Long-term effects of DHA and/or 5-MTHF supplementation in pregnant women on their offspring´s fatty-acid status, neurodevelopment and behavior

Abstract

The maternal intake of polyunsaturated fatty acids (PUFA) and their metabolism will determine the bioavailability of long-chain polyunsaturated fatty acids (LC-PUFAs) during the first months of life (1). However, the importance of the impact of altered maternal PUFA status on the scheduling and imprinting of PUFA metabolism in the foetus is unknown, and the long-term consequences on the functionality of the metabolic pathways involved in PUFA elongation and desaturation of the PUFAs that allow the endogenous synthesis of LC-PUFAs. The role of the genetic polymorphisms of fatty acid desaturases (FADS) in modulating the conversion of essential fatty acid (EFA) precursors of the n-3 and n-6 series into their consequent derivatives has been highlighted in the last 10 years (2). This may explain the heterogeneity of responses found in various studies on the effect of prenatal PUFA supplementation on growth and neurodevelopment (3-6). Genetic polymorphisms of FADS1, FADS2 and FADS3 (which encode the synthesis of δ5 and δ6 desaturases) have been identified as important determinants of plasma circulating LC-PUFAs (7-10), although due to the significant genetic variation in different populations, there is a lack of evidence of the effects of FADS polymorphisms on the metabolism of LC-PUFAs (11, 12). There has been increasing interest in the study of the fatty acid (FA) concentrations in the cells of the cheek mucosa in recent years, since it is considered that it could be a plausible alternative for following the nutritional status of the LC -PUFAs in early stages of life, thus avoiding blood extraction with the problems that this entails in young children. Currently, there is no information about a possible association between the genetic polymorphisms of FADS1 and FADS2 and the concentrations of these FAs in cheek cells. Moreover, in Europe, saturated FAs and the n-6 series have replaced the intake of n-3 FAs, in a different way in each country. Although the n-6 are also essential for health during growth and development, an appropriate balance is required with respect to n-3 PUFAs. It has been found that relative deficiencies of n-3 PUFAs are associated with a wide range of pathologies in relation to physical and mental health, which pose increasing problems in developed countries. Nutrition plays an important role in the structural and functional growth of the human brain, from conception and during childhood and adolescence to adulthood. There is scientific evidence that early nutrition may influence cognitive development and subsequent behaviour. It is known that an optimal contribution of macro and micronutrients is important for the synthesis of neurotransmitters (and their receptors and transporters), for the renewal and maintenance of the cytoskeleton of axons and myelin sheaths, for the growth of synaptic spines and, therefore, for neuronal plasticity and neuronal survival.