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.
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.
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.
Cord blood C-peptide is an important mediator of the association between maternal and infant adiposity, across the spectrum of maternal glucose tolerance.
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Diabetes in pregnancy
Gestational diabetes mellitus
Gestational weight gain
Hyperglycemia and Adverse Pregnancy Outcome
Large for gestational age
Normal glucose tolerance
Pregnancy and Neonatal Outcomes in Remote Australia
Randomised Control Trial of Low Glycaemic Index in Pregnancy
Sum of skinfold thickness
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We gratefully acknowledge all PANDORA study staff and participants, including: C. Whitbread (Wellbeing and Preventable Chronic Disease Division, Menzies School of Health Research, Australia), S. Svenson (Aboriginal Health Domain, Baker Heart and Diabetes Institute, Australia), S. Graham (Wellbeing and Preventable Chronic Disease Division, Menzies School of Health Research, Australia), A. Simmonds (Wellbeing and Preventable Chronic Disease Division, Menzies School of Health Research, Australia), P. Van Dokkum (Aboriginal Health Domain, Baker Heart and Diabetes Institute, Australia), J. Kelaart (Aboriginal Health Domain, Baker Heart and Diabetes Institute, Australia), L. Wood (Wellbeing and Preventable Chronic Disease Division, Menzies School of Health Research, Australia) and L. Davis (Wellbeing and Preventable Chronic Disease Division, Menzies School of Health Research, Australia), as well as Diabetes across the Lifecourse: Northern Australia Partnership investigators, partners, staff, Indigenous Reference Group and Clinical Reference Group, Northern Territory (NT) health professionals from NT Department of Health hospitals, remote primary healthcare, Healthy Living NT and Aboriginal Community Controlled Health Organizations. Diabetes across the Lifecourse: Northern Australia Partnership investigators not named as authors are E. Moore (Public Health Unit, Aboriginal Medical Services Alliance of Northern Territory, Australia), S. Thomas (Department of Obstetrics and Gynaecology, Royal Darwin Hospital, Australia), S. Eades (Clinical and Population Health, Baker Heart and Diabetes Institute, Australia), S. Corpus (Clinical Services, Danila Dilba Health Service, Australia) and S. Chitturi (Division of Medicine, Royal Darwin Hospital, Australia). The views expressed in this publication are those of the authors and do not reflect the views of the National Health and Medical Research Council of Australia. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
This work was supported by the National Health and Medical Research Council of Australia (NHMRC Partnership Project Grant no. 1032116, NHMRC no. 1078333). Additional support (including pilot funding) was received from NHMRC Program Grant no. 631947. LMB was supported by NHMRC Fellowship no. 605837 and NHMRC Practitioner Fellowship no. 1078477. IL was supported by an Australian Postgraduate award and Menzies scholarship. ELMB was supported by a Heart Foundation post-doctoral fellowship no. 101291. JAB was supported by NHMRC Career Development Fellowship. JES was supported by NHMRC Fellowship no. 1079438. AB was supported by a Viertel Senior Medical Research Fellowship and an NHMRC Senior Research Fellowship no. 1137563.
The authors declare that there is no duality of interest associated with this manuscript.
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Lee, I., Barr, E.L.M., Longmore, D. 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. Diabetologia 63, 497–507 (2020). https://doi.org/10.1007/s00125-019-05079-2
- Cord blood
- Diabetes in pregnancy
- Fetal hyperinsulinaemia
- Gestational diabetes
- Neonatal adiposity
- Neonatal fat mass
- Type 2 diabetes