Proxy-reported health-related quality of life in children with omphalocele: a cross-sectional study in China

Introduction

Omphalocele is a congenital malformation characterized by herniation of abdominal viscera through a defect in the abdominal wall, with an incidence ranging from 1 in 6,000 to 1 in 4,000 live births (1,2). The sac of the omphalocele is composed of peritoneum, Wharton’s jelly, and amnion, and may encompass various organs including intestine, liver, stomach, bladder, uterus and ovary (3,4). The exact etiology of omphalocele remains uncertain; however, it is widely hypothesized that the condition results from the failure of the physiologically herniated intestinal loop to reintegrate into the abdominal cavity by the 11th week of embryonic development. This failure is thought to contribute to the dysplasia of the abdominal wall surrounding the umbilical cord, culminating in the presentation of omphalocele (5). Omphalocele may be caused by a genetic error during embryonic development and is frequently concomitant with other structural malformations and chromosomal abnormalities (6). Consequently, similar to other congenital anomalies, omphalocele is often associated with additional congenital malformations and chromosomal abnormalities, including but not limited to congenital heart disease (7), pulmonary dysplasia (8), trisomy 18 or 21, and Beckwith-Wiedemann syndrome.

Minor omphalocele is typically treated successfully with primary surgery, closing the abdominal wall after removing the amnion. However, giant omphalocele often presents significant visceral-abdominal disproportion, making it difficult to safely return the sac to the abdomen without risking abdominal compartment syndrome (ACS). In such cases, a staged surgical approach or conservative management is typically needed. Staged operations often involve silo reduction, patch repair, and skin flap coverage. Conservative treatment may use drugs like sulfadiazine and povidone iodine on the amnion to aid healing before closing the abdominal cavity surgically (9-11).

The prognosis of omphalocele is contingent upon multiple determinants. Prior research has demonstrated that the survival rate for isolated omphalocele surpasses 90% (12). A retrospective study further revealed that children with omphalocele accompanied by two or more associated malformations exhibited a mortality risk 3.75 times greater than those with isolated omphalocele; and additionally, the presence of chromosomal abnormalities was associated with a tenfold increase in mortality risk (13). Giant omphalocele is associated with increased postoperative complications and a poorer prognosis compared to minor omphalocele (14,15). Overall mortality rates for omphalocele range from 14% to 30% in developed countries and from 41% to 50% in developing countries (16). In addition to the risks and costs associated with surgical intervention, conservative treatment can also be burdensome due to prolonged hospital stays and potential psychological effects resulting from scarring and wound care. These factors collectively have a detrimental impact on the overall quality of life (QoL) of the affected children and their families.

In recent years, the treatment of omphalocele has increasingly prioritized enhancing patients’ QoL through aesthetic repairs and promoting satisfactory growth and development. However, a comprehensive understanding of the disease burden, particularly in terms of QoL among individuals diagnosed with omphalocele, remains insufficient. The existing literature on this specific issue is notably limited and the conclusions are not consistent. For instance, Hijkoop et al. reported no significant difference in QoL between school-age children with omphalocele and healthy controls (17). However, children with giant omphalocele or multiple congenital malformations exhibited potential delays in cognitive function. Additionally, Amin et al. found that the QoL in these children was comparable to those with chronic illnesses, and children with congenital heart disease or cloacal exstrophy experienced poorer QoL (18). Furthermore, children with minor omphalocele expressed greater satisfaction with cosmetic outcomes compared to those with giant omphalocele, although both groups generally maintained a good QoL (19).

Despite growing recognition of health-related QoL (HRQoL) in congenital anomalies, existing studies on omphalocele suffer from limited samples (n=10–31), inconsistent findings, and geographic bias (predominantly high-income countries) (17-21). No study has assessed HRQoL in Chinese children with omphalocele, a critical gap given its higher mortality in developing settings. Our study aims to quantify HRQoL of children with omphalocele using the validated Pediatric Quality of Life Inventory (PedsQL) in a larger cohort (n=124), and to identify modifiable demographic and clinical predictors. This investigation represents the first large-scale assessment of HRQoL in omphalocele within China’s healthcare context, with findings poised to inform targeted interventions that may improve both surgical management strategies and psychosocial support systems for this vulnerable population. We present this article in accordance with the STROBE reporting checklist (available at https://tp.amegroups.com/article/view/10.21037/tp-2025-aw-678/rc).

