Home LiteratureArticle Details
PMID: 19874428 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Lower maternal folate status in early pregnancy is associated with childhood hyperactivity and peer problems in offspring.

Journal of child psychology and psychiatry, and allied disciplines ·Vol. 51 ·No. 5 ·2010-05-00 ·Pages 594-602

Schlotz W, Jones A, Phillips DI, Gale CR, Robinson SM, Godfrey KM

Abstract

Maternal nutrition during pregnancy has been linked with fetal brain development and psychopathology in the offspring. We examined for associations of maternal folate status and dietary intake during pregnancy with brain growth and childhood behavioural difficulties in the offspring. In a prospective cohort study, maternal red blood cell folate (RCF) was measured at 14 weeks of pregnancy and total folate intake (TFI) from food and supplements was assessed in early and late pregnancy. The offspring's head circumference and body weight were measured at birth and in infancy, and 100 mothers reported on children's behavioural difficulties at a mean age of 8.75 years using the Strengths and Difficulties Questionnaire. Lower maternal RCF and TFI in early pregnancy were associated with higher childhood hyperactivity (RCF: beta = -.24; p = .013; TFI: beta = -.24; p = .022) and peer problems scores (RCF: beta = -.28; p = .004; TFI: beta = -.28; p = .009) in the offspring. Maternal gestational RCF was positively associated with head circumference at birth (adjusted for gestational age), and mediation analyses showed significant inverse indirect associations of RCF with hyperactivity/inattention and peer problems via fetal brain growth. Adjustment for mother's smoking and drinking alcohol during pregnancy did not change the results. Although the associations are small and residual confounding is possible, our data provide preliminary support for the hypothesis that lower folate status in early pregnancy might impair fetal brain development and affect hyperactivity/inattention and peer problems in childhood.

