medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLC10.25557/2073-7998.2024.03.12-20medgen-2452Research ArticleНАУЧНЫЙ ОБЗОРREVIEWЭтические аспекты неинвазивного пренатального тестирования: автономия и информированный выборOrganisational complexities and ethical aspects of identifying incidental findings in whole-genome non-invasive prenatal testingБарановаЕ. Е.BaranovaE. E.

125993, г. Москва, ул. Баррикадная, д.2/1, стр.1;

115162, г. Москва, ул. Лестева, д. 18

2/1 Barrikadnaya st., Moscow, 125993

18, Lesteva st., Moscow, 115162

baranova.gen@gmail.comИжевскаяВ. Л.IzhevskayaV. L.

115522, г. Москва, ул. Москворечье, д. 1

1, Moskvorechie st., Moscow, 115478

ЕфремоваЕ. Е.EfremovaE. E.

125993, г. Москва, ул. Баррикадная, д.2/1, стр.1

2/1 Barrikadnaya st., Moscow, 125993

ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Министерства здравоохранения Российской Федерации; Общество с ограниченной ответственностью «Эвоген»РоссияRussian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation; Evogen Limited Liability CompanyRussian FederationФГБНУ «Медико-генетический научный центр имени академика Н.П. Бочкова»РоссияResearch Centre for Medical GeneticsRussian FederationФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Министерства здравоохранения Российской ФедерацииРоссияRussian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian FederationRussian Federation2024120720242331220Copyright © Баранова Е.Е., Ижевская В.Л., Ефремова Е.Е., 20242024Баранова Е.Е., Ижевская В.Л., Ефремова Е.Е.Baranova E.E., Izhevskaya V.L., Efremova E.E.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.medgen-journal.ru/jour/article/view/2452

Метод неинвазивного пренатального тестирования (НИПТ) получил широкое применение в клинической практике. Хотя показано положительное отношение к НИПТ как беременных женщин, так и медицинских работников, клиническое применение НИПТ привело к этическим дебатам с участием организаций пациентов, специалистов и представителей общественности. Этические проблемы, поднятые НИПТ, рассматриваются на основе ценностей свободного выбора, автономии и добровольного информированного согласия, избегания вреда, а также равенства, справедливости и инклюзивности. В представленной статье приведен обзор публикаций, посвященных защите автономии беременных и обеспечению осознанного информированного выбора при применении НИПТ в программах раннего пренатального скрининга.

Non-invasive prenatal testing (NIPT) is increasingly used in clinical practice. Although positive attitudes toward NIPT have been shown among both pregnant women and health care providers, the clinical use of NIPT has led to ethical debate involving patient organizations, professionals, and the public. The ethical issues raised by NIPT are discussed in relation to the values of free choice, autonomy, free informed consent, avoidance of harm, and equality, fairness and inclusion. This article provides an overview of publications devoted to protecting the autonomy of pregnant women and ensuring informed choices in NIPT in early prenatal screening programs.

