Search

Forsythia suspensa leaves (FSL), rich in phillyrin, forsythiaside A, phillygenin, rutin, and other compounds, is a known traditional Chinese medicine (TCM). It has been effective in heat retreat and detoxification. In this study, we performed the mutagenic and teratogenic toxicity evaluation of FSL aqueous extract (FSLAE) using the bacterial reverse mutation assay (Ames test), mouse bone marrow micronucleus assay, spermatocyte chromosomal aberration assay in mice. Kunming mice and SD rats were used were for the mutagenic and the teratogenic studies, respectively. We found that FSLAE was not mutagenic and did not induce unfavorable chromosomal events. Additionally, the Ames test revealed FSLAE was not genotoxic and showed no mutagenic activity in histidine dependent strains of Salmonella typhimurium at concentrations up to 5000 μg/plate. Likewise, in vivo test revealed no induced micronucleus of mouse bone marrow or chromosome aberration in spermatocytes up to the dose of 10.00 g/kg BW. For the teratogenic evaluations, pregnant rats were treated with 1.04, 2.08, and 4.17 g/kg FSL, and fetuses were examined on the 6–15 day of pregnancy. We observed no maternal toxicity and embryotoxicity related to the treatment. Based on these in vitro and in vivo studies, we concluded the genotoxic and teratogenic safety of FSL. [ABSTRACT FROM AUTHOR]

Acne vulgaris is quite common during adolescence but also occurs in children, adults, and pregnant women. It is a condition in which androgens are produced during puberty and induce hypertrophy of the sebaceous glands, and the excess secretory rate in predisposed individuals triggers acne. Sebum promotes the growth of a resident anaerobic bacterium on the skin, Propionibacterium acnes (P. acnes) also known as Cutibacterium acnes (C. acnes). Acne affects areas of the skin with large numbers of sebaceous glands. Treatment of acne can be done topically with retinoids, azelaic acid, benzoyl peroxide or topical antibacterials or systemically with oral antibacterials, hormonal therapies or isotretinoin. The pharmacist plays a particularly important role in educating patients about correct skin care products and medications used to treat acne, especially in women of childbearing age. This article is an update of the 2020 version and includes new insights regarding acne vulgaris. [ABSTRACT FROM AUTHOR]

The therapeutic management of women with epilepsy (WWE) of childbearing age can be complicated by the need to balance maternal/fetal risks related to seizure occurrence during gestation with the potential teratogenic risks related to the use of anti-seizure medications (ASMs). The authors review clinical evidence on seizure-related and ASM-related risks during pregnancy. Current regulatory indications are discussed, evaluating their impact on clinical practice, and ethical implications of pharmacological decisions are debated. If properly informed about the maternal/fetal risks carried by different pharmacological choices, WWE can become the final decision makers regarding their care in every phase of their life. Over the coming years, analysis of aggregated pregnancy registry data on the structural impact, on the fetus, of low doses of valproate and of newer ASMs, together with analysis of the main population study data on functional (cognitive and behavioral) outcomes, could lead to huge advances, making choosing an ASM a less complex process for the clinician and a less painful decision for the woman. Future objectives should include identification of the potential role of the pharmacogenomic profile of WWE in determining the risk of fetal malformations. [ABSTRACT FROM AUTHOR]

Therapeutic options are limited during pregnancy due to the safety of the fetus. Non-opioid analgesics (NOA) are among the most commonly prescribed medicaments by physicians. Many of them are available over-the-counter (OTC) without prescription and in non-pharmacy sales such as hypermarkets and petrol stations. There has been a steady increase in their sales due to their high availability, the spread of self-medication, and advertising. They are used for pain of various origins, inflammatory diseases, colds, and flu. Monitoring the safety of therapy with these drugs is particularly important in the population of pregnant women, due to their high popularity and the different pharmacokinetics during pregnancy. The number of clinical studies on pregnant women is very limited, so it is important to raise awareness and knowledge of the adverse effects (ADR) on the developing fetus. This study aimed to analyze and evaluate the safety of non-opioid analgesics in a population of pregnant women based on the results of an anonymous validated survey. It will increase awareness and enable women to make informed decisions and consider the potential risks associated with treating or not treating pain during pregnancy and breastfeeding. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the incidence of congenital malformations in children exposed prenatally to antiseizure medications (ASMs), to assess other perinatal and fetal complications, and to determine the potential predictors for these complications. Method: A retrospective review of pregnancy outcomes of women with epilepsy. Patients were followed up at the King Faisal Specialist Hospital and Research Centre, Riyadh and Jeddah, Saudi Arabia, between Dec 1993 and Oct 2020. Results: Of 162 pregnancies included, 10 (6.17%) congenital malformations were observed, 6.82% in ASM-exposed babies versus 3.33% in babies of epilepsy-untreated mothers (P = 0.69). The overall incidence of perinatal and fetal complications was 53%; most frequent were low birth weight (24%), preterm birth (19%), transfer to neonatal intensive care unit (18%) and abortion (8%). These complications were higher in the untreated group (66.67%) than in the ASM group (50%). The use of other non-antiseizure medications during pregnancy was the only factor that significantly increased the risk of complications. Conclusion: Prenatal exposure to ASMs was associated with increased risk of congenital malformations. However, overall perinatal and fetal complications were higher in the untreated group than in the ASM group, which could be explained by maternal seizures. Therefore, taking ASMs to control epilepsy and prevent perinatal complications may outweigh the risks of teratogenicity.

This review is a comprehensive summary of treatment options for pregnant patients with less common bacterial, fungal, and viral infections. It offers guidance to clinicians based on the most recently published evidence-based research and expert recommendations. A search of MEDLINE (inception to March 2021) and the CDC website was performed. Liposomal amphotericin B is the preferred therapy for cryptococcosis, histoplasmosis, oesophageal candidiasis, and coccidioidomycosis, especially during the first trimester due to teratogenic concerns with azole antifungals. For oral candidiasis, clotrimazole troches or miconazole mucoadhesive buccal tablets are recommended. A β-lactam antimicrobial is preferred over doxycycline for various manifestations of Lyme disease and the drug of choice for Pneumocystis pneumonia is trimethoprim/sulfamethoxazole. Acyclovir is the preferred antiviral for varicella zoster virus. Fluoroquinolones, macrolides, and aminoglycosides should be avoided if possible and there are alternate agents available for an effective treatment regimen. There is a scarcity of clinical data in pregnant patients with less common bacterial, fungal and viral infections. This population lacks definitive recommendations in many clinical practice guidelines. The key to optimizing therapy is a comprehensive review of the available evidence and a careful balance of risks and benefits before final treatment decisions.

The RXR agonist (triphenyltin, TPT) and the RXR antagonist (UVI3003) both show teratogenicity and, unexpectedly, induce similar malformations in Xenopus tropicalis embryos. In the present study, we exposed X. tropicalis embryos to UVI3003 in seven specific developmental windows and identified changes in gene expression. We further measured the ability of UVI3003 to activate Xenopus RXRα (xRXRα) and PPARγ (xPPARγ) in vitro and in vivo. We found that UVI3003 activated xPPARγ either in Cos7 cells (in vitro) or Xenopus embryos (in vivo). UVI3003 did not significantly activate human or mouse PPARγ in vitro; therefore, the activation of Xenopus PPARγ by UVI3003 is novel. The ability of UVI3003 to activate xPPARγ explains why UVI3003 and TPT yield similar phenotypes in Xenopus embryos. Our results indicate that activating PPARγ leads to teratogenic effects in Xenopus embryos. More generally, we infer that chemicals known to specifically modulate mammalian nuclear hormone receptors cannot be assumed to have the same activity in non-mammalian species, such as Xenopus. Rather they must be tested for activity and specificity on receptors of the species in question to avoid making inappropriate conclusions.

