Factors associated with serum ferritin levels and iron excess: results from the EPIC-EurGast study.

PURPOSE: Excess iron is involved in the development of non-communicable diseases such as cancer, type 2 diabetes and cardiovascular conditions. We aimed to describe the prevalence of excess iron and its determinants in healthy European adults. METHODS: Sociodemographic, lifestyle, iron status, dietary information, and HFE genotyping were obtained from controls from the nested case-control study EPIC-EurGast study. High sensitivity C-reactive protein (hsCRP) was measured to address possible systemic inflammation. Descriptive and multivariate analyses were used to assess iron status and its determinants. RESULTS: Out of the 828 participants (median age: 58.7 years), 43% were females. Median serum ferritin and prevalence of excess iron were 143.7 µg/L and 35.2% in males, respectively, and 77 µg/L and 20% in females, both increasing with latitude across Europe. Prevalence of HFE C282Y mutation was significantly higher in Northern and Central Europe (~ 11%) than in the South (5%). Overweight/obesity, age, and daily alcohol and heme iron intake were independent determinants for iron status, with sex differences even after excluding participants with hsCRP > 5 mg/L. Obese males showed a greater consumption of alcohol, total and red meat, and heme iron, compared with those normal weight. CONCLUSION: Obesity, higher alcohol and heme iron consumption were the main risk factors for excess iron in males while only age was associated with iron overload in females. Weight control and promoting healthy lifestyle may help prevent iron overload, especially in obese people. Further research is needed to clarify determinants of excess iron in the healthy adult population, helping to reduce the associated comorbidities.

Biologic therapies committee. What does it provide?

OBJECTIVE: To assess the general healthcare impact of a Biological  Therapies Commitee (immune-mediated inflammatory diseases) through  prescription habits, pre-biological studies and immunization. METHOD: A quasi-experimental study was conducted on all naïve patients  of legal age who started treatment with a biological agent for an immune- mediated inflammatory disease the year before and the year after the  creation of the Biological Therapies Committee. RESULTS: A total of 31 patients treated in 2016 and 40 patients treated in 2018 were included. Prescriptions of tumor necrosis factor alpha  inhibitor drugs decreased in 2018 (from 80.6% to 45.0%, p < 0.05), while prescriptions of interleukin 12/23 inhibitors increased (from 12.9% to  35.0%, p < 0.05). Tuberculosis screening was statistically different  between the two periods: the number of interferon gamma release assays  performed was higher in 2018 (from 9.7% to 80.0%, p < 0.01) and the  proportion of patients who successfully underwent chemoprophylaxis was  higher in 2018 (from 36.4% to 81.8%, p < 0.05). The proportion of tests  requested for the study of viral pathologies and the number of vaccines  administered were also higher in 2018. CONCLUSIONS: The development of a specific Biological Therapies  Committee allows healthcare improvements, contributing to a deeper  understanding of the medications and to preventing the infection-related  adverse events. It would therefore seem advisable to develop specialized  committees akin to the Biological Therapies Committee in other domains.

Objetivo: Evaluar el impacto general a nivel asistencial de una comisión  de terapias biológicas, en enfermedades inflamatorias inmunomediadas,  mediante los hábitos de prescripción, los estudios prebiológicos y la  inmunización.Método: Se realizó un estudio cuasiexperimental sobre todos los  pacientes naïve mayores de edad que iniciaron tratamiento con un  medicamento biológico por enfermedad inflamatoria inmunomediada el  año anterior y el año posterior a la creación de la comisión de terapias  biológicas.Resultados: Se incluyeron un total de 31 pacientes estudiados en 2016 y  40 pacientes estudiados en 2018. La prescripción de medicamentos inhibidores del factor de necrosis tumoral α se redujo en  2018 (80,6% versus 45,0%; p < 0,05), mientras que la prescripción de  inhibidores de la interleucina 12/23 aumentó (12,9% versus 35,0%; p <  0,05). El cribaje tuberculoso fue estadísticamente diferente entre los  periodos pre y postcomisión de terapias biológicas: la realización del  interferon gamma release assay fue superior en 2018 (9,7% versus  80,0%, p < 0,01) y la proporción de pacientes que realizaron  correctamente la quimioprofilaxis fue superior en 2018 (36,4% versus  81,8%, p < 0,05). La proporción de pruebas solicitadas para estudio de  patologías víricas, así como la administración de vacunas, fueron  superiores en 2018.Conclusiones: El desarrollo de una comisión específica de terapias biológicas aporta mejoras asistenciales en enfermedades  inflamatorias inmunomediadas, al contribuir a un mayor conocimiento  relacionado con los medicamentos y con la prevención de los efectos  adversos de carácter infeccioso, por lo que sería conveniente que se  impulsara el desarrollo de comisiones especializadas como la comisión de  terapias biológicas.

