Association between maternal hyperglycemia in pregnancy and offspring anthropometry in early childhood: the pandora wave 1 study.

BACKGROUND: In-utero hyperglycemia exposure influences later cardiometabolic risk, although few studies include women with pre-existing type 2 diabetes (T2D) or assess maternal body mass index (BMI) as a potential confounder. OBJECTIVE: To explore the association of maternal T2D and gestational diabetes mellitus (GDM) with childhood anthropometry, and the influence of maternal BMI on these associations. METHODS: The PANDORA cohort comprises women (n = 1138) and children (n = 1163). Women with GDM and T2D were recruited from a hyperglycemia in pregnancy register, and women with normoglycemia from the community. Wave 1 follow-up included 423 children, aged 1.5-5 years (median follow-up age 2.5 years). Multivariable linear regression assessed associations between maternal antenatal variables, including BMI and glycemic status, with offspring anthropometry (weight, height, BMI, skinfold thicknesses, waist, arm and head circumferences). RESULTS: Greater maternal antenatal BMI was associated with increased anthropometric measures in offspring independent of maternal glycemic status. After adjustment, including for maternal BMI, children exposed to maternal GDM had lower mean weight (-0.54 kg, 95% CI: -0.99, -0.11), BMI (-0.55 kg/m2, 95% CI: -0.91, -0.20), head (-0.52 cm, 95% CI: -0.88, -0.16) and mid-upper arm (-0.32 cm, 95% CI: -0.63, -0.01) circumferences, and greater mean suprailiac skinfold (0.78 mm, 95% CI: 0.13, 1.43), compared to children exposed to normoglycemia. Adjustment for maternal BMI strengthened the negative association between GDM and child weight, BMI and circumferences. Children exposed to maternal T2D had smaller mean head circumference (-0.82 cm, 95% CI: -1.33, -0.31) than children exposed to normoglycemia. Maternal T2D was no longer associated with greater child mean skinfolds (p = 0.14) or waist circumference (p = 0.18) after adjustment for maternal BMI. CONCLUSIONS: Children exposed to GDM had greater suprailiac skinfold thickness than unexposed children, despite having lower mean weight, BMI and mid-upper arm circumference, and both GDM and T2D were associated with smaller mean head circumference. Future research should assess whether childhood anthropometric differences influence lifetime cardiometabolic and neurodevelopmental risk.

Postpartum uptake of diabetes screening tests in women with gestational diabetes: The PANDORA study.

AIMS: To determine rates and predictors of postpartum diabetes screening among Aboriginal and/or Torres Strait Islander and non-Indigenous women with gestational diabetes mellitus (GDM). METHODS: PANDORA is a prospective longitudinal cohort of women recruited in pregnancy. Postpartum diabetes screening rates at 12 weeks (75-g oral glucose tolerance test (OGTT)) and 6, 12 and 18 months (OGTT, glycated haemoglobin [HbA1C ] or fasting plasma glucose) were assessed for women with GDM (n = 712). Associations between antenatal factors and screening with any test (OGTT, HbA1C , fasting plasma glucose) by 6 months postpartum were examined using Cox proportional hazards regression. RESULTS: Postpartum screening rates with an OGTT by 12 weeks and 6 months postpartum were lower among Aboriginal and/or Torres Strait Islander women than non-Indigenous women (18% vs. 30% at 12 weeks, and 23% vs. 37% at 6 months, p < 0.001). Aboriginal and/or Torres Strait Islander women were more likely to have completed a 6-month HbA1C compared to non-Indigenous women (16% vs. 2%, p < 0.001). Screening by 6 months postpartum with any test was 41% for Aboriginal and/or Torres Strait Islander women and 45% for non-Indigenous women (p = 0.304). Characteristics associated with higher screening rates with any test by 6 months postpartum included, insulin use in pregnancy, first pregnancy, not smoking and lower BMI. CONCLUSIONS: Given very high rates of type 2 diabetes among Aboriginal and Torres Strait Islander women, early postpartum screening with the most feasible test should be prioritised to detect prediabetes and diabetes for intervention.

Association between hyperglycaemia in pregnancy and growth of offspring in early childhood: The PANDORA study.

