Fatty Acids in Obese Pregnancies: Maternal and Child Outcomes

Abstract

Maternal obesity has implications on the health of future generations by early life programming. The mother is usually the main source of nutrients for the fetus and neonate, hence her nutritional status is crucial for child development. Fatty acids (FAs), especially long chain polyunsaturated fatty acids (LC-PUFAs), are key nutrients in fetal growth and development. Since these nutrients are known to be altered by conditions such as obesity, maternal obesity could impair fetal/neonatal FA supply, and consequently child outcomes. This thesis presents 4 manuscripts about the influence of maternal pre-pregnancy weight on FA quality and concentrations, along with the implications on maternal and child outcomes. We studied mother-child pairs selected from the total participants in the observational PREOBE cohort study and divided them into 4 groups according to maternal pre-pregnancy body mass index (BMI) and gestational diabetes status; 1) normal-weight, overweight, obese and gestational diabetic. We investigated if FADS and ELOVL genetic variants were associated with pre-pregnancy BMI or affected PUFA levels in plasma of pregnant women. We found that minor allele carriers of FADS1 and FADS2 SNPs had an increased risk for obesity and that the effects of genotype on plasma FA concentrations differed by maternal pre-pregnancy weight status. Enzymatic activity and FA levels were reduced in normal-weight women who were minor allele carriers of FADS SNPs; these reductions were not significant in overweight/obese participants. This suggests that women with a BMI>25 are less affected by FADS genetic variants in this regard. In the presence of FADS2 and ELOVL2 SNPs, overweight/obese women showed higher n-3 LC-PUFA production indexes in plasma than those women in the normal-weight group, but this was not enough to obtain a higher n3 LC-PUFA concentration. We also analyzed the differences in colostrum PUFA composition according to maternal pre-gestational BMI and FADS genotype. A high maternal pre-pregnancy BMI was associated with altered FA levels in colostrum, nevertheless FADS genotypes modulated these results. Minor allele carriers resulted with decreased enzymatic activity and PUFA levels only in normal-weight individuals, making their FA levels similar to those of overweight/obese women. Therefore, FADS genetic variation in overweight/obese women had a different impact, possibly improving their FA status. We also found that dietary intake of DHA in late pregnancy influenced colostrum levels of DHA, thus a high intake of this FA could be a recommendation to improve breast milk composition. Prior to FA analysis in the infants, we validated cheek cells and capillary blood as less invasive alternatives to traditional plasma sampling for FA analysis. We determined the impact of maternal BMI and/or infant feeding practice in infant FA concentrations, and analyzed if these FAs associated with cognitive performance. Maternal pre-pregnancy BMI altered the infant FA behavior in evolution, feeding practice and cognition. In general, FA concentrations decreased towards the 3 years of life, except for the SFAs, n6:n3 and LC-n6:n3 ratios which were increased. Exclusive breastfeeding seemed to rise crucial FAs (e.g. DHA) in infants at 6 months of age, and cognitive performance was found improved in infants with high levels of PUFAs (e.g. DHA, AA) until 1.5 years of age (e.g. n3 PUFAs).

These results are a contribution to the scientific evidence of the importance of a healthy pre-pregnancy weight, and identify groups of women who could benefit from an adequate FA intake to pursue better infant outcomes. We therefore should promote a healthy weight and diet in women before, during and after pregnancy to have beneficial effect in children, and consequently prevent some nutrition-related issues through their life.

La obesidad materna tiene implicaciones en la salud de futuras generaciones debido a la programación fetal. Los ácidos grasos (AGs), especialmente poliinsaturados de cadena larga (AGPICL), intervienen en el crecimiento y desarrollo fetal. Dado a que la obesidad puede alterar la concentración de estos AGs, la salud del feto y neonato se compromete. Esta tesis presenta 4 manuscritos sobre el peso materno pre-gestacional en los AGs y sus implicaciones en madre e hijo. Se incluyeron participantes del estudio observacional PREOBE donde se dividen en 4 grupos según el índice de masa corporal (IMC) materno pre-gestacional y estado de diabetes gestacional; 1)normopeso, 2)sobrepeso, 3) obesidad, 4) diabetes gestacional. Se muestra que el alto peso en las mujeres embarazadas altera el comportamiento de los genotipos de las enzimas que intervienen en el metabolismo de los AGs (FADS y ELOVL) y, consecuentemente, afectan los niveles de AGs tanto en plasma como leche materna. Para examinar el perfil de AGs en el niño, primero se validaron la mucosa bucal y sangre capilar como métodos confiables y menos invasivos que la extracción de plasma. Al analizar los AGs del infante, se determina que el IMC materno pre-gestacional altera los niveles de AGs en el niño y cómo éstos se comportan respecto a la evolución, lactancia y cognición. Los resultados de esta tesis aportan evidencia científica sobre la importancia de un peso materno pre- gestacional adecuado; e identifican grupos de mujeres que pueden verse beneficiadas con una apropiada ingesta de AGs con la finalidad de promover el óptimo desarrollo del niño. Por tanto, se debe promover un peso y una dieta adecuada en las mujeres antes, durante y después del embarazo para beneficiar al niño y, consecuentemente, prevenir condiciones adversas en el curso de vida.