Birth Defects Research最新文献

{"title":"Lessons Learned From the COVID-19 Vaccines International Pregnancy Exposure Registry: Insights for Designing and Implementing Global Pregnancy Safety Studies","authors":"Diego F. Wyszynski,&nbsp;Cheryl Renz","doi":"10.1002/bdr2.70082","DOIUrl":"10.1002/bdr2.70082","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Pregnant women are at increased risk of severe illness from COVID-19, yet they were excluded from the initial clinical trials of COVID-19 vaccines, resulting in limited pregnancy-specific safety data. The COVID-19 Vaccines International Pregnancy Exposure Registry (C-VIPER) was established to prospectively collect safety and birth outcome data following COVID-19 vaccination during pregnancy. This article summarizes key operational, methodological, and scientific lessons from implementation of the registry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The C-VIPER was designed as an international, noninterventional, postmarketing cohort study using a web-based platform to enroll pregnant women exposed to COVID-19 vaccines and collect longitudinal maternal, pregnancy, birth, neonatal, and infant outcome data. Registry implementation, recruitment, retention, questionnaire design, comparator selection, data completeness, and evolving vaccination patterns were reviewed to identify lessons relevant to future pregnancy safety studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Implementation during a global pandemic presented substantial challenges, including uncertainty regarding vaccine acceptance and study participation among pregnant women, widespread misinformation and vaccine hesitancy, evolving vaccination regimens, recruitment and long-term retention difficulties, and limitations in questionnaire design and data completeness. Despite these challenges, the C-VIPER demonstrated the feasibility of conducting a large-scale multinational, web-based pregnancy registry under emergency conditions and highlighted important methodological considerations for future postmarketing vaccine safety studies in pregnancy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The C-VIPER contributed to the broader evidence base evaluating COVID-19 vaccination during pregnancy and provided important lessons for the design and implementation of future pregnancy registries. Future studies should prioritize early planning, flexible protocol design, robust recruitment and retention strategies, careful comparator selection, and mechanisms to improve data completeness and quality.</p>\u0000 \u0000 <p><b>Trial Registration:</b> NCT04705116, EUPAS39096.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 6","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148275964","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":"Parenchymal Disruption of Thyroid Gland in Rat Offspring Following Maternal Khat Exposure","authors":"Thomas Amuti,&nbsp;Pamela Mandela,&nbsp;Mavine Omondi,&nbsp;Philip Mwachaka,&nbsp;Jeremiah Munguti,&nbsp;James Kigera,&nbsp;Julius Ogeng'o","doi":"10.1002/bdr2.70078","DOIUrl":"10.1002/bdr2.70078","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Maternal consumption of khat has been associated with adverse neonatal outcomes like preterm birth and low birth weight. These effects resemble those seen in neonatal hypothyroidism, suggesting that khat disrupts thyroid function in the fetus. There is, however, limited data on the microscopic alterations in the thyroid gland of offspring following maternal consumption of khat. We examined the same in rat offspring whose mothers were exposed to khat during pregnancy as the suitable animal model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Female rats were acquired and randomized into groups receiving khat extract (200 or 500 mg/kg) or distilled water. Maternal khat consumption was started 7 days before mating and continued throughout pregnancy. From the offspring born, 28 thyroid glands were harvested and processed for histological analysis with hematoxylin and eosin and Ki-67 staining. Data on the follicle density and diameter, follicular cell epithelia, follicular cell nuclear-cytoplasmic index, and expression of proliferation marker Ki-67 were collected. These were analyzed using SPSS and key findings presented in tables and photomicrographs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared to controls, khat-treated groups exhibited parenchymal disruption evidenced by a dose-dependent epithelial shift of follicular cells from columnar to cuboidal, reduced follicular diameter, reduced follicular density, and increased nuclear-cytoplasmic index. There was also suppressed proliferative activity evidenced by a reduction in cells expressing Ki-67. Infiltration of follicular cells into colloid was observed in treated groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The observed parenchymal insult of the fetal thyroid gland following maternal exposure to khat could partially explain the adverse birth outcomes seen in the offspring.