Desirée Valera-Gran1,2, Eva M Navarrete-Muñoz1,2, Manuela Garcia de la Hera1,2, Ana Fernández-Somoano2,3, Adonina Tardón2,3, Jesús Ibarluzea2,4, Nekane Balluerka2,5, Mario Murcia2,6, Llúcia González-Safont2,6, Dora Romaguera7,8,9, Jordi Julvez2,8, Jesús Vioque10,2. 1. Department of Public Health, History of Medicine, and Gynecology, University Miguel Hernández, Alicante Institute for Health and Biomedical Research (ISABIAL-FISABIO Foundation), Alicante, Spain. 2. Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain. 3. Department of Preventive Medicine and Public Health, University of Oviedo, Oviedo, Spain. 4. Health Research Institute (BIODONOSTIA), San Sebastian, Spain. 5. Department of Social Psychology and Behavioral Sciences Methods, University of the Basque Country, San Sebastian, Spain. 6. FISABIO-University of Valencia-University Jaume I Joint Research Unit of Epidemiology and Environmental Health, Valencia, Spain. 7. Health Research Institute of Palma (IdISPa), Palma de Mallorca, Spain. 8. ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; and. 9. Spanish Consortium for Research on Obesity and Nutrition (CIBEROBN), Madrid, Spain. 10. 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.
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.
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: Antonio J Signes-Pastor; Jesús Vioque; Eva M Navarrete-Muñoz; Manus Carey; Miguel García-Villarino; Ana Fernández-Somoano; Adonina Tardón; Loreto Santa-Marina; Amaia Irizar; Maribel Casas; Mònica Guxens; Sabrina Llop; Raquel Soler-Blasco; Manoli García-de-la-Hera; Margaret R Karagas; Andrew A Meharg Journal: Environ Res Date: 2019-04-29 Impact factor: 6.498
Authors: Marta Cosín-Tomás; Yan Luan; Daniel Leclerc; Olga V Malysheva; Nidia Lauzon; Renata H Bahous; Karen E Christensen; Marie A Caudill; Rima Rozen Journal: Nutrients Date: 2020-06-08 Impact factor: 5.717
Authors: Reema F Tayyem; Sabika S Allehdan; Razan M Alatrash; Fida F Asali; Hiba A Bawadi Journal: Int J Environ Res Public Health Date: 2019-09-17 Impact factor: 3.390
Authors: Henry Völzke; Iris Erlund; Alicja Hubalewska-Dydejczyk; Till Ittermann; Robin P Peeters; Margaret Rayman; Monika Buchberger; Uwe Siebert; Betina H Thuesen; Michael B Zimmermann; Stefan Grünert; John H Lazarus Journal: Eur Thyroid J Date: 2018-07-31