Serum choline in extremely preterm infants declines with increasing parenteral nutrition

Anders K Nilsson, Anders Pedersen, Daniel Malmodin, Anna-My Lund, Gunnel Hellgren, Chatarina Löfqvist, Ingrid Hansen Pupp, Ann Hellström, Anders K Nilsson, Anders Pedersen, Daniel Malmodin, Anna-My Lund, Gunnel Hellgren, Chatarina Löfqvist, Ingrid Hansen Pupp, Ann Hellström

Abstract

Purpose: Choline is an essential nutrient for fetal and infant growth and development. Parenteral nutrition used in neonatal care lack free choline but contain small amounts of lipid-bound choline in the form of phosphatidylcholine (PC). Here, we examined the longitudinal development of serum free choline and metabolically related compounds betaine and methionine in extremely preterm infants and how the concentrations were affected by the proportion of parenteral fluids the infants received during the first 28 postnatal days (PNDs).

Methods: This prospective study included 87 infants born at gestational age (GA) < 28 weeks. Infant serum samples were collected PND 1, 7, 14, and 28, and at postmenstrual age (PMA) 32, 36, and 40 weeks. The serum concentrations of free choline, betaine, and methionine were determined by 1H NMR spectroscopy.

Results: The median (25th-75th percentile) serum concentrations of free choline, betaine, and methionine were 33.7 (26.2-41.2), 71.2 (53.2-100.8), and 25.6 (16.4-35.3) µM, respectively, at PND 1. The choline concentration decreased rapidly between PND one and PND seven [18.4 (14.1-26.4) µM], and then increased over the next 90 days, though never reaching PND one levels. There was a negative correlation between a high intake of parenteral fluids and serum-free choline.

Conclusion: Circulating free choline in extremely preterm infants is negatively affected by the proportion of parenteral fluids administered.

Trial registration: ClinicalTrials.gov Identifier NCT02760472, April 29, 2016, retrospectively registered.

Keywords: Betaine; Enteral nutrition; Human milk; Methionine; Phosphatidylcholine; Proton nuclear magnetic resonance.

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Violin plots showing serum concentrations of choline (a), betaine (b), and methionine (c) according to postnatal day. n = 85 (PNA d1), 79 (PNA d7), 81 (PNA d14), 72 (PNA d28), 81 (PNA d33-74), 52 (PNA d75-99), and 54 (PNA > 100). The dashed line in A indicate concentrations of free choline in cord plasma as reported by Bernhard et al. [22] based on median PMA 25.4 weeks at PNA day 1 and PMA 40 weeks at PNA day 100–158; circles show postnatal serum concentrations in full-term infants as reported by Ilcol et al. [30]
Fig. 2
Fig. 2
Postnatal changes in serum metabolites with the intake of enteral and parenteral fluids. a Median amount (ml/kg/d) of enteral (mother’s milk and donor milk, solid lines) and parenteral fluids (dashed lines) given during the infants’ first 28 postnatal days. Error bars indicate 25th and 75th percentiles. Box plots showing the concentration of (b) choline, (c) betaine, and (d) methionine if the infant was receiving less or more (darker boxes) than the median parenteral fluids. Whiskers indicate 25th and 75th percentiles. *p < 0.05, Mann–Whitney U
Fig. 3
Fig. 3
Choline concentration on postnatal day 7 based on gestational age at birth. Infants are grouped based on gestational age at birth n = 30) or > 25 weeks (n = 51). The serum concentration of choline was significantly higher in infants born after 25 weeks (Mann–Whitney U, p = 0.002). Whiskers indicate 25th and 75th percentiles

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