Introduction: Oral isotretinoin is an effective agent for the treatment of severe cystic acne. Isotretinoin is a teratogen; there is an increased risk of congenital defects in infants exposed to the drug in the uterus. The Saudi Food and Drug Authority (SFDA) has implemented a pregnancy prevention program (PPP) to protect females from those teratogenic effects. Objectives: To investigate the awareness of women, of reproductive age who were using Isotretinoin or used it previously, about isotretinoin use and the SFDA-approved PPP in Riyadh, Saudi Arabia. Methods: This cross-sectional study was conducted during the period from June to October 2019. A questionnaire was developed based on the published literature and the PPP recommendations. The study was carried out online among female patients who were on Isotretinoin therapy or have used it previously in Riyadh city. The Statistical Package for Social Sciences (SPSS for Windows, version 24) was used to analyze the study data. Results: During the study period, 483 patients participated in the study. Among them, 97.3% reported that they used the drug based on a doctor’s prescription, 94.6% were aware of Isotretinoin’s teratogenic effect, and 30.6% confirmed their awareness of the PPP. Amongst the participants, 9.1% (n = 44) used Isotretinoin while being married or planning to get married within a one-month period after using it. Concerning the use of two contraceptive methods according to the PPP guidelines, of the participants, 43.2% reported that they have been informed by their healthcare providers to use two contraceptive methods before starting the medication. Also 43.2% reported that they have been informed to use two contraceptive methods while using the medication, and 50% reported that they have been informed to use two contraceptive methods for one month after stopping the medication. Regardless of the information they had, participants’ actual practice, was as follow: 15.9% used two contraceptive methods before starting the medication, 15.9% used two contraceptive methods during the treatment, and 13.6% used two contraceptive methods for one month after stopping the medication. Conclusions: Although this study revealed that the vast majority of participants were aware of isotretinoin’s teratogenic effect, still a considerable number of them had no idea about the PPP. This issue needs to greatly be addressed to minimize the risk of teratogenicity.

In this article, we present a review of ocular conditions related to alcohol consumption. A search of the literature published from 1952 to March 2020 was performed. The titles and abstracts were screened and the eligible studies were selected. PubMed, ISI Web of Knowledge database, Scopus, Embase, and the Cochrane Library were searched. We categorized the relationship between alcohol intake and ocular conditions by the type of ocular exposure to alcohol. Accordingly, ocular findings following acute alcohol intoxication, optic neuropathy following methanol toxicity, congenital conditions related to maternal alcohol consumption, and ocular disease related to chronic alcoholism are discussed. The main feature of alcohol intoxication in the eye is abnormal eye movement. Acute optic neuropathy secondary to methyl alcohol consumption is a serious ocular disease with permanent vision loss or scotoma. Prenatal exposure to ethanol may end in fetal alcohol spectrum disease, where ocular findings are a constant component. The association between chronic alcohol consumption and increased risks of cataract, age-related macular degeneration, diabetic retinopathy, different types of optic neuropathy, impairment of visual quality, retinal vascular disease, and ocular surface disease has also been reported. Along with detrimental medical and social effects, the role of alcohol consumption in different ocular conditions should be considered, as alcohol-induced visual disturbances may contribute to the heavy burden of alcohol abuse on the healthcare system and overall quality of life.

• One of the few population-based studies on AD & congenital malformation risk in Asia. • 1st trimester exposure to any AD not associated with raised major malformation risk. • Exposure to any AD may be related to raised risk of cardiac & respiratory anomalies. • SNRI & TCA related to specific cardiac defects but estimated imprecisely (wide CI). • Inconsistent sensitivity-analysis results preclude firm conclusions on raised risk. Previous studies examining antidepressants and congenital-malformations were primarily conducted in western countries, and many were constrained by important methodological limitations. This population-based study identified 465,069 women (including 1,705 redeemed ≥1 prescription of antidepressants during first-trimester) aged 15–50 years who delivered their first and singleton child between 2003 and 2018 in a predominantly-Chinese population in Hong Kong, using territory-wide medical-record database of public-healthcare services, and employed propensity-score fine-stratification-weighted logistic-regression analyses to evaluate risk of any major and organ/system-specific congenital-malformations following first-trimester exposure to antidepressants. Major malformation overall was not associated with any antidepressant (weighted-odds-ratio wOR, 0.88 [95 %CI, 0.44–1.76]), specific drug-class, or individual antidepressants. Exposure to any antidepressant was associated with increased risk of cardiac (wOR, 1.82 [95 %CI, 1.07–3.12]) and respiratory anomalies (wOR,4.11 [95 %CI, 1.61–10.45]). Exposure to selective-serotonin-reuptake-inhibitors (SSRI) and multiple-AD-classes were associated with respiratory and cardiac anomalies, respectively. However, these identified associations were not consistently affirmed across sensitivity analyses, precluding firm conclusion. Observed associations of specific cardiac defects with serotonin-norepinephrine-reuptake-inhibitors (SNRI), tricyclic-antidepressants (TCA) and multiple-AD-classes were noted with wide confidence-intervals, suggesting imprecise estimation. Overall, our findings suggest that first-trimester antidepressant exposure was not robustly associated with increased risk of congenital-malformations. Further research clarifying comparative safety of individual antidepressants on specific malformations is warranted. [ABSTRACT FROM AUTHOR]

Plant growth regulators (PGRs) are increasingly used to promote sustainable agriculture, but their unregulated use raises concerns about potential environmental risks. Indole-3-acetic acid (IAA), a commonly used PGR, has been the subject of research on its developmental toxicity in the in-vivo zebrafish model. IAA exposure to zebrafish embryos caused oxidative stress, lipid peroxidation, and cellular apoptosis. The study also revealed that critical antioxidant genes including sod , cat , and bcl2 were downregulated, while pro-apoptotic genes such as bax and p53 were upregulated. IAA exposure also hampered normal cardiogenesis by downregulating myl7 , amhc , and vmhc genes and potentially influencing zebrafish neurobehavior. The accumulation of IAA was confirmed by HPLC analysis of IAA-exposed zebrafish tissues. These findings underscore the need for further study on the potential ecological consequences of IAA use and the need for sustainable agricultural practices. [Display omitted] • Indole-3 acetic acid (IAA) induced embryotoxic and teratogenic effect in embryo. • IAA led to an increase in oxidative stress, lipid peroxidation and cellular apoptosis. • Down regulation in antioxidant and up regulation in pro-apoptotic genes due to IAA. • IAA exposure hindered cardiogenesis in developing embryos. • IAA is altering neurobehavior and tissue IAA accumulation in in-vivo larval model. [ABSTRACT FROM AUTHOR]

