Cord Blood Metabolome Is Highly Associated with Birth Weight, but Less Predictive for Later Weight Development

Abstract

Background/aims: Fetal metabolism may be changed by the exposure to maternal factors, and the route to obesity may already set in utero. Cord blood metabolites might predict growth patterns and later obesity. We aimed to characterize associations of cord blood with birth weight, postnatal weight gain, and BMI in adolescence.

Methods: Over 700 cord blood samples were collected from infants participating in the German birth cohort study LISAplus. Glycerophospholipid fatty acids (GPL-FA), polar lipids, non-esterified fatty acids (NEFA), and amino acids were analyzed with a targeted, liquid chromatography-tandem mass spectrometry based metabolomics platform. Cord blood metabolites were related to growth factors by linear regression models adjusted for confounding variables.

Results: Cord blood metabolites were highly associated with birth weight. Lysophosphatidylcholines C16:1, C18:1, C20:3, C18:2, C20:4, C14:0, C16:0, C18:3, GPL-FA C20:3n-9, and GPL-FA C22:5n-6 were positively related to birth weight, while higher cord blood concentrations of NEFA C22:6, NEFA C20:5, GPL-FA C18:3n-3, and PCe C38:0 were associated with lower birth weight. Postnatal weight gain and BMI z-scores in adolescents were not significantly associated with cord blood metabolites after adjustment for multiple testing.

Conclusion: Potential long-term programming effects of the intrauterine environment and metabolism on later health cannot be predicted with profiling of the cord blood metabolome.

Keywords: Childhood obesity; Cord blood; Early programming; Metabolomics.

Fig. 1

Birth weight associations. Manhattan plot of the association between birth weight and metabolites adjusted for study center, sex, gestational age, maternal BMI, weight gain during pregnancy, smoking in the third trimester and education. Cx:y = An acyl group of chain length x and y double bounds; NEFA = nonesterified fatty acids; GPL-FA = glycerophospholipid fatty acids; LPC = lysophosphatidylcholines; PC = phosphatidylcholines; SM = sphingomyelins. Bonferroni significance level of 2.39 ×10⁻⁴.

Fig. 2

Sex stratified birth weight associations. Estimates of the association between birth weight and metabolites for male (blue) and female (red) subgroup adjusted for study center, sex, gestational age, maternal BMI, weight gain during pregnancy, smoking in the third trimester and education. NEFA = Nonesterified fatty acids; LPCa = lysophosphatidylcholines; PCe = acyl-alkyl-phosphatidylcholines. Bonferroni significance level of 2.39 ×10⁻⁴.

Fig. 3

Associations to weight gain and zBMI. Comparison of the associations between cord blood metabolites and weight gain during the first 6 months of life as well as zBMI at the age of 15. + Birth weight-increasing metabolites (beta per SD > 10 g), – birth weight-decreasing metabolites (beta per SD > −10 g), size of the symbols corresponds to the significance of the association with birth weight. Cx:y = An acyl group of chain length x and y double bounds; NEFA = nonesterified fatty acids; GPL-FA = glycerophospholipid fatty acids; LPC = lysophosphatidylcholines; PC = phosphatidylcholines; SM = sphingomyelins.

Fig. 4

Partial correlation network. Partial correlation network of cord blood metabolites associated with birth weight. Red lines display positive correlations, whereas blue lines stand for negative associations. Cx:y = An acyl group of chain length x and y double bounds; NEFA = nonesterified fatty acids; GPL fatty acids = glycerophospholipid fatty acids; LPC = lysophosphatidylcholines; PC = phosphatidylcholines; SM = sphingomyelins.