Association of maternal prenatal urinary fluoride levels with ADHD symptoms in childhood.

BACKGROUND: Health concerns about the potential impact of exposure to fluoride via drinking water (DW) on neuropsychological development include behavioral outcomes such as ADHD. OBJECTIVE: We aimed to examine the association between prenatal maternal urinary fluoride and symptoms associated with attention-deficit/hyperactivity disorder (ADHD) at the age of 8 and 11 years. METHOD: Data from 255 to 236 mother-child pairs from the "Infancia y Medio Ambiente" (INMA) birth cohort (Gipuzkoa; Spain) with maternal urinary F adjusted for creatinine (MUFcr) during pregnancy (first and third trimester) and child assessments of ADHD-like symptoms reported by Conners' Rating Scales-Revised at age of 8 and 11 years was available. Clinical approach was also used: cut off criteria (T > 66). Multiple linear regression models were fitted when outcomes were analyzed as continuous, and logistic regression models when the outcomes were analyzed with a categorical clinical approach. Covariates related to maternal characteristics, birth outcomes, childhood, quality of family context and biomarkers of neuro-toxicants were used. RESULTS: No association was found between MUFcr levels during pregnancy and cognitive problems-inattention, hyperactivity or ADHD index score of symptoms at 8 or 11 years. When results were analyzed from the perspective of a clinical approach, at the age of 11 years, there were significant inverse association between MUFcr and being categorized as a cognitive problems-inattention case. ORs were also indicative of a lower risk, although not significant, for ADHD index at age 11. Sensitivity analyses, taking into consideration quality of family context or the levels of other toxicants during pregnancy showed similar results. CONCLUSIONS: Higher levels of MUFcr in pregnant women were associated with a lower risk of cognitive problems-inattention at 11 years. These findings are inconsistent with those from previous studies and indicate the need for other population-based studies to confirm or overturn these results.

Prenatal exposure to fluoride and neuropsychological development in early childhood: 1-to 4 years old children.

BACKGROUND: Cross-sectional and prospective studies have provided evidence of the neurotoxic effect of early exposure to fluoride (F) in pregnancy. It has been negatively associated with cognitive development during childhood, with most research conducted in areas with high F levels in community drinking water (CDW). METHOD: Data from 316 to 248 mother-child pairs from the Infancia y Medio Ambiente (Childhood and Environment, INMA) birth cohort project with maternal urinary F level adjusted for creatinine (MUFcr) measurements in the first and third trimesters of pregnancy. Children's cognitive domains and intelligence indexes were evaluated using the Bayley Scales (age of 1) and the McCarthy Scales (age of 4). Multiple linear regression analyses were carried out adjusting for a wide range of covariates related to the child, mother, family context and other potential neurotoxicants. RESULTS: No association was found between MUFcr levels and Bayley Mental Development Index score. Nevertheless, regarding the McCarthy scales, it was found that per unit (mg/g) of MUFcr across the whole pregnancy, scores in boys were greater for the verbal, performance, numeric and memory domains (ß = 13.86, CI 95%: 3.91, 23.82), (ß = 5.86, CI 95%: 0.32, 11.39), (ß = 6.22, CI 95%: 0.65, 11.79) and (ß = 11.63, CI 95%: 2.62, 20.63) respectively and for General Cognitive Index (ß = 15.4, CI 95%: 6.32, 24.48). For girls there was not any cognitive score significantly associated with MUFcr, being the sex-F interactions significant (P interaction <0.05). Including other toxicants levels, quality of family context or deprivation index did not substantially change the results. CONCLUSIONS: In boys, positive associations were observed between MUFcr and scores in cognitive domains at the age of 4. These findings are inconsistent with those from some previous studies and indicate the need for other population-based studies to confirm or overturn these results at low levels of F in CDW.

Dietary inflammatory index of mothers during pregnancy and Attention Deficit-Hyperactivity Disorder symptoms in the child at preschool age: a prospective investigation in the INMA and RHEA cohorts.

