Methodological Frameworks and Dimensions to Be Considered in Digital Health Technology Assessment: Scoping Review and Thematic Analysis.

BACKGROUND: Digital health technologies (dHTs) offer a unique opportunity to address some of the major challenges facing health care systems worldwide. However, the implementation of dHTs raises some concerns, such as the limited understanding of their real impact on health systems and people's well-being or the potential risks derived from their use. In this context, health technology assessment (HTA) is 1 of the main tools that health systems can use to appraise evidence and determine the value of a given dHT. Nevertheless, due to the nature of dHTs, experts highlight the need to reconsider the frameworks used in traditional HTA. OBJECTIVE: This scoping review (ScR) aimed to identify the methodological frameworks used worldwide for digital health technology assessment (dHTA); determine what domains are being considered; and generate, through a thematic analysis, a proposal for a methodological framework based on the most frequently described domains in the literature. METHODS: The ScR was performed in accordance with the guidelines established in the PRISMA-ScR guidelines. We searched 7 databases for peer reviews and gray literature published between January 2011 and December 2021. The retrieved studies were screened using Rayyan in a single-blind manner by 2 independent authors, and data were extracted using ATLAS.ti software. The same software was used for thematic analysis. RESULTS: The systematic search retrieved 3061 studies (n=2238, 73.1%, unique), of which 26 (0.8%) studies were included. From these, we identified 102 methodological frameworks designed for dHTA. These frameworks revealed great heterogeneity between them due to their different structures, approaches, and items to be considered in dHTA. In addition, we identified different wording used to refer to similar concepts. Through thematic analysis, we reduced this heterogeneity. In the first phase of the analysis, 176 provisional codes related to different assessment items emerged. In the second phase, these codes were clustered into 86 descriptive themes, which, in turn, were grouped in the third phase into 61 analytical themes and organized through a vertical hierarchy of 3 levels: level 1 formed by 13 domains, level 2 formed by 38 dimensions, and level 3 formed by 11 subdimensions. From these 61 analytical themes, we developed a proposal for a methodological framework for dHTA. CONCLUSIONS: There is a need to adapt the existing frameworks used for dHTA or create new ones to more comprehensively assess different kinds of dHTs. Through this ScR, we identified 26 studies including 102 methodological frameworks and tools for dHTA. The thematic analysis of those 26 studies led to the definition of 12 domains, 38 dimensions, and 11 subdimensions that should be considered in dHTA.

Organic food use, meat intake, and prevalence of gestational diabetes: KOALA birth cohort study.

PURPOSE: To evaluate whether consumption of organic food and reduced intake of meat products in pregnancy are associated with lower prevalence of gestational diabetes (GD). METHODS: Women participating in the KOALA Birth Cohort Study with valid informed consent, a singleton pregnancy and information on their food intake were considered in this cross-sectional analysis. Participants with and without GD were compared with each other in terms of dietary characteristics (n = 37 and n = 2766, respectively). Multivariable logistic regression (LR) was used to adjust for relevant covariates. RESULTS: Organic food consumption tended to be lower, although not significantly, in women with GD compared to women without GD, whereas consumption of meat was positively associated with GD prevalence. LR modelling showed that GD was significantly associated with higher consumption of meat and, in addition, also of cheese, after adjustment for other relevant covariates. GD was associated with some indicators of animal product intake, namely dietary animal to plant protein ratio and maternal plasma arachidonic acid (for the latter, data available for n = 16 and n = 1304, respectively). Food patterns of participants with GD were characterised by more meat products and less vegetarian products. CONCLUSIONS: Due to the low number of participants with GD, results have to be interpreted cautiously. Consumption of organic food during pregnancy does not seem to be markedly associated with a lower GD prevalence; lower intake of meat and cheese, irrespective of its origin (organic or conventional), does. The latter supports previous studies suggesting a causal association between consumption of animal products and GD.

Genomics of lactation: role of nutrigenomics and nutrigenetics in the fatty acid composition of human milk.

