Childhood Cancer Incidence and Survival in South Australia and the Northern Territory, 1990-2017, with Emphasis on Indigenous Peoples.

BACKGROUND & AIMS: Reports of a rise in childhood cancer incidence in Australia and globally prompted the investigation of cancer incidence and survival in South Australia (SA) and the Northern Territory (NT) over a 28-year period, with emphasis on Indigenous peoples. METHODS: This cross-sectional analysis of two prospective longitudinal databases, the SA and NT Cancer Registries (1990-2017), included all reported cases of childhood cancers. Poisson regression provided estimates of incidence rate ratios and survival was modelled using Cox proportional hazard models for children aged <5 and ≥5 years. RESULTS: A total of 895 patients across SA (N = 753) and the NT (N = 142) were ascertained. Overall and in the NT, childhood cancer incidence was higher in males compared with females (IRR 1.19 [1.04-1.35] and 1.43 [1.02-2.01], respectively). Lymphocytic leukemia was the most reported cancer type across all locations. With reference to the 1990-1999 era (181.67/100,000), cancer incidence remained unchanged across subsequent eras in the combined cohort (SA and NT) (2000-2009: 190.55/100,000; 1.06 [0.91-1.25]; 2010-2017: 210.00/100,000; 1.15 [0.98-1.35]); similar outcomes were reflected in SA and NT cohorts. Cancer incidence amongst non-Indigenous children significantly decreased from the 1990-1999 era (278.32/100,000) to the 2000-2009 era (162.92/100,000; 0.58 [0.35-0.97]). Amongst 39 Indigenous children in the NT, incidence rates remained unchanged across eras (p > 0.05). With reference to the 1990-1999 era, overall survival improved in subsequent eras in SA (2000-2009: HR 0.53 [0.38-0.73]; 2010-2017: 0.44 [0.28-0.68]); however, remained unchanged in the NT (2000-2009: 0.78 [0.40-1.51]; 2010-2017: 0.50 [0.24-1.05]). In the NT, overall survival of Indigenous patients was significantly lower compared with the non-Indigenous cohort (3.42 [1.92-6.10]). While the survival of Indigenous children with cancer significantly improved in the last two eras (p < 0.05), compared to the 1990-1999 era, no change was noted amongst non-Indigenous children in the NT (p > 0.05). CONCLUSIONS: The incidence of childhood cancers has remained unchanged over 28-years in SA and the NT. Encouragingly, improved survival rates over time were observed in SA and amongst Indigenous children of the NT. Nevertheless, survival rates in Indigenous children remain lower than non-Indigenous children.

Small for gestational age and anthropometric body composition from early childhood to adulthood: the Aboriginal Birth Cohort study.

Background: In Australia the estimated rate of small for gestational age (SGA) births is 9% among non-Indigenous births compared to 14% among Aboriginal and Torres Strait Islanders. There is limited research investigating the effect of being born SGA on body composition later in life in Indigenous Australians. Methods: Using data from the Aboriginal Birth Cohort longitudinal study, we compared the body composition of those born SGA to non-SGA by analysing anthropometric measures (height, weight, waist circumference, fat percentage [FAT%], body mass index [BMI], waist-to-height ratio, and A body shape index [ABSI]) collected at four follow-up periods (from childhood to adult). For cross-sectional analyses, linear regression models were employed to assess factors associated with anthropometric measures. For longitudinal analyses linear mixed models were employed to assess differences in anthropometric measures among SGA versus non-SGA individuals while adjusting for repeated measures. Results: The analytic baseline cohort were those who participated in Wave 2 (n = 570). In cross-sectional analyses, across all waves those born SGA had smaller anthropometric z-scores compared to non-SGA individuals (ß ranging from -0.50 to -0.25). Participants residing in urban environments were significantly larger in Waves 2 to 4 (ß ranged 0.26 to 0.65). Those born SGA had higher ABSI scores in Waves 2 and 4 (ß 0.26 and 0.37, respectively). In longitudinal analyses, those born SGA had smaller measures of body composition across the life course; these differences were larger in urban communities. In remote communities those born SGA had significantly higher ABSI scores during adolescence and young adulthood, and this difference was not observed in urban communities. Conclusion: Indigenous Australians born SGA are smaller anthropometrically later in life compared to their non-SGA counterparts. In remote communities, those born SGA had higher levels of central adiposity compared to non-SGA.

