Metabolic signatures of birthweight in 18 288 adolescents and adults

Peter Würtz; Qin Wang; Marjo Niironen; Tuulia Tynkkynen; Mika Tiainen; Fotios Drenos; Antti J Kangas; Pasi Soininen; Michael R Skilton; Kauko Heikkilä; Anneli Pouta; Mika Kähönen; Terho Lehtimäki; Richard J Rose; Eero Kajantie; Markus Perola; Jaakko Kaprio; Johan G Eriksson; Olli T Raitakari; Debbie A Lawlor; George Davey Smith; Marjo-Riitta Järvelin; Mika Ala-Korpela; Kirsi Auro

doi:10.1093/ije/dyw255

Metabolic signatures of birthweight in 18 288 adolescents and adults

Peter Würtz, Qin Wang, Marjo Niironen, Tuulia Tynkkynen, Mika Tiainen, Fotios Drenos, Antti J Kangas, Pasi Soininen, Michael R Skilton, Kauko Heikkilä, Anneli Pouta, Mika Kähönen, Terho Lehtimäki, Richard J Rose, Eero Kajantie, Markus Perola, Jaakko Kaprio, Johan G Eriksson, Olli T Raitakari, Debbie A LawlorGeorge Davey Smith, Marjo-Riitta Järvelin, Mika Ala-Korpela, Kirsi Auro

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Abstract

BACKGROUND: Lower birthweight is associated with increased susceptibility to cardiometabolic diseases in adulthood, but the underlying molecular pathways are incompletely understood. We examined associations of birthweight with a comprehensive metabolic profile measured in adolescents and adults.

METHODS: High-throughput nuclear magnetic resonance metabolomics and biochemical assays were used to quantify 87 circulating metabolic measures in seven cohorts from Finland and the UK, comprising altogether 18 288 individuals (mean age 26 years, range 15-75). Metabolic associations with birthweight were assessed by linear regression models adjusted for sex, gestational age and age at blood sampling. The metabolic associations with birthweight were compared with the corresponding associations with adult body mass index (BMI).

RESULTS: Lower birthweight adjusted for gestational age was adversely associated with cardiometabolic biomarkers, including lipoprotein subclasses, fatty acids, amino acids and markers of inflammation and impaired liver function (P < 0.0015 for 46 measures). Associations were consistent across cohorts with different ages at metabolic profiling, but the magnitudes were weak. The pattern of metabolic deviations associated with lower birthweight resembled the metabolic signature of higher adult BMI (R(2) = 0.77) assessed at the same time as the metabolic profiling. The resemblance indicated that 1 kg lower birthweight is associated with similar metabolic aberrations as caused by 0.92 units higher BMI in adulthood.

CONCLUSIONS: Lower birthweight adjusted for gestational age is associated with adverse biomarker aberrations across multiple metabolic pathways. Coherent metabolic signatures between lower birthweight and higher adult adiposity suggest that shared molecular pathways may potentially underpin the metabolic deviations. However, the magnitudes of metabolic associations with birthweight are modest in comparison to the effects of adiposity, implying that birthweight is only a weak indicator of the metabolic risk profile in adulthood.

Original language	English
Pages (from-to)	1539-1550
Number of pages	12
Journal	International Journal of Epidemiology
Volume	45
Issue number	5
Early online date	7 Nov 2016
DOIs	https://doi.org/10.1093/ije/dyw255
Publication status	Published - 2016

Keywords

Fetal programming
metabolic signatures
metabolomics
adiposity
fatty acids
amino acids

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10.1093/ije/dyw255

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MRC UoB UNITE Unit - Programme 1
Davey Smith, G. (Principal Investigator)
1/06/13 → 31/03/18
Project: Research
MRC UoB UNITE Unit - Programme 5
Lawlor, D. A. (Principal Investigator) & Lawlor, D. A. (Principal Investigator)
1/06/13 → 31/03/18
Project: Research

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Würtz, P., Wang, Q., Niironen, M., Tynkkynen, T., Tiainen, M., Drenos, F., Kangas, A. J., Soininen, P., Skilton, M. R., Heikkilä, K., Pouta, A., Kähönen, M., Lehtimäki, T., Rose, R. J., Kajantie, E., Perola, M., Kaprio, J., Eriksson, J. G., Raitakari, O. T., ... Auro, K. (2016). Metabolic signatures of birthweight in 18 288 adolescents and adults. International Journal of Epidemiology, 45(5), 1539-1550. https://doi.org/10.1093/ije/dyw255

