Pierre-Louis Forey, Maud Favier, Claire Beneteau, Sophie Berenguer, Lydie Da Costa, Virginie Guigue, Philippe Loget, Julia Torrents, Laura Samaison, Didier Riethmuller, Sophie Collardeau-Frachon
Introduction: Acute fetal leukemia is rare and characterized by a very poor prognosis. The aims of this study were to identify cases of acute fetal leukemia and to describe ultrasound and fetopathological findings that should lead to a suspicion of this diagnosis, as well as the investigations required to confirm it.
Methods: A national retrospective study was conducted. Clinical data, prenatal ultrasounds and postmortem findings of fetal acute leukemia cases were collected and analyzed.
Results: We collected seven cases: four in utero fetal deaths, two neonatal deaths and one termination of pregnancy. Prenatal ultrasounds showed fetal hydrops (42.9%) associated with hepatosplenomegaly (100%). In addition, post-mortem examination (n = 6) suggested a Down syndrome in one case and showed other organomegaly (83.3%) due to blastic infiltration, mainly in the liver, along with extrahepatic multivisceral hematopoiesis. Immunostainings allowed to specify the type of leukemia (71.4%). In one case, diagnosis was made on blood smear and flow cytometry was performed on fresh blood samples. All cases corresponded to acute myeloid leukemia. Karyotype was abnormal in 4 cases (66.7%), including one free trisomy 21, two mosaic trisomy 21 and one chromosome 15 deletion. GATA1 gene mutations were identified in two cases: one mosaic trisomy 21 and one with normal karyotype.
Conclusion: Any hepatosplenomegaly associated with fetal hydrops and a negative immune, infectious, and metabolic work-up, should suggest acute fetal leukemia and prompt additional investigations.
{"title":"Acute fetal leukemia: When should it be suspected? What assessment should be performed? A case series and review of literature.","authors":"Pierre-Louis Forey, Maud Favier, Claire Beneteau, Sophie Berenguer, Lydie Da Costa, Virginie Guigue, Philippe Loget, Julia Torrents, Laura Samaison, Didier Riethmuller, Sophie Collardeau-Frachon","doi":"10.1002/pd.6630","DOIUrl":"https://doi.org/10.1002/pd.6630","url":null,"abstract":"<p><strong>Introduction: </strong>Acute fetal leukemia is rare and characterized by a very poor prognosis. The aims of this study were to identify cases of acute fetal leukemia and to describe ultrasound and fetopathological findings that should lead to a suspicion of this diagnosis, as well as the investigations required to confirm it.</p><p><strong>Methods: </strong>A national retrospective study was conducted. Clinical data, prenatal ultrasounds and postmortem findings of fetal acute leukemia cases were collected and analyzed.</p><p><strong>Results: </strong>We collected seven cases: four in utero fetal deaths, two neonatal deaths and one termination of pregnancy. Prenatal ultrasounds showed fetal hydrops (42.9%) associated with hepatosplenomegaly (100%). In addition, post-mortem examination (n = 6) suggested a Down syndrome in one case and showed other organomegaly (83.3%) due to blastic infiltration, mainly in the liver, along with extrahepatic multivisceral hematopoiesis. Immunostainings allowed to specify the type of leukemia (71.4%). In one case, diagnosis was made on blood smear and flow cytometry was performed on fresh blood samples. All cases corresponded to acute myeloid leukemia. Karyotype was abnormal in 4 cases (66.7%), including one free trisomy 21, two mosaic trisomy 21 and one chromosome 15 deletion. GATA1 gene mutations were identified in two cases: one mosaic trisomy 21 and one with normal karyotype.</p><p><strong>Conclusion: </strong>Any hepatosplenomegaly associated with fetal hydrops and a negative immune, infectious, and metabolic work-up, should suggest acute fetal leukemia and prompt additional investigations.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141458823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: We aimed to investigate the yield of prenatal exome sequencing (pES) in morphologically normal fetuses.
Method: This retrospective study analyzed 254 families with morphologically normal fetuses who underwent prenatal trio exome sequencing based on parental request between September 2020 and October 2023.
Results: Overall, abnormal findings were detected in 8 families (3.1%, 8/254) by pES. Among these, 6 families (2.3%, 6/254) were found to have fetuses affected with monogenic disorders (2 autosomal recessive conditions and 4 autosomal dominant conditions), while 2 families (0.8%, 2/254) were incidentally found to be couples at risk of having a future pregnancy with a recessive condition. Among the six fetuses detected with monogenic disorders, two fetuses carried a de novo variant in OPA1 and NF1, which are known to cause Optic atrophy 1 and Neurofibromatosis, respectively. One fetus was detected with a maternally inherited variant in PKD2 related to polycystic kidney disease 2 (not known to the mother until then). One fetus was detected with a maternally inherited variant in SDHB associated with Pheochromocytoma. Two fetuses carried compound heterozygous variants in NAGLU and GJB2 associated with Mucopolysaccharidosis type IIIB and Deafness, respectively. In the 2 families where parents were found to be carriers but the fetuses were unaffected, heterozygous variants in the GJB2 and SERPINB7 genes were detected in the parents, respectively, which are associated with deafness and palmoplantar keratoderma.
Conclusion: Our research indicated that pES can provide significant critical information for families with morphologically normal fetuses. Prenatal screening with exome sequencing requires careful management and detailed pre-test and post-test genetic counseling.
