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BACKGROUND: Newborns in neonatal intensive care units (NICUs) are in contact with a variety of medical products whose production might include synthetic chemicals with hormonal activity. OBJECTIVES: Our aim was to assess the content of bisphenol A (BPA) and parabens (PBs) and the hormone-like activities of a subset of medical products commonly used in NICUs in prolonged intimate contact with NICU newborns. METHODS: Fifty-two NICU items were analyzed, determining the concentrations of BPA and PBs [methyl- (MeP), ethyl- (EtP), propyl- (PrP), and butylparaben (BuP)] and using the E-Screen and PALM-luciferase assays to measure the in vitro (anti-)estrogenic and (anti-)androgenic activity, respectively, of the extracts. Items found to have elevated BPA/PB content or hormone-like activities were further extracted using leaching methodologies. RESULTS: BPA was found in three-fifths and PBs in four-fifths of tested NICU items, and ~25% and ~10% of extracts evidenced estrogenic and anti-androgenic activity, respectively. The highest BPA content was found in the three-way stopcock (>7.000 ng/g), followed by patterned transparent film dressing, gastro-duodenal feeding tubes, sterile gloves, single-lumen umbilical catheters, and intravenous (IV) infusion extension sets (concentrations ranged from 100 to 700 ng/g BPA). A total PB concentration (?PPBs) >100 ng/g was observed in several items, including light therapy protection glasses, patterned transparent film dressing, winged IV catheters, IV infusion extension sets, and textile tape. The highest estrogenic activity [>450 pM estradiol equivalent (E2eq)] was found in small dummy nipples, three-way stopcocks, and patterned transparent film dressing and the highest anti-androgenic activity [>5 mM procymidone equivalent units per gram (Proceq/g)] in small dummy nipples and three-way stopcocks. DISCUSSION: According to these findings, neonates might be exposed to multiple sources of BPA and PBs in NICUs via inhalation, dermal, oral, and IV/parenteral routes. There is a need to address the future health implications for these extremely vulnerable patients and to adopt precautionary preventive measures as a matter of urgency. [ABSTRACT FROM AUTHOR]

Aluminum (Al), antimony (Sb), and lithium (Li) are relatively common toxic metal(oid)s that can be transferred into breast milk and potentially to the nursing infant. This study assessed concentrations of Al, Sb, and Li in breast milk samples collected from donor mothers and explored the predictors of these concentrations. Two hundred forty-two pooled breast milk samples were collected at different times post-partum from 83 donors in Spain (2015–2018) and analyzed for Al, Sb, and Li concentrations. Mixed-effect linear regression was used to investigate the association of breast milk concentrations of these elements with the sociodemographic profile of the women, their dietary habits and utilization of personal care products (PCPs), the post-partum interval, and the nutritional characteristics of milk samples, among other factors. Al was detected in 94% of samples, with a median concentration of 57.63 μg/L. Sb and Li were detected in 72% and 79% of samples at median concentrations of 0.08 μg/L and 0.58 μg/L, respectively. Concentrations of Al, Sb, and Li were not associated with post-partum time. Al was positively associated with total lipid content of samples, weight change since before pregnancy, and coffee and butter intakes and inversely with meat intake. Li was positively associated with intake of chocolate and use of face cream and eyeliner and inversely with year of sample collection, egg, bread, and pasta intakes, and use of hand cream. Sb was positively associated with fatty fish, yoghurt, rice, and deep-fried food intakes and use of eyeliner and inversely with egg and cereal intakes and use of eyeshadow. This study shows that Al, Sb, and Li, especially Al, are widely present in donor breast milk samples. Their concentrations in the milk samples were most frequently associated with dietary habits but also with the lipid content of samples and the use of certain PCPs. [Display omitted] • Al, Sb, and Li were widely detected in donor milk samples. • Concentrations of Al were several times higher than those of Sb and Li. • Concentrations of Al, Sb, and Li were associated with dietary habits. • Use of certain personal care products was associated with higher Sb and Li. [ABSTRACT FROM AUTHOR]

BACKGROUND: Prenatal exposure to bisphenol A (BPA) and phthalates may affect fetal growth; however, previous findings are inconsistent and based on few studies. OBJECTIVES: We assessed whether prenatal exposure to BPA and phthalates was associated with fetal growth in a Spanish birth cohort of 488 mother-child pairs. METHODS: We measured BPA and eight phthalates [four di(2-ethylhexyl) phthalate metabolites (DEHPm), mono-benzyl phthalate (MBzP), and three low-molecular-weight phthalate metabolites (LMWPm)] in two spot-urine samples collected during the first and third trimester of pregnancy. We estimated growth curves for femur length (FL), head circumference (HC), abdominal circumference (AC), biparietal diameter (BPD), and estimated fetal weight (EFW) during pregnancy (weeks 12-20 and 20-34), and for birth weight, birth length, head circumference at birth, and placental weight. RESULTS: Overall, results did not support associations of exposure to BPA or DEHPm during pregnancy with fetal growth parameters. Prenatal MBzP exposure was positively associated with FL at 20-34 weeks, resulting in an increase of 3.70% of the average FL (95% CI: 0.75, 6.63%) per doubling of MBzP concentration. MBzP was positively associated with birth weight among boys (48 g; 95% CI: 6, 90) but not in girls (-27 g; 95% CI: -79, 25) (interaction p-value = 0.04). The LMWPm mono-n-butyl phthalate (MnBP) was negatively associated with HC at 12-20 pregnancy weeks [-4.88% of HC average (95% CI: -8.36, -1.36%)]. CONCLUSIONS: This study, one of the first to combine repeat exposure biomarker measurements and multiple growth measures during pregnancy, finds little evidence of associations of BPA or phthalate exposures with fetal growth. Phthalate metabolites MBzP and MnBP were associated with some fetal growth parameters, but these findings require replication. [ABSTRACT FROM AUTHOR]

