The findings, which drew together analyses on over 4,131 pregnant mothers from the Children of the 90s study in the UK, with similar detailed studies in the Seychelles, are published in NeuroToxicology.
Importantly, the researchers also found that it does not appear to matter which types of fish are eaten because the essential nutrients in the fish could be protective against the mercury content of the fish.
The more important factor was whether the woman ate fish or not. This contrasts with current advice warning pregnant women not to eat certain types of fish that have relatively high levels of mercury.
Although there are several studies that have considered this question, this research has looked at two contrasting studies of populations with mercury levels measured during pregnancy where the children were followed up at frequent intervals during their childhood.
The second study considered analyses of data from the University of Bristol’s Children of the 90s study (also known as the Avon Longitudinal Study of Parents and Children (ALSPAC)), based in a relatively industrialised area in south-west England where fish are consumed far less frequently. No summary of the findings from this study has been published before.
Although it has been known for some time that the children of women who eat fish in pregnancy are likely to benefit in various ways in regard to their eyesight and intellectual abilities, official advice has included the warning not to eat certain types of fish that have relatively high levels of mercury.
As a result, there is the possibility that some women will stop eating any fish ‘to be on the safe side’.
“This could be because of the benefits from the mix of essential nutrients that fish provides, including long-chain fatty acids, iodine, vitamin D and selenium.”
Professor Jean Golding, co-author and Emeritus Professor of Paediatric and Perinatal Epidemiology at the University of Bristol, said: “It is important that advisories from health professionals revise their advice warning against eating certain species of fish.
“There is no evidence of harm from these fish, but there is evidence from different countries that such advice can cause confusion in pregnant women. The guidance for pregnancy should highlight ‘Eat at least two portions of fish a week, one of which should be oily’ – and omit all warnings that certain fish should not be eaten.”
In this population-based birth cohort study, some associations between maternal dietary n-3 PUFA intake during the first trimester of pregnancy and child neuropsychological scores at ages 4 and 7 years were found. The data suggest that the n-3 PUFA intakes in the third trimester of pregnancy seemed to be less related to later child neuropsychological function.
This finding shows a discrepancy with the established hypothesis that most of the n-3 PUFAs are transferred from mother to child in the third pregnancy trimester [8]. Young children’s general cognition, including executive and verbal functions, and children’s attention functioning, were positively associated with maternal intakes of these fatty acids during early pregnancy. However, this fact does not suggest causality in the association, and large randomized clinical trials are needed.
Furthermore, the study results were similar after applying inverse probability corrections for the missing cases. Finally, as expected, maternal social class and education level were the most important confounders in the exposure–outcome associations reported here.
The positive associations found here were also observed in other longitudinal cohort studies based on PUFA intakes (or similar nutrient compounds, such as seafood) during pregnancy and child neuropsychological development. For example, Mendez et al., 2009, in our previous study with 482 pregnant women from Minorca island, found that mothers who consumed two to three servings of fish per week during pregnancy had children with significantly higher scores in neuropsychological tests at 4 years of age, compared to mothers who had less than one serving of fish [31].
In this study, a statistical difference was found in all main McCarthy outcomes (general cognitive, perceptual performance, memory, verbal, numeric, and motor skills). Furthermore, a review paper from Weiser et al., 2016, described several studies about DHA intake during pregnancy and infancy, and showed positive associations similar to those seen in this study, for example, in child cognitive functions related to attention, memory, and verbal scores [9].
This review included a large cohort study report, including one by Hibbeln et al., 2007, who used pregnancy FFQs and child neuropsychological outcomes up until 8 years of age, and who discovered an association between a low intake of seafood, defined as less than 340 g per week during the third trimester of pregnancy, and an increased risk of suboptimal neuropsychological outcomes, affecting verbal function, fine motor, and social development scores [32].
These studies did not estimate the PUFA intake from FFQ, and used primary source compounds, such as fish intake, and neither assessed the exposure (PUFA intake) several times during pregnancy. Furthermore, there are a few randomized trials exploring the effect of pregnancy PUFA intake on later child neuropsychological development with positive results [8]. For example, in a randomized double-blinded clinical trial including 590 pregnant women, led by Helland in 2003, it was reported that daily n-3 PUFA supplementation during pregnancy had greater effects on mental processing outcomes at 4 years of age [33], which may be a similar outcome to our study’s ANT–HRT-SE assessed at 8 years of age.
In relation to the neuropsychological outcomes mostly related to maternal n-3 PUFA intake, it is interesting to see that executive and attention functions were highly associated. These functions are involved in the optimal prefrontal cortex development, the section of the brain that performs several complex cognitive functions, including the functions assessed in this study [34]. This brain area may need high amounts of n-3 PUFA during development due to the complexity of its synaptic connections.
