Esophageal atresia and tracheo-esophageal fistula in Western Australia: prevelence and trends

Objectives A recent international study reported a higher prevalence of esophageal atresia with or without tracheo-esophageal fistula (EA±TEF) in Western Australia (WA). The aim of this study was to examine the prevalence and trends of EA and/or TEF in WA; determine the proportion of cases with associated anomalies; and explore the impact of time of diagnosis. Methods The study population comprised all infants born in WA, 1980-2009 and registered with EA and/or TEF on the WA Register of Developmental Anomalies (WARDA). Results EA±TEF and TEF alone affect, on average, 1 in every 2,927 births in WA, with a total prevalence of 3.00 and 0.42 per 10,000 births, respectively. The prevalence of EA±TEF increased by 2.0% per annum, with only cases with associated anomalies (64% of cases) demonstrating an increase. TEF rates were stable. Among EA±TEF infants, the proportion of live births, stillbirths and elective terminations of pregnancy for fetal anomaly (TOPFA) was 79%, 6% and 15%, respectively; while the majority (94%) of TEF only cases were live births. In 2000-2009 there was 30% fall in EA±TEF live births with 61 (58%) cases diagnosed in first week of life, 10 (9%) prenatally and 34 (32%) at postmortem only. Conclusions A higher prevalence of EA±TEF in WA was observed with increase over time attributable to increase with associated anomalies. Consistent reporting, availability of prenatal diagnosis and ascertainment of cases following TOPFA or postmortem examinations can significantly affect prevalence of EA and/or TEF.NHMR

Review of Fetal Alcohol Spectrum Disorder (FASD) among Aboriginal and Torres Strait Islander people

Fetal Alcohol Spectrum Disorder (FASD) is a preventable, lifelong disability that disproportionately affects Aboriginal and Torres Strait Islander people. This review provides a comprehensive synthesis of the available information on FASD among Aboriginal and Torres Strait Islander people, with reference to the limitations on population-based data and evaluated programs. The review outlines; the harms of alcohol use in the context of colonisation, cultural perspectives on assessment and diagnosis, effective prevention programs and a summary of state and national policies. Health impacts, educational outcomes and the effects of FASD on vulnerable populations such as children in protection and young people in the justice system, are also discussed. Specific perspectives on why women drink during pregnancy and the role of Aboriginal women in preventing FASD are explored. Recommendations include that there be greater focus on the benefits of involving men in the prevention and management of FASD and that future FASD prevention strategies for Aboriginal and Torres Strait Islander people should be community identified, led, and driven. FASD assessment, treatment and public health programs must also consider the history of trauma incurred by Aboriginal and Torres Strait Islander communities as a result of colonisation. The Review of Fetal Alcohol Spectrum Disorder (FASD) among Aboriginal and Torres Strait Islander people is part of a suite of knowledge exchange products that includes a summary, video, and factsheet

Residential exposure to traffic emissions and adverse pregnancy outcomes

Motor vehicle traffic emissions are the single largest contributor to ambient air pollution in many developed countries and it has been suggested that these emissions can affect outcomes of pregnancy. An individual's exposure experience is greatly influenced by where they live as emission concentrations are much higher closer to roads. A systematic review was conducted using the MOOSE guidelines in order to synthesise studies published 1989-2009 which investigated pregnancy outcomes in relation to residential exposure to traffic emissions. Twelve studies met the inclusion criteria and were consequently reviewed. We identified exposure assessment methods and the scope of health endpoints that have been investigated. Gestational duration, intrauterine growth, mortality and pregnancy complications have been studied using simple distance, distance-weighted traffic density, annually averaged daily traffic counts, dispersion models and land-use regression models. Few studies investigated mortality and pregnancy complications and no study investigated the risk of congenital anomalies. The evidence to date suggests an adverse effect was consistently reported for gestational duration and less consistently reported yet plausible for intrauterine growth. However, the small number of studies, the possibility of publication bias and the limited research conducted on biological mechanisms precluded more formal statements on the existence of an effect. The ubiquity of motor vehicle traffic emissions, the biological vulnerability of the fetus, and the adverse associations detected among many of the twelve reviewed studies motivates a multidisciplinary collaborative effort toward further research on the topic

Are women with major depression in pregnancy identifiable in population health data?

