Birth Defects Research最新文献

{"title":"Correction to “Cognitive, Behavioral and Educational Outcomes in Children Aged 5–11 Years With Spina Bifida in Northern Ireland”","authors":"","doi":"10.1002/bdr2.2478","DOIUrl":"https://doi.org/10.1002/bdr2.2478","url":null,"abstract":"<p>Parajuli, Y. G. and Sinclair, M. 2025. “Cognitive, Behavioral and Educational Outcomes in Children Aged 5–11 Years With Spina Bifida in Northern Ireland.” <i>Birth Defects Research</i> 117: e2434. https://doi.org/10.1002/bdr2.2434.</p><p>In the originally published article, the Acknowledgments section omitted some names. The correct Acknowledgments section is shown below.</p>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 5","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bdr2.2478","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143896962","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":"Exome Sequencing to Identify Novel Susceptibility Genes for Nonsyndromic Split-Hand/Ft Malformation: A Report From the National Birth Defects Prevention Study","authors":"Tonia C. Carter,&nbsp;Denise M. Kay,&nbsp;Faith Pangilinan,&nbsp;Lynn M. Almli,&nbsp;Mary M. Jenkins,&nbsp;Elizabeth E. Blue,&nbsp;Pagna Sok,&nbsp;Janson J. White,&nbsp;Christopher M. Cunniff,&nbsp;A. J. Agopian,&nbsp;Michael J. Bamshad,&nbsp;Lorenzo D. Botto,&nbsp;Lawrence C. Brody,&nbsp;Muge Gucsavas-Calikoglu,&nbsp;Jessica X. Chong,&nbsp;Horacio Gomez-Acevedo,&nbsp;Philip J. Lupo,&nbsp;Cynthia A. Moore,&nbsp;Wendy N. Nembhard,&nbsp;Richard S. Olney,&nbsp;Andrew F. Olshan,&nbsp;Mohammed S. Orloff,&nbsp;Jennita Reefhuis,&nbsp;Paul A. Romitti,&nbsp;Gary M. Shaw,&nbsp;Martha M. Werler,&nbsp;Mahsa M. Yazdy,&nbsp;Marilyn L. Browne,&nbsp;Meredith M. Howley,&nbsp;University of Washington Center for Mendelian Genomics, NISC Comparative Sequencing Program, the National Birth Defects Prevention Study","doi":"10.1002/bdr2.2472","DOIUrl":"https://doi.org/10.1002/bdr2.2472","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Split-hand/foot malformation (SHFM) is a rare, genetically heterogeneous, congenital limb defect. Some but not all associated genes are known; therefore, the aim was to identify genes underlying SHFM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Buccal cell-derived DNA from 26 children with SHFM and their parents who participated in the National Birth Defects Prevention Study was exome sequenced. Family-based trio analyzes prioritized rare coding variants by inheritance patterns, predicted pathogenicity, and location within putative limb development genes. Copy-number variants in SHFM candidate genomic regions were also examined. Case–control analyzes compared coding variants between case children and 1191 controls (parents of children with non-limb birth defects). Variant validation was by Sanger sequencing or droplet digital polymerase chain reaction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In family-based analyzes, the prioritized and validated variants (each in a single family) included likely damaging variants that were heterozygous and <i>de novo</i> in speckle type BTB/POZ protein (<i>SPOP</i>) and ubiquitin-like modifier activating enzyme 2 (<i>UBA2</i>), X-linked recessive in fibroblast growth factor 13 (<i>FGF13</i>) and RNA binding motif protein 10 (<i>RBM10</i>), and compound heterozygous in interleukin enhancer binding factor 3 (<i>ILF3</i>). Validation assays did not confirm predicted <i>de novo</i> copy-number gains at chromosomes 10q24 and 19p13.11. Case–control analyzes did not identify statistically significant associations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Exome analysis nominated new susceptibility genes (<i>FGF13</i>, <i>ILF3</i>, <i>RBM10</i>, <i>SPOP</i>) and detected a variant in a known candidate gene (<i>UBA2</i>). Follow-up investigation is needed to ascertain damaging variants in these genes in additional cases with SHFM and evaluate the impact of the variants on gene expression, protein function, and limb development.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 5","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889015","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/bdr2.2475","DOIUrl":"https://doi.org/10.1002/bdr2.2475","url":null,"abstract":"","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 S1","pages":"S1-S100"},"PeriodicalIF":1.6,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143871852","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":"Domestic Use of Solvents and Pesticides and the Risk of Hypospadias in Offspring: A Case–Control Study From Brittany, France","authors":"Flore-Anne Martin,&nbsp;Ronan Garlantezec,&nbsp;Cécile Chevrier,&nbsp;Adèle Bihannic,&nbsp;Patrick Pladys,&nbsp;Rémi Béranger,&nbsp;Florence Rouget","doi":"10.1002/bdr2.2476","DOIUrl":"https://doi.org/10.1002/bdr2.2476","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>There is a growing concern about the potential role of environmental exposure in congenital male anomalies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>We aimed to assess the association between the domestic use of products containing solvents or pesticides during pregnancy and the risk of hypospadias in the offspring.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We included newborns from the PENEW case–control study, which took place in Brittany, France, from October 2012 to December 2018. Newborns affected with hypospadias (<i>n</i> = 100) were matched with one to four controls (<i>n</i> = 283) according to the biological sex assigned at birth, center of birth, year, and season of birth. We assessed self-reported domestic exposure to solvents (cosmetics, house cleaning, and home renovation products) and pesticides (used indoors and outdoors) through a maternal questionnaire at birth. We performed multivariable conditional logistic regression, adjusting for potential confounders.