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

Abstract

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.

Maternal Metabolome in Pregnancy and Childhood Asthma or Recurrent Wheeze in the Vitamin D Antenatal Asthma Reduction Trial

“…While there are a growing number of studies investigating the role of the metabolome in asthma [ 12 ], to date, none have considered the impact of the global maternal metabolome in pregnancy on the risk of asthma in her offspring. The developmental origins hypothesis states that the in utero environment has an impact on fetal development and childhood health [ 13 ]. A mother’s health, exposures, and genetics influence that environment and are reflected in her metabolomic profile, which is representative of her physiological state throughout pregnancy [ 13 ].…”

“…The developmental origins hypothesis states that the in utero environment has an impact on fetal development and childhood health [ 13 ]. A mother’s health, exposures, and genetics influence that environment and are reflected in her metabolomic profile, which is representative of her physiological state throughout pregnancy [ 13 ]. There is an increasing body of literature demonstrating that the metabolome during pregnancy is associated with newborn outcomes, such as birth weight, small-for-gestational-age status, and hyperinsulinaemia [ 13 , 14 , 15 ].…”

“…A mother’s health, exposures, and genetics influence that environment and are reflected in her metabolomic profile, which is representative of her physiological state throughout pregnancy [ 13 ]. There is an increasing body of literature demonstrating that the metabolome during pregnancy is associated with newborn outcomes, such as birth weight, small-for-gestational-age status, and hyperinsulinaemia [ 13 , 14 , 15 ]. Given that we know the in utero environment is crucial to the development of respiratory health, and that asthma is a whole system disorder that is reflected in the metabolome, in this study, we aimed to determine if and how the maternal metabolome associates with the risk of early life asthma or recurrent wheeze.…”

A non-targeted LC–MS metabolic profiling of pregnancy: longitudinal evidence from healthy and pre-eclamptic pregnancies

“…It should also be noted that the changes described in maternal metabolism across pregnancy may reflect changes in placental metabolism (Dunn et al 2012 ). Furthermore, the metabolome is affected by genetic, dietary and environmental contributors (Kadakia et al 2019 ). We were not able to control for all of these confounding factors.…”

Metabolic Signatures of Gestational Weight Gain and Postpartum Weight Loss in a Lifestyle Intervention Study of Overweight and Obese Women

“…Moreover, metabolic profiling is an established technique for identifying biomarkers of health risks in mother-child cohorts addressing issues such as gestational diabetes, preterm birth, and fetal growth restriction [25][26][27]. For example, women with normal weight have different placenta metabolic profiles compared with obese women [28], and the maternal metabolome during pregnancy has been associated with newborn body fat [29].…”