Association between perinatal and early life exposures and lung function in Australian Indigenous young adults: The Aboriginal Birth Cohort study.

BACKGROUND AND OBJECTIVE: Despite the high burden of respiratory disease amongst Indigenous populations, prevalence data on spirometric deficits and its determinants are limited. We estimated the prevalence of abnormal spirometry in young Indigenous adults and determined its relationship with perinatal and early life factors. METHODS: We used prospectively collected data from the Australian Aboriginal Birth Cohort, a birth cohort of 686 Indigenous Australian singletons. We calculated the proportion with abnormal spirometry (z-score <-1.64) and FEV1 below the population mean (FEV1 % predicted 0 to -2SD) measured in young adulthood. We evaluated the association between perinatal and early life exposures with spirometry indices using linear regression. RESULTS: Fifty-nine people (39.9%, 95%CI 31.9, 48.2) had abnormal spirometry; 72 (49.3%, 95%CI 40.9, 57.7) had a FEV1 below the population mean. Pre-school hospitalisations for respiratory infections, younger maternal age, being overweight in early childhood and being born remotely were associated with reduced FEV1 and FVC (absolute, %predicted and z-score). The association between maternal age and FEV1 and FVC were stronger in women, as was hospitalization for respiratory infections before age 5. Being born remotely had a stronger association with reduced FEV1 and FVC in men. Participants born in a remote community were over 6 times more likely to have a FEV1 below the population mean (odds ratio [OR] 6.30, 95%CI 1.93, 20.59). CONCLUSION: Young Indigenous adults have a high prevalence of impaired lung function associated with several perinatal and early life factors, some of which are modifiable with feasible interventions.

Aldosterone and renin concentrations and blood pressure in young Indigenous and non-Indigenous adults in the Northern Territory: a cross-sectional study.

OBJECTIVES: To evaluate aldosterone and renin levels and aldosterone-to-renin ratios (ARRs) in young Indigenous and non-Indigenous adults in the Northern Territory, and their association with blood pressure levels. DESIGN: Cross-sectional study; single time point sub-study of two prospective birth cohort studies. SETTING, PARTICIPANTS: Participants in the Aboriginal Birth Cohort (ABC) - born to Indigenous mothers at the Royal Darwin Hospital during 1987-1990 - and the Top End Cohort (TEC) - people born to non-Indigenous mothers in Darwin, recruited during 2007-2009 - aged 32-35 years at the time of this sub-study. MAIN OUTCOME MEASURES: Plasma aldosterone and direct renin concentrations; ARRs (positive screening test result for primary aldosteronism defined as > 70 pmol/mU); systolic and diastolic blood pressure. RESULTS: A total of 255 ABC (205 in remote, 50 in urban locations) and 76 TEC members participated. Median aldosterone concentration was similar for all three groups. The median renin concentration was 7.5 mU/L (interquartile range [IQR], 4.1-12.4 mU/L) in the TEC group, 12.4 mU/L (IQR, 5.1-19 mU/L) in the urban ABC group, and 29.3 mU/L (IQR, 15.0-52.9 mU/L) in the remote ABC group. The median ARR was 10 pmol/mU (IQR, 6-19 pmol/mU) in the remote ABC group, 28 pmol/mU (IQR, 16-70 pmol/mU) in the urban ABC group, and 43 pmol/mU (IQR, 26-74 pmol/mU) in the TEC group. Thirteen urban ABC participants (26%), 21 TEC participants (28%), and six people in the remote ABC group (3%) had ARR values above 70 pmol/mU. Adjusted for age and body mass index (BMI), mean systolic and diastolic blood pressure were lower for women than men in all participant groups; after adjusting for age, sex, and BMI, larger ARR was associated with higher systolic blood pressure in the TEC group but not the two ABC groups. CONCLUSION: Screening test results for primary aldosteronism were positive for about one-quarter of urban Indigenous and non-Indigenous participants. A prospective study that includes confirmatory testing would more accurately assess the prevalence of primary aldosteronism among Indigenous Australians in the Northern Territory.

