Determinants and Consequences of Parental Uncertainty in Childhood Cancer: A Systematic Review

Abstract

Purpose

Although illness uncertainty has been widely studied in adults, little is known about this issue in childhood cancer, particularly from parents’ perspectives. Unaddressed parental perception of illness uncertainty (parental uncertainty) may undermine both parental well-being and children’s treatment outcomes. This systematic review aims to synthesize existing evidence on the determinants and consequences of parental uncertainty in childhood cancer.

Methods

Following PRISMA guidelines, six databases (Scopus, SAGE, Taylor & Francis, MEDLINE Ultimate, PubMed, and ScienceDirect) were systematically searched. Eligible studies were appraised using the Mixed-Methods Appraisal Tool (MMAT), and data were narratively synthesized.

Results

From 979 initially identified records, 14 studies met the inclusion criteria. Parental uncertainty was found to be influenced by both risk and protective factors. Risk factors include older parental age, lower educational attainment, lower income, maternal unemployment, barriers to healthcare access, shorter time since diagnosis, and higher treatment intensity. Protective factors include active coping skills, parental education support, communication support from healthcare providers, and positive parent-child communication. Parental uncertainty was consistently associated with adverse psychological outcomes, such as anxiety, depression, rumination, post-traumatic stress symptoms (PTSS), parenting stress, and dysfunctional problem-solving, while reducing positive outcomes such as resilience, mastery, constructive coping, and health-related quality of life (HRQoL).

Conclusion

Parental uncertainty in childhood cancer is driven by multiple factors and linked to significant psychological burdens, with PTSS as the most prominent consequence. Early interventions targeting parental mental health soon after diagnosis are essential to reduce long-term risks, including PTSD.

Introduction

Childhood cancer is a global health concern with a significant increase in prevalence worldwide. Each year, approximately 400,000 children aged 0–19 receive a cancer diagnosis, with nearly 90% of cases occurring in low- and middle-income countries (LMICs).¹ In 2019, 291,319 new cancer cases were reported, increasing the global prevalence to 1,806,630 cases.² This rising incidence highlights not only the medical challenges but also the profound impact on the family system, particularly the parents who bear the primary responsibility for their child’s well-being.³

Throughout their child’s cancer trajectory, parents encounter a range of ambiguous and unpredictable situations. These include unclear information about the diagnosis and illness severity, complexity of the treatment and medical system, and unpredictability regarding future symptoms and treatment outcomes. This state of uncertainty, termed “illness uncertainty”, profoundly impacts their emotional well-being and coping mechanisms.^4–6

One significant challenge in the context of illness uncertainty is the difficulty parents face in recognizing early symptoms. For instance, symptoms such as pale lips may be overlooked or considered as insignificant, especially if the child has a prior history of good health.³ As symptoms worsen, parents become increasingly concerned and seek medical intervention. This uncertainty becomes even more pronounced during the diagnostic and treatment phases, where parents may be aware of the seriousness of their child’s condition but remain unclear about the illness severity.³ The experience of navigating invasive treatments, managing side effects, and addressing complications exacerbates their feelings of doubt and guilt. Furthermore, concerns regarding potential long-term side effects, potential treatment refusal by the child, and the overall efficacy of therapeutic interventions further contribute to sustained uncertainty.⁷

Post-treatment, parents face new uncertainties as they transition from hospital care to managing their child’s health at home, often without the continuous support of medical staff. This transition heightened fears of the unknown, including persistent concerns regarding the monitoring of their child’s condition and the potential for cancer recurrence.⁸ Regular check-ups, while necessary, continue to be a source of anxiety, as parents remain vigilant about the potential for cancer recurrence.^3,8

Illness uncertainty perceived by parents (parental uncertainty) occurs when parents are unable to determine the meaning of illness-related events.^4–6 This concept is vital in both clinical and empirical literature, as it profoundly influences how families cope with serious illnesses, including childhood cancer.⁹ Illness uncertainty is particularly pervasive in the context of pediatric cancer, where it can affect families from the initial diagnosis through various stages of treatment and remission. The uncertainty often endures throughout the illness trajectory and can resurface with cancer recurrence.^9,10

Parental uncertainty plays a crucial role in shaping how parents assess a child’s illness and affect both their psychosocial adaptation and that of their child.^4,6,11 Several studies indicate that parental uncertainty is associated with poorer psychological adjustment, particularly psychological distress.^12–15 Additionally, heightened parental uncertainty is associated with lower perceptions of their child’s quality of life,¹⁰ and increased depressive symptoms in the child, mediated by the child’s own perception of illness uncertainty.¹⁶ Moreover, parental uncertainty can complicate medical decision-making processes, often leading to increased anxiety and stress. This, in turn, interferes with effectively processing information from healthcare providers and making informed decisions about the child’s cancer care.^6,17

Existing studies have identified several antecedents and outcomes related to illness uncertainty, including sociodemographic variables (eg, age, gender, place of residence, and family income), stimuli frame (eg, severity of illness symptoms, family history of cancer, and disease phase), structure provider (eg, education level and social support), coping strategies (eg, problem-focused, active emotional, and avoidant emotional), and adaptation outcomes (eg, quality of life, anxiety, and depression).^12,18,19 Some research has specifically examined the relationship between illness uncertainty and social support in cancer patients,¹⁹ or focused on uncertainty in advanced-stage cancer patients undergoing therapy.¹⁸ However, illness uncertainty can persist throughout the entire trajectory of a child’s cancer.^9,10 Thus, it is essential to comprehensively understand the determinants and consequences of illness uncertainty across all phases of the cancer in children. Different phases-diagnosis, active treatment, remission, and potential relapse present unique challenges and uncertainties for parents.⁴

Given the adverse effects of parental uncertainty on the treatment success of childhood cancer, managing this uncertainty is a critical need for parents.^20–22 While some systematic reviews have examined factors related to parental uncertainty in cancer,¹² these studies mainly focus on adult cancer survivors and their caregivers. However, for parents of children with cancer, maintaining optimal psychological health is crucial. Despite the growing body of research on parental uncertainty over the past decade, no study has yet systematically synthesized these findings in the context of childhood cancer. Given the increasing prevalence of childhood cancer, developing interventions to improve treatment outcomes is crucial, with parental uncertainty being a key factor. Therefore, it is important to map the determinants and consequences of parental uncertainty to inform these interventions. To the best of our knowledge, no recent systematic review has explored the determinants and consequences of illness uncertainty in the context of childhood cancer, particularly from the perspective of parents as primary caregivers. Although children and adults experience similar stages in the cancer trajectory, the developmental characteristics of children and their unique needs for assistance significantly differ from those of adults. Therefore, the present study aims to synthesize existing evidence on the determinants and consequences of parental uncertainty among parents of children diagnosed with cancer, covering all phases of childhood cancer.

