Morbidities After Cardiac Surgery: Impact on Children's Quality of Life and Parents' Mental Health.

BACKGROUND: Most children now survive cardiac surgery, and the focus of quality improvement initiatives has shifted toward more complex outcome measures. The aim of this investigation was to study the impact of early postoperative morbidities on parent-reported patient quality of life and parental anxiety or depression over 6 months.
METHODS: This prospective case-matched cohort study was conducted in 5 UK children's cardiac centers. Measures of impact for patient categories of "single morbidity," "multiple morbidities," and "extracorporeal life support (ECLS)" were compared with "no morbidity." The measures used were the Pediatric Quality of Life Inventory (PedsQL) and the 4-item Patient Health Questionnaire (PHQ-4) at 6 weeks and 6 months postoperatively. The study modeled the outcomes using mixed effects regression, adjusting for case mix and clustering within centers.
RESULTS: The study included 666 patients who underwent operation at a median age of 81 days (interquartile range, 10 to 325 days). At 6-week follow-up, significant adjusted differences to the reference group with no morbidity were found for total PedsQL scores, which were lower in patients with ECLS (P = .01), multiple morbidities (P < .001), and a single morbidity (P = .04), as well as the proportion of parents with anxiety and depression, which were higher in the group with multiple morbidities (P = .04 and P = .01, respectively). At 6 months, measures had improved in all morbidity groups. The only significant adjusted difference in the reference group was for physical PedsQL scores in ECLS (P = .04) and multiple morbidities (P < .01).
CONCLUSIONS: Patient and parent well-being are strongly influenced by postoperative morbidities early after surgery, with improvement by 6 months. Family psychological support and holistic rehabilitation are vital for children who experience postoperative morbidities.

The Supplemental Tables can be viewed in the online version of this article [http://doi.org/10.1016/j.athoracsur.2020.11.003] on http://www.annalsthoracicsurgery.org.

Early survival after pediatric cardiac surgery is excellent: for instance, 30-day mortality in the United Kingdom is lower than 2%. Given this low mortality rate, there is international interest from all stakeholders in studying other (albeit more complex) outcome measures, including rates of specific adverse events, longer-term survival, neurodevelopmental outcomes, and health-related quality of life (HRQOL). Such outcomes are interrelated: periprocedural measures, including hospital length of stay and technical performance score of the operation, have implications for longer-term neurodevelopmental function, which is an important determinant of HRQOL. Although poorer HRQOL is associated with greater disease complexity, and medical care use, there can be considerable variation within specific diagnostic groups, a finding suggesting that other factors are also important. Specific individual postoperative adverse events have links to longer-term neurodevelopmental function (seizure, acute neurologic event, cardiac arrest)., Therefore, postoperative complications have become an important focus of clinician collaboratives seeking to leverage further improvements in outcome. For parents, the traumatic nature of cardiac surgery in their children and the subsequent stay in intensive care has been well described, as has the influence of parental functioning on child psychosocial outcomes.

Our qualitative research showed that clinicians and parents hold differing views about which specific postoperative events should be counted as adverse early outcomes of pediatric cardiac surgery.,, Therefore, we used the term morbidity, a state of health generally viewed as bad for you, to label the range of adverse early outcomes (excluding death). We recognized that not all such adverse early outcomes are directly caused by the surgical procedure, although they do arise as a direct consequence of children undergoing cardiac surgery. Our overarching study aim was to evaluate the important early morbidities after pediatric cardiac surgery, in terms of their incidence and impact on patients, families, and the UK National Health Service. We previously published13, 14, 15 the selection and definition of 9 key surgical morbidities (acute neurologic event, renal replacement therapy, necrotizing enterocolitis, major adverse events, extracorporeal life support [ECLS], postsurgical infection, prolonged pleural effusion or chylothorax, unplanned reintervention, and feeding problems [summarized in Supplemental Table 1]) and the incidence of these in a UK population, but we did not address the impact of these morbidities on patient and parent psychosocial outcomes. Our aim in this phase of the study, therefore, was to evaluate the impact of the selected morbidities on parent-reported patient HRQOL and parental anxiety or depression up to 6 months after surgery. We hypothesized that ECLS and multiple morbidities (excluding ECLS) would have a greater impact on parent-reported HRQOL and parental anxiety or depression than single morbidities or no morbidity.

