Impact of the use of small-area models on estimation of attributable mortality at a regional level.

The objective of this study is to assess the impact of applying prevalences derived from a small-area model at a regional level on smoking-attributable mortality (SAM). A prevalence-dependent method was used to estimate SAM. Prevalences of tobacco use were derived from a small-area model. SAM and population attributable fraction (PAF) estimates were compared against those calculated by pooling data from three national health surveys conducted in Spain (2011-2014-2017). We calculated the relative changes between the two estimates and assessed the width of the 95% CI of the PAF. Applying surveys-based prevalences, tobacco use was estimated to cause 53 825 (95% CI: 53 182-54 342) deaths in Spain in 2017, a figure 3.8% lower obtained with the small-area model prevalences. The lowest relative change was observed in the Castile-La Mancha region (1.1%) and the highest in Navarre (14.1%). The median relative change between regions was higher for women (26.1%), population aged ≥65 years (6.6%), and cardiometabolic diseases (9.0%). The differences between PAF by cause of death were never greater than 2%. Overall, the differences between estimates of SAM, PAF, and confidence interval width are small when using prevalences from both sources. Having these data available by region will allow decision-makers to implement smoking control measures based on more accurate data.

Serum concentrations of persistent organic pollutants mixture during pregnancy and anogenital distance in 8-year-old children from the INMA-Asturias cohort.

BACKGROUND: During pregnancy, women are commonly exposed to several endocrine-disrupting chemicals, including persistent organic pollutants (POPs). These compounds can transfer to the fetus through the placenta. Prenatal POP exposure is related to altered fetal genital and reproductive tract development. However, the relationship between exposure to POP mixtures and anogenital distance (AGD) is poorly investigated. This study investigated the association between prenatal exposure to POP mixtures and AGD in 8-year-old children. METHODS: Data were collected from the INMA-Asturias cohort. Maternal serum POP concentrations were measured during the first trimester of pregnancy. Anoscrotal distance (AGDAS) and anopenile distance (AGDAP) in males and anofourchetal distance (AGDAF) and anoclitoral distance (AGDAC) in females were recorded in 362 8-years-olds. Conventional linear regression, and the novel weighted quantile sum regression (WQSR) and Bayesian kernel machine regression (BKMR) models were applied to assess the relationships between AGD and POPs exposure stratified by sex. RESULTS: Among males, in the linear regression, b-hexachlorocyclohexane, PCB138, PCB153, and PCB180 were inversely associated with the anogenital index (AGI)AS (-0.06 mm/kg (95% confidence interval [CI]: -0.11, -0.02), -0.07 mm/kg (95% CI: -0.14, -0.01), -0.07 mm/kg (95% CI: -0.13, -0.01), and -0.08 mm/kg (95% CI: -0.14, -0.02), respectively). Among females, polybrominated diphenyl ether (PBDE)47 and PBDE154 were positively associated with increased AGIAF (0.02 mm/kg (95% CI: 0.00, 0.03) and 0.09 mm/kg (95% CI: 0.01, 0.17), respectively). BKMR confirmed these associations. WQSR found a negative combined effect of the POP mixture on AGD, and PCB138, PCB153, and PCB180 (weighted 0.18, 0.13, and 0.09, respectively) were identified as the most impacting chemicals. In females, WQSR found a positive combined effect and determined PBDE47 (weighted 0.35) as the most impacting. CONCLUSIONS: Maternal exposure to a POP mixture was negatively associated with AGD in male children and positively associated with AGD in female children, thus providing evidence of the adverse effects of POPs on genital development.

Dietary and Household Sources of Prenatal Exposure to Polybrominated Diphenyl Ethers (PBDEs) in the INMA Birth Cohort (Spain).

