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Updated: Nov 27, 2025
Author Spotlight: Studying the Impact of Maternal Dietary Deficiencies on Long-Term Offspring Health Outcomes
Published on: June 28, 2024
Maternal folate levels during pregnancy and offspring brain development in late childhood
Runyu Zou1, Hanan El Marroun2, Charlotte Cecil3
1Department 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.
Insights
Low maternal folate during pregnancy is linked to smaller brain volumes in children. This highlights the critical role of folate for healthy offspring brain development.
Area of Science:
- Neuroscience
- Developmental Biology
- Public Health
Background:
- Maternal folate deficiency is linked to offspring neuropsychiatric disorders.
- The impact of prenatal folate on late childhood brain development is understudied.
Purpose of the Study:
- To investigate the association between maternal folate levels during pregnancy and offspring brain development in late childhood.
- To analyze the long-term effects of in utero folate exposure on brain structure.
Main Methods:
- Prospective population-based cohort study of 2095 children.
- Maternal folate levels measured in early pregnancy blood samples.
- Child brain structure assessed via neuroimaging (MRI) and head circumference (ultrasound) at various ages.
Main Results:
- Maternal folate deficiency was associated with smaller total brain volume and cerebral white matter in children aged 9-11 years.
- Children exposed to folate deficiency in utero showed persistently smaller brains from the third trimester through childhood.
- No significant differences were observed in cortical thickness or surface area.
Conclusions:
- Low maternal folate levels during pregnancy are associated with altered offspring brain development.
- Adequate folate concentrations in early pregnancy are crucial for optimal fetal brain development.
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.
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