Early pregnancy metabolomic signatures for child growth trajectories: a prospective metabolome-wide association study

Suboptimal early-life growth trajectories are predictors of later cardiometabolic risk. Although mid- to late-pregnancy maternal metabolites have been linked to fetal and birth outcomes, the role of early pregnancy metabolomic profiles in child growth trajectories is underexplored.

We examined associations between early pregnancy metabolites and child growth acceleration and deceleration from birth to age 1 and 2 y.

Among 1152 mother-child dyads from the prospective Pregnancy Environment and Lifestyle Study, maternal untargeted metabolomics were measured by gas chromatography/time-of-flight mass spectrometry, reversed phase-, and hydrophilic interaction liquid chromatography/quadrupole time-of-flight mass spectrometry using fasting serum collected at gestational weeks 10 to 13. Of this sample, 813 had child anthropometric data at age 1 y and 770 at age 2 y. Growth trajectories were defined by changes in weight-for-length z-scores from birth to age 1 or 2 y: growth acceleration [≥0.67 standard deviation (SD)], growth deceleration (≤-0.67 SD), extreme growth acceleration (≥1.34 SD), and extreme growth deceleration (≤-1.34 SD), with normal growth (-0.67 to 0.67 SD) as reference. Poisson regression examined associations between metabolites and child growth trajectories. Chemical enrichment analysis identified metabolite clusters associated with child growth trajectories, adjusted for false discovery rate (FDR).

A total of 431 annotated metabolites were identified. From birth to age 1 y, the polyunsaturated plasmalogen phosphatidylcholine (PC) cluster was associated with growth acceleration, whereas unsaturated fatty acids and polyunsaturated fatty acids were associated with growth deceleration (all FDR-corrected P < 0.05). Polyunsaturated plasmalogen PC and unsaturated PC clusters were associated with extreme growth acceleration from birth to 1 y, dicarboxylic acids with extreme growth acceleration from birth to 2 y, and branched-chain amino acids with extreme growth deceleration from birth to 2 y (all FDR-corrected P < 0.05).

Early pregnancy lipids are positively associated with early-life growth acceleration and extreme growth acceleration. Findings may provide insights into how early pregnancy metabolomic changes shape development.