Morbidity Outcomes of Very Low Birth Weight Neonates Receiving Parenteral Nutrition with Fish Oil Enriched Lipid Emulsion or Lipid Emulsion with Soybean Oil: An Observational Study.

Intralipid (Fresenius Kabi) was the most commonly used lipid emulsion in parenteral nutrition (PN), with a 100% soybean oil composition, a low vitamin E content, and a ω-6: ω-3 ratio of 7:1. A recent alternative formulation is SMOFlipid (Fresenius Kabi), with a ω-6: ω-3 ratio of 5:2 and higher vitamin E content. A retrospective observational study was conducted to determine neonatal morbidity in very low birth weight (VLBW) premature infants during two periods: P1, when PN was based exclusively on Intralipid, and P2, when only SMOFlipid was supplied. In total, 170 VLBW neonates were analyzed, of whom 103 received PN for more than 6 days, 56 during P1, and 47 during P2. In both periods, the antenatal and neonatal characteristics of the cohort were comparable. In this analysis, the prevalence of associated comorbidities was determined. During P2, there were fewer cases of moderate to severe bronchopulmonary dysplasia (BPD) and of cholestasis, but more cases of late sepsis, mainly Staphylococcus epidermidis. No changes in the prevalence of other neonatal comorbidities were observed. We believe that the SMOFlipid used in PN could discreetly improve the prevalence of cholestasis or BPD.

Early energy restriction in premature infants and bronchopulmonary dysplasia: a cohort study.

Bronchopulmonary dysplasia (BPD) is a multifactor pathology. Animal studies and cohort studies suggest that poor nutrient intake after birth increases the risk of BPD. The objective of the present study was to determine the existence of association between BPD in very low birth weight (VLBW) and energy intake during the first week of life. We recorded in a retrospective cohort study the intake of enteral and parenteral macronutrients during this period by examining the nutritional and clinical history of 450 VLBW newborns admitted to the neonatal intensive care unit. After applying the relevant exclusion criteria, data for 389 VLBW infants were analysed, of whom 159 developed some degree of BPD. Among the newborns with BPD, energy and lipid intake was significantly lower and fluid intake was significantly higher. The energy intake for the 25th percentile in the group without BPD was 1778·2 kJ/kg during the first week of life. An energy intake <1778·2 kJ/kg in this period was associated with a 2-fold increase in the adjusted risk of BPD (OR 2·63, 95 % CI 1·30, 5·34). The early nutrition and the increase of energy intake in the first week of life are associated in our sample with a lower risk of BPD developing.

Relationship of NEFA concentrations to RBP4 and to RBP4/retinol in prepubertal children with and without obesity.

BACKGROUND: The regulation of adipose tissue metabolism in early childhood obesity is not well understood. Insulin levels are higher and insulin resistance seems to be present in prepubertal children with obesity but, differing from their behavior in adults with obesity, non-esterified fatty acid (NEFA) concentrations are not increased. Retinol-binding protein (RBP)-4 concentration is associated with obesity and insulin resistance conditions, but the means of this relationship remain unclear, and few studies have taken retinol values into account to evaluate it. OBJECTIVE: To analyze the relationship between RBP4 concentration and lipolytic products in plasma in 141 prepubertal children aged 6 to 8 years, with and without obesity. METHODS: Plasma glucose, insulin, triacylglycerols, NEFA, glycerol, leptin, RBP4, and retinol were analyzed in obese and in their normal-weight counterparts. Homeostatic model assessment, quantitative insulin sensitivity check index, and fasting glucose to insulin ratio were calculated as indicators of insulin resistance. RESULTS: Fasted plasma NEFA concentrations were lower in children with obesity than in their normal weight counterparts, despite leptin, insulin resistance indices, RBP4, retinol, and RBP4/retinol (an index of free-RBP4) being higher. NEFA and glycerol concentrations were inversely correlated with RBP4/retinol in children with obesity but not in those without obesity. In normal weight children, total RBP4 correlated negatively with NEFA and glycerol concentrations and positively with insulin and homeostasis model assessment for insulin resistance. These results indicate that a low saturation of RBP4 with retinol, which implies a higher concentration of free-RBP4, may preserve the antilipolytic function of insulin in adipose tissue in children with obesity. CONCLUSION: Our findings suggest that, in prepubertal children with obesity and insulin resistance, the amount of RBP4/retinol correlates with the antilipolytic response of the adipose tissue to insulin rather than the total RBP4 concentration.

