Design and ethics statement

A cross-sectional survey study was performed using questionnaires among participants and non-participants in the Dutch NBS program. The Medical Ethical Committee of the VU University Medical Center Amsterdam approved the study protocol (no. 2019–509). Before parents completed the (online) questionnaire, they were asked to tick a box (written consent) to confirm that they had read the information letter and that they gave their informed consent to participate in the study.

Setting

In the Netherlands, NBS is organized and coordinated by the Dutch National Institute for Public Health and the Environment (RIVM). Standardized information on NBS, including a leaflet, is provided during pregnancy by an obstetric healthcare provider, and issued before the screening is done, a few days after birth, at home by a youth health care worker, maternity nurse or midwife. When the baby is admitted to the hospital during the first week after birth, the blood spot is collected by a hospital health care worker. If the NBS result is good parents will get a letter from RIVM within five weeks, as from March 1st, 2020 (before that time, no result was given). If an abnormality is detected, the general practitioner will inform parents about the results.

Study population

During the last two weeks of December 2019, all parents whose child had been offered NBS five weeks earlier (n = 6,051), received a letter from the RIVM inviting them to participate in a survey study. The invitation could only be sent by the RIVM due to of privacy reasons, and therefore no reminders could be sent. A period of five weeks was chosen because almost all parents will know their child’s test result by then. In addition, all parents who declined participation in NBS in the whole of 2019 (n = 515) received an invitation to complete the same online questionnaire at the beginning of 2020, and all parents who declined participation in NBS in 2020 received an invitation at the beginning of 2021 (n = 647). When parents indicated that they did not participate in NBS, questions that were not relevant were automatically skipped. The questionnaire was available in Dutch and English and could be filled in online or could be sent to them on paper by post upon request. As the number of non-participants in 2019 who filled out the questionnaire was very low, all NBS non-participants in 2020 were sent a paper questionnaire, in addition to the online link, to lower the threshold for completing the questionnaire.

Questionnaire and procedure

The questionnaire was developed based on interviews with stakeholders [14], a previous questionnaire study about Dutch parents’ attitudes towards NBS [20, 21], and literature [19, 22]. The questionnaire was pre-tested among five parents. Readability of the questionnaire was evaluated by Pharos, the Dutch Centre of Expertise on Health Disparities. The questionnaire assessed reasons for participating and not participating, informed decision to participate or not, views on current NBS, views on expanding NBS, and background characteristics. NBS non-participants were not asked about their views on expanding NBS and views on current NBS to keep the questionnaire as short as possible and encourage completion. A copy of the entire questionnaire can be found in S1 Appendix. The different themes in the questionnaire are described below.

Statistical analyses

The frequencies or means and standard deviations were calculated using descriptive analyses.

Five-point scales were reduced to three categories (e.g. (completely) disagree/neutral/(completely) agree) to avoid empty or small cells. Differences between the respondents who participated in NBS and those who declined NBS were tested with Chi square tests, or Chi square tests for trend for ordinal categories such as single items on a 5-point scale. Non-parametric Mann-Whitney U tests were done to compare respondents who participated in NBS and those who declined NBS, and also to compare low-/middle- and high- educated parents that participated in NBS, on their attitudes (recoded into a score ranging from 2 (all negative attitudes) to 10 (all positive attitudes)) and knowledge (also recoded into a score ranging from 0 (none correct) to 10 (all correct))/. The comparison based on education, was only done within the group of NBS participants because the numbers of low-educated parents were small (n = 15) in the smaller group of parents that did not participate in NBS (n = 48). Answers to open questions were coded and categorized by one person (MvE) and were discussed with a second person (SW) until agreement was reached. All analyses were performed using SPSS version 25 for Windows (IBM Statistics for Windows, IBM, NY, USA).

Respondents’ characteristics

In total, 804 of 6,051 (13%) invited parents who participated in NBS completed the questionnaire. Among parents who declined NBS in 2019 and 2020, the questionnaire was completed by 3% (16/515) and 5% (32/647) respectively, meaning that 48 parents who declined participation in NBS were included in the analyses. The characteristics of parents who completed the questionnaire are shown in Table 1. Respondents who declined NBS were more often fathers (19% vs. 8%, p = .03), more often had more than one child (66% vs. 45%, p = .005), were more often actively religious than participants (57% vs. 23%, p < .001), considered alternative medicine/lifestyle as more important more often (67% vs. 21%, p < .001), and were less often inclined to vaccinate their child for infectious diseases (15% vs 96%, p < .001), compared to respondents who participated in NBS. Respondents were higher educated and more often born in the Netherlands, compared to the general Dutch population (2019).

