Reduction in Placental Metal and Metalloid in Preeclampsia: A Case-Control Study.

Preeclampsia is a primary placental disorder, with impaired placental vascularization leading to uteroplacental hypoperfusion. We aimed to investigate differences in metal and metalloid content between the placentas of women with preeclampsia and healthy controls. This was a case-control study in 63 women with preeclampsia and 113 healthy women. Clinical data were obtained from medical records. Inductively coupled plasma mass spectrometry (ICP-MS) was used to measure the placental metals and metalloids content. Compared with healthy control subjects, preeclampsia was associated with a significantly lower concentration of essential elements (magnesium, calcium, iron, copper, zinc, and selenium) in the placental tissue. After multivariable adjustment, an interquartile range (IQR) increase in selenium concentration was associated with a reduced risk of preeclampsia with an OR of 0.50 (95% CI: 0.33-0.77). The joint effects of multiple selected metals and metalloids were associated with a reduced risk of preeclampsia. The lower placental magnesium, chromium, iron, zinc, and selenium concentrations of preeclampsia cases indicate a potential link to its pathogenesis. It also provides an intriguing avenue for future research in revealing the underlying mechanisms and potential intervention strategies for preeclampsia.

Human placenta releases extracellular vesicles carrying corticotrophin releasing hormone mRNA into the maternal blood.

The human placenta releases diverse extracellular vesicles (EVs), including microvesicles (100-1000 nm) and exosomes (30-150 nm), into the maternal blood for feto-maternal communication. Exosomes and microvesicles contribute to normal pregnancy physiology and major pregnancy pathologies. Differences in miRNA expressions and protein content in placental exosomes have been reported in complicated pregnancies. During human pregnancy, Corticotropin-Releasing Hormone (CRH) is produced and released by the placenta into the maternal blood. CRH is involved in regulating gestational length and the initiation of labour. CRH mRNA levels in the maternal plasma rise with gestation. High levels of CRH mRNA are reported to be associated with preeclamptic and preterm pregnancies. However, the underlying mechanism of placental CRH mRNA secretion remains to be elucidated. We hypothesise that the placenta releases CRH mRNA packaged within extracellular vesicles (EVs) into the maternal blood. In this study, placental EVs (microvesicles and exosomes) were isolated from human term healthy placentas via villus washes and from explant culture media by differential centrifugation and purified by density gradient ultracentrifugation using a continuous sucrose gradient (0.25-2.5 M). Western blotting using placenta- and exosome-specific markers and electron microscopy confirmed exosomes and microvesicles in the placental wash and explant media samples. Real-time quantitative RT-PCR data detected CRH mRNA in placenta-derived EVs from placental washes and explants. We also sorted placenta-secreted EVs in maternal plasma samples (≥37 weeks) by high-resolution flow cytometry using a fluorescent-labelled PLAP antibody. CRH mRNA was demonstrated in placental EVs obtained from maternal blood plasma. We therefore show that human placental EVs carry CRH mRNA into the maternal blood. Our study implies that measuring CRH mRNA in placental EVs in the maternal plasma could beused for monitoring pregnancy.

Assessing chronic gestational exposure to environmental chemicals in pregnant women: Advancing the co-PBK model.

Vulnerable populations, such as pregnant women and their fetuses, confront potential health risks due to exposure to environmental toxic compounds. Computational methods have been popular in assessing chemical exposure to populations, contrasting with traditional cohort studies for human biomonitoring. This study proposes a screening-level approach based on physiologically based kinetic (PBK) modeling to evaluate the steady-state exposure of pregnant women to environmental chemicals throughout pregnancy. To exemplify the modeling application, naphthalene was chosen. Simulation results indicated that maternal fat exhibited significant bioaccumulation potential, with the log-transformed BTF of naphthalene at 0.51 mg kg-1 per mg d-1 in the steady state. The placenta was primarily exposed to 0.83 mg/d naphthalene for a 75.2 kg pregnant woman, considering all exposure routes. In the fetal structure, single-organ fetal PBK modeling estimated a naphthalene exposure of 123.64 mg/d to the entire fetus, while multiple-organ fetal PBK modeling further revealed the bioaccumulation highest in fat tissue. The liver identified as the vital organ for metabolism, kBioT,LiverM was demonstrated with the highest sensitivity among rate constants in the maternal body. Furthermore, the first-order kinetic rate constants related to the placenta and blood were found to impact the distribution process of naphthalene in the fetus, influencing gestational exposure. In conclusion, urgent attention is needed to develop a computational biomonitoring tool for assessing toxic chemical exposure in vulnerable populations.

