Technology-Specific Considerations

Although many of the information needs associated with screening and diagnostic tests apply across all protocols, advances in technology have modified some of these and added others. Increasingly, for many women and their partners, the choice is not only whether or not to have a screening test but also ‘which test to have’. Practitioners are familiar with the idea that women must be helped to find their own balance between safety and certainty, but that simple tension has been superseded by a much more complicated set of costs and benefits arising from the proliferation of different testing protocols.

Some of the ways in which screening protocols differ are the result of intentional additions to the options being made available to women, such as offering screening for different conditions, and others reflect different ways of trading off safety and certainty, such as introducing a noninvasive option after an initial screen positive result. Both are relevant to decision making, adding to the debate about how much information should be provided about screening tests and what aspects of information are most important to convey. The most salient dimensions on which current screening protocols differ and what relevance these may have for information provision are now discussed.

Noninvasive Prenatal Testing Using Cell-Free DNA

This important new technology changes both the means and the ends of screening–the means because the safety versus certainty tradeoff is altered and the ends because the range of potential tested-for conditions could more easily be extended.

It was initially hoped that NIPT would completely resolve the safety versus certainty dilemma, but at least in respect of the most common prenatal testing programmes, that simple, easy-to-explain goal has not been achieved. In some circumstances, the information-giving challenge may even have been increased. In part, this is because of the oversimplified and misleading media accounts which need rebuttal; however, it is also because the degree of certainty about the meaning of an NIPT result is not constant and varies in a number of ways which have important practical implications. Perhaps most important, and despite the original labelling of the technology as noninvasive prenatal diagnosis (NIPD), the sampled DNA does not come from the fetus as was first supposed (cell-free fetal DNA [cffDNA]) but from the genetically distinct placenta (cell free DNA [cfDNA]). As a result of this and other factors, such as a vanishing twin, or maternal cancer, NIPT does have a small but nonzero false-positive rate. This means that women with positive NIPT results still need to undergo an invasive diagnostic procedure–with its attendant miscarriage risk–to obtain definitive information that the baby is affected. All women contemplating NIPT need to know this, but the awareness is particularly important for those who are considering terminating a pregnancy after a positive diagnosis. The likelihood that a positive test result is a false positive depends on the condition (test performance being better for Down syndrome than for the other trisomies) and on the woman’s prior risk status, so it is important to know whether a positive NIPT result came from a test delivered in a private health care setting to a low-risk woman or from a test taken on a contingent basis as part of a screening programme. For women with positive NIPT results, the old safety versus certainty dilemma remains. Work is needed to find out how best to provide feedback and further information in these circumstances, in particular, how should the residual degree of uncertainty be conveyed, without creating false expectations in either direction? Clinicians used to conveying results from less accurate screening tests will need help in striking the right balance.

The uncertainty about the meaning of a negative NIPT result for Down syndrome is much less than a positive result. However, it must always be remembered that although the detection rate is very high, it is not 100%, and there will still be a small number of missed cases. Clinicians need to know that this apparent asymmetry exists (although fewer may want to know why) to enable them to give the appropriate degree of reassurance to women. It is through this ‘ruling out’ mechanism that the real benefit of NIPT for Down syndrome lies because it reduces the numbers of women having to face the invasive testing dilemma. The picture is less clear for other chromosomal conditions detected by current screening programmes, particularly when test failures or inconclusive results from NIPT are taken into account. The need for more comprehensive performance data has been identified.

Noninvasive prenatal testing is widely available internationally. In the United Kingdom, it can readily be obtained privately, and starting in 2018, it is also available through the National Health Service. Two substantial applied research projects have contributed a great deal to understanding how NIPT may work in UK clinical practice, but decisions have yet to be made about where in the current test pathway NIPT might be offered, about risk thresholds and about the choices available to women at each stage. Efforts to refine pathway components also continue. The most likely plan for England is that NIPT would be offered as a second-line, or contingent, test to women identified as at increased risk by current methods of combined testing, using the same 1 in 150 risk threshold as at present. As described earlier, NIPT used in a contingent role can provide reassurance to many women without the need for invasive testing–it can reduce, although not eliminate, the programme’s false-positive rate. However, it also follows logically that unless initial risk thresholds are changed, contingent use of NIPT cannot identify any affected pregnancies ‘missed’ by the first-round screen. Therefore, in test performance terms, this form of contingent NIPT cannot increase detection rates because screen negative women would not be offered the contingent test. If, however, the availability of contingent NIPT leads to an increase in the numbers of women choosing to be tested, then at programme level, more affected pregnancies may be identified. Pathways of care where the options available are contingent on previous events can be confusing, and achieving the right balance between technical correctness and oversimplification is no easy task.

