Pregnancy homocysteine and cobalamin status predict childhood metabolic health in the offspring.

BACKGROUND: Inadequate pregnancy cobalamin status has been associated with adverse offspring metabolic health in Indian and Nepalese studies. Studies of pregnancy cobalamin status and mid-childhood health outside of Asia are scarce. METHODS: Associations between pregnancy fasting plasma total homocysteine (tHcy), cobalamin status (plasma cobalamin, holotranscobalamin (holoTC), methylmalonic acid (MMA)) and mid-childhood metabolic score (MetSco) ((including fat mass index (zFMI), homeostatic model assessment of insulin resistance (zHOMA-IR) and dyslipidemia (zTG - zHDLc)/2) z-scores)) were investigated in a prospective study of 293 mother-child dyads. RESULTS: Highest versus low-mid pregnancy tHcy tertile was associated with higher mid-childhood MetSco, specifically with higher child zFMI. Stratifying by sex, the maternal tHcy-child MetSco association was limited to boys and confirmed for zFMI and zHOMA-IR. The maternal tHcy-child zFMI association was not mediated by birth weight z-score. First trimester plasma cobalamin was not associated with child outcomes, but other indicators of cobalamin status were. Lowest versus mid-high plasma holoTC tertile was associated with MetSco (specifically zFMI and zHOMA-IR) and highest versus low-mid plasma MMA tertile with higher MetSco and dyslipidemia in boys. CONCLUSIONS: Moderately elevated pregnancy tHcy and low cobalamin status were associated with mid-childhood metabolic score in boys. The pregnancy tHcy-child zFMI association was not mediated by birth weight. IMPACT: Fasting plasma total homocysteine (tHcy) during pregnancy and low cobalamin status during early pregnancy are associated with mid-childhood metabolic score and its components in the offspring. These findings were only significant in male offspring. The study provides new evidence that impaired one carbon metabolism during pregnancy is associated with negative health outcomes in the offspring, in a population with low prevalence of cobalamin deficiency. The maternal-offspring associations were observed in the functional markers of cobalamin status (holotranscobalamin and methylmalonic acid) and tHcy, not with plasma cobalamin concentration. Screening for low pregnancy cobalamin status should be considered.

Homocysteine, the methylenetetrahydrofolate reductase 677C>T polymorphism and hypertension: effect modifiers by lifestyle factors and population subgroups.

Evidence linking fasting plasma total homocysteine (tHcy) and methylenetetrahydrofolate reductase (MTHFR) 677C>T genotype with hypertension is inconsistent. Differences in B vitamin status, other lifestyle factors or their consideration in analyses might explain this. We investigated these associations in the absence of mandatory fortification with folic acid and B vitamin supplement use. A cross-sectional study was conducted in 788 adults, aged 18-75 years, randomly selected from three Catalonian town population registers. Fasting plasma folate, cobalamin, tHcy, erythrocyte folate, erythrocyte glutathione reductase activation coefficient (EGRAC, functional riboflavin status indicator; increasing EGRAC indicates worsening riboflavin status), MTHFR 677C>T and solute carrier family 1 (SLC19A1) 80 G>A genotypes were determined. Medical history and lifestyle habits were recorded. Principal tHcy determinants differed between women (age, plasma folate, plasma cobalamin, cigarettes/d) and men (MTHFR 677TT genotype, plasma folate, plasma cobalamin and CT genotype). The MTHFR 677C>T polymorphism-tHcy association (ß standardised regression coefficients) was stronger in male smokers (0·52, P < 0·001) compared with non-smokers (0·21, P = 0·001) and weaker in participants aged >50 years (0·19, P = 0·007) compared with ≤50 years (0·31, P < 0·001). Hypertension was more probable in the third tHcy tertile compared with other tertiles (OR 1·9; 95 % CI 1·2, 3·0), and in participants aged ≤50 years, for the MTHFR 677TT genotype compared with the CC genotype (OR 4·1; 95 % CI 1·0, 16·9). EGRAC was associated with increased probability of hypertension in participants aged >50 years (OR 6·2; 95 % CI 1·0, 38·7). In conclusion, moderately elevated tHcy and the MTHFR 677CT genotype were associated with hypertension. The MTHFR 677C>T genotype-hypertension association was confined to adults aged ≤50 years.

The effect of prenatal smoke exposure on child neuropsychological function: a prospective mother-child cohort study.