Disaccharide compositional analysis of chondroitin sulphate using WAX HILIC-MS with pre-column procainamide labelling; application to the placenta in pre-eclampsia.

Chondroitin sulphate (CS) and dermatan sulphate are negatively charged linear heteropolysaccharides. These glycosaminoglycans (GAG) are involved in cellular signalling via binding to growth factors. CS is expressed in a range of tissue and biological fluids and is highly expressed in the placenta. There is evidence that decorin; a CS proteoglycan is significantly decreased in pre-eclampsia and fetal growth restriction. It is considered that GAG chain composition may influence cellular processes that are altered in pre-eclampsia. The goal of the present study was to develop an LC-MS method with precolumn procainamide labelling for the disaccharide compositional analysis of CS. The method was used to investigate whether the disaccharide composition of placenta-extracted CS is altered in pre-eclampsia. The study revealed differential disaccharide compositions of placental chondroitin sulphate between pre-eclampsia and other pregnancy conditions. This suggests that the method may have diagnostic potential for pregnancy disorders. Furthermore, the findings suggest that CS sulphation might play a significant role in maternal labour.

Prenatal exposure to fine particulate matter chemical constituents and the risk of stillbirth and the mediating role of pregnancy complications: A cohort study.

Evidence on the association of fine particulate matter (PM2.5) exposure with stillbirth is limited and inconsistent, which is largely attributed to differences in PM2.5 constituents. Studies have found that the hazards of certain PM2.5 constituents to the fetus are comparable to or even higher than total PM2.5 mass. However, few studies have linked PM2.5 constituents to stillbirth. Moreover, the mediating role of pregnancy complications in PM2.5-related stillbirth remains unclear. To our knowledge, this study was the first to explore the individual and mixed associations of PM2.5 and its constituents with stillbirth in China. After matching the concentrations of PM2.5 and its constituents (sulfate [SO42-], nitrate [NO3-], ammonium [NH4+], organic matter [OM], and black carbon [BC]) for participants according to their geographical location, there were 170,507 participants included in this study. We found that stillbirth was associated with exposure to PM2.5 and its constituents in the year before pregnancy and during the entire pregnancy, and the associations in trimester 1 were strongest. The risk of stillbirth increased sharply when PM2.5 and its constituents during pregnancy exceeded the median concentrations. Moreover, stillbirth was associated with exposure to the mixtures of SO42-, NO3-, NH4+, OM, and BC before and during pregnancy (trimesters 1 and 2). Meanwhile, two-pollutant models also suggested stillbirth was associated with PM2.5 and its constituents in the year before and during pregnancy. The associations of PM2.5 and its constituents with stillbirth were stronger in mothers with advanced age and without cesarean delivery history. Additionally, hypertensive disorders in pregnancy, gestational diabetes, and placental abruption mediated the association of PM2.5 with stillbirth. Therefore, enhanced protection against PM2.5 for pregnant women before and during pregnancy and targeted interventions for pregnancy complications and anthropogenic sources of PM2.5 constituents are important to reduce stillbirth risk.

Placental concentrations of xenoestrogenic organochlorine pesticides and polychlorinated biphenyls and assessment of their xenoestrogenicity in the PA-MAMI mother-child cohort.