cвободно циркулирующая фетоплацентарная ДНК (вкДНК)неинвазивное пренатальное тестированиебиоэтикаэтические проблемыавтономияинформированный выбормедико-генетическое консультированиеfree circulating fetoplacental DNA (ccDNA)non-invasive prenatal testingbioethicsethical problemsautonomyinformed choicegenetic counselingИсследование выполнено при финансовой поддержке Российского научного фонда, проект № 19-18-00422.The research was supported by a grant from the Russian Science Foundation (project No. 19-18-00422).ReferencesChitty L.S., Lo Y.M. Noninvasive prenatal screening for genetic diseases using mass parallel sequencing of maternal plasma DNA. Cold Spring Harb Perspect Med. 2015; 5(9): a023085. Doi: 10.1101/cshperspect.a023085Chitty L.S., Lo Y.M. Noninvasive prenatal screening for genetic diseases using mass parallel sequencing of maternal plasma DNA. Cold Spring Harb Perspect Med. 2015;5 (9): a023085. Doi: 10.1101/cshperspect.a023085Bianchi D.W., Chiu R.W.K. Sequencing of circulating cell-free DNA during pregnancy. N Engl J Med. 2018;379:464–73.Bianchi D.W., Chiu R.W.K. Sequencing of circulating cell-free DNA during pregnancy. N Engl J Med. 2018;379:464–73.van Schendel R.W., van El C.G., Paikrt E., et al. Implementation of noninvasive prenatal testing for aneuploidy in the national health care system: global challenges and national solutions. BMC Health Serve 2017;17(1):670. Doi: 10.1186/s12913-017-2618-0van Schendel R.W., van El C.G., Paikrt E., et al. Implementation of noninvasive prenatal testing for aneuploidy in the national health care system: global challenges and national solutions. BMC Health Serve 2017;17(1):670. Doi: 10.1186/s12913-017-2618-0Gadsbøll K., Petersen O.B., Gatinois V., et al. Current use of noninvasive prenatal testing in Europe, Australia and the USA: a graphical presentation. Acta Obstet Gynecol Scand. 2020;99:722–30.Gadsbøll K., Petersen O.B., Gatinois V., et al. Current use of noninvasive prenatal testing in Europe, Australia and the USA: a graphical presentation. Acta Obstet Gynecol Scand. 2020; 99: 722–30.Калашникова Е.А., Глотов А.С., Андреева Е.Н., и др. Современное значение неинвазивного пренатального исследования внеклеточной ДНК плода в крови матери и перспективы его применения в системе массового скрининга беременных в Российской Федерации. Журнал акушерства и женских болезней. 2021; 70(1): 19–50. DOI: https://doi.org/10.17816/JOWD56573Kalashnikova E.A., Glotov A.S., Andreyeva E.N., et al. Sovremennoye znacheniye neinvazivnogo prenatal’nogo issledovaniya vnekletochnoy DNK ploda v krovi materi i perspektivy yego primeneniya v sisteme massovogo skrininga beremennykh v Rossiyskoy Federatsii [Current relevance of non-invasive prenatal studyof cell-free fetal DNA in the mother’s blood and prospects for its application in mass screening of pregnant women in the Russian Federation]. Zhurnal akusherstva i zhenskikh bolezney [Journal of Obstetrics and Women’s Diseases]. 2021;70(1):19–50. (In Russ.) Doi: 10.17816/JOWD56573Капланова М.Т., Галактионова А.М., Сагайдак О.В., и др. Применение неинвазивного пренатального теста в Ямало-Ненецком автономном округе. Акушерство и гинекология. 2022; 7:104-112. Doi:10.18565/aig.2022.7.104-112Kaplanova M.T., Galaktionova A.M., Sagaydak O.V., et al. Primeneniye neinvazivnogo prenatal’nogo testa v Yamalo-Nenetskom avtonomnom okruge [Application of a noninvasive prenatal test in the Yamal-Nenets Autonomous Area]. Akusherstvo i ginekologiya [Obstetrics and Gynegology]. 2022; 7:104-112. (In Russ.)Baranova E.E., Sagaydak O.V., Galaktionova A.M. et al. Whole genome non-invasive prenatal testing in prenatal screening algorithm: clinical experience from 12,700 pregnancies. BMC Pregnancy Childbirth. 