Validation of a Portable Coagulometer for Routine In-Hospital Use for Newborns.

OBJECTIVES: To verify the reliability and clinical benefits of the coagulation tests made by a point of care device in newborn admitted to a neonatal unit. DESIGN: We made a statistical comparison between results obtained by the point of care device versus conventional laboratory analysis. SETTING: Level 3 neonatal unit. PATIENTS: Thirty-one infants admitted to the neonatal unit at the San Cecilio University Hospital (Granada, Spain) were recruited to this study. INTERVENTIONS: All underwent a double analytical determination: a small drop of blood was taken for analysis with a portable coagulometer (qLabs Electrometer Plus) and the rest of the blood sample was analyzed with conventional hospital laboratory equipment. MEASUREMENTS AND MAIN RESULTS: According to the linearity test performed, the measuring methods presented a good linear regression fit. Lin's concordance coefficient showed a "good" agreement for activated partial prothrombin time and international normalized ratio (>0.61) and a moderate one for prothrombin time (0.41-0.6) for the sample of newborns. CONCLUSIONS: The portable coagulometer qLabs Electrometer Plus device has the potential to be an alternative to standard hospital coagulation autoanalyzers in a subset of patients where the amount of blood drawn can have significant risks. Our study is the first of its kind to analyze the use of this device with severely ill newborns.

Epidemiological factors involved in the development of bronchopulmonary dysplasia in very low birth-weight preterm infants.

BACKGROUND: In spite of the advances made in perinatal medicine, the incidence of bronchopulmonary dysplasia (BPD) has not decreased and the aetiopathogenesis of the "new" BPD is still a matter for debate. The objectives of the present study were to analyse the epidemiological factors and morbidity associated with the development of BPD in a cohort of very low birth-weight (VLBW) preterm infants. METHODS: This retrospective observational study included all the preterm infants with birth weight ≤1500 g who were admitted to a tertiary-level hospital NICU from 2008 to 2011. A neurological follow-up was also carried out during the first two years of life. RESULTS: A total of 140 VLBW infants were analyzed: 28.4% presented oxygen dependence at 28 days, and 17.2% at 36 weeks adjusted gestational age. Predictive factors for the development of BPD were gestational age, birth weight, number of days of parenteral nutrition, number of days to achieve full enteral feeding, number of transfusions, duration of respiratory support and insulin administration, vasoactive drugs, diuretics, sedoanalgesia and postnatal corticosteroids. The neonatal morbidity associated with the development of BPD was late neonatal sepsis, patent ductus arteriosus, retinopathy of prematurity (ROP) and intraventricular hemorrhage. Non-significant associations with neurodevelopmental impairment were observed. CONCLUSIONS: Predictive factors for the development of BPD were respiratory support, feeding and different types of medication. Moreover, patients with BPD had a higher associated morbidity than those who did not develop BPD.

Nutrition in extremely low birth weight infants: impact on bronchopulmonary dysplasia.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a chronic lung disease that affects premature infants with multifactorial etiology. Some authors have considered malnutrition to be a major factor promoting BDP. The aim of our study was to examine the contribution of enteral and parenteral nutritional intake in the first 14 days of life to the development of bronchopulmonary dysplasia in a sample of preterm infants. METHODS: A prospective cohort study was conducted on all preterm infants born between 1 January 2008 and 31 December 2013. The nutritional parameters compiled included the cumulative amount of fluids, calories, proteins, carbohydrates and lipids consumed. Statistical analysis of the data consisted of a descriptive analysis, Mann-Whitney pairwise comparison test and logistic regression. RESULTS: The total caloric intake in the infants studied was significantly lower in patients with subsequent bronchopulmonary dysplasia (76.1 kCal/kg, 95% CI: 71.2-81.1 vs. 91.1 kCal/kg, 95% CI: 87.5-94.8). The intake of carbohydrate and fat was significantly lower in the patients with BPD (11.6 g/kg, 95% CI: 11.1-12.0 vs. 12.6 g/kg, 95% CI: 12.1-13; and 2.5 g/kg, 95% CI: 2.3-2.7 vs. 3.4 g/kg, 95% CI: 2.9-3.9, respectively). CONCLUSIONS: Our study shows that infants who develop bronchopulmonary dysplasia receive a lower enteral intake of calories and total lipids during the first 14 days of life.

Plasma non-esterified fatty acid levels in children and their relationship with sex steroids.