BACKGROUND: Organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCB), they have contributed to the exposure of women to persistent organic pollutants (POPs). These compounds can cross the placental barrier and interfere with the hormonal system of newborns. AIM: To determine concentrations of OCPs and PCBs and their xenoestrogenic activity in placentas of women from the PA-MAMI cohort of Panama. METHODS: Thirty-nine placenta samples from women in the Azuero peninsula (Panama) were analyzed. Five OCPs [p-p'-dichlorodiphenyldichloroethylene (p-p'-DDE), beta-hexachlorohexane (ß-HCH), γ-hexachlorohexane (lindane), hexachlorobenzene (HCB) and mirex] and three PCB congeners (PCB-138, PCB-153 and PCB-180) were quantified in placenta extracts. The xenoestrogenic activity of extracts was assessed with the E-Screen bioassay to estimate the total effective xenoestrogen burden (TEXB). RESULTS: All placental samples were positive for at least three POP residues and >70% for at least six. The frequencies of quantified OCPs ranged from 100% for p,p'-DDE and HCB to 30.8% for ß-HCH. The highest median concentration was for lindane (380.0 pg/g placenta), followed by p,p'-DDE (280.0 pg/g placenta), and HCB (90.0 pg/g placenta). Exposure to p,p'-DDE was associated with greater meat consumption, suggesting that animal fat is a major source of exposure to DDT metabolites. The frequency of detected PCBs ranged between 70 and 90%; the highest median concentration was for PCB 138 (17.0 pg/g placenta), followed by PCB 153 (16.0 pg/g placenta). All placentas were positive in the estrogenicity bioassay with a median TEXB-α of 0.91 pM Eeq/g of placenta. Exposure to lindane was positively associated with the xenoestrogenicity of TEXB- α, whereas this association was negative in the case of exposure to PCB 153. CONCLUSIONS: To our best knowledge, this study contributes the first evidence on the presence of POPs and xenoestrogenic burden in placentas from Latin-American women. Given concerns about the consequences of prenatal exposure to these compounds on children's health, preventive measures are highly recommended to eliminate or minimize the risk of OCP exposure during pregnancy.

Exposure levels and determinants of placental polybrominated diphenyl ethers in Chinese pregnant women.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are a group of widely used chemicals and humans are exposed to them in their daily life. PBDEs exposure during pregnancy may have adverse effects on pregnant women and their fetuses. Nevertheless, limited information is available on the levels and determinants of PBDEs exposure in Chinese pregnant women. METHODS: The internal exposure levels of eight PBDEs (BDE-28, 47, 99, 100, 153, 154, 183, and 209) in placental samples of 1280 pregnant women from Zunyi birth cohort were analyzed using gas chromatography tandem mass spectrometry. All PBDEs concentrations were lipid adjusted (ng/g lw). Determinants of exposure were assessed by multivariable logistic regression model. RESULTS: Eight PBDE homologues were quantifiable in more than 70% of the samples. The highest median concentrations were found for BDE-209 (2.78 ng/g lw), followed by BDE-153 (1.00 ng/g lw) and BDE-183 (0.93 ng/g lw). The level of ΣPBDEs ranged from 0.90 to 308.78 ng/g lw, with a median concentration of 10.02 ng/g lw. Multivariate logistic regression analysis showed that maternal age older than 30 years old (OR: 1.59; 95% CI: 1.14, 2.23), pre-pregnancy obesity (1.51; 1.08, 2.10), home renovation within 2 years (1.43; 1.08, 1.91), spending more time outdoors during pregnancy (0.70; 0.55, 0.89), high consumption of fish/seafood (1.46; 1.13, 1.90) and eggs (1.44; 1.04, 2.00), male infant sex (1.69; 1.18, 2.42) were associated with PBDEs exposure. CONCLUSION: The study population is generally exposed to PBDEs, of which BDE-209 is the dominant congener, indicating extensive application of products containing deca-BDE mixtures. Maternal age, pre-pregnancy BMI, home decoration, average outdoor time during pregnancy, fish, seafood, eggs consumption, and fetal sex were exposure-determinning factors. This study contributes to the knowledge on region-specific PBDEs contamination in pregnant women and related risk factors.

Is carbon monoxide testing in pregnancy an acceptable and effective smoking cessation initiative? An integrative systematic review of evidence.

PROBLEM: Over 25000 Australian women smoke during pregnancy each year, with risks to mother and baby including miscarriage, pre-eclampsia, placental issues, premature birth, and stillbirth. BACKGROUND: Carbon Monoxide testing has been introduced in antenatal care settings to help identify smokers and motivate them to quit. AIM: This integrative systematic review aims to take a holistic look at Carbon Monoxide (CO) testing to understand how effective and acceptable this practice is in antenatal care. METHODS: PubMed, Scopus and CINAHL were searched for literature relating to pregnant women where CO testing has been used to identify smoking as part of a smoking cessation initiative. The search results were then screened and reviewed independently by two authors. A total of 15 studies were deemed relevant and proceeded to quality appraisal using the Crowe Critical Appraisal Tool. A Narrative Synthesis method was used to present the findings. DISCUSSION: Synthesis resulted in four themes: smoking identification and referral to cessation support, smoking cessation, midwifery usability of CO testing and women's perception of CO testing. Whilst carbon monoxide testing increased the identification and referral to cessation support for pregnant smokers, it did not make an overall difference to smoking cessation rates. Midwives frequently report having too little time to conduct carbon monoxide testing. Findings suggest that women accept the test, but their opinions are under-represented in the existing evidence. Midwives and women report concern for the midwife/woman relationship if testing is not conducted well. CONCLUSION: Whilst carbon monoxide testing can identify smoking, it does not appear to motivate pregnant smokers to quit.