{"title":"Prenatal exome sequencing for morphologically normal fetus: Should we be doing it?","authors":"Zhi Gao, Xiaofan Zhu, Huanan Ren, Yanfei Wang, Chunxiao Hua, Xiangdong Kong","doi":"10.1002/pd.6624","DOIUrl":"https://doi.org/10.1002/pd.6624","url":null,"abstract":"<p><strong>Objective: </strong>We aimed to investigate the yield of prenatal exome sequencing (pES) in morphologically normal fetuses.</p><p><strong>Method: </strong>This retrospective study analyzed 254 families with morphologically normal fetuses who underwent prenatal trio exome sequencing based on parental request between September 2020 and October 2023.</p><p><strong>Results: </strong>Overall, abnormal findings were detected in 8 families (3.1%, 8/254) by pES. Among these, 6 families (2.3%, 6/254) were found to have fetuses affected with monogenic disorders (2 autosomal recessive conditions and 4 autosomal dominant conditions), while 2 families (0.8%, 2/254) were incidentally found to be couples at risk of having a future pregnancy with a recessive condition. Among the six fetuses detected with monogenic disorders, two fetuses carried a de novo variant in OPA1 and NF1, which are known to cause Optic atrophy 1 and Neurofibromatosis, respectively. One fetus was detected with a maternally inherited variant in PKD2 related to polycystic kidney disease 2 (not known to the mother until then). One fetus was detected with a maternally inherited variant in SDHB associated with Pheochromocytoma. Two fetuses carried compound heterozygous variants in NAGLU and GJB2 associated with Mucopolysaccharidosis type IIIB and Deafness, respectively. In the 2 families where parents were found to be carriers but the fetuses were unaffected, heterozygous variants in the GJB2 and SERPINB7 genes were detected in the parents, respectively, which are associated with deafness and palmoplantar keratoderma.</p><p><strong>Conclusion: </strong>Our research indicated that pES can provide significant critical information for families with morphologically normal fetuses. Prenatal screening with exome sequencing requires careful management and detailed pre-test and post-test genetic counseling.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141306685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yada Kunpalin, Elka Miller, Kamini Raghuram, Patrick Shannon, Yael Fisher, Vann Chau, Ants Toi, David Chitayat, Susan Blaser, Shiri Shinar
Objective: To describe the association between prenatal imaging and neurodevelopmental outcomes of fetuses with rhombencephalosynapsis (RES).
Study design: Thirty-four pregnancies complicated by RES were identified from our institutional databases based on US and/or MRI findings. Genetic testing results were gathered. In cases of termination of pregnancy, we studied the association between prenatal imaging and neuropathologic findings. For those who opted for expectant management, comprehensive developmental assessments and postnatal MRI imaging were evaluated.
Results: Over one third of fetuses in our cohort had complete RES. Common intracranial anomalies identified were mesencephalosynapsis, aqueduct stenosis and diencephalosynapsis. The degree of RES was not associated with the frequency of additional central nervous system anomalies. MRI had a good correlation with neuropathologic findings with regard to the degree of RES, aqueduct stenosis and mesencephalosynapsis. Postmortem autopsy showed that one third of our cases had VACTERL-H and almost all of those had complete RES. All liveborn neonates(n = 6) had aqueduct stenosis requiring ventriculoperitoneal shunting within days of delivery (median 5 days). While a large proportion of prenatally suspected complete RES were found to have partial RES on postnatal imaging, prenatal diagnosis of aqueduct stenosis remained unchanged. All children that were at least 2 years old (n = 3) had global developmental delay.
Conclusion: Prenatal assessment of the RES severity is challenging and may be unreliable. Nevertheless, postnatal prognosis is poor for both complete and partial RES. Associated aqueductal stenosis, can be reliably assessed prenatally and this may contribute to worse postnatal prognosis than the degree of RES.
目的:描述菱脑综合征(RES)胎儿产前成像与神经发育结局之间的关联:研究设计:研究设计:根据 US 和/或 MRI 检查结果,从本机构数据库中确定了 34 例 RES 并发症妊娠。收集了基因检测结果。在终止妊娠的病例中,我们研究了产前成像与神经病理学结果之间的关联。对于那些选择期待管理的胎儿,我们对其综合发育评估和产后核磁共振成像进行了评估:结果:在我们的队列中,超过三分之一的胎儿有完整的RES。常见的颅内畸形包括中脑鞘膜积液、导水管狭窄和双脑鞘膜积液。RES的程度与其他中枢神经系统异常的频率无关。在RES、导水管狭窄和间脑发育不全的程度上,核磁共振成像与神经病理学结果有很好的相关性。尸检结果显示,三分之一的病例患有 VACTERL-H,几乎所有病例都患有完全性 RES。所有活产新生儿(n = 6)都有导水管狭窄,需要在产后几天内(中位数为 5 天)进行脑室腹腔分流。虽然很大一部分产前怀疑为完全RES的新生儿在出生后的造影检查中发现为部分RES,但产前对导水管狭窄的诊断没有变化。所有至少两岁的患儿(n = 3)均有全面发育迟缓:结论:对RES严重程度的产前评估具有挑战性,而且可能不可靠。尽管如此,完全性和部分性 RES 的产后预后都很差。相关的导水管狭窄可以在产前得到可靠的评估,这可能比RES的程度更不利于产后预后。