OBJECTIVE: Puberty is associated with decreased insulin sensitivity. Sexual hormones have been related with the onset of insulin resistance, but their relationship with non-esterified fatty acids (NEFA) remains unexplored. The aim of this study was to evaluate circulating NEFA levels in population-based samples of prepubertal children and adolescents and to analyze the association of NEFA with obesity, insulin resistance, and sexual hormones in adolescents. EXPERIMENTAL: The studied population included 854 randomly selected 6-8-year-old children and 822 children aged 12-16years. NEFA levels were determined using a commercial kit. Testosterone and estradiol levels were determined by RIA, and insulin and sex hormone binding protein by IRMA. HOMA was calculated as an indicator of insulin resistance. RESULTS: NEFA levels were lower in adolescents than in 6-8-year-old children, and decreased progressively with age between 12-year-olds and 16-year-olds. No significant differences in NEFA levels were observed between obese and non-obese adolescents. NEFA were not correlated with insulin or HOMA in 12-16-year-old girls, and appear negatively correlated with these variables in boys. Insulin and HOMA were negatively correlated with SHBG levels in both sexes adjusting by age but NEFA levels were not. CONCLUSIONS: NEFA levels decrease with age in adolescents and are not significantly increased in obese children, supporting the fact that the decreased insulin sensitivity at this age is not affecting NEFA metabolism. Although SHBG is related to insulin and HOMA independently of age in both sexes, SHBG levels are not associated with NEFA.

Influence of the interaction between the adiponectin G276T polymorphism and body mass index on lipid levels in healthy children.

Adiponectin is an adipose tissue-specific hormone which is inversely associated with metabolic alterations related to atherosclerosis. Polymorphisms in the adiponectin gene (AdipoQ) have been related to low adiponectin levels as well as several cardiovascular risk factors, but this association remains controversial. In our study we investigated the relationship between the AdipoQ T45G (rs: 2241766) and G276T (rs: 1501299) polymorphisms and adiponectin concentrations, blood pressure, and lipid and insulin levels, in a population-based sample of 12- to 16-year-old children. The study included 815 healthy Spanish children (388 boys and 427 girls). Plasma glucose and lipid levels were determined by standard methods. Insulin concentrations were measured by RIA, and serum adiponectin levels were determined by ELISA. The AdipoQ T45G and AdipoQ G276T polymorphisms were determined by TaqMan(®) allelic discrimination assays. ANOVA or t test allowed for comparison of the studied parameters across genotypes or genotype groups, respectively. A linear regression analysis was performed to examine the independent relationships of the lipid variables with BMI (body mass index), AdipoQ G276T polymorphism and the interaction between the two. When independently comparing the effect of these polymorphisms in normal-weight and overweight children, we observed that overweight boys carriers of the minor allele T had significantly lower TC, LDL-C and apo A-I levels than non-carriers, but these differences were not apparent in normal-weight boys. Furthermore, linear regression analysis demonstrated that interaction between the BMI and the AdipoQ G276T polymorphism is a significant factor explaining the variations of TC and LDL-C levels. To our knowledge, this is the first study to report an association between the AdipoQ G276T polymorphism and lipid levels in overweight boys alone, thereby suggesting that the influence of the AdipoQ polymorphisms on cardiovascular risk factors may be dependent on BMI.

Relationship of adiponectin with metabolic syndrome components in pubertal children.

OBJECTIVE: Adiponectin is an adipose tissue-derived adipocytokine which appears in decreased concentrations in obese patients and in several processes related to cardiovascular disease, such as type 2 diabetes or metabolic syndrome. The aim of this study was to analyze the relationship between adiponectin and components of metabolic syndrome (lipid profile, blood pressure, insulin and insulin resistance) in pubertal Spanish children. METHODS: The population-based sample included 810 healthy children (382 boys and 428 girls) 12-16 years of age. Anthropometric parameters and blood pressure were measured. Lipid levels were determined by standard methods, and insulin and adiponectin concentrations were measured by ELISA. Insulin resistance index was assessed by HOMA-IR. RESULTS: Adiponectin levels were negatively correlated with insulin and HOMA in both boys and girls, and remained significant after adjustment for BMI z-score in girls. After this adjustment, adiponectin maintained a positive correlation with HDL-cholesterol and HDL-phospholipids in both genders, and correlated with triglycerides in girls. Multiple linear regression analysis showed that, after adjustment for BMI z-score, adiponectin accounted for 15.8% of the variation of HDL-cholesterol in girls and for 5% of its variation in boys; meanwhile, it accounted for 15.8% and 12.7% of the variation of HDL-phospholipids in girls and boys, respectively. CONCLUSIONS: Adiponectin levels in 12- to 16-year-old children appear to be more strongly related to better lipid profile and insulin sensitivity in girls than in boys. Our study shows, for the first time to our knowledge, a significant positive correlation between adiponectin and HDL-phospholipids in pubertal children.

