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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 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

Background & aims: Maternal ultra-processed food (UPF) consumption during pregnancy may adversely affect child development. Pregnancy sugar-sweetened beverage consumption (as a part of UPF) has been associated with child cognitive dysfunction in the general population, but the role of total UPF con-sumption during pregnancy in later child neuropsychological development has not been studied. We aimed to analyse the association between maternal pregnancy UPF consumption and child neurodevelopment.Methods: This study involved 2377 pairs of pregnant women and their offspring from a Spanish birth cohort (recruitment period: 2004e20 08, INMA project). Dietary intake was estimated using a 101-item food frequency questionnaire in the third trimester of pregnancy. The NOVA classification was used to identify UPFs, and their consumption was calculated as the daily percentage of total food consumption and categorized into tertiles. Child neuropsychological development was assessed with the Bayley Scales of Infant and Toddler Development (1-year-old, n = 1929) and the McCarthy Scales of Children's Abilities (4-5 years-old, n = 1679). Potential associations were analysed using multivariate linear regression models adjusted for a range of family and child characteristics.Results: UPF consumption among pregnant women represented an average of 17% of the total diet, with sugar-sweetened beverages being the most commonly consumed type of UPF (40%). Children born to mothers in the highest tertile of UPF consumption (28.9% or more of the total diet) vs the lowest tertile (7.2% or less), showed a lower score (B =-2.29 [95% Confidence Interval (CI),-4.13;-0.46]) in the Verbal Scale of the McCarthy Scales (p-for-trend = 0.02). No associations were observed with the McCarthy Scales assessing other cognitive domains or with the Bayley Scales.Conclusion: Of the seven cognitive domains studied, we observed an adverse association between maternal consumption of UPF during pregnancy and verbal functioning in early childhood, which is an important cognitive domain of neurodevelopment.(c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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 (beta (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.

Background: Arsenic (As) is considered to be toxic for humans, the main routes of exposure being through drinking water and the diet. Once ingested, inorganic arsenic can be methylated sequentially to monomethyl and dimethyl arsenicals. Several factors can affect both As exposure and methylation efficiency. Objectives: To describe the urinary concentrations of the different As species and evaluate the methylation effi-ciency during pregnancy, as well as their associated factors in a birth cohort of pregnant Spanish women. Methods: Participants in this cross-sectional study were 1017 pregnant women from two areas of Spain who had taken part in the INMA (Environment and Childhood) project (2003 & ndash;2008). Total As (organic and inorganic compounds) and its main metabolites (monomethylarsonic acid, [MMA], dimethylarsinic acid, [DMA], inorganic As [iAs]) and arsenobetaine [AB]) were measured in urine samples collected during the first trimester. Socio-demographic and dietary information was collected through questionnaires. Multivariate linear regression models were used to explore the association between As species concentrations and covariates. Arsenic methylation efficiency was determined through the percentages of the metabolites and using As methylation phenotypes, obtained from principal component analysis. Results: Median urine concentrations were 33.0, 21.6, 6.5, 0.35 and 0.33 lig/g creatinine for total As, AB, DMA, MMA and iAs, respectively. Daily consumption of rice and seafood during the first trimester of pregnancy were positively associated with the concentration of As species (i.e., beta [CI95%] = 0.36 [0.09, 0.64] for rice and iAs, and 1.06 [0.68, 1.44] for seafood and AB). TAs, AB and iAs concentrations, and DMA and MMA concentrations were associated with legume and vegetable consumption, respectively. The medians of the percentage of As metabolites were 89.7 for %DMA, 5.1 for %MMA and 4.7 for %iAs. Non-smoker women and those with higher body mass index presented a higher methylation efficiency (denoted by a higher %DMA and lower %MMA). Discussion: Certain dietary, lifestyle, and environmental factors were observed to have an influence on both As species concentrations and methylation efficiency in our population. Further birth cohort studies in low exposure areas are necessary to improve knowledge about arsenic exposure, especially to inorganic forms, and its potential health impact during childhood.

