Paediatrics (RCH) - Research Publications
Now showing items 1-12 of 3170
Discussions about predictive genetic testing for Lynch syndrome: the role of health professionals and families in decisions to decline
Unaffected relatives of individuals with Lynch syndrome can be offered predictive genetic testing to guide surveillance recommendations. The decision-making process of those who decline testing, particularly those who do not attend a clinical genetics service, is poorly understood. We have addressed this gap by interviewing 33 individuals from Lynch syndrome mutation-carrying families, unaffected by cancer, who declined predictive genetic testing. Here, we analyse the data provided by 20 participants who unequivocally declined testing. Those who indicated they did not have enough information to make a decision or intended to undergo testing in the future were excluded. Analysis revealed that few decliners discussed their decision with general practitioners or genetic counsellors. Family members were commonly involved to varying degrees, with participants either (1) making group decisions with family members, (2) feeling persuaded by family members to either accept or decline testing, (3) discussing the test but making their own decision. A minority did not discuss testing with family members while making their decision. This research reveals the health communication activities of an understudied group, those declining predictive testing, and indicates that for many, health professionals play a minor role in the decision compared to family.
Epigenetics and developmental programming of adult onset diseases
Maternal perturbations or sub-optimal conditions during development are now recognized as contributing to the onset of many diseases manifesting in adulthood. This "developmental programming" of disease has been explored using animal models allowing insights into the potential mechanisms involved. Impaired renal development, resulting in a low nephron number, has been identified as a common outcome that is likely to contribute to the development of hypertension in the offspring as adults. Changes in other organs and systems, including the heart and the hypothalamic–pituitary–adrenal axis, have also been found. Evidence has recently emerged suggesting that epigenetic changes may occur as a result of developmental programming and result in permanent changes in the expression patterns of particular genes. Such epigenetic modifications may be responsible not only for an increased susceptibility to disease for an individual, but indirectly for the establishment of a disease state in a subsequent generation. Further research in this field, particularly examination as to whether epigenetic changes to genes affecting kidney development do occur, are essential to understanding the underlying mechanisms of developmental programming of disease.
Pathological fractures in paediatric patients with inflammatory bowel disease
UNLABELLED: Paediatric inflammatory bowel disease (IBD), especially Crohn's disease (CD), is commonly associated with poor skeletal health, related to the direct effects of chronic inflammation, prolonged use of glucocorticoid (GC), poor nutrition, delayed puberty and low muscle mass. Low bone mineral density is commonly reported, although the prevalence of long bone fractures may not be increased in these patients. Emerging evidence however suggests that there may be an increased risk of vertebral fractures (VFs) in this group. VFs presenting at diagnosis of paediatric CD, prior to any GC exposure, have been reported, highlighting the deleterious effect of inflammation on skeletal health. This paper reviews the published literature on pathophysiology of skeletal morbidity and fractures in paediatric IBD, illustrated with a new case report of multiple VFs in a prepubertal girl with CD, soon after diagnosis, who received minimal amounts of oral GC. Optimising control of disease, addressing vitamin D deficiency, encouraging physical activity and ensuring normal growth and pubertal progression are paramount to management of bone health in these patients. Despite the lack of evidence, there may be a place for bisphosphonate treatment, especially in the presence of symptomatic pathological fractures, but this requires close monitoring by clinicians with expertise in paediatric bone health. CONCLUSION: Chronic inflammation mediated by pro-inflammatory cytokines may have adverse effects on skeletal health in paediatric patients with IBD. The risk of vertebral fractures may be increased, even without exposure to glucocorticoid. Clinical monitoring of these patients requires careful attention to the various factors that impact on bone health.
Transport of infants with congenital heart disease: benefits of antenatal diagnosis
UNLABELLED: Infants with significant congenital heart disease (CHD) typically require transport from their birth centre to a regional paediatric cardiac centre. Antenatal diagnosis of CHD allows early pre-emptive stabilisation, and is associated with improved early clinical status. However, the effect of antenatal diagnosis on the transport characteristics of infants with CHD has not been previously investigated. The aim of this study was to compare the transport characteristics of infants with antenatal and postnatal diagnosis of CHD. This study is a retrospective cohort study of all infants of ≤10 days and ≥34 weeks of gestation with CHD admitted to the Royal Children's Hospital, Melbourne (RCH) over 5 years. Demographic, diagnosis, and transport data were recorded. Cases of complex CHD were included in this study. Of 320 infants with complex CHD, 198 (62 %) had antenatal diagnosis (ANdx) and 122 (38 %) had postnatal diagnosis (PNdx). There was no significant difference in sex, birth weight, or gestation between ANdx and PNdx groups. Average age of referral was 15 vs. 53.4 h in ANdx vs. PNdx groups. Aggregate transfer distance in the ANdx group was 2216 km and in the PNdx group was 10,274 km (P < 0.0001). Of the infants, 39 % in the PNdx group required highest-acuity "time critical" transports compared to 6 % of ANdx infants (P = 0.0001). Conversely, only 11 % of the infants in the PNdx group had lowest acuity "non-urgent" transfers, compared to 24 % of ANdx infants (P = 0.003). PNdx was associated with significantly higher rates of invasive ventilation (36 vs 20 %; P = 0.01) and higher rates of inotrope use (19 vs. 9 %; P = 0.007) during transport. CONCLUSIONS: Improved antenatal detection would allow for safer, less resource intense transfers of infants with CHD.
