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Background: Fluoroscopic hysterosalpingography (HSG) with Lipiodol® is safe and has a therapeutic effect on fertility: transient in endometriosis‐related infertility and sustained in unexplained infertility. Ultrasound is replacing fluoroscopy as the preferred imaging modality for HSG due to comfort and radiation safety (no ionising radiation). The safety of ultrasound‐guided Lipiodol® HSG is uncertain. Aims: Prospectively observe pregnancy and complication rates after ultrasound‐guided Lipiodol® HSG. Materials and Methods: A single‐centre prospective study of women with unexplained infertility undergoing ultrasound‐guided Lipiodol® uterine bathing and tubal flushing after tubal patency confirmed with ExEm® Foam HyFoSy (hysterosalpingo‐foam‐sonography). Pregnancy outcomes at six months and serum and urinary thyroid function at one, three and eight weeks were recorded. Pain scores were recorded during and immediately after HSG. Descriptive statistics are reported. Results: Fifty‐two participants were enrolled between July 2019 and April 2021, median age 33 years (range 21–45). Only 45 (87%, 45/52) completed the Lipiodol® HSG; 5/7 experienced intravasation during initial HyFoSy. Of 30 women at follow‐up, 57% had biochemical (17/30, 95% CI 37%–75%), 53% clinical (16/30 95% CI 34%–72%) and 35% ongoing pregnancies (11/30, 95% CI 20%–56%). The rate of subclinical hypothyroidism (SCH) at two months was 41% (7/17). One intravasation event occurred during Lipiodol® HSG (2%, 1/45). Median pain score was 5/10 (range 0–9, interquartile range 2.5–7). No anaphylaxis, infection or oil embolism was observed. Conclusion: Outpatient ultrasound‐guided Lipiodol® HSG was safe, with pregnancy rates comparable to previous studies of fluoroscopic guidance. Rates of intravasation and SCH were also similar, confirming the need to monitor thyroid function. [ABSTRACT FROM AUTHOR]

Aim: To assess participation with a structured transition programme for adolescents with diabetes. Methods: Data from a regional cohort aged less than 16 years of age with type 1 (T1) and type 2 diabetes (T2D) in Auckland, New Zealand (2006–2016). Participation was defined as opting into a structured transition programme. Results: Five hundrend and twelve adolescents who were to be transferred to adult care (476 type 1 (T1D) and 36 type 2 (T2D)), overall participation rate of 83%, 86% (408/476) with T1D compared to 47% (17/36) with T2D. Within the cohort of T1D, participation rates for Māori and Pacific were lower (74% and 77%, respectively) than New Zealand Europeans (88%, p = 0.020 and p = 0.039, respectively). Lower socio‐economic status was associated with reduced participation (77%) compared to higher socio‐economic status (90%, p = 0.002). Of the 476 T1D who participated, 408 (96%) subsequently attended at least one adult service clinic ("capture"). 42% attended an adult clinic within the planned 3 months, 87% at 6 months and retention in adult clinics over 5 years of follow‐up was 78%. By contrast, the 68 young people with T1D who did not participate in the structured transition had a capture rate of 78% (p < 0.001) and retention of 63% (p = 0.036). Conclusions: In adolescents with diabetes, a formal transition from a paediatric service was associated with high rates of adult capture and subsequent retention in adult care over a 5‐year follow‐up period. Low socio‐economic status, Māori or Pacific ethnicity and T2D were associated with reduced participation in the structured transition programme. [ABSTRACT FROM AUTHOR]

Aim: Obesity as a major risk factor for childhood hypertension necessitates careful blood pressure (BP) monitoring of those affected. This study aimed to compare BP classification in a cohort of children affected by obesity using tables versus digital calculations in two sets of guidelines. Methods: This study was a secondary analysis of data collected from a randomised clinical trial of a multidisciplinary life‐style assessment and intervention program. Baseline data from 237 children with a body mass index >99th percentile or >91st percentile with weight‐related comorbidities and available BP measurements were analysed. We assessed agreement between tables and algorithms in classification of elevated BP/pre‐hypertension and hypertension based on the American Academy of Paediatrics (AAP) clinical practice guidelines (CPG) and the older Fourth Report using Cohen's weighted kappa. The prevalence of hypertensive diagnoses was also compared between the two guidelines. Results: Agreement between BP tables and algorithmic calculation of percentiles was discordant, though improved in the AAP CPG compared to the Fourth Report (Cohen's kappa = 0.70 vs. 0.57, respectively). None (0%) were missed diagnoses, and 59 (24.9%) were false positives for the Fourth Report, and 0 (0%) were missed diagnoses, and 49 (20.9%) were false positives for the AAP CPG. Under the recent guidelines, there was an increase in prevalence of 6.0% (95% confidence interval (CI) 2.5–9.4%; P = 0.0001) for BP ≥90th percentile, and of 3.0% (95% CI 0.4–5.6%; p = 0.016) for hypertension (BP ≥ 95th percentile) in the cohort (18.0% and 6.8%, respectively, increased from 12.0% and 3.8%). Conclusions: Digital calculators over tables in clinical practice are recommended where possible to improve the accuracy of paediatric BP classification. Substantial rates of elevated BP/Hypertension were found in this cohort of children and adolescents with overweight and obesity. [ABSTRACT FROM AUTHOR]