Materials and Methods

We conducted a systematic review to identify articles examining factors related to illness uncertainty in parents of children with cancer, following a 24-step guide for designing and conducting a systematic review and meta-analysis in medical research.²³ We planned the scope, specified research questions, developed a search strategy, extracted data, assessed research quality, synthesized findings, and generated conclusions and implications. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines were applied to ensure accurate execution and reporting of this review’s findings.²⁴ To support open science and enhance trustworthiness, the research protocol was registered in the PROSPERO (ID: CRD42024566016).

Eligibility Criteria

At the beginning of our systematic review, we formulated a protocol based on population, interventions, comparator, outcomes, and study design (PICOS) framework. The inclusion and exclusion criteria were specified prior to beginning the search. These criteria were related to the types of studies, participants, and outcomes. Studies had to meet the following inclusion criteria: (a) involved parents of children diagnosed with cancer (≤18 years at diagnosis) as participants; (b) used quantitative measures of uncertainty; and (c) were published in a peer-reviewed journal in English (not limited by country) between January 1, 2014, and April 16, 2024, to capture the most recent advancements in understanding parental uncertainty.

Studies that did not address at least one of the objectives of the review were excluded. Articles were excluded if the study focus was specific to three key areas: “diagnostic uncertainty”, primarily concerned with a clinician’s subjective perceptions;²⁵ “intolerance of uncertainty”, which examines an individual’s negative beliefs about uncertainty;²⁶ and “tolerance of uncertainty”, which explores an individual’s psychological responses to uncertainty.²⁷ Articles that comprised parents who had children with illnesses other than cancer were also removed. Additionally, research on uncertainty was excluded if it did not provide data specific to illness uncertainty. We further excluded unpublished study results, editorials, commentaries, conference proceedings, review articles, research protocols, brief reports, and case reports.

Search Strategy

We conducted a systematic search of peer-reviewed research concerning the determinants and consequences of illness uncertainty in parents of children with cancer, published between January 1, 2014, and April 16, 2024, in the databases Scopus, SAGE, Taylor & Francis, MEDLINE Ultimate, PubMed, and ScienceDirect. For each database, we developed four search blocks using MeSH terms and thesaurus terms related to “parents”, “illness uncertainty”, “children”, and “cancer” (see Table S1). All searches were conducted using the databases’ default settings, with additional filters applied to meet the inclusion criteria and reduce irrelevant results: publication year (2014–2024), research articles, and English language. An additional filter for child age (0–18 years) was applied on the MEDLINE Ultimate database, while only the Behavioral Sciences subject category was selected on the Taylor & Francis database.

Study Selection and Data Extraction

All references identified through the database searches were imported into a Mendeley library, where duplicates were removed using Mendeley’s automatic function. The references were then converted into an Excel file and formatted as a template for the selection process. In the first stage, one reviewer (CT) independently conducted screening based on titles and abstracts that were potentially relevant according to the inclusion and exclusion criteria. This initial screening was validated by two other reviewers (AI, FA), who cross-checked the article to ensure consistency and minimize bias in the selection process. Subsequently, two reviewers (CT, AI) performed full-text screening, with both also conducting the quality assessment. One reviewer (CT) then created a template in Excel for data extraction, which was used to systematically record relevant data from the articles that were included in the review. Full-text articles that met inclusion criteria were then extracted into an Excel table by primary author (CT) and validated by another reviewer (AI) to ensure that the information was accurately recorded and consistent with the original articles. The data extracted included descriptive characteristics of the study, such as author, year, country of data collection, title, study design, participants details (sample size of fathers and mothers), information about childhood cancer patients/survivors (sample size, diagnosis, cancer stage). The extracted data were also categorized to identify determinants and consequences related to parental uncertainty. All reported associations between these determinants and consequences were considered. Any disagreements in the full-text screening and data extraction stages were discussed with a third reviewer (FA) to resolve.

Quality Assessment

Given the methodological heterogeneity of the studies included in this review, a quality assessment was conducted using the Mixed Methods Appraisal Tool (MMAT) Version 2018 guidelines, which evaluated methodological and reporting quality.²⁸ While there were five main design categories, each consisting of two screening questions and five methodological quality criteria, this study involved only three design categories: quantitative randomized controlled trials, quantitative non-randomized studies (eg, non-randomized controlled trials, cohort study and cross-sectional analytic study), and quantitative descriptive studies. In the first step, reviewers answered two screening questions to ensure the included studies were empirical. Each study was then assessed according to its design category, with reviewers selecting “Yes”, “No”, or “Can’t Tell” for each criterion. A higher number of criteria met indicated better study quality and more robust reporting, as per MMAT guidelines. Two authors (CT and AI) independently rated each study, resolving any disagreements through discussion. A third reviewer was consulted if needed.

Data Synthesis

The data synthesis for this systematic review followed a narrative synthesis approach based on the guidance on the conduct of narrative synthesis in systematic reviews.²⁹ Initially, a detailed description of the included studies was developed, followed by the identification of key themes and patterns. Next, heterogeneity was explored, and a coherent narrative was constructed to integrate the findings, ensuring transparency and minimizing bias. The synthesized data on the determinants and consequences of parental uncertainty were further summarized and visually represented in a figure to enhance clarity and understanding.

