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Correction to Teratogenic Effects of Serotonin Receptor 2B Disruption on the Migration and Cardiac Derivatives of the Cardiac Neural Crest 修正5 -羟色胺受体2B干扰对心脏神经嵴迁移和心脏衍生物的致畸作用
IF 1.6 4区 医学 Q4 DEVELOPMENTAL BIOLOGY Pub Date : 2025-09-08 DOI: 10.1002/bdr2.2519

Wells, B. K., G. K. Garramone, A. Mahomed, and M. Ezin. 2025. “Teratogenic Effects of Serotonin Receptor 2B Disruption on the Migration and Cardiac Derivatives of the Cardiac Neural Crest.” Birth Defects Research 117, no. 7: e2506. https://doi.org/10.1002/bdr2.2506.

The Data Availability Statement for this article has been updated from the originally-published version:

Incorrect:

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Correct:

Data Availability Statement

The data that support the findings of this study are available in the Supporting Information of this article.

The data for this article are available on the publisher's website, and the online version of the article has been updated.

We apologize for this error.

Wells, b.k., g.k. Garramone, A. Mahomed和M. Ezin, 2025。5 -羟色胺受体2B干扰对心脏神经嵴迁移和心脏衍生物的致畸作用出生缺陷研究117,no。7: e2506。https://doi.org/10.1002/bdr2.2506.The本文的数据可用性声明已从原始发布的版本更新:错误:数据可用性声明支持本研究结果的数据可根据通讯作者的合理要求获得。正确:数据可用性声明支持本研究结果的数据可在本文的支持信息中找到。这篇文章的数据可以在出版商的网站上找到,文章的在线版本已经更新了。我们为这个错误道歉。
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引用次数: 0
Association Between Socioeconomic Status and Major Congenital Anomalies: A Two-Sample Mendelian Randomization Study 社会经济地位与先天性畸形之间的关系:一项双样本孟德尔随机化研究
IF 1.6 4区 医学 Q4 DEVELOPMENTAL BIOLOGY Pub Date : 2025-09-05 DOI: 10.1002/bdr2.2524
Daniel Linares, Qun Miao, Beatriz Luna

Background

Traditional observational studies suggest that socioeconomic status (SES) may influence the risk of congenital anomalies; however, an association remains unclear due to residual confounding. This study used Mendelian randomization (MR) to explore the potential causal relationship between SES indicators and specific congenital anomalies.

Methods

We performed two-sample MR analyses to explore whether three indicators of SES—educational attainment, household income, and the Townsend Deprivation Index—have a relationship with the risk of major congenital anomalies. Genetic variants associated with these SES indicators were obtained from the MRC Integrative Epidemiology Unit (IEU) OpenGWAS database, based on UK Biobank data. Genetic associations with nine categories of congenital anomalies were sourced from the FinnGen study. The primary MR method was inverse-variance weighted (IVW), with sensitivity analyses and Bonferroni correction applied to account for multiple testing.

Results

Prior to correction for multiple testing, higher educational attainment was associated with reduced risk of congenital heart defects (CHDs) (OR = 0.60, 95% CI: 0.41–0.88; p = 0.001), congenital respiratory system malformations (OR = 0.20, 95% CI: 0.06–0.62; p = 0.005), and musculoskeletal malformations (OR = 0.47, 95% CI: 0.29–0.76; p = 0.002). A lower Townsend Deprivation Index was unexpectedly associated with a higher risk of congenital digestive tract anomalies (OR = 4.53, 95% CI: 1.10–18.63; p = 0.036). However, after Bonferroni correction, only the association between educational attainment and CHDs remained significant (adjusted p = 0.02).

Conclusions

We found limited evidence on the association between SES and congenital anomalies. Only higher educational attainment was significantly associated with reduced risk of CHDs after multiple testing correction. Further research with refined methods is needed to clarify these associations.

传统的观察性研究表明,社会经济地位(SES)可能影响先天性异常的风险;然而,由于残留的混淆,其关联仍不清楚。本研究采用孟德尔随机化(MR)方法探讨SES指标与特定先天性异常之间的潜在因果关系。方法采用两样本磁共振分析,探讨ses的三个指标——受教育程度、家庭收入和汤森剥夺指数——是否与重大先天性异常的风险有关。与这些SES指标相关的遗传变异来自MRC综合流行病学单位(IEU) OpenGWAS数据库,基于UK Biobank数据。与九类先天性异常的遗传关联来源于FinnGen研究。主要MR方法是反方差加权(IVW),采用敏感性分析和Bonferroni校正来解释多重检验。结果在校正多重测试之前,较高的教育程度与先天性心脏缺陷(CHDs) (OR = 0.60, 95% CI: 0.41-0.88; p = 0.001)、先天性呼吸系统畸形(OR = 0.20, 95% CI: 0.06-0.62; p = 0.005)和肌肉骨骼畸形(OR = 0.47, 95% CI: 0.29-0.76; p = 0.002)的风险降低相关。汤森剥夺指数越低,先天性消化道异常的风险越高(OR = 4.53, 95% CI: 1.10-18.63; p = 0.036)。然而,经Bonferroni校正后,只有受教育程度与冠心病之间的关系仍然显著(调整p = 0.02)。结论:我们发现有限的证据表明SES与先天性异常之间存在关联。在多次测试校正后,只有较高的教育程度与降低冠心病风险显著相关。需要用更精确的方法进行进一步的研究来澄清这些关联。
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引用次数: 0
Helical Body Axis Orientations in Human Embryonic Development 人类胚胎发育中的螺旋体轴取向
IF 1.6 4区 医学 Q4 DEVELOPMENTAL BIOLOGY Pub Date : 2025-09-05 DOI: 10.1002/bdr2.2527
Sena Fujii, Shigehito Yamada, Tetsuya Takakuwa

