Associations of maternal and infant metabolite profiles with foetal growth and the odds of adverse birth outcomes

Abstract

Background: Adaptations in maternal and foetal metabolic pathways may predispose to altered foetal growth and adverse birth outcomes.Objective: To assess the associations of maternal early-pregnancy metabolite profiles and infant metabolite profiles at birth with foetal growth from first trimester onwards and the odds of adverse birth outcomes.Methods: In a prospective population-based cohort among 976 Dutch pregnant women and their children, serum concentrations of amino acids, non-esterified fatty acids (NEFA), phospholipids (PL) and carnitines in maternal early-pregnancy blood and in cord blood were obtained by liquid-chromatography tandem mass spectrometry. Information on foetal growth was available from first trimester onwards.Results: After false discovery rate correction for multiple testing, higher infant total and individual NEFA concentrations were associated with a lower weight, length, and head circumference at birth. Higher infant total and individual acyl-lysophosphatidylcholine (lyso.PC.a) and alkyl-lysophosphatidylcholine concentrations were associated with higher weight and head circumference (lyso.PC.a only) at birth, higher odds of LGA and lower odds of SGA. Few individual maternal metabolites were associated with foetal growth measures in third trimester and at birth, but not with the odds of adverse birth outcomes.Conclusions: Our results suggest that infant metabolite profiles, particularly total and individual lyso.PC.a and NEFA concentrations, were strongly related to growth measures at birth and the odds of adverse birth outcomes. Few individual maternal earlypregnancy metabolites, but not total metabolite concentrations, are associated with foetal growth measures in third trimester and at birth.

Longitudinal lipidomic profiles during pregnancy and associations with neonatal anthropometry: findings from a multiracial cohort

“…In a prospective study of 976 Dutch pregnant women and their children, Voerman and colleagues observed several individual maternal phospholipids during early pregnancy significantly associated with femur length and head circumference in the third trimester and weight and head circumference at birth. 11 Morillon et al. performed a lipidomics analysis in a case–control study of 40 SGA cases and 40 controls and showed an association between elevated maternal levels of GPL at GW 20 and higher risk of SGA.…”

“… 7 Advanced lipidomics technologies permit the high-throughput assessment of a large number of lipid species in human bio-samples. Recently, maternal lipidomic profiles in plasma or serum samples have been associated with GDM 7 and perinatal outcomes, such as intrauterine growth restriction, pre-term birth, 8 birth weight (BW), 9 , 10 , 11 small size-for-gestational age at birth (SGA), 12 , 13 and large size-for-gestational age at birth (LGA). 10 …”

The Influence of Acitretin on Brain Lipidomics in Adolescent Mice—Implications for Pediatric and Adolescent Dermatological Therapy

“…While it has been described that lyso-PC is, for example, decreased in Alzheimer’s disease patients brains and in tissue of mouse models [ 62 , 63 ], we were not able to identify reports on its distinctive role in late brain development. Higher serum levels of acyl-lyso-PC and alkyl-lyso-PC were associated with higher weight, length, and head circumference in infants at birth [ 64 ], probably pointing at a beneficial effect. The cytosolic calcium-dependent phospholipase A2 (cPLA2) seems to preferably target phosphatidylcholine, resulting in release of lyso-PC and arachidonic acid (ARA) (for a review on PLA2: [ 65 ]).…”