妊娠期CLL的无创产前检测:一个警示故事。

EJHaem Pub Date : 2025-01-10 DOI:10.1002/jha2.1067
Jorn L. J. C. Assmann, Diane Van Opstal, Karin E. M. Diderich, Nicole Larmonie, Yorick Sandberg
{"title":"妊娠期CLL的无创产前检测:一个警示故事。","authors":"Jorn L. J. C. Assmann,&nbsp;Diane Van Opstal,&nbsp;Karin E. M. Diderich,&nbsp;Nicole Larmonie,&nbsp;Yorick Sandberg","doi":"10.1002/jha2.1067","DOIUrl":null,"url":null,"abstract":"<p>To the Editor:</p><p>Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world, with a median age at diagnosis of 72 years. An estimated 2% of the patients are females of childbearing age. CLL cases during pregnancy are rare and are associated with many complications. Although the implications and management of CLL in pregnancy have been discussed previously, issues related to noninvasive prenatal testing (NIPT) are often overlooked [<span>1</span>]. Various chromosomal changes are associated with CLL, with the deletion in the long arm of chromosome 13 at position q14 (deletion 13q14) being the most common alteration [<span>2</span>].</p><p>Since its implementation in clinical practice in 2011, NIPT was available to all pregnant women in the Netherlands in 2017. It has become a reliable and sensitive method of prenatal screening to evaluate the risk of fetal chromosomal imbalances. NIPT testing is primarily used to screen for Down (trisomy 21), Edwards (trisomy 18), or Patau (trisomy 13) syndromes. However, other deletions, such as del13q, can also be detected. NIPT can be performed as early as 10 weeks of gestations, and NIPT is based on the analysis of cell-free DNA (cfDNA) of which a small part is derived from the placenta, and the main part has a maternal origin [<span>3</span>]. However, with the NIPT test that is used in the Netherlands [<span>4, 5</span>], it is impossible to discriminate between fetal cfDNA and tumor-derived cfDNA, including CLL [<span>6</span>]. The finding of a chromosome aberration warrants further investigation using invasive prenatal procedures, such as chorionic villus sampling or amniocentesis. Maternal neoplasms causing aberrant NIPT results are a complex matter in prenatal diagnosis [<span>7</span>]. Cases describing discordant NIPT testing caused by a hematological malignancy remain very scarce [<span>8</span>], and this is the first report of a patient with diagnosed CLL having a discordant NIPT result post CLL diagnosis due to a molecular aberration of CLL cells.</p><p>A 33-year-old woman with a 1-year history of untreated CLL, had NIPT performed at 13 1/7 gestational weeks as a first-tier screening test for fetal aneuploidies. Ultrasound examinations at 6 and 12 gestational weeks showed a single viable intrauterine pregnancy, biometry appropriate for gestational age, and absence of gross fetal anomalies. The NIPT results indicated a high risk for chromosome 13q14 deletion (Figure 1). Genetic counseling of the woman and her partner was done. Our primary goal was to rule out the fetal origin of the abnormal result. Therefore, single nucleotide polymorphism array (SNP-array) on amniotic fluid cells and peripheral blood of the mother was performed to verify the abnormal NIPT result. While a mosaic loss of 10 Mb was identified in the maternal blood within the 13q14.11q14.3 region (arr[hg19] 13q14.11q14.3(40,484,657-50,909,942)x1∼2), the amniotic fluid was normal. Fluorescent in situ hybridization (FISH) on interphase nuclei cells of the mother confirmed a mosaic deletion on 13q (Figure 2). Ultrasound scans at 16, 20, and 24 gestational weeks reported no fetal anomalies. At 40 gestational weeks labor she gave birth to a healthy male baby.