Assessment of chemical mixtures using biomarkers of combined biological activity: A screening study in human placentas.

Humans are simultaneously exposed to complex mixtures of chemicals with limited knowledge on potential health effects, therefore improved tools for assessing these mixtures are needed. As part of the Human Biomonitoring for Europe (HBM4EU) Project, we aimed to examine the combined biological activity of chemical mixtures extracted from human placentas using one in vivo and four in vitro bioassays, also known as biomarkers of combined effect. Relevant endocrine activities (proliferative and/or reporter gene assays) and four endpoints were tested: the estrogen receptor (ER), androgen receptor (AR), and aryl hydrocarbon receptor (AhR) activities, as well as thyroid hormone (TH) signaling. Correlations among bioassays and their functional shapes were evaluated. Results showed that all placental extracts agonized or antagonized at least three of the abovementioned endpoints. Most placentas induced ER-mediated transactivation and ER-dependent cell proliferation, together with a strong inhibition of TH signaling and the AR transactivity; while the induction of the AhR was found in only one placental extract. The effects in the two estrogenic bioassays were positively and significantly correlated and the AR-antagonism activity showed a positive borderline-significant correlation with both estrogenic bioassay activities. However, the in vivo anti-thyroid activities of placental extracts were not correlated with any of the tested in vitro assays. Findings highlight the importance of comprehensively mapping the biological effects of "real-world" chemical mixtures present in human samples, through a battery of in vitro and in vivo bioassays. This approach should be a complementary tool for epidemiological studies to further elucidate the combined biological fingerprint triggered by chemical mixtures.

Bisphenol A and adiposity measures in peripubertal boys from the INMA-Granada cohort.

INTRODUCTION: 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. OBJECTIVE: To assess associations between urinary BPA concentrations and several adiposity measures in peripubertal boys from the Environment and Childhood (INMA) cohort in Granada, Spain. MATERIAL AND METHODS: 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. RESULTS: In adjusted models, each natural log-unit increase in urinary BPA concentrations was associated with higher BMI z-score (ß = 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 (ß = 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. CONCLUSIONS: 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.

Hidropesía fetal secundario a hemangioma cavernoso y síndrome polimalformativo / Fetal hydrops secondary to cavernous hemangioma and polymalformation syndrome

Presentamos un caso de hidropesía fetal no inmunitaria diagnosticada en la semana 32 de embarazo que finalizó con defunción fetal. Tras la necropsia se comprobó la coexistencia de un síndrome malformativo no filiado junto a la existencia de una tumoración hepática que invadía la cavidad torácica. Analizamos la posible asociación causal de ambos hallazgos (AU)

We report a case of non-immune fetal hydrops diagnosed at 32 weeks of pregnancy that ended in foetal death. Following the autopsy an unknown malformation syndrome was found together with a liver tumour that invaded the chest cavity. We analyse the possible causal association of both findings (AU)

First trimester serum 25-hydroxyvitamin D status and factors related to lower levels in gravids living in the Spanish Mediterranean coast.

OBJECTIVE: To assess first trimester serum 25-hydroxyvitamin D [25(OH)D] status and factors related to deficient levels in pregnant Spanish women. METHODS: This cross-sectional study was carried out among 502 gravids (11 to 14 weeks) living in the Spanish Mediterranean sea coast (near Almería at latitude 36° N, longitude 2° W) to whom serum 25(OH)D levels were measured by electrochemiluminescence immunoassay. Logistic and multiple linear regression analysis were performed to assess the influence of ethnicity, immigration status, season of the year at blood sampling, body mass index (BMI), parity and smoking habit over 25(OH)D levels. RESULTS: The median (interquartile range, IQR) serum 25(OH)D levels for the entire sample was 27.4 ng/mL (IQR = 20.9-32.8). Only 35.9% of participants had adequate serum 25(OH)D levels (≥30 ng/mL) whereas in 41.4% and 22.7% these levels were found to be insufficient (20-29.9 ng/mL) and deficient (<20 ng/mL), respectively. Vitamin D status was found to be significantly lower in Arab women as compared to Caucasian women. 25(OH)D levels were positively correlated with gestational age at sampling and inversely with BMI values (univariate analysis). Logistic regression analysis determined that non-Caucasian ethnicity, season at sampling (autumn/winter), and nulliparity were factors related to deficient 25(OH)D levels. Multiple linear regression found a similar model yet also including maternal weight inversely correlating with 25(OH)D levels. CONCLUSION: Despite living in one of the sunniest, warmest, and driest climates of Europe, gravids displayed a high prevalence of first trimester insufficient/deficient serum 25(OH)D levels related to season at sampling, nulliparity, maternal weight, and non-Caucasian ethnicity.