Effects of ganaxolone on non-seizure outcomes in CDKL5 Deficiency Disorder: Double-blind placebo-controlled randomized trial.

CDKL5 deficiency disorder (CDD) is a rare developmental and epileptic encephalopathy. Ganaxolone, a neuroactive steroid, reduces the frequency of major motor seizures in children with CDD. This analysis explored the effect of ganaxolone on non-seizure outcomes. Children (2-19 years) with genetically confirmed CDD and ≥ 16 major motor seizures per month were enrolled in a double-blind randomized placebo-controlled trial. Ganaxolone or placebo was administered three times daily for 17 weeks. Behaviour was measured with the Anxiety, Depression and Mood Scale (ADAMS), daytime sleepiness with the Child Health Sleep Questionnaire, and quality of life with the Quality of Life Inventory-Disability (QI-Disability) scale. Scores were compared using ANOVA, adjusted for age, sex, number of anti-seizure mediations, baseline 28-day major motor seizure frequency, baseline developmental skills, and behaviour, sleep or quality of life scores. 101 children with CDD (39 clinical sites, 8 countries) were randomized. Median (IQR) age was 6 (3-10) years, 79.2 % were female, and 50 received ganaxolone. After 17 weeks of treatment, Manic/Hyperactive scores (mean difference 1.27, 95%CI -2.38,-0.16) and Compulsive Behaviour scores (mean difference 0.58, 95%CI -1.14,-0.01) were lower (improved) in the ganaxolone group compared with the placebo group. Daytime sleepiness scores were similar between groups. The total change in QOL score for children in the ganaxolone group was 2.6 points (95%CI -1.74,7.02) higher (improved) than in the placebo group but without statistical significance. Along with better seizure control, children who received ganaxolone had improved behavioural scores in select domains compared to placebo.

Safety, tolerability, and effect of a single aural dose of Dornase alfa at the time of ventilation tube surgery for otitis media: A Phase 1b double randomized control trial.

BACKGROUND: One third of children require repeat ventilation tube insertion (VTI) for otitis media. Disease recurrence is associated with persistent middle ear bacterial biofilms. With demonstration that Dornase alfa (a DNase) disrupts middle ear effusion biofilms ex vivo, we identified potential for this as an anti-biofilm therapy to prevent repeat VTI. First, safety and tolerability needed to be measured. METHODS: This was a phase 1B double-blinded randomized control trial conducted in Western Australia. Children between 6 months and 5 years undergoing VTI for bilateral middle ear effusion were recruited between 2012 and 2014 and followed for two years. Children's ears were randomized to receive either Dornase alfa (1 mg/mL) or 0.9 % sodium chloride (placebo) at time of surgery. Children were followed up at 2 weeks post-VTI and at 3-monthly intervals for 2 years. Outcomes assessed were: 1) safety and tolerability, 2) otorrhoea frequency, 3) blocked or extruded ventilation tube (VT) frequency, 4) time to blockage or extrusion, 5) time to infection recurrence and/or need for repeat VTI. RESULTS: Sixty children (mean age 2.3 years) were enrolled with 87 % reaching study endpoint. Treatment did not change otorrhoea frequency. Hearing improved in all children following VTI, with no indication of ototoxicity. Dornase alfa had some effect on increasing time until VT extrusion (p = 0.099); and blockage and/or extrusion (p = 0.122). Frequency of recurrence and time until recurrence were similar. Fourteen children required repeat VTI within the follow-up period. CONCLUSION: A single application of Dornase alfa into the middle ear at time of VTI was safe, non-ototoxic, and well-tolerated. TRIAL REGISTRATION: ACTRN12623000504617.

Adapting a measure of gross motor skills for individuals with CDKL5 deficiency disorder: A psychometric study.

