Health-related quality of life in children and adolescents with congenital diaphragmatic hernia: a cross-sectional study

In accordance with the original PedsQL administration guidelines, questionnaires were completed by the participants and their parents before the completion of other health data forms or the child’s physical examination. Parents or participants independently completed the questionnaires without consultation.

We obtained permission to use the PedsQL questionnaire (version 4.0) [25]. This instrument has been validated to evaluate healthy children and adolescents, as well as patients with acute and chronic health conditions [26, 27]. The PedsQL questionnaire provides a child self-report (for children ≥5 years) and a parent-proxy report (for children > 2 years). Therefore, for children younger than 5 years, only their parents completed the age-appropriate HRQoL forms. For infants 1 to 12 and 13 to 24 months old, we obtained parent-proxy reports by using the PedsQL infant scales. Infant Scales, include 36 items for 1 to 12-month-old infants and 45 items for 13 to 24-month-old children that assess 5 dimensions (physical, emotional, social, and cognitive functioning and physical symptoms). For 2 to 4-year-old children, we used the PedsQL Parent Report for Toddlers, which includes 21 items that assess 4 dimensions (physical, emotional, social, and preschool functioning). For the children ages 5 to 7, 8 to 12, and 13 to 18 years old, and young adults older than 18 up to 25 years old (PedsQL Young Adult Version) the self-report scales include 23 items, which differ slightly according to age group, that assess 4 dimensions (physical, emotional, social, and school functioning). Parents and older children (≥5 years) self-administered PedsQL after receiving instructions. However, for 5 to 7-year-old children, PedsQL was administered by reading the instructions to them (each item was read word-for-word) and providing a separate page that showed 3 facial expressions (ie, pictorial representations) to help the child understand how to answer. Children aged 8 years and older scored questions using a 5-point Likert scale (0 [never] to 4 [almost always]), and 5- to 7-year-old children used a 3-point Likert scale anchored to the pictorial representations.

Although the PedsQL questionnaire introduces various items (ie, questions) for different ages, the forms, regardless of age group, are essentially identical and only differ in the developmentally appropriate language that is used. Each response receives a value of 0%, 25%, 50%, or 100% (representing a range from “never” to “always”) [25]. The sum of the items divided by the number of answered items generates the mean score. All responses were tabulated to generate an overall health score and physical health summary score. A psychosocial health summary score was calculated using the sum of the answered items in the emotional, social, school, and cognitive (or school) function domains; separate scores were also calculated for each of these subdomains in accordance with published recommendations [25].

After completion of PedsQL, all patients (or their parents) were interviewed to obtain their medical and surgical histories. This interview was conducted by a neonatologist (K.B.). In addition, participant health records were reviewed to determine their demographic, neonatal, and postnatal characteristics and medical histories. The collected perinatal variables were sex, gestational age, birth weight, postnatal duration of mechanical ventilation, duration of hospitalization, history of bronchopulmonary dysplasia (BPD) (as defined by Jobe and Bancalari) [28], type of CDH in regard to the liver position (“liver up” vs “liver down,” describes whether liver was herniated [“up”] or not [“down”] into the thoracic cavity), and congenital anomalies. By using birth weight and Apgar score at 5 min, we calculated probability of survival scores as proposed by the Congenital Diaphragmatic Hernia Study Group (Apgar score assesses 5 vital signs—appearance, pulse, grimace, activity, respiration—at 1 and 5 min after birth, with the final score ranging from 0–10) [29]. This score assigns the probability of survival after birth, and neonates are categorized as having low (0%–33%), intermediate (34%–66%), or high (67%–100%) survival probability. Of note, this score is the accepted tool for grading CDH severity after birth. A recurrent respiratory infection (RRI) was defined as at least 3 respiratory episodes per year (or per fall-winter season) for at least 2 years and included treatment for wheezing and breathlessness [30]. Gastroesophageal reflux disease was recorded when indicated in the health records or when the patient received treatment. Furthermore, patients with CDH and their parents were interviewed to obtain information about current and chronic clinical issues using an inventory that was partly adopted from Michel et al. [18]. We considered 4 major health categories: digestive, respiratory, neuropsychological, and orthopedic. Digestive issues included oral aversion and chronic problems (eg, vomiting, reflux, constipation, diarrhea, abdominal pain, history of gastrointestinal surgery). Chronic respiratory issues included dyspnea at rest, exertional dyspnea, nocturnal dyspnea, chest pain, RRI, use of respiratory medications, and hospitalization for respiratory illness. Neuropsychological issues included cerebral palsy and major cognitive impairment (all patients were formally tested for neurocognitive function, and the results were previously reported [9]). Orthopedic issues included skeletal deformities or any orthopedic treatment. Finally, patients and their parents were asked about all hospital readmissions (following the initial hospitalization for CDH treatment) and surgical history.

