Association of prenatal exposure to phthalates and synthetic phenols with pubertal development in three European cohorts.

BACKGROUND: There is limited epidemiological evidence on the association of prenatal exposure to phthalates and synthetic phenols with altered pubertal timing. OBJECTIVE: To examine the association of prenatal exposure to phthalates, bisphenol A (BPA), parabens, benzophenone 3 (BP-3), and triclosan (TCS) with pubertal development in girls and boys from three European cohorts. METHODS: Urinary metabolites of six different phthalate diesters (DEP, DiBP, DnBP, BBzP, DEHP, and DiNP), BPA, methyl- (MePB), ethyl- (EtPB), propyl- (PrPB), and butyl-paraben (BuPB), BP-3, and TCS were quantified in one or two (1st and 3rd trimester) urine samples collected during pregnancy (1999-2008) from mothers in three birth cohorts: INMA (Spain), EDEN (France), and MoBa (Norway). Pubertal development of their children was assessed at a single visit at age 7-12 years (579 girls, 644 boys) using the parent-reported Pubertal Development Scale (PDS). Mixed-effect Poisson and g-computation and Bayesian Kernel Machine Regression (BKMR) were employed to examine associations of individual and combined prenatal chemical exposure, respectively, with the probability of overall pubertal onset, adrenarche, and gonadarche (stage 2+) in girls and boys. Effect modification by child body mass index (BMI) was also assessed. RESULTS: Maternal concentrations of the molar sum of DEHP and of DiNP metabolites were associated with a slightly higher probability of having started puberty in boys (relative risk, RR [95% CI] = 1.13 [0.98-1.30] and 1.20 [1.06-1.34], respectively, for a two-fold increase in concentrations), with a stronger association for DiNP in boys with overweight or obesity. In contrast, BPA, BuPB, EtPB, and PrPB were associated with a lower probability of pubertal onset, adrenarche, and/or gonadarche in all boys (e.g. overall puberty, BPA: RR [95% CI] = 0.93 [0.85-1.01] and BuPB: 0.95 [0.90-1.00], respectively), and the association with BPA was stronger in boys with underweight/normal weight. In girls, MEHP and BPA were associated with delayed gonadarche in those with underweight/normal weight (RR [95% CI] = 0.86 [0.77-0.95] and 0.90 [0.84-0.97], respectively). Most of these associations were trimester specific. However, the chemical mixture was not associated with any pubertal outcome in boys or girls. CONCLUSIONS: Prenatal exposure to certain phthalates and synthetic phenols such as BPA may impact the pubertal development of boys, and weight status may modify this effect. BPA may also alter the pubertal development of girls.

The impact of prenatal mercury on neurobehavioral functioning longitudinally assessed from a young age to pre-adolescence in a Spanish birth cohort.

The objective is to investigate the relation between cord blood mercury concentrations and child neurobehavioural functioning assessed longitudinally during childhood until pre-adolescence. METHODS: The study involves mothers and their offspring engaged in the Spanish INMA birth cohort (n = 1147). Total mercury (THg) was determined in cord blood. Behavioural problems were assessed several times during childhood using the ADHD-DSM-IV at age 4, SDQ at ages 7 and 11, CPRS-R:S and the CBCL at ages 7, 9 and 11. Covariates were obtained through questionnaires during the whole period. Multivariate generalised negative binomial (MGNB) models or mixed-effects MGNB (for those tests with information at one or more time points, respectively) were used to investigate the relation between cord blood THg and the children's punctuations. Models were adjusted for prenatal fish intake. Effect modification by sex, prenatal and postnatal fish intake, prenatal fruit and vegetable intake, and maternal polychlorinated biphenyl concentrations (PCBs) was assessed by interaction terms. RESULTS: The geometric mean ± standard deviation of cord blood THg was 8.22 ± 2.19 µg/L. Despite adjusting for fish consumption, our results did not show any statistically significant relationship between prenatal Hg and the children's performance on behavioural tests conducted between the ages of 4 and 11. Upon assessing the impact of various factors, we observed no statistically significant interaction. CONCLUSION: Despite elevated prenatal THg exposure, no association was found with children's behavioural functioning assessed from early childhood to pre-adolescence. The nutrients in fish could offset the potential neurotoxic impact of Hg. Further birth cohort studies with longitudinal data are warranted.

Increased parental effort fails to buffer the cascading effects of warmer seas on common guillemot demographic rates.