BACKGROUND: Although record linkage of routinely collected health datasets is a valuable research resource, most datasets are established for administrative purposes and not for health outcomes research. In order for meaningful results to be extrapolated to specific populations, the limitations of the data and linkage methodology need to be investigated and clarified. It is the objective of this study to investigate the differences in ascertainment which may arise between a hospital admission dataset and a dispensing claims dataset, using major depression in pregnancy as an example. The safe use of antidepressants in pregnancy is an ongoing issue for clinicians with around 10% of pregnant women suffer from depression. As the birth admission will be the first admission to hospital during their pregnancy for most women, their use of antidepressants, or their depressive condition, may not be revealed to the attending hospital clinicians. This may result in adverse outcomes for the mother and infant. METHODS: Population-based de-identified data were provided from the Western Australian Data Linkage System linking the administrative health records of women with a delivery to related records from the Midwives’ Notification System, the Hospital Morbidity Data System and the national Pharmaceutical Benefits Scheme dataset. The women with depression during their pregnancy were ascertained in two ways: women with dispensing records relating to dispensed antidepressant medicines with an WHO ATC code to the 3rd level, pharmacological subgroup, ‘N06A Antidepressants’; and, women with any hospital admission during pregnancy, including the birth admission, if a comorbidity was recorded relating to depression. RESULTS: From 2002 to 2005, there were 96698 births in WA. At least one antidepressant was dispensed to 4485 (4.6%) pregnant women. There were 3010 (3.1%) women with a comorbidity related to depression recorded on their delivery admission, or other admission to hospital during pregnancy. There were a total of 7495 pregnancies identified by either set of records. Using data linkage, we determined that these records represented 6596 individual pregnancies. Only 899 pregnancies were found in both groups (13.6% of all cases). 80% of women dispensed an antidepressant did not have depression recorded as a comorbidity on their hospital records. A simple capture-recapture calculation suggests the prevalence of depression in this population of pregnant women to be around 16%. CONCLUSION: No single data source is likely to provide a complete health profile for an individual. For women with depression in pregnancy and dispensed antidepressants, the hospital admission data do not adequately capture all cases

Heavy maternal alcohol consumption and cerebral palsy in the offspring

AIM The aim of this study was to investigate the association between heavy maternal alcohol consumption and pre- peri- and postneonatally acquired cerebral palsy (CP). METHOD The records of all mothers with an International Classification of Diseases, revision 9 or 10 (ICD-9 ⁄ -10) alcohol-related diagnostic code, indicating heavy alcohol consumption, recorded on population-based health, mental health, and drug and alcohol data sets from 1983 to 2007, and their children were identified through the Western Australian Data-linkage System. This ‘exposed’ cohort was frequency matched with mothers without an alcohol-related diagnosis and their offspring (comparison group). Cases of CP were identified through linkage with the Western Australia CP Register. Analyses were undertaken using multivariate logistic regression. RESULTS There were 23 573 live births in the exposed group (58.6% non-Aboriginal; 41.4% Aboriginal) and 292 cases of CP. The odds of pre ⁄ perinatally acquired CP were elevated for children of non-Aboriginal mothers with an alcohol-related diagnosis recorded during pregnancy (adjusted odds ratio 3.32; 95% confidence interval [CI] 1.30–8.48) and for Aboriginal children when an alcohol-related diagnosis was recorded up to 12 months before the mother’s pregnancy (adjusted odds ratio 2.49; 95% CI 0.99–6.25). Increased odds of postneonatally acquired CP following any alcohol-related diagnosis were found for non-Aboriginal children (adjusted odds ratio 7.92; 95% CI 2.23–28.14). INTERPRETATION These results suggest that heavy maternal alcohol consumption is a direct cause of pre ⁄ perinatally acquired CP, and an indirect cause of postneonatally acquired CP, in non-Aboriginal children. The lack of an association for Aboriginal children requires further investigation but may be due to under ascertainment of alcohol use disorders during pregnancy and other aetiological pathways

Identification of a selective G1-phase benzimidazolone inhibitor by a senescence-targeted virtual screen using artificial neural networks

Cellular senescence is a barrier to tumorigenesis in normal cells and tumour cells undergo senescence responses to genotoxic stimuli, which is a potential target phenotype for cancer therapy. However, in this setting, mixed-mode responses are common with apoptosis the dominant effect. Hence, more selective senescence inducers are required. Here we report a machine learning-based in silico screen to identify potential senescence agonists. We built profiles of differentially affected biological process networks from expression data obtained under induced telomere dysfunction conditions in colorectal cancer cells and matched these to a panel of 17 protein targets with confirmatory screening data in PubChem. We trained a neural network using 3517 compounds identified as active or inactive against these targets. The resulting classification model was used to screen a virtual library of ~2M lead-like compounds. 147 virtual hits were acquired for validation in growth inhibition and senescence-associated β-galactosidase (SA-β-gal) assays. Among the found hits a benzimidazolone compound, CB-20903630, had low micromolar IC50 for growth inhibition of HCT116 cells and selectively induced SA-β-gal activity in the entire treated cell population without cytotoxicity or apoptosis induction. Growth suppression was mediated by G1 blockade involving increased p21 expression and suppressed cyclin B1, CDK1 and CDC25C. Additionally, the compound inhibited growth of multicellular spheroids and caused severe retardation of population kinetics in long term treatments. Preliminary structure-activity and structure clustering analyses are reported and expression analysis of CB-20903630 against other cell cycle suppressor compounds suggested a PI3K/AKT-inhibitor-like profile in normal cells, with different pathways affected in cancer cells