Abstract
Health-related quality of life (HRQoL) allows the acquisition of the subjective perspective of patients regarding their health and function; yet a very few studies have been evaluated HRQoL of patients treated for craniosynostosis (CS). In this retrospective, descriptive cohort study, school-aged children (7–16 years) treated for non-syndromic CS were assessed using the Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales. Seventy-three patients and their parents responded to the PedsQL (response rate: 80.2%). Patients generally estimated average HRQoL with no difference compared to the normal population sample. Further, no difference in HRQoL was found between treated sagittal (SS) or metopic synostosis. In the SS group, surgical methods involving spring-assisted surgery and pi-plasty were unrelated to HRQoL outcomes. Additionally, HRQoL was highly correlated with intelligence quotient (IQ, r = 0.42; p = 0.0004) and adaptive behavior skills (ABAS, r = 0.57; p = 0.0001). Furthermore, differences were observed in estimated physical function (p = 0.002) and school function (p = 0.012) between self- and proxy reports (i.e. parents estimated child HRQoL as higher than did the children). Children treated for CS have a generally average HRQoL, and neither CS type nor surgical method influenced HRQoL outcomes. Moreover, children and parents estimated HRQoL differently, suggesting the importance of using both self- and proxy reporting in patient-reported measures. HRQoL was strongly related to IQ and ABAS, indicating that the PedsQL can be used as a screening instrument to identify craniofacial patients in need of further psychological assessment.
Introduction
Treatment outcomes for non-syndromic craniosynostosis (CS) have been studied from multiple perspectives, with numerous previous studies assessing cognitive, behavioral, and emotional function and the impact of surgical methods or timing on development [Citation1–17]. However, little is known about the relationship between CS and health-related quality of life HRQoL, despite previous claims that QoL has been included as part of psychosocial assessment. In fact, few previous studies have used validated instruments for the purpose of measuring the HRQoL of treated CS patients [Citation18–20]. Previous studies report a high QoL in adult patients [Citation18], whereas in children treated for non-syndromic CS an elevated risk of lower HRQoL was revealed [Citation19]. Additionally, children with untreated sagittal synostosis (SS) score low in terms of positive emotions [Citation20].
In recent years, HRQoL has become increasingly clinically relevant as a tool for providing patient perspectives regarding their health; however, the relationship between health and HRQoL is not always consistent, as having a disease does not always negatively impact perceived QoL, and health does not always guarantee a better QoL [Citation21].
The definition of HRQoL is multifaceted, with several definitions existing in the literature. The World Health Organization's definition of QoL is described as the perception by an individual of their position in life regarding their physical health, psychological state, level of independence, and social relationships [Citation22]. HRQoL represents a multidimensional concept that also includes health status and its impact on well-being or QoL. The Pediatric Quality of Life Inventory (PedsQL) was developed to measure HRQoL associated with pediatric health care by James Varni in the late 1990s and covers important domains, including physical, psychological, and social function, with the recent addition of school function [Citation23–25].
The aim of this study was to evaluate the HRQoL of children treated for non-syndromic CS and using the Swedish version of the validated PedsQL 4.0 Generic Core Scales. The rational for the study was to contribute to fill the gap in knowledge about HRQoL in children treated for non-syndromic CS.
Patients and methods
Patients and procedures
In this retrospective, descriptive cohort study, children (aged 7–16 years) treated for non-syndromic CS and living in the regions of Västra Götaland and Halland in Sweden were included in this study. The exclusion criteria were language barriers and secondary CS. The patients were initially informed of the study by letter, and after 1 week, received a telephone call with additional information about the study and invited to participate by scheduling a visit to the clinic. Background data were extracted from the Gothenburg Craniofacial Registry and previous studies of the same patient cohort [Citation8,Citation26].
Measurements using PedsQL 4.0 generic score scales (swedish version)
PedsQL is a modular questionnaire that measures the HRQoL of children ages 2 to 18 years. The questionnaire comprises 23 items measuring four dimensions of HRQoL: physical (8 items), emotional (5 items), social (5 items), and school function (5 items). PedsQL comprises both self- and proxy reports and has four age- and language-appropriate versions (2–4 years, 5–7 years, 8–12 years, and 13–18 years).
The questionnaire asks about difficulties with functions during the previous month. The response alternatives are presented on a 5-point scale: 0, never a problem; 1, almost never a problem; 2, sometimes a problem; 3, often a problem; and 4, almost always a problem. The response alternatives are converted to an overall scale (0–100 points) and reversed, so that higher points indicate better HRQoL.
The Swedish version of PedsQL has been translated and validated as demonstrating good psychometric properties [Citation27]. Additionally, the instrument has been evaluated in large groups of Swedish school children (n = 1455) [Citation28]. In this study, used both self- and proxy reports were used, and children and parents responded separately.
