The Kansas University DHA Outcomes Study (KUDOS) clinical trial: long-term behavioral follow-up of the effects of prenatal DHA supplementation

Abstract

Background: Docosahexaenoic acid (DHA) is a long-chain polyunsaturated fatty acid that has been linked to improved vision and cognition in postnatal feeding studies and has been consistently associated with reduction of early preterm birth in prenatal supplementation trials. This is a report of the first long-term follow-up of infants from mothers receiving prenatal DHA supplementation in a US cohort.

Objective: Our objective was to evaluate the efficacy of the prenatal supplementation on both global and granular longitudinal assessments of cognitive and behavioral development.

Methods: In a randomized double-blind clinical trial, mothers received either 600 mg/d of DHA or a placebo beginning at 14.5 weeks of gestation and capsules were provided until delivery. Children from those pregnancies were followed by cognitive and behavioral assessments administered from 10 mo through 6 y of age. From 301 mothers in the initial study, ∼200 infants completed the longitudinal schedule.

Results: Although this intervention had been shown to reduce high-risk pregnancies and improve visual attention in infants during the first year, only a few positive long-term effects of prenatal DHA supplementation emerged from analyses of this follow-up. Increases in maternal blood DHA during pregnancy were related to verbal and full scale intelligence quotient (IQ) scores at 5 and 6 y, but these effects disappeared after controlling for SES. Maternal blood DHA concentrations at delivery were unrelated to outcomes, although maternal DHA at enrollment was related to productive vocabulary at 18 mo.

Conclusions: Although prenatal DHA supplementation substantially reduced early preterm birth and improved visual attention in infancy in this sample, no consistent long-term benefits were observed into childhood. Increases in maternal blood DHA concentration in pregnancy were related to higher IQs but this effect was confounded with SES and disappeared when SES was statistically controlled. This trial was registered at http://www.clinicaltrials.gov as NCT00266825 and NCT02487771.

Keywords: behavior; clinical trial; development; docosahexaenoic acid; longitudinal; prenatal.

FIGURE 1

Consolidated Standards of Reporting Trials (CONSORT) diagram for the follow-up study.

FIGURE 2

Plot of sex × visit × DHA group interaction for Sentence Repetition task scores. Overall sample sizes are 141 at 36 mo (n = 64 and 77 for placebo and DHA, respectively), 160 at 42 mo (n = 73 and 87, respectively), and 151 at 48 mo (n = 72 and 79, respectively). All means shown here are adjusted for covariates and the interaction represented here is statistically significant (P = 0.028). Error bars represent SEMs.

FIGURE 3

Plot of main effect for DHA group on Delayed Response accuracy across visits. Overall sample sizes are 161 at 24 mo (n = 77 and 84 for placebo and DHA, respectively) and 160 at 30 mo (n = 84 and 85, respectively). All means shown here are adjusted for covariates. The main effect for DHA group was statistically significant (P = 0.047) but was qualified by several significant higher-order interactions. Error bars represent SEMs.

FIGURE 4

Percentage of children passing the DCCS criterion as a function of age and DHA group. Overall sample sizes are 172 at 36 mo (n = 79 and 93 for placebo and DHA, respectively), 167 at 42 mo (n = 76 and 91, respectively), 167 at 48 mo (n = 78 and 89, respectively), and 158 at 60 mo (n = 74 and 84, respectively). All means shown here are adjusted for covariates and the interaction represented here is statistically significant (P = 0.048). DCCS, Dimensional Change Card Sort.

FIGURE 5

RBC DHA (percentage of total fatty acids) for “Flat” and “Increase” clusters across pregnancy. Overall sample size at both enrollment and delivery is 263 (n = 97 and 166 for Flat and Increase Clusters, respectively). Error bars represent SEMs. RBC, red blood cell.