Ethical considerations of early (first vs. second trimester) risk assessment disclosure for trisomy 21 and patient choice in screening versus diagnostic testingкод для вставкиСкачать
American Journal of Medical Genetics Part C (Seminars in Medical Genetics) 145C:99 – 104 (2007) A R T I C L E Ethical Considerations of Early (First vs. Second Trimester) Risk Assessment Disclosure for Trisomy 21 and Patient Choice in Screening Versus Diagnostic Testing GEETA SHARMA,* LAURENCE B. MCCULLOUGH, AND FRANK A. CHERVENAK We discuss the clinical implications regarding disclosure of risk assessment for trisomy 21 screening results in the first versus second trimester. Based on the ethical principles of respect for autonomy, beneficence, and justice, we argue that routinely offering first trimester risk assessment in centers qualified to provide it is ethically obligatory and routinely withholding the results of first trimester risk assessment is ethically unjustified. As risk for trisomy 21 occurs along a continuum, no pregnant woman is without risk; thus, offering diagnostic testing to all women is ethically justified. Informed consent and personal choice regarding diagnostic testing and termination of pregnancy shape patients’ decisions to undergo first trimester risk assessment for trisomy 21. Appropriate counseling is required to allow for individual choice regarding timing of disclosure. ß 2007 Wiley-Liss, Inc. KEY WORDS: ethics; screening; risk assessment How to cite this article: Sharma G, McCullough LB, Chervenak FA. 2007. Ethical considerations of early (first vs. second trimester) risk assessment disclosure for trisomy 21 and patient choice in screening versus diagnostic testing. Am J Med Genet Part C Semin Med Genet 145C:99–104. INTRODUCTION Ethical principles provide action guides for physician’s clinical judgment, deci- sion making, and behavior in patient care. The basic ethical principles of respect for autonomy, beneficence, and justice and are integral to patients’ Geeta Sharma, M.D., is an Assistant Professor of Obstetrics and Gynecology in the Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine at the New York Presbyterian Hospital, Weill Medical College of Cornell University. Laurence B. McCullough, Ph.D., is a philosopher who serves as Professor of Medicine and Medical Ethics, in the Center for Medical Ethics and Health Policy, Baylor College of Medicine, Houston, Texas. His research interests focus on ethics in obstetrics and gynecology, surgical ethics, and the history of medical ethics. Frank A. Chervenak, M.D., currently serves as the Given Foundation Professor and Chairman of the Department of Obstetrics and Gynecology, as well as Obstetrician and Gynecologist-in-Chief and the Director of Maternal Fetal Medicine at the New York Presbyterian Hospital, Weill Medical College of Cornell University. He has published over 200 papers in peer review literature and has co-authored or co-edited 18 textbooks. Research interests include ultrasound and ethics in obstetrics and gynecology and leadership. Dr. Chervenak has served on the Board of Governors of the American Institute in Ultrasound and Medicine and the Society of Perinatal Obstetricians. He has served as President of the International Fetal Medicine in Surgery Society, the New York Perinatal Society and the New York Academy of Medicine Section of Obstetrics and Gynecology, and the New York Obstetrical Society. Currently, Dr. Chervenak serves as President of the International Society of the Fetus as a Patient, President-elect of the World Association of Perinatal Medicine, Vice-president of the International Academy of Perinatal Medicine, and Co-director of The Ian Donald Inter-University School of Medicine and Ultrasound. He serves on the March of Dimes Bioethics Advisory Committee and National Children’s Study Federal Advisory Committee. He is an honorary member of the Italian Society of Obstetrics and Gynecology, Barcelona Society of Obstetrics and Gynecology and the Texas Society of Obstetrics and Gynecology, and a Corresponding Member of the Academy of Medical Science of Croatia. *Correspondence to: Geeta Sharma, M.D., Department of Obstetrics and Gynecology, Weill Medical College of Cornell University, 525 East 68th Street, J-130, New York, NY 10021. E-mail: email@example.com DOI 10.1002/ajmg.c.30118 ß 2007 Wiley-Liss, Inc. choices regarding individual risk assessment for trisomy 21. These ethical principles have important clinical implications for risk assessment for trisomy 21 via available screening and diagnostic tools and management of individual pregnancies. The purpose of this paper is to identify those implications. First, we describe these ethical principles and their implementation in the informed consent process. Second, we identify the ethics of routinely offering first trimester risk assessment or diagnostic testing in centers that are qualified to do so