This study looked at predictors of exposure to polybrominated diphenyl ethers (PBDEs) with a focus on dietary and household-level factors. Concentrations of BDE-47, -99, -153, and -209 and their sum (∑PBDEs) were measured in cord serum. Spanish women (n = 541) completed two semiquantitative food frequency questionnaires during the first and third trimesters of pregnancy. The daily mean intake (grams) of eggs, dairy products, meat, cereals and pasta, vegetables and pulses, fruits, shellfish and cephalopods, and fish, and the weekly mean intake (servings) of lean, large oily, other oily, and other fish from both questionnaires were averaged. Information on house size, curtains and carpets at home, mattress type, housekeeping frequency, and television use was also collected later in gestation. Multivariate censored regression was used to assess the association between PBDE concentration (log2 transformed) and potential predictors. BDE-47, -99, -209 and ∑PBDE concentrations increased by 13.6%(95% CI:0.0, 29.0%), 21.1%(2.3, 43.5%), 21.7%(0.4, 47.5%) and 11.5%(2.2, 21.7%), respectively, per interquartile range increment in daily intake of shellfish and cephalopods. Fish intake was associated with BDE-99 (20.8%[1.7, 43.4%]). When fish was disaggregated by types, BDE-99 and ∑PBDEs increased by 13.8%(4.0, 24.7%) and 5.7%(0.8, 10.8%), respectively, per 1-serving/week increment in large oily fish intake. BDE-153 was associated with higher housekeeping frequency (35.9%[0.4, 83.9%]) and BDE-209 with foam mattress use (48.9%[5.8, 109.7%]). In conclusion, seafood consumption, higher housekeeping frequency, and foam mattress were associated with prenatal PBDE exposure.

A global call for action to include gender in research impact assessment.

Global investment in biomedical research has grown significantly over the last decades, reaching approximately a quarter of a trillion US dollars in 2010. However, not all of this investment is distributed evenly by gender. It follows, arguably, that scarce research resources may not be optimally invested (by either not supporting the best science or by failing to investigate topics that benefit women and men equitably). Women across the world tend to be significantly underrepresented in research both as researchers and research participants, receive less research funding, and appear less frequently than men as authors on research publications. There is also some evidence that women are relatively disadvantaged as the beneficiaries of research, in terms of its health, societal and economic impacts. Historical gender biases may have created a path dependency that means that the research system and the impacts of research are biased towards male researchers and male beneficiaries, making it inherently difficult (though not impossible) to eliminate gender bias. In this commentary, we - a group of scholars and practitioners from Africa, America, Asia and Europe - argue that gender-sensitive research impact assessment could become a force for good in moving science policy and practice towards gender equity. Research impact assessment is the multidisciplinary field of scientific inquiry that examines the research process to maximise scientific, societal and economic returns on investment in research. It encompasses many theoretical and methodological approaches that can be used to investigate gender bias and recommend actions for change to maximise research impact. We offer a set of recommendations to research funders, research institutions and research evaluators who conduct impact assessment on how to include and strengthen analysis of gender equity in research impact assessment and issue a global call for action.

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 conducted multivariate linear regression analyses between PBDE congeners and their sum (ΣPBDEs) and outcomes. We found statistically significant inverse associations between ΣPBDEs and AC, EFW, and BPD at weeks 20-34 and HC at birth. Regarding congeners, the association was clearer with BDE-99, with inverse associations being found with AC, EFW, and BPD at weeks 20-34, and with BW and HC at delivery. These outcomes decreased between 1.3% and 3.5% for each 2-fold PBDE increase. Concerning matrices, we found statistically significant inverse associations with BPD, HC, and BW when using maternal serum, and for AC and EFW with cord serum. In conclusion, PBDEs may impair fetal growth in late pregnancy and reduce birth size.

Time Dependence Between Tobacco Consumption and Lung Cancer Mortality in Spain.

OBJECTIVES: Lung cancer is the leading cause of cancer death and the second most common cancer in both sexes worldwide, with tobacco being its main risk factor. The aim of this study is to establish the temporal relationship between smoking prevalence and lung cancer mortality in Spain. METHODS: To model the time dependence between smoking prevalence and lung cancer mortality, a distributed lag non-linear model was applied adjusting for sex, age, year of mortality and population at risk. Smoking prevalence data from 1991-2020 were used. Considering a maximum lag of 25 years, mortality data from 2016-2020 were included. The effect of prevalence on mortality for each lag is presented in terms of relative risk (RR). To identify the lag at which smoking prevalence has the greatest effect on mortality, the RR of the different lags were compared. RESULTS: The optimal lag observed between smoking prevalence and lung cancer mortality in Spain was 15 years. The maximum RR was 2.9 (95%CI: 2.0-4.3) for a prevalence of 71% and a 15-year lag. The RR was 1.8 for a prevalence of 33%, an approximate median value between 1991-2020, and a 15-year lag. CONCLUSIONS: In Spain, lung cancer mortality is affected by smoking prevalence 15 years prior. Knowing the evolution of the smoking prevalence series in a country and establishing a lag time is essential to predict how lung cancer incidence and mortality will evolve.