2022; 22: 633. Doi: 10.1186/s12884-022-04966-8Baranova E.E., Sagaydak O.V., Galaktionova A.M. et al. Whole genome non-invasive prenatal testing in prenatal screening algorithm: clinical experience from 12,700 pregnancies. BMC Pregnancy Childbirth. 2022; 22: 633. Doi: 10.1186/s12884-022-04966-8van Schendel R.V., Kleinveld J.H., Dondorp W.J., Pajkrt E., et al. Attitudes of pregnant women and male partners towards non-invasive prenatal testing and widening the scope of prenatal screening. Eur J Hum Genet. 2014;22:1345–50.van Schendel R.V., Kleinveld J.H., Dondorp W.J., Pajkrt E., et al. Attitudes of pregnant women and male partners towards non-invasive prenatal testing and widening the scope of prenatal screening. Eur J Hum Genet. 2014;22:1345–50.Hill M., Johnson J.-A., Langlois S., et al. Preferences for prenatal tests for Down syndrome: an international comparison of the views of pregnant women and health professionals. Eur J Hum Genet. 2015;24:968–75.Hill M., Johnson J.-A., Langlois S., et al. Preferences for prenatal tests for Down syndrome: an international comparison of the views of pregnant women and health professionals. Eur J Hum Genet. 2015;24:968–75.Dondorp W., de Wert G., Bombard Y., et al. Non-invasive prenatal testing for aneuploidy and beyond: challenges of responsible innovation in prenatal screening. Eur J Hum Genet. 2015;23:1438–50.Dondorp W., de Wert G., Bombard Y., et al. Non-invasive prenatal testing for aneuploidy and beyond: challenges of responsible innovation in prenatal screening. Eur J Hum Genet. 2015;23:1438–50.Nuffield Council on Bioethics. Non-invasive prenatal testing: ethical issues. March 2017:1-169.Nuffield Council on Bioethics. Non-invasive prenatal testing: ethical issues. March 2017:1-169.Потапов А.А., Капланова М.Т., Галактионова А.М., и др. Этические аспекты применения полногеномного неинвазивного пренатального тестирования. Медицинская генетика. 2023;22(11):3-12. Doi: 10.25557/2073-7998.2023.11.3-12Potapov A.A., Kaplanova M.T., Galaktionova A.M., et al. Eticheskiye aspekty primeneniya polnogenomnogo neinvazivnogo prenatal’nogo testirovaniya [Ethical aspects of whole-genome noninvasive prenatal testing]. Meditsinskaya genetika [Medical Genetics]. 2023;22(11):3-12. (In Russ.) Doi: 10.25557/2073-7998.2023.11.3-12Perrot A., Horn R. The ethical landscape(s) of non-invasive prenatal testing in England, France and Germany: findings from a comparative literature review. Eur J Hum Genet. 2022; 30: 676–681. Doi: 10.1038/s41431-021-00970-2Perrot A., Horn R. The ethical landscape(s) of non-invasive prenatal testing in England, France and Germany: findings from a comparative literature review. Eur J Hum Genet. 2022; 30: 676–681. Doi: 10.1038/s41431-021-00970-2Van Schendel R.V., Kleinveld J.H., Dondorp W.J., et al. Attitudes of pregnant women and male partners towards non-invasive prenatal testing and widening the scope of prenatal screening. Eur J Hum Genet. 2014;22:1345–50. doi: 10.1038/ejhg.2014.32.Van Schendel R.V., Kleinveld J.H., Dondorp W.J., et al. Attitudes of pregnant women and male partners towards non-invasive prenatal testing and widening the scope of prenatal screening. Eur J Hum Genet. 2014;22:1345–50. doi: 10.1038/ejhg.2014.32.Horn R., Parker M. Opening Pandora’s box? Ethical issues in prenatal whole genome and exome sequencing. Prenat Diagn. 2018;38:20–5.Horn R., Parker M. Opening Pandora’s box? Ethical issues in prenatal whole genome and exome sequencing. Prenat Diagn. 