcomes are mixed. This systematic review aims to synthesize gratitude intervention studies which assessed physical health and health behavior outcomes, as well as evaluate study quality, comment on their efficacy, and provide directions for future research., Methods: Relevant studies were identified through searches conducted in PsycINFO, MedLine, Embase and Cochrane Library databases, up until August 2019. Only studies that evaluated a gratitude intervention, randomly assigned participants to gratitude and control conditions, and assessed objective and subjective measures of physical health and health behaviors were included. The Revised Cochrane risk-of-bias (RoB2) tool was used to assess risk of bias., Results: Of the 1433 articles found, 19 were included in the review. Subjective sleep quality was improved in 5/8 studies. Improvements in blood pressure, glycemic control, asthma control and eating behavior were understudied yet demonstrated improvements (all 1/1). Other outcome categories remain understudied and mixed, such as inflammation markers (1/2) and self-reported physical symptoms (2/8). The majority of studies showed some risk of bias concerns., Conclusions: Although it was suggested gratitude interventions may improve subjective sleep quality, more research is still needed to make firm conclusions on the efficacy of gratitude interventions on improving health outcomes. Further research focusing on gratitude's link with sleep and causal mechanisms is needed, especially in patient populations where more 'clinically-usable' psychosocial interventions are urgently needed., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To investigate the effect of age and Gross Motor Function Classification System (GMFCS) level on walking endurance after 20 weeks of vibration therapy in children and young people with cerebral palsy (CP)., Design: The study was a clinical trial without control group comparing baseline and postintervention outcomes within participants., Setting: Vibration therapy was performed at school or at home. Assessments took place in a clinical research unit., Participants: Children and young people (N=59) with CP, aged 5-20 years, GMFCS level II, III, or IV, recruited through schools, physiotherapy services, and District Health Board clinics, Auckland, New Zealand., Interventions: Participants performed side-alternating whole-body vibration therapy (WBVT) at 20 Hz and 3-mm amplitude, 9 minutes per day, 4 times per week for 20 weeks., Main Outcome Measures: Distance walked in the 6-minute walk test (6MWT) was recorded before and after the intervention., Results: Participants baseline results for the 6MWT were lower, independent of age or GMFCS, when compared to non-CP literature. On average, participants walked 12% further in the 6MWT after the intervention ( P <.001). There was significant improvement in 6MWT distance in all age groups (5-10y: 16%, P <.001; 11-15y: 10%, P =.001; 16-20y: 13%, P <.001) and all GMFCS levels (level II: 10%, P <.001, level III: 40%, P =.013, level IV: 57%, P =.007). There was a greater percentage improvement in the distance walked in those with GMFCS level III and level IV than level II ( P =.049 and P <.001, respectively)., Conclusions: WBVT had a beneficial effect on walking endurance in children and young people with CP, independent of age and GMFCS., (© 2020 The Authors.)