Women with epilepsy (WWE) wishing for a child represent a highly relevant subgroup of epilepsy patients. The treating epileptologist needs to delineate the epilepsy syndrome and choose the appropriate anti-seizure medication (ASM) considering the main goal of seizure freedom, teratogenic risks, changes in drug metabolism during pregnancy and postpartum, demanding for up-titration during and down-titration after pregnancy. Folic acid or vitamin K supplements and breastfeeding are also discussed in this review. Lamotrigine and levetiracetam have the lowest teratogenic potential. Data on teratogenic risks are also favorable for oxcarbazepine, whereas topiramate tends to have an unfavorable profile. Valproate needs special emphasis. It is most effective in generalized seizures but should be avoided whenever possible due to its teratogenic effects and the negative impact on neuropsychological development of in utero- exposed children. Valproate still has its justification in patients not achieving seizure freedom with other ASMs or if a woman decides to or cannot become pregnant for any reason. When valproate is the most appropriate treatment option, the patient and caregiver must be fully informed of the risks associated with its use during pregnancies. Folate supplementation is recommended to reduce the risk of major congenital malformations. However, there is insufficient information to address the optimal dose and it is unclear whether higher doses offer greater protection. There is currently no general recommendation for a peripartum vitamin K prophylaxis. During pregnancy most ASMs (e.g. lamotrigine, oxcarbazepine, and levetiracetam) need to be increased to compensate for the decline in serum levels; exceptions are valproate and carbamazepine. Postpartum, baseline levels are reached relatively fast, and down-titration is performed empirically. Many ASMs in monotherapy are (moderately) safe for breastfeeding and women should be encouraged to do so. This review provides a practically oriented overview of the complex management of WWE before, during, and after pregnancy. [ABSTRACT FROM AUTHOR]

Zebrafish (Danio rerio), a freshwater fish, has become a favoured animal model to assess the teratogenicity effects of various compounds. Momordica charantia is a fruit traditionally used as a functional food to treat various ailments. In the present work, 80% ethanolic extract of M. charantia fruit was investigated for its teratogenicity effects on the zebrafish embryos. The embryos of 12 h post-fertilisation were immersed in the ethanolic extract at various concentrations of 250, 500, 750, 1,000, and 1,250 mg/L prepared in 2% DMSO. Microscopic observation was carried out every 24 h. Results showed an increased mortality rate, and a delayed hatching rate with increasing concentration. Some of the deformities observed included hyperactivity, crooked backbone, reduced pigmentation, awkward positioning, and coagulation at the highest concentration. Probit analysis resulted in 725.90 mg/L as the median lethal concentration (LC50). Chromatographic analysis revealed the presence of propanedioic acid, malic acid, contrunculin-A, glutamine, D-fructose, sorbopyranose, xylitol, galactonic acid, D-mannitol, and mannose. These compounds may contribute to the deformities observed in a concentration-dependent manner. Therefore, M. charantia fruit must be consumed with caution and within the recommended amount. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to examine trends in valproate use among women of childbearing potential (WCBP) aged 16–44 years in Ireland following two European‐directed regulatory interventions in December 2014 and April 2018. Methods: This was a repeated cross‐sectional study using monthly national pharmacy claims data, to examine trend changes in the prevalence of valproate use among WCBP pre and post two separate regulatory events in December 2014 and April 2018. Annual population estimates from the Central Statistics Office were used to calculate the prevalence rate per 1000 eligible women. Segmented regression analysis of interrupted time series with negative binomial regression was used to examine rates for WCBP aged 16–44 years, and by 10‐year age groups. Prevalence ratios (PR) are presented with 95% confidence intervals (CIs). Results: Among WCBP aged 16–44 years, there was no statistically significant change in the month‐to‐month prevalence ratio in the post‐ compared to pre‐December 2014 intervention period. A significant decline was, however, observed in the post‐, compared to pre‐April 2018 intervention period (PR = 0.998, [95% CIs: 0.996, 1.000]; p = 0.029). Among those aged 16–24 years, a significant decreasing trend in the month‐to‐month prevalence ratio was found in the post‐ compared to pre‐December 2014 intervention period (PR = 0.991, [95% CIs: 0.984, 0.998];p <0.01). A marginal effect was observed in the post‐ compared to pre‐April 2018 intervention period for those aged 25–34 years (PR = 0.996, [95% CIs: 0.992, 1.000]; p = 0.048). Conclusion: Although no evidence of change was observed following the December 2014 intervention period, a significant decline in the prevalence ratio of valproate use was observed after the 2018 intervention, which may reflect the introduction of the most recent contraindication measures. [ABSTRACT FROM AUTHOR]

Valproate (VPA) is an effective treatment for epilepsy and also used in bipolar disorder. However, VPA is associated with a significant risk of birth defects and developmental disorders if used during pregnancy. This has led to the introduction of measures to reduce the use of valproate in women of childbearing potential such as the 'Prevent' pregnancy prevention program (PPP) and the completion of an annual risk acknowledgement form (ARAF). The aim of the current audit was to assess compliance with the guidance. An audit tool was made available to neurologists registered with the Association of British Neurologists (ABN) and to epilepsy nurse specialists via the Epilepsy Nurses Association (ESNA) in the UK. Data were collected between November 2020 and March 2021. The main indication for valproate was generalised epilepsy (55.8%), followed by focal (22.5%). For most, there was documentation that the woman had been informed about the risks associated with taking valproate during pregnancy (93.1%) and the need to be on highly effective contraception or that this was not deemed appropriate (92.2%). A signed ARAF was available in the notes for 81.2% although only 66% were <12 months old. Although information had been made available for most women, there were still individuals where this was not documented. Further work is needed to facilitate identification of women taking valproate and implementation of a digital ARAF. For clinicians, the audit highlights a need to carefully counsel women about the teratogenic risks of continuing to take valproate versus the risk of deteriorating seizure control if the drug is withdrawn. This is particularly true of women with focal epilepsy, where there may be safer, equally effective, alternative anti-seizure medication (ASM). The aim should be to create a partnership of trust between the patient and clinician in order to arrive at the best clinical decision for that individual. [ABSTRACT FROM AUTHOR]

Maghemite nanoparticles ( Fe 2 O 3 NPs) have a wide array of applications in various industries including biomedical field. There is an absence of legislation globally for the regulation of the production, use, and disposal of such NPs as they are eventually dumped into the environment where these NPs might affect the living systems. This study evaluates the effect of the Fe 2 O 3 NP-induced developmental toxicity in zebrafish embryos/larvae. The commercially available Fe2O3 NPs were purchased, and zebrafish embryos toxicity test was done by exposing embryos to various concentrations of Fe 2 O 3 NPs at 1 hpf and analyzed at 96 hpf. Based on the LC50 value (60.17 ppm), the sub-lethal concentrations of 40 and 60 ppm were used for further experiments. Hatching, lethality, developmental malformations, and heartbeat rate were measured in the control and treated embryos/larvae. The ionic Fe content in the media, and the larvae was quantified using ICP-MS and AAS. The biomolecular alterations in the control and treated groups were analyzed using FT-IR. The Fe ions present in the larvae were visualized using SEM-EDXS. In situ detection of AChE and apoptotic bodies was done using staining techniques. Biochemical markers (total protein content, AChE, and Na+ K+-ATPase) along with oxidants and antioxidants were assessed. A significant decrease in the heartbeat rate and hatching delay was observed in the treated groups affecting the developmental processes. Teratogenic analysis showed increased developmental deformity incidence in treated groups in a dose-dependent manner. The accumulation of Fe was evidenced from the ICP-MS, AAS, and SEM-EDXS. Alterations in AChE and Na+ K+-ATPase activity were observed along with an increment in the oxidants level with a concomitant decrease in antioxidant enzymes. These results show Fe 2 O 3 NP exposure leads to developmental malformation and results in the alteration of redox homeostasis. [ABSTRACT FROM AUTHOR]