</p><p>In patients with malignancies, NIPT testing can potentially lead to discordant results when the malignant cells are affected with (a) chromosome aberration(s) like in the present case. As it will complicate the accurate interpretation of the NIPT results, a maternal malignancy is a contraindication for NIPT in the Netherlands, especially when it comes to hematological neoplasms [<span>9</span>]. Nevertheless, the incidence of pregnancy among patients diagnosed with malignancies is notably low; therefore, it is unknown how much routine counseling by medical specialists regarding NIPT is performed in this population. The laboratory—not knowing about the CLL—interpreted the deletion in 13q as potentially fetal, and invasive testing by amniocentesis was offered as this chromosome aberration can be associated with severe fetal malformations, depending on the exact breakpoints. These uncertainties led to a lot of stress for the parents. With prior knowledge of a maternal CLL, the patient and clinicians could have jointly opted to forgo invasive diagnostic testing as the detection of an aberration would likely have reflected the maternal hematological condition rather than a fetal chromosome aberration. As tumor cfDNA can mask fetal cfDNA, there is a considerable risk that NIPT will not provide an accurate assessment of the fetus. Therefore, in all cases of maternal malignancy where cytogenetic evaluation of the fetus is desired, amniocentesis should be recommended.</p><p>Our findings underline that NIPT is not advisable for pregnant women with confirmed malignancy [<span>10</span>]. In these cases, it can be difficult to accurately interpret the fetal genetic constitution.</p><p>Instead of NIPT, a detailed structural anomaly screening by ultrasound and an amniocentesis for karyotyping, if certainty on chromosomal abnormalities is desired, are the most appropriate options in these situations. If parents choose to forgo this invasive testing, they may still consider NIPT, but only after thorough genetic counseling by a clinical geneticist to ensure that they are aware of the risks associated with abnormal results.</p><p>With the advent of novel algorithms that account for the origin of circulating cfDNA, advancements in reliably measuring fetal fraction, and improved methodologies for detecting aneuploidies, future approaches may allow for the identification and exclusion of tumor-derived cfDNA from the NIPT analysis. Thereby reducing the risk of misdiagnoses [<span>9</span>]. Until then, NIPT testing in patients with malignancies should be avoided.</p><p><b>Jorn Assmann</b>: writing—original draft preparation. <b>Diane van Opstal</b>: writing; visualization. <b>Karin Diderich</b>: resources; visualization. <b>Nicole Larmonie</b>: writing; visualization. <b>Yorick Sandberg</b>: resources; supervision; writing—review and editing. <b>Yorick Sandberg</b>: had full access to all the data in the study and takes responsibility for the integrity of the data.</p><p>The authors do not report any potential conflicts of interest, including relevant financial interests, activities, relationships, and affiliations (e.g., employment, affiliation, grants or funding, consultancies, honoraria or payment, speakers’ bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued) with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript.</p><p>The authors have confirmed clinical trial registration is not needed for this submission.</p><p>This study was conducted in accordance with the ethical principles and guidelines established by the Declaration of Helsinki.</p><p>The authors received no specific funding for this work.</p><p>Informed consent was obtained from the patient prior to their inclusion in this study. The patient was provided with detailed information about the purpose, procedures, risks, and potential benefits of the research. The patient was given the opportunity to ask questions and was assured that participation was voluntary and that the patient could withdraw at any time without penalty. The patient was informed that data would be anonymized and kept confidential, with personal identifiers removed prior to analysis and publication. The study procedures and use of personal data were in compliance with the relevant data protection laws and institutional guidelines. By signing the informed consent form, the patient acknowledged understanding of the study's aims and willingness to take part in the research. A copy of the consent form was provided to the patient for her records.