The apolipoprotein A5 (APOA5) gene predisposes Caucasian children to elevated triglycerides and vitamin E (Four Provinces Study).

OBJECTIVE: Apolipoprotein A-V plays an important role in lipid metabolism regulation, particularly modulating triglyceride levels, as has been shown by many association studies in adults. The aim of this study was to analyse the effect of APOA5 on lipid profiles and fat-soluble vitamins (due to its strong relationship with triglyceride metabolism) in children. METHODS: We determined polymorphisms -1131T>C and S19W in the APOA5 gene in 964 6-8-year-old participants of the 4P study and analysed the influence of the APOA5 gene on plasma lipid levels (total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides), apolipolipoproteins (apo A-I and apo B) and fat-soluble antioxidant vitamin (α-tocopherol, γ-tocopherol, lycopene, α-carotene, ß-carotene and retinol) levels. RESULTS: The allele frequencies of both polymorphisms were comparable to those described in adult Caucasian populations (0.08 and 0.07 for -1131T>C and S19W, respectively). Boys carrying the -1131C allele have a 12% increase in circulating triglyceride levels (p=0.016) and a 7% decrease in HDL phospholipid levels (p=0.016). Linked to its effect on triglycerides, boys with the -1131C allele also have a 5% increase in plasma α-tocopherol levels (p=0.032). This effect was not observed in female participants. Boys carrying the rare allele for the S19W polymorphism have a 4% increase in circulating cholesterol levels (p=0.045), whereas girls have a 9% increase in circulating triglyceride levels (p=0.029). Linked to its effect on triglycerides, female carriers of the rare allele for S19W also have a 6% increase in α-tocopherol levels (p=0.009). CONCLUSION: In children, the effect of APOA5 gene variants on triglyceride levels is related to gender, and because of the strong relationship between lipid metabolism and fat-soluble antioxidant vitamins, it also involves a significant elevation in α-tocopherol concentrations.

Influence of the leptin G-2548A polymorphism on leptin levels and anthropometric measurements in healthy Spanish adolescents.

Polymorphisms in the leptin gene (LEP) have been associated with leptin levels and obesity in some studies in adults though this link has scarcely been investigated in children. In our study, we examined the relationship of the LEP G-2548A polymorphism with leptin levels, anthropometric variables and body composition in a population-based sample of pubescent children. Our study included 880 healthy schoolchildren (419 males and 461 females), 12-16 years of age. Plasma leptin levels were determined by ELISA. The LEP polymorphism was determined by allelic discrimination TaqMan assay. Male carriers of the AA genotype had significantly lower plasma leptin levels than GA (p < 0.008) and GG (p < 0.001) carriers and significantly lower mean hip circumference (HC) values than GG carriers (p = 0.04). In girls, leptin levels were also lower in A-allele carriers than in GG carriers, and BMI and HC were significantly lower in AA carriers as compared with GG carriers. In addition, the frequency of the A allele was significantly lower (chi(2): 4.58, p = 0.032) in the OW-obese than in the NW group. In conclusion, the LEP G-2548A polymorphism is associated with variations in leptin levels, BMI and HC in Spanish pubertal children, and evidence suggests a link between the G allele and presence of overweight in girls.

Evaluación de las tendencias temporales en las variables antropométricas y lipídicas en niños de 12 a 15 años de edad. Estudio Cuatro Provincias en niños de edad puberal / Analysis of temporal trends of anthropometric and lipid variables in 12- to 15-year-old children. The Four Provinces Study in pubertal children