{"title":"Associations and outcomes of prenatally detected rhombencephalosynapsis.","authors":"Yada Kunpalin, Elka Miller, Kamini Raghuram, Patrick Shannon, Yael Fisher, Vann Chau, Ants Toi, David Chitayat, Susan Blaser, Shiri Shinar","doi":"10.1002/pd.6620","DOIUrl":"10.1002/pd.6620","url":null,"abstract":"<p><strong>Objective: </strong>To describe the association between prenatal imaging and neurodevelopmental outcomes of fetuses with rhombencephalosynapsis (RES).</p><p><strong>Study design: </strong>Thirty-four pregnancies complicated by RES were identified from our institutional databases based on US and/or MRI findings. Genetic testing results were gathered. In cases of termination of pregnancy, we studied the association between prenatal imaging and neuropathologic findings. For those who opted for expectant management, comprehensive developmental assessments and postnatal MRI imaging were evaluated.</p><p><strong>Results: </strong>Over one third of fetuses in our cohort had complete RES. Common intracranial anomalies identified were mesencephalosynapsis, aqueduct stenosis and diencephalosynapsis. The degree of RES was not associated with the frequency of additional central nervous system anomalies. MRI had a good correlation with neuropathologic findings with regard to the degree of RES, aqueduct stenosis and mesencephalosynapsis. Postmortem autopsy showed that one third of our cases had VACTERL-H and almost all of those had complete RES. All liveborn neonates(n = 6) had aqueduct stenosis requiring ventriculoperitoneal shunting within days of delivery (median 5 days). While a large proportion of prenatally suspected complete RES were found to have partial RES on postnatal imaging, prenatal diagnosis of aqueduct stenosis remained unchanged. All children that were at least 2 years old (n = 3) had global developmental delay.</p><p><strong>Conclusion: </strong>Prenatal assessment of the RES severity is challenging and may be unreliable. Nevertheless, postnatal prognosis is poor for both complete and partial RES. Associated aqueductal stenosis, can be reliably assessed prenatally and this may contribute to worse postnatal prognosis than the degree of RES.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141262651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01Epub Date: 2024-05-29DOI: 10.1002/pd.6612
Henriette Kühle, Steven K S Cho, Alex J Charest-Pekeski, Jessica S M Chow, Fu-Tsuen Lee, Tanroop Aujla, Brahmdeep S Saini, Jessie Mei Lim, Jack R T Darby, Dariusz Mroczek, Alejandro A Floh, Mark J McVey, Janna L Morrison, Mike Seed, Liqun Sun, Christoph Haller
Objectives: We evaluated fetal cardiovascular physiology and mode of cardiac failure in premature miniature piglets on a pumped artificial placenta (AP) circuit.
Methods: Fetal pigs were cannulated via the umbilical vessels and transitioned to an AP circuit composed of a centrifugal pump and neonatal oxygenator and maintained in a fluid-filled biobag. Echocardiographic studies were conducted to measure ventricular function, umbilical blood flow, and fluid status. In utero scans were used as control data.
Results: AP fetuses (n = 13; 102±4d gestational age [term 115d]; 616 ± 139 g [g]; survival 46.4 ± 46.8 h) were tachycardic and hypertensive with initially supraphysiologic circuit flows. Increased myocardial wall thickness was observed. Signs of fetal hydrops were present in all piglets. Global longitudinal strain (GLS) measurements increased in the left ventricle (LV) after transition to the circuit. Right ventricle (RV) and LV strain rate decreased early during AP support compared with in utero measurements but recovered toward the end of the experiment. Fetuses supported for >24 h had similar RV GLS to in utero controls and significantly higher GLS compared to piglets surviving only up to 24 h.
Conclusions: Fetuses on a pump-supported AP circuit experienced an increase in afterload, and redistribution of blood flow between the AP and systemic circulations, associated with elevated end-diastolic filling pressures. This resulted in heart failure and hydrops. These preterm fetuses were unable to tolerate the hemodynamic changes associated with connection to the current AP circuit. To better mimic the physiology of the native placenta and preserve normal fetal cardiovascular physiology, further optimization of the circuit will be required.