Patients and Methods

The study received ethical approval from the London City Road Research Ethics Committee (14-LO-1442), and all participants provided written consent.

Our study design was a prospective, multicenter, case-matched cohort study in which HRQOL was prospectively assessed at 6 weeks and 6 months after cardiac surgery.

Patients were eligible to participate if they were younger than 17 years of age and had pediatric cardiac surgery in 1 of 5 participating centers in the United Kingdom either electively or as an emergency, were UK residents, and their families were able to speak and understand English to a reasonable standard.

From the eligible pediatric cardiac surgical patients who met the inclusion criteria, all patients with at least 1 of the selected morbidities were approached for participation as a morbidity case. A subset of patients with none of the selected morbidities were approached for participation as morbidity-free control subjects.

As described previously, within each center we aimed to match each morbidity case with the next patient who did not have a morbidity (a morbidity-free control subject) by using the following criteria:

Age within 3 months for children younger than 12 months of age, within 12 months for children 1 to 5 years of age, and within 2 years for children older than 5 years of age

Single or biventricular condition

Baseline clinical, and demographic data previously linked to early mortality or HRQOL were collected, the details of which are provided in Supplemental Tables 2 to 4. Further details of recruitment and baseline data collection processes are provided in Supplemental Table 5.

Follow-up Data

Outcome measure data were collected from families at 6 weeks and 6 months after surgery, except when the child had died. If a child was still in the hospital at follow-up, data were collected wherever possible. Data were collected either face to face, by telephone, or electronically, depending on parental preference.

Perceived HRQOL was assessed with the parent-completed Pediatric Quality of Life Inventory.(PedsQL) generic and infant scales,, which include parent-proxy assessment for children 1 month to 18 years of age. A total score, a physical health summary score, and a psychosocial summary score were computed (range, 0 to 100).

The 4-item Patient Health Questionnaire (PHQ-4) was used to assess parental anxiety and depression. This ultrashort screening measure comprises 4 questions, 2 each for anxiety and depression. Parental PHQ-4 scores were dichotomized to indicate the potential presence or absence of anxiety and depression.

The primary measure of impact was the PedsQL4.0 total score. A clinically meaningful difference in HRQOL scores between pairs corresponds to a mean difference of at least 0.5 SDs. To detect such a difference between cases and controls with 80% power and 5% significance would require 32 matched pairs of patients with and without morbidity. Allowing for an attrition rate of 10%, we aimed to recruit 36 matched pairs for each selected morbidity.

Data Analysis

In view of the small numbers in selected individual morbidity categories and our hypothesis related to ECLS and multiple morbidities, we categorized morbidities as follows: single morbidity (1 of the selected morbidities, excluding ECLS), multiple morbidity (more than 1 selected morbidity, excluding ECLS), and ECLS (patients with ECLS even if they had other morbidities).

PedsQL scores and categorized PHQ-4 scores were summarized using means (SD) and frequencies (proportions) as appropriate for each morbidity group at both 6 weeks and 6 months. We fitted separate mixed-effects regression models, for all outcomes at both time points, and included the 4-category morbidity factor and prespecified covariates (age, weight, cardiac diagnosis category, functionally univentricular heart, specific procedure type, bypass time, acquired comorbidity, congenital comorbidity excluding Down syndrome, additional cardiac risk factors, and severity of illness). The primary analysis considered all patients, and all models included a random factor for patient, nested within matched pairs, to account for the correlation between matched pairs.

Using the no morbidity group as the reference category, the absolute differences in means and 95% confidence intervals are presented for the 3 morbidity groups, for each of the continuous outcomes. Odds ratios are presented along with 95% confidence intervals for the categoric outcomes.

Multiple imputation using chained equations was used to account for missing data in all analyses. All analyses were performed using Stata software version 14 (StataCorp, College Station, Texas).

Results

We recruited 340 patients with at least 1 morbidity (60% of eligible patients) and 326 control subjects with none of the selected morbidities, of whom 558 were case-control matched.