Statistical analysis
Comparison of background variables between two groups was conducted using Fisher’s exact test for dichotomous variables, a Mann–Whitney U test for continuous variables, and a chi-squared test for unordered categorial variables. Comparisons with normative sample were analyzed with Fisher’s non-parametric one-sample permutation test on the z-scores, (value-mean norm/SD norm). Comparison between self- vs. proxy reports were analyzed using Fisher’s non-parametric permutation test for matched pairs. For the paired analysis between self- vs. proxy reports both effect size (mean difference/SD for the child) and standardized response mean, SRM, (mean difference/SD for the difference). Between-group comparisons were performed using Fisher’s non-parametric permutation test for continuous variables. Adjustment for confounders was performed by analyses of covariance (ANCOVA). Calculation of 95% confidence intervals for mean differences was based on using Fisher’s non-parametric permutation test between groups. The between-group effect size, ES, is defined as mean difference/pooled SD. The relationship between HRQoL (PedsQL), adaptive behavior skills (ABAS), and intelligence quotient (IQ) was analyzed by Spearman’s correlation coefficient (rs). All significance tests were two-sided, with a p < 0.05 considered significant. All statistical calculations were performed using SAS (v.9.4; SAS Institute, Cary, NC, USA).
Ethics
The study was approved by the Gothenburg Ethics Committee (no. 856-13) and conducted according to principles in the Declaration of Helsinki.
Results
Attrition analysis
Attrition analysis revealed no significant differences between the responding (n = 73) and non-responding (n = 18) groups regarding background variables, including gender, age at study, CS type, surgical method, age at surgery, and premature birth ().
Table 1. Attrition analysis.
Participants
A total of 73 patients (24 females and 49 males; response rate: 80.2%) and their parents participated in the study. The mean age at study was 11.0 ± 2.4 years (range: 7–15 years), and all patients were treated for non-syndromic CS [SS, n = 41; metopic (MS), n = 24; and other, n = 8]. Mean age at surgery was 237.0 days, and the mean IQ (98.1) and ABAS (94.4) were within average ranges ().
Table 2. Demographics and baseline characteristics.
Health-related QoL of patients treated for CS relative to normative sample
The HRQoL of treated CS patients was estimated as generally average, with no differences found on a full-scale level relative to normative sample. At a detailed level, the SS group reported significantly lower school function (p = 0.002) and psychosocial function (p = 0.031) as compared with normative sample. The MS group reported an average HRQoL, with no significant difference relative to normative sample ().
Table 3. Child-rated PedsQL generic core scales relative to normative sample.
The impact of CS type
Background data variables ‘age at study’ and ‘working memory IQ’ differed between the SS and MS groups, with this adjusted for prior to the analysis. No differences were found in HRQoL outcomes between the SS and MS groups ().
Table 4. Difference in the mean of child- and parent-rated PedsQL generic core scales between treated sagittal and metopic CS patients.
The impact of surgical method used to treat SS
Comparisons of SS treated with spring-assisted surgery and pi-plasty revealed no significant differences, indicating that the effect of the surgical method used to treat SS was unrelated to HRQoL outcomes ().
Table 5. Difference in the mean of child- and parent-rated PedsQL generic core scales between pi-plasty and spring-assisted surgery used to treat patients with sagittal CS.
HRQoL correlates with IQ and ABAS
HRQoL significantly correlated with ABAS (r = 0.57; p = 0.0001) and IQ (r = 0.42; p = 0.0004) ().
Table 6. Correlation analysis of the mean of child- and parent-rated PedsQL generic core scales with ABAS and IQ.
Conformity of self- and proxy reports
The conformity of self- and proxy reports was strong in regard to emotional function; however, significant differences were found in estimated physical function (p = 0.002) and school function (p = 0.012), for which the parents estimated better functions than the children ().
Table 7. Change in PedsQL generic core scales from child rater to parent rater.
Discussion
In this study of children treated for non-syndromic CS, patients were asked and their parents to estimate HRQoL using the PedsQL 4.0 Generic Core Scales as a reliable and validated HRQoL-measurement tool specifically constructed for children in pediatric care. Measuring HRQoL with a patient-reported instrument allows access to information directly from the perspective of the patient, which remains a rare but coveted phenomenon in both research and clinical settings. This cohort of 73 patients treated for non-syndromic CS, revealed a generally average HRQoL, with no significant differences identified between those treated for CS and normative sample or between those treated for SS and MS. However, reports of psychosocial and school functions were lower in the SS group, although no differences in functions were found between the SS and MS groups according to the estimated HRQoL. Furthermore, the surgical method used for treatment (i.e. spring-assisted surgery and pi-plasty) in the SS group was unrelated to better or worse HRQoL outcomes.
