Safety and efficacy of high dose docosahexaenoic acid for the preterm infant.

Abstract

There has been substantial research demonstrating improvements in visual and cognitive performance of preterm infants after feeding formulas containing n-3 long chain polyunsaturated fatty acid (LCPUFA). The amount of docosahexaenoic acid (DHA) estimated to be accrued by the fetus in the last trimester of gestation is greater than that supplied in current preterm formulas and breast milk of average DHA content (~0.3% of total fat in Western women). Yet many trials have compared infants fed formula containing concentrations near 0.3% DHA with infants fed formula containing no LCPUFA. No research has addressed whether the average breast milk DHA milk results in optimal development of preterm infants. The focus of this thesis was to compare the efficacy and safety of supplementing preterm infants with milk containing docosahexaenoic acid (DHA) at concentrations that meet the estimated in utero accretion rate (~1%) compared with current clinical practices (~0.3%). In a double-blind, randomised controlled trial (RCT), infants born <33 weeks gestation were assigned to receive milk containing one of two doses of DHA. Treatment group infants received milk containing high dose DHA (1%) and infants in the control group infants received milk containing standard levels DHA (0.2 - 0.35%). Lactating mothers consumed capsules containing either tuna oil (900mg DHA) or soy oil (no DHA) that resulted in breast milk with either a high or typical concentration of DHA. Standard preterm formula milk with a corresponding DHA composition was fed to infants if formula feeds were required. The intervention period was from five days of commencing enteral feeds through to the infants estimated due date (EDD). Primary efficacy assessment was sweep visual evoked potential (VEP) acuity at 4 months corrected age (CA). Secondary efficacy outcomes included VEP acuity at 2 months CA and VEP latency at 2 and 4 months CA. Infant anthropometry was assessed regularly throughout the trial and the primary safety outcome was weight at 4 months CA. Other clinical safety data including incidence and severity of diseases commonly associated with prematurity were also assessed. The success of the intervention was demonstrated with infants in the treatment group having a significantly higher level of erythrocyte membrane DHA at EDD compared with the control group (% total erythrocyte phospholipids (mean ± SD), treatment group 6.8 ±1.2, control group 5.2 ± 0.7, p<0.0005). The primary efficacy outcome of acuity at 4 months CA was significantly higher in the treatment compared with the control group infants (mean ± SD acuity (in cpd) treatment group 9.6 ± 3.7, control group 8.2 ± 1.8, p = 0.025). No significant differences were found in acuity at 2 months CA or latency at 2 or 4 months CA between infants in the control and treatment groups. No significant differences in weight, length or head circumference were found between treatment compared with control infants at EDD or at 4 months CA. Nor were any differences found in other clinical outcomes commonly associated with prematurity including, tolerance, necrotising enterocolitis, sepsis, retinopathy of prematurity, bronchopulmonary dysplasia or intraventricular haemorrhage. Increasing milk DHA to 1% of total fat suggests that the DHA requirement of preterm infants may be higher than the level available in preterm formula or breast milk of Australian women. Addressing both breast and formula milks demonstrates wide generalisability of these findings to common feeding practices in neonatal nurseries. Further studies are needed to determine whether this feeding strategy and dose of DHA is capable of improving other aspects of infant development.