Methods

Study design and participants

This was a cross-sectional, questionnaire-based survey that was led by the Department of Neonatal Surgery at the Children’s Hospital, Zhejiang University School of Medicine. Participants were primary caregivers of children with omphalocele who visited the hospital from 2016 to 2022. As part of the follow-up protocol, specialists conducted regular telephone consultations and facilitated a nationwide WeChat-based support network where caregivers could discuss clinical concerns and receive timely advice from fellow caregivers and surgical specialists. WeChat groups serve as an efficient digital platform for continuous patient follow-up, enabling real-time communication between clinicians and patients’ caregivers, which facilitates medical consultations, peer support, and remote monitoring.

Inclusion criteria were caregivers whose children: (I) had a confirmed diagnosis of omphalocele (ICD-10: Q79.201) through clinical examination and imaging; (II) received treatment or follow-up care at the Children’s Hospital of Zhejiang University School of Medicine; (III) survived after the initial surgical intervention (either primary repair or staged closure); and (IV) were not with concurrent life-threatening congenital anomalies that could independently significantly impact HRQoL assessments. Exclusion Criteria were caregivers who were (I) with cognitive or language impairments that would compromise their ability to comprehend the questionnaire content; (II) illiterate or unable to complete the survey in Mandarin Chinese; and (III) unwillingness to provide informed consent for participation.

From September 2023 to June 2024, we implemented a comprehensive follow-up system combining digital and traditional modalities. Primary caregivers were initially invited through multiple channels: (I) in-person recruitment during routine outpatient visits; (II) electronic invitations distributed via the hospital’s official WeChat patient management system; and (III) telephone outreach by trained research assistants. The study utilized Wenjuanxing (https://www.wjx.cn/), China’s leading professional survey platform, to host the electronic questionnaire developed by our multidisciplinary team comprising pediatric surgeons (minimum 5 years’ omphalocele management experience) and clinical methodologists.

Ethical approval statements

The study protocol adhered to the principles outlined in the Declaration of Helsinki and its subsequent amendments (22), and received approval from the Medical Ethics Committee of the Children’s Hospital, Zhejiang University School of Medicine (approval No. 2023-IRB-00154-P-01). All caregivers of the patients gave their consents to participate in the study.

Measurements of general and clinical characteristics

General characteristics of children with omphalocele and their caregivers were collected through questionnaire, including child’s age, gender, relationship with the child, marital status, highest educational level of parents, annual household income, residence, medical insurance, cost related to omphalocele treatment, perceived financial burden, and receiving social benefits/subsidies. Clinical characteristics were related to the disease and treatment, collected by questionnaire as well, including maternal age at gestation, gestational age at birth, preterm birth, low birth weight, structural malformations of the child after birth, times of surgeries, self-reported prognosis, current growth and developmental problems of the child.

HRQoL

We assessed children’s HRQoL using age-appropriate PedsQL instruments. For infants aged 1–12 months, we used the 36-item PedsQL Infant Scales assessing five domains: physical functioning (6 items), physical symptoms (10 items), emotional functioning (12 items), social functioning (4 items), and cognitive functioning (4 items) (23). For toddlers aged 13–24 months, we employed the expanded 45-item PedsQL Infant Scales, which maintains the same domains but includes additional items for physiological functioning (9 items) and cognitive functioning (9 items) (23). For children aged 2–4 years, we administered the 21-item PedsQL 4.0 Generic Core Modules (GCM) evaluating four domains: physical functioning (8 items), emotional functioning (5 items), social functioning (5 items), and school functioning (3 items) (24). All instruments were validated in Chinese pediatric populations (25-28). Primary caregivers completed the questionnaires based on the child’s health status in the last month, using a 5-point Likert scale (0= “never a problem” to 4= “always a problem”) that was linearly transformed to a 0-100 scale (0=0, 1=25, 2=50, 3=75, 4=100). Scale and total scores were calculated as the mean of corresponding items, with higher scores reflecting better HRQoL.