Background

In mouse embryos, the body axis typically follows a right-handed helical pattern; however, a definitive orientation in human embryos has not been established. This study aimed to characterize the body axis orientation in human embryos (CS13–CS17) from the Kyoto Collection.

Methods

Embryos were classified as right-helical (RH), left-helical (LH), and middle (M) using MRI-based morphological assessment.

Results

RH orientation was predominant at CS13, whereas it became comparable to LH at CS14. From CS15 to CS17, LH became dominant, nearly doubling the frequency of RH by CS15. The proportion of M-pattern embryos increased with advancing Carnegie Stages, reaching 70% at CS17. As vertebral column chondrification begins at CS17–18, these findings suggest that the helical body axis is established before chondrogenesis, particularly during CS13–CS15. Internal organ laterality (stomach, heart, intestines, and liver) appeared consistent among body axis orientations in CS15–CS17 embryos.

Conclusion

The results demonstrate substantial variability in human embryonic body axis orientation, in contrast to the well-defined pattern in mice, and provide insights into body axis formation in human embryos and their potential role in left–right asymmetry.

在小鼠胚胎中,身体轴通常遵循右旋螺旋模式;然而,在人类胚胎中尚未确定明确的定向。本研究旨在对京都收集的人类胚胎(CS13-CS17)的体轴取向进行表征。方法采用mri形态学鉴定方法将胚胎分为右螺旋形(RH)、左螺旋形(LH)和中螺旋形(M)。结果CS13以RH取向为主,CS14与LH取向相当。从CS15到CS17, LH成为优势,RH的频率几乎是CS15的两倍。m型胚的比例随着卡内基期的推进而增加,在CS17时达到70%。由于脊柱软骨形成开始于CS17-18,这些发现表明螺旋体轴在软骨形成之前就已经建立,特别是在CS13-CS15期间。内脏器官侧向(胃、心、肠和肝)在CS15-CS17胚胎中呈现一致的体轴方向。结论人类胚胎体轴方向与小鼠不同,具有明显的差异性,为人类胚胎体轴的形成及其在左右不对称中的潜在作用提供了新的思路。
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引用次数: 0
Spontaneous Resolution of Molar Tissue in Complete Hydatidiform Mole With a Coexisting Fetus 与胎儿共存的完整葡萄胎中磨牙组织的自发溶解
IF 1.6 4区 医学 Q4 DEVELOPMENTAL BIOLOGY Pub Date : 2025-09-04 DOI: 10.1002/bdr2.2525
Paz Ahumada-Droguett, Trinidad Arancibia, Helga Vera, Daniel Martin, Francisco Sánchez, Juan Carlos Bustos

Background

Complete hydatidiform mole with a coexisting fetus (CMCF) is a rare form of twin pregnancy associated with high maternal and perinatal risks, posing complex diagnostic and therapeutic challenges. The standard approach ranges from termination of pregnancy to conservative management to fetal viability. Recent evidence suggests that spontaneous regression of molar tissue may occur, supporting conservative treatment in selected cases. We present a new case and discuss the clinical consequences of this phenomenon.

Case

We report a 29-year-old woman with a history of a previous molar pregnancy who presented with CMCF during her second gestation. The diagnosis was established at 21 weeks' gestation based on ultrasound findings and an elevated beta-hCG level of 454,000 mIU/mL. After multidisciplinary counseling, expectant management was indicated with close clinical, sonographic, and biochemical surveillance. By 30 weeks, significant regression in molar tissue was observed, and by 36 weeks, the appearance on ultrasound was like a normal placenta with decreased beta-hCG levels. At 37 weeks, a cesarean section was performed, resulting in the delivery of a healthy female infant weighing 2585 g. The placenta was normal and small, necrotic-appearing placental tissue. Histopathological analysis confirmed the presence of gestational trophoblastic disease with extensive necrosis.

Conclusions

This is the third reported case of spontaneous regression of molar tissue in CMCF, with resolution occurring in the third trimester. This finding opens a new perspective for the management of these complex pregnancies, suggesting that conservative strategies may be justified in selected patients under close surveillance.

