The potential role for arachidonic and docosahexaenoic acids in protection against some central nervous system injuries in preterm infants

Abstract

The risk of central nervous, visual, and auditory damage increases from 2/1000 live births in the normal birthweight to > 200/1000 as birthweight falls below 1500 g. Such babies are most likely to be born preterm. Advances in infant care have led to increasing numbers of very-low-birthweight, preterm infants surviving to school age with moderate to severe brain damage. Steroids are one of the current treatments, but they cause significant, long-term problems. The evidence reported here suggests an additional approach to protecting the very preterm infant by supporting neurovascular membrane integrity. The complications of preterm, very-low-birthweight babies include bronchopulmonary dysplasia, retinopathy of prematurity, intraventricular hemorrhage, periventricular leukomalacia, and necrotizing enterocolitis, all of which have a vascular component. Arachidonic acid (AA) and DHA are essential, structural, and functional constituents of cell membranes. They are especially required for the growth and function of the brain and vascular systems, which are the primary biofocus of human fetal growth. Molecular dynamics and experimental evidence suggest that DHA could be the ligand for the retinoid X receptor (RXR) in neural tissue. RXR activation is an obligatory step in signaling to the nucleus and in the regulation of gene expression. Very preterm babies are born with minimal fat stores and suboptimal circulating levels of these nutrients. Postnatally, they lose the biomagnification of the proportions of AA and DHA by the placenta for the fetus. No current nutritional management repairs these deficits. The placental biomagnification profile highlights AA rather than DHA. The resultant fetal FA profile closely resembles that of the vascular endothelium and not the brain. Without this nourishment, cell membrane abnormalities would be predicted. We present a scientific rationale for a common pathogenic process in the complications of prematurity.

Omega-3 Long-Chain Polyunsaturated Fatty Acids for Extremely Preterm Infants: A Systematic Review

“…Considering the anti-inflammatory effect of DHA, and of its downstream metabolite eicosanoids, 51,52 authors have argued that DHA deficits in preterm infants may have considerable, underestimated adverse effects during the neonatal period. 9,10,53,54 In light of the strong association between elevated inflammation and both shortand long-term morbidities in extreme preterm infants, 48,55 we postulate that a DHA supplementation or a decrease in the omega-6/omega-3 reduces the occurrence of these major adverse neonatal outcomes, including BPD. Of note, when specifically examining studies in which omega-6 lipids were coadministered with DHA, we detected no additional benefit on BPD compared with studies using DHA alone (Fig 2B), indicating a selective role of DHA or the ratio omega-6/omega-3.…”

Polyunsaturated fatty acids: From diet to binding to ppars and other nuclear receptors

“…RXR is also able to bind FAs, and docosahexaenoic acid (DHA) has been shown to activate it (de Urquiza et al, 2000;Crawford et al, 2003). DHA deficiency in rat and humans results in abnormalities similar to those observed in RXR knock-out mice.…”

Polyunsaturated fatty acids and anthropometric indices of children in rural China

“…Docosahexaenoic acid and AA enhance growth in term and preterm infants (Clandinin et al, 1980, ) and have been shown to affect visual acuity and maturation of the visual cortex Birch et al, 2002). Docosahexaenoic acid and AA also affect cell signaling, maintain optimal states of fluidity and enhance neurovascular membrane integrity (Hardy and Kleinman, 1994;Jorgensen et al, 1996;Giovanni et al, 1998;Larque et al, 2002;Crawford et al, 2003;Uauy et al, 2003) as well as augment cognitive development (Agostoni et al, 1995;Birch et al, 2000,). Long-chain polyunsaturated fatty acids (LCPUFAs) may therefore play a very important role in growth and development in later childhood, yet intake data by preschool children are sparse, especially in developing countries.…”