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.

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.

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.

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.

[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.

Sistema de ayuda a la toma de decisiones sanitarias. propuesta de umbrales de riesgo epidemiológico ante SARS-CoV-2 / A proposed epidemiologic risk threshold for SARS-CoV-2 for assisting healthcare decision-making

INTRODUCCIÓN: La pandemia por SARS-CoV-2 es el mayor desafío sanitario en los últimos 100 años, ocasionando el mayor exceso de mortalidad no bélico en este período en el mundo occidental. Ante una enfermedad de elevada contagiosidad y asintomática en un tercio de los casos, es fundamental disponer de modelos que predigan su evolución. Pretendemos desarrollar un modelo de predicción de infección por COVID19 en provincias españolas. MÉTODO: Análisis de componentes principales funcional a datos epidemiológicos de las provincias españolas en función de su curva epidémica entre el 24 de febrero y el 8 de junio. Con este método se han clasificado las provincias en función de su evolución (peor, intermedia y mejor). Se han empleado los datos del Centro Nacional de Epidemiología. RESULTADOS: Se identificaron dos componentes que explican el 99% de la variabilidad de las 52 curvas. La primera componente es la tendencia global de la tasa de incidencia, y la segunda componente es la velocidad de crecimiento o decrecimiento de la incidencia durante el período. Se identificaron 10 provincias en el grupo de peor evolución y 17 en el de evolución intermedia. Los valores umbrales de la tasa de incidencia a 7 días fueron 134 casos/100.000 habitantes para un nivel de alerta 1 (medio) y 167 para el nivel 2 (alto), consiguiendo un elevado poder de discriminación entre provincias. CONCLUSIONES: Estos niveles de alerta podrían ser de utilidad para decidir medidas que puedan afectar a la movilidad de la población, siempre y cuando haya una situación de transmisión comunitaria de SARS-CoV-2. Esta información sería intercomparable entre áreas sanitarias o CCAA

INTRODUCTION: The SARS-CoV-2 pandemic is the most important health challenge encountered 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 two 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.

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.

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.

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.

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.

Organochlorine Compounds and Ultrasound Measurements of Fetal Growth in the INMA Cohort (Spain).

BACKGROUND: Several studies have reported decreases in birth size associated with exposure to organochlorine compounds (OCs), but uncertainties remain regarding the critical windows of prenatal exposure and the effects on fetal body segments. OBJECTIVE: We examined the relationship between prenatal OC concentrations and fetal anthropometry. METHODS: We measured 4,4´-dichlorodiphenyldichloroethylene (4,4´-DDE), hexachlorobenzene (HCB), and polychlorinated biphenyl (PCB) congeners (138, 153, and 180) in 2,369 maternal and 1,140 cord serum samples in four Spanish cohorts (2003-2008). We used linear mixed models to obtain longitudinal growth curves for estimated fetal weight (EFW), abdominal circumference (AC), biparietal diameter (BPD), and femur length (FL) adjusted by parental and fetal characteristics. We calculated standard deviation (SD) scores of growth at 0-12, 12-20, and 20-34 weeks of gestation as well as size at gestational week 34 for the four parameters. We studied the association between OCs and the fetal outcomes by cohort-specific linear models and subsequent meta-analyses. RESULTS: PCBs were associated with a reduction in AC up to mid-pregnancy, and BPD and FL from gestational week 20 onward. An inverse association was also found between HCB and AC growth in early pregnancy. The reduction of these parameters ranged from -4% to -2% for a doubling in the OC concentrations. No association between 4,4´-DDE and fetal growth was observed. CONCLUSIONS: To our knowledge, this is the first study to report an association between prenatal exposure to some PCBs and HCB and fetal growth: AC during the first two trimesters of pregnancy, and BPD and FL later in pregnancy. CITATION: Lopez-Espinosa MJ, Murcia M, Iñiguez C, Vizcaino E, Costa O, Fernández-Somoano A, Basterrechea M, Lertxundi A, Guxens M, Gascon M, Goñi-Irigoyen F, Grimalt JO, Tardón A, Ballester F. 2016. Organochlorine compounds and ultrasound measurements of fetal growth in the INMA cohort (Spain). Environ Health Perspect 124:157-163; http://dx.doi.org/10.1289/ehp.1408907.

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.

Gestational weight gain and exposure of newborns to persistent organic pollutants.