目的我们评估了早产微型猪在人工胎盘(AP)回路中的胎儿心血管生理学和心脏衰竭模式:方法:通过脐带血管为胎儿插管,将其过渡到由离心泵和新生儿氧合器组成的人工胎盘回路,并将其保存在充满液体的生物袋中。进行超声心动图检查以测量心室功能、脐血流量和体液状态。宫内扫描结果作为对照数据:AP胎儿(n = 13;胎龄102±4d [足月115d];体重616±139 g[g];存活46.4±46.8 h)心动过速、高血压,最初血流超生理水平。观察到心肌壁厚度增加。所有仔猪都有胎儿水肿的迹象。过渡到回路后,左心室的整体纵向应变(GLS)测量值增加。与子宫内测量结果相比,右心室(RV)和左心室应变率在AP支持期间早期下降,但在实验结束时恢复。支持时间超过24小时的胎儿的RV GLS与子宫内对照组相似,而与仅存活24小时的仔猪相比,GLS明显更高:结论:使用泵支持 AP 循环的胎儿后负荷增加,AP 和全身循环之间的血流重新分配,这与舒张末期充盈压升高有关。这导致了心力衰竭和肾积水。这些早产儿无法承受与当前 AP 回路连接相关的血流动力学变化。为了更好地模拟原生胎盘的生理结构并保护胎儿正常的心血管生理结构,需要进一步优化该回路。
{"title":"Echocardiographic assessment of cardiovascular physiology of preterm miniature piglets supported with a pumped artificial placenta system.","authors":"Henriette Kühle, Steven K S Cho, Alex J Charest-Pekeski, Jessica S M Chow, Fu-Tsuen Lee, Tanroop Aujla, Brahmdeep S Saini, Jessie Mei Lim, Jack R T Darby, Dariusz Mroczek, Alejandro A Floh, Mark J McVey, Janna L Morrison, Mike Seed, Liqun Sun, Christoph Haller","doi":"10.1002/pd.6612","DOIUrl":"10.1002/pd.6612","url":null,"abstract":"<p><strong>Objectives: </strong>We evaluated fetal cardiovascular physiology and mode of cardiac failure in premature miniature piglets on a pumped artificial placenta (AP) circuit.</p><p><strong>Methods: </strong>Fetal pigs were cannulated via the umbilical vessels and transitioned to an AP circuit composed of a centrifugal pump and neonatal oxygenator and maintained in a fluid-filled biobag. Echocardiographic studies were conducted to measure ventricular function, umbilical blood flow, and fluid status. In utero scans were used as control data.</p><p><strong>Results: </strong>AP fetuses (n = 13; 102±4d gestational age [term 115d]; 616 ± 139 g [g]; survival 46.4 ± 46.8 h) were tachycardic and hypertensive with initially supraphysiologic circuit flows. Increased myocardial wall thickness was observed. Signs of fetal hydrops were present in all piglets. Global longitudinal strain (GLS) measurements increased in the left ventricle (LV) after transition to the circuit. Right ventricle (RV) and LV strain rate decreased early during AP support compared with in utero measurements but recovered toward the end of the experiment. Fetuses supported for >24 h had similar RV GLS to in utero controls and significantly higher GLS compared to piglets surviving only up to 24 h.</p><p><strong>Conclusions: </strong>Fetuses on a pump-supported AP circuit experienced an increase in afterload, and redistribution of blood flow between the AP and systemic circulations, associated with elevated end-diastolic filling pressures. This resulted in heart failure and hydrops. These preterm fetuses were unable to tolerate the hemodynamic changes associated with connection to the current AP circuit. To better mimic the physiology of the native placenta and preserve normal fetal cardiovascular physiology, further optimization of the circuit will be required.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141161478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01Epub Date: 2024-05-26DOI: 10.1002/pd.6611
Adeline Walter, Ulrike Herberg, Elina Calite, Annegret Geipel, Florian Recker, Brigitte Strizek, Christoph Berg, Ulrich Gembruch
Objective: In our center, we observed an increased frequency of right aortic arch (RAA) with an agenesis of the ductus arteriosus (ADA) in prenatally diagnosed tetralogy of Fallot (ToF) and its variations. This study aimed to determine whether there is an association of RAA and ADA in fetuses with ToF. Distribution of genetic anomalies and impact on postnatal outcome were further evaluated.
Method: Single-center retrospective observational study including pregnancies with prenatal diagnosis of ToF from 2010 to 2023. All cases were subdivided into ToF with pulmonary stenosis (PS) and pulmonary atresia (PA). Clinical and echocardiographic databases were reviewed for pregnancy outcome, genetic anomalies, and postnatal course.
Results: The cohort included 169 cases, 124 (73.4%) with ToF/PS and 45(26.6%) with ToF/PA. Agenesis of the ductus arteriosus was significantly associated with RAA in both subtypes of ToF (p = 0.001) compared to left aortic arch and found in 82.5% (33/40) versus 10.7% (9/84) of fetuses with ToF/PS and in 57.1% (8/14) versus 12.9% (4/31) of fetuses with ToF/PA. In both ToF/PS and ToF/PA, RAA/ADA versus RAA/patent DA revealed a significantly higher risk for the presence of genetic abnormalities, especially microdeletion 22q11.2, major aorto-pulmonary collateral arteries and a shorter time to complete surgical repair.
Conclusion: We demonstrated a significantly increased frequency of RAA/ADA in patients with prenatally diagnosed ToF. Although this association revealed no significant impact on overall survival, the prenatal detection of RAA/ADA has implications for counseling, genetic evaluation and postnatal management.