BACKGROUND: Few studies have assessed whether children exposed to in utero hyperglycaemia experience different growth trajectories compared to unexposed children. OBJECTIVES: To assess association of type 2 diabetes (T2D) and gestational diabetes mellitus (GDM) with early childhood weight, length/height and body mass index (BMI) trajectories, and with timing and magnitude of peak BMI in infancy. METHODS: PANDORA is a birth cohort recruited from an Australian hyperglycaemia in pregnancy register, and women with normoglycaemia recruited from the community. Offspring growth measures were obtained from health records over a median follow-up of 3.0 years (interquartile range 1.9-4.0). This analysis included children born to Aboriginal mothers with in utero normoglycaemia (n = 95), GDM (n = 228) or T2D (n = 131). Growth trajectories (weight, length/height and BMI) were estimated using linear mixed models with cubic spline functions of child age. RESULTS: After adjustment for maternal factors (age, BMI, parity, smoking, and socioeconomic measures) and child factors (age, gestational age at birth, and sex), children born to mothers with T2D or GDM had lower weight, length/height and BMI trajectories in infancy than children born to mothers with normoglycaemia, but similar weight and BMI by completion of follow-up. Children exposed to T2D had lower mean peak BMI 17.6 kg/m2 (95% confidence interval [CI] 17.3-18.0) than children exposed to normoglycaemia (18.6 kg/m2 [18.1-18.9]) (p = 0.001). CONCLUSIONS: Maternal hyperglycaemia was associated with differences in early childhood growth trajectories after adjustment for maternal BMI. Exploration of associations between in utero hyperglycaemia exposure and growth trajectories into later childhood is required.

Hyperglycemia in pregnancy and developmental outcomes in children at 18-60 months of age: the PANDORA Wave 1 study.

This study aimed to explore the association between hyperglycemia in pregnancy (type 2 diabetes (T2D) and gestational diabetes mellitus (GDM)) and child developmental risk in Europid and Aboriginal women.PANDORA is a longitudinal birth cohort recruited from a hyperglycemia in pregnancy register, and from normoglycemic women in antenatal clinics. The Wave 1 substudy included 308 children who completed developmental and behavioral screening between age 18 and 60 months. Developmental risk was assessed using the Ages and Stages Questionnaire (ASQ) or equivalent modified ASQ for use with Aboriginal children. Emotional and behavioral risk was assessed using the Strengths and Difficulties Questionnaire. Multivariable logistic regression was used to assess the association between developmental scores and explanatory variables, including maternal T2D in pregnancy or GDM.After adjustment for ethnicity, maternal and child variables, and socioeconomic measures, maternal hyperglycemia was associated with increased developmental "concern" (defined as score ≥1 SD below mean) in the fine motor (T2D odds ratio (OR) 5.30, 95% CI 1.77-15.80; GDM OR 3.96, 95% CI 1.55-10.11) and problem-solving (T2D OR 2.71, 95% CI 1.05-6.98; GDM OR 2.54, 95% CI 1.17-5.54) domains, as well as increased "risk" (score ≥2 SD below mean) in at least one domain (T2D OR 5.33, 95% CI 1.85-15.39; GDM OR 4.86, 95% CI 1.95-12.10). Higher maternal education was associated with reduced concern in the problem-solving domain (OR 0.27, 95% CI 0.11-0.69) after adjustment for maternal hyperglycemia.Maternal hyperglycemia is associated with increased developmental concern and may be a potential target for intervention so as to optimize developmental trajectories.

0.1-5 MHz ultrahigh-speed gas density distributions using digital holographic interferometry.

Gas density distributions for an underexpanded jet at several different pressure ratios were measured at ultrahigh speeds in this work using digital holographic interferometry (DHI). DHI measurements have generally been performed on the order of several Hz in the literature, although some recent groups report measurements at 10 and 100 kHz. We demonstrate 2D imaging of gas density distributions at imaging rates up to 5 MHz, which is an increase by a factor of 50 compared to the previous DHI literature. A narrow-linewidth, continuous-wave laser was used in a Mach-Zehnder configuration, and the holograms were recorded using one of two different CMOS cameras. The interferograms were analyzed using the Fourier method, and a phase unwrapping was performed. Axisymmetric flow was assumed for the region near the nozzle exit, and an Abel inversion was performed to generate a planar-slice gas density distribution from the line-of-sight unwrapped phase. The challenges and opportunities associated with performing DHI measurements at ultrahigh speeds are discussed.

Gestational diabetes is associated with postpartum hemorrhage in Indigenous Australian women in the PANDORA study: A prospective cohort.