Contingent use of NIPT will also increase the length of time taken for a woman who tests positive on the initial screen and again on NIPT to obtain a definitive result: all women need to understand this and to understand that NIPT has a failure rate of about 3%. However, the extra time is likely to be particularly salient for some groups of women. In Islam, for example, termination of pregnancy for a condition such as Down syndrome is regarded by religious authorities as permissible but only before ‘breathing the soul’ takes place at 120 days of gestation. Muslim women, like all women, hold their own individual opinions about termination for congenital conditions, but many do (or would) choose termination if circumstances allow.

The reproductive options offered by the current first trimester pathway are known to be valued by many women, and plans for introducing NIPT have specifically taken that into account. Even within the planned timetable, however, it is recognised that some women will seek early certainty, so in a future UK programme, invasive diagnostic testing would also be offered as an alternative to NIPT to women screening positive on the combined test. Some women will be clear which of the available options is right for them, but others may need support in choosing between them.

In some respects, NIPT will add to the requirement to develop information that meets the needs of different women. Amongst those considering screening but previously deterred by miscarriage risk will be women who are clear they would like information about the baby if it could be obtained safely. There will also be women who have in effect ‘sheltered’ behind the miscarriage risk and not asked themselves what they would do if safer means of obtaining information were available. Concerns have been voiced in terms of needing to ensure that the option of ‘just having another blood test’ does not create pressures on women to be tested or more generally undermine informed choice. There is also concern that the potential for NIPT is to screen for other chromosomal anomalies, microdeletions or duplications and eventually the full fetal genome will result in generating incidental findings and identify variants of unknown significance will add to the information burden placed on women.

The more complex the pathway and the more that provision is made for individual values and preferences, the greater is the need for information to support women’s decision making. There is evidence from research that NIPT is welcomed by women, but that a significant proportion of those at elevated risk will prefer invasive testing. If contingent NIPT is introduced in the National Health Service, the impact on women’s decisions across the pathway will not be known for some time; behind the figures, dilemmas for some will decrease, but they may increase for others.

Ultrasound in Screening

The increasing use of ultrasound technology in screening brings with it additional challenges in relation to information provision. Scanning is very popular with women and their partners because of the opportunity it affords of ‘seeing the baby’ and in the event most scans are reassuring experiences that parents remember with pleasure. In the United Kingdom, scans are offered at two points in the screening programme: the early pregnancy scan at 11 to 14 weeks (the nuchal translucency [NT] scan), as one component of combined testing in the first trimester, and the fetal anomaly scan in the second trimester (18+0-20+6 weeks). In both cases, the main information challenge is to convey that the true purpose of scanning is to look for signs of problems. Women undergoing ultrasound testing need to be prepared for such an outcome even though the warning may be unwelcome and the information itself a possible cause of disquiet. For the early pregnancy scan, the second challenge is to convey that the stand-alone value of the NT measurement is limited; its value lies in its contribution to the combined test, so it is important that women who want screening complete both parts of the combined test protocol.

For the fetal anomaly scan, the challenge is how to convey that, unlike screening for a specific condition, scanning is a very open-ended investigation with many different possible outcomes and that the problems identified can be serious or minor, common or rare. It also needs to be explained that although a scan can sometimes function as a diagnostic test and identify some problems with certainty, in many other instances, the scan only functions as a screening test, and furthermore, probably invasive, diagnostic testing may be indicated. The more skilled the sonographer, the more likely it becomes that minor variations will be identified. Once called ‘soft markers’, these used to be routinely reported to women, causing unnecessary anxiety–some of it long lasting–and leading to an inappropriate use of invasive testing. In the UK screening programme, the policy now is not to report or act upon the presence of any marker not previously established as of prognostic significance.

Screening for Multiple Conditions

A related but distinct issue from ultrasound scanning is how to ensure informed choice when screening (of any form) is being explicitly offered for multiple conditions. It cannot be assumed that an individual woman’s views about testing and termination will be the same for all conditions, so the information provided must as far as possible support separate decision making for each condition.

In the United Kingdom, the Down’s Syndrome Screening Programme has recently been extended to include the offer of first trimester screening for two other trisomies, Edwards and Patau syndromes. The evidence suggests that many people see a clear distinction between the different conditions, the disabling effects of Edwards and Patau being regarded as much more serious and extensive. Some people will, of course, not want screening for any of these conditions, and some will want screening for all three, but it also seems likely that a proportion of those who see no reason to screen for Down syndrome will take a different view about Edwards and Patau syndromes. A small minority may draw the opposite conclusion. Information is being provided to support each of the possible choices.

