4. Discussion
weight gain, breast milk, VLBWI, breast milk fortifier
SECONDARY, PREMATURE BIRTH
Choline and its metabolites play a central role in parenchymal homeostasis and growth, osmoregulation, methyl group transfer, liver and lipoprotein metabolism and, notably, neurologic development [Presumably due to the high growth rate of the fetus between 24- and 34-weeks postmenstrual age and the resulting higher nutrient requirements, exceptionally high choline plasma levels were observed in cord blood (45 (36–60) µmol/L), as a surrogate for fetal blood, during this period. These levels are higher than after 34 weeks (37 (29–45) µmol/L) and, particularly, than in adults (10 (8–12) µmol/L) [Following premature birth, plasma levels fall to half the cord blood concentrations within 48 h and remain at this low concentration thereafter or decrease even further [Preclinical studies in rats showed improved neurocognitive development in the offspring after maternal choline supplementation, suggesting that optimized maternal choline supply may be important for infants as well [This secondary analysis of an RCT shows that this not only occurs in response to choline supplementation, but also under basic conditions of nutritional choline supply by feeding fortified breast milk to human preterm infants, suggesting that variable choline supply with breast milk impacts both choline as well as betaine/methyl group status of VLBWI [The remaining question is how much choline premature infants should be supplemented with to achieve normal growth and development. From our previous short-term supplementation study it appears that an extra enteral intake (supplementation in addition to milk and standard fortifier) of around 30 mg/kg/d of total choline equivalent is required to achieve near-fetal plasma levels of 35–45 µmol/L [Patients in the present analysis had a median enteral choline intake of 40 mg/kg/d, and thus an intake at the upper end recommended by the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) (8–55 mg/kg/d) [Considering that, in spite of near-in-utero weight gain, VLBWI still show deficits in fat free mass and brain growth compared to term infants [In this secondary analysis, about two thirds of enteral choline intake occurred through breast milk, and one third through breast milk fortifier. Choline concentration in breast milk shows relevant inter- and intra-individual variability, and a choline deficit could be underestimated if based on single measurements. Individual variability may arise from SNPs of enzymes involved in choline metabolism as well as variability in maternal choline intake (which is compromised in a substantial proportion of parturients) [Limitations: This study is a secondary analysis, and therefore only allows describing associations rather than causal relationships. Due to the protocol of the original study, choline content of breast milk was only measured twice a week. Therefore, breast milk data were not always available exactly on the day prior to blood sampling. However, to make a comparison possible, the breast milk sample taken closest to blood sampling was matched with the blood sample, which resulted in a proportion of 85% measured at ±1 day before blood sampling (max. 5 days).