Coffee Intake, Caffeine Metabolism Genotype, and Survival Among Men with Prostate Cancer.

BACKGROUND: Coffee intake may lower prostate cancer risk and progression, but postdiagnosis outcomes by caffeine metabolism genotype are not well characterized. OBJECTIVE: To evaluate associations between coffee intake, caffeine metabolism genotype, and survival in a large, multicenter study of men with prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: Data from The PRACTICAL Consortium database for 5727 men with prostate cancer from seven US, Australian, and European studies were included. The cases included had data available for the CYP1A2 -163C>A rs762551 single-nucleotide variant associated with caffeine metabolism, coffee intake, and >6 mo of follow-up. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable-adjusted Cox proportional hazards models across pooled patient-level data were used to compare the effect of coffee intake (categorized as low [reference], high, or none/very low) in relation to overall survival (OS) and prostate cancer-specific survival (PCSS), with stratified analyses conducted by clinical disease risk and genotype. RESULTS AND LIMITATIONS: High coffee intake appeared to be associated with longer PCSS (hazard ratio [HR] 0.85, 95% confidence interval [CI] 0.68-1.08; p = 0.18) and OS (HR 0.90, 95% CI 0.77-1.07; p = 0.24), although results were not statistically significant. In the group with clinically localized disease, high coffee intake was associated with longer PCSS (HR 0.66, 95% CI 0.44-0.98; p = 0.040), with comparable results for the group with advanced disease (HR 0.92, 95% CI 0.69-1.23; p = 0.6). High coffee intake was associated with longer PCSS among men with the CYP1A2 AA (HR 0.67, 95% CI 0.49-0.93; p = 0.017) but not the AC/CC genotype (p = 0.8); an interaction was detected (p = 0.042). No associations with OS were observed in subgroup analyses (p > 0.05). Limitations include the nominal statistical significance and residual confounding. CONCLUSIONS: Coffee intake was associated with longer PCSS among men with a CYP1A2 -163AA (*1F/*1F) genotype, a finding that will require further replication. PATIENT SUMMARY: It is likely that coffee intake is associated with longer prostate cancer-specific survival in certain groups, but more research is needed to fully understand which men may benefit and why.

Toenail zinc as a biomarker: Relationship with sources of environmental exposure and with genetic variability in MCC-Spain study.

BACKGROUND: Toenails are commonly used as biomarkers of exposure to zinc (Zn), but there is scarce information about their relationship with sources of exposure to Zn. OBJECTIVES: To investigate the main determinants of toenail Zn, including selected sources of environmental exposure to Zn and individual genetic variability in Zn metabolism. METHODS: We determined toenail Zn by inductively coupled plasma mass spectrometry in 3,448 general population controls from the MultiCase-Control study MCC-Spain. We assessed dietary and supplement Zn intake using food frequency questionnaires, residential proximity to Zn-emitting industries and residential topsoil Zn levels through interpolation methods. We constructed a polygenic score of genetic variability based on 81 single nucleotide polymorphisms in genes involved in Zn metabolism. Geometric mean ratios of toenail Zn across categories of each determinant were estimated from multivariate linear regression models on log-transformed toenail Zn. RESULTS: Geometric mean toenail Zn was 104.1 µg/g in men and 100.3 µg/g in women. Geometric mean toenail Zn levels were 7 % lower (95 % confidence interval 1-13 %) in men older than 69 years and those in the upper tertile of fibre intake, and 9 % higher (3-16 %) in smoking men. Women residing within 3 km from Zn-emitting industries had 4 % higher geometric mean toenail Zn levels (0-9 %). Dietary Zn intake and polygenic score were unrelated to toenail Zn. Overall, the available determinants only explained 9.3 % of toenail Zn variability in men and 4.8 % in women. DISCUSSION: Sociodemographic factors, lifestyle, diet, and environmental exposure explained little of the individual variability of toenail Zn in the study population. The available genetic variants related to Zn metabolism were not associated with toenail Zn.

Priorities for research on environment, climate and health, a European perspective.