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756964/pdf/","citationCount":"0","resultStr":"{\"title\":\"Noninvasive prenatal testing in CLL during pregnancy: A cautionary tale\",\"authors\":\"Jorn L. J. C. Assmann,&nbsp;Diane Van Opstal,&nbsp;Karin E. M. Diderich,&nbsp;Nicole Larmonie,&nbsp;Yorick Sandberg\",\"doi\":\"10.1002/jha2.1067\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>To the Editor:</p><p>Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world, with a median age at diagnosis of 72 years. An estimated 2% of the patients are females of childbearing age. CLL cases during pregnancy are rare and are associated with many complications. Although the implications and management of CLL in pregnancy have been discussed previously, issues related to noninvasive prenatal testing (NIPT) are often overlooked [<span>1</span>]. Various chromosomal changes are associated with CLL, with the deletion in the long arm of chromosome 13 at position q14 (deletion 13q14) being the most common alteration [<span>2</span>].</p><p>Since its implementation in clinical practice in 2011, NIPT was available to all pregnant women in the Netherlands in 2017. It has become a reliable and sensitive method of prenatal screening to evaluate the risk of fetal chromosomal imbalances. NIPT testing is primarily used to screen for Down (trisomy 21), Edwards (trisomy 18), or Patau (trisomy 13) syndromes. However, other deletions, such as del13q, can also be detected. NIPT can be performed as early as 10 weeks of gestations, and NIPT is based on the analysis of cell-free DNA (cfDNA) of which a small part is derived from the placenta, and the main part has a maternal origin [<span>3</span>]. However, with the NIPT test that is used in the Netherlands [<span>4, 5</span>], it is impossible to discriminate between fetal cfDNA and tumor-derived cfDNA, including CLL [<span>6</span>]. The finding of a chromosome aberration warrants further investigation using invasive prenatal procedures, such as chorionic villus sampling or amniocentesis. Maternal neoplasms causing aberrant NIPT results are a complex matter in prenatal diagnosis [<span>7</span>]. Cases describing discordant NIPT testing caused by a hematological malignancy remain very scarce [<span>8</span>], and this is the first report of a patient with diagnosed CLL having a discordant NIPT result post CLL diagnosis due to a molecular aberration of CLL cells.</p><p>A 33-year-old woman with a 1-year history of untreated CLL, had NIPT performed at 13 1/7 gestational weeks as a first-tier screening test for fetal aneuploidies. Ultrasound examinations at 6 and 12 gestational weeks showed a single viable intrauterine pregnancy, biometry appropriate for gestational age, and absence of gross fetal anomalies. The NIPT results indicated a high risk for chromosome 13q14 deletion (Figure 1). Genetic counseling of the woman and her partner was done. Our primary goal was to rule out the fetal origin of the abnormal result. Therefore, single nucleotide polymorphism array (SNP-array) on amniotic fluid cells and peripheral blood of the mother was performed to verify the abnormal NIPT result. While a mosaic loss of 10 Mb was identified in the maternal blood within the 13q14.11q14.3 region (arr[hg19] 13q14.11q14.3(40,484,657-50,909,942)x1∼2), the amniotic fluid was normal. Fluorescent in situ hybridization (FISH) on interphase nuclei cells of the mother confirmed a mosaic deletion on 13q (Figure 2). Ultrasound scans at 16, 20, and 24 gestational weeks reported no fetal anomalies. At 40 gestational weeks labor she gave birth to a healthy male baby.</p><p>In patients with malignancies, NIPT testing can potentially lead to discordant results when the malignant cells are affected with (a) chromosome aberration(s) like in the present case. As it will complicate the accurate interpretation of the NIPT results, a maternal malignancy is a contraindication for NIPT in the Netherlands, especially when it comes to hematological neoplasms [<span>9</span>]. Nevertheless, the incidence of pregnancy among patients diagnosed with malignancies is notably low; therefore, it is unknown how much routine counseling by medical specialists regarding NIPT is performed in this population. The laboratory—not knowing about the CLL—interpreted the deletion in 13q as potentially fetal, and invasive testing by amniocentesis was offered as this chromosome aberration can be associated with severe fetal malformations, depending on the exact breakpoints. These uncertainties led to a lot of stress for the parents. With prior knowledge of a maternal CLL, the patient and clinicians could have jointly opted to forgo invasive diagnostic testing as the detection of an aberration would likely have reflected the maternal hematological condition rather than a fetal chromosome aberration. As tumor cfDNA can mask fetal cfDNA, there is a considerable risk that NIPT will not provide an accurate assessment of the fetus. Therefore, in all cases of maternal malignancy where cytogenetic evaluation of the fetus is desired, amniocentesis should be recommended.