Birth weight for gestational age and later cardiovascular health: a comparison between longitudinal Finnish and indigenous Australian cohorts.

INTRODUCTION: Small or large birth weight for gestational age has been linked with later cardiovascular disease risk. However, cardiovascular risk markers from childhood to adulthood according to birth weight in diverse longitudinal settings globally have not been extensively studied. OBJECTIVES: To examine the relationship between birth weight and cardiovascular risk profile from childhood until young adulthood in two geographically and socioeconomically distinct cohorts. METHODS: Data were derived from two longitudinal birth cohort studies; one from southern Finland (Special Turku Coronary Risk Factor Intervention Project, STRIP) and one from northern Australia comprising Indigenous Australians (Aboriginal Birth Cohort, ABC). The sample included 747 Finnish participants and 541 Indigenous Australians with data on birth weight, gestational age and cardiovascular risk factors (body mass index [BMI]), waist-to-height ratio [WHtR], lipid profile, blood pressure) collected at ages 11, 18 and 25 or 26 years. Carotid intima-media thickness (cIMT) was assessed at age 18 or 19 years. Participants were categorised according to birth weight for gestational age (small [SGA], appropriate [AGA] or large [LGA]). Associations between birth weight category and cardiovascular risk markers were studied using a repeated measures ANOVA. RESULTS: Higher birth weight category was associated with higher BMI later in life in both cohorts (p=.003 for STRIP and p<.0001 for ABC). In the ABC, higher birth weight category was also associated with higher WHtR (p=.004). In the ABC, SGA participants had lower systolic and diastolic blood pressure than AGA participants (p=.028 for systolic, p=.027 for diastolic) and lower systolic blood pressure than LGA participants (p=.046) at age 25. In the STRIP cohort, SGA participants had lower cIMT than LGA participants (p=.024). CONCLUSIONS: Birth weight can predict future cardiovascular risk profile in diverse populations. Thus, it needs to be included in targeted public health interventions for tackling the obesity pandemic and improving cardiovascular health worldwide.Key messagesThe strongest association between birth weight and later cardiovascular risk profile was manifested as differences in body mass index in two culturally and geographically distinct cohorts.Foetal growth is a determinant for later cardiovascular health in diverse populations, indicating a need to focus on maternal and foetal health to improve cardiovascular health worldwide.

Computerised emotional well-being and substance use questionnaires in young Indigenous and non-Indigenous Australian adults.

BACKGROUND: Mental health disorders rank among the most substantial causes of morbidity and mortality worldwide. Almost half of Australian adults experience mental illness at some point in their lifetime, with Indigenous Australians disproportionally affected. Thus, it is imperative that effective, acceptable screening tools are used, which are tailored to the target population. OBJECTIVES: This research investigates the methodology of computerised questionnaires in assessing the emotional well-being and substance use in Indigenous and non-Indigenous young adults. METHODS: Cross-sectional data from young adults (21-28 years) in the Life Course Program, Northern Territory, Australia, are presented. Through an extensive consultation process, validated questionnaires were adapted to a computerised format suitable for both remote and urban residing Indigenous and non-Indigenous adults. RESULTS: Of the 576 participants (459 Indigenous, 117 non-Indigenous) available for assessment, high consent rates were seen, with completion rates >86%. One in three young adults in this cohort were highlighted as 'at risk' of psychological distress, and one in five as 'at risk' of suicidal ideation or self-harm. CONCLUSION: The target population of this study were at a critical age with high levels of psychological distress and suicidal ideation reported, particularly in Indigenous young adults. This simple, user-friendly, pictorial programme allowed assessment of a sensitive topic anonymously, while simultaneously collating data and identifying those at high risk, irrespective of literacy level or cultural background.