Preterm infants are exposed to major perinatal, post-natal, and early infancy events that could impact on the gut microbiome. These events include infection, steroid and antibiotic exposure, parenteral nutrition, necrotizing enterocolitis, and stress. Studies have shown that there are differences in the gut microbiome during the early months of life in preterm infants. We hypothesized that differences in the gut microbial composition and metabolites in children born very preterm persist into mid-childhood. Participants were healthy prepubertal children aged 5-11 years who were born very preterm (≤32 weeks of gestation; n = 51) or at term (37-41 weeks; n = 50). We recorded the gestational age, birth weight, mode of feeding, mode of birth, age, sex, and the current height and weight of our cohort. We performed a multi'omics [i.e., 16S rRNA amplicon and shotgun metagenomic sequencing, SPME-GCMS (solid-phase microextraction followed by gas chromatography-mass spectrometry)] analysis to investigate the structure and function of the fecal microbiome (as a proxy of the gut microbiota) in our cross-sectional cohort. Children born very preterm were younger (7.8 vs. 8.3 years; p = 0.034), shorter [height-standard deviation score (SDS) 0.31 vs. 0.92; p = 0.0006) and leaner [BMI (body mass index) SDS -0.20 vs. 0.29; p < 0.0001] than the term group. Children born very preterm had higher fecal calprotectin levels, decreased fecal phage richness, lower plasma arginine, lower fecal branched-chain amino acids and higher fecal volatile (i.e., 3-methyl-butanoic acid, butyrolactone, butanoic acid and pentanoic acid) profiles. The bacterial microbiomes did not differ between preterm and term groups. We speculate that the observed very preterm-specific changes were established in early infancy and may impact on the capacity of the very preterm children to respond to environmental changes., (Copyright © 2020 Jayasinghe, Vatanen, Chiavaroli, Jayan, McKenzie, Adriaenssens, Derraik, Ekblad, Schierding, Battin, Thorstensen, Cameron-Smith, Forbes-Blom, Hofman, Roy, Tannock, Vickers, Cutfield and O'Sullivan.)

Objective: To understand facilitators and barriers to engagement in a multidisciplinary assessment and intervention program for children and adolescents with obesity, particularly for Māori, the Indigenous people of New Zealand., Methods: Whānau Pakari participants and caregivers (n = 71, 21% response rate) referred to the family-based healthy lifestyles program in Taranaki, New Zealand, were asked to participate in a confidential survey, which collected self-reported attendance levels and agreement with statements around service accessibility and appropriateness and open-text comments identifying barriers and facilitators to attendance., Results: Self-reported attendance levels were higher when respondents reported sessions to be conveniently located (P = .03) and lower when respondents considered other priorities as more important for their family (P = .02). Māori more frequently reported that past experiences of health care influenced their decision to attend (P = .03). Facilitators included perceived convenience of the program, parental motivation to improve child health, and ongoing support from the program., Conclusions and Implications: Program convenience and parental and/or self-motivation to improve health were facilitators of attendance. Further research is required to understand the relationship between past experiences with health care and subsequent engagement with services., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Previous studies reported impaired glucose homeostasis among preterm survivors, but consisted almost exclusively of Caucasians. It is unknown whether Asians born preterm display similar impairments., Aim: To assess glucose homeostasis and other cardiometabolic outcomes among young adults born preterm in Thailand., Methods: Participants were 575 young adult offspring of mothers from the Chiang Mai Low Birth Weight Study, born in 1989 to 1990 and followed up in 2010: 54.1% females, median age 20.6 years, including 33 individuals (5.7%) born preterm. After an overnight fast, participants underwent clinical assessments, including blood sampling (glucose, insulin, and lipid profile). Insulin sensitivity was assessed using HOMA-IR and insulin secretion estimated using HOMA-β., Results: In unadjusted analyses, young Thai adults born preterm were 3.2 cm shorter (P = .037), 6 kg lighter (P = .016), and had HOMA-β 34% higher (P = .026) than those born at term. Adjusted analyses accounting for important confounders showed marked impairments in glucose homeostasis among preterm survivors: fasting insulin levels were 32% greater (P = .011), with HOMA-IR and HOMA-β that were 31% (P = .020) and 43% higher (P = .005), respectively, compared to peers born at term. There were no other contrasting observations between groups, with anthropometric differences disappearing after adjustment for confounders., Discussion: Young adults in Thailand born preterm were more insulin resistant than peers born at term. The observed impairments in glucose metabolism among young Thai adults born preterm corroborate findings reported mostly on Caucasians. The challenge for general practitioners and public health professionals is to encourage those born preterm to make healthier lifestyle choices early on., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Congenital myopathy is a heterogeneous group of muscle disorders characterized by muscle weakness and hypotonia. This condition is associated with a range of skeletal, respiratory, and ophthalmologic complications and requires a multidisciplinary therapeutic approach aimed at maximizing the function and independence of patients. One promising direction for therapeutic intervention is physical exercise rehabilitation, given its demonstrated ability to promote muscle and bone health of patients with a variety of neuromuscular conditions. However, there are few data to assist health care professionals identify the optimal physical activity levels and exercise type, including the intensity, frequency, and duration. This lack of empirical evidence is particularly problematic given the fact that inappropriate exercise modes can potentially cause muscle damage in patients with congenital myopathy. In this article, we discuss the rationale behind the incorporation of two types of physical exercises, strength and aerobic training, into the clinical care of patients with congenital myopathy. Given the paucity of literature on the management of congenital myopathy, we review the results of published research on the treatment of both congenital myopathy and other neuromuscular diseases that could provide helpful insights into the physical rehabilitation of patients with congenital myopathy. We also discuss the potential benefits of vibration therapy, which has been studied in patients with other neuromuscular disorders over the last two decades. We conclude by proposing directions for future research on physical rehabilitation of patients with congenital myopathy., (Copyright © 2019. Published by Elsevier Inc.)

