Fish oil supplementation during pregnancy changes two childhood brain metabolic markers

By Hugo Francisco de SouzaReviewed by Susha Cheriyedath, M.Sc.Jul 19 2026

A decade after mothers received EPA- and DHA-rich fish oil, MRI scans revealed subtle metabolic differences in their children, offering new clues about how prenatal nutrition may shape the developing brain.

Study: Fish oil-derived fatty acids in pregnancy and brain metabolism in middle childhood: results from a randomized controlled trial. Image Credit: MaximT / Shutterstock

In a recent study accepted for publication in the journal Translational Psychiatry, researchers conducted a randomized controlled trial (RCT) to examine the neurobiological effects of maternal supplementation with fish oil-derived n-3 long-chain polyunsaturated fatty acids (PUFAs) from pregnancy week 24 until one week postpartum on offspring brain metabolism at age 10.

The original Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC2010) cohort included 700 mother-child pairs. At the 10-year follow-up, participating children completed cognitive and psychopathological assessments. A total of 487 children underwent 3 Tesla magnetic resonance imaging (MRI) scans, of whom 460 had at least one usable brain metabolic measurement after processing and quality control.

The trial found that prenatal supplementation was associated with small but statistically significant reductions in childhood cerebral blood flow (CBF) and oxygen consumption. Placed in context using adult data, these findings suggest that maternal omega-3 intake may shift childhood brain metabolism toward a more mature profile, although the study could not establish accelerated maturation or clinical benefit.

Background

Decades of research have established that children's brains require substantially more energy to support synaptic formation, pruning, and myelination than adult brains.

Physiologically, the heightened state of the childhood human brain is characterized by elevated cerebral blood flow (CBF), with more recent research documenting that this is accompanied by increased cerebral metabolic rate of oxygen (CMRO₂) and high lactate production via aerobic glycolysis (AG). AG is a metabolic process in which the brain metabolizes glucose nonoxidatively, even when oxygen is abundant.

Data from early-life cohorts have revealed that CBF and CMRO₂ naturally peak around age 7 before steadily declining into adulthood as the brain matures, while cerebral lactate production is also higher in children than in adults. Within this specific developmental window, lower metabolic values may reflect a progressive shift toward a more mature adult state, but are not inherently beneficial or evidence of improved function.

Fish-oil supplementation has long been studied during pregnancy. These oils are rich in polyunsaturated fatty acids (PUFAs), specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and maternal PUFA status and supplementation have been associated with some favorable neurodevelopmental outcomes in offspring.

However, much of the available evidence did not directly address whether prenatal supplementation changes childhood brain metabolism, so its causal effects on these specific outcomes remained uncertain.

About the Study

The researchers aimed to address this knowledge gap by testing the effects of randomized maternal supplementation on childhood brain metabolism using data from the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC2010) cohort.

COPSAC2010 is a double-blind, randomized controlled trial (RCT) in which pregnant women (n = 700) at 24 weeks of gestation were assigned to receive either a daily dose of 2.4 grams of fish oil-derived polyunsaturated fatty acids (PUFAs), comprising 55% EPA and 37% DHA, or an olive oil placebo until one week postpartum.

A decade later, 487 children underwent a 3 Tesla MRI. After image processing and quality control, a final dataset comprising 460 children, with a mean age of 10.3 years and at least one eligible brain metabolic measurement, was obtained as part of the neurodevelopmental follow-up study. The fully adjusted analyses included 325 children for CBF, 271 for CMRO₂, and 380 for lactate.

Neuroimaging techniques included phase-contrast mapping (PCM) MRI to measure the total average cerebral blood flow (CBF) through the major cerebral arteries. The researchers calculated the total average cerebral metabolic rate of oxygen (CMRO₂) from CBF, venous hemoglobin concentration, an assumed arterial oxygen saturation of 98%, and venous oxygen saturation measured using susceptibility-based oximetry (SBO) MRI. Magnetic resonance spectroscopy (MRS) was used separately to determine tissue lactate concentrations in the precuneus.

In addition to neuroimaging, participants completed cognitive testing and diagnostic interviews at a separate visit approximately one week before MRI. The children's metabolic MRI measurements, rather than their cognitive or psychopathological results, were compared with those of 248 adults scanned on identical hardware using identical sequences, providing a developmental context for interpreting the metabolic findings.

Study Findings

The analyses revealed that children whose mothers received fish oil supplements during pregnancy exhibited small but significantly lower global CBF and CMRO₂ rates at age 10 than their placebo-group counterparts.

Statistical models adjusted for participants' sex, age, gestational age, socioeconomic measures, maternal baseline EPA and DHA levels, and outcome-specific variables identified that prenatal PUFA supplementation reduced CBF by an average of 2.3 mL/100 g/min, with an adjusted beta of −2.3, a 95% confidence interval (CI) of −4.42 to −0.25, and p = 0.03. It also decreased CMRO₂ by 17.38 µmol/100 g/min, with an adjusted beta of −17.38, a 95% CI of −33.15 to −1.60, and p = 0.03. However, PUFA supplementation did not statistically alter precuneus lactate levels, with an adjusted beta of 0.01 mmol/L, a 95% CI of −0.02 to 0.04, and p = 0.54.

Observational analyses of maternal baseline EPA and DHA levels measured before randomization demonstrated no statistically significant associations with childhood brain metrics at follow-up. This contrast may reflect the standardized exposure produced by randomized supplementation, which may not have captured variability in a single baseline biomarker measurement, but it does not prove an effect unique to high-dose supplementation.

Furthermore, the researchers found no statistically significant associations between CBF, CMRO₂, or lactate and the assessed cognitive or psychopathological outcomes. Participants' cognitive parameters and psychopathology scores, including attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder, therefore showed no detectable relationship with the metabolic measurements. However, this does not establish independence, and some diagnostic analyses involved few cases.

Finally, the cross-sectional age comparison showed markedly lower CBF, CMRO₂, and lactate values in adults than in 10-year-old children, supporting the interpretation that the supplementation group had a more adult-like metabolic profile. However, this comparison did not confirm individual developmental trajectories or demonstrate greater brain efficiency.

Conclusions

This study is the first, to the authors' knowledge, to directly examine, in a randomized controlled trial, whether maternal supplementation with fish oil-derived n-3 long-chain PUFAs from pregnancy week 24 through one week postpartum alters offspring brain metabolic markers in middle childhood. Although the metabolic measurements were not significantly associated with behavior or cognitive scores at age 10, the findings indicate that randomized prenatal supplementation was associated with differences in two brain metabolic markers detectable approximately 10 years later. However, the effects were relatively small, and the single-center design, a single childhood measurement, global CBF and CMRO₂ measures, a precuneus-only lactate assessment, and reduced complete-case samples relative to the original cohort mean that accelerated maturation and clinical benefit remain unproven.