</p><p>Our findings underline that NIPT is not advisable for pregnant women with confirmed malignancy [<span>10</span>]. In these cases, it can be difficult to accurately interpret the fetal genetic constitution.</p><p>Instead of NIPT, a detailed structural anomaly screening by ultrasound and an amniocentesis for karyotyping, if certainty on chromosomal abnormalities is desired, are the most appropriate options in these situations. If parents choose to forgo this invasive testing, they may still consider NIPT, but only after thorough genetic counseling by a clinical geneticist to ensure that they are aware of the risks associated with abnormal results.</p><p>With the advent of novel algorithms that account for the origin of circulating cfDNA, advancements in reliably measuring fetal fraction, and improved methodologies for detecting aneuploidies, future approaches may allow for the identification and exclusion of tumor-derived cfDNA from the NIPT analysis. Thereby reducing the risk of misdiagnoses [<span>9</span>]. Until then, NIPT testing in patients with malignancies should be avoided.</p><p><b>Jorn Assmann</b>: writing—original draft preparation. <b>Diane van Opstal</b>: writing; visualization. <b>Karin Diderich</b>: resources; visualization. <b>Nicole Larmonie</b>: writing; visualization. <b>Yorick Sandberg</b>: resources; supervision; writing—review and editing. <b>Yorick Sandberg</b>: had full access to all the data in the study and takes responsibility for the integrity of the data.</p><p>The authors do not report any potential conflicts of interest, including relevant financial interests, activities, relationships, and affiliations (e.g., employment, affiliation, grants or funding, consultancies, honoraria or payment, speakers’ bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued) with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript.</p><p>The authors have confirmed clinical trial registration is not needed for this submission.</p><p>This study was conducted in accordance with the ethical principles and guidelines established by the Declaration of Helsinki.</p><p>The authors received no specific funding for this work.</p><p>Informed consent was obtained from the patient prior to their inclusion in this study. The patient was provided with detailed information about the purpose, procedures, risks, and potential benefits of the research. The patient was given the opportunity to ask questions and was assured that participation was voluntary and that the patient could withdraw at any time without penalty. The patient was informed that data would be anonymized and kept confidential, with personal identifiers removed prior to analysis and publication. The study procedures and use of personal data were in compliance with the relevant data protection laws and institutional guidelines. By signing the informed consent form, the patient acknowledged understanding of the study's aims and willingness to take part in the research. A copy of the consent form was provided to the patient for her records.</p>\",\"PeriodicalId\":72883,\"journal\":{\"name\":\"EJHaem\",\"volume\":\"6 1\",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-01-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756964/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"EJHaem\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/jha2.1067\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"EJHaem","FirstCategoryId":"1085","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jha2.1067","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