Human milk covers the infant's nutrient requirements during the first 6 months of life. The composition of human milk progressively changes during lactation and it is influenced by maternal nutritional factors. Nowadays, it is well known that nutrients have the ability to interact with genes and modulate molecular mechanisms impacting physiological functions. This has led to a growing interest among researchers in exploring nutrition at a molecular level and to the development of two fields of study: nutrigenomics, which evaluates the influence of nutrients on gene expression, and nutrigenetics, which evaluates the heterogeneous individual response to nutrients due to genetic variation. Fatty acids are one of the nutrients most studied in relation to lactation given their biologically important roles during early postnatal life. Fatty acids modulate transcription factors involved in the regulation of lipid metabolism, which in turn causes a variation in the proportion of lipids in milk. This review focuses on understanding, on the one hand, the gene transcription mechanisms activated by maternal dietary fatty acids and, on the other hand, the interaction between dietary fatty acids and genetic variation in genes involved in lipid metabolism. Both of these mechanisms affect the fatty acid composition of human milk.

Organic food consumption during pregnancy and its association with health-related characteristics: the KOALA Birth Cohort Study.

OBJECTIVE: To investigate the associations of organic food consumption with maternal pre-pregnancy BMI, hypertension and diabetes in pregnancy, and several blood biomarkers of pregnant women. DESIGN: Prospective cohort study. SETTING: Pregnant women were recruited at midwives' practices and through channels related to consumption of food from organic origin. SUBJECTS: Pregnant women who filled in FFQ and donated a blood sample (n 1339). Participant groups were defined based on the share of consumed organic products; to discriminate between effects of food origin and food patterns, healthy diet indicators were considered in some statistical models. RESULTS: Consumption of organic food was associated with a more favourable pre-pregnancy BMI and lower prevalence of gestational diabetes. Compared with participants consuming no organic food (reference group), a marker of dairy products intake (pentadecanoic acid) and trans-fatty acids from natural origin (vaccenic and rumenic acids) were higher among participants consuming organic food (organic groups), whereas elaidic acid, a marker of the intake of trans-fatty acids found in industrially hydrogenated fats, was lower. Plasma levels of homocysteine and 25-hydroxyvitamin D were lower in the organic groups than in the reference group. Differences in pentadecanoic acid, vaccenic acid and vitamin D retained statistical significance when correcting for indicators of the healthy diet pattern associated with the consumption of organic food. CONCLUSIONS: Consumption of organic food during pregnancy is associated with several health-related characteristics and blood biomarkers. Part of the observed associations is explained by food patterns accompanying the consumption of organic food.

Organic food consumption during pregnancy is associated with different consumer profiles, food patterns and intake: the KOALA Birth Cohort Study.

OBJECTIVE: To find out how the consumption of organic food during pregnancy is associated with consumer characteristics, dietary patterns and macro- and micronutrient intakes. DESIGN: Cross-sectional description of consumer characteristics, dietary patterns and macro- and micronutrient intakes associated with consumption of organic food during pregnancy. SETTING: Healthy, pregnant women recruited to a prospective cohort study at midwives' practices in the southern part of the Netherlands; to enrich the study with participants adhering to alternative lifestyles, pregnant women were recruited through various specific channels. SUBJECTS: Participants who filled in questionnaires on food frequency in gestational week 34 (n 2786). Participant groups were defined based on the share of organic products within various food types. RESULTS: Consumers of organic food more often adhere to specific lifestyle rules, such as vegetarianism or anthroposophy, than do participants who consume conventional food only (reference group). Consumption of organic food is associated with food patterns comprising more products of vegetable origin (soya/vegetarian products, vegetables, cereal products, bread, fruits, and legumes) and fewer animal products (milk and meat), sugar and potatoes than consumed in conventional diets. These differences translate into distinct intakes of macro- and micronutrients, including higher retinol, carotene, tocopherol and folate intakes, lower intakes of vitamin D and B12 and specific types of trans-fatty acids in the organic groups. These differences are seen even in groups with low consumption of organic food. CONCLUSIONS: Various consumer characteristics, specific dietary patterns and types of food intake are associated with the consumption of organic food during pregnancy.

Maternal but not fetal FADS gene variants modify the association between maternal long-chain PUFA intake in pregnancy and birth weight.