Small-area models to assess the geographical distribution of tobacco consumption by sex and age in Spain.

INTRODUCTION: Complete and accurate data on smoking prevalence at a local level would enable health authorities to plan context-dependent smoking interventions. However, national health surveys do not generally provide direct estimates of smoking prevalence by sex and age groups at the subnational level. This study uses a small-area model-based methodology to obtain precise estimations of smoking prevalence by sex, age group and region, from a population-based survey. METHODS: The areas targeted for analysis consisted of 180 groups based on a combination of sex, age group (15-34, 35-54, 55-64, 65-74, and ≥75 years), and Autonomous Region. Data on tobacco use came from the 2017 Spanish National Health Survey (2017 SNHS). In each of the 180 groups, we estimated the prevalence of smokers (S), ex-smokers (ExS) and never smokers (NS), as well as their coefficients of variation (CV), using a weighted ratio estimator (direct estimator) and a multinomial logistic model with random area effects. RESULTS: When smoking prevalence was estimated using the small-area model, the precision of direct estimates improved; the CV of S and ExS decreased on average by 26%, and those of NS by 25%. The range of S prevalence was 11-46% in men and 4-37% in women, excluding the group aged ≥75 years. CONCLUSIONS: This study proposes a methodology for obtaining reliable estimates of smoking prevalence in groups or areas not covered in the survey design. The model applied is a good alternative for enhancing the precision of estimates at a detailed level, at a much lower cost than that involved in conducting large-scale surveys. This method could be easily integrated into routine data processing of population health surveys. Having such estimates directly after completing a health survey would help characterize the tobacco epidemic and/or any other risk factor more precisely.

Validation of a small-area model for estimation of smoking prevalence at a subnational level.

INTRODUCTION: Small-area estimation methods are an alternative to direct survey-based estimates in cases where a survey's sample size does not suffice to ensure representativeness. Nevertheless, the information yielded by small-area estimation methods must be validated. The objective of this study was thus to validate a small-area model. METHODS: The prevalence of smokers, ex-smokers, and never smokers by sex and age group (15-34, 35-54, 55-64, 65-74, ≥75 years) was calculated in two Spanish Autonomous Regions (ARs) by applying a weighted ratio estimator (direct estimator) to data from representative surveys. These estimates were compared against those obtained with a small-area model applied to another survey, specifically the Spanish National Health Survey, which did not guarantee representativeness for these two ARs by sex and age. To evaluate the concordance of the estimates, we calculated the intraclass correlation coefficient (ICC) and the 95% confidence intervals of the differences between estimates. To assess the precision of the estimates, the coefficients of variation were obtained. RESULTS: In all cases, the ICC was ≥0.87, indicating good concordance between the direct and small-area model estimates. Slightly more than eight in ten 95% confidence intervals for the differences between estimates included zero. In all cases, the coefficient of variation of the small-area model was <30%, indicating a good degree of precision in the estimates. CONCLUSIONS: The small-area model applied to national survey data yields valid estimates of smoking prevalence by sex and age group at the AR level. These models could thus be applied to a single year's data from a national survey, which does not guarantee regional representativeness, to characterize various risk factors in a population at a subnational level.

Pre-natal exposure to dichlorodiphenyldichloroethylene and infant lower respiratory tract infections and wheeze.