Results

Search Results and Study Quality

The search identified 979 articles from 6 databases. After exporting to Mendeley, 190 duplicates were removed. The remaining articles were converted to Excel, and title and abstract screening was conducted on 789 articles. Of these, 30 were considered potentially relevant for full-text screening; however, one could not be retrieved, and 15 did not meet the inclusion criteria. Ultimately, 14 articles were eligible for inclusion. The article selection process is presented in the PRISMA flow diagram (Figure 1).

Figure 1.

PRISMA Flow Diagram of the Study Selection Process.

Based on the MMAT quality assessment results, the studies included in this review demonstrated variations in methodological design categories. As noted by Hong et al²⁸ the results of the MMAT can be reported using descriptors such as stars (*) or percentage (%): 1* or 20% of quality criteria met, up to 5***** or 100% of quality criteria met, based on the five methodological quality criteria. Following the quality appraisal process, all studies were included in this review regardless of their quality, in line with MMAT’s recommendation against excluding studies, even if they exhibit lower methodological quality. Overall, more than 50% of the studies included in this review meet 100% of the MMAT quality criteria, indicating high methodological quality (see Table S2a–S2c).

Study Characteristics

Most of the included studies employed quantitative methods with cross-sectional design (n = 10). Ten studies were conducted in high-income countries and four were from upper-middle-income countries. Participants were mainly parents, although two studies included other primary caregivers (eg, foster parents, grandparents) whose role was similar to that of parents. Hence, the term “parents” will be used to refer to this group. Of the thirteen studies that included both mothers and fathers, most had a greater number of mothers, while only one study exclusively included mothers. Sample size varied, ranging from 13 participants to 315 participants.^30,31 Leukemia was the most common childhood cancer diagnosis. The majority of studies focused on parental uncertainty during the diagnosis and active treatment period (n = 7). Five studies addressed multiple stages along the cancer continuum (diagnosis, treatment, and/or survivorship), one study focused exclusively on survivorship, and one study included palliative/end-of-life stage.

Regarding the instruments employed, four distinct measures were utilized to evaluate parental illness uncertainty. Parent’s Perception of Uncertainty in Illness Scale (PPUS) was the most commonly used (n = 10), followed by the Parent Experience of Child Illness (PECI) in two studies, Situation-Specific Emotional Reaction Questionnaire (S-SERQ) in one study, and Decisional Conflict Scale (DCS) in one study. Detailed characteristics for each included study are presented in Table 1.

Table 1.

