Genomics touchpoints in pregnancy

Taking a medical history…

could reveal information about the expectant parent’s own genetic condition, and indicate if they require early referrals to specialist care. Examples of this are in the case of sickle cell disease or Marfan syndrome, which increase the chance of complications in pregnancy.

Taking a family history…

is a useful tool to identify any potential genetic conditions that may be present in the family. It is important to understand that genetic conditions that run in each parent’s side of the family, or that have been identified within a previous pregnancy, could be relevant for the current pregnancy.

Talking through screening options…

will ensure that the expectant parent has time to consider their options and make informed choices. There are many screening options available in pregnancy – some of which aim to identify genetic conditions that could affect the unborn baby.

Remember…

from a genomic perspective, the booking appointment is a form of screening test as, if appropriately managed, it has the power to reveal crucial information that could change how you approach the pregnancy.

• Does the expectant parent have a genetic condition? Remember – the booking appointment is an ideal time to gather information.
• Is there a family history of any genetic condition on either side of the family? If so, is prenatal diagnostic testing available for the condition? If it is, discuss the option of a referral to talk about this possibility in more detail.

• Is there a family history of metabolic disorders? If so, this should be clearly documented and followed up as there is a chance that the baby could also have the condition.
• Do you know the referral pathway/process for prenatal diagnosis testing so that families can have timely access to information and support if required?
• Is there anything unusual about the expectant parent’s previous pregnancy history, for example multiple miscarriages, babies born with multiple congenital anomalies, stillbirths etc, that could have a genetic cause? Consider the other parent’s history too – did they have previous children with another partner, and were there any concerns from a genetic or health perspective?
• Are the expectant parents related by blood? This is also known as a consanguineous relationship. You can read more about the genetic implications of consanguinity in this document from Guy’s and St Thomas’ NHS Foundation Trust.

• Referrals for genomic counselling or testing should be made at the earliest possible opportunity as the test results can provide information that can have a considerable impact on care. Some genomic tests can take several weeks to come back, so a fast referral is crucial.
• Our understanding of genomic information is increasing all the time. In addition, family histories change, and new information may alter clinical management or genetic risk assessment. If an expectant parent says something like “no-one was interested about this in my last pregnancy,” consider revisiting this information – there could be cause for referral to clinical genetics for further testing. It is also always worth taking another look at a family history, especially if the previous genomics consultation was several years ago.

It is important to ‘think genomics’ whenever you ask about a personal, obstetric and family history, and to take timely, appropriate action if you notice a red flag. You can find a list of some clinical red flags you might discover during the booking appointment in the table below:

*Please note that this list is not exhaustive, so always follow up on something that you think may be a red flag, even it does not appear here. Also remember that information associated with red flags can be difficult for families to discuss so care should be taken when asking any questions.

Screening tests include:

• Sickle cell and thalassaemia screening test before 10 weeks, to find out if the expectant parent is a carrier of a gene for sickle cell or thalassaemia. A blood test or family origin questionnaire will be offered, depending on the prevalence of the condition within the trust.
• Combined test in first trimester, to assess the chance of the baby having Down syndrome, Edwards syndrome or Patau syndrome.
• Quadruple test in the second trimester, to assess the chance of the baby having Down syndrome. This is offered if the combined test is missed.
• Non-invasive prenatal screening test (NIPT), offered following a higher chance result from either the combined or quadruple test. Please note that NIPT is being introduced as an evaluative roll out from 1 June 2021, so availability may be limited. More information and guidance for NIPT can be found on the gov.uk website.
• 20-week scan, to screen for 11 rare conditions.

Diagnostic tests on fetal DNA samples obtained from chorionic villus sampling (CVS) and amniocentesis, can be offered for a number of genomic reasons, including:

• unexpected findings from a screening test;
• a higher chance screening test result for a chromosomal condition;
• a previous pregnancy/baby with a genetic condition; and/or
• a confirmed family history of a genetic condition, such as sickle cell disease, thalassaemia major or cystic fibrosis, where the baby is known to have a high probability of having the condition.

As you can see, many of the reasons for a diagnostic test referral may be identified during the booking appointment, not just as a result of screening tests. The earlier these factors are identified, the more choice a couple may have for pregnancy management.

For more information about diagnostic tests, visit this Public Health England webpage.

• What types of screening will be available to the expectant parent throughout the pregnancy? Remember that this can depend on many factors, including age, health and ethnicity. Familiarise yourself with the tests available through the fetal anomaly screening programme (FASP) before the booking appointment so you’re prepared to answer any questions and can support the expectant parent to make an informed choice.
• How much do you know about NIPT? As a new addition to the FASP in June 2021, it is crucial that you accurately understand what the test is, the possible results, whether it is available in your area and its benefits and limitations. Be aware that information could change regularly as the service is rolled out.
• Would knowing if the baby was affected with a genetic condition in the pregnancy affect the pregnancy plan? For example, would it change the birth plan, allow time to psychologically prepare for the birth of a baby who has a genetic condition, or is termination something to consider?
• Would clinical management of the baby have to change, either in the pregnancy or directly after birth?
• Waiting for a diagnostic result can also be challenging for families. Understand and help them manage uncertainty by knowing what testing is offered, what it involves and what it might mean, whatever the result.