Case Mix

The number and proportion of patients with predefined baseline characteristics are shown in Supplemental Table 3, in the study population overall and by the morbidity groups. The study population was relatively young and complex: at the time of operation, 410 patients (76.6%) were younger than 12 months old; 121 (18%) had congenital comorbidities other than Down syndrome, and 135 (20%) had functionally univentricular hearts. Most lived in 2-parent families (n = 523; 93.7%) with an annual income of more than £25,000 (median for the United Kingdom) (n = 361; 63.3%) and were White (n = 501; 83%).

Loss to Follow-up

At 6 weeks, 19 (3%) patients had died and 70 of 647 (11%) were still in the hospital. At 6 months, 39 (6%) had died and 5 of 627 were in the hospital. PedsQL total scores were available for 477 (74% of surviving patients) at 6 weeks and 407 (65%) at 6 months. PHQ-4 data were available for 482 patients (74%) at 6 weeks and 394 (63%) at 6 months. Compared with patients with nonmissing data, the proportion with baseline severity of illness risk factors and acquired cardiac risk factors was higher (P < .01) in those with missing data at 6 weeks but not at 6 months. There were no differences in other baseline factors or in the proportion of patients with a morbidity between patients with and without missing follow-up information.

Morbidities

Figure 1, Figure 2, Figure 3, Figure 4 indicate the number of patients with each morbidity type and depict PedsQL physical and psychosocial summary scores and proportions of parents with anxiety or depression according to the presence of no selected morbidity, each individual single morbidity, multiple morbidities, and ECLS.

Figure 1

Pediatric Quality of Life Inventory (PedsQL) physical summary scores by morbidity type at 6 weeks and 6 months after the primary operation. The box plots show the PedsQL summary score, for no selected morbidities (blue), for each selected morbidity in isolation, and for multiple morbidities (red for 6 weeks postoperatively [post-op] and orange for 6 months postoperatively). The middle heavy bar represents the median, the box represents the interquartile range 25th (first quartile) to 75th centiles (third quartile), and the outer lines ending in a bar represent the threshold for lowest and highest deciles.

Figure 2

Pediatric Quality of Life Inventory (PedsQL) psychosocial summary scores by morbidity type at 6 weeks and 6 months after the primary operation. The box plots show the PedsQL summary score, for no selected morbidities (blue), for each selected morbidity in isolation, and for multiple morbidities (red for 6 weeks postoperatively [post-op] and orange for 6 months postoperatively). The middle heavy bar represents the median, the box represents the interquartile range 25th (first quartile) to 75th centiles (third quartile), and the outer lines ending in a bar represent the threshold for lowest and highest deciles.

Figure 3

Percentage of parents with potential anxiety, determined by the 4-item Patient Health Questionnaire (PHQ-4) at 6 weeks and 6 months after the primary operation. Percentages are shown for no selected morbidities (blue), for each selected morbidity in isolation, and for multiple morbidities (red for 6 weeks postoperatively [post-op] and orange for 6 months postoperatively), with 95% confidence intervals.

Figure 4

Percentage of parents with potential depression, determined by the 4-item Patient Health Questionnaire (PHQ-4) at 6 weeks and 6 months after the primary operation. Percentages are shown for no selected morbidities (blue), for each selected morbidity in isolation, and for multiple morbidities (red for 6 weeks postoperatively [post-op] and orange for 6 months postoperatively), with 95% confidence intervals.

Analyses of Morbidity Impact

Table 1 shows mean PedsQL scores at the 2 follow-up time points by the 4 morbidity groups and the adjusted comparisons of these scores on the basis of single morbidities, ECLS, and multiple morbidities with the reference category of no morbidities. After adjusting for covariates, at 6 weeks physical HRQOL was worse for single morbidities, ECLS, and multiple morbidities (P < .01). In contrast, for psychosocial HRQOL, we observed no difference for single morbidities and ECLS, but there was a reduction in adjusted psychosocial HRQOL with multiple morbidities (P = .03). By 6 months, the differences in adjusted PedsQL scores by the morbidity groups had narrowed considerably, and the only residual significant adjusted differences were for physical HRQOL in ECLS (P = .04) and multiple morbidities (P < .01).