Several studies have shown a positive association between maternal fish intake in pregnancy and pregnancy duration and child birth weight (BW), probably due to fish n-3 (ω-3) long-chain polyunsaturated fatty acids (LC-PUFAs). n-3 LC-PUFAs can also be synthesized endogenously, and their synthesis depends on single nucleotide polymorphisms (SNPs) in the fatty acid desaturase (FADS) gene encoding for FADS. We assessed the associations of maternal docosahexaenoic acid (DHA) intake in pregnancy with pregnancy duration and BW and investigated whether these associations are modified by maternal or fetal FADS SNP genotypes. We hypothesized that we would find stronger associations in minor allele homozygous mothers or fetuses due to their lower n-3 LC-PUFA endogenous synthesis and hence higher dependence on dietary supply. Data on maternal diet, pregnancy duration, and BW were available for 2622 mother-child pairs from the KOALA (Kind, Ouders en gezondheid: Aandacht voor Leefstijl en Aanleg) Birth Cohort Study. The rs174556 FADS SNP was genotyped in 1516 mothers and 1515 children. Associations and gene-diet interactions were tested with linear regression adjusting for potential confounders, including intake of other PUFAs. Women at the 75th percentile of DHA intake had 0.7-d longer pregnancies (P = 0.016) and 28-g heavier infants (P = 0.039) than did women at the 25th percentile of intake. Associations with arachidonic acid intake were of the same order but in the opposite direction. Mothers who were homozygous for the minor allele had 2-d shorter pregnancies (P = 0.035) and infants who were nearly 140 g lighter (P = 0.006) than did mothers who were major allele homozygotes. Post hoc analyses revealed that they had higher prepregnancy BMI (P = 0.020). Among the women homozygous for the minor allele, those at the 75th percentile of DHA intake had 226-g heavier infants than those at the 25th percentile of intake (P = 0.030), whereas DHA intake was not significantly associated with BW in major allele carriers. These findings suggest that maternal and fetal fatty acid requirements during pregnancy depend on maternal genetic variation in LC-PUFA synthesis.

Methodological Frameworks and Dimensions to Be Taken Into Consideration in Digital Health Technology Assessment: Protocol for a Scoping Review.

BACKGROUND: Health technology assessment (HTA) is one of the main tools that health systems have to appraise evidence and determine the value of a given health technology. Although the existing HTA frameworks are useful tools for the evaluation of a wide range of health technologies, more and more experts, organizations across the world, and HTA agencies are highlighting the need to update or develop specific methodological frameworks for the evaluation of digital health technologies in order to take into account additional domains that cover these technologies' intrinsic characteristics. OBJECTIVE: The purpose of our scoping review is to identify the methodological frameworks that are used worldwide for the assessment of digital health technologies; determine what dimensions and aspects are being considered; and generate, through a thematic analysis, a proposal for a methodological framework that is based on the most frequently described dimensions in the literature. METHODS: The scoping review will be performed in accordance with the guidelines established in the updated statement of the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews). We will search for peer-reviewed and grey literature published between 2011 and the date of the search execution. The retrieved references will be reviewed in a single-blind manner by 2 independent authors, and their quality will be assessed by using the Critical Appraisal Skills Program tool. The ATLAS.ti software (Scientific Software Development GmbH) will be used for data extraction and to perform the thematic analysis. RESULTS: The scoping review is currently (May 2022) in progress. It is expected to be completed in October 2022, and the final results of the research will be presented and published by November 2022. CONCLUSIONS: To our knowledge, no studies have been published to date that identify the existing methodological frameworks for digital HTA, determine which dimensions must be evaluated for correct decision-making, and serve as a basis for the development of a methodological framework of reference that health care systems can use to carry out this kind of assessment. This work is intended to address this knowledge gap of key relevance for the field of HTA. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/39905.

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-µmol/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 (ß: 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-µmol/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% CI: 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.

A logic model for pharmaceutical care.

