Benefits and harms of antenatal and newborn screening programmes in health economic assessments: the VALENTIA systematic review and qualitative investigation

Eligibility criteria

The Population, Intervention, Comparator, Outcome and Study design (PICOS) framework was used to develop the study eligibility criteria (Table 3) and applied to the literature searches. Searches were limited to studies published after 1 January 2000. Studies reporting health economic assessments, such as economic evaluations and studies that use economic frameworks of cost-effectiveness evidence or economic notions of value (e.g. multi-criteria decision analyses, programme budgeting and marginal analyses) of antenatal or newborn screening programmes, were included. Non-English language studies were included, but studies were limited to those conducted in developed countries (defined, for the purposes of this review, as a member of the OECD40).

Information sources

Systematic searches of both published and grey literature, including peer-reviewed journal articles controlled by commercial publishers and documents produced by all levels of government, academia, business and industry, were conducted. The following electronic bibliographic databases were searched: MEDLINE (OvidSP) (1946–present), EMBASE (OvidSP) (1974–present), NHS Economic Evaluation Database (via CRDWeb www.crd.york.ac.uk/CRDWeb/) (inception to 31 March 2015), EconLit (Proquest) (1969–present), Science Citation Index, Social Science Citation Index and Conference Proceedings Citation Index – Science (Web of Science Core Collection) (1945–present), CINAHL (EBSCOhost) (1982–present) and PsycINFO (OvidSP) (1806–present). SCOPUS (Elsevier) was used to run forward and backward citation searches once relevant studies were identified. The academic electronic database searches were supplemented by manual reference searching of bibliographies from studies that were included, contacts with experts in the field and author searching based on experts’ opinion. The first full search of published literature was conducted on 24 April 2020 with a top-up search conducted on 2 July 2020 to include the ‘perinatal’ search term while a refresh search was conducted on 22 January 2021.

The list of grey literature searched was derived from a pool of relevant websites that was informed by a recent systematic review of national policy recommendations on newborn screening that identified websites of national and regional screening organisations with documentation about antenatal and/or newborn screening recommendations. 41 This was widened to cover websites reported by the Health Grey Matters checklist and those for national and regional screening organisations, HTA agencies, paediatrics organisations, and obstetrics and gynaecology societies in OECD countries, as well as international decision-making bodies, such as the World Health Organization, the European Council, European Commission and the European Observer. 41,42 A customised web scraping tool that used the Google search engine was built using Python to directly query the stated websites (see Appendix 1) from 18 to 27 January 2021 using English search terms and from 14 to 17 February 2021 using translated search terms for non-English websites, as well as to automate the data extraction processes.

Search strategy

The search strategies applied to the published literature (see Appendix 2, Tables 21–26) were developed using a combination of medical subject headings (MeSH) and free-text keywords related to health economic assessments of antenatal and newborn screening programmes in collaboration with an information specialist (NR) with expertise in conducting systematic literature reviews in the health sciences. A simplified search strategy derived based on the Cochrane guidelines was applied to the grey literature search. 43 Translation of the simplified search terms for non-English websites was performed by professional translators.

Data management

The results of the literature searches were uploaded into the Endnote software package X9 (Clarivate, Philadelphia, PA, USA, 2019), a reference management system specifically designed for managing bibliographies and citations, to remove duplicates. Unique records were subsequently imported into Covidence,44 an online software program that facilitates collaboration among reviewers during the screening and data extraction stages. This software allows importation of references and files to be screened and information can be entered into a pre-created data extraction form after removing duplicates. Screening criteria based on the inclusion and exclusion criteria specified in Table 3 were developed and tested. A calibration exercise was undertaken to pilot and refine the screening criteria before the formal screening process started. For non-English language papers, Google Translate (Google, Mountain View, CA, USA) was used to translate relevant documents.

Selection process

For the published literature, two reviewers (MEP and MY) independently screened the titles and abstracts of all retrieved articles and documented the reasons for study exclusion according to the criteria specified in Table 3. Full texts of potentially relevant articles were reviewed independently by the same reviewers (MEP and MY), and study eligibility based on the inclusion and exclusion criteria was assessed. At each stage of the selection process, any disagreement was resolved by discussion and consensus between the two reviewers. When consensus could not be reached, input from the rest of the review team (ORA and SP) was obtained. For the grey literature, only one reviewer (MEP) did the title/abstract and full-text screening of all the retrieved articles, while another reviewer (SR) screened the titles/abstracts of a random sample of at least 10% (13%) of the retrieved articles due to a change and shortage in work force and limited time.

Data collection process

A data extraction form, which was piloted and refined using 10 randomly selected studies identified in the academic electronic databases, was created using Microsoft Excel following recommendations from the Cochrane Handbook for Systematic Reviews of Interventions. 43 As we had anticipated a large number of articles to data extract, after consulting our Independent Oversight Committee members and Information Specialist (NR), a selection of 10% of the articles/reports was extracted independently by two health economists (MEP and MY), followed by a reconciliation process. During this reconciliation process, MEP and MY had to extract the same key information from a random set of conference abstracts, journal articles and reports before they proceeded to extract the other studies independently and this was observed after assessing around 10% of the papers/reports. The rest of the published literature was subsequently divided between the two reviewers (MEP and MY), while data from the grey literature were extracted by one reviewer (MEP) only. Furthermore, any uncertainties related to data extracted by the two independent reviewers (MEP and MY) was discussed with the two senior investigators (ORA and SP) at weekly meetings. The list of variables extracted from each report included at the final stage of the review process was finalised following the piloting and refinement of the data extraction sheet.

The data extraction form consisted of two parts: (1) a section that contained items from the CHEERS checklist,45 modified where applicable to align with our research focus (i.e. benefits and harms within economic assessments) (see Appendix 3). This included bibliographic details; condition(s) screened; approaches for measuring and valuing health outcome measures; the journal impact factor quartile during the year that the article was published, obtained from Clarivate Analytics and SCImago; whether the authors made any policy recommendation based on their economic evaluation evidence; and whether the authors might have had any potential conflicts of interest in promoting their screening programme or mechanism (defined as a study that was funded by an industry sponsor, unless it was an unrestricted grant, and at least one of the authors being clearly employed by the industry sponsor); and (2) a bespoke form (see Appendix 4) created by the research team to extract benefits and harms adopted by economic assessments evaluating antenatal or newborn screening programmes. This form was created de novo as we could not find any previous examples in the published literature. A detailed description of the process to create the bespoke form is described in Chapter 4. This bespoke form contained consequences as reported by authors by screening test outcome (i.e. true positives, false positives, true negatives and false negatives) and type of data (i.e. probability, cost or outcome), which were captured and categorised as either a benefit or a harm. We also recorded the stage of the disease pathway at which the screening test was administered and the phase(s) of the screening programme using categorisations from recent guidance,1 as well as recorded whether the structure of decision-analytical models had been reported, and the consequences associated with treatment where applicable.

Data items

In order to reduce bias from including data from multiple reports of the same study, multiple articles published by the same authors with similar titles and abstracts were treated as linked companion studies (i.e. multiple reports from a single study) and only the most detailed publication was included in our final outputs. Similarly, if conference abstract(s) and a journal article by a similar group of authors had been published on the same topic, only the journal article was included at the full-text screening stage. Since we were interested in the methodological approaches to the measurement and valuation of benefits and harms and how the results were reported, if the article/report title suggested that an economic evaluation was conducted but neither the methods nor the results were presented in the abstract or full text, the article/report was excluded at the screening stage(s). Articles/reports that did not focus specifically on pregnant women or newborns but reported separate results of screening of pregnant women or newborns within broader populations were still included. In addition, authors were not contacted for missing data on individual data items included in our data extraction sheet, which were instead recorded as ‘not stated’.

Assessment of reporting quality of individual studies

Since only aggregated data and no effect sizes were sought, we did not assess the risk of bias or conduct a formal meta-analysis. Instead, the reporting quality of articles and reports (excluding conference abstracts) was assessed using the CHEERS reporting statement. 45 The items were considered as ‘satisfied’ if reported in full or ‘not satisfied’ if not reported or partially reported. The items were not scored as per the guidance in the CHEERS reporting statement. 45

Deviations from protocol

There were a few of deviations from the protocol. First, we used Endnote and Covidence for different components of the systematic review. Endnote was used to record all the studies identified as part of our searches and employed to identify and remove duplicates. Covidence was used as it can better facilitate collaboration among reviewers during the screening and data extraction stages than Endnote. Second, we did not use any risk of bias tools such as Cochrane ROBEQ tool and Risk Of Bias In Non-randomized Studies – of Interventions (ROBINS-I) for different study designs because the aim of the systematic review was to understand the benefits and harms of antenatal and newborn screening and not to extract any quantitative information from the papers. Therefore, we excluded any reference to risk of bias assessment from the final published protocol for the systematic review. For the same reason, we did not explore further the external validity of any of the cost-effectiveness results published in the studies. We have used the CHEERS statement to evaluate the reporting quality of the studies since understanding the reporting quality of these studies was a primary aim of our systematic review as it was good indicator of whether a particular study was going to provide all the information in our bespoke form. Last, data extraction was not conducted independently by the two reviewers and a 10% sample was used because the former was not feasible as we ended up including 336 articles and reports and it was decided given our timelines to change the strategy for the data extraction. All deviations were discussed and approved by our Independent Oversight Committee.

Search results

We identified 52,244 articles and reports from the searches of the published and grey literature. Among the 16,052 records that were sought for retrieval based on identification of records via other methods (i.e. grey literature), 7464 records were non-English (46.5%). Thirty-nine studies of the non-English records were assessed for eligibility with five subsequently included in the data extraction phase. A total of 336 records, 310 articles (1.4% of databases) and 26 reports (0.08% of websites), were included in the systematic review. One HTA report included two separate economic evaluations that were separated into two different reports, resulting in 337 outputs. Study selection and reasons for exclusion as well as data extraction of the bespoke form are summarised in the modified PRISMA diagram (Figure 3). The list of studies excluded is summarised in Report Supplementary Material 1.