Objective: To study prospectively the effect of prenatal smoke exposure (PSE) on child neuropsychological function and intelligence quotient (IQ).Background: PSE has been associated with adverse effects on child neurodevelopment. However, some studies reported that these associations disappear after adjustment for potential confounders.Methods: A cohortof 248 mothers-child dyad was followed from the first trimester of pregnancy until children were 7.5 years old. PSE was recorded during pregnancy by questionnaire and plasma cotinine. The Wechsler Intelligence Scale for Children, the Neuropsychological Assessment of Executive Functions for Children (ENFEN) and the School Neuropsychological Maturity Questionnaire were administered at 7.5 years of age. The effect of PSE on child IQ and neuropsychological function was assessed with ANCOVA, adjusting for obstetric, neonatal and sociodemographic factors.Results: Children whose mothers smoked throughout pregnancy scored lower in interference (ENFEN) compared to unexposed children (F = 4.1; p = .008). The results showed no differences in other executive functions, verbal and visual memory and IQ between the PSE groups.Conclusion: PSE had little effect on child neuropsychological outcome and was limited to mental flexibility. Nevertheless, these findings support further efforts aimed at encouraging mothers to quit smoking in pregnancy.

Moderately elevated preconception fasting plasma total homocysteine is a risk factor for psychological problems in childhood.

OBJECTIVE: We investigated the effect of maternal preconception fasting plasma total homocysteine (tHcy) on psychological problems in children aged 6 years from normal pregnancies. DESIGN: A longitudinal study was carried out from preconception, throughout each trimester of pregnancy, until 6 years of age in the offspring. Fasting blood samples at 2-10 weeks preconception and non-fasting samples at birth were collected. Parents completed the Child Behaviour Checklist (CBCL) and teachers the Inattention-Overactivity with Aggression (IOWA) scale for the 6-year-old children. SETTING: Elevated tHcy during pregnancy has been associated with several adverse outcomes and with neurodevelopmental impairment in the offspring.ParticipantsThe initial sample consisted of 139 healthy non-pregnant women who were planning on becoming pregnant. Eighty-one mother-child dyads were followed from preconception until 6 years of age. RESULTS: After adjusting for covariables, multiple linear regression models showed that higher preconception tHcy was associated with higher scores in internalizing dimension (ß=0·289; P=0.028), specifically in withdrawn behaviour (ß=0·349; P=0·009), anxiety/depression (ß=0·303; P=0·019) and social problems (ß=0·372; P=0·009). Aggressive behaviour in the school setting was higher in children whose mothers had higher preconception tHcy (ß=0·351; P=0·014). CONCLUSIONS: Moderately elevated preconception tHcy may increase the risk of psychological problems in offspring during childhood. These findings add to the evidence that maternal nutritional status, even before being pregnant, can affect later offspring health and may be important to consider when developing future public health policy.

Moderately elevated maternal homocysteine at preconception is inversely associated with cognitive performance in children 4 months and 6 years after birth.

Prenatal methyl donor deficiency leads to homocysteine accumulation in the brain and impaired neurodevelopment in rats. We investigated the effect of moderately elevated preconception fasting total plasma homocysteine (tHcy) on child neurodevelopment in a prospective study of 67 and 76 mother-child pairs at 4 months and 6 years of age, respectively. Fasting blood samples at 2-10 weeks preconception, from the cord (nonfasting) and the mother and child 6 years after birth, were collected. Psychomotor and mental development were assessed at 4 months using the Bayley Scale of Infant Development (BSID) and cognitive development at 6 years using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI). Highest tertile preconception tHcy (≥9.04 µmol/L) was categorized as moderately elevated and low-mid tertile tHcy as normal. Children, born to mothers with moderately elevated compared to normal preconception tHcy, scored lower [mean (95% CI)] in the BSID psychomotor [115 (105, 124) vs. 126 (121, 130), p = 0.03] and mental [101 (93, 109) vs. 113 (107, 119), p = 0.03] development tests. Multiple logistic regression analysis showed that moderately elevated compared to normal preconception tHcy was associated with greater probability, OR (95%CI), of scoring in the lowest tertile for BSID psychomotor development (≤120): 4.0 (1.1, 14.3) and lowest tertiles for WPPSI full (≤111), verbal (≤104) and performance (≤111), intellectual quotient: 6.0 (1.5, 23.7), 3.5 (1.1, 11.2) and 4.1 (1.1, 15.7), respectively. We conclude that moderately elevated preconception tHcy is inversely associated with psychomotor and cognitive development scores in infants and children.

