Showing papers by "Mariana F. Fernández published in 2020"

Bisphenol A shapes children’s brain and behavior: towards an integrated neurotoxicity assessment including human data

Abstract: Concerns about the effects of bisphenol A (BPA) on human brain and behavior are not novel; however, Grohs and colleagues have contributed groundbreaking data on this topic in a recent issue of Environmental Health. For the first time, associations were reported between prenatal BPA exposure and differences in children’s brain microstructure, which appeared to mediate the association between this exposure and children’s behavioral symptoms. Findings in numerous previous mother-child cohorts have pointed in a similar worrying direction, linking higher BPA exposure during pregnancy to more behavioral problems throughout childhood as assessed by neuropsychological questionnaires. Notwithstanding, this body of work has not been adequately considered in risk assessment. From a toxicological perspective, results are now available from the CLARITY-BPA consortium, designed to reconcile academic and regulatory toxicology findings. In fact, the brain has consistently emerged as one of the most sensitive organs disrupted by BPA, even at doses below those considered safe by regulatory agencies such as the European Food Safety Authority (EFSA). In this Commentary, we contextualize the results of Grohs et al. within the setting of previous epidemiologic and CLARITY-BPA data and express our disquiet about the “all-or-nothing” criterion adopted to select human data in a recent EFSA report on the appraisal methodology for their upcoming BPA risk assessment. We discuss the most relevant human studies, identify emerging patterns, and highlight the need for adequate assessment and interpretation of the increasing epidemiologic literature in this field in order to support decision-making. With the aim of avoiding a myopic or biased selection of a few studies in traditional risk assessment procedures, we propose a future reevaluation of BPA focused on neurotoxicity and based on a systematic and comprehensive integration of available mechanistic, animal, and human data. Taken together, the experimental and epidemiologic evidence converge in the same direction: BPA is a probable developmental neurotoxicant at low doses. Accordingly, the precautionary principle should be followed, progressively implementing stringent preventive policies worldwide, including the banning of BPA in food contact materials and thermal receipts, with a focus on the utilization of safer substitutes.

Bisphenols and Oxidative Stress Biomarkers-Associations Found in Human Studies, Evaluation of Methods Used, and Strengths and Weaknesses of the Biomarkers.

Abstract: Bisphenols, particularly bisphenol A (4,4′-(hexafluoroisopropylidene)-diphenol) (BPA), are suspected of inducing oxidative stress in humans, which may be associated with adverse health outcomes. We investigated the associations between exposure to bisphenols and biomarkers of oxidative stress in human studies over the last 12 years (2008‒2019) related to six health endpoints and evaluated their suitability as effect biomarkers. PubMed database searches identified 27 relevant articles that were used for data extraction. In all studies, BPA exposure was reported, whereas some studies also reported other bisphenols. More than a dozen different biomarkers were measured. The most frequently measured biomarkers were 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2α (8-isoprostane) and malondialdehyde (MDA), which almost always were positively associated with BPA. Methodological issues were reported for MDA, mainly the need to handle samples with caution to avoid artefact formation and its measurements using a chromatographic step to distinguish it from similar aldehydes, making some of the MDA results less reliable. Urinary 8-OHdG and 8-isoprostane can be considered the most reliable biomarkers of oxidative stress associated with BPA exposure. Although none of the biomarkers are considered BPA- or organ-specific, the biomarkers can be assessed repeatedly and non-invasively in urine and could help to understand causal relationships.

Exposure to Perflouroalkyl acids and foetal and maternal thyroid status: a review.

Abstract: Exposure to perfluorinated-alkyl-acids (PFAAs) is ubiquitous. PFAAs are hormone-disrupting compounds that are strongly suspected to affect mother-child-health such as fetal growth. Thyroid disruption is a plausible mechanism of action. We aim to summarize the epidemiological evidence for the relation between prenatal and postnatal exposure to PFAAs and disruption of thyroid homeostasis in mothers and/or infants. Fifteen original publications on PFAAs concentrations and thyroid hormones (TH) in pregnant women and/or infants were found upon a literature search in the PubMed database. Information on exposure to seven PFAAs congeners [Perfluorooctane sulfonate (PFOS), Perfluorooctanoate (PFOA), Perfluorohexane sulfonate (PFHxS), Perfluorononanoic acid (PFNA), Perfluorodecanoic acid (PFDA), Perfluoroundecanoic acid (PFUnA), and Perfluorododecanoic acid (PFDoA)] and thyroid stimulating hormone (TSH), free and total thyroxine (FT4 and TT4), free and total triiodothyronine (FT3 and TT3), T3RU (Free triiodothyronine resin uptake) and FT4-index (FT4I) levels were recorded. We evaluated sampling of maternal TH by trimester, and infant TH by sex stratification. Reported associations between mother or infant PFAAs and TH were not uniformly assessed in the selected studies. Ten out of the fifteen studies examined maternal PFAAs concentration and TSH level. Seven studies showed significant associations between TSH and exposure to six PFAAs congeners, most of them were positive. Maternal T4 and T3 were investigated in nine studies and five studies found inverse associations between exposure to six PFAAs congeners and TH (TT3, TT4, FT3, FT4 and FT4I) levels. Eight of the fifteen studies investigated PFAAs concentrations and infant TSH. Infant TSH level was significantly affected in four studies, positively in three studies. Nine studies investigated infant T4 and T3 and seven studies found significant associations with PFAAs exposure. However, both inverse and positive significant associations with infant TH were found eliciting no clear direction. Results indicate a mainly positive relationship between maternal PFAAs concentrations and TSH levels, and suggestion of an inverse association with T4 and/or T3 levels. Associations of infant TH with PFAAs concentration were less consistent.

