Mental health and professional outcomes in parents of children with chronic kidney disease

Background This study evaluated stress, anxiety and depression symptoms and their associated factors in parents of children with chronic kidney disease (CKD). Methods This cross-sectional study compared parents of CKD patients (0–18 years) with a matched control group of parents of healthy children. Both groups completed the Parenting Stress Index – Short Form, the Hospital Anxiety and Depression Scale, and a sociodemographic questionnaire. Results The study group consisted of 45 parents (median age 39; 32 mothers) of CKD patients (median age 8; 36% female). Nearly 75% of children had CKD stage 2, 3, or 4, and 44.5% had congenital anomaly of the kidney and urinary tract. Five children (11%) were on dialysis, and 4 (9%) had a functioning kidney graft. Compared with parents of healthy children, more stress and anxiety symptoms were reported. Since the CKD diagnosis, 47% of parents perceived a deterioration of their own health, and 40% reduced work on a structural basis. Higher levels of stress, anxiety and depression symptoms were associated with a more negative perception of own health, and more child medical comorbidities and school absence.


Introduction
Chronic kidney disease (CKD) has a signi cant impact on the psychosocial development of a child.Compared with healthy peers, lower quality of life (QoL) and more psychological problems are reported in children with mild to advanced stages of CKD or after kidney transplantation [1][2][3][4][5].Like numerous other chronic diseases in childhood, these children depend on their primary caregivers, mainly parents, for the challenging disease management, which heightens the risk of stress among these parents [1,6].Despite medical advances resulting in higher survival rates [7,8], parents have to face a far above average mortality risk in their child [7].Furthermore, parents are faced with the daily challenges of coping with their child's dietary and uid restrictions, complex and time-intensive medical treatments, frequent outpatient visits or hospitalizations, and lifelong consequences of the disease [9,10].
The impact of parenting a child with a chronic illness on parents' mental health has been a focus in several studies and systematic reviews.Compared with parents of healthy children, lower QoL [11], higher parental stress [12,6,13,14] and more frequent symptoms of anxiety and depression [15,16] were found in parents caring for a chronically ill child in general.Also more di culties with employment [17] and a higher nancial burden [6,18] have been reported in these parents.
Less is known about the impact on parents speci cally in a CKD population, although Bignall et al stated that the persistent nature of this chronic disease affects parents in such a way that it could be said that when a child is diagnosed with CKD, the whole family develops a "chronic condition" as well [19].
Reducing the impact of CKD on parents' mental health seems essential, not only for the parents themselves but also to improve the psychosocial functioning and physical health of the child, as parental stress was found to be associated with lower QoL scores in the child [20,21], a higher presence of behavioral problems, and lower adherence to immunosuppressant medications [22,23].Also, parental stress can negatively affect the children's and parents' perceptions of the child's CKD management [24], health and well-being [8].
Most studies with parents in a CKD population have focused on either parental stress, anxiety or depression, and only a minority has been focusing on how these mental health outcomes are associated with parent and child characteristics.A recent systematic review revealed that studies exploring physical health in parents of chronically ill children are scarce [16] and to our knowledge nonexistent speci cally for a CKD population.Also studies exploring child variables such as comorbid medical diagnoses or developmental disorders are scarce.Such studies are however needed to improve our understanding and to set up tailored interventions, as these parents are chronically exposed to these additional stressors [19,25].To address these research gaps, this study aims to 1/ compare the prevalence and clinical scores of both stress, anxiety and depression symptoms in parents of children with CKD with a matched control group of parents of healthy children, and 2/ explore the associations of these three mental health outcomes with several characteristics of the parent (e.g.parent's own health perception, structural work reduction, additional work leave) and the child with CKD (e.g.medical comorbidities, developmental disorders, school absence).Additionally, we sought to identify predictors of parental stress, anxiety and depression symptoms.

Study Population
This exploratory study consecutively included parents of children aged 0-18 years with CKD stages 1 to 5D or after transplantation managed at the Pediatric Nephrology Departments of three University Hospitals in Belgium, namely Ghent, Leuven, and Antwerp, between 2015 to 2017 (Table 1).CKD was de ned according to the KDIGO guidelines and classi ed in different stages (1 to 5) according to the estimated glomerular ltration rate (eGFR), determined by the updated bedside Schwartz formula (eGFR = 0.413*length/creatinin) [26,27].As this study is part of the multicentric UToPaed study, we refer to El Amouri et al for more detailed information concerning the methods [28].
The control group of parents of healthy children was recruited from the general population by snowball sampling and was individually matched by parent's gender and child's gender and age.Parents of children with a chronic medical condition were excluded for this control group.
Exclusion criteria for both groups were related to the possibility of adequate completion of questionnaires, such as severe cognitive disability or an insu cient knowledge of Dutch.
This study was approved by the Ethics Committee of the Ghent University Hospital (B670201524922 and B670201731893).A written informed consent was obtained from all parents.Participation was voluntary and no payments or other rewards were provided.
After informed consent had been provided, all parents were asked to complete the Parenting Stress Index -Short Form (PSI-SF), the Hospital Anxiety and Depression Scale (HADS), and a self-developed sociodemographic questionnaire.Additional medical information of the CKD patients was obtained from the medical les.