Climate change, urbanisation, chemical pollution and disruption of ecosystems, including biodiversity loss, affect our health and wellbeing. Research is crucial to be able to respond to the current and future challenges that are often complex and interconnected by nature. The HERA Agenda, summarised in this commentary, identifies six thematic research goals in the environment, climate and health fields. These include research to 1) reduce the effects of climate change and biodiversity loss on health and environment, 2) promote healthy lives in cities and communities, 3) eliminate harmful chemical exposures, 4) improve health impact assessment and implementation research, 5) develop infrastructures, technologies and human resources and 6) promote research on transformational change towards sustainability. Numerous specific recommendations for research topics, i.e., specific research goals, are presented under each major research goal. Several methods were used to define the priorities, including web-based surveys targeting researchers and stakeholder groups as well as a series of online and face-to-face workshops, involving hundreds of researchers and other stakeholders. The results call for an unprecedented effort to support a better understanding of the causes, interlinkages and impacts of environmental stressors on health and the environment. This will require breakdown of silos within policies, research, actors as well as in our institutional arrangements in order to enable more holistic approaches and solutions to emerge. The HERA project has developed a unique and exciting opportunity in Europe to consensuate priorities in research and strengthen research that has direct societal impact.

Setting the European environment and health research agenda -under-researched areas and solution-oriented research.

BACKGROUND: The aim of the EU-funded HERA (health and environment research agenda) project is to set priorities for the future European research agenda in the environment, climate and health nexus. We report results from a European researcher's perspective and identify research areas that have been inadequately investigated to date. METHODS: An online survey was completed by European researchers to assess, evaluate and visualise research gaps. These research gaps were identified for 21 predefined areas within 3 main categories: i) classical environment and health paradigm; ii) problem or sector-based research areas and approaches and iii) holistic research areas and concepts. All research gaps were then evaluated by expert groups with the pre-defined criteria and systematically summarized. For areas identified within the survey as under-reported, additional input was sought from a range of key selected experts. The EU project database Cordis was utilized to verify that these areas were under-researched. RESULTS: Between May and July 2019, 318 respondents from 38 countries reported 624 research gaps. The main areas for attention identified were: urban environments; chemicals; and climate change, (combined n = 313 gaps). Biodiversity loss and health; transport, mobility, sustainable solutions and health; energy transition and health; waste and the circular economy and health; ethics and philosophy and health were areas that were acknowledged as under-researched (combined n = 27 gaps). These under-researched areas were identified as having certain commonalities, they: i) mostly fell in the category "problem or sector based approaches"; ii) they are essential for developing and implementing solutions; and iii) require trans-disciplinary and cross-sectoral collaboration. CONCLUSIONS: Currently attention is given to topical and highly researched areas in environmental health. In contrast, this paper identifies key topics and approaches that are under-researched, yet, are critical for the implementation of the EU Green Deal, related strategies and action plans, and require further investigation and investment. The findings reveal the imperative to foster solutions-oriented, trans-disciplinary and participatory research and its implementation through changes in research funding and research structures.

Coffee consumption and colorectal cancer risk: a multicentre case-control study from Italy and Spain.

BACKGROUND: Coffee contains many bioactive substances that can play a role on colorectal cancer. Epidemiological evidence of coffee intake and colorectal cancer is, however, inconsistent. AIM: To provide further information on the risk of colorectal cancer in relation to coffee consumption. METHODS: Data derive from two companion case-control studies conducted in Italy and Spain within the European Union Project on Health Impacts of long-term exposure to disinfection by-products in Drinking Water and the Spanish Multi-Case Control study on Cancer. These included a total of 2289 incident cases with colorectal cancer and 3995 controls with information on coffee intake. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were derived from unconditional logistic regression models, adjusted for study centre, sex, age, education, smoking, and other covariates. RESULTS: Compared with never coffee drinkers, the OR was 0.99 (95% CI 0.95-1.02) for total coffee consumption. There was no significant trend in risk with dose or duration, the ORs being 0.95 (95% CI 0.72-1.25) for an amount of five or more cups per day of coffee and 0.95 (95% CI 0.75-1.19) for a duration of consumption of 50 years or longer. The OR was 1.04 (95% CI 0.87-1.25) for two or more cups per day of decaffeinated coffee. There were no heterogeneity across strata of various covariates, as well as no apparent differences between various anatomical subsites. CONCLUSION: This large pooled analysis of two studies shows no association of coffee and decaffeinated coffee with colorectal cancer risk.