@article{b231fbc6996c42f2a6f50082c78e21a4,

title = "Metabolic signatures of birthweight in 18 288 adolescents and adults",

abstract = "BACKGROUND: Lower birthweight is associated with increased susceptibility to cardiometabolic diseases in adulthood, but the underlying molecular pathways are incompletely understood. We examined associations of birthweight with a comprehensive metabolic profile measured in adolescents and adults.METHODS: High-throughput nuclear magnetic resonance metabolomics and biochemical assays were used to quantify 87 circulating metabolic measures in seven cohorts from Finland and the UK, comprising altogether 18 288 individuals (mean age 26 years, range 15-75). Metabolic associations with birthweight were assessed by linear regression models adjusted for sex, gestational age and age at blood sampling. The metabolic associations with birthweight were compared with the corresponding associations with adult body mass index (BMI).RESULTS: Lower birthweight adjusted for gestational age was adversely associated with cardiometabolic biomarkers, including lipoprotein subclasses, fatty acids, amino acids and markers of inflammation and impaired liver function (P < 0.0015 for 46 measures). Associations were consistent across cohorts with different ages at metabolic profiling, but the magnitudes were weak. The pattern of metabolic deviations associated with lower birthweight resembled the metabolic signature of higher adult BMI (R(2) = 0.77) assessed at the same time as the metabolic profiling. The resemblance indicated that 1 kg lower birthweight is associated with similar metabolic aberrations as caused by 0.92 units higher BMI in adulthood.CONCLUSIONS: Lower birthweight adjusted for gestational age is associated with adverse biomarker aberrations across multiple metabolic pathways. Coherent metabolic signatures between lower birthweight and higher adult adiposity suggest that shared molecular pathways may potentially underpin the metabolic deviations. However, the magnitudes of metabolic associations with birthweight are modest in comparison to the effects of adiposity, implying that birthweight is only a weak indicator of the metabolic risk profile in adulthood.",

keywords = "Fetal programming, metabolic signatures, metabolomics, adiposity, fatty acids, amino acids",

author = "Peter W{\"u}rtz and Qin Wang and Marjo Niironen and Tuulia Tynkkynen and Mika Tiainen and Fotios Drenos and Kangas, {Antti J} and Pasi Soininen and Skilton, {Michael R} and Kauko Heikkil{\"a} and Anneli Pouta and Mika K{\"a}h{\"o}nen and Terho Lehtim{\"a}ki and Rose, {Richard J} and Eero Kajantie and Markus Perola and Jaakko Kaprio and Eriksson, {Johan G} and Raitakari, {Olli T} and Lawlor, {Debbie A} and {Davey Smith}, George and Marjo-Riitta J{\"a}rvelin and Mika Ala-Korpela and Kirsi Auro",

note = "{\textcopyright} The Author 2016. Published by Oxford University Press on behalf of the International Epidemiological Association.",

year = "2016",

doi = "10.1093/ije/dyw255",

language = "English",

volume = "45",

pages = "1539--1550",

journal = "International Journal of Epidemiology",

issn = "0300-5771",

publisher = "Oxford University Press",

number = "5",

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Würtz, P, Wang, Q, Niironen, M, Tynkkynen, T, Tiainen, M, Drenos, F, Kangas, AJ, Soininen, P, Skilton, MR, Heikkilä, K, Pouta, A, Kähönen, M, Lehtimäki, T, Rose, RJ, Kajantie, E, Perola, M, Kaprio, J, Eriksson, JG, Raitakari, OT, Lawlor, DA , Davey Smith, G, Järvelin, M-R, Ala-Korpela, M & Auro, K 2016, 'Metabolic signatures of birthweight in 18 288 adolescents and adults', International Journal of Epidemiology, vol. 45, no. 5, pp. 1539-1550. https://doi.org/10.1093/ije/dyw255

