Residential Exposure to Outdoor Air Pollution during Pregnancy and Anthropometric Measures at Birth in a Multicenter Cohort in Spain

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 regress…

Exposure to mercury among 9-year-old Spanish children: Associated factors and trend throughout childhood

Mercury is considered a neurotoxicant and human exposure occurs mainly from the consumption of marine species. We aimed to describe total mercury concentrations (THg) and associated factors in 9-year old children, as well as to explore the trend in THg from 4 to 9 years of age. The study population consisted of 9-year-old children participating in the INMA (Environment and Childhood) birth cohort study in Valencia, Spain (n = 405, 2013–2014). THg in hair samples was measured by atomic absorption spectrometry at the age of 4 and 9 years. Sociodemographic and dietary data was obtained through questionnaires. Multiple linear regression was used to explore the association between THg and covari…

Genetic association study of childhood aggression across raters, instruments, and age

AbstractChildhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association meta-analysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGGoverall) was 3.31% (SE = 0.0038). We found no genome-wide significant SNPs for AGGoverall. The gene-based analysis returned three sign…

Additional file 1: Table S1. of Distributions and determinants of urinary biomarkers of organophosphate pesticide exposure in a prospective Spanish birth cohort study

Intake of fruit and vegetables according to the maternal sociodemographic and life style characteristics. (DOC 49 kb)

Association of Iron Status and Intake During Pregnancy with Neuropsychological Outcomes in Children Aged 7 Years: The Prospective Birth Cohort Infancia y Medio Ambiente (INMA) Study

Early iron status plays an important role in prenatal neurodevelopment. Iron deficiency and high iron status have been related to alterations in child cognitive development

Concentrations and determinants of organochlorine levels among pregnant women in Eastern Spain

Persistent organic pollutants (POPs) comprise a large variety of toxic substances with ample distribution. While exposure to these toxins occurs mainly through diet, maternal POP levels may be influenced by certain sociodemographic, environmental, or lifestyle factors. This is important given that these substances may have adverse effects on fetal development. The aim of this study is to examine the sociodemographic, environmental, lifestyle, and dietary determinants of the levels of hexachlorobenzene (HCB), b-hexachlorocyclohexane (b-HCH), 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (4,4′-DDT), 1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene (4,4′-DDE), and polychlorinated biphenyls (PCB co…

Prenatal exposure to persistent organic pollutants and rapid weight gain and overweight in infancy

Objective To examine the effects of prenatal exposure to persistent organic pollutants (POPs) on rapid growth in the first 6 months of life and overweight at 14 months of age. Design and Methods In a Spanish birth cohort study, the POPs dichlorodiphenyldichloroethylene (DDE), hexachlorobenzene (HCB), and polychlorinated biphenyls (PCBs—congeners 153, 138, 180) were measured in maternal serum collected in the first trimester of pregnancy during 2003–2008. Rapid growth was defined as a z-score weight gain >0.67 SD between 6 months of age and birth. Overweight at 14 months was defined as a BMI z-score ≥85th percentile. Generalized linear models examined the association between POPs and rapid g…

Maternal Perfluoroalkyl Substances, Thyroid Hormones, and DIO Genes: A Spanish Cross-sectional Study

Results of studies on perfluoroalkyl substances (PFASs) and thyroid hormones (THs) are heterogeneous, and the mechanisms underlying the action of PFASs to target THs have not been fully characterized. We examined the relation between first-trimester maternal PFAS and TH levels and the role played by polymorphisms in the iodothyronine deiodinase 1 (DIO1) and 2 (DIO2) genes in this association. Our sample comprised 919 pregnant Spanish women (recruitment = 2003-2008) with measurements of perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), thyroid-stimulating hormone (TSH), total triiodothyronine (TT3), and fr…

Exposure to trihalomethanes through different water uses and birth weight, small for gestational age, and preterm delivery in Spain

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 me…

Urinary Arsenic Species and Methylation Efficiency During Pregnancy: Concentrations and Associated Factors in Spanish Pregnant Women

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 (20…

Outdoor, but not indoor, nitrogen dioxide exposure is associated with persistent cough during the first year of life

Background and aims: Because their lungs and immune system are not completely developed, children are more susceptible to respiratory disease and more vulnerable to ambient pollution. We assessed the relation between prenatal and postnatal nitrogen dioxide (NO2) levels and the development of lower respiratory tract infections (LRTI), wheezing and persistent cough during the first year of life. Methods: The study population consisted of 352 children from a birth cohort in Valencia, Spain. Prenatal exposure to NO2, a marker of traffic related air pollution was measured at 93 sampling sites spread over the study area during four different sampling periods of 7 days each. It was modeled for eac…

Maternal copper status and neuropsychological development in infants and preschool children.