There are few studies examining the subjective perception of the HRQoL of patients treated for non-syndromic CS, with only one study focusing on children treated for CS and reporting results indicating a risk of low HRQoL [Citation19]. At the same time, in a series of untreated SS patients, there was a tendency toward a low score in relation to positive emotions [Citation20].
Numerous studies have focused on assessing neuropsychological and cognitive functions in order to reach a consensus regarding developmental impacts related to CS diagnosis and surgical treatment [Citation1–4,Citation6–15,Citation17]. Previous studies indicate that non-syndromic CS patients are generally expected to exhibit average cognitive development [Citation6,Citation8,Citation10,Citation12,Citation29]. The cohort of patients in this study showed average performance in terms of IQ and ABAS, which were extracted as background data from previous studies [Citation8,Citation26]. Notably, associations between HRQoL, IQ, and ABAS were significant, with moderate correlations. This is an important aspect to consider when measuring HRQoL, given that cognitive and adaptive abilities can affect HRQoL outcomes. Therefore, it is crucial to control for these variables in order to measure the intended phenomenon. In a clinical setting, HRQoL could be used to screen patients in need of further psychological assessment [Citation30].
Patient-reported outcomes can offer information regarding patient perspective through self- or proxy reports. In this study, both self- and proxy reports were used to assess HRQoL. Interestingly, there were differences in how children and parents estimated HRQoL, with parents inclined to report higher HRQoL than the children. Previous studies frequently used proxy reports, where parents were asked to assess different aspects of developmental questions regarding their child [Citation5,Citation31–34]. The results of this study indicate that it is important to also use self-reports before drawing conclusions about patient status. Even though the actual patients are young, primary information rather than information from their parents, may add value to caregivers.
Strengths and limitations
The primary strength of this study is its methodological approach using a validated, reliable measurement, and comparison with a normative sample to assess HRQoL. Additionally, methodological strength is the advantages of controlling for confounders through the use of comprehensive amounts of background data. Additionally, the high response rate (80.2%) and the attrition analysis minimized the risk of selection bias. However, there are also limitations, as a larger study group would have increased the probability of the assumptions from the results. Moreover, a limitation with this study is the use of normative data instead of controls. However, the normative data was based on a large sample of children of the same age and the same ethnical background.
Additionally, there were no un-operated cases included. Therefore, the fundamental question regarding the benefit of surgery itself remains unsolved.
Conclusions
In summary, these results concluded that children treated for non-syndromic CS have a generally average HRQoL, with neither CS type nor surgical method used in the SS group related to better or worse HRQoL outcomes. Moreover, measuring HRQoL in a clinical setting can be used as a screening method to detect patients in need of profound psychological assessment. Furthermore, using both self- and proxy reports is crucial, given that parents tend to overestimate the HRQoL of their child.
Disclosure statement
No potential conflict of interest was reported by the authors.
References
- Magge SN, Westerveld M, Pruzinsky T, et al. Long-term neuropsychological effects of sagittal craniosynostosis on child development. J Craniofac Surg. 2002;13(1):99–104.
- Collett BR, Kapp-Simon KA, Wallace E, et al. Attention and executive function in children with and without single-suture craniosynostosis. Child Neuropsychol. 2017;23(1):83–98.
- Kapp-Simon KA. Mental development and learning disorders in children with single suture craniosynostosis. Cleft Palate Craniofac J. 1998;35(3):197–203.
- Kapp-Simon KA, Speltz ML, Cunningham ML, et al. Neurodevelopment of children with single suture craniosynostosis: a review. Childs Nerv Syst. 2007;23(3):269–281.
- Speltz ML, Collett BR, Wallace ER, et al. Behavioral adjustment of School-Age children with and without Single-Suture craniosynostosis. Plast Reconstr Surg. 2016;138(2):435–445.
- Speltz ML, Collett BR, Wallace ER, et al. Intellectual and academic functioning of school-age children with single-suture craniosynostosis. Pediatrics. 2015;135(3):e615-23–e623.
- Speltz ML, Kapp-Simon KA, Cunningham M, et al. Single-suture craniosynostosis: a review of neurobehavioral research and theory. J Pediatr Psychol. 2004;29(8):651–668.
- Kljajic M, Maltese G, Tarnow P, et al. The cognitive profile of children with nonsyndromic craniosynostosis. Plast Reconstr Surg. 2019;143(5):1037e–52e.
- Kljajić M, Maltese G, Tarnow P, et al. Sustained attention and vigilance of children treated for sagittal and metopic craniosynostosis. Child Neuropsychol. 2020;26(4):475–488.
- Hashim PW, Patel A, Yang JF, et al. The effects of whole-vault cranioplasty versus strip craniectomy on long-term neuropsychological outcomes in sagittal craniosynostosis. Plast Reconstr Surg. 2014;134(3):491–501.
