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Background: Several studies have reported that prenatal exposure to some persistent organic pollutants (POPs) is associated with higher adiposity in childhood. Few studies have assessed whether this finding persists into adolescence, and few have considered exposure to POPs as a mixture. This study aims to assess the association between prenatal exposure to multiple POPs and adiposity markers and blood pressure in preadolescents., Methods: This study included 1667 mother-child pairs enrolled in the PELAGIE (France) and the INMA (Spain) mother-child cohorts. Three polychlorobiphenyls (PCB 138, 153 and 180, treated as a sum of PCBs) and three organochlorine pesticides (p,p'-Dichlorodiphenyldichloroethylene [p,p'-DDE], β-hexachlorocyclohexane [β-HCH], and hexachlorobenzene [HCB]) were assessed in maternal or cord serum. Body mass index z-score (zBMI), abdominal obesity (waist-to-height ratio > 0.5), percentage of fat mass, and blood pressure (mmHg) were measured at around 12 years of age. Single-exposure associations were studied using linear or logistic regressions, and the POP mixture effect was evaluated using quantile G-computation (qgComp) and Bayesian Kernel Machine Regression (BKMR). All models were adjusted for potential confounders and performed for boys and girls together and separately., Results: Prenatal exposure to the POP mixture was associated with higher zBMI (beta [95 % CI] of the qgComp = 0.15 [0.07; 0.24]) and percentage of fat mass (0.83 [0.31; 1.35]), with no evidence of sex-specific association. These mixture effects were also statistically significant using BKMR. These associations were driven mainly by exposure to HCB and, to a lesser extent, to β-HCH. In addition, the single-exposure models showed an association between β-HCH and p,p'-DDE and higher systolic blood pressure, especially in girls (p,p'-DDE for girls = 1.00 [0.15; 1.86]). No significant associations were found for PCBs., Conclusion: This study suggests that prenatal exposure to POPs, particularly organochlorine pesticides, remains associated with unfavorable cardiometabolic health up to the age of 12., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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 function was assessed by the Attention Network Test at 11 years old. Socio-demographic, lifestyle and dietary information was collected through questionnaires during pregnancy and childhood. Polymorphism in BDNF, APOE and GSTP1 were genotyped in cord blood DNA. Multivariable negative binomial regression models were built in order to study the association between THg concentrations and the scores obtained by the children at 9 and 11 years old. Effect modification by sex and genetic polymorphisms was assessed. The association between Hg levels and CBCL scores was positive (worse neurobehavioural development) for the CBCL internalizing and total problem scales (Incidence Rate Ratio [95% confidence interval] = 1.07 [1.01, 1.13] and 1.05 [0.99, 1.11], respectively). The association between Hg and the externalizing and total problems CBCL scales and the Attention Deficit Hyperactivity Disorder (ADHD) index of the CPRS-R:S was different according to sex, with boys obtaining worse scores with increasing Hg, compared to girls. Statistically significant interactions were also observed for genetic polymorphisms affecting the association between early exposure to Hg and both CBCL and CPRS-R:S scores. In conclusion, postnatal Hg exposure is associated with poorer neurobehavioural development in 9- and 11-year-old children. Sex and the presence of certain genetic polymorphisms modified this association., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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 covariates. The geometric mean (95% confidence interval) of hair THg at 9 years old was 0.89 μg/g (0.81, 0.98). Thirteen percent of children had THg above the equivalent to the Provisional Tolerable Weekly Intake proposed by the World Health Organization. THg were higher among children whose mothers had a healthy body mass index before pregnancy. Children with non-smoker mothers and worker fathers had also higher THg. Children's fish intake at 9 years-old was positively associated