Aim: Expert recommendations for child/adolescent obesity include extensive investigation for weight‐related comorbidities, based on body mass index (BMI) percentile cut‐offs. This study aimed to estimate the cost of initial investigations for weight‐related comorbidities in children/adolescents with obesity, according to international expert guidelines. Methods: The annual mean cost of investigations for weight‐related comorbidities in children/adolescents was calculated from a health‐funder perspective using 2019 cost data obtained from three New Zealand District Health Boards. Prevalence data for child/adolescent obesity (aged 2–14 years) were obtained from the New Zealand Health Survey (2017/2018), and prevalence of weight‐related comorbidities requiring further investigation were obtained from a previous New Zealand study of a cohort of children with obesity. Results: The cost of initial laboratory screening for weight‐related comorbidities per child was NZD 28.36. Based on national prevalence data from 2018/2019 for children with BMI greater than the 98th percentile (obesity cut‐off), the total annual cost for initial laboratory screening for weight‐related comorbidities in children/adolescents aged 2–14 years with obesity was estimated at NZD 2,665,840. The cost of further investigation in the presence of risk factors was estimated at NZD 2,972,934. Conclusions: Investigating weight‐related comorbidities in New Zealand according to international expert guidelines is resource‐intensive. Ways to further determine who warrants investigation with an individualised approach are required. [ABSTRACT FROM AUTHOR]

Background: Adolescents with type 1 diabetes (T1D) experience higher rates of psychological disorders compared with their healthy peers. As poor psychological health has been associated with suboptimal glycaemic control and more frequent complications, there is an urgent need to develop more 'clinically usable' interventions. Digital mental health interventions offer unique advantages compared with in‐person interventions; however, what adolescents with T1D want in terms of content and functionality is poorly understood. Accordingly, the current study conducted focus groups to examine the views of adolescents with T1D regarding digital mental health interventions. Methods: Four focus groups were conducted, including 16 adolescents with T1D, ranging from 13 to 17 years in age (69% female). Transcripts were analysed using directed content analysis to examine (1) 'what adolescents dislike about existing digital mental health interventions?' and (2) 'what adolescents want in future digital mental health interventions?'. Results: Findings provide a preliminary understanding of what adolescents dislike and also the type of content and functional features, which may be important to include in digital mental health programs for this population, such as a peer support feature (reported by 16 of 16), emotion and diabetes check‐in feature (11 of 16) and diabetes‐relevant content (12 of 16). Conclusions: Early data suggest that digital mental health interventions should include a significant peer support element, diabetes‐relevant content and examples, and check‐in on their mental health and diabetes self‐management regularly, while avoiding fixed responses or modules and non‐age‐appropriate content. Based on these findings, a digital intervention is currently being developed. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Aim Method Outcome There is increasing evidence that maternal factors such as nutritional status (both under and over‐nutrition) and diabetes, alongside prenatal exposure to endocrine disrupting chemicals (EDCs), are associated with early pubertal onset in offspring. Such children are also at increased risk of the metabolic syndrome during adolescence and young adulthood.This literature review focuses on the role of the prenatal environment in programming pubertal onset, and the impact of prenatal metabolic stressors on the declining average age of puberty.A review of all relevant literature was conducted in PubMed by the authors.The mechanism for this appears to be mediated through metabolic signals, such as leptin and insulin, on the kisspeptin‐neuronal nitric oxide‐gonadotropin releasing hormone (KiNG) axis. Exposed children have an elevated risk of childhood obesity and display a phenotype of hyperinsunlinaemia and hyperleptinaemia. These metabolic changes permit an earlier attainment of the nutritional “threshold” for puberty. Unfortunately, this cycle may be amplified across subsequent generations, however early intervention may help “rescue” progression of this programming. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