Common Polymorphisms That Affect Folate Transport or Metabolism Modify the Effect of the MTHFR 677C > T Polymorphism on Folate Status.

BACKGROUND: Although combinations of biologically relevant polymorphic variants affect folate status, most studies have focused on the effects of individual polymorphisms; however, these effects may be altered by interactions between polymorphisms. OBJECTIVE: We investigated the individual and combined effects of polymorphisms that affect folate transport or metabolism on folate status. METHODS: The associations between the methylenetetrahydrofolate reductase (MTHFR) 677C > T, methionine transferase reductase (MTRR) 66A > G, MTRR 524C > T, 5,10-methylenetetrahydrofolate dehydrogenase-5,10-methylenetetrahydrofolate cyclohydrolase-10-formyltetrahydrofolate synthetase (MTHFD1) 1958G > A, MTHFD1 -105C > T, dihydrofolate reductase (DHFR) 19-bp insertion/deletion, and solute carrier family 19A, member 1 (SLC19A1) 80G > A polymorphisms and fasting plasma folate (PF), red cell folate (RCF), and plasma total homocysteine (tHcy) were tested by ANCOVA and Cox regression analysis in 781 Spanish adults. RESULTS: Folate deficiency (PF <7 nmol/L) was observed in 18.8% of the participants. Geometric mean PF (nmol/L) was lower in MTHFR 677TT (10.0; 95% CI: 9.2, 11.9) compared with 677CC (12.4; 95% CI: 11.6, 13.2; P < 0.001). RCF (nmol/L) was lower in MTHFR 677TT (652; 95% CI: 611, 695) compared with 677CC (889; 95% CI: 851, 929; P < 0.001) and in SLC19A1 80AA (776; 95% CI: 733, 822) compared with 80GG (861; 95% CI: 815, 910; P < 0.01). RCF and tHcy (µmol/L) did not differ in MTHFR + MTRR 677TT/524TT compared with 677CC/524CC: 780 (95% CI: 647, 941) compared with 853 (95% CI: 795, 915; P = 0.99) and 10.2 (95% CI: 8.4, 12.3) compared with 8.9 (95% CI: 8.5, 9.4; P = 0.99), respectively. The RR of lowest-tertile RCF (≤680 nmol/L) was 2.1 (95% CI: 1.0, 4.5) for MTHFR + MTRR 677TT/66GG compared with 677CC/66AA, 2.2 (95% CI: 1.2, 4.1) for MTHFR + MTHFD1 677TT/1958AA compared with 677CC/1958GG, 2.9 (95% CI: 1.4, 6.0) for MTHFR + MTHFD1 677TT/-105TT compared with 677CC/-105CC, and 3.5 (95% CI: 1.5, 8.1) for MTHFR + SLC19A1 677TT/80AA compared with 677CC/80GG. Confining the analysis to the MTHFR 677TT genotype, the risk of lowest-tertile RCF was reduced for MTHFR + MTRR 677TT/66GG compared with 677TT/66AA (RR: 0.5; 95% CI: 0.3, 0.9). CONCLUSIONS: Folate status was lower in the MTHFR 677TT and SLC19A1 80AA genotypes compared with corresponding reference genotypes. Low folate status risk associated with the MTHFR 677TT genotype varied depending on its combination with other polymorphisms.

Dietary intake of vitamin K is inversely associated with mortality risk.