Characteristics of Studies Included

No.	Author, Year, Country	Title	Methods	Uncertainty Measure	Participants	Children Age (Mean (SD), Range)	Childhood Cancer Diagnoses	Childhood Cancer Stage	Determinant(s)	Consequence(s)
1.	Basile et al, 2021, USA (High-income)32	Relationship between caregiver uncertainty, problem-solving, and psychological adjustment in pediatric cancer	Quantitative (cross- sectional)	PPUS	Mothers (n=209) Fathers (n=25) Other (n=4)	7.63 (5.53), 0−19 years old	Leukemia (n=101) Solid tumor (n=69) Brain tumor (n=36) Lymphoma (n=32)	Newly diagnosed	NA	Dysfunctional problem-solving (r =0.44) Constructive problem-solving (r = −0.27) Anxiety (r =0.44) Depression (r =0.46) PTSS (r =0.45)
2.	Eche et al, 2019, USA (High-income)10	Parental uncertainty: Parents’ perceptions of health-related quality of life in newly diagnosed children with cancer	Quantitative (Longitudinal descriptive)	PPUS	Mothers (n=48) Fathers (n=7)	6.85, (4.23), 2−17 years old	Acute lymphoblastic leukemia (n=29) Acute myeloid leukemia (n=4) Burkitt lymphoma (n=4) Acute promyelocytic leukemia (n=1)	Newly diagnosed	NA	Parent proxy HRQoL 3 months following diagnosis (T0: r = −0.26; T1: r = −0.27)
3.	He et al, 2016, China (Upper-middle-income)33	Uncertainty and personal growth through positive coping strategies among Chinese parents of children with acute leukemia	Quantitative (cross- sectional)	PPUS	Mothers (n=62) Fathers (n=33)	6.0 (3.8), 0.1−14 years old	Acute lymphocytic leukemia (n=78) Acute myeloid leukemia (n=17)	Multiple stages (treatment, remission, and recurrence)	Month(s) since diagnosis of the child’s illness Parents’ age Parents’ educational level	Parents’ positive coping strategies (r = −0.225)
4.	Hendricks-Ferguson et al, 2017, USA (High-income)31	Pilot evaluation of a palliative and end- of-life communication intervention for parents of children with a brain tumor	Quantitative (Longitudinal single-group pilot study)	PECI	Mothers (n=11) Fathers (n=2)	(Not reported), 0.4−14.5 years old	Brain tumor (n=11)	Palliative/ End-of-life	Communication support	NA
5.	Joosten et al, 2024, Netherlands (High-income)34	Efficacy of Op Koers Online, an online group intervention for parents of children with cancer: Results of a randomized controlled trial	Quantitative (RCT)	SSERQ	Intervention group:Mothers (n=40) Fathers (n=3) Control group: Mothers (n=37) Fathers (n=9)	Intervention group: 10.5 (5.8), 0−12+ years old Control group: 9.7 (5.5), 0−12+ years old	Hematology (n=18) Solid tumors (n=13) Neuro (n=12)	Multiple stages (treatment and survivorship)	Coping skill relaxation (T2: β = −0.32)	NA
6.	Liu et al, 2023, China (Upper-middle-income)30	Decisional conflict, caregiver mastery, and depression among Chinese parental caregivers of children with leukemia	Quantitative (cross- sectional)	DCS	Mother (n=200) Father (n=125)	(Not reported), ≤18 years old	Leukemia (n=325)	Multiple stages (diagnosed, treatment, and survivorship)	NA	Depressive symptoms (r =0.158) Mastery (r = −0.174)
7.	Mullins et al, 2016, USA (High-income)35	Parent illness appraisals, parent adjustment, and parent-reported child quality of life in pediatric cancer	Quantitative (cross- sectional)	PPUS	Mother (n=106) Father (n=22) Custodial caregiver (n=7) Missing (n=3)	1−18 years old	Leukemia/ lymphoma (n=57) Non-CNS solid tumors (n=37) Brain tumors (n=19) Other cancers (n=25)	Treatment	NA	Parent general distress (β =0.38) Parenting stress (β =0.42) PTSS (β =0.35) Parent proxy HRQoL (β = −0.29)
8.	Nakajima-Yamaguchi et al, 2016, Japan (High-income)36	Parental post-traumatic stress symptoms as predictors of psychosocial problems in children treated for cancer	Quantitative (cross- sectional)	PPUS	Mothers (n=33) Fathers (n=1)	10.5 (3.9), 4−17 years old	Acute leukemia (n=19) Lymphoma (n=6) Brain tumor (n=4) Other solid tumor (n=5)	Treatment	Children’s age at diagnosis (r = −0.356) Intensity of treatment (r =0.600) Parent-child communication about the disease (r = −0.397)	PTSS (r =0.286)
9.	Okada et al, 2023, Japan (High-income)37	Factors associated with employment status among mothers of survivors of childhood cancer: a cross‐sectional study	Quantitative (cross- sectional)	PECI	Mothers (n=171)	(Not reported), 8−17 years old	Leukemia (n=94) Neuroblastoma (n=19) Lymphoma (n=14) Brain tumor (n=10)	Survivorship	Employment status	NA
10.	Perez et al, 2018, USA (High-income)13	Post traumatic stress symptoms in parents of children with cancer: A mediation model	Quantitative (cross- sectional)	PPUS	Mothers (n=48) Fathers (n=8) Other (n=3)	9.69 (5.14), 2−18 years old	Leukemia (n=20) Lymphoma (n=14) Solid tumors (n=21)	Diagnosed	NA	Rumination (r =0.372) PTSS (r =0.379)
11.	Perez et al, 2020, USA (High-income)14	Barriers to care in pediatric cancer: The role of illness uncertainty in relation to parent psychological distress	Quantitative (cross- sectional)	PPUS	Mothers (n=123) Fathers (n=19) Other (n=3)	9.24 (5.21), 2−18 years old	Leukemia/ lymphoma (n=80) Solid tumors (n=39) Brain tumors (n=12)	Multiple stages (Newly diagnosed and treatment)	Barriers to care (r ‐.32) Annual income (r = ‐.23)	Anxiety (r =0.32) Depression (r =0.39) PTSS (r =0.45)
12.	Tackett et al, 2016, USA (High-income)15	Illness uncertainty, global psychological distress, and posttraumatic stress in pediatric cancer: A preliminary examination using a path analysis approach	Quantitative (cross- sectional)	PPUS	Mothers (n=96) Fathers (n=9)	8.6 (5.0), 2−18 years old	Solid tumors (n=44) Lymphoma (n=15) Leukemia (n=46)	Newly diagnosed	NA	Global psychological distress (r =0.414) PTSS (r =0.332)
13.	Wang et al, 2018, China (Upper-middle-income)38	mHealth supportive care intervention for parents of children with acute lymphoblastic leukemia: Quasi-experimental pre- and postdesign study	Quantitative (Quasi- Experimental Pre- and Postdesign)	PPUS	Intervention group:Mothers (n=33) Fathers (n=16) Control group: Mothers (n=33) Fathers (n=10)	Intervention group: 5.74 (3.98), <1−18 years old Control group: 6.73 (4.44), <1−18 years old	Acute lymphoblastic leukemia (n=92)	Diagnosed	Parent education support	NA
14.	Ye et al, 2015, China (Upper-middle-income)39	Resilience and psychosocial function among mainland Chinese parents of children with cancer: A cross-sectional survey	Quantitative (cross- sectional)	PPUS	Mother (n=74) Father (n=37)	6.85 (4.37), (Not reported)	Leukemia (n=12) Lymphoma (n=34) CNS tumor (n=14) Soft tissue sarcoma (n=4) Rhabdomyosarcoma (n=12) Renal tumor (n=6) Hepatic tumor (n=5) Skeletal tumor (n=10) Medulloblastoma (n=5) Germinoma (n=5) Other/unspecified (n=4)	Multiple stages (diagnosed and treatment)	NA	Resilience (r = −0.357)

Abbreviations: PTSS, Posttraumatic Stress Symptomatology; HRQoL, health-related quality of life; CNS, central nervous system; PPUS, Parent’s Perception of Uncertainty in Illness Scale; SSERQ, Situation-Specific Emotional Reaction Questionnaire; DCS, Decisional Conflict Scale; PECI, Parent Experience of Child Illness.

Determinants and Consequences of Parental Uncertainty

Seven studies identified potential determinants of parental uncertainty, while ten studies explored potential consequences. Together, these factors and consequences of parental uncertainty are depicted in a model that organizes the primary findings of this review (see Figure 2).

Figure 2.

Diagram Depicting the Determinants and Consequences of Parental Uncertainty in This Review, Including the Number of Studies Investigating Each Variable.

Note: Labels (±) indicate the direction of the relationships between the variables. The sign (+) indicates a positive correlation, while the sign (-) indicates a negative correlation with parental uncertainty.

Abbreviations: PPUS, parent’s perception of uncertainty in illness scale; SSERQ, situation-specific emotional reaction questionnaire; PECI, parent experience of child illness; DCS, decisional conflict scale; HRQoL, health-related quality of life.

Determinants

Sociodemographic, psychological, psychosocial, and cancer-related factors were identified as determinants of parental uncertainty.