背景完全葡萄胎合并胎儿(CMCF)是一种罕见的双胎妊娠,具有较高的母体和围产期风险,具有复杂的诊断和治疗挑战。标准的方法包括从终止妊娠到保守管理到胎儿生存能力。最近的证据表明,磨牙组织可能发生自发退化,支持保守治疗。我们提出一个新的病例,并讨论这种现象的临床后果。病例我们报告了一位29岁的女性,她有过磨牙妊娠史,在她的第二次妊娠期间出现了CMCF。根据超声检查结果和45.4万mIU/mL的β - hcg水平升高,在妊娠21周时确诊。多学科咨询后,准管理指示密切的临床,超声和生化监测。到30周时,观察到磨牙组织明显退化,到36周时,超声外观与正常胎盘相似,β - hcg水平降低。37周时,进行了剖宫产手术,生下了一名体重2585克的健康女婴。胎盘正常,胎盘组织小,呈坏死状。组织病理学分析证实存在妊娠滋养细胞疾病伴广泛坏死。结论:这是第三例报道的CMCF磨牙组织自发消退的病例,在妊娠晚期出现消退。这一发现为这些复杂妊娠的管理开辟了一个新的视角,表明在密切监测下,保守策略可能是合理的。
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引用次数: 0
Leveraging Health Insurance Claims Data to Complement the Centers for Disease Control and Prevention Surveillance System for Birth Defects 利用健康保险索赔数据补充疾病控制和预防中心的出生缺陷监测系统
IF 1.6 4区 医学 Q4 DEVELOPMENTAL BIOLOGY Pub Date : 2025-09-02 DOI: 10.1002/bdr2.2523
Sharon Ng, Jeremy P. Brown, Loreen Straub, Brian Bateman, Kathryn J. Gray, Krista F. Huybrechts, Sonia Hernández-Díaz

Background

Birth defect surveillance can help identify temporo-spatial clusters and teratogenic signals to inform subsequent investigations or interventions. In the United States, state surveillance systems exist but collect limited information, prompting a complementary use of health insurance claims data to describe national birth defect prevalence trends and investigate signals.

Methods

The Merative MarketScan Commercial Claims and Encounters (MarketScan) database was used to identify liveborn infants from 2016 to 2022, with linkage to maternal health care records during pregnancy. Birth defects were identified using ICD-10-CM codes recorded in the first 3 months of life, and prevalence estimates with 95% confidence intervals were generated for birth defect categories and select birth defects.

Results

The study population included 943,855 liveborn infants. From 2016 to 2022, the prevalence increased for cardiac, central nervous system, ear, genital, urinary, musculoskeletal, and limb birth defect categories. Stable prevalence over the study period was observed for chromosomal, oral cleft, respiratory, gastrointestinal, vascular, and eye defects. For specific defects, we observed an increased prevalence of both ankyloglossia and lip-tie over the study period and a transient higher prevalence of omphalocele over 2017 and 2018. Within genital birth defects, we observed increasing prevalence trends for congenital malformations of the penis, while hypospadias and cryptorchidism remained relatively stable.

Conclusion

Health care utilization databases can complement existing surveillance systems by generating, confirming, or refuting signals based on ecological trends or clusters. The availability of patient information in claims databases can allow for further investigation of signals to inform birth defect etiology.

