Association of pre-pregnancy body mass index with offspring metabolic profile: Analyses of 3 European prospective birth cohorts.

<h4>Background</h4>A high proportion of women start pregnancy overweight or obese. According to the developmental overnutrition hypothesis, this could lead offspring to have metabolic disruption throughout their lives and thus perpetuate the obesity epidemic across generations. Concerns...

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Autores principales:	Diana L Santos Ferreira, Dylan M Williams, Antti J Kangas, Pasi Soininen, Mika Ala-Korpela, George Davey Smith, Marjo-Riitta Jarvelin, Debbie A Lawlor
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2017
Materias:	Medicine R
Acceso en línea:	https://doaj.org/article/fdba4bfeaf8d483b899fd6be8f8617df
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spelling	oai:doaj.org-article:fdba4bfeaf8d483b899fd6be8f8617df2021-12-02T19:55:40ZAssociation of pre-pregnancy body mass index with offspring metabolic profile: Analyses of 3 European prospective birth cohorts.1549-12771549-167610.1371/journal.pmed.1002376https://doaj.org/article/fdba4bfeaf8d483b899fd6be8f8617df2017-08-01T00:00:00Zhttps://doi.org/10.1371/journal.pmed.1002376https://doaj.org/toc/1549-1277https://doaj.org/toc/1549-1676<h4>Background</h4>A high proportion of women start pregnancy overweight or obese. According to the developmental overnutrition hypothesis, this could lead offspring to have metabolic disruption throughout their lives and thus perpetuate the obesity epidemic across generations. Concerns about this hypothesis are influencing antenatal care. However, it is unknown whether maternal pregnancy adiposity is associated with long-term risk of adverse metabolic profiles in offspring, and if so, whether this association is causal, via intrauterine mechanisms, or explained by shared familial (genetic, lifestyle, socioeconomic) characteristics. We aimed to determine if associations between maternal body mass index (BMI) and offspring systemic cardio-metabolic profile are causal, via intrauterine mechanisms, or due to shared familial factors.<h4>Methods and findings</h4>We used 1- and 2-stage individual participant data (IPD) meta-analysis, and a negative-control (paternal BMI) to examine the association between maternal pre-pregnancy BMI and offspring serum metabolome from 3 European birth cohorts (offspring age at blood collection: 16, 17, and 31 years). Circulating metabolic traits were quantified by high-throughput nuclear magnetic resonance metabolomics. Results from 1-stage IPD meta-analysis (N = 5327 to 5377 mother-father-offspring trios) showed that increasing maternal and paternal BMI was associated with an adverse cardio-metabolic profile in offspring. We observed strong positive associations with very-low-density lipoprotein (VLDL)-lipoproteins, VLDL-cholesterol (C), VLDL-triglycerides, VLDL-diameter, branched/aromatic amino acids, glycoprotein acetyls, and triglycerides, and strong negative associations with high-density lipoprotein (HDL), HDL-diameter, HDL-C, HDL2-C, and HDL3-C (all P < 0.003). Slightly stronger magnitudes of associations were present for maternal compared with paternal BMI across these associations; however, there was no strong statistical evidence for heterogeneity between them (all bootstrap P > 0.003, equivalent to P > 0.05 after accounting for multiple testing). Results were similar in each individual cohort, and in the 2-stage analysis. Offspring BMI showed similar patterns of cross-sectional association with metabolic profile as for parental pre-pregnancy BMI associations but with greater magnitudes. Adjustment of parental BMI-offspring metabolic traits associations for offspring BMI suggested the parental associations were largely due to the association of parental BMI with offspring BMI. Limitations of this study are that inferences cannot be drawn about the role of circulating maternal fetal fuels (i.e., glucose, lipids, fatty acids, and amino acids) on later offspring metabolic profile. In addition, BMI may not reflect potential effects of maternal pregnancy fat distribution.<h4>Conclusion</h4>Our findings suggest that maternal BMI-offspring metabolome associations are likely to be largely due to shared genetic or familial lifestyle confounding rather than to intrauterine mechanisms.Diana L Santos FerreiraDylan M WilliamsAntti J KangasPasi SoininenMika Ala-KorpelaGeorge Davey SmithMarjo-Riitta JarvelinDebbie A LawlorPublic Library of Science (PLoS)articleMedicineRENPLoS Medicine, Vol 14, Iss 8, p e1002376 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R
spellingShingle	Medicine R Diana L Santos Ferreira Dylan M Williams Antti J Kangas Pasi Soininen Mika Ala-Korpela George Davey Smith Marjo-Riitta Jarvelin Debbie A Lawlor Association of pre-pregnancy body mass index with offspring metabolic profile: Analyses of 3 European prospective birth cohorts.