and the ethical flaws of withholding the results of first trimester risk assessment until the second trimester. THREE ETHICAL PRINCIPLES Beneficence and its corollary, nonmaleficence can be simply described as the responsibility of physicians, acting with integrity, to do good and to avoid harm. The ethical principle of 100 AMERICAN JOURNAL OF MEDICAL GENETICS PART C (SEMINARS IN MEDICAL GENETICS): DOI 10.1002/ajmg.c Beneficence and its corollary, nonmaleficence can be simply described as the responsibility of physicians, acting with integrity, to do good and to avoid harm. beneficence directs the physician to identify and implement clinical management that is reliably expected, on the basis of the best available evidence, to result in a greater balance of clinical goods over clinical harms (risks) for the patient [Chervenak and McCullough, 2005; ACOG, 2002]. Respecting a patient’s autonomy, maintains her right to refuse or choose recommended treatments or tests. The ethical principle of respect for autonomy directs the physician to identify and implement clinical management that is reliably expected in the patient’s judgment to result in a greater balance of clinical and other goods that are important to the patient over clinical and other harms (risks) that the patient wants to avoid [ACOG, 2002; Chervenak and McCullough, 2005]. Justice relates to the fair distribution of the benefits and burdens of screening. Put more precisely, the ethical principle of justice directs the physician to prevent exploitation, that is, an outcome in which only a very few have access to significant benefit and the many experience only burden without the opportunity to experience off-setting benefit. The obligation to avoid exploitation shapes the ethics of the informed consent process and appropriate counseling [ACOG, 2002; Chervenak and McCullough, 2005]. Implications of Beneficence for Risk Assessment Physicians are obligated by the ethical principle of beneficence to seek a greater balance of clinical goods over clinical harms for patients. Using sound clinical judgment and professional integrity, physicians should identify and offer clinical treatments and screening tests in the general population that can achieve such a balance. In order to engage in a discussion with a patient regarding first trimester risk assessment, the first clinical ethical question to ask is whether it is medically reasonable. If it were not, physicians would have no ethical obligation to offer it to pregnant women. Conversely, if first trimester risk assessment is medically reasonable, which has been proven in international studies, [Nicolaides et al., 1992; Snijders if first trimester risk assessment is medically reasonable, which has been proven in international studies, et al., 1998; Wald et al., 2003; Wapner et al., 2003; Nicolaides, 2004; Malone et al., 2005] then the reasonable person standard requires disclosure of it to pregnant women in the informed consent process for the then the reasonable person standard requires disclosure of it to pregnant women in the informed consent process for the management of their pregnancies management of their pregnancies [Chervenak et al., 2005]. These studies demonstrated that first trimester risk assessment, using ultrasound and biochemistry in highquality centers, is medically reasonable, [Nicolaides et al., 1992; Snijders et al., 1998; Wald et al., 2003; Wapner et al., 2003; Nicolaides, 2004; Malone et al., 2005] especially if provision of its results reduces the incidence of invasive tests and thus unnecessary pregnancy loss. It follows from the ethics of informed consent that obstetricians have an ethical obligation to offer pregnant high-quality first trimester risk assessment as a ARTICLE medically reasonable component of the management of their pregnancies. Many authors have described the benefits of first trimester screening. Chasen and Skupski  noted potential benefits and harms of first trimester risk assessment. Benefits with early disclosure of results included improved aneuploid screening compared to age alone, for multiple gestations, association with cardiac and other congenital malformations, gestational age dating, and establishment of chorionicity in multiple gestations. The risks stem from poor information from poor technique and lack of quality control, which would also affect integrated and sequential screening, too, by means of propagation of error [Chasen and Skupski, 2003]. Since these risks can be reduced by limiting risk assessment to centers of excellence, the ethical principle of beneficence requires that risk assessment be performed in such centers. The American College of Obstetricians and Gynecologists and the American College of Medical Genetics both still recommend invasive diagnostic testing for aneuploidy in women aged 35 or older at time of delivery. However, offering first trimester risk assessment