Plasma Sphingomyelins and Carnitine Esters of Infants Consuming Whole Goat or Cow Milk-Based Infant Formulas or Human Milk.

BACKGROUND: Infant formulas are typically manufactured using skimmed milk, whey proteins, and vegetable oils, which excludes milk fat globule membranes (MFGM). MFGM contains polar lipids, including sphingomyelin (SM). OBJECTIVE: The objective of this study was comparison of infant plasma SM and acylcarnitine species between infants who are breastfed or receiving infant formulas with different fat sources. METHODS: In this explorative study, we focused on SM and acylcarnitine species concentrations measured in plasma samples from the TIGGA study (ACTRN12608000047392), where infants were randomly assigned to receive either a cow milk-based infant formula (CIF) with vegetable oils only or a goat milk-based infant formula (GIF) with a goat milk fat (including MFGM) and vegetable oil mixture to the age ≥4 mo. Breastfed infants were followed as a reference group. Using tandem mass spectrometry, SM species in the study formulas and SM and acylcarnitine species in plasma samples collected at the age of 4 mo were analyzed. RESULTS: Total SM concentrations (∼42 µmol/L) and patterns of SM species were similar in both formulas. The total plasma SM concentrations were not different between the formula groups but were 15 % (CIF) and 21% (GIF) lower in the formula groups than in the breastfed group. Between the formula groups, differences in SM species were statistically significant but small. Total carnitine and major (acyl) carnitine species were not different between the groups. CONCLUSIONS: The higher total SM concentration in breastfed than in formula-fed infants might be related to a higher SM content in human milk, differences in cholesterol metabolism, dietary fatty acid intake, or other factors not yet identified. SM and acylcarnitine species composition in plasma is not closely related to the formula fatty acid composition. This trial was registered at Australian New Zealand Clinical Trials Registry as ACTRN12608000047392.

Maternal and Offspring Fatty Acid Desaturase Variants, Prenatal DHA Supplementation, and Dietary n-6:n-3 Fatty Acid Ratio in Relation to Cardiometabolic Health in Mexican Children.

BACKGROUND: Single-nucleotide polymorphisms (SNPs) in fatty acid desaturase (FADS) genes may modify dietary fatty acid requirements and influence cardiometabolic health (CMH). OBJECTIVES: We evaluated the role of selected variants in maternal and offspring FADS genes on offspring CMH at the age of 11 y and assessed interactions of genotype with diet quality and prenatal docosahexaenoic acid (DHA) supplementation. METHODS: We used data from offspring (n = 203) born to females who participated in a randomized controlled trial of DHA supplementation (400 mg/d) from midgestation to delivery. We generated a metabolic syndrome (MetS) score from body mass index, high-density lipoprotein cholesterol, triglycerides, systolic blood pressure, and fasting glucose and identified 6 distinct haplotypes from 5 offspring FADS SNPs. Dietary n-6 (ω-6):n-3 fatty acid ratios were derived from 24-h recall data (n = 141). We used generalized linear models to test associations of offspring diet and FADS haplotypes with MetS score and interactions of maternal and offspring FADS SNP rs174602 with prenatal treatment group and dietary n-6:n-3 ratio on MetS score. RESULTS: Associations between FADS haplotypes and MetS score were null. Offspring SNP rs174602 did not modify the association of prenatal DHA supplementation with MetS score. Among children with TT or TC genotype for SNP rs174602 (n = 88), those in the highest n-6:n-3 ratio tertile (>8.61) had higher MetS score relative to the lowest tertile [<6.67) (Δ= 0.36; 95% confidence interval (CI): 0.03, 0.69]. Among children with CC genotype (n = 53), those in the highest n-6:n-3 ratio tertile had a lower MetS score relative to the lowest tertile (Δ= -0.23; 95% CI: -0.61, 0.16). CONCLUSIONS: There was evidence of an interaction of offspring FADS SNP rs174602 with current dietary polyunsaturated fatty acid intake, but not with prenatal DHA supplementation, on MetS score. Further studies may help to determine the utility of targeted supplementation strategies and dietary recommendations based on genetic profile.

Detailed knowledge of maternal and infant factors and human milk composition could inform recommendations for optimal composition.

