Association between birthweight, cardiovascular risk factors, and depression in young Mexican adults / Asociación entre peso al nacer, riesgo cardiovascular y depresión en adultos jóvenes mexicanos

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 c2 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. (AU)

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 c2. 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. (AU)

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.

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.

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.

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.

Determinants of nutritional status in children under five living in a rural area of Mozambique: a population survey / Determinantes del estado nutricional en niños menores de cinco años que viven en una zona rural de Mozambique: una encuesta de población

Background: Malnutrition in sub-Saharan Africa contributes to high rates of childhood morbidity and mortality. Little information is available regarding moderate malnutrition prevalence in children under five in rural areas. Methods: To assess nutritional status and the prevalence of malnutrition in children from Ibo Island, Mozambique, a nutritional population survey in children under 5 years was carried out. A structured questionnaire was administered from April 2009 to February 2010. Anthropometric measurements were recorded as z-scores and child nutritional status derived from the World Health Organization Child Growth Standards (WHO) reference population. Results: 3313 people on Ibo were identified and interviewed and nutritional assessment was carried out in the 526 children under five. Most children had been fully vaccinated (90.5%), breastfed (100%), and some were also bottle fed (22.0%). The mean duration of the different feeding regimes were 20.3±4.47 months for breastfeeding, 2.5±0.8 months for exclusive breastfeeding and 3.2±4.0 months for bottle feeding. The mean number of daily meals across the child age range was 2.3±0.5. More stunted children had been exclusively breastfed than mixed fed (p=0.058). Severe stunting was more likely in children in the ≤11 (26.3%) and 12-23 (21.2%) month age groups (p=0.007). 13.5% of severely stunted children had not been fully vaccinated (p=0.014), 72.7% ate unassisted (p=0.013) and 64.8% had their own dish to eat from (p=0.001) compared to the non-stunted group. More children from the 46-60 month age group (27.7%) were underweight compared to the other groups (p=0.047). Conclusions: moderate and severe malnutrition, especially stunting, in children under five in a rural setting in Mozambique are still prevalent. Strategies to tackle this problem are required (AU)

Fundamentos: La desnutrición en el África subsahariana contribuye a las elevadas tasas de morbilidad y mortalidad infantil, disponiéndose de poca información sobre la prevalencia moderada de la malnutrición en niños menores de cinco años de las zonas rurales. Métodos: se realizó una encuesta nutricional de población en niños menores de 5 años, para evaluar el estado nutricional y la prevalencia de malnutrición en los niños de Ibo Island, Mozambique. Se administró un cuestionario estructurado de abril de 2009 a febrero de 2010. Las medidas antropométricas se registraron como puntuaciones z y el estado nutricional de los niños se obtuvo de acuerdo a las referencias de la Organización Mundial de la Salud (OMS) para el Crecimiento Infantil. Resultados: 3313 personas en Ibo fueron identificadas y entrevistadas. Se realizó una evaluación nutricional en los 526 niños menores de cinco años. La mayoría de los niños habían sido totalmente vacunados (90,5%), amamantados (100,0%) y algunos también alimentados con biberón (22,0%). La duración media de los diferentes regímenes de alimentación fue de 20,3±4,47 meses para la lactancia materna, 2,5±0,8 meses para la lactancia materna exclusiva y 3,2±4,0 meses para la alimentación con biberón. El número medio de comidas diarias en el rango de edad de los niños fue de 2,3±0,5. Los niños más atrofiados habían sido alimentados exclusivamente con leche materna que los alimentados con leche materna (p = 0,058). El retraso en el crecimiento fue más probable en los niños en los grupos ≤ 11 (26,3%) y 12-23 (21,2%) meses (p = 0,007). El 13,5% de los niños gravemente atrofiados no habían sido vacunados totalmente (p=0,014), el 72,7% no asistió (p=0,013) y el 64,8% tenía su propio plato para comer (p=0,001) en comparación con el grupo no atrofiado. Más niños del grupo de edad de 46-60 meses (27,7%) tenían peso inferior al de los otros grupos (p = 0,047). Conclusiones: la malnutrición moderada y severa, especialmente el retraso en el crecimiento, en niños menores de cinco años en un entorno rural en Mozambique siguen siendo frecuentes. Se requieren estrategias para abordar este problema (AU)

Maternal Folate Status and the BHMT c.716G>A Polymorphism Affect the Betaine Dimethylglycine Pathway during Pregnancy.