to all pregnant women, even those 35 years and older, is supported by the American College of Obstetricians and Gynecologists and the National Institute of Child Health and Human Development, provided that adequate training and quality are assured [ACOG, 2004; Reddy and Mennuti, 2006. Alternatively, patients could choose no screening test or proceed directly to an invasive test. First trimester risk assessment with immediate disclosure is a medically reasonable choice for aneuploidy screening in beneficence-based clinical judgment First trimester risk assessment with immediate disclosure is a medically reasonable choice for aneuploidy screening in beneficence-based clinical judgment ARTICLE AMERICAN JOURNAL OF MEDICAL GENETICS PART C (SEMINARS IN MEDICAL GENETICS): DOI 10.1002/ajmg.c [ACOG, 2004; Chervenak and McCullough, 2005; Nicolaides et al., 2005; Reddy and Mennuti, 2006]. The integrated screen offers a marginal increase in sensitivity and a decrease in false positive screens. However, the benefits of second trimester disclosure are offset by later reassurance or later decision making for invasive testing and possible termination of pregnancy, at a time when fetal kicks may be felt and the termination may not be performed as discretely. As first trimester risk assessment is an acceptable means of aneuploidy screening and integrated screening is not clearly overall clinically superior, nondirective counseling of patients desiring screening requires the physician to present all options to patients and allow the best test for that individual to be selected by the individual [Berkowitz et al., 2006]. According to the American College of Obstetricians and Gynecologists: ‘‘although first-trimester screening for Down syndrome and trisomy 18 is an option, it should be offered only if the following criteria can be met: ‘‘Appropriate ultrasound training and ongoing quality monitoring programs are in place. Sufficient information and resources are available to provide comprehensive counseling to women regarding the different screening options and limitations of these tests. Access to an appropriate diagnostic test is available when screening test results are positive.’’ [ACOG, 2004]. These standards must be upheld in all first trimester risk assessment schemes involving nuchal translucency measurement, that is, integrated and sequential screening programs, too. In addition, offering aneuploidy detection via invasive diagnostic procedures such as CVS and amniocentesis to all pregnant women is ethically justifiable. As women under the age of 35 constitute the larger population having children—more neonates with T21 are born in this population. Thus, not offering a diagnostic test to these women negates their autonomy and exploits them based on their age, while ignoring that all women do carry some risk of carrying an affected child [Druzin et al., 1993]. It is important to recognize that aneuploidy screening and detection involves sensitive personal beliefs and perceived societal benefit should not completely overpower individual choice. Implications of Respect for Autonomy for Risk Assessment In the context of Down syndrome screening, this is clearly an era of women’s choice. Previously, a woman’s a priori risk for fetal Down syndrome was solely based on her age, a screening strategy with only 30% sensitivity. The American College of Obstetricians and Gynecologists recommends invasive diagnostic testing for all women over the age of 35 [ACOG, 2001]. Recent recommendations are to offer first trimester risk assessment where available, to women of advanced maternal age [ACOG, 2001]. The credibility of first trimester combined screening has been supported by large international trials [Nicolaides et al., 1992; Snijders et al., 1998; Wald et al., 2003; Wapner et al., 2003; Nicolaides, 2004; Malone et al., 2005]. However, the ideal triaging of first trimester screening results and timing of disclosure lacks consensus. Similar to second trimester serum screening permutations, which evolved into improved screening efficacy, first trimester risk assessment programs are effective, evolving, and medically reasonable screening tools. As practitioners debate the relative merits of integrated, sequential, step-wise, and contingent screening protocols, the absence of clear clinical superiority of any one of them means that patient opinions cannot be ignored and should be factored into these discussions. It would therefore be paternalistic to assume all patients would desire the integrated test, despite its slight incremental increased sensitivity and ability to reduce the false-positive rate [Berkowitz et al., 2006]. In a competent individual, autonomy encompasses a patient’s values, beliefs, interests, social 101 constructs, and medical and nonmedical issues [Chervenak and McCullough, In a competent individual, autonomy encompasses a patient’s