Zhi-Yu Chen, Wen-Li Xu, Yu-Yang Gao, Wen-Yan Li, Zhen Liu, Jia-Yuan Zhou, Li Dai
Background
The landscape of co-occurring birth defects among infants with congenital diaphragmatic hernia (CDH) remains underexplored.
Aims
This study aims to elucidate the complex patterns of co-occurring defects in Chinese population.
Materials and Methods
We analyzed cases from the Chinese Birth Defects Monitoring Network (2007-2019) with CDH that presented along with at least one additional defect but without a syndromic diagnosis. Adjusted observed-to-expected prevalence (O/E) ratios were calculated for all two- to five-way combinations to discern patterns of co-occurring defects with CDH more frequently than expected by chance.
Results
Among 1235 CDH cases associated with other birth defects, the top 30 combinations with the highest adjusted O/E ratios included musculoskeletal, cardiovascular, central nervous system, facial, and renal defects. Cardiovascular defects were involved in 76.7% of the top combinations, followed by central nervous system (23.3%) and musculoskeletal defects (20.0%). The combination of polydactyly and syndactyly anomalies exhibited the highest adjusted O/E ratio of 5963.37 (95% confidence interval: 5960.00–5966.73).
Discussion
The relationship between musculoskeletal malformation and CDH may be explained from the aspects of epidemiology, embryology and pathogenesis. And mechanisms for the co-occurrence of cardiovascular and CDH may involve disruption of common pathways.
Conclusion
Our analyses describe the co-occurrence patterns of birth defects in CDH infants and reveal several noteworthy patterns. The observed patterns can guide further study and enhance our comprehension understanding of the developmental mechanisms underlying multiple defects.
{"title":"Patterns of Co-Occurring Birth Defects in Chinese Infants With Congenital Diaphragmatic Hernia: A National Hospital-Based Surveillance Study","authors":"Zhi-Yu Chen, Wen-Li Xu, Yu-Yang Gao, Wen-Yan Li, Zhen Liu, Jia-Yuan Zhou, Li Dai","doi":"10.1002/bdr2.2432","DOIUrl":"10.1002/bdr2.2432","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The landscape of co-occurring birth defects among infants with congenital diaphragmatic hernia (CDH) remains underexplored.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study aims to elucidate the complex patterns of co-occurring defects in Chinese population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>We analyzed cases from the Chinese Birth Defects Monitoring Network (2007-2019) with CDH that presented along with at least one additional defect but without a syndromic diagnosis. Adjusted observed-to-expected prevalence (O/E) ratios were calculated for all two- to five-way combinations to discern patterns of co-occurring defects with CDH more frequently than expected by chance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 1235 CDH cases associated with other birth defects, the top 30 combinations with the highest adjusted O/E ratios included musculoskeletal, cardiovascular, central nervous system, facial, and renal defects. Cardiovascular defects were involved in 76.7% of the top combinations, followed by central nervous system (23.3%) and musculoskeletal defects (20.0%). The combination of polydactyly and syndactyly anomalies exhibited the highest adjusted O/E ratio of 5963.37 (95% confidence interval: 5960.00–5966.73).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>The relationship between musculoskeletal malformation and CDH may be explained from the aspects of epidemiology, embryology and pathogenesis. And mechanisms for the co-occurrence of cardiovascular and CDH may involve disruption of common pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our analyses describe the co-occurrence patterns of birth defects in CDH infants and reveal several noteworthy patterns. The observed patterns can guide further study and enhance our comprehension understanding of the developmental mechanisms underlying multiple defects.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 1","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11734095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982679","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}
<div> <section> <h3> Background</h3> <p>Neural tube defects (NTDs) are defined as an incomplete closure of the neural tube (NT), with a prevalence of 1.2 per 1000 live births around the world. Methylation of the maternally imprinted gene Insulin-like growth factor 2 (IGF2) is one of the epigenetic mechanisms that contribute significantly to the development of NTDs. Its important functions are the fetal growth and metabolism, as well as cell division and differentiation.</p> </section> <section> <h3> Objectives</h3> <p>In a couple of studies, individual changes in IGF2 with single nucleotide variants (SNVs) have been found to be linked with NTDs as well as with other diseases. However, there is more need of studying so that we can better understand precisely this mechanism at the molecular level. In this study we tried to investigate the relationship between genetic variants of IGF2 and NT closure by screening all SNVs of IGF2 using both in silico methods and clinical experiments on human samples.