{"title":"Association of right aortic arch and agenesis of ductus arteriosus in prenatal tetralogy of Fallot spectrum and its clinical implications.","authors":"Adeline Walter, Ulrike Herberg, Elina Calite, Annegret Geipel, Florian Recker, Brigitte Strizek, Christoph Berg, Ulrich Gembruch","doi":"10.1002/pd.6611","DOIUrl":"10.1002/pd.6611","url":null,"abstract":"<p><strong>Objective: </strong>In our center, we observed an increased frequency of right aortic arch (RAA) with an agenesis of the ductus arteriosus (ADA) in prenatally diagnosed tetralogy of Fallot (ToF) and its variations. This study aimed to determine whether there is an association of RAA and ADA in fetuses with ToF. Distribution of genetic anomalies and impact on postnatal outcome were further evaluated.</p><p><strong>Method: </strong>Single-center retrospective observational study including pregnancies with prenatal diagnosis of ToF from 2010 to 2023. All cases were subdivided into ToF with pulmonary stenosis (PS) and pulmonary atresia (PA). Clinical and echocardiographic databases were reviewed for pregnancy outcome, genetic anomalies, and postnatal course.</p><p><strong>Results: </strong>The cohort included 169 cases, 124 (73.4%) with ToF/PS and 45(26.6%) with ToF/PA. Agenesis of the ductus arteriosus was significantly associated with RAA in both subtypes of ToF (p = 0.001) compared to left aortic arch and found in 82.5% (33/40) versus 10.7% (9/84) of fetuses with ToF/PS and in 57.1% (8/14) versus 12.9% (4/31) of fetuses with ToF/PA. In both ToF/PS and ToF/PA, RAA/ADA versus RAA/patent DA revealed a significantly higher risk for the presence of genetic abnormalities, especially microdeletion 22q11.2, major aorto-pulmonary collateral arteries and a shorter time to complete surgical repair.</p><p><strong>Conclusion: </strong>We demonstrated a significantly increased frequency of RAA/ADA in patients with prenatally diagnosed ToF. Although this association revealed no significant impact on overall survival, the prenatal detection of RAA/ADA has implications for counseling, genetic evaluation and postnatal management.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141155711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01Epub Date: 2023-08-19DOI: 10.1002/pd.6420
Hiba J Mustafa, Faezeh Aghajani, Mohammad Jawwad, Nensi Shah, Alfred Abuhamad, Asma Khalil
To investigate outcomes of fetuses with hypoplastic left heart syndrome (HLHS) with an intact or restrictive atrial septum (I/RAS) managed expectantly or with fetal atrial septal intervention (FASI PubMed, Scopus, and Web of Science were searched systematically from inception until April 2023. Outcomes were classified by those who had FASI and those who had expectant management (EM). To estimate the overall proportion of each endpoint, a meta-analysis of proportions was employed using a random-effects model. Heterogeneity was assessed using the I2 value. Thirty-two studies reporting on 746 fetuses with HLHS and I/RAS met our inclusion criteria. Eleven studies (123 fetuses) were in the FASI group and 21 studies (623 fetuses) were in the EM group. Among the 123 FASI cases, 107 (87%) were reported to be technically successful. The mean gestational age (GA) at diagnosis was comparable between the groups (26.2 weeks FASI vs. 24.4 weeks EM group). The mean GA at FASI was 30.4 weeks (95% CI 28.5, 32.5). The mean GA at delivery was also comparable (37.7 weeks FASI vs. 38.1 weeks EM group). Neonatal outcomes, including live birth, neonatal death, and survival to hospital discharge pooled proportions, were also comparable between groups (live birth: 92% (95% CI 64, 99) FASI versus 93% (95% CI 79, 98) in EM, neonatal death: 32% (95% CI 11, 65) FASI versus 30% (95% CI 21, 41) EM, survival to hospital discharge: 37% (95% CI 25, 52) FASI versus 52% (95% CI 42, 61) EM). Age at neonatal death was higher in the FASI group (mean: 17 days FASI vs. 7.2 days EM group). There was a lower rate of postnatal atrial restrictive septum in the FASI group 38% (95% CI 17, 63) compared to the EM group 88% (95% CI 57, 98). Our review shows variations across centers in the selection criteria and techniques used for FASI. Although survival including livebirth, neonatal death, and survival to hospital discharge did not differ between groups, the procedure may translate into a less restrictive septum at birth. Future multicenter studies are needed to better identify the subset of cases that might have improved outcomes, use standardized definitions, unified techniques, utilize core outcome set, and assess long-term benefits.