values, beliefs, interests, social constructs, and medical and nonmedical issues 1992]. Implicit in respecting a patient’s autonomy is recognition of her negative rights to noninterference, that is, the right to refuse offered or recommended clinical management. Thus, offering only Implicit in respecting a patient’s autonomy is recognition of her negative rights to noninterference, that is, the right to refuse offered or recommended clinical management. integrated screening or a screening triage that leads to a default-integrated pathway does not integrate a patient’s individual wishes. In addition, patients may decline screening and/or move directly to invasive diagnostic testing, which are options in autonomy and beneficence-based clinical judgement [Druzin et al., 1993]. There is evidence that many women who desire aneuploidy screening desire earlier availability of results and that first trimester risk assessment influences their decision regarding invasive diagnostic testing. In a survey of Dutch women who were undergoing second trimester serum screening, the majority (76%) stated that first trimester screening would have been preferable due to facilitation of pregnancy termination and earlier reassurance. Additionally, 44% of women who underwent CVS stated that results of first trimester testing would have influenced their 102 AMERICAN JOURNAL OF MEDICAL GENETICS PART C (SEMINARS IN MEDICAL GENETICS): DOI 10.1002/ajmg.c decision to undergo an invasive diagnostic test [Kornman et al., 1997]. Similarly, Nicolaides et al.  demonstrated that women were able to make an informed choice based on first trimester risk assessment results. Invasive testing was chosen and performed in proportion to the degree of aneuploidy risk predicted. First trimester risk assessment can contribute to a reduction in invasive diagnostic procedures. Zoppi et al.  compared two groups of women of advanced maternal age before and after first trimester risk assessment was introduced. In this high-risk population, first trimester risk assessment significantly reduced the number of invasive diagnostic procedures and increased the number of aneuploid cases detected in the first trimester. Zoppi et al. compared two groups of women of advanced maternal age before and after first trimester risk assessment was introduced. In this high-risk population, first trimester risk assessment significantly reduced the number of invasive diagnostic procedures and increased the number of aneuploid cases detected in the first trimester. Wray et al.  also showed a significant reduction in invasive testing after the introduction of first trimester screening in patients of advanced maternal age. Chasen et al.  similarly demonstrated that first trimester risk assessment disclosure reduced the frequency of diagnostic testing which could be extrapolated to fewer procedure-related miscarriages. In England, Spencer and Aitken  presented women with different options regarding first trimester risk assessment disclosure. The majority, 75%, chose early disclosure within 2– 3 days. In Australia, Mulvey and Wallace  interviewed 100 women at their first antenatal visit after receiving counseling regarding the natural history of Down syndrome pregnancies and the abilities and limitations of prenatal screening and diagnostic testing. They found that 74 patients preferred first trimester over second trimester screening, even with the understanding that the fetuses that were identified as abnormal could miscarry naturally. In a later study from the same center, women undergoing prenatal genetic counseling were assessed by a questionnaire and older women stated that a higher detection rate was more important than a low screen-positive rate. These women did not wish to miss a diagnosis of Down syndrome and preferred the potential loss of a normal fetus [Mulvey et al., 2003]. De Graaf et al.  showed that 76% of patients who received pre-test counseling desired first trimester risk assessment with ultrasound and biochemistry. These patients were older and found the risk of miscarriage more acceptable than the risk of delivering a baby with trisomy 21. These findings are consistent with those in our study, in which a preference for early disclosure, 69.3% of patients undergoing first trimester ultrasound and biochemistry, was associated with both older age and a greater likelihood of terminating a fetus with trisomy 21 [Sharma et al., 2005]. The studies from Mulvey et al.  in Australia and de Graaf et al.  from The Netherlands both demonstrate an association between background knowledge of screening and diagnostic tests and Down syndrome and preference for early disclosure. These studies in conjuction with the United States studies by Wray et al.  and Sharma et al.  and Spencer and Aitken  in England, display a common significant preference, by at least 70% of women, for early disclosure of first trimester aneuploidy