Prenatal metal mixtures and child blood pressure in the Rhea mother-child cohort in Greece.

BACKGROUND: Child blood pressure (BP) is predictive of future cardiovascular risk. Prenatal exposure to metals has been associated with higher BP in childhood, but most studies have evaluated elements individually and measured BP at a single time point. We investigated impacts of prenatal metal mixture exposures on longitudinal changes in BP during childhood and elevated BP at 11 years of age. METHODS: The current study included 176 mother-child pairs from the Rhea Study in Heraklion, Greece and focused on eight elements (antimony, arsenic, cadmium, cobalt, lead, magnesium, molybdenum, selenium) measured in maternal urine samples collected during pregnancy (median gestational age at collection: 12 weeks). BP was measured at approximately 4, 6, and 11 years of age. Covariate-adjusted Bayesian Varying Coefficient Kernel Machine Regression and Bayesian Kernel Machine Regression (BKMR) were used to evaluate metal mixture impacts on baseline and longitudinal changes in BP (from ages 4 to 11) and the development of elevated BP at age 11, respectively. BKMR results were compared using static versus percentile-based cutoffs to define elevated BP. RESULTS: Molybdenum and lead were the mixture components most consistently associated with BP. J-shaped relationships were observed between molybdenum and both systolic and diastolic BP at age 4. Similar associations were identified for both molybdenum and lead in relation to elevated BP at age 11. For molybdenum concentrations above the inflection points (~ 40-80 µg/L), positive associations with BP at age 4 were stronger at high levels of lead. Lead was positively associated with BP measures at age 4, but only at high levels of molybdenum. Potential interactions between molybdenum and lead were also identified for BP at age 11, but were sensitive to the cutoffs used to define elevated BP. CONCLUSIONS: Prenatal exposure to high levels of molybdenum and lead, particularly in combination, may contribute to higher BP at age 4. These early effects appear to persist throughout childhood, contributing to elevated BP in adolescence. Future studies are needed to identify the major sources of molybdenum and lead in this population.

A call for urgent action to safeguard our planet and our health in line with the helsinki declaration.

In 2015, the Rockefeller Foundation-Lancet Commission launched a report introducing a novel approach called Planetary Health and proposed a concept, a strategy and a course of action. To discuss the concept of Planetary Health in the context of Europe, a conference entitled: "Europe That Protects: Safeguarding Our Planet, Safeguarding Our Health" was held in Helsinki in December 2019. The conference participants concluded with a need for action to support Planetary Health during the 2020s. The Helsinki Declaration emphasizes the urgency to act as scientific evidence shows that human activities are causing climate change, biodiversity loss, land degradation, overuse of natural resources and pollution. They threaten the health and safety of human kind. Global, regional, national, local and individual initiatives are called for and multidisciplinary and multisectorial actions and measures are needed. A framework for an action plan is suggested that can be modified for local needs. Accordingly, a shift from fragmented approaches to policy and practice towards systematic actions will promote human health and health of the planet. Systems thinking will feed into conserving nature and biodiversity, and into halting climate change. The Planetary Health paradigm ‒ the health of human civilization and the state of natural systems on which it depends ‒ must become the driver for all policies.

Quality of Life in a Cohort of 1078 Women Diagnosed with Breast Cancer in Spain: 7-Year Follow-Up Results in the MCC-Spain Study.

