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Background: Despite the potential foetal and maternal risks of self-medication, studies on self-medication practice and the safety profile of medicines used during pregnancy are scarce in our setting. This study determined the self-medication practice and safety profile of medicines used among pregnant women. Methods: This cross-sectional study was conducted in face-to-face interviews among 345 pregnant women at three hospitals in Sierra Leone. Data were analysed using descriptive statistics and binary logistic regression to determine the prevalence and associated factors of self-medication. Results: A total of 345 pregnant women participated in the study. The prevalence of self-medication prevalence among pregnant women with conventional and/or herbal medicine was 132 (38.3%). Also, 93 (75%) of the conventional medicines (CMs) were categorised as probably safe, of which paracetamol 36 (29.0%) was commonly used, followed by amoxicillin 23 (18.5%) and antimalarials 22 (17.7%) for common illnesses such as headache 30 (25.4%), urinary tract infection 23 (19.4%) and malaria 22 (18.6%). The most common reason for self-medication was previous experience with the disease 24 (27.3%). Luffa acutangula 19 (30.2%) was the most used herbal medicine (HM), and Oedema 30 (47.6%) was the most reported ailment. Among the HM users, 34 (54.0%) believe they are more effective than CMs. Secondary school education (AOR = 2.128, 95%CI = 1.191-3.804, p = 0.011), tertiary education (AOR = 2.915, 95%CI = 1.104-7.693, p = 0.031), monthly income of greater than NLe 1,000 (AOR = 4.084, 95% CI = 1.269-13.144, p = 0.018), and perceived maternal illness (AOR = 0.367, CI = 0.213-0.632, p = <0.001) were predictors of self-medication. Conclusion: Self-medication practice was highly prevalent and was associated with educational status, monthly income, and perceived maternal illness during pregnancy. Therefore, intervention programmes should be designed and implemented to minimise the practice and risk associated with self-medication among pregnant women.

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BACKGROUND: Several countries' most incorrectly discarded medicines are acetaminophen (ACM), metamizole (MTZ), and nimesulide (NMS). These xenobiotics easily reach the aquatic environment; such contamination is very important for the health of humans and other species, yet little explored. OBJECTIVES: To evaluate the cocktail effect of ACM, MTZ, and NMS during zebrafish's initial development. METHODS: Zebrafish embryos 6-8 h post-fertilization (hpf) were exposed to different concentrations of ACM, MTZ, and NMS, separately, to obtain the 50% lethal concentrations (LC50). Next, the embryos were exposed to distinct concentrations of the cocktail (LC50/2, LC50/5, LC50/10, and LC50/20) in a semi-static system. Samples were analyzed 0, 24, 48, and 96 h after exposure, and the drugs' concentrations in E3 medium were assessed by high-performance liquid chromatography. For embryotoxicity evaluation, the mortality, hatching, and heart rates; total length; and pericardial and yolk sac areas were determined. In addition, body malformations, edemas, presence of pigmentation, and histopathological assessments were also recorded. RESULTS: The LC50 values obtained for MTZ, ACM, and NMS were 4.69 mgmL-1, 799.98 µgmL-1, and 0.92 µgmL-1, respectively. No difference was observed between the drugs' nominal and observed concentrations at each time point. The cocktail significantly induced mortality and decreased hatching in the LC50/10, LC50/5, and LC50/2 groups. Additionally, body malformations, pigmentation loss, and yolk sac and pericardial edemas were observed in the cocktail groups. The cocktail groups' larvae had decreased total length and slower heart rates compared to the controls (p < 0.05). The histopathological assessment showed that yolk sac edema promoted severe histological changes in the esophageal-intestine junction and intestine in larvae treated with cocktails. Moreover, PAS-positive structures decreased in the esophageal-intestine junction, intestine, and liver in larvae exposed to pharmaceutical cocktails. CONCLUSION: This study's findings suggest the cocktail of ACM, MTZ, and NMS may be hazardous to aquatic organisms in case of environmental contamination.

