Birth Defects Research最新文献

{"title":"Folate Interaction With Genetic Risk for Neural Tube Defects Among Infants in Bangladesh","authors":"Enrique Mondragon-Estrada,&nbsp;Xingyan Wang,&nbsp;Michael D. Uhler,&nbsp;Afifah Farooque,&nbsp;Kelly Liu,&nbsp;Sudipta Kumer Mukherjee,&nbsp;Sheikh Muhammad Ekramullah,&nbsp;D. M. Arman,&nbsp;Joynul Islam,&nbsp;Hafiza Sultana Suchanda,&nbsp;David C. Christiani,&nbsp;Benjamin C. Warf,&nbsp;Maitreyi Mazumdar,&nbsp;Sarah U. Morton","doi":"10.1002/bdr2.70007","DOIUrl":"10.1002/bdr2.70007","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Neural tube defects such as spina bifida (SB) are congenital anomalies associated with significant morbidity and mortality worldwide. Environmental factors, particularly folate, modify SB risk. Based on recurrence rates of SB within families, genetic risk also contributes to SB development. However, the effect of maternal folate intake on genetic risk for SB in Bangladesh has not been quantified.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Genetic variants were imputed from array data of 112 infants with SB and 116 infants without SB. After quality filtering, genome-wide association was performed on 91 infants with SB and 97 without. Maternal folate intake and maternal nail arsenic concentration were included as covariates and interaction terms (SNP × Folate, SNP × Arsenic) along with maternal age, infant sex, and 10 principal components as covariates.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Two loci had variants nominally associated with SB: one within the coding region of <i>WWOX</i>, including rs7184417 (odds ratio [OR] = 6.20, <i>p</i> = 2.22E-06), and a second in the coding region of <i>ISOC2</i> (rs4801638; OR = 0.24, <i>p</i> = 5.75E-06). With the gene-folate interaction, a locus in <i>CNTN5</i> was associated with SB. After including the gene-arsenic interaction, the gene-folate interaction effect was nominally associated with a locus in <i>CTNNA2</i>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Inclusion of maternal folate intake as a covariate and interaction term identified three genomic loci that could impact the risk for SB. A fourth locus was identified when maternal arsenic level was included. These nominal associations should be assessed in additional cohorts with larger sample sizes. Novel genes impacted by these loci may interact with previously reported genes for SB.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 12","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12697008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145721092","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":"A Case of a Fetus With SETD5 Mutation: Prenatal Phenotype and Literature Review","authors":"Jiaqi Fan,&nbsp;Hairui Sun,&nbsp;Huan Jiang,&nbsp;Siyao Zhang,&nbsp;Hongmei Xia,&nbsp;Yihua He","doi":"10.1002/bdr2.70003","DOIUrl":"10.1002/bdr2.70003","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Pathogenic variants in the <i>SETD5</i> gene cause autosomal dominant intellectual developmental disorder 23. The limited number of published clinical case reports has hindered a comprehensive understanding of the associated phenotypic spectrum and mutational landscape.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We report a fetal case identified by cardiac ultrasound with an ostium primum atrial septal defect and a suspected high ventricular septal defect.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Whole-exome sequencing revealed a novel, previously unreported frameshift variant in <i>SETD5</i> (NM_001080517.3; exon21: c.3601_3605del, p. Trp1201GlufsTer2). Segregation analysis confirmed it to be a de novo variant.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This case expands the known mutational spectrum of <i>SETD5</i>. A review of the literature allows for a synthesis of the characteristic clinical features of this rare disorder. Congenital heart defects, including atrial and ventricular septal defects, can serve as early diagnostic indicators. Fetal cardiac ultrasound represents a valuable tool for early screening, underscoring the critical importance of prenatal whole-exome sequencing in such cases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 12","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145713287","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":"Utility of Electronic Case Reporting for Case Identification in Texas Birth Defects Surveillance","authors":"R. P. Allred,&nbsp;C. Yantz,&nbsp;H. Jeon,&nbsp;R. Howell,&nbsp;M. Kilburn,&nbsp;C. Shumate","doi":"10.1002/bdr2.70004","DOIUrl":"10.1002/bdr2.70004","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The utility of electronic case reporting (eCR) in birth defects surveillance is unknown. This evaluation assessed whether electronic initial case reports (eICRs) can serve as a potential case identification source and how eICRs compare to electronic health records (EHRs) in capturing demographic and diagnostic information.