2018;38:20–5.Brison N., Van den Bogaert K., Dehaspe L., et al. Accuracy and clinical value of maternal incidental findings during noninvasive prenatal testing for fetal aneuploidies. Obstetrical Gynecol Surv. 2017;72:469–70. doi: 10.1097/01.ogx.0000521918.86380.15.Brison N., Van den Bogaert K., Dehaspe L., et al. Accuracy and clinical value of maternal incidental findings during noninvasive prenatal testing for fetal aneuploidies. Obstetrical Gynecol Surv. 2017;72:469–70. doi: 10.1097/01.ogx.0000521918.86380.15.Minear M.A., Alessi S., Allyse M., Michie M., Chandrasekharan S. Noninvasive prenatal genetic testing: current and emerging ethical, legal, and social issues. Annu Rev Genomics Hum Genet. 2015;16:369–98. doi: 10.1146/annurev-genom-090314-050000.Minear M.A., Alessi S., Allyse M., Michie M., Chandrasekharan S. Noninvasive prenatal genetic testing: current and emerging ethical, legal, and social issues. Annu Rev Genomics Hum Genet. 2015;16:369–98. doi: 10.1146/annurev-genom-090314-050000.Grace M.R., Hardisty E., Dotters-Katz S.K., Vora N.L., Kuller J.A. Cell-free DNA screening: complexities and challenges of clinical implementation. Obstet. Gynecol. Surv. 2016; 71: 477–487. doi: 10.1097/OGX.0000000000000342Grace M.R., Hardisty E., Dotters-Katz S.K., Vora N.L., Kuller J.A. Cell-free DNA screening: complexities and challenges of clinical implementation. Obstet. Gynecol. Surv. 2016; 71: 477–487. doi: 10.1097/OGX.0000000000000342Bedei I., Wolter A., Weber A., Signore F., Axt-Fliedner R. Chances and challenges of new genetic screening technologies (NIPT) in prenatal medicine from a clinical perspective: a narrative review. Genes. 2021;12:1–14. doi: 10.3390/genes12040501.Bedei I., Wolter A., Weber A., Signore F., Axt-Fliedner R. Chances and challenges of new genetic screening technologies (NIPT) in prenatal medicine from a clinical perspective: a narrative review. Genes. 2021;12:1–14. doi: 10.3390/genes12040501.Deutscher Ethikrat. The future of genetic diagnosis—from research to clinical practice. 30/04/2013:1-191.Deutscher Ethikrat. The future of genetic diagnosis—from research to clinical practice. 30/04/2013:1-191.Hill M., Barrett A., Choolani M., Lewis C., Fisher J., Chitty L.S. Has noninvasive prenatal testing impacted termination of pregnancy and live birth rates of infants with Down syndrome? Prenat Diagn. 2017;37:1281–90. doi: 10.1002/pd.5182.Hill M., Barrett A., Choolani M., Lewis C., Fisher J., Chitty L.S. Has noninvasive prenatal testing impacted termination of pregnancy and live birth rates of infants with Down syndrome? Prenat Diagn. 2017;37:1281–90. doi: 10.1002/pd.5182.Vanstone M., Cernat A., Majid U., Trivedi F., De Freitas C. Perspectives of pregnant people and clinicians on noninvasive prenatal testing: a systematic review and qualitative meta-synthesis. Ont Health Technol Assess Ser. 2019;19:1–38.Vanstone M., Cernat A., Majid U., Trivedi F., De Freitas C. Perspectives of pregnant people and clinicians on noninvasive prenatal testing: a systematic review and qualitative meta-synthesis. Ont Health Technol Assess Ser. 2019;19:1–38.Cernat A., De Freitas C., Majid U., Trivedi F., Higgins C., Vanstone M. Facilitating informed choice about non-invasive prenatal testing (NIPT): a systematic review and qualitative meta-synthesis of women’s experiences. BMC Pregnancy Childbirth. 2019;19:27.Cernat A., De Freitas C., Majid U., Trivedi F., Higgins C., Vanstone M. Facilitating informed choice about non-invasive prenatal testing (NIPT): a systematic review and qualitative meta-synthesis of women’s experiences. BMC Pregnancy Childbirth. 2019;19:27.Kater-Kuipers A, de Beaufort ID, Galjaard R-JH, Bunnik EM. Ethics of routine: a critical analysis of the concept of ‘routinisation’ in prenatal screening. J Med Ethics. 2018;44:626–31.Kater-Kuipers A, de Beaufort ID, Galjaard R-JH, Bunnik EM. Ethics of routine: a critical analysis of the concept of ‘routinisation’ in prenatal screening. J Med Ethics. 2018;44:626–31.Marteau TM, Dormandy E, Michie S. A measure of informed choice. Health Expect. 