Birth Defects Research最新文献

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

{"title":"Mind the Litter: The Critical Role of Intralitter Variables in Reproductive and Developmental Toxicology Research.","authors":"Lauren T L Brown, Megan E Cull, Delaine Pereira, Perri M Grant, Louise M Winn","doi":"10.1002/bdr2.70044","DOIUrl":"10.1002/bdr2.70044","url":null,"abstract":"<p><strong>Background: </strong>Animal models remain essential for understanding developmental toxicology, providing insights into how in utero exposures affect fetal and placental outcomes. Litter-bearing species are widely used due to their efficiency and reproducibility, but conventional approaches often summarize outcomes at the litter level, masking meaningful within-litter variability.</p><p><strong>Aim: </strong>This review highlights three primary sources of intralitter variability: litter size, uterine implantation location, and fetal sex, and their influence on fetal and placental growth, mortality, and malformations.</p><p><strong>Discussion: </strong>Larger litters restrict fetal growth through intrauterine competition, while toxicant-induced changes in litter size can obscure or exaggerate effects. Implantation location within uterine horns influences perfusion, nutrient delivery, and local exposure to hormones or toxicants, introducing spatially dependent vulnerability. Fetal sex further modifies responses, as male and female fetuses and placentas differ in growth trajectories, gene expression, and adaptive capacity, leading to sex-specific susceptibility to toxicants.</p><p><strong>Conclusion: </strong>Ignoring these sources of variability risks overlooking subtle effects and vulnerable subpopulations, misinterpreting outcomes, and reducing the translational value of animal studies. We argue that incorporating intralitter variables into experimental design and statistical analyses enhances the accuracy, reproducibility, and interpretability of developmental toxicology research. By refining the use of animal models in line with the 3Rs framework, researchers can maximize the information gained per pregnancy and improve risk assessment for human maternal-fetal health.</p>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 4","pages":"e70044"},"PeriodicalIF":2.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13083546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147687626","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":"Analysis of Prevalence and Mortality Among Neonates and Children With Intestinal Atresia: A Multinational Study, 1974-2015.","authors":"Angie Carreño, Maria Paula Aguilera, Lina Ibañez, Karen Sarmiento, Juan A Gili, Csaba Siffel, Wendy N Nembhard, Jorieke E H Bergman, Eva Bermejo-Sánchez, Giovanna Tagliabue, Saeed Dastgiri, Marcia L Feldkamp, Stephanie Pocius, Miriam Gatt, Laura Martínez, María Aurora Canessa, Boris Groisman, Karin Källén, Danielle Landau, Nathalie Lelong, Margery Morgan, Jazmín Arteaga-Vázquez, Michele Santoroi, Anke Rissmann, Antonin Sipek, Elena Szabova, Wladimir Wertelecki, Mark A Canfield, Pierpaolo Mastroiacovo, Ignacio Zarante","doi":"10.1002/bdr2.70032","DOIUrl":"10.1002/bdr2.70032","url":null,"abstract":"<p><strong>Introduction: </strong>Small intestinal atresia (SIA) consists of a congenital obstruction of the lumen of the duodenum, jejunum, or ileum with varying severity. The aim of the investigation was to analyze the prevalence and mortality of SIA, using data from the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR).</p><p><strong>Methods: </strong>Data on SIA cases were collected from 25 ICBDSR members' surveillance programs in 17 countries over 1974-2015. All pregnancy outcomes were included, but terminations of pregnancy were not available for 11 programs. Statistical analysis is descriptive, and the prevalence is established by the total of SIA cases divided by the total of births. The survival time was calculated, and mortality was analyzed individually using the Kaplan-Meier method for comparison.</p><p><strong>Results: </strong>The total prevalence of SIA was 2.1 per 10,000 births. Iran had the highest prevalence with 11.5 per 10,000 total births (95% CI: 9-14.1); on the other hand, the lowest prevalence of SIA was in Mexico-Nuevo Leon with 0.5 per 10,000 births (95% CI: 0.3-0.8), and Cali-Colombia had zero cases. In South America, a higher prevalence of SIA was estimated compared to what was reported in 2000. Most deaths occurred between Day 2 and 6, except in Bogotá-Colombia, Spain, UK-Wales, and Mexico, where the deaths occurred on Day 1. The mortality in the first year was 4.3%, but the specific causes of death were not determined in this study.</p><p><strong>Conclusion: </strong>The prevalence of SIA was about 2.1 per 10,000 births during a 41-year period in 25 centers, with variations in prevalence according to geographical locations. Future research is suggested to analyze changes in trends and the impact of early diagnosis and treatment in mortality.</p>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 4","pages":"e70032"},"PeriodicalIF":2.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13094396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721612","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":"Teratogen Update: Fever in Pregnancy","authors":"Peeraya Sawangkum,&nbsp;Lilla Markel,&nbsp;Khush Shah,&nbsp;Sarah G. Običan","doi":"10.1002/bdr2.70041","DOIUrl":"10.1002/bdr2.70041","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Maternal fever is a common occurrence during pregnancy, but evidence increasingly links even transient hyperthermia to adverse fetal outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This review examines data from animal and human studies on the association between maternal hyperthermia and structural birth defects, neurodevelopmental disorders, fetal growth restriction, and pregnancy loss.