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A common chemical exposure in alumina refining is caustic mist. Although recognized as a strong airways irritant, little is known of the chronic respiratory effects of caustic mist in alumina refining. A suitable metric for caustic mist exposure assessment in alumina refining for epidemiological purposes has not been identified. Peak exposure is likely to be important, but is difficult to assess in epidemiological studies. In this study, we investigate the respiratory effects of caustic mist in an inception cohort (n = 416) of alumina refinery workers and describe the development and use of a peak exposure metric for caustic mist. We then compare the results with a metric based on duration of exposure. Participants were interviewed annually about respiratory symptoms and had a lung function test. Job history data were collected from each interview and levels of caustic mist were measured periodically by air monitoring. We found a weak association between the caustic mist peak exposure metric and reported cough (P for linear trend = 0.079) with the highest peak exposure group odds ratio = 2.32 (95% confidence interval: 1.27, 4.22). For lung function, we found declines in the forced expiratory volume in 1 second and forced vital capacity for changes in annual and absolute lung function for both metrics of exposure, but only the ratio of absolute lung function was statistically associated with an increasing duration of caustic exposure (P for linear trend = 0.011). In this cohort, we did not observe an association with respiratory symptoms or consistent decrements in lung function. There was little difference between the exposure metrics used for investigation of the chronic effects from caustic mist., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.)

Background: Significant progress has been made towards an effective respiratory syncytial virus (RSV) vaccine. Age-stratified estimates of RSV burden are urgently needed for vaccine implementation. Current estimates are limited to small cohorts or clinical coding data only. We present estimates of laboratory-confirmed RSV across multiple severity levels., Methods: We linked laboratory, perinatal, and hospital data of 469 589 children born in Western Australia in 1996-2012. Respiratory syncytial virus tests and detections were classified into community, emergency department (ED), and hospital levels to estimate infection rates. Clinical diagnoses given to children with RSV infection presenting to ED or hospitalized were identified., Results: In 2000-2012, 10% (n = 45 699) of children were tested for RSV and 16% (n = 11 461) of these tested positive. Respiratory syncytial virus was detected in community, ED (both 0.3 per 1000 child-years), and hospital (2.4 per 1000 child-years) settings. Respiratory syncytial virus-confirmed rates were highest among children aged <3 months (31 per 1000 child-years). At least one third of children with RSV infection presenting to ED were diagnosed as other infection, other respiratory, or other (eg, agranulocytosis)., Conclusions: Respiratory syncytial virus is pervasive across multiple severity levels and diagnoses. Vaccines targeting children <3 months must be prioritized. Given that most children are never tested, estimating the under-ascertainment of RSV infection is imperative., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

