Introduction

Retinoblastoma (Rb) is the most common primary ocular malignancy in childhood, accounting for 4% of childhood malignancies1 and 5% of childhood blindness2. Rb is difficult to treat, persists, and has high medical costs, causing great harm to the physical and mental health of the affected children and their parents3. Parents of children with Rb experience a variety of pessimistic emotions4, including anxiety, depression, and stress5. Most parents of children with cancer experience fatigue during caregiving6. Fatigue is a subjective feeling of tiredness or weariness caused by physical or mental exertion7, and family carers describe mental fatigue as feeling tired, having difficulty concentrating, and feeling overwhelmed by the environment in which they find themselves8. Fatigue increases the risk of adverse events, leads to cognitive decline9, directly affects the recovery of the disease and the growth and development of the child10,11, and endangers patient safety12. The fatigue status of parents of children with Rb, as the direct caregivers of their children, should be of concern. However, there is a lack of research related to fatigue in parents of children with Rb. The theory of unpleasant symptoms (TOUS) was proposed by a team led by Elizabeth R. Lenz, a member of the American Academy of Nursing13, and has been widely used in symptom-related research. This theory states that factors influencing symptoms are categorised into three main groups, namely physiological, psychological, and environmental factors. Focusing on the issue of fatigue in parents of children with Rb, this study, based on TOUS, aimed to investigate the three aspects of fatigue from the physiological, psychological, and environmental perspectives to analyse in depth the factors influencing fatigue, to provide theoretical support for the formulation of subsequent interventions for parents of children with RB, and subsequently improve the quality of life of both the children and their parents.

Methods

Study participants

The parents (father or mother) of children with Rb were selected as study participants using convenience sampling. The inclusion criteria were as follows: father or mother of a child with Rb; age ≥ 18 years; provided informed consent; and agreed to voluntary participation. The exclusion criterion was mental illness to the extent that the participants were unable to complete the survey independently.

Data collection

From 9 March to 1 June 2020, the parents of all children with Rb who were undergoing treatment at the Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine and Qilu Children’s Hospital of Shandong University were informed via a WeChat platform (https://www.wjx.cn) and informed them of the purpose, content and methodology of the study. Eligible parents were then selected to participate in our study based on the inclusion and exclusion criteria. Then, an online questionnaire was administered through the WeChat platform, which included both multiple-choice and open-ended questions; the questionnaire could only be submitted when fully completed. The survey was confidential and anonymous.

Questionnaire

General demographic and health data

These were collected for the (1) parents (including relationship to the child, age, marital status, working status, number of children, average daily time spent caring for the child, and health status) and (2) children (including sex, date of birth, diseased eye, and disease status).

Fatigue severity scale (FSS)

This scale was developed in 1989 by American scholars Krupp et al. and is effective in evaluating patients’ fatigue levels14. The scale consists of nine items, each rated from 1 (strongly disagree) to 7 (strongly agree), with a total score ranging from 0 to 63. The FSS score = total score/9, and a score > 4 is considered as severe fatigue, while a score ≤ 4 is no fatigue or a lesser degree of fatigue. This scale has been widely used by researchers to evaluate caregiver fatigue levels15,16.

Generalized anxiety disorder (GAD-7)

GAD-7 is a screening tool for generalised anxiety disorder and comprises seven items on how much the participant has been bothered by the corresponding symptom in the past two weeks. A four-point scale ranging from 0 (not at all) to 3 (almost every day) was used, with a total score of 0–21, with higher scores indicating greater severity, and a total GAD-7 score ≥ 10 considered a positive screening result for generalised anxiety17. The questionnaire has good reliability and validity18. It is a self-assessment tool that can be used quickly and effectively to detect the presence of anxiety symptoms in participants.

Two-item patient health questionnaire (PHQ-2)

Depressive symptoms were assessed using the validated Chinese version of PHQ-2, with scores ranging from 0 (“not at all”) to 3 (“Almost every day”)19. The PHQ-2 assesses the frequency of “feeling depressed, despondent, or hopeless” over a 2 week period. A score ≥ 3, which was considered as “depression,” had a sensitivity of 83% and specificity of 92% for major depression. The PHQ-2 has been validated and used in China20.

Statistical analysis

Statistical analyses were performed using IBM SPSS Statistics for Windows, version 24.0 (IBM Corp., Armonk, NY, USA). For continuous variables, the mean ± standard deviation was used for descriptive analysis, and the Mann–Whitney U test was used to compare the differences between the two groups. Categorical variables were described as the number of cases (percentage), and the chi-square test was used to analyse the differences between the groups. Correlations between fatigue and variables such as anxiety and depression were analysed using Spearman's correlation analysis; variables with P < 0.2 in the univariate analyses were included in the model, and multifactorial logistic regression analyses were performed using the forward stepwise regression method (likelihood ratio [LR]) to identify predictive factors related to fatigue. Differences were considered statistically significant at P < 0.05.