Vitamin K has been related to cardiovascular disease and cancer risk. However, data on total mortality are scarce. The aim of the present study was to assess the association between the dietary intake of different types of vitamin K and mortality in a Mediterranean population at high cardiovascular disease risk. A prospective cohort analysis was conducted in 7216 participants from the PREDIMED (Prevención con Dieta Mediterránea) study (median follow-up of 4.8 y). Energy and nutrient intakes were evaluated using a validated 137-item food frequency questionnaire. Dietary vitamin K intake was calculated annually using the USDA food composition database and other published sources. Deaths were ascertained by an end-point adjudication committee unaware of the dietary habits of participants after they had reviewed medical records and linked up to the National Death Index. Cox proportional hazard models were fitted to assess the RR of mortality. Energy-adjusted baseline dietary phylloquinone intake was inversely associated with a significantly reduced risk of cancer and all-cause mortality after controlling for potential confounders (HR: 0.54; 95% CI: 0.30, 0.96; and HR: 0.64; 95% CI: 0.45, 0.90, respectively). In longitudinal assessments, individuals who increased their intake of phylloquinone or menaquinone during follow-up had a lower risk of cancer (HR: 0.64; 95% CI: 0.43, 0.95; and HR: 0.41; 95% CI: 0.26, 0.64, respectively) and all-cause mortality (HR: 0.57; 95% CI: 0.44, 0.73; and HR: 0.55; 95% CI: 0.42, 0.73, respectively) than individuals who decreased or did not change their intake. Also, individuals who increased their intake of dietary phylloquinone had a lower risk of cardiovascular mortality risk (HR: 0.52; 95% CI: 0.31, 0.86). However, no association between changes in menaquinone intake and cardiovascular mortality was observed (HR: 0.76; 95% CI: 0.44, 1.29). An increase in dietary intake of vitamin K is associated with a reduced risk of cardiovascular, cancer, or all-cause mortality in a Mediterranean population at high cardiovascular disease risk. This trial was registered at http://www.controlled-trials.com as ISRCTN35739639.

Folate deficiency in rat pups during weaning causes learning and memory deficits.

Folate is essential for fetal development, and its deficiency during gestation causes behavioural deficits in the offspring. The present study investigated its influence during weaning on brain function in the pups of rats that were put on a folate-deficient (FD) diet on postnatal day (PND) 1. Systemic folate deficiency in pups on the FD diet (n 15) was evident from the dramatically lower hepatic folate concentrations (median 23·7, range 8·1-48·4 ng/mg protein) and higher homocysteine concentrations (median 27·7, range 14·7-45·5 pmol/mg protein), respectively, compared with those of pups on the normal diet (ND; n 9) (median 114·5, range 64·5-158·5 ng/mg protein and median 15·5, range 11·6-18·9 pmol/mg protein) on PND 23. Brain folate concentrations although low were similar in pups on the FD diet (median 10·5, range 5·5-24·5 ng/mg protein) and ND (median 11·1, range 7·1-24·2 ng/mg protein). There was a high accumulation of homocysteine in the brain of FD pups, mostly in the hippocampus (median 58·1, range 40·8-99·7 pmol/mg protein) and cerebellum (median 69·1, range 50·8-126·6 pmol/mg protein), indicating metabolic folate deficiency despite normal brain folate concentrations. Developmental deficits or autistic traits were more frequent in the FD group than in the ND group and repetitive self-grooming occurred, on average, three times (range 1-8) v. once (range 0-3) during 5 min, respectively. Long-term memory or spatial learning and set-shifting deficits affected 12 to 62% of rats in the FD group compared with none in the ND group. Post-weaning folic acid supplementation did not correct these deficits. These observations indicate that folate deficiency during weaning affects postnatal development even when gestational folate supply is normal.

Validation of a Mexican food photograph album as a tool to visually estimate food amounts in adolescents.

The aim of the present study was to validate a food photograph album (FPA) as a tool to visually estimate food amounts, and to compare this estimation with that attained through the use of measuring cups (MC) and food models (FM). We tested 163 foods over fifteen sessions (thirty subjects/session; 10-12 foods presented in two portion sizes, 20-24 plates/session). In each session, subjects estimated food amounts with the assistance of FPA, MC and FM. We compared (by portion and method) the mean estimated weight and the mean real weight. We also compared the percentage error estimation for each portion, and the mean food percentage error estimation between methods. In addition, we determined the percentage error estimation of each method. We included 463 adolescents from three public high schools (mean age 17·1 (sd 1·2) years, 61·8 % females). All foods were assessed using FPA, 53·4 % of foods were assessed using MC, and FM was used for 18·4 % of foods. The mean estimated weight with all methods was statistically different compared with the mean real weight for almost all foods. However, a lower percentage error estimation was observed using FPA (2·3 v. 56·9 % for MC and 325 % for FM, P< 0·001). Also, when analysing error rate ranges between methods, there were more observations (P< 0·001) with estimation errors higher than 40 % with the MC (56·1 %), than with the FPA (27·5 %) and FM (44·9 %). In conclusion, although differences between estimated and real weight were statistically significant for almost all foods, comparisons between methods showed FPA to be the most accurate tool for estimating food amounts.

The Reproducibility and Relative Validity of a Food Frequency Questionnaire for Identifying Iron-Related Dietary Patterns in Pregnant Women.