The Wittenoom crocidolite (blue asbestos) mine and mill ceased operating in 1966. The impact of this industry on asbestos-related disease in Western Australia has been immense. Use of the employment records of the Australian Blue Asbestos Company and records of the Wittenoom township residents has permitted two cohorts of people with virtually exclusive exposure to crocidolite to be assembled and studied. Follow-up of these two cohorts has been conducted through data linkage with available hospital, mortality and cancer records. The evolution of asbestos-related disease has been recorded and, with the establishment of exposure measurements, quantitative exposure-response relationships have been estimated. There has been an ongoing epidemic of mortality from lung cancer and malignant mesothelioma and, less so, from asbestosis. Wittenoom crocidolite was used extensively in asbestos-cement products in Western Australia. As a result, the state has recorded a higher malignant-mesothelioma mortality rate than in any other Australian state and in any defined general population in the world. Thus, the legacy of Wittenoom has extended beyond the mine and the town, and is still evident more than 50 years after the closure of the mine., (© The Author(s) 2019; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Objectives: An asbestos job-exposure matrix (AsbJEM) has been developed to systematically and cost-effectively evaluate occupational exposures in population-based studies. The primary aim of this study was to examine the accuracy of the AsbJEM in determining exposure-response relationships between asbestos exposure estimates and malignant mesothelioma (MM) incidence (indirect validation). The secondary aim was to investigate whether the assumptions used in the development of the original AsbJEM provided accurate asbestos exposure estimates., Methods: The study population consisted of participants in an annual health surveillance program, who had at least 3-month occupational asbestos exposure. Calculated asbestos exposure indices included cumulative asbestos exposure and the average exposure intensity, estimated using the AsbJEM and duration of employment. Asbestos and MM exposure-response relationships were compared between the original AsbJEM and its variations based on manipulations of the intensity, duration and frequency of exposure. Twenty-four exposure estimates were calculated for both cumulative asbestos exposure and the average exposure intensity using three exposure intensities (50th, 75th and 90th percentile of the range of mode exposure), four peak durations (15, 30, 60 and 120 min) and two patterns of peak frequency (original and doubled). Cox proportional hazards models were used to describe the associations between MM incidence and each of the cumulative and average intensity estimates., Results: Data were collected from 1602 male participants. Of these, 40 developed MM during the study period. There were significant associations between MM incidence and both cumulative and average exposure intensity for all estimates. The strongest association, based on the regression-coefficient from the models, was found for the 50th percentile of mode exposure, 15-min peak duration and the doubled frequency of peak exposure. Using these assumptions, the hazard ratios for mesothelioma were 1 (reference), 1.91, 3.24 and 5.37 for the quartiles of cumulative asbestos exposure and 1 (reference), 1.84, 2.31 and 4.40 for the quartiles of the average exposure intensity, respectively., Conclusion: The well-known positive exposure-response relationship between MM incidence and both estimated cumulative asbestos exposure and average exposure intensity was confirmed. The strongest relationship was found when the frequency of peak exposure in the AsbJEM was doubled from the originally published estimates., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.)

The association between a single interpregnancy interval (IPI) and birth outcomes has not yet been explored using matched methods. We modeled the odds of preterm birth, being small for gestational age, and having low birth weight in a second, live-born infant in a cohort of 192,041 sibling pairs born in Western Australia between 1980 and 2010. The association between IPI and birth outcomes was estimated from the interaction between birth order and IPI (with 18-23 months as the reference category), using conditional logistic regression. Matched analysis showed the odds of preterm birth were higher for siblings born following an IPI of <6 months (adjusted interaction odds ratio = 1.22, 95% confidence interval: 1.06, 1.38) compared with those born after an IPI of 18-23 months. There were no significant differences for IPIs of <6 months for other outcomes (small for gestational age or low birth weight). This is the first study to use matched analyses to investigate the association between a single IPI on birth outcomes. IPIs of <6 months were associated with increased odds of preterm birth in second-born infants, although the association is likely smaller than previously estimated by unmatched studies.

Background: The early life microbiome contributes to immune development. Antibiotics during pregnancy alter the microbiome and may influence disease risks in the offspring. We investigated the relationship between maternal antibiotic exposure before and during pregnancy, and risk of childhood hospitalization with infection., Methods: We used population-based Danish national databases for pregnancies between 1995 and 2009. Infants were followed from birth until their first infection-related hospitalization, death, 14th birthday, emigration or end-2009. Exposure was maternal antibiotics prescribed before and during pregnancy. Outcome was infection-related hospitalization., Results: 141 359 (18%) mothers had at least one antibiotic prescription during pregnancy, 230 886 (29.4% of those with complete data) in the 18 months before pregnancy. Of 776 657 live-born singletons, 443 546 infection-related hospitalizations occurred in 222 524 (28.6%) children. Pregnancy antibiotic exposure was associated with increased risk of childhood infection-related hospitalization [hazard ratio (HR) 1.18, 95% confidence interval (CI) 1.17-1.19]. In mothers prescribed antibiotics only during pregnancy whose child did not receive pre-hospitalization antibiotics, this association was present only in those born vaginally. Higher risks of infection-related hospitalization occurred when pregnancy antibiotic prescriptions were closer to birth and in mothers receiving more pregnancy antibiotics. Children born to mothers exposed to antibiotics before (but not during) pregnancy also had increased risk of infection-related hospitalization (HR 1.10, 95% CI 1.07-1.12)., Conclusions: Antibiotic exposure before or during pregnancy was associated with increased risk of childhood hospitalized infections. Alteration of the maternally derived microbiome and shared heritable and environmental determinants are possible contributory mechanisms.