</p> </section> <section> <h3> Methods</h3> <p>We enrolled 98 consecutive mothers carrying fetuses with NTDs as cases and 76 age-matched mothers with healthy babies as controls. Following an in silico analysis of the IGF2 gene, we designed three primers targeting a total of 180 exonic, 579 intronic, and 46 variants in the 3′ untranslated region (3′ UTR) for polymerase chain reaction (PCR) and subsequent sequencing. Statistical analyses were performed to assess associations between these genetic variants and NTDs. Additionally, quantitative real-time PCR (qRT-PCR) was conducted to analyze the mRNA expression levels of the target gene.</p> </section> <section> <h3> Results</h3> <p>This is the first study to enlist 11 non-synonymous variants [rs750845881(D93N), rs1290256492(P87H), rs755066389(P87T), rs150610908(G65D), rs762200142(R64C), rs868067982(G49C), rs778465733(R48L), rs1018841144(R48C), rs1057518115(C33R), rs112276039(C22R), rs1240151267(L16W)] in the regulation of IGF2 gene functions through in silico analysis. Further clinical validation in maternal samples showed a significant association between rs3213225 (C > T) (OR-2.076; CI-1.123-3.840; <i>p</i>-0.0209) and rs734351 (C > T) (OR-2.148; CI-1.167-3.956; <i>p</i>-0.0148) with increased disease risk. RNA expression study validated and supported all of these SNVs, indicating a strong correlation with NTD.</p> </section> <section> <h3> Conclusions</h3> <p>Our research strongly suggests that genetic variations in IGF2 may help explain the risk association with NTDs and could be valuable for diagnostic
{"title":"Novel Variants of IGF2 Gene Are Linked With Neural Tube Defects-An In Silico to Clinical Approach in West Bengal, India","authors":"Nirvika Paul, Susanta Sadhukhan, Srilagna Chatterjee, Anwesha Das, Dinesh Munian, Kausik Ganguly, Biswabandhu Bankura, Krishnendu Ghosh, Sudakshina Ghosh, Madhusudan Das","doi":"10.1002/bdr2.2428","DOIUrl":"https://doi.org/10.1002/bdr2.2428","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Neural tube defects (NTDs) are defined as an incomplete closure of the neural tube (NT), with a prevalence of 1.2 per 1000 live births around the world. Methylation of the maternally imprinted gene Insulin-like growth factor 2 (IGF2) is one of the epigenetic mechanisms that contribute significantly to the development of NTDs. Its important functions are the fetal growth and metabolism, as well as cell division and differentiation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>In a couple of studies, individual changes in IGF2 with single nucleotide variants (SNVs) have been found to be linked with NTDs as well as with other diseases. However, there is more need of studying so that we can better understand precisely this mechanism at the molecular level. In this study we tried to investigate the relationship between genetic variants of IGF2 and NT closure by screening all SNVs of IGF2 using both in silico methods and clinical experiments on human samples.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We enrolled 98 consecutive mothers carrying fetuses with NTDs as cases and 76 age-matched mothers with healthy babies as controls. Following an in silico analysis of the IGF2 gene, we designed three primers targeting a total of 180 exonic, 579 intronic, and 46 variants in the 3′ untranslated region (3′ UTR) for polymerase chain reaction (PCR) and subsequent sequencing. Statistical analyses were performed to assess associations between these genetic variants and NTDs. Additionally, quantitative real-time PCR (qRT-PCR) was conducted to analyze the mRNA expression levels of the target gene.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This is the first study to enlist 11 non-synonymous variants [rs750845881(D93N), rs1290256492(P87H), rs755066389(P87T), rs150610908(G65D), rs762200142(R64C), rs868067982(G49C), rs778465733(R48L), rs1018841144(R48C), rs1057518115(C33R), rs112276039(C22R), rs1240151267(L16W)] in the regulation of IGF2 gene functions through in silico analysis. Further clinical validation in maternal samples showed a significant association between rs3213225 (C > T) (OR-2.076; CI-1.123-3.840; <i>p</i>-0.0209) and rs734351 (C > T) (OR-2.148; CI-1.167-3.956; <i>p</i>-0.0148) with increased disease risk. RNA expression study validated and supported all of these SNVs, indicating a strong correlation with NTD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our research strongly suggests that genetic variations in IGF2 may help explain the risk association with NTDs and could be valuable for diagnostic","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 1","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143112456","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}
Michael G. Narotsky, Leslie S. Fuentes, Oluwabusola Ola, TaCriasha L. Willoughby, Katherine Lucas
Background
Epidemiological studies report associations of drinking water disinfection byproducts (DBPs) with adverse health outcomes, including birth defects. Here, we used a rat model susceptible to pregnancy loss (full-litter resorption; FLR) and eye malformations (anophthalmia, microphthalmia) to test 11 DBPs, including trihalomethanes, haloacetic acids (HAAs), and nitrogen-containing DBPs (N-DBPs).
