“The distinct “trimester-specific” associations observed here likely reflect the dynamic nature of neurodevelopment,” wrote researchers in Spain in Nutrients, noting that their results align with previous studies linking elevated ratios to an increased risk of ADHD in children.
However, the findings showed that general cognitive abilities were largely unaffected, and the associations between early neural development and omega fatty acid ratios require further study to elucidate the mechanisms and potential impacts on children.
The developing brain
Omega-3 fatty acids—specifically docosahexaenoic acid (DHA) — are vital structural components of the developing brain. DHA, which constitutes 7.7% of total brain fatty acids, regulates neuronal membrane fluidity and is required for synapse formation, the connections between brain cells.
Omega-6 fatty acids, such as arachidonic acid (ARA), also play an essential structural role in the brain, but the omega-6-to-omega-3 (n-6/n-3) ratio is critical because both families compete for the same desaturase enzymes involved in their processing in the body.
The current researchers noted that prior literature has focused on omega-3 levels in neurodevelopment; however, “because n-3 and n-6 LCPUFAs compete for the same enzymatic pathways, their relative balance is biologically more meaningful than absolute levels,” they wrote.
Previous studies have linked an elevated n-6/n-3 ratio to specific neurodevelopmental challenges, such as ADHD-related symptoms and poorer infant motor development.
“The first trimester is a period of intense neurogenesis and neuronal migration,” wrote the current researchers.
“An imbalance of n-6/n-3 fatty acids during this foundational stage may alter the composition of neuronal membranes, potentially disrupting the formation of fundamental neural circuits that underpin self-regulation,” they added, noting that the pro-inflammatory nature of omega-6 could modulate microglial and synaptic mechanisms that affect the development of executive function.
Many previous trials have focused on measuring maternal fatty acid (FA) status at a single time point and fail to capture shifts in concentrations driven by adipose tissue mobilization and placental transfer. The researchers also noted the importance of measuring the child’s development at critical times, such as the preschool years, when the prefrontal cortex matures.
Study details
The prospective follow-up study included 223 pregnant women from the ECLIPSES cohort, a community-based randomized controlled trial in Spain.
The women were enrolled before 12 weeks’ gestation and assessed at 12, 24, and 36 weeks’ gestation. Their children were assessed at approximately 54 days after birth and at 4 years of age.
Researchers measured maternal serum n-3 and n-6 fatty acids and assessed children’s cognitive and executive function using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI) and the Behavior Rating Inventory of Executive Function (BRIEF)—Preschool Version.
“In this study, higher prenatal n-6/n-3 ratio during the first trimester was associated with poorer executive functioning among children via BRIEF-P, particularly in inhibition, WM [working memory], and planning/organization,” the researchers wrote.
They also observed positive associations for the inhibitory self-control index, emergent metacognition index, and global executive composite. There were no significant associations for the third trimester.
“These findings highlight that associations between LCPUFA exposure and child neurodevelopment were primarily observed in the first trimester,” the researchers concluded.
They noted the observational nature of the study and recommended that further research is needed to translate the results into nutritional guidance.
Source: Nutrients 2026, 18(21), 3514; https://doi.org/10.3390/nu18213514, “Trimester-Specific Associations Between Maternal Fatty Acid Ratios and Cognitive and Executive Functioning in 4-Year-Old Children.” Authors: X.Kou et al.