Aim: To review indications and use of angiotensin-converting enzyme-inhibitor (ACEI) therapy for the treatment of persistent microalbuminuria (MA) and/or hypertension (HTN) in adolescents with type 1 diabetes mellitus (T1DM).Methods: Retrospective chart review of adolescent patients with T1DM seen within the paediatric diabetes service in Auckland, New Zealand, from 2006 to 2016. MA, HTN, patient demographic characteristics and ACEI prescribing and monitoring indices were examined.Results: Five hundred adolescents with T1DM were included. There were 26 patients (5%) with MA and/or HTN. MA alone was present in 16, HTN alone in 3 and both HTN and MA in 7. The 5-year MA/HTN-free rate was 98%, and the 10-year MA/HTN-free rate was 93%. Longer disease duration and earlier diagnosis were predictors of MA/HTN. There was no significant difference in standard clinical indices between study patients and others. ACEI was prescribed for 17 of 26 patients for either HTN or MA. Within 6 weeks of ACEI commencement, less than half of the subjects had repeat serum creatinine and MA screens and no record of repeat blood pressure measurement. Despite this, all patients had 3-monthly reviews within outpatient clinics where adjustments of ACEI doses were made.Conclusion: In our regional adolescent population with T1DM, there were low rates of both MA and/or HTN. In those who required treatment with ACEI, clinical monitoring post-commencement of therapy was inconsistent. Local consensus guidelines for the management of persistent MA in children and adolescents with diabetes mellitus were developed in response to this study. [ABSTRACT FROM AUTHOR]

Bisphosphonate therapy is the mainstay of pharmacological intervention in young people with skeletal fragility. The evidence of its use in a variety of conditions remains limited despite over three decades of clinical experience. On behalf of the Australasian Paediatric Endocrine Group, this evidence-based consensus guideline presents recommendations and discusses the graded evidence (using the GRADE system) for these recommendations. Primary bone fragility disorders such as osteogenesis imperfecta are considered separately from osteoporosis secondary to other clinical conditions (such as cerebral palsy, Duchenne muscular dystrophy). The use of bisphosphonates in non-fragility conditions, such as fibrous dysplasia, avascular necrosis, bone cysts and hypercalcaemia, is also discussed. While these guidelines provide an evidence-based approach where possible, further research is required in all clinical applications in order to strengthen the recommendations made. [ABSTRACT FROM AUTHOR]

Summary: Antibiotics have been hailed by many as “miracle drugs” that have been effectively treating infectious diseases for over a century, leading to a marked reduction in morbidity and mortality. However, with the increasing use of antibiotics, we are now faced not only with the increasing threat of antibiotic resistance, but also with a rising concern about potential long‐term effects of antibiotics on human health, including the development of obesity. The obesity pandemic continues to increase, a problem that affects both adults and children alike. Disruptions to the gut microbiome have been linked to a multitude of adverse conditions, including obesity, type 2 diabetes, inflammatory bowel diseases, anxiety, autism, allergies, and autoimmune diseases. This review focuses on the association between antibiotics and obesity, and the role of the gut microbiome. There is strong evidence supporting the role of antibiotics in the development of obesity in well‐controlled animal models. However, evidence for this link in humans is still inconclusive, and we need further well‐designed clinical trials to clarify this association. [ABSTRACT FROM AUTHOR]

Objective: To report 12-month outcomes from a multidisciplinary child obesity intervention program, targeting high-risk groups.Methods: In this unblinded randomized controlled trial, participants (recruited January 2012-August 2014) were aged 5 to 16 years, resided in Taranaki, Aotearoa/New Zealand, and had BMI ≥ 98th percentile or BMI > 91st percentile with weight-related comorbidities. Randomization was by minimization (age and ethnicity), with participants assigned to an intense intervention group (home-based assessments at 6-month intervals and a 12-month multidisciplinary program with weekly group sessions) or to a minimal-intensity control group with home-based assessments and advice at each 6-month follow-up. The primary outcome was the change in BMI standard deviation score (SDS) at 12 months from baseline. A mixed model analysis was undertaken, incorporating all 6- and 12-month data.Results: Two hundred and three children were randomly assigned (47% Māori, 43% New Zealand European, 53% female, 28% from the most deprived quintile, mean age 10.7 years, mean BMI SDS 3.12). Both groups displayed a change in BMI SDS at 12 months from baseline (-0.12 control, -0.10 intervention), improvements in cardiovascular fitness (P < 0.0001), and improvements in quality of life (P < 0.001). Achieving ≥ 70% attendance in the intense intervention group resulted in a change in BMI SDS of -0.22.Conclusions: This program achieved a high recruitment of target groups and a high rate of BMI SDS reduction, irrespective of intervention intensity. If retention is optimized, the intensive program doubles its effect. [ABSTRACT FROM AUTHOR]

