Researchers from Spain aimed to explore the association between maternal serum ratios of omega-6 (n-6) and omega-3 (n-3) in the first and third trimesters of pregnancy and the neurodevelopment of their children in the early days after birth in the population of Northern Spain’s Mediterranean region.
They wrote that previous studies have mostly measured maternal polyunsaturated fatty acid (PUFA) levels only in late gestation, which coincides with a surge in DHA transfer to the fetus, supporting rapid brain development.
However, they noted in the journal Nutrients that “findings confirm this period’s sensitivity, as the third-trimester n-6/n-3 ratio was linked to poorer outcomes, unlike the first trimester.”
Impact of maternal nutrition on prenatal brain development
N-6 and n-3 long-chain polyunsaturated fatty acids (LCPUFAs) are known to be essential for brain development, particularly docosahexaenoic acid (DHA) and arachidonic acid (ARA).
Previous studies have mostly focused on the effects of n-3 LCPUFAs on infant neurodevelopment, however results are mixed.
Some studies report no clear benefits of maternal DHA levels or supplementation during pregnancy on infant neurodevelopment, while others have suggested adverse associations, such as poorer neurodevelopment linked to higher DHA concentrations in early pregnancy.
According to the researchers on the new study, limited focus on n-6 fatty acids and their interaction with n-3 fatty acids may contribute to these inconsistencies.
These fatty acids compete for cellular incorporation and influence inflammatory processes differently, with n-6 promoting and n-3 mitigating inflammation. Maintaining a dietary n-6/n-3 ratio of 4:1 or less is recommended, but an optimal serum ratio remains undefined.
Previous studies linking maternal n-6/n-3 ratios to child neurodevelopment have produced conflicting results. Some research finds that higher ratios are associated with emotional and behavioral issues in children, while others find no significant correlations.
The researchers therefore sought to examine the association between maternal serum n-6/n-3 ratios in the first and third trimesters and early neurodevelopment in children.
They noted that gestational timing plays a pivotal role in neurodevelopment meaning there are different nutritional needs at different stages, and therefore research should separately consider these periods to understand the distinct impacts on neurodevelopment.
Impact of LCPUFA ratios on newborn motor skills
The researchers followed 791 pregnant women from their first trimester to early postpartum in a randomized controlled trial.
Eligible participants were evaluated at 12, 24 and 36 weeks of gestation and between six and eight weeks postpartum. Maternal blood samples, lifestyle data and infant neurodevelopment metrics were collected.
A subsample of 450 participants had their LCPUFA serum concentrations measured at 12 and 36 weeks, and 336 underwent postpartum cognitive assessments. The statistical analysis examined maternal serum n-6/n-3, ARA/DHA and ARA/EPA ratios.
Results showed that higher n-6/n-3 and ARA/DHA ratios in the third trimester were associated with poorer motor development in newborns, while no such associations appeared in the first trimester or for the ARA/EPA ratio in the third trimester.
“This highlights the importance of late-gestational fatty acid status in shaping early neurodevelopment,” the researchers wrote.
They hypothesized that the results could be due to the pro-inflammatory effects of an imbalanced n-6/n-3 ratio, explaining that excessive n-6 fatty acids may promote inflammation through eicosanoid production, disrupting processes like synaptic pruning and neurogenesis.
This could impair motor and cognitive outcomes, as neuroinflammation is tied to altered neuronal connectivity.
“The early assessment of infant neurodevelopment allows us to better isolate the gestational effects of maternal n-6/n-3 ratios before the impact of postnatal variables could occur,” the researchers concluded.
They did however note that the generalization of the results was limited to Mediterranean groups with similar social and environmental characteristics to those of Southern Europe, therefore excluding populations with different dietary patterns and genetic backgrounds.
“These factors should be considered in future studies to better understand the interaction between prenatal and postnatal factors in long-term follow-up research,” they wrote.
Source: Nutrients
2025, 17(1), 170; doi: 10.3390/nu17010170
“Maternal Omega-6/Omega-3 Concentration Ratio During Pregnancy and Infant Neurodevelopment: The ECLIPSES Study.”
Authors: B. Shahabi, et al.