Health-related quality of life of children born with very low birth weight and their caregivers in China: a cross-sectional survey

Abstract

Background

Very low birth weight (VLBW) poses a significant global health burden. Despite improved survival, the health-related quality of life (HRQoL) of VLBW survivors and their caregivers, particularly in China, where incidence is rising, remains largely unassessed. Therefore, we conducted this study aiming to assess and describe the HRQoL of children who were born with VLBW in China, as well as that of their parental caregivers, which will contribute to the limited body of evidence regarding the dyadic HRQoL of VLBW children and their caregivers in low- and middle-income settings.

Methods

A total of 241 parental caregivers were recruited from a children’s hospital. HRQoL was measured using the proxy-reported Pediatric Quality of Life Inventory (PedsQL) Infant Scales and Generic Core Module (GCM) for children, and the PedsQL Family Impact Module (FIM) for caregivers. Statistical analyses included t-tests, analysis of variance (ANOVA), effect sizes, multivariate linear regression, and Pearson correlation.

Results

The median child age was 2.0 years and the median birth weight was 1,032.5 grams. For children aged 1–24 months, financial burden, home oxygen use, and parent-reported developmental problems were significantly associated with children’s HRQoL (P<0.05). For children aged 2–7 years, developmental problems were significantly associated with HRQoL (P<0.05). Caregiver HRQoL was associated with child age, maternal employment, financial burden, oxygen dependency, and developmental issues (P<0.05). Child and caregiver HRQoL were significantly correlated (P<0.05).

Conclusions

The study highlights HRQoL profiles of VLBW children and caregivers, emphasizing modifiable factors such as maternal employment, financial strain, oxygen dependence, and developmental problems. These findings should inform targeted care strategies to improve outcomes for both groups.

Highlight box.

Key findings

• This study found significantly impaired health-related quality of life (HRQoL) in very low birth weight (VLBW) infants (<2 years) compared to healthy peers, with scores showing a catch-up trend in early childhood (2–7 years). Child and caregiver HRQoL were both significantly associated with modifiable factors including perceived financial burden, home oxygen dependency, and parent-reported growth/developmental problems. A strong correlation was observed between child and caregiver HRQoL.

What is known and what is new?

• Evidence from developed countries has established that VLBW is a significant risk factor for impaired HRQoL in survivors.

• This study provides the first comprehensive assessment of HRQoL in a Chinese VLBW cohort, highlighting a significant early impairment followed by recovery in childhood. It newly identifies the profound correlation between child and caregiver HRQoL in this context and pinpoints culturally relevant, modifiable risk factors such as maternal unemployment and perceived financial burden, which are critical for designing targeted interventions.

What are the implications, and what should change now?

• The findings advocate for a shift towards integrated, family-centered care. Clinical practice should implement systematic screening for caregiver distress and socioeconomic hardship. Policymakers and healthcare systems must develop tailored support strategies, including financial assistance, psychological counseling, and prioritize early intervention services, to help VLBW children and their families thrive beyond survival.

Introduction

Low birth weight and short gestation constitute substantial contributors to the global disease burden. They are ranked as the fifth leading risk factor for disability-adjusted life years (DALYs) among children under 14 years, accounting for 5.6% of total DALYs (1). In particular, very low birth weight (VLBW) infants, defined as those with a birth weight of less than 1,500 grams, experience significantly increased mortality risk after birth; 60–70% of VLBW infants develop at least one major complication (e.g., respiratory distress syndrome, bronchopulmonary dysplasia) during hospitalization (2). Additionally, they are more likely to experience long-term consequences such as neurodevelopmental impairment (3), diabetes and cardiovascular diseases (4) compared to individuals with normal birth weight.

The incidence of VLBW varies worldwide, and it remains a significant public health concern. In China, the incidence of VLBW has demonstrated a gradual increase, rising from 0.7% in 2010 to 0.8% in 2018 (5). This upward trend corresponds with increasing recognition of the health burdens associated with VLBW. Notably, over 70% of Chinese VLBW infants experience extrauterine growth restriction (EUGR), a condition associated with long-term metabolic and neurocognitive deficits (6). Despite advancements in neonatal intensive care that have reduced mortality rates, survivors often require extended multidisciplinary follow-up, placing substantial economic burdens on families and healthcare systems. Although survival rates have improved, the dual challenges of impaired child development and caregiver distress highlight the critical need to assess health-related quality of life (HRQoL), an approach that remains underexplored in low- and middle-income settings.