Embryotoxic and teratogenic effects were found in OTA-treated pregnant Swiss albino mice, which were particularly strong at OTA contamination levels of 20 ppm (corresponding to 2.8 mg OTA/kg bw per day), when fed between the day 7 and day 12 of the pregnancy. Slighter embryotoxic and teratogenic effects were found when OTA was given up to day 7 or after day 12 of mice pregnancy. The feed levels of 10 ppm OTA (corresponding to 1.4 mg OTA/kg bw per day) have a significantly weaker embryotoxic and teratogenic effects on pregnant mice and no such effects were found at 5 ppm OTA (corresponding to 0.7 mg OTA/kg gt per day). The main OTA-induced malformations wre seen in the craniofacial structures, e.g. anophthalmia, monophthalmia, microphthalmia, astomia, microstomia, maxillary hypoplasia, microcephaly, macrocephaly, in newborn mice as compared to OTA-induced somatic malformations, e.g. peromelia, micromelia, spina bifida and facial cleft. Phenylalanine given at 20 ppm in the diet was found to have a protective effect against embryotoxic and teratogenic effects of OTA. [Display omitted] • Ochratoxin A (10–20 ppm) exerts teratogenic effects in mice. • No teratogenic effect of 5 ppm OTA was seen in mice. • A protective effect of phenylalanine against OTA-induced teratogenicity was seen. • The main OTA-induced malformations were found in the craniofacial structures in newborn mice. • OTA has a stronger teratogenic effect between day 7 and day 12 of the mice pregnancy. [ABSTRACT FROM AUTHOR]

Myasthenia gravis (MG) is an autoimmune condition that mainly affects young women (in the second or third decade of life) and is characterized by clinical symptoms ranging from fluctuating muscle weakness in the scapular and pelvic girdle to respiratory, ocular and bulb symptoms. Counseling and preconception planning, the assessment of the impact of pregnancy on the disease, the possible maternal-fetal complications in the first trimester and postpartum, the prophylaxis of myasthenic and cholinergic seizures, the teratogenic potential of medication, the careful fetal monitoring, the intrapartum features of analgesia and anesthesia and the management of neonatal myasthenia gravis are many problems that must be carefully monitored during pregnancy. These goals are achieved through the efforts of a multidisciplinary team. Therefore, women with MG should be supported in their desire to become pregnant and advised to give birth in tertiary medical units that manage high-risk pregnancies and ensure good neonatal intensive care. [ABSTRACT FROM AUTHOR]

Aflatoxin B1 (AFB1) is a potent mycotoxin and natural carcinogen. The primary producers of AFB1 are Aspergillus flavus and A. parasiticus. Sterigmatocystin (STC), another mycotoxin, shares its biosynthetic pathway with aflatoxins. While there are abundant data on the biological effects of AFB1, STC is not well characterised. According to published data, AFB1 is more harmful to biological systems than STC. It has been suggested that STC is about one-tenth as potent a mutagen as AFB1 as measured by the Ames test. In this research, the biological effects of S9 rat liver homogenate-activated and non-activated STC and AFB1 were compared using two different biomonitoring systems, SOS-Chromotest and a recently developed microinjection zebrafish embryo method. When comparing the treatments, activated STC caused the highest mortality and number of DNA strand breaks across all injected volumes. Based on the E. coli SOS-Chromotest, the two toxins exerted the same genotoxicities. Moreover, according to the newly developed zebrafish microinjection method, STC appeared more toxic than AFB1. The scarce information correlating AFB1 and STC toxicity suggests that AFB1 is a more potent genotoxin than STC. Our findings contradict this assumption and illustrate the need for more complex biomonitoring systems for mycotoxin risk assessment. [ABSTRACT FROM AUTHOR]

Abstract Background Administration of gonadotropin-releasing hormone agonist (GnRH-a) in the luteal phase is commonly used for pituitary suppression during in vitro fertilisation (IVF). There is an ineluctable risk of inadvertent exposure of spontaneous pregnancy to GnRH-a. However, little is known about the pregnancy complications and repregnancy outcomes of the affected women and the neurodevelopmental outcomes of the GnRH-a-exposed children. Methods Retrospective analysis was used to determine obstetric and repregnancy outcomes after natural conception in 114 women who naturally conceived while receiving GnRH-a during their early pregnancy over the past 17 years. The GnRH-a-exposed children were evaluated to determine their neonatal characteristics and long-term neurodevelopmental outcomes. The outcomes were compared to those of relevant age-matched control groups. Results Sixty-five women had 66 live births. The neonatal health outcomes and the incidence of maternal complications were similar in the GnRH-a-exposed and control groups. Thirty-one GnRH-a-exposed children, aged 2–8 years, were available for investigation of neurodevelopment. Except for one case of autism spectrum disorder, the full-scale intelligence quotient score was within the normal range and similar to that of the control group. Most mothers with successful pregnancies and about one-third of the women who had spontaneous abortions were subsequently able to conceive naturally again. IVF is recommended for repregnancy in women who have experienced ectopic pregnancies. Conclusions Accidental exposure to GnRH-a in early pregnancy might be safe. Reproductive treatment suggestions for repregnancy should be made with consideration of the outcomes of the previously GnRH-a-exposed spontaneous pregnancy.

Introduction. Rubella virus has pronounced teratogenic properties that can cause generalized and persistent intrauterine infection of the fetus. As a result, the control of the loss of teratogenicity inherent in «wild-type» virus strains is a necessary stage of a preclinical study of the vaccine strain for a live attenuated rubella vaccine. The purpose of the study is to comprehensively study the teratogenic properties of the vaccine strain of rubella virus «Orlov-V» in the experiment on rhesus macaques. Material and methods. Seronegative to rubella virus female rhesus macaques in early pregnancy at the age of 4–7 years (n = 13) were used in the experiment. Animals of the experimental group (n = 9) received single immunization intramuscularly with a preparation from the «Orlov-V» strain. The control group of the monkeys (n = 3) were immunized with a commercial vaccine containing Wistar RA27/3 strain. The female of the control group (n = 1) was injected with a solvent used in the rubella vaccine. Study of possible teratogenic properties of vaccine strains of rubella virus was carried out using a complex of clinical, immunological, pathomorphological and virological methods. Clinical observations were made within 3 months after the monkeys’ birth. Determination of antibody titers in the blood serum of immunized monkeys was performed in HI test on the 28th–30th day after infection. The ELISA method was applied to determine IgM antibodies in the blood serum of newborns within the first month of life. Detection of rubella virus RNA was performed by PCR with electrophoretic detection of amplicons. Results. No markers of congenital rubella infection were found in infants born from monkeys vaccinated during the pregnancy. It is shown that PCR can be an informative method to confirm the absence of teratogenic properties of vaccine strains of rubella virus. Discussion. The obtained data demonstrated that vaccine strains of the «Orlov-V» rubella virus and Wistar RA27/3 have lost their teratogenic properties. The possibility of using an alternative strategy for preclinical assessment of specific safety of antiviral vaccines including a complex of clinical, immunological, pathologic and virological methods instead of the classical pathologic method is discussed. Conclusion. The results obtained in this study showed the absence of teratogenic properties and high immunogenic activity of the vaccine strain of rubella virus «Orlov-V».