Sociodemographic Factor

Two studies found that income and the child’s age at diagnosis were associated with parental uncertainty. One study explored age and educational level differences in parents, finding that older parents and those with only a high school education reported more uncertainty than younger parents and those with higher education.³³ Annual household income was negatively correlated with parental uncertainty.¹⁴ Parents of younger children at diagnosis reported higher levels of long-term uncertainty.³⁶ Another study investigated mothers’ employment status, finding that working mothers experienced lower long-term uncertainty compared to nonworking mothers.³⁷

Psychological Factor

One randomized control trial analyzed the potential psychological factor that had a beneficial effect on parental uncertainty. The Op Koers Online intervention, which teaches active coping skills based on cognitive behavioral therapy (CBT) and acceptance and commitment therapy (ACT) principles, significantly reduced uncertainty at the 6-month follow-up.³⁴

Psychosocial Factor

Three studies included potential psychosocial factors influencing parental uncertainty, such as barriers to care, parent-child communication about the disease, parent educational support, and communication support. Greater barriers to care were associated with higher level of parental uncertainty.¹⁴ During the treatment phase, parents who informed their children about the cancer had lower long-term uncertainty.³⁶ Providing parents with knowledge about cancer, treatment, and care had a beneficial effect in decreasing parental uncertainty over a 3-month observation period.³⁸ Longitudinal single-group pilot study found that during palliative or end-of-life care, communication support from healthcare providers reduced parents’ long-term uncertainty.³¹

Cancer-Related Factor

Two studies examined the association between cancer-specific factors and parental uncertainty. One study found that during the treatment phase, the treatment intensity was positively associated with parental uncertainty.³⁶ Another study examined the differences between time since diagnosis. Parents whose children had been diagnosed with cancer for 1–3 months experienced higher uncertainty compared to those whose children were diagnosed later.³³

Consequences

Ten studies focused on the consequences of parental uncertainty, including only one longitudinal study.¹⁰ The consequences included psychological and health-related outcomes.

Psychological Consequence

Seven studies examined the psychological consequences of parental uncertainty in parents, including anxiety, depression, posttraumatic stress symptoms (PTSS), global/general distress, parenting stress, rumination, resilience, mastery, coping, and problem-solving. PTSS was the most commonly reported outcome. Six studies indicated a positive correlation between parental uncertainty and PTSS in parents of newly diagnosed children and throughout the treatment phase.^{13–15,32,35,36} Three studies found that increased levels of parental uncertainty led to heightened anxiety in parents of newly diagnosed children as well as during the treatment phase.^14,32 Similarly, three studies found that increased levels of parental uncertainty were linked to higher depression during the newly diagnosed phase,³² and persisted throughout the treatment and survivorship phases.^14,30 Other psychological consequences include a positive association between parental uncertainty and rumination,¹³ and negative association with resilience,³⁹ and mastery.³⁰ Parental uncertainty was also negatively associated with parent’s positive coping strategies.³³ Additionally, one study found that parental uncertainty was positively associated with dysfunctional problem-solving and negatively associated with constructive problem-solving.³²

Health-Related Consequence

Two studies investigated the health-related consequences of parental uncertainty, specifically health-related quality of life/HRQoL. One study found that higher levels of parental uncertainty were associated with poorer child cancer-specific HRQoL three months after diagnosis.¹⁰ During the treatment phase, another study found that parental uncertainty was negatively associated with parent-reported general and cancer-specific HRQoL in children.³⁵

Discussion

This systematic review aimed to identify determinants and consequences of parental uncertainty in the context of childhood cancer—an area with limited comprehensive synthesis to date. Across 14 studies, we identified sociodemographic, psychological, psychosocial, and cancer-related factors as key determinants, and categorized consequences into psychological and health-related outcomes.

Determinants of Parental Uncertainty

Parental uncertainty was influenced by both the sociodemographic factors of the parents and those of the child. The parental sociodemographic risk factors associated with increased parental uncertainty included older parental age and lower educational attainment,³³ low annual household income,¹⁴ and maternal unemployment.³⁷ Education can help provide structure to events within a stimulus framework by enhancing individuals’ knowledge base, which can be used to associate these events, thereby providing clearer meaning and context.⁶ Consequently, parents with lower education levels may take longer to interpret events due to limited knowledge and low health literacy, leading to prolonged uncertainty compared to more educated individuals.^6,40 This prolonged uncertainty likely stems from the greater cognitive effort needed to manage complex care, compounded by unfamiliarity with medical terms and healthcare practices.

Caring for a child with cancer demands significant time and energy, with the added stress of potential relapse or death. Older parents may feel heightened distress due to fewer opportunities to have additional children.³³ Parents of children with cancer, as noted in the study by He et al mostly have one child due to the one-family-one-child policy in China.³³ In collectivist, high-fertility societies like China, children are highly valued as symbols of hope, sources of future support, and contributors to family social status.^41,42 A cancer diagnosis, seen as life-threatening, triggers emotional distress and fear of losing an only child. Consequently, reproductive stress and potential loss can intensify feelings of uncertainty.^3,43

Low annual household income exacerbates the financial strain which further adds to psychological burden.^44,45 Parents of children with cancer often experience a reduction in household income due to the need to take leave, reduce work hours, or even quit their jobs to care for their children.^3,46 Most parents in prior studies reported that pediatric cancer increased financial strain and worsened psychological symptoms, especially distress, anxiety, and sleep disturbances.^45,47 The study also found that lower-income parents experienced more severe symptoms than those with higher incomes. Financial strain depletes mental resources, impairing information processing, decision-making, and future confidence—factors that heighten illness uncertainty.^6,17,48

Maternal unemployment, combined with lower education, has been identified as a sociodemographic risk factor for adverse psychological outcomes in parents coping with a child’s cancer.¹⁷ Unemployed mothers might have faced higher distress and lacked a sense of mastery due to isolation and fewer social interactions, reducing their ability to manage uncertainty.^45,49,50

The child’s age at diagnosis significantly influenced parental uncertainty, with younger age identified as the key child-related factor linked to heightened uncertainty.³⁶ Younger children were more dependent and vulnerable to their parents, which heightened parental uncertainty.^3,36 This may be because younger children cannot provide input to help parents understand the illness, make treatment decisions, or assess treatment responses.⁹ Treating younger children is complex, requiring intensive care and monitoring. As a result, parents face greater difficulty making treatment decisions due to uncertainty about effectiveness and long-term side effects.^3,9,51 Younger children also often have limitations in communicating their symptoms and needs due to their cognitive development.⁵² Younger children often report more physical than psychological symptoms, prompting many studies to rely on parent proxy reports to capture their overall symptom experience. However, discrepancies frequently arise between children’s self-reports and parent proxies.