Parent- and child-reported HRQoL scores were compared between patients with CDH and control participants. Analysis of variance was used to adjust for sex and PedsQL questionnaire age group (infants: 1–12 months; infants: 13–24 months; toddlers: 2–4 years; young children: 5–7 years; children: 8–12 years; teens: 13–18 years; and young adults: 18–25 years). For these analyses, the age- and sex-adjusted differences between groups (patients with CDH vs control participants) are calculated using a multivariate regression mode with differences between groups (CDH vs control) presented for all scores using model estimates along with the corresponding 95% CI. Overall HRQoL scores were compared between parents and children using the paired t test when both assessments were available. To assess whether differences between parent-proxy report and child self-report were dependent on the age of the child, a repeated measure analysis of variance was performed with respondent (parent vs child), age group, and the respondent-by-age group interaction term included as the explanatory variables. In addition, in analyses restricted to CDH survivors and their parents, the association of HRQoL scores with CDH characteristics at initial hospitalization, postdischarge events, and comorbid conditions, was assessed using analysis of variance. Separate analyses were performed for parent proxy reports, and child self-reports. In order to create groups of sufficient size for meaningful comparisons when analyzing age at testing, the two infant groups (< 12 months, 13–24 months) were combined, as were children 5 to 7 and 8 to 12 years of age, and those 13 years of age and older. The analysis of child self-reports include only those ≥5 years of age at the time of testing since only parent reports were available for infants and children < 5 years old. Multiple comparison adjustments were not performed, and in all cases unadjusted 2-tailed P values are reported.

A total of 98 neonates with CDH were treated at University Hospital Centre from 1990 through 2015, and 44 neonates were known to have died at study recruitment (Fig. 1). Of the remaining 54 patients, 45 agreed to participate, 3 declined, and 6 were lost to follow-up. Therefore, in the current study, we examined self-reported HRQoL in 45 patients with CDH and 90 control participants. Patients with CDH had a mean (SD) age of 8.2 (5.7) years, and 29 patients (64%) were male. The number of CDH patients included in each of the PedsQL version– specific age groups is presented in the Fig. 1. The mean (SD) age of the control participants was 8.4 (6.1) years, and 40 participants (44%) were male.

Among patients with CDH, 39 had left-sided CDH and 6 had right-sided CDH; 12 patients were prenatally diagnosed. Additional demographic, disease, and immediate postnatal surgical characteristics of these patients are shown in Table 1. The burden of these residual comorbid conditions was substantial (see the patient summary in the Appendix). Thirty-three patients with CDH (73%) were readmitted to the hospital at least 1 time (115 total readmissions) following their initial hospital discharge. The most common reason for subsequent hospitalization was related to respiratory problems (62 readmissions, of which the majority were for RRI), followed by digestive problems (26 readmissions). The remaining 27 readmissions were for a variety of reasons.