Over the past years, many legitimate concerns have been raised about the effects of dibutyl phthalate (DBP) as an endocrine disruptor, especially on reproduction. The aim of this publication is to critically review the literature related to the developmental and reproductive toxicity of DBP in animals. Several electronic databases were systematically searched until 2019. Studies were qualified for the review if they: linked exposure to DPB with reproduction, were published in English after 1990, and were conducted on animals. In the studies of the testicular effects of DBP on experimental animals, the most common effects of exposure included reduced fertility, atrophic changes in male gonads, degenerative changes in the epididymis, as well as a reduction in sperm count and motility, cryptorchidism, hypospadias, poor sperm quality and other genital defects (decreased testicular weight, delayed spermatogenesis, Leydig cell aggregation, impaired Sertoli cell maturation, and significant inhibitions of testicular enzymes). The embryotoxic effects of DBP on laboratory animals included mainly an increase in fetal resorption and a decrease in live births. The teratogenic effects of DBP also manifest as skeletal malformations in fetuses, malformations of male gonads and other genital effects. On the basis of the literature data, it is clearly demonstrated that DBP shows anti-androgenic effects; however, there are also reports confirming its weak estrogenic effect. Additionally, lower doses cause more adverse effects than the highest dose, which is an important fact because of the widespread environmental exposure to DBP. The studies clearly confirm that DBP is an endocrine disruptor. Int J Occup Med Environ Health. 2021;34(1):15–37

Tremendous progress has been made in the field of toxicology leading to the advance of developmental toxicity assessment. Conventional animal models and in vitro two-dimensional models cannot accurately describe toxic effects and predict actual in vivo responses due to obvious inter-species differences between humans and animals, as well as the lack of a physiologically relevant tissue microenvironment. Human embryonic stem cell (hESC)- and induced pluripotent stem cell (iPSC)-derived three-dimensional organoids are ideal complex and multicellular organotypic models, which are indispensable in recapitulating morphogenesis, cellular interactions, and molecular processes of early human organ development. Recently, human organoids have been used for drug discovery, chemical toxicity and safety in vitro assessment. This review discusses the recent advances in the use of human organoid models, (i.e., brain, retinal, cardiac, liver, kidney, lung, and intestinal organoid models) for developmental toxicity and teratogenicity assessment of distinct tissues/organs following exposure to pharmaceutical compounds, heavy metals, persistent organic pollutants, nanomaterials, and ambient air pollutants. Combining next-generation organoid models with innovative engineering technologies generates novel and powerful tools for developmental toxicity and teratogenicity assessment, and the rapid progress in this field is expected to continue.

Copyright of Actualités Pharmaceutiques is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Paroxetine is a selective serotonin reuptake inhibitor (SSRI) used in the treatment of depression and anxiety disorders. In some epidemiological studies, slightly increased risks of major malformations and cardiac malformations have been reported following paroxetine exposure in the first trimester of pregnancy. However, such findings have been inconsistent. There is only one report of any overdose of an SSRI during pregnancy, and that involved escitalopram. The aim of this case report was to describe the impact of a paroxetine overdose in the first trimester of pregnancy on the health of the foetus. A 21-year-old mother of one child who was pregnant with a second child was prescribed 20 mg/day paroxetine hydrochloride for the treatment of anxiety/depression. The patient ingested 15 or 16 20-mg tablets of paroxetine hydrochloride (300–320 mg) during the 5th week of pregnancy as a suicide attempt. Within 15 min of ingestion, she was admitted to hospital and treated for intoxication. No evidence of maternal SSRI intoxication was observed after treatment. The patient consulted our teratology information service for further risk assessment regarding possible major congenital malformations following the paroxetine overdose. We were unable to find previous reports of paroxetine overdose during pregnancy in the literature. The timely administration of the overdose treatment and the lack of maternal intoxication symptoms were considered positive for the foetal well-being, and the patient was referred for perinatology and psychiatry follow-ups. A healthy, 3 500-g male infant was born at 38 weeks’ gestation, and his development at the age of 2 years was normal. This is the first reported case of paroxetine overdose during pregnancy. Comprehensive studies are needed to evaluate pregnancy outcomes after SSRI overdose.Key Points There are no reported data on paroxetine overdose during pregnancy. The aim of this case report was to describe the impact of a maternal paroxetine overdose in the first trimester of pregnancy on the health of the foetus. No evidence of maternal SSRI intoxication was observed. No congenital malformations or developmental disorders were observed in the child at 2 years of age. Comprehensive studies are needed to evaluate pregnancy outcomes following SSRI overdose.

Pregnant women constitute a vulnerable population, with 25.3% of pregnant women classified as suffering from a psychiatric disorder. Since childbearing age typically aligns with the onset of mental health disorders, it is of utmost importance to consider the effects that antipsychotic drugs have on pregnant women and their developing fetus. However, the induction of pharmacological treatment during pregnancy may pose significant risks to the developing fetus. Antipsychotics are typically introduced when the nonpharmacologic approaches fail to produce desired effects or when the risks outweigh the benefits from continuing without treatment or the risks from exposing the fetus to medication. Early studies of pregnant women with schizophrenia showed an increase in perinatal malformations and deaths among their newborns. Similar to schizophrenia, women with bipolar disorder have an increased risk of relapse in antepartum and postpartum periods. It is known that antipsychotic medications can readily cross the placenta, and exposure to antipsychotic medication during pregnancy is associated with potential teratogenicity. Potential risks associated with antipsychotic use in pregnant women include congenital abnormalities, preterm birth, and metabolic disturbance, which could potentially lead to abnormal fetal growth. The complex decision-making process for treating psychosis in pregnant women must evaluate the risks and benefits of antipsychotic drugs. [ABSTRACT FROM AUTHOR]

Monoterpenes make up the largest group of plant secondary metabolites. They can be found in numerous plants, among others, the Lamiaceae family. The compounds demonstrate antioxidative, antibacterial, sedative and anti-inflammatory activity, hence, they are often employed in medicine and pharmaceuticals. Additionally, their fragrant character is often made use of, notably in the food and cosmetic industries. Nevertheless, long-lasting studies have revealed their toxic properties. This fact has led to a detailed analysis of the compounds towards their side effects on the human organism. Although most are safe for human food and medical applications, there are monoterpene compounds that, in certain amounts or under particular circumstances (e.g., pregnancy), can cause serious disorders. The presented review characterises in vitro and in vivo, the toxic character of selected monoterpenes (α-terpinene, camphor, citral, limonene, pulegone, thujone), as well as that of their original plant sources and their essential oils. The selected monoterpenes reveal various toxic properties among which are embryotoxic, neurotoxic, allergenic and genotoxic. It is also known that the essential oils of popular plants can also reveal toxic characteristics that many people are unaware of. [ABSTRACT FROM AUTHOR]

