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.
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.
Results
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.
Conclusion
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.
Source:
https://www.news-medical.net/news/20260719/Fish-oil-supplementation-during-pregnancy-changes-two-childhood-brain-metabolic-markers.aspx