Prenatal choline supplementation improves child sustained attention: A 7-year follow-up of a randomized controlled feeding trial

Abstract

Numerous rodent studies demonstrate developmental programming of offspring cognition by maternal choline intake, with prenatal choline deprivation causing lasting adverse effects and supplemental choline producing lasting benefits. Few human studies have evaluated the effect of maternal choline supplementation on offspring cognition, with none following children to school age. Here, we report results from a controlled feeding study in which pregnant women were randomized to consume 480 mg choline/d (approximately the Adequate Intake [AI]) or 930 mg choline/d during the 3rd trimester. Sustained attention was assessed in the offspring at age 7 years (n = 20) using a signal detection task that showed benefits of maternal choline supplementation in a murine model. Children in the 930 mg/d group showed superior performance (vs. 480 mg/d group) on the primary endpoint (SAT score, p = .02) and a superior ability to maintain correct signal detections (hits) across the 12-min session (p = .02), indicative of improved sustained attention. This group difference in vigilance decrement varied by signal duration (p = .04). For the briefest (17 ms) signals, the 480 mg/d group showed a 22.9% decline in hits across the session compared to a 1.5% increase in hits for the 930 mg/d group (p = .04). The groups did not differ in vigilance decrement for 29 or 50 ms signals. This pattern suggests an enhanced ability to sustain perceptual amplification of a brief low-contrast visual signal by children in the 930 mg/d group. This inference of improved sustained attention by the 930 mg/d group is strengthened by the absence of group differences for false alarms, omissions, and off-task behaviors. This pattern of results indicates that maternal 3rd trimester consumption of the choline AI for pregnancy (vs. double the AI) produces offspring with a poorer ability to sustain attention-reinforcing concerns that, on average, choline consumption by pregnant women is approximately 70% of the AI.

Trial registration: ClinicalTrials.gov NCT01127022.

Keywords: attention; child development; choline; cognition; dietary supplements.

FIGURE 1

Time course of events within each trial of the Sustained Attention Task (SAT). Each trial began with a variable monitoring interval (500, 1000, or 1500 ms) to prevent anticipatory responding. Following the monitoring interval, a non‐signal or signal event occurred. The child was instructed to indicate whether they saw or did not see a brief, low‐contrast signal (a 5 mm × 5 mm gray square) of variable duration (17, 29, or 50 ms) on a light gray screen. A signal was presented randomly on 50% of the trials, with an equal number of signal and non‐signal trials occurring every 18 trials. One hundred ms after the signal or non‐signal event, a 430 ms auditory response cue (“Go”) indicated the opening of the response window; i.e., that it was time to respond. Children had 1500 ms to indicate whether they saw or did not see a signal by pressing the appropriate, pre‐specified key on the laptop keyboard (key assignments were determined by child handedness). Correct responses were followed by a 500 ms positively‐valenced tone. No feedback was given after incorrect responses or omissions (Icons sourced from Microsoft Powerpoint).

FIGURE 2

Participant flowchart for the assessment of the effect of 3rd trimester choline supplementation on child sustained attention task (SAT) performance at age 7 years

FIGURE 3

Effect of 3rd trimester choline intake and signal duration on SAT score. Children in the 930 mg/d group had a higher average SAT score than children in the 480 mg/d group (main effect of treatment group: p = .02). SAT score differed significantly by signal duration (p < .0001), but the 3rd trimester choline intake by signal duration interaction was non‐significant (p = .74). Values represent least square means ± SEM. 480 mg/d: n = 9; 930 mg/d: n = 11

FIGURE 4

Effect of 3rd trimester choline intake on vigilance decrement for percentage hits. Linear change in percentage hits (correct signal detections) across the task blocks varied by 3rd trimester choline intake (p = .02): the 480 mg/d group exhibited significant decline across blocks (p = .001) whereas the 930 mg/d group exhibited no change in performance across blocks (p = .71). Values represent least square means ± SEM. 480 mg/d: n = 9; 930 mg/d: n = 11

FIGURE 5

Effect of 3rd trimester choline intake on vigilance decrement for percentage hits as a function of signal duration. The choline group difference in the vigilance decrement varied by signal duration (p = .04). The vigilance decrement for 17 ms signals was significantly greater for the 480 mg choline/d group than for the 930 mg choline/d group (p = .04, Bonferroni corrected). The groups did not differ significantly in vigilance decrement for 29 and 50 ms trials. Notably, for the 480 mg/d group there is an apparent increase in the magnitude of the vigilance decrement for each decrease in signal duration, whereas the 930 mg/d group shows no vigilance decrement for any signal duration. Values represent least square means ± SEM. 480 mg/d: n = 9; 930 mg/d: n = 11