Food Consumption during Pregnancy and Post-Partum. ECLIPSES Study.

Inadequate maternal diet can adversely affect mother and child. Our aim was to assess adherence to the Spanish dietary guidelines and to the Mediterranean diet, to analyze changes in diet during pregnancy and post-partum, and to identify maternal factors associated with food consumption. A total of 793 healthy pregnant women were recruited during the first prenatal visit and followed until the post-partum period. Data from the clinical history, anthropometric measurements, and lifestyle habits were collected. Food consumption was evaluated using a food frequency questionnaire. The results show that in pregnant women the consumption of healthy foods did not meet recommendations, whereas consumption of red and processed meat and sweet food exceeded recommendations. The results also show a medium adherence to the Mediterranean diet that remained unchanged throughout pregnancy. A significant decrease was observed in the consumption of fruits, followed by vegetables and then salted and sweet cereals from pregnancy to post-partum. A better adherence to the Mediterranean diet has been reported by pregnant women that are older, of higher social class, and higher education level, and who do not smoke nor drink (p < 0.005). In conclusion, the diet of pregnant women from Spain departs from recommendations, medium adherence to the Mediterranean diet was maintained throughout the pregnancy and post-partum, and a decreasing consumption of healthy food from the first trimester to the post-partum period was observed. Maternal factors such as age, social class, education, and smoking influence diet quality.

The Effectiveness of Different Doses of Iron Supplementation and the Prenatal Determinants of Maternal Iron Status in Pregnant Spanish Women: ECLIPSES Study.

Iron deficiency (ID), anemia, iron deficiency anemia (IDA) and excess iron (hemoconcentration) harm maternal-fetal health. We evaluated the effectiveness of different doses of iron supplementation adjusted for the initial levels of hemoglobin (Hb) on maternal iron status and described some associated prenatal determinants. The ECLIPSES study included 791 women, randomized into two groups: Stratum 1 (Hb = 110-130g/L, received 40 or 80mg iron daily) and Stratum 2 (Hb > 130g/L, received 20 or 40mg iron daily). Clinical, biochemical, and genetic information was collected during pregnancy, as were lifestyle and sociodemographic characteristics. In Stratum 1, using 80 mg/d instead of 40 mg/d protected against ID on week 36. Only women with ID on week 12 benefited from the protection against anemia and IDA by increasing Hb levels. In Stratum 2, using 20 mg/d instead of 40 mg/d reduced the risk of hemoconcentration in women with initial serum ferritin (SF) ≥ 15 µg/L, while 40 mg/d improved SF levels on week 36 in women with ID in early pregnancy. Mutations in the HFE gene increased the risk of hemoconcentration. Iron supplementation should be adjusted to early pregnancy levels of Hb and iron stores. Mutations of the HFE gene should be evaluated in women with high Hb levels in early pregnancy.

Does the fortified milk with high iron dose improve the neurodevelopment of healthy infants? Randomized controlled trial.

BACKGROUND: Since iron plays an important role in several physiological processes, its deficiency but also overload may harm the development of children. The aim was to assess the effect of iron-fortified milk on the iron biochemical status and the neurodevelopment of children at 12 months of age. METHODS: Randomized controlled trial conducted in 133 Spanish children, allocated in two groups to receive formula milk fortified with 1.2 or 0.4 mg/100 mL of iron between 6 and 12 months of age. Psychomotor (PDI) and Mental (MDI) Development Index were assessed by the Bayley Scales before and after the intervention. Maternal obstetrical and psychosocial variables were recorded. The biochemical iron status of children was measured and data about breastfeeding, anthropometry and infections during the first year of life were registered. RESULTS: Children fortified with 1.2 mg/100 mL of iron, compared with 0.4 mg/100 mL, showed higher serum ferritin (21.5 vs 19.1 µg/L) and lower percentage of both iron deficiency (1.1 to 5.9% vs 3.8 to 16.7%, respectively, from 6 to 12 months) and iron deficiency anemia (4.3 to 1.1% vs 0 to 4.2%, respectively, from 6 to 12 months) at the end of the intervention. No significant differences were found on neurodevelopment from 6 to 12 months between children who received high dose of Fe compared with those who received low dose. CONCLUSION: Despite differences on the iron status were observed, there were no effects on neurodevelopment of well-nourished children in a developed country after iron supplementation with doses within dietary recommendations. Follow-up studies are needed to test for long-term neurodevelopmental improvement. TRIAL REGISTRATION: Retrospectively registered in ClinicalTrials.gov with the ID: NCT02690675.