The United Kingdom also has an antenatal screening programme for haemoglobinopathies, and it is clear that offering separate choices about each tested for condition will eventually become an unsustainable strategy. The performance of tests, including NIPT, varies by condition, and whole-genome sequencing with NIPT is technically some way off in terms of clinical implementation at least. A cautious, evaluative approach to new indications has been advocated. In the meantime, a new balance between supported choice and information overload will need to be found. The revealed choices of women in different parts of implemented screening programmes will be informative here, but a major consultation about future directions and about means and ends is also likely to be needed.

Prenatal Diagnosis of Fetal Anomaly

However ‘prepared’ parents might be for the possibility of the diagnosis of fetal anomaly, perhaps due to a screen positive result, when the problem is confirmed, the psychological impact is likely to be significant. This means how information is communicated about the findings is important, and this can be challenging for clinicians. It is more difficult to assimilate information when distressed, so consideration should be given to how to most effectively convey what parents need to know. Sensitive, individualised care from the point of diagnosis that is coordinated and combined with good communication can help parents take some positive memories from a difficult experience and will avoid adding to existing distress.

In the context of a wanted pregnancy, prenatal diagnosis of fetal anomaly requires parents to confront the loss of the ‘healthy’ baby they had previously conceptualised and built their hopes around. They may need time to accept the reality of the diagnosis and its possible implications. It may be difficult for them to fully grasp the potential outcomes in the space of a single consultation. Some parents may feel the need to have the anomaly confirmed by a second opinion and are likely to want further consultations. This should not be seen as undermining the initial clinical judgement. For some parents, it is an important part of the process of accepting the reality of the situation and understanding what it may mean for them.

Effective communication from clinicians involves more than choosing the right words. When shock means assimilation of information is hard, a clear, carefully paced explanation of the anomaly and the predicted prognosis is crucial. The clinician will need to gauge the response of parents and tailor the communication accordingly. Only by actively listening and responding to parents and involving them in discussions will it be possible to assess the meaning the diagnosis has for them and come to an agreement on the most appropriate plan for management. As a result, explanations need to be as jargon free as possible and logically sequenced with pausing to check that parents are able to take in the most essential information. It can be useful for them to have written information to take away to consolidate what has been said, as well as details of someone they can contact between appointments with any concerns. They may appreciate being signposted to reliable sources of information outside their health care providers to gain as much information as possible about the implications of the diagnosis for them.

It is helpful if parents experience good continuity of care and consistent information from all involved in their medical care. This is best achieved by ensuring that there is good multidisciplinary coordination and clear channels of communication among all clinicians working across regional and specialist centres.

Diagnosis From Ultrasound

The psychosocial significance of prenatal ultrasound for expectant parents is well established. We know that parents are never psychologically prepared for difficult news from a scan even if given information about the purpose of the examination. The distress can be particularly acute if the scan brings the first indication of a potential problem. Communication of findings in this situation can be particularly challenging because of the necessity of delivering the difficult news in real time, giving the clinician little opportunity to prepare. Therefore clear and concise explanation will be essential, along with due regard to the capacity of the parents to take in what they need to know. Along with clarity, there is evidence that parents value empathy and compassion from their providers.

The ultrasound room is not the ideal setting to deliver difficult and often unexpected news about a pregnancy. The woman will be in a prone and vulnerable position, especially if she is undergoing a transvaginal scan. However, it should not be assumed that news must be deferred until the woman can adjust her clothing and sit up. Some women appreciate the opportunity to see the scan finding, and this in turn may aid understanding. Others may feel the need to feel more ‘dignified’. The only way to know is to ask the woman for her preference. Although correct medical terminology will, of course, be required, every attempt should be made to pitch the information to make it comprehensible. Furthermore, parents appreciate the findings described respectfully and sensitively. This includes taking the lead from them in determining whether to use the term ‘baby’ rather than ‘fetus’ and being sensitive when describing certain ultrasound markers such as ‘strawberry signs’, ‘lemon-shaped head’ ‘Swiss-cheese pattern’.