Therefore, a mother’s n-3 PUFA intake during pregnancy may be vital for optimal long-term neuropsychological outcomes for the child. There are biological pathways facilitating the transfer between the mother and the offspring during pregnancy. One study from Koletzko et al., 2007, demonstrated an active and preferential maternal–foetal transfer of DHA across the human placenta, and that this pathway was a mechanism for the expression of human placental fatty acid binding and transport proteins [35].
Our results may be partly explained by this active transfer process of n-3 PUFAs from mother to foetus, and by the metabolic pathways involved, which are essential for the rapid cellular uptake of the n-3 PUFAs. Thus, both biological mechanisms may affect neurodevelopment during foetal growth [7,8,9,13]. For example, in our recent study conducted with this cohort (Julvez et al., 2020), we demonstrated the importance of some single nucleotide polymorphism (SNP) metabolizers of n-3 PUFAs, present in relation to maternal seafood intake, and later child attention function [36]. We further described stronger associations between early pregnancy n-3 PUFA intake and child neuropsychological development. We would have expected stronger associations at the end of the pregnancy, due to the fact that, in this period, neuron dendritic growth and myelination are highly activated [8].
However, the complexity of human brain growth during the entire gestational period and the related long-term behavioural consequences are difficult to assess. This fact requires more scientific work and a deeper analysis of the potential biological mechanisms. These finding needs to be confirmed in other epidemiological studies and further investigated in experimental studies, particularly in experiments focusing on the human brain development.
The main strengths of this study include its longitudinal cohort study design, with a large sample size from different regions of Spain, where all of the cohorts used common assessment protocols. The data in this study were collected prospectively and with standardized and valid methods and instruments regarding the exposure variables, covariates, and neuropsychological outcomes. For example, the neuropsychological assessments used validated and standardized tests, and the psychologists involved in the study underwent training and followed quality controls. The study also applied several statistical analyses in order to verify that the associations reported were independent to the main confounders, and also that the associations were not biased due to missing data.
The study design is not without limitations. Firstly, self-reported data from FFQ are subject to measurement errors and recall bias. The accuracy of the FFQ relies on the subject, which poses risks relating to the true representation of intake, leading to underestimation or overestimation. Furthermore, the conversion of results from the FFQ to nutrients are estimates at risk for variances, especially for foods with limited nutritional information, such as ready-to-eat meals prepared outside the home.
Secondly, although a lot of covariate information was available, the study lacked dietary and supplementary information and biomarkers of n-3 PUFA intake during lactation, which may have been relevant for analysis. Additionally, although confounding factors, based on a literature review and a DAG model, were reviewed during data analysis, there is still a risk of potential residual confounders due to the observational nature of the study, causing potential bias in the study. Furthermore, the data showing the important confounding effect of maternal social class are indicative of this risk of potential residual confounding due to socially advantageous families.
Furthermore, complete information for those that were lost or opted out are not available from all cohorts, creating possible selection bias. Nevertheless, we applied inverse probably weighting corrections in our study, with no changes observed in the main findings. However, some cohorts had certain information, such as low socioeconomic status, that were more prevalent amongst non-participants [17], and this has to be taken into consideration if results are generalized to the general population.
A slight correlation between omega-3 PUFA intakes during the third trimester of pregnancy and cord blood omega-3 fatty acid concentration was observed in a subsample, and this low biomarker correlation is usually observed in this type of exposure based on FFQs [20,21], and plasma PUFA biomarkers are used to indicate short-term—about a few weeks—PUFA consumption [20]. Furthermore, a few women (5%) reported using omega-3 supplements during pregnancy, and we treated this as a separate variable, but we observed no influence in the present results. Finally, the clinical interpretation of the findings is limited by the fact that the associations were modest, since only a few test scores (MCSA points or ANT–HRT-SE milliseconds) separated the differences between exposure groups.
Overall, this study found that higher maternal n-3 PUFA intake during the first trimester of pregnancy was associated with improved scores in some child neuropsychological outcomes at 4 years and 7 years of age. The associations were only found in maternal n-3 PUFA intake during the first pregnancy trimester compared with the third trimester period. Given the large number of potential covariates, the temporal distance between exposure and outcome, and the non-clinical significance of the associations found, this research topic needs more longitudinal cohort studies to continue exploring these associations, plus clinical and experimental studies to further explain the biological pathways of n-3 PUFAs during pregnancy and their potential role in child neuropsychological development.
reference link : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8838693/
Original Research: Open access.
“The benefits of fish intake: Results concerning prenatal mercury exposure and child outcomes from the ALSPAC prebirth cohort” by Caroline Taylor et al. NeuroToxicology
