Postnatal adaptations of phosphatidylcholine metabolism in extremely preterm infants: implications for choline and PUFA metabolism

Abstract

Background Lipid metabolism in pregnancy delivers PUFAs from maternal liver to the developing fetus. The transition at birth to diets less enriched in PUFA is especially challenging for immature, extremely preterm infants who are typically supported by total parenteral nutrition. Objective The aim was to characterize phosphatidylcholine (PC) and choline metabolism in preterm infants and demonstrate the molecular specificity of PC synthesis by the immature preterm liver in vivo. Methods This MS-based lipidomic study quantified the postnatal adaptations to plasma PC molecular composition in 31 preterm infants <28 weeks’ gestational age. Activities of the cytidine diphosphocholine (CDP-choline) and phosphatidylethanolamine-N-methyltransferase (PEMT) pathways for PC synthesis were assessed from incorporations of deuterated methyl-D9-choline chloride. Results The concentration of plasma PC in these infants increased postnatally from median values of 481 (IQR: 387–798) µM at enrollment to 1046 (IQR: 616–1220) µM 5 d later (P < 0.001). Direct incorporation of methyl-D9-choline demonstrated that this transition was driven by an active CDP-choline pathway that synthesized PC enriched in species containing oleic and linoleic acids. A second infusion of methyl-D9-choline chloride at day 5 clearly indicated continued activity of this pathway. Oxidation of D9-choline through D9-betaine resulted in the transfer of 1 deuterated methyl group to S-adenosylmethionine. A very low subsequent transfer of this labeled methyl group to D3-PC indicated that liver PEMT activity was essentially inactive in these infants. Conclusions This study demonstrated that the preterm infant liver soon after birth, and by extension the fetal liver, was metabolically active in lipoprotein metabolism. The low PEMT activity, which is the only pathway for endogenous choline synthesis and is responsible for hormonally regulated export of PUFAs from adult liver, strongly supports increased supplementation of preterm parenteral nutrition with both choline and PUFAs.

Effects of Dietary Choline Levels During Pregnancy on Reproductive Performance, Plasma Metabolome and Gut Microbiota of Sows

“…In contrast, the within-litter birth weight CV for piglets born alive and suckling piglet mortality decreased linearly. Consistent with our results, studies in animals and humans suggest that maternal choline supplementation during pregnancy has beneficial effects on fetal growth ( 17 , 18 ). As is generally known, fetal growth is dependent on the placental nutrient supply.…”

Sphingolipidomics of serum in extremely preterm infants: Association between low sphingosine-1-phosphate levels and severe retinopathy of prematurity

“…As expected, the PC species composition changes largely follow that of total phospholipid-bound fatty acids, as PC constitutes the major phospholipid class in serum. The serum total PC concentration, as well as changes in PC species composition during the first week of life in our study, were comparable to that reported in a similar cohort recently [ 32 ]. However, total PC concentration was somewhat lower, but SM concentration higher in this study than reported for a cohort of slightly less premature children [ 21 ].…”

Digestion and Absorption of Milk Phospholipids in Newborns and Adults

“…The metabolism of chylomicron PLs and TAGs after feeding milk fat thus contributes nitrogen bases and PUFAs to both the high PL turnover in the liver and to the lyso-PC formation that transports both fatty acids and nitrogen bases to extrahepatic tissues, including the brain. Recent studies have exemplified that analysis of time courses using stable isotopes ( 156 , 178 ) will clarify the nutritional, diurnal, and developmental regulations of these pathways in the near future.…”

“…In premature babies, PC levels increase via the formation of PC via the CDP-choline pathway weeks after birth ( 156 ). Since the PEMT is poorly expressed, the rate of formation of AA and DHA molecular species may be restricted, whereas, in utero , both choline and PUFAs are supplied indirectly via the PEMT pathway of the mother.…”