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Providing perspectives on recent research into vitamins and nutritionals


Benefits to Folic Acid Supplementation in Later Pregnancy on Child Cognition

By Julia Bird

The recommendation to consume adequate folic acid before conception and during early pregnancy to avoid neural tube defects is well known. Even fairly recently, large-scale clinical trials show that folic acid supplements are effective in preventing birth defects (see results from Chen and co-workers). However, there is less research that has looked into whether it is beneficial to continue supplementation after the first trimester. As folic acid is needed for proper neural development, the domain of cognition seems a logical one for further testing.

Researchers Catena and colleagues conducted a study to see whether there would be effects of folic acid supplementation during the second half of pregnancy on child cognition. This was a 2x2 factorial study in which pregnant women received either folic acid in the form of 5-MTHF, fish oil, both or neither in a milk drink from 20 weeks of pregnancy, as part of the NUHEAL study. 5-MTHF is the biologically active form of folate, and while its absorption and bioavailability is similar to folic acid, it may be less prone to masking the effects of vitamin B12 deficiency, according to Pietzrik, Bailey and Shane. Doses of 400 µg 5-MTHF, and the fish oil contained 500 mg DHA and 150 mg EPA. Of the 312 women originally recruited into the study, 270 were followed up until they gave birth. At 8.5 years of age, 136 children agreed to participate in the follow-up cognitive testing.

A large battery of tests that involved an evaluation of the three aspects of attention (alerting/vigilance, orientation/selection, executive function/conflict) were given. Electoencephalography was also used to measure brain responses to stimuli (ERP) and the sLORETA technique employed to measure brain responses at various locations in the brain.

The researchers found that concentrations of fatty acids and folate increased as would be expected from the supplementation regimen. There were positive changes in the executive and alerting parts of the attention network in supplemented children, especially those receiving 5-MTHF. The executive control of attention is a complex mental operation that enables people to  monitor and resolve conflict between thoughts, feelings and responses, such as planning or decision making tasks (see review from Raz). ERPs were more efficient in the left frontal hemisphere channels in 5-MTHF supplemented children,  leading the authors to suggest that folate can prevent prefrontal dopamine deficiency. On the other hand, children who were supplemented with 5-MTHF appeared to have an inhibited response in the alerting network, which means that they were less able to maintain a state of readiness for external stimuli. This may relate to folate affecting levels of the neurotransmitter norepinephrine in the brain.

These results suggest that 5-MTHF in pregnancy can improve school-aged children’s conflict resolution ability. Folate status has already been shown to be able to affect how the brain develops in early pregnancy by helping the neural tube to develop normally, and it is possible that folate status in later pregnancy can also affect the function of different areas of the brain, and some aspects of cognition.

This research paper joins others that TalkingNutrition has reported on in the field of folate supplementation in the later stages of pregnancy:

Update on Supplemental Folic Acid During Later Pregnancy

Following Folate Recommendations in Pregnancy Also Reduces Autism Risk

Is Folate Supplementation in Late Pregnancy Also Worthwhile?

Folate Recommendations during Pregnancy Intersect with Personalized Nutrition


Main citation:

Andrés Catena, J Angela Muñoz-Machicao, Francisco J Torres-Espínola, Cristina Martínez-Zaldívar, Carolina Diaz-Piedra, Angel Gil, Gudrun Haile, Eszter Györei, Anne M Molloy, Tamás Decsi, Berthold Koletzko, Cristina Campoy. 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. Am J Clin Nutr ajcn109108; First published online November 11, 2015. doi:10.3945/ajcn.115.109108


Supporting citations:

Chen G, Song X, Ji Y, Zhang L, Pei L, Chen J, Liu J, Li C, Zheng X. Prevention of NTDs with periconceptional multivitamin supplementation containing folic acid in China. Birth Defects Res A Clin Mol Teratol. 2008 Aug;82(8):592-6. doi: 10.1002/bdra.20471.

Pietrzik K, Bailey L, Shane B. Folic acid and L-5-methyltetrahydrofolate: comparison of clinical pharmacokinetics and pharmacodynamics. Clin Pharmacokinet. 2010 Aug;49(8):535-48. doi: 10.2165/11532990-000000000-00000.

Raz A. Anatomy of attentional networks. Anat Rec B New Anat. 2004 Nov;281(1):21-36.