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 6","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148275962","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":"Availability of Folic Acid Fortified Corn Masa Products in Selected Areas in the United States","authors":"Sharon Bustrak,&nbsp;Juan D. Rodriguez,&nbsp;Lorraine F. Yeung,&nbsp;Gabriella Salazar,&nbsp;Scarlett H. Kim,&nbsp;Dayana Betancourt,&nbsp;Sarah D. Smith,&nbsp;Nesreen Gusbi,&nbsp;Alexandra Simpson,&nbsp;Cara T. Mai","doi":"10.1002/bdr2.70084","DOIUrl":"10.1002/bdr2.70084","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To assess the availability of folic acid fortified corn masa (CM) products across selected areas/regions in the United States for neural tube defects (NTD) prevention 8 years after voluntary fortification of CM products was permitted.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Geographic selection using US census data included areas with majority Hispanic census tracts in California (CA), Georgia, and Texas (TX). A largely rural county in CA, an urban county in TX, and the metropolitan Atlanta area were selected as study sites. Stores selling groceries and snacks in the selected areas were visited and surveyed for CM products. A mobile application was used to record product data, including product identifiers (e.g., brand name, product type) and folic acid information (e.g., presence and amount of folic acid, folic acid graphical design element). Analyses were performed using R studio.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the 111 stores surveyed, products identified included 50 distinct retail CM flour bags, 178 distinct corn tortilla products, 88 distinct tostada products, and 223 other distinct CM products. Fifty percent of distinct CM flour bags (25/50) were fortified with folic acid. Additionally, 1% (2/178) of tortillas and about 3% (3/88) of tostadas were fortified. No other fortified products were identified.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Almost a decade after voluntary folic acid fortification of CM flour was allowed, very few ready-made CM products assessed in this study were fortified. As states work to initiate changes to increase the availability of fortified products, continued assessment can help monitor the availability of fortified products for NTD prevention.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 6","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148263337","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":"Prevalence, Temporal Trends, Diversity, and Associated Risk Factors of Isolated Cleft Lip With or Without Cleft Palate: A 20-Year Retrospective Hospital-Based Study in Iran (2003–2023)","authors":"Abdoljalil Kalantar-Hormozi,&nbsp;Reza Motallebi,&nbsp;Mehdi Abrishami","doi":"10.1002/bdr2.70079","DOIUrl":"10.1002/bdr2.70079","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cleft lip with or without cleft palate (CL/P) is a prevalent congenital anomaly influenced by multifactorial genetic and environmental factors. This study investigated the prevalence, temporal trends, diversity, unclassified cases, and associated risk factors for isolated CL/P in a tertiary Iranian hospital setting over two decades.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective analysis of 767 isolated CL/P cases from 620,000 live births at 15 Khordad Hospital (Tehran, Iran) from 2003 to 2023 was conducted. Data were extracted from anonymized medical records, focusing on demographic, perinatal, and clinical variables. Prevalence was calculated per 10,000 live births, with Cochran-Armitage trend tests for temporal patterns. Univariable and multivariable logistic regression assessed associations, adjusted for confounders (<i>p</i> &lt; 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Prevalence was 1.24 per 1000 live births (95% CI: 1.15–1.33), with male predominance (59.7%; ratio 1.59:1). A significant non-linear temporal pattern was observed (<i>p</i> = 0.045), with fluctuations peaking mid-2010s. Diversity included 48.4% combined CL/P, 71.6% unilateral (42.1% left), and 58.7% complete forms; 4.3% were unclassified “nasal-dominant variants.” Multivariable models identified maternal smoking (11–20 cigarettes/day: aOR 1.52, 95% CI 1.30–1.78), obesity (extreme: aOR 1.37, 95% CI 1.23–1.53), pre-pregnancy diabetes (aOR 2.00, 95% CI 1.68–2.38), hypertension (aOR 1.20, 95% CI 1.05–1.37), previous preterm birth (aOR 1.44, 95% CI 1.30–1.60), and assisted reproductive technology (aOR 1.42, 95% CI 1.18–1.71) as risks; higher education (aOR 0.82, 95% CI 0.74–0.91) and maternal age 30–34 years (aOR 0.90, 95% CI 0.81–1.00) were protective (Nagelkerke <i>R</i>² = 0.18).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Isolated CL/P in Iran exhibits stable yet fluctuating trends, driven by modifiable maternal risks amenable to preconception interventions. Enhanced public health strategies targeting smoking and obesity could reduce incidence by 15%–25%, aligning with global goals for congenital anomaly prevention.