Long-Chain Polyunsaturated Fatty Acids, Homocysteine at Birth and Fatty Acid Desaturase Gene Cluster Polymorphisms are Associated with Children's Processing Speed up to Age 9 Years

Abstract

Both pre- and early postnatal supplementation with docosahexaenoic acid (DHA), arachidonic acid (AA) and folate have been related to neural development, but their long-term effects on later neural function remain unclear. We evaluated the long-term effects of maternal prenatal supplementation with fish-oil (FO), 5-methyltetrahydrofolate (5-MTHF), placebo or FO + 5-MTHF, as well as the role of fatty acid desaturase (FADS) gene cluster polymorphisms, on their offspring's processing speed at later school age. This study was conducted in NUHEAL children at 7.5 (n = 143) and 9 years of age (n = 127). Processing speed tasks were assessed using Symbol Digit Modalities Test (SDMT), Children Color Trails Test (CCTT) and Stroop Color and Word Test (SCWT). Long-chain polyunsaturated fatty acids, folate and total homocysteine (tHcy) levels were determined at delivery from maternal and cord blood samples. FADS and methylenetetrahydrofolate reductase (MTHFR) 677 C > T genetic polymorphisms were analyzed. Mixed models (linear and logistic) were performed. There were significant differences in processing speed performance among children at different ages (p < 0.001). The type of prenatal supplementation had no effect on processing speed in children up to 9 years. Secondary exploratory analyses indicated that children born to mothers with higher AA/DHA ratio at delivery (p < 0.001) and heterozygotes for FADS1 rs174556 (p < 0.05) showed better performance in processing speed at 9 years. Negative associations between processing speed scores and maternal tHcy levels at delivery were found. Our findings suggest speed processing development in children up to 9 years could be related to maternal factors, including AA/DHA and tHcy levels, and their genetic background, mainly FADS polymorphism. These considerations support that maternal prenatal supplementation should be quantitatively adequate and individualized to obtain better brain development and mental performance in the offspring.

Keywords: FADS gene; children; folate; long-chain polyunsaturated fatty acids; neurodevelopment; prenatal supplementation; processing speed.

Figure 1

Flowchart of NUHEAL participants up to 9 years. FO: fish-oil; 5-MTHF: 5-methyltetrahydrofolate. ^a 4 participants who did not meet the inclusion criteria: 2 women weighed > 92 kg, 1 of whom used commercial FO preparations and 2 women regularly consumed FO preparations. ^b 41 participants did not complete the study: noncompliance (n = 2), relocation (n = 1), aversion to or bad taste of the supplement (n = 9), loss of contact (n = 2) and unknown reasons (n = 27). ^c 133 participants lost to follow up at 7.5 years: relocation (n = 3), loss of contact (n = 74), infants born prematurely (n = 4), congenital left-side anophthalmus (n = 1), craniosynostosis (n = 1), left-side deafness (n = 1), unwillingness to continue (n = 50). ^d Processing speed tasks were not entirely performed in 16 participants at 9 years.

Figure 2

Effects of prenatal supplementation on CCTT-1 test in children at 7.5 and 9 years. Level of significance was obtained from one-way ANOVA. * Significant differences between 7.5 years and 9 years were observed in time spent (s) to solve the CCTT-1 test between children whose mothers were supplemented with FO (p = 0.0001), 5-MTHF (p = 0.0113) or both treatments (FO + 5MTHF) (p = 0.038) during pregnancy. 5-MTHF: 5-Methyltetrahydrofolate; CCTT-1: Children´s Color Trails Test; FO: fish-oil.