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>A narrative review of published literature evaluating maternal hyperthermia and pregnancy outcomes was conducted, including both experimental animal models and observational human studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The teratogenic effects appear to be dose- and timing-dependent, with greatest vulnerability during the first trimester. Reported associations including neural tube defects, craniofacial anomalies, and congenital heart defects as well as neurodevelopmental disorders, fetal growth restriction, and pregnancy loss. Proposed mechanisms include heat-induced cellular stress and maternal immune activation, both of which can disrupt embryonic development. Folic acid supplementation and antipyretic use are associated with reduced risk.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Although the evidence is derived from observational studies and limited by difficulty of measuring temperatures, the consistency of findings from different models support the biologic plausability of a teratogenic effect of maternal fever. The variability in exposure assessment and confounding factors, including maternal comorbidities, remain important limitations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Maternal fever is a potentially modifiable risk factor for advere pregnancy outcomes. Preventative strategies that include preconception folic acid supplementation and maternal fever management are supported by the current literature. Further research is needed to define critical exposure windows and the impact of materanal comorbidities.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 4","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147520046","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":"Machine Learning-Based Risk Prediction Models for Pregnancy-Related Syndromes","authors":"Yanqi Wu","doi":"10.1002/bdr2.70038","DOIUrl":"10.1002/bdr2.70038","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Pregnancy-related syndromes, such as hypertensive disorders, gestational diabetes mellitus, and preterm birth, pose a significant global health burden, affecting maternal and fetal outcomes. Traditional screening methods, reliant on isolated biomarkers or linear models, often fail to address the complex pathophysiology of these conditions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>This review synthesizes current literature on machine learning applications in obstetric care, analyzing multimodal data integration from electronic health records, biochemical markers, multi-omics, and imaging. It outlines model development workflows, including preprocessing for class imbalance (e.g., SMOTE) and interpretability tools (e.g., SHAP), while addressing ethical and technical challenges.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Ensemble methods (e.g., Random Forest, XGBoost) and deep learning (e.g., CNNs) outperform logistic regression, achieving AUC values &gt; 0.90. Key advancements include federated learning for privacy and bias mitigation strategies to enhance generalizability across populations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Machine learning-based models enable predictive, preventive, and personalized obstetrics, facilitating early interventions and improved perinatal outcomes, though external validation and regulatory frameworks are essential for clinical adoption.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 3","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147430537","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 and Risk Factors of Postpartum Depression in Southeastern Iranian Women","authors":"Tania Dehesh,&nbsp;Samira Jafari,&nbsp;Paria Dehesh","doi":"10.1002/bdr2.70033","DOIUrl":"10.1002/bdr2.70033","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Postpartum depression (PPD) significantly impacts maternal mental health and child well-being, necessitating a clear understanding of its prevalence and risk factors to inform effective interventions in Iran.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This cross-sectional study, conducted in Kerman, eastern Iran, from April to December 2023, recruited 876 women from multiple healthcare centers. Data were collected using the validated Persian Edinburgh Postnatal Depression Scale (EPDS, score &gt; 12) with DSM-5 clinical confirmation, alongside a questionnaire assessing demographic characteristics, socioeconomic status, marital relationships, and support systems. Logistic regression analyses determined the point prevalence of PPD and identified significant risk and protective factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The point prevalence of PPD was 29.1% (255/876, 95% CI: 26.2–32.2). Independent predictors of higher PPD odds included delivery outside a healthcare facility (AOR = 1.60, 95% CI: 1.25–2.21, <i>p</i> = 0.015), maternal history of depression (AOR = 2.20, 95% CI: 1.60–3.00, <i>p</i> &lt; 0.001), infant abnormalities (AOR = 1.60, 95% CI: 1.10–2.40, <i>p</i> = 0.014), poor breastfeeding experience (AOR = 2.50, 95% CI: 1.30–4.70, <i>p</i> = 0.006), excessive infant crying (AOR = 1.70, 95% CI: 1.20–2.50, <i>p</i> = 0.003), husband's chronic illness (AOR = 1.32, 95% CI: 1.21–1.69, <i>p</i> = 0.043), and husband's history of depression (AOR = 1.43, 95% CI: 1.17–1.72, <i>p</i> = 0.045). Protective factors included husband's involvement in childcare (AOR = 0.61, 95% CI: 0.42–0.90, <i>p</i> = 0.017), adequate emotional support (AOR = 0.65, 95% CI: 0.45–0.95, <i>p</i> = 0.025), and satisfaction with the baby's gender (AOR = 0.71, 95% CI: 0.50–0.95, <i>p</i> = 0.023).