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Updated: Sep 24, 2025
Author Spotlight: Studying the Impact of Maternal Dietary Deficiencies on Long-Term Offspring Health Outcomes
Published on: June 28, 2024
Excessive folic acid intake combined with undernutrition during gestation alters offspring behavior and brain
Tetsuo Ono1,2, Kodai Hino3, Tomoko Kimura3,4
1Department of Obstetrics and Gynecology, Shiga University of Medical Science, Otsu, Shiga, Japan.
Insights
Excessive maternal folic acid intake during pregnancy may lead to hyperactivity and altered brain chemistry in male offspring. This study investigated the effects of high folic acid and poor nutrition on offspring behavior and neurodevelopment.
Area of Science:
- Neuroscience
- Developmental Biology
- Nutritional Science
Background:
- Maternal folic acid supplementation during pregnancy is known to reduce neurodevelopmental disorder risks.
- However, the potential impact of excessive folic acid intake on offspring brain function remains largely unexplored.
Purpose of the Study:
- To investigate the effects of excessive maternal folic acid intake throughout gestation on the behavior of male offspring, particularly under conditions of poor nutrition.
- To analyze the associated changes in brain monoamine levels and their correlation with observed behavioral alterations.
Main Methods:
- Pregnant dams were assigned to four groups: control, excessive folic acid, undernutrition, and combined undernutrition and excessive folic acid.
- Offspring behavior was assessed at 9 weeks of age using open-field and elevated plus maze tests.
- Brain monoamine concentrations (dopamine, norepinephrine, serotonin) and their metabolites were measured in specific brain regions using canonical discriminant analysis.
Main Results:
- Excessive maternal folic acid intake induced hyperactivity and reduced anxiety-like behavior in male offspring.
- These behavioral changes were associated with decreased dopamine in the prefrontal cortex, norepinephrine in the amygdala, and serotonin in the dorsal midbrain, prefrontal cortex, and amygdala.
- Discriminant analysis successfully classified offspring groups based on nutritional status and folic acid intake, highlighting the combined impact.
Conclusions:
- Excessive maternal folic acid intake, especially combined with undernutrition, significantly alters offspring behavior.
- Changes in brain monoamine profiles, including dopamine, norepinephrine, and serotonin, are implicated in these behavioral modifications.
- The findings suggest a complex interplay between maternal nutrition, folic acid levels, and offspring neurodevelopment.
Abstract:
Dietary folic acid augmentation during gestation reduces neurodevelopmental disorder risk in offspring; however, it is still unclear if excessive maternal folic acid intake can impair brain function in offspring. We examined if excessive folic acid intake throughout gestation altered the behavior of male offspring under poor nutrition during early gestation (E5.5-E11.5). Dams were divided into four groups: control (CON, 2 mg folic acid/kg of food), excessive folic acid fortification (FF, 10 mg folic acid/kg of food), undernutrition (UN, 40% food reduction from E5.5-E11.5), and excessive folic acid fortification plus undernutrition (UN-FF). Excess maternal folic acid fortification induced hyperactivity in the open-field and lower anxiety-like behavior in the elevated plus maze at 9 weeks of age. These behavioral changes were accompanied by reduced dopamine in the prefrontal cortex (PFC), norepinephrine in the amygdala, and 5-hydroxytryptamine (5-HT) in the dorsal midbrain (DM), PFC, and amygdala where 5-HT neurons project from the DM. Furthermore, canonical discriminant analysis, including dopamine and DOPAC concentrations in the PFC, norepinephrine concentrations in the PFC, amygdala, and pons, and 5-HT and 5-HIAA concentrations in the amygdala and DM, correctly classified 73.5% of the offspring in CON, FF, UN, and UN-FF groups. The first discriminant function mainly classified groups based on nutritional status, whereas the second function mainly classified groups based on folic acid intake. Our study suggests that combined transformations of brain monoamine profiles by maternal undernutrition and excess folic acid intake is involved in the behavioral alteration of offsprings.
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