Prenatal Diagnosis, Screening and Wrongful Birth

Prenatal diagnosis based on different technologies is increasingly used in developed countries and has become a common strategy in obstetric practice. The tests are crucial in enabling mothers to make informed decisions about the possibility of terminating pregnancy. They have generated numerous bioethical and legal controversies in the field of 'wrongful life' claims (action brought by or on behalf of a child against the mother or other people, claiming that he or she has to endure a not-worth-living existence) and 'wrongful birth' claims (action brought by the mother or parents against the physician for being burdened with an unwanted, often disabled child, which could have been avoided). The possibility which exists nowadays to intervene actively by programming and deciding the phases linked to procreation and birth has raised several questions worldwide. The mother's right to self-determination could be an end but whether or not this right is absolute is debatable. Freedom could, with time, act as a barrier that obstructs intrusion into other people's lives and their personal choices. Therapeutic choices may be manageable in a liberal sense, and the sanctity of life can be inflected in a secular sense. These sensitive issues and the various points of view to be considered have motivated this review. Literature searches were conducted on relevant demographic, social science and medical science databases (SocINDEX, Econlit, PopLine, Medline, Embase and Current Contents) and via other sources. Searches focused on subjects related to bioethical and legal controversies in the field of preimplantation and prenatal diagnosis, wrongful birth and wrongful life. A review of the international state of law was carried out, focusing attention on the peculiar issue of wrongful life and investigating the different jurisdictional solutions of wrongful life claims in a comparative survey. Courts around the world are generally reluctant to acknowledge wrongful life claims due to their ethical and legal implications, such as existence as an injury, the right not to be born, the nature of the harm suffered and non-existence as an alternative to a disabled life. Most countries have rejected such actions while at the same time approving those for wrongful birth. Some countries, such as France with a law passed in March 2002, have definitively excluded Wrongful Life action. Only in the Netherlands and in three states of the USA (California, Washington and New Jersey) Wrongful Life actions are allowed. In other countries, such as Belgium, legislation is unclear because, despite a first decision of the Court allowing Wrongful Life action, the case is still in progress. There is a complete lack of case law regarding wrongful conception, wrongful birth and wrongful life in a few countries, such as Estonia. The themes of 'wrongful birth' and 'wrongful life' are charged with perplexing ethical dilemmas and raise delicate legal questions. These have met, in various countries and on certain occasions, with different solutions and have triggered ethical and juridical debate. The damage case scenarios result from a lack of information or diagnosis prior to the birth, which deprives the mother of the chance to terminate the pregnancy.

Prenatal screening and diagnosis—An introduction

Background: In China, congenital heart disease (CHD) is the most common birth defect type, with approximately 13,000 new cases annually. This study aimed to investigate high-risk factors, prenatal screening and prenatal diagnosis as a basis for clinical decisions.Methods: All CHD cases identified from 2018 to 2020 were obtained from the Beijing city birth defect surveillance system and prenatal diagnosis institutions. The prenatal CHD diagnosis was confirmed by fetal echocardiography and amniotic fluid or cord blood genetic examination. Chi-square, odds ratio (OR), 95% confidence interval (CI), and univariate and multivariate logistic analyses were used to explore the high-risk factors, prenatal screening and prenatal diagnosis of CHD. Results: In total, 6,786/594,860 fetuses with CHD were diagnosed by prenatal echocardiography. The average incidence of CHD was 11.4 per 1,000 births, with an increase of 30.7 per 1,000 births from 2018 to 2020 (P < 0.05); the average incidence of complex CHD (CCHD) was 2.02 per 1,000 births, with no significant change from 2018 to 2020 (P > 0.05). Women age ≥35 years (OR 1.06, 95% CI 0.77–1.46) was at higher risk of having babies with CHD than women aged 21–34 years. Overall, CHD incidence increased with maternal age (OR1.03, 95% CI 1.02–1.03). Additionally, women who had a non-local household registration (OR 1.16, 95% CI 1.10–1.22) or had diabetes mellitus (DM) (OR 1.16, 95% CI 0.96–1.25) were at higher risk of CHD. As an independent factor, CCHD was related to maternal age, DM, fetal gender, and maternal education level (all P < 0.05). The prenatal ultrasound screening detection rate of CCHD was 97.59%, which was far higher than that of total CHD (51.67%) (P < 0.001). The prenatal ultrasound diagnosis rate of CCHD was higher than that of simple CHD (P < 0.001), but the coincidence rate in the ultrasound diagnosis of CCHD was lower than that of simple CHD (P < 0.001). Prenatal genetic testing revealed chromosomal abnormalities in 25.62% (279/1089) of CHD cases with indications for a prenatal diagnosis.Conclusions: Maternal age, household registration and DM were related to CHD occurrence. Prenatal ultrasound screening is a highly effective method for CCHD diagnosis, and CHD fetuses should be closely evaluated to exclude chromosomal abnormalities.