[Consumption of free sugars and excess weight in infants. A longitudinal study]. / Ingesta de azúcares libres y exceso de peso en edades tempranas. Estudio longitudinal.

INTRODUCTION: The consumption of free sugars has been related to excess weight, with the WHO recommending an intake of <10% of total energy. The aim of this study is to assess the association between the consumption of free sugars at 12 months and the risk of excess weight at 30 months in healthy children. MATERIAL AND METHODS: A longitudinal study was conducted on 81 children followed-up from birth to 30 months. A record was made of the clinical history and anthropometry, at birth, and at 12 and 30 months. Weight status was classified as with or without excess weight, according to WHO values. At 12 months, the intake of energy and nutrients was analysed by differentiating the intake of free and natural sugars. Multivariate analyses adjusted for the main confounding variables were performed. RESULTS: Free sugars were consumed by 40.4% of the 12-month-old children, being higher than that recommended, and being significantly higher in children with excess weight at 30 months (60.9%). The higher intake of free sugars at 12 months is associated with an increased risk of excess weight at 30 months (OR: 1.130, 95% CI: 1.032-1.238). CONCLUSIONS: The consumption of free sugars is much higher than that recommended in 12-month-old infants. This high intake could be a risk factor for excess weight, even at early ages.

Multicenter study of parenteral nutrition in non-critically ill elderly patients compared to younger patients - Study IAIOS-PN (Incidence and Assessment of Iatrogenesis in Older Subjects receiving Parenteral Nutrition).

OBJECTIVE: this study assessed the incidence of hyperglycemia, hypertriglyceridemia, and liver function test (LFT) alterations among patients older and younger than 65 years receiving parenteral nutrition (PN). A secondary objective was to compare the incidence of any of these three events. MATERIAL AND METHODS: inclusion criteria were non-critically ill adult inpatients receiving PN for ≥ 7 days in 15 hospitals in Spain. Exclusion criteria were hyperglycemia, hypertriglyceridemia, LFT alterations, sepsis, shock, pancreatic/hepatobiliary surgery, renal failure, diabetes mellitus (DM) type 1, insulin-treated DM type 2, acute DM complications, or obesity prior to PN. Patients were classified into groups YOUNG (aged 35-64) and OLD (aged 65-95). RESULTS: this study recruited 200 patients. Group YOUNG included 63 (31.5%) patients and OLD, 137 (68.5%). Hyperglycemia appeared in 37 (18.5%) patients, eight (12.7%) in group YOUNG and 29 (21.2%) in group OLD (p = 0.174). Hypertriglyceridemia appeared in only one (0.7%) patient. LFT alterations appeared in 141 (70.5%) patients, 44 (69.8%) in group YOUNG and 97 (70.8%) in group OLD (p = 1.000). The model for hyperglycemia included DM type 2, previous surgical procedure, and use of hyperglycemia-inducing medications. The model for LFT alteration included previous surgical procedure, amount of lipids and amino acids, medications causing LFT alterations and a trend for age group. The model for any event included surgical procedure, DM type 2, and medications causing alterations. CONCLUSION: patients of ≥ 65 years receiving PN had similar incidences of hyperglycemia, hypertriglyceridemia, and LFT alterations as younger patients. Additionally, older patients had trends toward lower LFT alterations.

Serum hepcidin levels, iron status, and HFE gene alterations during the first year of life in healthy Spanish infants.