Background: Analysis of the association between exposure to electromagnetic fields of non-ionising radiation (EMF-NIR) and health in children and adolescents is hindered by the limited availability of data, mainly due to the difficulties on the exposure assessment. This study protocol describes the methodologies used for characterising exposure of children to EMF-NIR in the INMA (INfancia y Medio Ambiente- Environment and Childhood) Project, a prospective cohort study.Methods/design: Indirect (proximity to emission sources, questionnaires on sources use and geospatial propagation models) and direct methods (spot and fixed longer-term measurements and personal measurements) were conducted in order to assess exposure levels of study participants aged between 7 and 18 years old. The methodology used varies depending on the frequency of the EMF-NIR and the environment (homes, schools and parks). Questionnaires assessed the use of sources contributing both to Extremely Low Frequency (ELF) and Radiofrequency (RF) exposure levels. Geospatial propagation models (NISMap) are implemented and validated for environmental outdoor sources of RFs using spot measurements. Spot and fixed longer-term ELF and RF measurements were done in the environments where children spend most of the time. Moreover, personal measurements were taken in order to assess individual exposure to RF. The exposure data are used to explore their relationships with proximity and/or use of EMF-NIR sources.Discussion: Characterisation of the EMF-NIR exposure by this combination of methods is intended to overcome problems encountered in other research. The assessment of exposure of INMA cohort children and adolescents living in different regions of Spain to the full frequency range of EMF-NIR extends the characterisation of environmental exposures in this cohort. Together with other data obtained in the project, on socioeconomic and family characteristics and development of the children and adolescents, this will enable to evaluate the complex interaction between health outcomes in children and adolescents and the various environmental factors that surround them. [ABSTRACT FROM AUTHOR]

This study assessed cross-sectional associations between urinary metabolites of non-persistent pesticides and pubertal development in boys and girls from urban and rural areas in Spain and examined effect modification by body mass index (BMI). Four metabolites of insecticides (TCPy, metabolite of chlorpyrifos; IMPy, metabolite of diazinon; DETP, non-specific metabolite of organophosphates; 3-PBA, metabolite of pyrethroids) and the metabolite of ethylene-bis-dithiocarbamate fungicides (ETU) were quantified in urine collected in 2010–2016 from 7 to 11-year-old children (606 girls, 933 boys) participating in the INMA Project. Pubertal development was ascertained by Tanner stages and/or parent-reported Pubertal Development Scale (PDS). Associations between pesticide metabolites and odds of being in stage 2+ for breast development (girls), genital development (boys), pubic hair growth (girls and boys), and/or overall puberty onset, gonadarche, and adrenarche (PDS for girls and boys) were examined by mixed-effect logistic regression. Effect modification by BMI was explored by interaction terms and stratified analysis. In girls, DETP and ETU concentrations>75th percentile (P75) were associated with higher odds of overall puberty development (OR [95%CI] = 1.86 [1.07–3.24] and 1.71 [1.03–2.83], respectively, for > P75 vs. undetected concentrations), while ETU > P75 was also associated with higher odds of breast development (OR [95%CI] = 5.55 [2.83–12.91]), particularly in girls with underweight/normal weight (OR [95%CI] = 10.08 [2.62–38.76]). In boys, detection of TCPy (40%) and 3-PBA (34%) was associated with higher odds of genital development (OR [95%CI] = 1.97 [1.08–3.57] and 2.08 [1.15–3.81], respectively), and the association with 3-PBA was observed in boys with overweight/obesity alone. In addition, ETU > P75 was associated with higher odds of genital development in boys with underweight/normal weight (OR [95%CI] = 2.89 [1.08–7.74]) but higher DETP with lower odds of puberty in boys with overweight/obesity (OR [95%CI] = 0.94 [0.89–0.99] per log-unit increase in concentration). Results suggest an association of childhood exposure to ETU and certain insecticides with earlier puberty in girls and boys that may be modified by child BMI. [Display omitted] • Higher urinary DETP and ETU were associated with earlier puberty development in girls. • Association between ETU and breast development was stronger in normal weight girls. • TCPy and 3-PBA were associated with earlier genital development in boys. • Higher ETU was associated with earlier genital development in normal weight boys. • Higher DETP was associated with delayed puberty development in overweight/obese boys. [ABSTRACT FROM AUTHOR]

The smoke-free legislation implemented in Spain in 2006 imposed a partial ban on smoking in public and work places, but the result did not meet expectations. Therefore, a more restrictive anti-smoking law was passed five years later in 2011 prohibiting smoking in all public places, on public transport, and the workplace. With the objective of assessing the impact of the latter anti-smoking legislation on children's exposure to second-hand smoke (SHS), we assessed parent’s smoking habits and children’s urine cotinine (UC) concentrations in 118 boys before (2005–2006) and after (2011–2012) the introduction of this law. Repeated cross-sectional follow-ups of the “Environment and Childhood Research Network” (INMA-Granada), a Spanish population-based birth cohort study, at 4–5 years old (2005–2006) and 10–11 years old (2011–2012), were designed. Data were gathered by ad-hoc questionnaire, and median UC levels recorded as an objective indicator of overall SHS exposure. Multivariable logistic regression was used to examine the association between parent’s smoking habits at home and SHS exposure, among other potential predictors. An increase was observed in the prevalence of families with at least one smoker (39.0% vs. 50.8%) and in the prevalence of smoking mothers (20.3% vs. 29.7%) and fathers (33.9% vs. 39.0%). Median UC concentration was 8.0 ng/mL (interquartile range [IQR]: 2.0–21.8) before legislation onset and 8.7 ng/mL (IQR: 2.0–24.3) afterwards. In the multivariable analysis, the smoking status of parents and smoking habits at home were statistically associated with the risk of SHS exposure and with UC concentrations in children. These findings indicate that the recent prohibition of smoking in enclosed public and workplaces in Spain has not been accompanied by a decline in the exposure to SHS among children, who continue to be adversely affected. There is a need to target smoking at home in order to avoid future adverse health effects in a population that has no choice in the acceptance or not of SHS exposure-derived risk. [ABSTRACT FROM AUTHOR]

There is an increasing trend in the incidence of cancer worldwide, and it has been accepted that environmental factors account for an important proportion of the global burden. The present paper reports preliminary findings on the influence of the historical exposure to a group of persistent organic pollutants on total cancer risk, at year 9 in the follow-up of a cohort from Southern Spain. A cohort of 368 participants (median age 51 years) was recruited in 2003. Their historical exposure was estimated by analyzing residues of persistent organic pollutants in adipose tissue. Estimation of cancer incidence was based on data from a population-based cancer registry. Statistical analyses were performed using multivariable Cox-regression models. In males, PCB 153 concentrations were positively associated with total cancer risk, with an adjusted hazard ratio (95% confidence interval) of 1.20 (1.01–1.41) for an increment of 100 ng/g lipid. Our preliminary findings suggest a potential relationship between the historical exposure to persistent organic pollutants and the risk of cancer in men. However, these results should be interpreted with caution and require verification during the future follow-up of this cohort. [ABSTRACT FROM AUTHOR]

