Effect of early postpartum EMDR on reducing psychological complaints in women with a traumatic childbirth experience

Abstract

This pilot study investigated the feasibility of postpartum Eye Movement Desensitization and Reprocessing (EMDR) for improving posttraumatic stress disorder (PTSD) symptoms, and its association with work absence, relationship difficulties, and development of psychiatric disorders in women with a traumatic childbirth experience who do not meet all criteria for PTSD. A randomized controlled study was conducted among 20 women (EMDR (N=11) vs. care as usual (CAU) (N=9)) who reported a traumatic birth. Outcomes were measured by questionnaires and a semi-structured interview. The results showed improvement of trauma-related psychological complaints for all women. EMDR appears to be more effective in reducing PTSD symptoms than CAU. Moreover, EMDR showed a small positive effect on work absence due to factors related to the traumatic childbirth experience. Results from the questionnaires were substantiated by interviews. However, due to the small size of the study, no statistically significant differences were found. In addition, no differences were found for relationship difficulties and development of psychiatric disorders. In conclusion, women with a traumatic birth experience may benefit from EMDR, even if they do not qualify for a diagnosis of PTSD. This study could be a starting point for future research aimed at early treatment that reduces trauma-related psychological complaints in postpartum women.

Keywords:

• EMDR
• traumatic
• PTSD
• childbirth
• postpartum

Introduction

Although for many women giving birth is a positive and empowering experience, 10–20% are left traumatized [1,2]. Only recently, traumatic birth experiences have become the subject of study, with a focus on prevalence, etiology [1,3–5] and women’s experiences of birth trauma [6,7]. Investigating these factors is necessary for understanding and preventing traumatic childbirth experiences. This is important because 1.2 to 4.7% of women eventually develop PTSD after childbirth [1,3,8].

PTSD can be characterized by four groups of symptoms: unwanted intrusions (e.g. nightmares and upsetting memories), avoidance (avoiding thoughts/actions that remind mothers of their traumatic birth experience), increased arousal (e.g. agitation and concentration problems) and negative changes in thinking and mood [9]. A meta-analysis of 78 studies found a prevalence of birth-related PTSD of 3–4% in community samples [8]. This means that the majority of women who had a traumatic experience do not qualify for a diagnosis of PTSD. However, postpartum-PTSD symptoms by themselves can cause significant suffering, which may negatively influence women’s mental health, the mother-infant bond, the intimate partner relationship, breastfeeding, subsequent pregnancy plans and work absence [4,5,10,11].

The national guideline of the Dutch Society for Obstetrics and Gynecology [12] recommends discussing a woman’s birth experience at the six-week postpartum checkup. When a traumatic birth experience is reported, screening for PTSD symptoms is recommended using validated questionnaires. With PTSD symptoms in absence of a diagnosis of PTSD, additional counseling by a primary care professional is recommended, but no evidence-based treatments are available. Existing evidence-based treatments for full-blown PTSD (regardless of the traumatic event) are different forms of Cognitive Behavioral Therapy (CBT) and EMDR [10,13,14]. EMDR as first-line treatment has already shown promising results for treating postpartum PTSD in small case studies by Sandström et al. [15] (N = 4) and Stramrood et al. [16] (N = 3), as well as in a pilot randomized controlled trial (RCT) by Chiorino et al. [17] (N = 37).

Thus far, there is little to no research on treatments for women who suffer from symptoms of birth-related PTSD, but do not qualify for the full diagnosis. For this reason, and to prevent progression to full-blown PTSD, it seems worthwhile to examine if EMDR is effective also for these women. Therefore, the purpose of this pilot study was to investigate the feasibility of early postpartum EMDR for improving PTSD symptoms and psychological complaints in women with a traumatic childbirth experience who do not meet all criteria for a diagnosis of PTSD. The primary outcome of this study was reduction of PTSD symptoms. Secondary outcomes were work absence, relationship difficulties, seeking professional help, and the development of psychiatric disorders.

Materials and methods

Study design

An explorative randomized controlled pilot study was conducted. This study was approved by the Medical Ethics Review Committee (METC). Duration of follow-up was twelve months. The intervention group received between one and three EMDR sessions, with each session taking 1–2 h. The control group received CAU, which is a postpartum checkup six weeks after birth. Women in the intervention group received the same checkup.