Background: Pneumococcal conjugate vaccine (PCV) was included in Australia's National Immunisation Program for all children from 2005. We assessed the impact of PCV on all-cause and pathogen-specific pneumonia hospitalizations in Western Australian (WA) children aged ≤16 years., Methods: All hospitalizations with pneumonia-related International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification diagnosis codes occurring in WA-born children (1996-2012) were linked to pathology records. Age-specific incidence rate ratios and temporal trends for all-cause and pathogen-specific pneumonia hospitalizations were calculated before and after PCV introduction., Results: Among 469589 births, there were 15175 pneumonia-related hospitalizations. Hospitalization rates were 6.7 (95% confidence interval, 6.4-6.9) times higher in Aboriginal than in non-Aboriginal children. Following PCV introduction, all-cause pneumonia hospitalizations showed significant declines across all age groups. A pathogen was identified in 2785 of 6693 (41.6%) pneumonia hospitalizations that linked to a pathology record. Respiratory syncytial virus (RSV) was most frequently identified, with RSV-associated pneumonia hospitalization rates of 89.6/100000 child-years in Aboriginal and 26.6/100000 child-years in non-Aboriginal children. The most common bacterial pathogen was Streptococcus pneumoniae in Aboriginal children (32.9/100000 child-years) and Mycoplasma pneumoniae in non-Aboriginal children (8.4/100000 child-years). Viral pneumonia rates declined in all children following PCV introduction, with the greatest declines seen in non-Aboriginal children; declines in bacterial pneumonia were observed in non-Aboriginal children., Conclusions: Based on our ecological analyses, PCV seems to have had an impact on hospitalizations for pneumonia, suggesting that the pneumococcus is likely to play a role in both bacterial and viral pneumonia. Respiratory viruses remain an important pathogen in childhood pneumonia. Vaccines targeting respiratory viruses are needed to combat the residual burden of childhood pneumonia.