出生缺陷监测可以帮助识别时空集群和致畸信号,为后续调查或干预提供信息。在美国,虽然存在州监测系统,但收集的信息有限,这促使人们补充使用健康保险索赔数据来描述国家出生缺陷流行趋势和调查信号。方法使用Merative MarketScan商业索赔和遭遇(MarketScan)数据库识别2016年至2022年的活产婴儿,并与妊娠期间的孕产妇保健记录相关联。使用出生前3个月记录的ICD-10-CM代码确定出生缺陷,并对出生缺陷类别和选定的出生缺陷产生95%置信区间的患病率估计。结果研究人群包括943,855名活产婴儿。从2016年到2022年,心脏、中枢神经系统、耳部、生殖器、泌尿、肌肉骨骼和肢体出生缺陷类别的患病率有所上升。在研究期间,观察到染色体、口腔裂、呼吸、胃肠道、血管和眼睛缺陷的稳定患病率。对于特定缺陷,我们观察到在研究期间,紧张症和唇系带的患病率均有所增加,而在2017年和2018年,脐膨出的患病率短暂上升。在生殖器出生缺陷中,我们观察到先天性阴茎畸形的患病率呈上升趋势,而尿道下裂和隐睾则保持相对稳定。结论卫生保健利用数据库可通过生成、确认或反驳基于生态趋势或群集的信号来补充现有的监测系统。索赔数据库中患者信息的可用性可以允许进一步调查信号,以告知出生缺陷病因。
{"title":"Leveraging Health Insurance Claims Data to Complement the Centers for Disease Control and Prevention Surveillance System for Birth Defects","authors":"Sharon Ng,&nbsp;Jeremy P. Brown,&nbsp;Loreen Straub,&nbsp;Brian Bateman,&nbsp;Kathryn J. Gray,&nbsp;Krista F. Huybrechts,&nbsp;Sonia Hernández-Díaz","doi":"10.1002/bdr2.2523","DOIUrl":"https://doi.org/10.1002/bdr2.2523","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Birth defect surveillance can help identify temporo-spatial clusters and teratogenic signals to inform subsequent investigations or interventions. In the United States, state surveillance systems exist but collect limited information, prompting a complementary use of health insurance claims data to describe national birth defect prevalence trends and investigate signals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The Merative MarketScan Commercial Claims and Encounters (MarketScan) database was used to identify liveborn infants from 2016 to 2022, with linkage to maternal health care records during pregnancy. Birth defects were identified using ICD-10-CM codes recorded in the first 3 months of life, and prevalence estimates with 95% confidence intervals were generated for birth defect categories and select birth defects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The study population included 943,855 liveborn infants. From 2016 to 2022, the prevalence increased for cardiac, central nervous system, ear, genital, urinary, musculoskeletal, and limb birth defect categories. Stable prevalence over the study period was observed for chromosomal, oral cleft, respiratory, gastrointestinal, vascular, and eye defects. For specific defects, we observed an increased prevalence of both ankyloglossia and lip-tie over the study period and a transient higher prevalence of omphalocele over 2017 and 2018. Within genital birth defects, we observed increasing prevalence trends for congenital malformations of the penis, while hypospadias and cryptorchidism remained relatively stable.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Health care utilization databases can complement existing surveillance systems by generating, confirming, or refuting signals based on ecological trends or clusters. The availability of patient information in claims databases can allow for further investigation of signals to inform birth defect etiology.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 9","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144927445","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}
引用次数: 0
Reply to Correspondence “Beyond Aggregate Risk: Drug- and Organ-Specific Nuances in Counseling on Antidepressant Teratogenicity” (Tsai et al. 2025) 回复信函“超越总体风险:抗抑郁药物致畸性咨询中药物和器官特异性的细微差别”(Tsai et al. 2025)
IF 1.6 4区 医学 Q4 DEVELOPMENTAL BIOLOGY Pub Date : 2025-08-28 DOI: 10.1002/bdr2.2522
Eydie L. Moses-Kolko, Loreen Straub, Kelly Fung, Krista F. Huybrechts

We thank the authors for their positive feedback on our recent publication “Synthesizing cohort study results to promote knowledge transfer of safety data regarding gestational antidepressant exposure and offspring congenital anomalies: A test of concept” (Moses-Kolko et al. 2025). We appreciate the commendation for our test-of-concept fact box that we used to illustrate a strategy to facilitate prescriber-patient communication regarding potential benefits and risks of use of antidepressants during pregnancy. The idea of a layered fact box is intriguing. Because many patient encounters are virtual, technology could indeed be harnessed to create and display digital image layers during a risk discussion (Tsai et al. 2025).

The authors raise the important point that we mention in our discussion; that presenting pooled relative risks for overall major congenital anomalies and cardiac anomalies can obscure specific risk data regarding individual drugs as well as anomalies in specific organ systems and subsystems. As the manuscript title implies, we presented the example of gestational antidepressant exposure and the risk of major congenital malformations overall and cardiac malformations as a test of concept. We agree that it would be meaningful to extend the example we provided in the manuscript to organ-specific malformations as well as specific drugs. Ideally, there would be ample studies which minimize confounding and misclassification bias available to generate pooled risk estimates on specific drug exposure-organ malformation outcomes for use in a fact box. As we mention in the manuscript, a current challenge for summarizing data for specific drugs, for new drugs, or for rare anomalies is the paucity of high-quality evidence (Covington et al. 2004).

The authors cite several studies they believe provide clinically actionable signals. One study is misquoted. The Huybrechts study (Huybrechts et al. 2014) did not report an organ-specific and agent-specific increase in risk. They reported an adjusted RR of 0.94 (95% CI 0.73–1.21) for the association between paroxetine and cardiac anomalies and an adjusted RR of 0.73 (95% CI 0.49–1.09) for the association with ventricular septal defects and 1.07 (95% CI 0.59–1.93) for the association with right ventricular outflow tract obstruction, specifically.

An important direction of pharmacoepidemiology research is the harmonization across studies of exposure and outcome definitions as well as methods to address confounding and bias (Richardson et al. 2025) to make replication and meta-analysis possible in future research. We eagerly anticipate such research advances that will generate greater confidence in drug and organ-specific signals that can be incorporated into clinical risk discussions as well as into clinically useful fact boxes.