Introduction: Adolescents with type 1 diabetes are at a higher risk of developing psychiatric disorders, particularly eating disorders, compared with their healthy peers. In turn, this increases the risk for sub-optimal glycaemic control and life-threatening diabetes-related complications. Despite these increased risks, standard diabetes care does not routinely provide psychological support to help prevent or reduce mental health risks. There is an urgent need to develop 'clinically usable' psychosocial interventions that are acceptable to patients and can be realistically integrated into clinical care. This study aims to examine the feasibility and acceptability of a brief self-compassion intervention for adolescents with type 1 diabetes and disordered eating behaviour., Methods and Analysis: This feasibility study will examine the effectiveness of a brief self-compassion intervention, compared with a waitlist control group. Participants aged 12-16 years will be recruited from three diabetes outpatient clinics in Auckland, New Zealand. The brief self-compassion intervention is adapted from the standardised 'Making Friends with Yourself' intervention and will be delivered in a group format over two sessions. Apart from examining feasibility and acceptability through the flow of participants through the study and qualitative questions, we will assess changes to disordered eating behaviour (primary outcome), self-care behaviours, diabetes-related distress, self-compassion, stress and glycaemic control (secondary outcomes). Such data will be used to calculate the required sample size for a fully powered randomised controlled trial., Ethics and Dissemination: This trial has received ethics approval from the Health and Disability Ethics Committee (research project number A+8467). Study results will be disseminated through peer-reviewed journals and conferences., Trial Registration Number: ANZCTR (12619000541101)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The positive predictive value of newborn screening for congenital adrenal hyperplasia due to 21-hydroxylase deficiency was <2% in New Zealand. This is despite a bloodspot second-tier immunoassay method for 17-hydroxyprogesterone measurement with an additional solvent extract step to reduce the number of false positive screening tests. We developed a liquid chromatography tandem mass spectrometry (LCMSMS) method to measure 17-hydroxyprogesterone in bloodspots to replace our current second-tier immunoassay method. The method was assessed using reference material and residual samples with a positive newborn screening result. Correlation with the second-tier immunoassay was determined and the method was implemented. Newborn screening performance was assessed by comparing screening metrics 2 years before and 2 years after LCMSMS implementation. Screening data analysis demonstrated the number of false positive screening tests was reduced from 172 to 40 in the 2 years after LCMSMS implementation. The positive predictive value of screening significantly increased from 1.71% to 11.1% (X 2 test, p < 0.0001). LCMSMS analysis of 17OHP as a second-tier test significantly improves screening specificity for CAH due to 21-hydroxylase deficiency in New Zealand., Competing Interests: Conflicts of InterestThe authors declare no conflict of interest., (© 2020 by the authors.)