At the time of HRQoL testing, 29 patients with CDH (64%) reported recent respiratory issues, of which RRI was the most common (25 patients [56%]). Of these 25 patients with RRI, 9 (36%) had a history of BPD (6 patients had severe to moderate BPD, and 3 patients had mild BPD). Interestingly, 6 patients with BPD did not report a recent RRI (all patients had mild BPD and were > 10 years).

Twenty-three patients (51%) had digestive issues. Constipation was the most commonly reported problem (23 patients [51%]), followed by recurrent diarrhea and gastroesophageal reflux disease (each reported by 5 patients [11%]). Orthopedic issues affected 6 patients (13%), including 1 patient with pectus excavatum and restrictive pulmonary disease and 1 patient with kyphoscoliosis that required bracing therapy. Neurologic issues were identified in 7 patients with CDH (16%); all of these patients had severe cognitive impairment (including 1 patient with cerebral palsy).

Table 2 shows the parent- and child-reported HRQoL scores of the patients with CDH and control participants. Patients with CDH had significantly lower HRQoL (as reported by the parent-proxy report and patient self-report) compared with control participants, as shown by the overall scores, physical health summary scores, and psychosocial health summary scores (all P < 0.001) and the scores on the emotional, social, and school subdomains (all P ≤ 0.02). The only nonsignificant finding between control participants and patients with CDH was the parent-reported cognitive scores for 1- to 24-month-old children (P = 0.69). In the analysis restricted to complete child and parent pairs (ie, both completed HRQoL assessments [28 patients with CDH and 60 control participants]), the child’s self-reported scores were significantly lower than the parent-reported scores. The mean (SD) overall scores were 75.0 (13.9) for patients with CDH and 80.6 (12.0) for their parents (P = 0.046). The difference between parent and child reports was not found to be dependent on the child’s at testing (respondent-by-age interaction P = 0.769). The mean (SD) overall scores were 85.4 (8.8) for control participants and 88.8 (6.8) for their parents (P < 0.001), with no evidence of an interaction between respondent and age at testing (respondent-by-age interaction P = 0.533).

Tables 3 and 4 present the HRQoL scores of the patients with CDH according to their characteristics at birth (including CDH severity) and after their initial hospital discharge. Among patients with CDH, these exploratory analyses showed that parent-reported HRQoL was lower when their children also had BPD, longer initial hospitalization, severe neurologic issues (most commonly severe cognitive impairment), or orthopedic symptoms; in addition, parent-reported HRQoL differed by the child’s age, and 5- to 12-year-old patients had the lowest HRQoL (Table 3). Among patients with CDH, a recent history of pulmonary symptoms was the only characteristic that was negatively associated with HRQoL (Table 4).

Because of the lower cognitive and language skills of young children, PedsQL includes parent-proxy reports to obtain information about children. The use of questionnaires with child and parent versions has raised questions about the level of agreement between children and their parents about child functioning. Some investigators reported poor parent-child agreement [32, 33], but others reported moderate to high agreement [34, 35]. One study used both child self-reports and parent-proxy reports to evaluate QoL of patients with CDH [18], but to our knowledge our study is the first to simultaneously obtain child self-reports and parent-proxy reports by using a validated instrument and to directly compare these sources. In our study, parent-reported HRQoL was slightly but consistently higher than child-reported HRQoL. When patient and disease characteristics were tested for potential associations with HRQoL, our findings were inconsistent between parent and child assessments. The lack of agreement among individual variables associated with child- and parent-reported HRQoL scores may be due to complex, interrelated, overlapping disease characteristics; thus, identifying a single characteristic that is consistently associated with low HRQoL is difficult. Patients with CDH may have complex comorbid conditions that contribute to low HRQoL scores in diverse ways when reported by a child versus a parent. In our study, the characteristics that are descriptors of the severity of the postnatal course were not associated with reduced HRQoL scores in the child self-reports. Similarly, Koivusalo et al. [17] observed lower than expected HRQoL in 25% of patients with CDH, but no correlation between CDH severity and HRQoL scores was reported. A single variable—chronic respiratory problems, which are often linked with multiple hospitalizations—was associated with low child self-reported HRQoL in our study. In contrast, longer initial hospitalization, postnatal BPD, severe cognitive impairment, and chronic orthopedic problems were all associated with lower HRQoL when reported by parents but not children.