Climate warming can reduce food resources for animal populations. In species exhibiting parental care, parental effort is a 'barometer' of changes in environmental conditions. A key issue is the extent to which variation in parental effort can buffer demographic rates against environmental change. Seabirds breed in large, dense colonies and globally are major predators of small fish that are often sensitive to ocean warming. We explored the causes and consequences of annual variation in parental effort as indicated by standardised checks of the proportions of chicks attended by both, one or neither parent, in a population of common guillemots Uria aalge over four decades during which there was marked variation in marine climate and chick diet. We predicted that, for parental effort to be an effective buffer, there would be a link between environmental conditions and parental effort, but not between parental effort and demographic rates. Environmental conditions influenced multiple aspects of the prey delivered by parents to their chicks with prey species, length and energy density all influenced by spring sea surface temperature (sSST) in the current and/or previous year. Overall, the mean annual daily energy intake of chicks declined significantly when sSST in the current year was higher. In accordance with our first prediction, we found that parental effort increased with sSST in the current and previous year. However, the increase was insufficient to maintain chick daily energy intake. In contrast to our second prediction, we found that increased parental effort had major demographic consequences such that growth rate and fledging success of chicks, and body mass and overwinter survival of breeding adults all decreased significantly. Common guillemot parents were unable to compensate effectively for temperature-mediated variation in feeding conditions through behavioural flexibility, resulting in immediate consequences for breeding population size because of lower adult survival and potentially longer-term impacts on recruitment because of lower productivity. These findings highlight that a critical issue for species' responses to future climate change will be the extent to which behavioural buffering can offer resilience to deteriorating environmental conditions.

Modelling seabirds biodiversity through Bayesian Spatial Beta regression models: A proxy to inform marine protected areas in the Mediterranean Sea.

Seabirds are bioindicators of marine ecosystems health and one of the world's most endangered avian groups. The creation of marine protected areas plays an important role in the conservation of marine environment and its biodiversity. The distributions of top predators, as seabirds, have been commonly used for the management and creation of these figures of protection. The main objective of this study is to investigate seabirds biodiversity distribution in the Mediterranean Sea through the use of Bayesian spatial Beta regression models. We used an extensive historical database of at-sea locations of 19 different seabird species as well as geophysical, climatology variables and cumulative anthropogenic threats to model species biodiversity. We found negative associations between seabirds biodiversity and distance to the coast as well as concavity of the seabed, and positive with chlorophyll and slope. Further, a positive association was found between seabirds biodiversity and coastal impact. In this study we define as hot spot of seabird biodiversity those areas with a posterior predictive mean over 0.50. We found potential hot spots in the Mediterranean Sea which do not overlap with the existing MPASs and marine IBAs. Specifically, our hot spots areas do not overlap with the 52.04% and 16.87% of the current MPAs and marine IBAs, respectively. Overall, our study highlights the need for the extension of spatial prioritization of conservation areas to seabirds biodiversity, addressing the challenges of establishing transboundary governance.

Association between phenols and thyroid hormones: The role of iodothyronine deiodinase genes.

Previous literature on prenatal phenol exposure and thyroid hormone (TH) alteration is conflicting, and the possible mechanisms of action involved remain unclear. We aimed to examine the association between prenatal phenol exposure and levels of maternal and neonatal THs, as well as the possible role of iodothyronine deiodinase (DIO) gene polymorphisms in this relation. We studied 387 Spanish mother-neonate pairs with measurements of maternal phenols, total triiodothyronine (TT3) and free thyroxine (FT4), maternal and neonatal thyroid-stimulating hormone (TSH), and maternal genotypes for single nucleotide polymorphisms in the DIO1(rs2235544) and DIO2(rs12885300) genes. We implemented multivariate linear and weighted quantile sum (WQS) regressions to examine the association between phenols and THs (including sex-stratified models for neonatal TSH) and investigated effect modification of genotypes in the maternal phenol-TH associations. In single exposure models, we found negative associations between maternal triclosan (TCS) and neonatal TSH (% change [95%CI]: -2.95 [-5.70, -0.11], per twofold phenol increase) - stronger for girls - and less clearly for maternal ethylparaben (EPB) and TSH (-2.27 [-4.55, 0.07]). In phenol mixture models, we found no association with THs. In the genetic interaction models, we found some evidence of effect modification of DIO gene polymorphisms with stronger negative associations between methylparaben (MPB), propylparaben (PPB), butylparaben (BPB) and TT3 as well as bisphenol A (BPA) and FT4 for DIO1(rs2235544)-CC. Stronger inverse associations for genotypes DIO2(rs12885300)-CC and DIO2(rs12885300)-CT and positive ones for DIO2(rs12885300)-TT were also reported for BPA and FT4. In conclusion, we found some evidence of an association between phenols and TSH during pregnancy and at birth in single exposure models, the latter being stronger for girls. Since no association was observed between maternal levels of phenols and TT3 or FT4, the possible role of the genetic background in these associations warrants further investigation.