Background: Partial remission (PREM) by the insulin dose-adjusted HbA1c (IDAA1c) method has not been evaluated for the combined associations of ethnicity and socioeconomic status in children and adolescents with type 1 diabetes (T1D)., Objective: To investigate prevalence and predictors of PREM defined by IDAA1c., Methods: Six hundred fourteen of 678 children (aged <15 years) with new-onset T1D (2000-2013) from a regional pediatric diabetes service (Auckland, New Zealand)., Results: Overall rate of PREM at 3 months was 42.4%, and lower in Māori/Pacific children (28.6%; P = .006) and those of other ethnicities (28.8%; P = .030) compared with New Zealand Europeans (50.4%). Comparing the most and least deprived socioeconomic quintiles, the odds of PREM were lower among the most deprived (adjusted odds ratio [aOR] 0.44; P = .019). Lower rates of PREM were seen in children aged 0 to 4.9 years (23.8%) and 10 to 14 years (40.9%) than in children aged 5 to 9.9 years (57.4%; P < .05). Further predictors of lower rates of PREM were ketoacidosis at diagnosis (aOR 0.54 with DKA; P = .002) and diabetes duration (aOR 0.84 per month; P < .0001). Patient's sex, body mass index standard deviation score, or autoantibodies were not associated with PREM. PREM at 3 months was associated with lower HbA1c over 18 months compared with children not in PREM (65.0 vs 71.3 mmol/mol; P < .0001), independent of ketoacidosis., Conclusions: This study on a regional cohort of youth with T1D showed social and ethnic disparities in rates of PREM defined by IDAA1c. Further research into reducing ketoacidosis rates at diagnosis and addressing factors associated with lower rates of PREM in non-European children are important health priorities., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Context: Optimal newborn screening thyroid-stimulating hormone (TSH) cut-offs are contentious. Analysis of demographic factors that impact screen TSH levels may help explain international variance and provide guidance to screening programmes., Objective: To determine the influence of demographic factors on newborn screening TSH levels and screening performance parameters., Design and Setting: National, retrospective population study using blood spot TSH cards from the New Zealand newborn screening programme in 2010-2015., Patients: 325 685 blood spot cards., Main Outcome Measures: Likelihood of exceeding specific TSH thresholds (TSH ≥5, ≥10 and ≥15 mIU/L) and group-specific screening performance parameters., Results: The likelihood of high TSH levels differed between ethnic groups. Pacific Island infants were more than twice as likely to have high-normal TSH levels (≥5 and ≥10 mIU/L) and nearly twice as likely to have a positive screen (≥15 mIU/L) as New Zealand Europeans. Māori or Chinese ethnicity, male sex, younger gestational age and greater socio-economic deprivation scores were also associated with high-normal TSH levels. At a TSH threshold ≥15 mIU/L, screening sensitivity was lowest (88.89% vs 95.83% overall) and PPV greatest (88.89% vs 62.84%) amongst Asian infants. Early samples were more than three times as likely to reach the screen-positive threshold and more likely to yield a false-positive result (PPV 20.00% vs 68.87%, P = 0.004)., Conclusions: Newborn TSH levels are impacted by a number of demographic variables, particularly ethnicity and age at sample collection. Screening performance may be improved through the use of targeted thresholds., (© 2019 John Wiley & Sons Ltd.)

SERPINH1 encodes the collagen chaperone HSP47 that binds to arginine-rich sequences in the type I procollagen trimers and provides the final steps in the folding and stabilization of the triple helical domain. Loss of both alleles in mice results in very early embryonic lethality. SERPINH1 mutations have been associated with one of the rarest forms of recessively inherited osteogenesis imperfecta (OI) with a moderate to severe phenotype. We identified a family with non-consanguineous unaffected parents who had two children with moderate short stature, low bone density, and fractures. Both children were compound heterozygotes for two mutations: a frameshift in the last exon that deleted the RER retention signal, and a 5,274 bp deletion 2.37 kb upstream from the transcription start site. The maternally-inherited frameshift allele was expressed at normal levels, but the protein was unstable. The mRNA encoded by the second allele represented about 50% of that from the frameshift-containing allele. The upstream deletion was inherited from the father, and the mRNA encoded by that allele in his cultured dermal fibroblasts was also expressed at a low level, which confirmed that this domain had a regulatory function for SERPINH1. Regulatory mutations are uncommon causes of human genetic disorders, and the ability to measure expression levels in appropriate cells is key to their identification., (© 2019 Wiley Periodicals, Inc.)