Methods
Timed-pregnant F344 rats received gavage doses of chloroform, chlorodibromomethane, iodoform, chloroacetic acid, bromoacetic acid, dibromoacetic acid (DBA), diiodoacetic acid (DIA), trichloroacetic acid (TCA), dibromonitromethane, and iodoacetonitrile on gestation days (GD) 6–10. Bromonitromethane and TCA were administered via drinking water on GD 6–11. Litters were examined on postnatal days 1 and 6.
Results
All trihalomethanes tested caused FLR. The di- and tri-halogenated HAAs, but not the mono-HAAs, caused eye malformations. N-DBPs caused neither effect at the dosages tested. TCA by gavage caused both FLR and eye defects, whereas drinking water exposure only caused eye defects. Potency rankings for causing FLR were chloroform ≥ iodoform > chlorodibromomethane and the rankings for causing eye defects were DIA > TCA = DBA.
Conclusion
We confirmed that trihalomethanes caused pregnancy loss and that di- and tri-HAAs were teratogenic. The N-DBPs induced neither effect. Potency rankings were inconsistent with rankings seen in vitro.
{"title":"Developmental Toxicity of Disinfection Byproducts in F344 Rats: Effects on Pregnancy Maintenance and Eye Development","authors":"Michael G. Narotsky, Leslie S. Fuentes, Oluwabusola Ola, TaCriasha L. Willoughby, Katherine Lucas","doi":"10.1002/bdr2.2427","DOIUrl":"https://doi.org/10.1002/bdr2.2427","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Epidemiological studies report associations of drinking water disinfection byproducts (DBPs) with adverse health outcomes, including birth defects. Here, we used a rat model susceptible to pregnancy loss (full-litter resorption; FLR) and eye malformations (anophthalmia, microphthalmia) to test 11 DBPs, including trihalomethanes, haloacetic acids (HAAs), and nitrogen-containing DBPs (N-DBPs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Timed-pregnant F344 rats received gavage doses of chloroform, chlorodibromomethane, iodoform, chloroacetic acid, bromoacetic acid, dibromoacetic acid (DBA), diiodoacetic acid (DIA), trichloroacetic acid (TCA), dibromonitromethane, and iodoacetonitrile on gestation days (GD) 6–10. Bromonitromethane and TCA were administered via drinking water on GD 6–11. Litters were examined on postnatal days 1 and 6.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>All trihalomethanes tested caused FLR. The di- and tri-halogenated HAAs, but not the mono-HAAs, caused eye malformations. N-DBPs caused neither effect at the dosages tested. TCA by gavage caused both FLR and eye defects, whereas drinking water exposure only caused eye defects. Potency rankings for causing FLR were chloroform ≥ iodoform > chlorodibromomethane and the rankings for causing eye defects were DIA > TCA = DBA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We confirmed that trihalomethanes caused pregnancy loss and that di- and tri-HAAs were teratogenic. The N-DBPs induced neither effect. Potency rankings were inconsistent with rankings seen in vitro.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 1","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143112454","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}
Given the increased concerns over reproducibility, replicability, and reliability of scientific studies, the embryo-fetal developmental toxicity (EFDT) study was examined from this perspective together with the classic 3Rs. These 6Rs contribute to external validity (i.e., applicability to human safety). Species differences and experimental conditions lower the validity of all preclinical studies to variable extents. The apparent lack/paucity of demonstrated replicate EFDT studies lowers reliability and thus validity. I make suggestions intended to add reliability for the continued use of these studies, which are a cornerstone for assessing safety during human pregnancies. Experienced readers will recognize that the suggestions would also apply to other guideline-mandated developmental and reproductive toxicity and toxicity studies.
