Birth Defects Research最新文献

{"title":"Developmental Toxicity Evaluation of the Dietary Supplement Vinpocetine Using Mouse and Human 3D Gastruloids.","authors":"Alexia Maki, Yusuke Marikawa","doi":"10.1002/bdr2.70060","DOIUrl":"10.1002/bdr2.70060","url":null,"abstract":"<p><strong>Background: </strong>Vinpocetine is marketed as a dietary supplement for cognitive enhancement, despite the absence of regulatory requirements for comprehensive toxicity testing. The FDA has issued a warning against vinpocetine use by individuals of childbearing potential based on animal studies demonstrating impaired embryonic development. However, the relevance of these findings to human embryogenesis, as well as the contribution of vinpocetine's activity as a cyclic nucleotide metabolism modulator, remains unclear. To address these gaps, gastruloids derived from pluripotent stem cells may provide in vitro models of embryogenesis for investigating chemical impacts.</p><p><strong>Methods: </strong>Gastruloids were generated from mouse P19C5 and human H9 pluripotent stem cells to evaluate the effects of vinpocetine, its major metabolite apovincaminic acid, and additional modulators of cyclic nucleotide metabolism. Morphological effects were measured using established morphometric parameters, and molecular effects were evaluated based on a previously validated panel of developmental regulator genes as sensitive biomarkers.</p><p><strong>Results: </strong>Vinpocetine induced distinct morphological changes in mouse gastruloids at concentrations ≥ 1 μM, whereas apovincaminic acid produced similar effects only at substantially higher concentrations. Other cyclic nucleotide-modulating compounds, including ITI-214, IBMX, forskolin, and cinaciguat, did not phenocopy vinpocetine-induced defects. In human gastruloids, vinpocetine impaired morphogenesis and altered developmental regulator expression at concentrations ≥ 0.2 μM.</p><p><strong>Conclusions: </strong>Vinpocetine disrupts gastruloid development in both mouse and human models at concentrations commonly used to elicit purported neuroprotective effects, supporting animal-based evidence of developmental toxicity and demonstrating human relevance. These findings highlight reproductive safety concerns associated with vinpocetine and underscore the need for systematic toxicity evaluation of dietary supplements.</p>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 5","pages":"e70060"},"PeriodicalIF":2.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13249007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147986531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of Multivitamin/Folic Acid Intake, Diabetes, and Other Risk Factors for Birth Defects Among Women in the United States, Pregnancy Risk Assessment Monitoring System, 2017-2022.","authors":"Eugene C Wong, Michelle Koh, Lorraine F Yeung, Mikyong Shin, Juan D Rodriguez, Cara T Mai","doi":"10.1002/bdr2.70057","DOIUrl":"10.1002/bdr2.70057","url":null,"abstract":"<p><strong>Background: </strong>Birth defects can cause significant morbidity and mortality. We examined the prevalence of maternal characteristics and risk factors associated with birth defects and examined their associations with prepregnancy multivitamin/folic acid (MVF) intake and diabetes.</p><p><strong>Methods: </strong>Data from 22 jurisdictions participating in the Pregnancy Risk Assessment Monitoring System (PRAMS) survey (2017-2022) of women with recent live births were used. Distributions were calculated for: prepregnancy health factors (MVF intake, diabetes status, obesity, smoking, alcohol use) and for participant characteristics (age, race/ethnicity, educational attainment, pregnancy intention, federal poverty level). Log-binomial regression was used to calculate adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs) for the associations between selected characteristics and MVF intake and diabetes. Associations between pregnancy intention and MVF intake stratified by selected characteristics were also examined. Finally, differences in longitudinal MVF intake across jurisdictions were assessed.</p><p><strong>Results: </strong>Almost half (48.2%) of women reported no prepregnancy MVF intake; before pregnancy, 52.0% were overweight or had obesity, 57.9% used alcohol, 15.2% smoked, and 3.1% had diabetes. Prepregnancy MVF intake was associated with increased age (≥ 30 years vs. 25-29: aPRs > 1.10), higher educational attainment (graduate degree vs. ≤ high school: aPR = 1.32, 95% CI: 1.17, 1.49), and intended pregnancies (aPR: 1.50, 95% CI: 1.42, 1.58). Diabetes status was not associated with MVF intake or pregnancy intention.</p><p><strong>Conclusions: </strong>Prevalence of risk factors for birth defects was high, and differences exist across groups of women. Findings from this study can help inform public health interventions on risk factors that may help improve birth outcomes.</p>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 5","pages":"e70057"},"PeriodicalIF":2.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13317058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147939579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational Studies of Satureja hortensis Phytochemicals as Inhibitors of AP-1 (FOS/JUN) Activation in Valproic Acid Teratogenicity.","authors":"Vindya Nagarakere Shankara, Syed Sagheer Ahmed, Bharathi Doddla Raghunathanaidu","doi":"10.1002/bdr2.70054","DOIUrl":"10.1002/bdr2.70054","url":null,"abstract":"<p><strong>Background: </strong>Valproic acid (VPA) is a widely used antiepileptic drug and known teratogen that induces developmental defects in part via aberrant activation of the AP-1 (c-Fos/c-Jun) transcription factor pathway. We investigated whether phytochemicals from Satureja hortensis L. (summer savory) can modulate this pathway.