OBJECTIVE: To assess associations of hyperglycemia in pregnancy with the risk of postpartum hemorrhage (PPH) in a prospective cohort of Indigenous and non-Indigenous women, compared with normoglycemia. METHODS: Data were from 1102 (48% Indigenous) women of the Pregnancy And Neonatal Diabetes Outcomes in Remote Australia (PANDORA) Study. Age-adjusted associations of gestational diabetes mellitus (GDM) or pre-existing type 2 diabetes mellitus (T2DM), obstetric and demographic covariables with PPH (blood loss ≥500 ml) were assessed using logistic regression. Multivariable-adjusted models included Indigenous ethnicity, diabetes type and their interaction. RESULTS: A higher proportion of Indigenous women developed PPH than non-Indigenous women (32% versus 22%; P < 0.001). Compared with non-Indigenous women with normoglycemia, risks of PPH for Indigenous women with GDM or T2DM were higher (odds ratio [OR] 1.83, 95% confidence intervals [CI] 1.11-3.02, and OR 1.72, 95% CI 0.99-3.00 after age adjustment, OR 1.84, 95% CI 1.06-3.19, and OR 1.33, 95% CI 0.70-2.54 after adjustment for school education and delivery mode, and OR 1.62, 95% CI 0.95-2.77, and OR 0.99, 95% CI 0.53-1.86 after adjustment for birth weight). Importantly, Indigenous women without hyperglycemia in pregnancy were not at increased risk of PPH. CONCLUSION: The significantly higher rates of PPH experienced by Indigenous women compared with non-Indigenous women may be explained by a greater effect of GDM among Indigenous women that was only partly accounted for by birth weight.

Femtosecond laser activation and sensing of hydroxyl for velocimetry in reacting flows.

A molecular tagging method for velocity measurements in reacting environments such as propulsion devices and high-temperature combustion-assisted wind tunnels is described. The method employs a femtosecond (write) laser to photodissociate H2O, a common combustion product, into a locally high concentration of OH radicals. These radicals are tracked by planar laser-induced fluorescence (PLIF) from the A2Σ-X2Π (1-0) vibrational band excited by a time-delayed 284 nm (read) laser sheet. As a variant of hydroxyl tagging velocimetry, the source laser can also be used to dissociate nitrogen for femtosecond laser electronic excitation tagging velocimetry to mark the time-zero location of the write laser for velocimetry in non-reacting regions using the same imaging system without OH PLIF. The OH tracer lifetime is studied in a hydrogen-air Hencken burner operating at Φ=0.5-1.8 to evaluate the tracking capability for velocimetry over a range of conditions. Effects of changing read laser wavelength, excitation energy, and influence of background flame emission are also studied. The data processing methodology and results are described for tracking displacements with 9-25 µm uncertainty in a hydrogen diffusion flame. This method presents several advantages in operational convenience and availability of laser sources, and it provides an avenue for improvements in the repetition rate, precision, and applicability over previously demonstrated hydroxyl tagging schemes.

Quantitative evaluation of an outreach case management model of care for urban Aboriginal and Torres Strait Islander adults living with complex chronic disease: a longitudinal study.

BACKGROUND: Chronic diseases are the leading contributor to the excess morbidity and mortality burden experienced by Aboriginal and Torres Strait Islander (hereafter, respectfully, Indigenous) people, compared to their non-Indigenous counterparts. The Home-based Outreach case Management of chronic disease Exploratory (HOME) Study provided person-centred, multidisciplinary care for Indigenous people with chronic disease. This model of care, aligned to Indigenous peoples' conceptions of health and wellbeing, was integrated within an urban Indigenous primary health care service. We aimed to determine the impact of this model of care on participants' health and wellbeing at 12 months. METHODS: HOME Study participants were Indigenous, regular patients of the primary health care service, with a diagnosis of at least one chronic disease, and complex health and social care needs. Data were collected directly from participants and from their medical records at baseline, and 3, 6 and 12 months thereafter. Variables included self-rated health status, depression, utilisation of health services, and key clinical outcomes. Participants' baseline characteristics were described using frequencies and percentages. Generalized estimating equation (GEE) models were employed to evaluate participant attrition and changes in outcome measures over time. RESULTS: 60 participants were enrolled into the study and 37 (62%) completed the 12-month assessment. After receiving outreach case management for 12 months, 73% of participants had good, very good or excellent self-rated health status compared with 33% at baseline (p < 0.001) and 19% of participants had depression compared with 44% at baseline (p = 0.03). Significant increases in appointments with allied health professionals (p < 0.001) and medical specialists other than general practitioners (p = 0.001) were observed at 12-months compared with baseline rates. Mean systolic blood pressure decreased over time (p = 0.02), but there were no significant changes in mean HbA1c, body mass index, or diastolic blood pressure. CONCLUSIONS: The HOME Study model of care was predicated on a holistic conception of health and aimed to address participants' health and social care needs. The positive changes in self-rated health and rates of depression evinced that this aim was met, and that participants received the necessary care to support and improve their health and wellbeing.

Associations of gestational diabetes and type 2 diabetes during pregnancy with breastfeeding at hospital discharge and up to 6 months: the PANDORA study.