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

Reliable tools to evaluate diet are needed, particularly in life periods such as adolescence in which a rapid rate of growth and development occurs. We assessed the biochemical validity of a self-administered food frequency questionnaire (FFQ) in a sample of Spanish male adolescents using carotenoids and vitamin E and D data. We analyzed data from 122 male adolescents aged 15–17 years of the INMA-Granada birth cohort study. Adolescents answered a 104-item FFQ and provided a non-fasting blood sample. Mean daily nutrient intakes and serum concentration were estimated for main carotenoids (lutein-zeaxanthin, β-cryptoxanthin, lycopene, α-carotene and β-carotene), vitamins E and D and also for fruit and vegetable intake. Pearson correlation coefficients (r) and the percentage of agreement (same or adjacent quintiles) between serum vitamin concentrations and energy-adjusted intakes were estimated. Statistically significant correlation coefficients were observed for the total carotenoids (r = 0.40) and specific carotenoids, with the highest correlation observed for lutein–zeaxanthin (r = 0.42) and the lowest for β-carotene (0.23). The correlation coefficient between fruit and vegetable intake and serum carotenoids was 0.29 (higher for vegetable intake, r = 0.33 than for fruit intake, r = 0.19). Low correlations were observed for vitamin E and D. The average percentage of agreement for carotenoids was 55.8%, and lower for vitamin E and D (50% and 41%, respectively). The FFQ may be an acceptable tool for dietary assessment among male adolescents in Spain. [ABSTRACT FROM AUTHOR]

Little information is available on the content of bisphenol A (BPA) and other endocrine-disrupting chemicals (EDCs) such as parabens in infant textiles and clothes. 1) To determine the concentrations of BPA and parabens in socks for infants and young children purchased in Spain, 2) to assess the (anti-)estrogenicity and (anti-)androgenicity of extracts from the socks, and 3) to estimate dermal exposure doses to these chemicals. Thirty-two pairs of socks for infants and young children (1–48 months) were purchased from 3 stores in Granada (Spain). Textile material was cut from the foot, toe, and leg of each sock (n = 96 samples) for chemical analysis. Hormone-like activities were determined in foot sections (n = 32 samples) by using the E-Screen assay for (anti-)estrogenicity and PALM luciferase assay for (anti-)androgenicity. BPA was present in 90.6% of samples at concentrations ranging from <0.70 to 3736 ng/g. BPA levels were around 25-fold higher in socks from store 1, which had a higher cotton content compared to stores 2 and 3. Ethyl-paraben was found in 100% of samples, followed by methyl-paraben (81.0%), and propyl-paraben (43.7%). No butyl-paraben was detected in any sample. Estrogenic activity was detected in 83.3% of socks from store 1 (range = 48.2–6051 pM E 2 eq/g) but in only three socks from stores 2 and 3. Anti-androgenic activity was detected in six of the 32 socks studied (range = 94.4–2989 μM Proceq/g), all from store 1. Estimated dermal exposure to BPA was higher from socks for children aged 36–48 months (median = 17.6 pg/kg/day), and dermal exposure to parabens was higher from socks for children aged 24–36 months (median = 0.60 pg/kg/day). This is the first report in Europe on the wide presence of BPA and parabens in socks marketed for infants and children. BPA appears to contribute to the hormone-like activity observed in sock extracts. Unlabelled Image • BPA was present in 91% of socks at concentrations ranging from <0.70 to 3736 ng/g. • Ethyl-paraben was found in 100% of socks, followed by methyl- and propyl-paraben. • Around 41% of socks extracts were estrogenic and 19% were anti-androgenic. • Hormone-like activities were higher in socks with higher BPA content. • The median estimated dermal exposure dose to BPA was 19.6 pg/kg/day. [ABSTRACT FROM AUTHOR]

Childhood obesity is one of the most serious public health challenges of our times. Although an important body of experimental evidence highlights the obesogenic potential of endocrine disruptors such as bisphenol A (BPA), the epidemiological evidence remains inconclusive and limited. To assess associations between urinary BPA concentrations and several adiposity measures in peripubertal boys from the Environment and Childhood (INMA) cohort in Granada, Spain. BPA concentrations were determined in spot urine samples from 298 boys aged 9–11, and their weight, height, waist circumference, and percentage body fat mass were measured. Overweight/obesity was defined as BMI z-score ≥85th percentile and abdominal obesity as waist-to-height ratio (WHtR) ≥0.5. Associations were assessed using multivariable linear and logistic regression models. In adjusted models, each natural log-unit increase in urinary BPA concentrations was associated with higher BMI z-score (β = 0.22; 95%CI = 0.03, 0.41) and increased odds of overweight/obesity (OR = 1.46; 95%CI = 1.05, 2.05). Children with higher BPA concentrations had higher WHtR values (β = 0.007; 95%CI = −0.001, 0.015), and BPA was associated with a greater risk of abdominal obesity (OR = 1.45; 95%CI = 1.03, 2.06). No associations were found with % body fat mass. BPA may exert an obesogenic effect in peripubertal boys, potentially increasing the risk of overweight/obesity, especially abdominal obesity. However, these results should be interpreted with caution given the modest sample size and the possibilities of reverse causality and residual confounding by diet and lifestyle patterns. • We assessed associations between BPA and adiposity measures in peripubertal boys. • Urinary BPA concentrations were associated with the risk of overweight/obesity. • BPA concentrations were also associated with abdominal obesity, but not body fat mass. • BPA could exert an obesogenic effect, preferentially targeting abdominal fat. • Prepuberty constitutes a less explored critical window for BPA effects. [ABSTRACT FROM AUTHOR]