Statistical analysis

Firstly, we employed descriptive statistical analysis. For continuous variables with a normal distribution, means and standard deviations were calculated, while for those with a non-normal distribution, medians and interquartile ranges were reported. We calculated numbers and percentages for categorical variables. In the following analysis, children older than 4 years (n=6) were excluded to ensure the consistency of age-appropriate HRQoL and its associated factors. Secondly, we compared the average PedsQL scale scores and total scores with those scores from healthy controls published in the literature. Thirdly, the differences in average scale scores and total score of PedsQL Infants Scales and GCM across subgroups in our study population were compared by applying two-independent-sample t-tests and one-way analysis of variance (ANOVA). Despite of the statistical significance, we additionally calculated effect sizes, i.e., Cohen’s d or partial eta square (η_p²), to evaluate the clinical relevance of the difference in HRQoL scores. Cohen’s d is calculated as the absolute value of the difference in mean scores between two groups divided by the largest standard deviation. The interpretation of Cohen’s d is as follows: 0.2≤ d <0.5 indicates a small effect size, 0.5≤ d <0.8 indicates a moderate effect size, and d ≥0.8 indicates a large effect size (29). η_p² was calculated to estimate the effect size of a difference across three or more subgroups. The interpretation of η_p² is as follows: 0.01≤ η_p² <0.06 indicates a small difference, 0.06≤ η_p² <0.14, a moderate difference, and η_p² ≥0.14, a large difference. Finally, we conducted the multivariate linear regression analysis with stepwise approach by including age, gender, highest educational level of parents, annual household income, cost related to the treatment, receiving social benefits, maternal age at gestation, preterm birth, low birth weight, other malformation, and times of surgeries in the model. All statistical analyses were performed using IBM SPSS Statistics (Version 27.0.1; IBM Corp., Armonk, NY, USA). Statistical significance was defined as a two-tailed p value <0.05.

Results

General characteristics of the study population

Table 1 presents the general characteristics of children and their caregivers included in this study. The median age of children was 2.0 years, and 46.8% were girls; 84.7% of questionnaires were filled out by mothers; 78.2% of parents had a high educational level, i.e., a Bachelor’s degree or above; 88.7% of families lived in urban areas; 96.0% of children with omphalocele received reimbursement of medical costs, and 21.8% received social benefits or subsidies; 4.0% of caregivers reported that it was difficult to afford the cost of treating omphalocele.

Clinical characteristics of children with omphalocele

Table 2 presents clinical characteristics of children with omphalocele. The average maternal age at gestation is 31.8 years, while 24.2% of mothers gave birth to a child with omphalocele at an age older than 35 years; 41.1% of children are reported as preterm births, while 25.0% of children had low birth weight; 46.8% of the children didn’t have any structural malformations after birth; 65.3% of children have undergone one surgery, 26.6% have had two surgeries, and 5.6% have had three or more surgeries. Caregivers rated the prognosis after surgery as good or very good for the majority of patients. Additionally, the current growth and development status of the children is rated as very good for 25.8% of children, good for 41.1%, fair for 26.6%, and bad for 6.5%.

Comparing the mean scores of HRQoL with the health reference

Table 3 presents the means and standard deviations of scale scores and total scores for the PedsQL Infants Scales and GCM in both patients and healthy reference data from the published literature (23,27). For children aged 1–24 months, the total score and scores of certain scales (i.e., physical functioning, physical symptoms, emotional functioning, cognitive functioning) were significantly lower in patients than scores in the healthy controls (p values <0.05) with the effect sizes ranging from 0.33 to 0.86. For children aged 2 to 4 years, the total score and the scores of three scales (i.e., physical, emotional, and social functioning) were statistically significantly higher in patients than in healthy controls (p values <0.05), with effect sizes ranging from 0.53 to 0.94.

Differences in the PedsQL scale scores and total score across subgroups

Table 4 presents the differences in the scale and total scores of PedsQL Infant Scales across subgroups for children with omphalocele aged 1 to 24 months. We did not observe statistically significant differences in scale scores and total scores across subgroups in terms of gender, educational level of parents, household income, cost related to the treatment, receiving social benefits/subsidies, maternal age at gestation, preterm birth, low birth weight, having other malformations and times of surgery (p values >0.05). However, the effect sizes indicate small differences in clinical relevance (0.2≤ Cohen’s d <0.5 or 0.01≤ η_p² <0.06).

Table 5 presents the differences in the scale and total scores of PedsQL GCM across subgroups for children with omphalocele aged 2 to 4 years. Notably, children whose medical costs due to treatment were higher than 100,000 RMB were reported to have relatively low physical, emotional, and school functioning, as well as overall HRQoL (p values <0.05), with effect sizes ranging from 0.12 to 0.15, indicating moderate to large differences. Children with other malformations were reported to have a lower score in social functioning than those without other malformations (p=0.002, Cohen’s d=0.85). Children who had two or more surgeries were reported to have lower scores on emotional functioning than those who had one or fewer surgeries (p=0.02, Cohen’s d=0.76).