Breast cancer is the most frequent cause of tumors and net survival is increasing. Achieving a higher survival probability reinforces the importance of studying health-related quality of life (HR-QoL). The main aim of this work is to test the relationship between different sociodemographic, clinical and tumor-intrinsic characteristics, and treatment received with HR-QoL measured using SF-12 and the FACT/NCCN (National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy) Breast Symptom Index (FBSI). Women with breast cancer recruited between 2008 and 2013 and followed-up until 2017-2018 in a prospective cohort answered two HR-QoL surveys: the SF-12 and FBSI. The scores obtained were related to woman and tumor characteristics using linear regression models. The telephone survey was answered by 1078 women out of 1685 with medical record follow-up (64%). Increases in all three HR-QoL scores were associated with higher educational level. The score differences between women with university qualifications and women with no schooling were 5.43 for PCS-12, 6.13 for MCS-12 and 4.29 for FBSI. Histological grade at diagnosis and recurrence in the follow-up displayed a significant association with mental and physical HR-QoL, respectively. First-line treatment received was not associated with HR-QoL scores. On the other hand, most tumor characteristics were not associated with HR-QoL. As breast cancer survival is improving, further studies are needed to ascertain if these differences still hold in the long run.

Possible role of chondroitin sulphate and glucosamine for primary prevention of colorectal cancer. Results from the MCC-Spain study.

A safe and effective colorectal cancer (CRC) chemoprevention agent remains to be discovered. We aim to evaluate the association between the use of glucosamine and/or chondroitin sulphate and risk of colorectal cancer (CRC) in the MCC-Spain study, a case-control study performed in Spain that included 2140 cases of CRC and 3950 population controls. Subjects were interviewed on sociodemographic factors, lifestyle, family and medical history and regular drug use. Adjusted odds ratios and their 95% confidence intervals were estimated. The reported frequency of chondroitin and/or glucosamine use was 2.03% in controls and 0.89% in cases. Users had a reduced risk of CRC (OR: 0.47; 95% CI: 0.28-0.79), but it was no longer significant when adjusted for NSAID (nonsteroidal anti-inflammatory drugs) use (OR: 0.82; 95% CI: 0.47-1.40). A meta-analysis with previous studies suggested a protective effect, overall and stratified by NSAID use (OR: 0.77; 95% CI: 0.62-0.97). We have not found strong evidence of an independent preventive effect of CG on CRC in our population because the observed effects of our study could be attributed to NSAIDs concurrent use. These results merit further research due to the safety profile of these drugs.

PUFA status at birth and allergy-related phenotypes in childhood: a pooled analysis of the Maastricht Essential Fatty Acid Birth (MEFAB) and RHEA birth cohorts.

Lower prenatal exposure to n-3 PUFA relative to n-6 PUFA has been hypothesised to influence allergy development, but evidence remains largely inconsistent. In the Dutch Maastricht Essential Fatty Acid Birth (MEFAB) (n 293) and Greek RHEA Mother-Child (n 213) cohorts, we investigated whether cord blood phospholipid PUFA concentrations are associated with symptoms of wheeze, asthma, rhinitis and eczema at the age of 6-7 years. Information on allergy-related phenotypes was collected using validated questionnaires. We estimated relative risks (RR) and 95 % CI for associations of PUFA with child outcomes using multivariable generalised linear regression models. In pooled analyses, higher concentration of the n-3 long-chain EPA and DHA and a higher total n-3:n-6 PUFA ratio were associated with lower risk of current wheeze (RR 0·61; 95 % CI 0·45, 0·82 per sd increase in EPA+DHA and 0·54; 95 % CI 0·39, 0·75 per unit increase in the n-3:n-6 ratio) and reduced asthma risk (RR 0·50; 95 % CI 0·31, 0·79 for EPA+DHA and 0·43; 95 % CI 0·26, 0·70 for the n-3:n-6 ratio). No associations were observed for other allergy-related phenotypes. The results were similar across cohorts. In conclusion, higher EPA and DHA concentrations and a higher n-3:n-6 fatty acid ratio at birth were associated with lower risk of child wheeze and asthma. Our findings suggest that dietary interventions resulting in a marked increase in the n-3:n-6 PUFA ratio, and mainly in n-3 long-chain PUFA intake in late gestation, may reduce the risk of asthma symptoms in mid-childhood.

Adherence to nutrition-based cancer prevention guidelines and breast, prostate and colorectal cancer risk in the MCC-Spain case-control study.

