Levels of a fatty acid in cord blood may help determine autism spectrum disorder (ASD) severity in childhood, according to work by a research team from University of Fukui, Japan. The researchers quantified polyunsaturated fatty acids (PUFAs) from cord blood and later used various tests to assess subsequent ASD symptoms and adaptive functioning in about 200 children at six years. They found that cord blood dihydroxyeicosatrienoic acids (diHETrE) levels were associated with severity of certain symptoms.
Higher levels of the molecule 11,12-diHETrE had an impact on social interactions, whereas low levels of 8,9-diHETrE impacted repetitive and restrictive behaviors. Notably, this correlation was more specific for girls than for boys. By measuring diHETrE levels at birth, these researchers suggest it may be possible to predict the likelihood of ASD development in children.
“The levels of diHETrE, an arachidonic acid-derived diol, in cord blood at birth significantly impacted subsequent ASD symptoms in children and were also associated with impaired adaptive functioning. These findings suggest that the dynamics of diHETrE during the fetal period is important in the developmental trajectory of children after birth,” said Senior author Hideo Matsuzaki, MD, PhD.
Their study was published July 23, 2024 in Psychiatry and Clinical Neurosciences. The lead author is Takaharu Hirai, PhD, of the Fukui School of Nursing.
ASD is a neurodevelopmental disorder that affects learning capability and social behavior. There are still many questions about why ASD occurs and how it progresses. Although the exact causes of ASD are unclear, currently available evidence points to neuroinflammation as a major factor. Several studies in mouse models have hinted at the importance of PUFAs and their metabolites during pregnancy in playing a key role in ASD development.
PUFAs, arachidonic acid and metabolites, are key mediators of immune modulatory processes. They are regulated by the cytochrome P450 pathway and can affect fetal development in mice causing impairments similar to ASD symptoms. However, it is still unclear if the same association is true for humans. This Japanese team analyzed the CYP-PUFA levels in neonatal umbilical cord blood samples and then looked at results from children’s behavioral tests.
Matsuzaki said, “CYP metabolism forms both epoxy fatty acids (EpFAs), which have anti-inflammatory effects, and dihydroxy fatty acids, or ‘diols,’ which have inflammatory properties. We hypothesized that the dynamics of CYP-PUFA metabolites during the fetal period, that is, lower EpFA levels, higher diol levels, and/or increased EpFA metabolic enzymes would influence ASD symptoms and difficulties with daily functioning in children after birth.”
The researchers investigated the link between PUFA metabolites in umbilical cord blood and ASD scores in 200 children. The cord blood samples had been collected immediately after birth and preserved appropriately, whereas ASD symptoms and adaptive functioning were assessed when the same children were six years old, with the help of their mothers.
Statistical analyses identified one compound in cord blood that may have strong implications for ASD severity—diHETrE.
“The effectiveness of early intervention for children with ASD is well established and detecting it at birth could enhance intervention and support for children with ASD,” added Matsuzaki. He also said that inhibiting diHETrE metabolism during pregnancy might be a promising avenue for preventing ASD traits in children, although more research will be needed in this regard.
