Runyu Zou1, Hanan El Marroun2, Charlotte Cecil3, Vincent W V Jaddoe4, Manon Hillegers5, Henning Tiemeier6, Tonya White7. 1. Department of Child and Adolescent Psychiatry, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands; The Generation R Study Group, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands. 2. Department of Child and Adolescent Psychiatry, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Pediatrics, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Psychology, Education and Child Studies, Erasmus School of Social and Behavioral Sciences, Erasmus University Rotterdam, Rotterdam, the Netherlands. 3. Department of Child and Adolescent Psychiatry, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, the Netherlands; Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, 2333 ZC, Leiden, the Netherlands. 4. The Generation R Study Group, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Pediatrics, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands. 5. Department of Child and Adolescent Psychiatry, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands. 6. Department of Child and Adolescent Psychiatry, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Social and Behavioral Sciences, T.H. Chan School of Public Health, Harvard University, Boston, MA, United States. 7. Department of Child and Adolescent Psychiatry, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Radiology and Nuclear Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands. Electronic address: t.white@erasmusmc.nl.
Abstract
BACKGROUND: Cumulative evidence shows that low maternal folate levels during pregnancy are associated with offspring neuropsychiatric disorders even in the absence of neural tube defects. However, the relationship between prenatal exposure to folate and brain development in late childhood has been rarely investigated. METHODS: In 2095 children from a prospective population-based cohort in Rotterdam, the Netherlands, we examined the association of maternal folate levels during pregnancy with downstream brain development in offspring. Maternal folate concentrations were measured from venous blood in early gestation. Child structural neuroimaging data were measured at age 9-11 years. In addition, measures of child head circumference using fetal ultrasound in the third trimester and total brain volume using magnetic resonance imaging at age 6-8 years were used for analyses with repeated assessments of brain development. RESULTS: Maternal folate deficiency (i.e., <7 nmol/L) during pregnancy was associated with smaller total brain volume (B = -18.7 cm3, 95% CI -37.2 to -0.2) and smaller cerebral white matter (B = -7.2 cm3, 95% CI -11.8 to -2.6) in children aged 9-11 years. No differences in cortical thickness or surface area were observed. Analysis of the repeated brain assessments showed that children exposed to deficient folate concentrations in utero had persistently smaller brains compared to controls from the third trimester to childhood (β = -0.4, 95% CI -0.6 to -0.1). CONCLUSIONS: Low maternal folate levels during pregnancy are associated with altered offspring brain development in childhood, suggesting the importance of essential folate concentrations in early pregnancy.
BACKGROUND: Cumulative evidence shows that low maternal folate levels during pregnancy are associated with offspring neuropsychiatric disorders even in the absence of neural tube defects. However, the relationship between prenatal exposure to folate and brain development in late childhood has been rarely investigated. METHODS: In 2095 children from a prospective population-based cohort in Rotterdam, the Netherlands, we examined the association of maternal folate levels during pregnancy with downstream brain development in offspring. Maternal folate concentrations were measured from venous blood in early gestation. Child structural neuroimaging data were measured at age 9-11 years. In addition, measures of child head circumference using fetal ultrasound in the third trimester and total brain volume using magnetic resonance imaging at age 6-8 years were used for analyses with repeated assessments of brain development. RESULTS: Maternal folate deficiency (i.e., <7 nmol/L) during pregnancy was associated with smaller total brain volume (B = -18.7 cm3, 95% CI -37.2 to -0.2) and smaller cerebral white matter (B = -7.2 cm3, 95% CI -11.8 to -2.6) in children aged 9-11 years. No differences in cortical thickness or surface area were observed. Analysis of the repeated brain assessments showed that children exposed to deficient folate concentrations in utero had persistently smaller brains compared to controls from the third trimester to childhood (β = -0.4, 95% CI -0.6 to -0.1). CONCLUSIONS: Low maternal folate levels during pregnancy are associated with altered offspring brain development in childhood, suggesting the importance of essential folate concentrations in early pregnancy.
Authors: Anna Suleri; Elisabet Blok; Melisa Durkut; Anna-Sophie Rommel; Lot de Witte; Vincent Jaddoe; Veerle Bergink; Tonya White Journal: Brain Behav Immun Date: 2022-04-02 Impact factor: 19.227
Authors: Eleonora Rubini; Inge M M Baijens; Alex Horánszky; Sam Schoenmakers; Kevin D Sinclair; Melinda Zana; András Dinnyés; Régine P M Steegers-Theunissen; Melek Rousian Journal: Genes (Basel) Date: 2021-10-17 Impact factor: 4.096