Study population and recruitment

All women who give birth at Radboudumc (tertiary referral center) routinely receive a telephone call from a nurse three weeks after giving birth to discuss their well-being. Between 1^st September 2019 and 1^st September 2020, the nurse additionally asked the women if they had experienced the birth as negative or traumatic. Those who answered affirmatively were asked if they were interested in receiving information about this study. This study partly took place during the COVID-19 pandemic. Women who wanted to receive the information and met the inclusion criteria were contacted by an obstetrician who elaborated more on the study. Inclusion criteria were: (1) negative or traumatic childbirth experience in the previous weeks; (2) age ≥ 18 years old; (3) sufficient knowledge of the Dutch language. Those women who were interested in participating in the study received an information package including an informed consent form. When informed consent was obtained, the women were asked to fill out the PTSD Checklist for DSM-5 (PCL-5) online. Each PTSD symptom, outlined by the DSM-5 [9], uses a scale ranging from 1 (= not at all) to 5 (= extremely). Women with a total score lower than 33, and a score higher than 2 on at least one of the DSM-5 clusters intrusion (B); avoidance (C); or alterations in arousal and reactivity (E) were included. A score of 33 represents the best cutoff for a probable diagnosis of PTSD [18] and is already an existing indication for treatment [9], therefore leading to exclusion from the current study. These women were referred to their general practitioner. A score of 2 or lower on all categories was deemed too low to be clinically significant. This cutoff was established in consultation with the scientific counsel of the EMDR association in the Netherlands (www.emdr.nl). In order to prevent including women with only symptoms of depression (DSM-5 criterion D), we did not take this cluster into account.

Instruments

The primary outcome was a reduction of trauma-related psychological complaints. Secondary outcomes were work absence, relationship difficulties, seeking professional help and development of psychiatric disorders. These parameters were measured by scores from questionnaires, supplemented by qualitative data from a semi-structured interview at six months of follow-up. The questionnaires were filled out by the participants before treatment (T0) and at all stages of follow-up (approximately three months (T1), six months (T2) and twelve months (T3) after randomization).

The instrument used for screening, the PCL-5, is a widely used DSM-correspondent self-report measure and demonstrates a strong reliability, validity and internal consistency (Cronbach’s α = 0.94).

The Perinatal PTSD Questionnaire (PPQ) measures the prevalence of different components of perinatal PTSD (according to DSM-5): unwanted intrusions, avoidance and increased arousal. It demonstrates adequate psychometric characteristics (Cronbach’s α = 0.896).

The Four-Dimensional Symptom Questionnaire (4DSQ) consists of the distress scale, depression scale, anxiety scale and somatization scale. All scales demonstrate a high validity and reliability in mental health settings (Cronbach’s α ≥ 0.90) [19]. There was also a purposefully designed questionnaire about absence from work. The minimal postpartum maternity leave in the Netherlands is ten weeks, so the participants filled out this questionnaire at the three-, six- and twelve-month follow-up.

The semi-structured interviews took half an hour each. The aim of the interviews was to examine more in-depth the women’s evaluation of the traumatic childbirth experience and their complaints related to their mental and physical health, mother-to-infant bond, intimate partner relationship and work. The interviews were not recorded or transcribed, although remarkable quotes were noted by the interviewer. Each interview was summarized and analyzed by the interviewer per participant. The analysis of the anonymized data focused on the experiences shared by the participants during the interviews and involved analyzing the content and meaning of these experiences to identify common themes and patterns for the study groups.

Statistical analyses

Data were analyzed using IBM SPSS Statistics (Version 27) predictive analytics software. Baseline group differences were assessed using descriptive statistics. A Mann-Whitney U test was used to compare the two groups for continuous variables and Fisher’s exact tests were used for comparing nominal variables. Scores from the PCL-5, PPQ and 4DSQ were analyzed using a mixed model for repeated measures (RM-MM). The mean change in score at T1, T2 and T3 relative to the baseline were compared between the EMDR group and the CAU group. Group differences in absence from work scores were assessed using descriptive statistics. All tests were two-sided and a p < 0.05 was considered statistically significant. However, significant results were not expected for this small explorative study, therefore, no power calculations were done.