Objective: To examine the association of placental levels of arsenic (As), cadmium (Cd), mercury (Hg), lead (Pb), manganese (Mn), and chromium (Cr) with birth outcomes (birth weight, length, and head circumference, low birth weight [LBW], gestational age, preterm delivery, and small for gestational age [SGA]) in mother-child pairs from the Environment and Childhood (INMA) Project in Spain.Methods: Metal concentrations were measured in placenta tissue samples randomly selected from five INMA cohorts. Data on birth outcomes were obtained from medical records. Associations were assessed in a sub-sample of 327 mother-infant pairs by regression models adjusted for confounding factors and for all metals simultaneously. Effect modification by sex was also evaluated.Results: Elevated placental Cd levels (>5.79 vs. <3.30 ng/g) were associated with reduced birth weight (-111.8 g, 95%CI = -215.6; -8.06, p-trend = 0.01) and length (-0.62 cm, 95%CI = -1.20; -0.04, p-trend = 0.02), while a 10% increase in Cd was associated with 1.21-fold increased odds (95%CI = 1.01; 1.43) of LBW in the global sample but with 14% lower odds (95%CI = 0.78; 0.96) of preterm delivery in males (Pinteraction = 0.10). Detected (vs. undetected) Hg was associated with reduced head circumference (-0.49 cm, 95%CI = -1.00; 0.03) in females (Pinteraction = 0.03). A 10% increase in placental Mn was associated with slight increases in gestational age (0.04 weeks, 95%CI = 0.01; 0.07) in the global sample and in head circumference (0.05 cm, 95%CI = -0.01; 0.10) in females (Pinteraction = 0.03). Elevated Cr levels (>99.6 vs. <56.1 ng/g) were associated with reduced birth length (-0.68 cm, 95%CI = -1.33; -0.04, p-trend = 0.02) and slightly increased gestational age (0.35 weeks, 95%CI = -0.07; 0.77, p-trend = 0.08) in the global sample. As and Pb were detected in few placentas (27% and 13%, respectively) and were not associated with any studied birth outcome.Conclusions: Data suggest that in utero exposure to Cd, Hg, and Cr could adversely affect fetal growth, whereas Mn and Cr appear to have a positive effect on gestational age. Given the relatively small number of subjects, sex-specific associations should be interpreted with caution. [ABSTRACT FROM AUTHOR]

Background: Benzophenone (BP)-type ultraviolet (UV) light filters are chemicals frequently added to personal care products, insect repellents, sunscreens, and beverage and food packaging to diminish the harmful effects of UV sunlight on human skin or foodstuffs. BP-type UV filters have shown negative effects on male reproduction function in in vitro and animal models, but human epidemiologic studies are limited. The goal of this study was to examine associations between urinary concentrations of BP-type UV filters and semen quality and reproductive hormone levels.Methods: This is a cross-sectional study with 215 young university students (18-23 years old) recruited between 2010 and 2011 in Southern Spain (Murcia Region). All men provided a urine, blood and semen sample on a single day. Urinary concentrations of 2,4-dihydroxybenzophenone (BP-1); 2,2',4,4'-tetrahydroxybenzophenone (BP-2); 2-hydroxy-4-methoxybenzophenone (BP-3); 2,2'-dihydroxy-4-methoxybenzophenone (BP-8) and 4-hydroxybenzophenone (4OH-BP) were measured by dispersive liquid-liquid microextraction and ultra-high performance liquid chromatography with tandem mass spectrometry detection. Semen quality was evaluated by measuring volume, sperm counts, motility and morphology. Serum samples were analyzed for reproductive hormones, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), inhibin B and estradiol (E2). Associations between urinary concentrations of BP-type UV filters and semen quality parameters and reproductive hormone levels were examined using linear regression, adjusting for potential confounders.Results: Ninety-seven percent of the men had detectable urinary concentrations of at least one of the five BP-type UV filters quantified. After adjustment for important covariates (body mass index, smoking status and time of blood sample collection), there was a significant positive association between urinary BP-1 and BP-3 concentrations and serum FSH levels (β = 0.08, 95%CI: 0.009; 0.15 and β = 0.04, 95%CI: 0.0002; 0.08, respectively). Urinary BP-1 concentration was also significantly positively associated with T/E2 (β = 0.04, 95%CI: 0.002; 0.07) and negatively with inhibin b/FSH (β = -0.11, 95%CI: -0.21; -0.006) ratio. No significant associations were found between other urinary BP-type UV filters and other reproductive hormone levels or between any semen parameters and any of the urinary BP-type UV filters quantified.Conclusions: Our results suggest that, in young men, urinary BP-type UV filters may be associated with a modest alteration of some reproductive hormones, but the effects we report on reproductive function are likely to be small, and of unclear clinical significance. Further research is needed to replicate these findings in other male populations. [ABSTRACT FROM AUTHOR]

Aim: To measure concentrations of lead (Pb), mercury (Hg), cadmium (Cd), and arsenic (As) in longitudinally collected donor breast milk samples and to determine associated factors.Methods: Pb, Hg, Cd, and As concentrations were measured in 242 pooled breast milk samples from 83 donors to a Human Milk Bank in Spain, in 2015-2018, determining their association with the donors' sociodemographic profile, dietary and lifestyle habits, and post-partum time, among other factors, and with the nutritional characteristics of samples. Mixed-effect linear regression was used to identify predictors of Hg and As concentrations in breast milk and mixed-effect logistic regression to identify predictors of the presence of Pb and Cd.Results: As was the element most frequently detected in milk samples (97.1%), followed by Hg (81.2%), Pb (50.6%), and Cd (38.0%). Their median breast milk concentrations were 1.49 μg/L, 0.26 μg/L, 0.14 μg/L, and <0.04 μg/L, respectively. Concentrations of As were higher in breast milk from primiparous donors, while Hg was higher in donors with a greater intake of fatty fish and meat and lower in samples collected after a longer post-partum time and with higher lactose content. Detection of Pb was higher among multiparous donors, those gaining weight since before pregnancy, and ex-smokers and was lower in samples collected more recently and from donors with greater intake of red meat and eggs. Cd detection was higher for donors with university education and those with greater intake of fried and canned food and more frequent use of hand cream and was lower for donors with greater bread intake.Conclusions: These findings reveal relatively high As concentrations, moderate Hg concentrations, and low Pb and Cd concentrations in pooled donor breast milk. Several factors including post-partum time, parity, smoking habit, and the intake of certain food items were associated with the metal content of milk samples. [ABSTRACT FROM AUTHOR]

