Neonatal Docosahexaenoic Acid in Preterm Infants and Intelligence at 5 Years.

The New England journal of medicine

Oct 2022

DOI: 10.1056/NEJMoa2206868

Citations:43

Influential Citations:1

Interventional (Human) Studies

Enhanced Details

Methods

Infants born before 29 weeks’ gestation were enrolled in a multicenter, blinded, parallel-group randomized trial with follow-up at 5 years of corrected age to assess cognitive outcomes; five centers in Australia contributed to the 5-year follow-up; cognitive performance assessed with the WPPSI-IV.

Intervention

Enteral DHA emulsion, 60 mg DHA per kg per day, started within the first 3 days of enteral feeds, given in three doses daily, for at least 7 weeks, ceasing at 36 weeks postmenstrual age or discharge home, whichever occurs first.

Results

At about 5 years of corrected age, mean FSIQ was 95.4 in the DHA group and 91.9 in the control group, an adjusted between-group difference of 3.45 points (95% CI 0.38 to 6.53; P = 0.03). Most secondary cognitive outcomes did not show consistent advantages. The authors concluded that neonatal DHA supplementation delivering 60 mg/kg/day is associated with a modestly higher FSIQ at 5 years and supports current recommendations that preterm infants born before 29 weeks’ gestation receive about 60 mg/kg/day of DHA to approximate fetal DHA supply.

Limitations

Covid-19-related attrition reduced follow-up; data for missing outcomes were imputed (about a quarter of participants); the age range for assessment was widened (4.0 to 7.5 years) and some assessments used WPPSI-III; secondary outcomes were not adjusted for multiplicity; generalizability may be limited to high-income settings.

Abstract

BACKGROUND Docosahexaenoic acid (DHA) is a component of neural tissue. Because its accretion into the brain is greatest during the final trimester of pregnancy, infants born before 29 weeks' gestation do not receive the normal supply of DHA. The effect of this deficiency on subsequent cognitive development is not well understood. METHODS We assessed general intelligence at 5 years in children who had been enrolled in a trial of neonatal DHA supplementation to prevent bronchopulmonary dysplasia. In the previous trial, infants born before 29 weeks' gestation had been randomly assigned in a 1:1 ratio to receive an enteral emulsion that provided 60 mg of DHA per kilogram of body weight per day or a control emulsion from the first 3 days of enteral feeds until 36 weeks of postmenstrual age or discharge home, whichever occurred first. Children from 5 of the 13 centers in the original trial were invited to undergo assessment with the Wechsler Preschool and Primary Scale of Intelligence (WPPSI) at 5 years of corrected age. The primary outcome was the full-scale intelligence quotient (FSIQ) score. Secondary outcomes included the components of WPPSI. RESULTS A total of 1273 infants underwent randomization in the original trial; of the 656 surviving children who had undergone randomization at the centers included in this follow-up study, 480 (73%) had an FSIQ score available - 241 in the DHA group and 239 in the control group. After imputation of missing data, the mean (±SD) FSIQ scores were 95.4±17.3 in the DHA group and 91.9±19.1 in the control group (adjusted difference, 3.45; 95% confidence interval, 0.38 to 6.53; P = 0.03). The results for secondary outcomes generally did not support that obtained for the primary outcome. Adverse events were similar in the two groups. CONCLUSIONS In infants born before 29 weeks' gestation who had been enrolled in a trial to assess the effect of DHA supplementation on bronchopulmonary dysplasia, the use of an enteral DHA emulsion until 36 weeks of postmenstrual age was associated with modestly higher FSIQ scores at 5 years of age than control feeding. (Funded by the Australian National Health and Medical Research Council and Nu-Mega Ingredients; N3RO Australian New Zealand Clinical Trials Registry number, ACTRN12612000503820.). show less