{"title":"The 6Rs of EFDT Studies","authors":"L. David Wise","doi":"10.1002/bdr2.2429","DOIUrl":"10.1002/bdr2.2429","url":null,"abstract":"<div>\u0000 \u0000 <p>Given the increased concerns over reproducibility, replicability, and reliability of scientific studies, the embryo-fetal developmental toxicity (EFDT) study was examined from this perspective together with the classic 3Rs. These 6Rs contribute to external validity (i.e., applicability to human safety). Species differences and experimental conditions lower the validity of all preclinical studies to variable extents. The apparent lack/paucity of demonstrated replicate EFDT studies lowers reliability and thus validity. I make suggestions intended to add reliability for the continued use of these studies, which are a cornerstone for assessing safety during human pregnancies. Experienced readers will recognize that the suggestions would also apply to other guideline-mandated developmental and reproductive toxicity and toxicity studies.</p>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 1","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909005","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}
Agnathia-otocephaly complex (AOC) is a rare and complex craniofacial malformation characterized by mandibular hypoplasia or agnathia, auricular fusion, microstomia with oroglossal hypoplasia or aglossia. It has a very bad prognosis and can arise alone or in conjunction with heart defects and forebrain abnormalities.
Case Report
A standard second-trimester ultrasound exam was recommended for, a 23-year-old primigravida woman who was at 22 weeks gestation. The oral fissure was “pinhole-shaped,” the mouth was incredibly small, and the usual lower jaw and lower lip had vanished from the S-curve. On the front of the neck were the two ears. Amniocentesis revealed a 46,XY normal karyotype. The family opted for a medically assisted termination. At 23 weeks, the pregnancy was ended by vaginal delivery. Observation of the specimen revealed that the ear placements were remarkably low, and the specimen's observation revealed that the two earlobes were joined at the front of the neck.
Conclusion
Identifying the development of the mandible and locating auricles during prenatal ultrasound diagnosis was particularly challenging could be a better way to phrase this like in our recent example, the combination of two-dimensional and three-dimensional ultrasound was able to confirm the prenatal diagnosis of AOC.
{"title":"Otocephaly Diagnosed Prenatally: A Case Study of a Rare Congenital Defect","authors":"Birsen Konukcu","doi":"10.1002/bdr2.2421","DOIUrl":"10.1002/bdr2.2421","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Agnathia-otocephaly complex (AOC) is a rare and complex craniofacial malformation characterized by mandibular hypoplasia or agnathia, auricular fusion, microstomia with oroglossal hypoplasia or aglossia. It has a very bad prognosis and can arise alone or in conjunction with heart defects and forebrain abnormalities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case Report</h3>\u0000 \u0000 <p>A standard second-trimester ultrasound exam was recommended for, a 23-year-old primigravida woman who was at 22 weeks gestation. The oral fissure was “pinhole-shaped,” the mouth was incredibly small, and the usual lower jaw and lower lip had vanished from the S-curve. On the front of the neck were the two ears. Amniocentesis revealed a 46,XY normal karyotype. The family opted for a medically assisted termination. At 23 weeks, the pregnancy was ended by vaginal delivery. Observation of the specimen revealed that the ear placements were remarkably low, and the specimen's observation revealed that the two earlobes were joined at the front of the neck.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Identifying the development of the mandible and locating auricles during prenatal ultrasound diagnosis was particularly challenging could be a better way to phrase this like in our recent example, the combination of two-dimensional and three-dimensional ultrasound was able to confirm the prenatal diagnosis of AOC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"116 12","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852573","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}
Qichang Zhou, Dongmei Liu, Jiawei Zhou, Qiao Guo, Hongxia Yuan, Yinchun Luo, Ling Wang, Chan Yin, Zhongshi Wu, Qinghai Peng, Zhang Ming, Zeng Shi, Xu Ganqiong, Dan Zhou, Yang Yang
Aim
This study investigated the major factors contributing to the missed diagnosis of total anomalous pulmonary venous connection (TAPVC) in fetal echocardiography.