Background: Children with acute respiratory tract infection (ARTI) frequently exhibit virus-virus codetection, yet the clinical significance of ARTI remains contentious. Using data from a prospective cohort of children with influenza-like illness, we examined the virology of ARTI and determined the clinical impact of virus-virus codetection., Methods: Children aged 6 to 59 months who presented to a tertiary pediatric hospital between influenza seasons 2008 and 2012 with fever and acute respiratory symptoms were enrolled, and nasal samples were collected. Respiratory viruses were identified by culture and polymerase chain reaction. We compared demographics, presenting symptoms, and clinical outcomes of children with a single-virus infection and those in whom 2 or more viruses were detected (virus-virus codetection). We used logistic regression models and estimated marginal means to calculate the adjusted odds ratios and probabilities of symptom presentation, prescription of antibiotics, and hospitalization., Results: Of 2356 children, a virus was detected in 1630 (69.2%) of them; rhinovirus (40.8%), influenza (29.5%), and respiratory syncytial virus (26.4%) were detected most commonly. Two or more viruses were detected in 25% of these children. After we adjusted for demographic factors, children with virus-virus codetection had greater odds of presenting with cough (adjusted odds ratio [aOR], 1.9; 95% confidence interval [CI], 1.2-3.1) and rhinorrhea (aOR, 1.8; 95% CI, 1.1-2.9) than those with a single-virus infection, although both symptoms were common. Children with influenza and respiratory syncytial virus combined had the highest probability of hospitalization (55%; 95% CI, 35%-73%), which was significantly greater than for those with influenza infection alone (22%; 95% CI, 16%-29%)., Conclusions: Overall, virus-virus codetection has limited impact on clinical severity among children with influenza-like illness. However, infection with specific pathogen pairs might be associated with more severe outcomes. Routine diagnostics to identify specific viruses should be restricted to common pathogens., (© The Author 2016. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Although antenatal influenza vaccination is an important public health intervention for preventing serious infection in pregnant women and newborns, reported vaccine coverage is often <50%. Concern for the safety to the fetus is a commonly cited reason for vaccine hesitancy and refusal. The incidence of stillbirth following pandemic vaccination has been previously studied; however, no population-based study has evaluated the incidence of stillbirth following seasonal trivalent influenza vaccination., Methods: We used probabilistic linking of perinatal and maternal vaccination records to establish a cohort of 58 008 births occurring between April 2012 and December 2013. Stillbirth was defined as birth ≥20 weeks' gestation with an Apgar score of zero at 1 and 5 minutes following delivery. Cox regression models adjusted for maternal smoking, Indigenous status, and propensity for vaccination were used to calculate adjusted hazard ratios (aHRs) in vaccinated and unvaccinated mothers., Results: A total of 5076 (8.8%) pregnant women received trivalent influenza vaccine and 377 stillbirths occurred. There were 5.0 and 3.0 stillbirths per 100 000 pregnancy-days among unvaccinated and vaccinated women, respectively. After adjustment, stillbirth was 51% less likely among vaccinated vs unvaccinated mothers (aHR, 0.49; 95% confidence interval [CI], .29-.84). The largest relative reduction in stillbirths was observed for births occurring just after influenza season (aHR, 0.33; 95% CI, .12-.88)., Conclusions: Mothers who received seasonal TIV during pregnancy were significantly less likely to experience stillbirth compared with unvaccinated mothers. These results support the safety of seasonal influenza immunization during pregnancy and suggest a protective effect., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Influenza and pertussis are major causes of pediatric morbidity. We measured the accuracy of their International Classification of Diseases (ICD-10-AM) diagnosis codes using linked population-based laboratory and hospital data in 245,249 children. Influenza diagnosis codes had high specificity (98.6%) and modest positive predictive value (PPV; 84.1%) and sensitivity (86.1%, 95% CI: 83.4%-88.6%) for a laboratory-confirmed episode. For pertussis diagnosis codes, PPV (86.8%) and specificity (98.9%) were high, but sensitivity was poor (27.8%, 95% CI: 23.5%-32.4%). Measures varied according to age, remoteness, Aboriginality, severity, and detection method. Both laboratory and hospitalization data are needed to accurately determine the burden of pediatric influenza and pertussis., (© The Author 2013. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Eumycetoma, a chronic granulomatous disease characterized by a subcutaneous mass, multiple sinuses and purulent discharge containing grains, remains difficult to diagnose and treat. Madurella mycetomatis is the most common causative agent of eumycetoma. Using a serum pool from patients with active mycetoma, we screened a M. mycetomatis-specific λgt11 cDNA library which was shown to contain 8% of cDNA inserts encoding proteins involved in glycolysis. Two of these enzymes, fructose-bisphosphate aldolase (FBA) and pyruvate kinase (PK), were produced in vitro and their antigenicity was studied with bead-based flow cytometry. It appeared that both FBA and PK IgG antibodies were present in eumycetoma patient sera. However, only FBA antibody levels were found to be significantly higher in eumycetoma patient sera when compared to healthy Sudanese controls. Furthermore, FBA and PK were also found to be expressed on the hyphae present in the mycetoma grain. In conclusion, this study presents two new antigenic proteins of M. mycetomatis next to the translationally controlled tumour protein (TCTP): the glycolytic enzymes FBA and PK. These antigens might be useful as vaccine-candidates in the prevention of mycetoma.

Background: We hypothesized that the inflammatory response in the lungs of children with cystic fibrosis (CF) would vary with the type of infecting organism, being greatest with Pseudomonas aeruginosa and Staphylococcus aureus., Methods: A microbiological surveillance program based on annual bronchoalveolar lavage (BAL) collected fluid for culture and assessment of inflammation was conducted. Primary analyses compared inflammation in samples that grew a single organism with uninfected samples in cross-sectional and longitudinal analyses., Results: Results were available for 653 samples from 215 children with CF aged 24 days to 7 years. A single agent was associated with pulmonary infection (≥10(5) cfu/mL) in 67 BAL samples, with P. aeruginosa (n = 25), S. aureus (n = 17), and Aspergillus species (n = 19) being the most common. These microorganisms were associated with increased levels of inflammation, with P. aeruginosa being the most proinflammatory. Mixed oral flora (MOF) alone was isolated from 165 BAL samples from 112 patients, with 97 of these samples having a bacterial density ≥10(5) cfu/mL, and was associated with increased pulmonary inflammation (P < .001). For patients with current, but not past, infections there was an association with a greater inflammatory response, compared with those who were never infected (P < .05). However, previous infection with S. aureus was associated with a greater inflammatory response in subsequent BAL., Conclusions: Pulmonary infection with P. aeruginosa, S. aureus, or Aspergillus species and growth of MOF was associated with significant inflammatory responses in young children with CF. Our data support the use of specific surveillance and eradication programs for these organisms. The inflammatory response to MOF requires additional investigation.