Background We aimed to evaluate metabolic outcomes in overweight/obese nulliparous and multiparous women and their offspring. Study design Seventy-two overweight and obese women who participated in a randomized controlled trial of exercise in pregnancy were included in the study, comparing 18 nulliparous and 54 multiparous women and their singleton offspring. Women were assessed at 19 and 36 weeks of gestation. Fetal growth was measured using standard obstetric ultrasound techniques. Cord blood was collected at birth. Maternal and offspring body composition was assessed using DXA ~2 weeks after delivery. Results Nulliparous women had higher HbA1c in the third trimester of pregnancy than multiparous women (5.48% vs 5.29%; P=.002) and were more insulin-resistant based on the surrogate marker sex hormone-binding globulin (354 vs 408 nmol/L; P=.047). Nulliparous women also had higher levels of the inflammatory marker tumour necrosis factor-alpha (4.74 vs 3.62 pg/mL; P=.025). At birth, the offspring of nulliparous women were on average 340 g ( P=.013) and 0.69 standard deviation scores ( P=.026) lighter than those born of multiparous women. Cord blood data showed lower insulin-like growth factor- II ( P=.026) and higher IGF binding protein-1 ( P=.002) levels in the offspring of nulliparous women. In addition, a less favourable metabolic profile was observed in the offspring of nulliparous women, as indicated by higher triglyceride ( P<.001) and interleukin-6 ( P=.039) concentrations. Conclusions Infants born of nulliparous overweight and obese women appear to be exposed to a less favourable metabolic environment in utero, with evidence of subtle adverse metabolic outcomes at birth compared to infants of overweight/obese multiparous women. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to assess the performance of the revised New Zealand ( NZ) newborn screening TSH cut-offs for congenital hypothyroidism ( CHT). Methods Screening data over 24 months were obtained from the NZ newborn metabolic screening programme, which utilizes a 2-tier system of direct clinical referral for infants with markedly elevated TSH, and second samples from those with mild TSH elevation. We evaluated the impact of a reduced TSH threshold (50 to 30 mIU/l blood) for direct notification and a lower cut-off (15 to 8 mIU/l blood) applied to second samples and babies older than 14 days. Results In 2013 and 2014, 117 528 infants underwent newborn screening for CHT. Fifty-two CHT cases were identified by screening (47 general newborn population, five repeat testing in low-birth-weight infants) and one case was missed. Thirty-two infants with screening TSH ≥30 mIU/l were directly referred at a median of 9 days (5-14) and 15 with TSH 15-29 mIU/l were referred after a second sample at a median of 20 days (9-52, P < 0·001). All directly referred infants were confirmed as CHT cases with no earlier referrals as a result of the reduced threshold. The lower TSH cut-off applied to second samples lead to the identification of six extra cases of CHT (15% increase) from seven extra clinical referrals. Conclusions The NZ screening programme achieved a 15% increase in CHT case detection for minimal increase in workload or anxiety for families of healthy infants. A further decrease in the threshold for direct referral may allow earlier diagnoses. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to describe the characteristics at enrolment of children and adolescents referred to an obesity programme and to determine how the prevalence of comorbidities differed in Indigenous versus non-Indigenous children.Methods: Participants were residents of a semi-rural region of New Zealand (NZ). Eligibility was defined by a body mass index (BMI) of ≥98th percentile or >91st centile with weight-related comorbidities. Fasting blood, medical and physical assessments were obtained.Results: During the recruitment period from January 2012 to August 2014, 239 participants, aged 4.8-16.8 years, undertook assessment. Average BMI standard deviation score was 3.09 (standard deviation (SD) = 0.60, range 1.52-5.34 SD). The majority of participants were of either Maori (NZ's indigenous people (45%)) or NZ European (45%) ethnicity; 29% of participants were from the most deprived quintile of household deprivation. Maori participants were more likely than NZ Europeans to have a mother who smoked during pregnancy (52% vs. 28%, P = 0.001), a family history of type 2 diabetes (66% vs. 53%, P = 0.04), acanthosis nigricans on examination (58% vs. 20%, P < 0.0001), a low serum high-density lipoprotein cholesterol (27% vs. 14%, P = 0.03) or high serum triglyceride (38% vs. 24%, P = 0.03) concentration.Conclusion: The unique aspect of this study was the ability to recruit high levels of Maori participants and those from most deprived areas, indicating a high level of acceptability for these target groups. Comorbidities were prevalent in this cohort of overweight/obese school-aged children. While there were some differences in comorbidity prevalence between Maori and NZ Europeans, the overall clinical picture in our cohort, irrespective of ethnicity, was of concern. [ABSTRACT FROM AUTHOR]