Background: Breast milk is considered to offer the best nutrition to infants; however, it may be a source of exposure to environmental chemicals such as perfluoroalkyl compounds (PFAS) for breastfeeding infants. PFAS are a complex group of synthetic chemicals whose high stability has led to their ubiquitous contamination of the environment.Objective: To assess the concentrations and profiles of PFAS in breast milk from donors to a human milk bank and explore factors potentially related to this exposure.Methods: Pooled milk samples were collected from 82 donors to the Human Milk Bank of the Virgen de las Nieves University Hospital (Granada, Spain). Ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) was applied to determine milk concentrations of 11 PFAS, including long-chain and short-chain compounds. A questionnaire was used to collect information on donors' socio-demographic characteristics, lifestyle, diet, and use of personal care products (PCPs). Factors related to individual and total PFAS concentrations were evaluated by multivariate regression analysis.Results: PFAS were detected in 24-100% of breast milk samples. PFHpA was detected in 100% of samples, followed by PFOA (84%), PFNA (71%), PFHxA (66%), and PFTrDA (62%). Perfluorooctane sulfonate (PFOS) was detected in only 34% of donors. The median concentrations ranged from <0.66 ng/dL (perfluorohexane sulfonic acid [PFHxS]) to 19.39 ng/L (PFHpA). The median of the sum of PFAS concentrations was 87.67 ng/L and was higher for short-chain than long-chain PFAS. Factors most frequently associated with increased PFAS concentrations included intake of creatin animal food items and use of PCPs such as skin care and makeup products.Conclusions: Several PFAS, including short-chain compounds, are detected in pooled donor milk samples. Breast milk may be an important pathway for the PFAS exposure of breastfed infants, including preterm infants in NICUs. Despite the reduced sample size, these data suggest that various lifestyle factors influence PFAS concentrations, highlighting the use of PCPs. [ABSTRACT FROM AUTHOR]

Scope: This work is part of the clinical study NCT03885648 registered in ClinicalTrials.gov, aimed at studying the relationship among breast cancer, microbiota, and exposure to environmental pollutants. As a first step, we characterized and evaluated risk factors of the participants., Methods and Results: A case-control study was designed with breast cancer (cases, n = 122) and healthy women (controls, n = 56) recruited in two hospitals of Andalusia (Southern Spain). Participants answered questionnaires of Mediterranean diet adherence and food frequency. Data were collected from medical histories and microbiota was analyzed on stool samples. Most cases (78.2%) were diagnosed as stages I and II. Cases had higher age, body mass index (BMI), glucose, cholesterol, and potassium values than controls. Cases exhibited higher adherence to the Mediterranean diet and their food consumption was closer to that dietary pattern. A hierarchical cluster analysis revealed that the Bacillota/Bacteroidota ratio was the most relevant variable in women with breast cancer, which was higher in this group compared with controls., Conclusion: Although cases exhibited higher adherence to the Mediterranean diet compared with controls, they presented features and microbiota alterations typical of the metabolic syndrome, probably due to their higher BMI and reflecting changes in their lifestyle around the time of diagnosis., (© 2024 The Author(s). Molecular Nutrition & Food Research published by Wiley‐VCH GmbH.)

Background: Bisphenol A (BPA) is one of the most common endocrine disruptor compounds in our environment, promoting a xenoestrogenic state. Numerous studies have shown a relationship between exposure to BPA and male infertility problems. Spermatic DNA integrity is a critical factor for the correct transmission of paternal genetic material to the embryo. However, only a very few studies have investigated the association between urinary BPA concentrations and human sperm DNA fragmentation (SDF)., Method: Cross-sectional study conducted with 158 healthy university students (18-23 years), recruited between 2010 and 2011 in the Region of Murcia (Spain). The subjects provided urine and semen samples on a single day. Urinary BPA concentrations were measured by dispersive liquid-liquid microextraction and ultrahigh performance liquid chromatography with tandem mass spectrometry detection, and SDF analysed using the Sperm Chromatin Dispersion test. Statistical analyses were made using linear regression adjusting for potential covariates and confounding factors., Results: No association was found between urinary BPA concentrations and SDF index in the total group. However, in the subgroup of men with SDF index> 30%, significant positive associations across quartiles (p-trend=0.02) and as a continuous BPA levels were observed (β = 0.055, 95%, CI: 0.002; 0.108)., Conclusion: Our results show that, within the subgroup of men with relatively high SDF index, the higher the concentration of BPA the greater the SDF index. Nonetheless, more studies are required to confirm these results and draw conclusions in other male populations., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To examine the association between urinary metabolites of organophosphate (OP) pesticides and serum concentrations of thyroid and reproductive hormones in male adolescents and to assess the potential effect of interactions between OP pesticides and paraoxonase 1 (PON1) polymorphisms on hormone levels., Methods: Study subjects (N = 117) were male 16- to 17-year-olds from the Environment and Childhood (INMA)-Granada cohort in Spain. Concentrations of 3,5,6-trichloro-2-pyridinol (TCPy), a metabolite of chlorpyrifos/chlorpyrifos-methyl, 2-isopropyl-6-methyl-4-pyrimidinol (IMPy), a metabolite of diazinon, and diethylthiophosphate (DETP) and diethyldithiophosphate (DEDTP), non-specific metabolites of OP pesticides, were measured in a spot urine sample from each subject and adjusted for creatinine. Levels of reproductive hormones (total testosterone [TT], estradiol [E 2 ], dehydroepiandrosterone sulfate [DHEAS], sex hormone binding globulin [SHBG], luteinizing hormone [LH], follicle stimulating hormone [FSH], anti-Müllerian hormone [AMH], insulin growth factor 1 [IGF-1], and prolactin), thyroid hormones (free thyroxine [FT4], total triiodothyronine [TT3], and thyroid stimulating hormone [TSH]), and PON1 Q192R and L55M polymorphisms were determined in blood drawn during the same clinical visit., Results: Multiple linear regression models showed that detectable levels of TCPy were associated with an increase in DHEAS and decreases in E 2 , FSH, and AMH; detectable IMPy with increases in E 2 , DHEAS, FSH, AMH, and prolactin and decreases in SHBG and LH; and detectable DETP with marginally-significant increases in TT and TT3 and decreases in FSH, AMH, and prolactin. The effect of IMPy and DETP on DHEAS and TT levels, respectively, was higher in subjects that carried the PON1 55MM genotype, while the effect of TCPy, IMPy, and DETP on thyroid hormone levels was higher in PON1 192QR/RR or 55MM genotype carriers., Conclusions: In male adolescents, non-occupational exposure to OP pesticides was associated with several changes in reproductive and thyroid hormone levels, and the magnitude of some associations was greater in adolescents genetically more susceptible to OP pesticide exposure who carry the PON1 55MM genotype., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)