Data management

After randomization an identification number was assigned to each participant. The EMDR therapist stored the code. The other investigators were blinded. Blinding ended after all data were analyzed. Questionnaires were sent and extracted from the Castor Electronic Data Capture program (Castor EDC, Amsterdam, The Netherlands 2019).

Results

Annually, approximately 1500 women give birth at Radboudumc. We estimate 80% were reached by the nurse at three weeks postpartum. A total of 70 women indicated a traumatic or negative childbirth experience between 1^st September 2019 and 1^st September 2020. The obstetrician was able to contact 66 women to give information about the study. Of these, 17 decided not to participate and 13 did not return a signed informed consent form. Informed consent was therefore received from 36 women. These women were asked to fill out the PCL-5 for screening. Six women presented a PCL-5 score above the cutoff (range = 40-51) and were referred to their general practitioner for probable PTSD. Ten women had a PCL-5 score of 2 or lower on all questions in clusters B, C and E (range = 4–19). They did not meet the lower threshold for the study. Therefore, a total of 20 women were included (range PCL-5 score = 10-31): eleven were randomly assigned to EMDR and nine to CAU. The moment of randomization (baseline/T0) was between six and twelve weeks after birth for each woman. A flow diagram of this selection procedure is presented in Figure 1.

Figure 1. Flowchart of selection of study population.

All women completed all assessments at all stages of follow-up and were included in the statistical analyses. There were no missing data. For the EMDR group, the first follow-up (T1) was on average two months after starting EMDR.

Quantitative results

The characteristics of participants at baseline (T0) are presented in Table 1. There were no statistically significant differences between the two groups. However, the largest numerical difference is seen for parity, with more multiparous women in the EMDR group.

Table 1. Characteristics of participants at baseline.

	EMDR	CAU	p
	Mean (SD)	Mean (SD)	Mann-Whitney U
Maternal age (years)	33.7 (3.7)	33.2 (2.9)	0.82
	%(n)	%(n)	Fisher’s exact test
Ethnicity			1000
Dutch	90.9 (10)	100 (9)
Not Dutch	9.1 (1)	0 (0)
Level of education			1000
Low	9.1 (1)	0 (0)
Intermediate	36.4 (4)	44.4 (4)
High	54.5 (6)	55.6 (5)
Parity			0.157
Primiparous	54.5 (6)	88.9 (8)
Multiparous	45.5 (5)	11.1 (1)
Mode of delivery			0.783
Spontaneous vaginal	36.4 (4)	22.2 (2)
Instrumental vaginal	27.3 (3)	22.2 (2)
Planned cesarean section	0 (0)	11.1 (1)
Not planned cesarean section	36.4 (4)	44.4 (4)
Responsible caregiver during delivery			1000
(Resident) obstetrician	54.5 (6)	55.6 (5)
Hospital-based midwife	45.5 (5)	44.4 (4)
Medical interventions/complications during delivery			1000
No	9.1 (1)	11.1 (1)
Yes	90.9 (10)	88.9 (8)

Subsequently, we evaluated whether the two groups (EMDR and CAU) had a different burden of trauma-related psychological complaints. Comparison of the mean PCL-5 and PPQ scores (EMDR vs CAU) at baseline (T0), three (T1), six (T2) and twelve-month follow-up (T3) is shown in Figure 2. Mean differences between the groups were analyzed using a RM-MM. Therefore, before performing the RM-MM, changes in clinical scores (PCL-5, PPQ, 4DSQ) had to be calculated between baseline and T1, T2 and T3. The calculated mean changes showed a decline for all questionnaires for both groups at all stages of follow-up. This means that, on average, women scored highest on the questionnaires at T0.

Figure 2. Comparison of mean PCL-5 and PPQ scores (EMDR vs. CAU) at T0, T1, T2 and T3.

Then, the T1, T2 and T3 decline in clinical scores relative to T0 were analyzed using the RM-MM, comparing group and time effects and interactions between group and time. The results for PCL-5 and PPQ are shown in Table 2. As expected, due to the small sample size, no statistically significant results were found. The result that most closely approached statistical significance was the mean difference between the two groups in PCL-5 score at T3 (p = 0.08, effect size (Cohen’s d) = 0.88), with the EMDR group showing a greater decline in score than the CAU group.

Table 2. Comparison of difference in mean decline in score of PCL-5 and PPQ between groups at T1, T2 and T3.