HRQoL refers to the influence of an individual’s health status on their overall well-being and functional capacity across diverse life domains (7,8). It is a subjective concept and encompasses multiple dimensions, taking into account how these factors influence physical, psychological, and social functioning as well as the individual’s overall health perception (7). Evaluations of HRQoL offer valuable supplementary insights beyond traditional health outcomes like morbidity and mortality (9). Over the past three decades, there has been an increasing scientific focus on the short- and long-term HRQoL outcomes for VLBW survivors. A substantial body of evidence from developed countries indicates that VLBW children experience significantly impaired HRQoL compared with their normal birth weight peers, with enduring deficits observed in physical, cognitive, and psychosocial domains (10-15). While advancements in neonatal intensive care have markedly improved survival rates for this vulnerable population, these successes have paradoxically shifted clinical challenges from the prevention of acute mortality to the management of chronic morbidity and the provision of family support (16). The birth of a VLBW infant represents a significant biopsychosocial stressor for families, with maternal caregivers facing notably higher risks of postpartum depression, chronic fatigue, and socioeconomic instability compared to mothers of infants born with normal birth weight (16,17). Emerging evidence suggests that cultural factors may influence the caregiving burden, but significant gaps remain in understanding how these dynamics unfold within China’s unique sociocultural context. Guided by the Family Stress Model, we hypothesized that the biological vulnerability of VLBW infants, combined with external stressors such as financial burden and caregiving demands (e.g., home oxygen therapy), creates a cascading effect on both child development and caregiver well-being. This framework justifies our inclusion of socioeconomic variables and clinical complications as potential determinants of the dyadic HRQoL.

Despite China’s leading survival rates for VLBW infants following the modernization of neonatal intensive care units (NICUs), there is a notable lack of systematic evaluation of HRQoL outcomes for both these children and their caregivers. Therefore, we conducted this study aims to assess and describe the HRQoL of children who were born with VLBW in China, as well as that of their parental caregivers, which will contribute to the limited body of evidence regarding the dyadic HRQoL of VLBW children and their caregivers in low- and middle-income settings. We aim to inform the development of culturally tailored intervention strategies that optimize the HRQoL of VLBW survivors while preserving family functioning, so that VLBW infants and their families may not simply survive but thrive. We present this article in accordance with the STROBE reporting checklist (available at https://tp.amegroups.com/article/view/10.21037/tp-2025-aw-812/rc).

Methods

Study design and participants

This cross-sectional study was conducted by the Department of NICUs at the Children’s Hospital, Zhejiang University School of Medicine in Hangzhou, China. Participants were recruited from a WeChat Group that functioned as an online community for pediatric patients born with VLBW. WeChat is a Chinese instant messaging, social media, and mobile payment app. The WeChat group was managed by nurses from the NICU and provided professional care guidance for caregivers of children with VLBW. It served as a primary online platform for peer support and informal follow-up for families of VLBW infants discharged from our NICU. The primary caregivers who were familiar with their children’s health were invited to fill out an electronic questionnaire. The criteria for inclusion were caregivers whose children were alive, aged 0–8 years, and born with VLBW, and who possessed sufficient Chinese reading/writing competency for questionnaire completion. Caregivers who were not willing or able to fill out the electronic questionnaires were excluded from the study. A convenience sampling strategy was employed, aiming for an exhaustive recruitment of all eligible families. This online survey was conducted from November 1, 2024 to February 2, 2025. At the time of data collection, the group consisted of 321 eligible families who met the inclusion criteria. The electronic questionnaire was distributed via a group announcement and remained open for 4 weeks. A total of 241 caregivers consented to participate in the study and completed the questionnaire resulting in a response rate of 75.1% (241/321).

Ethical approval statements

This study was conducted according to 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 (No. 2024-IRB-0297-P-01). All patients’ guardians consented and voluntarily participated in the study.

Data collection

Data were collected via a self-developed electronic questionnaire filled out by the primary caregivers. This questionnaire was designed based on literature review and expert opinions, including questions on general and clinical characteristics of children and their families, HRQoL of children, and HRQoL of their caregivers. It was created by a research assistant (L.G.) using a free website called Wenjuanxing (https://www.wjx.cn/), which is commonly-used to make questionnaires for online surveys in China. A QR code was generated for caregivers to fill out via their mobile phones. A pilot study was conducted by inviting 15 caregivers to fill out the questionnaire. We revised the questionnaire based on the feedback provided by the pilot group. From November 17, 2024, we distributed the final version of the questionnaire on the WeChat group. If the caregivers had any questions while filling out the questionnaire, they were able to contact the research coordinator (F.L.) on the group. The completed questionnaires were then reviewed and verified on a weekly basis by two research assistants (L.G. and M.G.) to ensure data integrity.