A new comprehensive paradigm for prenatal diagnosis: seeing the forest through the trees.

Prenatal screening and diagnosis concern the provision of information about the health or condition of a developing fetus to a pregnant woman or couple. One implication of receiving this information is that she, or they, may consider whether to continue a pregnancy in which the fetus’s health or condition appears or is in some way compromised. Unlike pre-implantation genetic diagnosis, which has recently been the subject of a public consultation exercise and a report by the Human Fertilisation and Embryology Authority (HFEA) and Human Genetics Commission (HGC), the issue of prenatal screening and diagnosis has, unfortunately, never received public appraisal. Yet there has been a burgeoning of philosophical, sociological and legal interest in this area. In part this has been fueled by concerns about developments in the relevant genetic technology, particularly the ability to screen and test for an increasingly wide range of sometimes not very significant conditions or features. People with disabilities have also voiced concerns, especially about the routine nature of prenatal screening and the implications for them of its widespread use. Numerous issues arise in the light of such concerns. This article focuses on one — the locus and extent of legal decision-making power as regards the disabled fetus. It does this by exploring how the relationship between the law of abortion and that of wrongful birth affects the scope of a pregnant woman’s decision-making abilities in this context. The connecting thread here is that a woman to whom the issue of fetal disability is important must be informed of the health or condition of the fetus if she is meaningfully to exercise whatever legal option she has in deciding whether to continue a given pregnancy.

Prenatal Screening for and Diagnosis of Aneuploidy in Twin Pregnancies

A new opinion from the American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-Fetal Medicine (SMFM) says obstetricians can offer noninvasive prenatal testing (NIPT) to women at high risk of delivering babies with Down syndrome and trisomies 13 and 18.

To evaluate the efficacy of non-invasive prenatal testing (NIPT) in the prenatal screening and its role in the system of prenatal diagnosis. A total of 22 649 singleton pregnant women who were registered and finally delivered or had induced labor at Beijing Obstetrics and Gynecology Hospital of Capital Medical University were enrolled. The routes of prenatal screening were analyzed to evaluate the efficacy of prenatal screening. Meanwhile, 9268 pregnant women who underwent invasive prenatal diagnosis procedure were enrolled. The indications and results of prenatal diagnosis were analyzed to evaluate the effectiveness of prenatal screening. 60.24% of singleton pregnant women have opted for Down syndrome screening, and their age was mainly under 35. The proportion of women opted for NIPT was 34.74%, and were mainly between 35 and 39. The overall diagnostic rate of trisomy 21, 18 and 13 trisomy for those with high risk by NIPT was 0.89%, which yielded a positive predictive value of 75.71%. For those with moderate risk by serum screening, 0.30% was predicted with a high risk by NIPT. Among women undergoing prenatal diagnosis, 63.04% and 21.22% had the indication of advanced age or high risk by serum screening, and the positive predictive values were 5.1% and 5.13%, respectively. By contrast, 2.30% of women undergoing prenatal diagnosis had a high risk by NIPT, which yielded a positive predictive value of 54.46%. With the change of the age composition of pregnant women and increase in the complexity of pregnancy in China, to build a prenatal screening system based on NIPT will be helpful to improve the efficiency of the current system of prenatal screening and diagnosis.