Measures
Clinical and sociodemographic data Sociodemographic information such as the parent's age, gender, marital status, country of birth, education level and number of children living at home was collected from all parents.Also, parents provided the following information about their child: age, gender, developmental disorders (e.g., autism spectrum disorder, attention problems or learning disabilities), psychosocial support (e.g., psychologist) or developmental support (physiotherapist, speech therapist, …), special educational needs, and absence from school (recall of number of days in the past 6 months).
Additionally, parents of children with CKD were asked to indicate if they had reduced their professional activities on a regular basis since the CKD diagnosis, and to report the number of additional days they had taken off from work in the past 6 months to care for their child with CKD.Also, we asked these parents how they perceived their own health since the diagnosis of their child (equal/better/worse).
Finally, parents were asked to report any medical comorbidities 1 in their child.Additional relevant clinical information was obtained from the child's medical chart such as underlying kidney disease, CKD stage, current treatment, kidney transplantation, and duration of CKD.

Parenting Stress Index -Short Form (PSI-SF)
The short version of the Dutch Parenting Stress Index (PSI-SF) is a 25-item screening questionnaire for parenting stress [29,30].Parents rate the items on a six-point Likert scale ranging from 1 ('totally disagree') to 6 ('totally agree').The PSI-SF total score is the sum score of the 25 items (maximum score 150), with higher scores indicating higher levels of parenting stress.

Hospital Anxiety & Depression Scale (HADS)
Symptoms of anxiety and depression in parents were assessed with the HADS [31].This 14-item selfreport screening tool is divided into two 7-item scales; anxiety and depression.The questions are answered on a four-point Likert scale (0-3) resulting in scores on each scale from 0 to 21.Higher scores indicate more symptoms of anxiety respectively depression in the past week.A scale score of 8 (cut-off score) or above is considered as an indicator for clinically signi cant anxiety or depression [31].The Dutch version of the HADS showed satisfactory validity and reliability [32].

Statistical methods
All statistical analyses were examined by using SPSS 25.0.Normality was checked with the Shapiro-Wilk test.
Parents' and children's characteristics in the CKD group and the non-clinical control group were compared using independent samples t-tests and Chi-square tests (as appropriate).Mann-Whitney U-tests were performed to compare the median levels, and Chi-square tests to compare the proportions in the clinical range.Correlations were calculated using Spearman correlations.Linear regression analyses were performed to explore which parental and child variables were associated with parental stress and symptoms of anxiety and depression.Due to the small sample size and to maximize the reliability of the analyses, only 5 predictors were included in the regression model (i.e., parents' own health perception, child age, CKD stage, child's medical comorbidities, child's developmental disorders).In order to determine multicollinearity between two or more predictor variables, variance in ation factors (VIF) were used.No problematic multicollinearity was detected, as all VIF values were lower than 2. To correct for multiple testing, Bonferroni correction was performed.

Clinical and sociodemographic data
The characteristics of the included parents of children with CKD (N = 45) and parents of healthy children (N = 45) are shown in Table 1.In the CKD group, the majority of parents (median age 39) who completed the questionnaires were mothers (71%), and most families had 2 to 3 children (60%).Parents in the CKD group did not differ from the parents in the control group with respect to their age, gender, or number of children (P > 0.05).Compared with the control group, less parents were born in Belgium (87% versus 98% in the control group; P = 0.01), were married or living together (76% versus 93% in the control group; P = 0.04) or completed higher education (56% versus 78% in the control group; P = 0.01).
In the CKD group, 40% of parents reduced work on a structural basis since the CKD diagnosis in order to take care for their child.On average, parents had taken 4 additional days off from work in the past 6 months (median 4 days [0.5; 13]), with a maximum of 90 days.Also, 47% of parents perceived a deterioration of their own health since the CKD diagnosis of their child.
Children with CKD (median age 8; 36% female) did not differ from the healthy controls with respect to their age or gender (P > 0.05).In the CKD group, nearly 75% of children were categorized in CKD stage 2 (N = 24) , 3 (N = 24) or 4 (N = 24), and 44.5% was diagnosed with congenital anomaly of kidney and urinary tract (CAKUT).Five children (11%) were on dialysis, 4 children (9%) had undergone a kidney transplantation.The time since CKD diagnosis was on average 6 years.For 14 children (31%), parents reported one or more comorbid medical conditions.We refer to the Appendix for more information about these medical comorbidities.
In this study sample, parent reports showed no signi cant differences in the presence of developmental disorders or absence from school.However, children in the CKD group made more use of professional psychosocial or developmental support on a regular basis (38% versus 9%; P < 0.001), and more often got special education versus the children in the control group (20% versus 2%; P = 0.01).

