**11. Changes in brain development during PN**

Preterm infants on PN long-term are at high risk of having compromised brain development and delayed cognitive skills. Neurodevelopmental delays and defects are commonly seen among 40–50% of preterm infants [121]. Preterm babies born during late second and third trimesters (30 weeks) with extremely low body weight < 1 kg with poorly developed GI tracts show delayed brain development and maturation. These preterm babies rely on PN for proper growth and development. Magnetic resonance imaging (MRI) technology has shown that the total brain development including white and gray matter happens around 25–37 weeks of gestation with cerebellum enlargement [126–129]. PMID: 17151398 showed that using a preterm pig model with EN vs. PN, preterm pigs on PN for 10 days had neurodevelopment delays, smaller brains, immature myelination patterns and compromised motor skills compared to those on EN [8]. In addition, PN pigs had smaller cerebellums with slower locomotion than EN pigs regardless of similar body weight. These results suggest that maintaining preterm infants on PN long-term may be detrimental for optimal brain development [8].

The effect of soybean derived fat components of PN and their association with fatty liver disease was discussed in an earlier section. Here, we discuss the effect of soybean derived oil on the brain in PN patients. Neurodevelopmental disorders among PN infants occurs due to the effects of soybean oil derived PN and its association with the gut microbiome, and the development of gut microbiome-brain axis [130].

This raises the prudence of replacing soybean oil derived lipid emulsions with fish oil derived lipid emulsions for protection against PNALD and to ensure support of optimal brain growth and development. It has also been shown that dietary ω-3 fatty acid docosahexaenoic acid (DHA) and arachidonic acid in fish oil modulate brain development in piglets [131–133]. To date, there are no specific clinical models established to study PN associated neurodevelopmental disorders in preterm infants and children. Therefore, further studies are needed to identify the cause of PN associated neurodevelopmental disorders.