AIMS/HYPOTHESIS: Women with gestational diabetes mellitus (GDM) and obesity experience lower rates of breastfeeding. Little is known about breastfeeding among mothers with type 2 diabetes. Australian Indigenous women have a high prevalence of type 2 diabetes in pregnancy. We aimed to evaluate the association of hyperglycaemia, including type 2 diabetes, with breastfeeding outcomes. METHODS: Indigenous (n = 495) and non-Indigenous (n = 555) participants of the Pregnancy And Neonatal Diabetes Outcomes in Remote Australia (PANDORA) cohort included women without hyperglycaemia in pregnancy (n = 222), with GDM (n = 684) and with type 2 diabetes (n = 144). The associations of hyperglycaemia in pregnancy and breastfeeding at hospital discharge, 6 weeks and 6 months post-partum were evaluated with logistic regression, after adjustment for maternal obesity, ethnicity, maternal and neonatal characteristics. RESULTS: Indigenous women were more likely to predominantly breastfeed at 6 weeks across all levels of hyperglycaemia. Compared with women with no hyperglycaemia in pregnancy, women with type 2 diabetes had lower odds for exclusive breastfeeding at discharge (adjusted OR for exclusive breastfeeding 0.4 [95% CI 0.2, 0.8] p = 0.006). At 6 weeks and 6 months, the relationship between type 2 diabetes and predominant breastfeeding was not statistically significant (6 weeks 0.7 [0.3, 1.6] p = 0.40, 6 months 0.8 [0.4, 1.6] p = 0.60). Women with gestational diabetes were as likely to achieve predominant breastfeeding at 6 weeks and 6 months as women without hyperglycaemia in pregnancy. CONCLUSIONS/INTERPRETATION: Indigenous women had high rates of breastfeeding. Women with type 2 diabetes had difficulty establishing exclusive breastfeeding at hospital discharge. Further research is needed to assess the impact on long-term breastfeeding outcomes. Graphical abstract.

Equitable Expanded Carrier Screening Needs Indigenous Clinical and Population Genomic Data.

Expanded carrier screening (ECS) for recessive monogenic diseases requires prior knowledge of genomic variation, including DNA variants that cause disease. The composition of pathogenic variants differs greatly among human populations, but historically, research about monogenic diseases has focused mainly on people with European ancestry. By comparison, less is known about pathogenic DNA variants in people from other parts of the world. Consequently, inclusion of currently underrepresented Indigenous and other minority population groups in genomic research is essential to enable equitable outcomes in ECS and other areas of genomic medicine. Here, we discuss this issue in relation to the implementation of ECS in Australia, which is currently being evaluated as part of the national Government's Genomics Health Futures Mission. We argue that significant effort is required to build an evidence base and genomic reference data so that ECS can bring significant clinical benefit for many Aboriginal and/or Torres Strait Islander Australians. These efforts are essential steps to achieving the Australian Government's objectives and its commitment "to leveraging the benefits of genomics in the health system for all Australians." They require culturally safe, community-led research and community involvement embedded within national health and medical genomics programs to ensure that new knowledge is integrated into medicine and health services in ways that address the specific and articulated cultural and health needs of Indigenous people. Until this occurs, people who do not have European ancestry are at risk of being, in relative terms, further disadvantaged.

Social and economic factors, maternal behaviours in pregnancy and neonatal adiposity in the PANDORA cohort.

BACKGROUND: Australian Indigenous women experience high rates of social disadvantage and type 2 diabetes (T2D) in pregnancy, but it is not known how social factors and maternal behaviours impact neonatal adiposity in offspring of women with hyperglycaemia in pregnancy. METHODS: Participants were Indigenous (n = 404) and Europid (n = 240) women with gestational diabetes mellitus (GDM) or T2D in pregnancy and their offspring in the Pregnancy and Neonatal Diabetes Outcomes in Remote Australia (PANDORA) study. Social, economic factors, and maternal behaviours were measured in pregnancy and six neonatal anthropometric outcomes were examined after birth. RESULTS: On univariate analysis, maternal education < 12 years (p = 0.03), unemployment (p = 0.001), welfare income vs no welfare income (p = 0.001), lower area based socio-economic score (p < 0.001), and fast food intake > 2 times/week (p = 0.002) were associated with increased sum of skinfolds (SSF) in offspring. Smoking was significantly associated with a reduction in anthropometric measures, except SSF. In multivariable models adjusted for ethnicity, BMI and hyperglycaemia, social and economic factors were no longer significant predictors of neonatal outcomes. Smoking was independently associated with a reduction in length, head circumference and fat free mass. Frequent fast food intake remained independently associated with SSF (ß-coefficient 1.08 mm, p = 0.02). CONCLUSION: In women with hyperglycaemia in pregnancy, social factors were associated with neonatal adiposity, particularly skinfold measures. Promoting smoking cessation and limited intake of energy-dense, nutrient-poor foods in pregnancy are important to improve neonatal adiposity and lean mass outcomes. Addressing inequities in social and economic factors are likely to be important, particularly for Indigenous women or women experiencing social disadvantage.