Background: There is a need to test the fetal programming theoretical framework in nutritional epidemiology. We evaluated whether maternal seafood intake during pregnancy was associated with 8-year-old attention outcomes after adjusting for previous child seafood intake and cognitive function. We also explored effect modification by several single nucleotide polymorphisms (SNPs) related with polyunsaturated fatty acid (PUFA) metabolism. Methods: Our final analyses included 1644 mother-child pairs from the prospective INMA (INfancia y Medio Ambiente) cohort study (Spain, recruitment between 2003 and 2008). We used food frequency questionnaires to assess prenatal and postnatal seafood consumption of the mother-child pairs. We evaluated attention function of the children through the computer-based Attention Network Test (ANT) and we used the number of omission errors and the hit reaction time standard error (HRT-SE). Parents reported child attention deficit hyperactivity disorder (ADHD) symptoms using the Revised Conners' Parent Rating Scale Short Form (CPRS-R: S). We measured seven candidate SNPs in a subsample of 845 children. We estimated associations using regression models, adjusting for family characteristics, child seafood intake and cognitive functions at early ages, and to explore SNP effect modifications. Results: Higher total seafood intake during early pregnancy was associated with a reduction of child ANT omission errors, 5th quintile (median=854 g/week) vs 1st quintile (median=195 g/week), incidence risk ratio (IRR) 0.76; 95% CI = 0.61, 0.94. Similar results were observed after adjusting the models for child seafood intake and previous cognitive status. Lean, large and small fatty fish showed similar results, and generally similar but less robust associations were observed with the other attention outcomes. Shellfish and canned tuna showed weaker associations. The association patterns were weaker in late pregnancy and null in child seafood consumption. Child rs1260326 (glucokinase regulator, GCKR) and child/maternal rs2281591 (fatty acid elongase 2, ELOVL2) polymorphisms showed nominal P-value for interactions

Background: Severe iodine deficiency during pregnancy can cause intellectual disability, presumably through inadequate placental transfer of maternal thyroid hormone to the fetus. The association between mild-to-moderate iodine deficiency and child neurodevelopmental problems is not well understood. Objectives: We investigated the association of maternal iodine status during pregnancy with child attention-deficit hyperactivity disorder (ADHD) and autistic traits. Methods: This was a collaborative study of 3 population-based birth cohorts: Generation R (n = 1634), INfancia y Medio Ambiente (n = 1293), and the Avon Longitudinal Study of Parents and Children (n = 2619). Exclusion criteria were multiple fetuses, fertility treatment, thyroid-interfering medication use, and pre-existing thyroid disease. The mean age of assessment in the cohorts was between 4.4 and 7.7 y for ADHD symptoms and 4.5 and 7.6 y for autistic traits. We studied the association of the urinary iodine-to-creatinine ratio (UI/Creat) = 93rd percentile cutoff), using logistic regression. The cohort-specific effect estimates were combined by random-effects meta-analyses. We also investigated whether UI/Creat modified the associations of maternal free thyroxine (FT4) or thyroid-stimulating hormone concentrations with ADHD or autistic traits. Results: UI/Creat

Background: The relationship between maternal selenium (Se) status and child neurodevelopment has been scarcely assessed. In a previous study we observed an inverse U-shaped association between maternal Se concentrations and infant neurodevelopment at 12 months of age. In this study, this non-linear association was explored at preschool age. The effect modification by breastfeeding, child's sex and cord blood mercury was also evaluated. Methods: Study subjects were 490 mother-child pairs from the Spanish Childhood and Environment Project (INMA, 2003-2012). Child neuropsychological development was assessed at around 5 years of age by the McCarthy Scales of Children's Abilities (MSCA). Sociodemographic and dietary characteristics were collected by questionnaire at the first and third trimester of gestation and at 5 years of age. Se was measured in serum samples by ICP-MS at the end of the first trimester of pregnancy (mean +/- standard deviation (SD) = 12.4 +/- 0.6 weeks of gestation). Results: The mean +/- SD of maternal serum Se concentrations was 79.9 +/- 8.1 mu g/L. In multivariate analysis, no linear association was found between Se concentrations and the nine MSCA scales. Generalized additive models indicated inverted U-shaped relationships between Se concentrations and the verbal and global memory scales. When assessing the influence of effect modifiers, breastfeeding played a role: the association between Se and neuropsychological development was inverted U-shaped for the quantitative, general cognitive, working memory, fine motor, global motor and executive function scales only for non-breastfed children. Conclusion: Low and high maternal Se concentrations seem to be harmful for child neuropsychological development, however further studies should explore this non-linear relationship.

