[Show abstract][Hide abstract] ABSTRACT: Rett syndrome is a pervasive neurodevelopmental disorder associated with a pathogenic mutation on the MECP2 gene. Impaired movement is a fundamental component and the Rett Syndrome Gross Motor Scale was developed to measure gross motor abilities in this population. The current study investigated the validity and reliability of the Rett Syndrome Gross Motor Scale. Video data showing gross motor abilities supplemented with parent report data was collected for 255 girls and women registered with the Australian Rett Syndrome Database, and the factor structure and relationships between motor scores, age and genotype were investigated. Clinical assessment scores for 38 girls and women with Rett syndrome who attended the Danish Center for Rett Syndrome were used to assess consistency of measurement. Principal components analysis enabled the calculation of three factor scores: Sitting, Standing and Walking, and Challenge. Motor scores were poorer with increasing age and those with the p.Arg133Cys, p.Arg294* or p.Arg306Cys mutation achieved higher scores than those with a large deletion. The repeatability of clinical assessment was excellent (intraclass correlation coefficient for total score 0.99, 95% CI 0.93-0.98). The standard error of measurement for the total score was 2 points and we would be 95% confident that a change 4 points in the 45-point scale would be greater than within-subject measurement error. The Rett Syndrome Gross Motor Scale could be an appropriate measure of gross motor skills in clinical practice and clinical trials.
[Show abstract][Hide abstract] ABSTRACT: Influenza is associated with significant morbidity and mortality in children receiving therapy for cancer, yet recommendation for, and uptake of the seasonal vaccine remains poor. One hundred children undergoing treatment for cancer were vaccinated with the trivalent inactivated influenza vaccine according to national guidelines in 2010 and 2011. Influenza-specific hemagglutinin inhibition antibody titers were performed on blood samples taken prior to each vaccination and 4 weeks following the final vaccination. A nasopharyngeal aspirate for influenza was performed on all children who developed an influenza-like illness. Following vaccination, seroprotection and seroconversion rates were 55 and 43% for H3N2, 61 and 43% for H1N1, and 41 and 33% for B strain, respectively. Overall, there was a significant geometric mean fold increase to H3N2 (GMFI 4.56, 95% CI 3.19-6.52, P < 0.01) and H1N1 (GMFI 4.44, 95% CI 3.19-6.19, P < 0.01) strains. Seroconversion was significantly more likely in children with solid compared with hematological malignancies and in children <10 years of age who received a two-dose schedule compared to one. Influenza infection occurred in 2% of the vaccinated study population, compared with 6.8% in unvaccinated controls, providing an adjusted estimated vaccine effectiveness of 72% (95% CI -26-94%). There were no serious adverse events and a low reactogenicity rate of 3%. The trivalent inactivated influenza vaccine is safe, immunogenic, provides clinical protection and should be administered annually to immunosuppressed children receiving treatment for cancer. All children <10 years of age should receive a two-dose schedule.
[Show abstract][Hide abstract] ABSTRACT: Study design:
Population-based longitudinal observational study.
To describe the prevalence of scoliosis in Rett syndrome, structural characteristics and progression, taking into account the influences of age, genotype and ambulatory status.
Summary of background data:
Scoliosis is the most common orthopaedic comorbidity in Rett syndrome yet very little is known about its natural history and influencing factors such as age, genotype and ambulatory status.
The infrastructure of the Australian Rett Syndrome Database was used to identify all cases with confirmed Rett syndrome in Australia and collect data on genotype and walking status. We identified radiological records and described the Cobb angle of each curve. Time to event analysis was used to estimate the median age of onset of scoliosis and the log rank test to compare by mutation type. Latent class group analysis was used to identify groups for the trajectory of walking status over time and a multilevel linear model used to assess trajectories of scoliosis development by mutation type and walking status. We used a logistic regression model to estimate the probability of developing a scoliosis with a Cobb angle >60° at 16 years in relation to Cobb angle and walking status at 10 years of age.
The median age of scoliosis onset was 11 years with earliest onset in those with a p.Arg255 mutation or large deletion. Scoliosis was progressive for all mutation types except for those with the p.Arg306Cys mutation. Scoliosis progression was reduced when there was capacity to walk independently or with assistance. Cobb angle and walking ability at age 10 can be reliably used to identify those who will develop a very severe scoliosis by age 16.
These data on prognosis of scoliosis inform clinical decision-making about the likelihood of progression to very severe scoliosis and the need for surgical management.