Measurements

The information gathered by the questions covered general characteristics, clinical characteristics, children’s HRQol and caregiver’s HRQoL. The information on general characteristics included the children’s age and gender, parents’ educational level, household income, employment status of parents, perceived financial burden due to the disease and therapy, and whether adequate assistance was being received. The information on clinical characteristics were the children’s birth weight, gestational age at birth, weight at discharge, length of hospital stays, complications, surgery, whether oxygen had to be used at home, readmission to hospital after discharge, and parent-reported current growth and development problems.

Children’s HRQoL was measured by the proxy-reported, age-appropriate versions of Pediatric Quality of Life Inventory^TM (PedsQL^TM). In the present study, we used the versions for children aged 1–12 months, 13–24 months, 2–4 years and 5–7 years. For children aged 0–12 and 13–24 months, the PedsQL^TM Infant scales that were applied encompassed five scales: physical functioning, physical symptoms, emotional functioning, social functioning and cognitive functioning. For children aged 2–7 years, PedsQL^TM 4.0 Generic Core Module (PedsQL^TM 4.0 GCM) was used, including four scales: physical functioning, emotional functioning, social functioning, and school functioning. The recall period was limited to the past month. Both instruments had been translated into Chinese and validated in China, demonstrating good reliability and validity (18,19).

Caregiver HRQoL was assessed using the PedsQL^TM 3.0 Family Impact Module (PedsQL^TM 3.0 FIM). Again, the recall period was limited to the past month. PedsQL^TM 3.0 FIM contained 36 items across six scales: physical functioning (six items), emotional functioning (five items), social functioning (four items), cognition functioning (five items), communication (three items), worry (five items), daily activity (three items) and family relationships (five items) (18). All of these instruments featured similar scoring algorithms. Response choices were on a scale from 0 to 4 (0= never a problem, 1= seldom a problem, 2= sometimes a problem, 3= often a problem, and 4= always a problem). The 0–4 scale is reversed-scored and transformed to a 0–100 scale (0=0, 1=25, 2=50, 3=75, 4=100). Scale scores and total scores were computed as the sum of the items divided by the number of items answered. A higher score indicates a better HRQoL.

Tables S1,S2 show the Cronbach’s alpha coefficients of PedsQL^TM Infant scales, PedsQL^TM 4.0 GCM and PedsQL^TM 3.0 FIM.

Statistical analysis

All statistical analyses were conducted using SPSS version 27.0 (SPSS Inc., Chicago, IL, USA). Firstly, we applied descriptive analysis to calculate means and standard deviations (SDs) for continuous variables with a normal distribution and medians with interquartile range (IQR) for continuous data with a non-normal distribution. For categorical variables, numbers and percentages were presented. Secondly, we compared the averages of the total score and the scale scores of PedsQL^TM Infant scales and PedsQL^TM 4.0 GCM with the norm average scores of healthy control children derived from the published literature (20,21). Thirdly, we used the two-independent-samples t-tests and one-way analysis of variance (ANOVA) to assess the differences in the average of scale scores and total scores of PedsQL^TM Infant scales, PedsQL^TM 4.0 GCM and PedsQL^TM 3.0 FIM across subgroups regarding the general and clinical characteristics. Furthermore, multivariate linear regression analyses were performed to identify factors associated with HRQoL for both children and their caregivers. Consistent with modern epidemiological recommendations, the selection of independent variables was guided by clinical relevance and the Family Stress Model rather than univariate statistical screening. Seven key biopsychosocial predictors were entered simultaneously into the models using the “Enter” method: child’s age and sex, maternal employment status, parental educational level, perceived financial burden, home oxygen dependency, and parent-reported growth and developmental problems. Lastly, we evaluated the correlations between children’s HRQoL and caregivers’ HRQoL using the Pearson correlation analysis.

A statistical significance was indicated when P<0.05. Despite the statistical significance, we additionally calculate the effect size, i.e., Cohen’s d and partial eta squared (η_p²), to assess the clinical relevance. Regarding the difference between two groups, Cohen’s d was interpreted as follows: 0.2≤ d <0.5, small difference; 0.5≤ d <0.8, moderate difference; and d ≥0.8, large difference (22). Regarding the difference across three or more groups, η_p² is used and is interpreted as follows: 0.01≤ η_p² <0.06, small difference; 0.06≤ η_p² <0.14, moderate difference; and η_p² ≥0.14, large difference.

Results

General and clinical characteristics of the study population

Table 1 presents the general and clinical characteristics of the study population. The median birth weight was 1,032.5 (IQR, 872.5–1,285.0) grams. The median age of children when this survey was conducted was 2.0 (IQR, 1.5–2.7) years and the proportions for each age group (1–12 months, 13–24 months, 2–4 years, and 5–7 years) were 27.4%, 46.1%, 13.7% and 12.9%, respectively. 44.8% were girls and 90.9% of questionnaires were filled out by mothers. Table S3 presents extra clinical characteristics such as diagnosis at admission, complications during hospitalization, surgery and readmission.