• When discussing screening, be accurate and thorough, and prepare by familiarising yourself with the FASP.
• The introduction of NIPT into the NHS has been widely publicised, so families may ask questions about it. Ensure that you have all the information you need to answer confidently and present its benefits and limitations.
• Do you understand what is involved in diagnostic testing, when CVS or amniocentesis can be performed, what tests to order and what the results may mean? The expectant parent may have a consultation with the obstetric team but may have follow-up questions that you may need to help answer. It is also important to understand the limitations of these tests and the uncertainty around diagnosis – you may not get an answer.
• If a diagnosis is made, caring for families during this period may include discussing termination of pregnancy or helping them to prepare for any health implications related to the condition when the baby is born. Entering these conversations with as much knowledge as possible can give families a better experience and help them to make more informed choices. An understanding of genomics and the ability to communicate effectively can make all the difference.

1. You could be the first to notice signs and symptoms that may indicate the baby has a genetic condition.

Remember to report and document anything unusual, different or unexpected. Take action to ensure that the baby receives the appropriate care. Understand the appropriate care pathway and refer accordingly.

2. You could be delivering a baby that was diagnosed with a genetic condition during the pregnancy or that has been identified as having a higher chance of having a condition, based on a screening test result or because of the family history.

Understandably, the family may find this a difficult time, depending on their situation and what has happened so far in their pregnancy journey. For example, in cases where screening may have indicated a high chance of a certain condition and the expectant parent has declined further testing, the family could be more anxious about the birth. It is always worthwhile to review their journey so far to understand how the family might be feeling and adjust care accordingly.

3. You might be caring for an expectant parent who has a genetic condition themselves, meaning they are at higher risk during labour.

Here are a list of some genetic conditions and the ways in which they can affect the pregnancy:

4. You could be delivering a baby following termination of pregnancy, or a stillborn baby due to genomic complications.

Depending on their circumstances, families in each of these situations may require additional support and you can make a big difference by signposting parents and their families to services and resources that can help them. Remember to link in with appropriate hospital services too, including bereavement care, if appropriate.

• Be aware that the family might not want or be able to process genomic information at this time. It is important to recognise when a conversation is unnecessary or could take place at a more appropriate moment. Consider providing information for them to take away, read and process in their own time.
• Support groups are a valuable resource for families during this difficult time, and they can help to answer questions and provide support in the days and weeks leading up to the birth and after birth. Make the expectant parent aware of these groups and how they can interact with them.
• Know where and what your referral pathways are and remember to treat any genomic red flags with the utmost importance. Your timely referral could make a huge difference.
• Remember that consideration should be given to future pregnancies. The family may need follow-up appointments to discuss any potential implications.
• Consider how individual, cultural and religious beliefs may impact on decisions made for testing and follow-up care.

Newborn and infant physical examination (NIPE) screening programme

At 72 hours and again at six weeks after birth, the child will have a physical examination that looks for anomalies in the eyes (including retinoblastoma – a rare inherited condition) heart, hips and testes.

Read the NIPE screening programme handbook for more information.

Although these examinations are performed by trained nurses, midwives, neonatologists or GPs, it’s important that all midwives have an understanding of what will be done, what can be found and what this might mean for the family.

Newborn blood spot (NBS) screening programme

At five days old, newborns have a blood spot test which looks for nine rare conditions.

It is crucial that a family history of any of the nine conditions is found earlier in the pregnancy so that an appropriate care plan can be created. In some cases, an early blood spot sample may be needed.

Samples should be sent to the screening laboratory for analysis on the same day they are taken, and parents should receive the results within six weeks.

The conditions are as follows:

• Sickle cell disease
• Cystic fibrosis
• Congenital hypothyroidism
• Phenylketonuria
• Medium-chain acyl-CoA dehydrogenase deficiency (MCADD)
• Maple syrup urine disease
• Isovaleric acidaemia
• Glutaric aciduria type 1
• Homocystinuria

The last six conditions on the list are metabolic. Without treatment, babies with these conditions can become suddenly and seriously ill.

If the baby is suspected to be at risk of a metabolic condition, special management is required depending on the condition. For example, MCADD can be especially complex, with strict requirements for feeding before blood spot test results come back. You can find comprehensive guidance here.

To learn more about the importance of blood spot screening, read Holly and Jack’s story, Emma’s story on Metabolic Support UK, or read the Public Health England guidance for the NBS screening programme.

Newborn hearing screening programme (NHSP)

Hearing screening is also offered soon after birth to identify congenital hearing problems, many of which are genomic in origin. The test is called the automated otoacoustic emission (AOAE) test, is non-invasive and takes just a few minutes.

In some cases, a second test will be offered because it is not always possible to get a clear response from the first test. This could happen for many reasons, and does not always mean that the baby has hearing loss. The second test could be the same as the first, or could be another type of a test, called the automated auditory brainstem response (AABR) test.

Although it is not mandatory, it is important to explain the benefits of hearing screening to parents. Finding out about hearing loss early gives babies a better chance of developing communication skills and makes sure that families have access to the support they need.

More information about the NHSP is available on the NHS website, with supporting guidance from Public Health England.

• Be aware that certain metabolic conditions, such as MCADD, dramatically affect the care plan during the neonatal period. Some may even require that an early blood spot sample be taken.
• Make sure that you are familiar with the different screening programmes, what the tests are, what the results could be, and what they could mean. Waiting to hear back about results can be an extremely stressful time for the family, and you can ease this burden of uncertainty by being a source of clear information.
• The neonatal period can be a high-risk time for the parent and child, with serious consequences for their health. Don’t take risks and stick to the care plan.