Discordant perceptions of HRQoL between child self-reports and parent-proxy reports have been reported [36, 37]. In many instances, when the parent and child disagree, the evidence does not clearly show that parents overestimated or underestimated HRQoL. Glaser et al. [35] suggested that parents can appropriately report information about their child’s HRQoL, but others indicated that parents tend to rate their child’s HRQoL lower than their child [32, 33]. Davis et al. [31] suggested that “discordance in HRQoL scores between parents and children may be due to different reasoning and response styles rather than item interpretation.” In a study by Saigal et al. [38], parents were asked to rate the HRQoL of their infants with extremely low birth weight, and, despite the presence of substantial disease burden, average HRQoL was high. In our study, the scores of the parent-proxy reports were consistently higher than the scores of the child self-reports. Investigations of adult populations have shown that patients are more reliable and consistent at scoring their own QoL than their physicians [39, 40]; therefore, patient reports should be the criterion standard when this information is used for interventions and treatments. Another study assessed QoL in children with chronic pain and suggested that, although merit should be given to parent-proxy reports, the child’s own perspective should be directly solicited whenever possible [2].

Because numerous comorbid conditions associated with CDH in early childhood resolve with age and chronic health conditions may affect a person’s subjective perception of HRQoL, self-reported HRQoL scores may be affected by the child’s age [19, 41]. Poley et al. [19] conducted a cross-sectional study and observed poor HRQoL in young patients with CDH but normal HRQoL in children older than 16 years. Poley et al. concluded that, despite considerable early morbidity, the ultimate prognosis of CDH as measured with HRQoL is favorable. In contrast, using PedsQL questionnaires, Sheikh et al. [41] reported good HRQoL scores in patients with CDH, even in younger patients (mean age, 5.5 years), regardless of CDH severity at birth. This discordance between studies may be due to the associations between CDH and various comorbid conditions (eg, cardiac, pulmonary), which have variable degrees of severity and potential to improve over time. In addition, given the cross-sectional nature of these studies, the association between QoL and age is difficult to interpret, because at the time they were surveyed for the present study, older patients had received treatments when contemporary therapeutic modalities were unavailable, resulting in survival of healthier children; therefore, these older CHD participants may have less-severe residual disease. For all of these reasons, comparison of outcomes in cross-sectional studies is associated with complexities related to unaccounted confounders.

In our study, HRQoL of the patients with CDH differed with the age of the child. Five- to 12-year-old children had considerably lower parent-reported HRQoL. A plausible, albeit speculative, explanation for this finding is that these children are more engaged in competitive school activities, and therefore parents may notice that their child does not perform at the same level as their peers. Whether this rationale would also apply to child self-reports cannot be assessed because children under the age of 5 years did not complete a questionnaire. However, it appears that a similar perception of low health status exists for 5- to 12-year-old children and their parents because both groups reported low scores (Tables 3 and 4).

This study is limited by its retrospective design. Evaluation of a wide range of ages with a cross-sectional study precludes the ability to precisely assess whether HRQoL changes with time. Given the rarity of CDH, the statistical power to assess differences across age groups is limited by the small number of patients in some age groups. In addition, a parent’s assessment of their child’s HRQoL may be influenced by unaccounted elements (eg, life experience, expectations for their child, physical and psychological health, socioeconomic status, sex, race and ethnicity, family relationships, and parental stress related to their child’s disease) [1, 2]. Furthermore, adaptation to disease may affect a child’s perception of HRQoL, but we cannot account for this possibility. In order to ensure that our control group was not skewed by individuals with chronic comorbidities, when selecting control participants, we excluded participants with chronic medical illness. This approach may have overestimated the HRQoL of our control participants compared with the general population.