Introduction: Copper (Cu) is an essential element involved in biological processes; however, excessive Cu could be harmful because of its reactive nature. Very few studies have evaluated its potential neurotoxic effects. We aimed to evaluate the association between maternal Cu levels and children's neuropsychological development. Methods: Study subjects were mother-child pairs from the Spanish INMA (i.e. Childhood and Environment) Project. Cu was measured by inductively coupled plasma mass spectrometry in serum samples taken at the first trimester of pregnancy (2003-2005). Neuropsychological development was assessed using the Bayley Scales of Infant Development (BSID) at 12 months (n = 651) a…

Prenatal and postnatal insecticide use and infant neuropsychological development in a multicenter birth cohort study

There is little evidence about exposure to currently used insecticides during early life periods and adverse effects on child neuropsychological development. The aim of this study is to examine the association between residential insecticide use during pregnancy and infancy, and the development of children.Study subjects were participants in the INMA (Environment and Childhood) Project, a Spanish multicenter birth cohort study. Prenatal and postnatal use of indoor insecticides and other variables were obtained from personal interview during pregnancy and infancy. Mental and psychomotor development was assessed around 14 months using the Bayley Scales of Infant Development. The associations …

Polymorphisms in ABC transporter genes and concentrations of mercury in newborns - Evidence from two Mediterranean birth cohorts

Background: The genetic background may influence methylmercury (MeHg) metabolism and neurotoxicity. ATP binding cassette (ABC) transporters actively transport various xenobiotics across biological membranes. Objective: To investigate the role of ABC polymorphisms as modifiers of prenatal exposure to MeHg. Methods: The study population consisted of participants (n = 1651) in two birth cohorts, one in Italy and Greece (PHIME) and the other in Spain (INMA). Women were recruited during pregnancy in Italy and Spain, and during the perinatal period in Greece. Total mercury concentrations were measured in cord blood samples by atomic absorption spectrometry. Maternal fish intake during pregnancy w…

Outdoor, indoor and personal distribution of BTEX in pregnant women from two areas in Spain - Preliminary results from the INMA project

Volatile organic compounds (VOCs), which are habitually found in both outdoor and indoor environments, may represent a significant health risk. In this context, pregnancy is a critical period since foetuses are more vulnerable than adults to exposure to toxic compounds. The objective of this study is to present the preliminary results of a series of measurements of outdoor (O), indoor (I) and personal exposure (P) to benzene, toluene, ethylbenzene, o-xylene and m,p-xylene (BTEX) in 107 pregnant women from two areas in Spain, namely Valencia and Sabadell. BTEX samplers were installed for 48 hours both inside and outside of the women’s homes, along with personal samplers. In addition, the tes…

Prenatal exposure to mercury and neuropsychological development in young children: the role of fish consumption

Background: Vulnerability of the central nervous system to mercury exposure is increased during early development. The aim of this study is to evaluate the association between prenatal exposure to mercury and child neuropsychological development in high-fish-intake areas in Spain. Methods: Study subjects were 1362 children, participants in the INMA (Environment and Childhood) birth cohort study. Cord blood total mercury (CB-Hg) and cord polyunsaturated fatty acids (PUFA) concentrations were analysed in samples collected between 2004 and 2008. Child neuropsychological development was assessed at age 4-5 years by the McCarthy Scales of Children's Abilities (MSCA). Socio-demographic, lifestyle…

Exposure to mercury among Spanish preschool children: Trend from birth to age four

The purpose of this study is to describe the total hair mercury concentrations and their determinants in preschool Spanish children, as well as to explore the trend in mercury exposure from birth to the age four. This evolution has been scarcely studied in other birth cohort studies. The study population was 580 four year old children participating in the INMA (i.e. Childhood and Environment) birth cohort study in Valencia (2008–2009). Total mercury concentration at age four was measured in hair samples by atomic absorption spectrometry. Fish consumption and other covariates were obtained by questionnaire. Multivariate linear regression models were conducted in order to explore the associat…

The INMA INfancia y Medio Ambiente-(Environment and Childhood) project: More than 10 years contributing to environmental and neuropsychological research

Background: In 2003 the INMA—INfancia y Medio Ambiente (Environment and Childhood) project, a Spanish national network of birth cohorts including more than 3500 participants, was set up with the aim to assess the health impacts of pre- and postnatal environmental exposures on children. The project has published more than 60 papers on maternal and environmental factors related to neuropsychological development in children, one of the main research interests within the project. With the present review, we evaluate the evidence provided by the INMA project on this topic and discuss how the data can contribute to cover the challenges that children’s environmental health research will face in th…

Prenatal mercury exposure in a multicenter cohort study in Spain

Background: Mercury is a ubiquitous heavy metal that may negatively affect human health. It is desirable to investigate mercury exposure in vulnerable populations. Objective: To determine the concentrations of total mercury (T-Hg) in cord blood and to evaluate the role of maternal fish consumption in a Spanish mother and child cohort. Methods: A total of 1883 mother and child pairs from a population-based cohort were included between 2004 and 2008. T-Hg concentrations were measured in whole cord blood and maternal seafood consumption was ascertained by means of a food-frequency questionnaire. Linear regression was used in stratified analyses, while a joint model was adjusted using a mixed-e…

Prenatal Exposure to Polybrominated Flame Retardants and Fetal Growth in the INMA Cohort (Spain)

Our aim was to investigate the relation between PBDEs and fetal growth or newborn anthropometry in a Spanish cohort (2003-2008). PBDE congeners (BDE-47, -99, -153, -154, and -209) were determined in serum of 670 mothers at gestational week 12 and in 534 umbilical cord samples. Abdominal circumference (AC), estimated fetal weight (EFW), femur length (FL), and biparietal diameter (BPD) during gestation were measured by ultrasounds. At birth, weight (BW), head circumference (HC), and length (BL) were also measured. We assessed growth in the intervals between 12-20 and 20-34 weeks of gestation and size at birth by standard deviation (SD)-scores adjusted for constitutional characteristics. We co…