Introducción Las diferencias entre sexos en la incidencia de enfermedad cardiovascular se han asociado con un diferente perfil lipídico en hombres y mujeres, relacionado con cambios en las hormonas sexuales a lo largo de la vida. La pubertad es el periodo del desarrollo en el que empieza a manifestarse la influencia de estas hormonas sobre el perfil lipídico. Por ello, en nuestro estudio, hemos analizado la relación de los niveles de testosterona, estradiol y sex hormone binding globulin (SHBG, ‘globulina transportadora de hormonas sexuales’) con los cambios en las variables antropométricas y lipídicas que tienen lugar en la pubertad.Métodos La población de nuestro estudio la constituyen 370 escolares sanos (175 varones y 195 mujeres) de edades comprendidas entre 12–15 años. Los niveles plasmáticos de lípidos se determinaron mediante métodos estandarizados. Los niveles de testosterona y estradiol fueron determinados mediante radioimmuno ensayo y los niveles de SHBG mediante ensayo immunoradiométrico. Resultado sEn niños, importantes aumentos del peso y la altura a lo largo del periodo puberal se acompañaron de un aumento significativo de la testosterona y un descenso de la SHBG. El cHDL fue significativamente más bajo en varones de 15 años que en los más jóvenes y la apo A-I disminuyó progresivamente en función de la edad. En niñas, no se observaron diferencias significativas. En niños, el cHDL y la apo A-I correlacionaron negativamente con la testosterona y positivamente con la SHBG. La correlación entre apo A-I y SHBG continuó significativa (p<0,001) después de ajustar por el IMC. Conclusiones El importante descenso de los niveles de cHDL y apo A-I observado durante la pubertad en los varones de nuestro estudio se relaciona no solo con el aumento de los niveles de testosterona, sino también con la bajada de los niveles de SHBG, apoyando el papel de la SHBG en dicho descenso (AU)

Introduction Sex-related differences in the prevalence of coronary heart disease have been associated to different lipid profiles in men and women, related to changes in sex hormones throughout life. Puberty is a period of development in which the influence of sex hormones on the lipid profile is starting to take place. Thus, we aimed to analyze the relationship between sex hormones (testosterone, oestradiol and SHBG (sex hormone binding globulin)) and changes in anthropometric variables and plasma lipid levels during puberty. Methods Our population-based sample included 370 healthy pubertal children (175 males and 195 females), ranging from 12–15 years old. Plasma lipid levels were measured by standarized methods. Testosterone and oestradiol levels were determined by RIA and SHBG levels were determined by IRMA. Results In boys, significant increases in weight and height across the period were accompanied by an increase in testosterone and a decrease in SHBG levels. HDL-cholesterol levels were significantly lower in 15-year-old than in younger boys and apo A-I levels steeply decreased across the studied age groups. No significant changes were observed in girls. In boys, HDL-cholesterol and apo A-I levels correlated negatively with testosterone and positively with SHBG. Apo A-I levels remained significantly (p<0.001) correlated to SHBG after adjusting for BMI. Conclusions The significant decrease in HDL-cholesterol and apo A-I levels observed during puberty in boys in our study seemed to be related to both testosterone and SHBG levels, supporting the role of SHBG on this decrease of HDL-cholesterol levels occurring during puberty in boys (AU)

Leptin and adiponectin levels in pubertal children: relationship with anthropometric variables and body composition.

BACKGROUND: Adipocytokines play an important role in controlling energy homeostasis, and in various metabolic processes related to obesity. The aim of this study was to describe serum leptin and adiponectin concentrations in a sample of pubertal Spanish children and to evaluate their association with anthropometric parameters and body composition. METHODS: The study included 833 pubertal boys and girls. Serum leptin and adiponectin concentrations were determined by ELISA. RESULTS: Leptin concentrations were significantly higher (p<0.0001) in obese or overweight (OW) children compared with children with normal weight (NW). Adiponectin was significantly lower (p<0.01) in obese or OW girls compared with girls of NW, although these findings were not the same for boys. Weight, body mass index (BMI), waist circumference (WC), hip circumference (HC), and waist to hip ratio were significantly correlated (p<0.01) with leptin concentrations in both genders. Correlation of leptin with fat mass and % fat mass was strong, particularly in boys. The association of adiponectin concentrations with anthropometric variables was weaker in both genders. No significant correlations were found between adiponectin concentrations and fat mass or % fat mass. CONCLUSIONS: In summary, our study showed that, in pubertal children, leptin is related to weight, BMI, WC and HC and correlates even more strongly with % fat mass. However, adiponectin was weakly related to anthropometric variables and was not correlated with body fat.

Sex hormone-binding globulin levels and metabolic syndrome and its features in adolescents.