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OBJECTIVE: Ellagic acid (EA) exerts, neuroprotective, mitoprotective, anti-oxidative and anti-inflammatory effects. We evaluated protective effect of EA on ethanol-induced fetal alcohol spectrum disorders (FASD). METHODS: A total of 35 newborn male rats were used, divided into five groups, including; control (normal saline), ethanol (5.25 g/kg per day), ethanol (5.25 g/kg per day) + EA (10 mg/kg), ethanol (5.25 g/kg per day) + EA (20 mg/kg) and ethanol (5.25 g/kg per day) + EA (40 mg/kg). Thirty-six days after birth behavioral tests (Morris water maze and Elevated Plus Maze), tumor necrosis factor-α (TNF-α) levels, oxidative markers (malondialdehyde, glutathione and superoxide dismutase), mitochondrial examination such as succinate dehydrogenases (SDH) activity, mitochondrial swelling, mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) formation were analyzed. RESULTS: The results revealed that ethanol exposure adversely affected cognitive and mitochondrial functions and as well as induced oxidative stress and inflammation in brain tissue. However, EA (20 and 40 mg/kg) administration effectively prevented the toxic effects of ethanol in FASD model. CONCLUSIONS: These findings demonstrate that ethanol application significantly impairs the brain development via mitochondrial dysfunction and induction of oxidative stress. These data indicate that EA might be a useful compound for prevention of alcohol-induced FASD.

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Exogenous teratogens contribute to approximately 10% of the human abnormality with exposure occurrence during the prenatal and fetal period. However, the assessment methods and underlying mechanism remain unclear. The nematode Caenorhabditis elegans has been recognized as one of the ideal model animals for toxicologic research as convenient culture, low cost, and complete phenotypes and genomic profiling. This chapter describes the protocols about the estimations on the teratogenic effects using nematodes as model organisms, including the growth, development, behavior, reproduction, energy balance, and transgenes.

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PURPOSE: Pregnant patients present a unique challenge to cancer therapy. Due to the potential catastrophic implications related to teratogenic effects or pregnancy loss, oncologic management of this vulnerable patient group must be strategic and personalized. METHODS: This article will discuss the unique treatment approach to the pregnant cancer patient. This includes discussion of the role of imaging during staging, treatment, and follow-up with an emphasis on avoiding ionizing radiation when possible. RESULTS AND CONCLUSION: Specific considerations and modifications to standard cancer treatments, including surgery and systemic therapies such as chemotherapy, immunotherapy, targeted and hormone therapies are crucial components of providing oncologic care to minimize negative effects to the mother and developing fetus. Radiation and proton therapy are also options that may be employed in specific circumstances. Finally, this article will address the long-term treatment effects of these therapies on future fertility.

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Tetracycline (TC) is one of the most consumed antibiotics worldwide. Due to its high consumption, recent studies have reported its presence in aquatic environments and have assessed its effects on fish, algae, and daphniids. However, in most of those works, authors have tested TC toxicity at concentrations higher than the ones reported in the water matrix. Herein, we aimed to assess the likely embryotoxic and oxidative damage induced by environmentally relevant concentrations of TC in embryos of Danio rerio. Moreover, we seek to determine whether or not an enriched diet with spirulina can alleviate the embryotoxic damage produced by TC. Our findings indicated that TC at concentrations of 50 to 500 ng/L induced pericardial edema, tail deformities, and absence of head and fin in embryos after 96 h of exposure. Moreover, this antibiotic prompted the death of embryos in a concentration-dependent manner. According to our integrated biomarker response index, TC induced oxidative damage on Danio rerio embryos, as star plots showed a tendency to lipoperoxidation, hydroperoxides, and protein carbonyl content. Spirulina reduced the toxicity of TC by diminishing the levels of oxidative damage biomarkers, which resulted in a decrease in the rate of death and malformed embryos. Overall, TC at concentrations of ng/L prompted oxidative stress and embryotoxicity in the early life stages of Danio rerio; nonetheless, the algae spirulina was able to reduce the severity of those effects.