Inorganic arsenic exposure and neuropsychological development of children of 4-5 years of age living in Spain

This study was funded by grants from Spanish Institute of Health Carlos III-Ministry of Economy and Competitiveness (INMA Network G03/176, CB06/02/0041, and FIS-FEDER: PI03/1615, PI04/1436, PI08/1151, PI04/2018, PI04/1509, PI04/1112, PI04/1931, PI05/1079, PI05/1052, PI06/1213, PI06/0867, PI07/0314, PI09/02647, PS09/00090, PI09/02311, MS11/0178, PI13/1944, PI13/2032, PI14/00891, PI16/1288, and PI17/00663). Miguel Servet-FEDER: MSII16/ 00051, CP14/00108 & PI16/00261 (Co-funded by European Regional Development Fund “A way to make Europe”), FEDER funds, MS13/00054. Generalitat de Catalunya-CIRIT 1999SGR 00241, JCI2011–09771–MICINN, Generalitat Valenciana (Conselleria de Sanitat048/2010 and 060/…

Gender differences in the neurotoxicity of metals in children

Gender-related differences in susceptibility to chemical exposure to neurotoxicants have not received sufficient attention. Although a significant number of epidemiological studies on the neurodevelopmental effects of metal exposure has been published in the last twenty years, not many of them have considered the possible gender-specific effects of such exposure. This review is focused on studies where the gender differences in pre- and/or postnatal exposure/s to five metals (mercury, lead, manganese, cadmium, and arsenic) and neurodevelopment were evaluated. We conducted a PubMed search in December 2012 and retrieved 20 studies that met the inclusion criteria. A large body of literature on…

Impact of maternal nutritional status during pregnancy on the associations between persistent organic pollutants and childhood overweight

Drinking water disinfection by-products during pregnancy and child neuropsychological development in the INMA Spanish cohort study.

Background: Disinfection by-products (DBPs) constitute a complex mixture of prevalent chemicals in drinking water and there is evidence of neurotoxicity for some of them. Objectives: We evaluated the association between estimates of DBP exposure during pregnancy and child neuropsychological outcomes at 1 and 4–5 years of age. Methods: We conducted a population-based mother-child cohort study in Spain with recruitment at first trimester of gestation (INMA Project, 2003–2008). Neuropsychological development was measured at 1 year of age using the Bayley Scales of Infant Development and at 4–5 years with the McCarthy Scales of Children's Abilities. Modeled tap water concentrations of trihalome…

Exposure to metals and metalloids among pregnant women from Spain: Levels and associated factors

This study was funded by Grants from EU (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1); Spain: ISCIII (Red INMA G03/176, CB06/02/0041; FIS-FEDER: PI03/1615, PI04/1509, PI04/1112, PI04/1931, PI05/1079, PI05/1052, PI06/0867, PI06/1213, PI07/0314, PI09/00090, PI09/02647, PI11/01007, PI11/02591, PI11/02038, PI13/1944, PI13/2032, PI13/02187, PI14/00891, PI14/01687, PI16/1288, PI17/00663, PI18/01142 and PI19/1338; Miguel Servet FEDER MS15/00025, MS20/0006, CPII16/00051, and FIS-FSE: 17/00260); CIBERESP; Generalitat Valenciana: FISABIO (UGP 15-230, UGP-15-244, and UGP-15-249), AICO/2020/285, and Alicia Koplowitz Foundation 2017; Generalitat de Catalunya-CIRIT 1999SGR 00241; Department of Health…

Placental metal concentrations and birth outcomes: The Environment and Childhood (INMA) project

To examine the association of placental levels of arsenic (As), cadmium (Cd), mercury (Hg), lead (Pb), manganese (Mn), and chromium (Cr) with birth outcomes (birth weight, length, and head circumference, low birth weight [LBW], gestational age, preterm delivery, and small for gestational age [SGA]) in mother-child pairs from the Environment and Childhood (INMA) Project in Spain.Metal concentrations were measured in placenta tissue samples randomly selected from five INMA cohorts. Data on birth outcomes were obtained from medical records. Associations were assessed in a sub-sample of 327 mother-infant pairs by regression models adjusted for confounding factors and for all metals simultaneous…

Methylmercury-induced developmental toxicity is associated with oxidative stress and cofilin phosphorylation. Cellular and human studies

Environmental exposure to methylmercury (MeHg) during development is of concern because it is easily incorporated in children’s body both pre- and post-natal, it acts at several levels of neural pathways (mitochondria, cytoskeleton, neurotransmission) and it causes behavioral impairment in child. We evaluated the effects of prolonged exposure to 10–600 nM MeHg on primary cultures of mouse cortical (CCN) and of cerebellar granule cells (CGC) during their differentiation period. In addition, it was studied if prenatal MeHg exposure correlated with altered antioxidant defenses and cofilin phosphorylation in human placentas (n = 12) from the INMA cohort (Spain). Exposure to MeHg for 9 days in v…

Prenatal co-exposure to neurotoxic metals and neurodevelopment in preschool children: The Environment and Childhood (INMA) Project