Breastfeeding is best for infants, but quantitative associations between specific milk components and infant biomarkers remain unclear. Methodological limitations include missing milk volume intake, variable milk composition and that standardised, fasted state blood sampling is impossible in infants. Milk protein and fat content appear marginally related to infant serum amino acid and phospholipid concentrations, with some association between milk fatty acid composition and lipid species levels. CONCLUSION: Detailed simultaneous examinations of maternal factors, milk composition and infant biomarkers or outcomes could identify the mechanistic basis of human milk effects and help develop dietary recommendations for optimal human milk composition.

Infant Metabolome in Relation to Prenatal DHA Supplementation and Maternal Single-Nucleotide Polymorphism rs174602: Secondary Analysis of a Randomized Controlled Trial in Mexico.

BACKGROUND: Although DHA (22:6n-3) is critical for fetal development, results from randomized controlled trials (RCTs) of prenatal DHA supplementation report inconsistent effects on offspring health. Variants in fatty acid desaturase (FADS) genes that regulate the conversion of n-3 and n-6 essential fatty acids into their biologically active derivatives may explain this heterogeneity. OBJECTIVES: We investigated the effect of prenatal DHA supplementation on the offspring metabolome at age 3 mo and explored differences by maternal FADS single-nucleotide polymorphism (SNP) rs174602. METHODS: Data were obtained from a double-blind RCT in Mexico [POSGRAD (Prenatal Omega-3 Fatty Acid Supplementation and Child Growth and Development)] in which women (18-35 y old) received DHA (400 mg/d) or placebo from mid-gestation until delivery. Using high-resolution MS with LC, untargeted metabolomics was performed on 112 offspring plasma samples. Discriminatory metabolic features were selected via linear regression (P < 0.05) with false discovery rate (FDR) correction (q = 0.2). Interaction by SNP rs174602 was assessed using 2-factor ANOVA. Stratified analyses were performed, where the study population was grouped into carriers (TT, TC; n = 70) and noncarriers (CC; n = 42) of the minor allele. Pathway enrichment analysis was performed with Mummichog (P < 0.05). RESULTS: After FDR correction, there were no differences in metabolic features between infants whose mothers received prenatal DHA (n = 58) and those whose mothers received placebo (n = 54). However, we identified 343 differentially expressed features in the interaction analysis after FDR correction. DHA supplementation positively enriched amino acid and aminosugars metabolism pathways and decreased fatty acid metabolism pathways among offspring of minor allele carriers and decreased metabolites within the tricarboxylic acid cycle and galactose metabolism pathways among offspring of noncarriers. CONCLUSIONS: Our findings demonstrate differences in infant metabolism in response to prenatal DHA supplementation by maternal SNP rs174602 and further support the need to incorporate genetic analysis of FADS polymorphisms into DHA supplementation trials.This trial was registered at clinicaltrials.gov as NCT00646360.

FADS1 and FADS2 Polymorphisms Modulate Fatty Acid Metabolism and Dietary Impact on Health.

Variants in the FADS gene cluster modify the activity of polyunsaturated fatty acid (PUFA) desaturation and the lipid composition in human blood and tissue. FADS variants have been associated with plasma lipid concentrations, risk of cardiovascular diseases, overweight, eczema, pregnancy outcomes, and cognitive function. Studies on variations in the FADS genecluster provided some of the first examples for marked gene-diet interactions in modulating complex phenotypes, such as eczema, asthma, and cognition. Genotype distribution differs markedly among ethnicities, apparently reflecting an evolutionary advantage of genotypes enabling active long-chain PUFA synthesis when the introduction of agriculture provided diets rich in linoleic acid but with little arachidonic and eicosapentaenoic acids. Discovering differential effects of PUFA supply that depend on variation of FADS genotypes could open new opportunities for developing precision nutrition strategies based either on an individual's genotype or on genotype distributions in specific populations.

In vivo kinetic study of materno-fetal fatty acid transfer in obese and normal weight pregnant women.