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 6","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148263361","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":"Regional Variations in Mortality, Surgical Treatment, and Hospitalization in Children With Congenital Diaphragmatic Hernia: A European Population-Based Data-Linkage Cohort Study","authors":"Mads Damkjær,&nbsp;Frederik Høst Meldgaard,&nbsp;Joachim Tan,&nbsp;Maria Loane,&nbsp;Joanne Given,&nbsp;Elisa Ballardini,&nbsp;Clara Cavero-Carbonell,&nbsp;Mika Gissler,&nbsp;Sue Jordan,&nbsp;Anna Pierini,&nbsp;Anke Rissmann,&nbsp;David Tucker,&nbsp;Ester Garne,&nbsp;Joan K. Morris","doi":"10.1002/bdr2.70083","DOIUrl":"10.1002/bdr2.70083","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>To describe mortality, surgical treatment, and hospitalization patterns in children with congenital diaphragmatic hernia (CDH) using population-based data, linked to congenital anomaly registries across Europe.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This cohort study used nine EUROCAT registries in five countries (Denmark, Finland, Italy, Spain, and the United Kingdom) linked to routinely collected hospital and mortality data. Children born alive with CDH between 2005 and 2014 were included and followed until age 5 in hospital data or age 10 in death data, with the final follow-up the end of 2015. Analyses were conducted for all CDH cases and separately for isolated CDH (CDH without additional major congenital anomalies). Standardized data processing and meta-analysis methods were used to generate pooled estimates of mortality, surgical interventions, and hospital stays.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 567 children with CDH, most were isolated CDH. First year survival was 74.5% for isolated CDH, ranging from 63% to 83% between registries. Similar survival was noted for all children with CDH. Most deaths occurred within the first week. Mortality rates plateaued after infancy, with no deaths recorded after age 5. The median age at surgery was approximately 2 weeks, although this varied by region. Median hospital length of stay in infancy varied from 14 to 29 days between regions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In children with CDH, mortality is highest in the neonatal period, with long-term survival stabilizing after infancy. No deaths occurred after age 5 years. Regional differences in mortality and surgical timing highlight the value of population-based, harmonized data for benchmarking and international comparisons.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 6","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148257289","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":"Opportunities and Challenges for Surveillance of Congenital Anomalies in Sub-Saharan Africa","authors":"Emma Kalk,&nbsp;Helen Louise Malherbe,&nbsp;Ushma C. Mehta,&nbsp;Daniel Mumpe-Mwanja,&nbsp;Modiegi Dianah Diseko,&nbsp;Adejumoke Idowu Ayede,&nbsp;Phyllis Kisa,&nbsp;Caroline Bonareri Osoro,&nbsp;George Bello,&nbsp;Lee Fairlie,&nbsp;Audrey Chepkemoi,&nbsp;Hamisi K. Shabani,&nbsp;Ali Sie,&nbsp;Samrawit Abebaw Tegene,&nbsp;Robert Serunjogi,&nbsp;Aminkeng Zawuo Leke,&nbsp;Helen Dolk,&nbsp;Linda Barlow Mosha,&nbsp;the sub-Saharan African Congenital Anomalies Network (sSCAN)","doi":"10.1002/bdr2.70075","DOIUrl":"10.1002/bdr2.70075","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Congenital anomalies (CA) are ranked as the 3rd and 4th leading cause of neonatal and under-5 mortality, respectively. Over 30% of infants born with a serious CA are found in sub-Saharan Africa. Yet there are few robust epidemiological data on the burden and distribution of CA and associated mortality, disability, and morbidity, which limits research and investment in clinical and public health interventions. The sub-Saharan African Congenital Anomalies Network (sSCAN) was established in 2021 to address the fragmented research, surveillance, and care programmes for children with CA in the region.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The sSCAN established a community of practice with the long-term aim to promote the prevention and early diagnosis of CA and care for children and families, determining prevalence, promoting preventive interventions, and improving health outcomes by: (1) Sharing resources and multidisciplinary expertise; (2) Establishing a common response to public health questions; (3) Pooling and comparing data between countries; (4) Capacity building.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The sSCAN includes 16 projects across 12 countries, in addition to other stakeholders in sub-Saharan Africa. Most projects are fully or jointly supported by donor partners with a specific disease/exposure focus: collaboration within Africa is uncommon. Lack of data harmonization, varied funding streams and related data access, and country- and institution-specific data-protection legislation limited regional data sharing. The sSCAN has hosted 15 webinars which are available with other resources on the website, and supported grant applications and publications.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The sSCAN platform can provide opportunities to build capacity, share expertise, and optimize data use toward contextually-relevant solutions for CA in sub-Saharan Africa.