We sought to determine whether prenatal co-exposure to As, Cd, Hg, Mn, and Pb was associated with impaired neurodevelopment in preschool children from the Spanish Environment and Childhood (INMA) Project, using the placenta as exposure matrix. We measured metal levels in placenta tissue samples randomly selected from five of the seven population-based birth cohorts participating in the INMA Project, collected between 2000 and 2008. Neuropsychological assessment of cognitive and motor function was carried through the use of the McCarthy Scales of Children's Abilities (MSCA) at the age of 4-5years. Data on placental metal levels, MSCA scores, and relevant covariates was available for 302 chil…

Prenatal exposure to lead in Spain: Cord blood levels and associated factors

Abstract Introduction and Objective Lead is a known neurotoxic. Fetuses and infants are very vulnerable to lead exposure, since their blood-brain barrier is not completely formed. Hence, there is an importance for monitoring of blood lead levels prenatally and during early infancy. The aim of this study is to evaluate the prenatal exposure to lead and its association with maternal factors in four population based mother–child cohorts in Spain. The present research was carried out within the framework of the INMA project INfancia y Medio Ambiente (Environment and Childhood). Methods A total of 1462 pregnant women were recruited between 2004 and 2008. Lead was analyzed in a sample of cord blo…

Additional file 1: Table S1. of Distributions and determinants of urinary biomarkers of organophosphate pesticide exposure in a prospective Spanish birth cohort study

Intake of fruit and vegetables according to the maternal sociodemographic and life style characteristics. (DOC 49 kb)

Exposure to ambient air pollution during pregnancy and preterm birth: A Spanish multicenter birth cohort study

Background and objective: Preterm birth is a major determinant of infant mortality and morbidity. Air pollution has been suggested as a risk factor for preterm delivery; however, the scientific evidence on this impact remains inconsistent. We assessed the association between residential exposure to air pollution during pregnancy and preterm birth (gestational age at delivery <37 weeks) in Spain. Methods: This study was based on 2409 pregnant women participating in the INMA birth cohorts in Asturias, Gipuzkoa, Sabadell and Valencia. Ambient levels of nitrogen dioxide (NO2) and benzene were estimated for each woman's residence for each trimester and for the whole pregnancy, using temporally a…

Distributions and determinants of urinary biomarkers of organophosphate pesticide exposure in a prospective Spanish birth cohort study

Background: Prenatal exposure to organophosphate pesticides (OPs) has been associated with impaired child development. Pesticide exposure determinants need to be studied in order to identify sources and pathways of pesticide exposure. The aim of this paper is to describe prenatal exposure to OPs and evaluate the associated factors in pregnant women. Methods: The study population consisted of pregnant women ( n = 573) who participated in the INMA birth cohort study in Valencia (Spain, 2003 – 2006). OP metabolites were analyzed in maternal urine at the 32nd week of gestation using a liquid chromatography-high resolution mass spectrometry method. The analysis included non-specific (diethyl pho…

Evolución de los riesgos ambientales en el contexto de la crisis económica. Informe SESPAS 2014

ResumenNuestro objetivo es analizar el impacto de la crisis económica-financiera en los determinantes ambientales de la salud. La Organización Mundial de la Salud estima que entre un 13% y un 27% de la carga de enfermedad de los países podría prevenirse mejorando el medio ambiente. Los efectos son de mayor magnitud en poblaciones más vulnerables, en especial entre los más pobres. En la última década, la contaminación atmosférica exterior (el riesgo ambiental más relevante, en términos de salud, para la mayoría de los países europeos) se ha reducido moderadamente, sobre todo por las políticas europeas de reducción de emisiones y por la disminución de la actividad con la crisis económica. En …

Prenatal manganese exposure and neuropsychological development in early childhood in the INMA cohort.

Abstract Introduction Manganese (Mn) is an essential element, diet being its main source. Some epidemiological studies have found that a prenatal excess of Mn could negatively affect neuropsychological development during infancy, but the evidence is inconclusive. The aim of this study was to explore the relationship between maternal serum Mn concentrations and child neuropsychological development assessed at 1 year of age. Methods study subjects were 1179 mother–child pairs from two Spanish cohorts (Valencia and Gipuzkoa) of the INMA (Environment and Childhood) Project. Mn was measured in serum samples collected during the first trimester of pregnancy. Child neuropsychological development w…

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 cop-per with excess body weight (p 71 g/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 <…

Concentrations of urinary arsenic species in relation to rice and seafood consumption among children living in Spain.

Inorganic arsenic (i-As) has been related to wide-ranging health effects in children, leading to lifelong concerns. Proportionally, dietary i-As exposure dominates in regions with low arsenic drinking water. This study aims to investigate the relation between rice and seafood consumption and urinary arsenic species during childhood and to assess the proportion of urinary i-As metabolites. Urinary arsenic species concentration in 400 4-year-old children living in four geographical areas of Spain, in addition to repeated measures from 100 children at 7 years of age are included in this study. Rice and seafood products intake was collected from children's parents using a validated food frequen…

Maternal Iodine Status During Pregnancy Is Not Consistently Associated with Attention-Deficit Hyperactivity Disorder or Autistic Traits in Children

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…

Association of Maternal Iodine Status With Child IQ: A Meta-Analysis of Individual Participant Data

Abstract Context Although the consequences of severe iodine deficiency are beyond doubt, the effects of mild to moderate iodine deficiency in pregnancy on child neurodevelopment are less well established. Objective To study the association between maternal iodine status during pregnancy and child IQ and identify vulnerable time windows of exposure to suboptimal iodine availability. Design Meta-analysis of individual participant data from three prospective population-based birth cohorts: Generation R (Netherlands), INMA (Spain), and ALSPAC (United Kingdom); pregnant women were enrolled between 2002 and 2006, 2003 and 2008, and 1990 and 1992, respectively. Setting General community. Participa…

Infants' indoor and outdoor residential exposure to benzene and respiratory health in a Spanish cohort.

