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Endocrine disrupting compounds (EDCs) need to be removed by efficient treatment methods as they are a major concern for both human and environmental health. To reduce the impact of EDCs in water, this review examines the use of ultrasonic degradation processes. Following an overview of EDCs and their origins, the basic concepts of sonochemistry are examined, highlighting the potential of ultrasound in chemical reactions. An in-depth analysis of the variables that affect the ultrasonic degradation of EDCs, such as frequency, intensity/power, temperature and solution chemistry, prepares the reader for a case study investigation focusing on specific EDCs. The study also looks at synergistic methods, emphasizing how hybrid ultrasonic systems can improve removal efficiency. The study provides a comprehensive overview of the use of sonochemistry in the treatment of EDCs by addressing current issues and suggesting future research directions. The aim of this review paper is to provide insightful analysis and useful suggestions for scientists working on EDC remediation projects.

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The continuous and rapid increase of chemical pollution in surface waters has become a pressing and widely recognized global concern. As emerging contaminants (ECs) in surface waters, pharmaceutical and personal care products (PPCPs), and endocrine-disrupting compounds (EDCs) have attracted considerable attention due to their wide occurrence and potential threat to human health. Therefore, a comprehensive understanding of the occurrence and risks of ECs in Chinese surface waters is urgently required. This study summarizes and assesses the environmental occurrence concentrations and ecological risks of 42 pharmaceuticals, 15 personal care products (PCPs), and 20 EDCs frequently detected in Chinese surface waters. The ECs were primarily detected in China's densely populated and highly industrialized regions. Most detected PPCPs and EDCs had concentrations between ng/L to µg/L, whereas norfloxacin, caffeine, and erythromycin had relatively high contamination levels, even exceeding 2000 ng/L. Risk evaluation based on the risk quotient method revealed that 34 PPCPs and EDCs in Chinese surface waters did not pose a significant risk, whereas 4-nonylphenol, 4-tert-octylphenol, 17α-ethinyl estradiol, 17ß-estradiol, and triclocarban did. This review provides a comprehensive summary of the occurrence and associated hazards of typical PPCPs and EDCs in Chinese surface waters over the past decade, and will aid in the regulation and control of these ECs in Chinese surface waters.

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The release of endocrine-disrupting compounds (EDCs) to the environment poses a health hazard to both humans and wildlife. EDCs can activate or inhibit endogenous endocrine functions by binding hormone receptors, leading to potentially adverse effects. Conventional analytical methods can detect EDCs at a high sensitivity and precision, but are blind to the biological activity of the detected compounds. To overcome this limitation, yeast-based bioassays have previously been developed as a pre-screening method, providing an effect-based overview of hormonal-disruptive activity within the sample prior to the application of analytical methods. These yeast biosensors express human endocrine-specific receptors, co-transfected with the relevant response element fused to the specific fluorescent protein reporter gene. We describe several molecular manipulations of the sensor/reporter circuit in a Saccharomyces cerevisiae bioreporter strain that have yielded an enhanced detection of estrogenic-like compounds. Improved responses were displayed both in liquid culture (96-well plate format) as well as in conjunction with sample separation using high-performance thin-layer chromatography (HPTLC). The latter approach allows for an assessment of the biological effect of individual sample components without the need for their chemical identification at the screening stage.

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The development of packaging technology has become a crucial part of the food industry in today's modern societies, which are characterized by technological advancements, industrialization, densely populated cities, and scientific advancements that have increased food production over the past 50 years despite the lack of agricultural land. Various types of food-packaging materials are utilized, with plastic being the most versatile. However, there are certain concerns with regards to the usage of plastic packaging because of unreacted monomers' potential migration from the polymer packaging to the food. The magnitude of monomer migration depends on numerous aspects, including the monomer chemistry, type of plastic packaging, physical-chemical parameters such as the temperature and pH, and food chemistry. The major concern for the presence of packaging monomers in food is that some monomers are endocrine-disrupting compounds (EDCs) with a capability to interfere with the functioning of vital hormonal systems in the human body. For this reason, different countries have resolved to enforce guidelines and regulations for packaging monomers in food. Additionally, many countries have introduced migration testing procedures and safe limits for packaging monomer migration into food. However, to date, several research studies have reported levels of monomer migration above the set migration limits due to leaching from the food-packaging materials into the food. This raises concerns regarding possible health effects on consumers. This paper provides a critical review on plastic food-contact materials' monomer migration, including that from biodegradable plastic packaging, the monomer migration mechanisms, the monomer migration chemistry, the key factors that affect the migration process, and the associated potential EDC human health risks linked to monomers' presence in food. The aim is to contribute to the existing knowledge and understanding of plastic food-packaging monomer migration.