Download:

• PPT
  PowerPoint slide
• PNG
  larger image
• TIFF
  original image

Table 1. Characteristics of respondents who participated in NBS participants or declined NBS, compared to the general Dutch population.

https://doi.org/10.1371/journal.pone.0272585.t001

Reasons to participate in NBS or decline NBS

Table 2 shows that the most important reasons to participate in NBS screening was that disease symptoms in the child can be prevented and because respondents were confident that the results of the heel prick test are reliable. The most important reasons for respondents not to participate were due to their view of life, because they think that the heel prick test is painful for the child, and how their data and their child’s data are handled. Among the 32 parents who declined NBS in 2020 (COVID-19 pandemic), two (6%) respondents reported that the COVID-19 virus was an important or very important reason to decline NBS. The open question where respondents described their reasoning in their own words did not reveal any additional reasons.

Download:

• PPT
  PowerPoint slide
• PNG
  larger image
• TIFF
  original image

Table 2. Reasons to participate in NBS or decline NBS.

https://doi.org/10.1371/journal.pone.0272585.t002

Informed decision to participate or not in NBS

Table 3 shows that 83% of respondents that participated in NBS made an informed decision to participate, based on 86% of respondents that showed sufficient knowledge and 97% that had a positive attitude towards NBS. Of the respondents that declined participation in NBS, 44% made an informed choice with sufficient knowledge (62%) and a negative attitude (71%). The difference in the percentage that made an informed decision to participate in NBS between respondents who participated in NBS (83%) and those who declined NBS (44%) was statistically significant (p < .001). S1 and S2 Tables show respondents’ answers per knowledge item and per attitude item, respectively, and show significant differences in knowledge-score (7.72 versus 5.87, p < .001) and attitude-score (8.33 vs 5.16, p < .001) between respondents who participated in NBS and those who declined NBS. S3 Table shows that respondents who participated in NBS made a more undisputed choice to participate (p < .001), while NBS non-participants indicated having more doubt (p < .001). S4 Table shows that of all respondents who participated in NBS, respondents with a high educational level had more knowledge about NBS (difference of 0.75, p<0.001) and a more positive attitude towards NBS (difference of 0.46, p<0.001), compared to respondents with a low/middle educational level.

Download:

• PPT
  PowerPoint slide
• PNG
  larger image
• TIFF
  original image

Table 3. Informed decision to participate in NBS or decline NBS.

https://doi.org/10.1371/journal.pone.0272585.t003

Parents’ views on current NBS

Table 4 shows that 92% of respondents who participated in NBS did not feel pressured by the person who carried out the heel prick. The majority (74%) reported to have received sufficient information about the heel prick test to make a decision about whether or not to participate. Overall, 47% reported that they were well informed about NBS during pregnancy. Most respondents (92%) trust that the government will inform them adequately about the screening results. Most respondents think that the heel prick is reliable (97%), and four respondents (0.5%) reported regretting NBS participation; one parent’s child was diagnosed with a condition after NBS, one parent was already in doubt about participating in NBS and did not get satisfactory answers to their questions about NBS, and the other two parents left no remarks on the questionnaire. Almost all respondents (99.6%) would participate again in the case of a future pregnancy.

Download:

• PPT
  PowerPoint slide
• PNG
  larger image
• TIFF
  original image

Table 4. Parents’ views on current Dutch newborn bloodspot screening.

https://doi.org/10.1371/journal.pone.0272585.t004

Parents’ views on expanding Dutch NBS

Most NBS participants (95%) thought it was a good idea to add new conditions to the NBS screening, whereas 4% did not know whether it was a good idea. Only two respondents thought it was a bad idea. Table 5 shows the degree of acceptance of specific conditions about which parents were asked if they thought it was a good idea to add these conditions to the heel prick test. For each condition, the majority of respondents thought it was a good or a very good idea, varying from 59% to 86% agreement. On average, the respondents scored the highest on: ‘a condition in which the result could indicate that the child is not sick but that the mother is sick’ (mean: 4.05; SD: 0.72) and the lowest on: ‘a condition for which there is no treatment or no medication’ (mean: 3.56; SD: 0.98). A minority (5%) believed it was a bad or very bad idea to include disorders for which the child’s DNA needs to be tested.