Fingernail cortisol as a marker of chronic stress exposure in Indigenous and non-Indigenous young adults.

Cumulative exposure to stress over a long period can negatively impact an individual's health. Significant advancements in biomarkers of chronic stress have been made, with the use of fingernails recently explored. Cross sectional data from the Australian Aboriginal Birth Cohort (Indigenous) and Top End Cohort (non-Indigenous) were used to investigate the associations (sociodemographic and emotional) of fingernail cortisol in Indigenous and non-Indigenous young adults. Details on sociodemographic (age, gender, and Indigenous identification), smoking and alcohol use, emotional wellbeing, and emotional stress (perceived stress and stressful events), and fingernail samples were obtained face-to-face. Fingernail samples were analyzed for 179 Indigenous and 66 non-Indigenous participants (21-28 years). Indigenous participants were subjected to higher rates of stressful events compared to non-Indigenous (Median 6.0; interquartile range (IQR) 4, 9 vs. 1.0; IQR 0, 2; p < .001). Median cortisol levels were similar between Indigenous and non-Indigenous participants (4.36 pg/mg; IQR 2.2, 10.0 vs. 3.87 pg/mg: IQR 2.0, 9.7; p = .68). However, Indigenous participants had a higher cortisol level on adjustment for emotional distress and exposure to stressful events (Geometric Mean 1.82; 95CI: 1.07-3.09), with a negative association with increasing number of stressful events (Geometric Mean 0.94; 95CI 0.90, 0.99). Collection of fingernails was an easily conducted, well-tolerated method to measure stress markers in this multicultural cohort. Indigenous young adults experienced a high number of stressful events which was associated with a lowering of fingernail cortisol levels.Lay abstractChronic stress can impact negatively on health and emotional wellbeing. A fingernail sample provided a culturally acceptable, noninvasive method of measuring chronic stress in Indigenous and non-Indigenous young adults. Cortisol levels, a marker of chronic stress, were different between Indigenous and non-Indigenous young adults and were influenced by emotional status and occurrence of multiple stressful events.

Renal dysfunction is already evident within the first month of life in Australian Indigenous infants born preterm.

Antecedents of the high rates of chronic kidney disease in Australian Indigenous peoples may originate early in life. Fourteen percent of Australian Indigenous infants are born preterm (under 37 weeks gestation) and, therefore, at risk. Here, our observational cohort study sought to determine the impact of preterm birth on renal function in Australian Indigenous and non-Indigenous infants. Renal function was assessed between 4-29 days postnatally in 60 Indigenous and 42 non-Indigenous infants born at 24-36 weeks gestation. Indigenous ethnicity was associated with impaired renal function, with significantly higher serum creatinine (geometric mean ratio (GMR) 1.15 [1.06, 1.25]), fractional excretion of sodium (GMR 1.21 [1.04, 1.39]), and urine albumin (GMR 1.57 [1.05, 2.34]), ß-2 microglobulin (GMR 1.82 [1.11, 2.98]) and cystatin C (GMR 3.27 [1.54, 6.95]) when controlling for gestational/postnatal age, sex and birth weight Z-score. Renal injury, as indicated by high urine neutrophil gelatinase-associated lipocalin levels, was associated with maternal smoking and postnatal antibiotic exposure. Indigenous infants appeared to be most susceptible to the adverse impact of antibiotics. These findings show that preterm Australian Indigenous infants are highly vulnerable to renal dysfunction. Preterm birth may contribute to their increased risk of chronic kidney disease. Thus, we recommended that renal function should be closely monitored life-long in Indigenous children born preterm.

The Australian Aboriginal Birth Cohort study: socio-economic status at birth and cardiovascular risk factors to 25 years of age.