PURPOSE: Validated measures capable of demonstrating meaningful interventional change in the CDKL5 deficiency disorder (CDD) are lacking. The study objective was to modify the Rett Syndrome Gross Motor Scale (RSGMS) and evaluate its psychometric properties for individuals with CDD. METHODS: Item and scoring categories of the RSGMS were modified. Caregivers registered with the International CDKL5 Clinical Research Network uploaded motor videos filmed at home to a protected server and completed a feedback questionnaire (n = 70). Rasch (n = 137), known groups (n = 109), and intra- and inter-rater reliability analyses (n = 50) were conducted. RESULTS: The age of individuals with CDD ranged from 1.5 to 34.1 years. The modified scale, Gross Motor-Complex Disability (GM-CD), comprised 17 items. There were no floor or ceiling effects and inter- and intra-rater reliability were good. Rasch analysis demonstrated that the items encompassed a large range of performance difficulty, although there was some item redundancy and some disordered categories. One item, Prone Head Position, was a poor fit. Caregiver-reported acceptability was positive. Scores differed by age and functional abilities. SUMMARY: GM-CD appears to be a suitable remotely administered measure and psychometrically sound for individuals with CDD. This study provides the foundation to propose the use of GM-CD in CDD clinical trials. Longitudinal evaluation is planned.

The effect of functioning on Quality of Life Inventory-Disability measured quality of life is not mediated or moderated by parental psychological distress.

PURPOSE: The measurement of quality of life (QOL) in children with intellectual disability often relies upon proxy report via caregivers. The current study investigated whether caregiver psychological distress mediates or moderates the effects of impairment on their ratings of QOL in children with intellectual disability. METHODS: Caregivers of 447 children with an intellectual disability reported their child's day-to-day functioning, their own psychological distress using the Kessler Psychological Distress Scale, and the Quality of Life Inventory-Disability (QI-Disability), a measure of QOL for proxy report of a child's observable behaviours that indicate quality of life. Linear regression was used to assess the effects of the child's functional abilities on their QI-Disability score and causal mediation analysis to estimate the extent to which these effects were mediated by caregivers' psychological distress. RESULTS: A minority of caregivers (n = 121, 27.1%) reported no psychological distress. Lower day-to-day functional abilities, such as being fully dependent on others to manage their personal needs were associated with lower total QOL scores. There was no significant mediation effect of caregiver psychological distress on the association between child functioning and total QOL scores. Moderation analyses revealed small and largely nonsignificant interaction coefficients, indicating that caregiver psychological distress did not influence the strength of the relationship between child functioning and total QOL scores. CONCLUSION: Caregiver psychological distress did not mediate or moderate the relationship between the level of functional abilities and QOL in children with intellectual disability. QI-Disability measured observable child behaviours which may reduce the influence of caregiver factors on the accurate measure of QOL for children with intellectual disability.

Survival of children and adolescents with intellectual disability following gastrostomy insertion.

BACKGROUND: Positive health outcomes have been observed following gastrostomy insertion in children with intellectual disability, which is being increasingly used at younger ages to improve nutritional intake. This study investigated the effect of gastrostomy insertion on survival of children with severe intellectual disability. METHODS: We used linked disability and health data of children and adolescents who were born in Western Australia between 1983 and 2009 to compare survival of individuals with severe intellectual disability by exposure to gastrostomy status. For those born in 2000-2009, we employed propensity score matching to adjust for confounding by indication. Effect of gastrostomy insertion on survival was compared by pertinent health and sociodemographic risk factors. RESULTS: Compared with children born in the 1980s-1990s, probability of survival following first gastrostomy insertion for those born in 2000-2009 was higher (2 years: 94% vs. 83%). Mortality risk was higher in cases than that in their matched controls (hazard ratio 2.9, 95% confidence interval 1.1, 7.3). The relative risk of mortality (gastrostomy vs. non-gastrostomy) may have differed by sex, birthweight and time at first gastrostomy insertion. Respiratory conditions were a common immediate or underlying cause of death among all children, particularly among those undergoing gastrostomy insertion. CONCLUSIONS: Whilst gastrostomy insertion was associated with lower survival rates than children without gastrostomy, survival improved with time, and gastrostomy afforded some protection for the more vulnerable groups, and earlier use appears beneficial to survival. Specific clinical data that may be used to prioritise the need for gastrostomy insertion may be responsible for the survival differences observed.