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Endocrine Disrupting Compounds or Chemicals (EDCs) constitute an extensive and varied group of mostly non-natural chemicals that have the ability to imitate any aspect of hormone action, perturbing many physiological functions in humans and animals. As for female fertility, several EDCs are associated with adverse effects in the regulation of steroidogenesis, higher miscarriage rates as well as lower fertilization and embryo implantation rates and some of them are considered to decrease the number of high-quality embryos in assisted reproductive technology (ART) pregnancy. The most common EDCs are pesticides, hexachlorobenzene (HCB), hexachlorocyclohexane (HCH) and especially phthalates and bisphenols which are used in thousands of products as plasticizers. Among all, Bisphenol A (BPA) is one of the most permeating and well-studied EDCs. BPA's action resembles that of estradiol affecting negatively the female reproductive system in various ways. This review summarizes the most recent literature on the impact of EDCs in female fertility.

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The sources and distribution characteristics of three phenolic endocrine-disrupting compounds (EDCs), e.g., alkylphenols (APs) (including nonylphenols (NPs) and 4-t-octylphenol (OP)) and Bisphenol A (BPA), were investigated in the rivers of the Pearl River Delta Region (PRDR) with complex land-use types. The mean concentrations of NPs, OP, and BPA in river water including wet and dry seasons were 87, 6, and 74 ng/L in the agricultural regions (n = 10), 135, 7, and 61 ng/L in the transitional regions (n = 8), and 249, 15, and 152 ng/L in the urban regions (n = 28). Contents of NPs and BPA were high in the river sediments (ranged from 7 to 3048 ng/g and 2 to 271 ng/g, respectively). Equilibrium analysis results suggested that sediment release was not the main source of the river EDCs. Principal component analysis (PCA) showed that sewage was the major source of EDCs in the dry season, while the leaching effect of rainfall on the agricultural soils, urban roads, and commercial products was an important source in the wet season. Furthermore, the ratio of APs and total concentration of phenolic EDCs (ΣEDCs) was used to characterize the agricultural regions and urban regions in the PRDR. The ratio was less than 0.6 in the agricultural regions while the ratio was large than 0.6 in the dry season and less than 0.6 in the wet season in urban regions. BPA and NPs in transitional region and urban region had small/medium potential risk to aquatic organisms.

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As a new and ubiquitous trace organic pollutant, endocrine-disrupting compounds (EDCs) can cause endocrine-disrupting effects on organisms even at low levels. However, little information is available on the resource and assessment of EDC risks in the water environment. The study area was selected based on the paucity of information on the pollution status of inland lakes. Wuhan has numerous and diverse types of lakes which receive micropollutants from different pathways. In this study, the spatial distribution, occurrence, quantity and ecological risks of EDCs in 12 lakes were investigated. Five EDCs, including 17-alpha-ethinylestradiol (17α-EE2), estrone (E1), ß-estradiol (ß-E2), estriol (E3) and bisphenol A (BPA) were detected in surface waters. The distribution of EDC content in the lakes was ordered as follows: exurban zone < suburban area < urban areas. The pollution sources in remote lakes mainly included agricultural and aquaculture wastewater, while those in suburban and urban areas included domestic or industrial wastewater. Areas with higher EDC content were frequently related to agricultural activities, aquaculture water or dense populations. Water quality parameters, including dissolved oxygen, pH and water temperature, were significantly related to the occurrence and distribution of EDCs in the lakes. Risk assessment demonstrated that the occurrence of EDCs posed minimum to medium risk to aquatic organisms in the lakes. The results showed that the lakes faced a threat hormone pollution though it was at lower doses and, thus, the ecological risk of EDCs should be considered in future environmental policies and decisions in China.