Prostate, breast and colorectal cancer are the most common tumours in Spain. The aim of the present study was to evaluate the association between adherence to nutrition-based guidelines for cancer prevention and prostate, breast and colorectal cancer, in the MCC-Spain case-control study. A total of 1,718 colorectal, 1,343 breast and 864 prostate cancer cases and 3,431 population-based controls recruited between 2007 and 2012, were included in the present study. The World Cancer Research Fund/American Institute for Cancer Research (WCRC/AICR) score based on six recommendations for cancer prevention (on body fatness, physical activity, foods and drinks that promote weight gain, plant foods, animal foods and alcoholic drinks; score range 0-6) was constructed. We used unconditional logistic regression analysis adjusting for potential confounders. One-point increment in the WCRF/AICR score was associated with 25% (95% CI 19-30%) lower risk of colorectal, and 15% (95% CI 7-22%) lower risk of breast cancer; no association with prostate cancer was detected, except for cases with a Gleason score ≥7 (poorly differentiated/undifferentiated tumours) (OR 0.87, 95% CI 0.76-0.99). These results add to the wealth of evidence indicating that a great proportion of common cancer cases could be avoided by adopting healthy lifestyle habits.

Fish and seafood consumption during pregnancy and the risk of asthma and allergic rhinitis in childhood: a pooled analysis of 18 European and US birth cohorts.

Background: It has been suggested that prenatal exposure to n-3 long-chain fatty acids protects against asthma and other allergy-related diseases later in childhood. The extent to which fish intake in pregnancy protects against child asthma and rhinitis symptoms remains unclear. We aimed to assess whether fish and seafood consumption in pregnancy is associated with childhood wheeze, asthma and allergic rhinitis. Methods: We pooled individual data from 60 774 mother-child pairs participating in 18 European and US birth cohort studies. Information on wheeze, asthma and allergic rhinitis prevalence was collected using validated questionnaires. The time periods of interest were: infancy (0-2 years), preschool age (3-4 years), and school age (5-8 years). We used multivariable generalized models to assess associations of fish and seafood (other than fish) consumption during pregnancy with child respiratory outcomes in cohort-specific analyses, with subsequent random-effects meta-analyses. Results: The median fish consumption during pregnancy ranged from 0.44 times/week in The Netherlands to 4.46 times/week in Spain. Maternal fish intake during pregnancy was not associated with offspring wheeze symptoms in any age group nor with the risk of child asthma [adjusted meta-analysis relative risk (RR) per 1-time/week = 1.01, 95% confidence interval 0.97-1.05)] and allergic rhinitis at school age (RR = 1.01, 0.99-1.03). These results were consistently found in further analyses by type of fish and seafood consumption and in sensitivity analyses. Conclusion: We found no evidence supporting a protective association of fish and seafood consumption during pregnancy with offspring symptoms of wheeze, asthma and allergic rhinitis from infancy to mid childhood.

Vitamin D insufficient levels during pregnancy and micronuclei frequency in peripheral blood T lymphocytes mothers and newborns (Rhea cohort, Crete).

BACKGROUND & AIMS: Vitamin D deficiency is common among pregnant women and may be associated with several adverse health outcomes including cancer. Micronuclei frequency is a biomarker of early genetic effects and has been used to examine the association between genotoxic exposures and cancer. We examined maternal vitamin D levels during pregnancy in associations with micronuclei frequency in maternal blood and in cord blood. METHODS: 173 mothers and 171 newborns born between 2007 and 2008 in Heraklion (Crete, Greece) were included in the study. Between 14th and 18th weeks of gestation we collected information on maternal diet using food frequency questionnaires (FFQs). We measured maternal serum concentrations of 25-hydroxyvitamin D [25(OH)D] between the first and second trimester of pregnancy. We estimated dietary vitamin D intake using information from FFQ. After delivery we collected cord blood and maternal peripheral blood. We used the cytokinesis-block micronucleus (CBMN) assay to assess the frequencies of micronucleated cells in binucleated T lymphocytes (MNBN). RESULTS: Maternal insufficient serum levels of 25(OH)D (<50 nmol/L) during pregnancy were associated with increased MNBN frequency in cord blood [IRR = 1.32 (95%CI: 1.00, 1.72)]. This increase was higher for newborns with birth weight above the third quartile [≥3.500 kg; IRR = 2.21 (1.26, 3.89)]. Similarly, low levels of dietary vitamin D were associated with increased MNBN frequency in cord blood [middle tertile IRR = 1.08 (0.78, 1.47), lower tertile IRR = 1.51 (1.06, 2.14)]. Insufficient levels of vitamin D were not associated with MNBN in mothers. CONCLUSION: Our results suggest that vitamin D deficiency during pregnancy increases genotoxic risks in newborns. The prevalence of vitamin D deficiency globally is high and it is important to further investigate whether vitamin D supplementation or similar interventions during pregnancy could prevent DNA damage at early stages of life.