Differences in parental stress and symptoms of anxiety and depression
In the present study sample, Cronbach's alpha for the total PSI-SF score was 0.93 in the CKD group and 0.88 in the control group, showing good internal consistency.Similar good internal consistency was observed in the HADS with a Cronbach's alpha score of 0.82 for the depression scale in the CKD group and 0.77 in the control group, and 0.84 for the anxiety scale in both groups.
Differences in stress, anxiety and depression symptoms between parents of CKD patients and parents of healthy children are presented in Table 2. Parents of children with CKD reported signi cantly higher levels of stress (P < 0.001) and anxiety symptoms (P < 0.01) compared with parents of healthy children.Considering symptoms of depression, no signi cant differences could be detected between both parent groups.Boxplots visualizing these comparisons are added as Supplemental Figures 1 to 3.
The proportions in the clinical range for stress, anxiety and depression are also shown in Table 2.No signi cant differences were found between parents of children with CKD and parents of healthy children.

Correlations
Scatterplots of the correlations between parental stress, anxiety and depression symptoms in parents of children with CKD are presented in Figures 1 to 3. Additionally, Table 3 shows the correlations of these 3 mental health outcomes with parental and child characteristics.
Correlation analyses indicated signi cantly positive correlations between parental stress, anxiety and depression symptoms (Figures 1 to 3).Table 3 shows that parental stress, anxiety and depression symptoms were negatively correlated with the parent's own health perception (P < 0.01), and positively correlated with the child's medical comorbidities (P < 0.01).Also, parental stress was positively correlated with child's absence from school (P < 0.05).