</p><p><strong>Methods: </strong>In this study, we employed structure-based computational methods to screen phytoconstituents of S. hortensis against the AP-1 (Fos/Jun) transcription factor.</p><p><strong>Results: </strong>Molecular docking predicted that the top ligands, cedrelanol and allo-aromadendrene, bound the DNA-bound AP-1 complex (1FOS) with affinities of -7.7 kcal/mol each, exceeding the -7.3 kcal/mol affinity of the reference inhibitor SR11302. Subsequent 100-ns molecular dynamics simulation of the cedrelanol-1FOS complex confirmed stable binding the protein backbone RMSD remained between 0.8-1.2 Å and the ligand RMSD stayed below 1.3 Å throughout the trajectory. MM/GBSA binding free energy analysis further indicated a highly favorable ΔG_binding of -75.04 kcal/mol for the cedrelanol-1FOS complex.</p><p><strong>Conclusion: </strong>These integrated results highlight cedrelanol as a potent AP-1 modulator, providing a molecular basis for exploring S. hortensis terpenoids to mitigate VPA-induced teratogenic AP-1 hyperactivation. These findings suggest that S. hortensis phytochemicals as plausible inhibitors of AP-1, with potential implications for developing plant-derived agents to mitigate VPA teratogenicity.</p>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 5","pages":"e70054"},"PeriodicalIF":2.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 S1","pages":"S1-S98"},"PeriodicalIF":1.6,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148097623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract Supplement","authors":"","doi":"10.1002/bdr2.70050","DOIUrl":"10.1002/bdr2.70050","url":null,"abstract":"","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 S1","pages":"S1-S98"},"PeriodicalIF":1.6,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147762167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 4","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148085252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 4","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148084670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 4","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148076616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Joint Position Statement from the Society for Birth Defects Research and Prevention, the Organization of Teratology Information Specialists, and the Developmental Neurotoxicology Society: A Call for Implementation of Risk Evaluation and Mitigation Strategies to Reduce Prenatal Exposure to Valproate.","authors":"Almut G Winterstein, Elizabeth Conover, Joan D Garey, Janet R Hardy, Lorrie Harris-Sagaribay, Vijaya Kancherla, Paige C Santos, Sonja A Rasmussen","doi":"10.1002/bdr2.70045","DOIUrl":"https://doi.org/10.1002/bdr2.70045","url":null,"abstract":"","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 4","pages":"e70045"},"PeriodicalIF":1.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147762242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of Maternal Pertussis Vaccination on Neonatal Health Outcomes in the Dutch Pregnancy Drug Register","authors":"Petra J. Woestenberg,&nbsp;Veronique Y. F. Maas,&nbsp;Maud de Feijter,&nbsp;Leontine van Balveren,&nbsp;Maartje Conijn,&nbsp;Sanne Boetzkes,&nbsp;Anneke J. L. M. Passier,&nbsp;Agnes C. Kant","doi":"10.1002/bdr2.70042","DOIUrl":"10.1002/bdr2.70042","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The currently high pertussis-related morbidity and mortality among infants has led to increased international attention for pertussis vaccination during pregnancy. We studied the safety of maternal pertussis vaccination in the Netherlands with respect to neonatal health.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data from the cohort the Dutch Pregnancy Drug Register were used. Pregnant participants self-reported their pertussis vaccination and the health outcomes of their offspring. Participants with a singleton live birth ≥ 24 weeks gestation were included. Using log-binomial regression analysis and correction for confounders, we studied the risk of maternal pertussis vaccination on various neonatal health outcomes. Moreover, we compared differences in health outcomes between second and third trimester vaccinations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The study population included 10,280 participants (74.8% vaccinated against pertussis during pregnancy and 25.3% not). The adjusted risk ratio (RR) was: 1.01 (95% confidence interval [CI]: 0.82–1.23) for small for gestational age; 0.90 (95% CI: 0.73–1.11) for large for gestational age; 0.86 (95% CI: 0.59–1.25) for low birth weight; 1.06 (95% CI: 0.90–1.25) for neonatal health problems, and 0.68 (95% CI: 0.47–0.99) for infant hospitalization due to (suspicion of) infection. Also for the secondary outcomes neonatal death, low Apgar score, and neonatal intensive care unit admission, no increased risk after maternal pertussis vaccination was observed. There was no difference in neonatal health outcomes between second and third trimester pertussis vaccinations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The maternal pertussis vaccination did not increase the risk of several adverse neonatal health outcomes, confirming the safety of pertussis vaccination during pregnancy with respect to neonatal health outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 4","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13044326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147590044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}