FIGURE 3.

Modified PRISMA flow diagram. a, One HTA report included two separate economic evaluations that were separated into two different reports, resulting in 242 outputs from the 241 records.

There was no trend in the publication year of the articles and reports (Figure 4). Characteristics of the included articles and reports are presented in Table 4. The majority of the articles and reports included were journal articles (228, 67.7%) and almost half of the studies were conducted in the USA (109, 32.2%) and the UK (43, 12.7%). The majority of the articles and reports also required further information to determine if the authors had potential conflicts of interests (221, 65.6%). Furthermore, the authors did not make any recommendation about the adoption of the screening programme based on the economic evidence generated for the majority of the articles and reports (273, 81.0%). The majority of the articles were published in top quartile medical journals (i.e. quartile one; 129, 38.3%).

FIGURE 4.

Number of articles and reports published from 2000 to January 2021. Note: Dotted lines were used to indicate that only January 2021 was included in this chart.

Target population and setting

The characteristics of screening programmes and populations in the included articles and reports are summarised in Table 5. There were 173 (71.5%) studies on antenatal screening and 63 (66.3%) studies on newborn screening that did not state the setting of the screening (236, 70.0%) or the women’s gestational stage at the time of screening (168, 65.4% of the antenatal screening studies). The majority of the studies were targeted at the general population of pregnant women (197, 57.1%) or infants (91, 26.4%). Many studies were investigations at the symptomless stage with pathologically definable change present (303, 89.9%) or involved all phases of the screening programmes (162, 48.1%).

Medical conditions investigated are summarised in Table 6. Genetic conditions and infectious diseases (153, 63.2%) were the main areas covered by the articles and reports assessing antenatal screening. Metabolic and structural conditions (57, 60.0%) were the main areas covered by health economic assessments evaluating newborn screening programmes.

The key methodological characteristics of the health economic assessments from the CHEERS checklist are summarised in Table 7 and in the following subsections.

Choice and time horizon of model

The most common type of economic evaluation used was ‘cost–utility analysis’, which reports outcomes in terms of QALYS or disability-adjusted life-years (DALYs), for antenatal screening (129, 53.3%), and cost-effectiveness analysis for newborn screening (47, 50.0%). Decision-analytical models were employed in 272 (81.0%) of the articles and reports for the economic evaluations – 200 (82.6%) in antenatal screening and 72 (76.6%) in newborn screening. Among these studies, the majority either employed a lifetime horizon (82, 41.0% for antenatal screening and 37, 51.4% in newborn screening) or did not state the time horizon (75, 37.5% for antenatal screening and 14, 19.4% for newborn screening).

Cost perspective

The costing perspective adopted was not stated in 117 (33.7%) articles and reports. Among those that stated a costing perspective, the majority adopted a health system or payer perspective (107, 43.5% for antenatal screening and 53, 52.5% for newborn screening).

Main outcome measures used in the economic evaluations

The source to inform the main outcome measures in the economic evaluations came predominantly from evidence synthesis of secondary data for both antenatal (167, 77.3%) and newborn (62, 67.4%) screening. Natural units such as number of cases averted and number of cases detected were the more commonly reported outcome measure in both antenatal (187, 59.2%) and newborn (73, 65.2%) screening studies. QALYs were used as the main outcome measure in 129 (39.9%) of antenatal screening and 36 (32.1%) of newborn screening studies. The DALY metric (an outcome measure that combines years of life lost due to premature mortality and years lived with a disability) was used in five studies across both types of screening programmes. Maternal preference-based outcomes (QALYs/DALYs) were reported in 94 (72.9%) of the antenatal screening evaluations, whereas infant preference-based outcomes were reported in 34 (89.5%) of the newborn screening evaluations.

Preference-elicitation methods for valuation of outcomes

Thirty out of 162 studies generated QALYs based on preferences for relevant health states using direct valuation exercises or preference-based instruments based on individual patient-level data. Thirteen out of the 65 studies (20%) reported that they had used a standard gamble and/or time trade-off method to obtain preferences directly from individuals within their studies; of which, 10/47 (21.3%) were antenatal screening programme assessments and 3/18 (16.7%) newborn screening programme evaluations. The use of preference-based instrument to describe health-related quality of life outcomes was limited with only 9/47 studies (19.1%) that investigated antenatal screening programmes and 7/18 (38.9%) that investigated newborn screening programmes stating clearly the instrument used and included the EQ-5D, Health Utilities Index 2 (HUI2), HUI3, 16-Dimension (16D) or the Quality of Well-Being Scale (QWB). There were two studies (one each for antenatal and newborn screening programmes) that used mapping of a non-preference-based survey [i.e. Edinburgh Postnatal Depression Scale and Adrenoleukodystrophy-Disability rating scale (ALD-DRS)] onto a generic preference-based measure.

Assessment of reporting quality

Reporting quality assessed using the CHEERS checklist was heterogeneous among the 264 full-length articles and reports (as summarised in Appendix 5). The top five items not satisfied among the studies for antenatal screening programmes were ‘Abstract’ (160, 88.4%), ‘Time horizon’ (153, 84.5%), ‘Choice of model’ (153, 84.5%), ‘Discount rate’ (130, 71.8%) and ‘Study funding, limitation, generalisability, and current knowledge’ (123, 68.0%). Similar results were found among studies assessing newborn screening programmes. The top five items not satisfied among these studies were ‘Abstract’ (69, 83.1%), ‘Time horizon’ (67, 80.7%), ‘Study funding, limitation, generalisability, and current knowledge’ (59, 71.1%), ‘Choice of model’ (55, 66.3%), ‘Discount rate’ (53, 63.9%) and ‘Setting and location’ (53, 63.9%). The majority of these items were partially satisfied as authors failed to justify the rationale of their methodology as required by the CHEERS checklist.

Development of bespoke form

A rapid review was conducted to identify previous checklists in the area of identification of benefits and harms associated with screening programmes. We evaluated checklists for the conduct of economic evaluations of screening programmes [i.e. Consensus Health Economic Criteria for trial-based studies and International Society of Pharmacoeconomics and Outcomes Research (ISPOR) checklist for model-based studies], and report of harms in clinical studies [i.e. PRISMA-Harms, PRIO-Harms, McHarm and Consolidated Standards of Reporting Trials (CONSORT)-Harm checklists]. This review suggested that no previous checklist was fit-for-purpose to identify benefits and harms associated with screening and adopted by economic evaluations. We therefore developed a de novo bespoke form for this purpose. Our starting point was that benefits and harms can manifest across the screening pathway and that ideally studies should report the following: the stage of the screening pathway; information on different phases of the screening programme such as the screening test, confirmatory diagnosis (if needed) and treatment; and description of consequences included, depending on the outcomes of the screening test (i.e. true positives, false positives, true negatives, false negatives as well as inconsequential conditions that will remain without symptoms during lifetime among the ‘true positives’ and ‘false negatives’) as set out in recent guidance. 1 Therefore, a bespoke form based on the aforementioned was created (see Appendix 3).

Development of the thematic framework

For all the studies included in the systematic review, we attempted to complete the bespoke form. The information captured in the bespoke form was used to create a framework of benefits and harms adopted by health economic assessments using a process of grouping themes derived from the data collected in the bespoke form. 47 An integrative descriptive analysis48 of the collated themes within each category was then conducted, resulting in a taxonomy of benefits and harms consisting of a primary theme and up to four levels of subtheme(s). In the first step, the description of consequences was categorised into specific themes by ST-P. This pool of themes was the starting point of an iterative process where members of the study team (ST-P, MEP, OR-A and SP) merged, separated and refined the wording of themes and subthemes. The iterative process was maintained until consensus was reached among the study team (ST-P, MEP, OR-A and SP). Articles and reports were categorised into themes and subtheme(s) according to the condition and screening type. Bar charts were generated to illustrate the framework across and by medical condition(s).

Deviation from protocol

As we developed our approach to reviewing the literature on experiences of newborn screening, we decided that using a meta-ethnography, rather than a scoping review, would allow give us more sophisticated purchase on the literature we sought to synthesise. The goal of this approach is to bring together, and interpret, insights from qualitative research and producing an in-depth understanding of their collective findings. This approach supported identification of the key themes of absorptive capacity, reported in the article in Social Science and Medicine. 52

Approach to meta-synthesis

We opted not to conduct a meta-ethnography of experiences of antenatal screening due to the existence of several reviews, meta-syntheses and meta-ethnographies in this area,53–56 including those published recently. 57,58 This literature highlights the sense of responsibility felt by parents to participate in antenatal screening,55,56 the shock and devastation experienced when an unanticipated result was returned54,55 as well as the significance of technology, and relationships with healthcare professionals as mediators of the antenatal screening experience. 57

Unlike antenatal screening, parents’ experiences of newborn screening have been less extensively reviewed. This is in spite of the newborn genomes programme gaining momentum59 and increasing calls to expand the newborn bloodspot test to include more conditions (e.g. SMA Newborn Screening Alliance, 2021). As such, the scope and delivery of newborn screening is currently high on both the research and policy agenda in the UK. In light of this context, our meta-ethnography was designed to analytically interrogate parents’ experiences of newborn screening to contribute to debates around expanded screening, and to interpret the findings as a contrast to the existing antenatal screening literature, where decisions, timeframes and outcomes of screening are entirely different.