Cord blood metabolic markers are strong mediators of the effect of maternal adiposity on fetal growth in pregnancies across the glucose tolerance spectrum: the PANDORA study.

AIMS/HYPOTHESIS: We aimed to assess associations between cord blood metabolic markers and fetal overgrowth, and whether cord markers mediated the impact of maternal adiposity on neonatal anthropometric outcomes among children born to Indigenous and Non-Indigenous Australian women with normal glucose tolerance (NGT), gestational diabetes mellitus (GDM) and pregestational type 2 diabetes mellitus. METHODS: From the Pregnancy and Neonatal Outcomes in Remote Australia (PANDORA) study, an observational cohort of 1135 mother-baby pairs, venous cord blood was available for 645 singleton babies (49% Indigenous Australian) of women with NGT (n = 129), GDM (n = 419) and type 2 diabetes (n = 97). Cord glucose, triacylglycerol, HDL-cholesterol, C-reactive protein (CRP) and C-peptide were measured. Multivariable logistic and linear regression were used to assess the associations between cord blood metabolic markers and the outcomes of birthweight z score, sum of skinfold thickness (SSF), being large for gestational age (LGA) and percentage of body fat. Pathway analysis assessed whether cord markers mediated the associations between maternal and neonatal adiposity. RESULTS: Elevated cord C-peptide was significantly associated with increasing birthweight z score (ß 0.57 [95% CI 0.42, 0.71]), SSF (ß 0.83 [95% CI 0.41, 1.25]), percentage of body fat (ß 1.20 [95% CI 0.69, 1.71]) and risk for LGA [OR 3.14 [95% CI 2.11, 4.68]), after adjusting for age, ethnicity and diabetes type. Cord triacylglycerol was negatively associated with birthweight z score for Indigenous Australian women only. No associations between cord glucose, HDL-cholesterol and CRP >0.3 mg/l (2.9 nmol/l) with neonatal outcomes were observed. C-peptide mediated 18% (95% CI 13, 36) of the association of maternal BMI with LGA and 11% (95% CI 8, 17) of the association with per cent neonatal fat. CONCLUSIONS/INTERPRETATION: Cord blood C-peptide is an important mediator of the association between maternal and infant adiposity, across the spectrum of maternal glucose tolerance.

Progress in adolescent health and wellbeing: tracking 12 headline indicators for 195 countries and territories, 1990-2016.

BACKGROUND: Rapid demographic, epidemiological, and nutritional transitons have brought a pressing need to track progress in adolescent health. Here, we present country-level estimates of 12 headline indicators from the Lancet Commission on adolescent health and wellbeing, from 1990 to 2016. METHODS: Indicators included those of health outcomes (disability-adjusted life-years [DALYs] due to communicable, maternal, and nutritional diseases; injuries; and non-communicable diseases); health risks (tobacco smoking, binge drinking, overweight, and anaemia); and social determinants of health (adolescent fertility; completion of secondary education; not in education, employment, or training [NEET]; child marriage; and demand for contraception satisfied with modern methods). We drew data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016, International Labour Organisation, household surveys, and the Barro-Lee education dataset. FINDINGS: From 1990 to 2016, remarkable shifts in adolescent health occurred. A decrease in disease burden in many countries has been offset by population growth in countries with the poorest adolescent health profiles. Compared with 1990, an additional 250 million adolescents were living in multi-burden countries in 2016, where they face a heavy and complex burden of disease. The rapidity of nutritional transition is evident from the 324·1 million (18%) of 1·8 billion adolescents globally who were overweight or obese in 2016, an increase of 176·9 million compared with 1990, and the 430·7 million (24%) who had anaemia in 2016, an increase of 74·2 million compared with 1990. Child marriage remains common, with an estimated 66 million women aged 20-24 years married before age 18 years. Although gender-parity in secondary school completion exists globally, prevalence of NEET remains high for young women in multi-burden countries, suggesting few opportunities to enter the workforce in these settings. INTERPRETATION: Although disease burden has fallen in many settings, demographic shifts have heightened global inequalities. Global disease burden has changed little since 1990 and the prevalence of many adolescent health risks have increased. Health, education, and legal systems have not kept pace with shifting adolescent needs and demographic changes. Gender inequity remains a powerful driver of poor adolescent health in many countries. FUNDING: Australian National Health and Medical Research Council, and the Bill & Melinda Gates Foundation.

Maternal body mass index, excess gestational weight gain, and diabetes are positively associated with neonatal adiposity in the Pregnancy and Neonatal Diabetes Outcomes in Remote Australia (PANDORA) study.