Objective We aimed to assess the effects of maternal prepregnancy body mass index ( BMI) on insulin sensitivity, metabolism and blood pressure in the offspring. Methods We studied 70 prepubertal children aged 8·9 ± 1·9 years (range 4-11 years), born 38-40 weeks of gestation and appropriate-for-gestational-age birthweight. Maternal prepregnancy body mass index ( MPP BMI) was calculated from self-reported weight. Children's insulin sensitivity was measured using intravenous glucose tolerance tests and Bergman's minimal model. Other clinical assessments included auxology, fasting lipid and hormonal profiles, DXA-derived body composition and 24-h ambulatory blood pressure monitoring. Data were analysed using random effect mixed models, adjusting for important confounders and a random factor to account for sibling clusters. Results Increasing MPP BMI was correlated with increasing BMI standard deviation scores ( SDS) ( r = 0·30; P = 0·012) and lower insulin sensitivity in their children ( r = −0·34; P = 0·004). In multivariate regression models, increasing MPP BMI was associated with lower insulin sensitivity (β = −0·040; P = 0·005), with every 1 kg/m2 increase in MPP BMI associated with a 4·0% decrease in offspring insulin sensitivity. Greater MPP BMI was associated with higher systolic blood pressure in the daytime (β = 0·794; P = 0·010) and night-time (β = 0·800; P = 0·017), as well as higher 24-h mean arterial pressure (β = 0·508; P = 0·025) in the offspring. Conclusion Greater maternal prepregnancy BMI is associated with lower insulin sensitivity and higher blood pressure in their children, effects that were independent of offspring adiposity. Thus, higher maternal BMI prior to pregnancy (even among women of normal BMI) may contribute to increased risk of type 2 diabetes and other metabolic diseases in the subsequent generation. [ABSTRACT FROM AUTHOR]

Objective To assess the effect of parental age at childbirth on insulin sensitivity and other metabolic outcomes in overweight middle-aged males. Methods We studied 73 men aged 46.0±5.4 years, who were overweight (body mass index, BMI 25-30 kg/m2) but otherwise healthy. Insulin sensitivity was assessed by the Matsuda method from an oral glucose tolerance test. Other assessments included dual-energy X-ray absorptiometry-derived body composition, lipid profile, 24-hour ambulatory blood pressure, and carotid intima-media thickness. Maternal and paternal ages were highly correlated ( r = 0.71; P < 0.0001), and the main parameter of interest in this study was the mean parental age at childbirth (MPAC), calculated as the average of maternal and paternal ages. Results Increasing MPAC was associated with a continuous increase in insulin sensitivity ( β = 0.193; P = 0.008), as well as reductions in insulin resistance (HOMA-IR; β = −0.064; P = 0.011), fasting insulin ( β = −0.221; P = 0.018) and fasting glucose ( β = −0.030; P = 0.033) concentrations. Increasing MPAC was also associated with reductions in night time systolic ( β = −0.500; P = 0.020) and diastolic ( β = −0.325; P = 0.047) blood pressure, as well as with improved (greater) nocturnal diastolic blood pressure dipping ( β = 0.413; P = 0.046). Subgroup analyses on participants of European descent ( n = 64) showed that increasing MPAC was associated with reduced carotid intima-media thickness ( β = −0.008; P = 0.018) and lower low-density lipoprotein cholesterol concentrations ( β = −0.042; P = 0.028). Conclusions Increasing parental age at childbirth was associated with a more favorable metabolic phenotype in overweight middle-aged males. However, it is unknown whether the effect was maternal, paternal, or both. Future studies on the effects of parental age at childbirth on the metabolism of males and females across the BMI range are required. Am. J. Hum. Biol. 27:380-386, 2015. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Objective We aimed to assess possible differences in insulin sensitivity and other metabolic, anthropometric and cardiovascular parameters between boys and girls prior to puberty. Methods We studied 85 healthy prepubertal children (33 girls and 52 boys) aged 8·7 ± 1·9 years (range 4·0-11·9 years), born 38-40 weeks gestation, and of birth weight appropriate-for-gestational-age. Insulin sensitivity was measured using frequently sampled intravenous glucose tests and Bergman's minimal model. Other clinical assessments included anthropometric measures, fasting lipid and hormonal profiles, body composition from whole-body dual-energy X-ray absorptiometry and 24-h ambulatory blood pressure monitoring. Results Prepubertal girls and boys were of similar parent-adjusted height SDS ( P = 0·26), but girls had considerably more body fat ( P < 0·0001), less fat-free mass ( P = 0·0002) and greater abdominal adiposity ( P < 0·0001). These differences in body composition were independent of adrenal androgens. Insulin sensitivity was 18% lower in girls (11·0 vs 13·4 × 10−4/min (mU/l); P = 0·028), but this difference disappeared with adjustment for adiposity and DHEAS concentrations. There were, however, some apparent sex differences in cardiovascular parameters, with girls displaying increased heart rate and reduced blood pressure dipping. Girls also had higher triglyceride concentrations (+23%; P = 0·036). Conclusion There are a number of anthropometric, metabolic and cardiovascular differences between sexes prior to the appearance of external signs of puberty. Although differences in insulin sensitivity were eliminated when adiposity and DHEAS concentrations were accounted for, there were independent differences in body composition and cardiovascular parameters. Thus, gender, adrenarche and adiposity should be accounted for in studies examining metabolic and cardiovascular outcomes prior to puberty. [ABSTRACT FROM AUTHOR]