Objective: We compared growth hormone sensitivity to an insulin-like growth factor I (IGF-I) generation test in children with idiopathic short stature (ISS) and of normal stature (NS) across the birthweight range., Methods: Forty-six prepubertal children (~7.1 years) born at term were studied: ISS (n = 23; 74% boys) and NS (n = 23; 57% boys). Children underwent a modified IGF-I generation test with recombinant human growth hormone (rhGH; 0.05 mg/kg/d) over four consecutive days. Hormonal concentrations were measured at baseline and day 5., Results: Children with idiopathic short stature were 1.90 SDS lighter (P < 0.0001) but had 4.5% more body fat (P = 0.0007) than NS children. Overall, decreasing birthweight SDS across the normal range (-1.9 to +1.5 SDS) was associated with lower percentage IGF-I response to rhGH stimulation in univariable (r = 0.45; P = 0.002) and multivariable models (β = 24.6; P = 0.006). Plasma IGF-I concentrations rose in both groups with rhGH stimulation (P < 0.0001). GHBP levels (P = 0.002) were suppressed in ISS children (-19%; P = 0.029) but increased among NS children (+18%; P = 0.028), with contrasting responses also observed for leptin and IGFBP-1. Further, the increase in insulin concentrations in response to rhGH stimulation was ~3-fold greater in NS children (142% vs 50%; P = 0.006)., Conclusions: A progressive decrease in birthweight SDS was associated with a reduction in GH sensitivity in both NS and ISS children. Thus, the lower IGF-I response to rhGH stimulation in association with decreasing birthweight indicates that the ISS children at the lower end of the birthweight spectrum may have partial GH resistance, which may contribute to their poorer growth., (© 2019 John Wiley & Sons Ltd.)

Objective/design: It remains unclear as to the efficacy of readiness for change measurements in child and adolescent obesity intervention programmes. This observational study aimed to determine whether the caregiver's stage of change could predict outcome and adherence to treatment in an intensive intervention programme for children and adolescents with obesity., Setting: Participants were from the Whānau Pakari randomised clinical trial, a community based multi-disciplinary intervention programme for obesity in Taranaki, New Zealand., Participants: Eligible participants (recruited January 2012 to August 2014) were aged 5-16 years and had a body mass index (BMI) ≥98th centile or BMI >91st centile with weight-related comorbidities., Interventions: This study only assessed participants randomised to the high-intensity intervention programme (6-month assessments with weekly group sessions for 12 months) given attendance data were required (n=96)., Primary and Secondary Outcome Measures: Primary trial outcome was BMI SD score (SDS). Secondary outcome measures included indices such as fruit and vegetable intake, 550-m run/walk time and quality of life scores. At baseline assessment, participants (if >11 years old) and their accompanying adult were assessed for readiness to make healthy lifestyle change., Results: A quantitative measure of stage of change in caregivers was not a predictor of primary or secondary outcomes (change in BMI SDS pre-contemplation/contemplation -0.08, 95% CI -0.18 to 0.03, action -0.16, 95% CI -0.27 to -0.05, p=0.27), or overall attendance in the weekly activity sessions (40.0% vs 37.1%, respectively, p=0.54) in the child or adolescent., Conclusions: Caregiver's stage of change was not a predictor of success in this multi-disciplinary assessment and intervention programme for children and adolescents with obesity. Future research needs to determine participants' factors for success., Trial Registration Number: ANZCTR12611000862943; Post-results., Competing Interests: Competing interests: YCA reports grants from Health Research Council of NZ, grants from Royal Australasian College of Physicians, grants from Maurice and Phyllis Paykel Trust, grants from Taranaki Medical Foundation during the conduct of the study; TLC and AS report grants from Taranaki Medical Foundation, grants from Maurice and Phyllis Paykel Trust, grants from Lotteries Health Research during the conduct of the study; PH reports grants from Lotteries Health