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The 29.1% point prevalence of PPD underscores the urgent need for enhanced screening, community-based support, and targeted interventions addressing modifiable factors like breastfeeding difficulties and partner support to improve maternal and child health outcomes in Iran.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 3","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147353856","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":"No Evidence of Impact of Genetic Sex on Hyperthermia-Induced Neural Tube Defects in Chicken Embryos","authors":"Yiting Wang,&nbsp;Aimee K. Ryan,&nbsp;Anna K. Naumova","doi":"10.1002/bdr2.70037","DOIUrl":"10.1002/bdr2.70037","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>In mammals, cranial neural tube defects (NTDs) are more likely to occur in females. It has been proposed that the sex bias in NTDs was due to the presence of the inactive X chromosome in the somatic cells of female embryos and that the inactive X acted as a heterochromatic sink, competing for silencing factors with the rest of the genome. Such competition increased the likelihood of abnormal gene regulation. To test this hypothesis, we used an animal model that lacks dosage compensation, the chicken <i>Gallus gallus</i>. If the heterochromatic sink hypothesis was correct, no sex bias will be found in chicken embryos with cranial NTDs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used in ovo heat treatment to induce NTDs in chicken embryos and PCR genotyping to determine embryos' genetic sex. Embryo phenotypes were examined using a dissecting microscope. Embryos were staged according to Hamburger and Hamilton criteria and scored for NTDs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We observed a statistically significant increase in NTDs following heat treatment (38.1% in the treatment group vs. 5.9% in the control group), but no sex bias. Next, we asked if heat treatment led to a developmental delay and found a significant association between the numbers of somite pairs and heat treatment and a reduced number of somites in the chicken embryos with cranial NTDs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In ovo hyperthermia during the developmental window when the neural tube is formed dramatically increases the rate of NTDs and delays the development of chicken embryos. However, there is no sex bias with respect to NTD risk.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 3","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12963691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147364134","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":"Recurrent Constellations of Embryonic Malformations (RCEM): Teratogenicity Linked to Transient Hypoxia and Hormone Pregnancy Tests Agrees With RCEM and Suggest a Reactive Oxygen Species Pathogenesis","authors":"Aaron P. Adam,&nbsp;Helen E. Ritchie,&nbsp;Margaret P. Adam,&nbsp;Bengt R. Danielsson","doi":"10.1002/bdr2.70036","DOIUrl":"10.1002/bdr2.70036","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>No consistent genetic etiology has been found for a group of six different conditions in humans with multiple malformations called “recurrent constellations of embryonic malformations” (RCEM). Recent studies indicate hypoxia/reoxygenation and generation Reactive Oxygen Species (ROS) as an underlying mechanism for RCEM with the specific manifestations related to the timing, severity and duration of the ROS exposure.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Medical literature was evaluated in relation to a hypoxia/ROS related mechanism for RCEM. Special attention was paid to investigate if the reported spectrum of multiple human malformations for Hormone Pregnancy Tests (HPTs), which have been associated with embryonic hypoxia due abnormal uterine contractions in early pregnancy, agrees with the RCEM spectrum.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The pattern of human multiple and single malformations associated with HPTs in 44 case reports with multiple defects, 86% (38/44) were consistent with RCEM spectrum, the most common was VACTERL. There was also a high consistency with regards to increases in single HPT malformations within the RCEM spectrum in a large case report study (&gt; 225 cases) and in more than 25 human epidemiological studies evaluating HPT teratogenicity. The RCEM spectrum is also consistent with reported malformations when the embryo has been exposed to periods of transient embryonic hypoxia/ROS in animal studies and when exposed to drugs associated with embryonic hypoxia/ROS (e.g., cocaine) and in some genetic diseases with malformations (e.g., NAD+ deficiency) when ROS overwhelms the antioxidant defense.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This review shows that HPTs are associated with human teratogenicity and ROS to be the proximate teratogen underlying RCEM.