Analyzing pregnant women's iron intake using dietary patterns would provide information that considers dietary relationships with other nutrients and their sources. The objective of this study was to evaluate the reproducibility and relative validity of a Qualitative Food Frequency Questionnaire to identify iron-related dietary patterns (FeP-FFQ) among Mexican pregnant women. A convenience sample of pregnant women (n = 110) completed two FeP-FFQ (FeP-FFQ1 and FeP-FFQ2) and a 3-day diet record (3DDR). Foods appearing in the 3DDR were classified into the same food groupings as the FeP-FFQ, and most consumed foods were identified. Exploratory factor analysis was used to determine dietary patterns. Scores were compared (FeP-FFQ for reproducibility and FeP-FFQ1 vs. 3DDR for validity) through intraclass correlation coefficients (ICC), cross-classification, Bland−Altman analysis, and weighed Cohen kappa (κw), using dietary patterns scores tertiles. Two dietary patterns were identified: "healthy" and "processed foods and dairy". ICCs (p < 0.01) for "healthy" pattern and "processed foods and dairy" pattern were 0.76 for and 0.71 for reproducibility, and 0.36 and 0.37 for validity, respectively. Cross-classification and Bland−Altman analysis showed good agreement for reproducibility and validity; κw values showed moderate agreement for reproducibility and low agreement for validity. In conclusion, the FeP-FFQ showed good indicators of reproducibility and validity to identify dietary patterns related to iron intake among pregnant women.

Changes in the Epidemiology of Diabetic Retinopathy in Spain: A Systematic Review and Meta-Analysis.

BACKGROUND: The aim of the present study was to determine the prevalence and incidence of diabetic retinopathy (DR) and its changes in the last 20 years in type 2 diabetes mellitus (T2DM) patients in Spain. METHODS: A systematic review with a meta-analysis was carried out on the studies published between 2001-2020 on the prevalence and incidence of DR and sight-threatening diabetic retinopathy (STDR) in Spain. The articles included were selected from four databases and publications of the Spanish Ministry of Health and Regional Health Care System (RHCS). The meta-analysis to determine heterogeneity and bias between studies was carried out with the MetaXL 4.0. RESULTS: Since 2001, we have observed an increase in the detection of patients with DM, and at the same time, screening programs for RD have been launched; thus, we can deduce that the increase in the detection of patients with DM, many of them in the initial phases, far exceeds the increased detection of patients with DR. The prevalence of DR was higher between 2001 and 2008 with values of 28.85%. These values decreased over the following period between 2009 and 2020 with a mean of 15.28%. Similarly the STDR prevalence decrease from 3.67% to 1.92% after 2008. The analysis of the longitudinal studies determined that the annual DR incidence was 3.83%, and the STDR annual incidence was 0.41%. CONCLUSION: In Spain, for T2DM, the current prevalence of DR is 15.28% and 1.92% forSTDR. The annual incidence of DR is 3.83% and is 0.41% for STDR.

Association between a healthy lifestyle and general obesity and abdominal obesity in an elderly population at high cardiovascular risk.

BACKGROUND: Diet, smoking and physical activity are important modifiable lifestyle factors that can influence body weight and fat accumulation. We assessed the relationship between lifestyle and obesity risk in a baseline analysis of the PREDIMED study, a randomized dietary primary prevention trial conducted in Spain. METHODS: 7000 subjects at high cardiovascular risk were assessed cross-sectionally. A healthy lifestyle pattern (HLP) was determined using a score including: adherence to the Mediterranean diet, moderate alcohol consumption, expending ≥200 kcal/day in leisure-time physical activity, and non-smoking. RESULTS: Inverse linear trends were observed between the HLP-score and body-mass-index (BMI) or waist circumference (p<0.001). The BMI and waist circumference of participants with a HLP-score=4 were, respectively, 1.3 kg/m(2) (95% CI: 0.9 to 1.7) and 4.3 cm (3.1 to 5.4) lower than those of subjects with an HLP≤1. The odds ratios of general obesity and abdominal obesity for an HLP score of 4 compared to an HPL score≤1 were 0.50 (0.42 to 0.60) and 0.51 (0.41 to 0.62), respectively. CONCLUSION: A combination of four healthy lifestyle behaviors was associated with a lower prevalence of general obesity and abdominal obesity in Mediterranean elderly subjects at high cardiovascular risk.

Neonatal Behavioral Assessment Scale as a predictor of cognitive development and IQ in full-term infants: a 6-year longitudinal study.