Determinants of the overall HRQoL of children with omphalocele

Table 6 shows the results of a multivariate linear regression analysis examining factors associated with HRQoL of children with omphalocele. Using stepwise regression (entry: p<0.05), age and the presence of other malformations were identified as significant predictors of overall QoL. Specifically, age was positively associated with GCM total scores (β=5.49, 95% CI: 3.38 to 7.60, P<0.001), indicating that older children tended to report higher QoL. In contrast, the presence of other malformations was negatively associated with GCM total scores (β=−6.78, 95% CI: −12.49 to −1.07, P=0.02) relative to those without additional malformations. The adjusted R² for the model was 0.202, suggesting that these variables explained approximately 20.2% of the variance in PedsQL GCM total scores.

Discussion

This study provides the first systematic evaluation of proxy-reported HRQoL in a Chinese pediatric omphalocele cohort, establishing preliminary national benchmarks for this congenital anomaly population. Our findings reveal an age-dependent HRQoL pattern: patients below age 2 years exhibited impaired HRQoL compared to healthy children, whereas the 2–4-year cohort showed comparable or better outcomes. Notably, we identified significant HRQoL disparities among children aged 2–4 years, with poorer outcomes associated with greater financial burden, associated congenital anomalies, or multiple surgical procedures. Furthermore, HRQoL in children with omphalocele demonstrated a positive correlation with advancing age, whereas the presence of comorbid congenital anomalies exerted a significant negative impact on HRQoL outcomes. By establishing China-specific HRQoL profiles, this study addresses a critical gap in international pediatric surgery outcomes research and extends beyond existing Western cohort studies.

Our analysis revealed significantly impaired HRQoL across multiple domains (physical functioning, physical symptoms, emotional functioning, and cognitive functioning) in patients with omphalocele aged 1–24 months compared to healthy controls, with particularly large differences in physical symptoms (d=0.86). A small but significant cognitive deficit was observed (d=0.33), consistent with prior reports of neurodevelopmental risks in congenital anomaly populations (30). The clinical course of omphalocele—typically involving staged surgical repairs, prolonged neonatal intensive care unit (NICU) stays (31), and management of associated anomalies—may synergistically compromise physical and psychological well-being through procedural stress, environmental deprivation, and pain/discomfort (15). Notably, the observed cognitive differences likely reflect surgical disruptions during critical neurodevelopmental windows, limited early stimulation due to hospitalization (31), and nutritional challenges from concomitant gastrointestinal anomalies (32). These findings advocate for integrated care models that concurrently address surgical reconstruction and structured neurodevelopmental surveillance, aiming to mitigate long-term cognitive impacts.

Our study revealed a counterintuitive pattern wherein children with omphalocele aged 2–4 years exhibited superior HRQoL in physical, emotional, and social functioning compared to healthy controls, with only school functioning remaining comparable. This phenomenon may be explained by a dual adaptation mechanism. Caregiver expectation recalibration occurs when prolonged medical engagement leads families to prioritize survival over developmental milestones, causing them to perceive normative achievements as significant improvements. Additionally, the positive outcomes of surgical interventions not only contribute to the child’s physical recovery but also triggers post-surgical psychological rebound by providing the child with a complete abdominal wall and a reconstructed umbilical region, which can improve body image and enhance social confidence in young patients.

Among infants and toddler patients aged 1–23 months, we found that no variables reached statistical significance in subgroup analyses (likely due to limited sample size), while effect sizes suggest small differences in terms of clinical meaningfulness. Specifically, children of highly-educated parents showed marginally better HRQoL across subdomains (d=0.19–0.40), aligning with existing literature on parental education and chronic disease management (33). When parents are well-educated about their child’s condition, they are better equipped to provide effective care, improve treatment adherence, and help their child achieve better health outcomes.