Background The effect of mild-to-moderate maternal iodine deficiency on the neuropsychological development of their offspring is uncertain. We aimed to assess the association between iodine status during pregnancy and the cognitive and motor development of children at 4-5 years. Methods We conducted a prospective cohort study in four Spanish regions with recruitment of pregnant women between 2003 and 2008 and follow-up of their children up to 4-5 years (mean (SD)=4.8 (0.6)). Cognitive and motor function was assessed in 1803 children using the McCarthy Scales of Children's Abilities. Dietary iodine and supplementation were measured through questionnaires twice during pregnancy. Urinary iodine concentration (UIC) was measured in spot samples. The residuals of a regression of UIC against creatinine were used to define a variable corrected for creatinine (UIC similar to Cr). Results Neither iodine supplements nor iodised salt consumption or maternal UIC were associated with cognitive or motor function. After adjusting for creatinine, children of women with UIC similar to Cr

There is a growing concern about the possible adverse effects of exposure to air pollution on health during pregnancy. Therefore, a priority of the INMA (environment and childhood) study was to estimate personal exposure to traffic-related air pollution. In the cohort from Valencia (n = 855). ambient levels of NO2 were measured at 93 sampling sites spread over the study area during four different sampling periods of 7 days each. Multiple regression models were used to map ambient NO2 over the area. Geographical data and predictions from kriging obtained by the "let one out" procedure were used a:; predictors. Individual exposure was assigned as 1) the estimated ambient NO2 level at the home address and 2) the average of estimated ambient NO2 levels at home and work addresses, weighted by the time spent in each environment. Estimations were temporally customised using the NO2 levels registered daily by the regional Air Pollution Monitoring Network. The entire pregnancy and each trimester were taken as exposure windows. The model for the mean levels of NO2 during the sampling periods explained 81% of the variation in NO2 levels. Relative percent differences between the two models of personal exposure assignment were less than 9% for more than 90% of the participants; however the rest of them showed marked differences. Personal exposure estimates were slightly higher in the second model. In both cases, exposure during the whole pregnancy was strongly correlated with exposure in the second trimester. Considering periods shorter than the entire pregnancy will provide us the opportunity to identify specific windows of susceptibility. (C) 2009 Elsevier B.V. All rights reserved.

The research leading to these results was funded by the Spanish Ministry of Health (FIS-PI11/00610, FIS-PI041436, FIS-PI081151, FIS-PI042018, and FIS-PI09/02311), the European Union (EU) (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1), the Instituto de Salud Carlos III (Red INMA G03/176, CB06/02/0041, FIS-FEDER 03/1615, 04/1509, 04/1112, 04/1931, 05/1079, 05/1052, 06/1213, 07/0314, 09/02647, 11/01007, 11/02591, CP11/00178, FIS-PI06/0867, and FIS-PS09/00090), the Conselleria de Sanitat Generalitat Valenciana, the Generalitat de Catalunya-CIRIT (1999SGR 00241), the Obre Social Cajastur, the Universidad de Oviedo, the Department of Health of the Basque Government (2005111093 and 2009111069), and the Provincial Government of Gipuzkoa (DFG06/004 and DFG08/001). The ENVIRONAGE cohort is supported by the EU Program “Ideas” (ERC-2012-StG 310898) and by the Flemish Fund for Scientific Research (FWO 1516112N and G073315N)., Clemente, D.B.P., Casas, M., Vilahur, N., Begiristain, H., Bustamante, M., Carsin, A., Fernández, M.F., Fierens, F., Gyselaers, W., Iñiguez, C., Janssen, B.G., Lefebvre, W., Llop, S., Olea, N., Pedersen, M., Pieters, N., Marina, L.S., Souto, A., Tardón, A., Vanpoucke, C., Vrijheid, M., Sunyer, J., Nawrot, T.S.

Background: A growing body of research suggests that prenatal exposure to air pollution may be harmful to fetal development. We assessed the association between exposure to air pollution during pregnancy and anthropometric measures at birth in four areas within the Spanish Children’s Health and Environment (INMA) mother and child cohort study. Methods: Exposure to ambient nitrogen dioxide (NO2) and benzene was estimated for the residence of each woman (n = 2,337) for each trimester and for the entire pregnancy. Outcomes included birth weight, length, and head circumference. The association between residential outdoor air pollution exposure and birth outcomes was assessed with linear regression models controlled for potential confounders. We also performed sensitivity analyses for the subset of women who spent more time at home during pregnancy. Finally, we performed a combined analysis with meta-analysis techniques. Results: In the combined analysis, an increase of 10 µg/m3 in NO2 exposure during pregnancy was associated with a decrease in birth length of –0.9 mm [95% confidence interval (CI), –1.8 to –0.1 mm]. For the subset of women who spent ≥ 15 hr/day at home, the association was stronger (–0.16 mm; 95% CI, –0.27 to –0.04). For this same subset of women, a reduction of 22 g in birth weight was associated with each 10-µg/m3 increase in NO2 exposure in the second trimester (95% CI, –45.3 to 1.9). We observed no significant relationship between benzene levels and birth outcomes. Conclusions: NO2 exposure was associated with reductions in both length and weight at birth. This association was clearer for the subset of women who spent more time at home. This study was funded by grants from the Instituto de Salud Carlos III (Red INMA G03/176 and CB06/02/0041), the Spanish Ministry of Health (FIS-FEDER 03/1615, 04/1509, 04/1112, 04/1931, 04/1436, 05/1079, 05/1052, 06/1213, 07/0314, 08/1151, 09/02311, 09/02647), Conselleria de Sanitat Generalitat Valenciana, Generalitat de Catalunya-CIRIT 1999SGR 00241, and the Fundación Roger Torné