description	<h4>Background</h4>A high proportion of women start pregnancy overweight or obese. According to the developmental overnutrition hypothesis, this could lead offspring to have metabolic disruption throughout their lives and thus perpetuate the obesity epidemic across generations. Concerns about this hypothesis are influencing antenatal care. However, it is unknown whether maternal pregnancy adiposity is associated with long-term risk of adverse metabolic profiles in offspring, and if so, whether this association is causal, via intrauterine mechanisms, or explained by shared familial (genetic, lifestyle, socioeconomic) characteristics. We aimed to determine if associations between maternal body mass index (BMI) and offspring systemic cardio-metabolic profile are causal, via intrauterine mechanisms, or due to shared familial factors.<h4>Methods and findings</h4>We used 1- and 2-stage individual participant data (IPD) meta-analysis, and a negative-control (paternal BMI) to examine the association between maternal pre-pregnancy BMI and offspring serum metabolome from 3 European birth cohorts (offspring age at blood collection: 16, 17, and 31 years). Circulating metabolic traits were quantified by high-throughput nuclear magnetic resonance metabolomics. Results from 1-stage IPD meta-analysis (N = 5327 to 5377 mother-father-offspring trios) showed that increasing maternal and paternal BMI was associated with an adverse cardio-metabolic profile in offspring. We observed strong positive associations with very-low-density lipoprotein (VLDL)-lipoproteins, VLDL-cholesterol (C), VLDL-triglycerides, VLDL-diameter, branched/aromatic amino acids, glycoprotein acetyls, and triglycerides, and strong negative associations with high-density lipoprotein (HDL), HDL-diameter, HDL-C, HDL2-C, and HDL3-C (all P < 0.003). Slightly stronger magnitudes of associations were present for maternal compared with paternal BMI across these associations; however, there was no strong statistical evidence for heterogeneity between them (all bootstrap P > 0.003, equivalent to P > 0.05 after accounting for multiple testing). Results were similar in each individual cohort, and in the 2-stage analysis. Offspring BMI showed similar patterns of cross-sectional association with metabolic profile as for parental pre-pregnancy BMI associations but with greater magnitudes. Adjustment of parental BMI-offspring metabolic traits associations for offspring BMI suggested the parental associations were largely due to the association of parental BMI with offspring BMI. Limitations of this study are that inferences cannot be drawn about the role of circulating maternal fetal fuels (i.e., glucose, lipids, fatty acids, and amino acids) on later offspring metabolic profile. In addition, BMI may not reflect potential effects of maternal pregnancy fat distribution.<h4>Conclusion</h4>Our findings suggest that maternal BMI-offspring metabolome associations are likely to be largely due to shared genetic or familial lifestyle confounding rather than to intrauterine mechanisms.
format	article
author	Diana L Santos Ferreira Dylan M Williams Antti J Kangas Pasi Soininen Mika Ala-Korpela George Davey Smith Marjo-Riitta Jarvelin Debbie A Lawlor
author_facet	Diana L Santos Ferreira Dylan M Williams Antti J Kangas Pasi Soininen Mika Ala-Korpela George Davey Smith Marjo-Riitta Jarvelin Debbie A Lawlor
author_sort	Diana L Santos Ferreira
title	Association of pre-pregnancy body mass index with offspring metabolic profile: Analyses of 3 European prospective birth cohorts.
title_short	Association of pre-pregnancy body mass index with offspring metabolic profile: Analyses of 3 European prospective birth cohorts.
title_full	Association of pre-pregnancy body mass index with offspring metabolic profile: Analyses of 3 European prospective birth cohorts.
title_fullStr	Association of pre-pregnancy body mass index with offspring metabolic profile: Analyses of 3 European prospective birth cohorts.
title_full_unstemmed	Association of pre-pregnancy body mass index with offspring metabolic profile: Analyses of 3 European prospective birth cohorts.
title_sort	association of pre-pregnancy body mass index with offspring metabolic profile: analyses of 3 european prospective birth cohorts.
publisher	Public Library of Science (PLoS)
publishDate	2017
url	https://doaj.org/article/fdba4bfeaf8d483b899fd6be8f8617df
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_version_	1718375879977992192

Association of pre-pregnancy body mass index with offspring metabolic profile: Analyses of 3 European prospective birth cohorts.

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