Table 1

Mean (SD) Pediatric Quality of Life Inventory Scores at Follow-up Points by the 4 Morbidity Groups and Fully Adjusted Comparison of These Scores by Morbidity Groups

PedsQL Scale: 6 wk	No Morbidity (n = 241) Mean Score (SD)	Single Morbidity (n = 145) Mean Score (SD)	ECLS Morbidity (n = 13) Mean Score (SD)	Multiple Morbidities (n = 78) Mean Score (SD)	Single vs None Difference in Means (95% CI) P Value	ECLS Vs None Difference In Means (95% CI) P Value	Multiple vs None Difference in Means (95% CI) P Value
Physical	79.0 (16.2)	72.4 (21.1)	50.4 (23.2)	66.1 (20.9)	−6.2 (−10.3, −2.1) <.01	−20.2 (−30.9, −9.5) <.001	−12.2 (−17.1, −7.3) <.001
Psychosocial	79.4 (14.7)	76.8 (17.3)	65.6 (24.1)	73.5 (20.9)	−1.7 (−5.4, 2.0) .37	−6.1 (−16.1, 3.8) .23	−5.1 (−9.6, −0.5) .03
Total score	79.3 (13.8)	74.5 (18.3)	59.4 (22.0)	69.6 (19.3)	−3.9 (−7.4, 0.3) .04	−12.4 (−21.7, −3.2) .01	−8.3 (−12.6, −4.0) <.001

CI, confidence interval; ECLS, extracorporeal life support; PedsQL, Pediatric Quality of Life Inventory.

Table 2 shows the PHQ-4 outcomes and adjusted comparisons on the basis of morbidity group. At 6 weeks, there was a higher adjusted rate of potential anxiety and depression in the multiple morbidity group (P = .04 and P = .01, respectively) referenced to the no morbidity group. For the single morbidities and ECLS groups at 6 weeks and for all 3 morbidity groups at 6 months, there were no significant differences in the rates of either anxiety or depression in comparison with the no morbidity group.

Table 2

Parents With Anxiety and Depression by 4 Morbidity Groups at Follow-up Time Points, as Well as Fully Adjusted Odds Ratios of Anxiety and Depression by Morbidity Groups at the 2 Time Points

Anxiety and Depression	No Morbidity, n (%)	Single Morbidity, n (%)	ECLS Morbidity, n (%)	Multiple Morbidities, n (%)	Single vs None Odds ratio (95% CI) P Value	ECLS vs None Odds ratio (95% CI) P Value	Multiple vs None Odds ratio (95% CI) P Value
Anxiety No anxiety (at 6 wk)	55 (23.7) 177 (76.3)	51 (33.8) 100 (66.2)	9 (56.3) 7 (43.7)	32 (38.6) 51 (61.4)	1.62 (1.00, 2.62) .05	3.09 (0.90, 10.61) .07	1.89 (1.04, 3.43) .04
Depression No depression (at 6 wk)	26 (11.2) 206 (88.8)	27 (18.0) 123 (82.0)	6 (37.5) 10 (62.5)	22 (26.5) 61 (73.5)	1.62 (0.88, 2.97) .12	3.18 (0.90, 11.24) .07	2.44 (1.21, 4.92) .01
Anxiety No anxiety (at 6 mo)	23 (11.5) 177 (88.5)	19 (15.5) 104 (84.5)	3 (27.3)8 (72.7)	12 (19.7) 49 (80.3)	1.25 (0.63, 2.45) .52	1.84 (0.43, 7.90) .41	1.53 (0.72, 3.21) .27
Depression No depression (at 6 mo)	15 (7.5) 185 (92.5)	9 (7.4) 113 (92.6)	2 (18.2) 9 (81.8)	12 (19.7) 49 (80.3)	1.16 (0.51, 2.64) .73	2.88 (0.39, 21.16) .30	2.04 (0.84, 4.97) .11

CI, confidence interval; ECLS, extracorporeal life support.

Outcome scores did not differ at 6 weeks between those who did and did not have 6-month data.

Comment

Our prospective case-matched multicenter cohort study enabled us to explore measures of early postoperative morbidity impact in a large group of vulnerable children and their families. HRQOL was significantly worse at 6 weeks after surgery on the basis of the presence of morbidity, after adjustment for case mix and family factors. This reduction in HRQOL was more pronounced for children who had multiple morbidities and ECLS than for patients with single morbidities, a finding supporting our hypothesis, and it involved marked impairments in physical HRQOL. Encouragingly, HRQOL improved between 6 weeks and 6 months.

