Periconceptional Maternal Mediterranean Diet Is Associated With Favorable Offspring Behaviors and Altered CpG Methylation of Imprinted Genes

Abstract

Background: Maternal diet during pregnancy has been shown to influence the child neuro-developmental outcomes. Studies examining effects of dietary patterns on offspring behavior are sparse.Objective: Determine if maternal adherence to a Mediterranean diet is associated with child behavioral outcomes assessed early in life, and to evaluate the role of differentially methylated regions (DMRs) regulating genomically imprinted genes in these associations.Methods: Among 325 mother/infant pairs, we used regression models to evaluate the association between tertiles of maternal periconceptional Mediterranean diet adherence (MDA) scores derived from a Food Frequency Questionnaire, and social and emotional scores derived from the Infant Toddler Social and Emotional Assessment (ITSEA) questionnaire in the second year of life. Methylation of nine genomically imprinted genes was measured to determine if MDA was associated with CpG methylation.Results: Child depression was inversely associated with maternal MDA (Bonferroni-corrected p = 0.041). While controlling for false-discovery, compared to offspring of women with the lowest MDA tertile, those with MDA scores in middle and high MDA tertiles had decreased odds for atypical behaviors [OR (95% CI) = 0.40 (0.20, 0.78) for middle and 0.40 (0.17, 0.92) for highest tertile], for maladaptive behaviors [0.37 (0.18, 0.72) for middle tertile and 0.42 (0.18, 0.95) for highest tertile] and for an index of autism spectrum disorder behaviors [0.46 (0.23, 0.90) for middle and 0.35 (0.15, 0.80) for highest tertile]. Offspring of women with the highest MDA tertile were less likely to exhibit depressive [OR = 0.28 (0.12, 0.64)] and anxiety [0.42 (0.18, 0.97)] behaviors and increased odds of social relatedness [2.31 (1.04, 5.19)] behaviors when compared to low MDA mothers. Some associations varied by sex. Perinatal MDA score was associated with methylation differences for imprinted control regions of PEG10/SGCE [females: Beta (95% CI) = 1.66 (0.52, 2.80) – Bonferroni-corrected p = 0.048; males: -0.56 (-1.13, -0.00)], as well as both MEG3 and IGF2 in males [0.97 (0.00, 1.94)] and -0.92 (-1.65, -0.19) respectively.Conclusion: In this ethnically diverse cohort, maternal adherence to a Mediterranean diet in early pregnancy was associated with favorable neurobehavioral outcomes in early childhood and with sex-dependent methylation differences of MEG3, IGF2, and SGCE/PEG10 DMRs.

The Impact of Nutrition and Environmental Epigenetics on Human Health and Disease

“…In relation to breast cancer, one study demonstrated that dietary patterns affect the mammary gland microbiome, establishing an alternative mechanistic pathway for breast cancer prevention [ 49 ]. The impact of maternal Mediterranean diet adherence during pregnancy on offspring behaviors has also been investigated, and maternal adherence to a Mediterranean diet in early pregnancy is associated with positive neurobehavioral outcomes in early childhood and with sex-dependent methylation differences in the control regions of imprinted genes [ 50 ]. Figure 1 summarizes how diet affects the epigenome to modify individual and transgenerational phenotypes.…”

Maternal Dietary Factors and the Risk of Autism Spectrum Disorders: A Systematic Review of Existing Evidence

“…M. Li et al, 2018;Schmidt et al, 2011Schmidt et al, , 2012Schmidt et al, , 2014Schmidt, Niu, et al, 2019;Tan et al, 2020;Whitehouse et al, 2013]. Finally, while a number of studies considered certain other dietary factors that may influence associations in their analyses [Braun et al, 2014;Chen et al, 2016;House et al, 2018;Huang et al, 2020;Julvez et al, 2016;Y. M. Li et al, 2018;Lyall et al, 2013;Schmidt et al, 2011Schmidt et al, , 2012Schmidt et al, , 2014Steenweg-de Graaff et al, 2016;Vecchione et al, 2020], the majority of studies included in this review did not(discussed below).…”

“…We identified three studies evaluating associations between combined dietary factors or dietary patterns and ASD [L. Gao, Cui, et al, 2016;House et al, 2018;Y. M. Li et al, 2018].…”

Mediterrane Diät vor und während der Schwangerschaft

“…Eine US-amerikanische Studie zeigte, dass ein höherer Score der mütterlichen MD mit einer niedrigeren Wahr-scheinlichkeit (Odds Ratio, OR) für Depressionen, Angstzustände, Anpassungsstörungen und Autismus bei Kindern im Alter von 12-24 Monaten (Durchschnitt 13,9 Monaten) assoziiert ist [8]. Die DNA-Methylierung mehrerer Gene (z.…”

“…Die DNA-Methylierung mehrerer Gene (z. B. IGF2) im Nabelschnurblut der Neugeborenen war mit der Einhaltung der MD bei der Mutter assoziiert und der Zusammenhang variierte zwischen weiblichen und männlichen Neugeborenen [8].…”