Level of evidence:
[Show abstract][Hide abstract] ABSTRACT: Background: Acute haematogenous osteomyelitis is a bacterial infection of bone, which occurs most frequently in children. Outcomes are excellent for the majority of children, but a minority develop complicated osteomyelitis. Predicting which children will develop complicated osteomyelitis remains a challenge, particularly in developed countries where most patients are discharged home after a relatively short period in hospital. Methods: We conducted a 5 year retrospective case note review of all children aged 3 months to 16 years admitted with a diagnosis of acute haematogenous osteomyelitis. We compared standardised clinical and laboratory parameters in those who developed simple and complicated osteomyelitis. Results: Of the 299 children who met inclusion, 241 (80.6%) had simple and 58 (19.4%) had complicated osteomyelitis. The major predictors of complicated disease were older age, a temperature greater than 38.5[degrees]C and a higher C-reactive protein at admission. Conclusions: A risk prediction model, utilising information available shortly after hospitalisation, allows early identification of children at greatest risk of developing complicated osteomyelitis. Copyright
No preview · Article · Dec 2015 · The Pediatric Infectious Disease Journal
[Show abstract][Hide abstract] ABSTRACT: Background:
Data demonstrating the effectiveness of inactivated trivalent influenza vaccine (TIV) for children at increased risk of severe disease are limited. Our objective was to determine the effectiveness of TIV in children with risk factors for severe disease and to compare vaccine uptake, parental attitudes and prescriber recommendations in children with and without risk factors for severe disease.
Children aged 6-59 months presenting for emergency care (2008-2014) with an influenza-like illness were eligible. Influenza PCR/culture were performed on nasopharyngeal samples. Vaccination status was confirmed via the national register and/or vaccine providers. The test-negative design was used to estimate vaccine effectiveness (VE). Risk factors, parental attitudes and prescriber recommendations were assessed by parental questionnaire.
2723 children were recruited. Risk factors for severe disease included comorbid medical conditions (11.6%), preterm birth (13.0%) and indigeneity (5.0%). Influenza was identified in 546 (20.1%) participants. Overall VE (2008, 2010-2014) was 70.0% (95%CI: 47.7,82.9); VE for children with medical comorbidities, children born preterm, and children <2 years were 82.5% (14.6,96.4), 79.2% (10.9,95.1) and 84.7% (49.6,95.3) respectively. Following adverse events in 2010, the number of children fully vaccinated with TIV declined significantly. This included children with and without risk factors for severe disease. Attitudes were similar in parents of children with and without risk factors for severe disease.
VE for TIV in young children with and without risk factors for severe disease was ≥70%. Despite this, participation in the preschool influenza vaccination program remains low with parents and prescribers unconvinced of the benefits and safety of TIV.
No preview · Article · Dec 2015 · The Pediatric Infectious Disease Journal
[Show abstract][Hide abstract] ABSTRACT: Background
Orofacial clefts are a group of frequently observed congenital malformations often requiring multiple hospital admissions over the lifespan of affected individuals. The aim of this study was to describe the total-population hospital admissions with principal diagnosis of cleft lip and/or palate in Australia over a 10 year period.
Data for admissions to hospitals were obtained from the Australian Institute of Health and Welfare National Hospital Morbidity Database (July 2000 to June 2010). The outcome variable was a hospital separation with the principal diagnosis of cleft palate, cleft lip or cleft lip and palate (ICD-10-AM diagnosis codes Q35-Q37 respectively). Trends in rates of admission and length of stay by age, gender and cleft type were investigated.
A total of 11, 618 admissions were identified; cleft palate (4,454; 0.22 per 10,000 people per year), cleft lip (2,251; 0.11) and cleft lip and palate (4,913; 0.25). Admission age ranged from birth to 79 years with males more frequently admitted. Most admissions occurred prior to adolescence in cleft palate and cleft lip and through to late teens in cleft lip and palate, declining for all groups after 25 years.
This study identified population level trends in hospital separations for orofacial cleft diagnosis in Australia.
