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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

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.

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Data availability

Data are available on request to the Partnership Steering Committee. They are not attached or on an online repository.

Abbreviations

CRP:

C-reactive protein

DIP:

Diabetes in pregnancy

GDM:

Gestational diabetes mellitus

GWG:

Gestational weight gain

HAPO:

Hyperglycemia and Adverse Pregnancy Outcome

LGA:

Large for gestational age

LPL:

Lipoprotein lipase

NGT:

Normal glucose tolerance

PANDORA:

Pregnancy and Neonatal Outcomes in Remote Australia

ROLO:

Randomised Control Trial of Low Glycaemic Index in Pregnancy

SSF:

Sum of skinfold thickness

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Acknowledgements

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.

Funding

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.

Author information

IL conducted the literature review and drafted the manuscript, with assistance from LMB, ELMB and FB. LMB and AB initiated the study concept, design and partnership. LMB led all aspects of the study including design of the study protocol for funding and ethics applications, supervision of data collection, study conduct, data management and data analysis. IL, DL, MK and VH contributed to data collection and MK contributed additionally to project management. FB performed the statistical analysis and prepared all tables and figures. ELMB assisted with analysis and interpretation of data and revised the article it critically for important intellectual content. CC, JAB, KOD, PZ, JO, HDM, AB and JES provided substantial contributions to conception and design of the study and revising the article critically for important intellectual content. ML and ZL contributed intellectually to laboratory methodology and supervised laboratory analyses of cord blood samples. All authors were involved in revising the manuscript for important intellectual content and read and approved the final manuscript. LMB is the guarantor of this work.

Correspondence to Louise J. Maple-Brown.

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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 (2020). https://doi.org/10.1007/s00125-019-05079-2

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Keywords

  • Cord blood
  • Diabetes in pregnancy
  • Fetal hyperinsulinaemia
  • Gestational diabetes
  • Neonatal adiposity
  • Neonatal fat mass
  • Type 2 diabetes