Cord blood metabolites and rapid postnatal growth as multiple mediators in the prenatal propensity to childhood overweight

Abstract

Background The mechanisms underlying childhood overweight and obesity are poorly known. Here, we investigated the direct and indirect effects of different prenatal exposures on offspring rapid postnatal growth and overweight in childhood, mediated through cord blood metabolites. Additionally, rapid postnatal growth was considered a potential mediator on childhood overweight, alone and sequentially to each metabolite. Methods Within four European birth-cohorts (N = 375 mother-child dyads), information on seven prenatal exposures (maternal education, pre-pregnancy BMI, weight gain and tobacco smoke during pregnancy, age at delivery, parity, and child gestational age), selected as obesogenic according to a-priori knowledge, was collected. Cord blood levels of 31 metabolites, associated with rapid postnatal growth and/or childhood overweight in a previous study, were measured via liquid-chromatography-quadrupole-time-of-flight-mass-spectrometry. Rapid growth at 12 months and childhood overweight (including obesity) between four and eight years were defined with reference to WHO growth charts. Single mediation analysis was performed using the imputation approach and multiple mediation analysis using the extended-imputation approach. Results Single mediation suggested that the effect of maternal education, pregnancy weight gain, parity, and gestational age on rapid postnatal growth but not on childhood overweight was partly mediated by seven metabolites, including cholestenone, decenoylcarnitine(C10:1), phosphatidylcholine(C34:3), progesterone and three unidentified metabolites; and the effect of gestational age on childhood overweight was mainly mediated by rapid postnatal growth. Multiple mediation suggested that the effect of gestational age on childhood overweight was mainly mediated by rapid postnatal growth and that the mediating role of the metabolites was marginal. Conclusion Our findings provide evidence of the involvement of in utero metabolism in the propensity to rapid postnatal growth and of rapid postnatal growth in the propensity to childhood overweight. We did not find evidence supporting a mediating role of the studied metabolites alone between the studied prenatal exposures and the propensity to childhood overweight.

Uncovering the relationship between gut microbial dysbiosis, metabolomics, and dietary intake in type 2 diabetes mellitus and in healthy volunteers: a multi-omics analysis

“…The data were consistent with findings in a previous western cohort 42 , 43 . Interestingly, however, the unidentified (U) metabolite U8 was found to be correlated with childhood overweight and rapid growth 44 . Moreover, a previous study determined that imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology, particularly with low Bacteroides 2 enterotype, which has previously been associated with obesity 45 .…”

Associations between cord blood metabolic factors and early-childhood growth and overweight and obesity

“…A meta-analysis reviewed 22 studies and concluded that umbilical cord blood leptin was inversely associated with adiposity up to 3 years of age (16). In addition, two recent studies provided evidence convincing the involvement of cord blood metabolites (including cholestenone, branched-chain amino acid, and other metabolites) in the tendency to rapid postnatal growth and of rapid postnatal growth in the tendency to childhood overweight (33,34). So far, explorations concerning the relationships between cord blood metabolites and childhood overweight and adiposity were very limited in past research.…”