Background Paternal age at childbirth has been increasing worldwide, and we assessed whether this increase affects growth, body composition and metabolism in their children. Methods We studied 277 children (aged 3-12 years) born to fathers aged 19·8-51·8 years. Clinical assessments were height and weight adjusted for parental measurements, DEXA-derived body composition, fasting lipids, glucose homoeostasis and hormonal profiles. Results Children born to fathers aged 31-35 ( P = 0·009) and >35 years ( P = 0·021) were 2 cm taller than those of fathers aged ≤30 years. Children of fathers aged >35 years at childbirth had a lower body mass index ( BMI) (−0·32 SDS) than offspring of fathers aged 31-35 (−0·01 SDS; P = 0·043) and ≤30 (0·22 SDS; P = 0·019). There were marked effects of paternal age at childbirth on childhood blood lipids. LDL-C concentrations in children born to fathers aged >35 years were 11% and 21% higher than in children of fathers aged 31-35 and ≤30 years, respectively ( P < 0·01). Total cholesterol to HDL-C ratio was also higher among the children of fathers aged 31-35 (12%; P = 0·014) and >35 (16%; P = 0·004) years at childbirth compared with the ≤30 group. In addition, HOMA- IR in girls (but not boys) born of fathers aged 31-35 (0·99) and >35 years (1·11) indicated better insulin sensitivity compared with offspring in the ≤30 group (1·63; P < 0·05). Conclusions Increasing paternal age at childbirth is associated with a more favourable phenotype in their children (taller and slimmer, with better insulin sensitivity in girls) but with a less favourable lipid profile. [ABSTRACT FROM AUTHOR]

Background There is evidence suggesting that first-born children and adults are anthropometrically different to later-borns. Thus, we aimed to assess whether birth order was associated with changes in growth and metabolism in childhood. Methods We studied 312 healthy prepubertal children: 157 first-borns and 155 later-borns. Children were aged 3-10 years, born 37-41 weeks gestation, and of birth weight appropriate-for-gestational-age. Clinical assessments included measurement of children's height, weight, fasting lipid and hormonal profiles and DEXA-derived body composition. Results First-borns were taller than later-borns ( P < 0·0001), even when adjusted for parents' heights (0·31 vs 0·03 SDS; P = 0·001). There was an incremental height decrease with increasing birth order, so that first-borns were taller than second-borns ( P < 0·001), who were in turn taller than third-borns ( P = 0·007). Further, among sibling pairs both height SDS ( P = 0·009) and adjusted height SDS ( P < 0·0001) were lower in second- vs first-born children. Consistent with differences in stature, first- ( P = 0·043) and second-borns ( P = 0·003) had higher IGF-I concentrations than third-borns. Both first- ( P < 0·001) and second-borns ( P = 0·004) also had reduced abdominal adiposity (lower android fat to gynoid fat ratio) when compared with third-borns. Other parameters of adiposity and blood lipids were unaffected by birth order. Conclusions First-borns were taller than later-born children, with an incremental height reduction from first to third birth order. These differences were present after correction for genetic height, and associated to some extent with alterations in plasma IGF-I. Our findings strengthen the evidence that birth order is associated with phenotypic changes in childhood. [ABSTRACT FROM AUTHOR]

Background Child abuse and other early-life environmental stressors are known to affect the hypothalamic-pituitary-adrenal axis. We sought to compare synacthen-stimulated cortisol responses in children who suffered inflicted or accidental traumatic brain injury ( TBI). Methods Children with a history of early-childhood TBI were recruited from the Starship Children's Hospital database ( Auckland, New Zealand, 1992-2010). All underwent a low-dose ACTH1-24 (synacthen 1 μg IV) test, and serum cortisol response was compared between inflicted ( TBII) and accidental ( TBIA) groups. Results We assessed 64 children with TBII and 134 with TBIA. Boys were more likely than girls to suffer accidental ( P < 0·001), but not inflicted TBI. TBII children displayed a 14% reduction in peak stimulated cortisol in comparison with the TBIA group ( P < 0·001), as well as reduced cortisol responses at + 30 ( P < 0·01) and + 60 min ( P < 0·001). Importantly, these differences were not associated with severity of injury. The odds ratio of TBII children having a mother who suffered domestic violence during pregnancy was 6·2 times that of the TBIA group ( P < 0·001). However, reported domestic violence during pregnancy or placement of child in foster care did not appear to affect cortisol responses. Conclusion Synacthen-stimulated cortisol response is attenuated following inflicted TBI in early childhood. This may reflect chronic exposure to environmental stress as opposed to pituitary injury or early-life programming. [ABSTRACT FROM AUTHOR]