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Persistent endocrine-disrupting compounds (EDCs) in bodies of water are a concern for human health and constitute an environmental issue, even if present in trace amounts. Conventional treatment systems do not entirely remove EDCs from discharge effluent. Due to the ultra-trace level of EDCs which affect human health and pose an environmental issue, developing new approaches and techniques to remove these micropollutants from the discharged effluent is vital. This review discusses the most common methods of eliminating EDCs through preliminary, primary, secondary and tertiary treatments. The adsorption process is favoured for EDC removal, as it is an economical and straightforward option. The NABC aspects, which are the need, approach, benefits and challenges, were analysed based on existing circumstances, highlighting biochar as a green and renewable adsorbent for the removal of organic contaminants. From the environmental point of view, the effectiveness of this method, which uses natural fibre from the kenaf plant as a porous and economical biochar material with a selected lignocellulosic biomass, provides insights into the advantages of biochar-derived adsorbents. Essentially, the improvement of the natural fibre as an adsorbent is a focus, using carbonisation, activation, and the physiochemical process to enhance the adsorption ability of the material for pollutants in bodies of water. This output will complement sustainable water management approaches presented in previous studies for combating the emerging pollutant crisis via novel green and environmentally safe options.

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Bisphenol A (BPA) and its alternative, bisphenol S (BPS), are widespread endocrine disrupting compounds linked in several studies to poor female fertility. Sufficient oocyte competence and subsequent embryo development are highly dependent on oocyte maturation, an intricate process that is vulnerable to BPA. These effects as well as the effects of its analog, BPS, have not been fully elucidated. Although the harmful consequences of bisphenols on the reproductive system are largely due to interferences with canonical gene expression, more recent evidence implicates noncoding RNAs, including microRNAs (miRNA), as significant contributors. The aim of this work was to test the hypothesis that abnormal expression of key miRNAs during oocyte maturation and embryo development occurs following BPA and BPS exposure during maturation. Using qPCR, primary and mature forms of miR-21, -155, -34c, -29a, -10b, -146a were quantified in an in vitro bovine model of matured cumulus-oocyte complexes, fertilized embryos, and cultured cumulus cells after exposure to BPA or BPS at the LOAEL dose (0.05 mg/mL). Expression of miR-21, miR -155, and miR-29a were markedly increased (P = 0.02, 0.04, <0.0001) while miR-34c and miR-10b were decreased (P = 0.01, 0.01), after BPA treatment. miR-146a expression remained stable. BPS had no effects, suggesting may not exert its actions through these six miRNAs examined. Overall, this study indicates that BPA effects are likely miRNA specific rather than a global effect on miRNA synthesis and processing mechanisms and that its analog, BPS, may not possess the same properties required to interfere with these miRNAs during bovine oocyte maturation.

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Endocrine disrupting compounds (EDCs), pharmaceuticals, and personal care products (PPCPs) have been of great concern as emerging contaminants of aquatic environments. In this study, the risks of EDCs and PPCPs in the Yangtze River Basin were ranked, based on their environmental exposure datasets and ecotoxicity datasets. The prioritized chemicals were then identified. The results found that EDCs and personal care products were deemed to represent higher risks to aquatic organisms, for example, estrone, estriol, 17ß-estradiol, bisphenol S, atrazine, triclocarban, and triclosan, while the risks of pharmaceuticals were 500-fold lower. Among the pharmaceuticals, antibiotics posed relatively higher risks. The Xiangjiang River and Honghu Lake with its surrounding rivers were hotspots where more chemicals were found with the highest concentrations, followed by Taihu Lake, Dongting Lake and the Yangtze River Delta. When comparing with algae and worms, fish were the most sensitive taxa to 17ß-estradiol and 17α-ethynylestradiol. The results of this work provide sound guidance for the future monitoring and management of chemicals in China.

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Polycyclic aromatic hydrocarbons (PAH) are a complex group of organic compounds, consisting of at least three fused aromatic rings, which are formed during combustion of organic matter. While some PAHs have been reported to have carcinogenic and/or mutagenic properties, another possible negative health impact is their endocrine disrupting potential. Therefore, the aim of this study was to determine both the agonistic and antagonistic endocrine activity of 9 environmentally relevant PAHs using three different CALUX bioassays: The AhR-CALUX, The ERα-CALUX and PPARγ-CALUX. For the PPARγ-CALUX anthracene, fluoranthene, pyrene and fluorene showed weak agonistic activity, whilst benzo(a)pyrene (B(a)P) was the only one exhibiting weak antagonistic activity. For the AhR-CALUX, chrysene was the only PAH that showed relatively strong agonist activity (except for B(a)P which was used as a standard). Pyrene, anthracene and fluoranthene showed weak AhR agonist activity. In the ERα-CALUX bioassay, fluoranthene had agonistic activity whilst B(a)P exhibited both agonistic and antagonistic activity (lowering E2 activity by 30%). Phenanthrene and anthracene had weak ERα agonist activities. These results indicate that certain PAHs have multiple modes of action and can activate/inhibit multiple receptor signaling pathways known to play critical roles in mediating endocrine disruption.