BACKGROUND: Low levels of sex hormone-binding globulin (SHBG) are associated with obesity, insulin resistance, and metabolic syndrome (MS) in men and women, and it has been suggested that SHBG could be a useful marker for MS risk. OBJECTIVE: The aim of this study was to analyze the relationship of SHBG levels with MS and its components in Spanish adolescents. METHODS: The sample population of this cross-sectional study was comprised of 386 male and 429 female adolescents, aged 12-16 yr. Anthropometric parameters and blood pressure (BP) were measured. Total cholesterol, high-density lipoprotein (HDL)-cholesterol, insulin, glucose, and SHBG levels were determined. The pediatric International Diabetes Federation (IDF) definition was used to classify adolescents for MS. RESULTS: SHBG levels were lower in adolescents with MS or with some MS features. More than 90% of the abdominally obese adolescents were in the lowest and medium SHBG tertiles. In girls, BP was significantly higher in the lowest SHBG tertile than in the two others, whereas in boys BP levels were significantly higher in the lowest and medium tertiles than in the highest one. Insulin levels and homeostasis model assessment (HOMA) index were also significantly higher in the lowest SHBG tertile than in the two others. CONCLUSIONS: The associations of SHBG with MS and its components, such as abdominal obesity, high BP or insulin levels, are already present in normal adolescents. This may suggest the possibility of using SHBG levels as a biomarker for MS risk in adolescents as well as adults.

Sex hormone-binding globulin and lipid profile in pubertal children.

Men and women have different lipid profiles throughout life, related to changes in sex hormones; and this has been associated with sex-related differences in the prevalence of coronary heart disease. The influence of sex hormone changes during puberty on the lipid profile has been reported, but levels of sex hormone-binding globulin (SHBG) (the specific plasma binding protein of sex hormones) have not been evaluated even though its regulatory role might be crucial. The aim of this study was to analyze the relationship between sex hormones and SHBG and changes in plasma lipid levels during puberty. Our population-based sample included 370 healthy schoolchildren (175 male and 195 female), ranging from 12 to 15 years old. High-density lipoprotein cholesterol (HDL-C) levels were significantly lower in 15-year-olds than in younger boys, and apolipoprotein (apo) A-I levels steeply decreased across the studied age groups. Parallel to these changes, testosterone levels increased whereas SHBG decreased as age increases in boys. In girls, no significant differences were observed in these variables among the age groups. Testosterone and SHBG were highly correlated with anthropometric variables. Sex hormone-binding globulin was negatively associated with triglycerides (TG) in both sexes, remaining statistically significant after further adjustment for age and body mass index (BMI) in girls. Sex hormone-binding globulin was the only predictive variable for HDL-C and TG in multiple linear regression analysis, after adjustment by BMI, in both sexes, accounting for 10% of the variance of HDL-C in boys and for around 5% of the variance of TG in both sexes. In boys, testosterone and SHBG remained significantly correlated to apo A-I levels, even after adjusting for age and BMI, and were the most important predictive variables for apo A-I in multiple linear regression analysis. In conclusion, SHBG levels are related to a decrease in HDL-C and apo A-I levels during puberty in boys and to a decrease in TG levels during puberty in both sexes.

Plasma homocysteine in adolescents depends on the interaction between methylenetetrahydrofolate reductase genotype, lipids and folate: a seroepidemiological study.

BACKGROUND: Many publications link high homocysteine levels to cardiovascular disease. In Spain there is little information on the prevalence of hyperhomocysteinaemia and associated vitamin factors among the general population, and less still among children. Cardiovascular risk factors in the childhood population may be related to the appearance of cardiovascular disease at adult age. The aim of this study is to establish a definition of hyperhomocysteinaemia in adolescents and to analyze the influence of vitamin and metabolic factors in homocysteine levels in this population group. METHODS: Descriptive, cross-sectional epidemiological study to estimate serum homocysteine, vitamin B12 and folate levels, as well as plasma total, HDL- and LDL- cholesterol in a schoolgoing population aged 13 to 17 years in Madrid, Spain.Spearman correlation analysis was performed to ascertain quantitative comparison, Pearson's chi2 test (frequency < 5, Fisher) was used for comparison of prevalences, Mann-Whitney U and Kruskal-Wallis test were used for comparison of means and Bonferroni correction was used for post-hoc tests. A multivariate logistic regression model was performed in the multivariate analysis. RESULTS: Based on the classic values for definition of hyperhomocysteinaemia in adults, prevalence of hyperhomocysteinaemia in the study population was: 1.26% for 15 mumol/L; and 2.52% for 12 mumol/L.Deficits in HDL cholesterol and serum folate levels yielded adjusted Odds Ratios (OR) for hyperhomocysteinemia of 2.786, 95% CI (1.089-7.126), and 5.140, 95% CI (2.347-11.256) respectively. Mutation of the methylenetetrahydrofolate reductase (MTHFR) C677T genotype also raises the risk of hyperhomocysteinaemia (CC-->CT: OR = 2.362; 95% CI (1.107-5.042) CC-->TT: OR = 6.124, 95% CI (2.301-16.303)) CONCLUSION: A good definition of hyperhomocysteinaemia in adolescents is the 90th percentile, equivalent to 8.23 mumol/L. Risk factors for hyperhomocysteinaemia are cHDL and folate deficiency, and the MTHFR C677T mutant genotype. No significant effect could be assessed for vitamin B12. Coexistence of all three factors increases the risk of suffering from hyperhomocysteinaemia 87-fold.