Download:

• PPT
  PowerPoint slide
• PNG
  larger image
• TIFF
  original image

Table 5. Degree of acceptance of adding a specific condition to the heel prick test.

https://doi.org/10.1371/journal.pone.0272585.t005

With regard to the “adrenoleukodystrophy (ALD) scenario” (see S1 Appendix, question B.3), only 8 out of 804 respondents (1%) did not think it was a good idea to add a condition to NBS with great differences in disease manifestation and treatability between males and females. Of the 796 respondents that thought it was a good idea to add ALD, a majority of respondents (665/796, 84%) thought it is a good idea to test for this disorder in both boys and girls. Respondents’ main reason was “the opportunity to know what to expect” (192/665, 29%), and “because the information is important for both sexes” (105/665, 16%). Only 131/796 respondents (16%) would test only boys because “boys have treatment options and girls do not have treatment options” (80/131, 61%), “consequences for boys are greater” (27/131, 21%), “girls can experience unnecessary stress or worries” (24/131, 18%).

Reasons to participate or not in NBS

The reason respondents reported as most important for participating in NBS was to prevent disease symptoms in their child, in line with the aim of screening [2], as well as with findings from other studies assessing parents’ views [25, 26]. For example, one interview study in Australia found that the majority of women with newborns thought screening was useful if it prevents a disease (85%) or reduces severity of a disease (87%) [25]. In an interview study with parents in the UK, the ability to act on screening results was also noted as important, with earlier knowledge on potential conditions in a child allowing for treatment strategies [26].

For parents that declined NBS, the highest rated reasons for declining NBS concerned their view of life, and because they thought that the heel prick test would be painful for their child. Parents who declined NBS were more often in doubt concerning whether to participate or not, compared to NBS participants. In the literature, studies including parents that declined NBS are scarce [27]. A Canadian qualitative study showed that decisions among three declining parents were shaped by their previous experiences with blood collection [11]. In that same interview study, healthcare professionals reflected on why parents reported to them that they did not wish to participate in NBS. Reasons included: to avoid pain for the baby, previous experiences with healthcare, perceiving the test as unnecessary, religious reasons, and not trusting the government with their child’s DNA [11]. Our study suggests that how the parents’ data and the child’s data are handled might play a role in parents’ decision to decline NBS.

Our results showed that parents who declined NBS were more actively religious and more often indicated that alternative medicine/lifestyle is important to them when compared to participating parents. Moreover, more than half of the parents that declined NBS indicated that they were not planning to vaccinate their child for childhood infectious diseases. Declining both the NBS and the vaccination program might therefore also be representative decisions for a way of life. One parent in our study stated that their main reason for declining NBS was ‘we live in trust and not in fear’ in the open-ended section of the question. Among the parents who declined NBS in 2020, when the COVID-19 pandemic might have caused additional concerns for parents, very few parents (n = 2; 6%) reported that the COVID-19 virus was an important reason to decline NBS.

Informed participation for current NBS

In the Netherlands, NBS is voluntary, however participation rates are nevertheless very high: above 99% [9]. In the Netherlands, parents are asked for verbal consent before the heel prick is carried out. According to the informed consent procedure [8], the screener should check beforehand whether the parent has both received the information leaflet on NBS screening and read it. If this is not the case, the screener should explain the main points of the screening to the parents. In some other countries, although informed (verbal) consent is likewise required for participation (e.g. United Kingdom) [28], a sense of routinization has been described in which parents did not feel they made an active choice or did not remember giving consent [11]. In the Netherlands, information leaflets on NBS screening are handed out on several occasions, including during pregnancy. However, leaflets are easily overlooked by parents [20, 21]. Given such circumstances of information provision, it has been questioned whether participants perceive participating in NBS as an actual choice [29]. Nevertheless, we have shown that most respondents believe that they were informed well enough to be able to decide to participate, although only 47% of participants said they were well-informed during pregnancy. Previous calls for information provision during pregnancy have been made, as this may allow parents to better absorb and understand the NBS process and the possible implications [13].

Our results indicate that the majority (83%) of the NBS participants made an informed decision, which is comparable to results of a similar study in 2008 (84%) carried out after the expansion of NBS screening from three to seventeen disorders [20, 21]. These results suggest that even with a greater number of conditions included in NBS, the proportion of parents making an informed decision to accept NBS remained the same. The current study found a lower percentage (44%) of informed choice in parents that declined NBS, mostly due to insufficient knowledge about NBS. For example, only 56% of declining parents were aware that conditions tested for with NBS can have serious consequences if untreated (S1 Table). This could indicate room for improvement in the information provision, by explaining or highlighting these consequences. A literature review showed that the main acceptability component identified for newborn screening and other screening interventions related to parental knowledge and understanding [27]. It remains to be seen whether improved information, or other factors such as timing of information provision, will increase knowledge and thus the willingness to participate among the parents who declined. On the one hand, our results indicate that parents mostly decline because of their beliefs, namely their way of life, religion or beliefs about pain. On the other hand, parents who did decline NBS also indicated having more doubt and a less undisputed choice not to participate.