The goal of a meta-synthesis is to bring together, examine and interpret findings from disparate qualitative research studies and produce a more in-depth understanding than is possible from looking at the studies individually. 50,60 It offers the opportunity to identify patterns, processes and contexts, as well as omissions from a body of work. 61 While there are multiple ways of synthesising qualitative research,62 we followed the stages of meta-ethnography as described by Toye et al. (2014). 63

Stages of meta-ethnography

We wanted to bring together qualitative studies that explored parents’ experiences of newborn screening. We opted to conduct a systematic literature search to provide evidence that we sought to capture as much of the evidence within the scope of our research question as possible. 63 Recognising that it can be challenging to locate qualitative research studies, we began with a broad, systematic search strategy. 64 We searched for any instance of the terms ‘newborn screen*’, ‘neonatal screen*’ or ‘newborn bloodspot’ in the title or abstract of academic journals published in English from January 2000 until December 2019 across five databases accessed through the University of Oxford Libraries (Table 9).

After running the search, AW removed duplicate records and reviewed titles and abstracts for eligibility. If it was unclear whether or not a record should be included based on the title and abstract, it remained in the pool until the next step. Next, AW read the remaining studies in their entirety to assess eligibility. LH provided a secondary ruling for articles that AW was uncertain about. As the final step, AW hand-searched the reference lists of included studies to identify additional research not identified through the search strategy. AW maintained a database of all decisions about inclusion and exclusion (Figure 7).

FIGURE 7.

Flow diagram of included and excluded studies.

Studies were eligible for inclusion if they focused on parental experiences of newborn bloodspot screening programmes and used qualitative methods. Non-research publications, such as commentaries or letters to editors, were excluded. Similarly, mixed-methods research was excluded, as the qualitative analysis was often secondary to reporting statistical findings. As we were interested in how parents experienced varying aspects of the newborn screening process, studies that included other stakeholders (e.g. genetic counsellors or midwives) alongside parents were excluded, as it was challenging to separate findings between stakeholder types. We also excluded studies that were beyond the scope of the review, including those focused on storing newborn blood spot cards, antenatal genetic counselling, being diagnosed with a screened-for condition in later life or living with a screened-for condition. We did not exclude any papers based on quality. We were aware that the authors of included papers were writing with varying aims for different audiences, and they ranged from healthcare providers to ethnographers. The papers included in this synthesis reflect the wide-ranging disciplinary backgrounds and purposes of the authors contributing to this field.

Once we had a finalised list of included studies, we divided the work of reviewing among the research team. AW read all of the studies and maintained an Excel database tracking study characteristics. We split the number of studies (n = 36) evenly among the remaining four members of the research team (AM, FB, LH, LL) so that each was responsible for focusing on nine studies. We read the included studies in their entirety, with particular attention focused on the findings and discussion sections of studies. We used a combination of computer-aided and paper-based reading and coding processes. AW uploaded PDFs for the included studies to NVivo 12 Pro (QSR International, Warrington, UK). She progressed from a line-by-line coding approach to organising codes into descriptive themes and then refining codes into conceptual categories. The remaining researchers used a paper-based approach to coding, where they read the studies and hand-coded higher-level concepts as they emerged. They made a note of these concepts and shared them with the research team during analysis meetings.

After we analysed the studies individually, we set about synthesising the literature and identifying meta-themes. This was an iterative process that took place over several months. We arranged evidence synthesis meetings to discuss our analysis and identify cross-cutting themes. We discussed overarching concepts and considered how they might apply to various other studies in the synthesis. Even though individuals were responsible for different subsets of studies, we generally found that we had developed overlapping concepts, albeit under slightly different names. As we reached consensus on the core experience dimensions drawn from the compiled literature, we synthesised these findings into higher-order interpretations across screening contexts and conditions from which substantive conclusions about the experiences and implications of newborn screening from a parental perspective could be drawn.

Mapping newborn screening pathways from included studies

Our systematic review yielded a total of 36 studies (see Appendix 7). Studies ranged from descriptive accounts of the newborn screening experience to theory generation about the meanings attached to those experiences. Given the complexity of newborn screening, many studies were focused on discrete points in the pathway, although collectively they covered the newborn bloodspot ‘journey’. Through a cross-study analysis, a broader, richer picture takes shape compared to what can be provided in the individual papers.

Newborn screening has become an embedded part of the neonatal experience for parents. Drawing on the included studies, we mapped the various pathways that parents and babies might take when experiencing newborn screening (Figure 8). The consent process varies across, and even within, countries. In the USA, for example, screening is compulsory across nearly, but not, all of the 50 states. In other countries, parents are nominally required to consent to newborn screening. For example, in the UK under the NHS guidelines, healthcare providers (HCPs) should offer parents screening, and parents may verbally agree. 65 In practice, however, the extent to which parents are aware of their ability to refuse newborn screening is unclear, as a mother whose child screened negative in England reported, ‘It’s a very, very quick process and you’re not given any option to think about it’. 66

FIGURE 8.

Map of newborn screening pathways.

Regardless of the differences in the consent process, our review suggests that newborn screening is poorly understood, and its potential ramifications are not readily considered by parents. Parents frequently reported not recalling the consent process, or much about the purpose of the screen. 66–69 Parents described putting their trust in the healthcare system and medical authority, with newborn screening being largely seen as something that ‘just happens’ after having a baby, rather than an active choice. For these screen-negative families, newborn screening is ushered in by trusted medical authorities and is typically an experience that passes with little concern or complication.

While the majority of families exit their newborn screening journey swiftly, there is a subset of families who will receive the news that their baby screened positive, and these families are typically offered further testing or investigations. This is a moment of no return for many families, which has implications not only for the infant and parents, but also for the family writ large. Before receiving the news, parents may not have realised or appreciated how much impact the ‘heel prick’ test could have on their lives. Most parents – unless they are known carriers or are living with a condition – tend to have limited knowledge of the various screened-for conditions. 70 This is exacerbated by the fact that for the vast majority of conditions identified through the newborn screening ‘heel prick’, such as inherited metabolic diseases like phenylketonuria (PKU), the infant is typically asymptomatic at the point a positive result is received. However, sometimes non-specific symptoms may have already been observed by the parent(s). 71 Regardless of context or condition, such news ushered families into a compressed, critical window of time characterised by waiting periods, strong affective responses and a need for more focused communication. 71–75

Positive screening results are followed up by the offer of confirmatory diagnostic testing, with the nature of this testing varying by condition. From the result of the diagnostic test, the condition is either confirmed (the screening result was a ‘true positive’) or ruled out (the screening result was a ‘false positive’). However, for a subset of families, the results of diagnostic testing are somewhat more ambiguous, indicating either a carrier status or a gene variant for which the link to phenotype is neither clear nor certain. Even in cases where a precise diagnosis is made, the broad spectrum of severities associated with the conditions screened for, combined with lack of experience with symptoms at the point of diagnosis (or potential lack of symptoms), can dramatically heighten uncertainty for parents, despite being presented with the seeming certainty of a confirmed diagnosis.

Assessing parents’ absorptive capacity

Across studies, participants frequently used descriptions and metaphors of ‘absorption’ and ‘digestion’ to describe their processing of screening and testing information. For example, ‘Your brain is a sponge’ (mother of child with cystic fibrosis76) and ‘There was just too much at that time to absorb’ (mother of child with cystic fibrosis77). These metaphors and descriptions were common and prompted us to apply the concept of ‘absorptive capacity’ to screening contexts. ‘Absorptive capacity’ is a term used widely in management studies to refer to a company’s ability to ‘recognise the value of new, external information, assimilate it and apply it’. 78 The term is not commonly used at the level of the individual but has value as a lens through which to examine and explain parents’ ability to process new diagnostic information.

For the subset of families that have a positive or inconclusive newborn ‘heel prick’ screen, the initial affective responses tended to be ones of shock and anxiety. 79–81 Parents were not necessarily aware of what they consented to (or did not give consent for), so hearing that their child tested positive ushered in a period of shock, confusion and fear. Before receiving the news, parents largely conceptualised their child as healthy and perfect, particularly if they had also gone through the process of antenatal screening without any positive screening results. Parents had to reconcile to the fact that their child might not be symptomatic and instead ‘looked’ healthy, yet still had a positive newborn screening test. In such cases, parents’ distress and shock limited their ability to absorb information in the moments following the news that their child screened positive and at later points in the diagnostic process.

Absorptive capacity is also dependent on an individual’s prior related knowledge, including familiarity with medical concepts and language. 78 Based on the studies in this review, we argue that even if parents remember consenting to, or being notified about, newborn screening, they do not necessarily have the tools to understand what it means. Parents’ distress and subsequent inability to absorb information were augmented by their own unfamiliarity with screened-for conditions and genetics. 70,72,82 Tluczek (2006)76 points out that even the language surrounding screening and testing can be fraught with confusion, including the counterintuitive meaning of the terms ‘positive’ and ‘negative’ when describing test results, compared to an everyday conversation where these indicate ‘good’ and ‘bad’, respectively. However, even this interpretation overlooks the complexity of ways these terms can be understood and experienced by families. There has been a more recent push from families living with a range of screened-for conditions to employ neutral language in screening contexts that do not pre-empt the parents’ reception of the news as either ‘good’ or ‘bad’ which has now filtered into professional guidelines. Nevertheless, the use of inaccessible medical language to describe screening and testing results and processes was a widespread concern across the data set, which in turn impacted on parents’ absorptive capacities.