MeSH Terms
Adult Attention Deficit Disorder with Hyperactivity/etiology Child Child Behavior/psychology Child Behavior Disorders/etiology Female Fetal Development/physiology Folic Acid/blood Gestational Age Head/embryology Humans Male Pregnancy Prenatal Exposure Delayed Effects/psychology Prenatal Nutritional Physiological Phenomena/physiology Prospective Studies Sex Factors
Chemicals
Folic Acid
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Schlotz Wolff
MRC Epidemiology Resource Centre, University of Southampton, Southampton SO17 1BJ, UK. [email protected]
Jones Alexander
Phillips David I W
Gale Catharine R
Robinson Sian M
Godfrey Keith M
References (47)
47 references, click to expand
  1. Effect of iron supplementation during pregnancy on the intelligence quotient and behavior of children at 4 y of age: long-term follow-up of a randomized controlled trial.
    Am J Clin Nutr. 2006 May;83(5):1112-7 PMID: 16685054
  2. Fetal growth and the adrenocortical response to psychological stress.
    J Clin Endocrinol Metab. 2006 May;91(5):1868-71 PMID: 16464950
  3. Fetal origins of mental health: evidence and mechanisms.
    Brain Behav Immun. 2009 Oct;23(7):905-16 PMID: 19217937
  4. Prenatal exposure to wartime famine and development of antisocial personality disorder in early adulthood.
    JAMA. 1999 Aug 4;282(5):455-62 PMID: 10442661
  5. Maternal DHA and the development of attention in infancy and toddlerhood.
    Child Dev. 2004 Jul-Aug;75(4):1254-67 PMID: 15260876
  6. Epigenetic control of fetal gene expression.
    BJOG. 2008 Jan;115(2):158-68 PMID: 17970798
  7. Role of dopamine transporter genotype and maternal prenatal smoking in childhood hyperactive-impulsive, inattentive, and oppositional behaviors.
    J Pediatr. 2003 Jul;143(1):104-10 PMID: 12915833
  8. Oily fish intake during pregnancy--association with lower hyperactivity but not with higher full-scale IQ in offspring.
    J Child Psychol Psychiatry. 2008 Oct;49(10):1061-8 PMID: 18422546
  9. Folate and human reproduction.
    Am J Clin Nutr. 2006 May;83(5):993-1016 PMID: 16685040
  10. The Strengths and Difficulties Questionnaire: a research note.
    J Child Psychol Psychiatry. 1997 Jul;38(5):581-6 PMID: 9255702
  11. Maternal seafood consumption in pregnancy and neurodevelopmental outcomes in childhood (ALSPAC study): an observational cohort study.
    Lancet. 2007 Feb 17;369(9561):578-85 PMID: 17307104
  12. 'Junk food' diet and childhood behavioural problems: results from the ALSPAC cohort.
    Eur J Clin Nutr. 2009 Apr;63(4):491-8 PMID: 18059416
  13. In utero physiology: role of folic acid in nutrient delivery and fetal development.
    Am J Clin Nutr. 2007 Feb;85(2):598S-603S PMID: 17284762
  14. A common haplotype of the dopamine transporter gene associated with attention-deficit/hyperactivity disorder and interacting with maternal use of alcohol during pregnancy.
    Arch Gen Psychiatry. 2006 Jan;63(1):74-81 PMID: 16389200
  15. Not all cases of neural-tube defect can be prevented by increasing the intake of folic acid.
    Br J Nutr. 2009 Jul;102(2):173-80 PMID: 19079944
  16. Nutrition and the developing brain: nutrient priorities and measurement.
    Am J Clin Nutr. 2007 Feb;85(2):614S-620S PMID: 17284765
  17. Persistent epigenetic differences associated with prenatal exposure to famine in humans.
    Proc Natl Acad Sci U S A. 2008 Nov 4;105(44):17046-9 PMID: 18955703
  18. Effortful control mediates associations of fetal growth with hyperactivity and behavioural problems in 7- to 9-year-old children.
    J Child Psychol Psychiatry. 2008 Nov;49(11):1228-36 PMID: 19043849
  19. Why does birthweight vary among ethnic groups in the UK? Findings from the Millennium Cohort Study.
    J Public Health (Oxf). 2009 Mar;31(1):131-7 PMID: 18647751
  20. Trends in folic acid supplement intake among women of reproductive age--California, 2002-2006.
    MMWR Morb Mortal Wkly Rep. 2007 Oct 26;56(42):1106-9 PMID: 17962802
  21. Evaluation of a food frequency questionnaire used to assess nutrient intakes in pregnant women.
    Eur J Clin Nutr. 1996 May;50(5):302-8 PMID: 8735311
  22. Predictors of red cell folate level in women attempting pregnancy.
    JAMA. 1997 Feb 19;277(7):548-52 PMID: 9032161
  23. Dietary patterns throughout adult life are associated with body mass index, waist circumference, blood pressure, and red cell folate.
    J Nutr. 2007 Jan;137(1):99-105 PMID: 17182808