为了调查患有左心室发育不全综合征(HLHS)且房间隔完整或受限(I/RAS)的胎儿的预后情况,我们对从开始到 2023 年 4 月的 PubMed、Scopus 和 Web of Science 进行了系统检索。研究结果按接受 FASI 和期待治疗(EM)的患者进行了分类。为了估计每个终点的总体比例,采用随机效应模型对比例进行了荟萃分析。异质性采用 I2 值进行评估。32项研究共报道了746名患有HLHS和I/RAS的胎儿,符合我们的纳入标准。11项研究(123个胎儿)属于FASI组,21项研究(623个胎儿)属于EM组。在 123 例 FASI 病例中,107 例(87%)在技术上是成功的。两组诊断时的平均胎龄(GA)相当(FASI 组为 26.2 周,EM 组为 24.4 周)。FASI时的平均胎龄为30.4周(95% CI 28.5,32.5)。分娩时的平均胎龄也相当(FASI 组为 37.7 周,EM 组为 38.1 周)。新生儿结局(包括活产、新生儿死亡和出院存活率)在各组之间也具有可比性(活产:FASI 组为 92% (95% CI 64, 99) ,EM 组为 93% (95% CI 79, 98);新生儿死亡:FASI 组为 32% (95% CI 11, 99) ,EM 组为 32% (95% CI 11, 98):新生儿死亡:32%(95% CI 11,65)FASI 对 30%(95% CI 21,41)EM,出院存活率:37% (95% CI 25, 52) FASI 对 52% (95% CI 42, 61) EM)。新生儿死亡年龄在 FASI 组更高(平均:17 天 FASI 组对 7.2 天 EM 组)。与EM组相比,FASI组产后心房局限性间隔发生率较低,为38%(95% CI 17-63),而EM组为88%(95% CI 57-98)。我们的回顾显示,各中心在 FASI 的选择标准和技术方面存在差异。虽然包括活产、新生儿死亡和出院存活率在内的存活率在各组间并无差异,但该手术可能会减少出生时鼻中隔的限制性。未来需要进行多中心研究,以更好地确定可能改善预后的病例子集、使用标准化定义、统一技术、利用核心结果集以及评估长期益处。
{"title":"Fetal cardiac intervention in hypoplastic left heart syndrome with intact or restrictive atrial septum, systematic review, and meta-analysis.","authors":"Hiba J Mustafa, Faezeh Aghajani, Mohammad Jawwad, Nensi Shah, Alfred Abuhamad, Asma Khalil","doi":"10.1002/pd.6420","DOIUrl":"10.1002/pd.6420","url":null,"abstract":"<p><p>To investigate outcomes of fetuses with hypoplastic left heart syndrome (HLHS) with an intact or restrictive atrial septum (I/RAS) managed expectantly or with fetal atrial septal intervention (FASI PubMed, Scopus, and Web of Science were searched systematically from inception until April 2023. Outcomes were classified by those who had FASI and those who had expectant management (EM). To estimate the overall proportion of each endpoint, a meta-analysis of proportions was employed using a random-effects model. Heterogeneity was assessed using the I<sup>2</sup> value. Thirty-two studies reporting on 746 fetuses with HLHS and I/RAS met our inclusion criteria. Eleven studies (123 fetuses) were in the FASI group and 21 studies (623 fetuses) were in the EM group. Among the 123 FASI cases, 107 (87%) were reported to be technically successful. The mean gestational age (GA) at diagnosis was comparable between the groups (26.2 weeks FASI vs. 24.4 weeks EM group). The mean GA at FASI was 30.4 weeks (95% CI 28.5, 32.5). The mean GA at delivery was also comparable (37.7 weeks FASI vs. 38.1 weeks EM group). Neonatal outcomes, including live birth, neonatal death, and survival to hospital discharge pooled proportions, were also comparable between groups (live birth: 92% (95% CI 64, 99) FASI versus 93% (95% CI 79, 98) in EM, neonatal death: 32% (95% CI 11, 65) FASI versus 30% (95% CI 21, 41) EM, survival to hospital discharge: 37% (95% CI 25, 52) FASI versus 52% (95% CI 42, 61) EM). Age at neonatal death was higher in the FASI group (mean: 17 days FASI vs. 7.2 days EM group). There was a lower rate of postnatal atrial restrictive septum in the FASI group 38% (95% CI 17, 63) compared to the EM group 88% (95% CI 57, 98). Our review shows variations across centers in the selection criteria and techniques used for FASI. Although survival including livebirth, neonatal death, and survival to hospital discharge did not differ between groups, the procedure may translate into a less restrictive septum at birth. Future multicenter studies are needed to better identify the subset of cases that might have improved outcomes, use standardized definitions, unified techniques, utilize core outcome set, and assess long-term benefits.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10401461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01Epub Date: 2024-05-06DOI: 10.1002/pd.6581
K Reilly, S Sonner, N McCay, D L Rolnik, F Casey, A N Seale, C J Watson, A Kan, T H T Lai, B H Y Chung, K E M Diderich, M I Srebniak, E Dempsey, S Drury, J Giordano, R Wapner, M D Kilby, L S Chitty, F Mone
Objectives: To determine the incremental yield of prenatal exome sequencing (PES) over standard testing in fetuses with an isolated congenital heart abnormality (CHA), CHA associated with extra-cardiac malformations (ECMs) and CHA dependent upon anatomical subclassification.
Methods: A systematic review of the literature was performed using MEDLINE, EMBASE, Web of Science and grey literature January 2010-February 2023. Studies were selected if they included greater than 20 cases of prenatally diagnosed CHA when standard testing (QF-PCR/chromosome microarray/karyotype) was negative. Pooled incremental yield was determined. PROSPERO CRD 42022364747.
Results: Overall, 21 studies, incorporating 1957 cases were included. The incremental yield of PES (causative pathogenic and likely pathogenic variants) over standard testing was 17.4% (95% CI, 13.5%-21.6%), 9.3% (95% CI, 6.6%-12.3%) and 35.9% (95% CI, 21.0%-52.3%) for all CHAs, isolated CHAs and CHAs associated with ECMs. The subgroup with the greatest yield was complex lesions/heterotaxy; 35.2% (95% CI 9.7%-65.3%). The most common syndrome was Kabuki syndrome (31/256, 12.1%) and most pathogenic variants occurred de novo and in autosomal dominant (monoallelic) disease causing genes (114/224, 50.9%).
Conclusion: The likelihood of a monogenic aetiology in fetuses with multi-system CHAs is high. Clinicians must consider the clinical utility of offering PES in selected isolated cardiac lesions.