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The present study is the first comprehensive monitoring of 13 selected endocrine disrupting compounds (EDCs) in untreated urban and industrial wastewater in Serbia to assess their impact on the Danube River basin and associated freshwaters used as sources for drinking water production in the area. Results showed that natural and synthetic estrogens were present in surface and wastewater at concentrations ranging from 0.1 to 64.8 ng L-1. Nevertheless, they were not detected in drinking water. For alkylphenols concentrations ranged from 1.1 to 78.3 ng L-1 in wastewater and from 0.1 to 37.2 ng L-1 in surface water, while in drinking water concentrations varied from 0.4 to 7.9 ng L-1. Bisphenol A (BPA) was the most abundant compound in all water types, with frequencies of detection ranging from 57% in drinking water, to 70% in surface and 84% in wastewater. Potential environmental risks were characterized by calculating the risk quotients (RQs) and the estrogenic activity of EDCs in waste, surface and drinking water samples, as an indicator of their potential detrimental effects. RQ values of estrone (E1) and estradiol (E2) were the highest, exceeding the threshold value of 1 in 60% of wastewater samples, while in surface water E1 displayed potential risks in only two samples. Total estrogenic activity (EEQt) surpassed the threshold of 1 ng E2 L-1 in about 67% of wastewater samples, and in 3 surface water samples. In drinking water, EEQt was below 1 ng L-1 in all samples.

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The current knowledge on bioaccumulation of emerging contaminants (ECs) in aquatic invertebrates exposed to the realistic environmental concentrations is limited. Even less is known about the effects of chemical pollution exposure on the metabolome of aquatic invertebrates. We conducted an in situ translocation experiment with passive filter-feeding caddisfly larvae (Hydropsyche sp.) in an effluent-influenced river in order to i) unravel the bioaccumulation (and recovery) dynamics of ECs in aquatic invertebrates, and ii) test whether exposure to environmentally realistic concentrations of ECs will translate into metabolic profile changes in the insects. The experiment was carried out at two sites, upstream and downstream of the discharge of an urban wastewater treatment plant effluent. The translocated animals were collected at 2-week intervals for 46 days. Both pharmaceuticals and endocrine disrupting compounds (EDCs) were detected in water (62 and 7 compounds, respectively), whereas in Hydropsyche tissues 5 EDCs accumulated. Overall, specimens from the upstream site translocated to the impacted site reached higher ECs concentrations in their tissues, as a reflection of the contaminants' water concentrations. However, bioaccumulation was a temporary process susceptible to change under lower contaminant concentrations. Non-targeted metabolite profiling detected fine metabolic changes in translocated Hydropsyche larvae. Both translocations equally induced stress, but it was higher in animals translocated to the impacted site.

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Endocrine-disrupting compounds (EDCs) such as hormones, pesticides, phenolic compounds, and pharmaceuticals compounds can cause adverse effects on humans, animals, and other living organisms. One of the largest mariculture areas situated in Pulau Kukup, Johor, Malaysia, is actively involved in exporting marine fish to other countries worldwide. This paper aims to provide baseline data on the level of EDC pollutants found in mariculture sediments in Malaysia since no reports have investigated this issue. Calculated samples recovered are between 50.39 and 129.10% at 100 ng/g spiking level. The highest concentration in the sediment samples was bisphenol A (0.072-0.389 ng/g dry weight) followed by diethylstilbestrol (<0.208-0.331 ng/g dry weight) and propranolol (<0.250-0.275 ng/g dry weight). Even though the concentrations of the targeted compounds obtained were low, their effects could become more evident longer term, which raises not only environmental health concerns but the potential risk to humans.