risk assessment results. Management of a pregnancy could involve a decision to continue or terminate one’s pregnancy—an autonomy-based decision. A woman’s ARTICLE decision is also influenced by her values and beliefs, including religious and upbringing, economic and family circumstances, and the views of those whose judgments she values. Physicians do not have special competence with regard to such decisions because they involve not just clinical concerns but broader human and social concerns. Medically and ethically, physicians do play an important role in the enhancement of women’s autonomy by providing them the best available information about medically reasonable alternatives [Chervenak et al., 2005]. Offering first trimester risk assessment supports women’s autonomy and we dispute the routine withholding of first trimester risk assessment. Withholding this information is paternalistic, denies women critical information, and conflicts with the principle of justice as withholding exploits pregnant women. They are then denied the benefit of early decision about invasive testing and possible termination, without offsetting benefit, because the incremental improvement in the integrated scheme is small. Implications of Justice for Risk Assessment The ethical principle of justice refers to fairness to the individual and physician and the impact on society. Justice is a population-based ethical principle, in contrast to the individual-patient focus of respect for autonomy and beneficence. Justice obligates the physician not to exploit a population of patients. Exploitation in a patient population occurs when a small number benefit but the great majority bear the iatrogenic burden with no off-setting benefit. Given the fact that first trimester risk assessment with ultrasound and biochemistry provides acceptable detection rates at a 5% false-positive rate and permits earlier reassurance or allows individuals to proceed with timely invasive diagnosis and safer termination of pregnancy procedures, justice-based considerations support the use of this screening modality and are violated when women are denied this option. ARTICLE AMERICAN JOURNAL OF MEDICAL GENETICS PART C (SEMINARS IN MEDICAL GENETICS): DOI 10.1002/ajmg.c Given the fact that first trimester risk assessment with ultrasound and biochemistry provides acceptable detection rates at a 5% false-positive rate and permits earlier reassurance or allows individuals to proceed with timely invasive diagnosis and safer termination of pregnancy procedures, justice-based considerations support the use of this screening modality and are violated when women are denied this option. Broadly applying routine use of the integrated screen and withholding results of first trimester information is not ethically sound, as doing so exploits pregnant women by violating the principle of justice. Although a marginal increase in precision in risk assessment with a lower false-positive rate can be achieved with this strategy, it should not be applied without patient choice. It can no longer be assumed that the integrated risk assessment is the only medically reasonable form risk assessment [Wald et al., 2003; Malone et al., 2005; Nicolaides et al., 2005; Wenstrom, 2005; Berkowitz et al., 2006; Reddy and Mennuti, 2006] as the other strategies are also acceptable, such as the combined first trimester risk assessment, integrated serum screen, second trimester quadruple screen, and sequential first and second trimester screening either performed in a step-wise or contingent fashion. If a woman prefers more precise risk assessment by incorporating first and second trimester screening results, she should be provided the first trimester risk assessment, and then she is certainly free to postpone a decision about invasive testing pending second trimester results. Even certain proposed formats of contingent screening would allow for first trimester disclosure with an option to obtain second trimester integrated results. Informed consent requires that patients are aware of the choices available to them and the possible risks of an increased false-positive screen and the benefits of earlier disclosure of results for reassurance, pregnancy management, or consideration of invasive diagnostic testing. Withholding first trimester results as a routine practice violates the ethical principle of informed consent and substitutes paternalism. As pointed out above in our consideration of the implications of respect for autonomy, the majority of patients across different geographic regions expressed a preference towards earlier disclosure of results. Although the screening efficacy of the integrated screen (8 pregnancy losses per 100,000 patients screened) is numerically better than that of the combined first trimester risk assessment and second trimester maternal serum quadruple screen (each is 66 pregnancy losses per 100,000 patients