Special Considerations 2In nutrition for premature infants, much interest is currently focusing on the importance of long chain polyunsaturated fatty acids (LCPUFA) and more specifically docosahexaenoic acid (DHA) and arachidonic acid (AA). The most recent official LCPUFA recommendation for premature infants was issued by the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) in 2010.1  However, the discussion on actual needs is still ongoing, as is illustrated by a recent article by Lapillonne et al.2

LCPUFA and their role in early development

LCPUFA have been recognized as playing an important role in early development for many years.1 During pregnancy, DHA and AA cross the placenta to the fetus. After birth they are supplied through breast milk or infant formula. Maternal intake of DHA, and after birth the infant’s own intake, are recognized by EFSA as contributing to normal brain and visual development of fetus and infant born at term3. In preterm infants, clinical trials with formula containing both AA and DHA have shown mixed, but mostly beneficial effects on cognitive and visual development during the first year of life.1

LCPUFA in breast milk, infant formula and parenteral feeding

Preterm infants can be fed enterally with breast milk or infant formula, or parenterally. The LCPUFA-supply varies with the feeding method. Mainly due to variations in maternal diet, the DHA-content of human milk is highly variable. While all recommendations endorse breast milk as the preferred food source for preterm infants, AA and DHA-containing fortifiers and supplements are advised to meet the specific needs of preterm infants, particularly very preterm infants. Nutritional counseling during the lactation period is also recommended to ensure the mother’s optimal intake of omega-3 fatty acids.1,2

Commercial infant formulas for preterm infants vary in fat quantity and quality. Preterm infant formula is routinely supplemented with LCPUFA but most intravenous lipid emulsions for parenteral feeding provide little if any LCPUFA. Preterm infants who receive many weeks of parenteral nutrition, followed by breast milk and/or commercial preterm formula, may therefore accumulate a DHA-deficit of up to 50% of the normal rate.2

Effects of LCPUFA-supplementation in preterm infants

The effects of LCPUFA-supplementation on the developing brain have been extensively reported.2  Usually these studies find benefits of LCPUFA-supplementation on neurological and visual development. The dosages of LCPUFA used in early studies were chosen to resemble the concentrations of AA and DHA in term breast milk. Three trials report outcome data in preterm infants fed formulae with a higher DHA-content than previous studies. Overall, these studies indicate that greater DHA-supplementation is associated with improved neurological outcomes.2

In contrast, two recent meta-analyses did not support a beneficial effect of DHA and AA on neurodevelopmental outcomes in premature infants.4,5  However, it has been argued that meta-analyses may not be the best tool when there is extreme variability in study design, end points and study population, as was the case in these studies.2


Various regulatory bodies, professional organizations, and expert panels have issued recommendations and consensus statements on LCPUFA-intake for preterm infants. These recommendations generally rely on the average composition of breast milk, as well as data on LCPUFA-intake, blood and tissue levels, anthropometric parameters, and visual and neurocognitive outcomes. In 2005, Koletzko and Innis were the first to recognize the necessity of AA and DHA, and proposed a minimum value for the requirements of preterm infants.6 More recently, the ESPGHAN supported these recommendations but expressed them as mg/kg/day rather than a percentage of total fatty acids, as proportions only apply when full enteral feeding is reached.1  According to Lapillone et al., current nutritional management does not provide sufficient amounts of preformed DHA during the parenteral and enteral nutrition periods, especially in very preterm/very low birth weight infants. They suggest larger amounts are associated with better neurological outcomes, and are needed to compensate for intestinal malabsorption, DHA-oxidation, and early deficits. Their recommendation therefore is to extend the DHA-intake range from 12-30, as recommended by ESPGHAN, to 12-60 mg/kg/day (table 1).2

In addition to DHA, both recommendations advise supplementing AA to ensure adequate AA-levels during the period of DHA-supplementation.1,2  When a high dose of DHA is provided, 45 mg/kg/day of AA has been shown to support growth and normal AA-status.2  The Codex Alimentarius states  that in infant formula – when DHA is added – at least the same concentration of AA should be supplemented to the formula.7

Table 1 DHA- and AA- recommendations for premature infants

  Koletzko and Innis 20056 ESPGHAN 20101 Lapillonne 20132
AA 0.3-0.7 % of total fatty acids 16-39 mg/100kcal
18-42 mg/kg/day
18-45 mg/kg/day
DHA 0.2-0.5 % of total fatty acids 11-27 mg/100 kcal
12-30 mg/kg/day
12-60 mg/kg/day


While much is still unclear on the exact amounts of LCPUFA needed by preterm infants of varying size and age, as well as the long term consequences, their essential role is increasingly being recognized as scientific data suggest benefits of supplementation related to neurological and visual outcomes.


  1. Agostoni et al. Enteral Nutrient Supply for Preterm Infants: Commentary From the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition Committee on Nutrition. JPGN 2010;50:85–91.
  2. Lapillonne A, et al. Lipid Needs of Preterm Infants: Updated Recommendations. J Pediatr 2013;162:S37-47.
  3. EU claims register, accessed via: http://ec.europa.eu/nuhclaims/?event=search&CFID=628600&CFTOKEN=5c8b8945cec83c49-AF22CCB3-03F0-5A85 6F54514AB0BFB3DB&jsessionid=921220c37f1d9701fdda394837333752692eTR.
  4. Schulzke SM, Patole SK, Simmer K. Long-chain polyunsaturated fatty acid supplementation in preterm infants. Cochrane Database Syst Rev 2011;CD000375.
  5. Smithers LG et al. Effect of long-chain polyunsaturated fatty acid supplementation of preterm infants on disease risk and neurodevelopment: a systematic review of randomized controlled trials. Am J Clin Nutr 2008;87:912-20.
  6. Koletzko B, Innis SM. Lipids. In: Tsang RC, et al. Nutrition of the preterm infant: scientific basis and practical guidelines. Cincinnati (OH): Digital Educational Publishing; 2005. p. 97-140.
  7. Codex Alimentarius. Codex Standard 72 on Infant Formula. 1987; 1–7. Available at: www.codexalimentarius.net/download/standards/288/cxs_072e.pdf