Parental Views on the Psychosocial Impact of False-Positive Results Following Newborn Screening for Severe Combined Immunodeficiency in England
, Chloe Musa 2,†, Anju Keetharuth 3, Fiona Ulph 2, Jim B. Chilcott 3, Louise Moody 4, Ellinor K. Olander 5 and Jane Chudleigh 1
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsThis manuscript reports an assessment of the psychosocial impacts on parents of false positive newborn screening results for SCID in the English health system. The topic remains timely. This manuscript is nicely written and the conclusions follow from the data and analysis. The number of parents recruited is not large but it is adequate given the rare nature of the target experience. I have only a few relatively minor recommendations.
1) The Introduction should include a brief discussion of the nature and timing of information regarding NBS that is routinely provided to parents or prospective parents. Is the information provided prenatally or postnatally and what, if anything, is currently provided about false positive results? This information will tie into the recommendations at the end regarding better educating parents with respect to false positive results. With this addition, it might be noted whether parents provide informed permission for NBS in England.
2) The material in section 3.1 Demographics might better be presented in a table.
3) At several points, the authors raise the prospect of getting consent from parents to delay the communication of initial results until after the confirmatory testing is complete. I understand the potential value of this but I am entirely unsure how that conversation would go. Would the conversation be for all potential abnormal results in the NICU pending confirmation or would this be specific to, say, SCID or any NBS result once an initial abnormal test was obtained? I don't have a good sense of how this conversation would go - parents would want to know about abnormal results if they had been reported already. An additional sentence about how this permission would be obtained would be helpful.
4) The recommendation regarding the possibility of clinicians revisiting the topic of the false positive result at a later medical visit is very important. Thank you.
Author Response
We would like to thank you for the positive feedback and helpful comments that have supported the revised manuscript. We have made every attempt to fully address these comments and believe the manuscript has benefited as a result. Details on how the comments have been addressed can be found below. Please let us know if you require any further clarifications. Thank you once again.
Comment 1: The Introduction should include a brief discussion of the nature and timing of information regarding NBS that is routinely provided to parents or prospective parents. Is the information provided prenatally or postnatally and what, if anything, is currently provided about false positive results? This information will tie into the recommendations at the end regarding better educating parents with respect to false positive results. With this addition, it might be noted whether parents provide informed permission for NBS in England.
Response 1: Thank you for pointing this out. We agree with this comment and have expanded the introduction to explain that parents are informed about NBS antenatally and consent to the heel-prick test before the sample is taken on day 5 of life. The information provided does not routinely include details about the nature of false positive results (page 2, paragraph 3, lines 75-79).
Comment 2: The material in section 3.1 Demographics might better be presented in a table.
Response 2: Thank you for pointing this out. We agree with this comment and have added Table 2: Demographic Characteristics (page 6, line 229-234).
Comment 3: At several points, the authors raise the prospect of getting consent from parents to delay the communication of initial results until after the confirmatory testing is complete. I understand the potential value of this but I am entirely unsure how that conversation would go. Would the conversation be for all potential abnormal results in the NICU pending confirmation or would this be specific to, say, SCID or any NBS result once an initial abnormal test was obtained? I don't have a good sense of how this conversation would go - parents would want to know about abnormal results if they had been reported already. An additional sentence about how this permission would be obtained would be helpful.
Response 3: Thank you for pointing this out. We agree with this comment and have expanded the discussion to explain that ideally permission would be obtained at the point that consent for NBS screening is already acquired and would enable a discussion of the possibility of a false positive result (page 13, paragraph 3, line 533-537; and page 14, final paragraph, line 603).
Comment 4: The recommendation regarding the possibility of clinicians revisiting the topic of the false positive result at a later medical visit is very important. Thank you.
Response 4: Thank you, we also agree that this is an important recommendation.
Reviewer 2 Report
Comments and Suggestions for AuthorsIJNS Review comments on Holder et al. 2026
The authors present in this manuscript the experiences and psychological impact on parents whose babies received a positive NBS for SCID in England. After confirmatory diagnostics, the affected babies were referred as healthy (false positive screening). Using a mixed methods design, the authors conducted interviews with 28 parents. They commonly reported negative emotions when receiving the positive SCID screening result, especially during the waiting period before confirmatory testing. Most parents felt relief after the healthy diagnosis confirmation, but some parents experienced ongoing worries about their child’s health. Despite the emotional distress caused by false positive results, all parents supported NBS for SCID. Early detection outweighs the temporary anxiety, and parents suggested the need for better pre-screening information, clearer communication and follow up support for affected families.
The manuscript is well written and I do not have any major comments or critique. However, I would like to ask the authors the following:
Could the authors point our possible causes for false positive results during SCID screening? Do they have an efficiency and specificity percentage for the TREC Assay?
Additionally, is there any documented false negative case? If so, is there any information on how false negative affects parents?
On line 501 the authors refer to false-positive CF results and the impact on the parents. Are there any other similar studies or information for other diseases in the UK NBS program and their impact on parents?
Author Response
We would like to thank you for the positive feedback and helpful comments that have supported the revised manuscript. We have made every attempt to fully address these comments and believe the manuscript has benefited as a result. Details on how the comments have been addressed can be found below. Please let us know if you require any further clarifications. Thank you once again.
Comment 1: Could the authors point our possible causes for false positive results during SCID screening? Do they have an efficiency and specificity percentage for the TREC Assay?
Response 1: Thank you for pointing this out. We agree with this comment and have expanded the introduction to explain that low TREC levels can result from other factors such as such as prematurity or low birth weight and have provided the sensitivity, specificity and PPV from the SCID ISE (page 2, paragraph 2, lines 69-74).
Comment 2: Additionally, is there any documented false negative case? If so, is there any information on how false negative affects parents?
Response 2: Thank you for pointing this out. We agree with this comment and have expanded the discussion to include an example from CF screening: the diagnostic process for CF has been shown to be worse after a false negative screening result leading to negative impacts on parental employment, childcare arrangements and parent/child relationships (Chudleigh et al, 2024, https://doi.org/10.1016/j.ssmqr.2024.100455). Page 14, paragraph 3, lines 590-596.
Comment 3: On line 501 the authors refer to false-positive CF results and the impact on the parents. Are there any other similar studies or information for other diseases in the UK NBS program and their impact on parents?
Response 3: Thank you for pointing this out. We agree with this comment and have expanded the references in the discussion to highlight that the range of negative emotions experienced by parents have been shown across other diseases (page 13, paragraph 1, lines 507-509).
