Long-chain Polyunsaturated Fatty Acid Supplementation in Preterm Infants

Long-chain polyunsaturated fatty acids (LCPUFA) are fatty acids of 20 or more carbon atoms and two or more double bonds. These molecules are components of all cell membranes but are particularly concentrated in neural (synapsis) and retinal (outer segment of photoreceptor cells) tissues. During gestation, the placenta actively enriches the fetal circulation with LCPUFA. Therefore, preterm infants are denied the usual gestational accretion of LCPUFA, and there are few alternative sources of LCPUFA for the infant born preterm. After birth, concentrations of circulating LCPUFA drop rapidly and the preterm infant may require a postnatal source of LCPUFA to support tissue demands. Considerable research has focused on the relationship between dietary LCPUFA and visual and cognitive functions in preterm infants. As a result of this research effort, nearly all formula milks for preterm infants now are enriched with LCPUFA.
It should be noted, however, that most trials have tested formulas that have concentrations of LCPUFA similar to the average milk of Western women (around 0.3% of total fat), while the concentrations of LCPUFA may vary widely from 0.1% to 1.4%. Importantly, a comparison of the rate of fetal accretion of LCPUFA against the average LCPUFA content of human milk of Western women or preterm formula suggests that preterm infants are not receiving as much LCPUFA in the postnatal period as they would have received in utero.
Although trials involving electrophysiologic assessment of visual maturation consistently show improved retinal sensitivity and visual acuity with LCPUFA supplementation, the concentration of LCPUFA in milk necessary to support optimal visual development is not known, even if the greatest improvement was observed in association with the highest dose of n-3 LCPUFA.
It has been demonstrated that children born preterm have poorer cognitive performance if compared with children born at term. It has also been suggested that preterm infants fed at least in part with human milk have better cognitive performance than those fed other infant milks. On these basis, it was possible to speculate that the LCPUFA present in human milk might enhance cognitive development. Results of some randomised trials have provided different indications. Therefore, at present it is not possible to immediately translate results of these trials into clinically meaningful assessments.
In the past, there has been some controversy over the introduction of LCPUFA in infant formula, due to a possible effect on .physical and antropometrical development. Recently, some randomised clinical trials have compared anthropometry of preterm infants fed LCPUFA enriched formula and infants fed unsupplemented formula. Even in this context, results of clinical trials are contoversal, because of various LCPUFA doses administrated and different methodologies. 
It is also important to evaluate other LCPUFA potential effects, particularly for vulnerable preterm infants. Overall, comparative trials have shown no increased incidence of sepsis, necrotizing enterocolitis, or bronchopulmonary dysplasia among preterm infants fed LCPUFA-supplemented formulas.
In conclusion, data from the efficacy trials indicate that LCPUFA supplementation of infant formulas provides short-term benefits for visual maturation, especially on electrophysiologic assessments. However, it has been difficult to translate these benefits to more clinically meaningful long-term assessments of cognitive abilities. Further research is required to determine the overall balance of LCPUFA in the diets of preterm infants fed either human milk or infant formula.

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