KEY POINTS: Placental structure and function can be modified as a result of maternal obesity affecting materno-fetal fatty acids (FA) transport. We report for the first time, in humans and in vivo, the kinetics of placental FA transfer in normo-weight and in normolipemic obese pregnant women using stable isotopes. The administration of different tracer FA with similar behaviour to the mother at different time points allows the collection of kinetic information on materno-fetal transfer of FA despite only one sample of placenta and cord can be collected per subject. Computational modelling showed a good fit to the data when considering all maternal plasma lipid classes but not when based only on non-esterified FA. The novel approach using multiple tracer FA administration combined with computational modelling shows a consistent time course of placental tracer FA and predicted total FA accumulation. ABSTRACT: We analyse for the first time the in vivo materno-fetal kinetic transfer of fatty acids (FA) labelled with stable isotopes in control and obese (OB) pregnant women. Labelled FA with a similar metabolism (stearic acid: 13 C-SA; palmitic acid: 13 C-PA; oleic acid: 13 C-OA) were orally administered at -4 h, -8 h and -12 h, respectively prior to elective caesarean section to 10 pregnant women with a body mass index >30 (OB) and 10 with a body mass index in the range 20-25 (NW). Placenta, venous and arterial cord blood were collected obtaining a wide range of FA enrichments. A combined experimental and computational modelling analysis was applied. FA fractional synthesis rate (FSR) in placenta was 11-12% h-1 . No differences were observed between NW and normo-lipidemic OB. It was not possible to estimate FA FSR in cord blood with this oral bolus dose approach. Computational modelling demonstrated a good fit to the data when all maternal plasma lipid classes were included but not with modelling based only on the non-esterified FA fraction. The estimated materno-fetal 13 C-FA transfer was ∼1%. In conclusion, our approach using multiple 13 C-FA tracers allowed us to estimated FSR in placental/maternal plasma but not in fetal/maternal compartments. Computational modelling showed a consistent time course of placental 13 C-FA transfer and predicted total fetal FA accumulation during the experiment. We conclude that, in addition to non-esterified FA fraction in the maternal circulation, maternal plasma very low-density lipoprotein and other lipoproteins are important contributors to placental FA transfer to the fetus.

Early nutrition in combination with polymorphisms in fatty acid desaturase gene cluster modulate fatty acid composition of cheek cells' glycerophospholipids in school-age children.

Variants in the human genes of fatty acid (FA) desaturase 1 (FADS1), 2 (FADS2) and 3 (FADS3) are associated with PUFA blood levels. We explored if maternal prenatal supplementation and children's genetic variation in seventeen SNP of the FADS1, FADS2 and FADS3 gene cluster influence twenty-one of the most relevant cheek cells' derived FA in glycerophospholipids (GPL-FA). The study was conducted in 147 Spanish and German mother-children pairs participating in the Nutraceuticals for a Healthier Life (NUHEAL) study at 8, 9 and 9·5 years. Linear and mixed model longitudinal regression analyses were performed. Maternal fish-oil (FO) or FO+5-methyltetrahydrofolate (5-MTHF) supplementation during pregnancy was associated with a significant decrease of arachidonic acid (AA) concentrations in cheek cell GPL in the offspring, from 8 to 9·5 years; furthermore, maternal FO+5-MTHF supplementation was associated with higher n-6 docosapentaenoic acid concentrations in their children at age 8 years. FADS1 rs174556 polymorphism and different FADS2 genotypes were associated with higher concentrations of linoleic and α-linolenic acids in children; moreover, some FADS2 genotypes determined lower AA concentrations in children's cheek cells. It is suggested an interaction between type of prenatal supplementation and the offspring genetic background driving GPL-FA levels at school age. Prenatal FO supplementation, and/or with 5-MTHF, seems to stimulate n-3 and n-6 FA desaturation in the offspring, increasing long-chain PUFA concentrations at school age, but depending on children's FADS1 and FADS2 genotypes. These findings suggest potential early nutrition programming of FA metabolic pathways, but interacting with children's FADS polymorphisms.

Phospholipids in lipoproteins: compositional differences across VLDL, LDL, and HDL in pregnant women.