Implications of Our Study

Registries and collaboratives have supplemented mortality data with reports of postoperative complications across multiple centers. These initiatives have been complemented by single-center and cross-sectional studies of HRQOL in survivors of pediatric cardiac surgery, and they have shown poorer HRQOL in patients with more complex disease.,, However, prospective multicenter studies of postoperative HRQOL related to morbidity are lacking. A strength of our study was the heterogeneous sample and prospective multicenter data collection, thus increasing the potential for our findings to be generalizable. Nonetheless, generalizability is influenced by the sample characteristics: in previous retrospective studies, complex congenital heart disease has been linked to worse HRQOL, and more privileged sociodemographic characteristics have been linked to better HRQOL.,

Neurologic Events and Neurodevelopmental Surveillance

In earlier stages of our research, parents and other stakeholders reported that neurologic events were the morbidity they were most concerned about. The rate of acute neurologic events was very low, and it did not enable us to look at the impact of this morbidity in isolation. However, there were higher rates of scores suggestive of potential anxiety in this group at 6 months. There is a wealth of data on neurodevelopmental sequelae of cardiac surgery in the longer term,, but our measurement of acute neurologic events during the perioperative period was not able to capture the extent of this morbidity. Our findings nonetheless support the recommendation of regular neurodevelopmental surveillance after hospital discharge.

Rehabilitation After Heart Surgery

Physical HRQOL was most severely affected. This finding may relate to the physical demands and effects of living with a complex heart defect, and it is consistent with other studies.,, As could be expected, children’s physical HRQOL improved over time as they recovered after surgery. There is growing interest in the area of rehabilitation after critical illness and surgery in children, and our study supports this interest for pediatric cardiac surgery.

Psychological Support

A high proportion of parents whose children had morbidity had scores suggestive of anxiety, and to a lesser extent depression, at 6 weeks, in line with previous findings. Of interest, depression scores in the ECLS and multimorbidity groups increased between 6 weeks and 6 months, likely related to the residual effects of these morbidities. There have been relatively few trials of psychosocial interventions for parents of children with congenital heart disease, and provision of psychological support varies. Although all centers in the United Kingdom offer psychological support, it is unlikely that the needs of all parents are recognized and met. The use of screening tools such as the PHQ-4 may facilitate early, targeted referral.

Feeding Problems

“Feeding problems” were reported as a common morbidity, identified by our lay advisers as particularly important. The negative impact on parents and the challenges of feeding babies with congenital heart disease are widely reported in the literature, with some parents reporting that feeding problems after discharge overshadow any other cardiac concerns. Children requiring tube feeding are also more likely to experience neurodevelopmental delay, which may also contribute to parental anxiety. Our results support these findings as indicated by the higher anxiety scores in this group at 6 months.

Study Limitations

Although we recruited 60% of eligible patients and had a high response rate, those patients who died or who were sickest could not participate, thus introducing a source of bias. The measures we used required at least 1 parent to speak English, and this may have contributed to the relatively high proportion of White British families and also introduces a further source of bias. We found a lower than anticipated incidence of some specific morbidities, and this prevented us from exploring links between single morbidities and outcome. The prospective, observational design of the study limits the interpretation of our findings to inference rather than direct attribution of cause. A further potential limitation is the use of a generic measure (PedsQL), which is less able to discriminate among severity levels of a condition than a disease-specific measure. Finally, all outcome data were provided by parents because most of the children (92.4%) were younger than 5 years of age.

Conclusion

Postoperative morbidities significantly affect patient and family well-being early after pediatric cardiac surgery, although they improve over 6 months. Family psychological support and efforts at holistic rehabilitation are important for patients with postoperative morbidities. Patients and families should be appropriately prepared before surgery for the risk and consequences of morbidities because normalizing experiences and managing expectations may help to reduce anxiety and depression. In addition, investigation is warranted to understand and learn from families who report coping well through their cardiac surgical pathway and hence aid the design of effective psychosocial support strategies. Finally, ensuring that non–English-speaking families are able to access appropriate information and support needs to be addressed. Further longitudinal research now needs to be undertaken to identify the longer-term impacts of surgical morbidities, to monitor how HRQOL and parental anxiety and depression change over time, and to inform the implementation of appropriate screening and intervention programs for at-risk groups.