Respondents’ profiles
Among the respondents, 37 (32%) worked in either a NICU or PICU, 40 (35%) were affiliated with clinical genetics, 22 (19%) were associated with genetics laboratories, and 12 (10%) practised in both clinical and biological genetics (Table 1). These proportions reflect a balanced distribution of areas of practice among the different healthcare professionals who may potentially play a role in urGS for NICUs/PICUs.
Table 1: Respondents profile. The ‘other’ category in area of practice is composed of standard paediatric wards and a clinical research activity. The ‘other’ category in status corresponds to a clinical research associate, a psychologist and a genetic counsellor. Participants were asked to categorise the frequency of their involvement in patient critical care and genetic test prescription. MD: Medical Doctor; NICU: Neonatal Intensive Care Unit; PICU: Paediatric Intensive Care Unit.
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Respondents
n (%)
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Area of practice
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Paediatric/neonatal intensive care
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37 (32)
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Clinical genetics
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40 (35)
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Combined clinical and biological genetics
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12 (10)
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Biological genetics
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22 (19)
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Other
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5 (4)
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Status
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MD >5 years experience
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64 (55)
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MD <5 years experience
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34 (29)
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Medical trainee
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15 (13)
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Other
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3 (3)
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Frequency in NICU/PICU patient care involvement
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Very often (>20 times / year)
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46 (40)
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Often (6 et 20 times / year)
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26 (22)
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Sometimes (<6 times / year)
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28 (24)
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Never
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16 (14)
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Frequency of genetic test prescription
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Often (>1 time / month)
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70 (60)
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Sometimes (<1 time / month)
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26 (23)
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Never
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20 (17)
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Out of 116 respondents, 15 were medical trainees (13%), and among them, 5 (4%) were in their final year of training. Thirty-four respondents were medical doctors (MDs) with less than five years experience (29%), while 64 (55%), had more than five years professional experience. Thus, over half of the respondents can be considered as experienced in their respective fields. It is important to note that French laboratory geneticists are medically-qualified. Four MDs self-identified as working in standard paediatric wards and were grouped with three non-medical healthcare professionals (research assistant, psychologist, genetic counsellor) in an ‘Other specialty’ category for general statistics that was considered too heterogeneous for further analyses.
Ninety-four percent of the respondents (109/116) worked in university-affiliated hospitals located throughout France consistent with the distribution of NICU/PICU and genetics departments.
A total of 46% (37/79) of respondents were very frequently (>20 times/year) or frequently (between 6 and 20 times/year) involved in neonatal or paediatric intensive care patients. Nineteen percent (15/79), mostly laboratory geneticists, were never involved in the care of critically ill neonatal or paediatric patients in their regular practice.
All clinical participants, except the clinical research associate, prescribe genetic tests in their regular practice.
Medical genetics knowledge and training
To evaluate the need for specific training, respondents were asked to self-evaluate their knowledge on medical genetics, including legal aspects, techniques and limitations of the test, understanding of genomic reports, and genetic counselling. As expected, an average of 96% of clinical geneticists and molecular geneticists considered their knowledge of genetics as ‘very good’ or ‘good’. In contrast, an average of 55% of the NICU/PICU professionals considered their knowledge level as moderate and 14% as poor (Figure 1).
When asked if specific training was necessary before the first prescription of an urGS for NICU or PICU patients, an average of 97% agreed that healthcare professionals should receive specific training before a first prescription, this opinion being shared throughout specialties (Figure 1). Three respondents commented that the training should be basic knowledge tailored to their field of practice, in order to give them the minimal knowledge useful to them.
Perceived utility and possible impact
Ninety-four percent of respondents (109/116) considered urGS very useful or useful in a NICU/PICU situation (Figure 2). Six respondents considered the test moderately useful, five were from clinical genetics and genetics laboratories, and one paediatric specialist (dermatologist). A single respondent (clinical geneticist with <6 times/year interactions with NICU/PICU patients) disagreed with clinical utility.
The majority of NICU/PICU MDs, who are more likely to prescribe medical examinations, said they would not cancel or postpone a biological (non genetic) or an imaging prescription (65 and 73% respectively) while waiting for urGS results. However, 65% (24/37) would cancel or postpone an ethical discussion on the decision to withhold or withdraw life-sustaining treatments. Forty-nine percent (18/37) said they would cancel or postpone surgery, while 35% (13/37) said they would not change their surgical plan. After reception of the urGS results, they would cancel biological (non genetic) or imaging prescriptions, or surgery (70%, 60% and 51% respectively) (Figure 2). Ninety-seven percent (112/116) of all the respondents considered that a genome result (conclusive or not) could alter the decision to withhold or withdraw life-sustaining treatments (Figure 2). Nine participants commented that it was difficult to answer as the question was not focused on a specific situation.
