Desirée Valera-Gran1, Manuela García de la Hera1, Eva María Navarrete-Muñoz1, Ana Fernandez-Somoano2, Adonina Tardón2, Jordi Julvez3, Joan Forns4, Nerea Lertxundi5, Jesús María Ibarluzea5, Mario Murcia6, Marisa Rebagliato7, Jesús Vioque1. 1. Consorcio de Investigación Biomédica de Epidemiología y Salud Pública, Madrid, Spain2Department of Public Health, History of Science, and Gynecology, Miguel Hernández University, Sant Joan d'Alacant Campus, Sant Joan d'Alacant, Spain. 2. Consorcio de Investigación Biomédica de Epidemiología y Salud Pública, Madrid, Spain3University of Oviedo, Asturias, Spain. 3. Consorcio de Investigación Biomédica de Epidemiología y Salud Pública, Madrid, Spain4Centre for Research in Environmental Epidemiology, Barcelona, Spain. 4. Consorcio de Investigación Biomédica de Epidemiología y Salud Pública, Madrid, Spain4Centre for Research in Environmental Epidemiology, Barcelona, Spain5Department of Genes and Environment, Division of Epidemiology, Norwegian Institute of Public Health, O. 5. Consorcio de Investigación Biomédica de Epidemiología y Salud Pública, Madrid, Spain6Subdirección de Salud Pública de Gipuzkoa, San Sebastian, Spain. 6. Consorcio de Investigación Biomédica de Epidemiología y Salud Pública, Madrid, Spain7Centre of Public Health Research, Valencia, Spain. 7. Consorcio de Investigación Biomédica de Epidemiología y Salud Pública, Madrid, Spain7Centre of Public Health Research, Valencia, Spain8James I University, Castelló de la Plana, Spain.
Abstract
IMPORTANCE: Folate intake during pregnancy has been associated with improved neuropsychological development in children, although the effects of high dosages of folic acid (FA) supplements are unclear. OBJECTIVE: To examine the association between the use of high dosages of FA supplements during pregnancy and child neuropsychological development after the first year of life. DESIGN, SETTING, AND PATIENTS: The multicenter prospective mother-child cohort Infancia y Medio Ambiente (INMA) Project recruited pregnant women from 4 areas of Spain (Asturias, Sabadell, Gipuzkoa, and Valencia) between November 2003 and January 2008. Pregnant women completed an interviewer-administered questionnaire on the usual dietary folate intake and FA supplements at 10 to 13 weeks and 28 to 32 weeks of gestation. The main analyses were based on a sample of 2213 children with complete information on neuropsychological development and FA supplement intake during pregnancy. Multiple linear and logistic regression analyses were used to explore the effects of FA supplements on child neuropsychological development. MAIN OUTCOMES AND MEASURES: Neuropsychological development was assessed using the Bayley Scales of Infant Development. We calculated mental scale and psychomotor scale scores. One SD below the mean established a delay in neurodevelopment (score <85). RESULTS: A high proportion of women (57.3%) did not reach the recommended dosages of FA supplements (400 μg/d), but 25.2% women took more than 1000 μg/d of FA supplements (3.5% consuming >5000 μg/d). In multivariate analysis, we observed that children whose mothers used FA supplement dosages higher than 5000 μg/d during pregnancy had a statistically significantly lower mean psychomotor scale score (difference, -4.35 points; 95% CI, -8.34 to -0.36) than children whose mothers used a recommended dosage of FA supplements (400-1000 μg/d). An increased risk of delayed psychomotor development (psychomotor scale score <85) was also evident among children whose mothers took FA supplement dosages higher than 5000 μg/d, although the association was not statistically significant (odds ratio = 1.59; 95% CI, 0.82-3.08). CONCLUSIONS AND RELEVANCE: To our knowledge, this is the first time a detrimental effect of high dosages of FA supplements during pregnancy on psychomotor development after the first year of life has been shown. Further research from longitudinal studies is warranted to confirm these results.
IMPORTANCE: Folate intake during pregnancy has been associated with improved neuropsychological development in children, although the effects of high dosages of folic acid (FA) supplements are unclear. OBJECTIVE: To examine the association between the use of high dosages of FA supplements during pregnancy and child neuropsychological development after the first year of life. DESIGN, SETTING, AND PATIENTS: The multicenter prospective mother-child cohort Infancia y Medio Ambiente (INMA) Project recruited pregnant women from 4 areas of Spain (Asturias, Sabadell, Gipuzkoa, and Valencia) between November 2003 and January 2008. Pregnant women completed an interviewer-administered questionnaire on the usual dietary folate intake and FA supplements at 10 to 13 weeks and 28 to 32 weeks of gestation. The main analyses were based on a sample of 2213 children with complete information on neuropsychological development and FA supplement intake during pregnancy. Multiple linear and logistic regression analyses were used to explore the effects of FA supplements on child neuropsychological development. MAIN OUTCOMES AND MEASURES: Neuropsychological development was assessed using the Bayley Scales of Infant Development. We calculated mental scale and psychomotor scale scores. One SD below the mean established a delay in neurodevelopment (score <85). RESULTS: A high proportion of women (57.3%) did not reach the recommended dosages of FA supplements (400 μg/d), but 25.2% women took more than 1000 μg/d of FA supplements (3.5% consuming >5000 μg/d). In multivariate analysis, we observed that children whose mothers used FA supplement dosages higher than 5000 μg/d during pregnancy had a statistically significantly lower mean psychomotor scale score (difference, -4.35 points; 95% CI, -8.34 to -0.36) than children whose mothers used a recommended dosage of FA supplements (400-1000 μg/d). An increased risk of delayed psychomotor development (psychomotor scale score <85) was also evident among children whose mothers took FA supplement dosages higher than 5000 μg/d, although the association was not statistically significant (odds ratio = 1.59; 95% CI, 0.82-3.08). CONCLUSIONS AND RELEVANCE: To our knowledge, this is the first time a detrimental effect of high dosages of FA supplements during pregnancy on psychomotor development after the first year of life has been shown. Further research from longitudinal studies is warranted to confirm these results.
Authors: Olga Egorova; Robin Myte; Jörn Schneede; Bruno Hägglöf; Sven Bölte; Erik Domellöf; Barbro Ivars A'roch; Fredrik Elgh; Per Magne Ueland; Sven-Arne Silfverdal Journal: Mol Autism Date: 2020-01-16 Impact factor: 7.509