Potential first trimester metabolomic biomarkers of abnormal birth weight in healthy pregnancies

Ciborowski, Michał; Zbucka-Krętowska, Monika; Bomba‐Opoń, Dorota; Wielgoś, Mirosław; Brawura-Biskupski-Samaha, Robert; Pierzyński, Piotr; Szmitkowski, Maciej; Wołczyński, S; Lipińska, Danuta; Citko, Anna; Bauer, Witold; Górska, Maria; Krętowski, Adam

doi:10.1002/pd.4386

Cited by 33 publications

(29 citation statements)

References 48 publications

(57 reference statements)

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“…Few existing studies have investigated associations between maternal pregnancy metabolites and newborn size [9,10] and none have examined maternal metabolite profiles post glucose load or evaluated the relationship between maternal metabolites and newborn adiposity or cord C-peptide. A Spanish cohort of 800 mother-newborn pairs related maternal urinary metabolites during pregnancy with fetal and newborn size and similarly found that maternal urinary BCAAs, alanine, steroid hormones and choline were associated with greater intrauterine fetal growth and birthweight [9].…”

Section: Discussionmentioning

confidence: 99%

“…In adults, branched-chain amino acids (BCAAs), aromatic amino acids (AAAs), short-chain acylcarnitines (C2, C6, C8; see ESM Table 1 for acylcarnitine nomenclature) and the carnitine ester of 3-hydroxybutyrate (acylcarnitine C4-OH) have all been associated with insulin resistance, higher HbA 1c and/or postprandial glucose levels [5][6][7][8]. However, the impact of the maternal metabolome on the developing fetus, as evidenced by newborn outcomes, is largely unknown and understudied [9,10].…”

Section: Introductionmentioning

confidence: 99%

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Maternal metabolites during pregnancy are associated with newborn outcomes and hyperinsulinaemia across ancestries

et al. 2018

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Aims/hypothesis We aimed to determine the association of maternal metabolites with newborn adiposity and hyperinsulinaemia in a multi-ethnic cohort of mother-newborn dyads. Methods Targeted and non-targeted metabolomics assays were performed on fasting and 1 h serum samples from a total of 1600 mothers in four ancestry groups (Northern European, Afro-Caribbean, Mexican American and Thai) who participated in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study, underwent an OGTT at~28 weeks gestation and whose newborns had anthropometric measurements at birth. Results In this observational study, meta-analyses demonstrated significant associations of maternal fasting and 1 h metabolites with birthweight, cord C-peptide and/or sum of skinfolds across ancestry groups. In particular, maternal fasting triacylglycerols were associated with newborn sum of skinfolds. At 1 h, several amino acids, fatty acids and lipid metabolites were associated with one or more newborn outcomes. Network analyses revealed clusters of fasting acylcarnitines, amino acids, lipids and fatty acid metabolites associated with cord C-peptide and sum of skinfolds, with the addition of branched-chain and aromatic amino acids at 1 h. Conclusions/interpretation The maternal metabolome during pregnancy is associated with newborn outcomes. Maternal levels of amino acids, acylcarnitines, lipids and fatty acids and their metabolites during pregnancy relate to fetal growth, adiposity and cord C-peptide, independent of maternal BMI and blood glucose levels.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Maternal metabolites during pregnancy are associated with newborn outcomes and hyperinsulinaemia across ancestries

et al. 2018

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“…For example, increased maternal glycerol in the first trimester predicts subsequent pre-eclampsia (107), while lower levels of phospholipids, lysolipids, monoacylglyerols and FA binding protein predict fetal macrosomia (105). Small for gestational age (SGA) can be predicted by a panel of maternal metabolites assayed at 15 weeks of pregnancy, including sphingolipids, phospholipids, and carnitines (108).…”

Section: The Lipid Metabolomementioning

confidence: 99%

What Have Metabolomics Approaches Taught Us About Type 2 Diabetes?

et al. 2016

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Type 2 diabetes (T2D) is increasing worldwide, making identification of biomarkers for detection, staging, and effective prevention strategies an especially critical scientific and medical goal. Fortunately, advances in metabolomics techniques, together with improvements in bioinformatics and mathematical modeling approaches, have provided the scientific community with new tools to describe the T2D metabolome. Among the metabolomics signatures associated with T2D and obesity include increased levels of lactate, glycolytic intermediates, branched-chain and aromatic amino acids, and long-chain fatty acids. Conversely, tricarboxylic acid cycle intermediates, betaine and other metabolites decrease. Future studies will be required to fully integrate these and other findings into our understanding of the diabetes pathophysiology and to identify biomarkers of disease risk, stage, and responsiveness to specific treatments.

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“…Mothers with poor pregnancy outcomes showed differences in plasma levels during the second trimester of pregnancy in lipids (sterols, glycerophospholipids, sphingolipids), steroid hormones (progesterone metabolites) and vitamin D metabolites compared to controls (n=40) (23). Another recent study using LC-MS on maternal serum in early pregnancy (12–14th weeks) could predict the risk for birthweight >4000 g (n=20) but not LBW (n=19) (24). Mechanistic insights were provided based on lower levels of phospholipids, lysophospholipids, and monoacylglycerols early in pregnancy in mothers with fetal macrosomia, suggesting an increased transport of lipids to the fetus (also supported by an indirect correlation between placental lipid transporters adipocyte fatty acid-binding protein and maternal free lipids).…”

Section: Applications Of Metabolic Profilingmentioning

confidence: 99%

Importance of metabolomics analyses of maternal parameters and their influence on fetal growth

Liu

2017

Experimental and Therapeutic Medicine

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Metabolomics is the scientific study of chemical processes involving metabolites. Specifically, metabolomics is the systematic study of the unique chemical fingerprints that specifically conveys cell processes. Fetal growth aberrations, including fetal growth restriction and macrosomia, convey the highest risk of perinatal mortality and morbidity, as well as increasing the chance of developing chronic disease in later life. We searched the electronic database PubMed for preclinical as well as clinical controlled studies pertaining to metabolomics analyses of maternal parameters and their influence on fetal growth. It was observed clearly that metabolic profiling/metabolomics approaches in maternal urine samples provide information on early-life exposure and are potentially linked to child health outcomes, in addition to identifying new biomarkers of exposure. This review article is aimed to discuss intra- and inter-individual variations in maternal urine profiles during pregnancy, fetal growth outcomes and environmental sources of metabolic variations. The review concludes that metabolic profiling of mother is a useful tool for the evaluation of influences on the growth of the fetus.

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Potential first trimester metabolomic biomarkers of abnormal birth weight in healthy pregnancies

Abstract: Serum fingerprinting in early pregnancy can predict the risk of macrosomia. Serum levels of A-FABP and several lipids are promising prognostic markers for macrosomia in healthy pregnancies.

Cited by 33 publications

References 48 publications

Maternal metabolites during pregnancy are associated with newborn outcomes and hyperinsulinaemia across ancestries

Maternal metabolites during pregnancy are associated with newborn outcomes and hyperinsulinaemia across ancestries

What Have Metabolomics Approaches Taught Us About Type 2 Diabetes?

Importance of metabolomics analyses of maternal parameters and their influence on fetal growth

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