OBJECTIVE: The aim of this study was to analyse the differences in the phospholipid composition of very low density (VLDL), low density (LDL) and high density lipoprotein (HDL) monolayers in pregnant lean and obese women. METHODS: LDL, HDL, and VLDL were isolated from plasma samples of 10 lean and 10 obese pregnant women, and their species composition of phosphatidylcholines (PC) and sphingomyelins (SM) was analysed by liquid-chromatography tandem mass-spectrometry. Wilcoxon-Mann-Whitney U test and principal component analysis (PCA) were used to investigate if metabolite profiles differed between the lean/obese group and between lipoprotein species. RESULTS: No significant differences have been found in the metabolite levels between obese and non-obese pregnant women. The PCA components 1 and 2 separated between LDL, HDL, and VLDL but not between normal weight and obese women. Twelve SM and one PCae were more abundant in LDL than in VLDL. In contrast, four acyl-alkyl-PC and two diacyl-PC were significantly higher in HDL compared to LDL. VLDL and HDL differed in three SM, seven acyl-alkyl-PC and one diacyl-PC (higher values in HDL) and 13 SM (higher in VLDL). We also found associations of some phospholipid species with HDL and LDL cholesterol. CONCLUSION: In pregnant women phospholipid composition differs significantly in HDL, LDL and VLDL, similar to previous findings in men and non-pregnant women. Obese and lean pregnant women showed no significant differences in their lipoprotein associated metabolite profile.

Fatty fish intake and cognitive function: FINS-KIDS, a randomized controlled trial in preschool children.

BACKGROUND: Marine resources including fatty fish are important sources of n-3 long chain polyunsaturated fatty acids (n-3 LC-PUFAs), which are important for brain development. To our knowledge, this is the first randomized controlled trial (RCT) investigating the impact of fatty fish on cognition in preschool children. The purpose of the trial was to investigate whether an increased intake of fatty fish compared to meat improves cognitive function in children 4-6 years old. METHODS: The children (n = 232) in this two-armed RCT, Fish Intervention Studies-KIDS (FINS-KIDS) were recruited from 13 kindergartens in Bergen, Norway. They were randomly assigned to lunch meals with fatty fish (herring/mackerel) or meat (chicken/lamb/beef) three times a week for 16 weeks. The fish and meat were weighed before and after the meals to record the exact consumption (dietary compliance). The primary outcome was cognitive function measured by the Wechsler Preschool and Primary Scale of Intelligence, 3rd edition (WPPSI-III) and fine-motor coordination measured by the 9-Hole Peg Test (9-HPT) at pre- and post-intervention. Biological samples (blood, urine, hair), and questionnaires to the caregivers were included at both time points. Linear mixed effect models with a random intercept for kindergarten were used to analyze changes from pre- to post-intervention in the primary outcome variables. RESULTS: There were 218 children included in the trial (105 in the fish, and 113 in the meat group). The children consumed a mean (standard deviation) of 2070 (978) g fish or 2675 (850) g meat from the study meals (p < 0.0001). The fish group had a significant increase of red blood cell n-3 LC-PUFAs. The intervention had no effect on the WPPSI-III scores (mean change total raw score; fish group 17.7, 95% confidence interval (CI) 14.8-20.7 vs meat group 17.8, 95% CI 15.0-20.6, p = 0.97) in the main analyses. In the sub-analyses, adjusting for dietary compliance, the fish group showed a higher improvement on total raw score (20.4, 95% CI 17.5-23.3) compared to the meat group (15.2, 95% CI 12.4-18.0, p = 0.0060); docosahexaenoic acid mediated this effect. CONCLUSIONS: There was no beneficial effect of fatty fish compared to meat on cognitive functioning in the preschool children. When considering dietary compliance, we found a beneficial effect of fatty fish on cognitive scores. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02331667 December 17, 2014.

Role of selected amino acids on plasma IGF-I concentration in infants.

PURPOSE: Insulin-like growth factor-I (IGF-I) is related to growth and its secretion is modified by protein intake in early infancy. We examined the relationship of dietary protein and circulating amino acids on plasma IGF-I levels and early growth. METHODS: Healthy formula-fed infants (n = 213) were randomly assigned to receive either a protein-reduced infant formula with alpha-lactalbumin-enriched whey and free tryptophan and phenylalanine (IF) or an isocaloric standard formula without free amino acids (CF) for the first 120 days of life. A group of breastfed (BF) infants was studied as a non-randomized reference cohort. Biochemical variables were measured shortly after birth (subpopulation) and at an age of 120 days. A path analysis was used to explore the relationship between IGF-I, insulin and amino acids. Results are derived from secondary analyses of a randomized controlled trial. RESULTS: Plasma concentrations of IGF-I at 120 days were significantly higher in IF than in CF infants [58.5 (15.0) vs. 53.7 (9.95) ng/mL; p = 0.020]. BF infants showed lower IGF-I concentrations of 41.6 (10.7) ng/mL. All amino acids but Thr and Cit had a more marked effect on insulin than on IGF-I level. Considering weight, sex and feeding group, Trp explained an equal percentage of variance of IGF-I and insulin (total R 2 12.5 % of IGF-I and 12.3 % of insulin), while branched-chain AA explained an up to twofold higher variance of insulin than IGF-I. Compared to CF, IF explained 18.9 % of the IGF-I level (p = 0.03), while for insulin no direct effect was detectable. CONCLUSION: Higher IGF-I concentrations and growth velocities in infants receiving protein-reduced IF indicate that the protein concentration of an infant formula alone does not control IGF-I levels and growth. Other components (e.g., selected amino acids) of infant formulae might control directly or indirectly via insulin influence IGF-I.

