Dataset Information

Maternal Metabolomic Profile and Fetal Programming of Offspring Adiposity: Identification of Potentially Protective Lipid Metabolites.

ABSTRACT: SCOPE:The fetal programming paradigm posits that the origins of obesity can be traced, in part, to the intrauterine period of life. However, the mechanisms underlying fetal programming are not well understood, and few studies have measured offspring adiposity in the neonatal period. The aim of this study is to identify maternal metabolites, and their determinants, that are associated with neonatal adiposity. METHODS AND RESULTS:A targeted metabolomics approach is applied to analyze plasma samples collected across gestation from a well-characterized cohort of 253 pregnant women participating in a prospective study at the University of California, Irvine. Whole-body dual X-ray absorptiometry (DXA) imaging of body composition is obtained in N = 121 newborns. Statistical models are adjusted for potential confounders and multiple testing. The authors identify six alkyl-linked phosphatidylcholines (PCae), containing fatty acid 20:4, that are significantly and negatively associated with neonatal body fat percentage. Factors indicating higher socioeconomic status, non-Hispanic ethnicity, and higher nonesterified fatty acid percentages are positively associated with these PCae. CONCLUSIONS:The polyunsaturated fatty acid 20:4 contained in PCae may exert a beneficial effect with respect to future propensity for obesity development. Prepregnancy and early pregnancy factors are determinants of these PCae, highlighting the importance of addressing preconceptional conditions for fetal programming of newborn adiposity.

SUBMITTER: Hellmuth C

PROVIDER: S-EPMC6455915 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Maternal Metabolomic Profile and Fetal Programming of Offspring Adiposity: Identification of Potentially Protective Lipid Metabolites.

Hellmuth Christian C Lindsay Karen L KL Uhl Olaf O Buss Claudia C Wadhwa Pathik D PD Koletzko Berthold B Entringer Sonja S

Molecular nutrition & food research 20180528 1

<h4>Scope</h4>The fetal programming paradigm posits that the origins of obesity can be traced, in part, to the intrauterine period of life. However, the mechanisms underlying fetal programming are not well understood, and few studies have measured offspring adiposity in the neonatal period. The aim of this study is to identify maternal metabolites, and their determinants, that are associated with neonatal adiposity.<h4>Methods and results</h4>A targeted metabolomics approach is applied to analyz ...[more]

PMID: 29714050

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Project description:Aims/hypothesisHigher maternal BMI during pregnancy is associated with higher offspring birthweight, but it is not known whether this is solely the result of adverse metabolic consequences of higher maternal adiposity, such as maternal insulin resistance and fetal exposure to higher glucose levels, or whether there is any effect of raised adiposity through non-metabolic (e.g. mechanical) factors. We aimed to use genetic variants known to predispose to higher adiposity, coupled with a favourable metabolic profile, in a Mendelian randomisation (MR) study comparing the effect of maternal 'metabolically favourable adiposity' on offspring birthweight with the effect of maternal general adiposity (as indexed by BMI).MethodsTo test the causal effects of maternal metabolically favourable adiposity or general adiposity on offspring birthweight, we performed two-sample MR. We used variants identified in large, published genetic-association studies as being associated with either higher adiposity and a favourable metabolic profile, or higher BMI (n = 442,278 and n = 322,154 for metabolically favourable adiposity and BMI, respectively). We then extracted data on the metabolically favourable adiposity and BMI variants from a large, published genetic-association study of maternal genotype and offspring birthweight controlling for fetal genetic effects (n = 406,063 with maternal and/or fetal genotype effect estimates). We used several sensitivity analyses to test the reliability of the results. As secondary analyses, we used data from four cohorts (total n = 9323 mother-child pairs) to test the effects of maternal metabolically favourable adiposity or BMI on maternal gestational glucose, anthropometric components of birthweight and cord-blood biomarkers.ResultsHigher maternal adiposity with a favourable metabolic profile was associated with lower offspring birthweight (-94 [95% CI -150, -38] g per 1 SD [6.5%] higher maternal metabolically favourable adiposity, p = 0.001). By contrast, higher maternal BMI was associated with higher offspring birthweight (35 [95% CI 16, 53] g per 1 SD [4 kg/m2] higher maternal BMI, p = 0.0002). Sensitivity analyses were broadly consistent with the main results. There was evidence of outlier SNPs for both exposures; their removal slightly strengthened the metabolically favourable adiposity estimate and made no difference to the BMI estimate. Our secondary analyses found evidence to suggest that a higher maternal metabolically favourable adiposity decreases pregnancy fasting glucose levels while a higher maternal BMI increases them. The effects on neonatal anthropometric traits were consistent with the overall effect on birthweight but the smaller sample sizes for these analyses meant that the effects were imprecisely estimated. We also found evidence to suggest that higher maternal metabolically favourable adiposity decreases cord-blood leptin while higher maternal BMI increases it.Conclusions/interpretationOur results show that higher adiposity in mothers does not necessarily lead to higher offspring birthweight. Higher maternal adiposity can lead to lower offspring birthweight if accompanied by a favourable metabolic profile.Data availabilityThe data for the genome-wide association studies (GWAS) of BMI are available at https://portals.broadinstitute.org/collaboration/giant/index.php/GIANT_consortium_data_files . The data for the GWAS of body fat percentage are available at https://walker05.u.hpc.mssm.edu .

Dataset Information

Maternal Metabolomic Profile and Fetal Programming of Offspring Adiposity: Identification of Potentially Protective Lipid Metabolites.

Publications

Maternal Metabolomic Profile and Fetal Programming of Offspring Adiposity: Identification of Potentially Protective Lipid Metabolites.

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