Variants of the FADS1 FADS2 Gene Cluster, Blood Levels of Polyunsaturated Fatty Acids and Eczema in Children within the First 2 Years of Life

Association of genetic-variants in the FADS1-FADS2-gene-cluster with fatty-acid-composition in blood of adult-populations is well established. We analyze this genetic-association in two children-cohort-studies. In addition, the association between variants in the FADS-gene-cluster and blood-fatty-acid-composition with eczema was studied. Data of two population-based-birth-cohorts in The Netherlands and Germany (KOALA, LISA) were pooled (n = 879) and analyzed by (logistic) regression regarding the mutual influence of single-nucleotide-polymorphisms (SNPs) in the FADS-gene-cluster (rs174545, rs174546, rs174556, rs174561, rs3834458), on polyunsaturated fatty acids (PUFA) in blood and parent-reported eczema until the age of 2 years. All SNPs were highly significantly associated with all PUFAs except for alpha-linolenic-acid and eicosapentaenoic-acid, also after correction for multiple-testing. All tested SNPs showed associations with eczema in the LISA-study, but not in the KOALA-study. None of the PUFAs was significantly associated with eczema neither in the pooled nor in the analyses stratified by study-cohort. PUFA-composition in young children's blood is under strong control of the FADS-gene-cluster. Inconsistent results were found for a link between these genetic-variants with eczema. PUFA in blood was not associated with eczema. Thus the hypothesis of an inflammatory-link between PUFA and eczema by the metabolic-pathway of LC-PUFAs as precursors for inflammatory prostaglandins and leukotrienes could not be confirmed by these data

FADS2 Genetic Variance in Combination with Fatty Acid Intake Might Alter Composition of the Fatty Acids in Brain

Multiple lines of evidence suggest that fatty acids (FA) play an important role in cognitive function. However, little is known about the functional genetic pathways involved in cognition. The main goals of this study were to replicate previously reported interaction effects between breast feeding (BF) and FA desaturase (FADS) genetic variation on IQ and to investigate the possible mechanisms by which these variants might moderate BF effect, focusing on brain expression. Using a sample of 534 twins, we observed a trend in the moderation of BF effects on IQ by FADS2 variation. In addition, we made use of publicly available gene expression databases from both humans (193) and mice (93) and showed that FADS2 variants also correlate with FADS1 brain expression (P-value<1.1E-03). Our results provide novel clues for the understanding of the genetic mechanisms regulating FA brain expression and improve the current knowledge of the FADS moderation effect on cognition

Genetic Variants of the FADS Gene Cluster and ELOVL Gene Family, Colostrums LC-PUFA Levels, Breastfeeding, and Child Cognition

Introduction: Breastfeeding effects on cognition are attributed to long-chain polyunsaturated fatty acids (LC-PUFAs), but controversy persists. Genetic variation in fatty acid desaturase (FADS) and elongase (ELOVL) enzymes has been overlooked when studying the effects of LC-PUFAs supply on cognition. We aimed to: 1) to determine whether maternal genetic variants in the FADS cluster and ELOVL genes contribute to differences in LC-PUFA levels in colostrum; 2) to analyze whether these maternal variants are related to child cognition; and 3) to assess whether children's variants modify breastfeeding effects on cognition. Methods: Data come from two population-based birth cohorts (n = 400 mother-child pairs from INMA-Sabadell; and n = 340 children from INMA-Menorca). LC-PUFAs were measured in 270 colostrum samples from INMA-Sabadell. Tag SNPs were genotyped both in mothers and children (13 in the FADS cluster, 6 in ELOVL2, and 7 in ELOVL5). Child cognition was assessed at 14 mo and 4 y using the Bayley Scales of Infant Development and the McCarthy Scales of Children"s Abilities, respectively. Results: Children of mothers carrying genetic variants associated with lower FADS1 activity (regulating AA and EPA synthesis), higher FADS2 activity (regulating DHA synthesis), and with higher EPA/AA and DHA/AA ratios in colostrum showed a significant advantage in cognition at 14 mo (3.5 to 5.3 points). Not being breastfed conferred an 8- to 9-point disadvantage in cognition among children GG homozygote for rs174468 (low FADS1 activity) but not among those with the A allele. Moreover, not being breastfed resulted in a disadvantage in cognition (5 to 8 points) among children CC homozygote for rs2397142 (low ELOVL5 activity), but not among those carrying the G allele. Conclusion: Genetically determined maternal supplies of LC-PUFAs during pregnancy and lactation appear to be crucial for child cognition. Breastfeeding effects on cognition are modified by child genetic variation in fatty acid desaturase and elongase enzymes