The aims of this study were to describe hepcidin levels and to assess their associations with iron status and the main variants in the HFE gene in healthy and full-term newborns during the first year of life, as a longitudinal study conducted on 140 infants. Anthropometric and biochemical parameters, hepcidin, hemoglobin (Hb), serum ferritin (SF), transferrin saturation (TS), mean corpuscular volume (MCV), and C-reactive protein (CRP), were assessed in 6- and 12-month-olds. Infants were genotyped for the three main HFE variants: C282Y, H63D, and S65C. Hepcidin levels increased from 6 to 12 months of age (43.7 ± 1.5 to 52.0 ± 1.5 ng/mL; p < 0.001), showing higher levels in infants with better iron status compared to those with iron deficiency (ID) (44.8 ± 1.5 vs 37.9 ± 1.3 ng/mL, p < 0.018, and 54.3 ± 1.5 vs 44.0 ± 1.4 ng/mL, p < 0.038, in 6- and 12-month-olds, respectively). In multivariate linear regression models, iron status was found to be associated with hepcidin levels in infants with wild-type HFE gene (p = 0.046 and p = 0.048 in 6- and 12-month-olds, respectively). However, this association was not found in HFE-alteration-carrying infants. Hepcidin levels increased in healthy infants during the first year of life and were positively associated with iron levels only in infants with wild-type HFE gene, a situation that requires further investigation.

Influence of breastfeeding and iron status on mental and psychomotor development during the first year of life.

Breastfeeding (BF) confers numerous benefits on the developing infant in both the short and the long term including psychological development, but there are multiple other factors that must be taken into account when these relationships are studied. To analyse how breastfeeding during the first 4 months of life affects infant mental and psychomotor development (MPD) at 6 and 12 months in a group of healthy infants from a Mediterranean Spanish city considering many important potential confounds. This is a longitudinal study conducted on infants from birth until the age of 12 months. A total of 154 healthy infants were evaluated by Paediatric Unit of Sant Joan University Hospital in Reus, Spain. Type of feeding, clinical history, anthropometry, iron status and mental and psychomotor development were assessed and analysed. At 4 months, 24% of infants received BF and 26% received mixed feeding (MF). Multiple Linear Regression models were applied adjusting for potential prenatal, perinatal and postnatal confounds showing that infants who received BF for at least four months presented higher psychomotor development index (PDI) at 6 and at 12 months of age. Also, gestational age and BMI at 6m were associated positively with PDI at 6 m, and haemoglobin levels at 12m and birth height were associated with PDI and MDI at 12m (respectively). In conclusion, after the adjustment of important potential confounds, BF during at least four months and adequate infant iron status are related to better psychomotor development during the first year. No associations were found between BF and mental development.

Hepcidin levels and gastric cancer risk in the EPIC-EurGast study.

Hepcidin is the main regulator of iron homeostasis and dysregulation of proteins involved in iron metabolism has been associated with tumorogenesis. However, to date, no epidemiological study has researched the association between hepcidin levels and gastric cancer risk. To further investigate the relationship between hepcidin levels and gastric cancer risk, we conducted a nested case-control study (EURGAST) within the multicentric European Prospective Investigation into Cancer and Nutrition study. The study included 456 primary incident gastric adenocarcinoma cases and 900 matched controls that occurred during an average of 11 years of follow-up. We measured serum levels of hepcidin-25, iron, ferritin, transferrin and C-reactive protein. Odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of gastric cancer by hepcidin levels were estimated from multivariable conditional logistic regression models. Mediation effect of the ferritin levels on the hepcidin-gastric cancer pathway was also evaluated. After adjusting for relevant confounders, we observed a statistically significant inverse association between gastric cancer and hepcidin levels (OR 5 ng/l = 0.96, 95% CI = 0.93-0.99). No differences were found by tumor localization or histological type. In mediation analysis, we found that the direct effect of hepcidin only represents a nonsignificant 38% (95% CI: -69%, 91%). In summary, these data suggest that the inverse association of hepcidin levels and gastric cancer risk was mostly accounted by ferritin levels. Further investigation including repeated measures of hepcidin is needed to clarify their role in gastric carcinogenesis.

Elevated iron status and risk of gestational diabetes mellitus: A systematic review and meta-analysis.