Parents’ views on expanding Dutch NBS

Our results suggest that NBS participants are generally positive towards the expansion of NBS. Even for conditions for which there is no treatment or medication available or a condition in which it is uncertain whether the child will develop complaints, more than half of the participants thought inclusion of these disorders in the NBS program would be a good idea. This is also supported by earlier research [6, 18, 19]. For example, a Canadian survey study showed that only 38% of parents believed that NBS should only be available for health conditions for which treatment or even supportive treatment is available [6]. Ataxia Telangiectasia (AT) is a specific example of an untreatable condition which occurs as an incidental finding in NBS when screening for severe combined immunodeficiency (SCID). A Dutch survey study found that the most important arguments given by the majority of parents that supported early detection of AT were to prevent a long period of uncertainty between first symptoms and diagnosis (often referred to as a “diagnostic odyssey”) and immediate optimal guidance when first symptoms occur [30].

In the United States, the public is generally positive about NBS expansion [5], despite a persistent lack of knowledge about NBS [31]. Our interview study among NBS stakeholders including healthcare professionals, NBS policy makers, researchers, laboratory specialists, and parents in the Netherlands showed that they had a positive attitude toward NBS expansion provided that it is aimed at detecting treatable disorders and achieving health gain [14]. Stakeholders with a “targeted-scope perspective” thought that the focus should be on achieving health gain for the newborn, while other stakeholders expressed broader aims and beneficiaries of NBS, for example also taking reproductive choices for family members into account [14]. Among health professionals, the topic of benefits to family members has been controversial. For example, United States research on healthcare practitioners views on Pompe disease showed that opinions on the use of reproductive benefit as a justification for NBS were markedly divided [32].

In 2021 a pilot study was carried out in four provinces in the Netherlands in which only boys were screened for ALD [33]. For this disorder, the Dutch Health Council advised screening only boys, because only boys are at risk of developing adrenal insufficiency or cerebral ALD for which treatment is available, whereas symptoms in girls usually only develop in adulthood and are untreatable [34]. In our earlier Dutch interview study, we showed that most parents did not seem to perceive the screening of subgroups as problematic in itself [14]. However, the current study showed that most parents that participated in NBS believed that both boys and girls should be tested for a disorder such as ALD, as is the case in the United States [35]. Our findings also showed that these parents support screening for a condition that may not cause symptoms until later in a child’s life.

Our study showed that 86% of NBS participants would support the addition of a disorder where NBS reveals that the mother has a certain condition as opposed to the newborn (such as OCTN2 deficiency). Most NBS participants did not object to including conditions in NBS for which DNA needs to be tested. Although many obstacles still need to be addressed before Next Generation Sequencing (NGS) can be implemented in practice, it is likely that NGS will be increasingly applied in NBS [36]. A recent UK public dialogue showed support for the potential use of whole genome sequencing in NBS provided that appropriate resources and safeguards are in place [37]. Additionally, 60 of 66 (91%) US parents indicated they definitely wanted genomic sequencing in general for their newborn if presented with this option [38].

Strengths and limitations

A significant strength of this study pertains to the inclusion of parents who declined NBS. Due to the high uptake of NBS in general, non-participants are low in numbers. Parents that declined NBS also tend to decline participating in studies on NBS, while including non-participants’ views and attitudes can be valuable [26].

This study also has some limitations. Due to privacy and data protection issues, only the RIVM could invite the participants to complete the questionnaire. This also meant that no reminders could be sent. Due to the low numbers of NBS non-participants, analytical tests between NBS participants and non-participants were not possible. It is possible that respondents were more positive or more negative based on their experiences than parents in general (potential selection bias). Furthermore, the majority of NBS-participating parents were highly educated and of Dutch origin, which may have led to an overestimation of the proportion of parents making an informed decision. Additional subgroup analyses within NBS participants showed that higher educated parents have more knowledge and are more positive about NBS (S4 Table). More research is needed among parents with lower education levels and of non-Dutch origin. Also, different NBS test results (i.e. negative, inconclusive, abnormal) could influence views and attitudes toward the NBS screening. However, in this study only few parents with abnormal and inconclusive test results responded; subgroup analyses for these groups were therefore not possible. More insight into their perceptions is needed—also regarding NBS expansion—as screening for more disorders will result in more abnormal results, including false positives. Finally, parents might not oversee all ethical, social, and financial implications of NBS expansion. Qualitative research methodologies such as in-depth interviews and focus groups give more room for explanation and are more suitable to further explore motivations behind parents’ responses in detail [14, 39].