Prenatal exposure to air pollution and BWGA Z-score: Modifying effects of placenta leukocyte telomere length and infant sex.

BACKGROUND: Air pollutants, such as fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3), have been associated with adverse birth outcomes, including low birth weight, often exhibiting sex-specific effects. However, the modifying effect of placental telomere length (TL), reflecting cumulative lifetime oxidative stress in mothers, remains unexplored. METHOD: Using data from a Northeastern U.S. birth cohort (n = 306), we employed linear regression and weighted quantile sum models to assess trimester-average air pollution exposures and birth weight for gestational age (BWGA) z-scores. Placental TL, categorized by median split, was considered as an effect modifier. Interactions among air pollutants, placental TL, infant sex, and BWGA z-score were evaluated. RESULTS: Without placental TL as a modifier, only 1st trimester O3 was significantly associated with BWGA z-scores (coefficient: 0.33, 95% CI: 0.03, 0.63). In models considering TL interactions, a significant modifying effect was observed between 3rd trimester NO2 and BWGA z-scores (interaction p-value = 0.02). Specifically, a one interquartile range (1-IQR) increase in 3rd trimester NO2 was linked to a 0.28 (95% CI: 0.06, 0.52) change in BWGA z-score among shorter placental TL group, with no significant association among longer TL group. Among male infants, there were significant associations between 3rd trimester PM2.5 exposure and BWGA z-scores in the longer TL group (coefficient: -0.34, 95% CI: -0.61, -0.02), and between 1st trimester O3 exposure and BWGA z-scores among males in the shorter TL group (coefficient: 0.59, 95% CI: 0.06, 1.08). For females, only a negative association in 2nd trimester mixture model was observed within the longer TL group (coefficient: -0.10, 95% CI: -0.21, -0.01). CONCLUSION: These findings highlight the need to consider the complex interactions among prenatal air pollutant exposures, placental TL, and fetal sex to better elucidate those at greatest risk for adverse birth outcomes.

Exposure to pesticides during pregnancy and the risk of neural tube defects: A systematic review.

Exposure to pesticides during pregnancy has been associated with several serious congenital malformations, such as neural tube defects, therefore, is a cause for concern in terms of human health. This review aims to gather information related to maternal exposure during pregnancy and the risk of triggering neural tube defects in the offspring. The search strategy for the studies followed the PRISMA guidelines. We conducted a systematic search in the Science Direct, PubMed, Cochrane Library, Embase, Scopus, and Web of Science databases for all epidemiological studies that sought to associate exposure to pesticides during embryonic development with the risk of neural tube defects (NTDs). The keywords used were "pesticide", "herbicide", "congenital" and "neural". Of the 229 articles, 8 eligible ones (7 case-control and 1 cross-sectional) evaluated pesticide exposure in pregnancy. Different methods were used, including analysis of biological samples and questionnaires. The pesticides studied included insecticides, herbicides, fungicides, and nematicides. Insecticides were the most studied, with variations in concentrations between tissues and studies. Distinct levels of pesticides have been detected in maternal serum, placenta, and umbilical cord. Models were statistically adjusted for confounding factors, such as smoking and dietary supplement intakes. Concentrations were measured in different exposure windows (periconception and prenatal), related to NTDs such as anencephaly and spina bifida. Different data collection techniques, types of biological samples, and exposure windows were used, which made comparison difficult. The main pesticides studied included DDT, DDE, HCH, and endosulfan. Maternal serum showed the highest concentrations of pesticides, but detection in placental tissue and umbilical cord confirms embryonic exposure. Confounding variables were adjusted for in the analysis of the articles, but they may still contribute to the risk of NTDs. All the studies analyzed pesticide exposure and the relationship with NTDs. However, a more standardized survey would be ideal for better comparisons.