Diagnosis From Genetic Testing

Diagnosis of most genetic conditions requires a woman to undergo invasive procedures such as chorionic villus sampling (CVS) or amniocentesis. Agreeing to have either procedure involves her acceptance of the possibility that her quest for a diagnosis may lead to a procedure-related miscarriage. Although the miscarriage risk may have led to deliberation and difficulty in taking up the testing, it does not mean she has made the psychological leap to the actuality of a confirmed diagnosis and is committed to a particular course of action in this instance. In other words, it is important that clinicians do not make assumptions about how news from a CVS or amniocentesis result will be received or that intentions expressed in the abstract will be retained in the face of the reality of a diagnosis.

There is little research data to suggest that the timing of the delivery of test results (i.e., at an agreed time or as soon as results available) or method of communication (i.e., face to face, telephone or email) reduces anxiety levels. We do know that parents are likely to be anxious about the result, so the waiting time should be minimised, and how they might prefer the results to be delivered should be discussed with them beforehand. Although some results will give a clear diagnosis, in the case of common trisomies and well-described genetic conditions, some parents will face chromosomal changes or genetic variants about which little or nothing is known. (Even in the case of well-described genetic conditions, there will be a level of uncertainty which must be acknowledged.) This is becoming more common with the move to using more sensitive testing than conventional karyotyping, such as microarray. Whole fetal genome sequencing is also on the horizon. Potentially complex scenarios arising from the detection of genetic variants of uncertain or unknown significance will require a close collaborative relationship between fetal medicine and clinical genetics. Furthermore, the challenge for parents in dealing with results that represent a very uncertain prognosis postnatally must be acknowledged and access to genetic counselling provided when appropriate.

Pregnancy Management After Diagnosis

Postdiagnosis pregnancy management options available to parents will most often depend on the nature of the anomaly and the legal framework relating to abortion. In a limited number of circumstances, in utero interventions may be possible, such as fetal surgery for diaphragmatic hernia, catheters used to drain excess fluid from fetal organs or laser ablation for twin-to-twin transfusion. Here, particularly for fetal medicine specialists, a conflict can arise between the perceived best interests of two ‘patients’, the mother and the fetus. It is therefore essential to present a clear picture and discuss the risks and benefits of any possible interventions, not just what might apply to the fetus but also the potential for maternal morbidity.

There is scarce evidence on exactly how parents make decisions about continuing or ending a pregnancy after diagnosis of fetal anomaly. Clearly, there are practical and ethical constraints to obtaining this information concurrently with the decision making. The existing literature attests to the immense difficulty in making the decision even for parents who know what they want to do. What emerges from published accounts is the way parents weigh the impact of the anomaly on the child when born, on themselves and on other immediate family members (including existing and potential siblings) in the context of any attitudes and beliefs they may hold about abortion. Such data as available suggest that few parents regret their decisions, although this work is mostly in the context of a decision to terminate.

In the absence of a firm evidence base, the question arises as to how clinicians might best support parents so they are enabled to make a decision that they can best live with. It is often a psychologically complex situation for parents who are desperate to make the ‘right’ decision. In view of this, some parents will look to their clinicians for direction or advice. When they ask questions such as, ‘What do you think I should do?’ or ‘What would you do?’, parents are often seeking acknowledgement of the magnitude of their dilemma or acceptance of the decision they have tentatively made. There has been ongoing debate about whether the principle of ‘nondirective counselling’ is achievable or even desirable in these situations. Some argue that parents use advice from a clinician along with many other contributory factors in their decision making and are not unduly influenced. However, clinicians may be on safer ground empathising with the difficulty the parents face and helping them to weigh the competing benefits and harms in their unique circumstances (particularly when most often, there will be some measure of uncertainty about potential outcomes).

As first trimester screening for fetal anomalies and genetic conditions has become the norm in most developed countries, more parents are faced with decisions at an earlier stage of pregnancy. It is unwarranted to assume that an earlier diagnosis is always psychologically easier to cope with. If ending the pregnancy, parents still have to come to terms with the loss of, what is in most cases, a much desired pregnancy. Also, they may have less recourse to external support because many couples will have delayed announcement of the pregnancy until the first trimester is over. If continuing, they will have longer to adjust to a different reality but also longer to cope with the anxieties around the potential outcomes.

Information Needs When Parents Decide to Terminate an Affected Pregnancy

In jurisdictions where termination is an option, it is unhelpful to assume that the diagnosis of a definitely lethal or severely life-limiting condition will always make a decision about terminating the pregnancy more psychologically tolerable. Parents have to contend with the devastating news that their baby will not survive, coupled with the fact that they can choose the timing of their baby’s death.