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The results presented in this study illustrate the multiple roles of seawater salinity toward the sonochemical degradation, at variable frequencies (300-1700 kHz), of several hazardous substances, i.e. propylparaben (PPR) endocrine disruptor and several synthetic dyes: naphthol blue black (NBB), malachite green (MG), basic red 29 (BR29), acid orange 7 (AO7), Rhodamine B (RhB) and basic fuchsin (BF). Sonochemical treatment degraded all pollutants in seawater at faster rates than in deionized water. The seawater-salts through increasing the ionic strength of the solution act as a potential pusher of hydrophilic pollutants toward the reactive interfacial area of cavitation bubbles. Additionally, the salts reduce the bubble coalescence, which yields higher number of active bubbles in the irradiating media. Analysing the degradation rate of PPR and NBB with two heterogeneous models based on Langmuir kinetics mechanism indicated that the bubble interfacial area was the preferred reaction zone for the ultrasonic degradation of PPR and NBB in seawater.

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A novel unique adsorbent (Fe3O4@Co/Ni-LDH) has been successfully synthesized and applied for removal of bisphenols (BPs) from aqueous solution. The prepared adsorbent was characterized to appear in a hierarchical rattle-like structure, and possesses high specific surface area, abundant pore system, and magnetic properties. Adsorption kinetics fitted well with the pseudo-second-order model. Adsorption isotherms abide by the Langmuir model, and the maximum adsorption capacity for bisphenol A (BPA), F (BPF), AF (BPAF) and S (BPS) on Fe3O4@Co/Ni-LDH at pH of 7.0 were 238.96, 177.09, 320.56 and 345.84 mg/g, respectively. Moreover, it was found that the high pH and NaCl concentration were not conducive to the removal of BPs. The humic acid and real waters had no significant effects on the removal of BPs on Fe3O4@Co/Ni-LDH. Furthermore, the FT-IR spectra indicated that the removal of four BPs were primarily Hydrogen bond interaction between BPs and Fe3O4@Co/Ni-LDH. The Fe3O4@Co/Ni-LDH was regenerated effectively by methanol and can be repeatedly used. This novel Fe3O4@Co/Ni-LDH can be applied as a promising adsorbent for removal of BPs from aqueous matrices.

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The distribution of emerging organic contaminants in drinking water sources in Africa is a subject with very scanty data and information. In order to fill knowledge gaps, we report here the distribution and potential ecological risks of three phenolic compounds (bisphenol A (BPA), 4-nonylphenol (NP), and 4-tert-octylphenol (OP)), which have been previously identified to have the potential of endocrine disrupting activity, in surface water and sediment of the New Calabar River. The compounds were quantified using GC-MS. At all sampling sites, a similar concentration pattern of BPA > NP > OP was recorded, with the exception of Choba sampling station in which the levels of these endocrine disrupting compounds were low or undetectable. The levels of BPA in surface water ranged from 1.20 to 63.64 µg/L, whereas those of NP and OP ranged from < 0.20 to 2.15 µg/L and from < 0.10 to 0.68 µg/L, respectively. For sediments, measured levels were from 1.20 to 66.57 µg/kg for BPA, from < 0.35 to 3.37 µg/kg for NP, and from < 0.13 to 0.90 µg/kg for OP. Risk quotients (RQs) assessed for some sensitive organisms (algae, Daphnia magna, and fish) were above 1 for BPA and NP, whereas RQs for OP were below 1. This implies that BPA and NP at the levels detected could have potential risks to the sensitive organisms considered, but low risk for OP.