BACKGROUND: Exposure to persistent organic pollutants (POPs) during fetal development can increase the risk of adverse health effects during childhood. Maternal characteristics and physiological changes during gestation, such as gestational weight gain (GWG), may have an influence in the overall burden of POPs in neonates. However, the associations between GWG and POP concentrations are still not well established. OBJECTIVE: We examined the association of GWG with cord serum POPs concentrations after adjusting for prepregnancy maternal body mass index (BMI) and other potential determinants of the transfer of POPs into newborns. The GWG values were evaluated after grouping by the reference guidelines of the Institute of Medicine (IOM). METHODS: We measured levels of 14 organochlorine pesticides, 7 polychlorobiphenyls (PCBs), and 14 polybrominated diphenyl ethers (PBDEs) in 325 cord serum samples from a Spanish birth cohort. Multivariable models were used to estimate associations of GWG, prepregnancy BMI, and other maternal determinants on cord serum concentrations of POPs. RESULTS: Neonatal concentrations of POPs were inversely associated with GWG after adjustment for age, prepregnancy BMI, educational level, and fish consumption. On average, neonates of women with IOM-recommended GWG have lower POP concentrations than do neonates of mothers with inadequate GWG. CONCLUSIONS: The present findings suggest an association between neonatal exposure to POPs and inadequate GWG during pregnancy. Encouraging pregnant women to meet the recommended IOM guidelines for GWG may reduce the accumulation of POPs in newborns.

Transport of persistent organic pollutants across the human placenta.

Prenatal life is the most sensitive stage of human development to environmental pollutants. Early exposure to persistent organic pollutants (POPs) may increase the risk of adverse health effects during childhood. The mechanisms of transference of POPs during pregnancy are still not well understood. The present study is aimed to investigate the transfer of POPs between mother and fetus. The concentrations of 14 organochlorine pesticides, 7 polychlorinated biphenyls (PCBs) and 14 polybromodiphenyl ether (PBDEs) congeners have been measured in 308 maternal serum samples, their respective umbilical cords and 50 placental tissues from a mother-infant cohort representative of Spanish general population. In general, the adjusted lipid-basis concentrations were higher in maternal serum than in cord serum and placenta. The concentrations of most pollutants between maternal serum and cord serum and between maternal serum and placenta were significantly correlated. These distributions were consistent with a predominant maternal source that transfers the pollutants into the placenta and the fetus. However, this distribution did not correspond to passive diffusion of these compounds between these tissues according to lipid content. The compounds more readily metabolized were higher in newborns, which suggest that differences in metabolic capabilities may be responsible of the observed variations in POP distributions between mother and newborns. Prenatal exposure to 4,4'-DDT and some PBDEs such as BDE 99 and BDE 209 is much higher than it could be anticipated from the composition of maternal serum. POP exposure assessment studies of newborns may overlook the effects of some of these pollutants if they only consider maternal determinations.

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 growth (N = 1285) and overweight (N = 1198). RESULTS: The analysis population included 24% rapid growers and 30% overweight infants. DDE and HCB were positively associated with rapid growth and with overweight. There was some indication that infant sex and exclusive breastfeeding duration may modify the effects of DDE, and that maternal prepregnancy BMI status may influence the effects of HCB. PCBs were not related to postnatal growth. CONCLUSION: Prenatal exposure to DDE and HCB may be associated with early postnatal growth. Further research is needed to evaluate the persistence of these associations at older ages.

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 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 (ß=-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.

Associations between blood persistent organic pollutants and 25-hydroxyvitamin D3 in pregnancy.

Persistent organic pollutants (POPs) are suggested to contribute to lower vitamin D levels; however, studies in humans are scarce and have never focused on pregnancy, a susceptibility period for vitamin D deficiency. We investigated whether serum levels of POPs were associated with circulating 25-hydroxyvitamin D3 [25(OH)D3] concentration in pregnancy. Cross-sectional associations of serum concentrations of eight POPs with plasma 25(OH)D3 concentration were analyzed in 2031 pregnant women participating in the Spanish population-based cohort INfancia y Medio Ambiente (INMA) Project. Serum concentrations of POPs were measured by gas chromatography and plasma 25(OH)D3 concentration was measured by high-performance liquid chromatography in pregnancy (mean 13.3±1.5weeks of gestation). Multivariable regression models were performed to assess the relationship between blood concentrations of POPs and 25(OH)D3. An inverse linear relationship was found between serum concentration of PCB180 and circulating 25(OH)D3. Multivariate linear regression models showed higher PCB180 levels to be associated with lower 25(OH)D3 concentration: quartile Q4 vs. quartile Q1, coefficient=-1.59, 95% CI -3.27, 0.08, p trend=0.060. A non-monotonic inverse relationship was found between the sum of predominant PCB congeners (PCB 180, 153 and 138) and 25(OH)D3 concentration: coefficient (95% CI) for quartile Q2 vs. Q1 [-0.50 (-1.94, 0.94)], quartile Q3 vs. Q1 [-1.56 (-3.11, -0.02)] and quartile Q4 vs. Q1 [-1.21 (-2.80, 0.38)], p trend=0.081. No significant associations were found between circulating 25(OH)D3 and serum levels of p,p'-DDE, p,p'-DDT, HCB, and ß-HCH. Our results suggest that the background exposure to PCBs may result in lower 25(OH)D3 concentration in pregnant women.