Our findings identified relatively low HRQoL among children aged 2-4 years with greater medical costs, associated congenital anomalies, and multiple surgical procedures. First, financial strain may limit access to timely interventions (e.g., rehabilitation therapies) and exacerbate family stress, indirectly impacting the child’s HRQoL. Second, the presence of additional anomalies (e.g., cardiac or chromosomal defects) likely compounds medical complexity, prolonging recovery and restricting developmental opportunities. Third, repeated surgeries—while often medically necessary—may disrupt critical neurodevelopmental windows, delay school integration, and heighten psychological distress. These results align with the cumulative risk model observed in other congenital conditions (34), where socioeconomic and clinical factors interact to amplify long-term morbidity. Importantly, the persistence of disparities in this age group—despite surgical “success”—highlights the need for multidisciplinary transition programs that integrate financial counseling, developmental monitoring, and psychosocial support alongside routine surgical follow-up.

To explore the associated factors of HRQoL, a multiple linear regression model was constructed, adjusting for potential confounders such as age, gender, family income, birth weight, other malformations, and number of surgeries, etc. We found that age is a significant positive predictor of HRQoL in children with omphalocele and the presence of other malformations was identified as a significant negative predictor. HRQoL in children with omphalocele improves as they grow older, which is in agreement with earlier reports (17,19). Baerg and Munoz (15) found that children with omphalocele experienced difficulty gaining weight and decreased height during the first few years after birth. However, their nutritional status improved over time. Dunn and Fonkalsrud (35) conducted a longitudinal cohort study of 31 infants with omphalocele, with 77% (n=24) available for follow-up evaluation. Participants were maintained on age-appropriate dietary regimens for a mean duration of 4.6 years. This can serve to mitigate the distress experienced by parents at the onset of caregiving for an infant with omphalocele. Moreover, the presence of other congenital structural malformations in children with omphalocele significantly compromises their HRQoL. This adverse impact is often attributed to factors such as the need for multiple surgical procedures, prolonged hospitalizations, and intensive postoperative care, all of which can disrupt the child’s daily routines and emotional well-being. Furthermore, the comprehensive treatment imposes a substantial financial burden and caregiving burden on the family, contributing to heightened psychological distress among parents. This parental stress can, in turn, negatively affect the child’s overall health and developmental outcomes.

Strengths and limitations

There are several notable strengths in this study. Firstly, to our best knowledge, this is the pioneering investigation of HRQoL in Chinese children with omphalocele, providing crucial reference data particularly for infants (0–2 years) and preschoolers (2–4 years) using the validated PedsQL Infants Scales and GCM. Secondly, the sample size of this study was relatively large, with 124 caregivers completing the questionnaires. Notably, our center achieved a remarkably low mortality rate of 4.5% for omphalocele cases, significantly surpassing the mortality from the Chinese national birth defects monitoring network, reflecting the effectiveness of our standardized perinatal-surgical management protocol. Thirdly, our tertiary referral center receives patients from all over China, reflecting a nationally representative case distribution. Last but not least, we analyzed a comprehensive range of potential factors affecting HRQoL in children with omphalocele, including subgroup comparisons with effect sizes for PedsQL scores.

Some limitations of this study should be noted as well. First, selection bias may exist due to our recruitment approach. The exclusive use of digital follow-up likely skewed participation toward caregivers with higher education and health literacy. Second, the cross-sectional design precludes causal inference regarding observed HRQoL determinants. Future longitudinal studies should utilize multi-center recruitment to achieve a larger sample size, which will be essential to validate, extend, or challenge the findings of the present study.

Conclusions

The present study conducted a thorough assessment of HRQoL of Chinese children with omphalocele for the first time. It identifies age-specific patterns: infants/toddlers (1–24 months) show significant impairment, while preschoolers (2–4 years) demonstrate post-surgical rebound. Financial burden, associated anomalies, and repeated surgeries are key modifiable risk factors of HRQoL among children aged 2–4 years. Future longitudinal studies are needed to confirm these findings.

Acknowledgments

We gratefully thank all the parental caregivers of children with omphalocele who participated in the present study and provided valuable data on health-related quality of life of their children. We also thank all the clinicians, nurses, researchers and volunteers who contributed to the data collection. In addition, we thank all members of the Pediatric Evidence-based Medical and Clinical Laboratory, an internal institute in the Children’s Hospital, Zhejiang University School of Medicine, for the interesting discussions and significant contributions on methodology of this study.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-aw-678/rc

Data Sharing Statement: Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-aw-678/dss

Peer Review File: Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-aw-678/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-2025-aw-678/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study protocol was approved by the Medical Ethics Committee of the Children’s Hospital, Zhejiang University School of Medicine (approval No. 2023-IRB-00154-P-01). All caregivers of the patients gave their consents to participate in the study.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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