DNA methylation profiles reveal sex-specific associations between gestational exposure to ambient air pollution and placenta cell-type composition in the PRISM cohort study.

BACKGROUND: Gestational exposure to ambient air pollution has been associated with adverse health outcomes for mothers and newborns. The placenta is a central regulator of the in utero environment that orchestrates development and postnatal life via fetal programming. Ambient air pollution contaminants can reach the placenta and have been shown to alter bulk placental tissue DNA methylation patterns. Yet the effect of air pollution on placental cell-type composition has not been examined. We aimed to investigate whether the exposure to ambient air pollution during gestation is associated with placental cell types inferred from DNA methylation profiles. METHODS: We leveraged data from 226 mother-infant pairs in the Programming of Intergenerational Stress Mechanisms (PRISM) longitudinal cohort in the Northeastern US. Daily concentrations of fine particulate matter (PM2.5) at 1 km spatial resolution were estimated from a spatiotemporal model developed with satellite data and linked to womens' addresses during pregnancy and infants' date of birth. The proportions of six cell types [syncytiotrophoblasts, trophoblasts, stromal, endothelial, Hofbauer and nucleated red blood cells (nRBCs)] were derived from placental tissue 450K DNA methylation array. We applied compositional regression to examine overall changes in placenta cell-type composition related to PM2.5 average by pregnancy trimester. We also investigated the association between PM2.5 and individual cell types using beta regression. All analyses were performed in the overall sample and stratified by infant sex adjusted for covariates. RESULTS: In male infants, first trimester (T1) PM2.5 was associated with changes in placental cell composition (p = 0.03), driven by a decrease [per one PM2.5 interquartile range (IQR)] of 0.037 in the syncytiotrophoblasts proportion (95% confidence interval (CI) [- 0.066, - 0.012]), accompanied by an increase in trophoblasts of 0.033 (95% CI: [0.009, 0.064]). In females, second and third trimester PM2.5 were associated with overall changes in placental cell-type composition (T2: p = 0.040; T3: p = 0.049), with a decrease in the nRBC proportion. Individual cell-type analysis with beta regression showed similar results with an additional association found for third trimester PM2.5 and stromal cells in females (decrease of 0.054, p = 0.024). CONCLUSION: Gestational exposure to air pollution was associated with placenta cell composition. Further research is needed to corroborate these findings and evaluate their role in PM2.5-related impact in the placenta and consequent fetal programming.

Characteristic and health risk of per- and polyfluoroalkyl substances from cosmetics via dermal exposure.

In this work, 45 cosmetic samples were collected from China, and 27 target per- and polyfluoroalkyl substances (PFAS) were analyzed by ultrahigh-performance liquid chromatography-high resolution mass spectrometry. PFAS were found in all samples, including the products marketed for pregnant women, and the total concentrations of PFAS measured in each sample were in the range of 4.05 - 94.9 ng/g. Short-chain perfluorinated carboxylic acids were the dominant compounds contributing to over 60% of the total content. Perfluorobutanoic acid, with high placental transfer efficiency, was the major PFAS in cosmetics for pregnant women. Three emerging PFAS, 2-perfluorohexyl ethanoic acid, 3-perfluoropentyl propanoic acid (5:3) and perfluoro-2-propoxypropanoic acid, were also identified in the cosmetic samples at quantifiable levels. Significantly, positive correlations between individual PFAS were observed, indicating that there may be a common source for PFAS in these samples. Statistical analyses suggested that using plastic containers and precursor substances may be potential sources of PFAS in terminal products, and product aging may increase PFAS levels. From the PFAS analysis of the cosmetics, the margin of safety (MoS) and hazard quotient (HQ) were calculated to assess human health risks through dermal exposure by using these products. Although the MoS and HQ values obtained were deemed acceptable, the cumulative effect caused by composite and long-term exposure to these contaminants needs to be given greater attention by health authorities.

Early life exposure to F-53B induces neurobehavioral changes in developing children and disturbs dopamine-dependent synaptic signaling in weaning mice.

