Increased innate immune responses in adolescents with obesity and its relation to subclinical cardiovascular measures: An exploratory study.

Cardiometabolic risk accrues across the life course and childhood and adolescence are key periods for effective prevention. Obesity is associated with inflammation in adults, but pediatric data are scarce. In a cross-sectional and longitudinal study, we investigated immune cell composition and activation in 31 adolescents with obesity (41.9% male, BMIz>2.5, 14.4 years) and 22 controls with healthy weight (45.1% male, -1.5

Prevalence of type 2 diabetes risk factors, including overweight and obesity, among youth attending hospital-based paediatric care in Western Melbourne.

AIM: To determine the prevalence of risk factors for type 2 diabetes in overweight and obese adolescents attending hospital-based paediatric care in Western Melbourne. METHODS: One hundred overweight and obese adolescents (aged 10-17 years) who attended an outpatient clinic at Sunshine Hospital between May 2019 and May 2020 were randomly selected following a retrospective chart review of 10-17 years old for whom a height and weight had been documented. Additional risk factors for type 2 diabetes were ascertained via structured telephone interview. Data were analysed to determine the overall prevalence of risk factors for type 2 diabetes, and to evaluate for associations between each parameter with body mass index and the number of risk factors. RESULTS: Of the 487 adolescents who had height and weight data recorded, 45% were overweight or obese. 77% of those who were interviewed had an additional risk factor for type 2 diabetes. No association between the number of risk factors and body mass index standard deviation score was found. Additionally, there was no association between the number of risk factors for type 2 diabetes and either family history of type 2 diabetes or ethnicity. CONCLUSIONS: This paediatric subpopulation had a high rate of risk factors for type 2 diabetes in addition to overweight and obesity, and are at risk of premature mortality and chronic morbidity should they develop type 2 diabetes.

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.

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.

Type 2 diabetes after a pregnancy with gestational diabetes among first nations women in Australia: The PANDORA study.

AIMS: To determine among First Nations and Europid pregnant women the cumulative incidence and predictors of postpartum type 2 diabetes and prediabetes and describe postpartum cardiovascular disease (CVD) risk profiles. METHODS: PANDORA is a prospective longitudinal cohort of women recruited in pregnancy. Ethnic-specific rates of postpartum type 2 diabetes and prediabetes were reported for women with diabetes in pregnancy (DIP), gestational diabetes (GDM) or normoglycaemia in pregnancy over a short follow-up of 2.5 years (n = 325). Pregnancy characteristics and CVD risk profiles according to glycaemic status, and factors associated with postpartum diabetes/prediabetes were examined in First Nations women. RESULTS: The cumulative incidence of postpartum type 2 diabetes among women with DIP or GDM were higher for First Nations women (48%, 13/27, women with DIP, 13%, 11/82, GDM), compared to Europid women (nil DIP or GDM p < 0.001). Characteristics associated with type 2 diabetes/prediabetes among First Nations women with GDM/DIP included, older age, multiparity, family history of diabetes, higher glucose values, insulin use and body mass index (BMI). CONCLUSIONS: First Nations women experience a high incidence of postpartum type 2 diabetes after GDM/DIP, highlighting the need for culturally responsive policies at an individual and systems level, to prevent diabetes and its complications.

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.

Diabetes and Overweight/Obesity Are Independent, Nonadditive Risk Factors for In-Hospital Severity of COVID-19: An International, Multicenter Retrospective Meta-analysis.

OBJECTIVE: Obesity is an established risk factor for severe coronavirus disease 2019 (COVID-19), but the contribution of overweight and/or diabetes remains unclear. In a multicenter, international study, we investigated if overweight, obesity, and diabetes were independently associated with COVID-19 severity and whether the BMI-associated risk was increased among those with diabetes. RESEARCH DESIGN AND METHODS: We retrospectively extracted data from health care records and regional databases of hospitalized adult patients with COVID-19 from 18 sites in 11 countries. We used standardized definitions and analyses to generate site-specific estimates, modeling the odds of each outcome (supplemental oxygen/noninvasive ventilatory support, invasive mechanical ventilatory support, and in-hospital mortality) by BMI category (reference, overweight, obese), adjusting for age, sex, and prespecified comorbidities. Subgroup analysis was performed on patients with preexisting diabetes. Site-specific estimates were combined in a meta-analysis. RESULTS: Among 7,244 patients (65.6% overweight/obese), those with overweight were more likely to require oxygen/noninvasive ventilatory support (random effects adjusted odds ratio [aOR], 1.44; 95% CI 1.15-1.80) and invasive mechanical ventilatory support (aOR, 1.22; 95% CI 1.03-1.46). There was no association between overweight and in-hospital mortality (aOR, 0.88; 95% CI 0.74-1.04). Similar effects were observed in patients with obesity or diabetes. In the subgroup analysis, the aOR for any outcome was not additionally increased in those with diabetes and overweight or obesity. CONCLUSIONS: In adults hospitalized with COVID-19, overweight, obesity, and diabetes were associated with increased odds of requiring respiratory support but were not associated with death. In patients with diabetes, the odds of severe COVID-19 were not increased above the BMI-associated risk.

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.

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.

Post-transplant lymphoproliferative disorder: no relationship to recombinant human growth hormone use in Australian and New Zealand pediatric kidney transplant recipients.

PTLD is a potentially life-limiting complication of pediatric transplantation. Previous registry-based studies in renal transplantation have suggested a link between rhGH use and PTLD. In this study, demographic and transplant data on those aged <18 yr and transplanted between 1991 and 2008 were collected from the ANZDATA Registry. Associations between gender, age at time of transplant, recipient CMV and EBV status, use of monoclonal antibody therapy, and use of rhGH were studied as potential predictors of PTLD. Among 650 transplants, there were 20 cases (3.1%) of PTLD, with half presenting within two yr post-transplant. Eight patients exposed to rhGH at any time developed PTLD, and this association was not statistically significant (RR = 1.5[0.6-3.4], p = 0.36). On multivariate analysis, there were no significant predictors for PTLD. In this study, previously identified potential risk factors were not identified as significant predictors for the development of PTLD. Although limited sample size may affect our ability to infer safety, this large retrospective cohort study does not suggest an increased risk of PTLD in pediatric kidney transplant recipients who received rhGH treatment.

Klebsiella pneumoniae bacteraemia complicating rotavirus gastroenteritis in two infants with glucocorticoid deficiency.

Rotavirus gastroenteritis was complicated by Klebsiella Pneumoniae bacteraemia in two infants with glucocorticoid deficient conditions who were treated with 'stress dose' hydrocortisone during their illness. Delayed healing in the context of glucocorticoid administration combined with damage from rotavirus infection may result in increased risk of mucosal invasion by gastrointestinal bacteria and subsequent enteric gram-negative bacteraemia.