[Controversy about the critical role of long-chain polyunsaturated fatty acids, arachidonic acid (ARA) and docosahexaenoic acid (DHA), during infancy]. / Controversia actual sobre el papel crítico de los ácidos grasos poliinsaturados de cadena larga, araquidónico (ARA) y docosahexaenoico (DHA), en el lactante.

INTRODUCTION: Long-chain polyunsaturated fatty acids (LC-PUFAs) are critical for infant growth and development, particularly arachidonic acid (ARA, C20:4n-6) and docosahexaenoic acid (DHA, C22:6n-3). ARA and DHA are components of cell membrane phospholipids and play an important role in cell division, differentiation, and signaling; and DHA is the n-3 fatty acid predominant in the developing brain and retina. During the third trimester of pregnancy, LC-PUFAs increase substantially in fetal circulation, and a "biomagnification" process in the fetal brain is observed. Moreover, LC-PUFAs are precursors of eicosanoids and metabolites, which modulate the intensity and duration of the immune response. LC-PUFA synthesis implies complex desaturation and elongation processes on their principal precursors, linoleic acid (LA) (18:3 n-6) (series n-6) and α-linolenic acid (LNA) (20:3 n-3) (series n-3), where fatty acid desaturases (FADS) and elongases (ELOVL) are competing. It is important to notice that during the first months of life, as a consequence of low enzymatic activity, LC-PUFA synthesis from LA and LNA is reduced, especially in those infants carrying variations in the FADS and ELOVL genes, which are involved in LC-PUFA synthesis, and so they are unable to supply their own DHA and ARA needs. Homozygote infants for FADS haplotype A (97 % of the Latinoamerican population) show low levels of ARA (only 43 %) and DHA (only 24 %) when compared to those carrying haplotype D (more prevalent in Europe, Africa and Asia). Human milk is the only source of LA, LNA, ARA, and DHA for the neonate and infant till complementary feeding (CF) is introduced. Infants fed with infant formulas must receive enough amounts of LA, LNA, ARA, and DHA to cover their nutritional requirements. The new guidelines by the European Food Safety Authority (EFSA) (2016) recommend that infant formulas and follow-on formulas must contain 20-50 mg of DHA/100 kcal (0.5-1 % of total fatty acids, which is higher than in human milk and the majority of infant formulas in the market), and it is not necessary to add ARA. This new regulation, which is already applicable since February 2020, has resulted in profound controversy because there is no scientific evidence about its appropriateness and safety for healthy children. Then, different international expert groups have revised the research already published about the effects of ARA and DHA addition to infant formulas, and discussed different emerging questions from this European directive. The expert group led from the University of Granada (Spain) recommends the addition of ARA in similar or higher concentrations than those of DHA, at least equal to those present in human milk (0.3 % of total fatty acids), although preferably 0.5 % and up to around 0.64 % of total fatty acids, since new studies confirm the optimal intake of ARA and DHA during the different developmental stages. This recommendation could be of particular importance for infants carrying the haplotype A of FADS.