AIM: To evaluate the predictive capacity of neonatal behaviour on infant mental and psychomotor development at 4 and 12 months, and infant intelligence at 6 years. METHOD: Eighty full-term newborns were followed from 3 days until 6 years. Neonatal behaviour was assessed by the Neonatal Behavior Assessment Scale (NBAS) at 3 days postpartum, infant mental and psychomotor development was assessed by the Bayley Scales for Infant Development at 4 and 12 months, and child intelligence was assessed by the Wechsler Preschool and Primary Scale of Intelligence at 6 years. RESULTS: Neonatal general irritability was the predictor of mental development at 12 months. Self-regulation behaviours were predictors of psychomotor development at 4 and 12 months and verbal and total intelligence quotient at 6 years. Neonatal orientation was a predictor of performance Wechsler subtests related to visomotor abilities and attention. CONCLUSIONS: Neonatal self-regulation behaviours were the best predictors of infant development and intelligence. We suggest that the NBAS could be a useful tool to observe behaviours related to later development in healthy infants.

Association between birthweight, cardiovascular risk factors, and depression in young Mexican adults.

INTRODUCTION: Background: the aim of this study was to investigate the association between birthweight, cardiovascular disease (CVD) risk factors, and depression in young Mexican adults. Methods: birthweight reports, family history of CVD and diabetes-related diseases, anthropometrics, serum lipid profile (total cholesterol [TC], triglycerides [TG], high-density lipoprotein-cholesterol [HDL-C], low-density lipoprotein-cholesterol [LDL-C], and very-low density lipoprotein-cholesterol [VLDL-C]), and depressive symptoms were measured in 778 subjects of the UP-AMIGOS cohort study. To investigate the association between birthweight categories and CVD risk factors and depression, a one-way analysis of variance with post-hoc test was performed of quantitative variables, and 2 test for qualitative variables. Results: mean age was 17.8 years and 469 (60.3 %) of patients were female (n = 469, 60.3 %). The percentage of patients with low birthweight (LBW) was 8.1 % (n = 63), and 3.3 % (n = 26) reported high birthweight (HBW). Young adults with HBW were associated with elevated diastolic blood pressure (DBP), and high weight and body mass index (BMI) when compared to LBW subjects, the difference being statically significant (p < 0.05). Birthweight had no significant association with depression (p > 0.67). Conclusion: the findings from this population-based study revealed a positive relation between birthweight categories and some CVD risk factors. Depression was not related to birthweight.

INTRODUCCIÓN: Introducción: el objetivo de este estudio fue investigar la asociación entre el peso al nacer, los factores de riesgo de las enfermedades cardiovasculares (ECV) y la depresión en adultos mexicanos jóvenes. Métodos: se obtuvieron como variables el peso al nacer, los antecedentes heredofamiliares de ECV y diabetes, la antropometría, el perfil lipídico (colesterol total [CT], triglicéridos [TG], lipoproteína de alta densidad [C-HDL], lipoproteína de baja densidad [C-LDL] y lipoproteína de muy baja densidad [C-VLDL]) y los síntomas de depresión de 778 participantes del estudio de cohortes UP-AMIGOS. Se realizó un análisis de la varianza de 1 vía con pruebas post hoc para investigar la asociación entre las categorías de peso al nacer, riesgo ECV y depresión entre las variables cuantitativas; para las variables cualitativas se realizaron pruebas del 2. Resultados: la edad media fue de 17,8 años y 469 (60,3 %) de los participantes eran mujeres. El porcentaje de pacientes con bajo peso al nacer (BPN) fue del 8,1 % (n = 63) y el 3,3 % (n = 26) tenían elevado peso al nacer (EPN). Se encontró una asociación en el grupo de EPN con la elevación de la presión arterial diastólica (PAS), el peso y el índice de masa corporal (IMC) al compararlo con el grupo de BPN, con una diferencia significativa de p < 0,05. No se encontró ninguna asociación entre el peso al nacer y la depresión (p > 0,67). Conclusiones: se encontró una relación positiva entre las categorías de peso al nacer con algunos factores de riesgo de ECV. La depresión no se asoció con el peso al nacer según los resultados de este estudio poblacional.

Relative validity of a semi-quantitative food-frequency questionnaire in an elderly Mediterranean population of Spain.