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In Mexico, the use of medicinal plants is the first alternative to treat the diseases of the most economically vulnerable population. Therefore, this review offers a list of Mexican plants (native and introduced) with teratogenic effects and describes their main alterations, teratogenic compounds, and the models and doses used. Our results identified 63 species with teratogenic effects (19 native) and the main alterations that were found in the nervous system and axial skeleton, induced by compounds such as alkaloids, terpenes, and flavonoids. Additionally, a group of hallucinogenic plants rich in alkaloids employed by indigenous groups without teratogenic studies were identified. Our conclusion shows that several of the identified species are employed in Mexican traditional medicine and that the teratogenic species most distributed in Mexico are Astragalus mollissimus, Astragalus lentiginosus, and Lupinus formosus. Considering the total number of plants in Mexico (≈29,000 total vascular plants), to date, existing research in the area shows that Mexican plants with teratogenic effects represent ≈0.22% of the total species of these in the country. This indicates a clear need to intensify the evaluation of the teratogenic effect of Mexican plants.

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Reports of adverse pregnancy outcomes after in utero exposure to very low levels of ionizing radiation are inconsistent with a threshold dose of 100 mSv for teratogenic effects in humans. In the present study, it is hypothesized that the shape of the dose-response relationship for teratogenic effects is a cumulative lognormal distribution without threshold. This hypothesis relies on the assumption that both doses and radiosensitivities in human populations exposed to ionizing radiation are random variables, modeled by lognormal density functions. Here, radiosensitivity is defined as the dose limit up to which radiation damage can be repaired by the cellular repair systems, in short, the repair capacity. Monte Carlo simulation is used to generate N pairs of individual doses and repair capacities. Radiation damage occurs whenever the dose exceeds the related repair capacity. The rate of radiation damage is the number of damages, divided by the number N of pairs. Monte Carlo simulation is conducted for a sufficient number of ascending median doses. The shape of the dose-response relationship is determined by regression of damage rates on mean dose. Regression with a cumulative lognormal distribution function yields a perfect fit to the data. Acceptance of the hypothesis means that studies of adverse health effects following in-utero exposure to low doses of ionizing radiation should not be discarded primarily because they contradict the concept of a threshold dose for teratogenic effects.

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17-Alpha-ethinylestradiol (EE2) is an estrogen derived from estradiol (E2). This compound and is one of the most widely used drugs both in humans and animals. Numerous studies have reported the ability of EE2 to alter sex determination and delay sexual maturity, but there are toxic effects that need to be explored. In this work, we analyzed the effect of EE2 on embryonic development and oxidative stress biomarkers in Danio rerio. For this effect, zebrafish embryos in the blastula period (2.5 h post fecundation) were exposed to different concentrations of EE2 (36-106 ng L-1) until 96 hpf. Survival, alterations to embryonic development, and teratogenic effects were evaluated using a stereomicroscope. Furthermore, oxidative stress biomarkers: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) activities, lipid peroxidation (LPX), hydroperoxide content (HPX), and protein carbonyl content (POX) were evaluated at 72 and 96 hpf using spectrophotometric methods. LC50 and EC50 of malformations got values of 82 ng L-1 and 57.7 ng L-1, respectively. The main teratogenic effects found were: chorda malformation, body malformation, and developmental delay. These alterations occurred at 86, 96, and 106 ng L-1. Integrated biomarker index showed that the oxidative stress biomarkers that had the most influence on embryos were SOD, CAT, GPX, and LPX. Overall, our results allow us to conclude that low concentrations of EE2 may potentially alter the development and oxidative status in the early life stages of zebrafish. Therefore, this bio-active estrogen can be considered a hazardous substance for fish.

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Irregular-shaped and partially degraded secondary microplastics (SMP) account for the majority of MPs in marine environments, yet little is known about their effects on marine organisms. In this study, we investigated the embryotoxicity of polyvinyl chloride SMP and primary microplastics (PMP) to the marine medaka Oryzias melastigma. This study aimed to determine the physical impacts of MPs and, for the first time, elucidate the underlying mechanisms of physical toxicity. SMP shortened hatching time and induced higher teratogenic effects on larvae relative to PMP, indicating a higher toxicity from SMP. Physical damage from SMP to the chorion surface appears to be the main toxicity mechanism, caused by their irregular shape and reduced aggregation relative to PMP. In contrast, real-time changes in oxygen demonstrated that hypoxia caused by greater PMP adsorption to the chorion surface contributes to the toxicological responses of this material relative to SMP. Modulation of genes involved in hypoxia-response, cardiac development and hatching confirmed the toxicity mechanisms of PMP and SMP. The chemical contribution to observed toxicity was negligible, confirming impacts derived from physical toxicity. Our findings highlight the negative effects of environmentally relevant SMP on the marine ecosystems.