K.F.H. reports being an investigator on grants to her institution from UCB, GSK, and

我们感谢作者对我们最近发表的“综合队列研究结果以促进妊娠期抗抑郁药暴露和后代先天性异常安全数据的知识转移:概念测试”(Moses-Kolko et al. 2025)的积极反馈。我们感谢对我们的概念测试事实盒的赞扬,我们用它来说明一种策略,以促进医生和病人就怀孕期间使用抗抑郁药的潜在益处和风险进行沟通。分层事实盒的想法很有趣。由于许多患者的接触是虚拟的,技术确实可以用来在风险讨论期间创建和显示数字图像层(Tsai et al. 2025)。作者提出了我们在讨论中提到的重要观点;总体主要先天性异常和心脏异常的综合相对风险可能会模糊个别药物以及特定器官系统和子系统异常的具体风险数据。正如论文标题所暗示的那样,我们提出了妊娠期抗抑郁药暴露与主要先天性畸形和心脏畸形风险的例子,作为概念的检验。我们同意将我们在手稿中提供的例子扩展到器官特异性畸形以及特定药物将是有意义的。理想情况下,应该有充分的研究,尽量减少混淆和错误分类偏差,以产生特定药物暴露-器官畸形结果的综合风险估计,用于事实框。正如我们在论文中提到的,当前总结特定药物、新药或罕见异常数据的挑战是缺乏高质量的证据(Covington et al. 2004)。作者引用了几项研究,他们认为这些研究提供了临床可操作的信号。一项研究被错误引用。Huybrechts研究(Huybrechts et al. 2014)没有报告器官特异性和药物特异性的风险增加。他们报道帕罗西汀与心脏异常相关的校正RR为0.94 (95% CI 0.73 - 1.21),与室间隔缺损相关的校正RR为0.73 (95% CI 0.49-1.09),与右室流出道梗阻相关的校正RR为1.07 (95% CI 0.59-1.93)。药物流行病学研究的一个重要方向是协调暴露和结果定义的研究,以及解决混淆和偏倚的方法(Richardson et al. 2025),以便在未来的研究中进行复制和荟萃分析。我们热切地期待着这样的研究进展,这将对药物和器官特异性信号产生更大的信心,这些信号可以纳入临床风险讨论以及临床有用的事实箱。报告称她是UCB, GSK和武田向她的机构提供资助的研究员,与这项工作无关。L.S.报告说,她是葛兰素史克向她的机构提供的一项拨款的研究员,与这项工作无关。E.L.M.-K。和K.F.没有商业或财务利益冲突。
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引用次数: 0
Thyroid Hormone Deficiency Disrupts Embryonic Ventral Body Wall Development and Myogenesis With Partial Recovery Following LevothyroxineTherapy 甲状腺激素缺乏破坏胚胎腹壁发育和肌肉发生,左旋甲状腺素治疗后部分恢复
IF 1.6 4区 医学 Q4 DEVELOPMENTAL BIOLOGY Pub Date : 2025-08-25 DOI: 10.1002/bdr2.2520
Juhi Vaishnav, Suresh Balakrishnan

Background

Ventral body wall defects (VBWDs), including omphalocele and gastroschisis, result from failed embryonic midline closure and contribute to high neonatal morbidity. While thyroid hormones (THs) are essential for morphogenesis, their role in VBWD pathogenesis is not well defined.

Aim

To investigate the impact of TH deficiency on ventral body wall development in chick embryos and evaluate levothyroxine as a therapeutic intervention.

Materials and Methods

Hypothyroidism was induced on embryonic day 3 using thiourea (2.5 mg/50 μL), a thyroid peroxidase inhibitor. A rescue group received levothyroxine (2.5 μg/50 μL) on day 5.5. Embryos were harvested on days 6 and 10 for analysis of thyroid peroxidase activity, morphology, skeletal patterning, and expression of morphogenetic (SHH, MYOD, MSX1/2), epithelial/mesenchymal (CDH1/2, VIM, TGFβ1), and apoptotic (Cleaved CASPASE 3) markers.

Results

Thiourea-treated embryos exhibited incomplete ventral closure, skeletal abnormalities, impaired myogenesis, and disrupted epithelial–mesenchymal transition. Gene profiling showed downregulation of SHH, MYOD, and MSX1/2, with concomitant upregulation of CDH1, VIM, TGFβ1, and Cleaved CASPASE 3. Levothyroxine administration partially restored thyroid activity, improved wall integrity, and normalized developmental gene expression.

Discussion

TH deficiency perturbs morphogenetic signaling, leading to defective mesodermal differentiation, epithelial–mesenchymal imbalance, and enhanced apoptosis. Partial rescue with levothyroxine underscores the hormone's developmental role and therapeutic relevance.

Conclusion

TH insufficiency contributes to VBWDs by disrupting key pathways in myogenesis and tissue remodeling. Early levothyroxine supplementation may offer a strategy to mitigate endocrine-related congenital malformations.