Discussion
The primary objective of this study was to compare the levels of stress, anxiety and depression symptoms between parents of children with chronic kidney disease (CKD) and parents of healthy children.Additionally, we aimed to investigate the associations of various parental and child variables with these mental health outcomes.Furthermore, we sought to identify predictors of parental stress, anxiety and depression symptoms.
First, we showed that parents of children with CKD reported higher levels of stress and anxiety symptoms.These ndings are consistent with earlier research reporting more stress and anxiety symptoms in parents of CKD patients when compared with parents of healthy children [33][34][35][36]24].Also studies with caregivers of children diagnosed with other chronic illnesses reported higher levels of parental stress [6, 13,14], anxiety or depression [15,16].Even after kidney transplantation, which may lead to a substantial improvement in the child's health condition, parents still report more psychological distress compared with parents of non-transplants or healthy controls [37,38,20].As possible explanations, however not questioned in this study, other studies often refer to the high responsibility for the child's health, the enduring insecurity about the child's future [37], fear for kidney loss [39], and the challenging transition to adulthood [40,21].Tong et al also refer to the traumatizing effect on parents of watching their child undergo invasive medical procedures [41].
Second, we found the presence of medical comorbidities in the child being associated with more parental stress, anxiety and depression symptoms.Also a more negative perception of the own health was associated with higher levels of parental stress, anxiety and depression symptoms, and 47% of our parents perceived a deterioration of their own health since the CKD diagnosis of their child.It can be considered as a limitation that this study only used a subjective health measurement, as parents rated their own health since their child's diagnosis in terms of equal, better or worse.Also, it is possible that parent's perception of health deterioration might be predicted by parental stress, anxiety or depression symptoms, rather than otherwise.Nevertheless, these study ndings can already shed some light on the possible physical impact of caring for a child with CKD, even in an early stage, as CKD stage was not found to be a signi cant predictor for parental stress, anxiety or depression in our study.To our knowledge, the impact of a child's illness on the parents' physical health had not been examined in a CKD population before, although more research exists in other chronic diseases.For instance, a large study involving patients with cerebral palsy found that caregivers experienced lower levels of psychological and physical health when the child exhibited more behavioral problems.Conversely, less caregiving demands were associated with better physical and psychological well-being among caregivers [42].Also, two metaanalyses reported greater levels of parental stress [18] and poorer physical health among parents of children with developmental disabilities (e.g., autism spectrum disorder, Down syndrome, vision/hearing loss, or epilepsy) and chronic health conditions (such as growth de ciencies, asthma, feedings problems, congenital heart diseases) [18,43].
Concerning the professional impact, 40% of the parents reduced work on a structural basis to care for their child with CKD.In addition to the structural work reduction, parents had taken a median of 4 days off from work in the last 6 months.However, 20% of parents reported more than 15 days of work leave, and even up to 90 days, in these past 6 months, showing that some parents reported a much larger professional impact than others.This nding is consistent with Grootenhuis et al who reported that parents taking care of a chronically ill child have greater di culties with employment in general [17].In another study using focus-group methodology, parents of chronically ill children expressed their struggles with balancing between work, life and caring for their child, next to other issues like transport, nancial management, and the child's school [33].Speci cally in a CKD population, frequent and sometimes long distance clinic visits, dialysis treatments, and medical and non-medical expenses result in a great burden for parents with lost time, income from work and nancial stress [44].According to Tsai et al [45], caregivers of children on peritoneal dialysis were less likely to hold a full-time job and had lower average earnings.They also revealed that these caregivers were found to have threefold higher likelihood of experiencing symptoms of depression compared with caregivers of healthy children [45].Future research should further explore these additional social and nancial variables, as this nancial stress may contribute to the worse mental health outcomes in these parents [24,37,44].
As a limitation it can be addressed that our study group of parents of children with CKD consisted of mainly mothers being married or living together with a partner.Future research should aim to explore larger and more representative sample sizes that include both mothers and fathers in various marital states, as the levels of stress, anxiety and depression might be lower in fathers compared with mothers based on earlier studies with parents of children with a chronic illness or developmental disorders [18,46,15].Furthermore, considering the possibility of higher stress and anxiety/depression levels in single parent families, particularly in single mothers, could provide valuable insights [17,47].Also, the majority of parents were born in Belgium and we excluded parents with an insu cient knowledge of Dutch, whereas more inclusion of non-native speaking parents (e.g.refugees and migrants) could result in even worse mental health outcomes due to additional burden [48,18].Finally, compared with the control group, in the CKD group less parents completed higher education, which may have in uenced our worse mental health outcomes in this parent group.Evidence for this hypothesis can be found in earlier studies reporting a negative impact of lower socioeconomic status on the physical and psychological health in parents of children with chronic conditions or developmental disabilities [43,18].
Despite the limitations of the study, this research has several strengths.This study is -to our knowledgethe rst to compare both parental stress, anxiety and depression symptoms in parents of CKD patients with a matched control group of parents of healthy children.Also, no earlier research explored the association of these mental outcomes with variables such as parent's own health perception and professional background, or child's medical and developmental comorbidities.
In conclusion, this study has provided valuable insights into the mental health and professional burden experienced by parents of children with CKD.Our ndings revealed that these parents face higher levels of parental stress and anxiety symptoms compared with parents of healthy children.These outcomes were primarily associated with the child's medical comorbidities and the parents' negative perception of their own health, and secondly with the child's absence from school.In addition to addressing the psychological and physical health of parents, this study also shed light on the professional challenges they face.Therefore, it is crucial to incorporate psychosocial interventions as an integral part of the comprehensive care provided to these families.By doing so, we can potentially reduce parental stress and improve the overall health outcomes for both parents and their children.CKD: chronic kidney disease; N: number; ρ: Spearman's correlation coe cient; P: p-value.

Figures
Figures

Table 3 .
Spearman correlations between parental stress, anxiety and depression symptoms, and clinical and sociodemographic variables in parents of children with CKD (N=45) * p< 0.05; ** p< 0.01; *** p< 0.001.Statistically signi cant p-values are highlighted in bold.a According to the Parenting Stress Index -Short Form; b According to the Hospital Anxiety and Depression Scale.CKD: chronic kidney disease; N: number; Perception own health: parent's perception of own health since child's CKD diagnosis; Work leave: days of work leave in addition to structural work reduction past 6 months due to child's health problems; Med.comorb.child: Medical comorbidities in child (number); Developm.Dis child: developmental disorders in child (number); School absence: School absence past 6 months (days).

Table 4 .
Standardized regression coe cients for parental stress and symptoms of anxiety and depression predicted by clinical and sociodemographic variables of parents and children with CKD p< 0.05; ** p< 0.01; *** p< 0.001.Statistically signi cant p-values are highlighted in bold.According to the Parenting Stress Index -Short Form; b According to the Hospital Anxiety and Depression Scale.