Methods
We retrospectively analyzed the prenatal ultrasonic images of 32 fetuses with missed diagnoses of TAPVC, compared them with autopsy and postnatal surgical records, and summarized the most likely reasons leading to the missed diagnoses.
Results
We studied a total of 157 fetuses with TAPVC, 32 (20.3%) of whom were missed in prenatal echocardiography. The main factors for the missed diagnoses of TAPVC in the 32 fetuses were anatomic variants leading to the formation of a false pulmonary venous horn-like structure, the combination of TAPVC with other intracardiac anomalies, difficulty or inability to show the course and abouchement of TAPVC on conventional color Doppler flow imaging (CDFI), and excessive color flow gain, with a rate of approximately 53.1% (17/32). A decreased left atrial size and augmentation of the PLAS index may be indicators of false pulmonary venous horn-like structure.
Conclusion
False pulmonary venous horn-like structures due to anatomic variants are a major factor in the missed diagnosis of fetal TAPVC. The presence of pulmonary venous horn-like structure in a four-chamber view does not completely exclude TAPVC.
{"title":"Factor Analysis of the Missed Diagnosis of Total Anomalous Pulmonary Venous Connection in Prenatal Echocardiography","authors":"Qichang Zhou, Dongmei Liu, Jiawei Zhou, Qiao Guo, Hongxia Yuan, Yinchun Luo, Ling Wang, Chan Yin, Zhongshi Wu, Qinghai Peng, Zhang Ming, Zeng Shi, Xu Ganqiong, Dan Zhou, Yang Yang","doi":"10.1002/bdr2.2426","DOIUrl":"10.1002/bdr2.2426","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>This study investigated the major factors contributing to the missed diagnosis of total anomalous pulmonary venous connection (TAPVC) in fetal echocardiography.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrospectively analyzed the prenatal ultrasonic images of 32 fetuses with missed diagnoses of TAPVC, compared them with autopsy and postnatal surgical records, and summarized the most likely reasons leading to the missed diagnoses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We studied a total of 157 fetuses with TAPVC, 32 (20.3%) of whom were missed in prenatal echocardiography. The main factors for the missed diagnoses of TAPVC in the 32 fetuses were anatomic variants leading to the formation of a false pulmonary venous horn-like structure, the combination of TAPVC with other intracardiac anomalies, difficulty or inability to show the course and abouchement of TAPVC on conventional color Doppler flow imaging (CDFI), and excessive color flow gain, with a rate of approximately 53.1% (17/32). A decreased left atrial size and augmentation of the PLAS index may be indicators of false pulmonary venous horn-like structure.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>False pulmonary venous horn-like structures due to anatomic variants are a major factor in the missed diagnosis of fetal TAPVC. The presence of pulmonary venous horn-like structure in a four-chamber view does not completely exclude TAPVC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"116 12","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845986","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}
Marlissa A. Campbell, Shannon R. Murphy, Susan A. Klasing, Yassaman Niknam, Poorni Iyer, Beckye Stanton, Lauren Zeise
Background
Current US federal action levels for domoic acid (DA) in seafood are based on acute toxicity observed in exposed adult humans. Life course considerations have not been incorporated. The potential for developmental neurotoxicity (DNT) at permissible DA levels has previously been noted, but not methodically assessed.