OBJECTIVES: To determine whether socio-economic status at birth is associated with differences in risk factors for cardiovascular disease - body mass index (BMI), blood pressure, blood lipid levels - during the first 25 years of life. DESIGN: Analysis of prospectively collected data. SETTING, PARTICIPANTS: 570 of 686 children born to Aboriginal mothers at the Royal Darwin Hospital during 1987-1990 and recruited for the Aboriginal Birth Cohort Study in the Northern Territory. Participants resided in 46 urban and remote communities across the NT. The analysed data were collected at three follow-ups: Wave 2 in 1998-2001 (570 participants; mean age, 11 years), Wave 3 in 2006-2008 (442 participants; mean age, 18 years), and Wave 4 in 2014-2016 (423 participants; mean age, 25 years). MAIN OUTCOME MEASURES: Cardiovascular disease risk factors by study wave and three socio-economic measures at the time of birth: area-level Indigenous Relative Socioeconomic Outcomes (IRSEO) index score and location (urban, remote) of residence, and parity of mother. RESULTS: Area-level IRSEO of residence at birth influenced BMI (P < 0.001), systolic blood pressure (P = 0.024), LDL-cholesterol (P = 0.010), and HDL-cholesterol levels (P < 0.001). Remoteness of residence at birth influenced BMI (P < 0.001), HDL-cholesterol (P < 0.001), and triglyceride levels (P = 0.043). Mother's parity at birth influenced BMI (P = 0.039). CONCLUSIONS: Our longitudinal life course analyses indicate that area-level socio-economic factors at birth influence the prevalence of major cardiovascular disease risk factors among Indigenous Australians during childhood and early adulthood.

Iodine status of Indigenous and non-Indigenous young adults in the Top End, before and after mandatory fortification.

OBJECTIVE: To assess the median urine iodine concentration (UIC) of young adults in the Top End of Northern Territory, before and after fortification of bread with iodised salt became mandatory. DESIGN, SETTING: Analysis of cross-sectional data from two longitudinal studies, the Aboriginal Birth Cohort and the non-Indigenous Top End Cohort, pre- (Indigenous participants: 2006-2007; non-Indigenous participants: 2007-2009) and post-fortification (2013-15). PARTICIPANTS: Indigenous and non-Indigenous Australian young adults (mean age: pre-fortification, 17.9 years (standard deviation [SD], 1.20 years); post-fortification, 24.9 years (SD, 1.34 years). MAIN OUTCOME MEASURE: Median UIC (spot urine samples analysed by a reference laboratory), by Indigenous status, remoteness of residence, and sex. RESULTS: Among the 368 participants assessed both pre- and post-fortification, the median UIC increased from 58 µg/L (interquartile range [IQR], 35-83 µg/L) pre-fortification to 101 µg/L (IQR, 66-163 µg/L) post-fortification (P < 0.001). Urban Indigenous (median IUC, 127 µg/L; IQR, 94-203 µg/L) and non-Indigenous adults (117 µg/L; IQR, 65-160 µg/L) were both iodine-replete post-fortification. The median UIC of remote Indigenous residents increased from 53 µg/L (IQR, 28-75 µg/L) to 94 µg/L (IQR, 63-152 µg/L; p < 0.001); that is, still mildly iodine-deficient. The pre-fortification median UIC for 22 pregnant women was 48 µg/L (IQR, 36-67 µg/L), the post-fortification median UIC for 24 pregnant women 93 µg/L (IQR, 62-171 µg/L); both values were considerably lower than the recommended minimum of 150 µg/L for pregnant women. CONCLUSIONS: The median UIC of young NT adults increased following mandatory fortification of bread with iodised salt. The median UIC of pregnant Indigenous women in remote locations, however, remains low, and targeted interventions are needed to ensure healthy fetal development.

Hair cortisol and cortisone as markers of stress in Indigenous and non-Indigenous young adults.