BACKGROUND: Previous studies have shown that F-53B exposure may be neurotoxic to animals, but there is a lack of epidemiological evidence, and its mechanism needs further investigation. METHODS: Serum F-53B concentrations and Wisconsin Card Sorting Test (WCST) were evaluated in 314 growing children from Guangzhou, China, and the association between them were analyzed. To study the developmental neurotoxicity of F-53B, experiments on sucking mice exposed via placental transfer and breast milk was performed. Maternal mice were orally exposed to 4, 40, and 400 µg/L of F-53B from postnatal day 0 (GD0) to postnatal day 21 (PND 21). Several genes and proteins related to neurodevelopment, dopamine anabolism, and synaptic plasticity were examined by qPCR and western blot, respectively, while dopamine contents were detected by ELISA kit in weaning mice. RESULTS: The result showed that F-53B was positively associated with poor WCST performance. For example, with an interquartile range increase in F-53B, the change with 95 % confidence interval (CI) of correct response (CR), and non-perseverative errors (NPE) was -2.47 (95 % CI: -3.89, -1.05, P = 0.001), 2.78 (95 % CI: 0.79, 4.76, P = 0.007), respectively. Compared with the control group, the highest exposure group of weaning mice had a longer escape latency (35.24 s vs. 51.18 s, P = 0.034) and a lesser distance movement (34.81 % vs. 21.02 %, P < 0.001) in the target quadrant, as observed from morris water maze (MWM) test. The protein expression of brain-derived neurotrophic factor (BDNF) and growth associated protein-43 (GAP-43) levels were decreased, as compared to control (0.367-fold, P < 0.001; 0.366-fold, P < 0.001; respectively). We also observed the upregulation of dopamine transporter (DAT) (2.940-fold, P < 0.001) consistent with the trend of dopamine content (1.313-fold, P < 0.001) in the hippocampus. CONCLUSION: Early life exposure to F-53B is associated with adverse neurobehavioral changes in developing children and weaning mice which may be modulated by dopamine-dependent synaptic plasticity.

[Heavy metal exposure and reproductive toxicity: Advances in studies].

Heavy metals are among the major pollutants affecting the environment, with a higher density of metal element than that of water and an extensive presence in the natural environment. Trace elements such as zinc, copper, nickel and chromium mediate important physiological functions and metabolic regulation at normal levels, and insufficient intake of them will lead to related diseases. Heavy metals such as cadmium, lead and mercury do not participate in the normal metabolism of the human body and will cause damage to the body even at an extremely low dose. Heavy metal pollution mainly comes from industrial wastewater, fossil fuel combustion, wastewater, smelting, mining, vehicle exhaust, hazardous waste dumping, and fertilizer abuse. Unable to be biodegraded, heavy metals have a long biological half-life in nature, which in turn leads to bio-accumulation and -amplification. Eating contaminated vegetables is one way of being exposed to heavy metals. Heavy metals produce adverse effects not only on the human reproductive system, but also on the fetus by penetrating the placental barrier, and on the hypothalamic-pituitary-gonadal axis as well, consequently affecting sexual maturation and reproductive function. With the sharp increase of heavy metals in the environment, researches on their reproductive toxicity and antagonistic drugs have an important clinical significance.

Assessment of urinary aromatic amines in Brazilian pregnant women and association with DNA damage: Influence of genetic diversity, lifestyle, and environmental and socioeconomic factors.

Aromatic amines (AAs) are polar organic chemicals with a wide environmental distribution originating from various sources, such as tobacco smoke, diesel exhaust, and dermal absorption from textile products with azo dyes. The toxicity profile of AAs is directly related to the amino group's metabolic activation and the generation of the reactive intermediate, forming DNA adducts and potential carcinogenicity. Urinary levels of 8-hydroxy-2'-deoxyguanosine (8OHdG) are an important biomarker of DNA damage. Since AAs have been shown to cross the placental barrier, being a risk factor for adverse birth outcomes, prenatal exposure is a great public health concern. The present study aimed to measure the urinary levels of 58 AAs in Brazilian pregnant women (n = 300) and investigated the impact of this exposure on DNA damage by quantifying 8OHdG levels. The influence of tobacco smoke exposure and dermal absorption of AAs by clothes on urinary levels was also assessed. The results showed a 100% detection rate for eight AAs, two of them regulated by the European Union (2,6-dimethylaniline and 2,4-diaminotolune). Hundreds of AAs may be derived from aniline, which here showed a median of 1.38 ng/mL. Aniline also correlated positively with 2,6-dimethylaniline, p-aminophenol, and other AAs, suggesting exposure to multiple sources. The present findings suggest that both tobacco smoke and dermal contact with clothes containing azo dyes are potential sources that might strongly influence urinary levels of AAs in Brazilian pregnant women. A multiple regression linear model (R2 = 0.772) suggested that some regulated AAs (i.e., 2-naphthylamine and 4-aminobiphenyl), nicotine, smoke habit, age, and Brazilian region could induce DNA damage occurrence, increasing the levels of 8OHdG. Given the limited available data on human exposure to carcinogenic AAs, as well as the lack of toxicological information on those non-regulated, further studies focused on measuring their levels in human fluids and the potential exposure sources are clearly essential.