Objectives To develop a logic model for pharmaceutical care that can be used by stakeholders as a tool to support innovation and to monitor the performance of the pharmaceutical care system in the Netherlands and abroad. The ultimate aim of such a system is the responsible provision of drug therapy to improve patients' quality of life. Methods The logic model for pharmaceutical care was created following a process consisting of four steps: (1) a literature review to identify what pharmaceutical care is and what elements it consists of; (2) separate interviews with 10 stakeholder organizations to discuss the results of the literature review; (3) construction of the logic model based on the findings from steps 1 and 2; and (4) separate interviews with three stakeholder organizations to discuss and fine-tune the model. This project was carried out by the National Institute for Public Health and the Environment ( Rijksinstituut voor Volksgezondheid en Milieu) in the Netherlands. Results According to the proposed logic model, pharmaceutical care is care defined as: (1) patient-centred; (2) effective and safe; (3) efficient and affordable; (4) in physical, financial and timely ways; and (5) with minimal environmental impact. Conclusion The proposed logic model provides stakeholders with a common framework for the innovation or further development of pharmaceutical care.

Fish and seafood consumption during pregnancy and the risk of asthma and allergic rhinitis in childhood: a pooled analysis of 18 European and US birth cohorts.

Background: It has been suggested that prenatal exposure to n-3 long-chain fatty acids protects against asthma and other allergy-related diseases later in childhood. The extent to which fish intake in pregnancy protects against child asthma and rhinitis symptoms remains unclear. We aimed to assess whether fish and seafood consumption in pregnancy is associated with childhood wheeze, asthma and allergic rhinitis. Methods: We pooled individual data from 60 774 mother-child pairs participating in 18 European and US birth cohort studies. Information on wheeze, asthma and allergic rhinitis prevalence was collected using validated questionnaires. The time periods of interest were: infancy (0-2 years), preschool age (3-4 years), and school age (5-8 years). We used multivariable generalized models to assess associations of fish and seafood (other than fish) consumption during pregnancy with child respiratory outcomes in cohort-specific analyses, with subsequent random-effects meta-analyses. Results: The median fish consumption during pregnancy ranged from 0.44 times/week in The Netherlands to 4.46 times/week in Spain. Maternal fish intake during pregnancy was not associated with offspring wheeze symptoms in any age group nor with the risk of child asthma [adjusted meta-analysis relative risk (RR) per 1-time/week = 1.01, 95% confidence interval 0.97-1.05)] and allergic rhinitis at school age (RR = 1.01, 0.99-1.03). These results were consistently found in further analyses by type of fish and seafood consumption and in sensitivity analyses. Conclusion: We found no evidence supporting a protective association of fish and seafood consumption during pregnancy with offspring symptoms of wheeze, asthma and allergic rhinitis from infancy to mid childhood.

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 >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 >1 but <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 >1 but <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 weight.

Genetic variation in FADS genes and plasma cholesterol levels in 2-year-old infants: KOALA Birth Cohort Study.

OBJECTIVE: Single nucleotide polymorphisms (SNPs) in genes involved in fatty acid metabolism (FADS1 FADS2 gene cluster) are associated with plasma lipid levels. We aimed to investigate whether these associations are already present early in life and compare the relative contribution of FADS SNPs vs traditional (non-genetic) factors as determinants of plasma lipid levels. METHODS: Information on infants' plasma total cholesterol levels, genotypes of five FADS SNPs (rs174545, rs174546, rs174556, rs174561, and rs3834458), anthropometric data, maternal characteristics, and breastfeeding history was available for 521 2-year-old children from the KOALA Birth Cohort Study. For 295 of these 521 children, plasma HDLc and non-HDLc levels were also known. Multivariable linear regression analysis was used to study the associations of genetic and non-genetic determinants with cholesterol levels. RESULTS: All FADS SNPs were significantly associated with total cholesterol levels. Heterozygous and homozygous for the minor allele children had about 4% and 8% lower total cholesterol levels than major allele homozygotes. In addition, homozygous for the minor allele children had about 7% lower HDLc levels. This difference reached significance for the SNPs rs174546 and rs3834458. The associations went in the same direction for non-HDLc, but statistical significance was not reached. The percentage of total variance of total cholesterol levels explained by FADS SNPs was relatively low (lower than 3%) but of the same order as that explained by gender and the non-genetic determinants together. CONCLUSIONS: FADS SNPs are associated with plasma total cholesterol and HDLc levels in preschool children. This brings a new piece of evidence to explain how blood lipid levels may track from childhood to adulthood. Moreover, the finding that these SNPs explain a similar amount of variance in total cholesterol levels as the non-genetic determinants studied reveals the potential importance of investigating the effects of genetic variations in early life.