Green gentrification in European and North American cities.

Although urban greening is universally recognized as an essential part of sustainable and climate-responsive cities, a growing literature on green gentrification argues that new green infrastructure, and greenspace in particular, can contribute to gentrification, thus creating social and racial inequalities in access to the benefits of greenspace and further environmental and climate injustice. In response to limited quantitative evidence documenting the temporal relationship between new greenspaces and gentrification across entire cities, let alone across various international contexts, we employ a spatially weighted Bayesian model to test the green gentrification hypothesis across 28 cities in 9 countries in North America and Europe. Here we show a strong positive and relevant relationship for at least one decade between greening in the 1990s-2000s and gentrification that occurred between 2000-2016 in 17 of the 28 cities. Our results also determine whether greening plays a "lead", "integrated", or "subsidiary" role in explaining gentrification.

Pre and postnatal exposure to mercury and sexual development in 9-year-old children in Spain: The role of brain-derived neurotrophic factor.

Early exposure to mercury has been related to endocrine disruption. Steroid hormones play a crucial role in neural cell migration, differentiation, etc., as well as protecting against several neurotoxic compounds. We investigate the relation between mercury exposure and children's sexual development, and we evaluate the possible influence of different brain-derived neurotrophic factor (BDNF) polymorphisms on this association. Our study sample comprised 412 9-year-old children participating in the INMA cohort (2004-2015). Mercury concentrations were measured at birth (cord blood) and at 4 and 9 years of age (hair). Sexual development was assessed by levels of sex steroid hormones (estradiol and testosterone) in saliva and the Tanner stages of sex development at 9 years (categorized as 1: prepuberty and >1: pubertal onset). Covariates and confounders were collected through questionnaires during pregnancy and childhood. Polymorphisms in the BDNF gene were genotyped in cord blood DNA. Multivariate linear regression analyses were performed between mercury levels and children's sexual development by sex. Effect modification by genetic polymorphisms and fish intake was assessed. We found marginally significant inverse associations between postnatal exposure to mercury (at 9 years) and testosterone levels (ß[95%CI] = -0.16[-0.33,0.001], and -0.20[-0.42,0.03], for boys and girls, respectively). Additionally, we found that prenatal mercury was negatively associated with Tanner stage >1 in boys. Finally, we found significant genetic interactions for some single nucleotide polymorphisms in the BDNF gene. In conclusion, pre and postnatal exposure to mercury seems to affect children's sexual development and BDNF may play a role in this association, but further research would be needed.

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

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 arsenobetaine were measured in the first trimester of pregnancy. Methylation efficiency was determined through the percentages of the metabolites and using principal component analysis. Children's neuropsychological development was assessed at the age of 4-5 years using the McCarthy Scales of Children's Abilities (MSCA). Multivariable linear regression models were built to assess the association between TAs, the As species and the maternal methylation efficiency, and the neuropsychological scores. We explored effect modification by sex, iron status, maternal nutrients status (serum manganese and selenium, and urinary zinc), and maternal vitamins intake (folate, and vitamins B12 and B6). RESULTS: The geometric mean (95%CI) of ∑As (sum of DMA, MMA and iAs) was 7.78 (7.41, 8.17) µg/g creatinine. MMA concentrations were inversely associated with the scores for the general, verbal, quantitative, memory, executive function and working memory scales (i.e. ß [CI95%] = -1.37 [-2.33, -0.41] for the general scale). An inverse association between %MMA and the memory scores was found. Children whose mothers had lower manganese, zinc and ferritin concentrations obtained lower scores on several MSCA scales with decreasing As methylation efficiency. DISCUSSION: An inverse association was observed between MMA concentrations and children's neuropsychological development. Maternal levels of manganese, zinc and ferritin affected the association between As methylation efficiency and MSCA scores.

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 free thyroxine (FT4), and we genotyped for single-nucleotide polymorphisms in the DIO1 (rs2235544) and DIO2 (rs12885300) genes. We performed multivariate regression analyses between PFASs and THs and included the interaction term PFAS-genotypes in the models. PFHxS was associated with an increase in TSH (% change in outcome [95% CI] per 2-fold PFAS increase = 6.09 [-0.71, 13.4]), and PFOA and PFNA were associated with a decrease in TT3 (-7.17 [-13.5, -0.39] and -6.28 [-12.3, 0.12], respectively). We found stronger associations between PFOA, PFNA, and TT3 for DIO1-CC and DIO2-CT genotypes, although interaction p-values were not significant. In conclusion, this study found evidence of an inverse association between PFOA and TT3 levels. No clear effect modification by DIO enzyme genes was observed.

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 efficiency 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 (2003-2008). 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. Sociodemographic 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 µg/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., ß [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.