Benzene exposure represents a potential risk for children's health. Apart from being a known carcinogen for humans (group 1 according to IARC), there is scientific evidence suggesting a relationship between benzene exposure and respiratory problems in children. But results are still inconclusive and inconsistent. This study aims to assess the determinants of exposure to indoor and outdoor residential benzene levels and its relationship with respiratory health in infants. Participants were 1-year-old infants (N = 352) from the INMA cohort from Valencia (Spain). Residential benzene exposure levels were measured inside and outside dwellings by means of passive samplers in a 15-day campaign. Pe…

A Genome-Wide Association Study of Attention Function in a Population-Based Sample of Children

BACKGROUND: Attention function filters and selects behaviorally relevant information. This capacity is impaired in some psychiatric disorders and has been proposed as an endophenotype for Attention-Deficit/Hyperactivity Disorder; however, its genetic basis remains largely unknown. This study aimed to identify single nucleotide polymorphism (SNPs) associated with attention function. MATERIALS AND METHODS: The discovery sample included 1655 children (7-12 years) and the replication sample included 546 children (5-8 years). Five attention outcomes were assessed using the computerized Attentional Network Test (ANT): alerting, orienting, executive attention, Hit Reaction time (HRT) and the stand…

DNA methylation in childhood asthma

Background: DNA methylation profiles associated with childhood asthma might provide novel insights into disease pathogenesis. We did an epigenome-wide association study to assess methylation profiles associated with childhood asthma. Methods: We did a large-scale epigenome-wide association study (EWAS) within the Mechanisms of the Development of ALLergy (MeDALL) project. We examined epigenome-wide methylation using Illumina Infinium Human Methylation450 BeadChips (450K) in whole blood in 207 children with asthma and 610 controls at age 4–5 years, and 185 children with asthma and 546 controls at age 8 years using a cross-sectional case-control design. After identification of differentially m…

Air pollution exposure during pregnancy and reduced birth size: a prospective birth cohort study in Valencia, Spain

Abstract 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 circumf…

Association between exposure to organochlorine compounds and maternal thyroid status: Role of the iodothyronine deiodinase 1 gene.

Introduction: Exposure to organochlorine compounds (OCs) may interfere with thyroid hormone (TH) homeostasis. The disruption of the deiodinase (DIO) enzymes has been proposed as a mechanism of action. Aim: To evaluate the association between exposure to OCs and TH status in pregnant women, as well as to explore the role of genetic variations in the DIO1 and DIO2 genes. Methods: The study population (n = 1128) was composed of pregnant women who participated in the INMA Project (Spain, 2003–2006). Hexachlorobenzene (HCB), 1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene (4,4´-DDE), b-hexachlorocyclohexane (b-HCH), polychlorobiphenyl (PCB) congeners 138, 153 and 180, thyroid stimulating hormone (T…

Exposure to mercury among 9-year-old children and neurobehavioural function

Abstract Mercury (Hg) is an environmental neurotoxicant whose main route of exposure in humans is the consumption of seafood. The aim of this study was to explore the relationship between Hg exposure at 9 years old and behaviour assessed at 9 and 11 years old. Study subjects were mother–child pairs participating in the INMA (Environment and Childhood) Project in Valencia (Spain). Total Hg (THg) was measured in hair samples from the children at 9 years old. Behaviour and emotions were assessed at 9 (n = 472) years and 11 (n = 385) years of age using the Child Behaviour Checklist test (CBCL) and the Conners Parents Rating Scale-Revised: Short Form (CPRS-R:S). Furthermore, the attention functi…

Maternal selenium status and neuropsychological development in Spanish preschool children

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 theMcCarthy Scales of Children's Abilities (MSCA). Sociodem…

Iodine intake from supplements and diet during pregnancy and child cognitive and motor development: the INMA Mother and Child Cohort Study

BackgroundThe 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.MethodsWe 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 c…

Pre and postnatal exposure to mercury and respiratory health in preschool children from the Spanish INMA Birth Cohort Study

Effects of mercury on maturing immune system have been reported, however the association with respiratory and allergy problems during infancy remains unclear. The aim of this study is to evaluate the association between pre and postnatal mercury exposure and respiratory and allergy problems among preschool children and to examine the role of potential modifying factors. Study subjects were children participant in Spanish Childhood and Environment Project (INMA, 2003-2008). We measured total mercury levels in cord blood (n = 1868) and hair at 4 years of age (n = 1347). Respiratory outcomes (wheezing, severe wheezing, chestiness, persistent cough, eczema and otitis) were obtained by questionn…

A genome-wide association meta-analysis of diarrhoeal disease in young children identifies FUT2 locus and provides plausible biological pathways

More than a million childhood diarrhoeal episodes occur worldwide each year, and in developed countries a considerable part of them are caused by viral infections. In this study, we aimed to search for genetic variants associated with diarrhoeal disease in young children by meta-analyzing genome-wide association studies, and to elucidate plausible biological mechanisms. The study was conducted in the context of the Early Genetics and Lifecourse Epidemiology (EAGLE) consortium. Data about diarrhoeal disease in two time windows (around 1 year of age and around 2 years of age) was obtained via parental questionnaires, doctor interviews or medical records. Standard quality control and statistic…

Prenatal arsenic exposure, arsenic methylation efficiency, and neuropsychological development among preschool children in a Spanish birth cohort.