Summary Objective Poor growth during childhood is a common problem associated with preterm birth, but few studies have examined the associations between linear growth, weight and body composition with the postnatal hormonal milieu in preterm children. We aimed to define the IGF-IGFBP axis in preterm children and its association with growth. Design and patients A cohort of healthy 2- to 20-year-old subjects who were born prematurely (<37 weeks gestation) and experienced normal neurological development were recruited. In total, 54 premature and 82 control subjects were included in this study. Results Preterm subjects were relatively shorter ( P < 0·001) and leaner ( P < 0·05) than their parents in contrast to the term cohort. Preterm children also appeared to fail to reach their genetic height potential (prepuberty: P < 0·01; puberty: P < 0·05). Only IGFBP-2 differed between preterm and term cohorts, with higher levels observed in prepubertal preterm subjects ( P < 0·01). In the term group, height SDS was positively associated with IGF-I ( P < 0·01) and IGFBP-3 ( P < 0·001) concentrations, but no such associations were observed for preterm subjects. Conclusion Preterm children are shorter and lighter than controls throughout childhood, remaining below their genetic height potential. Preterm birth appears to alter the endocrine regulation of postnatal growth in childhood and adolescence, so growth is no longer associated with its normal endocrine regulators. [ABSTRACT FROM AUTHOR]

To investigate response to growth hormone (GH) in the first, second and third years of treatment in the total clinical cohort of Turner syndrome (TS) patients in Australia. Short stature is the most common clinical manifestation of TS. GH treatment improves growth. Response was measured for each year of treatment. Stepwise multiple regression analyses were used to identify factors that significantly influenced response. Prepubertal TS patients who completed 1 year ( n = 176), 2 year ( n = 148), or 3 year ( n = 117) of treatment and were currently receiving GH. Change in TS specific Height Standard Deviation Score (ΔTSZ) was the main response variable used. Major influencing variables considered included dose, starting age and height, BMI, bone age delay, karyotype, parental height, and interactions between dose and starting age or height. Response was greatest in first year and declined thereafter (median ΔTSZ: 1st year = +0·705, 2nd year = +0·439, 3rd year = +0·377) despite the median dose increasing [1st year = 5·5 mg/m/week (0·23 mg/kg/week), 2nd year = 6·4(0·24), 3rd year = 7·2(0·26)]. An Age*Dose interaction was identified influencing first, second year, and total ΔTSZ. The ΔTSZ over 3 years was significantly influenced by first-year dose. Dose increments only attenuated the general decline in response. An acceptable first-year response (ΔTSZ > 1·01) was achieved by only 17·6% of patients. Growth response is greatest and most influenced by dose in the first year. Dose in first year is a major factor contributing to total response. A starting Age*Dose interaction effect was observed such that young girls on a high dose respond disproportionately better. Optimal GH treatment of short stature in TS thus requires early initiation with the highest safe dose in the first year. [ABSTRACT FROM AUTHOR]

A recent paper by our group reported that regular aerobic exercise during pregnancy led to lower foetal IGF-I and IGF-II concentrations and a modest reduction in offspring birth weight when compared with the offspring of nontraining control participants. Maternal hormonal alterations in response to exercise training may be associated with the regulation of nutrient availability for foetal growth through placental regulation of maternal metabolism. To determine whether the reduction in offspring size was associated with changes in the maternal IGF axis [including placental growth hormone (PGH)], leptin and/or free fatty acids (FFA) in response to aerobic exercise training in the second half of pregnancy. A randomized, controlled trial of exercise in pregnancy. Eighty-four healthy nulliparous women (mean ± SD age 30 ± 4 year, BMI 25·5 ± 4 kg/m). Serum samples were drawn at 19 and 35 weeks gestation to determine serum IGF-I, IGF-II, IGF-binding protein-1, IGF-binding protein-3, PGH, leptin and FFA. Exercise training in pregnancy had no impact on the pregnancy-related changes in the maternal IGF axis. Women in the exercise group experienced a 29% increase in leptin in late gestation ( P = 0·026 vs control) and a trend towards lower FFA ( P = 0·07 vs control). Late pregnancy changes in maternal leptin were inversely related to offspring birth weight ( r = −0·24, P < 0·05) and BMI ( r = −0·25, P < 0·05). An increase in leptin in exercising pregnant women may reflect subtle changes within the placenta in response to regular exercise and may contribute to the reduction in offspring size previously reported in this cohort. [ABSTRACT FROM AUTHOR]