摘要

致编辑:慢性淋巴细胞白血病(CLL)是西方世界最常见的白血病,诊断时的中位年龄为72岁。估计有2%的患者是育龄女性。妊娠期CLL病例很少见,并伴有许多并发症。尽管之前已经讨论过CLL在妊娠期的影响和管理,但与无创产前检查(NIPT)相关的问题经常被忽视。各种染色体变化与CLL相关,13号染色体长臂q14位置的缺失(13q14缺失)是最常见的改变[2]。自2011年在临床实践中实施以来,NIPT于2017年在荷兰对所有孕妇开放。它已成为一种可靠和敏感的产前筛查方法,以评估胎儿染色体失衡的风险。NIPT检测主要用于筛查唐氏综合症(21三体)、爱德华兹综合症(18三体)或帕陶综合症(13三体)。但是,也可以检测到其他缺失,例如del13q。NIPT早在妊娠10周就可以进行,NIPT是基于游离DNA (cell-free DNA, cfDNA)的分析,其中一小部分来自胎盘,主要部分来自母体来源[3]。然而,在荷兰使用NIPT检测[4,5],不可能区分胎儿cfDNA和肿瘤来源的cfDNA,包括CLL[6]。染色体畸变的发现值得使用侵入性产前程序进一步调查,如绒毛膜绒毛取样或羊膜穿刺术。在产前诊断中,引起异常NIPT结果的母体肿瘤是一个复杂的问题。由血液学恶性肿瘤引起的NIPT检测结果不一致的病例仍然非常少,这是第一例诊断为CLL的患者在CLL诊断后由于CLL细胞分子畸变而出现NIPT结果不一致的报告。一名患有1年未经治疗的CLL病史的33岁女性,在13又1/7孕周时进行NIPT,作为胎儿非整倍体的一级筛查试验。6和12孕周超声检查显示单活宫内妊娠,生物测量与胎龄相符,无明显胎儿异常。NIPT结果显示染色体13q14缺失的风险很高(图1)。对该妇女及其伴侣进行了遗传咨询。我们的主要目的是排除胎儿来源的异常结果。因此,我们对母亲的羊水细胞和外周血进行单核苷酸多态性阵列(SNP-array)来验证NIPT结果是否异常。虽然在母体血液13q14.11q14.3区域(arr[hg19] 13q14.11q14.3(40,484,657-50,909,942)x1 ~ 2)中发现了10 Mb的嵌合缺失,但羊水正常。母体间期细胞核的荧光原位杂交(FISH)证实了13q上的马赛克缺失(图2)。孕16、20和24周的超声扫描未发现胎儿异常。在怀孕40周时,她生下了一个健康的男婴。在恶性肿瘤患者中,当恶性细胞受到(a)染色体畸变(s)的影响时,NIPT检测可能导致不一致的结果,就像本病例一样。由于会使NIPT结果的准确解释复杂化,在荷兰,母体恶性肿瘤是NIPT的禁忌症,特别是当涉及血液肿瘤bbb时。然而,被诊断为恶性肿瘤的患者的怀孕率明显较低;因此,目前尚不清楚在这一人群中有多少医学专家进行了关于NIPT的常规咨询。不知道cll的实验室将13q的缺失解释为潜在的胎儿,并通过羊膜穿刺术进行侵入性检测,因为这种染色体畸变可能与严重的胎儿畸形有关,这取决于确切的断点。这些不确定性给父母带来了很大的压力。由于对母体CLL的先验知识,患者和临床医生可能会共同选择放弃侵入性诊断测试,因为检测畸变可能反映母体血液学状况,而不是胎儿染色体畸变。由于肿瘤cfDNA可以掩盖胎儿cfDNA,因此NIPT不能提供胎儿的准确评估存在相当大的风险。因此,在所有母体恶性肿瘤的情况下,胎儿的细胞遗传学评估是需要的,应推荐羊膜穿刺术。我们的研究结果强调NIPT不适用于确诊为恶性肿瘤的孕妇。在这些情况下,很难准确地解释胎儿的遗传结构。 在这种情况下,如果需要确定染色体异常,则通过超声和羊膜穿刺术进行详细的结构异常筛查是最合适的选择,而不是NIPT。如果父母选择放弃这种侵入性检测,他们可能仍然会考虑NIPT,但只有在经过临床遗传学家的彻底遗传咨询以确保他们意识到异常结果相关的风险之后。随着解释循环cfDNA起源的新算法的出现,可靠测量胎儿分数的进步,以及检测非整倍体的改进方法的出现,未来的方法可能允许从NIPT分析中识别和排除肿瘤来源的cfDNA。从而减少误诊bbb的风险。在此之前,应该避免在恶性肿瘤患者中进行NIPT检测。Jorn Assmann:写作-原始草稿准备。Diane van Opstal:写作;可视化。Karin Diderich:资源;可视化。妮可·拉莫尼:写作;可视化。约里克·桑德伯格:资源;监督;写作-审查和编辑。约里克·桑德伯格:可以完全访问研究中的所有数据,并对数据的完整性负责。作者不报告任何潜在的利益冲突,包括相关的经济利益、活动、关系和从属关系(例如,就业、从属关系、赠款或资助、咨询、酬金或报酬、演讲者的机构、股票所有权或期权、专家证词、版税、医疗设备捐赠、或计划中的、待审的专利、与任何组织或实体有经济利益或与手稿中讨论的主题或材料有经济冲突。作者已确认该提交不需要临床试验注册。这项研究是按照《赫尔辛基宣言》所确立的伦理原则和准则进行的。作者没有得到这项工作的特别资助。在纳入本研究之前获得了患者的知情同意。向患者提供了有关研究目的、程序、风险和潜在益处的详细信息。患者有机会提出问题,并保证参与是自愿的,患者可以在任何时候退出而不会受到惩罚。患者被告知,数据将匿名化并保密,在分析和发表之前删除个人标识符。研究程序及个人资料的使用均符合有关的资料保障法例及机构指引。通过签署知情同意书,患者承认了解研究的目的并愿意参加研究。一份同意书副本已提供给病人作记录。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Noninvasive prenatal testing in CLL during pregnancy: A cautionary tale