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 6","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bdr2.70075","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148216504","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":"Identification of Neonatal Prevalence Trends in Gastroschisis: 2016–2024","authors":"Stephanie A. Eyerly-Webb,&nbsp;Amanda J. Nickel,&nbsp;Eric Dion,&nbsp;Clifton O. Brock,&nbsp;Saul Snowise,&nbsp;James Fisher","doi":"10.1002/bdr2.70066","DOIUrl":"10.1002/bdr2.70066","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Gastroschisis prevalence in the United States has varied over the last several decades, with recent reports indicating a downward trend through 2022.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective/Methods</h3>\u0000 \u0000 <p>To determine if this trend continued beyond the COVID-19 Public Health Emergency, we examined data from the Children's Hospital Association's Pediatric Health Information System (PHIS) for critically ill neonates admitted from 2016 to 2024.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The national prevalence for critically ill neonates with gastroschisis significantly decreased (<i>p</i> ≤ 0.0001) between 2016 and 2024, with consistent declines across all regions in the United States. In contrast, trends for congenital diaphragmatic hernia and intestinal atresias remained stable or increased during the same period. We observed a −31.1% change in the prevalence of gastroschisis in critically ill neonates using PHIS, which was similar to the changes reported using population-level data sets from the Centers for Disease Control (−34.2%, −32.3%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These results indicate an ongoing decline in gastroschisis prevalence in the critically ill neonatal population, similar to changes seen at the population level, highlighting the need to explore potential causes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 6","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148155335","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":"Health Care Utilization in Adults With Congenital Heart Disease: Population-Based Findings","authors":"Tessa L. Crume,&nbsp;Amber D. Khanna,&nbsp;Alexandra Tillman,&nbsp;George K. Lui,&nbsp;Aida S. Soim,&nbsp;Daphne T. Hsu,&nbsp;Kristin Sommerhalter,&nbsp;Anaclare Sullivan,&nbsp;Jennifer S. Li,&nbsp;Alfred D′Ottavio II,&nbsp;Wendy M. Book,&nbsp;Cheryl Raskind-Hood,&nbsp;Kevin Whitehead,&nbsp;Nelangi Pinto,&nbsp;Marcia L. Feldkamp,&nbsp;Matthew R. Reeder,&nbsp;Sergey Krikov,&nbsp;Lorenzo D. Botto","doi":"10.1002/bdr2.70063","DOIUrl":"10.1002/bdr2.70063","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Population-based data on healthcare utilization in adults with congenital heart disease (CHD) are limited. We examined utilization patterns in a multi-site, population-based U.S. cohort of adults with CHD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective cohort linked health and administrative records from five regions (Colorado, North Carolina, Utah, metropolitan Atlanta, and New York). Adults aged 19–64 years with at least one CHD-related ICD-9-CM code recorded during 2011–2013 were included. We evaluated inpatient, emergency department (ED), outpatient, and cardiology outpatient encounters, as well as cardiac diagnostic/imaging, therapeutic/interventional, and vascular procedures. Multivariable mixed-effects logistic regression models compared utilization by CHD severity (severe vs. non-severe), adjusting for sex, race/ethnicity, insurance, comorbidity, and site, and including age group as an effect modifier.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Over 3 years, this cohort of 18,877 adults (20.7% severe CHD), 45.9% had at least one hospitalization, 35.1% had an ED visit, 92.1% had an outpatient encounter, and 43.8% had a cardiology outpatient visit. Cardiac diagnostic/imaging procedures occurred in 67.8%, cardiac interventions in 20.3%, and vascular procedures in 10.5%. Severe CHD was associated with higher odds of cardiac procedures but lower odds of ED use than non-severe CHD. Age modified these associations, and site-level variation was marked, with cardiology visit rates ranging from 21% to 59%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Adults with CHD had high healthcare utilization, including frequent ED use, yet fewer than half saw a cardiology specialist, particularly at older ages. These findings highlight persistent gaps in lifelong care and substantial geographic variation, underscoring the need to improve access to specialized care for adults with CHD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 6","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bdr2.70063","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148161864","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":"Nonclinical Considerations for Support of Pregnancy and Lactation in Clinical Trials","authors":"Dinesh Stanislaus,&nbsp;Christopher J. Bowman,&nbsp;Kimberly