Methods
Studies of DNT following DA exposure in experimental and wild animals were identified through a comprehensive search strategy. Evidence from papers meeting inclusion criteria was evaluated for specific outcomes reported for doses at which adverse effects were observed. Exposure levels associated with DNT were compared with those known to cause adult toxicity. The findings are discussed in the context of the well-characterized mechanism of DA neurotoxicity, as well as the toxicokinetics of DA across species and life stages.
Conclusions
DNT outcomes were reported with a no observed adverse effect level (NOAEL) 10 times lower than the NOAEL of 0.75 mg DA/kg for acute effects in adults. Apart from reviewing current regulatory action levels, public health outreach messaging to health care professionals and sensitive populations, such as pregnant or breastfeeding women, should be considered as a means of increasing awareness about risk for DNT from consumption of potentially DA-contaminated seafood.
{"title":"Life Course Considerations in Environmental Health: Developmental Neurotoxicity of Domoic Acid at Doses Below Acute Effect Levels in Adult Humans","authors":"Marlissa A. Campbell, Shannon R. Murphy, Susan A. Klasing, Yassaman Niknam, Poorni Iyer, Beckye Stanton, Lauren Zeise","doi":"10.1002/bdr2.2419","DOIUrl":"10.1002/bdr2.2419","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Current US federal action levels for domoic acid (DA) in seafood are based on acute toxicity observed in exposed adult humans. Life course considerations have not been incorporated. The potential for developmental neurotoxicity (DNT) at permissible DA levels has previously been noted, but not methodically assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Studies of DNT following DA exposure in experimental and wild animals were identified through a comprehensive search strategy. Evidence from papers meeting inclusion criteria was evaluated for specific outcomes reported for doses at which adverse effects were observed. Exposure levels associated with DNT were compared with those known to cause adult toxicity. The findings are discussed in the context of the well-characterized mechanism of DA neurotoxicity, as well as the toxicokinetics of DA across species and life stages.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>DNT outcomes were reported with a no observed adverse effect level (NOAEL) 10 times lower than the NOAEL of 0.75 mg DA/kg for acute effects in adults. Apart from reviewing current regulatory action levels, public health outreach messaging to health care professionals and sensitive populations, such as pregnant or breastfeeding women, should be considered as a means of increasing awareness about risk for DNT from consumption of potentially DA-contaminated seafood.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"116 12","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11639046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817039","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}
Amin Moqadami, Mohammad Khalaj-Kondori, Mehdi Haghi
Background and Objective(s)
Human leukocyte antigen-G (HLA-G) is a critical protein in immune regulation and tolerance. Recurrent spontaneous abortion (RSA) is a complex disease influenced by genetic, immune dysfunction, and environmental factors. This study investigates the role of HLA-G polymorphisms in the development of RSA.
Methods
Blood samples were collected from 80 women with RSA and 200 women without a history of RSA. After DNA extraction, PCR was used to sequence the 3′-UTR region. Allelic and genotypic frequencies were analyzed, and Haploview software was used for haplotype analysis.
Results
Individual polymorphisms did not significantly differ between the two groups. However, haplotype analysis revealed significant differences. The UTR-2 haplotype was more frequent in the RSA group compared to the healthy control group (p = 0.020), suggesting a potential association. Conversely, the UTR-4 haplotype had a significantly lower frequency in the RSA group (p = 0.041), indicating a protective role against RSA.
Conclusions
While individual polymorphisms did not differ significantly, haplotype analysis identified significant associations with RSA. These findings provide valuable insights into the genetic basis of the disease and may contribute to the development of new treatments and diagnostic tools.