Association of Urinary Levels of Bisphenols A, F, and S with Endometriosis Risk: Preliminary Results of the EndEA Study

Abstract: Aim: The aim of this study was to explore associations of urinary concentrations of bisphenols A (BPA), S (BPS), and F (BPF) and of thiobarbituric acid reactive substances (TBARS) with the risk of endometriosis in women of childbearing age. Methods: This case-control study enrolled 124 women between January 2018 and July 2019: 35 women with endometriosis (cases) and 89 women without endometriosis undergoing abdominal surgery for other reasons (controls). Endometriosis was diagnosed (cases) or ruled out (controls) by laparoscopic inspection of the pelvis and the biopsy of suspected lesions (histological diagnosis). Fasting urine samples were collected before surgery to determine concentrations of BPA, BPS, BPF, and TBARS. Associations of bisphenol and TBARS concentrations with endometriosis risk were explored with multivariate logistic and linear regression analyses. Results: After adjustment for urinary creatinine, age, BMI, parity, and residence, endometriosis risk was increased with each 1 log unit of BPA [OR 1.5; 95%CI 1.0-2.3] and Σbisphenols [OR 1.5; 95%CI 0.9-2.3] but was not associated with the presence of BPS and BPF. Classification of the women by tertiles of exposure revealed statistically significant associations between endometriosis risk and the second tertile of exposure to BPA [OR 3.7; 95%CI 1.3-10.3] and Σbisphenols [OR 5.4; 95%CI 1.9-15.6]. In addition, TBARS concentrations showed a close-to-significant relationship with increased endometriosis risk [OR 1.6; 95%CI 1.0-2.8], and classification by TBARS concentration tertile revealed that the association between endometriosis risk and concentrations of BPA [OR 2.0; 95%CI 1.0-4.1] and Σbisphenols [OR 2.2; 95%CI 1.0-4.6] was only statistically significant for women in the highest TBARS tertile (>4.23 μM). Conclusion: Exposure to bisphenols may increase the risk of endometriosis, and oxidative stress may play a crucial role in this association. Further studies are warranted to verify these findings.

Influence of a Multidisciplinary Program of Diet, Exercise, and Mindfulness on the Quality of Life of Stage IIA-IIB Breast Cancer Survivors.

Abstract: Background: Integrative oncology has proven to be a useful approach to control cancer symptoms and improve the quality of life (QoL) and overall health of patients, delivering integrated patient care at both physical and emotional levels. The objective of this randomized trial was to evaluate the effects of a triple intervention program on the QoL and lifestyle of women with breast cancer. Methods: Seventy-five survivors of stage IIA-IIB breast cancer were randomized into 2 groups. The intervention group (IG) received a 6-month dietary, exercise, and mindfulness program that was not offered to the control group (CG). Data were gathered at baseline and at 6 months postintervention on QoL and adherence to Mediterranean diet using clinical markers and validated questionnaires. Between-group differences at baseline and 3 months postintervention were analyzed using Student's t test for related samples and the Wilcoxon and Mann-Whitney U tests. Results: At 6 months postintervention, the IG showed significant improvements versus CG in physical functioning (p = .027), role functioning (p = .028), and Mediterranean diet adherence (p = .02) and a significant reduction in body mass index (p = .04) and weight (p = .05), with a mean weight loss of 0.7 kg versus a gain of 0.55 kg by the CG (p = .05). Dyspnea symptoms were also increased in the CG versus IG (p = .066). Conclusions: These results demonstrate that an integrative dietary, physical activity, and mindfulness program enhances the QoL and healthy lifestyle of stage IIA-IIB breast cancer survivors. Cancer symptoms may be better managed by the implementation of multimodal rather than isolated interventions.

Reproducibility and Validity of a Food Frequency Questionnaire for Dietary Assessment in Adolescents in a Self-Reported Way.

Abstract: 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.