目的确定与标准检测相比,产前外显子组测序(PES)对孤立先天性心脏异常(CHA)、伴有心外畸形(ECMs)的CHA以及依赖于解剖亚分类的CHA胎儿的增量:采用 MEDLINE、EMBASE、Web of Science 和灰色文献对 2010 年 1 月至 2023 年 2 月的文献进行了系统性回顾。在标准检测(QF-PCR/染色体微阵列/核型)呈阴性的情况下,如果产前诊断为CHA的病例超过20例,则选取这些研究。确定了汇总增量。PROSPERO CRD 42022364747.结果:共有 21 项研究纳入了 1957 个病例。与标准检测相比,PES(致病变异和可能致病变异)对所有 CHA、孤立的 CHA 和与 ECMs 相关的 CHA 的增量分别为 17.4%(95% CI,13.5%-21.6%)、9.3%(95% CI,6.6%-12.3%)和 35.9%(95% CI,21.0%-52.3%)。复杂病变/动脉导管未闭是发病率最高的亚组;占 35.2%(95% CI 9.7%-65.3%)。最常见的综合征是歌舞伎综合征(31/256,12.1%),大多数致病变异发生在新发和常染色体显性(单偶)致病基因中(114/224,50.9%):结论:多系统CHA胎儿的单基因病因可能性很高。临床医生必须考虑在选定的孤立心脏病变中提供 PES 的临床实用性。
{"title":"The incremental yield of prenatal exome sequencing over chromosome microarray for congenital heart abnormalities: A systematic review and meta-analysis.","authors":"K Reilly, S Sonner, N McCay, D L Rolnik, F Casey, A N Seale, C J Watson, A Kan, T H T Lai, B H Y Chung, K E M Diderich, M I Srebniak, E Dempsey, S Drury, J Giordano, R Wapner, M D Kilby, L S Chitty, F Mone","doi":"10.1002/pd.6581","DOIUrl":"10.1002/pd.6581","url":null,"abstract":"<p><strong>Objectives: </strong>To determine the incremental yield of prenatal exome sequencing (PES) over standard testing in fetuses with an isolated congenital heart abnormality (CHA), CHA associated with extra-cardiac malformations (ECMs) and CHA dependent upon anatomical subclassification.</p><p><strong>Methods: </strong>A systematic review of the literature was performed using MEDLINE, EMBASE, Web of Science and grey literature January 2010-February 2023. Studies were selected if they included greater than 20 cases of prenatally diagnosed CHA when standard testing (QF-PCR/chromosome microarray/karyotype) was negative. Pooled incremental yield was determined. PROSPERO CRD 42022364747.</p><p><strong>Results: </strong>Overall, 21 studies, incorporating 1957 cases were included. The incremental yield of PES (causative pathogenic and likely pathogenic variants) over standard testing was 17.4% (95% CI, 13.5%-21.6%), 9.3% (95% CI, 6.6%-12.3%) and 35.9% (95% CI, 21.0%-52.3%) for all CHAs, isolated CHAs and CHAs associated with ECMs. The subgroup with the greatest yield was complex lesions/heterotaxy; 35.2% (95% CI 9.7%-65.3%). The most common syndrome was Kabuki syndrome (31/256, 12.1%) and most pathogenic variants occurred de novo and in autosomal dominant (monoallelic) disease causing genes (114/224, 50.9%).</p><p><strong>Conclusion: </strong>The likelihood of a monogenic aetiology in fetuses with multi-system CHAs is high. Clinicians must consider the clinical utility of offering PES in selected isolated cardiac lesions.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140869961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01Epub Date: 2024-05-23DOI: 10.1002/pd.6591
Cynthie K Wautlet, Samantha A Kops, Lori J Silveira, Krista Young, Nicholas J Behrendt, Michael V Zaretsky, Bettina F Cuneo, Henry L Galan
Objectives: To describe and compare maternal and fetal comorbidities and obstetrical outcomes in pregnancies with hypoplastic left and right heart (HLHS and HRH) single ventricle cardiac defects (SVCD) from a single center under a multidisciplinary protocol.
Method: A single center retrospective review of fetal SVCD from 2013 to 2022. Maternal-fetal comorbidities, delivery, and postnatal outcomes were compared between HLHS and HRH using descriptive statistics and univariate and multivariate analyses.
Results: Of 181 SVCD pregnancies (131 HLHS; 50 HRH), 9% underwent termination, 4% elected comfort care, 5 died in utero and 147/152 liveborns survived to the first cardiac intervention. Cesarean delivery occurred in 57 cases (37%), planned in 36 and unplanned in 21. Comorbidities, which did not differ between HLHS and HRH, included fetal growth restriction (FGR, 17%), prematurity (14%), maternal hypertension (9%), maternal obesity (50%), fetal extracardiac anomalies and chromosome anomalies (12%, 13%). In multivariate analysis, only earlier gestational age at delivery and oligohydramnios predicted decreased odds of survival at one year.
Conclusion: Maternal-fetal comorbidities are common in both HLHS and HRH. Earlier gestational age at delivery and oligohydramnios predict lower postnatal survival. FGR, even with severe early onset, did not significantly impact short- or long-term neonatal survival in single ventricle conditions.