BACKGROUND: In-utero exposures likely influence the onset and severity of obesity in youth. With increasing rates of type 2 diabetes mellitus (T2DM) and maternal adiposity in pregnancy globally, it is important to assess the impact of these factors on neonatal adipose measures. OBJECTIVES: To evaluate the contribution of maternal ethnicity, body mass index (BMI), gestational weight gain, and hyperglycaemia to neonatal adiposity. METHODS: Pregnancy and Neonatal Diabetes Outcomes in Remote Australia (PANDORA) is a longitudinal cohort study of Australian mother and neonate pairs. In this analysis, Indigenous (n = 519) and Europid (n = 358) women were included, of whom 644 had hyperglycaemia (type 2 diabetes [T2DM], diabetes in pregnancy [DIP], or gestational diabetes [GDM]). Associations between maternal ethnicity, hyperglycaemia, BMI and gestational weight gain, and the neonatal outcomes of length, head circumference, sum of skinfolds, total body fat, and percentage body fat were examined. Models were adjusted for maternal age, smoking status, parity, education, neonatal gender, and gestational age. RESULTS: Among those with hyperglycaemia in pregnancy, Indigenous women had a higher proportion of T2DM and DIP (36%, 13%) compared with Europid women (4%, 3%). In multivariate analysis, maternal T2DM (compared with no hyperglycaemia), BMI during pregnancy, and excess compared with appropriate gestational weight gain, were significantly associated with greater neonatal measures. DIP was associated with greater sum of skinfolds, total body fat, and percentage body fat. Indigenous ethnicity was associated with greater sum of skinfolds. CONCLUSIONS: Maternal BMI, excess gestational weight gain, and hyperglycaemia operated as independent factors influencing neonatal adiposity. Interventions addressing these factors are needed to reduce neonatal adiposity.

Pregnancy And Neonatal Diabetes Outcomes in Remote Australia: the PANDORA study-an observational birth cohort.

BACKGROUND: In Australia's Northern Territory, 33% of babies are born to Indigenous mothers, who experience high rates of hyperglycemia in pregnancy. We aimed to determine the extent to which pregnancy outcomes for Indigenous Australian women are explained by relative frequencies of diabetes type [type 2 diabetes (T2DM) and gestational diabetes (GDM)]. METHODS: This prospective birth cohort study examined participants recruited from a hyperglycemia in pregnancy register. Baseline data collected were antenatal and perinatal clinical information, cord blood and neonatal anthropometry. Of 1135 women (48% Indigenous), 900 had diabetes: 175 T2DM, 86 newly diagnosed diabetes in pregnancy (DIP) and 639 had GDM. A group of 235 women without hyperglycemia in pregnancy was also recruited. RESULTS: Diabetes type differed for Indigenous and non-Indigenous women (T2DM, 36 vs 5%; DIP, 15 vs 7%; GDM, 49 vs 88%, p < 0.001). Within each diabetes type, Indigenous women were younger and had higher smoking rates. Among women with GDM/DIP, Indigenous women demonstrated poorer birth outcomes than non-Indigenous women: large for gestational age, 19 vs 11%, p = 0·002; neonatal fat 11.3 vs 10.2%, p < 0.001. In the full cohort, on multivariate regression, T2DM and DIP were independently associated (and Indigenous ethnicity was not) with pregnancy outcomes. CONCLUSIONS: Higher rates of T2DM among Indigenous women predominantly contribute to absolute poorer pregnancy outcomes among Indigenous women with hyperglycemia. As with Indigenous and minority populations globally, prevention or delay of type 2 diabetes in younger women is vital to improve pregnancy outcomes and possibly to improve the long-term health of their offspring.

High Baseline Levels of Tumor Necrosis Factor Receptor 1 Are Associated With Progression of Kidney Disease in Indigenous Australians With Diabetes: The eGFR Follow-up Study.

