Antenatal health and perinatal outcomes of Pacific Islander women in Australia with and without gestational diabetes: A ten-year retrospective cohort study.

BACKGROUND: Pacific Islander (PI) women in Australia have an increased risk of gestational diabetes (GDM); however, their perinatal outcomes are poorly understood. AIM: The aim was to determine the maternal characteristics and perinatal outcomes of PI women with and without GDM compared to Australian/European (AE)-born women. METHODS: A retrospective analysis of perinatal outcomes of singleton deliveries >20 weeks' gestation between 1 January 2011 and 31 December 2020 was conducted at a tertiary provider (Melbourne, Australia). Antenatal details and birth outcomes were extracted from the Birth Outcome Systems database. t-Tests and χ2, univariate and multivariable logistic regression analyses assessed the relationship between ethnicity and outcomes. RESULTS: Of 52,795 consecutive births, 24,860 AE women (13.3% with GDM) and 1207 PI-born women (20.1% with GDM) were compared. PI women had significantly greater pre-pregnancy body mass index (BMI) and significantly lower rates of smoking and nulliparity. PI women with GDM had higher rates of pre-eclampsia (P < 0.001), large-for-gestational age (LGA) neonates (P = 0.037) and neonatal hypoglycaemia (P = 0.017) but lower rates of small-for-gestational age neonates (P = 0.034). Neonatal intensive care unit (NICU)/special care nursery requirements did not increase. After having adjusted for covariates, PI women's risk of LGA neonates (adjusted odds ratio (aOR): 1.06, 95% confidence interval (CI): 0.86-1.31) was attenuated; however, risk of pre-eclampsia (aOR: 1.49, 95% CI: 1.01-2.21) and neonatal hypoglycaemia (aOR: 1.40, 95% CI: 1.01-1.96) still increased. They were less likely to require a primary caesarean section (aOR: 0.86, 95% CI: 0.73-0.99). CONCLUSION: PI women have higher BMI and GDM rates, contributing to an increased likelihood of adverse perinatal outcomes. BMI is a modifiable risk factor that could be addressed prenatally.

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.

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.

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.

Simplified gestational diabetes screening with a triaging fasting plasma glucose reduces the burden of oral glucose tolerance tests during pregnancy - A large tertiary comparative cohort study.

AIMS: The study aimed to evaluate the impact of a simplified screeningapproach for gestational diabetes (GDM) compared to conventional screening on OGTT rates, GDM prevalence, and perinatal outcomes. METHOD: A retrospective comparative cohort study included singleton births from 20 weeks' gestation. Pregnancies without diagnostic glucose results from 13 weeks' gestation or incomplete screenings were excluded. Simplified screening consisted of a triaging fasting plasma glucose (FPG), where only those with FPG levels between 4.7 and 5.0 mmol/L proceeded to the 2hr 75 g oral glucose tolerance test (OGTT).The study period was divided into conventional screening (1st January 2019-30th June 2020) and simplified screening (1st January 2021-31st December 2021). RESULTS: Out of 15,138 pregnancies, 12,035 met the inclusion criteria: 7385 underwent conventional and 4650 underwent simplified screening. In the simplified group, 82.9 % avoided an OGTT. The simplified screening group also had a lower GDM prevalence compared to the conventional group ((18.7 % vs. 21.7 %, p < 0.001). Perinatal outcomes, including the rate of large-for-gestational-age infants, were similar between the groups. CONCLUSION: The simplified GDM screening strategy for significantly reduced OGTTs by over 80% without impacting perinatal outcomes. It suggests that prospective studies are necessary to further evaluate this approach.

Pregnancy And Neonatal Diabetes Outcomes in Remote Australia (PANDORA) Study.