Fatty acid supply with complementary foods and LC-PUFA status in healthy infants: results of a randomised controlled trial.

PURPOSE: Introduction of complementary food usually leads to decreasing intakes of long-chain n-3 polyunsaturated fatty acids (n-3 LC-PUFA), compared to full breastfeeding. In the randomised controlled PINGU intervention trial, we tested the effects of complementary foods with different contents of alpha-linolenic acid (ALA) and docosahexaenoic acid (DHA) on term infant LC-PUFA status. METHODS: Healthy infants born at term were randomised to receive from the introduction of complementary feeding at the age of 4 to 6 months until age of 10 months ready-made complementary meals either with ALA-rich rapeseed oil (intervention group (IG)-R), with salmon twice weekly to provide preformed DHA (IG-F), or with linoleic acid-rich corn oil (control group, CG). Fatty acid composition was assessed in erythrocyte (RBC) and plasma glycerophospholipids. RESULTS: Complete data of fatty acids in RBC (plasma) were available from 158 (155) infants. After intervention, infants assigned to IG-F showed higher RBC and plasma percentages of eicosapentaenoic acid (EPA), DHA, and total n-3 LC-PUFA than CG (each p < 0.001). In IG-R, levels of ALA and the ratio of ALA to LA in plasma and RBC (all p < 0.0001) as well as RBC-EPA (p < 0.0001) were higher than in CG, while DHA levels did not differ between IG-R and CG. CONCLUSIONS: Regular fish consumption during complementary feeding enhances infant EPA and DHA status. The usage of rapeseed oil in small amounts concordant with EU-law for commercial meals enhances endogenic EPA-synthesis, but does not affect DHA status. Provision of oily fish with complementary feeds is advisable to prevent a decline of DHA status. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov , identifier: NCT01487889, title: Polyunsaturated fatty acids in child nutrition-a German multimodal optimisation study (PINGU).

Maternal LC-PUFA status during pregnancy and child problem behavior: the Generation R Study.

BACKGROUND: Omega 3 (n-3) and 6 (n-6) long-chain polyunsaturated fatty acids (LC-PUFAs) and the n-3:n-6 ratio are important for brain development. Whether maternal LC-PUFA status during pregnancy affects risk of problem behavior in later childhood is unclear. METHODS: Within a population-based cohort, we measured maternal plasma docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (AA) concentrations and n-3:n-6-ratio in mid-pregnancy. Child emotional and behavioral problems at 6 y of age were assessed by parents (child behavior checklist), teachers (teacher report form), and combined parent/teacher report. RESULTS: Higher maternal DHA and n-3:n-6 ratio were associated with fewer child emotional problems using parent (odds ratio (OR)DHA = 0.82; 95% confidence interval (CI): 0.70, 0.96; P = 0.02 and OR(n-3:n-6) = 0.83; 95% CI: 0.71, 0.96; P = 0.01; n = 5,307) and combined parent/teacher scores (ORDHA = 0.79; 95% CI: 0.66, 0.95; P = 0.01 and OR(n-3:n-6) = 0.77; 95% CI: 0.65, 0.92; P < 0.01; n = 2,828). Higher AA was associated with more child behavioral problems using teacher (OR = 1.10; 95% CI: 1.00, 1.20; P = 0.04; n = 3,365) and combined parent/teacher scores (OR = 1.12; 95% CI: 1.02, 1.22; P = 0.02; n = 2,827). Maternal EPA was not associated with child problem behavior. CONCLUSION: Indications of associations of maternal LC-PUFA status with child emotional and behavioral problems were found. Future research is needed to identify LC-PUFA-sensitive periods of fetal brain development by including multiple assessments of prenatal LC-PUFA status.