2001;4:99–108.Marteau TM, Dormandy E, Michie S. A measure of informed choice. Health Expect. 2001;4:99–108.Lewis C., Hill M., Skirton H., Chitty L.S. Development and validation of a measure of informed choice for women undergoing non-invasive prenatal testing for aneuploidy. Eur J Hum Genet. 2016;24:809–16.Lewis C., Hill M., Skirton H., Chitty L.S. Development and validation of a measure of informed choice for women undergoing non-invasive prenatal testing for aneuploidy. Eur J Hum Genet. 2016;24:809–16.van Schendel R.V., Page-Christiaens G.C., Beulen L., et al. Trial by Dutch laboratories for evaluation of non-invasive prenatal testing. Part II-women’s perspectives. Prenat Diagn. 2016;36:1091–8.van Schendel R.V., Page-Christiaens G.C., Beulen L., et al. Trial by Dutch laboratories for evaluation of non-invasive prenatal testing. Part II-women’s perspectives. Prenat Diagn. 2016;36:1091–8.van der Meij K.R.M., Njio A., Martin, L., et al. Routinization of prenatal screening with the non-invasive prenatal test: pregnant women’s perspectives. Eur J Hum Genet. 2022; 30: 661–668. Doi:10.1038/s41431-021-00940-8van der Meij K.R.M., Njio A., Martin, L., et al. Routinization of prenatal screening with the non-invasive prenatal test: pregnant women’s perspectives. Eur J Hum Genet. 2022; 30: 661–668. Doi:10.1038/s41431-021-00940-8van Bruggen M.J., Henneman L., Timmermans D.R.M. Women’s decision making regarding prenatal screening for fetal aneuploidy: a qualitative comparison between 2003 and 2016. Midwifery. 2018;64:93–100van Bruggen M.J., Henneman L., Timmermans D.R.M. Women’s decision making regarding prenatal screening for fetal aneuploidy: a qualitative comparison between 2003 and 2016. Midwifery. 2018;64:93–100Bakkeren I.M., Kater-Kuipers A., Bunnik E.M., et al. Implementing non-invasive prenatal testing (NIPT) in the Netherlands: an interview study exploring opinions about and experiences with societal pressure, reimbursement, and an expanding scope. J Genet Couns. 2020;29:112–21.Bakkeren I.M., Kater-Kuipers A., Bunnik E.M., et al. Implementing non-invasive prenatal testing (NIPT) in the Netherlands: an interview study exploring opinions about and experiences with societal pressure, reimbursement, and an expanding scope. J Genet Couns. 2020;29:112–21.Ravitsky V., Birko S., Le Clerc-Blain J., et al. Noninvasive prenatal testing: views of Canadian pregnant women and their partners regarding pressure and societal concerns. AJOB Empir Bioeth. 2021;12:53–62.Ravitsky V., Birko S., Le Clerc-Blain J., et al. Noninvasive prenatal testing: views of Canadian pregnant women and their partners regarding pressure and societal concerns. AJOB Empir Bioeth. 2021;12:53–62.Crombag N.M., Vellinga Y.E., Kluijfhout S.A., et al. Explaining variation in Down’s syndrome screening uptake: comparing the Netherlands with England and Denmark using documentary analysis and expert stakeholder interviews. BMC Health Serv Res. 2014;14:437.Crombag N.M., Vellinga Y.E., Kluijfhout S.A., et al. Explaining variation in Down’s syndrome screening uptake: comparing the Netherlands with England and Denmark using documentary analysis and expert stakeholder interviews. BMC Health Serv Res. 2014;14:437.Chitty L.S., Wright D., Hill M., et al. Uptake, outcomes, and costs of implementing non-invasive prenatal testing for Down’s syndrome into NHS maternity care: prospective cohort study in eight diverse maternity units. BMJ. 2016;354:i3426.Chitty L.S., Wright D., Hill M., et al. Uptake, outcomes, and costs of implementing non-invasive prenatal testing for Down’s syndrome into NHS maternity care: prospective cohort study in eight diverse maternity units. BMJ. 2016;354:i3426.Gregg A.R., Skotko