with THg, being swordfish, canned tuna and lean fish (i.e. hake, sea bream and sole) the most associated categories. Levels decreased by around 22% between 4 and 9 years old. Birth cohort studies, such as the INMA Project, allow the longitudinal evaluation of Hg exposure and the possible effects on children's health. This information can be used to formulate diet recommendations in vulnerable populations., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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 4-5years 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 1year of age using the Bayley Scales of Infant Development and at 4-5years with the McCarthy Scales of Children's Abilities. Modeled tap water concentrations of trihalomethanes (THM) were combined with personal ingestion, showering and bathing habits to estimate exposure as ingestion uptake, all route (showering, bathing, ingestion) uptake (μg/day) and crude levels (μg/l) in the residence. Chloroform, brominated THMs (bromodichloromethane, dibromochloromethane, bromoform) and total THMs (chloroform and brominated THMs) were analysed separately. Nine haloacetic acids levels were available in one of the areas. Linear regression was used to estimate associations in 1855 subjects adjusting for covariables., Results: The median concentration of total THMs, chloroform, brominated THMs, total haloacetic acids, dichloroacetic acid, and trichloroacetic acid were, respectively 30.3μg/L, 9.4μg/L, 11.6μg/L, 10.5μg/L, 2.7μg/L, and 3.1μg/L. The associations between THM exposure and neuropsychological outcomes were null, except for total and brominated THM uptake though all routes and the general cognitive score at 4-5years, with a decrease in -0.54 points (95%CI -1.03, -0.05) and -0.64 (95%CI -1.16, -0.12), respectively, for doubling total and brominated THM uptake. A positive association found between dichloroacetic acid and the mental score at 1year did not persist at 4-5years., Conclusions: Minor associations observed between DBP exposure during gestation and child neuropsychological development at 1year disappeared at 4-5years. Although a suggestive association is identified for exposure to brominated THMs and the cognitive score at 4-5years, chance cannot be ruled out., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Results on the association between prenatal exposure to methylmercury (MeHg) and child neuropsychological development are heterogeneous. Underlying genetic differences across study populations could contribute to this varied response to MeHg. Studies in Drosophila have identified the cytochrome p450 3A (CYP3A) family as candidate MeHg susceptibility genes., Objectives: We evaluated whether genetic variation in CYP3A genes influences the association between prenatal exposure to MeHg and child neuropsychological development., Methods: The study population included 2639 children from three birth cohort studies: two subcohorts in Seychelles (SCDS) (n=1160, 20 and 30months of age, studied during the years 2001-2012), two subcohorts from Spain (INMA) (n=625, 14months of age, 2003-2009), and two subcohorts from Italy and Greece (PHIME) (n=854, 18months of age, 2006-2011). Total mercury, as a surrogate of MeHg, was analyzed in maternal hair and/or cord blood samples. Neuropsychological development was evaluated using Bayley Scales of Infant Development (BSID). Three functional polymorphisms in the CYP3A family were analyzed: rs2257401 (CYP3A7), rs776746 (CYP3A5), and rs2740574 (CYP3A4)., Results: There was no association between CYP3A polymorphisms and cord mercury concentrations. The scores for the BSID mental scale improved with increasing cord blood mercury concentrations for carriers of the most active alleles (β[95% CI]:=2.9[1.53,4.27] for CYP3A7 rs2257401 GG+GC, 2.51[1.04,3.98] for CYP3A5 rs776746 AA+AG and 2.31[0.12,4.50] for CYP3A4 rs2740574 GG+AG). This association was near the null for CYP3A7 CC, CYP3A5 GG and CYP3A4 AA genotypes. The interaction between the CYP3A genes and total mercury was significant (p<0.05) in European cohorts only., Conclusions: Our results suggest that the polymorphisms in CYP3A genes may modify the response to dietary MeHg exposure during early life development., (Copyright © 2017. Published by Elsevier Ltd.)