Genetic Variants of the FADS Gene Cluster and ELOVL Gene Family, Colostrums LC-PUFA Levels, Breastfeeding, and Child Cognition

Introduction: Breastfeeding effects on cognition are attributed to long-chain polyunsaturated fatty acids (LC-PUFAs), but controversy persists. Genetic variation in fatty acid desaturase (FADS) and elongase (ELOVL) enzymes has been overlooked when studying the effects of LC-PUFAs supply on cognition. We aimed to: 1) to determine whether maternal genetic variants in the FADS cluster and ELOVL genes contribute to differences in LC-PUFA levels in colostrum; 2) to analyze whether these maternal variants are related to child cognition; and 3) to assess whether children's variants modify breastfeeding effects on cognition. Methods: Data come from two population-based birth cohorts (n = 400 mother-child pairs from INMA-Sabadell; and n = 340 children from INMA-Menorca). LC-PUFAs were measured in 270 colostrum samples from INMA-Sabadell. Tag SNPs were genotyped both in mothers and children (13 in the FADS cluster, 6 in ELOVL2, and 7 in ELOVL5). Child cognition was assessed at 14 mo and 4 y using the Bayley Scales of Infant Development and the McCarthy Scales of Children"s Abilities, respectively. Results: Children of mothers carrying genetic variants associated with lower FADS1 activity (regulating AA and EPA synthesis), higher FADS2 activity (regulating DHA synthesis), and with higher EPA/AA and DHA/AA ratios in colostrum showed a significant advantage in cognition at 14 mo (3.5 to 5.3 points). Not being breastfed conferred an 8- to 9-point disadvantage in cognition among children GG homozygote for rs174468 (low FADS1 activity) but not among those with the A allele. Moreover, not being breastfed resulted in a disadvantage in cognition (5 to 8 points) among children CC homozygote for rs2397142 (low ELOVL5 activity), but not among those carrying the G allele. Conclusion: Genetically determined maternal supplies of LC-PUFAs during pregnancy and lactation appear to be crucial for child cognition. Breastfeeding effects on cognition are modified by child genetic variation in fatty acid desaturase and elongase enzymes

Maternal plasma choline and betaine in late pregnancy and child growth up to age 8 years in the KOALA Birth Cohort Study

Background: Sufficient choline and betaine during pregnancy are needed for fetal growth and development.Objectives: We aimed to investigate the associations between maternal plasma choline and betaine in the third trimester of pregnancy and child growth from birth up to 8 years of age.Methods: Concentrations of choline and betaine were measured in plasma of 1331 pregnant women from the KOALA (Kind. Ouders en gezondheid: Aandacht voor Leefstijl en Aanleg) Birth Cohort Study in the Netherlands. Child weight and height were measured at birth and at 1 (91% complete), 2 (86%), and 6-8 y (76%). Birth weight. weight gain in the first year, and z scores for weight and height at 1 and 2 y were used as continuous outcome variables. BMI z scores at 1 and 2 y were used as continuous and dichotomous outcomes, and BMI z scores at age 6-8 y were used to study overweight at that age.Results: Each 1-mu mol/L increase of maternal plasma choline was associated with a mean 20-g (95% CI: 1.1, 38.0 g) higher weight gain in the first year of life, and a higher BMI z score (beta: 0.02; 95% CI: 0.00, 0.04) and slightly higher odds of BMI z score >85th percentile (OR: 1.08; 95% CI: 1.03, 1.10) at 1-2 y. Each 1-mu mol/L increase of plasma betaine was associated with a mean 12-g (95% CI: 0.8, 23.9 g) higher weight gain in the first year of life and higher odds of BMI z score >85th percentile at 1-2 y (OR: 1.03: 95% Cl: 1.00, 1.07). Lastly, betaine was associated with overweight at 6-8 y (OR: 1.17: 95% CI: 1.02, 1.34). only in boys.Conclusions: Third-trimester pregnancy plasma choline and betaine were positively associated with childhood anthropometric measures. In boys, some of the associations may have persisted up to 8 y of age. Further studies may investigate the validity of maternal plasma choline and betaine concentrations as markers of maternal intake and fetal transfer