The aim of our study was to examine whether pre-natal exposure to dichlorodiphenyldichloroethylene (DDE) increases the risk of lower respiratory tract infections (LRTIs) and wheeze in infants. The study is based on a birth cohort of 1,455 mother-child pairs. Maternal serum concentrations of DDE, polychlorinated biphenyls (PCBs) and hexachlorobenzene (HCB) were measured during pregnancy. Parental reports on LRTI and wheeze were obtained when children were 12-14 months old. 35.4% of children developed at least one LRTI episode and 33.6% at least one wheezing episode during their first 12-14 months of life. Median DDE, PCBs and HCB concentrations were 116.3, 113.7 and 46.4 ng · g(-1) lipid, respectively. DDE concentrations were associated with LRTI risk (relative risk (RR) per 10% increase 1.11, 95% CI 1.00-1.22), also after adjustment for PCBs and HCB. In all quartiles of DDE exposure, the risk of LRTI was increased compared with the lowest quartile, but the increase was statistically significant only in the third quartile (RR 1.33, 95% CI 1.08-1.62). No association was observed for PCBs and HCB. Results were similar for wheeze. This study suggests that pre-natal DDE exposure is associated with a higher risk of LRTI and wheeze in infants independently of exposure to other organochlorine compounds.

Small area estimation of expenditure means and ratios under a unit-level bivariate linear mixed model.

Under a unit-level bivariate linear mixed model, this paper introduces small area predictors of expenditure means and ratios, and derives approximations and estimators of the corresponding mean squared errors. For the considered model, the REML estimation method is implemented. Several simulation experiments, designed to analyze the behavior of the introduced fitting algorithm, predictors and mean squared error estimators, are carried out. An application to real data from the Spanish household budget survey illustrates the behavior of the proposed statistical methodology. The target is the estimation of means of food and non-food household annual expenditures and of ratios of food household expenditures by Spanish provinces.

Assessment of prenatal exposure to persistent organohalogen compounds from cord blood serum analysis in two Mediterranean populations (Valencia and Menorca).

Prenatal levels of organohalogen compounds (OHCs), including polybromodiphenyl ethers (PBDEs), polychlorobiphenyls (PCBs), hexachlorobenzene (HCB), hexachlorocyclohexanes and DDTs, have been investigated in two different cohorts from the Spanish Mediterranean area, Valencia and Menorca, by analysis of cord blood serum. Comparison of the observed median concentrations to other cohorts shows low PBDE levels (2.8-6.5 ng g(-1) lipid) but high values of HCB (0.68 ng ml(-1), 260 ng g(-1) lipid) and PCBs (0.65 ng ml(-1), 240 ng g(-1) lipid) in the cohort of Menorca indicating that Mediterranean areas, and not only high latitude regions, may contain population groups highly exposed to some of these pollutants. Significant differences in the concentrations of these compounds have been found between the two cohorts. Differences in maternal population such as age or body mass index cannot explain this variation. One possible cause of variability is the seven year time period elapsed between the two cohort recruitments but the strong differences observed do not allow exclusion of local diet differences. Thus, the different average PCB congener distributions between the two cohorts suggest an influence from materials containing diverse PCB mixtures. The congener mixtures found in Menorca could reflect a diet contribution from some western Mediterranean fish species. These results provide baseline information on prenatal OHC background levels in the Mediterranean area.

[A Proposed Epidemiologic Risk Threshold for SARS-CoV-2 for Assisting Healthcare Decision-Making]. / Sistema de ayuda a la toma de decisiones sanitarias. Propuesta de umbrales de riesgo epidemiológico ante SARS-CoV-2.

INTRODUCTION: The SARS-CoV-2 pandemic is the most important health challenge observed in 100 years, and since its emergence has generated the highest excess of non-war-related deaths in the western world. Since this disease is highly contagious and 33% of cases are asymptomatic, it is crucial to develop methods to predict its course. We developed a predictive model for Covid-19 infection in Spanish provinces. METHODS: We applied main components analysis to epidemiological data for Spanish provinces obtained from the National Centre of Epidemiology, based on the epidemiological curve between 24 February and 8 June 2020. Using this method, we classified provinces according to their epidemiological progress (worst, intermediate, and good). RESULTS: We identified 2 components that explained 99% of variability in the 52 epidemiological curves. The first component can be interpreted as the crude incidence rate trend and the second component as the speed of increase or decrease in the incidence rate during the period analysed. We identified 10 provinces in the group with the worst progress and 17 in the intermediate group. The threshold values for the 7-day incidence rate for an alert 1 (intermediate) were 134 cases/100,000 inhabitants, and 167 for alert 2 (high), respectively, showing a high discriminative power between provinces. CONCLUSIONS: These alert levels might be useful for deciding which measures may affect population mobility and other public health decisions when considering community transmission of SARS-CoV-2 in a given geographical area. This information would also facilitate intercomparison between healthcare areas and Autonomous Communities.