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Cases were identified from the Texas Birth Defects Registry's eCR data stream. Upon case confirmation, the EHR was requested and abstracted following routine abstraction processes. Next, the eICR html file was abstracted. The number, range, and mean of coded birth defects, as well as pre- and postnatal procedures were calculated for both data sources. Concordance between abstracted variables from the EHR and the eICR was evaluated for non-missing data using weighted kappa agreement statistics in SAS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>There were many missing data from the eICR. Fewer birth defects and pre- and postnatal procedures were reported in the eICR compared to the EHR. Most variables had low concordance, while a few variables had high concordance (e.g., infant sex [kappa = 0.95], infant birthdate [kappa = 0.99], primary defect code/diagnosis [kappa = 0.83 using 6-digit British Pediatric Association [BPA] codes; kappa = 0.92, 4-digit BPA codes]).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>eCR may be a viable source for timely potential case identification and may also facilitate timelier referral to social services among eligible cases. eCR data files are not standardized across facilities, lack critical variables permitting examination of birth defect risk factors, and are generally not a comprehensive resource for all pertinent data related to a birth defect case.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 12","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145713324","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":"Imbalance of Fetal Growth Factor Levels in Congenital Heart Disease Pathology: A Systematic Review","authors":"Yazdan Ghandi,&nbsp;Samira Zakeri Shahvari,&nbsp;Negar Poor Ahmadian,&nbsp;Mahbod Soltani,&nbsp;Seyed Amir Hossein Musavi,&nbsp;Mohammad Satarzadeh","doi":"10.1002/bdr2.70006","DOIUrl":"10.1002/bdr2.70006","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Vascular endothelial growth factor (VEGF) is a factor that is responsible for cell proliferation, growth of vascular endothelial cells, and angiogenesis. Changes in the level of this factor are associated with the pathology of structural disorders such as CHD. This systematic study assesses previous studies in order to find the VEGF influences on congenital heart disorders.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>This systematic review was written based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, and the principle of non-bias was respected. All the articles from 2014 to 2024 were extracted from Web of Science, PubMed, and Scopus databases. We investigated the role of VEGF in the pathology of cardiovascular structural disorders, the therapeutic and diagnostic effects of VEGF, and related factors that are influenced by this factor.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Studies assessed based on PRISMA search steps and 22 were included in our study. Any disturbance in the production and functioning of VEGF is known as a genetic disorder in tetralogy of Fallot (TOF). VEGF caused abnormal elongation of the heart tubes, as well as disproportionate growth of cardiovascular tissue just before full formation. The increase of Hypoxia-inducible factor (HIF) with the increase of VEGF function precedes the development of the fetal heart. HIF also mediates endothelial formation through endothelial nitric oxide synthases (eNOS); HIF in children with cyanotic CHD (CCHD) and acyanotic CHD (ACHD) is significantly higher than in the control group, and its value is higher in complex CHD children than in the other groups. EGFR, inducible NOS (iNOS), and ET-1 were more in ACHD than in CCHD, and their amounts showed a positive correlation with HIF.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The increase in the level of VEGF and HIF before the completion of the heart tissue is the main cause of CHD pathology; after the completion of the heart tissue, these factors help in the regeneration of the heart tissue. The regulation of VEGF and HIF levels during the fetal period is of great importance for the diagnosis and pathological aspect of CHD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 12","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145707207","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":"Spatial and Temporal Analysis of Hospital Discharges due to Congenital Malformations in Argentina","authors":"Marcelo I. Figueroa,&nbsp;Lautaro D. Andrade,&nbsp;Jorge S. López-Camelo,&nbsp;Hernán J. Dopazo,&nbsp;José E. Dipierri","doi":"10.1002/bdr2.70001","DOIUrl":"10.1002/bdr2.70001","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hospital discharges (HD) provide population data that can be used to define specific epidemiological profiles.