The number of man-made chemicals has increased rapidly in recent decades, with certain chemicals potentially causing malformations in fetuses. Although the toxicities of chemicals have been tested in animals, chemicals that are not teratogenic in rodents can cause severe malformations in humans, owing to the differences in the susceptibility to the teratogenicity of chemicals among species. One possible cause of such species differences, other than pharmacokinetics, could be the difference in sensitivity to such chemicals at the cellular level. Therefore, a human cell-based high-throughput assay system is needed for detecting potential teratogenic chemicals. In this study, we proposed a signal reporter assay using human induced pluripotent stem cells (iPSCs). Because developmental processes are governed by highly intricate and precisely programmed signaling pathways, external chemical-induced disruption of these pathways often triggers developmental toxicities. The reporter assay using hiPSCs was used to detect changes in the fibroblast growth factor (FGF) signaling pathway, a pathway essential for limb morphogenesis. The method was based on monitoring and time-accumulation of the signal disruption over time, rather than the classical endpoint detection of the signal disruption. This approach was useful for detecting signal disruptions caused by the malformation chemicals listed in the ICH S5 guideline, including thalidomide. The human iPSC-based signal disruption assay could be a promising tool for the initial screening of developmental toxicants. [ABSTRACT FROM AUTHOR]

Xylan is the second most abundant polysaccharide group in plants and has a wide variety of food and pharmaceutical applications. However, little information on the safety assessment of extracted xylan as dietary supplement is available. As part of a comprehensive toxicological assessment, this study examined the potential toxicity of xylan extracted from sugarcane bagasse by three genotoxicity studies (Ames test, in vivo mice bone marrow micronucleus test, and mice sperm abnormality test) and a teratogenicity study in rats. In the Ames test, xylan showed no mutagenic activity on histidine dependent strains of Salmonella typhimurium at concentrations up to 5000 μg/plate; results of the in vivo mice bone marrow micronucleus test and mice sperm abnormality test indicated no significant effect on sperm morphology and micronucleus rate of polychromatic erythrocytes in mice at doses up to 5 g/kg body weight. In the teratogenicity study, a total of 60 pregnant rats were exposed to 10, 5, and 2.5% xylan in diet, from gestation days 7 to 16, and the no-observed-adverse-effect levels (NOAEL) of xylan was determined to be 9.8 g/kg body weight. The safe dose of xylan for human was estimated to be 98 mg/kg/day (i.e., 6.86 g/day for a 70-kg person), using a 100-fold safety factor. Taken together, results of this study indicated that xylan is practically nontoxic in terms of potential dietary consumption by humans in food or as a dietary supplement. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) in pregnancy is rare and often presents at a late stage due to the masking of signs by pregnancy. A typical chemotherapeutic regimen for stage III and IV CRC comprised 5-Fluorouracil (5-FU) and oxaliplatin. The treatment of CRC during pregnancy is complicated owing to the potential risk of teratogenicity with chemotherapy, especially in the first trimester. Data suggest that the administration of chemotherapy beyond the first trimester may be relatively safe. Previous reports have shown success with the use of FOLFOX (folinic acid, 5-FU, oxaliplatin) and FOLFIRI (folinic acid, 5-FU, irinotecan) during pregnancy. Moreover, neoadjuvant FOLFOXIRI (folinic acid, 5-FU, oxaliplatin, irinotecan) resulted in improved outcomes when compared to standard preoperative chemoradiotherapy in the treatment of locally advanced and metastatic CRC. The use of FOLFOXIRI in pregnancy is not currently documented, and therefore, the outcomes of using this chemotherapeutic regimen are unclear. The aim of this case report was to demonstrate the use of FOLFOXIRI in pregnancy. A retrospective chart review was performed to assess the clinical course and fetal outcome of 2 patients presented in this case report. FOLFOXIRI was initiated in two pregnant women with nonmetastatic and metastatic CRC, resulting in successful delivery of healthy infants. FOLFOXIRI is an effective chemotherapy regimen for the treatment of advanced CRC and may be used during the second and third trimesters of pregnancy. [ABSTRACT FROM AUTHOR]

Background: Sodium valproate is considered the most teratogenic of all anticonvulsant drugs. Internationally, new regulations require women to sign risk assessment forms if initiated on it. Aim: This study aimed to explore patients' awareness of the teratogenic risk of sodium valproate. Setting: Weskoppies Psychiatric Hospital, Tshwane, Gauteng. Methods: We conducted a qualitative study comprising 23 semi-structured interviews with female bipolar patients of reproductive age at a tertiary psychiatric hospital in South Africa. Results: Patient psychoeducation and self-education is improving as many patients were aware of the risk of teratogenicity of sodium valproate either by being educated or by searching online after developing an interest. Our study identified the need for female patients to be educated about contraceptive use when starting on sodium valproate to avoid pregnancy. Conclusion: Our study shows that patients are becoming more aware of the teratogenic risk of sodium valproate. This suggests that consultations focusing on the issues of conception and the use of sodium valproate in women of childbearing potential has improved. [ABSTRACT FROM AUTHOR]

The objective of this study was to determine the single and simultaneous toxic effects of chlorpyrifos containing insecticide formulation (Pyrinex 48 EC) and tebuconazole containing fungicide formulation (Mystic 250 EW) on the development of chicken embryos. Amount of 0.1 ml of 1% Pyrinex 48 EC and of 0.4% Mystic 250 EW was alone and concomitantly injected into the air chamber of eggs on the first day prior to incubation. The chicken embryos were examined on day 19 of incubation for the followings: number of embryonic deaths, body, liver and heart weight of the embryos, and type of developmental anomalies. The body, liver and heart weight data were evaluated statistically by One-Way ANOVA, Tukey and Dunnett tests, the embryonic mortality and the developmental abnormalities were analysed by Fisher's exact test. The combined administration of Pyrinex 48 EC and Mystic 250 EW pesticides on the chick embryo had shown to be embryotoxic to the chick. The rate of mortality and the incidence of developmental anomalies were increased due to the simultaneous application of them. The body and liver weight were significantly reduced. Our teratogenicity study revealed that the combined administration of both chlorpyrifos (Pyrinex 48 EC) and tebuconazole (Mystic 250 EW) pesticides on the chick embryo had shown to be embryotoxic to the chick. They had a slight addition effect on the rate of embryonic mortalities, however, the toxic interaction of both pesticides on developmental anomalies, liver and body weight was not proven. [ABSTRACT FROM AUTHOR]

Background: Valproate use during pregnancy increases risk in malformations and neurodevelopmental disorders. Data from the experimental setting in mice showed valproate is a direct inhibitor of histone deacetylase, inducing histone hyperacetylation, histone methylation, and DNA demethylation causing congenital malformations with an epigenetic inheritance. We investigated potential transgenerational adverse effects of valproate. Methods: We questioned 108 individuals (from 90 families) suffering complications due to valproate exposure in utero who were parents themselves (85 women and 23 men) about the occurrence of malformations and neurodevelopmental disorders in their children. All were member of Aide aux Parents d'Enfants souffrants du Syndrome de l'AntiConvulsivant (APESAC), a charity created in 2011 to provide personal assistance and support to families suffering complications due to valproate exposure during pregnancy. Results: Among their 187 children they reported 43 (23%) children with malformation(s) (26 hand or foot malformations; 15 dysmorphic facial features; 10 renal/urologic malformations; 6 spina bifida; 4 cardiac malformation; 2 craniosynostosis; 2 cleft lip and palate) and 82 (44%) children with neurodevelopmental disorders (63 problematic behaviors and autism; 41 psychomotor disorders; 16 language problems; 16 attention deficit; 5 mental retardation). Only 88 (47%) children had neither malformation nor developmental disorders. Conclusion: These data add to the need for funding pharmacoepidemiological investigations of epigenetic inheritance caused by drugs causing malformations or neurodevelopmental disorders. Individuals exposed in utero to valproate must be informed about the risk, so they can consider fertility options, antenatal diagnosis, and adequate early surveillance. [ABSTRACT FROM AUTHOR]