Background: Evidence associating exposure to water disinfection by-products with reduced birth weight and altered duration of gestation remains inconclusive. Objective: We assessed exposure to trihalomethanes (THMs) during pregnancy through different water uses and evaluated the association with birth weight, small for gestational age (SGA), low birth weight (LBW), and preterm delivery. Methods: Mother–child cohorts set up in five Spanish areas during the years 2000–2008 contributed data on water ingestion, showering, bathing, and swimming in pools. We ascertained residential THM levels during pregnancy periods through ad hoc sampling campaigns (828 measurements) and regulatory data (264 measurements), which were modeled and combined with personal water use and uptake factors to estimate personal uptake. We defined outcomes following standard definitions and included 2,158 newborns in the analysis. Results: Median residential THM ranged from 5.9 μg/L (Valencia) to 114.7 μg/L (Sabadell), and speciation differed across areas. We estimated that 89% of residential chloroform and 96% of brominated THM uptakes were from showering/bathing. The estimated change of birth weight for a 10% increase in residential uptake was –0.45 g (95% confidence interval: –1.36, 0.45 g) for chloroform and 0.16 g (–1.38, 1.70 g) for brominated THMs. Overall, THMs were not associated with SGA, LBW, or preterm delivery. Conclusions: Despite the high THM levels in some areas and the extensive exposure assessment, results suggest that residential THM exposure during pregnancy driven by inhalation and dermal contact routes is not associated with birth weight, SGA, LBW, or preterm delivery in Spain., We particularly thank all the participants for their generous collaboration. A full roster of the Infancia y Medio Ambiente (INMA) Project investigators can be found at http://www.proyectoinma.org/presentacion-inma/listado-investigadores/en_listado-investigadores.html. We are also grateful to G.J. Álvarez Alija for contributing to the fieldwork.

Background Maternal exposure to air pollution has been related to fetal growth in a number of recent scientific studies. The objective of this study was to assess the association between exposure to air pollution during pregnancy and anthropometric measures at birth in a cohort in Valencia, Spain. Methods Seven hundred and eighty-five pregnant women and their singleton newborns participated in the study. Exposure to ambient nitrogen dioxide (NO2) was estimated by means of land use regression. NO2 spatial estimations were adjusted to correspond to relevant pregnancy periods (whole pregnancy and trimesters) for each woman. Outcome variables were birth weight, length, and head circumference (HC), along with being small for gestational age (SGA). The association between exposure to residential outdoor NO2 and outcomes was assessed controlling for potential confounders and examining the shape of the relationship using generalized additive models (GAM). Results For continuous anthropometric measures, GAM indicated a change in slope at NO2 concentrations of around 40 μg/m3. NO2 exposure >40 μg/m3 during the first trimester was associated with a change in birth length of -0.27 cm (95% CI: -0.51 to -0.03) and with a change in birth weight of -40.3 grams (-96.3 to 15.6); the same exposure throughout the whole pregnancy was associated with a change in birth HC of -0.17 cm (-0.34 to -0.003). The shape of the relation was seen to be roughly linear for the risk of being SGA. A 10 μg/m3 increase in NO2 during the second trimester was associated with being SGA-weight, odds ratio (OR): 1.37 (1.01-1.85). For SGA-length the estimate for the same comparison was OR: 1.42 (0.89-2.25). Conclusions Prenatal exposure to traffic-related air pollution may reduce fetal growth. Findings from this study provide further evidence of the need for developing strategies to reduce air pollution in order to prevent risks to fetal health and development.