- Patel A, Yang JF, Hashim PW, et al. The impact of age at surgery on long-term neuropsychological outcomes in sagittal craniosynostosis. Plast Reconstr Surg. 2014;134(4):608e–617e.
- Bellew M, Chumas P. Long-term developmental follow-up in children with nonsyndromic craniosynostosis. J Neurosurg Pediatr. 2015;16(4):445–451.
- Bellew M, Liddington M, Chumas P, et al. Preoperative and postoperative developmental attainment in patients with sagittal synostosis: 5-year follow-up. J Neurosurg Pediatr. 2011;7(2):121–126.
- Bellew M, Mandela RJ, Chumas PD. Impact of age at surgery on neurodevelopmental outcomes in sagittal synostosis. J Neurosurg Pediatr. 2019;23(4):434–441.
- Mandela R, Bellew M, Chumas P, et al. Impact of surgery timing for craniosynostosis on neurodevelopmental outcomes: a systematic review. J Neurosurg Pediatr. 2019;23(4):442–454.
- van der Vlugt JJ, van der Meulen JJ, Creemers HE, et al. Cognitive and behavioral functioning in 82 patients with trigonocephaly. Plast Reconstr Surg. 2012;130(4):885–893.
- Kapp-Simon KA, Wallace E, Collett BR, et al. Language, learning, and memory in children with and without single-suture craniosynostosis. J Neurosurg Pediatr. 2016;17(5):578–588.
- Mazzaferro DM, Naran S, Wes AM, et al. Quality of life in adults with nonsyndromic craniosynostosis. Plast Reconstr Surg. 2018;141(6):1474–1482.
- Cloonan YK, Collett B, Speltz ML, et al. Psychosocial outcomes in children with and without non-syndromic craniosynostosis: findings from two studies. Cleft Palate Craniofac J. 2013;50(4):406–413.
- Boltshauser E, Ludwig S, Dietrich F, et al. Sagittal craniosynostosis: cognitive development, behaviour, and quality of life in unoperated children. Neuropediatrics. 2003;34(6):293–300.
- Fayers PM, Machin D. Quality of life: the assessment. Analysis and reporting of patient-reported outcomes. Chichester, Wiley; 2015.
- International Health C Constitution of the world health organization. Bull World Health Organ. 1946;80(12):983–984. 2002
- Varni JW, Katz ER, Seid M, et al. The pediatric cancer quality of life inventory (PCQL). I. Instrument development, descriptive statistics, and cross-informant variance. J Behav Med. 1998;21(2):179–204.
- Varni JW, Seid M, Rode CA. The PedsQL: measurement model for the pediatric quality of life inventory. Med Care. 1999;37(2):126–139.
- Varni JW, Burwinkle TM, Katz ER, et al. The PedsQL in pediatric cancer: reliability and validity of the pediatric quality of life inventory generic core scales, multidimensional fatigue scale, and cancer module. Cancer. 2002;94(7):2090–2106.
- Kljajić M, Maltese G, Tarnow P, et al. Children treated for nonsyndromic craniosynostosis exhibit average adaptive behavior skills with only minor shortcomings. Plast Reconstr Surg. 2021;147(2):453–464.
- Petersen S, Hägglöf B, Stenlund H, et al. Psychometric properties of the swedish PedsQL, pediatric quality of life inventory 4.0 generic core scales. Acta Paediatr. 2009;98(9):1504–1512.
- Petersen S, Hägglöf BL, Bergström EI. Impaired health-related quality of life in children with recurrent pain. Pediatrics. 2009;124(4):e759-67–e767.
- Chieffo D, Tamburrini G, Massimi L, et al. Long-term neuropsychological development in single-suture craniosynostosis treated early. J Neurosurg Pediatr. 2010;5(3):232–237.
- Buratti S, Ryberg C, Broberg M, et al. Do self- and proxy reports of cognitive problems reflect intellectual functioning in children and adolescents with congenital heart defects? Front Pediatr. 2016;4:127.
- Bottero L, Lajeunie E, Arnaud E, et al. Functional outcome after surgery for trigonocephaly. Plast Reconstr Surg. 1998;102(4):952–958. discussion 9–60.
- Sidoti EJ, Jr., Marsh JL, Marty-Grames L, et al. Long-term studies of metopic synostosis: frequency of cognitive impairment and behavioral disturbances. Plast Reconstr Surg. 1996;97(2):276–281.
- Snyder H, Pope AW. Psychosocial adjustment in children and adolescents with a craniofacial anomaly: diagnosis-specific patterns. Cleft Palate Craniofac J. 2010;47(3):264–272.
- Kelleher MO, Murray DJ, McGillivary A, et al. Behavioral, developmental, and educational problems in children with nonsyndromic trigonocephaly. J Neurosurg. 2006;105(5 Suppl):382–384.