[Show abstract][Hide abstract] ABSTRACT: The evidence regarding older parental age and incidence of mood disorder symptoms in offspring is limited, and that which exists is mixed. We sought to clarify these relationships by using data from the Western Australian Pregnancy Cohort (Raine) Study. The Raine Study provided comprehensive data from 2,900 pregnancies, resulting in 2,868 live born children. A total of 1,220 participants completed the short form of the Depression Anxiety Stress Scale (DASS-21) at the 20-year cohort follow-up. We used negative binomial regression analyses with log link and with adjustment for known perinatal risk factors to examine the extent to which maternal and paternal age at childbirth predicted continuous DASS-21 index scores. In the final multivariate models, a maternal age of 30-34 years was associated with significant increases in stress DASS-21 scores in female offspring relative to female offspring of 25- to 29-year-old mothers. A maternal age of 35 years and over was associated with increased scores on all DASS-21 scales in female offspring. Our results indicate that older maternal age is associated with depression, anxiety, and stress symptoms in young adult females. Further research into the mechanisms underpinning this relationship is needed. (PsycINFO Database Record
No preview · Article · Nov 2015 · Journal of Abnormal Psychology
[Show abstract][Hide abstract] ABSTRACT: Background:
There is increasing evidence demonstrating influenza vaccine effectiveness (VE) in the prevention of influenza in children, including the very young. Data demonstrating the effectiveness against severe disease, including hospitalisation, are limited. We aimed to determine the VE of the southern hemisphere trivalent inactivated influenza vaccine (TIV) in preventing laboratory-confirmed influenza-associated hospitalisation in children.
Patients and methods:
Laboratory records were used to identify children with confirmed influenza hospitalised (i.e., cases) during a 5 year period (2008, 2010-2013) at the only tertiary paediatric facility in Western Australia. Cases and time, age and ward matched controls were retrospectively reviewed to determine risk factors, vaccination status and outcome. Adjusted odds ratios and VE estimates were derived using conditional logistic regression models.
Three hundred and eighty five cases were identified (Influenza A, 64.9%; Influenza B: 35.1%). Influenza-like illness and pneumonia were the most frequent presentation (74.5% and 23.9%, respectively). The median length of stay was 2 days (Interquartile range 1-4 days). Twenty children (5.2%) required admission to the intensive care unit. Vaccine uptake in cases and controls was low (4.9% and 8.5%, respectively). Three hundred and six case-control pairs were included in the VE analysis, of which 19 pairs were informative with discrepant vaccination status. VE (fully vaccinated vs. unvaccinated) was estimated to be 62.3% (95% CI: -6.6%, 86.7%).
In this study, the point estimate for the effectiveness of TIV in preventing influenza-associated hospitalisation in children was similar to that reported for emergency or outpatient attended, laboratory-confirmed influenza, yet confidence intervals were wide. Vaccine uptake remains low. Studies, enroling larger numbers of children, ideally with higher vaccine uptake, are needed to provide additional evidence on TIV protection against influenza hospitalisation in children.
[Show abstract][Hide abstract] ABSTRACT: People with intellectual disabilities are at a higher risk for experiencing behavioral, emotional, and psychiatric problems in comparison with the general population. People with Down syndrome have been reported as experiencing fewer behavioral problems than others with intellectual disability, although still at a greater level than the non-intellectually disabled population, except for depression and Alzheimer disease. The aim of this study was to describe the trajectories of subscales of behavior, including depressive symptoms, communication disturbance, anxiety, disruptiveness, and social relating abilities, for young adults with Down syndrome.
Families of young adults with Down syndrome living in Perth, Western Australia, participated in a questionnaire study over 8 years, 2004 (n = 255), 2009 (n = 191), and 2011 (n = 188). Questionnaires collected information about young person characteristics and family functioning. The parent-completed Developmental Behavior Checklist-Adult (DBC-A) and Developmental Behavior Checklist-Primary Carer Version (DBC-P) were used to measure emotional and behavioral problems. These measures include the following subscales: disruptive, communication and anxiety disturbances, self-absorbed, antisocial, depressive, and social relating.
DBC score declined from 2004 to 2011 reflecting an improvement in behavior in the self-absorbed (coeff −0.011, 95% confidence interval (CI) −0.031, −0.008), anxiety (coef −0.009 95%CI −0.129, −0.006), communication disturbances (coeff −0.008, 95% CI −0.012, −0.005) and disruptive/antisocial behavior (coeff −0.013, 95% CI −0.016, −0.009) subscales. Subscales for depressive symptoms and social relating problems decreased less (coeff −0.003, 95% CI −0.007, −0.0001) (coeff −0.003 95% CI −0.007, 0.001). Young people who were lower functioning were reported as exhibiting significantly more behavioral problems across every subscale when compared with those who were higher functioning.
Behavior of young adults with Down syndrome improves over time but depressive symptoms and social relating behavior problems persist into adulthood. It is possible that those with persistent depressive symptoms are at a high risk for developing depressive illness in adulthood. Identifying young people with Down syndrome who are at risk for developing depression in adult life has implications for prevention and early treatment.