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To quantify the prevalence of CM among all hospital discharges and its spatiotemporal patterns across Argentina. Furthermore, the study will benchmark these estimates against RENAC to contextualize agreement and discrepancies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>HD data (2005–2020) from the National Ministry of Health were analyzed at national, regional, and provincial levels. We estimated the proportion of HD due to CM (HDCM; ICD-10 Q00–Q99) overall and by age (&lt; 1 year, 1–5 years, &gt; 5 years). For infants &lt; 1 year, CM prevalence per 100 live births (LB) was computed and compared with RENAC. Temporal trends were assessed with Joinpoint regression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>HDCM represented 0.71% of all HD; 63.4% occurred in children ≥ 1 year, indicating substantial CM-related care beyond infancy. Spatial differences were directionally consistent across sources: nationally and in the Center, RENAC estimates were higher than HDCM; Cuyo showed higher HDCM throughout; NWA shifted to higher HDCM from mid-decade; NEA/Patagonia displayed small gaps with occasional crossovers. Temporally, Joinpoint analyses revealed heterogeneous regional trends without a common timing of inflections: HDCM increased in NWA, the gap widened in Cuyo toward the late decade, while national and Center trajectories were relatively stable; RENAC series remained more tightly clustered around the national pattern. In infants &lt; 1 year, structural cardiac malformations were the leading HD diagnoses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>HD-based metrics and RENAC provide complementary views of the CM burden; their systematic divergence with regional heterogeneity indicates that HD can robustly contextualize spatiotemporal differences where birth-surveillance alone is insufficient.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 12","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145653470","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":"FGFR1 Tyrosine Kinase Domain Variant p.Val561Met in Caudal Dysraphism: A Case Report","authors":"Himanshu Goel,&nbsp;Victoria Yachmenikova,&nbsp;Tanya Mckenny,&nbsp;Hannah Klucknow,&nbsp;Sheridan O'Donnell","doi":"10.1002/bdr2.70000","DOIUrl":"10.1002/bdr2.70000","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Neural tube defects (NTDs) are complex congenital malformations with both environmental and genetic contributions. Monogenic causes of NTDs are increasingly recognized, particularly those involving genes that regulate key morphogenetic pathways. FGFR1, a receptor tyrosine kinase, is crucial for axial and neural development; however, its role in caudal dysraphism remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We report a female fetus delivered at 25 weeks of gestation following prenatal diagnosis of severe lumbosacral spina bifida. Comprehensive postmortem and genetic investigations, including trio exome sequencing, were performed to identify potential causal variants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Postmortem examination revealed Chiari II malformation, dysmorphic features, bilateral talipes, and a large caudal spinal defect. Trio exome sequencing identified a de novo heterozygous FGFR1 variant (c.1681G&gt;A; p.Val561Met) affecting the conserved tyrosine kinase domain. This variant has been reported in somatic and developmental contexts, where it may modulate FGFR1 signaling, although evidence for constitutive activation remains limited and context-dependent. The variant has not been previously associated with NTD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This single case raises the possibility that altered FGFR1 signaling may contribute to defective neurulation and warrants further investigation in larger cohorts. Our findings support considering FGFR1 in the differential diagnosis of complex or syndromic spinal dysraphism, though additional evidence is required before recommending its inclusion in routine panels for isolated cases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 11","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145533990","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":"Effects of Pre-Conception Stress and Dracocephalum moldavica Extract on Sperm Parameters and Sex Hormones in Parents and Offspring","authors":"Leila Ghassemifard,&nbsp;Hajar Ramezanikhah,&nbsp;Parisa Jafari,&nbsp;Fatemeh Amiri,&nbsp;Ehsan Saboory","doi":"10.1002/bdr2.2545","DOIUrl":"10.1002/bdr2.2545","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Stress is one of the causes of fertility weakness in both females and males and herbal approaches may reduce this harmful effect. This study aimed to investigate the effect of <i>Dracocephalum moldavica</i> (<i>DM</i>) on the reproductive system in parental pre-pregnancy stress.