	T1			T2			T3
	EMDR (n = 11) Mean	CAU (n = 9) Mean	Mean difference (95%-CI)	EMDR (n = 11) Mean	CAU (n = 9) Mean	Mean difference (95%-CI)	EMDR (n = 11) Mean	CAU (n = 9) Mean	Mean difference (95%-CI)
PCL-5	13.84	9.64	−4.21 (−11.80; 3.38)	11.19	11.44	0.26 (−7.72; 8.23)	14.87	9.38	−5.50 (−11.74; 0.75)
PPQ	8.01	4.33	−3.68 (−12.62; 5.26)	9.30	6.31	−2.99 (−11.50; 5.52)	11.59	10.17	−1.42 (−7.07; 4.23)

The mean PPQ score of the EMDR group was showing a greater decline at all stages of follow-up than the CAU group (see Figure 2). However, the difference in decline became smaller over time (see Table 2). The largest decline in PCL-5 and PPQ scores was between the baseline and the three-month follow-up for both groups, with the EMDR group showing a slightly larger decline (see Figure 2).

The results from the 4DSQ showed no significant differences (see supplementary material). Finally, there appears to be an effect of time for all questionnaires. The more time passed after the traumatic birth experience, the lower the burden of psychological complaints in both groups, with the greatest decline at T1 and the EMDR group showing a slightly larger decline than the CAU group (see Table 2 and supplementary material).

The differences in absence from work between the EMDR group and CAU group at T1, T2 and T3 are presented in Table 3 (see also supplementary material). Total women and per group at T1, T2 and T3 per statement. Again, no statistically significant differences were found. However, there were some noteworthy findings, also marked bold in Table 3: most women resumed work directly after their maternity leave, with larger participation in the CAU group (At T1: CAU 88.9%; EMDR 63.6%). However, women in the CAU group took sick days more often and worked less hours due to the traumatic birth experience.

Table 3. Statements about work absence related to traumatic birth experience: point prevalence (at T1, T2 and T3) and total amount of women to whom the statement applied (EMDR vs. CAU).

	EMDR N = 11				CAU N = 9
	T1 %(n)	T2 %(n)	T3 %(n)	Total N	T1 %(n)	T2 %(n)	T3 %(n)	Total N
Had a paying job before their pregnancy	100 (11)			11	100 (9)			9
Resumed working (after maternity leave)	63.6 (7)	72.7 (8)	81.8 (9)	9	88.9 (8)	77.8 (7)	100 (9)	9
Of the women who resumed working: took sick days related to the traumatic birth experience	0 (0)	12.5 (1)	33.3 (3)	4	37.5 (3)	28.6 (2)	33.3 (3)	4
Of the women who resumed working: worked less hours after maternity leave	28.6 (2)	25.0 (2)	22.2 (2)	4	50.0 (4)	14.3 (1)	44.4 (4)	4
Women who worked less hours/did not resume working after maternity leave due to the traumatic birth experience	16.7 (1)	0 (0)	25.0 (1)	2	40.0 (2)	66.7 (2)	25.0 (1)	2
Sought professional help for trauma-related psychological complaints	27.3 (3)	45.5 (5)	63.6 (7)	8	33.3 (3)	33.3 (3)	44.4 (4)	4
Received a psychiatric diagnosis	9.1 (1)	0 (0)	9.1 (1)	2	11.1 (1)	11.1 (1)	11.1 (1)	2

The number of women who sought professional help for their trauma-related psychological complaints was twice as high in the EMDR group (8) than in the CAU group (4). Sought professional help consisted mainly of psychologists, but also general practitioners, psychiatric-mental health nurse practitioners, obstetricians and a haptotherapist. Seeking professional help increased over time from T1 to T3 in the EMDR group, while it remained relatively constant in the CAU group.

Qualitative results

Women were interviewed about their work, physical and mental complaints, evaluation of the traumatic childbirth experience, mother-to-infant bond, and intimate partner relationship.

Work

The majority of women in both groups mentioned either working fewer hours than before the pregnancy, taking days off, calling in sick or leaving their job. Next to factors as motherhood, fatigue, trauma-related or medical complaints, also the concurrent COVID-19 pandemic was stated as reason.