腹壁缺陷(VBWDs),包括脐膨出和胃裂,是胚胎中线闭合失败的结果,是新生儿高发病率的原因之一。虽然甲状腺激素(THs)对形态发生至关重要,但其在VBWD发病机制中的作用尚未明确。目的探讨促甲状腺素缺乏对鸡胚胎腹壁发育的影响,评价左旋甲状腺素的治疗干预作用。材料与方法用甲状腺过氧化物酶抑制剂硫脲(2.5 mg/50 μL)诱导胚胎第3天甲状腺功能减退。抢救组于第5.5天给予左旋甲状腺素(2.5 μg/50 μL)。在第6天和第10天收获胚胎,分析甲状腺过氧化物酶活性、形态学、骨骼模式以及形态发生(SHH、MYOD、MSX1/2)、上皮/间充质(CDH1/2、VIM、TGFβ1)和凋亡(Cleaved CASPASE 3)标志物的表达。结果经硫脲处理的胚胎表现为腹侧不完全闭合,骨骼异常,肌肉发生受损,上皮-间质转化中断。基因分析显示SHH、MYOD和MSX1/2下调,同时CDH1、VIM、tgf - β1和Cleaved CASPASE 3上调。左旋甲状腺素可部分恢复甲状腺活性,改善甲状腺壁完整性,并使发育基因表达正常化。TH缺乏扰乱形态发生信号,导致中胚层分化缺陷、上皮-间质失衡和细胞凋亡增强。左甲状腺素的部分挽救强调了激素的发育作用和治疗相关性。结论TH不足通过破坏肌肉发生和组织重塑的关键通路参与了vbwd的发生。早期补充左甲状腺素可能提供一种策略,以减轻内分泌相关的先天性畸形。
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引用次数: 0
Comorbidity and Multimorbidity in Adults With Congenital Heart Disease: Findings From a Multi-Site Population-Based Study 成人先天性心脏病的共病和多病:一项基于多地点人群的研究结果
IF 1.6 4区 医学 Q4 DEVELOPMENTAL BIOLOGY Pub Date : 2025-08-21 DOI: 10.1002/bdr2.2515
Lorenzo D. Botto, Matthew R. Reeder, George K. Lui, M. Jill Glidewell, Wendy M. Book, Tessa L. Crume, Jesse M. DeLaRosa, Alfred d'Ottavio, Karrie F. Downing, Marcia L. Feldkamp, Daphne T. Hsu, Amber D. Khanna, Sergey Krikov, Nelangi M. Pinto, Cheryl L. Raskind Hood, Fred H. Rodriguez III, Aida S. Soim, Kevin J. Whitehead, Karen Chiswell, Jennifer S. Li

Background

Survival of individuals with congenital heart disease (CHD) has improved, leading to a growing and aging population of adults living with these conditions. Over their lifetime, they often face an array of comorbidities that affect outcomes and complicate medical management. However, population-based information on such comorbidities is scarce, reducing opportunities for prevention.

Methods

This population-based, cross-sectional study assessed comorbid conditions in adults with CHD residing in five geographic areas in the United States (in Colorado, Georgia, New York, North Carolina, and Utah). The study included 18,672 adults aged 19 to 64 years who had a healthcare encounter between 2011 and 2013 associated with ≥ 1 CHD-related diagnosis code. Data were derived from linked clinical and administrative sources, reflecting inpatient, outpatient, and emergency department encounters.

Results

Most adults with CHD experienced at least one (88.5%) and usually multiple (76%) comorbidities. Overall, noncardiac comorbidities exceeded cardiac comorbidities. The most frequent noncardiac comorbidities were endocrine/metabolic conditions (e.g., diabetes, hyperlipidemia, hypothyroidism), hypertension, and neuropsychiatric conditions (e.g., anxiety, depression). The presence and number of comorbidities varied in different sociodemographic groups. Men and older individuals experienced higher rates of many comorbidities, cardiac and noncardiac, regardless of CHD type.

Conclusions

Preventable and treatable comorbidity and multimorbidity are common in adults with CHD, with patterns shaped by sociodemographic factors and CHD type. Reducing preventable mortality in this growing population will require sustained tracking of health metrics and coordinated, data-driven, and lifelong care.