BACKGROUND: Diabetes in pregnancy carries an increased risk of adverse pregnancy outcomes for both the mother and foetus, but it also provides an excellent early opportunity for intervention in the life course for both mother and baby. In the context of the escalating epidemic of chronic diseases among Indigenous Australians, it is vital that this risk is reduced as early as possible in the life course of the individual. The aims of the PANDORA Study are to: (i) accurately assess rates of diabetes in pregnancy in the Northern Territory (NT) of Australia, where 38% of babies are born to Indigenous mothers; (ii) assess demographic, clinical, biochemical, anthropometric, socioeconomic and early life development factors that may contribute to key maternal and neonatal birth outcomes associated with diabetes in pregnancy; and (iii) monitor relevant post-partum clinical outcomes for both the mothers and their babies. METHODS/DESIGN: Eligible participants are all NT women with diabetes in pregnancy aged 16 years and over. Information collected includes: standard antenatal clinical information, diagnosis and management of diabetes in pregnancy, socio-economic status, standard clinical birth information (delivery, gestational age, birth weight, adverse antenatal and birth outcomes). Cord blood is collected at the time of delivery and detailed neonatal anthropometric measurements performed within 72 hours of birth. Information will also be collected regarding maternal post-partum glucose tolerance and cardio-metabolic risk factor status, breastfeeding and growth of the baby up to 2 years post-partum in the first instance. DISCUSSION: This study will accurately document rates and outcomes of diabetes in pregnancy in the NT of Australia, including the high-risk Indigenous Australian population. The results of this study should contribute to policy and clinical guidelines with the goal of reducing the future risk of obesity and diabetes in both mothers and their offspring.

Breastfeeding and infant growth in offspring of mothers with hyperglycaemia in pregnancy: The pregnancy and neonatal diabetes outcomes in remote Australia study.

BACKGROUND: Benefits of breastfeeding on infant growth in children born to mothers with gestational diabetes mellitus (GDM) are uncertain. OBJECTIVES: To describe growth trajectories between birth and 14 months according to breastfeeding and maternal hyperglycaemia in pregnancy, and assess associations between breastfeeding and 14 month growth outcomes among children born to mothers with GDM. SUBJECTS/METHODS: Data on 258 Aboriginal and Torres Strait Islander infants from the PANDORA study born to mothers with normoglycaemia (n = 73), GDM (n = 122), or with pre-existing type 2 diabetes (n = 63) in pregnancy were assessed. Infant weight and BMI growth trajectories according to predominant breastfeeding at 6 months and hyperglycaemia in pregnancy were developed using mixed-effect models and cubic splines. Associations between breastfeeding and 14-month growth outcomes (z-scores: weight-for-age, weight-for-length and BMI) were evaluated using linear regression in a subgroup of infants born to mothers with GDM. RESULTS: Predominantly breastfed infants had lower BMI trajectories compared to those not predominantly breastfed, irrespective of maternal hyperglycaemia in pregnancy status (p < 0.01 for all groups), and lower weight trajectories among those born to mothers with GDM (p = 0.006). Among offspring of women with GDM, predominant breastfeeding was only associated with lower weight-for-age at 14 months, however adjusting for maternal obesity, smoking, and parity attenuated observed associations. Maternal obesity remained significantly associated with greater infant growth. CONCLUSIONS: Predominant breastfeeding was associated with reduced growth among children born to women with and without hyperglycaemia in pregnancy. However, among children exposed to GDM in utero, maternal obesity largely explained this association.

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.

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.

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.

Real-world experience of metformin use in pregnancy: Observational data from the Northern Territory Diabetes in Pregnancy Clinical Register.