Approximately 50% of patients with inflammatory bowel disease including both Crohn's disease and ulcerative colitis are female with many being diagnosed and treated during their reproductive years. It is important for women to be in remission prior to and during pregnancy. There have been many advances in the treatment of inflammatory bowel disease, including new therapies. In this review, we summarize the currently approved medications for Crohn's disease and their safety in pregnancy and postpartum. The totality of evidence suggests that the majority of therapies are low-risk before and during pregnancy, and should be continued to control maternal disease. [ABSTRACT FROM AUTHOR]

Objective To evaluate whether the Pandanus amaryllifolius Roxb. powder had reproductive toxicity to the SD rat and whether it was teratogenic to theembryo, perform toxicological evaluation of its safety, and provide the basis of the toxicology safety for the development of food additive. Methods Pregnant rats were randomly divided into negative control group, positive control group, Pandanus amaryllifolius Roxb. powder sample high-dose group, middle dose group and low-dose group (2.50, 1.25 and 0.60 g/kg BW respectively), using the teratogenic test method in GB 15193.14-2015. The test substance was orally administered on the 6th to 15th day of conception, and was administered by intragastric administration. The vehicle control group was intragastrically administered with the same amount of pure water; the positive control group was intraperitoneally injected with cyclophosphamide 15 mg/kg. The pregnant rats were sacrificed on the 20th day of pregnancy, and the abnormalities of the fetal rats were examined, dissected and recorded. Results The groups intervened with Pandanus amaryllifolius Roxb. powder showed no producematernal toxicity, mbryonic toxicity nor teratogenicity, compared with the negative control group. No significant abnormality was found in the indicators, and the overall analysis did not have a dose-response relationship. The positive control group showed obvious embryonic toxicity and teratogenicity. The no observed adverse effect level (NOAEL) was 2.50 g/kg BW. Conclusion In the dose range of this experimental study, there was no teratogenic effect in the sample of Pandanus amaryllifolius Roxb. powder.

The aim of present study was to evaluate the possibility of teratogenicity in rats when exposed to zinc chloride (ZnCl2) pre and post pregnancy. To achieve this goal, a total of 40 mature Albino Wistar female rats were divided equally into four groups as follows: T1, dosed 0.7 mg/day ZnCl2 for two months before mating and till to the day 5th of pregnancy, the females of this group were mated with males dosed 0.7 mg/day ZnCl2 for two weeks before mating; T2, dosed 0.7 mg/day ZnCl2 for two months before mating and till to the day 16th of pregnancy and then were mated with control males (not exposed to any level of ZnCl2); T3, dosed 0.7mg/day ZnCl2 for two months before mating and till the end of pregnancy and were mated with control males; Control, dosed with water free from ZnCl2 along the period of experiment and were mated with control males. At the end of each pregnancy phase, results revealed that alpha fetoprotein serum levels were significantly (P

Background: Sodium valproate is considered the most teratogenic of all anticonvulsant drugs. Internationally, new regulations require women to sign risk assessment forms if initiated on it. Aim: This study aimed to explore patients’ awareness of the teratogenic risk of sodium valproate. Setting: Weskoppies Psychiatric Hospital, Tshwane, Gauteng. Methods: We conducted a qualitative study comprising 23 semi-structured interviews with female bipolar patients of reproductive age at a tertiary psychiatric hospital in South Africa. Results: Patient psychoeducation and self-education is improving as many patients were aware of the risk of teratogenicity of sodium valproate either by being educated or by searching online after developing an interest. Our study identified the need for female patients to be educated about contraceptive use when starting on sodium valproate to avoid pregnancy. Conclusion: Our study shows that patients are becoming more aware of the teratogenic risk of sodium valproate. This suggests that consultations focusing on the issues of conception and the use of sodium valproate in women of childbearing potential has improved.

The pharmacological and toxicological effects of active metabolites of enzymes including cytochrome P450 (CYP) are important. While it has been believed for a long time that thalidomide causes characteristic limb malformation only in rabbits and primates including humans, the involvement of their CYP3A subtypes (CYP3As) has been suggested. Recently, however, it was reported that zebrafish were sensitive to thalidomide, showing defects of pectoral fins, homologous organs of forelimbs in mammals, as well as other deformities. In this study, we prepared human CYP3A7 (hCYP3A7)-expressing zebrafish (F0) using a transposon system. Thalidomide caused pectoral fin defects and other malformations including pericardial edema in hCYP3A7-expressing embryos/larvae but not in wild-type and hCYP1A1-expressing embryos/larvae. Thalidomide also reduced the expression of fibroblast growth factor 8 in pectoral fin buds in only hCYP3A7-expressing embryos/larvae. The results suggest the involvement of human-type CYP3A in thalidomide teratogenicity.

Background Practicing and following a Pregnancy Prevention Program (PPP) is crucial to prevent isotretinoin-induced teratogenicity. Our study aims to assess the current practice of dermatologists about PPP when prescribing oral isotretinoin and the compliance of the patients toward contraceptive methods. Methods The research used a cross-sectional design and utilized a probability sampling method in Saudi Arabia. An online self-administered questionnaire was used to collect data that included female participants who were previously treated/being treated with isotretinoin for acne. Data was analyzed using SPSS (IBM Inc., Armonk, New York). Results Our study examined 359 female patients receiving isotretinoin treatment. Isotretinoin was primarily used for severe nodular forms of acne resistant to regular treatment 229 (63.8%). Regarding awareness, 326 (90.8%) were familiar with isotretinoin's teratogenic effects, and 112 (31.2%) were familiar with the Saudi Food and Drug Authority's Pregnancy Prevention Program. Physicians were among the most prevalent information sources 254 (71%). In terms of isotretinoin usage, 227 (63.2%) had one course. Regarding contraceptive practice, 167 (46.5%) were informed about the necessity of a negative pregnancy test before starting treatment, and 29 (50.9%) of those who received more than two courses had good awareness. Conclusion The study identified a notable awareness gap among the participants, as over two-thirds demonstrated a poor awareness level regarding isotretinoin. A significant proportion of participants were informed about the importance of contraceptive practices, including the necessity of a negative pregnancy test before, during, and after treatment., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Deanship of Scientific Research of King Faisal University issued approval KFU-REC-2023-MAY-ETHICS828. The Research Ethics Committee of King Faisal University grants its ethical approval to the protocol. The researchers are held accountable for the storage, retention, and security of original data obtained from projects. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Almarri et al.)