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 (TSH), total triiodothyronine (TT3) and free thyroxine (FT4) were measured in serum samples taken during the first trimester of pregnancy (mean [standard deviation (SD)]: 13.5 [2] weeks of gestation). Polymorphisms in DIO1 (rs2235544) and DIO2 (rs12885300) were genotyped in maternal DNA. Sociodemographic and dietary characteristics were obtained by questionnaire., Results: A 2-fold increase in HCB was associated with lower TT3 (% change=-1.48; 95%CI: -2.36, -0.60). Women in the third tertile for b-HCH had lower TT3 (% change=-3.19; 95%CI: -5.64, -0.67). The interactions between DIO1 rs2235544 and PCB153 and b-HCH were statistically significant. The inverse association between PCB153 and TT3 was the strongest among women with AA genotype. Women with CC genotype presented the strongest inverse association between b-HCH and FT4., Conclusion: Exposure to HCB and b-HCH was associated to a disruption in maternal TT3. The DIO1 rs2235544 SNP modified the association between exposure to some of the OCs (specifically b-HCH and PCB153) and maternal thyroid hormone levels. These results strengthen the hypothesis that DIO enzymes play a role in explaining the disruption of thyroid hormones in relation to exposure to OCs., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

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 14months using the Bayley Scales of Infant Development. The associations were analyzed by linear regression models. 54% of women used indoor insecticides at home during pregnancy and 47% postnatally. 34% of women used insecticide sprays and 33% used plug-in devices during pregnancy. During infancy, the percentage of women who used insecticide sprays decreased (22%), but the use of plug-in devices was similar to the prenatal period (32%). The use of insecticide sprays during pregnancy was associated with a decrement in psychomotor development (β=-1.9; 95%CI: -3.4, -0.5) but postnatal use did not associate with mental and psychomotor development. The negative effect was enhanced according to some modifying factors, such as being female, higher levels of prenatal exposure to PCB and mercury and belonging to the lowest social class. We found certain evidence about the adverse effect of using insecticide sprays during pregnancy on the psychomotor development of children. Some socio-demographic factors and other exposures could enhance that effect., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Phthalate and phenol exposure is prevalent among the general population and of potential concern for pregnant women and children because of their suspected susceptibility to endocrine effects., Objectives: To evaluate the extent of exposure to several phthalates and phenols in a sample of Spanish pregnant women - according to their individual characteristics (age, social class, education, and body mass index) - and children who participated in the INMA - Infancia y Medio Ambiente (Environment and Childhood) project., Methods: One spot urine sample was taken during the third trimester of pregnancy from 120 pregnant women and from 30 4-year old children belonging to 5 Spanish birth cohorts, and analyzed for 11 phthalate metabolites and 9 phenols., Results: Three metabolites of di(2-ethylhexyl) phthalate, mono-2-ethyl-5-carboxypentyl phthalate, mono-2-ethyl-5-hydroxyhexyl phthalate, and mono-2-ethyl-5-oxohexyl phthalate; two metabolites of dibutyl phthalates, mono-isobutyl phthalate and mono-n-butyl phthalate; monoethyl phthalate (MEP), the main metabolite of diethyl phthalate; and two phenols, methyl paraben (M-PB) and 2,5-dichlorophenol were detected in the urine samples of all women. The highest urinary concentrations were for MEP and M-PB. Urinary concentrations of all phthalate metabolites and of 2,4-dichlorophenol, 2,5-dichlorophenol, and bisphenol A were lower in the pregnant women than in the children. Among women, a positive relationship with social class and education was shown for most of the phthalate metabolites and phenols. Almost all phthalate metabolites varied by region even after adjusting for social class and education., Conclusions: Phthalate and phenol exposures are prevalent in a group of pregnant women and young children, two susceptible populations, and these exposures might be positively related to social class., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Polybromodiphenyl ethers (PBDEs) were analyzed in blood serum of pregnant women and in cord blood serum of their newborns from a general population cohort (n = 174; Valencia, Spain). The most abundant PBDE congeners identified were BDE 47, BDE 99, BDE 153, BDE 154 and BDE 209. Their cord blood serum concentrations were about 45% of those in maternal serum but after lipid normalization about the same concentrations were observed in both types of samples. Thus, median of total PBDEs was 9.6 ng/g lipid in cord serum (range between not detected and 140 ng/g lipid) and 