The article discusses the study on effect of structural traumatic brain injury (TBI) in childhood produces disturbances in pituitary function and abnormalities in thyroid function. It presents reports for the study of short term impact of TBI on 45 patients of age between 15-70 years and reports serum thyroid stimulating hormone (TSH) concentrations progressively decreased with increasing injury severity.

Objectives To compare the efficacy of goserelin and leuprolide on initial deceleration of growth and weight gain during the first 12 months of GnRH analogue treatment for precocious puberty. Design Retrospective cohort analysis. Patients Forty children with precocious puberty treated with either goserelin or leuprolide (33 females, mean age 7·3 and 7·7 years, respectively, at the start of treatment). Measurements The primary outcomes were baseline-to-6-months and 6-months-to-12-months change in height standard deviation score (SDS) and body mass index (BMI). Relative tall stature was calculated as the difference between height SDS and mid-parental height (MPH) SDS at baseline. Results Goserelin and leuprolide were associated with similar suppression of serum LH during the first 12 months of treatment ( P = 0·62). Greater relative tall stature was strongly associated with more advanced bone age, greater BMI SDS and with greater reduction in height SDS in the first 6 months. Adjusted for relative tall stature, goserelin therapy was associated with significantly greater suppression of growth than leuprolide ( P = 0·025) in the first 6 months of treatment, with no subsequent change in the second 6 months. A similar, significant increase in BMI was seen with both analogues. Conclusions Both GnRH analogues were associated with effective biochemical suppression of puberty; however, goserelin was more effective at reducing linear growth during the first 6 months. Relative tall stature was a major determinant of the initial response to treatment. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding the addition of follicle-stimulating hormone (FSH) to clomiphene citrate to stimulate an ovary which do not affect offspring stature but might change body composition in childhood.

We compared the thickness of both dermis and subcutis (measured using ultrasound) in overweight and obese adults with type 1 (n = 10) or type 2 (n = 8) diabetes mellitus. When adjusted for confounding factors, patients with type 1 diabetes had thicker subcutis than those with type 2 diabetes, with this difference being particularly marked in the abdomen. There were no observed differences in dermal thickness between the groups. [ABSTRACT FROM AUTHOR]

Newborn screening for congenital hypothyroidism has been remarkably effective, although rare cases of false negative screening have been reported in same sex twins, presumptively due to fetal blood exchange. We report a case in which the diagnosis of congenital hypothyroidism due to thyroid ectopia in a monozygotic twin was delayed by 8 months, with a normal newborn screening TSH level of 11 mIU/L blood (normal < 15 mIU/L) at 2 days of life. This is the first such case since the national New Zealand newborn screening programme introduced screening for congenital hypothyroidism in 1981 (30 years ago). Repeating thyroid studies at 14 days of age in same-sex twins has been advocated to avoid delayed diagnosis, but given the low risk, may not be cost effective. It is important to maintain a high index of suspicion in same-sex twin pregnancies of potential congenital hypothyroidism. [ABSTRACT FROM AUTHOR]

Aim: There are currently no clinical guidelines concerning the administration of growth attenuation therapy (GAT) for children (regardless of gender) with both severe physical and cognitive disability in New Zealand (NZ). This survey aimed to explore the attitudes of paediatricians towards GAT and the frequency of requests and initiation of GAT in NZ.Methods: An online survey of paediatricians in NZ was undertaken. Questions covered both clinical experience with GAT and attitudes towards it.Results: Overall, the response rate was 55% (173/317) with 162 complete responses; 25% of respondents (41/166) reported enquiries about GAT. Five had personally prescribed GAT; in total, six NZ children have undergone GAT. A total of 77% of respondents either believed GAT is appropriate or were neutral on the subject. The majority of responders (59%) believed ethical approval should be obtained as part of preparation for GAT.Conclusions: This is the first study to investigate attitudes and practices of NZ paediatricians regarding GAT for severely disabled children. Results indicate a range of views but suggest that family requests for GAT do occur and that the majority of paediatricians are not opposed to GAT in the appropriate ethical and clinical context. The development of practice guidelines for GAT may lead to a more informed decision-making process about GAT for families and paediatricians. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented on preterm birth associated with an intergenerational effect on cardio-metabolic risk.