Impact of prenatal exposure to cadmium on cognitive development at preschool age and the importance of selenium and iodine.

The evidence regarding a potential link of low-to-moderate iodine deficiency, selenium status, and cadmium exposure during pregnancy with neurodevelopment is either contradicting or limited. We aimed to assess the prenatal impact of cadmium, selenium, and iodine on children's neurodevelopment at 4 years of age. The study included 575 mother-child pairs from the prospective "Rhea" cohort on Crete, Greece. Exposure to cadmium, selenium and iodine was assessed by concentrations in the mother's urine during pregnancy (median 13 weeks), measured by ICPMS. The McCarthy Scales of Children's Abilities was used to assess children's general cognitive score and seven different sub-scales. In multivariable-adjusted regression analysis, elevated urinary cadmium concentrations (≥0.8 µg/L) were inversely associated with children's general cognitive score [mean change: -6.1 points (95 % CI -12; -0.33) per doubling of urinary cadmium; corresponding to ~0.4 SD]. Stratifying by smoking status (p for interaction 0.014), the association was restricted to smokers. Urinary selenium was positively associated with children's general cognitive score [mean change: 2.2 points (95 % CI -0.38; 4.8) per doubling of urinary selenium; ~0.1 SD], although the association was not statistically significant. Urinary iodine (median 172 µg/L) was not associated with children's general cognitive score. In conclusion, elevated cadmium exposure in pregnancy of smoking women was inversely associated with the children's cognitive function at pre-school age. The results indicate that cadmium may adversely affect neurodevelopment at doses commonly found in smokers, or that there is an interaction with other toxicants in tobacco smoke. Additionally, possible residual confounding cannot be ruled out.

Health effects of non-occupational exposure to oil extraction.

Oil extraction may cause extensive environmental impact that can affect health of populations living in surrounding areas. Large populations are potentially exposed to oil extraction related contamination through residence in areas where oil extraction is conducted, especially in low and middle income countries (LMICs). Health effects among people residentially exposed to upstream oil industry contaminants have been poorly studied. Health effects of exposure to oil related contamination have been mainly studied among cleanup workers after oil spills from tankers or offshore platforms.In this paper we aim to identify the type and extension of residential exposures related to oil extraction activities and to comment on the few health studies available. We estimated that 638 million persons in LMICs inhabit rural areas close to conventional oil reservoirs. It is relevant to specifically study people residentially exposed to upstream oil industry for the following reasons: First, persons are exposed during long periods of time to oil related contamination. Second, routes of exposure differ between workers and people living close to oil fields, who can be exposed by ingestion of contaminated waters/foods and by dermal contact with contaminated water and/or land during daily activities (e.g. bathing, agricultural activities, etc.). Third, individuals potentially more susceptible to the effect of oil related contamination and not normally occupationally exposed, such as infants, children, pregnant women, elderly or people with previous health conditions, are also exposed.There are few papers studying the potential health effects of residential exposure to oil related contamination, and most of them share important limitations. There is a need for more research through the conduct of methodologically robust studies in exposed populations worldwide. Despite the difficulties in the conduct of studies in remote areas, novel approaches, such as measurement of individual exposure using biomarkers of exposure and effect, should be used. These studies should be promoted to understand the health risks associated to residential exposure to oil related contamination, support effective control policies to avoid such contamination and to sustain public health recommendations and policies to avoid exposure in already contaminated areas.