Fat intake influences the effect of the hepatic lipase C-514T polymorphism on HDL-cholesterol levels in children.

Polymorphisms in the hepatic lipase gene have been associated with variability in plasma HDL-C concentrations, but contradictory results have been reported regarding the effect of diet on this association in adults. In our study, we examined whether dietary fat intake modified the association between lipid levels and the C-514T polymorphism in the hepatic lipase gene (LIPC C-514T) in prepubescent children. The LIPC C-514T polymorphism was determined by PCR and restriction analysis in 1260 healthy school children, aged 6-8. Information on the children's nutrient intake was obtained by means of a validated food frequency questionnaire. We found that regardless of gender, carriers of the minor allele had significantly higher apo A-I levels compared to noncarrier subjects. The effect of the polymorphism, however, was modified by dietary fat intake. In boys, the presence of the LIPC C-514T polymorphism was associated with significantly higher HDL-C among children within the highest tertiles of total, saturated, monounsaturated, or polyunsaturated fat intake. Apo A-I levels were significantly higher in carriers of the LIPC C-514T polymorphism, but only among boys who consumed high total as well as monounsaturated fat and among girls who consumed high total, saturated, monounsaturated, and polyunsaturated fat. Our data show that dietary fat intake modifies the effect of the LIPC C-514T polymorphism on plasma HDL-C and apo A-I levels in prepubescent children, being associated with higher levels of HDL-C and apo A-I only when fat intake is high. This significant gene-nutrient interaction could help to explain inter-individual variations in the plasma lipid response to fat intake.

Genetic determinants of plasma HDL-cholesterol levels in prepubertal children.

INTRODUCTION: Genetic determinants have been related to variation of high-density lipoprotein cholesterol (HDL-C) levels, but the extension of this association remains controversial. In our study, we analyzed the contribution of several polymorphisms on HDL-C-related genes to variation of plasma HDL-C in prepubertal children. METHODS: We studied 1269 (641 males and 628 females) 6-8 years old healthy children, who participated in a cross-sectional study examining cardiovascular risk factors in Spain. Common genetic variants in the apolipoprotein AI, apolipoprotein AII, cholesteryl ester transfer protein (CETP), hepatic lipase, ATP-binding cassette transporter A1, and paraoxonase genes were determined by PCR. RESULTS: CETP TaqI B2 carrier girls had significantly higher HDL-C levels than B1B1 girls. B2B2 boys had significantly higher (p<0.001) HDL-C than B1B1and B1B2 boys. In linear regression analysis, CETP TaqIB appears as the main predictor of HDL-C plasma levels, accounting for 4.5% and 1.8% of HDL-C variation in girls and boys respectively. CONCLUSIONS: Our data showed that among the studied polymorphisms only the CETP TaqIB polymorphism contributes to the variation in HDL-C levels in prepubertal children, particularly in girls, but overall these polymorphisms explain a small part of the variation of HDL-C plasma levels at this age.

[Serum folate levels in adolescent population in Madrid, Spain]. / Folato sérico en población adolescente de la Comunidad de Madrid.