背景:先天性心脏病(CHD)患者的生存率有所提高,导致患有这些疾病的成人人口不断增长和老龄化。在他们的一生中,他们经常面临一系列影响结果并使医疗管理复杂化的合并症。然而,关于这些合并症的基于人群的信息很少,减少了预防的机会。方法:这项以人群为基础的横断面研究评估了居住在美国五个地理区域(科罗拉多州、佐治亚州、纽约州、北卡罗来纳州和犹他州)的成年冠心病患者的合并症。该研究纳入了18672名年龄在19至64岁之间的成年人,他们在2011年至2013年期间接受过与冠心病相关诊断代码≥1的医疗服务。数据来源于相关的临床和行政来源,反映了住院、门诊和急诊部门的情况。结果大多数成年冠心病患者至少有一种合并症(88.5%),通常有多种合并症(76%)。总的来说,非心脏合并症超过心脏合并症。最常见的非心脏合并症是内分泌/代谢疾病(如糖尿病、高脂血症、甲状腺功能减退)、高血压和神经精神疾病(如焦虑、抑郁)。合并症的存在和数量在不同的社会人口群体中有所不同。无论冠心病类型如何,男性和老年人的许多合并症发生率更高,包括心脏和非心脏疾病。结论成人冠心病患者可预防和可治疗的合并症和多病普遍存在,其模式受社会人口学因素和冠心病类型的影响。在这一不断增长的人口中,要降低可预防的死亡率,需要持续跟踪卫生指标和协调一致的、数据驱动的终身护理。
{"title":"Comorbidity and Multimorbidity in Adults With Congenital Heart Disease: Findings From a Multi-Site Population-Based Study","authors":"Lorenzo D. Botto,&nbsp;Matthew R. Reeder,&nbsp;George K. Lui,&nbsp;M. Jill Glidewell,&nbsp;Wendy M. Book,&nbsp;Tessa L. Crume,&nbsp;Jesse M. DeLaRosa,&nbsp;Alfred d'Ottavio,&nbsp;Karrie F. Downing,&nbsp;Marcia L. Feldkamp,&nbsp;Daphne T. Hsu,&nbsp;Amber D. Khanna,&nbsp;Sergey Krikov,&nbsp;Nelangi M. Pinto,&nbsp;Cheryl L. Raskind Hood,&nbsp;Fred H. Rodriguez III,&nbsp;Aida S. Soim,&nbsp;Kevin J. Whitehead,&nbsp;Karen Chiswell,&nbsp;Jennifer S. Li","doi":"10.1002/bdr2.2515","DOIUrl":"https://doi.org/10.1002/bdr2.2515","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Survival of individuals with congenital heart disease (CHD) has improved, leading to a growing and aging population of adults living with these conditions. Over their lifetime, they often face an array of comorbidities that affect outcomes and complicate medical management. However, population-based information on such comorbidities is scarce, reducing opportunities for prevention.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This population-based, cross-sectional study assessed comorbid conditions in adults with CHD residing in five geographic areas in the United States (in Colorado, Georgia, New York, North Carolina, and Utah). The study included 18,672 adults aged 19 to 64 years who had a healthcare encounter between 2011 and 2013 associated with ≥ 1 CHD-related diagnosis code. Data were derived from linked clinical and administrative sources, reflecting inpatient, outpatient, and emergency department encounters.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Most adults with CHD experienced at least one (88.5%) and usually multiple (76%) comorbidities. Overall, noncardiac comorbidities exceeded cardiac comorbidities. The most frequent noncardiac comorbidities were endocrine/metabolic conditions (e.g., diabetes, hyperlipidemia, hypothyroidism), hypertension, and neuropsychiatric conditions (e.g., anxiety, depression). The presence and number of comorbidities varied in different sociodemographic groups. Men and older individuals experienced higher rates of many comorbidities, cardiac and noncardiac, regardless of CHD type.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Preventable and treatable comorbidity and multimorbidity are common in adults with CHD, with patterns shaped by sociodemographic factors and CHD type. Reducing preventable mortality in this growing population will require sustained tracking of health metrics and coordinated, data-driven, and lifelong care.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 8","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bdr2.2515","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144881352","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}
引用次数: 0
Progress, Challenges, and Prospects of Short-Read Genome Sequencing in Prenatal Diagnosis 短读基因组测序在产前诊断中的进展、挑战与展望
IF 1.6 4区 医学 Q4 DEVELOPMENTAL BIOLOGY Pub Date : 2025-08-20 DOI: 10.1002/bdr2.2516
Yanfei Wang, Xiaofan Zhu, Zhi Gao, Kong Xiangdong

Background

Whole-genome sequencing (WGS) has been studied increasingly as a genetic testing technology in clinical applications, and its clinical validity has been preliminarily verified. In recent years, WGS has been employed in prenatal diagnosis.

Methods

This review synthesizes the current research and existing guidelines on the use of WGS for prenatal diagnosis. The methods, diagnostic scope, diagnostic rate, clinical usefulness, feasibility, limitations, and ethical issues of WGS in prenatal diagnosis are also presented.

Results

After reviewing the relevant studies, evidence indicated that WGS can improve the diagnostic rate for fetuses with abnormal development. At the same time, WGS also has significant challenges, such as a higher detection rate of variants of uncertain significance.

Conclusion

WGS has great potential in prenatal diagnosis, but more research is needed to advance its clinical application.

背景全基因组测序(WGS)作为一种基因检测技术在临床应用中得到越来越多的研究,其临床有效性已得到初步验证。近年来,WGS已被应用于产前诊断。方法对WGS用于产前诊断的研究现状和现有指南进行综述。介绍了WGS在产前诊断中的方法、诊断范围、诊断率、临床应用、可行性、局限性及伦理问题。结果回顾相关研究,有证据表明WGS可提高发育异常胎儿的诊断率。同时,WGS也面临着重大的挑战,例如对不确定意义变异的检出率较高。结论WGS在产前诊断中具有较大的应用潜力,但其临床应用仍需进一步研究。
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引用次数: 0
PTBP3 Associated With 9q32 Locus Is a Candidate Gene for Nager Syndrome 与9q32位点相关的PTBP3是Nager综合征的候选基因
IF 1.6 4区 医学 Q4 DEVELOPMENTAL BIOLOGY Pub Date : 2025-08-17 DOI: 10.1002/bdr2.2518
Jose Antonio Gonzalez, Arun Devotta, Chang-Soo Hong, Casey Griffin, Jean-Pierre Saint-Jeannet

Background

Mandibulofacial dysostosis (MFD) is a congenital disorder characterized by defects in facial bones of neural crest origin. Nager syndrome combines many features of MFD with limb defects. Mutations in SF3B4, a gene located on chromosome 1 that encodes a protein of the spliceosome, were identified as a cause for Nager syndrome in approximately 60% of patients.