Body mass index, gestational weight gain and fatty acid concentrations during pregnancy: the Generation R Study.

Obesity during pregnancy may be correlated with an adverse nutritional status affecting pregnancy and offspring outcomes. We examined the associations of prepregnancy body mass index and gestational weight gain with plasma fatty acid concentrations in mid-pregnancy. This study was embedded in a population-based prospective cohort study among 5636 women. We obtained prepregnancy body mass index and maximum weight gain during pregnancy by questionnaires. We measured concentrations of saturated fatty acid (SFA), monounsaturated fatty acid (MUFA), n-3 polyunsaturated fatty acid (n-3 PUFA) and n-6 polyunsaturated fatty acid (n-6 PUFA) at a median gestational age of 20.5 (95% range 17.1-24.9) weeks. We used multivariate linear regression models. As compared to normal weight women, obese women had higher total SFA concentrations [difference: 0.10 standard deviation (SD) (95% Confidence Interval (CI) 0, 0.19)] and lower total n-3 PUFA concentrations [difference: - 0.11 SD (95% CI - 0.20, - 0.02)]. As compared to women with sufficient gestational weight gain, those with excessive gestational weight gain had higher SFA concentrations [difference: 0.16 SD (95% CI 0.08, 0.25)], MUFA concentrations [difference: 0.16 SD (95% CI 0.08, 0.24)] and n-6 PUFA concentrations [difference: 0.12 SD (95% CI 0.04, 0.21)]. These results were not materially affected by adjustment for maternal characteristics. Our results suggest that obesity and excessive weight gain during pregnancy are associated with an adverse fatty acids profile. Further studies are needed to assess causality and direction of the observed associations.

Dietary Effects on Plasma Glycerophospholipids.

OBJECTIVE: Human milk provides a complex mixture of animal lipids, whereas the fat supply of most modern infant formula is based on vegetable oils. We studied the effects of breast-feeding and of feeding infant formula either without or with dairy goat lipids on the composition of infant plasma glycerophospholipids. METHODS: Healthy-term infants were randomized double blind to feeding with infant formula based on whole goats' milk (GIF, approximately 60% milk fat and 40% vegetable oils) or a control cows' milk infant formula based on vegetable oils (VIF) from 2 weeks after birth. A reference group of fully breast-fed infants was also followed. At the age 4 months, blood samples were collected and plasma glycerophospholipids were analyzed with liquid chromatography coupled to triple quadrupole mass spectrometry. RESULTS: The group of breast-fed infants showed significantly higher contents of glycerophospholipid species containing sn-2 palmitic acid [PC(16:0/16:0) and PC(18:0/16:0)] and significantly higher contents of glycerophospholipid species containing long-chain polyunsaturated fatty acids than infants in both formula groups. The GIF group demonstrated significantly higher glycerophospholipid species containing myristic acid [LPC(14:0), PC(14:0/18:1), PC(16:0/14:0)] and palmitoleic acid [LPC(16:1), PC(16:0/16:1), and PC(16:1/18:1)] than the VIF group. CONCLUSIONS: We conclude that breast-feeding induces marked differences in infant plasma glycerophospholipid profiles compared with formula feeding, whereas the studied different sources of formula fat resulted in limited effects on plasma glycerophospholipids.

Cord blood LC-PUFA composition and allergic diseases during the first 10 yr. Results from the LISAplus study.

BACKGROUND: It has been suggested that n-6 and n-3 long-chain polyunsaturated fatty acids (LC-PUFAs) in blood are associated with risk of allergic diseases, although results are inconclusive. Low levels of n-6 LC-PUFA and high levels of n-3 LC-PUFA are anticipated to have beneficial effects. Pregnancy is considered a critical time period for imprinting the developing immune system. We examined whether n-6 LC-PUFA, n-3 LC-PUFA concentrations or the n-6/n-3 ratio in cord blood (CB) serum are associated with allergic diseases up to the age of 10 yr. METHODS: This analysis included 436 children from the Munich LISAplus birth cohort study. Information on doctor-diagnosed asthma, hay fever/allergic rhinitis, and eczema was collected using questionnaires completed at the ages 6 and 10 yr, and for eczema additionally at 2 yr. Specific immunoglobulin E (IgE) against inhalant allergens was measured at 6 and 10 yr. Fatty acid composition was measured by gas chromatography in serum from CB and from blood collected at 2, 6, and 10 yr. Associations between n-3, n-6 LC-PUFA concentrations, and the n-6/n-3 ratio in CB serum and allergic diseases or atopy were assessed using generalized estimating equations (GEE) considering the longitudinal structure. Models were adjusted for LC-PUFA concentrations at follow-up and potential confounding factors. RESULTS: There was no significant association between n-3 LC-PUFA, n-6 LC-PUFA, or the n-6/n-3 ratio in CB serum with eczema, asthma, hay fever/allergic rhinitis, or aeroallergen sensitization. CONCLUSIONS: There is no indication of a beneficial effect of increased n-3 LC-PUFA in CB serum on the development of any of the disease entities.