The aim of this systematic review and meta-analysis of observational studies was to assess the relationship between elevated iron status, measured as hemoglobin and ferritin levels, and the risk of gestational diabetes mellitus (GDM). The present study was recorded in PROSPERO (2013:CRD42013005717). The selected studies were identified through a systematic review of scientific literature published in The Cochrane Library and PubMed/MEDLINE databases from their inception until March 10, 2016, in addition to citation tracking and hand-searches. The search strategy of original articles combined several terms for hemoglobin, ferritin, pregnancy, and GDM. OR and 95% CI of the selected studies were used to identify associations between hemoglobin and/or ferritin levels with the risk of GDM. Summary estimates were calculated by combining inverse-variance using fixed-effects model. 2468 abstracts were initially found during the search. Of these, 11 with hemoglobin and/or ferritin data were selected for the meta-analyses. We observed that high hemoglobin (OR = 1.52; 95% CI: 1.23-1.88), as well as ferritin (OR = 2.09; 95% CI: 1.48-2.96) levels were linked to an increased risk of GDM. Low heterogeneity was observed in hemoglobin (I2  = 33.3%, P = 0.151) and ferritin (I2  = 0.7%, P = 0.418) meta-analyses, respectively. Publication bias was not appreciated. High hemoglobin or ferritin levels increase the risk of GDM by more than 50% and more than double, respectively, in the first and third trimester. Therefore, determining of hemoglobin or ferritin concentration in early pregnancy might be a useful tool for recognizing pregnant women at risk of GDM.

Increased iron levels and lipid peroxidation in a Mediterranean population of Spain.

BACKGROUND: Many chronic diseases are adversely affected by elevated iron levels. It has been speculated that this relationship is mediated by increased oxidative stress, due to the ability of iron to generate reactive oxygen species. The aim of this study was to assess the relationship between elevated iron levels and lipid peroxidation in Caucasian adults residing in the north-eastern Mediterranean region of Spain. MATERIALS AND METHODS: This cross-sectional case-control study included 300 subjects: 150 adults displaying elevated iron levels (cases) selected from a representative sample of our general population and 150 age- and sex-matched adults exhibiting normal iron levels (controls). Dietary assessment (3-day food records), iron biomarkers (serum iron, ferritin and transferrin saturation) and lipid profile were determined. Elevated iron levels were defined by high serum ferritin (SF>110 µg/L in women and>200 µg/L in men) and/or transferrin saturation (TS)>45%. Oxidized low-density lipoprotein (oxLDL) plasma levels were measured, and oxLDL/LDL-cholesterol ratio was calculated to estimate lipid peroxidation. Multiple linear regression (MLR) models were applied. RESULTS: Individuals with elevated serum iron levels showed increased oxLDL/LDL ratio, but not oxLDL levels, compared to control subjects (20·92 ± 4·89 U/mmol vs. 19·72 ± 3·573 U/mmol, P = 0·028). These results were further confirmed by the regression models adjusted for demographic characteristics, diet, lipid profile and inflammation. Importantly, higher serum levels of triglycerides, LDL-cholesterol and lower intake of Vitamin E increased lipid peroxidation. CONCLUSIONS: In our general population, we have observed that higher circulating levels of iron, measured by serum ferritin and/or TS, increased lipid peroxidation (measured by oxLDL/LDL ratio).

Body iron status and gastric cancer risk in the EURGAST study.

Although it appears biologically plausible for iron to be associated with gastric carcinogenesis, the evidence is insufficient to lead to any conclusions. To further investigate the relationship between body iron status and gastric cancer risk, we conducted a nested case-control study in the multicentric European Prospective Investigation into Cancer and Nutrition (EPIC) study. The study included 456 primary incident gastric adenocarcinoma cases and 900 matched controls that occurred during an average of 11 years of follow-up. We measured prediagnostic serum iron, ferritin, transferrin and C-reactive protein, and further estimated total iron-binding capacity (TIBC) and transferrin saturation (TS). Odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of gastric cancer by iron metrics were estimated from multivariable conditional logistic regression models. After adjusting for relevant confounders, we observed a statistically significant inverse association between gastric cancer and ferritin and TS indices (ORlog2 = 0.80, 95% CI = 0.72-0.88; OR10%increment = 0.87, 95% CI = 0.78-0.97, respectively). These associations appear to be restricted to noncardia gastric cancer (ferritin showed a p for heterogeneity = 0.04 and TS had a p for heterogeneity = 0.02), and no differences were found by histological type. TIBC increased risk of overall gastric cancer (OR50 µg/dl = 1.13, 95% CI = 1.02-1.2) and also with noncardia gastric cancer (p for heterogeneity = 0.04). Additional analysis suggests that time between blood draw and gastric cancer diagnosis could modify these findings. In conclusion, our results showed a decreased risk of gastric cancer related to higher body iron stores as measured by serum iron and ferritin. Further investigation is needed to clarify the role of iron in gastric carcinogenesis.