Identifying sensitive windows of prenatal household air pollution on birth weight and infant pneumonia risk to inform future interventions.

BACKGROUND: Prenatal household air pollution impairs birth weight and increases pneumonia risk however time-varying associations have not been elucidated and may have implications for the timing of public health interventions. METHODS: The Ghana Randomized Air Pollution and Health Study (GRAPHS) enrolled 1,414 pregnant women from Kintampo, Ghana and measured personal carbon monoxide (CO) exposure four times over pregnancy. Birth weight was measured within 72-hours of birth. Fieldworkers performed weekly pneumonia surveillance and referred sick children to study physicians. The primary pneumonia outcome was one or more physician-diagnosed severe pneumonia episode in the first year of life. We employed reverse distributed lag models to examine time-varying associations between prenatal CO exposure and birth weight and infant pneumonia risk. RESULTS: Analyses included n = 1,196 mother-infant pairs. In models adjusting for child sex; maternal age, body mass index (BMI), ethnicity and parity at enrollment; household wealth index; number of antenatal visits; and evidence of placental malaria, prenatal CO exposures from 15 to 20 weeks gestation were inversely associated with birth weight. Sex-stratified models identified a similar sensitive window in males and a window at 10-weeks gestation in females. In models adjusting for child sex, maternal age, BMI and ethnicity, household wealth index, gestational age at delivery and average postnatal child CO exposure, CO exposure during 34-39 weeks gestation were positively associated with severe pneumonia risk, especially in females. CONCLUSIONS: Household air pollution exposures in mid- and late- gestation are associated with lower birth weight and higher pneumonia risk, respectively. These findings support the urgent need for deployment of clean fuel stove interventions beginning in early pregnancy.

Xeno-estrogenic activity of real-life mixtures of perfluoroalkylated substances in human placenta homogenates.

Humans are simultaneously exposed to complex chemical mixtures, and its combined effect can affect human health. As part of the HBM4EU project, the actual mixture of perfluoroalkylated substances (PFAS) in 25 human placenta samples was extracted by chromatographic methods and assessed for xeno-estrogenic activity using two in-vitro bioassays: the estrogen receptor transactivity and the E-Screen assay. Most of the PFAS extracts displayed xeno-estrogenic activity, in one or both assays. The xeno-estrogenic activities in the two bioassays were not correlated, but both assays showed an overall negative correlation with placenta concentrations of single PFAS. Xeno-estrogenic activities were significantly related to maternal characteristics; being higher in young, smokers and primiparous women, but not with fetal growth (birth weight, birth length, head circumference, gestational age, placenta weight). The presented extraction method can be used to study the combined effect of real-life mixtures of PFAS in relation to health outcomes in large-scale human biomonitoring studies.

Associations among bisphenol A, its analogs, and chlorinated derivatives in placenta and risk for neural tube defects: A case-control study.