Ethics approval and consent to participate

This study was approved by the Institutional Review Board of Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine [approval number (SH9H-2019-T289-2)]. All the procedures were performed in accordance with the relevant guidelines and regulations and in accordance with the Declaration of Helsinki.

Results

Fatigue among parents of children with Rb

The total fatigue score of the parents of children with Rb was 39.65 ± 10.29, with a mean score of 4.41 ± 1.14. The number of fatigue-positive cases was 213 (67.19%). Only the “Working out makes me tired” score was < 4, whereas other scores were > 4. The specific scores and rankings are shown in Table 1.

Table 1 The scores of each item of parental fatigue in children with Rb (N = 317).
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Comparison of scores for each entry for fatigue in parents of children with Rb

There was a significant difference in the five entry scores between fathers and mothers (P < 0.05), as shown in Table 2.

Table 2 Comparison of scores for each entry for fatigue in parents of children with Rb (N = 317).
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Univariate analysis of the occurrence of fatigue in parents of children with Rb

Parental fatigue in children with Rb was significantly different between the involvement of unilateral or bilateral eyes and disease status (P < 0.05). Further details are presented in Table 3.

Table 3 Univariate analysis of the occurrence of fatigue in parents of children with Rb (N = 317).
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Correlation analysis of parental fatigue and related indexes in children with Rb

The correlation analysis results showed that the fatigue level was positively correlated with anxiety, depression, education, times of hospitalisations, and treatment types (r = 0.125–0.468, P < 0.05) and negatively correlated with health status, sleep quality, economic status, and family economic situation (r =  − 0.120 to − 0.322, P < 0.05). Further details are presented in Table 4.

Table 4 Correlation analysis of parental fatigue and related indexes in children with Rb (N = 317).
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Multifactorial analysis of fatigue in parents of children with Rb

When the risk factors of fatigue in the parents were analysed in the regression analysis model, unconditional logistic regression analysis showed that anxiety, child sex, and the number of children had a significant effect on fatigue; that is, parents of children with Rb who were anxious, whose child was a girl, or who was an only child were more likely to be fatigued. Further details are presented in Table 5.

Table 5 Multifactorial analysis of fatigue affecting parents of children with Rb.
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Discussion

Higher levels of fatigue in parents of children with Rb

In this study, the parental fatigue score of the 317 children with Rb of 4.88 ± 1.42 was high, and more than half (67.19%) of the parents were fatigued. Callaham et al.21 reported that parental fatigue has a significant impact on the family and also affects the recovery of the child from disease. In the present study, 84.22% of the children were aged under 5 years, which is the stage when children are dependent on their parents for care. Moreover, 75% of the children were either under treatment or follow-up. While being diagnosed, treated, or being followed up, children with Rb require multiple and repeated hospital admissions, and their parents have to provide them with daily life care and emotional support, as well as bear the pressure of sudden deterioration in the condition of their children, or even death. Children with Rb undergo repeated hospital admission. Rb treatment is difficult, the treatment cycle is long, and the medical costs are high3; therefore, the process involves physical activities and also places a heavy mental burden on parents4. Therefore, the parents of children with Rb are prone to physical and psychological fatigue. In this study, 41.01% of the parents were unemployed, which, to some extent, may imply that the parents had to reduce their working hours to care for their children. Furthermore, 53.00% of the parents indicated that the family income could not meet the children’s medical expenses and that the search for treatment for the children involves a large amount of costs. Also, families with limited income felt that the costs were high and unattainable and that they were bearing a heavy financial burden. Besides caring for children with Rb, clinicians should pay attention to the occurrence of fatigue in the parents, provide necessary humanistic care, and strengthen patient-care skills, to minimise fatigue.

