title: 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.
abstract: BACKGROUND
  During fetal and perinatal periods, many nutrients, such as long-chain polyunsaturated fatty acids [contained in fish oil (FO)] and folate, are important in achieving normal brain development. Several studies have shown the benefits of early nutrition on children's neurocognitive development. However, the evidence with regard to the attention system is scarce.
  
  
  OBJECTIVE
  The aim of this study was to analyze the long-term effects of FO, 5-methyltetrahydrofolate (5-MTHF), or FO+5-MTHF prenatal supplementation on attention networks.
  
  
  METHODS
  Participants were 136 children born to mothers from the NUHEAL (Nutraceuticals for a Healthy Life) project (randomly assigned to receive FO and/or 5-MTHF or placebo prenatal supplementation) who were recalled for a new examination 8.5 y later. The response conflict-resolution ability (using congruent and incongruent conditions)), alerting, and spatial orienting of attention were evaluated with behavioral measures (Attention Network Test), electroencephalography/event-related potentials (ERPs), and standardized low-resolution brain electromagnetic tomography (sLORETA).
  
  
  RESULTS
  Children born to mothers supplemented with 5-MTHF alone solved the response conflict more quickly than did the placebo and the FO+5-MTHF groups (all P < 0.05). Differences between ERP amplitudes for the conflict conditions were also observed. sLORETA analysis showed higher activation of the right midcingulate cortex for the incongruent condition. In addition, a significant slowing down of response speed depending on the warning cue in the 5-MTHF and FO groups was observed.
  
  
  CONCLUSIONS
  Folate supplementation during pregnancy, rather than FO or FO+5-MTHF supplementation, improves children's ability to solve response conflicts. This advantage seems to be based on the higher activation of the midcingulate cortex, indicating that early nutrition influences the functionality of specific brain areas involved in executive functions. This trial was registered at clinicaltrials.gov as NCT01180933.
authors.affiliation: Mind, Brain, and Behavior Research Center-CIMCYC.
authors.forename: Andrés
authors.initials: A
authors.lastname: Catena
authors.affiliation: EURISTIKOS Excellence Center for Pediatric Research, and.
authors.forename: J Angela
authors.initials: JA
authors.lastname: Muñoz-Machicao
authors.affiliation: EURISTIKOS Excellence Center for Pediatric Research, and.
authors.forename: Francisco J
authors.identifier: http://orcid.org/0000-0000-0000-0000
authors.initials: FJ
authors.lastname: Torres-Espínola
authors.affiliation: EURISTIKOS Excellence Center for Pediatric Research, and.
authors.forename: Cristina
authors.initials: C
authors.lastname: Martínez-Zaldívar
authors.affiliation: Mind, Brain, and Behavior Research Center-CIMCYC.
authors.forename: Carolina
authors.initials: C
authors.lastname: Diaz-Piedra
authors.affiliation: Departments of Biochemistry and Molecular Biology and.
authors.forename: Angel
authors.initials: A
authors.lastname: Gil
authors.affiliation: Dr. von Hauner Children's Hospital, Ludwig-Maximilians University of Munich Medical Center, Munich, Germany;
authors.forename: Gudrun
authors.initials: G
authors.lastname: Haile
authors.affiliation: Department of Pediatrics, University of Pécs, Pécs, Hungary; and.
authors.forename: Eszter
authors.initials: E
authors.lastname: Györei
authors.affiliation: School of Clinical Medicine, Trinity College, Dublin, Ireland.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Molloy
authors.affiliation: Department of Pediatrics, University of Pécs, Pécs, Hungary; and.
authors.forename: Tamás
authors.initials: T
authors.lastname: Decsi
authors.affiliation: Dr. von Hauner Children's Hospital, Ludwig-Maximilians University of Munich Medical Center, Munich, Germany;
authors.forename: Berthold
authors.initials: B
authors.lastname: Koletzko
authors.affiliation: EURISTIKOS Excellence Center for Pediatric Research, and Pediatrics, University of Granada, Granada, Spain; ccampoy@ugr.es.
authors.forename: Cristina
authors.initials: C
authors.lastname: Campoy
mesh_terms: D000328:Adult; D001288:Attention / Q000502:physiology*; D001921:Brain / Q000254:growth & development* / Q000502:physiology; D002648:Child; D002657:Child Development; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology*; D019587:Dietary Supplements; D004311:Double-Blind Method; D056344:Executive Function / Q000502:physiology*; D005260:Female; D047109:Fetal Development; D005395:Fish Oils / Q000494:pharmacology; D005492:Folic Acid / Q000494:pharmacology; D006801:Humans; D008297:Male; D011247:Pregnancy; D039401:Prenatal Nutritional Physiological Phenomena; D013763:Tetrahydrofolates / Q000494:pharmacology*; D014803:Vitamin B Complex / Q000494:pharmacology
chemical_list: D004042:Dietary Fats, Unsaturated; D005395:Fish Oils; D013763:Tetrahydrofolates; D014803:Vitamin B Complex; D005492:Folic Acid; C005984:5-methyltetrahydrofolate
keywords: attention; child development; evoked potentials; folate; polyunsaturated fatty acids; prenatal nutrition