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Fluoxetine (FLX) is a psychoactive drug that acts as an antidepressant. FLX is one of the world's best-selling prescription antidepressants. FLX is widely used for the treatment of various psychiatric disorders. For these reasons, this drug may eventually end up in the aquatic environment via municipal, industrial, and hospital discharges. Even though the occurrence of FLX in aquatic environments has been reported as ubiquitous, the toxic effects that this drug may induce, especially at environmentally relevant concentrations, on essential biological processes of aquatic organisms require more attention. In the light of this information, this work aimed to investigate the influence that fluoxetine oxidative stress-induced got over the embryonic development of Danio rerio. For this purpose, D. rerio embryos (4 h post fertilization) were exposed to environmentally relevant concentrations (5, 10, 15, 20, 25, 30, 35, and 40 ng L-1) of fluoxetine, until 96 h post fecundation. Along the exposure, survival, alterations to embryonic development, and teratogenic effects were evaluated using a stereomicroscope. Furthermore, oxidative stress biomarkers (superoxide dismutase, catalase, glutathione peroxidase, lipid peroxidation, hydroperoxide, and carbonyl content) were evaluated at 72 and 96 h post fecundation. LC50, EC50m, and teratogenic index were 30 ng L-1, 16 ng L-1, and 1.9, respectively. The main teratogenic effects induced by fluoxetine were pericardial edema, hatching retardation, spine alterations and craniofacial malformations. Concerning oxidative stress, our integrated biomarkers (IBR) analysis demonstrated that as the concentration increased, oxidative damage biomarkers got more influence over the embryos than antioxidant enzymes. Thus, fluoxetine induces an important oxidative stress response on the embryos of D. rerio. Collectively, our results allow us to concluded that FLX is a dangerous drug in the early life stages of D. rerio due to its high teratogenic potential and that FLX-oxidative stress induced may be involved in this toxic process.

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INTRODUCTION: Preclinical studies with tofacitinib demonstrated teratogenic effects. Data about effects on human fetuses are limited and current recommendations are to immediately discontinue the treatment. Our purpose is to report a case of exposure to tofacitinib during the first trimester of pregnancy. CASE SUMMARY: A 40-year-old woman with psoriatic arthritis became pregnant during the first month of treatment with tofacitinib. Tofacitinib was interrupted immediately, and parents were informed about the possible risks of teratogenicity. At the end of pregnancy, our patient gave birth to a healthy newborn. CONCLUSION: All the available evidence of tofacitinib exposure during pregnancy in humans belongs to outcomes of unexpected pregnancies in the context of clinical trials and post-marketing cases. This case may contribute to enriching available data about teratogenic risks of tofacitinib exposure during pregnancy.

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The NBOMe (N-2-methoxybenzyl-phenethylamines) family of compounds are synthetic hallucinogens derived from the 2C series. Although this family of compounds has been responsible for multiple cases of acute toxicity and several deaths around the world, to date there are few studies. These compounds act as potent 5-HT2A receptor agonists, including the hallucinogen 25C-NBOMe (2-(4-chloro-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine). In this study, we first evaluated the toxicity of 25C-NBOMe in two animal models: Artemia salina and zebrafish using the lethality test of Meyer et al. (1982) modified for Artemia salina and the Fish Embryo Toxicity test (FET) for zebrafish (Danio rerio). Subsequently, we determined the behavioral and morphological effects using different concentrations of the 25C-NBOMe. As a result, we found that this substance is highly toxic according to lethality tests in both animal models. We also observe that this hallucinogen induces alterations in swimming and motility patterns in Artemia salina. Similarly, there were alterations in the motor response to a stimulus, as well as abnormal development in the zebrafish. The developmental effects of zebrafish suggest a teratogenic potential for 25C-NBOMe. Therefore, these findings are correlated with side effects, such as motor response abnormalities and muscle deterioration, clinically reported for consumers of this recreational drug. Finally, although recent studies are addressing the neurotoxicity and cardiotoxicity of 25C-NBOMe in cell cultures, to the best of our knowledge, this is the first in vivo report for 25C-NBOMe related to toxicological parameters and their global effects on development. Therefore, it could represent an advance in the study of the substance that contributes to the understanding of the effects on behavior and development in humans.