Age-dependent effects of cord blood long-chain PUFA composition on BMI during the first 10 years of life.

In the present study, we investigated whether n-6 and n-3 long-chain PUFA (LC-PUFA) concentrations in cord blood (CB) serum are associated with BMI up to 10 years of age, after accounting for LC-PUFA composition at 2, 6 and 10 years. The study was based on 388 participants of the German LISAplus (Influence of Lifestyle-Related Factors on the Immune System and the Development of Allergies in Childhood Plus the Influence of Traffic Emissions and Genetics) birth cohort study carried out in Munich. BMI was measured at 2, 6 and 10 years of age. Serum phospholipid fatty acid concentrations were measured by GC in CB and in blood collected at 2, 6 and 10 years of age. The association between n-3 LC-PUFA and n-6 LC-PUFA concentrations and n-6:n-3 LC-PUFA ratio in CB serum glycerophospholipids and BMI z-scores was assessed using linear mixed models adjusted for LC-PUFA composition at follow-up and potential confounders. Interaction terms between time of follow-up and LC-PUFA concentrations in CB were included. There was no consistent association between n-6 and n-3 LC-PUFA concentrations in CB and BMI over time. However, there was a significant interaction between n-6:n-3 LC-PUFA ratio in CB and time of follow-up with respect to BMI (P= 0·0415): a negative effect at 2 years; no effect at 6 years; a positive effect at 10 years. BMI up to 10 years of age may be influenced by the n-6:n-3 ratio in CB serum glycerophospholipids in a time-varying fashion. The present results thereby highlight the importance of considering age when examining associations between fatty acid concentrations and BMI.

Three-month B vitamin supplementation in pre-school children affects folate status and homocysteine, but not cognitive performance.

BACKGROUND: Suboptimal vitamin B status might affect cognitive performance in early childhood. We tested the hypothesis that short-term supplementation with folic acid and selected B vitamins improves cognitive function in healthy children in a population with relatively low folate status. METHODS: We screened 1,002 kindergarten children for suboptimal folate status by assessing the total urinary para-aminobenzoylglutamate excretion. Two hundred and fifty low ranking subjects were recruited into a double blind, randomized, controlled trial to receive daily a sachet containing 220 µg folic acid, 1.1 mg vitamin B2, 0.73 mg B6, 1.2 µg B12 and 130 mg calcium, or calcium only for 3 months. Primary outcomes were changes in verbal IQ, short-term memory and processing speed between baseline and study end. Secondary outcomes were urinary markers of folate and vitamin B12 status, acetyl-para-aminobenzoylglutamate and methylmalonic acid, respectively, and, in a subgroup of 120 participants, blood folate and plasma homocysteine. RESULTS: Pre- and post-intervention cognitive measurements were completed by 115 children in the intervention and 122 in the control group. Compared to control, median blood folate increased by about 50% (P for difference, P < 0.0001). Homocysteine decreased by 1.1 µmol/L compared to baseline, no change was seen in the control group (P for difference P < 0.0001) and acetyl-para-aminobenzoylglutamate was 4 nmol/mmol higher compared to control at the end of the intervention (P < 0.0001). We found no relevant differences between the groups for the cognitive measures. CONCLUSION: Short-term improvement of folate and homocysteine status in healthy children does not appear to affect cognitive performance.

Energetic efficiency of infant formulae: a review.

