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.

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.

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.

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.

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.

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.

Association of a polymorphism in the promoter of the cellular retinoic acid-binding protein II gene (CRABP2) with increased circulating low-density lipoprotein cholesterol.

BACKGROUND: The cellular retinoic acid-binding protein II (CRABP-II), together with nuclear receptors such as the retinoid X receptor (RXR) and retinoic acid receptor (RAR), is involved in the transcriptional regulation of genes that control lipid metabolism via the retinoid signaling pathway and, as such, may be associated with disorders of lipid metabolism. Interestingly, the gene for CRABP-II is located on chromosome 1q21-23, which is a region that has been linked with disorders such as familial combined hyperlipidemia (FCHL), type 2 diabetes mellitus, and partial lipodystrophy, all of which are characterized by dyslipidemia. METHODS: We investigated the hypothesis that the CRABP2 gene is involved in the regulation of lipid metabolism. Using the promoter -394T>C polymorphism of the CRABP2 gene, we performed association studies in three different cohorts: 299 healthy males, 182 HIV-infected patients and 151 patients with familial hypercholesterolemia (FH). All cholesterol measurements were performed in the absence of any lipid-lowering agents. ANOVA was performed on data adjusted for age, body mass index (BMI), gender, and use of protease inhibitors. RESULTS: The frequency of the C allele was 0.03 in the three groups. Among healthy males, carriers of the C allele had 9% higher total plasma cholesterol (p=0.027) and 13% higher low-density lipoprotein cholesterol (LDL-C) concentrations (p=0.020). In HIV-infected patients, multivariate analysis of four measures over a 1-year period showed that carriers of the C allele had significantly higher LDL-C of between 10% and 31% (p=0.001) compared with non-carriers of the allele. FH patients who were carriers of the C allele had 16% higher LDL-C (p=0.038). The C allele was significantly over-represented among hypercholesterolemic patients (p=0.001). CONCLUSIONS: Our results show that the CRABP2 gene, a member of the retinoid signaling pathway, is associated with increased plasma LDL-C concentrations.