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.
Highlights
Numerous prenatal environmental exposures including smoking, stress, maternal obesity, and dietary factors have been associated with health and neurodevelopmental outcomes in children (Huizink et al, 2002; Wiebe et al, 2009; Steenweg-de Graaff et al, 2012; Gartstein and Skinner, 2017), with some exposures conferring life-long associations (House et al, 2016; Wyss et al, 2017)
Child behavior can vary by sex; we examined if associations between maternal Mediterranean diet adherence (MDA) and offspring behaviors did so (Supplementary Figure 3)
To test the hypothesis that associations of maternal MDA on offspring behavior are mediated through epigenetic mechanisms and taking into consideration work linking differential methylation control regions of imprinted genes with both offspring behavioral outcomes (Fuemmeler et al, 2016), and maternal diet (Rijlaarsdam et al, 2017), we examined the relationship of diet on CpG methylation of differentially methylated regions (DMRs) regulating nine imprinted genes
Summary
Numerous prenatal environmental exposures including smoking, stress, maternal obesity, and dietary factors have been associated with health and neurodevelopmental outcomes in children (Huizink et al, 2002; Wiebe et al, 2009; Steenweg-de Graaff et al, 2012; Gartstein and Skinner, 2017), with some exposures conferring life-long associations (House et al, 2016; Wyss et al, 2017). Numerous studies suggest that there may be beneficial effects of maternal diet in pregnancy on child neurodevelopment, albeit, again with mixed results (Borge et al, 2017). 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
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