Inflammation provides a substrate for mechanisms that underlie the association of maternal diet during pregnancy with Attention Deficit-Hyperactivity Disorder (ADHD) symptoms in childhood. However, no previous study has quantified the proinflammatory potential of maternal diet as a risk factor for ADHD. Thus, we evaluated the association of maternal dietary inflammatory index (DII®) scores during pregnancy with ADHD symptoms in 4-year-old children born in two Mediterranean regions. We analyzed data from two population-based birth cohort studies-INMA (Environment and Childhood) four subcohorts in Spain (N = 2097), and RHEA study in Crete (Greece) (N = 444). The DII score of maternal diet was calculated based on validated food frequency questionnaires completed during pregnancy (12th and/or 32nd week of gestation). ADHD symptoms were assessed by ADHD-DSM-IV in INMA cohort and by ADHDT test in RHEA cohort, with questionnaires filled-out by teachers and parents, respectively. The associations between maternal DII and ADHD symptoms were analysed using multivariable-adjusted zero-inflated negative binomial regression models in each cohort study separately. Meta-analysis was conducted to combine data across the cohorts for fitting within one model. The DII was significantly higher in RHEA (RHEA = 2.09 [1.94, 2.24]) in comparison to INMA subcohorts (Asturias = - 1.52 [- 1.67, - 1.38]; Gipuzkoa = - 1.48 [- 1.64, - 1.33]; Sabadell = - 0.95 [- 1.07, - 0.83]; Valencia = - 0.76 [- 0.90, - 0.62]). Statistically significant reduced risk of inattention symptomatology (OR = 0.86; CI 95% = 0.77-0.96), hyperactivity symptomatology (OR = 0.82; CI 95% = 0.72-0.92) and total ADHD symptomatology (OR = 0.82; CI 95% = - 0.72 to 0.93) were observed with increased maternal DII in boys. No statistically significant associations were observed in girls between maternal DII and inattention, hyperactivity and total ADHD symptomatology. We found reduced risk of ADHD symptomatology with increased DII only in boys. This relationship requires further exploration in other settings.

Prenatal manganese serum levels and neurodevelopment at 4 years of age.

BACKGROUND: The excess of manganese (Mn) causes severe deleterious effects in the central nervous system, and the developing brain is especially sensitive to Mn overload. However, results of prospective studies regarding Mn neurodevelopmental effects remain inconclusive. The present study aims at studying the association of prenatal Mn exposure and neurodevelopment at 4-5 years of age. METHODS: Mn serum concentration was measured in 1465 pregnant women from the INMA (INfancia y MedioAmbiente, Environment and Childhood) Project. Neurodevelopment was assessed using a standardized version of the McCarthy Scales of Children's Abilities (MSCA). Multivariate regression models were used for data analysis. RESULTS: No association was found between Mn levels in serum and any of the McCarthy scales. However, the stratification by sex showed a positive and beneficial association of prenatal Mn levels and the verbal, quantitative and general-cognitive scales in girls (ß (95%CI): 4 (0.03, 7.96), 4.5 (0.43, 8.57) and 4.32 (0.6, 8.05), respectively). CONCLUSIONS: A beneficial association was found for the first time between prenatal Mn levels measured in serum and neurodevelopment of female offspring at 4 years of age, which could have implications on public health policies, specifically on the establishment of policies promoting prenatal health related to dietary deficits of micronutrients such as Mn.

Association between prenatal exposure to air pollutants and newborn thyroxine (T4) levels.