Noninvasive prenatal testing in CLL during pregnancy: A cautionary tale

To the Editor:

Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world, with a median age at diagnosis of 72 years. An estimated 2% of the patients are females of childbearing age. CLL cases during pregnancy are rare and are associated with many complications. Although the implications and management of CLL in pregnancy have been discussed previously, issues related to noninvasive prenatal testing (NIPT) are often overlooked [1]. Various chromosomal changes are associated with CLL, with the deletion in the long arm of chromosome 13 at position q14 (deletion 13q14) being the most common alteration [2].

Since its implementation in clinical practice in 2011, NIPT was available to all pregnant women in the Netherlands in 2017. It has become a reliable and sensitive method of prenatal screening to evaluate the risk of fetal chromosomal imbalances. NIPT testing is primarily used to screen for Down (trisomy 21), Edwards (trisomy 18), or Patau (trisomy 13) syndromes. However, other deletions, such as del13q, can also be detected. NIPT can be performed as early as 10 weeks of gestations, and NIPT is based on the analysis of cell-free DNA (cfDNA) of which a small part is derived from the placenta, and the main part has a maternal origin [3]. However, with the NIPT test that is used in the Netherlands [4, 5], it is impossible to discriminate between fetal cfDNA and tumor-derived cfDNA, including CLL [6]. The finding of a chromosome aberration warrants further investigation using invasive prenatal procedures, such as chorionic villus sampling or amniocentesis. Maternal neoplasms causing aberrant NIPT results are a complex matter in prenatal diagnosis [7]. Cases describing discordant NIPT testing caused by a hematological malignancy remain very scarce [8], and this is the first report of a patient with diagnosed CLL having a discordant NIPT result post CLL diagnosis due to a molecular aberration of CLL cells.

A 33-year-old woman with a 1-year history of untreated CLL, had NIPT performed at 13 1/7 gestational weeks as a first-tier screening test for fetal aneuploidies. Ultrasound examinations at 6 and 12 gestational weeks showed a single viable intrauterine pregnancy, biometry appropriate for gestational age, and absence of gross fetal anomalies. The NIPT results indicated a high risk for chromosome 13q14 deletion (Figure 1). Genetic counseling of the woman and her partner was done. Our primary goal was to rule out the fetal origin of the abnormal result. Therefore, single nucleotide polymorphism array (SNP-array) on amniotic fluid cells and peripheral blood of the mother was performed to verify the abnormal NIPT result. While a mosaic loss of 10 Mb was identified in the maternal blood within the 13q14.11q14.3 region (arr[hg19] 13q14.11q14.3(40,484,657-50,909,942)x1∼2), the amniotic fluid was normal. Fluorescent in situ hybridization (FISH) on interphase nuclei cells of the mother confirmed a mosaic deletion on 13q (Figure 2). Ultrasound scans at 16, 20, and 24 gestational weeks reported no fetal anomalies. At 40 gestational weeks labor she gave birth to a healthy male baby.