[Show abstract][Hide abstract] ABSTRACT: Mothers of children with intellectual disability or autism spectrum disorder (ASD) have poorer health than other mothers. Yet no research has explored whether this poorer health is reflected in mortality rates or whether certain causes of death are more likely. We aimed to calculate the hazard ratios for death and for the primary causes of death in mothers of children with intellectual disability or ASD compared to other mothers.
The study population comprised all mothers of live-born children in Western Australia from 1983-2005. We accessed state-wide databases which enabled us to link socio-demographic details, birth dates, diagnoses of intellectual disability or ASD in the children and dates and causes of death for all mothers who had died prior to 2011. Using Cox Regression with death by any cause and death by each of the three primary causes as the event of interest, we calculated hazard ratios for death for mothers of children intellectual disability or ASD compared to other mothers.
During the study period, mothers of children with intellectual disability or ASD had more than twice the risk of death. Mothers of children with intellectual disability were 40% more likely to die of cancer; 150% more likely to die of cardiovascular disease and nearly 200% more likely to die from misadventure than other mothers. Due to small numbers, only hazard ratios for cancer were calculated for mothers of children with ASD. These mothers were about 50% more likely to die from cancer than other mothers. Possible causes and implications of our results are discussed.
Similar studies, pooling data from registries elsewhere, would improve our understanding of factors increasing the mortality of mothers of children with intellectual disability or ASD. This would allow the implementation of informed services and interventions to improve these mothers' longevity.
[Show abstract][Hide abstract] ABSTRACT: Background:
Rett syndrome is a pervasive neurological disorder with impaired gait as one criterion. This study investigated the capacity of three accelerometer-type devices to measure walking activity in Rett syndrome.
Twenty-six participants (mean 18 years, SD 8) wore an Actigraph, ActivPAL and StepWatch Activity Monitor (SAM) during a video-taped session of activities. Agreement was determined between step-counts derived from each accelerometer and observation. Repeatability of SAM-derived step counts was determined using pairs of one-minute epochs during which the same participant was observed to walk with the same cadence.
The mean difference (limit of agreement) for the Actigraph, ActivPAL and SAM were -41 (SD 33), -16 (SD 21) and -1 (SD 16) steps/min, respectively. Agreement was influenced by a device/cadence interaction (p < 0.001) with greater under-recording at higher cadences. For SAM data, repeatability of step-count pairs was excellent (intraclass correlation coefficient 0.91, 95% CI 0.79-0.96). The standard error of measurement was 6 steps/min and we would be 95% confident that a change ≥17 steps/min would be greater than within-subject measurement error.
The capacity of the SAM to measure physical activity in Rett syndrome allows focus on participation-based activities in clinical practice and clinical trials. Implications for Rehabilitation Many girls and women with Rett syndrome are able to walk on their own or with assistance but with altered movement patterns. Validated measures of physical activity, such as step counts, have potential to monitor function during daily life. Compared with other forms of accelerometer-type devices, such as ActiGraph and ActivPAL, the StepWatch Activity Monitor (SAM) measured step counts with good accuracy and repeatability. The capacity of the SAM to measure physical activity in Rett syndrome allows focus on participation-based activities in clinical practice and clinical trials.