Beyond parents’ (un)familiarity, the format of information presentation also influenced parents’ absorptive capacity. To effectively absorb information ‘it is insufficient merely to expose an individual briefly to the relevant prior knowledge’ (p. 131). 78 Consent, or lack thereof, for newborn screening is taken at a time when new parents are simultaneously exhausted, distracted and busy caring for their new child. New mothers may also be experiencing postnatal physical and mental health concerns of their own. Any information given about the screen at that point does not seem to be experienced as a choice or an active conversation, but rather a minimal (if any) conveyance of information. 66–69 For the subset of families who are notified of a positive or inconclusive screen, the limited prior communication about the potential implications of newborn screening sets the stage for what is often perceived to be a period of problematic communication. 72,75,80,83–85

By looking across the studies, we considered how parents’ information needs varied by condition detected and context. We identified a continuum of informational needs, with parents preferring different levels of information at different points in the screening process, based on their absorptive capacities at that time. Some parents wanted to dive in and ‘consume’ as much information as possible, while others wanted ‘bite-sized’ chunks. Others wanted to hold back from obtaining information until there was diagnostic clarity. Unfortunately, parents’ needs were not always met. In some cases, parents reported being given a volume of information that they were ill-prepared to receive and unable to absorb. In other cases, parents reported wanting more information than was given by their HCPs. As a result, they sought other sources – primarily the internet or support organisations – in an attempt to increase their knowledge. 86–88

Informational needs became more complicated in instances where HCPs themselves, who were looked to as the experts, did not have the expertise to provide answers to parents’ questions. 81,86,89,90 HCPs may be counselling families with a rare condition for the first time, and this could undermine parents’ confidence in the information provided. Although we acknowledge that there may be a discrepancy between what HCPs say and what parents hear, it seems there is room for improving communication and information provision during this critical window when absorptive capacity is in its highest state of flux. 91

Newborn screening, uncertainty and the concertinaing of time

There is a crucial temporal component to parents’ experiences of newborn screening. Throughout the critical window, time expands and contracts, generating ripple effects into the past, present, and future. During the period between a positive screen and (potentially) receiving definitive diagnostic results, families are often living through a state of ambiguity or disorientation. How people approached living in the liminal space during the critical window varied considerably.

Families who viewed ambiguity as a negative state desired definitive answers as a means of gaining control. Such families may want to find out as much as possible about a potential condition and turn to information seeking online and from those with lived experience of the condition. 82,87,92 Once these families received a diagnosis, they were more able to make sense of the condition and how to manage it in the future. 70 Even among those with an ambiguous diagnosis, there may be a drive towards labelling as an attempt to gain control and make the situation more concrete, as explored in a study of families whose children screened positive for cystic fibrosis, yet received an inconclusive diagnosis. 90 For these families, knowledge about the condition allowed them to feel prepared to manage the health and social needs of their infant moving forward. However, such families must still live with the uncertainty of how/whether the condition will manifest in their child in the future and hold out hope that they will not need to use the information in the future.

While some families sought to learn, as much as possible, other families viewed the inherent ambiguity of this liminal period in a more positive light. In such cases, families rejected in-depth information about the condition in order to retain the hope that they will never need it. 92,93 These families adopted a ‘wait and see’ approach to the period between screening positive and receiving a diagnosis, on the basis that ‘too much information can be hurtful in a sense’. 92 If they are notified that the initial ‘heel prick’ result was a false positive, such families will have avoided the anxiety and stress that additional information can bring. However, if the child is diagnosed with a condition, these families may opt for ‘ “easy-to digest” information and “just the facts, because you can’t handle anything else” ’,83 reflecting again the concept of absorptive capacity. These families continued to look towards the future as a coping mechanism, hopeful that the condition will not manifest or will be of limited severity, or perhaps that treatments will improve over time.

While families were found to take a range of differing approaches as they moved through the critical window, they all shared a common experience that was found to have long-term ramifications for everyone involved. Indeed, for screen-positive families, the experience had ripple effects that stretched both backwards and forward in time. If an inheritable condition was detected, families found themselves looking backwards in their family tree, in an expansion of time, trying to work out where the trait might have ‘come from’. 70,82,94 As families looked backwards, some grappled with shame, blame, and guilt as they considered what might have been for their child, particularly when a child inherits a condition. 77,82,86,90,94,95

The impact of newborn screening was also found to flow forwards in time from the moment of notification of positive results, as parents found themselves reconsidering their expectations of the life they had imagined for their child and for themselves as parents. In quick succession, parents had to initiate a chain of emotional processing, discussion and medical appointments, involving not just the child but sometimes also the parents and wider family members. 73,74,94 For the parents of children who were asymptomatic at the time of the results, one particularly significant part of the screening journey was a loss of what should have been a happy time with their child – of ‘blissful ignorance’. This impact was particularly pronounced when compared to the experiences of families who received a later diagnosis. 73 For some, the pre-symptomatic diagnosis ushered in by newborn screening interrupted, and limited, the joyful time families were experiencing at the birth of their child. For these families, the positive or ambiguous screening result effectively extended the length and reach of the condition earlier into the infant’s life than otherwise would have been the case.

Newborn screening also has ripple effects that extended into the future, and across generations. As families moved away from receiving a diagnosis, time expands into uncertainty and the unknown. Parents of children living with conditions or ambiguous health statuses (e.g. cystic fibrosis screen positive, inconclusive diagnosis) have to consider how, when and to whom they disclose their child’s condition. 90 Parents also have to consider their own future reproductive intentions, including whether or not they want further children and, if so, what role antenatal or newborn screening may play in any subsequent pregnancies. 96 Parents of children who are found to be carriers of a condition through newborn screening also need to consider if, when, and how they will tell their child about their result. 97 These planning conversations were found to take place even as children were still newborns, even though disclosure might not take place for many years to come. Looking further into the future, the child will also have to consider how they manage their condition or carrier status, how/whether to disclose it to others, as well as their own reproductive intentions. 86 The implications of newborn screening therefore play out in the months, years and even decades following diagnosis, suggesting that the aspects of screening are enduring over the life course.

Data

We conducted secondary analysis of qualitative interviews derived from previously conducted studies exploring antenatal and newborn screening experiences and attitudes (n = 256; Table 10). These in-depth narrative interviews were conducted over the last 13 years by FB at the University of Warwick, and LH, LL et al. at the Medical Sociology and Health Experience Research Group, University of Oxford. While some interviews were conducted over 10 years ago, the majority were conducted within the past 5 years. Interviews included perspectives of people with a wide range of experiences in relation to screening, testing, pregnancy termination and continuation, as well as parents and affected adults living with genetic and chromosomal conditions.

Analysis

We used a situational mapping exercise to analyse this large data set. Situational maps ‘lay out the major human, non-human, discursive, and other elements in the research situation of concern and provoke analyses of relations among them’ (p. 554). 99 Situational maps are a reflexive, subjective form of data interpretation which aim to capture the complexities of a situation and their relations. 99,100 They are useful for rendering large data sets manageable and identifying complexity within the data. Our aim was to understand the people, objects, places and discourses that influenced antenatal and newborn screening experiences and attitudes. AW read the interview transcripts and used concept coding to assign meanings to chunks of the data. 91 These concepts represented higher-order themes that went beyond an individual narrative, and they typically included nouns (e.g. time) or processes (e.g. conceptualising normality). Concept coding was deemed appropriate since we were interested in meta-themes across the vast data sets and progressing towards an understanding of key concepts surrounding antenatal and newborn screening. 101

We used the concept codes to develop a situational map through an iterative, increasingly ordered representation of the elements related to antenatal and newborn screening. 99 Initially, this was a messy list of elements rooted in the empirical evidence from the conceptual codes. Over several weeks, we iteratively discussed the elements and considered the content of the data and boundaries of this project. 100 We refined the elements and organised them based on Clarke’s (2003)99 categories. Our situational map has both human elements and non-human elements. Human elements include the key individuals, groups and institutions involved in screening. Non-human elements include the technologies, materials and information that ‘structurally condition the interactions within the situation through their specific properties and requirements’ (p. 561). 99 We also considered the ‘ideas, concepts, ideologies, discourses, symbols, sites of debate’ that are involved in antenatal and newborn screening (p. 563). 99 Thus, we developed categories for economic elements (e.g. funding), sociocultural elements (e.g. gender or ethnicity), temporal elements (e.g. waiting periods), spatial elements (e.g. geographical differences) and related discourses (e.g. conceptualising quality of life).

As the situational map took shape, we conducted several rounds of revision to condense and clarify the categories. We asked PPI members to review the list of human elements (see Human elements involved in antenatal and newborn screening) and we also presented the entire situational map to our independent oversight committee. We used the input of these groups to make final minor adjustments to our meta-themes (e.g. naming conventions) but they deemed that no other adjustments were necessary.

Stakeholder mapping

We identified stakeholders for inclusion in our primary data collection as part of the situational analysis exercise (i.e. the individual and collective human elements). We compiled the list of stakeholders and presented it to our PPI members. We asked PPI members to review the list and brainstorm if there were any missing stakeholders based on their knowledge and/or experiences. The PPI members named different types of HCPs, but we have condensed these into broad categories in our situational analysis map (e.g. doctor, nurse). They also named different types of charities. Again, we condensed these into a broad category (i.e. ‘charity organisations’); however, we did seek out the identified charities for our later primary data collection (see Chapter 7). We also sought approval for our stakeholder list from our independent oversight committee. Nothing further was added and the stakeholder list was approved.

Using comments submitted to the National Screening Committee

Additionally, we reviewed comments sent to the UK NSC for previous reviews of antenatal and newborn screening that went to consultation within the last 5 years. We wanted to verify that the stakeholder groups identified in our secondary analysis were reflective of the stakeholders that typically submit comments. We observed good correlation between our stakeholder list and those submitting responses to UK NSC policy reviews, and as such were satisfied with the robustness of our approach.

Human elements involved in antenatal and newborn screening

The secondary analysis revealed that there are many varied human elements involved in antenatal and newborn screening. During antenatal screening, the mother’s well-being is at the centre of these discussions. During newborn screening, the baby’s well-being is at the centre of these discussions. Other family actors include the father, other children, and extended family members such as grandparents, aunts, or uncles. Friends can also be closely involved in screening conversations, as sources of information or support. In addition to the family members, our analysis shows the myriad types of HCPs involved in screening. This list includes, but is not limited to, general practitioners (GPs), specialist consultants, nurses, midwives, obstetricians, gynaecologists, genetic counsellors, physiotherapists, pharmacists and psychologists.