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The self-reported use of indoor pesticides during pregnancy was associated with an increased risk of hypospadias in offspring (adjusted odds ratio [aOR] = 2.68, 95% CI = 1.5, 4.81), especially those against wood insects (aOR = 13.19, 95% CI = 1.11, 59.57), rodents (aOR = 4.61, 95% CI = 1.03, 20.7), and flying and crawling insects (aOR = 2.77, 95% CI = 1.46, 5.28). Other studies have shown that domestic exposure was not statistically significantly associated with a risk of hypospadias.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The use of indoor pesticides during pregnancy may be associated with a higher risk of hypospadias in offspring, especially those against flying and crawling insects. Further studies might be needed to identify specific molecules to target and confirm our results on a larger sample.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 5","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143871850","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":"MotherToBaby and CDC: Partnering to Provide a Rapid and Personalized Response to COVID-19 Vaccine Inquiries During Pregnancy and Lactation","authors":"Kirstie Perrotta,&nbsp;Lorrie Harris-Sagaribay,&nbsp;Gretchen Bandoli","doi":"10.1002/bdr2.2477","DOIUrl":"https://doi.org/10.1002/bdr2.2477","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>When coronavirus disease 2019 (COVID-19) vaccines first became available, pregnancy and lactation data were lacking. This void was often filled by misinformation. Even as data about pregnancy outcomes following COVID-19 vaccination began to emerge, the public was often unsure how to interpret the information, and many pregnant women remained unclear on whether to get vaccinated. MotherToBaby and Centers for Disease Control and Prevention (CDC) quickly partnered to direct the public to MotherToBaby, a nationwide teratogen information service, for free and confidential discussions about COVID-19 vaccines in pregnancy and lactation. This paper describes the partnership between MotherToBaby and CDC and the resulting COVID-19 vaccine inquiries received.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Aggregate, deidentified data were extracted from a centralized database utilized by MotherToBaby to capture information about exposure inquiries. The data include exposure topics, caller characteristics, and specific questions about COVID-19 vaccination.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Between March 1, 2021 and February 28, 2023, MotherToBaby answered 11,064 questions about COVID-19 vaccines. Most (68.5%) were related to vaccine safety, with common safety-related themes including perceived haste in vaccine development, hesitancy about mRNA technology, and concerns about infertility, miscarriage, and long-term effects on the child. Lessons learned include the essential role of partnerships to educate the public during emergencies, the importance of building staff capacity during nonemergency times, and the need for one-on-one conversations to counter vaccine misinformation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>During the COVID-19 pandemic, MotherToBaby met a critical need by providing individualized, evidence-based information to the public. During future public health emergencies, teratogen information services are uniquely suited to provide unbiased information about the risks and benefits of vaccines and other exposures.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 4","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143865852","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":"Using Residual Newborn Blood Spots to Investigate CpG Methylation in Relation to Air Pollution and Congenital Heart Defects","authors":"Thomas J. Luben,&nbsp;Kyle Roell,&nbsp;Cailee E. Harrington,&nbsp;Jeanette A. Stingone,&nbsp;Cavin K. Ward-Caviness,&nbsp;Tania A. Desrosiers,&nbsp;Rebecca C. Fry,&nbsp;Andrew F. Olshan","doi":"10.1002/bdr2.2473","DOIUrl":"https://doi.org/10.1002/bdr2.2473","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The prevalence of tetralogy of Fallot (TOF), a common congenital heart defect, has increased over the last two decades.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Genome-wide CpG methylation patterns were assessed and analyzed in relation to gestational air pollution exposure among 24 infants with TOF and 24 sex-matched control infants without a birth defect from a North Carolina population-based, case–control study of major structural birth defects (2006–2011). Air pollution exposure during obstetric weeks 3–8 was assigned based on self-reported residence. DNA was extracted from residual newborn blood spots, and DNA methylation levels were measured using the Illumina EPIC Array.