Characterizing the risk of respiratory syncytial virus in infants with older siblings: a population-based birth cohort study.

From a population-based birth cohort of 245 249 children born in Western Australia during 1996-2005, we used linkage of laboratory and birth record datasets to obtain data including all respiratory syncytial virus (RSV) detections during infancy from a subcohort of 87 981 singleton children born in the Perth metropolitan area from 2000 to 2004. Using log binomial regression, we found that the risk of infant RSV detection increases with the number of older siblings, with those having ⩾3 older siblings experiencing almost three times the risk (relative risk 2·83, 95% confidence interval 2·46-3·26) of firstborn children. We estimate that 45% of the RSV detections in our subcohort were attributable to infection from an older sibling. The sibling effect was significantly higher for those infants who were younger during the season of peak risk (winter) than those who were older. Although older siblings were present in our cohort, they had very few RSV detections which could be temporally linked to an infant's infection. We conclude that RSV infection in older children leads to less severe symptoms but is nevertheless an important source of infant infection. Our results lend support to a vaccination strategy which includes family members in order to provide maximum protection for newborn babies.

Effect of sitting posture on development of scoliosis in Duchenne Muscular Dystrophy cases.

BACKGROUND: Scoliosis is a frequent association in boys with Duchenne Muscular Dystrophy when the ability to walk is lost around nine to 12 years of age. This study assessed the contribution of physical factors including lumbar posture to scoliosis in non-ambulatory youth with DMD in Nepal. METHODS: Linear regression was used to assess effects of time since loss of ambulation, muscle strength, functional severity and lumbar angle as a binary variable on coronal Cobb angle; again logistic regression was used to assess effects of muscle strength and cross-legged sitting on the presence of a lordotic lumbar posture in 22 non-ambulant boys and young men. RESULTS: The boys and young men had a mean (SD) age of 15.1 (4.0) years, had been non-ambulant for 48.6 (33.8) months and used a median of 3.5 (range 2 to 7) postures a day. The mean Cobb angle was 15.1 (range 0 to 70) degrees. Optimal accuracy in predicting scoliosis was obtained with a lumbar angle of -6° as measured by skin markers, and both a lumbar angle ≤-6° (P=0.112) and better functional ability (P=0.102) were associated with less scoliosis. Use of cross-legged sitting postures during the day was associated with a lumbar angle ≤-6° (OR 0.061; 95% CI 0.005 - 0.672; P=0.022). CONCLUSIONS: Use of cross-legged sitting posture was associated with increase in lumbar lordosis. Higher angle of lumbar lordosis and better functional ability are associated with lesser degree of scoliosis.

Changes in risk factors for preterm birth in Western Australia 1984-2006.

OBJECTIVE: To characterise changing risk factors of preterm birth in Western Australia between 1984 and 2006. DESIGN: Population-based study. SETTING: Western Australia. POPULATION: All non-Aboriginal women giving birth to live singleton infants between 1984 and 2006. METHODS: Multinomial, multivariable regression models were used to assess antecedent profiles by preterm status and labour onset types (spontaneous, medically indicated, prelabour rupture of membranes [PROM]). Population attributable fraction (PAF) estimates characterized the contribution of individual antecedents as well as the overall contribution of two antecedent groups: pre-existing medical conditions (including previous obstetric history) and pregnancy complications. MAIN OUTCOME MEASURE: Antecedent relationships with preterm birth, stratified by labour onset type. RESULTS: Marked increases in maternal age and primiparous births were observed. A four-fold increase in the rates of pre-existing medical complications over time was observed. Rates of pregnancy complications remained stable. Multinomial regression showed differences in antecedent profiles across labour onset types. PAF estimates indicated that 50% of medically indicated preterm deliveries could be eliminated after removing six antecedents from the population; estimates for PROM and spontaneous preterm reduction were between 10 and 20%. Variables pertaining to previous and current obstetric complications (previous preterm birth, previous caesarean section, pre-eclampsia and antepartum haemorrhage) were the most influential predictors of preterm birth and adverse labour onset (PROM and medically indicated). CONCLUSIONS: Preterm antecedent profiles have changed markedly over the 23 years studied. Some changes may be attributable to true change, others to advances in surveillance and detection. Still others may signify change in clinical practice.

