Discussion
breast milk
PRETERM BIRTH, MINOR
In this study, we investigated the metabolism of four different choline compounds, which all might be suitable to optimize choline supplementation of very preterm infants. To better follow the differences in the kinetics of individual compounds, we applied stable isotope labeling of the tri-methyl-ammonium group of the choline unit with Deuterium (D9-choline) of supplements, as previously used for choline chloride only [Following D9-POPC administration, however, D9-choline was not detected at any time point. D9-betaine was detected only at 12–60 h, but not at 1 h, and D9-betaine maximum plasma concentrations were lower compared to water-soluble compounds. This is important for three reasons: first, betaine is synthesized from free choline by choline dehydrogenase and betaine-aldehyde dehydrogenase [The concept of PC supplementation in preterm infants may additionally be useful with respect to the de-acylation/re-acylation process that PC undergoes during assimilation. We have previously shown that following preterm birth, linoleic acid-containing PC (C18:2-PC) increases at the expense of compounds comprising arachidonic (C20:4-PC) or docosahexaenoic acid (C22:6-PC). This is due to the low supply with these fatty acids and high supply with linoleic acid from breast milk and formula, which is in contrast to placental retention of linoleic acid and preferential arachidonic and docosahexaenoic acid delivery to the fetus [Finally, experiments in adults have shown that TMAO is formed from water-soluble choline supplements but not from PC [Our findings are important to optimize future preterm infant nutrition. Assuming that the prenatal choline plasma concentrations are optimal for rapid fetal growth and development, we previously showed that an enteral supply of 50–60 mg/kg/d choline is needed to achieve these prenatal choline plasma concentrations in enterally fed preterm infants [We detected similarly high D9-choline concentrations in plasma after supplementation with D9-choline chloride, D9-phosphoryl-choline and D9-GPC. Due to sparse sampling, it remains unclear whether the minor differences in maximal plasma concentrations at 1 h are clinically relevant and due to substance-specific differences in the absorption kinetics. Previous data from adults may point in this direction [The observation that native choline concentrations weakly correlated with D9 choline plasma concentrations may indicate that there may be inter-individual differences in absorption and availability of enterally administered choline, which must be considered in future studies. The observation that the GPC group had lower native choline concentrations may indicate that we underestimate the effect of supplementation with GPC on choline plasma concentrations. It may have been of additional interest to determine exact daily baseline choline intake in the study subjects, to see whether native choline concentrations correlate with this intake.Optimizing fatty acid composition of plasma PC is key to plasma transport and organ delivery of PUFA, such as arachidonic and docosahexaenoic acid [