Background: It is unclear whether the increase in autism over the past two decades is a real increase or due to changes in diagnosis and ascertainment of autism spectrum disorders (ASDs), which include autism, Asperger syndrome and pervasive developmental disorder not otherwise specified (PDD-NOS). The aim of this study was to examine the trends in ASD over time in Western Australia (WA) and the possible effects and contribution of changes in diagnostic criteria, age at diagnosis, eligibility for service provision based on ASD diagnoses and changes in diagnostic practices., Methods: A population-based study was conducted among the cohort of children born in WA between 1983 and 1999 and diagnosed with ASD between the age of 2 and 8 years up to December 31, 2004. The trend in ASD diagnosis over the study period was assessed by investigating birth cohort and period effects, and examining whether these were modified by age of diagnosis. ASD diagnosis corresponding with changes in diagnostic criteria, funding and service provision over time were also investigated. A subgroup analysis of children aged

Background: Compared with spontaneously conceived (SC) singletons, adverse perinatal outcome, neonatal intensive care unit (NICU) admission and hospital admission in infancy are more common in those born following Assisted Reproductive Technology (ART). Similar comparisons for twins have shown conflicting results., Methods: We investigated perinatal outcome and hospital admission during the first 3 years of life for all twin children born in Western Australia between 1994 and 2000 [700 ART, 4097 SC]., Results: ART twins had a greater risk of adverse perinatal outcome including preterm birth, low birthweight and death compared with SC twins of unlike-sex. In their first year of life, ART twins had a longer birth admission; were 60% more likely to be admitted to a NICU; and had a higher risk of hospital admission. The increased risk of hospital admission continued in the second and third year but was not statistically significant in the third year., Conclusions: Couples undertaking ART should be aware that in addition to the known increased perinatal risks associated with a twin birth, ART twins are more likely than SC twins to be admitted to a NICU and hospitalized in the first 3 years of life.

The relation between intrauterine growth and risk of childhood acute lymphoblastic leukemia was investigated in an Australian population-based case-control study that included 347 cases and 762 controls aged <15 years recruited from 2003 to 2006. Information on proportion of optimal birth weight, a measure of the appropriateness of fetal growth, was collected from mothers by questionnaire. Data were analyzed by using logistic regression. Risk of acute lymphoblastic leukemia was positively associated with proportion of optimal birth weight; the odds ratio for a 1-standard-deviation increase in proportion of optimal birth weight was 1.18 (95% confidence interval: 1.04, 1.35) after adjustment for the matching variables and potential confounders. This association was also present among children who did not have a high birth weight, suggesting that accelerated growth, rather than high birth weight per se, is associated with risk of acute lymphoblastic leukemia. Similar associations between proportion of optimal birth weight and acute lymphoblastic leukemia were observed for both sexes and across age groups and leukemia subtypes. Results of this study confirm earlier findings of a positive association between rapidity of fetal growth and subsequent risk of acute lymphoblastic leukemia in childhood, and they are consistent with a role for insulin-like growth factors in the causal pathway.

In epidemiologic studies, researchers often need to establish a nonlinear exposure-response relation between a continuous risk factor and a health outcome. Furthermore, periodic interviews are often conducted to take repeated measurements from an individual. The authors proposed to use fractional polynomial models to jointly analyze the effects of 2 continuous risk factors on a health outcome. This method was applied to an analysis of the effects of age and cumulative fluoride exposure on forced vital capacity in a longitudinal study of lung function carried out among aluminum workers in Australia (1995-2003). Generalized estimating equations and the quasi-likelihood under the independence model criterion were used. The authors found that the second-degree fractional polynomial models for age and fluoride fitted the data best. The best model for age was robust across different models for fluoride, and the best model for fluoride was also robust. No evidence was found to suggest that the effects of smoking and cumulative fluoride exposure on change in forced vital capacity over time were significant. The trend 1 model, which included the unexposed persons in the analysis of trend in forced vital capacity over tertiles of fluoride exposure, did not fit the data well, and caution should be exercised when this method is used.