COVID-19 Variability Within European Countries Sourced From ECDC Data. Is Variability Explained by Specific Country Policies?

Background: Europe has had a large variability in COVID-19 incidence between and within countries, particularly after June 2020. We aim to assess the variability between European countries and regions located in a given country. Methods: We used ECDC information including countries having 7 regions or more. The metric used to assess the regional variability within a country was the intercuartilic range in a weekly basis for 32 weeks between June 29th 2020 and February 1st 2021. We also calculated each country's overall variability across the 32 weeks using the distances from the regional curves of the 14-day incidence rates to the corresponding national curve, using the L2 metric for functional data. We afterwards standardised this metric to a scale from 0 to 100 points. We repeated the calculations excluding island regions. Results: The variability between and within countries was large. Slovenia, Spain and Portugal have the greatest variability. Spain and Slovenia held also the top three places for the greatest number of weeks (Spain for 19 weeks and Slovenia for 10) with the highest variability. For variability among the incidence curves across the 32-week period, Slovenia, Portugal and Spain ranked first in functional variability, when all the regions were analysed but also when the island regions were excluded. Conclusions: These differences might be due to how countries tackled the epidemiological situation. The persistent variability in COVID-19 incidence between regions of a given country suggests that governmental action may have an important role in applying epidemiological control measures.

Maternal origin and other determinants of cord serum organochlorine compound concentrations in infants from the general population.

Organochlorine compounds (OCs), including pesticides and polychlorobiphenyls (PCBs), were determined in the serum of 499 cord blood samples from infants born during 2004-2006 in Valencia (Spain). The concentrations were found to be correlated with the region of origin of the mothers. Those from Latin-America gave birth to infants with higher 4,4'-DDE and 4,4'-DDT concentrations than those from Europe. On the contrary, European mothers had children with higher concentrations of hexachlorobenzene and PCBs than Latin-American mothers. These associations were independent of maternal period of stage in Valencia. Data examination with a multivariate model including maternal region of origin described 39-44% of the concentration variability of 4,4'-DDE and total PCBs with statistic significance. Other maternal variables found to significantly influence OC burden in newborns were age, education level, and body mass index (BMI). In general, older women, with higher education standards and higher BMI had infants with higher OC serum concentrations than younger women, with lower education scores and low BMI. The increase of 4,4'-DDT in newborns from mothers with high education levels and high BMI suggest that dissimilar maternal diets may be at the origin of some of these OC body burden differences.

Integrated analysis of halogenated organic pollutants in sub-millilitre volumes of venous and umbilical cord blood sera.

A rapid, robust and economical method for the analysis of persistent halogenated organic compounds in small volumes of human serum and umbilical cord blood is described. The pollutants studied cover a broad range of molecules of contemporary epidemiological and legislative concern, including polychlorobiphenyls (PCBs), polychlorobenzenes (CBs), hexachlorocyclohexanes (HCHs), DDTs, polychlorostyrenes (PCSs) and polybromodiphenyl ethers (PBDEs). Extraction and clean-up with n-hexane and concentrated sulphuric acid was followed with analysis by gas chromatography coupled to electron capture (GC-ECD) and GC coupled to negative ion chemical ionisation mass spectrometry (GC-NICI-MS). The advantages of this method rest in the broad range of analytes and its simplicity and robustness, while the use of concentrated sulphuric acid extraction/clean-up destroys viruses that may be present in the samples. Small volumes of reference serum between 50 and 1000 microL were extracted and the limits of detection/quantification and repeatability were determined. Recoveries of spiked compounds for the extraction of small volumes (> or = 300 microL) of the spiked reference serum were between 90% and 120%. The coefficients of variation of repeatability ranged from 0.1-14%, depending on the compound. Samples of 4-year-old serum and umbilical cord blood (n = 73 and 40, respectively) from a population inhabiting a village near a chloro-alkali plant were screened for the above-mentioned halogenated pollutants using this method and the results are briefly described.

Association between pre/perinatal exposure to POPs and children's anogenital distance at age 4 years: A study from the INMA-Asturias cohort.