Abstract Background Prenatal arsenic (As) exposure could negatively affect child neuropsychological development, but the current evidence is inconclusive. Objectives To explore the relationship between prenatal urinary total As (TAs) concentrations, the As species and the methylation efficiency, and child neuropsychological development in a Spanish birth cohort. We also studied the effect modification produced by sex and several nutrients and elements. Materials and methods Study subjects were 807 mother–child pairs participating in the INMA (Childhood and Environment) Project. Urinary TAs and its metabolites, monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), inorganic As (iAs) and …

Annoyance Caused by Noise and Air Pollution during Pregnancy: Associated Factors and Correlation with Outdoor NO2 and Benzene Estimations

This study aimed to describe the degree of annoyance among pregnant women in a Spanish cohort and to examine associations with proximity to traffic, NO2 and benzene exposure. We included 2457 participants from the Spanish Childhood and Environment study. Individual exposures to outdoor NO2 and benzene were estimated, temporally adjusted for pregnancy. Interviews about sociodemographic variables, noise and air pollution were carried out. Levels of annoyance were assessed using a scale from 0 (none) to 10 (strong and unbearable)

Prenatal perfluoroalkyl substance exposure and neuropsychological development throughout childhood: The INMA Project.

Abstract Background Perfluoroalkyl substances (PFASs) have been related to neurodevelopmental toxicity in animals. However, human studies are inconclusive. Objectives To evaluate the association between prenatal PFAS exposure and neuropsychological development during childhood. Methods 1240 mother–child pairs from the Spanish INMA Project were analyzed. Perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), and perfluorononanoic acid (PFNA) were measured in first-trimester maternal plasma. Neuropsychological development was assessed at 14 months, 4–5 and 7 years covering four domains: general cognitive, general motor, attention, and working me…

Prenatal ambient air pollution exposure, infant growth and placental mitochondrial DNA content in the INMA birth cohort

Background: The association between prenatal air pollution exposure and postnatal growth has hardly been explored. Mitochondrial DNA (mtDNA), as a marker of oxidative stress, and growth at birth can play an intermediate role in this association. Objective: In a subset of the Spanish birth cohort INMA we assessed first whether prenatal nitrogen dioxide (NO2) exposure is associated with infant growth. Secondly, we evaluated whether growth at birth (length and weight) could play a mediating role in this association. Finally, the mediation role of placental mitochondrial DNA content in this association was assessed. Methods: In 336 INMA children, relative placental mtDNA content was measured. L…

Prenatal exposure to mercury and longitudinally assessed fetal growth: Relation and effect modifiers.

Background: Prenatal mercury exposure has been related to reductions in anthropometry at birth. Levels of mercury have been reported as being relatively elevated in the Spanish population. Objective: To investigate the relation between prenatal exposure to mercury and fetal growth. Methods: Study subjects were pregnant women and their newborns (n:1867) participating in a population-based birth cohort study set up in four Spanish regions from the INMA Project. Biparietal diameter (BPD), femur length (FL), abdominal circumference (AC), and estimated fetal weight (EFW) were measured by ultrasounds at 12, 20, and 34 weeks of gestation. Size at and growth between these points were assessed by st…

Estado actual sobre la exposición alimentaria al mercurio durante el embarazo y la infancia, y recomendaciones en salud pública

La exposición a dosis altas de mercurio durante periodos vulnerables (como el embarazo y la infancia) puede tener serias consecuencias para el desarrollo cognitivo, tal como se ha constatado tras los episodios de envenenamiento agudo ocurridos en Japón e Irak. El consumo de ciertos tipos de pescado es la fuente principal de exposición a mercurio de la población general. Existe una creciente preocupación por los posibles efectos neurotóxicos del mercurio, especialmente a edades tempranas en poblaciones donde el consumo de pescado es moderado-alto. La evidencia científica hasta el momento no es concluyente. En el ámbito español, el Proyecto INMA (Infancia y Medio Ambiente) ha proporcionado in…

Prenatal Se concentrations and anthropometry at birth in the INMA study (Spain).

Abstract We assessed whether prenatal selenium (Se) exposure is associated with anthropometry at birth, placental weight and gestational age. Study subjects were 1249 mother-child pairs from the Valencia and Gipuzkoa cohorts of the Spanish Childhood and Environment Project (INMA, 2003–2008). Se was determined in serum samples taken at the first trimester of pregnancy. Socio-demographic and dietary characteristics were also collected by questionnaires. Mean (SD) serum Se concentration was 79.57 (9.64) μg/L. Se showed weak associations with both head circumference and gestational age. The association between serum Se concentration and birth weight and length was negative, and direct for place…

Preterm birth and exposure to air pollutants during pregnancy.