BACKGROUND: In Australia's Northern Territory, Indigenous mothers account for 33% of births and have high rates of hyperglycemia in pregnancy. The prevalence of type 2 diabetes (T2D) in pregnancy is up to 10-fold higher in Indigenous than non-Indigenous Australian mothers, and the use of metformin is common. We assessed birth outcomes in relation to metformin use during pregnancy from a clinical register. METHODS: The study included women with gestational diabetes (GDM), newly diagnosed diabetes in pregnancy (DIP), or pre-existing T2D from 2012 to 2016. Data were analyzed for metformin use in the third trimester. Regression models were adjusted for maternal age, body mass index, parity, and insulin use. RESULTS: Of 1649 pregnancies, 814 (49.4%) were to Indigenous women, of whom 234 (28.7%) had T2D (vs 4.6% non-Indigenous women; P < 0.001). Metformin use was high in Indigenous women (84%-90% T2D, 42%-48% GDM/DIP) and increased over time in non-Indigenous women (43%-100% T2D, 14%-35% GDM/DIP). Among Indigenous women with GDM/DIP, there were no significant differences between groups with and without metformin in cesarean section (51% vs 39%; adjusted odds ratio [aOR] 1.25, 95% confidence interval [CI] 0.87-1.81), large for gestational age (24% vs 13%; aOR 1.5, 95% CI 0.9-2.5), or serious neonatal adverse events (9.4% vs 5.9%; aOR 1.32, 95% CI 0.68-2.57). Metformin use was independently associated with earlier gestational age (37.7 vs 38.5 weeks), but the risk did not remain independently higher after exclusion of women managed with medical nutrition therapy alone, and the increase in births <37 weeks was not significant on multivariate analysis. CONCLUSIONS: We found no clear evidence of any adverse outcomes related to the use of metformin for the treatment of hyperglycemia in pregnancy.

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.

Evaluation of collagen and methylated collagen as gene carriers.

This study explores the potential of DNA complexes prepared with methylated collagen (MC) and unmodified native collagen (NC) to deliver genes into cells. The physicochemical properties and transfection abilities of these two types of complexes are studied in parallel. MC was prepared by methylation of the carboxyl groups of collagen, rendering the collagen net positively charged at neutral pH. NC/DNA complexes were prepared at pH approximately 3, but aggregated rapidly at neutral pH. These complexes did not confer significant protection to DNA due to its poor stability in serum. MC carried a positive charge at neutral pH and formed complexes with DNA in PBS; therefore MC improved DNA binding ability and the stability of the complexes at physiological conditions. MC/DNA complexes were smaller and more stable than NC/DNA complexes in PBS, and sustained released of DNA from MC/DNA complexes was observed for up to 3 weeks in PBS at 37 degrees C. In contrast, NC/DNA complexes released almost all the DNA within 6h under the same condition. In vitro gene transfection experiments revealed that MC mediated a higher gene expression than NC, although the level of gene expression was still much lower than that achieved with polyethyleneimine/DNA complexes. In contrast to in vitro results, NC/DNA complexes yielded a 3.8-fold higher gene expression than naked DNA and MC/DNA complexes (P < 0.05) at week 2 following intramuscular injection at a DNA dose of 3 microg per muscle and a weight ratio of 1. Higher weight ratios resulted in significant decrease of transfection efficiency, particularly for MC/DNA complexes. The results suggested that gene delivery via the intramuscular route followed a different mechanism that demands a different set of physiochemical properties of the carrier from other parental routes. The potential of these collagen-based gene carriers for other administration routes remain to be further investigated.

Survival after cardiopulmonary arrest with extreme hyperkalaemia and hypothermia in a patient with metformin-associated lactic acidosis.

Potassium levels are regularly used as a prognostic factor to cease resuscitation in significant hypothermia. In this case report, we highlight how survival is still possible with extreme hyperkalaemia in severe hypothermia. We present a case of a 65-year-old Caucasian man who presented with metformin associated lactic acidosis. On presentation he had potassium of 9.1 mmol/l and a temperature of 31.5 °C. Cardiopulmonary resuscitation was commenced when he went into asystolic arrest. This presentation would commonly make attempts at resuscitation futile with a 100% death rate. However, with appropriate management this patient's condition improved and survival was possible. We provide evidence that survival is possible in profound hyperkalaemia and hypothermia. Effective cardiopulmonary resuscitation with early haemofiltration can be successful.