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Material and Methods</h3>\u0000 \u0000 <p>In this experimental study, male and female rats were divided into four groups as follows: control, stress (restraint stress daily for 50 and 15 days for male and female, respectively), extract, and stress + extract. After treatment, the control and experimental rats were mated. Pregnant females were kept undisturbed until delivery and weaning. Offspring were divided into four groups according to the parents’ treatment: McFc, McFc+EX, MsFs, MsFs+EX (M: male, F: female, C: control, S: stress, and EX: extract). Epididymis and vagina were dissected from adult rats; sperm parameters, the thickness of vaginal epithelium, vaginal pH, sex hormone levels were assessed; in pups, testosterone/estradiol, litter size and sex ratio were investigated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p><i>DM</i> extract significantly reduced immotile, dead, and abnormal sperms (<i>p</i> &lt; 0.001) and led to increased levels of testosterone/estradiol in parents and offspring (<i>p</i> &lt; 0.01); the sex ratio was changed among the groups (<i>p</i> = 0.036); the highest number of female pups belonged to the MsFs group. Stress led to a decrease in vaginal thickness and pH while <i>DM</i> extract increased them (<i>p</i> &lt; 0.01).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The results indicate that <i>DM</i> extract may have a beneficial effect on some reproductive parameters affected by pre-conception stress. Notably, it was associated with improvements in sperm quality, hormone levels in parents and offspring, and certain vaginal health measures. Further research is needed to confirm these effects and better understand the underlying mechanisms.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 11","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145534003","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":"Understanding Clubfoot: Integrating Historical Origins, Embryologic Foundations, Epidemiology and Etiology—A Review","authors":"J. S. R. G. Saran,&nbsp;Varun Devdass,&nbsp;Durai Anand","doi":"10.1002/bdr2.2543","DOIUrl":"https://doi.org/10.1002/bdr2.2543","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>Congenital talipes equinovarus (CTEV) or idiopathic clubfoot, is a common yet complex congenital musculoskeletal deformity characterized by cavus, adductus, varus and equinus components. Despite advances in conservative and surgical management, recurrence and long-term functional limitations remain unresolved challenges. This review aims to provide an integrative synthesis of the historical evolution, embryological basis, etiological theories and clinical implications of idiopathic clubfoot.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A narrative literature review was conducted, synthesizing data from historical records, embryological studies, genetic and developmental biology research and clinical reports. Key theories of etiology, including embryological, genetic, vascular, neuromuscular, environmental and structural mechanisms, were critically examined to highlight converging and divergent perspectives.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The evidence suggests that idiopathic clubfoot arises from a multifactorial interplay of genetic predisposition, aberrant embryological signaling pathways, vascular dysgenesis, and environmental influences. While molecular studies implicate <i>PITX1–TBX4</i> pathways and extracellular matrix remodeling, developmental hypotheses highlight disruptions in muscle patterning, connective tissue organization and vascular development. Clinically, even well-corrected cases demonstrate persistent sequelae such as restricted ankle mobility, muscle weakness and altered biomechanics, predisposing to early degenerative joint changes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>CTEV should be considered a systemic developmental dysplasia rather than an isolated foot deformity. The persistence of recurrence and long-term morbidity underscores the need for multidisciplinary research integrating genetics, developmental biology, biomechanics and rehabilitation. Improved understanding of the etiological mechanisms may enable earlier detection, targeted interventions and ultimately better long-term outcomes for affected individuals.