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Cases had higher exposure to both PM₂_.5 and O₃ compared to controls. No specific CpG loci were statistically significantly associated with TOF status or air pollution exposure; however, we observed associations between TOF case status and DNA methylation at specific genomic regions with genes enriched for functions in metabolism. Additionally, there were significant regions that displayed differential DNA methylation in relation to air pollution exposure within genes involved in apoptosis, necrosis, inflammation, and immune response pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Generally, air pollution exposure and TOF were associated with differential DNA methylation in distinct genes. These results highlight suggestive links between the environment, epigenome, and TOF to be further investigated in larger studies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 4","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143865927","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 Power and Importance of 25,000 Words","authors":"S. C. Fisher,&nbsp;W. N. Nembhard","doi":"10.1002/bdr2.2454","DOIUrl":"https://doi.org/10.1002/bdr2.2454","url":null,"abstract":"&lt;p&gt;Since 2000, the National Birth Defects Prevention Network (NBDPN), in collaboration with the U.S. National Center on Birth Defects and Developmental Disabilities at the Centers for Disease Control and Prevention, has published a special issue of &lt;i&gt;Birth Defects Research&lt;/i&gt; to highlight advances in birth defects surveillance data, methodology, and research applications. Conservatively, over the past 25 years, more than 350,000 words of this journal were dedicated to this purpose. These 350,000+ words are important; authors labored over them, reviewers critiqued them, and editors ultimately approved them. These words are also powerful; after being published, readers read and cited them, researchers developed hypotheses based on them, and policymakers crafted policy or changed public health practice based on them. Most importantly, those words represent the children, families, and communities that are included in surveillance systems and research projects, and they helped shape the programs designed to meet their needs. These families and their experiences are an integral part of the work presented here. And yet, their experiences—joys and sorrows from the birth or death of a child; heartbreak, fear, or anxiety from a diagnosis or surgical procedure; and frustration over yet one more extended hospital stay—can never be fully captured in the neat and orderly rows and columns filled with numbers in spreadsheets or databases. It is therefore researchers' responsibility to not just analyze data, but to represent people's stories when they translate those numbers into words. Words are powerful and important.&lt;/p&gt;&lt;p&gt;In this issue, Bascom and Agopian directly consider the power of words to tell stories about individuals with birth defects by reviewing the use of person-first language as opposed to identity-first language in papers published using NBDPN data between 2002 and 2024. The authors report that only 13% of published articles during this time period used person-first language when describing individuals with birth defects in epidemiologic studies. Although the use of this language has evolved over time, we can and should do better. This is not the first time the NBDPN special issue has highlighted the importance of word choice for the birth defects community. In our 2012 special issue, Mai et al. (&lt;span&gt;2012&lt;/span&gt;) explored public perception of birth defects terminology and reported that “birth defects,” although imperfect, is generally preferred over older terminology such as “congenital malformations” or “congenital anomalies.” More than a decade later, Bascom and Agopian's publication underscores the need to continue to practice introspection about how our word choices represent people affected by birth defects.&lt;/p&gt;&lt;p&gt;Also in this issue, we include original research articles about important issues for the birth defects field. Allred et al. (&lt;span&gt;2024&lt;/span&gt;) describe the prevalence and characteristics of children born with macrocephaly, an","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 4","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bdr2.2454","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143845871","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":"Evaluation of Gadolinium-Based Contrast Agents in Juvenile Non-Human Primates Including Behavioral Evaluations Such as Learning and Memory","authors":"Daniela Smieja,&nbsp;Oliver Czupalla,&nbsp;Clemens Günther,&nbsp;Simona Bussi,&nbsp;Alessandra Coppo,&nbsp;Paul Jones,&nbsp;Matilde Forni,&nbsp;Nathalie Fretellier,&nbsp;Philippe Bourrinet,&nbsp;C. Marc Luetjens","doi":"10.1002/bdr2.2470","DOIUrl":"https://doi.org/10.1002/bdr2.2470","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The US Food and Drug Administration (FDA) requested the four Gadolinium-Based Contrast Agents (GBCA) New Drug Application (NDA) holders to investigate the effects of gadolinium (Gd) retention on fetal and neonatal development in mice and juvenile non-human primates (NHP) as well as the effects of repeated GBCA administrations on behavioral, neurological, and histopathological endpoints.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Two linear (gadodiamide and gadobenate dimeglumine) and one macrocyclic (gadobutrol) GBCA, intended to be representative of linear non-ionic, linear ionic, and macrocyclic GBCAs, were investigated in a juvenile toxicity study in the cynomolgus monkey. Clinical observations, body weight, food consumption, clinical chemistry, full histopathology, and behavioral/neurological parameters including learning and memory were assessed. Additionally, Gd was quantified in the brain and other selected organs/tissues. A total of 84 juvenile animals (<i>n</i> = 12/group) were intravenously dosed every 4 weeks from postnatal day 28 for a total of 8 administrations over 29 weeks. Evaluation at the end of dosing, or after a recovery phase, was conducted to assess the reversibility of any observed effects. Necropsy was performed on Day 198 of the dosing phase for four animals/group and Day 365 of the recovery phase for the remaining eight animals/group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>No GBCA-related adverse effects were observed in juvenile cynomolgus monkeys either at the end of the dosing or recovery periods. The no-observed-effect-levels (NOEL) for gadobutrol and gadodiamide administration were 0.9 mmol/kg and, for gadobenate dimeglumine, 0.3 mmol/kg (due to a non-adverse difference in learning during the recovery phase in the high dose group). The no-observed-adverse-effect-level (NOAEL) for all GBCAs was established as at least 0.9 mmol/kg.