This research aims to explore clusters of a mixture of 15 Persistent Toxic Substances (PTSs) in the adipose tissue of 227 individuals of an adult cohort from Granada Province (Southern Spain). Information about residence and occupation during participants lifetime was gathered by means of validated questionnaires. Clusters of pollutants in the study population were identified by Principal Component Analyses (PCA). PCA analyses revealed three major clusters of pollutants: PC1, representing predominantly an assortment of metal(loid)s, namely aluminium, arsenic, chromium, nickel and lead; PC2, including mostly Organochlorine Pesticides (OCPs), such as HCB, β-HCH and p,p'-DDE; and PC3, gathering mainly a mixture of Polychlorinated Biphenyls (PCB-138, PCB-153 and PCB-180) and metals (cadmium, cobalt and chromium). The patterns of distribution of individual pollutants and their mixtures were explored through Geographic Information Systems and multivariable linear regression models. Living in rural areas was associated with decreased levels of the mixture of PCBs and metals. Residents of industrial and heavy traffic areas showed increased levels of the mixture of metal(loid)s. Those living in rural and semi-rural areas at recruitment had decreased levels of the OCP mixture. Occupational history related to agriculture and food industry was associated with increased levels of the mixture of metal(loid)s, whereas those who had been involved in motor and industrial activities showed increased levels of the OCP mixture. Participants who had worked in cleaning and housekeeping activities for long periods showed decreased levels of the mixture of PCBs and metals. Our research revealed suggestive clusters of exposure, that emphasized the need for further epidemiological studies to address the effect of environmental pollutants from a mixture perspective. Results also highlight the potential of adipose tissue as a matrix for exposure assessment to combinations of different families of contaminants., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Tools to assess diet in a reliable and efficient way are needed, particularly in children and adolescents. In this study, we assess the reproducibility and validity of a semiquantitative food frequency questionnaire (FFQ) among adolescents in Spain. We analyzed data of 51 male adolescents aged 15-17 years from a prospective birth cohort study. Participants answered the FFQ twice in a self-administered way over a 12-month period. Reproducibility was assessed by comparing nutrient and food intakes from the FFQs, and validity by comparing nutrient intakes from the average of two FFQs and the average of two 24-Hour Dietary Recalls obtained in the period. Pearson correlation coefficients were calculated. The average of reproducibility correlation coefficients for food group intakes was 0.33, with the highest correlation for vegetable intake (r = 0.81); and the average for nutrient intake was 0.32, with the highest coefficients for α- and β-carotene (r = 0.65). Validity correlation coefficients ranged from 0.07 for carbohydrates to 0.53 for dietary fiber. The average of the validity correlation coefficients was r = 0.32. This study suggests that our FFQ may be a useful tool for assessing dietary intake of most nutrient and food groups among Spanish male adolescents in a self-administered way, despite reproducibility and, particularly validity, being low for some nutrients and food groups.