BACKGROUND: Prenatal exposure to endocrine-disrupting chemicals may impair genital development and alter reproductive tract anatomy. Anogenital distance (AGD) is a useful biomarker of exposure to chemicals that act as endocrine disruptors. We evaluated associations between prenatal and perinatal exposure to several persistent organic pollutants (POPs) and AGD in 4-year-old children. METHODS: Data were drawn from the INMA-Asturias cohort. Pediatricians measured the anofourchetal distance in female children and anoscrotal distance in male children. The anogenital index (AGI) was defined as the AGD divided by the child's weight at age of examination. We measured the levels of two hexachlorocyclohexane isomers, hexachlorobenzene, dichlorodiphenyltrichloroethane (DDT) and its metabolites, six polychlorinated biphenyl (PCB) congeners, and six polybrominated diphenyl ether (PBDE) congeners in maternal serum at 12 gestational weeks (n = 155) and in cord blood serum (n = 229). Anthropometric and parental sociodemographic variables were collected via face-to-face interviews. Linear regression models were used to evaluate the relationship between exposure to POPs and AGI, adjusted for confounders and stratified by sex. RESULTS: In male children, we found inverse associations between AGI and maternal concentrations of PCB-138 (ß = -0.041, 95% confidence interval [CI]: -0.074, -0.008, second tertile), PCB-153 (ß = -0.052, 95% CI: -0.085, -0.020, second tertile), PCB-180 ß = -0.065, 95% CI: -0.096, -0.035, second tertile; ß = -0.042, 95% CI: -0.073, -0.011, third tertile), PBDE-209 (ß = -0.031, 95% CI: -0.058, -0.006), cord serum concentrations of PCB-153 (ß = -0.029, 95% CI: -0.059, -0.000, second tertile; ß = -0.047, 95% CI: -0.085, -0.008, third tertile), and PCB-180 (ß = -0.041, 95% CI: -0.078, -0.005, third tertile). In female children, AGI was positively associated with maternal serum concentrations of PCB-101 (ß = 0.039, 95% CI: 0.002, 0.076, second tertile), and higher cord serum levels of 4,4'-DDT (ß = 0.032, 95% CI: 0.003, 0.061, third tertile) and 4,4'-DDE (ß = 0.040, 95% CI: 0.011, 0.069, third tertile). CONCLUSIONS: Our findings provide evidence of associations between specific POPs and AGI in boys and girls aged 4 years, and suggest that pre/perinatal exposure to POPs has a feminizing effect in males and a masculinizing effect in females.

Association between thyroid hormone levels and 4,4'-DDE concentrations in pregnant women (Valencia, Spain).

INTRODUCTION: Several epidemiological studies have reported that some organochlorine compounds (OCs), such as polychlorobiphenyls (PCBs) and 1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene (4,4'-DDE), may alter thyroid function. OBJECTIVE: The aim of the present study was to investigate the association of maternal serum OC concentrations of 4,4'-DDE and the sum of seven PCB congeners (PCB 28, 52, 101, 118, 138, 153, and 180) with thyroid hormone (TH) status. METHODS: We measured OC concentrations in 157 maternal serum samples at 12 weeks of pregnancy in a cohort from Valencia (Spain). Thyroid-stimulating hormone (TSH), total triiodothyronine (TT3), and free thyroxine (FT4) were measured as biomarkers of thyroid function in the same samples. Linear and logistic regression analyses were performed between OCs and TH levels, and variables were log transformed. RESULTS: Mothers with higher levels of 4,4'-DDE had higher odds of having TSH levels >2.5 mIU/L (OR=2.53; 95% CI=1.36; 4.73; p=0.004), and we found a significant negative association between serum 4,4'-DDE concentrations and FT4 levels (beta=-0.03; 95% CI=-0.05; 0.00; p=0.050) after adjustment for covariates and total lipids. No association was found between sum of PCBs and TH levels. CONCLUSION: Serum concentrations of 4,4'-DDE were associated with increased TSH and reduced FT4 but not TT3 levels. Our results suggest that some environmental chemicals may interfere with the thyroid system of pregnant women. The major role that maternal THs may play in fetal neurodevelopment makes these findings especially relevant.

Mother-child transfer rates of organohalogen compounds up to four years of age.