OBJECTIVE: To examine the association between soluble tumor necrosis factor receptor 1 (sTNFR1) levels and kidney disease progression in Indigenous Australians at high risk of kidney disease. RESEARCH DESIGN AND METHODS: This longitudinal observational study examined participants aged ≥18 years recruited from >20 sites across diabetes and/or kidney function strata. Baseline measures included sTNFR1, serum creatinine, urine albumin-to-creatinine ratio (uACR), HbA1c, C-reactive protein (CRP), waist-to-hip ratio, systolic blood pressure, and medical history. Linear regression was used to estimate annual change in estimated glomerular filtration rate (eGFR) for increasing sTNFR1, and Cox proportional hazards were used to estimate the hazard ratio (HR) and 95% CI for developing a combined renal outcome (first of a ≥30% decline in eGFR with a follow-up eGFR <60 mL/min/1.73 m2, progression to renal replacement therapy, or renal death) for increasing sTNFR1. RESULTS: Over a median of 3 years, participants with diabetes (n = 194) in the highest compared with the lowest quartile of sTNFR1 experienced significantly greater eGFR decline (-4.22 mL/min/1.73 m2/year [95% CI -7.06 to -1.38]; P = 0.004), independent of baseline age, sex, eGFR, and uACR. The adjusted HR (95% CI) for participants with diabetes per doubling of sTNFR1 for the combined renal outcome (n = 32) was 3.8 (1.1-12.8; P = 0.03). No association between sTNFR1 and either renal outcome was observed for those without diabetes (n = 259). CONCLUSIONS: sTNFR1 is associated with greater kidney disease progression independent of albuminuria and eGFR in Indigenous Australians with diabetes. Further research is required to assess whether TNFR1 operates independently of other metabolic factors associated with kidney disease progression.

Health and wellbeing of Indigenous adolescents in Australia: a systematic synthesis of population data.

BACKGROUND: Indigenous populations have high rates of disease and premature mortality. Most Indigenous communities are young, and adolescence (age 10-24 years) provides great opportunities for population health gain. However, the absence of a comprehensive account of Indigenous adolescents' health has been a barrier to effective policy. We aimed to report a national health profile for Indigenous adolescents in Australia. METHODS: We undertook a systematic synthesis of population data to report the health and wellbeing of Indigenous adolescents in Australia. A reporting framework for Indigenous adolescent health in Australia was defined to measure health outcomes, health risks, and sociocultural determinants. Available data (primary data from national surveys and administrative datasets, and available published data) were mapped against the defined reporting framework, and the quality graded, with the highest quality data selected to report a health profile for Indigenous adolescents. Comparison with non-Indigenous adolescents was made where possible, and estimates (disaggregated by age, sex, and remoteness) were reported as relative risks. A national advisory group (six Indigenous young people, three Indigenous adult community members, three researchers, three policy makers, and two service providers, all aged ≥16 years) provided input about the reporting framework, interpretation of findings, and policy recommendations. FINDINGS: Data were available for 184 (79%) of 234 elements of the reporting framework. All-cause mortality for Indigenous adolescents (70 per 100 000) was more than twice that of non-Indigenous adolescents, with about 60% of deaths due to intentional self-harm and road traffic injury. 80% of all deaths among Indigenous adolescents were considered as potentially avoidable in the current health system. Communicable diseases (particularly sexually transmitted infections) were leading contributors to morbidity. Almost a third of Indigenous adolescents aged 18-24 years reported high levels of psychological distress (twice the non-Indigenous rate). There was an excess burden of mental disorders and substance use, alongside emerging type 2 diabetes and ischaemic heart disease. Additionally, there were excess intentional and unintentional injuries. Many aspects of this health profile differed markedly from that of non-Indigenous adolescents: rates of acute rheumatic fever, pneumococcal infection, gonorrhoea, and type 2 diabetes resulting in admission to hospital were ten times higher; rates of assault and childbirth in those aged 15-19 years were five times higher; whereas rates of eating disorders, melanoma and other skin cancers, and anaphylaxis were significantly lower. Risks for future ill-health were common; 43% of 15-24 year olds were current tobacco smokers and about 45% had high body mass (overweight or obese). Disadvantage across sociocultural health determinants also emerged, particularly around education. INTERPRETATION: Despite Australia's adolescents having one of the best health profiles globally, Indigenous adolescents have largely been left behind. Adequate responses will require intersectoral actions, including a health system responsive to the needs of Indigenous adolescents. Without a specific focus on adolescents, Australia will not redress Indigenous health inequalities. FUNDING: Australia's National Health and Medical Research Council, Sidney Myer Foundation, and the Murdoch Children's Research Institute.

Investigating the feasibility, acceptability and appropriateness of outreach case management in an urban Aboriginal and Torres Strait Islander primary health care service: a mixed methods exploratory study.