背景和目的：人白细胞抗原- g （HLA-G）是免疫调节和耐受的关键蛋白。复发性自然流产（RSA）是一种受遗传、免疫功能障碍和环境因素影响的复杂疾病。本研究探讨HLA-G多态性在RSA发展中的作用。方法：采集80例RSA女性和200例无RSA病史女性的血液样本。提取DNA后，采用PCR对3’-UTR区进行测序。分析等位基因和基因型频率，采用Haploview软件进行单倍型分析。结果：两组间个体多态性无显著差异。然而，单倍型分析显示了显著差异。与健康对照组相比，RSA组的UTR-2单倍型更常见（p = 0.020），提示可能存在关联。相反，UTR-4单倍型在RSA组中出现的频率明显较低（p = 0.041），表明其对RSA具有保护作用。结论：虽然个体多态性没有显著差异，但单倍型分析确定了与RSA的显著关联。这些发现为了解该病的遗传基础提供了有价值的见解，并可能有助于开发新的治疗方法和诊断工具。
{"title":"Association of HLA-G 3′-UTR Haplotypes With Recurrent Spontaneous Abortion in Women From Northwest Iran","authors":"Amin Moqadami, Mohammad Khalaj-Kondori, Mehdi Haghi","doi":"10.1002/bdr2.2418","DOIUrl":"10.1002/bdr2.2418","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Objective(s)</h3>\u0000 \u0000 <p>Human leukocyte antigen-G (HLA-G) is a critical protein in immune regulation and tolerance. Recurrent spontaneous abortion (RSA) is a complex disease influenced by genetic, immune dysfunction, and environmental factors. This study investigates the role of HLA-G polymorphisms in the development of RSA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Blood samples were collected from 80 women with RSA and 200 women without a history of RSA. After DNA extraction, PCR was used to sequence the 3′-UTR region. Allelic and genotypic frequencies were analyzed, and Haploview software was used for haplotype analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Individual polymorphisms did not significantly differ between the two groups. However, haplotype analysis revealed significant differences. The UTR-2 haplotype was more frequent in the RSA group compared to the healthy control group (<i>p</i> = 0.020), suggesting a potential association. Conversely, the UTR-4 haplotype had a significantly lower frequency in the RSA group (<i>p</i> = 0.041), indicating a protective role against RSA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>While individual polymorphisms did not differ significantly, haplotype analysis identified significant associations with RSA. These findings provide valuable insights into the genetic basis of the disease and may contribute to the development of new treatments and diagnostic tools.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"116 12","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811877","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}
Janet D. Cragan, Sook-Ja Cho, Nina Forestieri, Michele Hort, Eirini Nestoridi, Cynthia A. Moore, Erin Stallings, Elizabeth B. Gray, Jennita Reefhuis
Background
Reports from China describe an increase in the frequency of fetal situs inversus in 2023 after the country's “zero-Covid” policy was lifted, suggesting an association with maternal SARS-CoV-2 infection. However, a report of birth defects surveillance data from Scandinavia observed no sustained increase during the SARS-CoV-2 pandemic (2020–2022 vs. 2018–2019). We examined birth defects surveillance data to assess any increase in situs inversus in the U.S. during the SARS-CoV-2 pandemic.
Methods
We combined data from four population-based birth defects programs in Massachusetts, Minnesota, North Carolina, and Atlanta, Georgia, to compare the prevalence of situs inversus among infants and fetuses delivered before (2017–2019) and during (2021–2022) the SARS-CoV-2 pandemic. We defined situs inversus as mirror-image transposition of the heart and/or other organs, or primary ciliary dyskinesis with situs inversus, excluding isolated dextrocardia. The programs varied in the pregnancy outcomes included (live births ± non-live births); all included both prenatal and postnatal diagnoses.
Results
We identified 294 infants and fetuses with situs inversus (6.8% non-live births). We estimated the combined prevalence per 10,000 live births as 1.72 during the pandemic versus 1.71 before the pandemic (OR = 1.005; 95% CI: 0.778–1.297). The estimated annual prevalence ranged from 1.41 in 2017 to 2.21 in 2019 with no significant trend across the study period (p = 0.39).
Conclusions
We did not observe an increase in situs inversus during the SARS-CoV-2 pandemic. Because information about SARS-CoV-2 infection among individual pregnancies was not available from all programs, we could not assess a specific association with maternal infection.