While HCPs provide tangible medical services to the mother, fetus/baby and other family members, our data also revealed the importance of other actors on the periphery. Data highlighted the importance of employers for understanding pregnancy and maternal health needs, particularly when things did not go as expected. Social workers were essential for connecting families with disparate services to manage living with conditions. Religious leaders, and church organisations, were named as sources of comfort and community, again especially important when screening resulted in the unexpected. Charity organisations and online communities that specialised in providing information about screening or screened-for conditions were named, repeatedly, as vital elements for (potential) parents on their screening journey. These organisations not only provide support and information, but also provide a collective sense of community for people at a time that may be emotionally challenging. Charities and online communities also link people going through screening to people who are living (or caring for someone) with a condition. People living with a condition, or those caring for someone with a condition, are a vital source of experiential knowledge that is valued as separate from what one may hear from other sources – such as the media or HCPs.

In addition to the named individual and collective human elements, our secondary analysis also implicated three important actors. The first is academic or scientific researchers – including ourselves. Researchers discuss what is (un)known about screening and screened-for conditions. Findings from research may be used by others to make political, healthcare or social care decisions. Researchers can develop treatment breakthroughs and give voice to those affected by screening. The second implicated actor is the UK NSC. The UK NSC advises the NHS and Members of Parliament (MPs) about screening programmes. An independent panel of experts, they weigh evidence to make recommendations on expanding screening programmes and support the implementation of existing programmes. While not always named in the data, the UK NSC makes decisions that shape the screening landscape. Similarly, MPs may go unnamed but are the decision-makers who determine screening and healthcare policies.

In addition to the individual and collective human elements, we noticed a number of recurring discourses constructed about humans and screening. Within the data, parents made assumptions made about their (partner’s) pregnancy or newborn child. For those who had not previously had a screen-positive experience, participants generally assumed that nothing would come of the antenatal or newborn screening (i.e. ‘everything will be fine’). Conversely, for those who had previously experienced unexpected news from antenatal or newborn screening, there were assumptions that perhaps their pregnancy or child would continue to have problems. For such people, this feeling of ‘something could be wrong’ continued through subsequent pregnancies.

Alongside the assumptions about one’s pregnancy or newborn were regularly expressed points about what it was like to live with a condition or as a carrier. Constructions of what it was like to live with a condition varied based on perceived severity and nature of the condition as well as whether the participant had direct lived experience with the condition itself. Constructions of what it was like to be a carrier also varied based on whether the participant had direct experience with the condition but tended to centre on reproductive decision-making. These discourses intersected with (generally negative) stereotypes about what it was like to live with a disability, such as inability to join the workforce, having to attend specialist education, or leading a life that was somehow ‘less than’. Similarly, there were stereotypes about who might be diagnosed with particular conditions which tended to focus on ethnicity (e.g. linking being of African or Caribbean background with sickle cell disease) or maternal age (e.g. linking ‘older’ motherhood with Down syndrome).

Within the data of people who had screen-positive experiences and/or lived experience of a condition, much was said about how little public awareness there is of screened-for conditions. This lack of awareness was perceived to make positive screening results more difficult to absorb, while also perpetuating stereotypes about life with the conditions. These same participants also talked regularly about what made HCPs (un)supportive. Supportive HCPs were constructed as listening to concerns, providing sufficient information, and being available to answer questions. Unsupportive HCPs, on the other hand, were those who tended to do the opposite. This included saying things that participants perceived as negative about a given condition, or focusing solely on clinical complications, rather than abilities and potential. Such unsupportive actions by HCPs ran counter to the recurring parental narratives that their child was special or a gift, and that their experiences had been far more positive than anticipated at the point of diagnosis. Finally, narratives tended to construct antenatal and newborn screening as having ‘spillover effects’. There were regular references to how screening had significant personal, relational and resource implications on individuals above and beyond the medical purview of screening.

Non-human elements related to antenatal and newborn screening

The secondary analysis revealed a range of recurring non-human elements, such as technologies and materials, related to antenatal and newborn screening. These included the screening tools themselves [i.e. antenatal screens, non-invasive prenatal testing (NIPT), and the heel prick test] as well as diagnostic tests [i.e. amniocentesis and chorionic villus sampling (CVS)]. For antenatal screening, there were differing interpretations of the purpose of ultrasound scans. For those who had not had an unexpected screening result or pregnancy complications, scans were constructed as an opportunity to ‘see’ their unborn baby and viewed in a positive manner. For those who had pregnancy complications, scans were something that were medically necessary and worrying. If a diagnostic test was offered, pregnant women and their partners considered the invasiveness and potential risks in their decision-making. The policies and procedures around termination were of vital importance as were ideas about whether or not termination would be appropriate. The decision about whether or not to terminate was sometimes complicated by the wide spectrums of presentation associated with the conditions, such as Down syndrome. Similarly, concerns about, or experiences of, miscarriage were also central to testing decisions, particularly for conditions like Edwards syndrome or Patau syndrome where there were higher chances of not carrying to term. Women who terminated pregnancies for medical reasons or those who experienced a miscarriage (or stillbirth) described them as bereavements involving mourning and adjustment.

Individuals who received positive screening result frequently recalled the exact moment of ‘getting the phone call’ which first alerted them to the finding, and some held onto the hope that the screen was a false positive. ‘Getting the phone call’ was often followed up by considering one’s family history and looking online or for other sources of information. Medical histories and notes might be accessed. Participants stressed how communication could drastically alter their experience of receiving this result, depending on what was said, how and by whom. Good communication was essential since the science behind screening, genetics and probability was constructed as mystifying. While people placed their trust in the NHS, this trust could be violated if communication was poor or if they felt misled. The NHS and private non-NHS services were sites of screening and follow-up, while nurseries and schools influenced how children living with screened-for conditions might learn and grow.

Temporal elements related to antenatal and newborn screening

Temporality was an important category related to antenatal and newborn screening. Within screening stories, the timing and journey to pregnancy were important factors. Some pregnancies were unintended; in these circumstances, antenatal screening was considered alongside decisions about proceeding with pregnancy overall. Other people spent months or years trying to conceive. These individuals had more time to think about pregnancy, screening and parenthood. Besides the timing of the pregnancy itself, it is important to consider overall the reproductive life course. Individuals bring their experiences with fertility, pregnancy, contraception, disability, health and relationships to their screening narratives. The moment of having blood drawn, or an ultrasound scan, and experiencing the results does not exist in a vacuum. Rather, the entirety of a person’s history over time is implicated.

The timing of screening itself was also important. People discussed antenatal screening moments as pregnancy milestones for themselves and their unborn child. Newborn screening, on the other hand, was seen as a blurred moment in time where the tired parent is adjusting to caring for a baby, potentially for the first time. As a result, it became less of an event, particularly as it was often folded into a consultation with other well-baby checks (e.g. weight gain or feeding). For both antenatal and newborn screening, the period of time between receiving a positive screen result and getting additional (often diagnostic) information was a slowing down of time where hours felt like days and days like years.

For families who receive positive screening results, their feelings about the condition may vary over time. How people feel about the condition varies based on the condition, timing of diagnosis, and decision-making trajectory. For people living with a screened-for condition, or their carers, the cumulative effects of a diagnosis – the emotional, social, financial and physical toll – were important discussion points. These cumulative effects intersect with knowledge of historical eugenic practices in the past, which some contend continue into the present. People living with screened-for conditions, and their carers, also have to think about when it might be appropriate to disclose their diagnosis to others; a decision, which varies, again based on the condition and the nature of the relationship. This can be complicated by the future uncertainty over what an individual’s future with the condition might look like.

Spatial elements related to antenatal and newborn screening

When it came to spatial elements, the data included many references to the sites of antenatal and newborn screening tests. People considered how rooms looked, noting that ‘nicer’ rooms were the ones where ‘bad’ news might be received. People also discussed how prior experiences in a particular room, unit or hospital, such as being told of a miscarriage, could haunt them in subsequent visits to the same place. These feelings held for sites of specialist intervention, such as neonatal intensive care units, the availability of which depended on location. Our data also touched on the need to travel to and from healthcare settings; the ease of travel depended on individual’s geographic location, employment circumstances, financial resources, health (physical and mental), and caring responsibilities. The need to travel intersected with recognised local and regional variations in care. Differences in medical practices, facilities and expertise were consistently referenced as important to the outcomes of antenatal and newborn screening. Further, international differences in approaches to screening and health care were referenced. The data mentioned the more liberal approaches to screening as performed in other countries, primarily other European nations or the USA, but also the benefits of free (at point of access) healthcare that is available in the UK but not in other countries.

Sociocultural elements related to antenatal and newborn screening

The secondary analysis revealed a range of recurring sociocultural elements related to antenatal and newborn screening. Much of the data reflected traditional gendered caring practices. Pregnant women and mothers of newborns were constructed as having heightened responsibility for reproduction – as needing to reduce working hours, manage the household and do the emotional work of being a (potential) parent. Male partners, on the other hand, were constructed as being less involved with pregnancy, including understanding the intricacies of screening, although they might provide ‘strong but silent’ emotional support. Regardless of gender, parents were constructed as accepting of making sacrifices for their pregnancy or child, wanting to provide the ‘best’. However, there were varying interpretations of what the ‘best’ was; for some it was having all possible screening or diagnostic tests, for others it was declining what was offered.

In addition to gender and parenting, religious practices were also important to people on their screening journeys. While religious beliefs can affect how an individual approaches medical care, in the data it most often came up related to beliefs around termination or coping with loss. Similarly, the data indicated the importance of ethnicity as part of the antenatal or newborn screening experience. Ethnicity was implicated in discussions of an individual’s chance of having a condition or being a carrier. The data held numerous references of people saying they were (not) likely to have a condition because they were (not) of a certain ethnic background. Ethnicity intersects with the practice of arranged marriages. While not common among those of white-European descent, arranged marriage continues to be practised among certain ethnic groups, including (but not limited to) people of Indian, Japanese and Pakistani descent. Arranged marriages take place in communities that have higher rates of carriers for certain conditions, such as sickle cell and thalassaemia. Participants discussed the importance of knowing one’s carrier status prior to such arranged marriages in order to prevent passing conditions on to their unborn children.