Background: Adipose tissue has been acknowledged as a potential target for obesogenic pollutants, including toxic metal(loid)s. However, the presence of these chemicals in the adipose tissue has been poorly characterized., Objective: To examine the distributions of adipose tissue concentrations of five toxic metal(loid)s (i.e., arsenic [As], nickel [Ni], lead [Pb], tin [Sn], and titanium [Ti]) in adults, and potential socio-demographic and lifestyle factors associated with metal(loid) concentrations., Methods: The study population consisted of a subsample of 228 subjects from GraMo cohort in Southern Spain (N = 387). Adipose tissue samples were intra-operatively collected from adults recruited in 2003-2004 in two public hospitals, and concentrations of metal(loid)s in adipose tissue were analyzed in 2015 by High-Resolution Inductively Coupled Plasma Mass Spectrometry. Data on socio-demographic and lifestyle factors were obtained by baseline questionnaire completion. Linear and multinomial regression was used to identify factors associated with metal(loid) levels., Results: Ni, Pb, Sn, and Ti were detected in all adipose tissue samples, and As in 51% of them. Ni was the metal showing the highest median concentration (0.56 μg/g), followed by Ti (0.31 μg/g), Pb (0.08 μg/g), Sn (0.06 μg/g), and As (0.003 μg/g). Predictors of As levels included area of residence, social class, and oily fish intake; for Ni: area of residence and consumption of cheese, meat, eggs, and canned food; for Pb: vegetables intake and industrial occupation; for Sn: age, body mass index, and consumption of lean fish, eggs, and milk; and cheese intake for Ti. Some of these predictors were sex-specific, particularly those regarding dietary intake., Conclusions: This exploratory study provides the first evidence of the occurrence of Ni, Pb, Sn, Ti, and As in adipose tissue from adult population, and highlights the potential of this tissue as a biological matrix for studying exposure levels and chronic health effects of toxic metal(loid)s., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The present study was conceived on the basis of the few previous reports suggesting a potential relevance of the oxidative stress microenvironment in the adipose tissue, a biological matrix which is closely related to the development of several chronic pathologies. Thus, our aim was to describe the levels of enzymatic and non-enzymatic antioxidants and markers of oxidative damage in adipose tissue samples from a Spanish cohort, as well as their main sociodemographic, lifestyle, and dietary predictors. The study was conducted in a subsample (n = 271 adults) of GraMo cohort, recruited in Granada (Southern Spain). A face-to-face questionnaire was used to gather data regarding sociodemographic characteristics, lifestyle, dietary habits, health status, and perceived exposure to chemicals. We analyzed adipose tissue levels of lipid peroxidation (TBARS), total superoxide dismutase (SOD) activity, heme oxygenase-1 (HO-1) activity, and glutathione cycle biomarkers. Potential predictors of oxidative stress markers were assessed using stepwise multivariable linear regression analyses. SOD and TBARS levels were mainly related to sociodemographic and occupational characteristics, while the components of the glutathione cycle and HO-1 were predominantly associated with dietary habits. Men showed significantly lower levels of oxidative stress levels than women. In the regression models including only women, the use of oral contraceptive and hormonal therapy was associated with lower levels of oxidative stress, while the number of children was positively associated with increased oxidative biomarkers. Our results suggest that adipose tissue is potentially important matrix for the assessment of oxidative stress, which can be affected by specific environmental factors. These findings might be relevant for public health., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Bisphenol A (BPA) is a pervasive environmental toxicant with known reproductive effects on sperm parameters and hormone levels. Several observational studies have investigated the associations between BPA exposure and male reproductive function, but findings are inconsistent. The objective of this study was to assess the associations between urinary BPA concentrations and semen quality and reproductive hormone levels in a cross-sectional study with 215 healthy young university students (18-23 years old), investigated between 2010 and 2011 in Southern Spain (Murcia Region). All subjects provided urine, blood serum and semen samples on a single day. Urinary BPA concentrations were measured by dispersive liquid-liquid microextraction and ultra-high performance liquid chromatography with tandem mass spectrometry detection. Semen quality was evaluated by measuring volume, concentration, motility, morphology and total sperm count (TSC). Serum samples were analyzed for reproductive hormones, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, inhibin B and estradiol. Relationships between urinary BPA concentrations and semen quality parameters and reproductive hormone levels were examined using linear regression, adjusting for potential confounders and covariates. Ninety-five percent of the men had detectable urinary BPA concentrations with unadjusted median (5th-95th) of 2.8 (0.16-11.5) ng/mL. After adjustment for important covariates, there was a significant positive association between urinary BPA concentrations and serum LH levels (β = 0.07, 95%CI: 0.02;0.12, p-value < 0.01). Urinary BPA concentration was also significantly and inversely associated with sperm concentration (β = - 0.04, 95%CI: - 0.07;- 0.02, p-value < 0.01) and TSC (β = - 0.05, 95%CI: - 0.08;- 0.02, p-value < 0.01). No significant associations were found between BPA and other semen parameters or reproductive hormone levels. Our results support the hypothesis that BPA exposure may be associated with a reduction in Leydig cell capacity (increased LH levels) and decreased sperm counts in young men., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The aim of this study was to assess the influence of adipose tissue concentrations of a group of persistent organic pollutants (POPs) on the risk of hypertension in an adult cohort of residents of Granada (Southern Spain) over a 10-year follow-up. No chemical was significantly associated with the risk of hypertension in the overall population or when models were stratified by sex or median age. However, we found positive associations between log-transformed POP concentrations and hypertension risk in participants with body mass index (BMI) above the median value of 26.3kg/m(2), which were statistically significant for hexachlorobenzene (HR=1.26, 95% CI=1.03-1.56), β-hexachlorocyclohexane (HR=1.25, 95% CI=1.03-1.51), and polychlorinated biphenyl congeners -138 (HR=1.32, 95% CI=1.04-1.69) and -153 (HR=1.36, 95% CI=1.00-1.84). Inverse associations were observed in the subgroup with BMI≤26.3kg/m(2), but none was statistically significant. More research and a longer follow-up period are warranted to verify these associations and elucidate the role of obesity as a potential effect modifier. Given the elevated worldwide frequency of POP exposure and hypertension, the public health impact of this relationship may be substantial., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Bottled water consumption is a putative source of human exposure to endocrine-disrupting chemicals (EDCs). Research has been conducted on the presence of chemicals with estrogen-like activity in bottled waters and on their estrogenicity, but few data are available on the presence of hormonal activities associated with other nuclear receptors (NRs). The aim of this study was to determine the presence of endocrine activities dependent on the activation of human estrogen receptor alpha (hERa) and/or androgen receptor (hAR) in water in glass or plastic bottles sold to consumers in Southern Spain. Hormone-like activities were evaluated in 29 bottled waters using receptor-specific bioassays based on reporter gene expression in PALM cells [(anti-)androgenicity] and cell proliferation assessment in MCF-7 cells [(anti-)estrogenicity] after optimized solid phase extraction (SPE). All of the water samples analyzed showed hormonal activity. This was estrogenic in 79.3% and anti-estrogenic in 37.9% of samples and was androgenic in 27.5% and anti-androgenic in 41.3%, with mean concentrations per liter of 0.113pM 17β-estradiol (E2) equivalent units (E2Eq), 11.01pM anti-estrogen (ICI 182780) equivalent units (ICI 182780Eq), 0.33pM methyltrienolone (R1881) equivalent units (R1881Eq), and 0.18nM procymidone equivalent units (ProcEq). Bottled water consumption contributes to EDC exposure. Hormone-like activities observed in waters from both plastic and glass bottles suggest that plastic packaging is not the sole source of contamination and that the source of the water and bottling process may play a role, among other factors. Further research is warranted on the cumulative effects of long-term exposure to low doses of EDCs., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: To characterize the exposure to electric fields and magnetic fields of non-ionizing radiation in the electromagnetic spectrum (15 Hz to 100 kHz) in the dwellings of children from the Spanish Environment and Childhood-"INMA" population-based birth cohort., Methodology: The study sample was drawn from the INMA-Granada cohort. Out of 300 boys participating in the 9-10 year follow-up, 123 families agreed to the exposure assessment at home and completed a specific ad hoc questionnaire gathering information on sources of non-ionizing radiation electric and magnetic fields inside the homes and on patterns of use. Long-term indoor measurements were carried out in the living room and bedroom., Results: Survey data showed a low exposure in the children's homes according to reference levels of the International Commission on Non-Ionizing Radiation Protection but with large differences among homes in mean and maximum values. Daytime electrostatic and magnetic fields were below the quantification limit in 78.6% (92 dwellings) and 92.3% (108 dwellings) of houses, with an arithmetic mean value (± standard deviation) of 7.31±9.32 V/m and 162.30±91.16 nT, respectively. Mean magnetic field values were 1.6 lower during the night than the day. Nocturnal electrostatic values were not measured. Exposure levels were influenced by the area of residence (higher values in urban/semi-urban versus rural areas), type of dwelling, age of dwelling, floor of the dwelling, and season., Conclusion: Given the greater sensitivity to extremely low-frequency electromagnetic fields of children and following the precautionary principle, preventive measures are warranted to reduce their exposure.