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Coronavirus disease 2019 (COVID-19) is a viral illness caused by severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) presenting with pulmonary and extra-pulmonary manifestations. The first case was reported in Wuhan, China in December 2019 and it has rapidly progressed to the form of a pandemic. The presentation is mild in about 80 percent of the cases but the disease can also progress to a severe form of respiratory illness leading to acute respiratory distress syndrome (ARDS) and sometimes multi-organ failure, especially in people with other co-morbidities. Pregnant women also appear to be at a greater risk of acquiring a severe infection due to physiological changes during pregnancy. Many drugs with in vitro activity against the virus or an immunomodulatory effect have been considered for repurposing or have been tried as off-label drugs. The safety data regarding the use of newly approved or off-label or investigational drugs in pregnant women is limited and this poses a great challenge for clinicians. Therefore, it is important to know the utility and safety of the medications to avoid untoward adverse effects on pregnant women and fetuses. In this review, we aim to provide an overview of the approved, off-label, unlicensed, new and some promising pharmacological options for their use in the treatment of COVID-19 and the safety profile in pregnancy in an Indian scenario.

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Protective effects of quercetin (QUE), polydatin (POL), and folic acid (FA) and their mixtures were tested using zebrafish to model fetal alcohol spectrum disorder in this study. Zebrafish embryos were exposed to 150 mM ethanol for 6 or 22 h and co-treated with QUE, POL, FA, and their mixtures (37.5-100.0 µM). Epiboly progression, teratogenic effects, and behavior were evaluated. Ethanol exposure reduced epiboly, and FA and QUE protected against these ethanol-induced defects. POL did not reduce epiboly defects. The mixture QUE + FA showed a possible antagonistic effect. The observed teratogenic effects were similar in all ethanol exposed groups. QUE, FA and QUE + POL reduced the percentage of affected animals, but treatments did not eliminate teratogenic effects. Behavioral measurements were divided into small (between 4 and 8 mm/s) and high swimming activity (>8 mm/s). All experimental groups displayed a reduction in small swimming activity as compared to control and ethanol groups when exposed to bright light. Additionally, larvae exposed to ethanol were more inhibited than control, not showing a habituation period (after 60 min of experiment) in high swimming activity. Chemical treatments like QUE and POL reduced behavioral defects induced by ethanol exposure. In conclusion, this study presents new evidence that QUE, POL, FA and their mixtures partially protected epiboly, teratogenic, and behavioral defects induced by ethanol exposure. QUE, FA and QUE + POL were more effective in reducing these defects than the other studied compounds and mixtures.

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In the United States, there are over one million women with epilepsy (WWE) in their childbearing years. Pregnancy can be challenging for this population. A number of international registries have documented that children born to these women are at increased risk for major congenital malformations (MCM), lower intelligence quotient scores and neurodevelopmental disorders, when the mother is managed on antiseizure medications (ASMs). To prevent poor neonatal outcomes for this population, safe and thoughtful management strategies are necessary. We propose to divide these management strategies into five principles. These include (I) choosing suitable ASMs for the patient's seizure type, (II) choosing an ASM with the least teratogenic and cognitive side effects, (III) dosing at the lowest possible effective dosage, (IV) selecting the best ASM regimen as promptly as possible, even before a woman has her first menses, and (V) supplementing these patients with folic acid in order to try to enhance cognition and reduce neural tube defects.

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Tamoxifen is frequently used as adjuvant treatment in premenopausal patients with hormone receptor-positive early breast cancer. According to guidelines, the use of nonhormonal barrier contraception is recommended during tamoxifen treatment and up to 3 months after its interruption prior to attempting conception. Nevertheless, when conception occurs inadvertently during tamoxifen treatment, the effects on the fetus and on the course of pregnancy are still not completely known. Here, we report 3 cases of young women who accidentally became pregnant while taking tamoxifen and perform a systematic review of the literature to provide more elements for better and clear multidisciplinary counselling of women facing this challenging situation.