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 11","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145522258","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":"Pregnancy Outcomes Following Paternal Methotrexate Exposure: A Systematic Review and Meta-Analysis","authors":"Nusret Uysal,&nbsp;Hüseyin Yilmaz,&nbsp;Mesut Gungor,&nbsp;Ahmet Ozyurek,&nbsp;Tijen Kaya-Temiz,&nbsp;Baris Karadas,&nbsp;Yusuf C. Kaplan","doi":"10.1002/bdr2.2542","DOIUrl":"https://doi.org/10.1002/bdr2.2542","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Evidence guiding the management of pregnancies fathered by men exposed to methotrexate (MTX) remains limited. This systematic review and meta-analysis evaluated whether paternal MTX exposure before or at conception is associated with major congenital malformations or other adverse pregnancy outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Data Sources</h3>\u0000 \u0000 <p>PubMed, Web of Science, and Reprotox were searched from inception to May 2025, supplemented by manual reference screening.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Study Eligibility Criteria</h3>\u0000 \u0000 <p>Eligible studies were cohort or case–control designs assessing paternal MTX exposure during preconception or conception period with an unexposed control group. Reviews, editorials, animal studies, case reports, and overlapping datasets were excluded.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Study selection and data extraction were conducted independently. Risk of bias was assessed with ROBINS-I, quality with the Newcastle-Ottawa Scale, and certainty of evidence with GRADE. Adjusted odds ratios (aORs) were used for random-effects meta-analysis; outcomes lacking sufficient data were narratively synthesized. The primary outcome was major congenital malformations following paternal MTX exposure. Secondary outcomes included cardiac malformations, spontaneous abortion, live birth, elective termination, stillbirth, and preterm birth.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>No increased risks were observed for congenital malformations (aOR 1.00; 95% CI 0.62–1.61; <i>I</i>² = 0%), stillbirth (OR 0.85; 95% CI 0.11–6.45; <i>I</i>² = 0%), or preterm birth (OR 0.95; 95% CI 0.59–1.53; <i>I</i>² = 26%). In the qualitative review of case reports, case series, and noncomparable cohort data, no consistent or recurring patterns of malformations were identified.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Paternal MTX exposure was not associated with increased risks of congenital malformations, stillbirth, or preterm birth, nor with a consistent or recurrent pattern of anomalies. These findings provide reassurance regarding fetal safety following paternal MTX exposure.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 11","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145522171","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":"Infant Mortality due to Congenital Diaphragmatic Hernia, United States 2007–2021","authors":"Ramesh Vidavalur,&nbsp;Kanekal S. Gautham","doi":"10.1002/bdr2.2544","DOIUrl":"10.1002/bdr2.2544","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To analyze temporal trends and geographic variations in infant mortality rate associated with congenital diaphragmatic hernia (CDH-IMR) in the United States.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>From 2007 to 2021, we used CDC-WONDER linked birth/death data to identify CDH-related infant deaths (ICD-10 code: Q79 as the underlying cause of death), analyze annual CDH-IMR trends, and explore associations with sex, gender, gestational age (GA), and U.S. state of birth. Descriptive statistics were derived, and bivariate analyses were conducted to discern differences in CDH-IMR by gender, race, and GA. CDH-IMR was expressed per 100,000 live births with Poisson-modeled 95% confidence intervals, and trends were assessed through joinpoint regression to extrapolate annual percent change (APC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Between 2007 and 2021, 59,117,761 live births and 3391 CDH-related infant deaths were recorded. CDH infant deaths accounted for 0.96% of all infant deaths and occurred in 0.006% of live births. The mean CDH-IMR was 5.7 (95% CI: 5.5–5.9) per 100,000 live births, with a significant downward trend (APC: −1.3%, [95% CI: −2.0, −0.5, <i>p</i> &lt; 0.01]). Asian infants had a lower risk of mortality (RR 0.66 [95% CI: 0.55, 0.79]) compared to White infants, and higher GA at birth correlated with better survival. Regional analysis revealed a median CDH-IMR (IQR) of 5.9 (4.7, 7.2), with a three-fold variation across U.S. states.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In this national population-based U.S. study, we observed a decreasing trend in CDH-IMR. However, significant variation in CDH mortality persists by region, gender, and race. Despite evidence of current CDH care is associated with a decreasing trend in mortality, there remain many opportunities for equitable improvement in outcomes across race, gender and by geographic region.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 11","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145494475","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}