The aim of the present study was to assess reproducibility and relative validity of a self-administered FFQ used in the PREDIMED Study, a clinical trial for primary prevention of CVD by Mediterranean diet in a population at high cardiovascular risk. The FFQ was administered twice (FFQ1 and FFQ2) to explore reproducibility at 1 year. Four 3 d dietary records (DR) were used as reference to explore validity; participants therefore recorded their food intake over 12 d in the course of 1 year. The degree of misclassification in the FFQ was also evaluated by a contingency table of quintiles comparing the information from the FFQ2 and the DR. A total of 158 men and women (aged 55-80 years) were asked not to modify their dietary habits during the study period. Reproducibility for food groups, energy and nutrient intake, explored by the Pearson correlation coefficient (r) ranged 0.50-0.82, and the intraclass correlation coefficient (ICC) ranged from 0.63 to 0.90. The FFQ2 tended to report higher energy and nutrient intake than the DR. The validity indices of the FFQ in relation to the DR for food groups and energy and nutrient intake ranged (r) from 0.24 to 0.72, while the range of the ICC was between 0.40 and 0.84. With regard to food groups, 68-83 % of individuals were in the same or adjacent quintile in both methods, a figure which decreased to 55-75 % for energy and nutrient intake. We concluded that FFQ measurements had good reproducibility and a relative validity similar to those of FFQ used in other prospective studies.

Moderately elevated first trimester fasting plasma total homocysteine is associated with increased probability of miscarriage. The Reus-Tarragona Birth Cohort Study.

The association between elevated early pregnancy fasting plasma total homocysteine (tHcy) and miscarriage risk was investigated prospectively in participants (n = 544) from the Reus-Tarragona Birth Cohort study. Pregnancy was confirmed before 12 gestational weeks (GW) by ultrasound scan and a fasting blood sample collected. Pregnancies with complications other than miscarriages were excluded. Miscarriages were diagnosed by ultrasound scan and gestational age at the time of miscarriage estimated by embryo size, where possible. Cases in which blood samples were collected more than a week after the miscarriage, or the miscarriage was of known cause, were excluded. Fasting plasma folate, vitamin B12, tHcy, cotinine (biomarker of smoking), red blood cell (RBC) folate, MTHFR 677C > T (rs1801133) and SLC19A1 80G>A (rs1051266) genotypes were determined. The exposed group consisted of participants with first trimester tHcy ≥ P90 (7.1 µmol/L) (n = 57) and unexposed of those with tHcy < P90 (n = 487). Adherence to folic acid supplement recommendations, plasma folate, plasma vitamin B12, RBC folate and prevalence of optimal RBC folate status (≥ 906 µmol/L) were lower in the exposed compared to unexposed group. The prevalences of the MTHFR 677 TT genotype and miscarriage were higher in the exposed group. The relative risks (95% CI) of pregnancy ending in miscarriage were 2.5 (1.1, 5.7) and 2.1 (1.0, 4.5) for participants in the high tHcy and suboptimal RBC folate groups (compared to the reference groups) respectively. Adherence to folic acid supplement recommendations was positively associated, while the MTHFR 677 TT versus CC genotype and smoking versus non-smoking were negatively associated, with RBC folate status.

Efficacy of liposomal amphotericin B combined with gamma interferon or granulocyte-macrophage colony-stimulating factor for treatment of systemic zygomycosis in mice.

Granulocyte-macrophage colony-stimulating factor enhanced the efficacy of liposomal amphotericin B (LAMB) in a murine model of disseminated infection by Rhizopus oryzae, significantly prolonging survival and reducing tissue burden. The use of gamma interferon (IFN-gamma) alone was ineffective, and IFN-gamma combined with LAMB did not improve the results obtained with LAMB alone.

High milk consumers have an increased risk of folate receptor blocking autoantibody production but this does not affect folate status in Spanish men and women.