In the twentieth century, technological capacities to surveil and monitor pregnancies have expanded dramatically. Prenatal screening refers to systematic, population-wide efforts to identify health problems during the development of a fetus, while prenatal diagnosis refers to the biomedical conclusions made regarding the nature of such problems. Technologies for prenatal screening and testing were increasingly incorporated in routine pregnancy care in affluent parts of the world during the 1980s and 1990s and are currently routinizing across the globe. This article highlights key themes in anthropological studies of prenatal screening and diagnosis, dividing the literature into three main themes: Pregnancy experiences; pregnancy decision-making; and pregnancy governance. Anthropologists have, firstly, produced detailed accounts of the ways in which prenatal diagnosis changes pregnancy experiences, deepening the uncertainties that surround childbearing. Secondly, anthropological research has documented the—sometimes excruciating—decision-making processes that prenatal screening and diagnosis may entail. Finally, anthropologists have produced critical analyses of the political and economic forces that drive the introduction and uptake of new technologies for selective reproduction. We conclude by summarizing the contributions made by research in this field to the anthropology of reproduction.

Congenital defects and genetic diseases in the fetus are the focus of prenatal screening and prenatal diagnosis. Obstetrics and gynecology, pediatrics, medical imaging (ultrasound and magnetic resonance imaging), clinical laboratory, pathology, and other disciplines are mostly involved in this multidisciplinary work on maternal and infant health care, which aims to prevent birth defects in strict accordance with laws, regulations, and pertinent industry standards, such as the Notice of the National Health Commission on Issuing the Basic Standards for Prenatal Screening Technical Medical Institutions and the Basic Standards for Prenatal Diagnosis Technical Medical Institutions (Guowei Maternal and Child Letter [2019] No. 297). To further support the implementation of prenatal screening and diagnosis work and streamline workflow, this study has compiled the timing, inspection, and testing procedures of various projects in each link from the standpoint of the disease clinical laboratory diagnostic pathway. This approach improves communication amongst various disciplines in prenatal screening and diagnosis work and offers clinical service quality, and it also helps improve the standard of the birth population and prevent and controll severe birth defects.

To evaluate a microarray-based mutation screening method for genetic deafness and its application in prenatal diagnosis. Mutation screening of common deafness genes was performed in pregnant women and volunteers spouses. Nine common mutations in four major deafness genes, GJB2, GJB3, SLC26A4 and mitochondrial 12S rRNA, were detected simultaneously by a microarray-based method. Genetic counseling was given based on their testing results. 5.11% of pregnant women carried at least one mutation. Among them, seven carried mutation in the mitochondria 12S rRNA gene and were offered aminoglycoside-induced ototoxicity warning. For other mutation carriers of GJB2 or SLC26A4 genes, additional mutation screening was performed in their husbands by direct sequencing. A total of 20 couples were at risk of giving birth to children with genetic deafness. Of five couples who selected to undergo prenatal diagnostic testing of the fetus, four were diagnosed as wild type or heterozygous for the tested genes and one as p.V37I/c.235delC compound heterozygous for GJB2. DNA microarray is a quick, easy and reliable method to screen mutations in genetic deafness genes. Application of this method in prenatal screening and diagnosis might effectively reduce the occurrence of genetic deafness.

To what extent should parents be able to choose the kind of child they have? The unfortunate phrase ‘designer baby’ has become familiar in debates surrounding reproduction. As a reference to current possibilities the term is misleading, but the phrase may indicate a societal concern of some kind about control and choice in the course of reproduction. Typically, people can choose whether to have a child. They may also have an interest in choosing, to some extent, the conditions under which they do so, such as whether they have a child with a serious disability or disease. The purpose of this book is to explore the difficult and controversial question of the appropriate ethical and legal extent of reproductive autonomy in this context.

