Daily Enteral DHA Supplementation Alleviates Deficiency in Premature Infants

Abstract

Docosahexaenoic acid (DHA) is an essential fatty acid (FA) important for health and neurodevelopment. Premature infants are at risk of DHA deficiency and circulating levels directly correlate with health outcomes. Most supplementation strategies have focused on increasing DHA content in mother's milk or infant formula. However, extremely premature infants may not reach full feedings for weeks and commercially available parenteral lipid emulsions do not contain preformed DHA, so blood levels decline rapidly after birth. Our objective was to develop a DHA supplementation strategy to overcome these barriers. This double-blind, randomized, controlled trial determined feasibility, tolerability and efficacy of daily enteral DHA supplementation (50 mg/day) in addition to standard nutrition for preterm infants (24-34 weeks gestational age) beginning in the first week of life. Blood FA levels were analyzed at baseline, full feedings and near discharge in DHA (n = 31) or placebo supplemented (n = 29) preterm infants. Term peers (n = 30) were analyzed for comparison. Preterm infants had lower baseline DHA levels (p < 0.0001). Those receiving DHA had a progressive increase in circulating DHA over time (from 3.33 to 4.09 wt% or 2.88 to 3.55 mol%, p < 0.0001) while placebo-supplemented infants (receiving standard neonatal nutrition) had no increase over time (from 3.35 to 3.32 wt% or 2.91 to 2.87 mol%). Although levels increased with additional DHA supplementation, preterm infants still had lower blood DHA levels than term peers (4.97 wt% or 4.31 mol%) at discharge (p = 0.0002). No differences in adverse events were observed between the groups. Overall, daily enteral DHA supplementation is feasible and alleviates deficiency in premature infants.

Trial registration: ClinicalTrials.gov NCT01908907.

Keywords: Docosahexaenoic acid (DHA); Essential dietary lipids; Long chain polyunsaturated fatty acids (LCPUFA); Neonatal nutrition; Premature infants.

Fig. 1

Postnatal growth model estimates for (A.) weight, (B.) length, and (C.) head circumference are represented graphically for infants born at the mean of 30 weeks GA. Dashed lines represent placebo controls and solid lines represent DHA supplemented infants. *Compared to controls, the DHA supplemented infants had increased length over time (p=0.04), otherwise, DHA supplementation did not affect postnatal growth.

Fig. 2

Fatty acid levels at baseline (first week), after reaching full feedings (100kcal/kg/d) and near discharge in placebo (dashed black line) and DHA supplemented (solid black line) preterm infants. Levels expressed as mol % with mean ± SD. For illustration only, a solid gray line represents the mean DHA level in the term reference group; the dashed gray line illustrates the 95% CI. ^†group comparison, p<0.01; *discharge level compared to that of term peers, p<0.01.