Table 1. General and clinical characteristics of the study population (n=241).

Characteristics	Values
Birth weight (gram)	1,032.5 [872.5, 1,285.0]
Weight at discharge (gram)	2,675.0 [2,300.0, 3,300.0]
Gestational age at birth (weeks)	28.0 [27.0, 29.0]
Length of hospital stay (weeks)	12.0 [8.0, 14.0]
Current weight (kilogram)	10.0 [8.3, 13.0]
Current height (centimeter)	80.0 [72.0, 89.0]
Age (years)	2.0 [1.5, 2.7]
Child’s sex
Boy	133 (55.2)
Girl	108 (44.8)
Age group of the child
1–12 months	66 (27.4)
13–24 months	111 (46.1)
2–4 years	33 (13.7)
5–7 years	31 (12.9)
Relationship with the child
Mother	219 (90.9)
Father	22 (9.1)
Maternal educational level
Low	15 (6.2)
Middle	34 (14.1)
High	192 (79.7)
Employment status of mother
Employed	163 (67.6)
Unemployed	78 (32.4)
Paternal educational level
Low	22 (9.1)
Middle	45 (18.7)
High	174 (72.2)
Household income per year (RMB)
Less than 100,000	53 (22.0)
100,000 to 199,999	46 (19.1)
200,000 to 500,000	83 (34.4)
More than 500,000	18 (7.5)
Unknown	41 (17.0)
Perceived financial burden due to the disease and therapy
No	100 (41.5)
Yes	141 (58.5)
Receiving adequate assistance to take care of the sick child
No	66 (27.4)
Yes	175 (72.6)
Complications during hospitalization
No	75 (31.1)
Yes	166 (68.9)
Surgery during hospitalization
No	120 (49.8)
Yes	121 (50.2)
Bringing oxygen home upon discharge
No	185 (76.8)
Yes	56 (23.2)
Regular health check after discharge from the hospital
Yes	211 (87.6)
No	30 (12.4)
Readmission after discharge from the hospital
Yes	132 (54.8)
No	109 (45.2)
Parent-reported growth and developmental problems
No problem	128 (53.1)
Growth retardation	59 (24.5)
Neurodevelopmental abnormalities	24 (10.0)
Social and emotional issues	22 (9.1)
Learning problem	20 (8.3)
Other problem(s)	23 (9.5)

Values are presented as median [interquartile range] or n (percentage).

Comparison of HRQoL of children born with VLBW with healthy references

Table 2 demonstrates the average scores of scales and total scores of VLBW children’s HRQoL measurements as well as those scores from healthy references that were published in previous articles (20,21). All scale scores, summary score and total score are significantly lower in infants born with VLBW (P values <0.05). Additionally, we compared children’s HRQoL scores across age groups (see Table S4).

Table 2. Comparison of the average scale, summary and total scores of the PedsQL Infant Scales and Generic Core Module between patients and healthy reference.

Item	0–24 months					2–7 years
	Patients (n=177)	Healthy reference† (n=246)	d	P		Patients (n=64)	Healthy reference‡ (n=36)	d	P
Physical functioning	77.79 (19.47)	87.54 (11.16)	0.61	<0.001		85.16 (18.38)	81.25 (11.60)	0.25	0.20
Physical symptoms	72.68 (14.37)	83.45 (10.39)	0.86	<0.001		–	–	–	–
Emotional functioning	71.36 (16.28)	76.59 (13.71)	0.35	0.001		82.73 (18.32)	72.36 (14.66)	0.63	<0.001
Social functioning	85.65 (18.64)	89.62 (14.87)	0.24	0.02		85.94 (19.66)	82.64 (13.44)	0.20	0.32
Cognitive functioning	66.74 (27.21)	83.11 (20.65)	0.68	<0.001		–	–	–	–
School functioning	–	–	–	–		71.60 (29.85)	76.62 (14.34)	0.21	0.26
Psychosocial health summary score	–	–	–	–		80.96 (17.59)	77.30 (10.90)	0.25	0.20
Total score	73.79 (14.37)	82.47 (9.95)	0.70	<0.001		82.54 (16.76)	78.80 (9.70)	0.27	0.16

Values are presented as mean (standard deviation). Effect sizes (Cohen’s d) are indicated as small (0.2≤ d <0.5), medium (0.5≤ d <0.8), and large (d ≥0.8) difference. ^†, healthy reference values for children aged 0–2 years are cited from the study by Varni et al. (23); ^‡, healthy reference values for children aged 2–7 years are cited from the study by Chan et al. (20). PedsQL, Pediatric Quality of Life Inventory.