This study investigated the relation between birth characteristics and numeracy attainment at age 8 years. Using a multilevel approach, the authors analyzed all non-Aboriginal singletons born in Western Australia who attended government schools and participated in a Western Australia-wide numeracy test in grade 3 between 1999 and 2005. Appropriateness of intrauterine growth was expressed as the proportion of optimal growth parameters for gestational duration, infant sex, and maternal height and parity, which was derived from a total population of births without risk factors for growth restriction. After the authors controlled for sociodemographic factors, term birth and proportion of optimal head circumference at birth were associated with higher numeracy scores. Increasing proportion of optimal birth length and being firstborn were associated with relatively higher numeracy scores among children born to mothers residing in the most educationally deprived area. The relative advantage of being born first was also higher for children born to single mothers. In contrast, higher Apgar scores and greater proportion of optimal birth weight were associated with a lower relative advantage for children born to single mothers. In summary, term birth and increased growth in head circumference and length are key birth characteristics associated with higher numeracy scores, especially among disadvantaged children.

Background: Adverse perinatal outcomes are more common in singletons born following assisted reproductive technology (ART) and this would predict an increase in hospitalization during infancy and early childhood., Methods: We investigated hospital admissions during the first 3 years of life for all singleton children born in Western Australia between 1994 and 2000 [1328 ART, 162 350 spontaneously conceived (SC)]., Results: ART infants had a significantly longer birth admission and were four times more likely to be admitted to neonatal intensive care units (NICU) than SC infants. ART children had a 60% greater risk of one or more admissions in their first year and an equal risk of admission in their second and third years. Their length of stay in hospital was longer in each age period. Maternal, infant and socio-economic confounders accounted for most of the increased admission risk in the first year. However, after adjustment, a 20% increase in the risk of admission to NICU (P < 0.05) and admission to hospital during the first year (P < 0.05) remained., Conclusions: Couples undertaking ART should be aware that ART infants are more likely to be admitted to a NICU, to be hospitalized in the first year of life and to stay in hospital longer than other children.

The authors investigated the association between intrauterine growth and intellectual disability (ID). The appropriateness of intrauterine growth was assessed using percentage of optimal birth weight, a measure that accounts for gestational age, maternal height, parity, and infant sex. Using population-based record linkage, singleton Caucasian and Aboriginal children born in Western Australia in 1983-1992 and alive in 2002 with ID of unknown cause (n = 2,625) were compared with children without ID (n = 217,252). The odds of ID increased with less-than-optimal intrauterine growth. In Caucasian children, after adjustment for sociodemographic factors, severe growth restriction was associated with development of mild-moderate ID among preterm births (<37 weeks) (odds ratio (OR) = 1.71, 95% confidence interval (CI): 1.06, 2.77) and term births (> or =37 weeks) (OR = 2.42, 95% CI: 1.88, 3.12) and with severe ID (OR = 4.79, 95% CI: 2.59, 8.83) among term births. Effects were similar among Aboriginal children. Severe growth restriction (OR = 3.2, 95% CI: 1.3, 7.9) and poor head growth (OR = 3.6, 95% CI: 1.4, 9.0) were independently associated with severe ID. Infants with excess intrauterine growth were more likely to be diagnosed with ID associated with autism spectrum disorder (OR = 2.36, 95% CI: 0.93, 6.03). These findings suggest that inappropriate intrauterine growth, less than or greater than optimal birth weight, is associated with development of ID.

Many studies have looked at the association between birth weight and risk of acute lymphoblastic leukaemia in children, but few have been able to examine the growth by incorporating estimates of gestational age. Recent results suggest that increased growth is associated with increased risk of childhood leukaemia. Evidence is also gathering that certain dietary intakes, possibly folate, in mothers, are also related to leukaemia occurrence. If these associations are real, they may be operating through growth factor pathways.