Anxious parents of children with Rb are easily fatigued

The current study found that anxiety was an independent factor of fatigue in the parents, and these anxious parents were more likely to be fatigued. This finding may be related to the uncertainty faced by parents and the experience of side effects of their children’s treatment. With advances in tumour biology and drug development, Rb treatment has gradually shifted from eye removal and external radiation therapy to chemoreduction combined with local therapy22. Chemotherapy is the most commonly used treatment for Rb. A preliminary investigation in this study group showed an incidence of vomiting, anaemia, and bone marrow suppression in the children after chemotherapy to be 19.30%23, 64.18%24, and 34.40%24, respectively. Chemotherapy toxicity is common during the treatment of children with tumours and seriously affects the functional status and quality of life of the children25. A tumour may spread beyond the eye or develop into a tumour in the eye. If extraocular spread or metastasis of the tumour occurs, the survival rate of the child is greatly reduced26. Thus, anxiety in the child’s family increases by the fear of tumour recurrence, extraocular spread, or even metastasis, which undoubtedly aggravates fatigue in the child’s parents. Therefore, while administering treatment and care for these children, comprehensive and evidence-based care should be provided by medical personnel, including skills education and psychological care. Furthermore, medical personnel should pay more attention to the causes of emotional challenges and stressful conditions in the parents to provide the necessary help, psychological counselling, and intervention when necessary.

Parents of children with Rb who have only one child are prone to fatigue

This study showed that parents of an only child with Rb are prone to fatigue. This is because having a single child or young child is associated with a relative lack of parental knowledge and skills in providing care, particularly for a child with cancer. Besides raising the children, parents must cope with the discomfort caused by Rb treatment in their daily lives. With fewer children, parents may have excessive worries about child loss that can lead to severe trauma both physically and mentally, as well as face greater difficulties in old age, including financial and cultural pressure. Fei et al.27 found that in the context of traditional Chinese culture, parents who have lost their children have more serious mental difficulties, which are mainly reflected in the continuous grief reaction and grief process of “never going out”, with a dynamic and recurring grief process. Compared to non-only child families, the loss of an only child is more traumatising28. Parents with fewer children face tremendous energy and mental trauma after such a loss, which undoubtedly aggravates their fatigue. Interviews with some parents of only children with Rb revealed great pressure to have another child and fear of having another child with cancer. Furthermore, due to the sudden illness in the child, overprotective behaviour develops in the parents to compensate for the child, coupled with the fear of poor treatment outcomes and perception of poor prognosis of cancer, leading to accompanying guilt in parents29,30,31. Therefore, parents often experience guilt, anxiety, stress, and other negative emotions that make them susceptible to fatigue32. Therefore, the fatigue status of such parents with only one child should receive more attention.

Parents of female children with Rb are more likely to be fatigued

This may be related to parental concerns about the tumour affecting the child’s physical appearance. Chemotherapy is the most commonly used and viable treatment for Rb, especially in resource-poor areas where alternative treatment options are limited33. Although chemotherapy is effective in controlling tumour progression in the long term, it may lead to serious systemic complications such as bone marrow suppression, gastrointestinal toxicity, and stunting1. These complications have a serious impact on the patient’s ability to survive as well as on the appearance of the child, especially when eye removal is required or even enucleation of the eye contents, which further affects the child’s appearance. Womanhood is synonymous with “beauty” throughout history, and parental concern about a female child’s appearance is a result of their cultural background. However, these parents may be more concerned about their children’s survival rates. A study by the Global Retinoblastoma Study Group found that female children with Rb have a higher mortality rate compared to male children34. The study also showed that such female children have a higher mortality rate than the male. Parents are concerned in many ways, which undoubtedly adds to the fatigue felt by parents of children with Rb. Caregivers should pay more attention to the fatigue status of the parents of female children with Rb and provide knowledge about disease treatment and emotional support. The use of social media to disseminate information and provide emotional support to parents of children with cancer has been shown to be effective, and a tool to facilitate this can be subsequently validated and scaled up for implementation35. The programme will be implemented in subsequent years.

Limitations

The limitations of this study are that the data were obtained from only two hospitals, the sample size was limited, and the findings may have been biased. In the future, we plan to conduct a multi-regional, multicentre study, and establish a long-term follow-up to further validate the reliability of the findings of this study. Although there was no statistical difference in the occurrence of parental fatigue, some aspects of parental fatigue did differ significantly, and follow-up studies should further explore the differences in parental fatigue and develop or use simple and easy-to-use objective measurement tools to assess fatigue in parents of children with Rb. Moreover, attention should be paid to whether there are differences in parental fatigue at different stages of Rb treatment to enrich the knowledge in this field and provide theoretical support for subsequent interventions.

Conclusion

This study discovered that parent’s anxiety level, being an only child and female sex of child were the primary factors contributing to the high prevalence of parental fatigue in children with Rb. This discovery has significant ramifications for clinical practice as it emphasises the necessity of giving special consideration to the psychological well-being and overall life satisfaction of those in these specific demographics when caring for children with Rb and their families. It also underscores the importance of offering appropriate support and interventions to help these families effectively navigate the challenges associated with the disease.