Associated factors for HRQoL of children and their caregivers

Tables S5,S6 present the comprehensive profiles of differences in average scores of PedsQL^TM Infant scales and GCM, respectively, at scale level and overall level across specific subgroups. For infants, we observed significantly lower HRQoL scores when mothers were unemployed, parents perceived financial burden due to disease and treatment and had inadequate assistance to take care of the child, as well as when children had complications during hospitalization, required regular health checks after discharge, and were readmitted to hospital and presented with growth and developmental problems (P values <0.05). For children aged 2–7 years, HRQoL scores were significantly lower when children brought oxygen home after discharge, were readmitted to hospital and presented with growth and developmental problems (P values <0.05). The effect sizes indicated small to large differences regarding the clinical relevance. Table S7 presents differences in the average total score of PedsQL^TM FIM across subgroups. A statistically lower total score was observed in the following situations: younger age groups, mother being unemployed, parents perceiving financial burden due to disease and treatment, having inadequate assistance to take care of the sick child, having complications during hospitalization, taking oxygen home after discharge, and having growth and developmental problems (P values <0.05). The effect sizes range from 0.08 to 0.59.

Table 3 demonstrates the results from multivariate linear regression analyses to assess the independent associated factors of the HRQoL for infants, children and caregivers. For infants (1–24 months), PedsQL GCM total score was significantly associated with maternal unemployment [β: −4.71; 95% confidence interval (CI): −8.91, −0.50; P=0.03], perceived financial burden (β: −5.14; 95% CI: −9.25, −1.04; P=0.01), home oxygen dependency (β: −6.95; 95% CI: −11.69, −2.22; P=0.004), and parent-reported growth and developmental problems (β: −7.77; 95% CI: −11.82, −3.73; P<0.001). For children aged 2–7 years, parent-reported growth and developmental problems (β: −12.13; 95% CI: −20.66, −3.60; P=0.006) remained the only significant predictor of the child’s HRQoL. Regarding caregivers’ HRQoL, higher scores were significantly associated with the child’s age (β: 2.71; 95% CI: 1.56, 3.85; P<0.001), while lower scores were significantly associated with maternal unemployment (β: −6.88; 95% CI: −11.82, −1.95; P=0.006), perceived financial burden (β: −7.35; 95% CI: −12.04, −2.66; P=0.002), home oxygen dependency (β: −7.51; 95% CI: −12.80, −2.23; P=0.006), and growth and developmental problems (β: −8.09; 95% CI: −12.70, −3.48; P=0.001). The adjusted R² values for the three models were 0.23, 0.28, and 0.25, respectively, indicating a stable model fit across all cohorts.

Table 3. Associated factors for HRQoL of children and their caregivers using multivariate linear regression analyses.

Variable	Total score of PedsQL GCM (age 0–24 months)			Total score of PedsQL GCM (age 25–84 months)			Total score of PedsQL FIM
	β (95% CI)	P		β (95% CI)	P		β (95% CI)	P
Age	2.08 (−0.01, 4.17)	0.052		0.12 (−1.98, 2.23)	0.91		2.71 (1.56, 3.85)	<0.001
Child’s sex
Boy	Reference			Reference			Reference
Girl	1.75 (−2.17, 5.68)	0.38		3.60 (−4.65, 11.84)	0.39		−0.38 (−4.92, 4.16)	0.87
Employment of mother
Yes	Reference			Reference			Reference
No	−4.71 (−8.91, −0.50)	0.03		−0.20 (−9.97, 9.58)	0.97		−6.88 (−11.82, −1.95)	0.006
Parents’ educational level
High	Reference			Reference			Reference
Low and middle	1.49 (−4.18, 7.15)	0.61		−6.33 (−18.29, 5.64)	0.29		−3.29 (−9.76, 3.19)	0.32
Perceived financial burden
No	Reference			Reference			Reference
Yes	−5.14 (−9.25, −1.04)	0.01		3.95 (−4.25, 12.14)	0.34		−7.35 (−12.04, −2.66)	0.002
Bringing oxygen home
No	Reference			Reference			Reference
Yes	−6.95 (−11.69, −2.22)	0.004		−8.77 (−17.99, 0.44)	0.06		−7.51 (−12.80, −2.23)	0.006
Growth and developmental problems
No	Reference			Reference			Reference
Yes	−7.77 (−11.82, −3.73)	<0.001		−12.13 (−20.66, −3.6)	0.006		−8.09 (−12.70, −3.48)	0.001
Adjusted R2	0.23			0.28			0.25

Low and middle education levels refer to below junior college or undergraduate degree, while high education level refers to junior college or undergraduate degree and above. CI, confidence interval; FIM, Family Impact Module; GCM, Generic Core Module; HRQoL, health-related quality of life; PedsQL, Pediatric Quality of Life Inventory.