Effects of prolonged breastfeeding and colostrum fatty acids on allergic manifestations and infections in infancy

In developed countries World Health Organization recommendation of 6 months' exclusive breastfeeding is under debate.We assessed the impact of predominant breastfeeding (PBF) duration and colostrum long-chain polyunsaturated fatty acids (LC-PUFAs) profile on the risk of allergic manifestations (wheezing and atopic eczema) and infections [low respiratory tract infections (LRTIs) and gastroenteritis] in infancy.Information on child feeding practices was obtained from 580 infants of a pregnancy cohort. Presence of infant's health outcomes was documented through questionnaires at 6 and 14?months of age. The LC-PUFAs were measured in colostrum. Adjusted odds ratios (adjOR) and 95% confidence intervals (CI) were estimated using multivariable logistic regression models.In comparison with never breastfeeding, PBF for 4-6?months was associated with lower risk of wheezing (adjOR?=?0.53; 95% CI, 0.32, 0.89), LRTIs (adjOR?=?0.51; 95% CI, 0.31, 0.83) and atopic eczema (adjOR?=?0.58; 95% CI, 0.32, 1.04) between months 7 and 14 of life. Results of a risk period-specific analysis (restricted to infants at risk for outcome onset after 6?months of age), showed no indication for reverse causation (results were not very different compared with an overall analysis). Predominantly breastfeeding for 4-6?months was associated with lower risk of gastroenteritis during the first 6?months of life (adjOR?=?0.34; 95% CI, 0.18, 0.64). Among breastfed infants higher doses of arachidonic acid (AA), docosahexaenoic acid, and total n-3 in were associated with a decreased risk of gastroenteritis, but no association was found for allergic manifestations or LRTI.Promotion of PBF for 4-6?months could reduce the burden of allergic manifestations and infections in infancy. Beneficial effects of breastfeeding on gastroenteritis were explained in part by exposure to higher doses of n-3 and AA received from colostrum. No significant effects from fatty acid dose were found on risk of allergic manifestations or LRTIs.? 2012 Blackwell Publishing Ltd

Fish intake during pregnancy, fetal growth, and gestational length in 19 European birth cohort studies

Background: fish is a rich source of essential nutrients for fetal development, but in contrast, it is also a well-known route of exposure to environmental pollutants.Objective: we assessed whether fish intake during pregnancy is associated with fetal growth and the length of gestation in a panel of European birth cohort studies.Design: the study sample of 151,880 mother-child pairs was derived from 19 population-based European birth cohort studies. Individual data from cohorts were pooled and harmonized. Adjusted cohort-specific effect estimates were combined by using a random- and fixed-effects meta-analysis.Results: women who ate fish &gt;1 time/wk during pregnancy had lower risk of preterm birth than did women who rarely ate fish (?1 time/wk); the adjusted RR of fish intake &gt;1 but &lt;3 times/wk was 0.87 (95% CI: 0.82, 0.92), and for intake ?3 times/wk, the adjusted RR was 0.89 (95% CI: 0.84, 0.96). Women with a higher intake of fish during pregnancy gave birth to neonates with a higher birth weight by 8.9 g (95% CI: 3.3, 14.6 g) for &gt;1 but &lt;3 times/wk and 15.2 g (95% CI: 8.9, 21.5 g) for ?3 times/wk independent of gestational age. The association was greater in smokers and in overweight or obese women. Findings were consistent across cohorts.Conclusion: this large, international study indicates that moderate fish intake during pregnancy is associated with lower risk of preterm birth and a small but significant increase in birth weigh