The effect of the betaine: homocysteine methyltransferase BHMT c.716G>A (G: guanosine; A: adenosine) single nucleotide polymorphism (SNP) on the BHMT pathway is unknown during pregnancy. We hypothesised that it impairs betaine to dimethylglycine conversion and that folate status modifies its effect. We studied 612 women from the Reus Tarragona Birth Cohort from ≤12 gestational weeks (GW) throughout pregnancy. The frequency of the variant BHMT c.716A allele was 30.8% (95% confidence interval (CI): 28.3, 33.5). In participants with normal-high plasma folate status (>13.4 nmol/L), least square geometric mean [95% CI] plasma dimethylglycine (pDMG, µmol/L) was lower in the GA (2.35 [2.23, 2.47]) versus GG (2.58 [2.46, 2.70]) genotype at ≤12 GW (p < 0.05) and in the GA (2.08 [1.97, 2.19]) and AA (1.94 [1.75, 2.16]) versus GG (2.29 [2.18, 2.40]) genotypes at 15 GW (p < 0.05). No differences in pDMG between genotypes were observed in participants with possible folate deficiency (≤13.4 nmol/L) (p for interactions at ≤12 GW: 0.023 and 15 GW: 0.038). PDMG was lower in participants with the AA versus GG genotype at 34 GW (2.01 [1.79, 2.25] versus 2.44 [2.16, 2.76] and at labour, 2.51 [2.39, 2.64] versus 3.00 [2.84, 3.18], (p < 0.01)). Possible deficiency compared to normal-high folate status was associated with higher pDMG in multiple linear regression analysis (ß coefficients [SEM] ranging from 0.07 [0.04], p < 0.05 to 0.20 [0.04], p < 0.001 in models from early and mid-late pregnancy) and the AA compared to GG genotype was associated with lower pDMG (ß coefficients [SEM] ranging from -0.11 [0.06], p = 0.055 to -0.23 [0.06], p < 0.001). CONCLUSION: During pregnancy, the BHMT pathway is affected by folate status and by the variant BHMT c.716A allele.

Exposure to Folate Receptor Alpha Antibodies during Gestation and Weaning Leads to Severe Behavioral Deficits in Rats: A Pilot Study.

The central nervous system continues to develop during gestation and after birth, and folate is an essential nutrient in this process. Folate deficiency and folate receptor alpha autoantibodies (FRα-AuAb) have been associated with pregnancy-related complications and neurodevelopmental disorders. In this pilot study, we investigated the effect of exposure to FRα antibodies (Ab) during gestation (GST), the pre-weaning (PRW), and the post weaning (POW) periods on learning and behavior in adulthood in a rat model. In the open field test and novel object recognition task, which examine locomotor activity and anxiety-like behavior, deficits in rats exposed to Ab during gestation and pre-weaning (GST+PRW) included more time spent in the periphery or corner areas, less time in the central area, frequent self-grooming akin to stereotypy, and longer time to explore a novel object compared to a control group; these are all indicative of increased levels of anxiety. In the place avoidance tasks that assess learning and spatial memory formation, only 30% of GST+PRW rats were able to learn the passive place avoidance task. None of these rats learned the active place avoidance task indicating severe learning deficits and cognitive impairment. Similar but less severe deficits were observed in rats exposed to Ab during GST alone or only during the PRW period, suggesting the extreme sensitivity of the fetal as well as the neonatal rat brain to the deleterious effects of exposure to Ab during this period. Behavioral deficits were not seen in rats exposed to antibody post weaning. These observations have implications in the pathology of FRα-AuAb associated with neural tube defect pregnancy, preterm birth and neurodevelopmental disorders including autism.

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.

Early pregnancy B vitamin status, one carbon metabolism, pregnancy outcome and child development.

Periconception supplementation with folic acid is recommended until 12 gestational weeks to prevent neural tube defects. Doses of folic acid contained in supplements and timing and length of use during pregnancy vary. The effects of status in periconception and pregnancy folate, cobalamin, betaine and their interactions on one carbon metabolism (1C), as well as the global effect of 1C on foetal growth and pregnancy outcome, are reviewed. Results from prospective studies are reviewed. Cessation of folic acid supplement use after the first trimester is associated with a sharp drop in plasma folate status and enhanced conversion of betaine to dimethylglycine. Dimethylglycine production is also higher in mothers with low folate status than in those with normal-high folate status. The effects of high doses of folic acid on one carbon metabolism in mothers with low early pregnancy cobalamin status and on foetal growth are also reviewed. Several studies report that moderately elevated early pregnancy fasting plasma total homocysteine (tHcy) is inversely associated with birth weight and a predictor of intrauterine growth retardation. There is also evidence for increased risk of preterm birth when maternal folate status is low.