Research during the conduct of the study., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: It is unclear whether an association exists between obesity in children/adolescents and cognitive function, and whether the latter can be altered by body mass index (BMI) standard deviation score (SDS) reductions. We aimed to determine whether an association exists between BMI SDS and cognitive function in children/adolescents with obesity engaged in an obesity intervention. Second, we sought to determine if BMI SDS reduction at 12 months was associated with improved cognitive function., Design: Secondary analysis of a clinical trial., Participants: Participants (n=69) were recruited from an obesity intervention. Eligible participants (recruited June 2013 to June 2015) were aged 6-16 years, with a BMI ≥98th centile or BMI >91st centile with weight-related comorbidities., Outcome Measures: Primary outcome measure was change in BMI SDS from baseline at 12 months. Dependent variables of cognitive functioning and school achievement were assessed at baseline and 12 months, using dependent variables of cognitive functioning (elements of Ravens Standard Progressive Matrices, Wide Range Achievement Test-fourth edition and Wechsler Intelligence Scale for Children-fourth edition)., Results: At baseline, BMI SDS was not associated with all aspects of cognitive function tested (n=69). Reductions in BMI SDS over time did not alter cognitive function overall. However, there was a greater reduction in comprehension standard scores in participants who increased their BMI SDS (adjusted estimated difference -6.1, 95% CI -11.6 to -0.6; p=0.03)., Conclusions: There were no observed associations between BMI SDS and cognitive function in participants, apart from comprehension in the exploratory analyses, which may have been a random finding. Further studies need to include larger longitudinal cohorts incorporating a wider BMI range at entry to determine whether our findings persist., Trial Registration Number: ANZCTR12611000862943; Pre-results., Competing Interests: Competing interests: YCA and PLH have been recipients of these grants to undertake clinical research in relation to Whānau Pakari, YCA has been paid in a fellowship capacity from the Health Research Council of New Zealand, TLC and CEKW have been paid as research assistants, JGBD has been paid for data analysis., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The Growth Hormone Research Society (GRS) convened a Workshop in March 2019 to evaluate the diagnosis and therapy of short stature in children. Forty-six international experts participated at the invitation of GRS including clinicians, basic scientists, and representatives from regulatory agencies and the pharmaceutical industry. Following plenary presentations addressing the current diagnosis and therapy of short stature in children, breakout groups discussed questions produced in advance by the planning committee and reconvened to share the group reports. A writing team assembled one document that was subsequently discussed and revised by participants. Participants from regulatory agencies and pharmaceutical companies were not part of the writing process. Short stature is the most common reason for referral to the pediatric endocrinologist. History, physical examination, and auxology remain the most important methods for understanding the reasons for the short stature. While some long-standing topics of controversy continue to generate debate, including in whom, and how, to perform and interpret growth hormone stimulation tests, new research areas are changing the clinical landscape, such as the genetics of short stature, selection of patients for genetic testing, and interpretation of genetic tests in the clinical setting. What dose of growth hormone to start, how to adjust the dose, and how to identify and manage a suboptimal response are still topics to debate. Additional areas that are expected to transform the growth field include the development of long-acting growth hormone preparations and other new therapeutics and diagnostics that may increase adult height or aid in the diagnosis of growth hormone deficiency., (© 2019 The Author(s)Published by S. Karger AG, Basel.)