BACKGROUND: Thyroid hormones play a key role in fetal and child development. Recent studies have linked prenatal exposure to atmospheric contaminants with changes in thyroid hormone levels in newborns, but the data from the few studies that have explored this issue are inconclusive. The present study aims to assess the association of total thyroxine (TT4) levels in newborns with weekly prenatal exposure to PM2.5 and NO2 and to identify sensitivity windows to exposure to air pollution in different developmental stages. METHODS: This prospective cohort study included mother-child pairs from the INMA-Gipuzkoa project. Specifically, 463 mother-child pairs with data on PM2.5 and NO2 exposure during pregnancy and TT4 levels at birth were included. PM2.5 and NO2 levels were measured by high-volume aerosol samplers and passive samplers respectively during the women's pregnancies. TT4 levels were measured in heel-prick blood samples from infants. Data on maternal and infant covariates were gathered through questionnaires administered in the first and third trimesters of pregnancy and review of clinical records. Potential associations of PM2.5 and NO2 with TT4 levels over the entire pregnancy was assessed by linear regression models and DLMs were used to identify susceptibility windows. RESULTS: The exposure of pregnant women to PM2.5 during pregnancy was positively associated with infant TT4 level at birth (ß [95% CI] = 0.198 [0.091, 0.305]. DLMs identified three different sensitivity windows, one in the periconceptional period with a negative association between PM2.5 exposure and TT4 levels at birth, and a second (weeks 12-17) and a third one (weeks 31-37) with a positive association. In addition, the later the exposure, the stronger the association. In contrast, no association was observed between NO2 exposure and TT4 levels. CONCLUSIONS: The results indicate that prenatal exposure to PM2.5 could lead to a thyroid function impairment in newborns.

Tumour characteristics and survivorship in a cohort of breast cancer: the MCC-Spain study.

PURPOSE: The objective of this study is to analyse the relative survival with breast cancer in women diagnosed after new treatments were generalised and to ascertain the current effect that tumour characteristics such as grade, stage or subtype have on survival as well as the new AJCC-pathological prognostic score. METHODS: The breast cancer MCC-Spain follow-up study is a prospective cohort study of 1685 incident breast cancer cases. Women between 20 and 85 years old were recruited between the years 2008 and 2013 in 18 hospitals located in 10 Spanish provinces and they have been followed until 2017/2018. Relative survival was estimated after 3, 5 and 8 years of follow-up using Ederer II method. In addition, Weibull regression adjusted by age, hospital, grade and stage was used to investigate prognosis factors. RESULTS: Among components of TNM staging system, tumour size greater than 50 mm (i.e. T3 or T4) more than doubled the risk of dying, while N3 nodal involvement and presence of metastasis had a huge effect on mortality. The AJCC pathological prognostic score strongly correlated with survival; thus, hazard ratios increased as the score rose, being 2.31, 4.00, 4.94, 7.92, 2.26, 14.9 and 58.9 for scores IB, IIA, IIB, IIIA, IIIB, IIIC and IV, respectively. CONCLUSION: Both TNM staging and histological/molecular biomarkers are associated with overall survival in Spanish women with breast cancer; when both are combined in the AJCC pathological prognosis score, the prognostic value improved with risk indices that increased rapidly as the pathological prognosis score increased.

Who feels a greater environmental risk? Women, younger adults and pro-environmentally friendly people express higher concerns about a set of environmental exposures.

Health-related risk perceptions concerning environmental exposures reflect the public's awareness of certain environmental issues that may compromise their health. These perceptions may trigger coping strategies and self-protective behaviors, which are key for protecting people's health. With this study, we sought 1) to assess the general public's perceptions of risk from a set of environmental exposures compared with the assessment of experts; and 2) to build predictive models of the general public's risk perceptions using a comprehensive set of sociodemographic and psycho-environmental variables. We recruited a sample of 338 inhabitants (208 women, 45.8 years on average) of Gipuzkoa (Basque Country). Participants completed a paper-and-pencil questionnaire comprising questions on general sociodemographic characteristics and on health-related behaviors, and several psycho-environmental scales assessing general environmental knowledge, nature relatedness, pro-environmental behavior, environmental concerns and place attachment. Additionally, we contacted 33 regional experts who also evaluated the risk associated with the given set of exposures. Risk scores assigned by participants ranged from 1.51 to 3.42 (out of 4) and were higher than those assigned by the experts. Nonetheless, the pattern of risk prioritization was similar in the two groups. Explanatory models accounted for small to moderate shares of the variance in environmental exposure risk (R2 = 0.05 to 0.17). The best predictors of risk perceptions were gender, age, environmental knowledge and egoistic environmental concerns. Biospheric concerns, nature relatedness and educational level hardly made any contribution. Assessment of past experiences with each environmental exposure, affective reactions towards them and psychological traits could enrich future explanatory models.