B.G., Benkendorf J.L., et al. Noninvasive prenatal screening for fetal aneuploidy, 2016 update: a position statement of the American College of Medical Genetics and Genomics. Genet Med. 2016;18(10):1056–1065. doi: 10.1038/gim.2016.97Gregg A.R., Skotko B.G., Benkendorf J.L., et al. Noninvasive prenatal screening for fetal aneuploidy, 2016 update: a position statement of the American College of Medical Genetics and Genomics. Genet Med. 2016;18(10):1056–1065. doi: 10.1038/gim.2016.9733 11 Bianchi DW, Chiu RWK. Sequencing of circulating cell-free DNA during pregnancy. N Engl J Med. 2018;379(5):464–473. doi: 10.1056/NEJMra1705345Bianchi DW, Chiu RWK. Sequencing of circulating cell-free DNA during pregnancy. N Engl J Med. 2018;379(5):464–473. doi: 10.1056/NEJMra1705345Sachs A., Blanchard L., Buchanan A., et al. Recommended pretest counseling points for noninvasive prenatal testing using cellfree DNA: a 2015 perspective. Prenat Diagn. 2015;35:968–971. doi: 10.1002/pd.4666Sachs A., Blanchard L., Buchanan A., et al. Recommended pretest counseling points for noninvasive prenatal testing using cellfree DNA: a 2015 perspective. Prenat Diagn. 2015;35:968–971. doi: 10.1002/pd.4666Heinrichs B. Moral ambivalence. Commentary on noninvasive prenatal testing from an ethical perspective. 2021 DOI: 10.1515/jpm2021-0194Heinrichs B. Moral ambivalence. Commentary on noninvasive prenatal testing from an ethical perspective. 2021 DOI:10.1515/jpm2021-0194de Jong A., Dondorp W., de Die-Smulders C. et al. Non-invasive prenatal testing: ethical issues explored. Eur J Hum Genet. 2010; 18: 272–277). doi:10.1038/ejhg.2009.203de Jong A., Dondorp W., de Die-Smulders C. et al. Non-invasive prenatal testing: ethical issues explored. Eur J Hum Genet. 2010; 18: 272–277). doi:10.1038/ejhg.2009.203Hartwig T.S., Ambye L., Sørensen S., Jørgensen F.S. Discordant non-invasive prenatal testing (NIPT) — a systematic review. Prenat. Diagn. 2017; 37(6): 527–539. doi: 10.1002/pd.5049Hartwig T.S., Ambye L., Sørensen S., Jørgensen F.S. Discordant non-invasive prenatal testing (NIPT) — a systematic review. Prenat. Diagn. 2017; 37(6): 527–539. doi: 10.1002/pd.5049Petersen O.B., Vogel I., Eklund C., et al. Potential diagnostic consequences of applying non-invasive prenatal testing: Population-based study from a country with existing first-trimester screening. Ultrasound Obstet Gynecol 2014;43(3):265–71Petersen O.B., Vogel I., Eklund C., et al. Potential diagnostic consequences of applying non-invasive prenatal testing: Population-based study from a country with existing first-trimester screening. Ultrasound Obstet Gynecol 2014;43(3):265–71Moufarrej M.N., Bianchi D.W., Shaw G.M., Stevenson D.K., Quake S.R. Noninvasive Prenatal Testing Using Circulating DNA and RNA: Advances, Challenges, and Possibilities. Annu Rev Biomed Data Sci. 2023;6:397-418. doi: 10.1146/annurev-biodatasci-020722-094144.Moufarrej M.N., Bianchi D.W., Shaw G.M., Stevenson D.K., Quake S.R. Noninvasive Prenatal Testing Using Circulating DNA and RNA: Advances, Challenges, and Possibilities. Annu Rev Biomed Data Sci. 2023;6:397-418. doi: 10.1146/annurev-biodatasci-020722-094144.Баранова Е.Е., Беленикин М.С., Жученко Л.А., Ижевская В.Л. Неинвазивные пренатальные тесты: европейские и американские рекомендации по применению в клинической практике. Медицинская генетика. 2017;16(8):3-10.Baranova E.E., Belenikin M.S., Zhuchenko L.A., Izhevskaya V.L. Neinvazivnyye prenatal’nyye testy: yevropeyskiye i amerikanskiye rekomendatsii po primeneniyu v klinicheskoy praktike [Non-invasive prenatal tests: European and American recommendations]. Meditsinskaya genetika [Medical Genetics]. 2017;16(8):3-10. (In Russ.)

The authors declare that there are no conflicts of interest present.