Differences in fat content and fatty acid proportions among colostrum, transitional, and mature milk from women delivering very preterm, preterm, and term infants.

BACKGROUND & AIMS: Human milk composition changes according to gestational age and stage of lactation, but infants fed banked human milk often receive pooled milk. We studied the changes in fat content and fatty acid proportions throughout lactation in very preterm, preterm, and full term milk, and the differences among gestational age groups. METHODS: Samples from women delivering before 30 (n = 10), between 30 and 37 (n = 10), and between 38 and 42 (n = 23) weeks of gestation were analyzed. RESULTS: Fat content was higher in very preterm than in preterm and full term samples (p < 0.05). Medium-chain saturated fatty acids, alpha-linolenic acid, and rumenic acid proportions increased (p < 0.05) during lactation, while those of most long-chain saturated fatty acids and most long-chain polyunsaturated fatty acids from the n-3 and n-6 families decreased (p < 0.05). In colostrum and transitional milk, medium-chain saturated fatty acid proportions were highest in the very preterm group, and decreased with gestational age (p < 0.05). CONCLUSIONS: The differences in fat and fatty acids of human milk obtained at different gestational ages and stages of lactation may impact preterm infants' health. Therefore they could be taken into account when feeding newborns banked human milk and when designing infant formulas or human milk fortifiers.

Enhancement of antibody synthesis in rats by feeding cis-9,trans-11 conjugated linoleic acid during early life.

Previous studies have demonstrated that the intake of a 1% conjugated linoleic acid (CLA) diet in an 80:20 mixture of cis-9,trans-11 and trans-10,cis-12 exerts age-specific effects on the immune system: immunoglobulin enhancement and proliferative down-modulation in neonatal and adult rats, respectively. The present study evaluates the influence of the same diet on antibody synthesis of early infant Wistar rats during suckling and/or after weaning. Dietary supplementation was performed during suckling and early infancy (4 weeks), only during suckling (3 weeks), or only in early infancy (1 week). CLA content in plasma and serum immunoglobulin (Ig) G, IgM and IgA concentration were determined. Proliferation, cytokines and Ig production were evaluated on isolated splenocytes. Cis-9,trans-11- and trans-10,cis-12-CLA isomers were detected in the plasma of all CLA-supplemented animals, and the highest content was quantified in those rats supplemented over the longest period. These rats also exhibited higher concentrations of serum IgG, IgM and IgA. Moreover, splenocytes from CLA-supplemented rats showed the highest IgM and IgG synthesis and interleukin (IL)-6 production, whereas their proliferative ability was lower. In summary, in infant rats, we observed both the enhance antibody synthesis previously reported in neonates, and the reduced lymphoproliferation previously reported in adults.

Breastfeeding, long-chain polyunsaturated fatty acids in colostrum, and infant mental development.

BACKGROUND: Breastfeeding has been associated with improved neurodevelopment in children. However, it remains unknown to what extent nutritional advantages of breast milk may explain this relationship. OBJECTIVE: We assessed the role of parental psychosocial factors and colostrum long-chain polyunsaturated fatty acid (LC-PUFA) levels in the relationship between breastfeeding and children's neurodevelopment. METHODS: A population-based birth cohort was established in the city of Sabadell (Catalonia, Spain) as part of the INMA-INfancia y Medio Ambiente Project. A total of 657 women were recruited during the first trimester of pregnancy. Information about parental characteristics and breastfeeding was obtained by using a questionnaire, and trained psychologists assessed mental and psychomotor development by using the Bayley Scales of Infant Development in 504 children at 14 months of age. RESULTS: A high percentage of breastfeeds among all milk feeds accumulated during the first 14 months was positively related with child mental development (0.37 points per month of full breastfeeding [95% confidence interval: 0.06-0.67]). Maternal education, social class, and intelligence quotient only partly explained this association. Children with a longer duration of breastfeeding also exposed to higher ratios between n-3 and n-6 PUFAs in colostrum had significantly higher mental scores than children with low breastfeeding duration exposed to low levels. CONCLUSIONS: Greater levels of accumulated breastfeeding during the first year of life were related to higher mental development at 14 months, largely independently from a wide range of parental psychosocial factors. LC-PUFA levels seem to play a beneficial role in children's mental development when breastfeeding levels are high.