In patients with malignancies, NIPT testing can potentially lead to discordant results when the malignant cells are affected with (a) chromosome aberration(s) like in the present case. As it will complicate the accurate interpretation of the NIPT results, a maternal malignancy is a contraindication for NIPT in the Netherlands, especially when it comes to hematological neoplasms [9]. Nevertheless, the incidence of pregnancy among patients diagnosed with malignancies is notably low; therefore, it is unknown how much routine counseling by medical specialists regarding NIPT is performed in this population. The laboratory—not knowing about the CLL—interpreted the deletion in 13q as potentially fetal, and invasive testing by amniocentesis was offered as this chromosome aberration can be associated with severe fetal malformations, depending on the exact breakpoints. These uncertainties led to a lot of stress for the parents. With prior knowledge of a maternal CLL, the patient and clinicians could have jointly opted to forgo invasive diagnostic testing as the detection of an aberration would likely have reflected the maternal hematological condition rather than a fetal chromosome aberration. As tumor cfDNA can mask fetal cfDNA, there is a considerable risk that NIPT will not provide an accurate assessment of the fetus. Therefore, in all cases of maternal malignancy where cytogenetic evaluation of the fetus is desired, amniocentesis should be recommended.

Our findings underline that NIPT is not advisable for pregnant women with confirmed malignancy [10]. In these cases, it can be difficult to accurately interpret the fetal genetic constitution.

Instead of NIPT, a detailed structural anomaly screening by ultrasound and an amniocentesis for karyotyping, if certainty on chromosomal abnormalities is desired, are the most appropriate options in these situations. If parents choose to forgo this invasive testing, they may still consider NIPT, but only after thorough genetic counseling by a clinical geneticist to ensure that they are aware of the risks associated with abnormal results.

With the advent of novel algorithms that account for the origin of circulating cfDNA, advancements in reliably measuring fetal fraction, and improved methodologies for detecting aneuploidies, future approaches may allow for the identification and exclusion of tumor-derived cfDNA from the NIPT analysis. Thereby reducing the risk of misdiagnoses [9]. Until then, NIPT testing in patients with malignancies should be avoided.

Jorn Assmann: writing—original draft preparation. Diane van Opstal: writing; visualization. Karin Diderich: resources; visualization. Nicole Larmonie: writing; visualization. Yorick Sandberg: resources; supervision; writing—review and editing. Yorick Sandberg: had full access to all the data in the study and takes responsibility for the integrity of the data.

The authors do not report any potential conflicts of interest, including relevant financial interests, activities, relationships, and affiliations (e.g., employment, affiliation, grants or funding, consultancies, honoraria or payment, speakers’ bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued) with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript.

The authors have confirmed clinical trial registration is not needed for this submission.

This study was conducted in accordance with the ethical principles and guidelines established by the Declaration of Helsinki.

The authors received no specific funding for this work.

Informed consent was obtained from the patient prior to their inclusion in this study. The patient was provided with detailed information about the purpose, procedures, risks, and potential benefits of the research. The patient was given the opportunity to ask questions and was assured that participation was voluntary and that the patient could withdraw at any time without penalty. The patient was informed that data would be anonymized and kept confidential, with personal identifiers removed prior to analysis and publication. The study procedures and use of personal data were in compliance with the relevant data protection laws and institutional guidelines. By signing the informed consent form, the patient acknowledged understanding of the study's aims and willingness to take part in the research. A copy of the consent form was provided to the patient for her records.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信