Folate receptor (FR)-blocking autoantibodies (FR-autoantibodies) have been reported in women with neural tube defect-affected pregnancies and subfertility and in children with progressive neurodevelopment disorders. We investigated their prevalence and association with folate status and milk intake in adults unexposed to folic acid fortification. A cross-sectional study of a randomly selected representative sample of a Spanish population (aged 18-75 y) stratified by age and gender was performed. Plasma and red cell folate, plasma cobalamin, fasting plasma total homocysteine (tHcy) concentration, methylenetetrahydrofolate reductase C677T polymorphism, and FR-autoantibody titer were determined in blood samples from 787 fasting participants. Lifestyle data were collected and milk intake estimated from a 3-d dietary record. FR-autoantibody prevalence was 7.2% [0.30 +/- 0.27 nmol (mean +/- SD) FR blocked/L], equally affecting men and women of all ages. Plasma and red cell folate and tHcy did not differ between carriers and noncarriers of FR-autoantibodies. Milk intake was higher in carriers (225 +/- 199 g/d) than in noncarriers (199 +/- 147 g/d) (P < 0.01). The risk of having FR-autoantibodies increased progressively with increasing quintile of milk intake and was significant in the highest quintile (> or =307 g/d) compared with the lowest (< or =67 g/d) [odds ratio (OR), 2.41 [95% CI: 1.02, 5.69]; P < 0.05; linear trend, P = 0.02]. We concluded that FR-autoantibodies occur in men and women of all ages and do not affect indicators of folate status such as plasma and red cell folate and tHcy. Higher milk intake is associated with increased risk of having FR-autoantibodies.

Early pregnancy folate-cobalamin interactions and their effects on cobalamin status and hematologic variables throughout pregnancy.

Background: Periconception folic acid supplementation is widespread, but how it interacts with cobalamin status is rarely considered. Objective: The aim of this study was to investigate whether first-trimester folate-cobalamin interactions affect pregnancy cobalamin status, hematologic variables, and pregnancy outcomes. Design: In the longitudinal Reus-Tarragona Birth Cohort study from <12 gestational weeks throughout pregnancy, fasting plasma and red blood cell (RBC) folate, plasma cobalamin, holotranscobalamin (holoTC), methylmalonic acid (MMA), total homocysteine (tHcy), hemoglobin, mean cell volume (MCV), postglucose-load serum glucose, gestational hypertension, gestational age at birth, and birth weight were recorded in 563 participants. Results: The highest plasma folate concentrations occurred in the first trimester when folic acid supplement use was extensive. Supplementation beyond the first trimester interacted with time of pregnancy on plasma folate, RBC folate, and tHcy throughout pregnancy (P-interaction <0.001). Plasma folate and RBC folate were higher and tHcy was lower in continued supplement users than in nonusers. Elevated plasma folate (≥30 nmol/L) occurred in 78.9% of women who exceeded the recommended 400 µg folic acid/d. First-trimester folate-cobalamin status interactions were associated with MMA (P-interaction <0.001) throughout pregnancy. When plasma cobalamin was suboptimal (≤221 pmol/L; n = 36), participants with elevated plasma folate (n = 11) had higher MMA concentrations than did those with nonelevated plasma folate (n = 23). First-trimester folate-MMA status interactions were associated with MCV throughout pregnancy (P-interaction <0.01) and with cord plasma holoTC (P-interaction <0.05). The mean difference (95% CI) in MCV (fL) between women with elevated and nonelevated plasma folate status was -2.12 (-3.71, -0.52) for top-quartile plasma MMA (≥0.139 µmol/L) and 0.60 (-0.39, 1.60) for plasma MMA <0.139 µmol/L. Cord plasma holoTC was higher in women with elevated compared with nonelevated plasma folate status only for MMA <0.139 µmol/L. Folate-cobalamin interactions were not associated with the other investigated outcomes. Conclusion: First-trimester folate-cobalamin status interactions were associated with plasma MMA and MCV throughout pregnancy. This trial was registered at www.clinicaltrials.gov as NCT01778205.

Frequency of the hemochromatosis gene (HFE) 282C-->Y, 63H-->D, and 65S-->C mutations in a general Mediterranean population from Tarragona, Spain.

Three mutations have recently been detected in the hereditary hemochromatosis HFE gene (282C-->Y, 63H-->D, and 65S-->C). To determine their prevalence in a northeastern Spanish Mediterranean population, we studied 812 subjects between 18 and 75 years of age, randomly selected from the electoral roll of three villages. There were no homozygotes for the 282C-->Y or S65D mutations in this sample. For the 63H-->D mutation, 4.8% were homozygotes; 4.3, 32.3, and 2% were heterozygotes for the 282C-->Y, 63H-->D, and 65S-->C mutations, respectively. The prevalence of compound heterozygotes was 2% for 282C-->Y/63H-->D and 0.6% for 63H-->D /65S-->C. We found no significant differences between men and women. In conclusion, 46% of this Mediterranean population of Spain are carriers of at least one of the three mutations that can increase iron absorption.