Chronic, ongoing stress can impact negatively on health and wellbeing. Indigenous Australians are at an increased risk of experiencing multiple stressors. Hair glucocorticoids have been used as a marker for chronic stress. This study aimed to assess the associations of hair cortisol and cortisone with sociodemographic (age, gender, Indigenous Identification), substance use, emotional wellbeing, and emotional stress, in a cohort at increased risk of stressful events and psychological distress. Cross-sectional data (age 21-28 years) are presented from two Australian longitudinal studies; the Aboriginal Birth Cohort (n = 253) and non-Indigenous Top End Cohort (n = 72). A third of the cohort reported psychological distress, with Indigenous participants reporting higher rates of stressful events compared to non-Indigenous (6 vs. 1; p < .001). Significantly higher levels of cortisone were seen in Indigenous women compared to non-Indigenous women (ß 0.21; p = .003). A positive association with age was present in hair cortisol and cortisone in Indigenous young adults (ß 0.29 and ß 0.41; p < .001, respectively). No association with substance use, emotional wellbeing or emotional stress was seen. Sub-analysis in women suggested a possible curvilinear relationship between hair cortisone and the number of stressful events. In this culturally diverse cohort, hair sampling provides a noninvasive, easily conducted and generally well tolerated mechanism to measure stress markers. The association with age, even in this narrow age range, likely represents the manifold changes in circumstances (financial independence, becoming parents, increased risk of substance use and mental illness) that occur during this transitional period of life, particularly for young Indigenous women. LAY ABSTRACT Chronic stress can impact negatively on health and emotional wellbeing. A hair sample is an easy way to measure chronic stress in Indigenous and non-Indigenous young people. The markers of chronic stress, cortisol and cortisone, were different between Indigenous and non-Indigenous, men and women and increased with age in Indigenous young adults.

Sub-optimal protection against past hepatitis B virus infection where subtype mismatch exists between vaccine and circulating viral genotype in northern Australia.

BACKGROUND: In Australia's Northern Territory, the hepatitis B virus (HBV) subgenotype A2 (subtype adw2) vaccine was introduced in 1988 for Indigenous infants. Subsequently, the circulating viral genotype has been identified as subgenotype C4 (subtype ayw3). We assessed HBV vaccine effectiveness (VE) in light of this subtype mismatch. METHODS: Participants of the Aboriginal Birth Cohort (ABC) study were recruited at birth (1987-1990), with HBV serology obtained at follow-up waves 3 (2005-2007) and 4 (2013-2015). Participants were immune if HBV surface antibody levels exceeded 10 IU/L. We determined the VE against any HBV infection (anti-HBc+) and against chronic infection (HBsAg+ or HBV DNA+), comparing non-vaccinated participants with those fulfilling United States Centers for Disease Control and Prevention (CDC) criteria for full HBV immunisation. RESULTS: Of 686 participants in the ABC study, we obtained HBV serology from 388 at wave 4. 181 participants were immune to HBV and 97 had evidence of any infection. Seven participants were chronically infected, of whom five had received three vaccine doses, and anti-HBc seroconversion had occurred subsequent to the three vaccine doses for two of these seven participants. Comparing the 107 participants who had been vaccinated in accordance with CDC recommendations and 127 who had not been vaccinated, VE against any infection was 67% (95%CI, 43-104%). The odds of being anti-HBc+ was 87% lower in participants raised in urban settings compared to those born into families from remote areas (OR, 0.1; 95%CI, 0.03-0.4). CONCLUSIONS: In a setting where there exists a subtype mismatch between vaccine and circulating genotype, the vaccine was largely effective in preventing chronic infection but sub-optimal against any infection. The implications of a high prevalence of anti-HBc seropositivity in this population are unclear and require further study. The fact that anti-HBc seropositivity was strongly associated with remote dwelling suggests ongoing viral exposure in remote settings.

Indigenous Australian household structure: a simple data collection tool and implications for close contact transmission of communicable diseases.

Households are an important location for the transmission of communicable diseases. Social contact between household members is typically more frequent, of greater intensity, and is more likely to involve people of different age groups than contact occurring in the general community. Understanding household structure in different populations is therefore fundamental to explaining patterns of disease transmission in these populations. Indigenous populations in Australia tend to live in larger households than non-Indigenous populations, but limited data are available on the structure of these households, and how they differ between remote and urban communities. We have developed a novel approach to the collection of household structure data, suitable for use in a variety of contexts, which provides a detailed view of age, gender, and room occupancy patterns in remote and urban Australian Indigenous households. Here we report analysis of data collected using this tool, which quantifies the extent of crowding in Indigenous households, particularly in remote areas. We use these data to generate matrices of age-specific contact rates, as used by mathematical models of infectious disease transmission. To demonstrate the impact of household structure, we use a mathematical model to simulate an influenza-like illness in different populations. Our simulations suggest that outbreaks in remote populations are likely to spread more rapidly and to a greater extent than outbreaks in non-Indigenous populations.