Changes in individual and contextual socio-economic level influence on reproductive behavior in Spanish women in the MCC-Spain study.

BACKGROUND: The association between socioeconomic level and reproductive factors has been widely studied. For example, it is well known that women with lower socioeconomic status (SES) tend to have more children, the age at first-born being earlier. However, less is known about to what extent the great socioeconomic changes occurred in a country (Spain) could modify women reproductive factors. The main purpose of this article is to analyze the influence of individual and contextual socioeconomic levels on reproductive factors in Spanish women, and to explore whether this influence has changed over the last decades. METHODS: We performed a cross-sectional design using data from 2038 women recruited as population-based controls in an MCC-Spain case-control study. RESULTS: Higher parent's economic level, education level, occupational level and lower urban vulnerability were associated with higher age at first delivery and lower number of pregnancies. These associations were stronger for women born after 1950: women with unfinished primary education had their first delivery 6 years before women with high education if they were born after 1950 (23.4 vs. 29.8 years) but only 3 years before if they were born before 1950 (25.7 vs. 28.0 years). For women born after 1950, the number of pregnancies dropped from 2.1 (unfinished primary school) to 1.7 (high education), whereas it remained almost unchanged in women born before 1950. CONCLUSIONS: Reproductive behavior was associated with both individual and area-level socio-economic indicators. Such association was stronger for women born after 1950 regarding age at first delivery and number of pregnancies and for women born before 1950 regarding consumption of hormonal contraceptives or postmenopausal therapy.

Association study of dietary non-enzymatic antioxidant capacity (NEAC) and colorectal cancer risk in the Spanish Multicase-Control Cancer (MCC-Spain) study.

PURPOSE: Studies attempting to link dietary non-enzymatic antioxidant activity (NEAC) and colorectal cancer (CRC) risk have reported mixed results. We examined this association in the Spanish Multicase-Control Study considering the likely influence of coffee and other dietary factors. METHODS: 1718 CRC cases and 3312 matched-controls provided information about diet through a validated 140-item food frequency questionnaire. Dietary NEAC was estimated for three methods [total radical-trapping antioxidant parameters (TRAP), ferric reducing/antioxidant power (FRAP) and TEAC-ABTS] using published values of NEAC content in food, with and without coffee's NEAC. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated through unconditional logistic regression models adjusted for lifestyle and dietary factors. RESULTS: Overall dietary intake of NEAC was significantly lower in cases compared to controls and associated with a significantly reduced CRC risk, in both men (ORQ5vsQ1 = 0.67, 95% CI 0.47-0.96 for FRAP) and women (ORQ5vsQ1 = 0.53, 95% CI 0.32-085 for FRAP), in multivariate models with and without the antioxidant contribution from coffee. The effect was similar for all the NEAC methods evaluated and for both colon and rectum. The association between dietary NEAC and CRC risk became non-significant when adjusting for fiber intake. However, intakes of NEAC and fiber were correlated. CONCLUSION: This study indicates that intake of an antioxidant-rich plant-based diet, both with and without NEAC from coffee, is associated with decreased CRC risk.

Exposure and health risks perception of extremely low frequency and radiofrequency electromagnetic fields and the effect of providing information.

