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

PANDORA study team, I-Lynn Lee, Elizabeth L M Barr, Danielle Longmore, Federica Barzi, Alex D H Brown, Christine Connors, Jacqueline A Boyle, Marie Kirkwood, Vanya Hampton, Michael Lynch, Zhong X Lu, Kerin O'Dea, Jeremy Oats, H David McIntyre, Paul Zimmet, Jonathan E Shaw, Louise J Maple-Brown

Research output: Contribution to journalArticle

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.

LanguageEnglish
JournalDiabetologia
DOIs
Publication statusE-pub ahead of print - 8 Jan 2020
Externally publishedYes

Keywords

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

Cite this

@article{2c76ce0afe2e4851a79454f009f90695,
title = "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.",
keywords = "Fetal hyperinsulinaemia, Diabetes in pregnancy, Neonatal adiposity, Gestational diabetes, Cord blood, Neonatal fat mass, Type 2 Diabetes",
author = "{PANDORA study team} and I-Lynn Lee and Barr, {Elizabeth L M} and Danielle Longmore and Federica Barzi and Brown, {Alex D H} and Christine Connors and Boyle, {Jacqueline A} and Marie Kirkwood and Vanya Hampton and Michael Lynch and Lu, {Zhong X} and Kerin O'Dea and Jeremy Oats and McIntyre, {H David} and Paul Zimmet and Shaw, {Jonathan E} and Maple-Brown, {Louise J}",
year = "2020",
month = "1",
day = "8",
doi = "10.1007/s00125-019-05079-2",
language = "English",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer Verlag",

}

TY - JOUR

T1 - Cord blood metabolic markers are strong mediators of the effect of maternal adiposity on fetal growth in pregnancies across the glucose tolerance spectrum

T2 - Diabetologia

AU - PANDORA study team

AU - Lee, I-Lynn

AU - Barr, Elizabeth L M

AU - Longmore, Danielle

AU - Barzi, Federica

AU - Brown, Alex D H

AU - Connors, Christine

AU - Boyle, Jacqueline A

AU - Kirkwood, Marie

AU - Hampton, Vanya

AU - Lynch, Michael

AU - Lu, Zhong X

AU - O'Dea, Kerin

AU - Oats, Jeremy

AU - McIntyre, H David

AU - Zimmet, Paul

AU - Shaw, Jonathan E

AU - Maple-Brown, Louise J

PY - 2020/1/8

Y1 - 2020/1/8

N2 - 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.

AB - 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.

KW - Fetal hyperinsulinaemia

KW - Diabetes in pregnancy

KW - Neonatal adiposity

KW - Gestational diabetes

KW - Cord blood

KW - Neonatal fat mass

KW - Type 2 Diabetes

U2 - 10.1007/s00125-019-05079-2

DO - 10.1007/s00125-019-05079-2

M3 - Article

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

ER -