Excess body iron and the risk of type 2 diabetes mellitus: a nested case-control in the PREDIMED (PREvention with MEDiterranean Diet) study.

A prospective nested case-control study within the PREvention with MEDiterranean Diet (PREDIMED) was conducted to evaluate the relationship between excess body Fe (measured as serum ferritin (SF), soluble transferrin receptor (sTfR) and sTfR:ferritin ratio) and the risk of type 2 diabetes mellitus (T2DM) in a Mediterranean population at a high risk of CVD, without T2DM at the start of the study. The study contained 459 subjects, 153 with incident T2DM (cases) and 306 without incident T2DM (controls). The follow-up period was for 6.0 (interquartile range 3.9-6.5) years. For each incident diabetic subject, two subjects were selected as controls who were matched broadly for age as well as for sex, intervention group and BMI. We observed a relationship between SF values >257 µg/l in males and >139 µg/l in females and the risk of T2DM, following adjustment in the conditional logistic regression model for high-sensitivity C-reactive protein, fasting glucose and other components of the metabolic syndrome (OR 3.62, 95% CI 1.32, 19.95; P= 0.022). We also found an association between low sTfR:ferritin ratio levels and the incidence of T2DM (OR 3.02, 95% CI 1.09, 8.39; P= 0.042), but no association with sTfR (OR 1.29, 95% CI 0.51, 3.23; P= 0.722). Oxidative stress has been hypothesised to contribute to the development of insulin resistance and ß-cell dysfunction, the two key events in the clinical development of T2DM. Following adjustment for other risk factors for T2DM, excess body Fe (measured as SF and sTfR:ferritin ratio) was associated with an increased risk of developing T2DM in a Mediterranean population at a high risk of CVD.

Nanoparticle albumin-bound paclitaxel in a patient with locally advanced breast cancer and taxane-induced skin toxicity: a case report.

INTRODUCTION: Taxanes have demonstrated effectiveness in the treatment of breast cancer, the most common type of cancer in women. The toxicity profile of taxanes (including skin toxicities) induces dose adjustment, delay, or discontinuation, which prevents a sufficient dose intensity to achieve a response. Nanoparticle albumin-bound paclitaxel, a solvent-free form of paclitaxel, prevents toxicities and reduces the pharmacokinetic interferences between paclitaxel and other drugs. CASE PRESENTATION: We describe the case of a 55-year-old Caucasian woman with locally advanced breast cancer treated with neoadjuvant therapy who developed secondary skin toxicity due to delayed hypersensitivity to taxanes. She received Adriamycin® (doxorubicin), cyclophosphamide and docetaxel and developed toxicity that promoted treatment delay and a switch to weekly paclitaxel. After the third and fourth weeks of treatment, paclitaxel toxicities also induced treatment delay and paclitaxel was switched to nanoparticle albumin-bound paclitaxel. She completed the five planned nanoparticle albumin-bound paclitaxel cycles with acceptable tolerability (including persistent grade 2 neuropathy) and without dose delay or adjustments. Clinical response was achieved although pathological response was not good. CONCLUSIONS: Nanoparticle albumin-bound paclitaxel treatment is a good option for patients with breast cancer with taxanes-related skin toxicity. This drug allows the treatment to be completed with acceptable tolerance in our case.

Adapting iron dose supplementation in pregnancy for greater effectiveness on mother and child health: protocol of the ECLIPSES randomized clinical trial.