Dietary patterns in early childhood and child cognitive and psychomotor development: the Rhea mother-child cohort study in Crete.

Early-life nutrition is critical for optimal brain development; however, few studies have evaluated the impact of diet as a whole in early childhood on neurological development with inconsistent results. The present analysis is a cross-sectional study nested within an ongoing prospective birth cohort, the Rhea study, and aims to examine the association of dietary patterns with cognitive and psychomotor development in 804 preschool (mean age 4·2 years) children. Parents completed a validated FFQ, and dietary patterns were identified using principal component analysis. Child cognitive and psychomotor development was assessed by the McCarthy Scales of Children's Abilities (MSCA). Multivariable linear regression models were used to investigate the associations of dietary patterns with the MSCA scales. After adjustment for a large number of confounding factors, the 'Snacky' pattern (potatoes and other starchy roots, salty snacks, sugar products and eggs) was negatively associated with the scales of verbal ability (ß=-1·31; 95 % CI -2·47, -0·16), general cognitive ability (ß=-1·13; 95 % CI -2·25, -0·02) and cognitive functions of the posterior cortex (ß=-1·20; 95 % CI -2·34, -0·07). Further adjustment for maternal intelligence, folic acid supplementation and alcohol use during pregnancy attenuated the observed associations, but effect estimates remained at the same direction. The 'Western' and the 'Mediterranean' patterns were not associated with child neurodevelopmental scales. The present findings suggest that poorer food choices at preschool age characterised by foods high in fat, salt and sugar are associated with reduced scores in verbal and cognitive ability.

The effect of high doses of folic acid and iron supplementation in early-to-mid pregnancy on prematurity and fetal growth retardation: the mother-child cohort study in Crete, Greece (Rhea study).

PURPOSE: We examined whether high doses of folic acid and iron supplementation in early-to-mid pregnancy affect the risk of preterm birth, low birth weight, and small for gestational age neonates, in the mother-child cohort in Crete, Greece (Rhea study). METHODS: We included 1,279 women with singleton pregnancies with complete data on supplements use in early-to-mid pregnancy and birth outcomes. Anthropometric measurements at birth were obtained from medical records. Red blood cell folate concentrations in cord blood were measured in a subsample of the study population (n = 58). RESULTS: Sixty-six percent of the study participants reported high doses of supplemental folic acid use (5 mg/day), while 21 % reported excessive doses of folic acid use (>5 mg/day) in early-to-mid pregnancy. Daily intake of 5-mg supplemental folic acid was associated with a 31 % decrease in the risk of preterm birth (RR, 0.69; 95 % CI, 0.44, 0.99), 60 % decrease in the risk of delivering a low birth weight neonate (RR, 0.40; 95 % CI, 0.21, 0.76), and 66 % decrease in the risk of delivering a small for gestational age (SGA) neonate (RR, 0.34; 95 % CI, 0.16, 0.73). Daily doses of iron supplementation more than 100 mg were associated with a twofold increased risk for SGA neonates (RR, 2.14; 95 % CI, 0.99, 5.97). CONCLUSION: These findings suggest that high daily doses of supplementary folic acid in early-to-mid pregnancy may be protective for preterm birth, low birth weight, and small for gestational age neonates, while high daily doses of supplementary iron may be harmful for fetal growth.

Effect of high doses of folic acid supplementation in early pregnancy on child neurodevelopment at 18 months of age: the mother-child cohort 'Rhea' study in Crete, Greece.

