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.

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.

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.

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.

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.

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.

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.

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.

The Reproducibility and Relative Validity of a Mexican Diet Quality Index (ICDMx) for the Assessment of the Habitual Diet of Adults.

The study of diet quality in a population provides information for the development of programs to improve nutritional status through better directed actions. The aim of this study was to assess the reproducibility and relative validity of a Mexican Diet Quality Index (ICDMx) for the assessment of the habitual diet of adults. The ICDMx was designed to assess the characteristics of a healthy diet using a validated semi-quantitative food frequency questionnaire (FFQ-Mx). Reproducibility was determined by comparing 2 ICDMx based on FFQs (one-year interval). Relative validity was assessed by comparing the ICDMx (2nd FFQ) with that estimated based on the intake averages from dietary records (nine days). The questionnaires were answered by 97 adults (mean age in years = 27.5, SD = 12.6). Pearson (r) and intraclass correlations (ICC) were calculated; Bland-Altman plots, Cohen's κ coefficients and blood lipid determinations complemented the analysis. Additional analysis compared ICDMx scores with nutrients derived from dietary records, using a Pearson correlation. These nutrient intakes were transformed logarithmically to improve normality (log10) and adjusted according to energy, prior to analyses. The ICDMx obtained ICC reproducibility values ranged from 0.33 to 0.87 (23/24 items with significant correlations; mean = 0.63), while relative validity ranged from 0.26 to 0.79 (mean = 0.45). Bland-Altman plots showed a high level of agreement between methods. ICDMx scores were inversely correlated (p < 0.05) with total blood cholesterol (r = -0.33) and triglycerides (r = -0.22). ICDMx (as calculated from FFQs and DRs) obtained positive correlations with fiber, magnesium, potassium, retinol, thiamin, riboflavin, pyridoxine, and folate. The ICDMx obtained acceptable levels of reproducibility and relative validity in this population. It can be useful for population nutritional surveillance and to assess the changes resulting from the implementation of nutritional interventions.

Related factors to semi-recumbent position compliance and pressure ulcers in patients with invasive mechanical ventilation: An observational study (CAPCRI study).

BACKGROUND: Semi-recumbent position is recommended to prevent ventilator-associated pneumonia. Its implementation, however, is below optimal. OBJECTIVES: We aimed to assess real semi-recumbent position compliance and the degree of head-of-bed elevation in Spanish intensive care units, along with factors determining compliance and head-of-bed elevation and their relationship with the development of pressure ulcers. Finally, we investigated the impact that might have the diagnosis of pressure ulcers in the attitude toward head-of-bed elevation. METHODS: We performed a prospective, multicenter, observational study in 6 intensive care units. Inclusion criteria were patients ≥18 years old and expected to remain under mechanical ventilator for ≥48h. Exclusion criteria were patients with contraindications for semi-recumbent position from admission, mechanical ventilation during the previous 7 days and prehospital intubation. Head-of-bed elevation was measured 3 times/day for a maximum of 28 days using the BOSCH GLM80(®) device. The variables collected related to patient admission, risk of pressure ulcers and the measurements themselves. Bivariate and multivariate analyses were carried out using multiple binary logistic regression and linear regression as appropriate. Statistical significance was set at p<0.05. All analyses were performed with IBM SPSS for Windows Version 20.0. RESULTS: 276 patients were included (6894 measurements). 45.9% of the measurements were <30.0°. The mean head-of-bed elevation was 30.1 (SD 6.7)° and mean patient compliance was 53.6 (SD 26.1)%. The main reasons for non-compliance according to the staff nurses were those related to the patient's care followed by clinical reasons. The factors independently related to semi-recumbent position compliance were intensive care unit, ventilation mode, nurse belonging to the research team, intracranial pressure catheter, beds with head-of-bed elevation device, type of pathology, lateral position, renal replacement therapy, nursing shift, open abdomen, abdominal vacuum therapy and agitation. Twenty-five patients (9.1%) developed a total of 34 pressure ulcers. The diagnosis of pressure ulcers did not affect the head-of-bed elevation. In the multivariate analysis, head-of-bed elevation was not identified as an independent risk factor for pressure ulcers. CONCLUSIONS: Semi-recumbent position compliance is below optimal despite the fact that it seems achievable most of the time. Factors that affect semi-recumbent position include the particular intensive care unit, abdominal conditions, renal replacement therapy, agitation and bed type. Head-of-bed elevation was not related to the risk of pressure ulcers. Efforts should be made to clarify semi-recumbent position contraindications and further analysis of its safety profile should be carried out.

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.

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.

Corneal endothelial changes in patients with chronic obstructive pulmonary disease and corneal vulnerability to cataract surgery.

PURPOSE: To determine whether chronic obstructive pulmonary disease (COPD) is a risk factor for a reduced corneal endothelium functional reserve after cataract surgery. SETTING: Department of Ophthalmology, Hospital Universitari Sant Joan, Reus, Spain. DESIGN: Prospective clinical observational cohort study. METHODS: Patients were assigned to 1 of the following 3 groups: mild-to-moderate COPD, severe-to-very severe COPD, and without COPD (control). Before and 3 months after phacoemulsification, specular microscopy was used to evaluate the number and morphology of endothelial cells and the central corneal thickness (CCT) was measured to evaluate corneal decompensation. RESULTS: Preoperative results were recorded for 165 eyes. The mild-to-moderate COPD group comprised 67 eyes; the severe-to-very severe COPD group, 40 eyes; and the control group, 58 eyes. Cataract surgery was performed in 112 eyes. Significant differences in nearly all preoperative and 3-month postoperative corneal endothelial parameters were observed between the COPD groups and the control group, the former having a lower cell density and percentage of hexagonal cells and a higher coefficient of variance of the mean cell area. Two weeks postoperatively, the percentage of mild central corneal edema was 0%, 36%, and 31% in the control group, mild-to-moderate COPD group, and severe-to-very severe COPD group, respectively. There was no significant difference in the preoperative or 3-month postoperative mean CCT between the groups. CONCLUSION: Chronic obstructive pulmonary disease reduced endothelial functional reserve and increased corneal endothelial vulnerability to intraocular surgical stress. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

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.

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.

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.