Functioning and post-school transition outcomes for young people with Down syndrome.

AIM: To investigate the relationship between functioning and post-school day occupation for young adults with Down syndrome. METHODS: Families of young people with Down syndrome (n = 269) aged 15-30 years in 2009 were recruited from the population-based Down syndrome 'Needs Opinion Wishes' database in Western Australia. Questionnaires were mailed to participating families and involved two parts, young person characteristics and family functioning; 203 were returned (75%). Of those families who returned questionnaires, 164 (80.8%) of their young adults had left school. Participation in post-school day occupations was the main outcome and included; open employment, training, sheltered employment or alternatives to employment (ATE). RESULTS: Young adults were reported as participating in open employment (n = 42), training (n = 17), sheltered employment (n = 64) or ATE (n = 41) post-school. Those who reported better functioning in self-care, community and communication skills were more likely to be in open employment and/or attending Technical and Further Education compared with those attending sheltered employment and/or ATE after adjusting for age, gender and rural/metropolitan regions. Current health as measured by visits to a general practitioner (GP) and hospitalizations revealed a weak relationship with post-school day occupations, with increasing likelihood of participating in open employment or training with increasing hospitalizations and GP visits. CONCLUSIONS: Our analysis shows that functioning in activities of daily living was related to post-school day occupation. Current health status and behaviour were found to have a weak relationship with post-school day occupation adjusting for functioning in the final model.

Pre-pregnancy maternal overweight and obesity increase the risk for affective disorders in offspring.

Maternal pre-pregnancy obesity has been linked with an increased risk for negative emotionality and inattentiveness in offspring in early childhood. The aim of this study was to examine the association between maternal pre-pregnancy body mass index (BMI) and the development of affective problems (dysthymic disorder, major depressive disorder) throughout childhood and adolescence. In the Western Australian Pregnancy Cohort (Raine) Study, 2900 women provided data on their pre-pregnancy weight, and height measurements were taken at 18 weeks of gestation. BMI was calculated and categorized using standardized methods. Live-born children (n = 2868) were followed up at ages 5, 8, 10, 14 and 17 years using the Diagnostic and Statistical Manual of Mental Disorders-oriented scales of the Child Behavior Checklist (CBCL/4-18). Longitudinal models were applied to assess the relationships between maternal pre-pregnancy BMI and affective problems from age 5 through 17. There was a higher risk of affective problems between the ages of 5 and 17 years among children of women who were overweight and obese compared with the offspring of women in the healthy pre-pregnancy weight range (BMI 18.5-24.99) after adjustment for confounders, including paternal BMI. Maternal pre-pregnancy overweight and obesity may be implicated in the development of affective problems, including depression, in their offspring later in life.

Heavy prenatal alcohol exposure and increased risk of stillbirth.