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.

FADS1 FADS2 gene variants modify the association between fish intake and the docosahexaenoic acid proportions in human milk.

BACKGROUND: The genes encoding Delta(5)- and Delta(6)-desaturases (FADS1 FADS2 gene cluster) were reported to be associated with n-3 (omega-3) and n-6 (omega-6) fatty acid proportions in human plasma, tissues, and milk. Docosahexaenoic acid (DHA) can be supplied especially by dietary fish or fish oil and synthesized from alpha-linolenic acid through a pathway involving these desaturases. OBJECTIVE: We evaluated whether FADS gene variants modify the effect of maternal fish and fish-oil intake on plasma and milk DHA proportions. DESIGN: FADS1 rs174561, FADS2 rs174575, and intergenic rs3834458 single nucleotide polymorphisms were genotyped in 309 women from the KOALA Birth Cohort Study in The Netherlands. Plasma was collected at 36 wk of pregnancy, and milk was collected at 1 mo postpartum. Fish and fish-oil intake was assessed by using a food-frequency questionnaire at 34 wk of pregnancy and updated for the week of milk collection. Gene-diet interactions were tested by linear regression analysis. RESULTS: DHA proportions were lower in women homozygous for the minor allele than in women who were homozygous for the major allele (DHA proportions in plasma phospholipids: P < 0.01; DHA proportions in milk: P < 0.05). Fish intake ranged from 0 to 2.5 portions of fatty fish/wk, and 12 women took fish-oil supplements during pregnancy. DHA proportions in plasma phospholipids increased with increasing fish and fish-oil intake, irrespective of the genotype. DHA proportions in milk increased only with fish and fish-oil intake in the major-allele carriers. CONCLUSION: Lower proportions of DHA in milk from women who were homozygous for the minor allele could not be compensated for by increasing fish and fish-oil intake, possibly because of limited incorporation into milk.

Ultra-High-Pressure Liquid Chromatographic method for the analysis of tocopherols in human colostrum and milk.

A rapid, highly sensitive and direct Ultra-High-Pressure Liquid Chromatographic method was developed and validated for quantifying delta-, beta+gamma-, and alpha-tocopherol in human colostrum and milk. Two reversed-phase chromatographic columns and two detectors (Fluorescence Detector or FD and Photodiode Detector Array or PDA) were used and both methods were independently validated. Two internal standards were selected according to the detector used. Recoveries ranged from 96.71% to 103.55% and the relative standard deviations for the within-day precision were below 6% (PDA) and 3% (FD). Both approaches enabled to achieve low detection limits, on the order of ng (PDA) or pg (FD). Only 300muL of sample and a chromatographic run of less than 1.6min were enough to efficiently quantify the isomers in the colostrum and milk of Spanish women.

Conjugated linoleic acid determination in human milk by fast-gas chromatography.

An efficient direct method for measuring c9,t11- and t10,c12-conjugated linoleic acid (CLA) isomer content in human and rat milk was developed and validated using an RTX-2330 capillary column (40 m x 0.18 mm x 0.1 microm). In comparison with the commonly used 100 m x 0.25 mm x 0.20 microm columns, this new type of fast column allowed the separation of FAMEs with the same resolution but in much less time. An additional advantage for biological samples was that only a small volume of sample was needed. Two different procedures were tested in order to select the best methylation of CLA isomers, and the alkali plus acid-catalyzed procedure was selected. The precision results showed relative standard deviations (R.S.D.) of repeatability and reproducibility ranging between 0.10 and 8.71%. The application of this method to human and rat milk samples showed that it was a rapid, simple and reliable method for the analysis of biological samples.