Given that regardless of actual exposure levels, high-risk perceptions of electromagnetic fields of non-ionizing radiation (EMF-NIR) may cause health effects, it is important to understand the mechanisms behind perceptions in the general population. The aims of this study were to assess perceptions of both exposure and health-risk among mothers of the INMA (Environment and childhood)-Gipuzkoa child cohort; to explore possible determinants that explain such perceptions; and to evaluate whether providing information on exposure levels has any effect on perceptions. Overall, 387 mothers completed a questionnaire composed of four questions on perceived exposure and perceived health-risk of exposure to extremely low frequency (ELF) and radiofrequency (RF) fields answered on a Likert-type scale from 0 to 10. Later, measurements of ELF and RF fields were conducted in the houses of a subsample of 104 participants. All measured levels were far below the levels established by the European Council recommendation. This was explained in the individual reports sent to the families. After reading the results, mothers completed the aforementioned questionnaire a second time, plus two additional questions regarding the role of public health bodies in risk communication. The association between perceived and measured levels as categorical variables was assessed with a chi-square test. Multiple linear regressions were conducted for each of the questions related to perceived exposure and health-risk perceptions. Wilcoxon signed-rank test was conducted to assess the effect of receiving information. Both exposure and health risk were perceived to be very high for both ELF and RF fields, with mean and medians of 7 on a 10-point scale. Reporting higher perception levels was not associated with higher levels of exposure measured at home. Variables that were repeatedly associated with higher perceptions included: manual social class, not having the feeling of living in a good neighborhood, difficulty getting by financially, not having a television antenna within 600 m, being younger and having fewer devices at home. Providing information on EMF-NIR exposure levels at home did not alter health-risk perceptions, but mean perceived RF exposure decreased significantly (by 0.7 points). Most of the participants claimed to have received no or insufficient information regarding exposure and health-risks of EMF-NIR from public bodies and considered it very important that they should.

Methodological issues in a prospective study on plasma concentrations of persistent organic pollutants and pancreatic cancer risk within the EPIC cohort.

BACKGROUND: The use of biomarkers of environmental exposure to explore new risk factors for pancreatic cancer presents clinical, logistic, and methodological challenges that are also relevant in research on other complex diseases. OBJECTIVES: First, to summarize the main design features of a prospective case-control study -nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort- on plasma concentrations of persistent organic pollutants (POPs) and pancreatic cancer risk. And second, to assess the main methodological challenges posed by associations among characteristics and habits of study participants, fasting status, time from blood draw to cancer diagnosis, disease progression bias, basis of cancer diagnosis, and plasma concentrations of lipids and POPs. Results from etiologic analyses on POPs and pancreatic cancer risk, and other analyses, will be reported in future articles. METHODS: Study subjects were 1533 participants (513 cases and 1020 controls matched by study centre, sex, age at blood collection, date and time of blood collection, and fasting status) enrolled between 1992 and 2000. Plasma concentrations of 22 POPs were measured by gas chromatography - triple quadrupole mass spectrometry (GC-MS/MS). To estimate the magnitude of the associations we calculated multivariate-adjusted odds ratios by unconditional logistic regression, and adjusted geometric means by General Linear Regression Models. RESULTS: There were differences among countries in subjects' characteristics (as age, gender, smoking, lipid and POP concentrations), and in study characteristics (as time from blood collection to index date, year of last follow-up, length of follow-up, basis of cancer diagnosis, and fasting status). Adjusting for centre and time of blood collection, no factors were significantly associated with fasting status. Plasma concentrations of lipids were related to age, body mass index, fasting, country, and smoking. We detected and quantified 16 of the 22 POPs in more than 90% of individuals. All 22 POPs were detected in some participants, and the smallest number of POPs detected in one person was 15 (median, 19) with few differences by country. The highest concentrations were found for p,p'-DDE, PCBs 153 and 180 (median concentration: 3371, 1023, and 810 pg/mL, respectively). We assessed the possible occurrence of disease progression bias (DPB) in eight situations defined by lipid and POP measurements, on one hand, and by four factors: interval from blood draw to index date, tumour subsite, tumour stage, and grade of differentiation, on the other. In seven of the eight situations results supported the absence of DPB. CONCLUSIONS: The coexistence of differences across study centres in some design features and participant characteristics is of relevance to other multicentre studies. Relationships among subjects' characteristics and among such characteristics and design features may play important roles in the forthcoming analyses on the association between plasma concentrations of POPs and pancreatic cancer risk.