Background Research has shown that prenatal exposure to air pollutants may have a detrimental effect on fetal development with the strength of the relationship depending on the effect being studied The evidence to date however is insufficient to establish a direct causal link between such exposure and preterm delivery This study evaluates the specific effect of prenatal exposure to NO2 and benzene on preterm births Methods The population under study comprised 785 pregnant women who formed part of the INMA cohort in Valencia Spain (2003-2005) Multiple regression models were used for mapping outdoor nitrogen dioxide (NO2) and benzene levels throughout the area Individual exposure was assigned…

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

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, β = -0.19 …

Maternal Consumption of Seafood in Pregnancy and Child Neuropsychological Development: A Longitudinal Study Based on a Population With High Consumption Levels

Seafood consumption during pregnancy is thought to be beneficial for child neuropsychological development, but to our knowledge no large cohort studies with high fatty fish consumption have analyzed the association by seafood subtype. We evaluated 1,892 and 1,589 mother-child pairs at the ages of 14 months and 5 years, respectively, in a population-based Spanish birth cohort established during 2004-2008. Bayley and McCarthy scales and the Childhood Asperger Syndrome Test were used to assess neuropsychological development. Results from multivariate linear regression models were adjusted for sociodemographic characteristics and further adjusted for umbilical cord blood mercury or long-chain p…

Social factors associated with nitrogen dioxide (NO2) exposure during pregnancy: The INMA-Valencia project in Spain

Numerous studies have focused on the effects of exposure to air pollution on health: however, certain subsets of the population tend to be more exposed to such pollutants depending on their social or demographic characteristics. In addition, exposure to toxicants during pregnancy may play a deleterious role in fetal development as fetuses are especially vulnerable to external insults. The present study was carried out within the framework of the INMA (Infancia y Medio Ambiente or Childhood and the Environment) multicenter cohort study with the objective of identifying the social, demographic, and lifestyle factors associated with nitrogen dioxide (NO2) exposure in the subjects in the cohort…

Selenium status during pregnancy: Influential factors and effects on neuropsychological development among Spanish infants

Selenium(Se) has been positively associated with neurodevelopment in early life. However, its margin of safety is rather narrow, and few prospective studies have evaluated its potential neurotoxic effects at intermediate levels. We aimed to explore the association between maternal Se concentrations and child neuropsychological development, including the genetic effect modification of the Se metabolizing gene INMT. Study subjects were 650 mother-child pairs from the Spanish Childhood and Environment Project (INMA, 2003-2005). Infant neuropsychological development was assessed around 12 months of age by the Bayley Scales of Infant Development. Sociodemographic and dietary characteristics were…

Genome-wide DNA methylation study in human placenta identifies novel loci associated with maternal smoking during pregnancy

BACKGROUND: We conducted an epigenome-wide association study (EWAS) of DNA methylation in placenta in relation to maternal tobacco smoking during pregnancy and examined whether smoking-induced changes lead to low birthweight. METHODS: DNA methylation in placenta was measured using the Illumina HumanMethylation450 BeadChip in 179 participants from the INfancia y Medio Ambiente (INMA) birth cohort. Methylation levels across 431 311 CpGs were tested for differential methylation between smokers and non-smokers in pregnancy. We took forward three top-ranking loci for further validation and replication by bisulfite pyrosequencing using data of 248 additional participants of the INMA cohort. We ex…

Prenatal Exposure to Organochlorine Compounds and Birth Size

Objective: To investigate the possible association between birth size and cord concentrations of some organochlorine compounds (OCs), including 4,4′-dichlorodiphenyltrichloroethane (DDT), 4,4′-1,1-dichloro-2,2-bis(p-dichlorodiphenyl)ethylene (DDE), hexachlorobenzene (HCB), β-hexachlorocyclohexane (β-HCH), 4 polychlorinated biphenyl (PCB) congeners (118, 138, 153, and 180), and their sum (ΣPCBs) in a birth cohort in Valencia, Spain. Study Design: A total of 494 mothers and their newborns (born 2003–2006) participated in the study. Multivariate linear regression analyses were performed between birth weight, length, or head circumference and OC concentrations. Results: Median concentrations of…

Evaluating the neurotoxic effects of lactational exposure to persistent organic pollutants (POPs) in Spanish children.

Although the brain continues developing in the postnatal period, epidemiological studies on the effects of postnatal exposure to neurotoxic POPs through breast-feeding remain mostly inconclusive. Failure to detect associations between postnatal exposure and health outcomes may stem from the limitations of commonly employed approaches to assess lactational exposure. The aim of the present study was to assess whether lactational exposure to polychlorinated biphenyl-153 (PCB-153), dichlorodiphenyldichloroethylene (DDE), or hexachlorobenzene (HCB) as estimated with a physiologically based pharmacokinetic (PBPK) model, is associated with decrements in mental and psychomotor development scores of…

Prenatal manganese serum levels and neurodevelopment at 4 years of age

Abstract 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 fo…

Prenatal and postnatal residential usage of insecticides in a multicenter birth cohort in Spain

Abstract: This study aimed to describe the residential use of insecticides in a birth cohort in Spain. Study subjects were 2 456 women enrolled into the INMA (Environment and Childhood) birth cohort followed prospectively during pregnancy and in the early postnatal period. The women were recruited at the beginning of their pregnancy between 2003 and 2008 in four regions of Spain. Socio-demographic, environmental and lifestyle information was obtained at two interviews during pregnancy, one at the first (mean:13.8 +/- 2.6 weeks of gestation) and the other at the third trimester (mean: 33.3 +/- 23 weeks of gestation). Information about prenatal use of indoor and outdoor insecticides (type, ti…

Prenatal Ambient Air Pollution, Placental Mitochondrial DNA Content, and Birth Weight in the INMA (Spain) and ENVIRONAGE (Belgium) Birth Cohorts

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),…

Estudio de la evolución de la exposición a plomo en la población infantil española en los últimos 20 años: ¿un ejemplo no reconocido de «salud en todas las políticas»?