The authors examined the relation between birth weight, intrauterine growth, and risk of childhood leukemia using population-based linked health data from Western Australia. A cohort of 576,593 infants born in 1980-2004 were followed from birth to diagnosis of acute lymphoblastic leukemia (ALL) (n = 243) or acute myeloid leukemia (AML) (n = 36) before their 15th birthday, death, or the end of follow-up (December 31, 2005). Data were analyzed using Cox regression. Risk of ALL was positively associated with the proportion of optimal birth weight--a measure of the appropriateness of fetal growth--particularly among children younger than 5 years; the hazard ratio for a 1-standard-deviation increase in proportion of optimal birth weight was 1.25 (95% confidence interval: 1.07, 1.47). Among children younger than 5 years not classified as having high birth weight (defined as >3,500 g, >3,800 g, and >4,000 g), a 1-unit increase in proportion of optimal birth weight was associated with an approximately 40% increase in ALL risk. This suggests that accelerated growth, rather than high birth weight per se, is involved in the etiology of ALL. These findings are consistent with a role for insulin-like growth factor I in the causal pathway. Findings for AML were inconclusive, probably because of small numbers.

Background: The risk of birth defects in infants born following assisted reproductive technology (ART) treatment is a controversial question. Most publications examining the prevalence of birth defects in ICSI and IVF infants compared to spontaneously conceived infants have serious methodological limitations; despite this, most researchers have concluded that there is no increased risk., Methods: We carried out a systematic review to identify all papers published by March 2003 with data relating to the prevalence of birth defects in infants conceived following IVF and/or ICSI compared with spontaneously conceived infants. Independent expert reviewers used criteria defined a priori to determine whether studies were suitable for inclusion in a meta-analysis. Fixed effects meta-analysis was performed for all studies and reviewer-selected studies., Results: Twenty-five studies were identified for review. Two-thirds of these showed a 25% or greater increased risk of birth defects in ART infants. The results of meta-analyses of the seven reviewer-selected studies and of all 25 studies suggest a statistically significant 30-40% increased risk of birth defects associated with ART., Conclusions: Pooled results from all suitable published studies suggest that children born following ART are at increased risk of birth defects compared with spontaneous conceptions. This information should be made available to couples seeking ART treatment.

Unlabelled: Occupational exposure limits for crystalline silica are under review worldwide because of the large numbers of exposed people and, especially, because of the recent International Agency for Research on Cancer classification of silica as a human carcinogen., Objectives: The aims of this study were to (i) re-examine the incidence of silicosis in Western Australian gold miners and, using estimates of the total population at risk, (ii) estimate the upper confidence limit for the risk of silicosis in Western Australian gold miners since 1974, when the current exposure standard for crystalline silica was implemented., Methods: Work histories of cases compensated for pneumoconiosis after 1974 were examined. Numbers of workers in the total workforce likely to be exposed to crystalline silica in Western Australia were estimated as the population at risk., Results: There were no cases of compensated silicosis in Western Australian miners whose first dust exposure began during or after 1974. The upper 95% confidence interval for this zero rate was estimated to be 4.8 per 100,000 person-yr., Conclusions: There have been no compensated cases of silicosis in Western Australia among miners first exposed to crystalline silica after introduction of the current exposure standard. A rate of compensated silicosis higher than five cases per 100,000 person-yr is unlikely.

Background: Acquired resistance to standard chemotherapy for tuberculosis (TB) is an increasing problem worldwide. Vietnam has one of the highest incidences of TB and also has a large population of potential migrants to other countries. Since 1979 the International Organisation for Migration (IOM) has been running a supervised programme of TB treatment for intending migrants from Vietnam where few facilities for bacteriological culture and sensitivity testing exist. This study aimed to assess the most important factors for predicting non-response to first-line treatment as treatment starts and whether any further indicators occur during the course of treatment which may enable more accurate prediction of non-response., Methods: In all, 130 subjects failing to respond to first-line therapy (cases) between 1990 and 1995 were compared with 673 subjects who responded to therapy (controls) on various demographic and clinical characteristics using logistic regression to create a prognostic index. Variables analysed included the patient history of past TB treatment, weight, age, sex and radiological and bacteriological findings. All subjects also tested negative for HIV status., Results: The chief markers of successful response were x-ray signs and degree of sputum smear positivity. These markers provided a prognostic index with an optimal cutoff providing about 70% sensitivity and 80% specificity. Incorporating further measures obtained through the first 3 months of treatment improved the sensitivity to 80%., Conclusion: While this study enabled prediction of the majority of subjects failing to respond to first-line therapy, other factors need to be assessed before recommendations for altering treatment regimens can be made. The prognostic index could be useful in assessing subjects for closer supervision.