OBJECTIVE: To investigate the association between heavy prenatal alcohol exposure and stillbirth. DESIGN: Data linkage cohort study. SETTING: Western Australia (WA). POPULATION: The exposed cohort included mothers with an alcohol-related diagnosis (International Classification of Diseases, ninth/tenth revisions) recorded in health data sets and all their offspring born in WA (1983-2007). Mothers without an alcohol-related diagnosis and their offspring comprised the comparison cohort. METHODS: Exposed and comparison mothers were identified through the WA Data Linkage System. Odds ratios for stillbirth at 20+ weeks of gestation were estimated by logistic regression, stratified by Aboriginal status. MAIN OUTCOME MEASURES: The proportion of stillbirths at 20+ weeks of gestation is presented per 1000 births, as well as adjusted odds ratios (aOR) and 95% confidence intervals (95% CI), and population-attributable fractions. RESULTS: Increased odds of stillbirth were observed for mothers with an alcohol-related diagnosis at any stage of their life for both non-Aboriginal (aOR 1.36; 95% CI 1.05-1.76) and Aboriginal (aOR 1.33; 95% CI 1.08-1.64) births. When an alcohol diagnosis was recorded during pregnancy, increased odds were observed for non-Aboriginal births (aOR 2.24; 95% CI 1.09-4.60), with the highest odds of Aboriginal stillbirth occurring when an alcohol diagnosis was recorded within 1 year postpregnancy (aOR 2.88; 95% CI 1.75-4.73). The population-attributable fractions indicate that 0.8% of non-Aboriginal and 7.9% of Aboriginal stillbirths are the result of heavy alcohol consumption. CONCLUSIONS: Prevention of heavy maternal alcohol use has the potential to reduce stillbirths. The lack of an association between exposure during pregnancy and Aboriginal stillbirth in this study needs further investigation.

Low-moderate prenatal alcohol exposure and risk to child behavioural development: a prospective cohort study.

OBJECTIVE: To examine the association of fetal alcohol exposure during pregnancy with child and adolescent behavioural development. DESIGN: The Western Australian Pregnancy Cohort (Raine) Study recruited 2900 pregnancies (1989-91) and the 14-year follow up was conducted between 2003 and 2006. SETTING: Tertiary obstetric hospital in Perth, Western Australia. POPULATION: The women in the study provided data at 18 and 34 weeks of gestation on weekly alcohol intake: no drinking, occasional drinking (up to one standard drink per week), light drinking (2-6 standard drinks per week), moderate drinking (7-10 standard drinks per week), and heavy drinking (11 or more standard drinks per week). Methods Longitudinal regression models were used to analyse the effect of prenatal alcohol exposure on Child Behaviour Checklist (CBCL) scores over 14 years, assessed by continuous z-scores and clinical cutoff points, after adjusting for confounders. MAIN OUTCOME MEASURE: Their children were followed up at ages 2, 5, 8, 10 and 14 years. The CBCL was used to measure child behaviour. RESULTS: Light drinking and moderate drinking in the first 3 months of pregnancy were associated with child CBCL z-scores indicative of positive behaviour over 14 years after adjusting for maternal and sociodemographic characteristics. These changes in z-score indicated a clinically meaningful reduction in total, internalising and externalising behavioural problems across the 14 years of follow up. CONCLUSIONS: Our findings do not implicate light-moderate consumption of alcohol in pregnancy as a risk factor in the epidemiology of child behavioural problems.

Evaluation of the processes of family-centred care for young children with intellectual disability in Western Australia.

INTRODUCTION: Government early intervention services for children with intellectual disability (ID) in Western Australia have adopted the model of family-centred care. The aim of this study was to evaluate how well it was being practised, to describe the pattern of service utilization and to identify factors influencing parental perceptions of family-centred care. METHODS: The study included children aged 0-6 years with ID, who were registered clients of Disability Services Commission, Western Australia. Parents completed a postal survey questionnaire about the frequency and type of services received and their perceptions of services using the Measure of Processes of Care (MPOC-56) questionnaire. Mean scores for the five MPOC domains were compared using anova against the independent variables of child age group, child diagnostic group, service type and frequency, place of residence, family and demographic variables. Significant variables in each domain were then entered into multivariate analyses. RESULTS: Of 292 eligible families, 165 (59%) returned a completed questionnaire. While over 50% of children had contact with occupational, speech and physical therapists at least once per month, less than 20% of children had at least annual contact with either psychology or dental services. Families rated their satisfaction highest for 'respectful and supportive care' and lowest for 'providing general information'. Individual item analyses indicated less satisfaction with 'co-ordinated and comprehensive care'. Higher means were associated with more frequent contact with occupational therapy. CONCLUSION: Overall respondents reported early intervention services for young children with ID in Western Australia provided satisfactory family-centred care by means of the 56-item MPOC. The frequency of contact with allied health professionals was positively associated with parental ratings of family-centred care. The study indicates under-servicing in dental care and psychology services.

