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Effect of maternal high dosages of folic acid supplements on neurocognitive development in children at 4-5 y of age: the prospective birth cohort Infancia y Medio Ambiente (INMA) study.
Am J Clin Nutr. 2017 Sep; 106(3):878-887.AJ

Abstract

Background:

The benefits of the use of folic acid supplements (FASs) during the periconception period to prevent neural tube defects and to ensure normal brain development in offspring are well known. There is concern, however, about the long-term effects of the maternal use of high dosages of FASs that exceed the Tolerable Upper Intake Level (UL) (≥1000 μg/d) on child neurocognitive outcomes.

Objective:

The objective of the study was to examine the association between the use of high dosages of FASs during pregnancy and child neuropsychological development at ages 4-5 y.

Design:

The multicenter prospective mother-child cohort study, the Infancia y Medio Ambiente (INMA) Project, was conducted in 4 regions of Spain: Asturias, Sabadell, Gipuzkoa, and Valencia. Pregnant women were recruited between 2003 and 2008. Data on 1682 mother-child pairs were included in the final analyses. The pregnant women completed an interviewer-administered questionnaire that was validated to estimate typical dietary folate intake and the use of FASs at 10-13 and 28-32 wk of gestation. Neuropsychological development scores at 4-5 y of age were estimated with the use of the McCarthy Scales of Children's Abilities. Multiple linear regression and meta-analysis were used to obtain combined-effect estimates.

Results:

During the periconception period, one-third of the women (n = 502) took FAS dosages ≥1000 μg/d. The use of FAS dosages ≥1000 μg/d in this period was negatively associated with several neuropsychological outcomes scores in children: global verbal (β = -2.49; 95% CI: -4.71, -0.27), verbal memory (β = -3.59; 95% CI: -6.95, -0.23), cognitive function of posterior cortex (β = -2.31; 95% CI: -4.45, -0.18), and cognitive function of left posterior cortex (β = -3.26; 95% CI: -5.51, -1.01).

Conclusions:

The use of FAS dosages exceeding the UL (≥1000 μg/d) during the periconception period was associated with lower levels of cognitive development in children aged 4-5 y. The use of FAS dosages ≥1000 μg/d during pregnancy should be monitored and prevented as much as possible, unless medically prescribed.

Authors+Show Affiliations

Department of Public Health, History of Medicine, and Gynecology, University Miguel Hernández, Alicante Institute for Health and Biomedical Research (ISABIAL-FISABIO Foundation), Alicante, Spain. Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain.Department of Public Health, History of Medicine, and Gynecology, University Miguel Hernández, Alicante Institute for Health and Biomedical Research (ISABIAL-FISABIO Foundation), Alicante, Spain. Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain.Department of Public Health, History of Medicine, and Gynecology, University Miguel Hernández, Alicante Institute for Health and Biomedical Research (ISABIAL-FISABIO Foundation), Alicante, Spain. Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain.Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain. Department of Preventive Medicine and Public Health, University of Oviedo, Oviedo, Spain.Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain. Department of Preventive Medicine and Public Health, University of Oviedo, Oviedo, Spain.Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain. Health Research Institute (BIODONOSTIA), San Sebastian, Spain.Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain. Department of Social Psychology and Behavioral Sciences Methods, University of the Basque Country, San Sebastian, Spain.Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain. FISABIO-University of Valencia-University Jaume I Joint Research Unit of Epidemiology and Environmental Health, Valencia, Spain.Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain. FISABIO-University of Valencia-University Jaume I Joint Research Unit of Epidemiology and Environmental Health, Valencia, Spain.Health Research Institute of Palma (IdISPa), Palma de Mallorca, Spain. ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; and. Spanish Consortium for Research on Obesity and Nutrition (CIBEROBN), Madrid, Spain.Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain. ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; and.Department of Public Health, History of Medicine, and Gynecology, University Miguel Hernández, Alicante Institute for Health and Biomedical Research (ISABIAL-FISABIO Foundation), Alicante, Spain; vioque@umh.es. Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain.No affiliation info available

Pub Type(s)