OBJECTIVE: To investigate whether high doses of folic acid supplementation in early pregnancy are associated with child neurodevelopment at 18 months of age. DESIGN: The study uses data from the prospective mother-child cohort 'Rhea' study. Pregnant women completed an interviewer-administered questionnaire on folic acid supplementation at 14-18 weeks of gestation. Neurodevelopment at 18 months was assessed with the use of the Bayley Scales of Infant and Toddler Development (3rd edition). Red-blood-cell folate concentrations in cord blood were measured in a sub-sample of the study population (n 58). SETTING: Heraklion, Crete, Greece, 2007-2010. SUBJECTS: Five hundred and fifty-three mother-child pairs participating in the 'Rhea' cohort. RESULTS: Sixty-eight per cent of the study participants reported high doses of supplemental folic acid use (5 mg/d), while 24 % reported excessive doses of folic acid (>5 mg/d) in early pregnancy. Compared with non-users, daily intake of 5 mg supplemental folic acid was associated with a 5-unit increase on the scale of receptive communication and a 3·5-unit increase on the scale of expressive communication. Doses of folic acid supplementation higher than 5 mg/d were not associated with additional increase in the neurodevelopmental scales. CONCLUSIONS: This is the first prospective study showing that high doses of supplementary folic acid in early pregnancy may be associated with enhanced vocabulary development, communicational skills and verbal comprehension at 18 months of age. Additional longitudinal studies and trials are needed to confirm these results.

Pancreatic cancer risk and levels of trace elements.

BACKGROUND AND AIMS: Knowledge on the aetiology of exocrine pancreatic cancer (EPC) is scant. The best established risk factor for EPC is tobacco smoking. Among other carcinogens, tobacco contains cadmium, a metal previously associated with an increased risk of EPC. This study evaluated the association between concentrations of trace elements in toenails and EPC risk. METHODS: The study included 118 EPC cases and 399 hospital controls from eastern Spain. Levels of 12 trace elements were determined in toenail samples by inductively coupled plasma mass spectrometry. OR and 95% CI, adjusted for potential confounders, were calculated using logistic regression. RESULTS: Significantly increased risks of EPC were observed among subjects whose concentrations of cadmium (OR 3.58, 95% CI 1.86 to 6.88; p(trend)=5×10(-6)), arsenic (OR 2.02, 95% CI 1.08 to 3.78; p(trend)=0.009) and lead (OR 6.26, 95% CI 2.71 to 14.47; p(trend)=3×10(-5)) were in the highest quartile. High concentrations of selenium (OR 0.05, 95% CI 0.02 to 0.15; p(trend)=8×10(-11)) and nickel (OR 0.27, 95% CI 0.12 to 0.59; p(trend)=2×10(-4)) were inversely associated with the risk of EPC. CONCLUSION: Novel associations are reported of lead, nickel and selenium toenail concentrations with pancreas cancer risk. Furthermore, the results confirm previous associations with cadmium and arsenic. These novel findings, if replicated in independent studies, would point to an important role of trace elements in pancreatic carcinogenesis.

Dietary patterns during pregnancy and the risk of postpartum depression: the mother-child 'Rhea' cohort in Crete, Greece.

OBJECTIVE: To identify and describe dietary patterns in a cohort of pregnant women, and investigate whether dietary patterns during pregnancy are related to postpartum depression (PPD). DESIGN: The study uses data from the prospective mother-child cohort 'Rhea' study. Pregnant women completed an FFQ in mid-pregnancy and the Edinburg Postpartum Depression Scale (EPDS) at 8-10 weeks postpartum. Dietary patterns during pregnancy ('health conscious', 'Western') were identified using principal component analysis. Associations between dietary patterns categorized in tertiles and PPD symptoms were investigated by multivariable regression models after adjusting for confounders. SETTING: Heraklion, Crete, Greece, 2007-2010. SUBJECTS: A total of 529 women, participating in the 'Rhea' cohort. RESULTS: High adherence to a 'health conscious' diet, characterized by vegetables, fruit, pulses, nuts, dairy products, fish and olive oil, was associated with lower EPDS scores (highest v. lowest tertile: ß-coefficient = -1·75, P = 0·02). Women in the second (relative risk (RR) = 0·52, 95 % CI 0·30, 0·92) or third tertile (RR = 0·51, 95 % CI 0·25, 1·05) of the 'health conscious' dietary pattern were about 50 % less likely to have high levels of PPD symptoms (EPDS ≥ 13) compared with those in the lowest tertile. CONCLUSIONS: This is the first prospective study showing that a healthy diet during pregnancy is associated with reduced risk for PPD. Additional longitudinal studies and trials are needed to confirm these findings.