Correlations between children’s HRQoL and caregivers’ HRQoL

Table 4 shows the results of the Pearson correlation analysis among PedsQL^TM Infant scales, GCM and FIM scores at scale level and overall level. In both age groups, children’s HRQoL was significantly correlated to caregivers’ HRQoL at scale level and overall level, except for the correlation between children’s physical functioning and caregivers’ worry scale, and between children’s school functioning and caregivers’ cognitive functioning (P values >0.05). There were strong correlations between total scores of HRQoL of infants/children and parents’ HRQoL (r=0.68 and r=0.57, P values <0.001, respectively).

Table 4. Correlations between children’s HRQoL and caregivers’ HRQoL.

Children’s HRQoL	Caregivers’ HRQoL
	Physical functioning	Emotional functioning	Social functioning	Cognitive functioning	Communication	Worry	Daily activities	Family relationships	Total score
Infants (0–24 months)
Physical functioning	0.52**	0.46**	0.41**	0.49**	0.51**	0.48**	0.40**	0.42**	0.57**
Physical symptoms	0.43**	0.43**	0.38**	0.33**	0.45**	0.50**	0.37**	0.41**	0.51**
Emotional functioning	0.49**	0.50**	0.40**	0.49**	0.46**	0.48**	0.42**	0.43**	0.56**
Social functioning	0.41**	0.41**	0.36**	0.39**	0.44**	0.40**	0.27**	0.35**	0.47**
Cognitive functioning	0.44**	0.33**	0.31**	0.43**	0.36**	0.40**	0.31**	0.36**	0.46**
Total score	0.59**	0.55**	0.49**	0.58**	0.58**	0.59**	0.47**	0.52**	0.68**
Children (2–7 years)
Physical functioning	0.50**	0.35**	0.37**	0.40**	0.35**	0.23	0.36**	0.32**	0.42**
Emotional functioning	0.46**	0.42**	0.46**	0.45**	0.40**	0.34**	0.27*	0.38**	0.47**
Social functioning	0.60**	0.50**	0.54**	0.58**	0.47**	0.50**	0.47**	0.49**	0.61**
School functioning	0.40**	0.39**	0.32*	0.22	0.32*	0.37**	0.39**	0.47**	0.42**
Total score	0.59**	0.49**	0.50**	0.50**	0.46**	0.41**	0.44**	0.48**	0.57**

*, P<0.05; **, P<0.001. HRQoL, health-related quality of life.

Discussion

This cross-sectional study demonstrates fundamental patterns of HRQoL among Chinese children born with VLBW and their caregivers, while identifying modifiable biopsychosocial determinants across developmental stages. We observed that while infants (<24 months) exhibited global HRQoL impairments, children in the older age group (2–7 years) showed higher HRQoL scores that were comparable to those of healthy references. This study also identified multiple influencing factors that were associated with the HRQoL of VLBW children and their parental caregivers. Furthermore, the study demonstrated a significant correlation between the HRQoL of VLBW children and the HRQoL of parental caregivers.

HRQoL of VLBW children and its associated factors

Our study demonstrated that the HRQoL of VLBW children under the age of two was significantly inferior to that of the healthy population across all domains, as well as their overall HRQoL. The universal HRQoL impairment in infants likely reflects cumulative biological stressors including higher prevalence of neuromotor comorbidities (e.g., cerebral palsy, developmental coordination disorder) and multi-organ immaturity, which globally leads to functional limitations. Additionally, extended hospital stays and medical monitoring unintentionally restrict environmental enrichment, which may exacerbate early socio-cognitive deficits due to sensory-motor deprivation. This is the so-called therapeutic paradox of survival.

In the present study, for children aged 2–7 years, we found their physical, social, and school functioning domains seemed to be comparable to those of healthy children, which was not consistent with previous findings (14,23,24). On one hand, this unexpected finding may be attributed to factors including the efficacy of medical interventions, the child’s intrinsic capacity for recovery, and the support provided by family and environmental contexts (25). Early intervention and rehabilitation can help VLBW children achieve normal functioning, while family and school support systems may offset deficiencies from premature birth (12). Furthermore, the adjustment of caregiver expectations may account for this finding. Caregivers are likely to dynamically recalibrate developmental goals in response to the child’s health status. Notably, the initial parental stress related to concerns about survival transitions into hopeful engagement as medical vulnerabilities decrease (25), particularly as children attain critical developmental milestones (26). The optimism expressed by caregivers likely mirrors this transformative journey from crisis management to the celebration of developmental accomplishments.