Complaints

In the EMDR group, half of the women did not have any mental or physical complaints anymore after treatment. The other half still mentioned some complaints. In the CAU group, the majority of women mentioned still having complaints. In both groups, women mentioned that complaints decreased over time, both in number and severity. The main complaints that were mentioned included fatigue, fear of the next pregnancy, anxiety (after being triggered by pain, memory or a loud noise), fear of losing control and being troubled by thoughts of the traumatic birth experience. Sometimes external factors, including COVID-19 and work, played a role. In the CAU group, three women had sought professional help, one of them received EMDR. All felt that this had helped them. Some examples of different participants describing their experience with EMDR (translated from Dutch):

• “Initially, I absolutely did not want to think about having another child. EMDR helped me get rid of this. Previously, I would panic at the sight of a pregnant woman. That is now gone.”

• “After EMDR, I was able to look at birth photos again.”

• “I am very happy with the EMDR treatment. Now I can see that I actually experienced something very beautiful.”

• “The EMDR treatment helped immediately after the first time.”

Evaluation of the traumatic childbirth experience

Almost all women in the EMDR group mentioned looking back at the traumatic birth experience as less stressful than before. Most women were no longer afraid to get pregnant again, although some wanted more control and/or emotional support the next time they would give birth.

Most women in the CAU group had a more negative perception of the traumatic birth experience in hindsight than the women in the EMDR group. Only one mentioned still wanting another child.

Other results

As to the mother-to-infant bond and intimate partner relationship, no notable differences between the two groups (EMDR and CAU) were mentioned.

Discussion

Main findings

This study found that EMDR may help to reduce psychological complaints in women who had a traumatic birth experience but do not meet all criteria for PTSD. Due to the small sample size, no results reached statistical significance.

Other findings

EMDR showed a positive effect on work absence due to factors related to the traumatic childbirth experience. However, the differences were small. No differences were found between the two groups for relationship difficulties and the development of psychiatric disorders. In both groups, no women developed PTSD.

Discussion of the findings

To the best of our knowledge, this is the first study investigating the effect of postpartum EMDR on women with a traumatic birth experience who do not fully meet the criteria for PTSD. One prevention study recently investigated the effectiveness of early-intervention EMDR in women with clinically significant postpartum-PTSD symptoms [17]. This study compared standard psychological supportive therapy (n = 18), with a 90-min EMDR session within 72 h after childbirth (n = 19). Statistically significant differences were found in reducing flashbacks, distress levels and the proportion of women with postpartum-PTSD symptoms at six to twelve weeks postpartum, in favor of the EMDR group [17]. This is in line with our findings of EMDR possibly reducing flashbacks and distress symptoms (interviews), as well as birth-related psychological complaints (questionnaires). Despite similarities between these two studies, the results of the study by Chiorino et al. [17] were statistically significant. This might be explained by the slightly larger sample size of that study, higher severity of the PTSD symptoms, and the earlier timing of the EMDR intervention (0–3 days postpartum vs 10–16 weeks postpartum). In this current study, there were 8 out of 11 women in the EMDR group and 5 out of 9 women in the control group achieving a clinically significant improvement at the last stage of follow-up, meaning they had a 10–20-point change in PCL-score [18]. This could mean that other factors play a role in reducing PTSD symptoms. The effects of time on PTSD are often mentioned in literature. Over time there can be a reduction or even a remission of PTSD symptoms without specific treatment, although this varies and can take months to decades [20–22]. In our study, we also saw an effect of time. The largest decline in PCL-5 and PPQ scores between two consecutive stages of follow-up was between the baseline and the three-month follow-up for both groups, with the EMDR group showing a slightly larger decline. This is in accordance with an RCT that demonstrated the response pattern of EMDR, in which the fastest decline in PTSD symptoms was seen in the short term (the first six weeks after EMDR treatment) [23]A notable finding in this current study was the relatively large mean difference between the two groups in PCL-5 score at the twelve-month follow-up (p = 0.08), with the EMDR group showing a greater decline in the score (14.87 pts) than the CAU group (9.38 pts). This suggests that approximately a third of this decline could be attributed to EMDR. One explanation could be the higher percentage of women in the EMDR group who sought additional professional help for trauma-related psychological complaints. This may, in turn, be due to an increased awareness of the problem and access to appropriate services, both known in the literature to predispose people to seek help for mental health problems [24,25].