No obvious impact of caesarean delivery on childhood allergic outcomes: findings from Australian cohorts
(BMJ PUBLISHING GROUP, 2020-07-01)
BACKGROUND AND OBJECTIVE: As caesarean delivery and childhood allergy continue to rise, their inter-relationships may change. We examined whether caesarean delivery predicts allergic disease and impaired lung function in two contemporary harmonised population-based cohorts. METHODS: Parent-reported asthma and eczema data were drawn from two prospective Australian infant cohorts, HealthNuts (n=5276, born 2006-2010) and the Longitudinal Study of Australian Children (LSAC, n=5107, born 2003-2004) at age 6-7 years, and spirometric lung function from LSAC's Child Health CheckPoint (n=1756) at age 11-12 years. Logistic regression estimated associations between delivery mode and current asthma and eczema at 6-7 years, and linear regression examined lung function at 11-12 years. Models were adjusted for potential confounding factors. RESULTS: Complete case analysis included 3135 HealthNuts and 3654 LSAC children (32.2% and 30.9% born by caesarean, respectively). An association was evident between caesarean delivery and asthma at age 6-7 years in HealthNuts (adjusted OR (aOR) 1.25, 95% CI 1.00 to 1.57) but not in LSAC (aOR 1.05, 95% CI 0.86 to 1.28), while neither study showed clear associations with eczema (HealthNuts: aOR 1.09, 95% CI 0.88 to 1.35; LSAC: aOR 0.89, 95% CI 0.69 to 1.15). Spirometric lung function parameters at age 11-12 years were similar by delivery mode. Associations were not modified by duration of breast feeding, maternal history of asthma/eczema, childcare attendance, number of older siblings or pet exposure. CONCLUSIONS: In two unselected populations using harmonised protocols, the likely association of caesarean delivery with developing childhood allergy was small.
A multicenter randomized clinical trial of pharmacological vitamin B1 administration to critically ill patients who develop hypophosphatemia during enteral nutrition (The THIAMINE 4 HYPOPHOSPHATEMIA trial)
(CHURCHILL LIVINGSTONE, 2021-08-01)
BACKGROUND: Hypophosphatemia may be a useful biomarker to identify thiamine deficiency in critically ill enterally-fed patients. The objective was to determine whether intravenous thiamine affects blood lactate, biochemical and clinical outcomes in this group. METHOD: This randomized clinical trial was conducted across 5 Intensive Care Units. Ninety critically ill adult patients with a serum phosphate ≤0.65 mmol/L within 72 h of commencing enteral nutrition were randomized to intravenous thiamine (200 mg every 12 h for up to 14 doses) or usual care (control). The primary outcome was blood lactate over time and data are median [IQR] unless specified. RESULTS: Baseline variables were well balanced (thiamine: lactate 1.2 [1.0, 1.6] mmol/L, phosphate 0.56 [0.44, 0.64] mmol/L vs. control: lactate 1.0 [0.8, 1.3], phosphate 0.54 [0.44, 0.61]). Patients randomized to the intervention received a median of 11 [7.5, 13.5] doses for a total of 2200 [1500, 2700] mg of thiamine. Blood lactate over the entire 7 days of treatment was similar between groups (mean difference = -0.1 (95 % CI -0.2 to 0.1) mmol/L; P = 0.55). The percentage change from lactate pre-randomization to T = 24 h was not statistically different (thiamine: -32 (-39, -26) vs. control: -24 (-31, -16) percent, P = 0.09). Clinical outcomes were not statistically different (days of vasopressor administration: thiamine 2 [1, 4] vs. control 2 [0, 5.5] days; P = 0.37, and deaths 9 (21 %) vs. 5 (11 %); P = 0.25). CONCLUSIONS: In critically ill enterally-fed patients who developed hypophosphatemia, intravenous thiamine did not cause measurable differences in blood lactate or clinical outcomes. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (ACTRN12619000121167).