Some clinicians working in fetal medicine may believe their responsibility stops at the offer of termination. However, parents often look to the clinician who has provided the diagnosis to provide information and guidance on what the termination process will involve. It has been shown that information about what might be ahead is valued by parents and can be empowering at a time of crisis. Their information needs will include options for method of termination (surgical or medical) and what both procedures involve, whether feticide will be offered and whether postmortem investigations are likely to provide information that will have implications for future pregnancies. It is important that all such information is evidence-based and takes account of the woman’s preferences and individual coping strategies.

Information Needs When Parents Decide to Continue With an Affected Pregnancy

Research into the impact of continuing a pregnancy after a confirmed prenatal diagnosis was, until recently, relatively rare compared with that on the experiences of termination. Much research focused on when a lethal abnormality had been discovered, and there was some suggestion that in this situation, the decision not to terminate may be better for a woman’s emotional well-being because women who continue a pregnancy could avoid the guilt they might have felt had they terminated. For many women, however, the thought of continuing a pregnancy with a baby who they know will die is as unthinkable as termination is for others. The important issue is that parents are enabled to make the right decision for them. Care for parents continuing a pregnancy has been reported as poor during the remainder of the pregnancy. The development of planned palliative care programmes for women, with intense pregnancy support and clear planning around the birth of the baby and for the neonatal period is clearly to be welcomed for the women who choose this option or cannot access termination. Although evidence suggests that when termination is available in this circumstance, most women will take up this option, this must not preclude carefully coordinated and supportive care for women continuing their pregnancies.

There are very many parents who continue pregnancies after the diagnosis of one of the many anomalies that are not lethal and in which termination might not be offered, such as cleft lip or talipes. Sometimes prenatally diagnosed conditions require ongoing monitoring; sometimes there will be treatment available, and other times there will be no treatment. Whatever the prognosis, the diagnosis means that parents have lost the healthy baby they had expected and will be adjusting to the uncertainty of the remainder of the pregnancy and after the baby is born and will be experiencing many complex emotions. In a growing base of qualitative data, researchers have explored the nature and experience of an ongoing pregnancy after a prenatal diagnosis, as well as how to care for the mother who remains a pregnant woman but who can appear to be forgotten when antenatal care focuses on the health of the baby. Issues of shock at diagnosis, grief for the loss of the expected healthy baby and isolation from family and clinicians after the decision to continue are highlighted. Even in the Republic of Ireland, a country where prenatal diagnosis is undertaken but until very recently termination of pregnancy was not legal, except in very restricted circumstances, recent data suggest that systems of care for parents continuing pregnancies are not ideal to meet women’s needs.

Subsequent Pregnancies

After the diagnosis of fetal anomaly and particularly it has led to pregnancy loss, the perception of the pregnancy experience will change for most women. This means that subsequent pregnancies (not just the one after the affected pregnancy) can be anxiety laden for parents, and it will be important that all involved in their care are cognisant of and sensitive to their history. Many women will want to be seen again by the clinician who diagnosed the previous anomaly, but others may wish to avoid those who are associated with previous anguish.

Anxieties in a subsequent pregnancy do not necessarily subside completely when the moment of the previous diagnosis has passed or when all possible testing has revealed no major problems. Those who had a termination or miscarriage after diagnosis can find the gestational weeks after the time the previous loss took place difficult because it is ‘uncharted water’ or evokes guilt because the previous baby did not make it this far. Others, having had a bad experience in pregnancy, find it almost impossible to believe they will have a happy outcome. For many, even the birth of a healthy child is tinged with sadness because it serves as a reminder of ‘what should have been’ in the previous pregnancy. In short, the majority of parents in the pregnancy after a loss will need extra support and carefully coordinated care from their obstetric team.

‘Human Aspects of Care’

No matter how skilled or experienced a clinician may be, working with distressed parents will take its personal toll. It is also significant that in the context of a diagnosis of serious fetal anomaly, there are few interventions that can be offered prenatally to guarantee a positive outcome for fetus and mother. This can evoke feelings of failure on the part of the clinician. Indeed, whatever strategies clinicians use to mitigate against the inevitable distress that comes with the territory, if they find themselves able to cut off completely from the human sadness of the situation of prenatal diagnosis, it will be necessary to reflect on the quality of care they are able to offer. The majority of women who see obstetricians have good outcomes to their pregnancies; this can make the occasions when fetal abnormality occurs harder to manage. We argue for the provision of specialised training for clinicians to help them develop the requisite skills to provide the very best individualised care, along with appropriate support to ensure they can manage the emotional dimension without becoming inured to the impact on parents.