Economic elements related to antenatal and newborn screening

Our situational mapping exercise revealed personal, organisational and structural economic elements related to antenatal and newborn screening. Personal financial and employment resources dictated whether or not individuals could afford or access private healthcare coverage to bypass or supplement what was available on the NHS. Additionally, greater financial resources could make travel, time off work, or caring for a child with a condition more feasible. From an organisational standpoint, much was made of the role of charities in providing essential information and support for people receiving unexpected screening news, yet the ability of charities to provide services is directly related to the financial and other resources they may have.

Our data regularly implicated the NHS infrastructure and practices, which are dependent on funding and other limited resources – including the number of HCPs. Related to screening, the structure of the NHS influences the amount of time people have with HCPs to ask questions, the availability of specialists to provide care and the types of treatments available. In some cases, people may consider private healthcare options. Typically, this meant paying for additional scans beyond the standard dating and anomaly scans, or paying for NIPT. While the NHS is dependent on government funding decisions, so too are medical and scientific researchers who often depend on grant dispensing organisations (e.g. NIHR) to drive forward screening and treatment innovations. Finally, while private pharmaceutical companies may not compete for government funding, they are also part of this landscape. These companies sell technologies and treatments related to screened-for conditions then reinvest the profits to continue development and production activities.

Related discourses and debates surrounding antenatal and newborn screening

There were several larger discourses and debates related to screening. These include conversations about the rapidly expanding genetic and genomic technologies and the role of screening. The UK NSC currently has a more conservative set of criteria than other countries; they take into account the condition, the test, the intervention and available scientific evidence. As other countries expand their screening programmes, it is easy to imagine that pressure will correspondingly continue to mount to do so in the UK, especially as new treatments become available and methods of delivering screening (e.g. whole genome sequencing) expand. The debate about the role of screening intersects with conversations about what it means to live a ‘quality life’ and how people conceptualise (dis)ability. Within the data, these perceptions seem to be heavily based on individuals’ (lack of) first-hand experiences with conditions. However, these conversations continue to be a source of debate within society.

Antenatal screening also comes with additional caveats that centre on termination. Currently, England, Scotland and Wales allow termination up to 24 weeks of pregnancy, although this limit does not apply if there is a risk to maternal life or if there is evidence of ‘serious’ fetal anomalies. Termination has long been a contested social arena. Debates position beliefs in women’s rights to have bodily autonomy against beliefs about the rights of the (disabled) fetus/baby. These debates continue to shape the personal and social landscape of antenatal screening.

Ethical considerations

This study was approved by the University of Oxford’s Central University Research Ethics Committee (approval R70422) on 22 July 2020 and was carried out in compliance with the research and information governance policies of the University of Oxford. Potential participants were directed to a study website that provided information about the research and AW’s contact information. Interested people got in contact and AW sent a participant information sheet that detailed the aims and methods of the study (see Appendix 8). Participants had the opportunity to discuss participation with AW before agreeing to take part and gave consent to taking part in an interview or focus group. AW conducted the focus groups, with LH and AM also in attendance to support. AW collected all the interviews. We carefully planned the focus groups around shared experiences in order to minimise the risk of emotional harm, and participants were offered the option of a one-to-one interview if they preferred. All participants were informed that they were under no obligation to take part and could withdraw at any stage of the data collection process until the point of analysis, without questions asked. Each participant was offered a £20 voucher to thank them for their time. All research data have been treated in strict adherence to the General Data Protection Regulation. We have given participants pseudonyms and use those names here. While we have attempted to remove all personally identifiable information from the data, participants were made aware that in some cases – particularly if they are high-profile stakeholders or speaking about a rare condition – full anonymity could not be guaranteed.

Group 1: people who have made decisions about antenatal or newborn screening

This group was made up of people who had decided to use, or not use, antenatal or newborn screening within the past 4 years. Potential participants needed to be 18 years or older and live in the UK. We recruited participants through social media posts, our PPI network, professional contacts and paid Facebook advertising. We asked people who were interested in participating to complete a questionnaire to ascertain their experiences with screening and their demographic characteristics. We used this information to purposively sample a variety of people to participate in focus groups about screening experiences. We sought to recruit participants with a range of screening trajectories, including:

• people who declined (aspects of) screening

• people who received false-positive results from screening

• people who terminated a pregnancy for medical reasons following antenatal diagnosis

• people who continued a pregnancy following antenatal diagnosis

• people who experienced miscarriage or stillbirth

• people who received a positive newborn screening result.

We completed six focus groups from February to March 2021 (n = 30). We carefully planned the focus groups around shared experiences in order to minimise the risk of emotional harm. For example, we convened a focus group entirely of parents whose children are living with Down syndrome and another entirely with people who were pregnant for the first time. In addition, we reminded participants that they could decline to answer any question and that they were at liberty to leave the focus group at any point without giving a reason. Focus groups took place on a bespoke online platform over two, 1-hour-long sessions that took place several days apart. Each focus group had between three and six participants. For each chat, two or three researchers acted as moderators (AW, LH, AM) and drove the conversation. Our PPI partners helped shaped the focus group questions (see Appendix 9). The text from the chat functioned as the data from the focus groups.

After the first focus group session, we asked participants to respond to three fictional screening scenarios on a forum. Scenarios covered: (1) finding out about carrier status, (2) finding out about a positive newborn screening result and (3) finding out there is a high chance of a pregnancy resulting in a trisomy condition. We asked participants to read the scenarios and reflect on what they might be feeling or want to know if this happened to them. Participants could respond at any point between their first focus group chat session and the second chat session. The text from their responses was integrated into our analysis. Our PPI partners helped shaped the fictional scenarios.

We also offered participants who had sensitive or complex experiences the chance to take part in a telephone interview at a time of their choosing instead of participating in a focus group (n = 19). Our PPI partners helped shape the interview questions (see Appendix 9). AW reminded participants that they could decline to answer questions and end the interview at any point. AW attended to signs of emotional distress and offered to pause or halt interviews when participants became upset. Interviews lasted an average of 66 minutes (range 35–93 minutes). All interviews were audio-recorded and professionally transcribed verbatim.

Group 2: charity and professional stakeholders involved in antenatal or newborn screening

This group was made up of stakeholders involved in supporting those going through screening, or supporting families affected by conditions that can be identified through screening (n = 17). It also included people involved in shaping screening policy and practice within the UK. We purposively recruited stakeholder groups who were named in our situational mapping exercise or named by our PPI partners as important. We recruited some stakeholders through personal networking and others through cold e-mailing. AW e-mailed individuals or organisations, provided information about the study, and requested to conduct a 1-hour interview. Interviews took place between February and April 2021 over the telephone or using Microsoft Teams depending on participants’ preferences. AW obtained consent to audio-record conversations (see Appendix 9). Interviews lasted an average of 60 minutes (range 42–76 minutes). All interviews were professionally transcribed verbatim.

Group 3: healthcare professionals involved in antenatal or newborn screening

We had intended to interview up to 20 HCPs involved in screening, such as midwives, sonographers, obstetricians and genetic counsellors. However, the ongoing pandemic during our recruitment period (spring 2021) meant that HCPs were overworked and had little time or energy to take part. We exhausted multiple recruitment avenues, including personal networks, multiple rounds of social media posts, and advertising with professional colleges and organisations. We managed to generate interest from a small number of midwives over several months but had no other leads as of June 2021.

After discussing within the research team and our independent oversight committee members, we decided that the best course was to conduct a focus group with the midwives who volunteered to take part at the end of June 2021 (n = 4). The purpose of the focus group was to sense-check the themes we had identified in the data collected from groups 1 and 2. AW and LH worked together to compile a discussion guide and met with the midwives for approximately 90 minutes using Microsoft Teams (see Appendix 9). Participants had the option of turning their cameras on or off; all opted to keep them on. With participants’ permission, we recorded both the video and audio of the meeting. The audio was used to create a transcript. The video was used to confirm the identity of speakers during transcription before being deleted.

Analytical approach

All focus groups and interviews were recorded for transcription and analysis, and anonymised. We used thematic analysis to identify key themes in the data, including the benefits and harms of antenatal and newborn screening. 102,103 AW completed the initial data coding using NVivo12 software. The qualitative team (FB, LH, LL, AM, AW) met several times to discuss the coding progress and develop themes. While the codebook primarily focused on drawing out the benefits and harms of screening, it also captured other additional themes, such as emotional impacts, temporality, consent and information needs. These results are presented below (see Methods) but also informed WP3 (see Chapter 8).

Group 1: results

We collected data from 49 individuals in total; 30 participated in focus groups and 19 participated in interviews (Table 12). Participants were between 24 and 48 years old, with a mean age of 35 years old. While most of our participants were women (reflecting trends observed in other research of screening), we also spoke with nine men about their experiences as current or expectant fathers. The majority of participants lived in England, were married, and had completed at least a bachelor’s degree. We made concerted efforts to recruit people from ethnically diverse groups through multiple rounds of targeted recruitment; however, the majority of our participants identified as white. These participants represented a diversity of nationalities – including people who identified as American, English, Irish, Scottish, South African and Welsh – but the study may have been strengthened by those from additional ethnicities. We did our best to build a purposive sample that reflected a range of varying screening pathways from a variety of points of view (Table 13). Our data cover a variety of (non)screened-for conditions and the views of people living with conditions and their family members. While the data set does not represent all conditions, those included are highly diverse, and the data therefore do provide rich insights into the practical and emotional experiences related to a range of screening experiences and outcomes. See Appendix 10 for additional demographic details.