{"title":"Maternal-fetal comorbidities and obstetrical outcomes of fetal single ventricle cardiac defects: 10 years' experience with a multidisciplinary management protocol at a single center.","authors":"Cynthie K Wautlet, Samantha A Kops, Lori J Silveira, Krista Young, Nicholas J Behrendt, Michael V Zaretsky, Bettina F Cuneo, Henry L Galan","doi":"10.1002/pd.6591","DOIUrl":"10.1002/pd.6591","url":null,"abstract":"<p><strong>Objectives: </strong>To describe and compare maternal and fetal comorbidities and obstetrical outcomes in pregnancies with hypoplastic left and right heart (HLHS and HRH) single ventricle cardiac defects (SVCD) from a single center under a multidisciplinary protocol.</p><p><strong>Method: </strong>A single center retrospective review of fetal SVCD from 2013 to 2022. Maternal-fetal comorbidities, delivery, and postnatal outcomes were compared between HLHS and HRH using descriptive statistics and univariate and multivariate analyses.</p><p><strong>Results: </strong>Of 181 SVCD pregnancies (131 HLHS; 50 HRH), 9% underwent termination, 4% elected comfort care, 5 died in utero and 147/152 liveborns survived to the first cardiac intervention. Cesarean delivery occurred in 57 cases (37%), planned in 36 and unplanned in 21. Comorbidities, which did not differ between HLHS and HRH, included fetal growth restriction (FGR, 17%), prematurity (14%), maternal hypertension (9%), maternal obesity (50%), fetal extracardiac anomalies and chromosome anomalies (12%, 13%). In multivariate analysis, only earlier gestational age at delivery and oligohydramnios predicted decreased odds of survival at one year.</p><p><strong>Conclusion: </strong>Maternal-fetal comorbidities are common in both HLHS and HRH. Earlier gestational age at delivery and oligohydramnios predict lower postnatal survival. FGR, even with severe early onset, did not significantly impact short- or long-term neonatal survival in single ventricle conditions.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141088410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01Epub Date: 2024-05-27DOI: 10.1002/pd.6613
Lindsay R Freud, Lynn L Simpson, Louise E Wilkins-Haug
{"title":"The bright future of fetal cardiology.","authors":"Lindsay R Freud, Lynn L Simpson, Louise E Wilkins-Haug","doi":"10.1002/pd.6613","DOIUrl":"10.1002/pd.6613","url":null,"abstract":"","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141155719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01Epub Date: 2024-03-06DOI: 10.1002/pd.6540
Scott Bennett, Lisa K Hornberger, Deborah Fruitman, Timothy J Bradley, Gitanjali P Mansukhani
Objective: Pulmonary artery sling is a rare congenital anomaly accounting for 2% of all patients with vascular anomalies that cause airway obstruction. In the normal heart, the left (LPA) and right (RPA) pulmonary arteries arise in the intrapericardial space. However, in the pulmonary artery sling, the LPA trunk arises in the extrapericardial space from the posterior aspect of the mid RPA and courses posterior to the trachea causing tracheal compression and, at times, bronchial compression. While a full spectrum of congenital cardiac pathology can be identified before birth, only a few case reports document the prenatal diagnosis of an Left pulmonary artery sling (LPAS).
Method: We retrospectively identified all cases of prenatal LPAS from three Canadian fetal cardiology centers (2015-2022).
Results: Using the 3-vessel-tracheal view via fetal echocardiography (FE), four fetuses from three pregnancies demonstrated abnormal origin of the LPA from RPA and echogenic trachea. In one of two affected monochorionic twins coronal imaging demonstrated a significant narrowing of the large airways consistent with significant airway obstruction.
Conclusion: Prenatal detection of LPAS by FE is possible and should prompt an evaluation for airway obstruction in the coronal view. Investigating associated lesions and genetic testing are recommended for informed shared decision making.
目的:肺动脉斜坡是一种罕见的先天性畸形,占导致气道阻塞的血管畸形患者总数的 2%。在正常心脏中,左肺动脉(LPA)和右肺动脉(RPA)发源于心包内间隙。然而,在肺动脉吊带中,左肺动脉干从 RPA 中段的后方发源于心包外间隙,并向气管后方延伸,导致气管受压,有时还会导致支气管受压。虽然先天性心脏病的所有病变都可以在出生前发现,但只有少数病例报告记录了左肺动脉吊带(LPAS)的产前诊断:方法:我们回顾性地鉴定了加拿大三家胎儿心脏病学中心(2015-2022年)的所有产前LPAS病例:结果:通过胎儿超声心动图(FE)的三血管-气管视图,三胎中的四名胎儿显示出异常的LPA起源于RPA和回声气管。在两个受影响的单绒毛膜双胎中,有一个的冠状造影显示大气管明显狭窄,与明显的气道阻塞一致:结论:通过 FE 可以在产前检测到 LPAS,并应及时评估冠状切面的气道阻塞情况。建议对相关病变进行调查并进行基因检测,以做出知情的共同决策。
{"title":"Fetal diagnosis and management of pulmonary artery sling: A case series.","authors":"Scott Bennett, Lisa K Hornberger, Deborah Fruitman, Timothy J Bradley, Gitanjali P Mansukhani","doi":"10.1002/pd.6540","DOIUrl":"10.1002/pd.6540","url":null,"abstract":"<p><strong>Objective: </strong>Pulmonary artery sling is a rare congenital anomaly accounting for 2% of all patients with vascular anomalies that cause airway obstruction. In the normal heart, the left (LPA) and right (RPA) pulmonary arteries arise in the intrapericardial space. However, in the pulmonary artery sling, the LPA trunk arises in the extrapericardial space from the posterior aspect of the mid RPA and courses posterior to the trachea causing tracheal compression and, at times, bronchial compression. While a full spectrum of congenital cardiac pathology can be identified before birth, only a few case reports document the prenatal diagnosis of an Left pulmonary artery sling (LPAS).</p><p><strong>Method: </strong>We retrospectively identified all cases of prenatal LPAS from three Canadian fetal cardiology centers (2015-2022).</p><p><strong>Results: </strong>Using the 3-vessel-tracheal view via fetal echocardiography (FE), four fetuses from three pregnancies demonstrated abnormal origin of the LPA from RPA and echogenic trachea. In one of two affected monochorionic twins coronal imaging demonstrated a significant narrowing of the large airways consistent with significant airway obstruction.</p><p><strong>Conclusion: </strong>Prenatal detection of LPAS by FE is possible and should prompt an evaluation for airway obstruction in the coronal view. Investigating associated lesions and genetic testing are recommended for informed shared decision making.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140050216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}