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

First published: 29 May 2022Background: 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 usinglinear mixed models with cubic spline functions of child age. Results:After adjustment for maternal factors (age, BMI, parity, smoking, and socio-economic 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 childrenexposed to normoglycaemia (18.6 kg/m2[18.1–18.9]) (p=0.001). Conclusions: Maternal hyperglycaemia was associated with differences in early child-hood growth trajectories after adjustment for maternal BMI. Exploration of associations between in utero hyperglycaemia exposure and growth trajectories into later childhood is required.Angela Titmuss, Danielle K. Longmore, Federica Barzi, Elizabeth L. M. Barr, Vanya Webster, Anna Wood, Alison Simmonds, Alex D. H. Brown, Christine Connors, Jacqueline A. Boyle, Jeremy Oats, H. David McIntyre, Jonathan E. Shaw, Maria E. Craig, Louise J. Maple-Brown, the PANDORA Study Research Tea

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

OnlinePublAims 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 [HbA₁Cₓ ] or fasting plasma glucose) were assessed for women with GDM (n = 712). Associations between antenatal factors and screening with any test (OGTT, HbA₁Cₓ, 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 HbA₁Cₓ 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.Anna J. Wood, I-Lynn Lee, Elizabeth L. M. Barr, Federica Barzi, Jacqueline A. Boyle, Christine Connors, Elizabeth Moore, Jeremy J. N. Oats, Harold D. McIntyre, Angela Titmuss, Alison Simmonds, Paul Z. Zimmet, Alex D. H. Brown, Sumaria Corpus, Jonathan E. Shaw, Louise J. Maple-Brown, on behalf of PANDORA Study tea

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.Angela Titmuss, Federica Barzi, Elizabeth L. M. Barr, Vanya Webster, Anna Wood, Joanna Kelaart, Marie Kirkwood, Christine Connors, Jacqueline A. Boyle, Elizabeth Moore, Jeremy Oats, H. David McIntyre, Paul Zimmet, Alex D. H. Brown, Jonathan E. Shaw, Maria E. Craig, and Louise J. Maple-Brow

Response to letters regarding article, "television viewing time and mortality : the Australian diabetes, obesity and lifestyle study (AusDiab)"

Abstract not available

Screening rates for diabetic retinopathy among Aboriginal and Torres Strait Islander women with hyperglycaemia in pregnancy: the PANDORA cohort study

Abstract not available.Athira Rohit, Tania Roulston, Tim Henderson, I-Lynn Lee, Vanya Webster, H. David McIntyre, Christine Connors, Alex Brown, Jonathan E. Shaw, Louise J. Maple-Brown, Elizabeth L.M. Bar

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.Danielle K. Longmore, Elizabeth L.M. Barr, I‐Lynn Lee, Federica Barzi, Marie Kirkwood... Alex D.H. Brown ... et al. (on behalf of the PANDORA study research team

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 to normoglycemia.MethodsData were from 1,102 (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 ≥500ml) were assessed using logistic regression. Multivariable-adjusted models included Indigenous ethnicity, diabetes type and their interaction.ResultsA higher proportion of Indigenous women developed PPH than non-Indigenous women (32% vs. 22%; p<0.001). Compared to non-Indigenous women with normoglycemia, risks of PPH for Indigenous women with GDM or T2DM were (OR=1.83 [95%CI: 1.11-3.02] and 1.72 [0.99-3.00] after age adjustment, 1.84 [1.06-3.19] and 1.33 [0.70-2.54] after adjustment for school education and delivery mode, and 1.62 [0.95-2.77] and 0.99 [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 compared to non-Indigenous women may be explained by a greater effect of GDM among Indigenous women that was only partly accounted for by birth weight.Isabelle M. Lucas, Elizabeth L. M. Barr, Federica Barzi, Danielle K. Longmore, I-Lynn Lee, Marie Kirkwood ... et al

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 (β 0.57 [95% CI 0.42, 0.71]), SSF (β 0.83 [95% CI 0.41, 1.25]), percentage of body fat (β 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.I-Lynn Lee, Elizabeth L. M. Barr, Danielle Longmore, Federica Barzi, Alex D. H. Brown ... Louise J. Maple-Brown .... at al. (on behalf of the PANDORA study team

Performance of cardiovascular risk prediction equations in Indigenous Australians

OBJECTIVE:To assess the performance of cardiovascular disease (CVD) risk equations in Indigenous Australians. METHODS:We conducted an individual participant meta-analysis using longitudinal data of 3618 Indigenous Australians (55% women) aged 30-74 years without CVD from population-based cohorts of the Cardiovascular Risk in IndigenouS People(CRISP) consortium. Predicted risk was calculated using: 1991 and 2008 Framingham Heart Study (FHS), the Pooled Cohorts (PC), GloboRisk and the Central Australian Rural Practitioners Association (CARPA) modification of the FHS equation. Calibration, discrimination and diagnostic accuracy were evaluated. Risks were calculated with and without the use of clinical criteria to identify high-risk individuals. RESULTS:When applied without clinical criteria, all equations, except the CARPA-adjusted FHS, underestimated CVD risk (range of percentage difference between observed and predicted CVD risks: -55% to -14%), with underestimation greater in women (-63% to -13%) than men (-47% to -18%) and in younger age groups. Discrimination ranged from 0.66 to 0.72. The CARPA-adjusted FHS equation showed good calibration but overestimated risk in younger people, those without diabetes and those not at high clinical risk. When clinical criteria were used with risk equations, the CARPA-adjusted FHS algorithm scored 64% of those who had CVD events as high risk; corresponding figures for the 1991-FHS were 58% and were 87% for the PC equation for non-Hispanic whites. However, specificity fell. CONCLUSION:The CARPA-adjusted FHS CVD risk equation and clinical criteria performed the best, achieving higher combined sensitivity and specificity than other equations. However, future research should investigate whether modifications to this algorithm combination might lead to improved risk prediction.Elizabeth Laurel Mary Barr, Federica Barzi, Athira Rohit, Joan Cunningham, Shaun Tatipata ... Alex Brown ... et al