Group 2: results

We interviewed 17 stakeholders about the benefits and harms of antenatal and newborn screening (Table 14). We had conversations with people who represented single-condition charities and multiple-condition charities, both screened for and not screened for. We also spoke with people involved in charities with a wider focus around pregnancy or parenthood as well as a number of people involved in policy development (see Table 14). We cannot provide further details about our participants because they may become identifiable.

Charity and professional stakeholder views on the harms of screening

Interestingly, some stakeholders expressed the idea that a harm of screening can be its absence. These participants mentioned conditions that are currently screened for in other countries but not offered as part of the standardised NHS programmes in the UK. As one stakeholder said, these conditions ‘could have, should have been prevented if only [children were] born in France or Germany or America or Singapore’ [8]. Another stakeholder went on to say, ‘I think the harm from our community’s viewpoint is just where we’re not screening’ [10]. This subset of stakeholders suggested that by not screening for certain conditions, pregnant women or newborns might come to harm. Thus, this is a harm associated with how screening is implemented, and not screening itself.

Regarding screening programmes themselves, stakeholders named a variety of screening harms (see Report Supplementary Material 3 for supporting quote details):

• Screening may provide unexpected news.

• Screening may lead to devastating emotional impacts.

• It is difficult to achieve fully informed consent.

• Screening may imply pressure to have a termination.

• Communication about screened-for conditions may not be handled well.

• Screening may identify carriers.

• It may be difficult for HCPs to retain specialist knowledge about conditions.

Stakeholders regularly mentioned the emotional toll that screening might have on individuals and families. They mentioned that it could be considered harmful to receive unexpected news from screening. Generally, stakeholders felt that people were ‘nowhere near the position of being able to hear’ unexpected news [1]. Another stakeholder shared that ‘raising the possibility that that child is affected by a lifelong, you know, potentially a lethal condition through a screening test is potentially really, really difficult conversation to have’ [4]. The unexpected news and fallout from screening may lead to devastating emotional impacts. Sometimes, ‘women will blame themselves’ and ‘fall into a pit of guilt and shame’ [6]. The effect, as one stakeholder [2] shared, can have long-term implications:

I think it’s very difficult to explain, explain to people just how devastated parents are when they are faced with this sort of information and it leads to the loss of their baby, it completely destroys people’s lives, not only in the short term but also in the very long term … it just devastates people and that requires, when you have to make a choice or when you are, you feel you’re forced into making a choice about whether your baby lives or dies, that is a choice you have to live with for the rest of your life and all of the questions and things that surround that and that is, yeah, that is one of the hardest things people I think would ever be faced with.

The emotional harms are exacerbated because of two other potential harms: (1) people may not understand what screening tests are for, and (2) it is difficult to achieve fully informed consent. Stakeholders routinely questioned what people knew about screening. As one participant said, ‘I’m just a bit concerned that do people really know what they’re screening for? Do they have an idea in their heads of why this is a good thing and what they might do as a result?’ [12]. Similarly, stakeholders discussed that it was difficult for HCPs to ensure informed consent because of the ‘amount of information and tasks they have to perform in those initial [pregnancy] booking appointments’ [5]. While HCPs might intend to ‘have a proper discussion about screening’, the fact is that ‘various studies have shown that the average length of time that they spend talking about screening is a few minutes. And that probably isn’t sufficient’ [5]. We discuss the challenges with information provision further in Charity and professional stakeholder views on the harms of screening.

Another potential harm of screening stakeholders discussed was that offering screening may imply pressure to have a termination. While stakeholders generally affirmed the right to have a termination, some questioned whether people were making the decision to terminate ‘without adequate information and support’ [3]. They worried that screening inferred a judgement on ‘which lives matter’ [12] and suggested that in the future ‘there’ll be less and less people’ with specific conditions [13]. This harm intersects with the harm that communication about screened-for conditions may not be well-handled. Stakeholders mentioned how HCPs might ‘talk about anomalies, abnormality, disorder, problem, you know, and all of that has negative connotations and, you know, is prejudicial and it influences a person’s perspective’ [3]. Poor communication may be exacerbated by the fact that it can be difficult for HCPs to retain specialist knowledge about conditions. While this was considered a harm, it was understandable since HCPs would not be ‘seeing cases on a sort of regular basis’ [1].

Group 3: results

We conducted an online focus group with four midwives to sense check the themes derived from people who have experienced screening and other stakeholders. The four women work in different regions in the UK: London, Birmingham, Yorkshire and Belfast. Each had experiences as a midwife involved in screening and two had additional training in sonography. Below we discuss how these participants considered the themes pulled from focus groups and interviews with the other two groups (see Report Supplementary Material 3 for supporting quote details).

Midwife focus group participants corroborated that antenatal and newborn screening can be emotionally challenging. Participants reflected that it was their job to sometimes tell ‘devastating news’. In these cases, participants recognised it was good practice to ensure that patients ‘know your contact details’ so they could absorb information and get back in touch as needed. Participants also discussed how these emotionally laden moments with patients stick with them, sometimes for years. As one participant shared, ‘that’s probably the hardest part of the job’.

Participants also verified that people may feel pressured to accept screening because it was offered. One participant discussed having patients who have declined antenatal screening but have ‘gone on to consultant appointments’ where ‘they are pressured quite a lot’ to have had things done. Another participant countered that perhaps patients perceive pressure, but it is ‘literally just trying to explain to them what could actually happen’. While participants were quick to affirm the right of anyone to make decisions about screening, they themselves wished that people would take it up, if only to catch any potential conditions or anomalies. In the event that someone does decline screening, one participant shared that it is her job to say ‘you have the right to make this choice. And it is my responsibility to make sure that you understand the implications’. This way a patient’s wishes are respected, but the midwife leaves feeling like ‘I’ve done the best I can for them’.

Participants spent much of the conversation reflecting on the challenges of providing appropriate information while still maintaining informed choice. Participants mentioned the difficulty of providing comprehensive screening information when pregnant women and their partners are being ‘bombarded’ with ‘the vast amount of information we’re giving them at [the booking] appointment’. Participants realise they are ‘up against Google’ and wish that patients would ask HCPs to put information ‘in context’ rather than fixating on things that are statistically unlikely. Participants explained that it was difficult to know just how much information to give, saying, ‘It’s like where do you start and where do you stop?’. They did not want to scare patients but hold that ‘a woman should know what she’s consenting to’. Ultimately, participants questioned whether sharing all possible outcomes was ‘necessary and does it add anything to it? I don’t know’. There were no easy answers and participants acknowledged there was not one solution; much depended on how information was delivered and whom it was delivered to.

Developing scenarios for valuation

To assess the feasibility of applying alternative economic (preference-based) techniques to scenarios of antenatal and newborn screening, we developed two scenarios, one describing a scenario of antenatal screening and the other describing a scenario of newborn screening with each scenario reflecting benefits and harms identified by the thematic framework outlined in Chapter 8. It would clearly have been possible to have generated far more scenarios that reflect the permutations of benefits and harms described by the thematic framework. However, increasing the number of scenarios would have added significantly to participant burden. The final scenarios were presented as hypothetical, but nevertheless representative of the types of decisions people might have to make about antenatal or newborn screening.

The preamble for the antenatal screening scenario asked participants to imagine a hypothetical women named Sophie and her partner Jamie who had been trying to have a baby for 3 years. The preamble for this antenatal screening scenario was presented as follows:

Sophie is currently pregnant after having two miscarriages. She had the combined test that showed there was a higher than average chance that Sophie’s pregnancy would result in having a baby with an inherited genetic condition. Sophie had an amniocentesis test to see if the blood test was right. Results from the amniocentesis test confirmed that Sophie’s pregnancy was affected by this condition. Sophie’s doctor explained that pregnancies affected by this condition may end in miscarriage or still birth. The doctor also said that children born with the condition will require specialist care. The doctor says Sophie can work with a team to continue her pregnancy or she can terminate the pregnancy for medical reasons. The doctor tells Sophie about some support organisations and tells her to think about what she wants to do.

The patient and public members were then presented with seven attributes that characterised this hypothetical antenatal screening scenario: history of prior miscarriages, accuracy of screening test, time to wait for screening test results, the risk of miscarriage associated with the diagnostic test, the psychological/emotional impact of a termination decision on the woman and her partner (Sophie and Jamie), the perceived severity of the diagnosed condition and the parents’ ability to make a decision about screening. The potential attributes and levels of those attributes that might influence the antenatal screening decision are presented in Table 17.

The preamble for the newborn screening scenario asked participants to imagine a hypothetical newborn baby named Ella. The preamble for the newborn screening scenario framed around a parent’s consent to the heel prick test for newborn Ella was presented as follows:

Thea has a newborn baby named Ella. Five days after Ella is born a midwife comes to the house. The midwife does a physical examination and asks Thea if she wants Ella to have newborn bloodspot screening. Sometimes this is called the ‘heel prick’ test. The midwife explains that newborn blood spot screening involves taking a blood sample to find out if Ella might have one of a range of health conditions. Often, it is too early to tell if Ella might have a health condition any other way. The midwife explains that the blood spot screening is optional. Thea needs to decide what she wants to do.

The patient and public members were then presented with six attributes that characterised this hypothetical newborn screening scenario: age of child when symptoms manifest, timing of start of treatment, the likelihood of success of treatment, perceived severity of diagnosed condition, likelihood of a false-positive result, and likelihood of overdiagnosis. The potential attributes and levels of those attributes that might influence the newborn screening decision are presented in Table 18.

