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This is a plain English summary of an original research article. The views expressed are those of the author(s) and reviewer(s) at the time of publication.

Parents-to-be are offered a range of tests to predict whether their baby is likely to have certain health conditions. Many are keen to have these pre-natal tests for reassurance. But sometimes the results are unclear, leaving parents to deal with uncertainty.

New types of genetic tests look in detail at the baby’s genetic material (the genome). They are carried out after an ultrasound scan detects problems that suggest the baby may have a genetic condition. These tests can diagnose rare genetic conditions in the baby but in some cases no genetic cause is found and in a few, results may be unclear.  Parents-to-be may find this increases their anxiety about the pregnancy, especially if they had not realised before taking the test that the results could be uncertain.

A review of research in this area suggested ways of preparing parents-to-be for receiving uncertain results. They could be helped if, before having the test, they were given a clear explanation of the testing process and had discussed the possibility of receiving uncertain results. Parents may also require time and support after receiving uncertain results, to help them understand the implications.

What’s the issue?

Around 3% of all pregnancies are diagnosed with a structural abnormality during ultrasound scans. Parents may then be offered further tests to find the underlying cause of the abnormality.

Genetic tests in pregnancy traditionally involve looking at pairs of chromosomes, which are structures in cells that carry a person’s genetic material. Some of these tests identify conditions caused by changes in the number of chromosomes, such as Down syndrome, and others look at individual genes on the chromosomes.

More recently, tests called chromosome microarray analysis (CMA), and exome sequencing have become available. These newer tests give more detail about the baby’s genetic makeup and increase the chance of diagnosing rare genetic conditions during pregnancy. These diagnoses can help parents decide whether to continue or end the pregnancy and inform the management of pregnancy and delivery, pre- and post-natal care.

However, tests do not always give clear results. It may be, for example, that a genetic change is found in the baby but the significance of the change is unknown. Or no genetic change may be found to explain the results of the ultrasound scan.  These findings can be distressing for parents, especially if they are considering whether or not to continue with the pregnancy.

What’s new?

The researchers reviewed four quantitative studies and ten qualitative studies. In all there were 914 participants (678 women and 236 partners). All were asked about their experience of uncertainty during the process of having CMA or exome sequencing during pregnancy.

They identified three main types of uncertainty:

  • uncertainty among parents-to-be about the testing procedure, what was being tested, how they would get the results, and what the results might mean
  • uncertain results, such as those that did not give a clear diagnosis
  • uncertainty among healthcare professionals, who themselves had limited knowledge about the significance of the result.

Some parents felt anxious and overwhelmed after receiving uncertain test results. Some found it difficult to make decisions or long-term plans because of the lack of certainty. Some regretted having the test, while others were glad to have had it, even if the results were uncertain.

Many parents needed support from family, friends and healthcare professionals in managing the uncertainty. Some found it helpful to talk to genetic counsellors or specialists, or to other families who had been through a similar situation.

Eight of the 14 papers included in the review were from the USA, where prenatal testing may be offered in a different way. When fetal exome sequencing is implemented in the English NHS, a targeted approach to analysis will be used which will significantly reduce the number of tests reported with uncertain results. In addition, tests will be requested by clinical geneticists who are experienced in explaining what results might be obtained and helping patients manage uncertainty.

Why is this important?

This review demonstrates the importance of good communication in helping parents through the process. Good communication may reduce uncertainty, for example about the test procedure, and may prepare parents for the possibility of uncertain results.

The researchers make a series of recommendations for healthcare professionals. They say that parents considering having these tests need to know what to expect. Healthcare professionals should ensure parents understand in advance that the results may be uncertain and that they may not find a reason for the findings on the ultrasound. They should discuss whether and how parents want to be informed about uncertain test results.

When discussing test results, healthcare professionals need to allow parents time to consider uncertainty and to ask questions. Parents receiving uncertain results may need support from specialists, counsellors or to be signposted to support groups. They may value being told what is certain – for example, being reassured that certain genetic conditions have been ruled out. They may also value additional ultrasounds during the pregnancy so that the development of the baby can be monitored.

What’s next?

The review was part of a larger international study looking at uncertainty in pregnancy. In the larger study, the team is exploring the preferences of parents-to-be for receiving uncertain results. The team is also interviewing health professionals who report or return uncertain results. They want to know what types of uncertainty arise in their day-to-day practice, and how these types of uncertainty are managed in different countries.

Further research would be useful to assess different ways of communicating uncertain results and to look at the longer-term impact of uncertain prenatal results on parents who continue their pregnancy. For example, it would be helpful to know whether uncertain results during pregnancy impact on anxiety about the child’s development later on.  The researchers believe that longer term research will be important to find optimal ways of managing uncertainty during pregnancy and minimising the potential for harm.

For the launch of exome sequencing in pregnancy, NHS England is developing a guidance document, patient information written in accessible language and a detailed record of patient consent. It is delivering webexes for fetal medicine and genetic services and their associated midwives and counsellors. The service will be launched when funding is confirmed.

You may be interested to read

The full paper is: Harding E, and others. Couples experiences of receiving uncertain results following prenatal microarray or exome sequencing: A mixed-methods systematic review. Prenatal Diagnosis. 2020;40:1–12.

Two studies that informed NHS England’s decision to implement prenatal exome testing: Lord J, and others. Prenatal exome sequencing analysis in fetal structural anomalies detected by ultrasonography (PAGE): a cohort study. The Lancet. 2019; 393: 10173, 747-757

and the BOOSTb4 study: Chandler N, and others. Rapid prenatal diagnosis using targeted exome sequencing: a cohort study to assess feasibility and potential impact on prenatal counseling and pregnancy management.Genet Med. 2018;20:1430-1437

Guidelines for implementing fetal whole exome sequencing: Joint position statement from the International Society for Prenatal Diagnosis (ISPD), the Society for Maternal Fetal Medicine (SMFM), and the Perinatal Quality Foundation (PQF) on the use of genome-wide sequencing for fetal diagnosis. Prenat Diagn. 2018;38:6–9.

A website from the charity Antenatal Results and Choices (ARC), which helps parents and healthcare professionals through antenatal screening and its consequences


Funding: This research was funded by the Wellcome Trust. The research was supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre.

Conflicts of Interest: The study authors declare no conflicts of interest.

Disclaimer: Summaries on NIHR Evidence are not a substitute for professional medical advice. They provide information about research which is funded or supported by the NIHR. Please note that the views expressed are those of the author(s) and reviewer(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.

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