No preview · Article · Dec 2014 · Disability and Rehabilitation
[Show abstract][Hide abstract] ABSTRACT: The time interval between pregnancies is a modifiable risk factor of adverse birth outcomes, including preterm birth, small for gestational age (SGA), and low birth weight. Variations in birth outcomes might be explained by risk factors that vary greatly among women but tend to persist between pregnancies (eg, genetics, lifestyle, or social conditions). Among women who have had 3 births, each mother can be her own control for risk factors that affect outcomes. This retrospective cohort study was performed to examine the effect of interpregnancy interval after adjusting for maternal factors by using within-mother analyses. The association between interpregnancy interval and the incidence of preterm birth, SGA, and low birth weight among the second and third births was determined using data from a population-wide database. Among 84,151 mothers, 40,441 all had their first 3 births as live singletons during 1980 to 2010. Outcome variables were preterm birth (<37 weeks), SGA, and low birth weight (<2500 g). Interpregnancy intervals (in months) were 0 to 5, 6 to 11, 12 to 17, 18 to 23 (reference category), 24 to 59, 60 to 119, and 120 or longer. A maternally matched design was used to model the odds of preterm birth, SGA, and low birth weight as a function of interpregnancy interval. Conditional logistic regression was used to measure this association for an individual woman, which allowed inferences based only on within-mother effects. Confounding factors that can vary between births and affect interpregnancy interval were maternal age, parity, birth year, ethnicity, socioeconomic status, and outcome of the previous birth. The terms matched and unmatched referred to the within-mother design based on conditional and unconditional logistic regression, respectively. Among the 40,441 pairs of second and third births, matched by mother, the mean incidence rates for preterm birth, SGA, and low birth weight for second births were 5.3%, 7.4%, and 3.5%, respectively. For third births, the rates were 5.8%, 6.3%, and 3.6%, respectively. Unconditional logistic regression suggested a strong effect of short interpregnancy interval on the incidence of preterm birth and low birth weight but not SGA, after adjustment for confounders. Among interpregnancy intervals of less than 18 to 23 months, the highest odds ratios (ORs) for preterm birth (adjusted OR [aOR], 1.41; 95% confidence interval [CI], 1.31–1.51) and low birth weight (aOR, 1.26; 95% CI, 1.15–1.37) were for intervals of 0 to 5 months. The incidence of SGA birth was similar across 0 to 23 months, with ORs ranging from 0.98 to 1.03. Among interpregnancy intervals of more than 18 to 23 months, the highest OR of preterm birth (aOR, 1.35; 95% CI, 1.26–1.45) was 60 to 119 months; the highest ORs of low birth weight (aOR, 1.67; 95% CI, 1.42–1.97) and SGA (aOR, 1.98; 95% CI, 1.74–2.24) were for intervals of more than 119 months. In the matched model, among intervals of less than 18 to 23 months, the highest ORs of preterm birth (aOR, 1.07; 95% CI, 0.86–1.34) and low birth weight (aOR, 1.03; 95% CI, 0.79–1.34) were for 0 to 5 months. The OR for SGA was estimated at 1.08 for all 3 categories of interpregnancy intervals of less than 18 months. For preterm birth at intervals of more than 23 months, ORs ranged from 1.01 (0.86–1.18) for 24 to 59 months to 0.88 (0.54–1.46) for more than 119 months. For intervals of more than 23 months, ORs for low birth weight ranged from 1.07 (0.88–1.30) for 24 to 59 months to 1.58 (0.82–3.06) for more than 119 months. Odds ratios for SGA ranged from 1.11 (0.96–1.28) for 24 to 59 months to 1.72 (1.04–2.85) for intervals of more than 119 months. These results do not support the concept of a causal effect of short interpregnancy interval on adverse birth outcomes. However, short interpregnancy interval remains a strong predictor of the risk for adverse birth outcomes, but correlated maternal risk factors must be considered. Clinicians should treat a short interpregnancy interval as a possible risk of adverse birth outcomes but remain aware of other maternal risk factors.
No preview · Article · Dec 2014 · Obstetrical and Gynecological Survey
[Show abstract][Hide abstract] ABSTRACT: Rett syndrome is one of many severe neurodevelopmental disorders with feeding difficulties. In this study, associations between feeding difficulties, age, MECP2 genotype, and utilization of gastrostomy were investigated. Weight change and family satisfaction following gastrostomy were explored.
Data from the longitudinal Australian Rett Syndrome Database whose parents provided data in the 2011 family questionnaire (n = 229) were interrogated. We used logistic regression to model relationships between feeding difficulties, age group, and genotype. Content analysis was used to analyze data on satisfaction following gastrostomy.
In those who had never had gastrostomy and who fed orally (n = 166/229), parents of girls <7 years were more concerned about food intake compared with their adult peers (odds ratio [OR] 4.26; 95% confidence interval [CI] 1.29, 14.10). Those with a p.Arg168∗ mutation were often perceived as eating poorly with nearly a 6-fold increased odds of choking compared to the p.Arg133Cys mutation (OR 5.88; 95% CI 1.27, 27.24). Coughing, choking, or gagging during meals was associated with increased likelihood of later gastrostomy. Sixty-six females (28.8%) had a gastrostomy, and in those, large MECP2 deletions and p.Arg168∗ mutations were common. Weight-for-age z-scores increased by 0.86 (95% CI 0.41, 1.31) approximately 2 years after surgery. Families were satisfied with gastrostomy and felt less anxious about the care of their child.
Mutation type provided some explanation for feeding difficulties. Gastrostomy assisted the management of feeding difficulties and poor weight gain, and was acceptable to families. Our findings are likely applicable to the broader community of children with severe disability.