Our multivariate analysis revealed that for infants, HRQoL is influenced by multiple socioeconomic and clinical factors. Specifically, maternal unemployment and perceived financial burden were significantly associated with lower infant HRQoL scores. According to the Family Stress Model, material deprivation and financial strain can limit a family’s ability to access essential rehabilitation and nutritional resources necessary for early brain development, while also creating a stressful home environment that negatively impacts the infant’s well-being (27). Furthermore, home oxygen dependency served as a significant clinical predictor in this age group, reflecting the impact of chronic respiratory vulnerabilities (such as bronchopulmonary dysplasia) on the daily physical and emotional functioning of infants (14).

In contrast, for older children (2–7 years), the determinants of HRQoL appeared more concentrated. Parent-reported growth and developmental problems emerged as the sole significant predictor of HRQoL in this cohort. This finding suggests that as VLBW survivors transition into early childhood, their perceived HRQoL becomes less sensitive to early risk factors and is primarily driven by their functional and neurodevelopmental status. Across both age groups, growth and developmental problems remained a consistent threat to children’s HRQoL. In our study, 46.9% of children were reported by their parents to have one or more developmental challenge(s), which aligns with existing evidence that VLBW survivors are at elevated risk for suboptimal cognitive and motor outcomes (28-30). The profound impact of these deficits on HRQoL—particularly the large effect size observed in the older cohort—underscores the imperative for systematic developmental screening and the provision of accessible early intervention services to support VLBW children as they grow.

HRQoL of caregivers of VLBW children and associated factors

Results in both univariate and multivariate regression analysis confirmed that caregivers of older children reported significantly higher HRQoL scores compared to those of infants, aligning with existing literature (14,28). This observed difference is likely associated with the varying health status and functional outcomes across age groups. For families of older VLBW children, the absence or resolution of early neonatal complications and developmental challenges may correspond to lower caregiving demands. Consequently, caregivers in the older child cohort may experience fewer care-related stressors and report more favorable psychological status compared to those currently caring for VLBW infants, who are often in the acute or high-intensity stage of caregiving. In addition, it is important to note that the observed differences between age groups should not be interpreted as a longitudinal recovery trajectory. These findings represent different birth cohorts, and the higher HRQoL scores in the older children (2–7 years) may reflect a survival bias, where only those with more favorable clinical outcomes survived or remained accessible for long-term follow-up.

This study showed that maternal unemployment and perceived financial burden emerged as crucial modifiable determinants of diminished caregiver HRQoL. This correlation can be explained through two interconnected mechanisms. Firstly, unemployed mothers frequently assume primary caregiving responsibilities, which can result in social isolation and intensified psychological distress (31-33). Secondly, maternal unemployment and financial strain present dual socioeconomic challenges (34): diminished household income restricts access to specialized medical care (35), while financial hardship heightens familial conflict (36). These findings emphasize that socioeconomic interventions are as vital as clinical care in preserving family functioning.

Finally, we found that dependency on home oxygen therapy and parent-reported growth and developmental problems were significantly linked to lower caregiver HRQoL. The requirement for supplemental oxygen imposes a heavy burden involving equipment management and emergency readiness, demanding significantly more time and vigilance than typical neonatal care. Similarly, developmental challenges—reported by 46.9% of families—impose complex demands such as managing frequent healthcare appointments and navigating long-term functional limitations (37). These medical and developmental complexities likely exacerbate caregiver fatigue and disrupt social interaction, collectively impairing the overall well-being of the family unit (37).

Correlation between children’s HRQoL and their caregivers’ HRQoL

Our findings reveal substantial correlations between the HRQoL of children and that of their caregivers, both at the domain-specific and overall levels. The majority of scales within the PedsQL^TM Infants Scales, GCM and FIM demonstrate moderate to strong correlations. This pattern is consistent with existing evidence indicating that parents of VLBW children frequently encounter more significant physical and psychosocial health challenges compared to their counterparts with healthy children. These challenges are likely attributable to the extended caregiving demands that affect both the practical and emotional dimensions of family life (14,34,38). Approximately one-third of caregivers demonstrated resilience patterns despite the complex medical needs of their children (25,39). These findings yield two important insights: first, the health status of the child alone is insufficient to fully predict family outcomes; second, the perceptions held by parents regarding their child’s condition—especially their capacity to derive meaning from caregiving challenges—may play a significant role in influencing family adaptation (25,40). Our results underscore the necessity for clinical interventions that address both the health outcomes of the child and the support strategies for caregivers. Future research should focus on longitudinally examining the reciprocal influences of child and caregiver well-being.