Poor mothers, unhealthy children: the transmission of health inequalities in the INMA study, Spain.

BACKGROUND: The health of pregnant women and their fetuses are especially sensitive to socioeconomic conditions. This study analyzes the impact of maternal socioeconomic status (SES), evaluated by occupation and maternal education level, in preterm births (PTBs) and in small for gestational age (SGA) fetuses, considering the effect of the potential mediating factors on the SES and birth outcomes. METHODS: A total of 2497 mother/newborn dyads from the INMA-Spain project were studied. We examined maternal occupation and education in relation to PTB and SGA along with covariate data, using logistic regression analysis. Adjusted models for each of the outcome variables in relation to SES indicators were estimated, considering potential mediating factors. RESULTS: About 4.7% of babies were PTB and 9.7% SGA. Full adjusted logistic regression models showed similar odds ratio (OR) for SGA in both SES indicators. Manual working women or without university studies had higher risk of SGA than their counterpart groups (OR = 1.39% CI = 1.03-1.88 and OR = 1.39% CI = 1.00-2.00, respectively). Likewise, mothers with a manual occupation were at more risk of PTB than those with a non-manual occupation (OR = 1.74 95% CI = 1.13-2.74), but there was no association between education and PTB. Smoking, pre-pregnancy BMI and underweight gain during pregnancy were significantly associated to SGA births. The mother's age, presence of complications and overweight gain during pregnancy were related to PTB. CONCLUSION: The mother's socioeconomic disadvantage was consistently associated with birth outcomes giving rise to intergenerational transmission of health inequalities. Reducing inequalities requires eliminating the upstream causes of poverty itself.

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.

Antibody reactivity against Helicobacter pylori proteins in a sample of the Spanish adult population in 2008-2013.

BACKGROUND: Differences in Helicobacter pylori protein expression have been related to the risk of severe gastric diseases. In Spain, a marked geographic pattern in gastric cancer mortality has long been reported. OBJECTIVE: To characterize antibody reactivity patterns against 16 H. pylori proteins, by age, sex, and region of birth, in a large sample of the Spanish adult population. MATERIALS AND METHODS: Antibody reactivity was quantified by H. pylori multiplex serology in a sample from the control group of the multicase-control study MCC-Spain. For this analysis, 2555 population-based controls were included. Each participant was classified as seropositive or seronegative for each protein according to specific cutoffs. Overall H. pylori seroprevalence was defined as positivity against ≥4 proteins. Descriptive analyses by age, sex, and region of birth were performed for both seroprevalence and seroreactivity (continuous measure). Differences among groups were tested by logistic and linear regression models. RESULTS: Overall H. pylori seroprevalence increased with age in both sexes. For ages 55-74, seroprevalence was lower in women than in men (84% vs 92%, P<.001). Region of birth explained 7% of the variability in seroprevalence. Among H. pylori seropositive subjects, proteins with the highest seroprevalence were GroEL, NapA, HP231, and Omp. Seropositivity for most of the proteins increased or remained stable with age, rising mainly for CagA, GroEL, and HyuA in women. A clear cohort effect was not observed. CONCLUSIONS: This is the first study to describe the antibody patterns against 16 H. pylori proteins in the Spanish population. We found variability in the H. pylori antibody profiles according to both individual factors such as age and sex, and environmental factors such as the region of birth. The slightness of the reduction in seropositivity with decreasing age highlights the ongoing importance of this infection.

