A Phosphatidylserine Source of Docosahexanoic Acid Improves Neurodevelopment and Survival of Preterm Pigs

Abstract

The amount, composition, and sources of nutrition support provided to preterm infants is critical for normal growth and development, and particularly for structural and functional neurodevelopment. Although omega-3 long chain polyunsaturated fatty acids (LC-PUFA), and particularly docosahexanoic acid (DHA), are considered of particular importance, results from clinical trials with preterm infants have been inconclusive because of ethical limitations and confounding variables. A translational large animal model is needed to understand the structural and functional responses to DHA. Neurodevelopment of preterm pigs was evaluated in response to feeding formulas to term-equivalent age supplemented with DHA attached to phosphatidylserine (PS-DHA) or sunflower oil as the placebo. Newborn term pigs were used as a control for normal in utero neurodevelopment. Supplementing formula with PS-DHA increased weight of the brain, and particularly the cerebellum, at term-equivalent age compared with placebo preterm pigs (P’s < 0.10 and 0.05 respectively), with a higher degree of myelination in all regions of the brain examined (all p < 0.06). Brains of pigs provided PS-DHA were similar in weight to newborn term pigs. Event-related brain potentials and performance in a novel object recognition test indicated the PS-DHA supplement accelerated development of sensory pathways and recognition memory compared with placebo preterm pigs. The PS-DHA did not increase weight gain, but was associated with higher survival. The benefits of PS-DHA include improving neurodevelopment and possibly improvement of survival, and justify further studies to define dose-response relations, compare benefits associated with other sources of DHA, and understand the mechanisms underlying the benefits and influences on the development of other tissues and organ systems.

DHA Esterified to Phosphatidylserine or Phosphatidylcholine is More Efficient at Targeting the Brain than DHA Esterified to Triacylglycerol

“…Most report no difference in brain DHA accretion or subtle differences between the groups. More recently, other studies have focused on DHA‐PtdSer against a placebo only, DHA esterified to PtdCho or a DHA‐rich phospholipid blend with conflicting results. Others have suggested that DHA‐PtdSer could be efficient in the prevention of cognitive decline or in the treatment of ADHD, but both studies were conducted with a placebo that did not contain DHA as the only comparator.…”

Effects of Phosphatidylserine Source of Docosahexaenoic Acid on Cerebellar Development in Preterm Pigs

“…Preterm pigs were obtained via caesarean section at gestation day 105 (which corresponds to 91% of 115-day term). This stage of development is relevant to preterm infants born at week 32 [16]. A feeding tube and an umbilical artery catheter (Umbili-Cath, Utah Medical Products, Midvale, UT, USA) were placed in each preterm pig.…”

“…The amount of DHA that accumulates in the brain is higher when DHA is conjugated to PS, compared to triacylglycerol, likely because of the superior ability of PS-DHA to cross the blood-brain barrier [24,25]. Recently, using preterm pigs as a translational model for preterm infants, we showed that the use of a formula supplemented with PS-DHA results in cerebella that are heavier than those of control preterm pigs and not significantly smaller than those of pigs born at term [16]. This suggests that PS-DHA helps to promote cerebellar growth after preterm birth, but whether it enhances the development of specific cerebellar populations or key cerebellar developmental processes remains unknown.…”

“…The developing brain is sensitive to nutritional support [16]. Thus, optimizing early nutrition is a promising strategy for improving cerebellar development of infants born preterm.…”

A More Comprehensive Approach to the Neuroprotective Potential of Long-Chain Polyunsaturated Fatty Acids in Preterm Infants Is Needed—Should We Consider Maternal Diet and the n-6:n-3 Fatty Acid Ratio?

“…preclinical evidence suggesting that n-3 LCPUFAs, such as DHA are neuroprotective (26)(27)(28). Inflammation appears to play an important causal role in preterm birth, with ongoing inflammatory responses evident in the post-natal period (29).…”