Background: Despite its high efficacy in treating severe acne, isotretinoin is associated with serious side effects, including teratogenicity. However, the extent of isotretinoin exposure during pregnancy in Saudi Arabia remains unknown., Objectives: This study aims to quantify the extent of fetal exposure to isotretinoin in Saudi Arabia and to evaluate adherence to risk minimization measures approved by the Saudi Food and Drug Authority., Design: Retrospective cohort study., Methods: This multicenter retrospective study included a cohort of 6233 women of childbearing ages (WCBAs) who had received isotretinoin therapy between 2015 and 2020. Exposure to isotretinoin use was ascertained from patients' electronic health records and was defined as any positive pregnancy test (urine or serum) or any diagnosis or procedure related to pregnancy occurring during the risk period. We defined the risk period starting from isotretinoin initiation until up to 30 days after the last prescription. We quantified the overall incidence proportion of fetal exposure to isotretinoin by dividing the number of pregnancy cases during the risk period by the total study sample of WCBAs., Results: The cohort predominantly included young females (20-29 years), with a mean age of 24 years. Only 5% of the WCBAs used contraceptives, and 10% have a record of pregnancy testing. During the risk period, 34 pregnancies were identified, yielding a cumulative pregnancy incidence of 5.6 per 1000 WCBAs. Pregnancy outcomes for exposed women were about 5% of births had defects, while abortions accounted for 14.3% of pregnancies., Conclusion: Our investigation shows an alarming incidence of fetal exposure to isotretinoin in Saudi Arabia, substantially surpassing global estimates. These results underscore a critical need for enhanced interventions and robust risk minimization strategies tailored to the distinct challenges faced by the Saudi Arabian population., (© The Author(s), 2024.)

Drug use during pregnancy is an important issue that must be investigated due to its adverse effects on maternal and foetal health. This study aimed to determine the embryotoxic and teratogenic effects of in-ovo administered metamizole (dipyrone), which can be used when needed during pregnancy and has potent analgesic, antipyretic, anti-inflammatory, and long bone (tibia and femur) effects. This study used 240 fertile eggs from Atak S breed chickens, divided into eight equal groups: control, vehicle control, and 15.62, 31.25, 62.5, 125, 250 and 500 mg/kg metamizole. The eggs were hatched on the 21st day of incubation, and the chicks' body weights and mortality rates were determined. The right and left femur and tibia bones were resected from the chicks. Anatomical reference points were determined after removing the soft tissues of the bones, and necessary morphometric measures were taken from these points with a 0.01 mm precision using digital callipers. The 100% lethal dose (LD 100 ) was identified in the highest examined dose (500 mg/kg) in the Chicken Embryotoxicity Screening Test (CHEST)-I stage. The CHEST-II stage determined the 50% lethal dose (LD 50 ). High-dose metamizole affected skeletal development, significantly decreasing tibia and femur lengths and corpus thicknesses and increasing mortality., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

Glucagon-like peptide-1 receptor agonists are peptide analogues that are used to treat type 2 diabetes mellitus and obesity. The first medication in this class, exenatide, was approved in 2005, and these medications, specifically semaglutide, have become more popular in recent years due to their pronounced effects on glycemic control, weight reduction, and cardiovascular health. Due to successful weight loss from these medications, many women previously diagnosed with oligomenorrhea and unable to conceive have experienced unplanned pregnancies while taking the medications. However, there are currently little data for clinicians to use in counseling patients in cases of accidental periconceptional exposure. In some studies examining small animals exposed to glucagon-like peptide-1 receptor agonists in pregnancy, there has been evidence of adverse outcomes in the offspring, including decreased fetal growth, skeletal and visceral anomalies, and embryonic death. Although there are no prospective studies in humans, case reports, cohort studies, and population-based studies have not shown a pattern of congenital anomalies in infants. A recent large, observational, population-based cohort study examined 938 pregnancies affected by type 2 diabetes mellitus and compared outcomes from periconceptional exposure to glucagon-like peptide-1 receptor agonists and insulin. The authors concluded there was not a significantly increased risk of major congenital malformations in patients taking glucagon-like peptide-1 receptor agonists, although there was no information on maternal glycemic control or diabetic fetopathy. As diabetic embryopathy is directly related to the degree of maternal hyperglycemia and not the diagnosis of diabetes itself, it is not possible to make this conclusion without this information. Furthermore, there is little evidence available regarding fetal growth restriction, embryonic or fetal death, or other potential complications. At this time, patients should be counseled there is not enough evidence to predict any adverse effects, or the lack thereof, of periconceptional exposure of glucagon-like peptide-1 receptor agonists during pregnancy. We recommend that all patients use contraception to prevent unintended pregnancy while taking glucagon-like peptide-1 receptor agonists., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Silver nanotechnology is widely applied in industry and medicine, with an increased likelihood of environmental and food contamination., Aim: This study aimed to explore the adverse effects of orally administering silver nanoparticles (AgNPs) to pregnant or lactating female rats on adults and the development of their offspring., Methods: Forty female albino rats were used to assess the immediate impacts of AgNPs in two separate experiments. The experimental group received 1 ml of AgNPs, dissolved in deionized water, at doses of 0, 50, and 100 mg/kg of body weight from the 6th to the 15th day of gestation in pregnant albino rats. After a 20-day gestation period, euthanasia was performed on the female rats, followed by a gross examination post-dissection., Results: The feti were preserved in ethyl alcohol and Poin's solution for the identification of skeletal and visceral malformations. It was noticed that feti of dams that received AgNPs showed teratogenicities such as delayed ossification and deletion of bones or ribs. Notably, dams showed necrosis and satellitosis with evidence of behavioral alteration. While rats' pups showed only brain edema and no behavioral changes., Conclusion: AgNPs at a dose of 50 or 100 mg/kg induced teratogenic effect in terms of delayed ossification, abnormal limb formation, and brain edema in rat pups, however, induced necrosis and satellitosis in dam rats. Hence, greater emphasis should be placed on preventing exposure to Ag-NPs, especially among pregnant females., Competing Interests: All authors had no conflict of interest regarding any aspect of this publication.

Bulk zinc oxide (ZnO-BPs) and its nanoparticles (ZnO-NPs) are frequently used in various products for humans. Helisoma duryi embryos can serve as effective model organisms for studying the toxicity of NPs. This study aimed to compare the teratogenic potency of ZnO-BPs and ZnO NPs in the embryonic stages of H. duryi to evaluate the utility of this snail as a bioindicator for ZnO-NPs in the aquatic environment. The mechanisms of teratogenesis were evaluated by determination of the LC 50 , studying the effect of sub-lethal concentrations of both ZnO forms on the embryos, and studying their enzyme activity, oxidative stress, and biochemical analysis. The SDS-PAGE electrophoresis was undertaken to assess the effect of ZnO-BPs and ZnO NPs on protein synthesis. The results revealed that the veliger stage of H. duryi is the specific stage for bulk and nano ZnO. ZnO-NPs proved to be more toxic to snails' embryos than ZnO-BPs. Exposure to ZnO influences specific types of defects in development, which in the case of BPs are far less drastic than those caused by NPs. Thus, the toxicity of ZnO-NPs in embryonic development is due to their unique physicochemical properties. The observed malformations include mainly hydropic malformation, exogastrulation, monophthalmia, shell misshapen, and cell lyses. Almost all tested oxidative biomarkers significantly changed, revealing that ZnONPs display more oxidative stress than ZnO-BPs. Also, the low concentration of ZnO induces many disturbances in the organic substances of veliger larvae, such as a decrease in the total protein and total lipid levels and an increase in the glycogen level. The results indicated that ZnO-BPs increase the number of protein bands. Conversely, ZnO-NPs concealed one band from treated egg masses, which was found in the control group. Embryos of snail are an appropriate model to control freshwater snails. This study demonstrates that H. duryi embryos can serve as effective model organisms to study the toxicity of ZnO-NPs., (© 2024. The Author(s).)