TY - JOUR

T1 - Metabolic signatures of birthweight in 18 288 adolescents and adults

AU - Würtz, Peter

AU - Wang, Qin

AU - Niironen, Marjo

AU - Tynkkynen, Tuulia

AU - Tiainen, Mika

AU - Drenos, Fotios

AU - Kangas, Antti J

AU - Soininen, Pasi

AU - Skilton, Michael R

AU - Heikkilä, Kauko

AU - Pouta, Anneli

AU - Kähönen, Mika

AU - Lehtimäki, Terho

AU - Rose, Richard J

AU - Kajantie, Eero

AU - Perola, Markus

AU - Kaprio, Jaakko

AU - Eriksson, Johan G

AU - Raitakari, Olli T

AU - Lawlor, Debbie A

AU - Davey Smith, George

AU - Järvelin, Marjo-Riitta

AU - Ala-Korpela, Mika

AU - Auro, Kirsi

PY - 2016

Y1 - 2016

N2 - BACKGROUND: Lower birthweight is associated with increased susceptibility to cardiometabolic diseases in adulthood, but the underlying molecular pathways are incompletely understood. We examined associations of birthweight with a comprehensive metabolic profile measured in adolescents and adults.METHODS: High-throughput nuclear magnetic resonance metabolomics and biochemical assays were used to quantify 87 circulating metabolic measures in seven cohorts from Finland and the UK, comprising altogether 18 288 individuals (mean age 26 years, range 15-75). Metabolic associations with birthweight were assessed by linear regression models adjusted for sex, gestational age and age at blood sampling. The metabolic associations with birthweight were compared with the corresponding associations with adult body mass index (BMI).RESULTS: Lower birthweight adjusted for gestational age was adversely associated with cardiometabolic biomarkers, including lipoprotein subclasses, fatty acids, amino acids and markers of inflammation and impaired liver function (P < 0.0015 for 46 measures). Associations were consistent across cohorts with different ages at metabolic profiling, but the magnitudes were weak. The pattern of metabolic deviations associated with lower birthweight resembled the metabolic signature of higher adult BMI (R(2) = 0.77) assessed at the same time as the metabolic profiling. The resemblance indicated that 1 kg lower birthweight is associated with similar metabolic aberrations as caused by 0.92 units higher BMI in adulthood.CONCLUSIONS: Lower birthweight adjusted for gestational age is associated with adverse biomarker aberrations across multiple metabolic pathways. Coherent metabolic signatures between lower birthweight and higher adult adiposity suggest that shared molecular pathways may potentially underpin the metabolic deviations. However, the magnitudes of metabolic associations with birthweight are modest in comparison to the effects of adiposity, implying that birthweight is only a weak indicator of the metabolic risk profile in adulthood.

AB - BACKGROUND: Lower birthweight is associated with increased susceptibility to cardiometabolic diseases in adulthood, but the underlying molecular pathways are incompletely understood. We examined associations of birthweight with a comprehensive metabolic profile measured in adolescents and adults.METHODS: High-throughput nuclear magnetic resonance metabolomics and biochemical assays were used to quantify 87 circulating metabolic measures in seven cohorts from Finland and the UK, comprising altogether 18 288 individuals (mean age 26 years, range 15-75). Metabolic associations with birthweight were assessed by linear regression models adjusted for sex, gestational age and age at blood sampling. The metabolic associations with birthweight were compared with the corresponding associations with adult body mass index (BMI).RESULTS: Lower birthweight adjusted for gestational age was adversely associated with cardiometabolic biomarkers, including lipoprotein subclasses, fatty acids, amino acids and markers of inflammation and impaired liver function (P < 0.0015 for 46 measures). Associations were consistent across cohorts with different ages at metabolic profiling, but the magnitudes were weak. The pattern of metabolic deviations associated with lower birthweight resembled the metabolic signature of higher adult BMI (R(2) = 0.77) assessed at the same time as the metabolic profiling. The resemblance indicated that 1 kg lower birthweight is associated with similar metabolic aberrations as caused by 0.92 units higher BMI in adulthood.CONCLUSIONS: Lower birthweight adjusted for gestational age is associated with adverse biomarker aberrations across multiple metabolic pathways. Coherent metabolic signatures between lower birthweight and higher adult adiposity suggest that shared molecular pathways may potentially underpin the metabolic deviations. However, the magnitudes of metabolic associations with birthweight are modest in comparison to the effects of adiposity, implying that birthweight is only a weak indicator of the metabolic risk profile in adulthood.

KW - Fetal programming

KW - metabolic signatures

KW - metabolomics

KW - adiposity

KW - fatty acids

KW - amino acids

U2 - 10.1093/ije/dyw255

DO - 10.1093/ije/dyw255

M3 - Article (Academic Journal)

C2 - 27892411

SN - 0300-5771

VL - 45

SP - 1539

EP - 1550

JO - International Journal of Epidemiology

JF - International Journal of Epidemiology

IS - 5

ER -

Metabolic signatures of birthweight in 18 288 adolescents and adults

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Keywords

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Projects

MRC UoB UNITE Unit - Programme 1

MRC UoB UNITE Unit - Programme 5

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