Methods

A region of chromosome 9 (9q32) that contains 35 genes has also been linked to Nager syndrome and may account for some affected individuals for which the causes of the disease have not been identified. Because Nager syndrome belongs to a rapidly growing list of craniofacial syndromes caused by pathogenic variants of splicing factors, we focused our attention on two genes in the 9q32 region that encode factors involved in pre-mRNA processing, PRPF4 and PTBP3, and analyzed their role in craniofacial development in Xenopus embryos.

Results

Loss-of-function experiments in Xenopus laevis embryos indicate that Ptbp3 is required while Prpf4 is dispensable for neural crest gene expression at the neurula stage, a phenotype that is partially rescued by expression of human PTBP3. At the tadpole stage, Ptbp3-depleted embryos have severely hypoplastic craniofacial cartilages, phenocopying the defects observed in Sf3b4 morphant tadpoles. Furthermore, ptbp3 expression is significantly increased in Xenopus tropicalis sf3b4 Null embryos as compared to wild-type siblings.

Conclusion

We propose that dysregulation of PTBP3 expression may cause Nager syndrome in a subset of patients who do not have a mutation in SF3B4.

背景:颌面部骨缺损(MFD)是一种先天性疾病,其特征是神经嵴源面骨缺损。Nager综合征结合了MFD和肢体缺陷的许多特征。位于1号染色体上编码剪接体蛋白质的SF3B4基因突变被确定为约60%患者Nager综合征的原因。方法9号染色体(9q32)的一个包含35个基因的区域也与Nager综合征有关,并且可能解释了一些尚未确定病因的受影响个体。由于Nager综合征属于由剪接因子致病性变异引起的快速增长的颅面综合征,因此我们将重点放在9q32区编码pre-mRNA加工因子的两个基因PRPF4和PTBP3上,并分析它们在爪蟾胚胎颅面发育中的作用。结果非洲爪蟾胚胎的功能缺失实验表明,Ptbp3是神经发育阶段神经嵴基因表达所必需的,而Prpf4是不需要的,人类Ptbp3的表达部分挽救了这一表型。在蝌蚪期,pptp3缺失的胚胎颅面软骨严重发育不良,与Sf3b4形态蝌蚪中观察到的缺陷表型相似。此外,ptbp3在热带非洲爪蟾sf3b4零胚中的表达比野生型兄弟显著增加。结论:我们认为,在SF3B4基因没有突变的患者中,PTBP3表达失调可能导致Nager综合征。
{"title":"PTBP3 Associated With 9q32 Locus Is a Candidate Gene for Nager Syndrome","authors":"Jose Antonio Gonzalez,&nbsp;Arun Devotta,&nbsp;Chang-Soo Hong,&nbsp;Casey Griffin,&nbsp;Jean-Pierre Saint-Jeannet","doi":"10.1002/bdr2.2518","DOIUrl":"https://doi.org/10.1002/bdr2.2518","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Mandibulofacial dysostosis (MFD) is a congenital disorder characterized by defects in facial bones of neural crest origin. Nager syndrome combines many features of MFD with limb defects. Mutations in <i>SF3B4</i>, a gene located on chromosome 1 that encodes a protein of the spliceosome, were identified as a cause for Nager syndrome in approximately 60% of patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A region of chromosome 9 (9q32) that contains 35 genes has also been linked to Nager syndrome and may account for some affected individuals for which the causes of the disease have not been identified. Because Nager syndrome belongs to a rapidly growing list of craniofacial syndromes caused by pathogenic variants of splicing factors, we focused our attention on two genes in the 9q32 region that encode factors involved in pre-mRNA processing, <i>PRPF4</i> and <i>PTBP3</i>, and analyzed their role in craniofacial development in <i>Xenopus</i> embryos.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Loss-of-function experiments in <i>Xenopus laevis</i> embryos indicate that Ptbp3 is required while Prpf4 is dispensable for neural crest gene expression at the neurula stage, a phenotype that is partially rescued by expression of human PTBP3. At the tadpole stage, Ptbp3-depleted embryos have severely hypoplastic craniofacial cartilages, phenocopying the defects observed in Sf3b4 morphant tadpoles. Furthermore, <i>ptbp3</i> expression is significantly increased in <i>Xenopus tropicalis</i> <i>sf3b4</i> Null embryos as compared to wild-type siblings.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We propose that dysregulation of PTBP3 expression may cause Nager syndrome in a subset of patients who do not have a mutation in <i>SF3B4</i>.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 8","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861893","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}
引用次数: 0
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Birth Defects Research
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