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This study aimed to investigate the effectiveness of leaf ethanolic extract of Etlingera hemisphaerica (LE3H) against the teratogenic effects of mercuric chloride (HgCl2) in mice (Mus musculus). Pregnant M. musculus were divided into four groups, each consisting of 10 dams, and received drink and food ad libitum. The first, second, and third, and fourth (control) groups were administered with LE3H, HgCl2, HgCl2 + LE3H, and double-distilled water alone, respectively. HgCl2 (5 mg/kg bw) was administered by injection on gestation day (GD) 9, and LE3H (0.39 mg/g bw) was administered by gavage on GD 10. Treated and control animals were killed by cervical dislocation on GD 18, dissected, and the fetuses were collected for evaluation of maternal, embryonic, and fetal toxicity. Eight parameters were measured: (a) embryo resorption or resorbed embryo, (b) dead fetus, (c) living fetus, (d) morphologically normal living fetus, (e) malformed living fetus, (f) number of MLF, (g) length of MNLF, and (h) weight of MNLF. LE3H caused 4 (50.00%), whereas HgCl2 resulted in 7 (87.50%) parameters that were significantly different from those of the control, indicating that the teratogenicity of HgCl2 was significantly higher than that of LE3H. HgCl2 + LE3H showed two effects of LE3H on the teratogenicity of HgCl2: increased 2 (25.00%), and decreased 6 (75.00%). Thus, LE3H decreased the teratogenic effects of HgCl2 in M. musculus.

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In the Western world, 2-5 % of pregnant women use selective serotonin reuptake inhibitor (SSRI) antidepressants. There is no consensus on the potential long-term neurodevelopmental outcomes of early SSRI exposure. Our aim was to determine whether there is an overall effect of perinatal SSRI exposure in animals on a spectrum of behavioral domains. After a comprehensive database search in PubMed, PsycINFO, and Web of Science, we included 99 publications. We performed nine meta-analyses and two qualitative syntheses corresponding to different behavioral categories, aggregating data from thousands of animals. We found evidence for reduced activity and exploration behavior (standardized mean difference (SMD) -0.28 [-0.38, -0.18]), more passive stress coping (SMD -0.37 [-0.52, -0.23]), and less efficient sensory processing (SMD -0.37 [-0.69, -0.06]) in SSRI- versus vehicle-exposed animals. No differences were found for anxiety (p = 0.06), social behavior, learning and memory, ingestive- and reward behavior, motoric behavior, or reflex and pain sensitivity. Exposure in the period equivalent to the human third trimester was associated with the strongest effects.

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Ibuprofen (IBU) is a non-steroidal anti-inflammatory (NSAIDs) that is used in various conditions. The prescriptions and the global consumption of this drug are very high and its annual production oscillates in millions of tons, this generates that the IBU is present in many waterbodies because it is discharged through the municipal, hospital and industrial effluents. For the above, the purpose of this work was to determine if IBU at environmentally relevant concentrations was capable of inducing alterations to embryonic development, teratogenic effects and oxidative stress in oocytes and embryos of Cyprinus carpio. Oocytes of common carp were exposed to IBU concentrations between 1.5 and 11.5 µg L-1 (environmentally relevant). LC50 and EC50 of malformations were determined to calculate the teratogenic index (TI). Also, main alterations to embryonic development and teratogenic effects were evaluated. Oxidative stress was evaluated by determining biomarkers of cellular oxidation and antioxidation using the same concentrations at 72 and 96 hpf in embryos of Cyprinus carpio. The results showed a LC50 of 4.17 µg L-1, EC50 of 1.39 µg L-1 and TI of 3.0. The main embryonic development disorders and teratogenic effects were delayed hatching, hypopigmentation, pericardial edema, yolk deformation, and developmental delay. Biomarkers of cellular oxidation and antioxidants were increased with respect to the control in a concentration-dependent manner. The results of the study allow us to conclude that IBU at environmentally relevant concentrations is capable of inducing embryotoxicity and teratogenicity in a fish of commercial interest like Cyprinus carpio.

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