p,p'-Dichlorodiphenyldichloroethylene (p,p'-DDE) is the main metabolite of pesticide dichlorodiphenyltrichloroethane and a marker of past exposure to this organochlorine pesticide. p,p'-DDE is considered a persistent organic pollutant with potential adverse effects on human health. The aims of the present study were to assess p,p'-DDE levels in serum and adipose tissue from a cohort of adults in southern Spain and to explore the predictors of exposure from a gender perspective. Chemical analyses were performed using gas chromatography-coupled mass spectrometry in tandem mode. The study population (n=387) was intraoperatively recruited in two areas of Granada Province (southern Spain), and data on potential predictors of these concentrations were gathered by questionnaire. The statistical analysis was performed by means of multivariable linear regression models. All participants showed detectable concentrations of p,p'-DDE in both serum and adipose tissue, with median concentrations of 175.7 and 93.0 ng/g lipid, respectively (p<0.001), and the two measurements showed positive correlations. Women showed higher concentrations than men (115.8 and 66.2 ng/g lipid, respectively, p<0.001). Concentrations in both matrices were positively associated with fatty food consumption, as well as with age and BMI, the latter only in adipose tissue. The multivariate model showed that, among women, adipose tissue concentrations were approximately 40% higher in those residing in the semi-rural area and 2-fold higher in those whose mothers had participated in agricultural activities during the pregnancy. In this study population, gender and place of residence play a key role in human exposure to p,p'-DDE and can be used to identify subjects at special risk of long-term exposure., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Several studies have investigated temporal trends in semen quality in Northern Europe, but none has examined this question in Southern Europe. A prior study conducted in Almeria Province (Southern Spain) reported higher sperm count and concentration among Spanish young men recruited from 2001 to 2002 compared with young men from Northern Europe. The aim of this new study was to examine whether semen quality has changed among Spanish young men in the last decade. In this cross-sectional study, questionnaires and semen samples were collected from 215 healthy young university students from Murcia Region between 2010 and 2011. The 273 men from the Almeria study previously studied were included in a trend analysis of the two populations from Southern Spain. Descriptive statistics were calculated for the Murcia study population and these and semen variables for the Murcia and Almeria study populations were compared. Study methods and population characteristics were similar across the two studies. Therefore, we used multiple linear regression analyses on the combined population (controlling for study centre, age, ejaculation abstinence time, season, smoking, medication during the last 3 months, Body mass index (BMI), presence of varicocoele and prenatal exposure to tobacco) to look for a birth-cohort effect over the combined study period (2001-2011). Sperm concentration and total sperm count declined significantly with year of birth in the pooled analysis (β = -0.04 and β = -0.06, respectively, both p < 0.01). Sperm counts were significantly lower in Murcia study subjects than in the Almeria participants; sperm concentration median (5th-95th) = 44.0 (8.9-129) million/mL vs. 51.0 (5.0-206) million/mL; p < 0.01 and total sperm count = 121 (17.8-400) million vs. 149 (8.0-599) million; p < 0.01. Other semen variables did not differ significantly between the two studies. Our study suggests that total sperm count and sperm concentration may have declined in young Spanish men over the last decade., (© 2013 American Society of Andrology and European Academy of Andrology.)

Objective: To describe the time trend in atmospheric lead concentrations in Spain, from before lead was banned as a gasoline additive to the present, and to determine the trend in lead body burden in the Spanish child population., Methods: We obtained the annual average for atmospheric lead levels in several Spanish cities from the 1980s to the present. A literature search was conducted to identify published studies on lead concentrations in populations of Spanish children., Results: Overall, atmospheric lead levels decreased, particularly between 1991 and 1999. This downward trend was related to a decrease in lead concentrations in Spanish children from 1989, the year in which the first study of childhood lead exposure was published, until the present. The decreased concentrations in both air and in children was most probably a result of legislative measures regulating the maximum amount of lead in gasoline in 1987 until a complete ban in August 2001., Conclusions: From a public health point of view, the banning of leaded gasoline has significantly increased health protection in the Spanish population., (Copyright © 2011 SESPAS. Published by Elsevier Espana. All rights reserved.)

Background: Evidence associating exposure to water disinfection by-products with reduced birth weight and altered duration of gestation remains inconclusive., Objective: We assessed exposure to trihalomethanes (THMs) during pregnancy through different water uses and evaluated the association with birth weight, small for gestational age (SGA), low birth weight (LBW), and preterm delivery., Methods: Mother-child cohorts set up in five Spanish areas during the years 2000-2008 contributed data on water ingestion, showering, bathing, and swimming in pools. We ascertained residential THM levels during pregnancy periods through ad hoc sampling campaigns (828 measurements) and regulatory data (264 measurements), which were modeled and combined with personal water use and uptake factors to estimate personal uptake. We defined outcomes following standard definitions and included 2,158 newborns in the analysis., Results: Median residential THM ranged from 5.9 μg/L (Valencia) to 114.7 μg/L (Sabadell), and speciation differed across areas. We estimated that 89% of residential chloroform and 96% of brominated THM uptakes were from showering/bathing. The estimated change of birth weight for a 10% increase in residential uptake was -0.45 g (95% confidence interval: -1.36, 0.45 g) for chloroform and 0.16 g (-1.38, 1.70 g) for brominated THMs. Overall, THMs were not associated with SGA, LBW, or preterm delivery., Conclusions: Despite the high THM levels in some areas and the extensive exposure assessment, results suggest that residential THM exposure during pregnancy driven by inhalation and dermal contact routes is not associated with birth weight, SGA, LBW, or preterm delivery in Spain.

Objectives: Drinking water chlorination generates potentially harmful by-products, such as trihalomethanes. Trihalomethane levels are high in some parts of Spain. The aim of the present study was to investigate trihalomethane concentrations in drinking water from distinct water supplies in the province of Granada, within the framework of the Childhood and Environment (INMA) study., Methods: Eighty-two tap water samples were collected in two campaigns during the winter and summer of 2006. An optimized procedure based on gas chromatography and mass spectrometry was used to determine concentrations of chloroform, bromodichloromethane, dibromochloromethane, and bromoform in the samples., Results: Total trihalomethane concentrations ranged from 0.14 to 18.75 microg/l in winter samples and from 0.01 to 31.87 microg/l in summer samples. The most abundant compound was chloroform. Mean trihalomethane concentrations were 10.13 in surface waters and 1.41 microg/l in ground waters., Conclusions: The trihalomethane levels found were considerably below the maximum permitted level of 100 microg/l in the European Union. The values obtained varied widely according to the type of water source: the highest concentrations were found in urban and sub-urban areas, where the water is largely of surface origin. The presence of trihalomethanes was lower than that reported in other Spanish regions.