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.

Riboflavin status modifies the effects of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) polymorphisms on homocysteine.

Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR), riboflavin-dependent enzymes, participate in homocysteine metabolism. Reported effects of riboflavin status on the association between the MTHFR 677C>T polymorphism and homocysteine vary, and the effects of the MTRR 66A>G or MTRR 524C>T polymorphisms on homocysteine are unclear. We tested the hypothesis that the effects of the MTHFR 677C>T, MTRR 66A>G and MTRR 524C>T polymorphisms on fasting plasma total homocysteine (tHcy) depend on riboflavin status (erythrocyte glutathionine reductase activation coefficient, optimum: <1.2; marginally deficient: 1.2-1.4; deficient: ≥1.4) in 771 adults aged 18-75 years. MTHFR 677T allele carriers with middle or low tertile plasma folate (<14.7 nmol/L) had 8.2 % higher tHcy compared to the 677CC genotype (p < 0.01). This effect was eliminated when riboflavin status was optimal (p for interaction: 0.048). In the lowest cobalamin quartile (≤273 pmol/L), riboflavin status modifies the relationship between the MTRR 66 A>G polymorphism and tHcy (p for interaction: 0.034). tHcy was 6.6 % higher in MTRR 66G allele carriers compared to the 66AA genotype with marginally deficient or optimal riboflavin status, but there was no difference when riboflavin status was deficient (p for interaction: 0.059). tHcy was 13.7 % higher in MTRR 524T allele carriers compared to the 524CC genotype when cobalamin status was low (p < 0.01), but no difference was observed when we stratified by riboflavin status. The effect of the MTHFR 677C>T polymorphism on tHcy depends on riboflavin status, that of the MTRR 66A>G polymorphism on cobalamin and riboflavin status and that of the MTRR 524C>T polymorphism on cobalamin status.

Validation of a semi-quantitative food frequency questionnaire to assess food groups and nutrient intake / Validación de un cuestionario semi-cuantitativo de frecuencia de consumo de alimentos para determinar la ingestión de grupos de alimentos y nutrientes

Introduction: Semi-quantitative Food Frequency Questionnaires (FFQs) analyze average food and nutrient intake over extended periods to associate habitual dietary intake with health problems and chronic diseases. A tool of this nature applicable to both women and men is not presently available in Mexico. Objective: To validate a FFQ for adult men and women. Methods: The study was conducted on 97 participants, 61% were women. Two FFQs were administered (with a one-year interval) to measure reproducibility. To assess validity, the second FFQ was compared against dietary record (DR) covering nine days. Statistical analyses included Pearson correlations and Intraclass Correlation Coefficients (ICC). The de-attenuation of the ICC resulting from intraindividual variability was controlled. The validity analysis was complemented by comparing the classification ability of FFQ to that of DR through concordance between intake categories and Bland-Altman plots. Results: Reproducibility: ICC values for food groups ranged 0.42-0.87; the range for energy and nutrients was between 0.34 and 0.82. Validity: ICC values for food groups ranged 0.35-0.84; the range for energy and nutrients was between 0.36 and 0.77. Most subjects (56.776.3%) classified in the same or adjacent quintile for energy and nutrients using both methods. Extreme misclassification was <6.3% for all items. Bland-Altman plots reveal high concordance between FFQ and DR. 
Conclusions: FFQ produced sufficient levels of repro-ducibility and validity to determine average daily intake over one year. These results will enable the analysis of possible associations with chronic diseases and dietary diagnoses in adult populations of men and women (AU)