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 3","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12961259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147353817","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":"Novel Homozygous DLX5 and WNT10B Variants Expand the Genetic and Phenotypic Spectrum of Autosomal Recessive Split-Hand/Foot Malformations (SHFM1D and SHFM6)","authors":"Heba A. Hassan,&nbsp;Asmaa M. Esmail,&nbsp;Mervat Elbelbesy,&nbsp;Nargues M. Hassanein,&nbsp;Mona S. Aglan,&nbsp;Mona L. Essawi","doi":"10.1002/bdr2.70031","DOIUrl":"10.1002/bdr2.70031","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Split-hand/foot malformations (SHFM) have both dominant and recessive inheritance patterns, but the autosomal recessive forms (SHFM1D and SHFM6) are much rarer and often present with more severe and asymmetrical limb defects compared to the dominant forms. This study aimed to investigate the genetic basis of SHFM in patients presenting with limb anomalies and associated features, contributing to the understanding of autosomal recessive SHFM subtypes (SHFM1D and SHFM6).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Clinical and radiological assessments were performed on the patients, followed by exome sequencing and segregation analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Two patients exhibited median clefts in hands/feet, aplasia/hypoplasia of phalanges. Patient 1 also presented with genital anomalies (hypospadias), hearing loss, and atrial defect detected in one patient. Exome sequencing identified two novel homozygous variants: A nonsense variant (p.Glu33*) in DLX5 (SHFM1D) in Patient 1 and a missense variant (p.Leu87Pro) in WNT10B (SHFM6) in Patient 2. Parental sequencing confirmed heterozygous carrier status. The DLX5 variant truncates the protein upstream of the DNA-binding domain, while the WNT10B variant disrupts a conserved palmitoylation site, impairing WNT signaling.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study expands both the genetic and phenotypic spectra of autosomal recessive SHFM. We report the second documented case of SHFM1D worldwide. It is the first case to link the recessive SHFM1D with hypospadias, thereby expanding its clinical spectrum. Our findings also distinguish the distinct pathogenic mechanisms of <i>DLX5</i> and <i>WNT10B</i>-related malformations. Further research into the DLX5/WNT10B pathways may provide insights into human development and differentiation in the context of SHFM and associated anomalies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 3","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147316166","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":"Maternal Analgesic Exposure and Fetal Ductal Constriction: A Prospective Cohort Study in Late Pregnancy","authors":"Isaura Elaine Gonçalves Moreira Rocha,&nbsp;Andresa Carvalho Nobre,&nbsp;Beatriz Gonçalves Rocha,&nbsp;Paulo Henrique Benevides Siqueira,&nbsp;Estelita Lima Cândido,&nbsp;Simone Cristina Soares Brandão","doi":"10.1002/bdr2.70039","DOIUrl":"10.1002/bdr2.70039","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;To evaluate the association between maternal analgesic exposure in late pregnancy and fetal ductal and pulmonary hemodynamics using serial echocardiographic assessment, and to explore potential differences between metamizole and acetaminophen.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;In this prospective cohort study, 67 third-trimester pregnancies were evaluated: 47 exposed to analgesics (27 metamizole and 20 acetaminophen) and 20 unexposed controls. Two standardized fetal echocardiograms were performed: during exposure (T1) and after a 5–7 day drug-free interval (T2). Ductal Doppler parameters, including systolic velocity, diastolic velocity, and pulsatility index (PI), were used to define ductal constriction based on established criteria (PI &lt; 1.9 and/or increased velocities). Right-heart and pulmonary hemodynamic parameters, including mean pulmonary artery pressure (MPAP) and acceleration time/ejection time ratio (AT/ET), were also assessed.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;In the primary pooled analysis, ductal constriction occurred in 38.3% (18/47) of exposed fetuses and in 0% (0/20) of controls (&lt;i&gt;p&lt;/i&gt; = 0.00065). When stratified by exposure, constriction was observed in 52% (14/27) of metamizole-exposed fetuses and in 20% (4/20) of acetaminophen-exposed fetuses. In multivariable analysis, metamizole use (OR 2.05; 95% CI 1.28–3.28), exposure within 48 h (OR 1.96; 95% CI 1.12–3.44), and dose &gt; 1 g (OR 2.64; 95% CI 1.31–5.32) were independently associated with ductal constriction. Within the metamizole group, higher doses were associated with a greater proportion of constriction, although subgroup size limited statistical precision. After metamizole withdrawal, PI increased significantly (1.86 ± 0.43 to 2.28 ± 0.41; &lt;i&gt;p&lt;/i&gt; &lt; 0.001), accompanied by reductions in systolic and diastolic velocities (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). In the acetaminophen group, mild and reversible constriction was observed, with modest PI improvement at T2 (2.20 ± 0.44 to 2.40 ± 0.29; &lt;i&gt;p&lt;/i&gt; = 0.040) and no major velocity changes. Neither exposure significantly altered MPAP or AT/ET.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Maternal exposure to analgesics in late pregnancy was associated with fetal ductal constriction compared with unexposed controls. The association was stronger for metamizole and consistent with a dose-related pattern. Acetaminophen was associated with mild, reversible ductal involvement in a subset of fetuses. Reversibility after drug withdrawal supports a functional, prostagland","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 3","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12948653/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147316140","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}