Valproate and risk of fracture in Rett syndrome.

OBJECTIVES: Some associations between antiepileptic drugs (AEDs) and fracture risk have been reported in the general population. This study investigated the relationships between fracture risk and commonly used AEDs in Rett syndrome, a genetic disorder associated with intellectual and physical disability. STUDY DESIGN: Cases (n=233) were sourced from the population-based Australian Rett Syndrome Database and longitudinal data were used. The Cox proportional hazard model was used to analyse relationships between fracture and prescribed AEDs, mobility, epilepsy diagnosis and genotype. RESULTS: After controlling for mobility, epilepsy diagnosis and genotype, use of valproate increased the risk of fracture threefold after at least 1 year (HR 3.56; 95% CI 1.85 to 6.82) and after 2 or more years (HR 3.02; 95% CI 1.90 to 4.80). There was a lesser increased risk (HR 1.99; 95% CI 0.99 to 4.02) with lamotrigine in the first year of use but not for subsequent years of use. Carbamazepine slightly decreased the risk (HR 0.60; 95% CI 0.35 to 1.02) after 2 or more years of use. CONCLUSIONS: The effect of valproate on bone health should be considered when managing epilepsy in Rett syndrome. Multiple mechanisms could be contributing to this effect.

Updating the profile of C-terminal MECP2 deletions in Rett syndrome.

OBJECTIVES: This study aimed to compare the phenotype of Rett syndrome cases with C-terminal deletions to that of cases with different MECP2 mutations and to examine the phenotypic variation within C-terminal deletions. METHODS: Cases were selected from InterRett, an international database and from the population-based Australian Rett Syndrome Database. Cases (n=832) were included if they had a pathogenic MECP2 mutation in which the nature of the amino acid change was known. Three severity scale systems were used, and individual aspects of the phenotype were also compared. RESULTS: Lower severity was associated with C-terminal deletions (n=79) compared to all other MECP2 mutations (e.g. Pineda scale C-terminals mean 15.0 (95% CI 14.0-16.0) vs 16.2 (15.9-16.5). Cases with C-terminal deletions were more likely to have a normal head circumference (odds ratio 3.22, 95% CI 1.53 - 6.79) and weight (odds ratio 2.97, 95% CI 1.25-5.76). Onset of stereotypies tended to be later (median age 2.5 years vs 2 years, p<0.001 from survival analysis), and age of learning to walk tended to be earlier (median age 1.6 years vs 2 years, p=0.002 from survival analysis). Those with C-terminal deletions occurring later in the region had lower average severity scores than those occurring earlier in the region. CONCLUSION: In terms of overall severity C-terminal deletion cases would appear to be in the middle of the range. In terms of individual aspects of phenotype growth and ability to ambulate appear to be particular strengths. By pooling data internationally this study has achieved the case numbers to provide a phenotypic profile of C-terminal deletions in Rett syndrome.

Rates and types of hospitalisations for children who have subsequent contact with the child protection system: a population based case-control study.

OBJECTIVES: To determine whether children who have child maltreatment allegation or substantiation have a higher rate of general hospital admissions and injury related admissions when compared to other children and to investigate other types of admissions, such as mental health, infections and admissions due to external causes. STUDY DESIGN: A prospective matched case-control study of children born in Western Australia between 1990 and 2005 using de-identified record linked Child Protection and Hospital Morbidity data. Rates of prior hospital admissions for cases versus controls were calculated, and conditional logistic regression was used to estimate the effect of hospital admission rate on the risk of child maltreatment allegation and substantiated allegation. RESULTS: Children with child maltreatment allegations and substantiations had higher mean prior admission rates compared to controls. Higher rates of general admissions and admissions for injuries, infections, mental and behavioural disorders, and external causes of morbidity, were associated with a markedly increased risk of child maltreatment allegations and substantiation. CONCLUSIONS: The hospital system plays not only an important role both in the surveillance of maltreatment-related injuries and conditions but also in the role of prevention in the referral of families who may need support and assistance in ensuring the health and safety of their children. This research highlights the importance of moving to electronic patient records in identifying children who have high rates of admissions and the types of conditions they have previously presented with, particularly for injuries, mental and behavioural disorders and external causes of admissions.