Introducción: Los cuestionarios semicuantitativos de frecuencia de consumo (CFC) analizan ingestión promedio de alimentos y nutrimentos en períodos extensos para asociar consumo habitual con problemas de salud, como enfermedades crónicas. En México, no existe una herramienta similar, aplicable en mujeres y hombres. Objetivo: Validar un CFC en mujeres y hombres adultos. Métodos: El estudio incluyó 97 participantes (61% mujeres). Dos CFC fueron aplicados (un año entre ambos) para medir reproducibilidad. Para validez, se comparó el segundo CFC con registros dietéticos de nueve días. Los análisis incluyeron correlaciones de Pearson y coeficientes de correlación intraclase (CCI). Se controló desatenuación de CCI provocada por la variabilidad intraindividual. El análisis de validez se complementó con la comparación de la capacidad de clasificación entre CFC y registros dietéticos, mediante concordancia de categorías de consumo y gráficos de Bland y Altman. Resultados: Reproducibilidad: los CCI para grupos de alimentos oscilaron entre 0,42-0,87 y para nutrimentos entre 0,34-0,82. Validez: los CCI para grupos de alimentos variaron entre 0,35-0,84 y para nutrimentos entre 0,360,77. La mayoría de sujetos (56,7-76,3%) clasificaron en el mismo quintil o adyacente por ambos métodos (media 66,1%), para energía y nutrimentos. La mala clasificación extrema para todos los ítems fue <6,3%. El análisis con gráficos de Bland y Altman determinó una buena capacidad de acuerdo del CFC, respecto a registros dietéticos. Conclusiones: El CFC obtuvo reproducibilidad y validez adecuadas para determinar ingestión diaria promedio, en un año. Esto permitirá analizar posibles asociaciones con enfermedades crónicas y diagnósticos dietéticos poblacionales en mujeres y hombres adultos (AU)

Low folate status enhances pregnancy changes in plasma betaine and dimethylglycine concentrations and the association between betaine and homocysteine.

BACKGROUND: Folate, choline, and betaine participate in homocysteine metabolism. It is not known whether they interact during pregnancy. OBJECTIVE: The objective was to investigate how folate status affects choline, betaine, and dimethylglycine during pregnancy. DESIGN: Fasting plasma folate, cobalamin, free choline, betaine, dimethylglycine, and total homocysteine (tHcy) were measured longitudinally at <12, 15, 24-27, and 34 gestational weeks (GW); at labor (nonfasting); and in the cord in participants (n = 522) from the Reus-Tarragona Birth Cohort (NUTrició i Creixement Intrauterí Retardat phase). Timing, dose, and duration of folic acid supplement use were recorded. Folate status was classified as below (low) or above (high) median plasma folate at baseline (27.6 nmol/L) and at 24-27 GW (11.4 nmol/L). Associations between folate or betaine with tHcy were investigated by using multiple linear regression analysis. RESULTS: Plasma betaine decreased by 34.8% (1.0%) throughout pregnancy, and dimethylglycine increased by 39.7% (2.7%) between 24-27 GW and labor (all P < 0.001). Compared with high folate status, low status was associated with a higher dimethylglycine/betaine ratio from 15 GW and with lower plasma betaine and higher dimethylglycine from 24 to 27 GW, for the rest of pregnancy. Regression analysis showed that by 24-27 GW, both plasma folate and betaine were inversely associated with tHcy when folate status was low and that the association between betaine and tHcy depended on folate status at 24-27 and 34 GW (interaction terms: P < 0.001 and P < 0.01). Betaine was inversely associated with tHcy at labor regardless of folate status. CONCLUSION: Low folate status enhances the reduction in betaine and the increase in dimethylglycine during pregnancy and strengthens the association between betaine and tHcy. This trial was registered at clinicaltrials.gov as NCT01778205.

Validation of a semi-quantitative food frequency questionnaire to assess food groups and nutrient intake.

INTRODUCTION: Semi-quantitative Food Frequency Questionnaires (FFQs) analyze average food and nutrient intake over extended periods to associate habitual dietary intake with health problems and chronic diseases. A tool of this nature applicable to both women and men is not presently available in Mexico. OBJECTIVE: To validate a FFQ for adult men and women. METHODS: The study was conducted on 97 participants, 61% were women. Two FFQs were administered (with a one-year interval) to measure reproducibility. To assess validity, the second FFQ was compared against dietary record (DR) covering nine days. Statistical analyses included Pearson correlations and Intraclass Correlation Coefficients (ICC). The de-attenuation of the ICC resulting from intraindividual variability was controlled. The validity analysis was complemented by comparing the classification ability of FFQ to that of DR through concordance between intake categories and Bland-Altman plots. RESULTS: Reproducibility: ICC values for food groups ranged 0.42-0.87; the range for energy and nutrients was between 0.34 and 0.82. VALIDITY: ICC values for food groups ranged 0.35-0.84; the range for energy and nutrients was between 0.36 and 0.77. Most subjects (56.7-76.3%) classified in the same or adjacent quintile for energy and nutrients using both methods. Extreme misclassification was <6.3% for all items. Bland-Altman plots reveal high concordance between FFQ and DR. CONCLUSIONS: FFQ produced sufficient levels of reproducibility and validity to determine average daily intake over one year. These results will enable the analysis of possible associations with chronic diseases and dietary diagnoses in adult populations of men and women.