9.6 ng/g lipid in maternal serum (range between not detected and 120 ng/g lipid). The distributions of these compounds were dominated by BDE 47 in both cases. In cord blood serum the decreasing order of abundance was BDE 47>BDE 99>BDE 209>BDE 153>BDE 154. The congener composition in maternal serum followed a similar trend: BDE 47>BDE 153>BDE 154>BDE 209>BDE 99. The congener concentrations exhibited a higher degree of correlation in cord blood than in maternal serum. Use of the maternal determinants for categorization of the observed maternal and fetal PBDE concentrations only showed significant associations for the levels in umbilical cord. Neonates from rural areas exhibited statistically significantly lower concentrations than those from urban, semi-urban or metropolitan sites. Maternal serum also showed this difference but the higher dispersion of the concentrations in maternal serum did not afford its recognition with statistical significance. The lower qualitative and quantitative variability in the PBDE concentrations of cord blood serum than maternal serum suggest that the latter is reflecting PBDE contributions from a wider diversity of sources than the former whereas cord blood sera seem to represent the long term standing stock of these compounds accumulated in the maternal tissues., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Determinants of outdoor, indoor and personal concentrations of nitrogen dioxide (NO(2)) were assessed in a subset of pregnant women of the Spanish INMA (Environment and Childhood) Study. Home indoor and outdoor NO(2) concentrations were measured during 48 h with passive samplers for 50 and 58 women from the INMA cohorts of Valencia and Sabadell, respectively. Women from Sabadell also carried personal NO(2) samplers during the same period. Data on time-activity patterns, socio-economic characteristics, and environmental exposures were obtained through questionnaires. Multiple linear regression models were developed to predict NO(2) levels. In Valencia, median outdoor NO(2) levels (42 microg/m(3)) were higher than median indoor levels (36 microg/m(3)). In Sabadell, personal NO(2) showed the highest median levels (40 microg/m(3)), followed by indoor (32 microg/m(3)) and outdoor (29 microg/m(3)) levels. Personal exposure to NO(2) correlated best with the indoor NO(2) levels. Temporal and traffic-related variables were significant predictors for outdoor NO(2) levels. Thirty-two percent of the indoor NO(2) variability in the two cohorts was explained by outdoor NO(2) levels and the use of the gas appliances. The model for personal exposure accounted for 59% of the variance in NO(2) levels in Sabadell with four predictor variables (outdoor and indoor NO(2) levels, time spent in outdoor environments and time exposed to a gas cooker). No significant association was found between personal or indoor NO(2) levels and exposure to environmental tobacco smoke (ETS) at home. Personal NO(2) levels were found to be strongly influenced by indoor NO(2) concentrations. The study supports the use of time-activity patterns along with indoor measurements to predict personal exposure to traffic-related air pollution.

Assessing the adverse effects on human health of persistent organic pollutants (POPs) and the impact of policies aiming to reduce human exposure to POPs warrants monitoring body concentrations of POPs in representative samples of subjects. While numerous ad hoc studies are being conducted to understand POPs effects, only a few countries are conducting nationwide surveillance programs of human concentrations of POPs, and even less countries do so in representative samples of the general population. We tried to identify all studies worldwide that analyzed the distribution of concentrations of POPs in a representative sample of the general population, and we synthesized the studies' main characteristics, as design, population, and chemicals analyzed. The most comprehensive studies are the National Reports on Human Exposure to Environmental Chemicals (USA), the German Environmental Survey, and the Arctic Monitoring and Assessment Programme. Population-wide studies exist as well in New Zealand, Australia, Japan, Flanders (Belgium) and the Canary Islands (Spain). Most such studies are linked with health surveys, which is a highly-relevant additional strength. Only the German and Flemish studies analyzed POPs by educational level, while studies in the USA offer results by ethnic group. The full distribution of POPs concentrations is unknown in many countries. Knowledge gaps include also the interplay of age, gender, period and cohort effects on the prevalence of exposures observed by cross-sectional surveys. Local and global efforts to minimize POPs contamination, like the Stockholm convention, warrant nationwide monitoring of concentrations of POPs in representative samples of the general population. Results of this review show how such studies may be developed and used.