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 early-pregnancy metabolites, but not total metabolite concentrations, are associated with foetal growth measures in third trimester and at birth.

Keywords: birth weight; foetal growth; metabolite profiles; metabolomics; pre-term birth; size-for-gestational age at birth.

FIGURE 1

Associations of cord blood total metabolite groups and individual metabolites with growth measures at birth. Values are regression coefficients (95% CI) representing the difference in growth measures per SD increase in total metabolite group concentrations (A) or individual metabolite concentrations (B). (B) Presents only FDR significant effect estimates. All estimates are given in Table S2. Models are adjusted for maternal age, parity, education level, pre‐pregnancy BMI, smoking and alcohol consumption during pregnancy and total energy intake. AA, amino acids; NEFA, non‐esterified fatty acids; PC.aa, diacyl‐phosphatidylcholines; PC.ae, acyl‐alkyl‐phosphatidylcholines; Lyso.PC.a, acyl‐lysophosphatidylcholines; Lyso.PC.e, alkyl‐lysophosphatidylcholines; SM, sphingomyelines; Free Carn: free carnitine; Carn.a, acyl‐carnitines; HC, Head circumference. *p values < 0.002 (FDR‐adjusted significance threshold). **p values < 1.05e‐5 (Bonferroni‐adjusted significance threshold)

FIGURE 2

Associations of cord blood total metabolite groups and individual metabolites with the odds of adverse birth outcomes. Values are odds ratios (95% CI) representing the risk of adverse birth outcomes per SD increase in total metabolite group concentrations (A) or individual metabolite concentrations (B). (B) presents only FDR significant effect estimates are presented. All estimates are given in Table S2. Models are adjusted for maternal age, parity, education level, pre‐pregnancy BMI, smoking and alcohol consumption during pregnancy and total energy intake. AA, amino acids; NEFA, non‐esterified fatty acids; PC.aa, diacyl‐phosphatidylcholines; PC.ae, acyl‐alkyl‐phosphatidylcholines; Lyso.PC.a, acyl‐lysophosphatidylcholines; Lyso.PC.e, alkyl‐lysophosphatidylcholines; SM, sphingomyelines; Free Carn: free carnitine, Carn.a, acyl‐carnitines; SGA, small size‐for‐gestational age at birth; LGA, large size‐for gestational age at birth. *p values <0.002 (FDR‐adjusted significance threshold). **p values < 1.05e‐5 (Bonferroni‐adjusted significance threshold)