Examining the Effects of Ambient Temperature on Pre-Term Birth in Central Australia.

Preterm birth (born before 37 completed weeks of gestation) is one of the leading causes of death among children under 5 years of age. Several recent studies have examined the association between extreme temperature and preterm births, but there have been almost no such studies in arid Australia. In this paper, we explore the potential association between exposures to extreme temperatures during the last 3 weeks of pregnancy in a Central Australian town. An immediate effect of temperature exposure is observed with an increased relative risk of 1%-2% when the maximum temperature exceeded the 90th percentile of the summer season maximum temperature data. Delayed effects are also observed closer to 3 weeks before delivery when the relative risks tend to increase exponentially. Immediate risks to preterm birth are also observed for cold temperature exposures (0 to -6 °C), with an increased relative risk of up to 10%. In the future, Central Australia will face more hot days and less cold days due to climate change and hence the risks posed by extreme heat is of particular relevance to the community and health practitioners.

The influence of birthweight, past poststreptococcal glomerulonephritis and current body mass index on levels of albuminuria in young adults: the multideterminant model of renal disease in a remote Australian Aboriginal population with high rates of renal disease and renal failure.

BACKGROUND: Australian Aborigines in remote areas have very high rates of kidney disease, which is marked by albuminuria. We describe a 'multihit' model of albuminuria in young adults in one remote Aboriginal community. METHODS: Urinary albumin/creatinine ratios (ACRs) were measured in 655 subjects aged 15-39 years and evaluated in the context of birthweights, a history of 'remote' poststreptococcal glomerulonephritis (PSGN; ≥5 years earlier) and current body mass index (BMI). Birthweight had been <2.5 kg (low birthweight, LBW) in 25.4% of subjects and 22.8% had a remote history of PSGN. RESULTS: ACR levels rose with age. It exceeded the microalbuminuria threshold in 33.6% of subjects overall (25% of males and 45% of females). In multivariate models, birthweight (inversely), remote PSGN and current BMI were all independent predictors of ACR levels. The effects of birthweight and PSGN and their combination were expressed through amplification of ACR levels in relation to age and around the group median BMI of 20.8 kg/m(2). In people with BMI <20.8 (57.8% of all males and 40.3% of the females), LBW and PSGN alone had minimal effects on ACR, but in combination they strikingly amplified ACR in relation to age. Those with BMI ≥20.8 (which included 42.2% of the males and 59.7% of the females) had higher ACR levels, and both LBW and a PSGN history, separately and in combination, were associated with striking further amplification of ACR in the context of age. CONCLUSION: Much of the great excess of disease in this population is explained by high rates of the early life risk factors, LBW and PSGN. Their effects are expressed through amplification of ACR in the context of increasing age and are further moderated by levels of current body size. Both early life risk factors are potentially modifiable.

Childhood metabolic syndrome, inflammation and carotid intima-media thickness. The Aboriginal Birth Cohort Study.