C. Brannen,&nbsp;Sarah N. Campion,&nbsp;Laura M. Carlson,&nbsp;Stephan Chalon,&nbsp;Anthony M. DeLise,&nbsp;Claudia Demarta-Gatsi,&nbsp;Brian P. Enright,&nbsp;Wendy Halpern,&nbsp;Shermaine Mitchell-Ryan,&nbsp;Vicki Sutherland,&nbsp;Karen Thacker,&nbsp;Kary Thompson,&nbsp;Belen Tornesi,&nbsp;Steven Van Cruchten,&nbsp;Ronald L. Wange,&nbsp;Tacey White,&nbsp;Connie L. Chen","doi":"10.1002/bdr2.70074","DOIUrl":"10.1002/bdr2.70074","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Pregnant and breastfeeding individuals remain underrepresented in clinical drug development, leaving health care providers and patients with limited data to inform treatment decisions. Current practice relies heavily on nonclinical developmental and reproductive toxicity (DART) studies in animals, while clinical trials typically exclude pregnant and breastfeeding populations or require highly effective contraception for women of childbearing potential. Consequently, medications may be used during pregnancy or lactation despite limited supporting evidence, which can lead to treatment interruption, suboptimal dosing, and increased maternal or fetal risk. Emerging regulatory guidance, including draft ICH Guideline on Inclusion of Pregnant and Breastfeeding Individuals in Clinical Trials (E21), highlights the ethical and clinical need to generate data directly in these populations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This paper evaluates the current regulatory framework for nonclinical studies described in ICH S5(R3) and M3(R2) and examines how these studies can support the enrollment of pregnant and breastfeeding individuals in clinical trials. It proposes pragmatic adaptations to align nonclinical testing with the anticipated clinical context of use and considers the role of new approach methodologies (NAMs) and alternative study designs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Potential DART strategies are described that could enable the inclusion of pregnant individuals in clinical trials based on factors such as dosing duration, route of administration, and study type (e.g., pharmacokinetic studies). The paper also considers the use of NAMs, including physiologically based pharmacokinetic modeling and in vitro assays, as well as alternative study designs such as preliminary pre- and postnatal development or extended embryo–fetal development studies. Approaches to inform studies in breastfeeding populations, including milk–plasma ratio modeling and translation from nonclinical data, are also discussed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These approaches support a shift from routine exclusion toward proactive and ethical inclusion of pregnant and breastfeeding individuals in clinical research, helping address longstanding evidence gaps and improving therapeutic decision-making.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 6","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bdr2.70074","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148161843","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":"Perinatal Exposure Profiles to Bisphenols and Their Associations With Thyroid Hormones Changes","authors":"Abderrezak Khelfi,&nbsp;Inas Aouissi,&nbsp;Iyad Fara,&nbsp;Chakib Fesraoui,&nbsp;Mohamed Azzouz","doi":"10.1002/bdr2.70077","DOIUrl":"10.1002/bdr2.70077","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Bisphenols are ubiquitous endocrine disruptors suspected of interfering with several physiological functions. Their effects during the perinatal period are of particular concern due to the high vulnerability of this stage of development.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to evaluate fetal exposure to bisphenols and to investigate possible associations between thyroid hormone levels and bisphenol concentrations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>A total of 154 mother–child pairs were included and umbilical cord blood samples were collected. Thyroid hormones (TSH, FT4, and FT3) and bisphenols (BPA, BPF, and BPS) were quantified in these samples. Relevant information about participants was obtained through a structured questionnaire.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The prevalence of bisphenol detection in umbilical cord blood samples was 92.8% for BPA, 65.5% for BPS, and 57.8% for BPF. Mean concentrations in umbilical cord blood were 2.456, 0.646, and 0.660 ng/mL. Significant positive associations were observed between FT4 and the three bisphenols with <i>β</i> values of 0.740, 0.897, and 1.045, respectively. A significant positive association was also found between FT3 levels and BPA concentrations (<i>β</i> = 0.119).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study highlights the detectable exposure of Algerian women to bisphenols, as well as the association of these compounds with thyroid changes during the perinatal period, with potential consequences for fetal development.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 6","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148148293","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}