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Gd levels observed in brain tissue of cynomolgus monkey after juvenile exposure to multiples of equivalent clinical doses of all GBCAs tested did not correlate with any adverse morphological or functional findings. This study showed no evidence that exposure to GBCA during development presents a potential risk for long-term effects such as behavioral, neurological, or histopathological findings in the brain, and/or impaired learning or memory.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 4","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143835949","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":"A Narrative Review on the Effect of Valproic Acid on the Placenta","authors":"Lauren T. L. Brown,&nbsp;Delaine Pereira,&nbsp;Louise M. Winn","doi":"10.1002/bdr2.2471","DOIUrl":"https://doi.org/10.1002/bdr2.2471","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Valproic acid (VPA) is an antiepileptic and mood-stabilizing drug with well-established teratogenic risks when taken during pregnancy. While its harmful effects on fetal development are well known, less attention has been given to its impact on placental development and function, despite the placenta's critical role in pregnancy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>This narrative review examines how VPA exposure affects placental growth, morphology, nutrient transport, and epigenetic modifications. It also considers whether placental dysfunction may contribute VPA's teratogenic effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Evidence suggests that VPA disrupts placental structure and growth, alters the expression of nutrient transporters, such as those for folate, glucose, and amino acids, and modifies the placental epigenome, including globally decreased DNA methylation and increased histone acetylation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>It is hypothesized that these epigenetic changes may influence chromatin remodelling and trophoblast gene expression, though this connection has not been fully established. Such epigenetic dysregulation may result in aberrant gene expression that underlies the structural and functional impairments observed in the placenta, potentially compromising its ability to support fetal development and contributing to VPA's teratogenic effects. Findings across studies, however, are inconsistent, varying with dose, timing of exposure, and model system. Furthermore, there is a lack of research examining sex-specific differences in placental responses to VPA, despite evidence that male and female placentas exhibit distinct growth patterns, gene expression profiles, and susceptibilities to environmental insults.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Addressing these knowledge gaps through targeted research will improve our understanding of how VPA affects the placenta and its role in teratogenesis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 4","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bdr2.2471","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143818708","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":"Embryonic Vascular Dysgenesis: The Origin of Proximal Femoral Focal Deficiency","authors":"David R. Hootnick,&nbsp;Neil Vargesson,&nbsp;Jason A. Horton,&nbsp;Jiri Chomiak","doi":"10.1002/bdr2.2465","DOIUrl":"https://doi.org/10.1002/bdr2.2465","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Proximal Femoral Focal Deficiency (PFFD) is the most proximal manifestation of a syndrome involving Congenitally Shortened lower Limbs (CSL), which also affects the fibula and midline metatarsals. This pattern of congenital human long bone deficiencies corresponds, in a time dependent manner, to the failed ingrowth pathways of new blood vessels of the growing embryonic limb. The distal femoral condyles are, in contrast, served by an alternative vascular supply from around the knee joint, and so remain resistant to the CSL deficiency.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>We hypothesize that embryonic vascular dysgenesis causes PFFD, as well as the cardinal features of the Femoral, Fibular and midline Metatarsal deficiencies (FFM) syndrome.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Arteriography of CSL with PFFD reveals diminution or failed formation of the Femoral Artery (FA), which corresponds to downstream skeletal reductions. It may also reveal preservation of the primitive Axial Artery (AA) of the embryonic limb. The combination of missing and retained primitive vessels inform the time, place, and nature of the etiologic vascular events. This suggests that PFFD is the visible expression of a normally prefigured cartilaginous scaffold of the femur, which develops in conformity with the available pattern of blood vessels present. The teratogen thalidomide, known to affect the forming embryonic vasculature, also produces PFFD indistinguishable from the naturally occurring entity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The entire spectrum of PFFD, including phocomelia, fibular, and metatarsal dystrophisms, should thus be regarded as downstream skeletal results of embryonic arterial dysgeneses.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 4","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143786714","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}