Breast-fed and formula-fed infants differ in terms of nutrient intake, growth, and metabolic and endocrine responses. The energetic efficiency, i.e. the weight or length gain per 100 kcal of energy intake, of breast-fed infants is about 11% higher than the energetic efficiency of formula-fed infants. Only limited data is available on the influence of formula composition on the energetic efficiency of infant formulae. We conducted a review of controlled trials to identify the impact of the macronutrient composition of infant formulae on energetic efficiency. An electronic literature search was conducted in February 2014. Intervention trials that investigated the effect of an infant formula with a modified macronutrient composition and reported the weight, length, and nutritional intake of apparently healthy, term, fully formula-fed infants with a normal weight were included. Thirteen trials met the inclusion criteria. The results showed no effect of the total content of energy, carbohydrate, protein, or fat on energetic efficiency. In contrast, small increasing effects of higher glycemic carbohydrates on energetic efficiency were identified. Improved fat absorption via the use of palmitic acid at the sn-2 ester position of triacylglycerol increased the energetic efficiency by 11%. The quality of formula protein, specifically an increased whey-to-casein ratio, an increased α-lactalbumin content, or a higher tryptophan content increased the energetic efficiency by about 13%. We conclude that fat absorption and protein quality have the potential to modulate energetic efficiency and may contribute to the observed differences in growth and metabolism between breast-fed and formula-fed infants.

Excessive weight gain during full breast-feeding.

BACKGROUND: Breast-feeding is considered to offer optimal nutrition for healthy infant growth and development. Observational studies have linked breast-feeding to reduced obesity. CASE OBSERVATION: We observed an infant who was born macrosomic (4.56 kg) and showed excessive weight gain markedly exceeding the 97th percentile of weight during full breast-feeding. At the age of 4 months, the weight was greater than 11 kg. Clinical evaluation did not reveal any underlying pathology. After the introduction of complementary feeding and hence reduction of the breast milk intake, the excessive weight gain was attenuated and the slope of the percentile curve paralleled upper percentiles. Since this pattern suggested full breast-feeding as the driver of excessive weight gain, we analyzed the human milk composition at the infant age of 1 year and compared the results with published data on composition at this stage of lactation. RESULTS: The milk contents of lactose, fat, fatty acids, polar lipids, carnitine species, and insulin were similar to the reference data. The adiponectin content was increased. The most remarkable alteration was a high milk protein content (mean 1.25 g/dl, reference 0.8 g/dl). CONCLUSIONS: A very high protein supply in infancy has been previously shown to increase plasma concentrations of the growth factors insulin and IGF-1, weight gain, and later obesity. We speculate that interindividual variations in human milk adiponectin and protein contents may contribute to modulation of the growth of fully breast-fed infants and in this case may have contributed to excessive weight gain during full breast-feeding. This hypothesis merits being tested in future cohort studies.

Placental fatty acid transfer: a key factor in fetal growth.

The functionality of the placenta may affect neonatal adiposity and fetal levels of key nutrients such as long-chain polyunsaturated fatty acids. Fetal macrosomia and its complications may occur even in adequately controlled gestational diabetic (GDM) mothers, suggesting that maternal glycemia is not the only determinant of fetal glycemic status and wellbeing. We studied in vivo the placental transfer of fatty acids (FA) labeled with stable isotopes administered to 11 control and 9 GDM pregnant women (6 treated with insulin). Subjects received orally ¹³C-palmitic, ¹³C-oleic, and ¹³C-linoleic acids and ¹³C-docosahexaenoic acid (¹³C-DHA) 12 h before an elective caesarean section. FA were quantified by gas chromatography and ¹³C enrichments by gas chromatography-isotope ratio mass spectrometry. The ¹³C-FA concentration was higher in total lipids of maternal plasma in GDM patients versus controls, except for ¹³C-DHA. Moreover, ¹³C-DHA showed a lower placenta/maternal plasma ratio in GDM patients versus controls and a significantly lower cord/maternal plasma ratio. Other FA ratios studied were not different between GDM and controls. A disturbed ¹³C-DHA placental uptake occurred in GDM patients treated with diet or insulin, while the latter also had lower ¹³C-DHA levels in the venous cord. The tracer study pointed towards an impaired placental DHA uptake as a critical step, while the transfer of other ¹³C-FA was less affected. Patients with GDM treated with insulin could also have a greater fetal fat storage, which may have contributed to the reduced ¹³C-DHA in the venous cord observed. The DHA transfer to the fetus was reduced in GDM pregnancies compared to controls. This might have an influence on fetal neurodevelopment and long-term consequences for the child.