Journal Article
Multicenter Study

Language

eng

PubMed ID

28724645

Citation

Valera-Gran, Desirée, et al. "Effect of Maternal High Dosages of Folic Acid Supplements On Neurocognitive Development in Children at 4-5 Y of Age: the Prospective Birth Cohort Infancia Y Medio Ambiente (INMA) Study." The American Journal of Clinical Nutrition, vol. 106, no. 3, 2017, pp. 878-887.
Valera-Gran D, Navarrete-Muñoz EM, Garcia de la Hera M, et al. Effect of maternal high dosages of folic acid supplements on neurocognitive development in children at 4-5 y of age: the prospective birth cohort Infancia y Medio Ambiente (INMA) study. Am J Clin Nutr. 2017;106(3):878-887.
Valera-Gran, D., Navarrete-Muñoz, E. M., Garcia de la Hera, M., Fernández-Somoano, A., Tardón, A., Ibarluzea, J., Balluerka, N., Murcia, M., González-Safont, L., Romaguera, D., Julvez, J., & Vioque, J. (2017). Effect of maternal high dosages of folic acid supplements on neurocognitive development in children at 4-5 y of age: the prospective birth cohort Infancia y Medio Ambiente (INMA) study. The American Journal of Clinical Nutrition, 106(3), 878-887. https://doi.org/10.3945/ajcn.117.152769
Valera-Gran D, et al. Effect of Maternal High Dosages of Folic Acid Supplements On Neurocognitive Development in Children at 4-5 Y of Age: the Prospective Birth Cohort Infancia Y Medio Ambiente (INMA) Study. Am J Clin Nutr. 2017;106(3):878-887. PubMed PMID: 28724645.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of maternal high dosages of folic acid supplements on neurocognitive development in children at 4-5 y of age: the prospective birth cohort Infancia y Medio Ambiente (INMA) study. AU - Valera-Gran,Desirée, AU - Navarrete-Muñoz,Eva M, AU - Garcia de la Hera,Manuela, AU - Fernández-Somoano,Ana, AU - Tardón,Adonina, AU - Ibarluzea,Jesús, AU - Balluerka,Nekane, AU - Murcia,Mario, AU - González-Safont,Llúcia, AU - Romaguera,Dora, AU - Julvez,Jordi, AU - Vioque,Jesús, AU - ,, Y1 - 2017/07/19/ PY - 2017/01/15/received PY - 2017/06/15/accepted PY - 2017/7/21/pubmed PY - 2017/9/14/medline PY - 2017/7/21/entrez KW - child neurocognitive development KW - folate KW - folic acid supplements KW - periconception period KW - pregnancy SP - 878 EP - 887 JF - The American journal of clinical nutrition JO - Am J Clin Nutr VL - 106 IS - 3 N2 - Background: The benefits of the use of folic acid supplements (FASs) during the periconception period to prevent neural tube defects and to ensure normal brain development in offspring are well known. There is concern, however, about the long-term effects of the maternal use of high dosages of FASs that exceed the Tolerable Upper Intake Level (UL) (≥1000 μg/d) on child neurocognitive outcomes.Objective: The objective of the study was to examine the association between the use of high dosages of FASs during pregnancy and child neuropsychological development at ages 4-5 y.Design: The multicenter prospective mother-child cohort study, the Infancia y Medio Ambiente (INMA) Project, was conducted in 4 regions of Spain: Asturias, Sabadell, Gipuzkoa, and Valencia. Pregnant women were recruited between 2003 and 2008. Data on 1682 mother-child pairs were included in the final analyses. The pregnant women completed an interviewer-administered questionnaire that was validated to estimate typical dietary folate intake and the use of FASs at 10-13 and 28-32 wk of gestation. Neuropsychological development scores at 4-5 y of age were estimated with the use of the McCarthy Scales of Children's Abilities. Multiple linear regression and meta-analysis were used to obtain combined-effect estimates.Results: During the periconception period, one-third of the women (n = 502) took FAS dosages ≥1000 μg/d. The use of FAS dosages ≥1000 μg/d in this period was negatively associated with several neuropsychological outcomes scores in children: global verbal (β = -2.49; 95% CI: -4.71, -0.27), verbal memory (β = -3.59; 95% CI: -6.95, -0.23), cognitive function of posterior cortex (β = -2.31; 95% CI: -4.45, -0.18), and cognitive function of left posterior cortex (β = -3.26; 95% CI: -5.51, -1.01).Conclusions: The use of FAS dosages exceeding the UL (≥1000 μg/d) during the periconception period was associated with lower levels of cognitive development in children aged 4-5 y. The use of FAS dosages ≥1000 μg/d during pregnancy should be monitored and prevented as much as possible, unless medically prescribed. SN - 1938-3207 UR - https://www.unboundmedicine.com/medline/citation/28724645/Effect_of_maternal_high_dosages_of_folic_acid_supplements_on_neurocognitive_development_in_children_at_4_5_y_of_age:_the_prospective_birth_cohort_Infancia_y_Medio_Ambiente__INMA__study_ L2 - https://academic.oup.com/ajcn/article-lookup/doi/10.3945/ajcn.117.152769 DB - PRIME DP - Unbound Medicine ER -