Serum metal levels in a population of Spanish pregnant women.

OBJECTIVE: To describe serum levels of calcium, copper, selenium, magnesium, iron and zinc and evaluate their relationship with maternal socio-demographic characteristics and dietary variables in women in the first trimester of pregnancy. METHOD: Cross-sectional study with 1279 participants from the INMA cohorts. RESULTS: The concentrations of the elements analyzed were within the normal range. Associations with higher levels of these metals were found for calcium with white meat intake (p=0.026), for copper with excess body weight (p <0.01), low social class (p=0.03) and being multipara (p <0.01), for magnesium with being over 35 years old (p=0.001), high social class (p=0.044), primiparous status (p=0.002) and low daily intake of bread (p=0.009) and legumes (p=0.020); for zinc with university education (p=0.039) and residence in Gipuzkoa (p <0.01), and for selenium with residence in Valencia (p <0.01), university education (p=0.001), vitamin B6 supplementation (p=0.006), fish intake (> 71g/day) (p=0.014) and having been born in Spain (p=0.001). Further, lower iron levels were associated with being overweight (p=0.021) or obese (p <0.001) and vitamin B12 supplementation (p=0.006). CONCLUSIONS: Our results suggest that trace elements in the analyzed cohorts are adequate for this stage of pregnancy. The variability in these elements is mainly linked to socio-demographic and anthropometric variables.

Cancer Survival in Adults in Spain: A Population-Based Study of the Spanish Network of Cancer Registries (REDECAN).

The assessment of cancer survival at the population level is essential for monitoring progress in cancer control. We aimed to assess cancer survival and its trends in adults in Spain. Individual records of 601,250 adults with primary cancer diagnosed during 2002-2013 and followed up to 2015 were included from 13 population-based cancer registries. We estimated net survival up to five years after diagnosis and analyzed absolute changes between 2002-2007 and 2008-2013. Estimates were age-standardized. Analyses were performed for 29 cancer groups, by age and sex. Overall, age-standardized five-year net survival was higher in women (61.7%, 95% CI 61.4-62.1%) than in men (55.3%, 95% CI 55.0-55.6%), and ranged by cancer from 7.2% (pancreas) to 89.6% (prostate) in men, and from 10.0% (pancreas) to 93.1% (thyroid) in women in the last period. Survival declined with age, showing different patterns by cancer. Between both periods, age-standardized five-year net survival increased overall by 3.3% (95% CI 3.0-3.7%) in men and 2.5% (95% CI 2.0-3.0%) in women, and for most cancer groups. Improvements were greater in patients younger than 75 years than in older patients. Chronic myeloid leukemia and myeloma showed the largest increases. Among the most common malignancies, the greatest absolute increases in survival were observed for colon (5.0%, 95% CI 4.0-6.0%) and rectal cancers (4.5%, 95% CI 3.2-5.9%). Survival improved even for some cancers with poor prognosis (pancreas, esophagus, lung, liver, and brain cancer). Further investigation of possible sociodemographic inequalities is warranted. This study contributes to the evaluation of cancer control and health services' effectiveness.

Correction: Santa-Marina et al. Maternal Ferritin Levels during Pregnancy and ADHD Symptoms in 4-Year-Old Children: Results from the INMA-INfancia y Medio Ambiente (Environment and Childhood) Prospective Birth Cohort Study. Int. J. Environ. Res. Public Health 2020, 17, 7704.

In the original article [...].

Consumption of ultra-processed foods and drinks and colorectal, breast, and prostate cancer.