Contrary to previous findings, some studies indicated that older children reported higher levels of uncertainty, which was directly linked to parental uncertainty.⁵³ However, the positive correlation between age and uncertainty requires careful interpretation. Although greater cognitive complexity with age may aid in interpreting illness-related stimuli, Mishel emphasized that the sufficiency—not merely the complexity—of the cognitive schema is what reduces uncertainty.^4,6 Uncertainty arises when the illness schema is insufficient to interpret illness-related events. Thus, a more complex cognitive schema in older children does not necessarily reduce uncertainty. In fact, younger children’s simpler schemas may be more resilient to unstructured experiences, while older children may perceive illness-related ambiguity as more threatening to their expectations of understanding and interpreting symptoms. Additionally, the family environment shapes children’s cognitive development and symptom vocabulary, influencing their ability to report their condition.⁵² These contrasting findings highlight the importance of considering developmental factors, such as age, in understanding illness uncertainty. There is also a need for self-report measures tailored to younger children to assess cognitive development and illness-specific knowledge, allowing clearer distinctions in maturity levels. Additionally, research should explore how different experiences trigger uncertainty across developmental stages and how this relationship evolves with age.

Psychological factors, such as active coping skills can serve as protective factors of parental uncertainty.³⁴ This review found that online group interventions effectively improved relaxation coping skills at T1 (6-week follow-up) and T2 (6-month follow-up) and reduced uncertainty at T2. Previous systematic reviews also showed that uncertainty management interventions teaching coping skills positively influenced uncertainty outcomes in cancer patients and caregivers. These interventions were most effective when combined with resources such as illness education, cognitive restructuring, trigger identification, emotional expression, and confronting specific fears.⁵⁴ Another systematic review found that coping skills played a protective role against distress for parents during both the treatment and survivorship phases.¹⁷ Coping skills were known to be pre-existing factors that remained stable throughout the cancer trajectories and were crucial for parents’ psychological adjustment.^55,56 A child’s cancer diagnosis and treatment often create a shocking, traumatic experience for parents, heightening psychological arousal and emotional responses. This elevated state can impair their cognitive ability to process illness-related information, contributing to uncertainty. Relaxation coping skills help parents manage stress, enhance their sense of control, and enable them to reinterpret the illness, making the traumatic experience feel more manageable.^54,57

Psychosocial risk and protective factors of parental uncertainty were also identified. Barriers to care were found to be risk factors for developing parental uncertainty.¹⁴ In contrast, parent education, communication support from healthcare providers, and parent-child communication, served as protective factors that could reduce parental uncertainty.^31,36,38 Barriers to care, parent education, and communication support are structural factors that influence parental uncertainty. Structural providers—such as education, social support, and credible authorities—serve as key antecedents. Education, in particular, helps parents understand where and how to access health information, thereby reducing illness uncertainty.^4,6 Previous systematic reviews found that social support, especially informational support from healthcare providers, positively impacted patients and their family caregivers’ uncertainty.^12,54 Social support interventions help manage uncertainty by fostering positive coping strategies, promoting cognitive reappraisal, and improving basic illness knowledge.⁵⁴ According to Mishel,^4,6 credible authorities (ie, healthcare providers) and social support helped prevent uncertainty by providing a meaningful structure related to aspects of physical care, care efficacy, relationships with healthcare providers, expectations about care outcomes, and the performance of the healthcare system.

This review highlights cancer-related factors such as time since diagnosis and treatment intensity, with parental uncertainty being notably higher during the initial phase of the child’s treatment.³³ Previous studies on parents with children with cancer also found that a shorter time since diagnosis correlated with higher parental uncertainty.⁵³ Time since diagnosis reflects changes in treatment patterns and symptoms, shaping how parents interpret illness-related cues. During the first 1–3 months, or the initial treatment phase, parents are often unfamiliar with symptom patterns and lack adequate information to understand the illness. Studies show that many parents initially fail to recognize cancer symptoms or grasp the severity of their child’s diagnosis.³ During the initial phase of their child’s illness, parents also faced many new challenges and confusion regarding the hospital environment and system.⁶ Over time, parents acquire more information about their child’s illness and become familiar with the hospital environment, which helps reduce uncertainty. However, mixed findings from a meta-analysis study by Guan et al found that cancer survivors in the early diagnosis phase had higher levels of uncertainty compared to those under treatment or in the follow-up stage.⁵⁴ Interestingly, some findings showed that survivors diagnosed for one year reported greater uncertainty than newly diagnosed individuals. These variations suggest that different cancer trajectories and stages must be considered to understand the fluctuating intensity of uncertainty.

Parental uncertainty that began during the diagnostic phase often continued into the child’s treatment phase. The intensity of the treatment varied, ranging from level 1 (least intensive treatment) to level 4 (most intensive treatment).⁵⁸ This review found that the more intensive the treatment, the higher the long-term uncertainty experienced by parents.³⁶ The complexity of cancer treatment protocols and the pediatric care system, the lack of information about treatment effectiveness and side effects, and the unpredictability of treatment outcomes contributed to this uncertainty.^4,51 The child’s treatment also disrupted routines, making it challenging for parents to balance intensive care with daily life, including work and family time.⁵⁹ As treatment intensity and complexity increased—resulting in more frequent healthcare visits, procedures, and side effects—the unpredictability of the child’s care trajectory heightened parental uncertainty during and after cancer treatment.^51,60

Consequences of Parental Uncertainty

The most commonly reported psychological effects of parental uncertainty include anxiety, depression, rumination, post-traumatic stress symptoms (PTSS), and parenting stress. In this review, PTSS emerged as the most prevalent form of distress linked to uncertainty.^{13–15,32,35,36} Previous research also found that parental uncertainty was a significant predictor of PTSS in parents of childhood cancer survivors.⁶¹ A similar finding from a meta-analysis revealed a significant association between parental uncertainty and PTSS among caregivers of children with chronic illnesses.⁶²