BACKGROUND: Currently, there is no consensus regarding iron supplementation dose that is most beneficial for maternal and offspring health during gestation. Recommended iron supplementation dose does not preempt anemia in around 20% of the pregnancies, nor the risk of hemoconcentration in 15%. This deficit, or excess, of iron prejudices the mother-child wellbeing. Therefore the aims of the study are to determine the highest level of effectiveness of iron supplementation adapted to hemoglobin (Hb) levels in early pregnancy, which would be optimum for mother-child health. DESIGN: Randomized Clinical Trial (RCT) triple-blindedSetting: 10 Primary Care Centers from Catalunya (Spain)Study subjects: 878 non-anemic pregnant women at early gestation stage, and their subsequent newborns METHODS: The study is structured as a RCT with 2 strata, depending on the Hb levels before week 12 of gestation. Stratum #1: If Hb from 110 to 130 g/L, randomly assigned at week 12 to receive iron supplement of 40 or 80 mg/d. Stratum #2: If Hb >130 g/L, randomly assigned at week 12 to receive iron supplement of 40 or 20 mg/d. MEASUREMENTS: In the mother: socio-economic data, clinical history, food item frequency, lifestyle and emotional state, and adherence to iron supplement prescription. Biochemical measurements include: Hb, serum ferritin, C reactive protein, cortisol, and alterations in the HFE gene (C282Y, H63D). In children: ultrasound fetal biometry, anthropometric measurements, and temperament development.Statistical analyses, using the SPSS program for Windows, will include bivariate and multivariate analyses adjusted for variables associated with the relationship under study. DISCUSSION: Should conclusive outcomes be reached, the study would indicate the optimal iron supplementation dose required to promote maternal and infant health. These results would contribute towards developing guidelines for good clinical practice.

[Effects of tobacco habit, second-hand smoking and smoking cessation during pregnancy on newborn's health]. / Impacto del tabaquismo, la exposición pasiva al tabaco y el dejar de fumar sobre la salud del recien nacido.

BACKGROUND AND OBJECTIVE: Tobacco during pregnancy affects the health of the newborn. The aim was to assess the effect of maternal exposure to active and passive tobacco and of smoking cessation on the risk of preterm deliveries and birth weight, taking into account other risk factors. PATIENTS AND METHOD: Longitudinal study conducted in 282 healthy pregnant women. General, obstetrical and hematological data were collected as it was the smoking habit during pregnancy. Pregnant women were classified as "exposed to smoke" (active smoker and passive smoker) and "unexposed to smoke" (non-smokers and women who quitted smoking during pregnancy). RESULTS: A percentage of 59.2 were non-smokers, 18.4% active smokers, 8.5% second-hand smokers and 13.8% had stopped smoking. Unexposed pregnant women who stopped smoking had the same risk of premature deliveries and children with similar birth weight as non-smoker women. Active and second-hand smokers were at higher risk of preterm deliveries than non-smokers (odds ratio [OR] 6.5, 95% confidence interval [95% CI] 1.4-30.8 and OR 6.2, 95% CI 1.0-38.9, respectively); however, higher levels of hemoglobin in the 1st and 3rd trimester exerted a protective effect (OR 0.9, 95% CI 0.8-0.9). Active and second-hand smokers had babies weighing less than non-smokers (around 129 and 178g less, respectively). CONCLUSIONS: Active or passive exposure to smoke during pregnancy and lower hemoglobin levels are associated with an increased risk of premature deliveries and lower birth weight. Stopping smoking during pregnancy prevents these detrimental effects.

Heme iron intake and risk of new-onset diabetes in a Mediterranean population at high risk of cardiovascular disease: an observational cohort analysis.

BACKGROUND: Several epidemiological studies have observed an increased risk of type 2 diabetes mellitus (T2DM) among subjects with a higher consumption of red and processed meat. Heme iron intake has been directly associated with a higher risk of T2DM in healthy adult Chinese and U.S populations. The objective of the present study was to evaluate the association between heme iron intake and the incidence of T2DM in a Mediterranean population at high cardiovascular risk. METHODS: We assessed a subset of participants in the PREDIMED trial as an observational cohort, followed up for a maximum of eight years. We initially included 1073 non-diabetic subjects (57.1% women) aged 67.3 ± 6.0 years, at high cardiovascular risk. Diet was assessed at the study baseline using a validated, semi-quantitative food frequency questionnaire. RESULTS: During the follow-up period 131 diabetics were newly diagnosed. The risk of developing T2DM was assessed using baseline heme iron intake and proportional hazard models, first unadjusted, then adjusted for energy, and finally adjusted for dietary, anthropometric, socio-demographic and lifestyle variables. Significant direct associations with the incidence of T2DM were found for heme iron (Hazard Ratio [HR] 1.30, 95% confidence interval [CI], 1.02 to 1.66). Secondarily, we have also observed that coffee (HR:0.93, 95% CI, 0.89 to 0.98) and alcoholic beverages (HR: 1.02, 95% CI, 1.01 to 1.04) were also found to reduce and increase the risk of T2DM, respectively. CONCLUSION: High dietary intake of heme iron was associated with an increased risk of developing T2DM in a Mediterranean population at high cardiovascular risk. TRIAL REGISTRATION: Identifier: ISRCTN35739639.