  24. The developmental origins of chronic adult disease.
    Acta Paediatr Suppl. 2004 Dec;93(446):26-33 PMID: 15702667
  25. Behavioral effects of prenatal folate deficiency in mice.
    Birth Defects Res A Clin Mol Teratol. 2005 Apr;73(4):249-52 PMID: 15744731
  26. Developmental psychopathology: concepts and challenges.
    Dev Psychopathol. 2000 Summer;12(3):265-96 PMID: 11014739
  27. Folic acid: influence on the outcome of pregnancy.
    Am J Clin Nutr. 2000 May;71(5 Suppl):1295S-303S PMID: 10799405
  28. Increased risk of affective disorders in males after second trimester prenatal exposure to the Dutch hunger winter of 1944-45.
    Br J Psychiatry. 1995 May;166(5):601-6 PMID: 7620744
  29. Maternal lifestyle factors in pregnancy risk of attention deficit hyperactivity disorder and associated behaviors: review of the current evidence.
    Am J Psychiatry. 2003 Jun;160(6):1028-40 PMID: 12777257
  30. Folic acid deficiency during late gestation decreases progenitor cell proliferation and increases apoptosis in fetal mouse brain.
    J Nutr. 2004 Jan;134(1):162-6 PMID: 14704311
  31. Psychometric properties of the strengths and difficulties questionnaire.
    J Am Acad Child Adolesc Psychiatry. 2001 Nov;40(11):1337-45 PMID: 11699809
  32. Comparing the Strengths and Difficulties Questionnaire and the Child Behavior Checklist: is small beautiful?
    J Abnorm Child Psychol. 1999 Feb;27(1):17-24 PMID: 10197403
  33. Impact of educational attainment on the quality of young women's diets.
    Eur J Clin Nutr. 2004 Aug;58(8):1174-80 PMID: 15054431
  34. Folate and neural tube defects.
    Am J Clin Nutr. 2007 Jan;85(1):285S-288S PMID: 17209211
  35. Developmental trajectories of brain volume abnormalities in children and adolescents with attention-deficit/hyperactivity disorder.
    JAMA. 2002 Oct 9;288(14):1740-8 PMID: 12365958
  36. Food additives and hyperactive behaviour in 3-year-old and 8/9-year-old children in the community: a randomised, double-blinded, placebo-controlled trial.
    Lancet. 2007 Nov 3;370(9598):1560-7 PMID: 17825405
  37. Prenatal disruption of neocortical development alters prefrontal cortical neuron responses to dopamine in adult rats.
    Neuropsychopharmacology. 2005 Aug;30(8):1426-35 PMID: 15827574
  38. Neurochemical and behavioral effects of diet related perinatal folic acid restriction.
    Pharmacol Biochem Behav. 1976 Aug;5(2):129-34 PMID: 996047
  39. 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 Jan;73(1):6-28 PMID: 15641086
  40. Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models.
    Environ Health Perspect. 2000 Jun;108 Suppl 3:511-33 PMID: 10852851
  41. Dietary patterns in infancy: the importance of maternal and family influences on feeding practice.
    Br J Nutr. 2007 Nov;98(5):1029-37 PMID: 17532867
  42. Relationship between head circumference and brain volume in healthy normal toddlers, children, and adults.
    Neuropediatrics. 2002 Oct;33(5):239-41 PMID: 12536365
  43. Peer functioning in children with ADHD.
    J Pediatr Psychol. 2007 Jul;32(6):655-63 PMID: 17556400
  44. Pre- and peri-natal environmental risks for attention-deficit hyperactivity disorder (ADHD): the potential role of epigenetic processes in mediating susceptibility.
    J Child Psychol Psychiatry. 2008 Oct;49(10):1020-30 PMID: 18492038
  45. Effect of iron supplementation during pregnancy on the behaviour of children at early school age: long-term follow-up of a randomised controlled trial.
    Br J Nutr. 2008 May;99(5):1133-9 PMID: 17967217
  46. Small body size at birth and behavioural symptoms of ADHD in children aged five to six years.
    J Child Psychol Psychiatry. 2006 Nov;47(11):1167-74 PMID: 17076756
  47. Neonatal bone mass: influence of parental birthweight, maternal smoking, body composition, and activity during pregnancy.
    J Bone Miner Res. 2001 Sep;16(9):1694-703 PMID: 11547840
Article Info
Journal
Journal of child psychology and psychiatry, and allied disciplines
Abbr.
J Child Psychol Psychiatry
ISSN
1469-7610
Published
2010-05-00
Epub
2009-00-28
Pages
594-602
Language
English
Region
England
NLM ID
0375361
PMCID
PMC2862762
Subset
IM
Grants
Medical Research Council · MC_UP_A620_1015 · United Kingdom
Medical Research Council · MC_UP_A620_1017 · United Kingdom
NICHD NIH HHS · R01 HD041107-01 · United States
NICHD NIH HHS · 1 R01 HD41107-01 · United States
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]