Folate supplementation during pregnancy may improve child’s attention system

Children 8.5 years of age, whose mothers have been supplemented with 5-methyltetrahydrofolate (5-MTHF) while pregnant, performed faster during an electroencephalography test compared to children whose mothers were supplemented with either fish oil, fish oil and 5-MTHF, or a placebo.

So goes the results of a study​ conducted on 312 women in three European countries (Germany, Hungary, and Spain). The study was a follow-up of the Nutraceuticals for a Healthy Life (NUHEAL)​ cohort, “a multicentre, randomized, double-blind, 2 x 2 factorial placebo-controlled trial aimed at determining the long-term effects of [fish oil] and folate supplementation during the second half of pregnancy,” ​the researchers wrote.

Researchers were affiliated with various institutions across the continent, including the University of Granada, Spain; Ludwig-Maximilians University of Munich Medical Center, Germany; Trinity College, Ireland; and University of Pécs, Hungary.

Supplementation​

Pregnant mothers were supplemented with 1 sachet of a milk-based supplement called Blemil Plus Matter by Ordesa Laboratories S.L. The sachet contained one of four formulas: modified fish oil with 500mg of DHA + 150mg EPA (Pronova Biocare); 400 micrograms of 5-MTHF (BASF); a mixture of the aforementioned two; or a placebo.

“Detailed instructions were given on the label of each sachet,”​ the researchers wrote. “Sufficient supplement was provided at each visit to last until the next one or, in the last visit until delivery. Subjects were instructed to return leftover sachets to the study center.”​

For accountability, the subjects were given standardized questionnaires at gestation week 30 and at delivery which asked how many days of dosing she had missed.

Interdisciplinary data​

Not all the children of the 312 mothers were included in the study 8.5 years later. Only 136 children accepted to participate in the follow-up assessment—the main reasons for dropping out included relocation, loss of contact, and unwillingness to continue. Moreover, several children weren’t considered for the follow-up study due to premature births or developmental illnesses.

A study expanding borders means cultural and sociodemographic influences must be taken into account as much as the clinical and biochemical ones. Mothers filled out a survey at the beginning of the study for sociodemographic data; children filled out a similar survey during the present evaluation time.

In addition, maternal blood samples were obtained by venipuncture at different stages of pregnancy—20 and 30 weeks into pregnancy, at delivery, and from the umbilical cord.

The last stage of the study involved an electroencephalographic test that recorded reaction times and response accuracy of children using the child version of the Attention Network Test.

Catching fish​

“The test was designed to evaluate the three attention networks: Executive, alerting, and orienting,” ​the researchers explained in their paper.

On a screen, children saw a target horizontal array of either five fish (a central target flanked on each side by two distractors) or a single fish  displayed above or below a central fixation cross.

One of four warning cues would then appear: A single central asterisk, a double asterisk above and below the fixation, no asterisk, or a single asterisk located at the same position as the incoming target.

The child then had to click on a mouse indicating whether the central target fish pointed to the left or the right. The whole task takes around 25 minutes.

Findings​

“Our study showed that 5-MTHF supplementation during pregnancy, rather than [fish oil] alone or the combination of [fish oil] and 5-MTHF, improves children’s ability to solve conflicts,”​ the researchers concluded.

However, children whose mothers were supplemented with 5-MTHF during pregnancy showed a reduced readiness to respond to an incoming target, which leads the researchers to argue that “this conflict-resolution advantage seems to be based on the activation of the cingulate cortex, a core area in the executive network.”​

The researchers contend that further studies should be conducted to improve the knowledge on how plasma folate concentrations during pregnancy affect the cingulate cortex, “as well as the direct influence of early folic acid and [fish oil] supplementation on cingulate cortex function and the optimal doses at different stages.”​

Source: The American Journal of Clinical Nutrition​

Published online ahead of print, doi: 10.3945/ajcn.115.109108

Folate and long-chain polyunsaturated fatty acid supplementation during pregnancy has long-term effects on the attention system of 8.5-y-old offspring: a randomized controlled trial.​

Authors: A. Catena, et al.