Parental uncertainty is also associated to other forms of psychological distress, such as anxiety,^14,32 depression,³² rumination,¹³ and parenting stress.³⁵ Similar findings indicated that parental uncertainty was a significant predictor of psychological distress in parents of children with type 1 diabetes.⁶³ Furthermore, uncertainty has been associated with poorer psychological adjustment in lung cancer patients, including increased depression, heightened perceived stress, and reduced emotional well-being.⁶⁴

Parental uncertainty is also related to resilience, mastery, coping, and problem-solving strategies. Elevated levels of parental uncertainty are associated with diminished resilience.³⁹ Parental uncertainty serves as a baseline psychosocial outcome that shapes resilience in the context of pediatric cancer.⁶⁵ A childhood cancer diagnosis often leads to a heightened perception of danger, causing parents to feel a significant loss of control over the situation.^4,6 Consequently, these negative appraisals diminish their perceived ability to cope with stressful and traumatic circumstances, thereby undermining a core component of resilience.⁶⁶

The feeling of losing control over the situation can lead parents to experience a low sense of mastery as caregivers.³⁰ In contrast, higher levels of perceived control and mastery can buffer the negative impact of uncertainty, helping parents manage stress more effectively.⁴⁹ When parents possess a strong sense of mastery, they may view uncertain situations not as dangers but as opportunities they can navigate.⁶ Conversely, a lack of mastery weakens parents’ ability to cope with stress, increasing feelings of helplessness and vulnerability to the psychological strain of uncertainty as they struggle to predict or control outcomes of major health-related decisions for their children.

The level of unpredictability in parental uncertainty also influences coping strategies, with lower unpredictability allowing parents to adopt more positive coping mechanisms.³³ This finding was consistent with Mishel’s Uncertainty in Illness Theory,^4,6 which suggested that illness unpredictability is negatively correlated with effective coping. As unpredictability in parental uncertainty decreases, parents are more likely to adopt positive coping strategies, enabling them to reframe uncertainty as an opportunity rather than a threat—promoting better psychological adjustment and personal growth. Ko and Lee further confirmed that reduced unpredictability facilitates the use of more effective coping strategies, thereby improving quality of life among Korean women with gynecological cancer.⁶⁷ In contrast, higher uncertainty was linked to less effective coping, as it was more often appraised as a threat. When uncertainty was perceived as dangerous, it heightened anxiety and depression, reducing parents’ ability to cope effectively.⁶⁸ Uncertainty-induced stress disrupted daily routines and strained family interactions, further complicating parents’ coping efforts.

This review also found that lower levels of parental uncertainty were associated with the use of constructive problem-solving strategies, while higher uncertainty led to more dysfunctional problem-solving strategies.³² Constructive and dysfunctional problem-solving served as multidimensional coping strategies that managed daily challenges by directing coping efforts toward changing the situation or adjusting one’s cognitions.⁶⁹ Constructive problem-solving involves strategies like positive problem orientation and rational thinking, while dysfunctional problem-solving includes maladaptive approaches such as negative orientation, impulsivity, and avoidance. Interventions that strengthen caregiver problem-solving skills suggest these strategies may mediate caregiver adjustment in the context of pediatric chronic illness.^70,71 However, only dysfunctional problem-solving strategies were associated with increased uncertainty and lower adjustment outcomes, whereas constructive problem-solving strategies were linked to a reduction in uncertainty levels but not to adjustment outcomes.³² In other words, illness uncertainty often prompted the use of dysfunctional rather than constructive problem-solving strategies. Even individuals with strong problem-solving skills found it difficult to apply them under high uncertainty. The cognitive burden of uncertainty increased susceptibility to negative emotions such as anxiety and depression, which impaired rational thinking and led to maladaptive coping strategies.

Regarding health-related consequences of parental uncertainty, one cross-sectional and longitudinal study found an association between parental uncertainty and both the child’s general health-related quality of life (HRQoL) and cancer-specific HRQoL as reported by parents.^10,35 Previous research also found that child uncertainty was a significant predictor of both general child-reported HRQoL as well as child- and parent-reported cancer-specific HRQoL.⁵¹ These findings indicate that uncertainty affects both parents’ and children’s adaptation to cancer, aligning with the social-ecological or contextual approach. This perspective views children within multiple interacting contexts and acknowledges the complex factors influencing their well-being in pediatric healthcare.^55,72 Thus, these findings highlight the need for family-centered support programs to improve the overall adaptation of both parents and children.

However, there were differences in agreement between parent proxy reports and child self-reports of HRQoL: fair agreement at diagnosis but poor agreement at three months following diagnosis.¹⁰ Poor agreement in HRQoL reports was also found in a previous systematic review by Ferraz et al reflecting differences in interpretation or parental evaluation bias regarding their child’s health condition due to the parent’s emotional state.¹⁷ According to the uncertainty in illness theory, emotional states (eg, anxiety and stress) are psychological factors that can impair an individual’s cognitive capacity.^4,6,50 Impaired cognitive capacity can hinder the ability to recognize familiar situations, align expectations with reality, and identify symptom patterns. This suggests that parents’ emotional responses may influence their experience of uncertainty and their struggle to make sense of their child’s illness, leading to difficulty in accurately assessing the child’s health status. The poor agreement in HRQoL reports at three months following diagnosis coincides with the start of cancer treatment for children, a phase marked by intense illness uncertainty.⁶⁰ Uncertainty due to a cancer diagnosis can lead parents to appraise the situation as dangerous, which is associated with lower HRQoL evaluations.⁷³ This often results in discrepancies between parents’ reports and the child’s self-reports.