Diet, iron biomarkers and oxidative stress in a representative sample of Mediterranean population.

BACKGROUND: The consumption pattern characterized by high consumption of vegetables, fruit, fish, olive oil and red wine has been associated with improvements in the total antioxidant capacity of individuals and reduced incidence of diseases related to oxidation. Also, high body iron levels may contribute to increase the oxidative stress by the generation of reactive oxygen species. The objective of this study is to analyze the relationship between antioxidant and pro-oxidant factors obtained from the diet and iron biomarkers on lipoprotein oxidation and total antioxidant capacity in a representative sample of the Mediterranean population. METHODS: Cross-sectional prospective study, carried out with 815 randomly selected subjects (425 women and 390 men). Dietary assessment (3-day food records), iron biomarkers (serum ferritin, serum iron and transferrin saturation), biochemical markers of lipoperoxidation (TBARS), antioxidant capacity (ORAC) and CRP (C-Reactive Protein) were determined. Multiple Linear Regression (MLR) models were applied to analyze the association between diet factors and iron biomarkers on TBARS and ORAC levels. RESULTS: We observed that lipoperoxidation measured by TBARS increased by age but no differences were observed by sex. Antioxidant capacity measured by ORAC is independent of age and sex. In general, increasing age, tobacco, heme iron intake from meat and fish and transferrin saturation were independently and positively associated with TBARS, while non-heme iron was negatively associated. Vegetables, vitamin C intake and serum ferritin were positively associated with ORAC, whereas saturated fatty acids and meat intake were negatively associated. CONCLUSIONS: In our general population, we observed that oxidative stress is related to aging, but antioxidant capacity is not. The highest intake of dietary non-heme iron, vegetables and vitamin C intake exerts a protective effect against oxidation while the highest intake of dietary heme iron from meat and fish and saturated fatty acids are associated with increased oxidative stress. High levels of circulating iron measured by transferrin saturation are associated with increased oxidative stress in women however its association with the higher levels of serum ferritin is controversial.

Prevalence of iron deficiency states and risk of haemoconcentration during pregnancy according to initial iron stores and iron supplementation.

OBJECTIVE: To describe the prevalence of iron depletion (ID), iron-deficiency anaemia (IDA) and risk of haemoconcentration during pregnancy and at delivery and to assess the influence of initial Fe stores and Fe supplementation on that prevalence. DESIGN: Longitudinal study. SETTING: Hospital Universitari Sant Joan de Reus (Catalonia, Spain). SUBJECTS: Two hundred and eighty-five pregnant women. Serum ferritin and Hb were measured in the first, second and third trimesters and at delivery. Women were classified according to initial Fe stores as ID or no ID (serum ferritin $12mg/l) and according to Fe supplement use as supplemented or nonsupplemented. RESULTS: Initial ID was 16.2%. At delivery, 45.7% had ID, 13.5% IDA and 13.3% had risk of haemoconcentration. Initial ID and non-supplemented groups had significantly higher prevalences of ID and IDA and lower risk of haemoconcentration at delivery than the other groups. In the multiple logistic models, no initial ID and Fe supplementation exerted a protective effect against ID at delivery (adjusted OR50.28; 95% CI 0.13, 0.58 and adjusted OR50.39; 95% CI 0.22, 0.69, respectively). Moderate Fe supplementation did not seem to clearly prevent IDA (adjusted OR50.91; 95% CI 0.42, 1.96) or to enhance the haemoconcentration (adjusted OR51.42; 95% CI 0.58, 3.50). CONCLUSIONS: The prevalence of ID and IDA was high in late pregnancy in healthy pregnant women, particularly in those with initial ID and/or those not taking supplements. Starting pregnancy with no ID and/or taking moderate Fe supplementation decreased the likelihood of ID at delivery. The risk of haemoconcentration was high at delivery, but did not seem to be promoted by Fe supplementation. Further research is necessary to determine the most appropriate nutritional advice for pregnant women.