INTRODUCCIÓN: Los ácidos grasos poliinsaturados de cadena larga (AGPI-CL) son críticos para el crecimiento y desarrollo infantil, en particular los ácidos araquidónico (ARA, C20:4n-6) y docosahexaenoico (DHA, C22:6n-3). El ARA y el DHA son componentes de los fosfolípidos de las membranas celulares y desempeñan importantes funciones en la división, diferenciación y señalización celular, siendo el DHA el ácido graso de la serie n-3 predominante en el cerebro y la retina en desarrollo. Durante el tercer trimestre de la gestación, los AGPI-CL aumentan de forma sustancial en la circulación fetal, observándose un proceso de "biomagnificación" en el cerebro fetal. Además, los AGPI-CL son precursores de los eicosanoides y metabolitos implicados en la modulación de la intensidad y duración de la respuesta inmunitaria. La síntesis de AGPI-CL implica un complejo proceso de desaturación y elongación desde los precursores principales, el ácido linoleico (18:3 n-6) (LA) (serie n-6) y el ácido α-linolénico (20:3 n-3) (LNA) (serie n-3), por los cuales compiten las enzimas desaturasas (FADS) y elongasas (ELOVL). Es importante indicar que en los primeros meses de vida, como consecuencia de la baja actividad enzimática, la síntesis de AGPI-CL a partir de LA y LNA es reducida, especialmente en los niños con variaciones en los genes que codifican las FADS y ELOVL involucradas en la síntesis de AGPI-CL y que, por tanto, son incapaces de cubrir por sí mismos sus necesidades de ARA y DHA. Los homocigotos para el haplotipo A de las FADS (97 % de la población latinoamericana) muestran niveles de ARA y DHA de tan solo un 43 % y un 24 %, respectivamente, inferiores a los de los individuos con haplotipo D (más frecuente en Europa, África y Asia). La leche humana constituye la única fuente de LA, LNA, ARA y DHA para el recién nacido y el lactante hasta la introducción de la alimentación complementaria (AC). Los niños alimentados con fórmulas infantiles deben recibir las cantidades de LA, LNA, ARA y DHA suficientes para cubrir los requerimientos nutricionales. La nueva normativa de la Autoridad Europea de Seguridad Alimentaria (EFSA) (2016) indica que las fórmulas infantiles de inicio y continuación deben contener entre 20 y 50 mg de DHA/100 kcal (0,5-1 % del total de ácidos grasos: más elevado que en la leche humana y en la mayoría de fórmulas infantiles comercializadas) sin la necesidad de incluir también ARA. Esta nueva regulación, que está vigente desde febrero de 2020, ha despertado una gran controversia, al no existir evidencia científica acerca de su pertinencia y seguridad para los niños sanos. Por ello, diferentes grupos de expertos internacionales han revisado la investigación publicada acerca del ARA y el DHA, y discutido diferentes cuestiones emergentes a partir de esta nueva directiva Europea. El grupo de expertos, liderado desde la Universidad de Granada (España), recomienda la adición de ARA en concentraciones iguales o mayores que las de DHA, alcanzando al menos el contenido presente en la leche humana (0,3 % del total de ácidos grasos), aunque preferiblemente un 0,5 % y hasta alrededor del 0,64 % del total de AG, hasta que nuevos estudios confirmen la ingesta óptima de ARA y DHA durante las distintas etapas del desarrollo. Esta recomendación podría ser de especial importancia para los niños portadores del haplotipo A de las FADS.

The Effect of Maternal Obesity on Breast Milk Fatty Acids and Its Association with Infant Growth and Cognition-The PREOBE Follow-Up.

This study analyzed how maternal obesity affected fatty acids (FAs) in breast milk and their association with infant growth and cognition to raise awareness about the programming effect of maternal health and to promote a healthy prenatal weight. Mother-child pairs (n = 78) were grouped per maternal pre-pregnancy body mass index (BMI): normal-weight (BMI = 18.5-24.99), overweight (BMI = 25-29.99) and obese (BMI > 30). Colostrum and mature milk FAs were determined. Infant anthropometry at 6, 18 and 36 months of age and cognition at 18 were analyzed. Mature milk exhibited lower arachidonic acid (AA) and docosahexaenoic acid (DHA), among others, than colostrum. Breast milk of non-normal weight mothers presented increased saturated FAs and n6:n3 ratio and decreased α-linolenic acid (ALA), DHA and monounsaturated FAs. Infant BMI-for-age at 6 months of age was inversely associated with colostrum n6 (e.g., AA) and n3 (e.g., DHA) FAs and positively associated with n6:n3 ratio. Depending on the maternal weight, infant cognition was positively influenced by breast milk linoleic acid, n6 PUFAs, ALA, DHA and n3 LC-PUFAs, and negatively affected by n6:n3 ratio. In conclusion, this study shows that maternal pre-pregnancy BMI can influence breast milk FAs and infant growth and cognition, endorsing the importance of a healthy weight in future generations.

The Effect of an Infant Formula Supplemented with AA and DHA on Fatty Acid Levels of Infants with Different FADS Genotypes: The COGNIS Study.

Polymorphisms in the fatty acid desaturase (FADS) genes influence the arachidonic (AA) and docosahexaenoic (DHA) acid concentrations (crucial in early life). Infants with specific genotypes may require different amounts of these fatty acids (FAs) to maintain an adequate status. The aim of this study was to determine the effect of an infant formula supplemented with AA and DHA on FAs of infants with different FADS genotypes. In total, 176 infants from the COGNIS study were randomly allocated to the Standard Formula (SF; n = 61) or the Experimental Formula (EF; n = 70) group, the latter supplemented with AA and DHA. Breastfed infants were added as a reference group (BF; n = 45). FAs and FADS polymorphisms were analyzed from cheek cells collected at 3 months of age. FADS minor allele carriership in formula fed infants, especially those supplemented, was associated with a declined desaturase activity and lower AA and DHA levels. Breastfed infants were not affected, possibly to the high content of AA and DHA in breast milk. The supplementation increased AA and DHA levels, but mostly in major allele carriers. In conclusion, infant FADS genotype could contribute to narrow the gap of AA and DHA concentrations between breastfed and formula fed infants.