AIMS: To study whether the consumption of ultra-processed foods and drinks is associated with breast, colorectal, and prostate cancers. METHODS: Multicentric population-based case-control study (MCC-Spain) conducted in 12 Spanish provinces. Participants were men and women between 20 and 85 years of age with diagnoses of colorectal (n = 1852), breast (n = 1486), or prostate cancer (n = 953), and population-based controls (n = 3543) frequency-matched by age, sex, and region. Dietary intake was collected using a validated food frequency questionnaire. Foods and drinks were categorized according to their degree of processing based on the NOVA classification. Unconditional multivariable logistic regression was used to evaluate the association between ultra-processed food and drink consumption and colorectal, breast, and prostate cancer. RESULTS: In multiple adjusted models, consumption of ultra-processed foods and drinks was associated with a higher risk of colorectal cancer (OR for a 10% increase in consumption: 1.11; 95% CI 1.04-1.18). The corresponding odds for breast (OR 1.03; 95% CI 0.96-1.11) and prostate cancer (OR 1.02; 95% CI 0.93-1.12) were indicative of no association. CONCLUSIONS: Results of this large population-based case-control study suggest an association between the consumption of ultra-processed foods and drinks and colorectal cancer. Food policy and public health should include a focus on food processing when formulating dietary guidelines.

Prenatal Manganese Exposure and Long-Term Neuropsychological Development at 4 Years of Age in a Population-Based Birth Cohort.

Background: Manganese (Mn) is an essential micronutrient for humans, the diet being the main source of exposure. Some epidemiological studies describe a negative association between prenatal Mn and later neuropsychological development, but results are inconsistent. The aim of this study was to explore the association between prenatal Mn exposure and neuropsychological development assessed at 4 years of age. Methods: Study subjects were 304 mother-child pairs from the Gipuzkoa cohort of the INMA (Environment and Childhood) Project. Mn was measured in newborns' hair. Children's neuropsychological development was assessed at 4 years of age using the McCarthy Scales of Children's Abilities. Multivariate linear regression models were built. Stratified analysis by sex was performed. Generalized additive models were used to assess the shape of the relation. Results: The median Mn concentration in newborns' hair was 0.42 µg/g (95% CI = 0.38, 0.46). The association between Mn levels and the neuropsychological development was not statistically significant for the general cognitive scale (ß [95% CI] = 0.36 [-5.23, 5.95]), motor scale (ß [95% CI] = 1.9 [-3.74, 7.55]) or any of the other outcomes. No sex-specific pattern was found. The best shape describing the relationship was linear for all the scales. Conclusion: Our results suggest that prenatal Mn concentrations measured in newborns' hair do not affect cognitive or motor development at 4 years of age in boys or in girls at the observed Mn levels.

Maternal Ferritin Levels during Pregnancy and ADHD Symptoms in 4-Year-Old Children: Results from the INMA-INfancia y Medio Ambiente (Environment and Childhood) Prospective Birth Cohort Study.

Ferritin status during prenatal brain development may influence the risk of attention deficit and hyperactivity disorder (ADHD) symptoms in childhood. We investigated the association of maternal ferritin in pregnancy and ADHD-like symptoms in offspring. A total of 1095 mother-child pairs from three birth cohorts of the INMA Project (Spain) were studied. Maternal plasma ferritin in pregnancy was measured at 11.57 weeks of gestation. Children's ADHD-like symptoms at ages 4-5 years were assessed using the ADHD Rating Scale-IV. The count model of the zero-inflated Poisson regression model showed a significant inverse association between ferritin (continuous variable) and inattention, ß = -0.19 (-0.32, -0.07), for boys. Comparing ferritin level by tertiles, significant differences were observed between the first tertile ([1.98, 20.92]) and the second ([20.92, 38.79]) and third tertiles ([38.79, 216.5]) (mg/L).The number of symptoms was lower for those in the third tertile, ß = -0.3 (-0.55, -0.5), and for those in the second one, ß = -0.37 (-0.6, -0.14). The model stratification by sex also showed this inverse association for boys only, ß = -0.21 (-0.34, -0.08). No associations were found between ferritin level and hyperactivity or total ADHD symptoms. High ferritin levels during pregnancy show a protective association with child inattentive-type ADHD symptoms.