Selection of valuation methods

The VALENTIA research team reviewed alternative economic (preference-based) techniques that can be used to value the hypothetical antenatal and newborn screening scenarios described in Developing scenarios for valuation. A pool of 10 potential valuation techniques previously used by economists to value healthcare processes was initially identified: allocation of points, analytical hierarchical process, best–worst scaling, contingent valuation, discrete choice experiments, measure of value, person trade-off, rating scale, standard gamble and time trade-off. 104,105 The VALENTIA research team applied a number of criteria to prioritise the valuation techniques that could be applied in the patient and public member workshops. These included broader application of the valuation technique in health economics or healthcare decision-making contexts; foundation of the valuation technique in economic theory; applicability of the technique to the valuation of antenatal and newborn screening scenarios delineated in terms of benefits and harms described by our thematic framework; and practicality of application given the mode and time constraints of the online workshops. Allocation of points, analytical hierarchical process and measure of value were excluded on the basis of limited previous application in health economics or healthcare decision-making contexts. The rating scale approach and its variants were excluded because of disagreement among health economists of their theoretical basis as preference-based techniques. 106 The standard gamble and time trade-off approaches were excluded because of the challenges surrounding the labelling of upper and lower anchors in the context of the hypothetical antenatal and newborn screening scenarios where there is no meaningful risk of death or severe disability. Concerns around the practicality of the number of valuation techniques that could be applied within the online workshops then led to the selection of best–worst scaling and discrete choice experiments, which had previously been used to value scenarios of antenatal and newborn screening. 107 For both the hypothetical antenatal and newborn screening scenarios, the patient and public members were presented with a best–worst scaling task and a discrete choice experiment task. They were then asked to provide their insights on: (1) whether they were able to imagine the scenario that was being valued and what factors influenced their ability to imagine the scenario; (2) whether they understood each task; (3) their main considerations when attempting to complete the tasks; (4) whether they drew on personal experiences or experiences of their families/friends when completing the tasks; and (5) which valuation method they preferred and why. The best–worst scaling task that related to the hypothetical newborn screening scenario is presented in Table 19, while the discrete choice experiment task that related to the hypothetical antenatal screening scenario is presented in Table 20.

Insights from patient and public member workshops

When assessing the hypothetical antenatal and newborn screening scenarios that were being valued, participants could generally imagine the scenarios, although for some participants this highlighted the complexity of the screening decisions often made in the antenatal and newborn screening contexts:

Yeah. I think it was, in my opinion, easy to put yourself in either scenario and say, yes, that could apply with lots of, obviously, differing factors. But yes.

Participant 5

I find it easy enough to imagine myself in each of the scenarios, but I don’t think … I don’t know if this is what you’re after, but for me, it wouldn’t have been clear cut what the decision would’ve been for either [00:31:30] scenario. I don’t think that was particularly easy to imagine the outcome, I guess, and how each would progress.

Participant 2

The level of understanding of each valuation task varied between patient and public members with some participants reporting that their level of understanding increased through the course of workshop and clarification provided by members of the VALENTIA research team and other patient and public members:

I think the more we’ve talked about it, the more I’ve understood it. I don’t think I understood it to begin with, but with everybody having a discussion around the pair comparison I’m talking about, mostly. I have to say, I didn’t understand it completely to begin with, but now I think I do.

Participant 5

Participants considered a number of factors when attempting to complete the valuation tasks or, at least, expressed a desire for more information on factors that would influence their preference structures. These factors included the background and reproductive history of the hypothetical parents described in the examples, the number of attributes reflected in the tasks, the labelling of adjectives such as ‘minor’ or ‘major’, which carried subjective connotations and timing at which a preference elicitation study would be conducted:

I think there’s maybe additional information about the parents themselves that could be explored a little more, and their history, not just their history with pregnancy, but their history in a wider context.

Participant 2

I just was going to just agree with that point really. I found it a bit overwhelming some of the information in the two alternatives. And I agree, a lot of these things are quite hard. Well, take a lot of thought, and maybe just some of the variables, kind of reducing the difference in the number of variables would’ve been helpful.

Participant 6

And one of the things that is constantly asked is this idea of major or minor, and whether your participants understand what that means. Because a major psychological impact will mean something very, very different to different people. And they need to understand the context of what is meant by that and whether that’s going to needs to be provided to them before they understand what does it mean? What does a major psychological impact mean?

Participant 6

Just quickly also, I guess one of the questions is you might be asking these, giving these surveys at a time that’s quite a stress. And I don’t know when you’re going to give these to parents, for example, it might be quite a stressful time.

Participant 6

Several patient and public members revealed that they drew on their personal experiences or experiences of their families/friends when completing the tasks, perhaps reflecting the composition of the sample that was selected from:

But actually, I was pretty clueless in terms of how it did affect me. So this is where my personal experiences come in to definitely influence certain parts of my answer.

Participant 4

I felt like my own experiences and priorities probably came into that quite a lot. But, in terms of kind of empathizing with the person in that situation, I could totally put myself in that context.

Participant 9

Finally, in terms of the two valuation methods that were assessed, there appeared to be a general preference for the best–worst scaling method with several participants describing it as easier to understand and process, although the one participant disputed the ‘best’ and ‘worst’ labels in the hypothetical scenarios provided:

The paired comparison, I felt, could be quite confusing. Because, the attributes that were there, some of them weren’t really comparable. For me, it felt quite challenging to think ‘I’ve got to choose between this one or this one.’ Because, I think people value different things in different ways and what might be higher value to someone else is lower value to another.

Participant 10

And I really like the best-case, worst-case scenario. It’s [inaudible] for me for just ease of understanding, and I could do it whilst sitting somewhere.

Participant 6

I have to say, I think the best worst scenarios are … I think the wording is potentially, I don’t know, because there’s no best scenario, I think, in some of them. So it may be the wording of how it’s come across, but it’s more easy to understand from my point of view. If that makes sense.

Participant 5

In summary, the patient and public participants in the online workshops highlighted a number of factors that influence their preferences for antenatal and newborn screening scenarios, but generally understood the two preference-based techniques presented. Notably, however, they were not presented with some methods developed by economists, such as contingent valuation, which could plausibly be applied to value scenarios delineated in terms of benefits and harms from our thematic framework (see Chapter 4).

Identification of benefits and harms

Our evidence synthesis around benefits and harms related to antenatal and newborn screening was informed by a systematic review of economic assessments identified from the published and grey literature and qualitative research that took the form of a meta-ethnography, a secondary analysis and primary data collection with three different stakeholder groups. As part of our primary data collection, we had intended to interview healthcare professionals from a breadth of healthcare backgrounds involved in antenatal and newborn screening, such as midwives, sonographers, obstetricians, neonatologists, neonatal nurses and genetic counsellors. However, despite multiple approaches through different routes, the ongoing pandemic during our recruitment period (Spring 2021) meant that healthcare professionals were overworked and had little time or energy to take part. This meant that our primary data collection from healthcare professionals was limited to a focus group conducted with four midwives. Clearly, this represents a limitation of our research and primary data collection from healthcare professionals operating at different stages of the screening pathways is likely to offer new perspectives and highlight potential gaps in our synthesis of benefits and harms. Their inclusion would most likely have offered further insight into our synthesis of relevant benefits and harms. Beyond the composition of the stakeholders from which we collected primary data, the topic guides for our focus groups and one-on-one interviews were necessarily constrained by the limited time available for each research contact. Further research around how people’s feelings about positive screening results and/or diagnosis change over time after receiving results, and around how people’s relationship to screening varies over the reproductive life course, may offer new perspectives on our study outputs.

Measurement of benefits and harms

Economic evaluations of antenatal and newborn screening are constrained by a number of methodological limitations that our research has highlighted. There is a particular need for further research, or methods guidance from screening organisations, in the following areas:

1. Where benefits and harms associated within antenatal screening are synthesised within composite outcome measures such as life-years or QALYs gained or DALYs averted, methods guidance is needed around approaches to aggregating consequences across the mother, fetus or unborn child and potentially other family members. This will clearly be influenced by moral perspectives on the status of the fetus or unborn child with different moral perspectives on when human life commences likely to have a significant impact upon cost effectiveness or cost–benefit estimates. 21,22 Beyond consideration of when to commence ‘counting’ the life of the fetus or unborn child in the calculus, this still leaves the issues of what weight to place on prenatal time lost or gained compared with postnatal time, and what weights to place on measures of consequence to the fetus or unborn child, the mother and potentially to other family members.

2. Where benefits and harms associated within newborn screening are synthesised within QALY metrics, there is a need for development of patient-reported outcome measures (PROMs) with preference-based value sets validated for use in infancy and across other stages of childhood. A recent system review108 of generic multidimensional childhood PROMs revealed 17 measures (incorporating two versions each for the HUI2 and HUI3 and two variants of the EQ-5D-Y) designed to be accompanied by preference-based value sets. Notably, only 2 of the 17 measures, the Infant health-related Quality of Life Instrument (IQI)109 and the Toddler and Infant health-related Quality of Life Instrument (TANDI),110 have been validated for use during infancy and their preference-based value sets are still under development. No preference-based measure is validated for use across all developmental stages from infancy to adolescence, which constrains the potential for QALY estimation in economic evaluations that extrapolate cost effectiveness over a childhood time horizon or beyond.

Valuation of benefits and harms

Economists have developed several possible methods for valuing antenatal and newborn screening scenarios. Our feasibility work focused on testing the application of discrete choice experiments and best–worst scaling in these contexts. Other valuation methods, such as contingent valuation, could conceivably be applied in these contexts,111,112 However, the application of such methods will need to be assessed drawing upon the broad sets of benefits and harms that our research has identified. Valuation techniques such as standard gamble and time trade-off approaches are widely used in other areas of health economics to value health states without consideration for non-health outcomes and process attributes. We identified methodological challenges surrounding the labelling of upper and lower anchors within standard gamble and time trade-off tasks aimed at valuing antenatal and newborn screening scenarios that do not contain a meaningful risk of death or severe disability. Research is required to test the application of these approaches in two-stage processes where the first stage is used to value scenarios of benefits and harms that our research has identified, and the second stage is used to score anchors on the full health-immediate death scale. Finally, consideration should be given to the development of methods for weighting disparate consequences of antenatal and newborn screening, drawn from our taxonomy and accompanying qualitative research, within a cost–consequences analysis framework.