BACKGROUND: Breastfed children absorb persistent and toxic chemicals such as organohalogen compounds (OHCs) during the entire lactation period. Nursing is a main contributor to the burden of these pollutants in the first years of life, hence further assessments on the OHC load processes are needed. OBJECTIVES: To identify the determinants of OHC increase in children at four years of age, considering concentration gains, maternal venous concentrations and breastfeeding time. METHODS: Concentrations of 19 organochlorine compounds (OCs) and 14 polybrominated diphenyl ethers (PBDEs) were analyzed in maternal venous (n = 466), cord blood (n = 326) and children venous serum at four years of age (n = 272) in the Asturias INMA cohort representing the Spanish general population. Data were evaluated considering the socio-demographic and individual information collected at recruitment and follow up surveys, as well as the OHC physical-chemical constants. RESULTS: The four years-old children concentration gains of the most abundant OHCs showed strong correlations (R2 = 0.65-0.93) with the maternal concentrations during pregnancy and lactation period. The child gain/maternal transfer rates of most correlated pollutants were similar. DISCUSSION: Between 65 and 93% of the variance of OCs in four years-old children was explained by the maternal concentrations during pregnancy and the lactation period. The compounds with log(Kow) > 3.7 (hydrophobic) showed analogous child gain/maternal transfer rates indicating similar processes of membrane lipid dissolution and passive diffusion from the epithelial cells into the milk. Molecular weight of these pollutants did not influence on these rates. Compounds with low log(Koa) such as hexachlorobenzene are more volatile and less retained, involving lower child gain/maternal transfer rates. These results may be useful to anticipate the increase of the concentrations of OCs in children using the maternal concentration of these compounds during pregnancy and the planned lactation period and to implement prophylactic measures in mothers with high venous pollutant concentrations.

Prenatal Exposure to Persistent Organic Pollutants and Anogenital Distance in Children at 18 Months.

BACKGROUND: Anogenital distance (AGD) is a measure of in utero exposure to hormonally active agents. The aim of the present study was to evaluate the association between prenatal exposure to persistent organic pollutants (POPs) and AGD. METHODS: POP levels were measured in pregnant women, and the AGD was recorded in 43 offspring at 18 months. We used linear regression models to analyze the association between maternal POP exposure and offspring AGD. We defined the anogenital index (AGI) as AGD divided by weight at 18 months (AGI = AGD / weight at 18 months [mm/kg]) and included this variable in the regression models. RESULTS: AGI measure was 2.35 (0.61) and 1.38 (0.45) in males and females, respectively. AGI was inversely associated with lipid-adjusted concentrations of PBDE-99 (ß = -0.28, 95% confidence interval [CI]: -0.51, -0.04) and PBDE-153 (ß = -0.61, 95% CI: -1.11, -0.11) in males. We did not find any statistically significant relationship between any POPs and AGI in females. CONCLUSIONS: Environmental exposure to POPs may affect genital development and result in reproductive tract alterations with potentially relevant health consequences in maturity.

Assessment of metabolic phenotypic variability in children's urine using 1H NMR spectroscopy.

The application of metabolic phenotyping in clinical and epidemiological studies is limited by a poor understanding of inter-individual, intra-individual and temporal variability in metabolic phenotypes. Using 1H NMR spectroscopy we characterised short-term variability in urinary metabolites measured from 20 children aged 8-9 years old. Daily spot morning, night-time and pooled (50:50 morning and night-time) urine samples across six days (18 samples per child) were analysed, and 44 metabolites quantified. Intraclass correlation coefficients (ICC) and mixed effect models were applied to assess the reproducibility and biological variance of metabolic phenotypes. Excellent analytical reproducibility and precision was demonstrated for the 1H NMR spectroscopic platform (median CV 7.2%). Pooled samples captured the best inter-individual variability with an ICC of 0.40 (median). Trimethylamine, N-acetyl neuraminic acid, 3-hydroxyisobutyrate, 3-hydroxybutyrate/3-aminoisobutyrate, tyrosine, valine and 3-hydroxyisovalerate exhibited the highest stability with over 50% of variance specific to the child. The pooled sample was shown to capture the most inter-individual variance in the metabolic phenotype, which is of importance for molecular epidemiology study design. A substantial proportion of the variation in the urinary metabolome of children is specific to the individual, underlining the potential of such data to inform clinical and exposome studies conducted early in life.