BACKGROUND AND OBJECTIVE: Serum folate concentrations in children are essential to establish values which allow to compare different regions or countries, and raise the possibility of fortifying diet with group B vitamins and folic acid as a secondary prevention against cardiovascular diseases. SUBJECTS AND METHOD: A cross-sectional epidemiological study was performed to assess serum folate levels in school children, aged 13-15 years, in Madrid. Folate and vitamin B12 determinations were determined in blood samples of fasting children. Genotype C677T of methylentetrahydrofolate reductase (MTHFR) enzyme was determined by polymerase chain reaction. RESULTS: Average folate levels obtained in our study were 7.83 nmol/l (95% confidence interval, 7.42 to 8.23 nmol/l). Median was 6.89 nmol/l (interquartilic range: 5.30 to -9.30 nmol/l). No statistically significant differences were found by gender, age or presence of menstruation. Serum folate concentration decreased significantly with the mutation of the C677T genotype for MTHFR. Prevalence of deficits of folate (< 5.3 nmol/l) was 23.8% and raised significantly with the mutation of the C677T genotype for MTHFR: 18.8% for CC, 20.4% for CT, and 46.7% for TT. This effect was mainly observed in girls after menstruation. CONCLUSIONS: Homozygosis mutation in C677T genotype of the enzyme MTHFR induces lower folate levels, mainly in girls after menstruation. 5.3 nmol/l is proposed as a threshold to define deficient serum folate levels in the Spanish adolescent population.

Folato sérico en población adolescente de la Comunidad de Madrid / Serum folate levels in adolescent population in Madrid, Spain

FUNDAMENTO Y OBJETIVO: Conocer los valores séricos de folato en niños es imprescindible para establecerunos percentiles que permitan realizar comparaciones entre regiones o países, asícomo para plantear la suplementación de la dieta con vitaminas del grupo B y ácido fólicocomo prevención secundaria frente a las enfermedades cardiovasculares. El objetivo de este estudioha sido analizar las concentraciones de folatos en adolescentes de la Comunidad de Madrid.SUJETOS Y MÉTODO: Se ha realizado un estudio epidemiológico descriptivo de tipo transversal conel fin de estimar los valores séricos de folato en la población escolar de 13 a 15 años de la Comunidadde Madrid. Se determinaron las concentraciones de folato y vitamina B12 en las muestrasde sangre de 311 adolescentes (141 niños y 170 niñas) obtenidas en ayunas. Se determinóel genotipo C677T de la enzima metilentetrahidrofolato reductasa (MTHFR) por reacción encadena de la polimerasa.RESULTADOS: Los valores medios de folato obtenidos en nuestro estudio fueron de 7,83 nmol/l(intervalo de confianza del 95%, 7,42-8,23 nmol/l) y la mediana fue de 6,89 nmol/l (recorridointercuartílico: 5,30-9,30 nmol/l).No se encontraron diferencias estadísticamente significativas por sexo, edad o presencia o ausenciade menstruación. La concentración sérica de folato disminuyó significativamente con lamutación del genotipo C677T de la enzima MTHFR. La prevalencia de valores deficitarios defolato (< 5,3 nmol/l) fue del 23,8% y aumentó significativamente con el genotipo C677TMTHFR mutado en homocigosis: un 18,8% para CC; un 20,4% para CT, y un 46,7% para TT.Este aumento se produjo en mayor medida en las mujeres a partir de la primera menstruación.CONCLUSIONES: El genotipo mutado C677T en homocigosis de la enzima MTHFR produce déficitde folato, especialmente en mujeres a partir de la pubertad. Se propone el valor de 5,3 nmol/lcomo posible punto de corte para definir el déficit de folato sérico en la población adolescentede nuestro país

BACKGROUND AND OBJECTIVE: Serum folate concentrations in children are essential to establish valueswhich allow to compare different regions or countries, and raise the possibility of fortifyingdiet with group B vitamins and folic acid as a secondary prevention against cardiovascular diseases.SUBJECTS AND METHOD: A cross-sectional epidemiological study was performed to assess serum folatelevels in school children, aged 13-15 years, in Madrid. Folate and vitamin B12 determinationswere determined in blood samples of fasting children. Genotype C677T of methylentetrahydrofolatereductase (MTHFR) enzyme was determined by polimerase chain reaction.RESULTS: Average folate levels obtained in our study were 7.83 nmol/l (95% confidence interval,7.42 to 8.23 nmol/l). Median was 6.89 nmol/l (interquartilic range: 5.30 to –9.30 nmol/l).No statistically significant differences were found by gender, age or presence of menstruation.Serum folate concentration decreased significantly with the mutation of the C677T genotypefor MTHFR. Prevalence of deficits of folate (< 5.3 nmol/l) was 23.8% and raised significantlywith the mutation of the C677T genotype for MTHFR: 18.8% for CC, 20.4% for CT, and46.7% for TT. This effect was mainly observed in girls after menstruation.CONCLUSIONS: Homozygosis mutation in C677T genotype of the enzyme MTHFR induces lowerfolate levels, mainly in girls after menstruation. 5.3 nmol/l is proposed as a threshold to definedeficient serum folate levels in the Spanish adolescent population