Development of brain white matter and math computation ability in children born very preterm and full-term.
(Elsevier BV, 2021-07-12)
Children born very preterm (VPT; <32 weeks' gestation) have alterations in brain white matter and poorer math ability than full-term (FT) peers. Diffusion-weighted magnetic resonance imaging studies suggest a link between white matter microstructure and math in VPT and FT children, although longitudinal studies using advanced modelling are lacking. In a prospective longitudinal cohort of VPT and FT children we used Fixel-Based Analysis to investigate associations between maturation of white matter fibre density (FD), fibre-bundle cross-section (FC), and combined fibre density and cross-section (FDC) and math computation ability at 7 (n = 136 VPT; n = 32 FT) and 13 (n = 130 VPT; n = 44 FT) years, as well as between change in white matter and math computation ability from 7 to 13 years (n = 103 VPT; n = 21 FT). In both VPT and FT children, higher FD, FC and FDC in visual, sensorimotor and cortico-thalamic/thalamo-cortical white matter tracts were associated with better math computation ability at 7 and 13 years. Longitudinally, accelerated maturation of the posterior body of the corpus callosum (FDC) was associated with greater math computation development. White matter-math associations were similar for VPT and FT children. In conclusion, white matter maturation is associated with math computation ability across late childhood, irrespective of birth group.
Distal rectus femoris surgery in children with cerebral palsy: results of a Delphi consensus project.
(British Editorial Society of Bone & Joint Surgery, 2021-06-01)
Purpose: The purpose of this study was for an international panel of experts to establish consensus indications for distal rectus femoris surgery in children with cerebral palsy (CP) using a modified Delphi method. Methods: The panel used a five-level Likert scale to record agreement or disagreement with 33 statements regarding distal rectus femoris surgery. The panel responded to statements regarding general characteristics, clinical indications, computerized gait data, intraoperative techniques and outcome measures. Consensus was defined as at least 80% of responses being in the highest or lowest two of the five Likert ratings, and general agreement as 60% to 79% falling into the highest or lowest two ratings. There was no agreement if neither threshold was reached. Results: Consensus or general agreement was reached for 17 of 33 statements (52%). There was general consensus that distal rectus femoris surgery is better for stiff knee gait than is proximal rectus femoris release. There was no consensus about whether the results of distal rectus femoris release were comparable to those following distal rectus femoris transfer. Gross Motor Function Classification System (GMFCS) level was an important factor for the panel, with the best outcomes expected in children functioning at GMFCS levels I and II. The panel also reached consensus that they do distal rectus femoris surgery less frequently than earlier in their careers, in large part reflecting the narrowing of indications for this surgery over the last decade. Conclusion: This study can help paediatric orthopaedic surgeons optimize decision-making for, and outcomes of, distal rectus femoris surgery in children with CP. Level of evidence: V.
Split anterior tibialis tendon transfer to peroneus brevis for spastic equinovarus in children with hemiplegia
(BRITISH EDITORIAL SOC BONE & JOINT SURGERY, 2021-06-01)
Purpose: The aim of this study is to report the safety and eff-cacy of soft-tissue surgery incorporating split transfer of tibi-alis anterior to peroneus brevis (SPLATT-PB) for children with hemiplegic spastic equinovarus. Methods: This was a retrospective case series of children and adolescents with spastic hemiplegia who had a novel combination of SPLATT-TB, intramuscular tenotomy of tibialis posterior and either spasticity management or gastrocsole-us lengthening as the index surgery. The principal outcome measures were changes in pain and difficulty with shoe wear and radiological parameters obtained from weight-bearing anteroposterior and lateral radiographs of the affected foot before and after surgery. Results: A total of 63 patients with symptomatic spastic equinovarus met the inclusion criteria. Mean age at surgery was 9.8 years (6 to 18) and the mean follow-up was seven years (range 3 to 10 years). Foot pain and problems with shoe wear improved after surgery. Seven radiological criteria showed a clinically and statistically significant improvement at follow-up, the majority being in the normal range. There were 11 surgical adverse events, all classified as Modified Cla-vien-Dindo Grade II. Three patients required further surgery for recurrent equinus, eight patients required further surgery for valgus deformities and four patients required bony surgery for residual varus deformities. Conclusion: Soft-tissue surgery for spastic equinovarus was successful in the majority of children with spastic hemiplegia, particularly between ages eight and 12 years, resulting in a plantigrade, flexible foot with minimal pain or limitations in shoe-wear. Children younger than 8 years at index surgery were more prone to overcorrection into valgus. Children older than 12 years had persistent varus deformities requiring bony surgery. Level of evidence: Level IV, retrospective case series.