Prenatal exercise interventions result in subtle changes in the human breast milk metabolome and lipidome 7-14 days postpartum: exploratory analyses of the FitMum randomized controlled trial.

BACKGROUND

Prenatal exercise has been linked to positive effects on offspring health in animal and human studies, with changes in breast milk composition suggested as a possible explanatory mechanism. This exploratory study investigated whether prenatal exercise interventions affected the metabolome and lipidome of transitional human breast milk in healthy pregnant women compared to standard care.

METHODS

The present study is based on the FitMum randomized controlled trial (Copenhagen University Hospital - North Zealand, 2018-2021), which included in total 220 healthy inactive pregnant women (≤15+0 weeks' gestation). Participants were randomly assigned to structured supervised exercise training (EXE) three times per week throughout pregnancy, motivational counselling on physical activity (MOT) offered as seven individual and group sessions during pregnancy, or standard care (CON). Physical activity was monitored continuously from inclusion throughout one year postpartum by a wrist-worn activity tracker. Samples of transitional breast milk were collected from 99 participants 7-14 days postpartum and exploratory and hypothesis-generating analyses were conducted using untargeted metabolomics and lipidomics.

RESULTS

After adjustment for multiple comparisons, no significant overall differences in metabolites or lipids were observed between EXE or MOT and CON. However, subsequent nominal and secondary analyses of specific subsets revealed subtle distinctions. Cluster analysis identified higher levels of 1,7-Dimethyluric acid in both EXE and MOT versus CON (p < 0.05) and elevated oxoglutarate in EXE relative to MOT (p = 0.04). Further nominal species-level analyses of triglycerides and lipid reactions, along with pathway enrichment, showed an overall reduction in triglyceride species in EXE and a predicted conversion pathway from diacylglycerol to phospholipid species in both intervention groups. Importantly, the two interventions impacted different lipid processes and pathways.

CONCLUSIONS

While prenatal exercise interventions did not induce major metabolomic or lipidomic changes in breast milk early postpartum, subsequent nominal analyses uncovered specific metabolite and lipid differences that may influence offspring metabolism.

TRIAL REGISTRATION: ClinicalTrial.gov; NCT03679130; Sep 20, 2018. A study protocol paper has been published (http://dx.doi.org/10.1136/bmjopen-2020-043671) and a statistical analysis plan is available with the trial registration at (https://clinicaltrials.gov/ct2/show/NCT03679130?cond=fitmum&draw=2&rank=1).