Bisphenol A (BPA) and its analogs such as bisphenol Z (BPZ) are widely used in the production of consumer products, but few studies have investigated the associations among BPA, its analogs, and chlorinated derivatives (collectively, BPs) and risk for NTDs. This study investigated the associations between concentrations of BPs in the placenta and risk for NTDs. This was a case-control study including 122 NTDs and 164 controls. BPs in the placenta were determined using liquid chromatography-tandem mass spectrometry. The associations between BPs and NTD risk were evaluated using conventional logistic regression and weighted quantile sum regression (WQS) models. In the logistic regression, exposure to higher levels of BPA and BPZ was associated with increased NTD risk (odds ratio [OR] = 3.17, 95 % confidence interval [CI], 1.22-8.22; OR = 3.11, 95 % CI, 1.20-8.09, respectively). Meanwhile, a significant dose-response relationship was found between BPA and BPZ concentrations and NTD risk. In the WQS model, a quartile increase in WQS index resulted in 4.34 (95 % CI: 1.69, 11.20) higher odds for NTDs, and BPA and BPZ accounted for most of the weight index in the joint effects of BPs. In conclusion, high levels of BPs in the placenta are associated with increased risk for NTDs, of which BPA and BPZ are important risk factors.

Placental expression of striatin & endothelial nitric oxide synthase in women with & without pre-eclampsia.

Background & objectives: Striatin is a multi-domain scaffolding protein essential for activating endothelial nitric oxide synthase (eNOS). However, its role in pre-eclampsia remains use explored. Hence, this study aimed to investigate the association between striatin and eNOS in regulating nitric oxide (NO) production in the placenta of women with and without pre-eclampsia. Methods: Forty pregnant women each without (controls) and with pre-eclampsia (cases) were enrolled in the study. Blood striatin and NO concentrations were detected by the ELISA. Protein expression of striatin, phosphorylated eNOS (peNOS), inducible NOS (iNOS) and phosphorylated NF-κB were measured in the placental tissues by Western blot. Twenty four hour urinary protein and serum urea, uric acid and creatinine were analyzed as an autoanalyzer. Placental histology was analyzed by haematoxylin and eosin staining. Results: Compared to normotensive pregnant women, the levels of serum NO and striatin were decreased in pre-eclamptic women. The protein expression of striatin and peNOS was significantly reduced (P<0.05) while p65NF-κB and iNOS were upregulated considerably (P<0.05) in the placenta of cases compared to controls. Interpretation & conclusions: Our results show for the first time that decreased striatin expression was associated with decreased peNOS protein expression in the placental tissue of pre-eclamptic women. Interestingly, no significant difference was found in blood striatin or NO levels between controls and cases. Thus, therapies that improve placental striatin expression are attractive possibilities, both for prevention as well as treatment of endothelial dysfunction in pre-eclampsia.

Pesticides exposure in pregnant Argentinian women: Potential relations with the residence areas and the anthropometric neonate parameters.

Intrauterine environment is the first chemical exposure scenario in life, through transplacental transfer. In this study, the aim was to determine concentrations of organochlorine pesticides (OCPs) and selected current use pesticides in the placentas of pregnant women from Argentina. Socio-demographic information, the mother's lifestyle and neonatal characteristics were also analysed and related to pesticides residue concentrations. Thus, 85 placentas were collected at birth, from an area of intensive fruit production for the international market, in Patagonia Argentina. Concentrations of 23 pesticides including, trifluralin (herbicide), the fungicides chlorothalonil and HCB, and the insecticides chlorpyrifos, HCHs, endosulfans, DDTs, chlordanes, heptachlors, drins and metoxichlor, were determined by GC-ECD and GC-MS. Results were first analysed all together and then grouped by their residential settings, in urban and rural groups. Total mean pesticide concentration was 582.6 ± 1034.4 ng/g lw, where DDTs (325.9 ± 950.3 ng/g lw) and chlorpyrifos (188.4 ± 365.4 ng/g lw) showed a high contribution. Pesticide levels found exceeded those reported in low, middle and high income countries from Europe, Asia and Africa. In general, pesticides concentrations were not associated with neonatal anthropometric parameters. When the results were analysed by residence place, significantly higher concentrations of total pesticides and chlorpyrifos (Mann Whitney test p = 0.0003 and p = 0.032, respectively) were observed in placentas collected from mothers living in rural settings compared to urban areas. Rural pregnant women presented the highest pesticide burden (5.9 µg), where DDTs and chlorpyrifos were the major constituents. These results suggested that all pregnant women are highly exposed to complex pesticide mixtures, including banned OCPs and the widely used chlorpyrifos. Based on the pesticide concentrations found, our results warn of possible health impacts from prenatal exposure through transplacental transfer. This is one of the first reports of both chlorpyrifos and chlorothalonil concentrations in placental tissue, and contributes to the knowledge of current pesticide exposure in Argentina.