In addition to findings on the determinants and consequences of parental uncertainty, this review also highlights the influence of demographic, geographic, and cultural factors. Research from high-income countries (eg, the United States and the Netherlands) often spans the full cancer trajectory—from diagnosis and treatment to palliative care—supported by more comprehensive healthcare systems and greater funding. These resources enable earlier detection of psychological distress and timely access to appropriate palliative care.⁷⁴ The supporting systems and funding enable them to dominate pediatric oncology research, conducting the majority of clinical trials and producing most published studies,^75,76 which aligns with the findings of this review. In contrast, upper-middle-income countries (eg, China) tend to focus more on research related to cancer diagnosis and treatment, with less emphasis on palliative care. One of the findings of this review is that low- and middle-income countries often focus more on supportive care (as exemplified by Wang et al³⁸) or diagnostic challenges, rather than palliative care, reflecting differences in healthcare resources and infrastructure available in each country.^75,77 In addition to differing focus on cancer stages, there is also a disparity in research output. Low- and middle-income countries often contribute less to the literature, partly due to limited research support and barriers to publishing in high-impact journals—factors that widen the gap in global pediatric oncology research.^75,78

In high-income countries, parental uncertainty is commonly linked to adverse psychological outcomes, including post-traumatic stress symptoms (PTSS),^{13–15,32,35,36} anxiety,^14,32 depression,^14,30,32 and general distress.^15,35 These studies emphasize the psychological burden parents face as they navigate the uncertainty surrounding their child’s illness. In contrast, research from upper-middle-income countries highlights both negative outcomes (eg, depressive symptoms, maladaptive coping) and positive ones, such as resilience and sense of mastery. This contrast may reflect differences in healthcare systems, cultural contexts, and available support. Upper-middle-income countries, such as China, often have more collectivist cultures where informal support networks play a key role in managing uncertainty due to limited professional resources.^79,80 As a result, the focus shifts to parents’ capacity to persevere and develop resilience despite limited structured interventions. Meanwhile, high-income countries benefit from greater access to comprehensive healthcare and psychological services. Interventions in these settings are more structured and typically focus on reducing distress, such as anxiety and depression, reflecting the availability of formal mental health support.

Limitations and Future Directions

This study synthesizes literature from the past 10 years on the determinants and consequences of parental uncertainty, offering valuable insights into recent developments, trends, and advancements in the field. This time frame ensures the review aligns with current scientific knowledge and healthcare practices, including the integration of digital health solutions identified in this review. However, limiting the scope to the last decade may exclude foundational studies and earlier insights that have shaped the current understanding, potentially overlooking important shifts in the field.

Despite offering valuable insights, this review also identifies several underexplored areas that merit further research. First, it primarily focuses on the individual-level perspective of parental uncertainty in parents of children with cancer. However, findings suggest that uncertainty is also shaped by interactions with both the child and healthcare providers. Future research should therefore adopt a dyadic (eg, parent–child) or broader relationship-based perspective to better understand how parents, children, and healthcare providers collectively navigate uncertainty throughout the cancer trajectory. Second, almost all of the studies reviewed involved more mothers than fathers, and several included only mothers as participants. This imbalance limits the generalizability of the findings and overlooks the experiences of fathers, who may face different forms or intensities of uncertainty. Future research should intentionally include more representative samples of fathers to capture the full spectrum of parental experiences and to inform more inclusive interventions. Third, around 71% of the studies reviewed were conducted in high-income countries (HICs), despite World Health Organization (WHO) data showing that nearly 90% of childhood cancer cases occur in low- and middle-income countries (LMICs). This highlights a significant evidence gap in LMIC contexts, where the burden is greatest. Future research is urgently needed in these settings to examine how structural inequities and healthcare system limitations shape parental uncertainty.

This systematic review also has several limitations that should be considered in future research. First, the review included only studies reported in English, which may have reduced the fidelity of the exact data due to the exclusion of relevant non-English publications. Second, the majority of studies (71%) employed cross-sectional designs, which limit causal interpretations. As a result, the classification of determinants and consequences must be interpreted cautiously. Longitudinal or experimental designs are recommended to explore these relationships more robustly. Third, due to the limited number of eligible studies, this review was only able to map general variables related to the determinants and consequences of parental uncertainty. However, outcomes may vary across different cancer trajectories and stages at diagnosis. Future research should consider this heterogeneity and examine how time since diagnosis influences parental uncertainty by analyzing its determinants and consequences in relation to specific cancer stages and treatment phases.

Implication and Conclusion

Parental uncertainty in childhood cancer is shaped by a complex interplay of risk and protective factors, resulting in significant psychological and health-related outcomes. The findings of this review highlight several modifiable variables that may serve as promising targets for interventions aimed at managing parental uncertainty. Effective management should address multiple dimensions, including sociodemographic, psychological, psychosocial, and cancer-specific factors, that collectively influence how parents perceive and respond to uncertainty throughout their child’s cancer trajectory. Thus, beyond individual-level responses, future research should adopt dyadic perspectives and developmentally appropriate communication approaches to better understand how parents and children navigate uncertainty together across the illness trajectory.

Among the consequences, post-traumatic stress symptoms (PTSS) emerged as the most frequently reported outcome of parental uncertainty. Given the risk of PTSS progressing into post-traumatic stress disorder (PTSD), early identification and timely intervention are essential to mitigate long-term psychological consequences for parents. From both policy and clinical perspectives, these findings underscore the importance of integrating parental uncertainty into structured psychosocial screening and early intervention protocols within pediatric oncology care. Hospitals and pediatric oncology units should also institutionalize training programs that strengthen the implementation of family-centered care by enhancing clinicians’ ability to recognize sources of parental uncertainty and support families in managing it effectively. These recommendations align with the Standards for the Psychosocial Care of Children With Cancer and Their Families,⁸¹ which emphasize comprehensive and continuous psychosocial support as a standard of care. In line with the WHO CureAll Framework,¹ such strategies not only improve treatment adherence but also enhance family well-being and long-term survivorship outcomes.

Funding Statement

This study was funded by a postgraduate scholarship (PMDSU Scholarship) from the Indonesian Ministry of Education, Culture, Research, and Technology (Grant No. 3839/UN6.3.1/PT.00/2024) and publication funding supported by Universitas Padjadjaran.

Disclosure

The authors report no conflicts of interest in this work.