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

On behalf of PANDORA Study research team

    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.

    Original languageEnglish
    Pages (from-to)497-507
    Number of pages11
    JournalDiabetologia
    Volume63
    Issue number3
    Early online date8 Jan 2020
    DOIs
    Publication statusE-pub ahead of print - 8 Jan 2020

    Fingerprint

    Adiposity
    Pregnancy Outcome
    Fetal Development
    Fetal Blood
    C-Peptide
    Mothers
    Glucose
    Pregnancy
    Gestational Age
    Skinfold Thickness
    Gestational Diabetes
    C-Reactive Protein
    Type 2 Diabetes Mellitus
    HDL Cholesterol
    Adipose Tissue
    Triglycerides
    Protein C
    Observational Studies
    Linear Models
    Cohort Studies

    Cite this

    @article{8e04912ae7f64906a2a46a33979edad4,
    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 = "Cord blood, Diabetes in pregnancy, Fetal hyperinsulinaemia, Gestational diabetes, Neonatal adiposity, Neonatal fat mass, Type 2 diabetes",
    author = "{On behalf of PANDORA Study research team} and Lee, {I. Lynn} 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",
    volume = "63",
    pages = "497--507",
    journal = "Diabetologia",
    issn = "0012-186X",
    publisher = "Springer",
    number = "3",

    }

    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. / On behalf of PANDORA Study research team.

    In: Diabetologia, Vol. 63, No. 3, 03.2020, p. 497-507.

    Research output: Contribution to journalArticle

    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 - the PANDORA study

    AU - On behalf of PANDORA Study research 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 - Cord blood

    KW - Diabetes in pregnancy

    KW - Fetal hyperinsulinaemia

    KW - Gestational diabetes

    KW - Neonatal adiposity

    KW - Neonatal fat mass

    KW - Type 2 diabetes

    UR - http://www.scopus.com/inward/record.url?scp=85077617278&partnerID=8YFLogxK

    U2 - 10.1007/s00125-019-05079-2

    DO - 10.1007/s00125-019-05079-2

    M3 - Article

    AN - SCOPUS:85077617278

    VL - 63

    SP - 497

    EP - 507

    JO - Diabetologia

    JF - Diabetologia

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    ER -