screened), [Wenstrom, 2005] the emotional and personal preferences can not be quantified as easily. The principle of justice also requires nondirective counseling about alternatives for risk assessment, as well as invasive testing. Patients should therefore be presented with options for screening and invasive testing and allowed to select the best choice for their needs. Withholding this choice exploits women. Implications for the Informed Consent Process Appropriate counseling is necessary for patients to choose what they judge to be the best screening paradigm for their individual situation. The informed consent process is the clinical tool that implements the ethical principles of beneficence and respect for autonomy in the decision-making process with patients about the clinical management of their pregnancies. As Spencer and Aitken  showed, 24% of patients desired integrated screening. Physicians ethically should acknowledge competent adults 103 or alternatively an appointed surrogate as able to make an informed choice based on discussion of risks, benefits and alternative treatments, and ability to decline treatment. Patients’ understanding of Down syndrome and screening versus diagnostic testing are important aspects to address in the informed consent process. Our data demonstrated that educated patients in the United States can develop a good understanding of both screening and Down syndrome, which is critical to the informed consent process [Sharma et al., 2005]. In addition, both de Graaf et al.  and Mulvey and Wallace  studies showed an association with pretest counseling and patient-informed choice. In the first step of the informed consent process, the ethical principle of beneficence directs the physician to identify all medically reasonable alternatives for the management of the patient’s pregnancy, that is, those alternatives for which there is an evidencebased expectation that they will, on balance, clinically benefit the patient. This involves expert clinical judgment that conforms to the discipline of evidence-based clinical reasoning. In the second step of the informed consent process, the ethical principle of respect for autonomy directs the physician to present all of the medically reasonable alternatives to the patient, along with information about their clinical benefits and risks. The rule of thumb is that clinically salient information should be provided to the patient. Doing so meets the ethically accepted reasonable person standard for disclosure. In the third step of the informed consent process, the patient exercises her autonomy by understanding this information, especially the nature and expected outcomes of different alternatives (cognitive understanding), appreciating that the outcomes described could happen to her (appreciation), and assessing information on the basis of her values and beliefs (evaluative understanding). All adult patients should be presumed to have these capacities. The burden of proof is on the physician 104 AMERICAN JOURNAL OF MEDICAL GENETICS PART C (SEMINARS IN MEDICAL GENETICS): DOI 10.1002/ajmg.c to establish that the patient’s decisionmaking capacity in one or more of these domains is significantly impaired. In the fourth step of the informed consent process, the physician may make a recommendation of an alternative, when evidence-based reasoning supports it as clearly clinically superior (directive counseling). In the absence of such evidence-based clinical evaluation of alternatives, the physician should refrain from making a recommendation (non-directive counseling). In the fifth step of the process, the patient exercises her autonomy by expressing her preference from among the alternatives presented or rejects them all. The ethical principle of respect for autonomy directs the physician to protect the patient from substantially controlling or coercive influences on the patient’s expression of her preference. CONCLUSION The ethical principles of respect for patient autonomy, beneficence, justice, and the informed consent are essential components of first trimester risk assessment for trisomy 21. These principles support the routine counseling and offering of first trimester risk assessment in centers that are qualified to provide it. These standards also rule out as ethically unacceptable techniques of risk assessment that routinely fail to disclose the results of first trimester risk assessment when they become available to women who desire early disclosure of results. REFERENCES American College of Obstetricians and Gynecologists Practice Bulletin #27. 2001. Prenatal diagnosis of fetal chromosomal abnormalities. Obstet Gynecol 97: Suppl 1–12. American College of Obstetricians and Gynecologists. 2002. Patient choice and the maternal-fetal relationship. Ethics in Obstetrics and Gynecology. Washington, D.C.: ACOG. p 61–63. 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