BACKGROUND: The disparities in health and life expectancy of Aboriginal and Torres Strait Islander peoples compared to non-Indigenous Australians are well documented. Chronic diseases are a leading contributor to these disparities. We aimed to determine the feasibility, acceptability and appropriateness of a case management approach to chronic disease care integrated within an urban Aboriginal and Torres Strait Islander primary health care service. METHODS: The Home-based, Outreach case Management of chronic disease Exploratory (HOME) Study provided holistic, patient centred multidisciplinary care for Aboriginal and Torres Strait Islander people with chronic disease. A developmental evaluation approach supported the implementation and ongoing adaptations in the delivery of the model of care, and ensured its alignment with Aboriginal and Torres Strait Islander peoples' understandings of, and approaches to, health and wellbeing. In-depth, semi-structured interviews were conducted with nine patient participants (one interview also included a participant's spouse) and 15 health service staff and key themes were identified through an iterative reflective process. Quantitative data were collected directly from patient participants and from their medical records at baseline, 3 and 6 months. Patient participants' baseline characteristics were described using frequencies and percentages. Attrition and patterns of missing values over time were evaluated using binomial generalized estimating equation (GEE) models and mean differences in key clinical outcomes were determined using normal GEE models. RESULTS: Forty-one patients were recruited and nine withdrew over the 6 month period. There was no evidence of differential attrition. All participants (patients and health service staff) were very positive about the model of care. Patient participants became more involved in their health care, depression rates significantly decreased (p = 0.03), and significant improvements in systolic blood pressure (p < 0.001) and diabetes control (p = 0.05) were achieved. CONCLUSIONS: The exploratory nature of our study preclude any definitive statements about the effectiveness of our model of care. However, staff and patients' high levels of satisfaction and improvements in the health and wellbeing of patients are promising and suggest its feasibility, acceptability and appropriateness. Further research is required to determine its efficacy, effectiveness and cost-effectiveness in improving the quality of life and quality of care for Aboriginal and Torres Strait Islander peoples living with chronic disease.

Progression of Kidney Disease in Indigenous Australians: The eGFR Follow-up Study.

BACKGROUND AND OBJECTIVES: Indigenous Australians experience a heavy burden of CKD. To address this burden, the eGFR Follow-Up Study recruited and followed an Indigenous Australian cohort from regions of Australia with the greatest ESRD burden. We sought to better understand factors contributing to the progression of kidney disease. Specific objectives were to assess rates of progression of eGFR in Indigenous Australians with and without CKD and identify factors associated with a decline in eGFR. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This observational longitudinal study of Indigenous Australian adults was conducted in >20 sites. The baseline cohort was recruited from community and primary care clinic sites across five strata of health, diabetes status, and kidney function. Participants were then invited to follow up at 2-4 years; if unavailable, vital status, progression to RRT, and serum creatinine were obtained from medical records. Primary outcomes were annual eGFR change and combined renal outcome (first of ≥30% eGFR decline with follow-up eGFR<60 ml/min per 1.73 m(2), progression to RRT, or renal death). RESULTS: Participants (n=550) were followed for a median of 3.0 years. Baseline and follow-up eGFR (geometric mean [95% confidence interval], 83.9 (80.7 to 87.3) and 70.1 (65.9 to 74.5) ml/min per 1.73 m(2), respectively. Overall mean annual eGFR change was -3.1 (-3.6 to -2.5) ml/min per 1.73 m(2). Stratified by baseline eGFR (≥90, 60-89, <60 ml/min per 1.73 m(2)), annual eGFR changes were -3.0 (-3.6 to -2.4), -1.9 (-3.3 to -0.5), and -5.0 (-6.5 to -3.6) ml/min per 1.73 m(2). Across baseline eGFR categories, annual eGFR decline was greatest among adults with baseline albumin-to-creatinine ratio (ACR) >265 mg/g (30 mg/mmol). Baseline determinants of the combined renal outcome (experienced by 66 participants) were higher urine ACR, diabetes, lower measured GFR, and higher C-reactive protein. CONCLUSIONS: The observed eGFR decline was three times higher than described in nonindigenous populations. ACR was confirmed as a powerful predictor for eGFR decline across diverse geographic regions.

A framework for overcoming disparities in management of acute coronary syndromes in the Australian Aboriginal and Torres Strait Islander population. A consensus statement from the National Heart Foundation of Australia.

Aboriginal and Torres Strait Islander patients with acute coronary syndromes (ACS) experience lower intervention rates and poorer outcomes compared with non-Indigenous patients. A broad range of geographical, cultural and systemic factors contribute to delays and suboptimal treatment for ACS. Every Indigenous ACS patient, regardless of where they live, should be able to expect a coordinated, patient-centred pathway of care provided by designated provider clinical networks and supported by Indigenous cardiac coordinators, Aboriginal liaison officers (ALOs) and health workers. These designated provider clinical networks provide: appropriate prehospital and inhospital treatment an individualised patient care plan developed jointly with the patient and his or her family culturally appropriate education initiated within the hospital setting and involving families with support from ALOs effective follow-up care and access to relevant secondary prevention programs. We outline generic pathways to provide policymakers, health planners and health care providers with a framework for ACS diagnosis and management that can be implemented across the diverse settings in which Aboriginal and Torres Strait Islander people reside and their care is delivered, in order to optimise care and assertively address the current disparities in outcomes.