BACKGROUND/OBJECTIVES: We evaluated whether atherosclerotic changes associated with MetS in Australian Aboriginals are reversible in childhood. In addition, we investigated whether heightened inflammation is mediating the adverse effects of MetS. METHODS: The study cohort comprised of 351 children from the Aboriginal Birth Cohort Study (a longitudinal study based in the Northern Territory of Australia) aged 9-13 years at baseline examination who were followed up 6 years later. MetS was defined by at least three of the following parameters within the extreme sex- and age-specific quartile: highest quartile for waist circumference, blood pressure, triglycerides, and glucose, and lowest quartile for HDL-cholesterol. Carotid intima-media thickness (IMT) and C-reactive protein (CRP) were assessed at follow-up. RESULTS: Individuals with MetS at baseline or follow-up had increased carotid IMT at follow-up (mean ± SEM 539 ± 3 vs. 561 ± 8 µm, P=0.007; and 537 ± 3 vs. 567 ± 8 µm, P<0.0001 respectively). In combined analyses from baseline and follow-up studies, those individuals with MetS only at baseline had partially improved vascular status; their IMT was not significantly increased compared to those without MetS at both time-points (534 ± 3 vs. 550 ± 10 µm, P=0.09). At the follow-up examination, MetS status was associated with increased IMT levels only among individuals with CRP levels above the median (≥ 2.1mg/l) (536 ± 5 vs. 573 ± 9 µm, P<0.0001, P for interaction 0.01). CONCLUSIONS: MetS in childhood is associated with subclinical atherosclerosis in an Australian Aboriginal population and the effects appear to be mediated by increased inflammation. The extent of atherosclerosis was partially reduced if metabolic status improved during the follow-up.

Pathways between birth weight and later body size in predicting blood pressure: Australian Aboriginal Cohort Study 1987-2007.

BACKGROUND: Although a large number of previous studies suggest an association between birth weight and later blood pressure, others do not. Controversy surrounds the relative importance of these associations, in particular in relation to more modifiable factors in later life and whether the association would be seen in a, relatively disadvantaged, Indigenous population. The aim of this study, within the Aboriginal Birth Cohort study, was to examine the relative contributions and mediating pathways of birth weight, and later growth and lifestyle factors to variation in blood pressure at age 16-20 years. METHODS: Detailed information was collected prospectively, including maternal smoking, birth weight, childhood BMI. At age 16-20 years, 451 underwent clinical examination, including the measurement of diastolic and systolic blood pressures. These data were analyzed using linear regression and path analyses, incorporating adjustment for potential confounders. RESULTS: Increased BMI at age 18 years was significantly associated with both increasing systolic and diastolic blood pressures. BMI had the highest relative importance and mediated the effects from earlier in life, including birth weight. Being female and living in remote residence were also independently associated with a reduction in systolic blood pressure. CONCLUSION: Blood pressure in this cohort is primarily influenced by contemporaneous BMI, which in this population at this age is generally lower than that seen in non-Indigenous populations in developed countries. However, other factors, including birth weight, do appear to play a role that is mediated through later BMI.

Challenges and strategies for cohort retention and data collection in an indigenous population: Australian Aboriginal Birth Cohort.

BACKGROUND: Longitudinal prospective birth cohort studies are pivotal to identifying fundamental causes and determinants of disease and health over the life course. There is limited information about the challenges, retention, and collection strategies in the study of Indigenous populations. The aim is to describe the follow-up rates of an Australian Aboriginal Birth Cohort study and how they were achieved. METHODS: Participants were 686 babies enrolled between January 1987 and March 1990, born to a mother recorded in the Delivery Suite Register of the Royal Darwin Hospital (RDH) as a self-identified Aboriginal. The majority of the participants (70%) resided in Northern Territory within rural, remote and very remote Aboriginal communities that maintain traditional connections to their land and culture. The Aboriginal communities are within a sparsely populated (0.2 people/ km2) area of approximately 900,000 km² (347 sq miles), with poor communication and transport infrastructures. Follow-ups collecting biomedical and lifestyle data directly from participants in over 40 locations were conducted at 11.4 years (Wave-2) and 18.2 years (Wave-3), with Wave-4 follow-up currently underway. RESULTS: Follow-ups at 11 and 18 years of age successfully examined 86% and 72% of living participants respectively. Strategies addressing logistic, cultural and ethical challenges are documented. CONCLUSIONS: Satisfactory follow-up rates of a prospective longitudinal Indigenous birth cohort with traditional characteristics are possible while maintaining scientific rigor in a challenging setting. Approaches included flexibility, respect, and transparent communication along with the adoption of culturally sensitive behaviours. This work should inform and assist researchers undertaking or planning similar studies in Indigenous and developing populations.