Objective: New-onset diabetic ketoacidosis (NO-DKA) is entirely preventable with early recognition of the symptoms of type 1 diabetes mellitus (T1D). In this study, we aimed to assess whether a simple and easily delivered educational campaign could reduce the risk of DKA., Methods: A poster highlighting key features of new-onset T1D was delivered once a year over 2 years to mailboxes of over 460 000 individual residential households in the Auckland region (New Zealand). In the first year, the campaign poster was also delivered to all general practices in the region. Families of all newly diagnosed cases of T1D in children answered a brief questionnaire to ascertain whether the campaign reached them., Results: Over the 24-month period covered by this study, 132 new cases of T1D were diagnosed in children and adolescents in Auckland. There were 38 cases (28.8%) of DKA, which is similar to the average over the previous 5-year period (27.0%). The caregivers of three children reported both seeing the campaign poster and seeking medical attention as a result. None of these three children were in DKA at diagnosis; they were aged 6.3 to 9.7 years, and of New Zealand European ethnicity., Conclusions: A non-targeted campaign to raise awareness of diabetes symptoms in youth led only a few caregivers to seek timely medical attention. Overall, this once-yearly untargeted campaign to raise awareness of diabetes symptoms in youth had limited impact. More effective strategies are required, possibly involving sustained targeted education of medical practitioners., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Duchenne Muscular Dystrophy is the most common paediatric neuromuscular disorder. Mutations in the DMD gene on the X-chromosome result in progressive skeletal muscle weakness as the main clinical manifestation. However, cardiac muscle is also affected, with cardiomyopathy becoming an increasingly recognised cause of morbidity, and now the leading cause of mortality in this group. The diagnosis of cardiomyopathy has often been made late due to technical limitations in transthoracic echocardiograms and delayed symptomatology in less mobile patients. Increasingly, evidence supports earlier pharmacological intervention in cardiomyopathy to improve outcomes. However, the optimal timing of initiation remains uncertain, and the benefits of prophylactic therapy are unproven. Current treatment guidelines suggest initiation of therapy once cardiac dysfunction is detected. This review focuses on new and evolving techniques for earlier detection of Duchenne muscular dystrophy-associated cardiomyopathy. Transthoracic echocardiography or cardiac magnetic resonance imaging performed under physiological stress (dobutamine or exercise), can unmask early cardiac dysfunction. Cardiac magnetic resonance imaging can define cardiac function with greater accuracy and reliability than an echocardiogram, and is not limited by body habitus. Improved imaging techniques, used in a timely fashion, offer the potential for early detection of cardiomyopathy and improved long-term outcomes., (Copyright © 2018 Elsevier B.V. All rights reserved.)

There is some evidence that children born post-term (≥42 weeks of gestation) have metabolic abnormalities that may be associated with an increased risk of adverse health outcomes in adulthood. However, there are no data as to whether adolescents born post-term display alterations in aerobic capacity or cardiovascular function. We studied 48 adolescents (56% males) in Auckland (New Zealand) with a mean age of 14.3 years (SD = 1.7): 25 born post-term and 23 born at term (37-41 weeks of gestation). Assessments included metabolic markers in blood, whole body DXA scans, 24-hour ambulatory blood pressure monitoring, maximal exercise capacity, as well as cardiac MRI scan at rest and during submaximal exercise. Exercise capacity was lower in the post-term than in control participants (44.5 vs 47.8 ml/kgffm/min; p = 0.04). There were no differences in left ventricular volumes at rest and during exercise between groups. The 24-hour ambulatory blood pressure monitoring also showed no differences between the two groups. Being born post-term was associated with reduced exercise capacity, but with no observed differences in central cardiac function. We speculate that the reduction in exercise capacity may be due to changes in the peripheral vascular system.