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Bisphenol analogues and alkyl esters of p-hydroxybenzoic (parabens) can be defined as emerging endocrine-disrupting compounds (EDCs) due to their similar characteristics. This study analyzed eight bisphenol analogues, six parabens, and five paraben metabolites in seawater (including aqueous and suspended particle matter (SPM)), as well as organism samples from the Pearl River Estuary, in order to determine their occurrence, distribution, bioaccumulation, and ecological and human health risk in South China's marine environment. The aggregation concentrations of bisphenol analogues, parabens, and paraben metabolites were 106 ng/L, 4.53 ng/L, and 231 ng/L in aqueous samples, 868 ng/g, 173 ng/g, and 9320 ng/g in SPM samples, 41.6 ng/g, 6.46 ng/g, and 460 ng/g in marine organisms, respectively. This study identified significantly higher concentrations of paraben metabolites than their parent parabens in the marine environment, which has not yet been reported in previous studies. These findings call for greater attention on the contamination of paraben metabolites in marine environments. Moreover, the median values of the logarithm of bioaccumulation factors (BAF) for the detected 20 target compounds ranged from 0.11 to 5.07. Bisphenol analogues including bisphenol A (BPA), bisphenol S (BPS), bisphenol F (BPF), bisphenol B (BPB), bisphenol P (BPP), and Fluornen-9-bisphenol (BPFL) (3.3 < lg BAF < 3.7), and three paraben metabolites including 4-hydroxybenzoic acid (4-HB) (3.3 < lg BAF < 3.7), methyl protocatechuate (OH-MeP), and ethyl protocatechuate (OH-EtP) (Log BAF > 3.7), exhibited varying degrees of potential bioaccumulation effect in the majority of organism samples. Furthermore, all tested chemicals in this study were at low risk quotient (RQ) levels for acute and chronic toxicity in seawater. However, the target hazard quotient (THQ) values of two paraben metabolites, 4-HB and benzoic acid (BA), were higher than 1, which indicates that paraben metabolites have the potential to adsorb into organisms, and their associated human health risks should be of great concern. Overall, the study results suggest that the occurrence and risks of emerging EDCs in coastal waters are deserving of further studies, especially in densely populated regions of the world.

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Endocrine disrupting compounds (EDCs) are an emerging environmental concern and commonly occur as a mixture of compounds. The EDC mixture can be more toxic than any single compound. The present study analyses EDCs in surface water in the case of an urban tropical river, the Langat River, using the multiresidue analytical method of solid phase extraction and liquid chromatography-tandem mass spectrometry (SPE-LC-MS/MS). The Langat River is used as a drinking water source and is treated for Malaysian drinking water supply. A total of 14 EDCs i.e. five hormones, seven pharmaceuticals, one pesticide, and one plasticizer were detected. Caffeine was observed to be highest at 19.33 ng/L, followed by bisphenol A and diclofenac at 8.24 ng/L and 6.15 ng/L, respectively. Using a conservative risk quotient (RQ) method, EDCs were estimated for having negligible risks under acute and chronic exposure (RQ < 0.002 and RQmix < 0.003; RQ < 0.01), suggesting that there is currently an insignificant ecological risk related to these compounds in the Langat River riverine ecosystem. However, the presence of EDCs in surface water raises concerns about potential human exposure to EDCs via dietary intake i.e. food and drinking water supply. Although the ecological risks are considered negligible, these risks should not be neglected in terms of future prioritization and risk management. Improvements in water quality monitoring and risk assessment in water source protection are required to support a multibarrier approach to managing drinking water supply systems for safe water supply. The present study proposes a risk management and monitoring framework for EDCs to support the aforementioned multibarrier approach.

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BACKGROUND: Worldwide approximately 2.6 million are stillborn, mostly occurring in developing countries. In the great part these deaths are inexplicable. The evenness and standardisation of the diagnostic criteria are prerequisites to understand their pathogenesis. The core goal of this article is to propose new evidence based investigative post-mortem guidelines that should be adopted in all the Institutions especially when a fetal death, after a routine autopsy procedure, is diagnosed as "unexplained". The proposed protocol is mainly focused on the anatomopathological examination of the autonomic nervous system and in particular of the brainstem where the main centers that control vital functions are located. METHODS: Updated investigative guidelines for the examination of unexplained stillbirths, prevalently focused on the histological examination of the brainstem, where the main centers that are involved in monitoring the vital functions are located, are here presented. A section of this protocol concerns the Immunohistochemical evaluation of specific functional markers such as the neuronal nuclear antigen, nicotinic acetylcholine receptors, serotonin, orexin, apoptosis and gliosis. The important role of risk factors, having regard in particular to maternal smoking and air pollution is also contemplated in these guidelines. RESULTS: Specific morphological and/or functional alterations of vital brainstem structures have been found with high incidence in over 100 cases of unexplained fetal death sent to the "Lino Rossi Research Center" of the Milan University according to the Italian law. These alterations were rarely detected in a group of control cases. CONCLUSIONS: We hope this protocol can be adopted in all the Institutions notably for the examination of unexplained fetal deaths, in order to make uniform investigations. This will lead to identify a plausible explanation of the pathogenetic mechanism behind the unexplained fetal deaths and to design preventive strategies to decrease the incidence of these very distressing events for both parents and clinicians. TRIAL REGISTRATION: not applicable for this study.

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