Objective To evaluate the value of non-invasive prenatal testing (NIPT) in pregnancies with anomaly in prenatal screening. Methods This was a retrospective study of 2 837 singleton pregnancies who performed NIPT indicated by isolated anomaly in prenatal screening at Guangdong Women and Children Hospital between November 2014 and August 2016. All pregnancies were divided into 3 groups by single indication: advanced maternal age ( AMA, ≥35), abnormal multiples of the median (MoM) in standard screening, increased nuchal translucency thickness (NT, 2.5-3.0 mm). High risk results were verified by prenatal diagnosis. Low risk cases were followed by a 22-26 week anatomical ultrasound examination. All of the cases were followed up and the performance of NIPT for every single indication was evaluated. Results There were total of 2 837 pregnant women who underwent NIPT. Twenty-five of 2 448 pregnancies indicated by AMA had high risk results, among which 17 were confirmed by invasive genetic testing, except 1 case rejecting prenatal diagnosis. In 351 pregnant women with abnormal MoM, NIPT found 3 cases of sex chromosome aneuploidies (SCA) and 2 of them were validated by invasive prenatal diagnosis. Increased NT group included 38 cases, NIPT found 1 case of trisomy 21 which was consistent with karyotype analysis. For common aneuploidies and SCA, the performance of NIPT in the pregnant women who indicated by AMA, abnormal MoM and increased NT were as the follows: the sensitivity were 17/17, 2/2 and 1/1 respectively, the specificity were 99.7% (2 423/2 431), 99.7% (348/349) and 100%(37/37), the positive predictive value were 68% (17/25), 2/3 and 1/1, the negative predictive value were 100% (2 423/2 423), 100% (348/348) and 100% (38/38), respectively. By follow-up survey, a total of 8 cases of abnormal fetus were recorded in NIPT low-risk women, including 5 cases of termination of pregnancy due to abnormal ultrasound findings, 2 cases of abortion as a result of severe obstetric complications and 1 case of stillbirth. Conclusions To the pregnant women who indicated by advanced maternal age, abnormal MoM and increased NT (2.5-3.0 mm), NIPT had satisfactory performance for common aneuploidies, and also had potential value for SCA, resulting in a significant reduction in diagnostic procedures. However, for NIPT low-risk pregnancies, routine antenatal examination and anatomical ultrasound detection would be highly necessary to avoid missing abnormal fetuses.(Chin J Lab Med, 2018, 41: 509-513) Key words: Aneuploidy; Prenatal diagnosis; Genetic testing; Nuchal translucency measurement

In Reply .— “Prenatal Screening and Diagnosis for Pediatricians”1 is published as a clinical report, intended to provide guidance to the clinician in rendering pediatric care. The report clearly identifies the risks and benefits of prenatal diagnosis and screening procedures at an appropriate level for pediatric practice. Cost-benefit analyses are far beyond the scope of such a statement and are not pertinent to pediatric practice, which does not involve prenatal diagnostic procedures. Dr Chilton takes issue with our assertion that prenatal diagnosis is indicated whenever certain high-risk situations arise. In this context it is important to recognize that prenatal diagnosis is not just a procedure, it is a process that involves pretest counseling, history taking, physical examination, clinical procedures, laboratory testing, and posttest counseling. Responsible and prudent practice requires at-risk families …

Great efforts have been made in the prenatal screening and prenatal diagnosis of aneuploidy in China.Nevertheless, the coverage percentage of screening is still low, and the capability of diagnosis is far from enough.To elevate the efficacy of prenatal screening, developing fast aneuploidy diagnositic techniques is quite important.Cell-free DNA testing is believed to be a confirmatory screening test of aneuploidy.Fluorescence in situ hybridization, fluorescence quantitative PCR might be used in the prenatal diagnosis in high risk women. Chromosomal microarray analysis has high sensitivity in the diagnosis of microdeletion and microduplication.The era of cytomolecular diagnosis is coming.（Chin J Lab Med,2014,37:245-247） Key words: Prenatal diagnosis; Molecular diagnostic techniques; Genetic screening