Our findings offer essential insights for optimizing care delivery systems for VLBW children. Firstly, the significantly impaired HRQoL of infants and modifiable risk factors enable NICUs teams to develop personalized care protocols. This includes the implementation of structured post-discharge monitoring frameworks to ensure continuity of care and facilitate the early detection of complications. Secondly, our identification of caregiver distress profiles—encompassing psychological, occupational, and financial dimensions—highlights the need for systematic screening of caregivers for stress during follow-up visits. This screening should be complemented by targeted psychological counseling programs and socioeconomic support. The link between growth issues and reduced HRQoL in VLBW children and their caregivers calls for new resource strategies. We recommend creating multidisciplinary teams in pediatric rehabilitation, mental health, and social work. High-risk infants with growth problems should take priority in early intervention programs, such as motor therapy and cognitive stimulation, to minimize long-term disabilities and HRQoL decline. Our findings advocate for policy changes to address systemic barriers faced by VLBW populations. Mandatory insurance should include developmental technologies and essential therapies to prevent care gaps. Socioeconomic measures such as targeted tax relief and community respite care could alleviate caregiving burdens. These steps would collectively establish a comprehensive care continuum from neonatal to long-term health, tackling both biological and structural challenges for this high-risk group.

Strengths and limitations

This study significantly contributes to research on health outcomes for VLBW children and their families in China. This study represents one of the limited investigations assessing the HRQoL of VLBW children and their families, utilizing reliable and validated instruments, specifically the PedsQL Infant scales, GCM and FIM. The sample size comprised 241 caregivers of VLBW children, which, to our best knowledge, constitutes a relatively large survey examined in the context of HRQoL for this population in developing countries. Moreover, we conducted assessments of HRQoL in children under 2 years of age, a population that has been critically understudied due to the lack of reliable and valid instruments, thereby providing unique insights into early developmental stages. Secondly, the present study has measured a comprehensive set of potential determinants of HRQoL of children and parental caregivers. Finally, clinical insights were enhanced by incorporating effect sizes alongside statistical significance, such as P values. Additionally, we compared our HRQoL data with that of healthy controls, offering essential contextualization for interpreting disparities in health outcomes.

However, there are several limitations warranting attention. The absence of norm data of PedsQL^TM Infant scales, GCM and FIM for Chinese children and their caregivers hinders direct comparisons with normative populations. In the present study, we cited the HRQoL data of healthy controls from previously published studies. Secondly, the cross-sectional design limits the ability to draw causal inferences and analyze longitudinal trajectories. Particularly, we have observed differences in caregivers’ HRQoL scores between age-group cohorts rather than tracking a true longitudinal trajectory, which should be interpreted with caution. Because it may reflect birth cohort effects or survival bias, where the older group represents survivors with more favorable outcomes, rather than a definitive “catch-up” trend. Future longitudinal studies are essential to confirm whether a true developmental recovery occurs in the same individuals over time. Thirdly, the use of non-validated items for the assessment of growth and developmental problems compromises measurement precision compared to standardized instruments. Furthermore, due to the lack of socio-demographic information in our hospital’s routine clinical electronic medical record system, we were unable to conduct a quantitative comparison of household characteristics between the study participants and the general VLBW population at our center. Our findings should be interpreted with caution regarding their generalizability to the most marginalized families who may face barriers beyond digital access. Fourth, the sample size of the older child cohort (n=64) was relatively smaller than that of the infant cohort (n=177). While this sample size is substantial for a specialized VLBW follow-up study, the lower sample-to-variable ratio in this subgroup may have limited the statistical power to detect small-to-medium effects that might otherwise reach significance in a larger sample. Consequently, the non-significant findings for certain predictors in the older cohort should be interpreted with caution and warrant further verification in larger multicenter longitudinal studies. Lastly, although we achieved a relatively high response rate of 75.1%, our study may still be subject to selection bias. The participants recruited through the WeChat group might represent a subset of caregivers who are more digitally literate, more engaged in peer support, or perhaps seeking more assistance for ongoing health issues compared to those who did not participate. This may limit the generalizability of our findings to the broader VLBW population who do not utilize online support platforms.

Conclusions

This study delineates the HRQoL profiles of VLBW children and their parental caregivers. It identifies key modifiable factors, including maternal employment status, perceived financial burden due to disease and treatment, home oxygen dependency, and parent-reported growth and developmental problems, which should inform the formulation of comprehensive care strategies. The findings highlight the imperative for family-centered interventions that address pediatric outcomes as well as the psychological burdens encountered by caregivers.

Supplementary

The article’s supplementary files as

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 according to 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 (No. 2024-IRB-0297-P-01). All patients’ guardians consented and voluntarily participated in the study.

Data Sharing Statement

Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-aw-812/dss

tp-15-02-47-dss.pdf ^{(122KB, pdf)}

DOI: 10.21037/tp-2025-aw-812