Organisation of ultra-rapid genome sequencing prescription
Ninety-three percent of participants agreed that a dedicated workflow with designated ‘referents’ in each ward would be a relevant organisation.
Participants were asked which clinical presentations in a list would lead them ordering urGS: 82% (95/116) selected neonatal hypotonia, 79% (91/116) multiple malformative features, 79% (91/116) neonatal epilepsy, 58% (67/116) prematurity with atypical complications and 57% (66/116) for cardiopathy. Twenty-eight percent (32/116) said they would prescribe an urGS in the presence of additional clinical presentations, with the main presentation being suspicion of a metabolic disorder (11 out of 29 detailed answers). Four participants said it was difficult to identify a specific clinical presentation, as for them urGS would guide management more in a situation with short-term resuscitation or surgical considerations.
Eighty-seven percent of respondents (101/116) considered that a multidisciplinary validation of genome sequencing is necessary (Figure 3). Among them, 95% (96/101) thought that a clinical geneticist should be mandatory for multidisciplinary validation, 90% (90/101) a NICU/PICU MD, and 52% (52/101) a biological geneticist. Regarding the way of organising this validation, the majority (71%, 72/101) of respondents ranked a meeting (in-person or virtual) as the best option, and 63% (3/101) ranked a digital multidisciplinary meeting tool for asynchronous assessment by each professional as second best option. Two participants commented that email exchange was not a good option for validation. Twelve percent (14/116) were not in favour of a multidisciplinary validation of the test: 5 of them were clinical geneticists, 2 laboratory geneticists.
Consent and psychological assistance
The majority of the clinical and laboratory geneticists (90%, 56/62) said that a clinical geneticist was the first choice for providing pre-test information and obtaining parental (or legal representative) consent for urGS, compared with 59% (20/34) of the NICU/PICU MDs. A genetic counsellor was the second choice for 49% (57/116) overall , and a NICU/PICU MD (senior or trainee) was the third choice for 53% (61/116) of respondents.
Fifty-four percent (20/37) of NICU/PICU MDs thought they would be able to prescribe the test, while giving appropriate pre-test information on the analysis and consent.
The French standard consent form was considered appropriate for 84% (97/116) of participants. Fourteen percent (16/116) considered it was not appropriate. Eight respondents detailed their concerns about incidental findings.
Ninety-one percent (106/116) of respondents thought that psychological assistance was crucial before the prescription, 59% (68/116) during the prescription, 81% (94/116) when the result was given, almost all (99%, 115/116) after the result.
Results and report content
Eighty-four percent of participants thought that a multidisciplinary discussion of the result was necessary before using it for clinical care (Figure 3), and 82% of them were in favour of a quorum of intensivist, clinical geneticist and biological geneticist to discuss it. Among those who disagreed, two said that a specialist for the pathology seen in the patient or identified through the test should be involved.
We asked the respondents to choose an option in a time-frame for receiving a result for genome sequencing from the time of deciding to request the sequencing from less than 6 hours to more than 2 weeks. Only one respondent said the optimal turnaround time for receiving a urGS result, starting from the moment the analysis was considered, would be less than 6 hours, 8% (9/116) said less than 36 hours, 24% (28/116) said less than three days, 35% (41/116) said less than 7 days and 21% (24/116) less than 2 weeks (Figure 3). Forty-five percent (10/22) of professionals working in genetic laboratories considered the optimal turnaround time to be less than 2 weeks, compared with only 11% of NICU/PICU MDs.
Healthcare professionals were asked if variants of uncertain significance (VUS) should be included in the report in the context of urGS in NICU/PICU: 36% were in favour, 58% were against (Figure 4). Two comments underlined the fact that it depended on whether or not the VUS was likely to rapidly become a diagnosis.
Seventy-eight percent (90/116) of respondents were against additional findings being reported at the same time as the result of the urGS in NICU/PICU (Figure 4).
Communication of the result to the patient and patient management
A joint report by a clinical geneticist and the NICU/PICU MD was considered as the ideal way to communicate the result to the patient’s family for 91% (105/116) of respondents, but was judged to be feasible by only 59% (68/116) (Figure 3). A report to the family by the clinical geneticist alone was ranked as 2nd ideal choice by 73% (85/116), and by the NICU/PICU MD alone was ranked as third ideal choice by 58% (67/116). Report by a genetic counsellor alone was ranked as the last ideal option by 74% (86/116) of respondents.
Ninety-five percent (110/116) of the respondents were in favour of informing the family prior to specific treatment initiation following a genetic diagnosis, which could be a challenge in a NICU/PICU situation, particularly depending on who reported the results to the family.
Finally, 89% (103/116) of respondents thought that a systematic follow-up consultation with a clinical geneticist is advisable.