Gross motor profile in rett syndrome as determined by video analysis.

Movement impairment is a fundamental but variable component of the Rett syndrome phenotype. This study used video supplemented by parent report data to describe the gross motor profile in females with Rett syndrome (n=99) and to investigate the impact of age, genotype, scoliosis and hand stereotypies. Factor analysis enabled the calculation of general and complex gross motor skills scores. Most subjects were able to sit, slightly less than half were able to walk and a minority were able to transfer without assistance. General gross motor skills declined with age and were poorer in those who had surgically treated scoliosis but not conservatively managed scoliosis. Complex gross motor skills did not decline with age and were better in those without scoliosis. Those with a p.R133C, p.R294X, or a p.R255X mutation appear to have better motor skills overall than those with a p.R270X or large deletion mutation. Motor scores were not related to the frequency of hand stereotypies. This information is useful for the clinician and family when planning support strategies and interventions.

Maternal mortality in Yunnan, China: recent trends and associated factors.

OBJECTIVE: Yunnan Province, located in southwest China, is one of the poorest province in China. The maternal mortality ratio (MMR) is about twice the national average (56.2/100,000 live births), and in remote mountainous regions, the rate is five times higher. This study aimed to examine the progress in reduction of maternal mortality in the 1990s and early 2000s and the factors associated with this reduction in Yunnan. DESIGN: A population-based, longitudinal, ecological correlation study. SETTING: A remote province of China with a proportionately large indigenous population. POPULATION: Populations at county, prefecture and provincial level. METHODS: Using maternal mortality data collected at the province, prefecture/region and county levels, trend and time series analyses and multivariate linear regression analyses were performed using SPSS (Version 13). MAIN OUTCOME MEASURE: MMR and its change over time. RESULTS: MMR declined substantially in the 1990s at a rate of 3.0% per year. Utilisation of prenatal and obstetric care increased and was significantly correlated with the declining trend in MMR. Hospital delivery was a strong predictor of MMR, independent of social and economic development. Both low income and illiteracy were significantly associated with increased MMR. CONCLUSIONS: Declines in maternal mortality in Yunnan over the past 14 years appear to reflect health, social and economic interventions implemented in the 1990s. The association of hospital delivery with maternal mortality may be due to the effective management of severe pregnancy and birth complications. Low income and illiteracy were associated with MMR but primarily through their impact on the use of prenatal and obstetric care.

The relationship between changes in daily air pollution and hospitalizations in Perth, Australia 1992-1998: a case-crossover study.

A case-crossover study was undertaken to investigate the relationship between daily air pollutant concentrations and daily hospitalizations for selected disease categories in Perth, Western Australia. Daily measurements of particles (measured by nephelometry and PM2.5), photochemical oxidants (measured as ozone), nitrogen dioxide (NO2) and carbon monoxide (CO) concentrations were obtained from 1992 to 1998 via a metropolitan network of monitoring stations. Daily PM2.5 concentrations were estimated using monitored data, modelling and interpolation. Hospital morbidity data for respiratory, cardiovascular (CVD), gastrointestinal (GI) diseases, chronic obstructive pulmonary diseases (COPD) excluding asthma; pneumonia/influenza diseases; and asthma were obtained and categorized into all ages, less than 15 years and greater than 65 years. Gastrointestinal morbidity was used as a control disease. The data were analyzed using conditional logistic regression. The results showed a small number of significant associations for daily changes in particle concentrations, nitrogen dioxide and carbon monoxide for the respiratory diseases, CODP, pneumonia, asthma and CVD hospitalizations. Changes in ozone concentrations were not significantly associated with any disease outcomes. These data provide useful information on the potential health impacts of air pollution in an airshed with very low sulphur dioxide concentrations and lower nitrogen dioxide concentrations commonly found in many other cities.