There are limited data on long-term outcomes of mothers or their offspring following exercise interventions during pregnancy. We assessed long-term effects of an exercise intervention (home-based stationary cycling) between 20-36 weeks of gestation on anthropometry and body composition in mothers and offspring after 1 and 7 years. 84 women were randomised to intervention or usual activity, with follow-up data available for 61 mother-child pairs (38 exercisers) at 1 year and 57 (33 exercisers) at 7 years. At 1 year, there were no observed differences in measured outcomes between mothers and offspring in the two groups. At the 7-year follow-up, mothers were mostly similar, except that exercisers had lower systolic blood pressure (-6.2 mmHg; p = 0.049). However, offspring of mothers who exercised during pregnancy had increased total body fat (+3.2%; p = 0.034) and greater abdominal (+4.1% android fat; p = 0.040) and gynoid (+3.5% gynoid fat; p = 0.042) adiposity compared with controls. Exercise interventions beginning during pregnancy may be beneficial to long-term maternal health. However, the initiation of exercise during pregnancy amongst sedentary mothers may be associated with adverse effects in the offspring during childhood. Larger follow-up studies are required to investigate long-term effects of exercise in pregnancy.

Adrenocortical carcinoma (ACC) during childhood is a rare malignant tumor that frequently results in glucocorticoid and/or androgen excess. When there are signs of microscopic or macroscopic residual disease, adjuvant therapy is recommended with mitotane, an adrenolytic and cytotoxic drug. In addition to the anticipated side effect of adrenal insufficiency, mitotane is known to cause gynecomastia and hypothyroidism in adults. It has never been reported to cause precocious puberty. A 4-year-old girl presented with a 6-week history of virilization and elevated androgen levels and 1-year advancement in bone age. Imaging revealed a right adrenal mass, which was subsequently surgically excised. Histology revealed ACC with multiple unfavorable features, including high mitotic index, capsular invasion and atypical mitoses. Adjuvant chemotherapy was started with mitotane, cisplatin, etoposide and doxorubicin. She experienced severe gastrointestinal side effects and symptomatic adrenal insufficiency, which occurred despite physiological-dose corticosteroid replacement. She also developed hypothyroidism that responded to treatment with levothyroxine and peripheral precocious puberty (PPP) with progressive breast development and rapidly advancing bone age. Five months after discontinuing mitotane, her adrenal insufficiency persisted and she developed secondary central precocious puberty (CPP). This case demonstrates the diverse endocrine complications associated with mitotane therapy, which contrast with the presentation of ACC itself. It also provides the first evidence that the known estrogenic effect of mitotane can manifest as PPP., Learning Points: Adrenocortical carcinoma is an important differential diagnosis for virilization in young childrenMitotane is a chemotherapeutic agent that is used to treat adrenocortical carcinoma and causes adrenal necrosisMitotane is an endocrine disruptor. In addition to the intended effect of adrenal insufficiency, it can cause hypothyroidism, with gynecomastia also reported in adults.Patients taking mitotane require very high doses of hydrocortisone replacement therapy because mitotane interferes with steroid metabolism. This effect persists after mitotane therapy is completedIn our case, mitotane caused peripheral precocious puberty, possibly through its estrogenic effect.

Socioeconomic status is a known determinant of health. In secondary data analyses, we assessed whether socioeconomic status affected health-related quality of life in a group of overweight (body mass index 25-30 kg/m 2 ) middle-aged (45.9 ± 5.4 years) men, recruited in Auckland (New Zealand). Health-related quality of life was assessed with SF-36v2 three times: at baseline, and 12 and 30 weeks later. Socioeconomic status was determined by geo-coded deprivation scores derived from current address using the New Zealand Index of Deprivation 2006 (NZDep2006), as well as capital value of residence. Univariable and multivariable analyses showed no associations between measures of socioeconomic status and any mental or physical health domains. Our findings may reflect the fact that these men are not currently experiencing comorbidities associated with overweight., Competing Interests: José G.B. Derraik is an Academic Editor for PeerJ. The authors have no financial or non-financial conflicts of interest to disclose that may be relevant to this work.