Pre-conception folic acid intake and attention deficit and hyperactivity disorder in children

Abstract

Objectives: Attention Deficit Hyperactivity Disorder (ADHD) is a common disorder in children. It is thought to occur due to the interaction of many genetic and environmental factors during early  development. Many studies have been conducted to investigate the etiology of ADHD. Some have investigated neurobiology, and others have investigated malnutrition and trace element deficiency. To investigate the effect of folic acid intake during the pre-conception period in terms of ADHD development. 

Methods: Five hundred and ninety-eight participants, 246 children with ADHD, and 352 healthy controls were enrolled. A questionnaire was completed, including socio-demographic information and the use of folic acid and other supplements such as a multivitamin, iron, and omega 3 during pregnancy. Data were examined to determine associations with ADHD. Mann-Whitney U tests for continuous variables, Pearson’s chi-square, and Fisher’s exact tests for categorical variables were used to compare groups. 

Results: The use of folic acid during pre-pregnancy among mothers who had a child with ADHD was 13% and this was 31% in the control group (p < 0.001). There was no statistically significant difference between the groups’ use of folic acid in pregnancy (p = 0.617). Other situations related to ADHD were advanced maternal age (p < 0.001 for both groups), abnormal double screening test results in pregnancy (27% vs. 5%, p < 0.001) and omega 3 use in pregnancy (p < 0.001). 

Conclusions: The use of folic acid before and during pregnancy is important for neurological development. However, there is little data on use before pregnancy in the literature. This study shows that folic acid taken before pregnancy may prevent ADHD in childhood. The present study recommends folic acid usage in planned pregnancy to prevent ADHD in the child. 

Keywords

• Pre-pregnancy
• folic acid
• attention deficit hyperactivity disorder
• children

References

1. 1. Friel JK, Frecker M, Fraser FC. Nutritional patterns of mothers of children with neural tube defects in Newfoundland. Am J Med Genet 1995;55:195-9.
2. 2. Lakhan SE, Vieira KF. Nutritional therapies for mental disorders. Nutr J 2008;7:2.
3. 3. Chan A, Tchantchou F, Graves V, Rozen R, Shea TB. Dietary and genetic compromise in folate availability reduces acetylcholine, cognitive performance and increases aggression: Critical role of S-adenosyl methionine. J Nutr Health Aging 2008;12:252-61.
4. 4. Moretti P, Peters SU, del Gaudio D, Sahoo T, Hyland K, Bottiglieri T, et al. Brief report: Autistic symptoms, developmental regression, mental retardation, epilepsy, and dyskinesias in CNS folate deficiency. J Autism Dev Disord 2008;38:1170-77.
5. 5. Antai-Otong, D, Zimmerman ML. Treatment approaches to attention deficit hyperactivity disorder. Nurs Clin North Am 2016;51:199-211.
6. 6. Nigg JT. Attention-deficit/hyperactivity disorder and adverse health outcomes. Clin Psychol Rev 2013;33:215-28.
7. 7. Biederman J. Attention-deficit/hyperactivity disorder: a selective overview. Biol Psychiatry 2005;57:1215-20.
8. 8. Biederman J, Faraone SV. Attention-deficit hyperactivity disorder. Lancet. 2005;366:237-48.

9. 9. Schlotz W, Jones A, Phillips DIW, Gale CR, Robinson SM, Godfrey KM. Lower maternal folate status in early pregnancy is associated with childhood hyperactivity and peer problems in offspring. J Child Psychol Psychiatry 2010;51:594-602.
10. 10. Georgieff MK. Nutrition and the developing brain: nutrient priorities and measurement. Am J Clin Nutr 2007;85:614S-20S.
11. 11. Gale CR, Robinson SM, Godfrey KM, Law CM, Schlotz W, O’Callaghan FJ. Oily fish intake during pregnancy–association with lower hyperactivity but not with higher full‐scale IQ in offspring. J Child Psychol Psychiatry 2008;49:1061-8.
12. 12. Zeisel SH. Importance of methyl donors during reproduction. Am J Clin Nutr 2009;89:673S-77S.
13. 13. Scholl TO, Johnson WG. Folic acid: influence on the outcome of pregnancy. Am J Clin Nutr 2000;71:1295S-303S.
14. 14. Xiao S, Hansen DK, Horsley ET, Tang YS, Khan RA, Stabler SP, et al. Maternal folate deficiency results in selective upregulation of folate receptors and heterogeneous nuclear ribonucleoprotein‐E1 associated with multiple subtle aberrations in fetal tissues. Birth Defects Res A Clin Mol Teratol 2005;73:6-28.
15. 15. Middaugh LD, Grover TA, Blackwell LA, Zemp JW. Neurochemical and behavioral effects of diet related perinatal folic acid restriction. Pharmacol Biochem Behav 1976;5:129-34.
16. 16. Castellanos FX, Lee PP, Sharp W, et al. Developmental trajectories of brain volume abnormalities in children and adolescents with attention-deficit/hyperactivity disorder. JAMA 2002;288:1740-48.
17. 17. De Lau LM, Refsum H, Smith AD, Johnston C, Breteler MM. Plasma folate concentration and cognitive performance: Rotterdam Scan Study. Am J Clin Nutr 2007;86:728-34.
18. 18. Pangilinan, F, Molloy, AM, Mills JL, Troendle JF, Parle-McDermott A, Signore C, et al. Evaluation of common genetic variants in 82 candidate genes as risk factors for neural tube defects. BMC Med Genet 2012;13:62.
19. 19. Hall JG, Solehdin F. Genetics of neural tube defects. Mental Retard Dev Disabil Res Rev 1998;4:269-81.
20. 20. Steenweg-de Graaff J, Ghassabian A, Jaddoe VW, Tiemeier H, Roza SJ. Folate concentrations during pregnancy and autistic traits in the offspring. The Generation R Study. Eur J Publ Health 2015;25:431-33.
21. 21. Bos DJ, van Montfort SJ, Oranje B, Durston S, Smeets PA. Effects of omega-3 polyunsaturated fatty acids on human brain morphology and function: what is the evidence? Eur Neuropsychopharmacol 2016;26:546-61.
22. 22. Crippa A, Agostoni C, Mauri M, Molteni M, Nobile M. Polyunsaturated fatty acids are associated with behavior but not with cognition in children with and without ADHD: an Italian study. J Atten Disord 2018;22:971-83.
23. 23. Bloch MH, Qawasmi A. Omega-3 fatty acid supplementation for the treatment of children with attention-deficit/hyperactivity disorder symptomatology: systematic review and meta-analysis. J Am Acad Child Adolesc Psychiatry 2011;50:991-00.
24. 24. Strickland AD. Prevention of cerebral palsy, autism spectrum disorder, and attention deficit-hyperactivity disorder. Med Hypotheses 2014;82:522-8.
25. 25. Reichman NE, Pagnini DL. Maternal age and birth outcomes: data from New Jersey. Fam Plann Perspect 1997;29:268-95.
26. 26. Gustafsson P, Källén K. Perinatal, maternal, and fetal characteristics of children diagnosed with attention‐deficit-hyperactivity disorder: results from a population‐based study utilizing the Swedish Medical Birth Register. Dev Med Child Neurol 2011;53:263-68.
27. 27. Chudal R, Joelsson P, Gyllenberg D, Lehti V, Leivonen S, Hinkka-Yli-Salomäki S, et al. Parental age and the risk of attention-deficit/hyperactivity disorder: a nationwide, population-based cohort study. J Am Acad Child Adolescent Psychiatry 2015;54:487-94.e1.