Associations were sought between prevalence of nevi on the arms and other variables in controls from a case-control study of cutaneous malignant melanoma. The prevalence of nevi was higher in women than men, fell with age up to about 35 years of age, and was low in those born outside Australia. Among pigmentary characteristics, there was strong evidence only of an association with skin color of the upper inner arm. The highest prevalence of nevi was in those with skin of intermediate darkness. Peak prevalence of nevi was also seen in intermediate categories of variables indicating sun exposure, particularly mean annual hours of bright sunlight at places of residence when 10-24 years of age, total outdoor exposure time per week in the summer at 10-24 years of age, and usual summer suntan on the arms in the last 10 years. These dose-effect patterns may indicate conflicting effects of sun exposure on appearance and disappearance of nevi. The protective effect of birthplace outside Australia appeared to be due to the corresponding low mean annual hours of bright sunlight at places of residence when 10-24 years of age. The prevalence of nevi was comparatively lower in those who drank alcohol and in those who had average or high daily intakes of retinol. These associations were not explained by those of any of the other variables.

The hypothesis that dietary fat acts as a promotional agent for the development of breast cancer by influencing sex hormone levels was tested in a dietary intervention study. Thirty-three women in good health were randomly allocated to commence either a standard diet (deriving 40% of their energy from fat) or a low-fat diet (deriving 20% of their energy from fat). After 2 months, the women were crossed over to the alternative diet for another 2 months. Serum hormone and lipid levels were measured in the middle and at the end of each dietary period. In premenopausal women, the low-fat diet appeared to decrease levels of both non-protein-bound estradiol (1.48 down to 1.27%; P = .07) and non-protein-bound testosterone (1.06 down to 0.86%; P = .11). Cholesterol levels were lowered by the low-fat diet and were significantly associated with estradiol, testosterone, and dehydroepiandrosterone. High-density lipoprotein (HDL) cholesterol was associated with estradiol and prolactin. For the postmenopausal women, the low-fat diet lowered cholesterol and HDL cholesterol levels, but there were not the same associations with the hormones. These findings add weight to the concept that attention to diet may be a means of reducing the incidence of breast cancer in our community.

Trends in the incidence of and mortality from myocardial infarction in Perth, Western Australia, were studied for the period 1971 to 1982. The estimated age-adjusted incidence rate of myocardial infarction fell by 24% in males and 37% in females over this period. The rate fell in each of six age-sex groups, but the proportional decrease in those aged less than 45 years was nearly double that in those aged 45 years and over, as it was in females compared with males and in fatal cases compared with nonfatal cases. Over 80% of the decline in mortality was in deaths outside hospital. This and seven other comparable studies all showed a net decrease in the estimated incidence of myocardial infarction in both sexes, with median annual decreases of 2% in males and 3% in females. It is concluded that the decline in the incidence of myocardial infarction contributed substantially to the observed decrease in ischemic heart disease mortality, and that the most plausible explanation for the decline in incidence is a reduction in the prevalence of risk factors for myocardial infarction.

Many articles in the recent epidemiological literature have discussed the effects of random error and misclassification on effect estimation, but many of these have been unclear and hard to follow. This paper reviews and interprets many of these and summarizes the use of the correlation coefficient in assessing the likely effect of measurement error on relative risk estimates for variables that are either continuous or ordered. A table of expected values of relative risks (RRs) calculated in different ways for different levels of random error is presented and the typically large expected attenuation in RR values is shown. The recommendation of taking repeated or multiple measurements whenever possible is endorsed.