ResumenObjetivoDescribir la evolución temporal de las concentraciones de plomo en el aire en España, desde antes de su prohibición como aditivo de la gasolina hasta la actualidad, así como estudiar la evolución de la carga corporal de plomo en la población infantil española.MétodosSe obtuvieron las concentraciones medias anuales de plomo en el aire en diversas ciudades españolas, desde la década de 1980 hasta la actualidad. Se realizó una búsqueda bibliográfica con el fin de identificar estudios publicados sobre concentraciones de plomo en la población infantil española.ResultadosEn general se observó una disminución de las concentraciones de plomo, de mayor magnitud entre 1991 y 1999. Esta…

Maternal seafood consumption during pregnancy and child attention outcomes: a cohort study with gene effect modification by PUFA-related genes

Abstract 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 …

Prenatal exposure to traffic-related air pollution and fetal growth in a cohort of pregnant women

Objectives Scant evidence is available on effects of air pollution on longitudinally measured fetal biometry, and thus it remains unclear as to whether there are critical windows of exposure or specificity of effects. Our objective was to examine the association between exposure to nitrogen dioxide (NO2) during pregnancy and fetal and neonatal anthropometry in a cohort of Spanish women. Methods Temporally adjusted land-use regression was used to estimate exposure to NO2 at home addresses. Biparietal diameter (BPD), abdominal circumference (AC), femur length (FL) and estimated fetal weight (EFW) were evaluated in each trimester by ultrasound. As neonatal outcomes, weight, length and head cir…

Prenatal mercury exposure and birth outcomes

Background: Results regarding the association between mercury exposure and anthropometry at birth, gestational length and placental weight are inconsistent, as is the role of seafood intake in these asso- ciations. Objective: We assessed whether prenatal mercury exposure is associated with anthropometry at birth, placental weight and gestational length in a population with a relatively high exposure to mercury from seafood consumption. Methods: Total mercury (T – Hg) was determined in cord blood from 1869 newborns with birth outcome measures, within the Spanish multicenter INMA cohort from 2004 to 2008. We adjusted cohort speci fi c linear and Cox regression models to evaluate the associati…

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&prime

Lifelong Residential Exposure to Green Space and Attention: A Population-based Prospective Study

C.T. is a recipient of a European Respiratory Society Fellowship (RESPIRE2–2015–7251) P.D. is funded by a Ramón y Cajal fellowship (RYC-2012-10995) awarded by the Spanish Ministry of Economy and Competitiveness. S.L. is funded by a Miguel Servet-FEDER fellowship (MS15/0025) awarded by the Spanish Ministry of Economy and Competitiveness. M.G. is funded by a Miguel Servet-FEDER fellowship (MS13/00054) awarded by the Spanish Ministry of Economy and Competitiveness

DNA methylation changes associated with prenatal mercury exposure:A meta-analysis of prospective cohort studies from PACE consortium

Mercury (Hg) is a ubiquitous heavy metal that originates from both natural and anthropogenic sources and is transformed in the environment to its most toxicant form, methylmercury (MeHg). Recent studies suggest that MeHg exposure can alter epigenetic modifications during embryogenesis. In this study, we examined associations between prenatal MeHg exposure and levels of cord blood DNA methylation (DNAm) by meta-analysis in up to seven independent studies (n = 1462) as well as persistence of those relationships in blood from 7 to 8 year-old children (n = 794). In cord blood, we found limited evidence of differential DNAm at cg24184221 in MED31 (β = 2.28 × 10-4, p-value = 5.87 × 10-5) in relat…

Ancient Haplotypes at the 15q24.2 Microdeletion Region Are Linked to Brain Expression of MAN2C1 and Children's Intelligence

The chromosome bands 15q24.1-15q24.3 contain a complex region with numerous segmental duplications that predispose to regional microduplications and microdeletions, both of which have been linked to intellectual disability, speech delay and autistic features. The region may also harbour common inversion polymorphisms whose functional and phenotypic manifestations are unknown. Using single nucleotide polymorphism (SNP) data, we detected four large contiguous haplotype-genotypes at 15q24 with Mendelian inheritance in 2,562 trios, African origin, high population stratification and reduced recombination rates. Although the haplotype-genotypes have been most likely generated by decreased or abse…

Synergism between exposure to mercury and use of iodine supplements on thyroid hormones in pregnant women

Objective: To evaluate the association between mercury exposure and thyroid-stimulating hormone (TSH), total triiodothyronine (TT3) and free thyroxine (FT4) levels during pregnancy as well as to explore if there is any synergic action between mercury and intake of iodine from different sources. Methods: The study population was 1407 pregnant women participating in the Spanish INMA birth cohort study. Total mercury concentrations were analyzed in cord blood. Thyroid hormones (THs) were measured in serum samples collected at 13.2 +/- 1.5 weeks of gestation. The association between mercury and TH levels was evaluated with multivariate linear regression models. Effect modification caused by iod…