I-Lynn Lee1, Elizabeth L M Barr1,2, Danielle Longmore1, Federica Barzi1, Alex D H Brown3,4, Christine Connors5, Jacqueline A Boyle6, Marie Kirkwood1, Vanya Hampton1, Michael Lynch7, Zhong X Lu8,9, Kerin O'Dea10, Jeremy Oats11, H David McIntyre12, Paul Zimmet13, Jonathan E Shaw2, Louise J Maple-Brown14,15. 1. Wellbeing and Preventable Chronic Disease Division, Menzies School of Health Research, Charles Darwin University, PO Box 41096, Casuarina, NT, 0811, Australia. 2. Baker Heart and Diabetes Institute, Melbourne, VIC, Australia. 3. South Australian Health and Medical Research Institute, Adelaide, SA, Australia. 4. Faculty of Health and Medical Sciences, the University of Adelaide, Adelaide, SA, Australia. 5. Northern Territory Department of Health, Darwin, NT, Australia. 6. Monash Centre for Health Research and Implementation, School of Public Health and Preventative Medicine, Monash University, Clayton, VIC, Australia. 7. Pathology Network, Top End Health and Hospital Services, Darwin, NT, Australia. 8. Monash Pathology, Monash Health, Melbourne, VIC, Australia. 9. Department of Medicine, Monash University, Melbourne, VIC, Australia. 10. School of Health Sciences, University of South Australia, Adelaide, SA, Australia. 11. Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia. 12. Mater Medical Research Institute, University of Queensland, Brisbane, QLD, Australia. 13. Department of Diabetes, Central Clinical School, Monash University, Melbourne, VIC, Australia. 14. Wellbeing and Preventable Chronic Disease Division, Menzies School of Health Research, Charles Darwin University, PO Box 41096, Casuarina, NT, 0811, Australia. Louise.Maple-Brown@menzies.edu.au. 15. Division of Medicine, Royal Darwin Hospital, Darwin, NT, Australia. Louise.Maple-Brown@menzies.edu.au.
Abstract
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.
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.
Entities:
Keywords:
Cord blood; Diabetes in pregnancy; Fetal hyperinsulinaemia; Gestational diabetes; Neonatal adiposity; Neonatal fat mass; Type 2 diabetes
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