Introducción. Los cuestionarios semicuantitativos de frecuencia de consumo (CFC) analizan ingestión promedio de alimentos y nutrimentos en períodos extensos para asociar consumo habitual con problemas de salud, como enfermedades crónicas. En México, no existe una herramienta similar, aplicable en mujeres y hombres. Objetivo. Validar un CFC en mujeres y hombres adultos. Métodos. El estudio incluyó 97 participantes (61% mujeres). Dos CFC fueron aplicados (un año entre ambos) para medir reproducibilidad. Para validez, se comparó el segundo CFC con registros dietéticos de nueve días. Los análisis incluyeron correlaciones de Pearson y coeficientes de correlación intraclase (CCI). Se controló desatenuación de CCI provocada por la variabilidad intraindividual. El análisis de validez se complementó con la comparación de la capacidad de clasificación entre CFC y registros dietéticos, mediante concordancia de categorías de consumo y gráficos de Bland y Altman. Resultados. Reproducibilidad: los CCI para grupos de alimentos oscilaron entre 0.42-0.87 y para nutrimentos entre 0.34-0.82. Validez: los CCI para grupos de alimentos variaron entre 0.35-0.84 y para nutrimentos entre 0.36-0.77. La mayoría de sujetos (56.7-76.3%) clasificaron en el mismo quintil o adyacente por ambos métodos (media 66.1%), para nutrimentos. La mala clasificación extrema para todos los ítems fue.

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.

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.

Homocysteine in pregnancy.

The aim of this review is to evaluate the evidence for and against fasting plasma total homocysteine (tHcy) as a biomarker/risk factor of impaired reproductive function before and during pregnancy. Apart from nutritional and lifestyle factors, tHcy is also influenced by physiological factors specific to pregnancy such as hemodilution, increased glomerular filtration rate, and endocrinological changes. These lead to a considerable reduction under normal circumstances in tHcy by midpregnancy. Stimulating excess endogenous homocysteine production before and during pregnancy in animal experiments and adding exogenous homocysteine to cell cultures result in the impairment of reproductive and developmental processes from preconception throughout pregnancy and during subsequent development of the offspring. Different studies have confirmed that elevated tHcy is a risk factor for subfertility, congenital developmental defects, preeclampsia, and intrauterine growth retardation. There is conflicting evidence that elevated tHcy is a risk factor for miscarriage, gestational diabetes, premature rupture of the membranes, placental abruption, and offspring with Down syndrome. Prospective, sufficiently powered, studies from preconception/early pregnancy are required to determine whether tHcy is a risk factor for these pregnancy complications.

Relationships between early behavioural characteristics and temperament at 6 years.

The aim of this study was to analyze the extent to which the relations and the stability of the neonatal behaviour and the infant behaviour at both 4 and 12 months could be used to predict the infant temperament at 6 years. Seventy-two full-term, normal-weight, healthy children were followed from 3 days postpartum to 6 years. Neonatal behaviour at 3 and 30 days was assessed using the Neonatal Behaviour Assessment Scale (NBAS), behaviour at 4 and 12 months was assessed using the Infant Behaviour Record (IBR) from the Bayley Scales for Infant Development (BSID) and temperament at 6 years was assessed using the Dimensions of Temperament Survey-Revised (DOTS-R). Negative and positive affectivity and attention were the factors extracted from the behaviours of the IBR. Our results showed a low/moderate correlation between neonatal behaviour on the one hand and behaviour at 4 and 12 months and temperament at 6 years on the other hand. The motor performance, orientation and ANS stability of the neonate at 3 and 30 days were predictors of positive and negative affectivity at 4 months. State regulation and ANS stability at 3 days were predictors of negative affectivity and attention respectively at 12 months. Negative affectivity at 12 months and endurance at 30 days were predictors of general activity and persistence/attention at 6 years. Also, an inverse relation was found between state regulation at 30 days and general activity at 6 years, and a positive relation was found between attention at 4 months and persistence/attention at 6 years. We conclude that neonatal behaviour and behaviour in the first year of life are good predictors of temperament at 6 years and that early negative affectivity has an important role on infant temperament development.

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.