{"title":"Observed Prevalence of Congenital Situs Inversus in the United States Before and During the SARS-CoV-2 Pandemic, 2017–2022","authors":"Janet D. Cragan, Sook-Ja Cho, Nina Forestieri, Michele Hort, Eirini Nestoridi, Cynthia A. Moore, Erin Stallings, Elizabeth B. Gray, Jennita Reefhuis","doi":"10.1002/bdr2.2424","DOIUrl":"10.1002/bdr2.2424","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Reports from China describe an increase in the frequency of fetal situs inversus in 2023 after the country's “zero-Covid” policy was lifted, suggesting an association with maternal SARS-CoV-2 infection. However, a report of birth defects surveillance data from Scandinavia observed no sustained increase during the SARS-CoV-2 pandemic (2020–2022 vs. 2018–2019). We examined birth defects surveillance data to assess any increase in situs inversus in the U.S. during the SARS-CoV-2 pandemic.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We combined data from four population-based birth defects programs in Massachusetts, Minnesota, North Carolina, and Atlanta, Georgia, to compare the prevalence of situs inversus among infants and fetuses delivered before (2017–2019) and during (2021–2022) the SARS-CoV-2 pandemic. We defined situs inversus as mirror-image transposition of the heart and/or other organs, or primary ciliary dyskinesis with situs inversus, excluding isolated dextrocardia. The programs varied in the pregnancy outcomes included (live births ± non-live births); all included both prenatal and postnatal diagnoses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified 294 infants and fetuses with situs inversus (6.8% non-live births). We estimated the combined prevalence per 10,000 live births as 1.72 during the pandemic versus 1.71 before the pandemic (OR = 1.005; 95% CI: 0.778–1.297). The estimated annual prevalence ranged from 1.41 in 2017 to 2.21 in 2019 with no significant trend across the study period (<i>p</i> = 0.39).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We did not observe an increase in situs inversus during the SARS-CoV-2 pandemic. Because information about SARS-CoV-2 infection among individual pregnancies was not available from all programs, we could not assess a specific association with maternal infection.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"116 12","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811881","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}
Daria Sosińska, Andrzej Gołębiewski, Piotr Czauderna
Introduction
Sirenomelia is a very rare congenital structural anomaly characterized by abnormal development of the caudal region of the body with varying degrees of fusion of lower limbs. Mostly, the condition is lethal for the baby. Most babies do not survive even after surgery. Fifty percent of cases are seen as stillbirths, and it is much more common in identical twins.
Case Report
We present a case of a boy born in 38th week of gestation (hebdomas graviditatis—HBD) with diagnosed sirenomelia, microcephaly, bilateral renal agenesis, duodenal atresia, imperforate anus, and agenesis of external genitalia. We provide a brief review of the literature and discussion concerning similar cases, determinants, pathogenesis and suspected genetic factors.
Conclusions
Due to accompanying malformations, there is often no treatment for sirenomelia. Avoidance of risk factors, early diagnosis, multidisciplinary approach and psychological preparation of parents to help them cope emotionally and mentally with the challenges, seem to be the key factors of management. It is very important to diagnose this condition by ultrasonography prenatally so that termination of pregnancy can be carried out.
{"title":"Sirenomelia—Challenges and Treatment Approach in a Rare Case","authors":"Daria Sosińska, Andrzej Gołębiewski, Piotr Czauderna","doi":"10.1002/bdr2.2425","DOIUrl":"10.1002/bdr2.2425","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Sirenomelia is a very rare congenital structural anomaly characterized by abnormal development of the caudal region of the body with varying degrees of fusion of lower limbs. Mostly, the condition is lethal for the baby. Most babies do not survive even after surgery. Fifty percent of cases are seen as stillbirths, and it is much more common in identical twins.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case Report</h3>\u0000 \u0000 <p>We present a case of a boy born in 38th week of gestation (hebdomas graviditatis—HBD) with diagnosed sirenomelia, microcephaly, bilateral renal agenesis, duodenal atresia, imperforate anus, and agenesis of external genitalia. We provide a brief review of the literature and discussion concerning similar cases, determinants, pathogenesis and suspected genetic factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Due to accompanying malformations, there is often no treatment for sirenomelia. Avoidance of risk factors, early diagnosis, multidisciplinary approach and psychological preparation of parents to help them cope emotionally and mentally with the challenges, seem to be the key factors of management. It is very important to diagnose this condition by ultrasonography prenatally so that termination of pregnancy can be carried out.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"116 12","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811883","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号