In addition, according to the interviews, the women in the EMDR group evaluated their birth experience as less stressful after treatment. Fear of losing control was mentioned as a complaint as well as an attribution of the traumatic experience. This was a recurring theme during the interviews and in line with studies by Hollander et al. [6] and van der Pijl et al. [26].

During the interviews, women were also asked about their intimate partner relationships. Several studies suggest that postpartum PTSD can have a negative impact on this relationship [27,28]. However, in this study, no notable relationship difficulties due to the traumatic birth experience were mentioned by women from either group. However, this study did not include full-blown PTSD. Perhaps more severe symptoms are needed to interfere with an intimate partner relationship. On the other hand, it could also be related to a small sample size. Another possibility is that relationship difficulties due to factors related to the COVID-19 pandemic overshadowed possible negative effects of trauma on the relationship. Several recent studies suggest that the COVID-19 pandemic negatively affects postpartum women, with participants showing higher levels of stress, anxiety and depression [29–31].

Our study found that EMDR may reduce work absence due to factors related to a traumatic birth experience. We found a significant amount of work absence in both groups, mainly due to the COVID-19 pandemic. However, according to both the questionnaires and interviews, women in the CAU group more often reported absence from work due to factors related to the traumatic birth experience. Absence from work can be detrimental to the economy, society, and to an individual’s (mental) health [32,33]. Nevertheless, to our knowledge, no studies have examined work absence due to factors related to traumatic birth experiences. Therefore, if EMDR were proven to reduce work absence after a traumatic childbirth experience (with an incidence of 10-20%), this could have a significant impact on society.

Statement of limitations

This study has several limitations. The data were collected specifically for this study. No power calculation was done beforehand. Reasons for this were the aim of doing a feasibility study, not to prove a significant difference. With the time and money available, in a single center, statistical significance would not be possible. Nevertheless, feasibility was demonstrated with this study. Another limitation was the inconsistent time at which questionnaires were received. Not all women filled out the questionnaires exactly on time, resulting in a few weeks’ difference for each stage of follow-up. In addition, a significant number of women sought professional help, including EMDR, outside this study, which could have interfered with the results as well. Therefore, while the study provides valuable insights, caution should be taken when generalizing the findings to larger populations or different settings.

A strength of this study is that it is a mixed methods study, which provides a broad and complete picture of the psychological complaints of the participants. Another strength is that follow-up was 100% complete, meaning there were no missing data. Finally, all EMDR sessions and interviews were performed by the same therapist, ensuring there were no differences in approach.

Conclusion

The findings of this pilot study suggest that early postpartum EMDR therapy holds promise as a feasible and potentially effective intervention for reducing PTSD symptoms in women with a traumatic birth experience but without a diagnosis of PTSD. As this was a pilot feasibility study with a small sample size, no definitive conclusions can be drawn. However, there was a trend indicating the potential benefits of EMDR therapy. Quantitative results demonstrated a decline in clinical scores over time for both the EMDR and CAU groups. Although there was a trend suggesting that EMDR therapy may be more effective in reducing the burden of psychological complaints. The qualitative data complemented the quantitative results and provided valuable insights. Participants in the EMDR group reported a reduction in mental and physical complaints, decreased fear of subsequent pregnancies, and a more positive evaluation of their traumatic birth experiences. These findings support the need for further research with larger sample sizes to provide more evidence regarding the effectiveness of early postpartum EMDR in reducing PTSD symptoms and improving the overall well-being of women with traumatic birth experiences.

Ethics approval and consent to participate

This study was conducted in accordance with the Medical Research Involving Human Subjects Act (WMO) and approved by the local Central Committee on Research Involving Human Subjects (CCMO, Nijmegen/Arnhem, study number: 2019-5177). In addition, this study was conducted according to the principles of the Declaration of Helsinki. Written informed consent was obtained from all individual participants included in the study.

Author’s contributions

Martine Hollander managed the study conception and design. Data analysis was performed by Emma Kopmeiners. The manuscript was written by Emma Kopmeiners and all authors commented on previous versions of the manuscript. The final version of the article was read and approved by all authors.

Acknowledgements

We would like to thank all women who participated in this study.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Data used in this analysis are stored digitally in a password-protected University database. Contact Dr. Martine Hollander ([email protected]) if you wish to request the data.

Additional information

Funding

Financial support was received from Radboudumc by means of a grant awarded to Dr. Hollander.