Growth hormone (GH) deficiency (GHD) in the pediatric population causes short stature [1]. Children affected by GHD have also been reported to have worse quality of life, cognitive function, and fatigue than those with normal height [2,3]. Short stature in children is also associated with anxiety, depression, and social withdrawal [4-11]. Importantly, recent findings suggest that poor emotional well-being and health-related quality of life (HrQoL) of caregivers and/or parents are also negatively related to children’s HrQoL, particularly in the context of pediatric health conditions.

These children’s families are responsible for managing the disease. Within the family, family caregivers are the ones managing its treatment (daily injections of recombinant human GH) and the children’s mental health. Caring might be burdensome and challenging [12,13], exposing the family caregiver to the risk of developing psychological problems [14]. Indeed, parental stress has been described as one of the consequences of managing GHD in children, leading to poorer adherence to GH therapy (GHt) and an impact on their environment and health [15,16]. Overall, family caregiver fatigue has been found to significantly impact the well-being of the caregiver and the patient living with a chronic condition [17]. However, the impact of the family caregiver specifically on GHDs remains unclear [18,19].

Digital health (DH) solutions are transforming the health care sector, as they can be a cost-effective option that allows accessible family-centered and personalized interventions. Indeed, mobile interventions have been proven effective in supporting caregivers in the management of chronic conditions [20]. One such innovation is the Easypod system, an electronic, fully automated device designed to streamline the GH treatment process. This system provides reliable real-time injection data, enabling health care providers to monitor patients’ progress and make more informed treatment decisions. By identifying nonadherent patients earlier, the Easypod allows for more targeted support, enhancing both treatment adherence and outcomes [21].

The Adhera Caring Digital Program (ACDP) is a comprehensive, digitally delivered program designed to support the physical and mental well-being of family caregivers of individuals with chronic conditions. It aims to improve self-management and health outcomes for both the patient and their family caregiver [22]. The ACDP includes access to a mobile app for family caregivers, which is integrated into an artificial intelligence–powered platform that includes integrated data from injector devices, as well as tools for supporting clinicians to follow up on the health of the families.

This study aimed to evaluate the clinical feasibility of a digital intervention to support families by focusing on caregivers of children undergoing GHt and its impact on treatment adherence.

GHt for children is a critical yet challenging process that often demands significant effort from family caregivers. The burden of managing GHt can negatively impact the psychological well-being of caregivers and adherence to the treatment protocol, which, in turn, affects the health outcomes of the children undergoing treatment. This challenge necessitates the development of effective support systems for caregivers to ensure better adherence and overall health outcomes.

Recent advancements in digital health interventions have shown promising results in supporting caregivers of children with chronic conditions, including those undergoing GHt. Studies have demonstrated that digital tools can provide substantial benefits by improving treatment adherence and enhancing the mental health of caregivers. For instance, a recent study by Dimitri et al (2021) [23] found that digital interventions could significantly enhance treatment adherence in children with GHDs by providing real-time support and monitoring capabilities.

In another study, Savage et al [13] highlighted the transformative potential of DH platforms in pediatric endocrinology, emphasizing how patient-generated data and interactive support can lead to more integrated and personalized care models. This approach improves not only adherence but also the overall quality of care provided to patients.

The mental health and well-being of caregivers are crucial factors in ensuring successful GHt management. Zhai et al [24] reported the positive impact of DH interventions on reducing caregiver stress and anxiety, which, in turn, improved their ability to manage the treatment regimen effectively [24]. These findings underscore the importance of addressing the psychological needs of caregivers through innovative digital solutions.

Additionally, Lorca-Cabrera et al [25] explored the role of mobile health applications in supporting self-management and emotional well-being among caregivers. Their research showed that these applications could reduce the psychological burden on caregivers, thereby improving their overall quality of life and enhancing their capacity to support their children’s treatment [25].

The ACDP builds upon these foundations by offering a comprehensive digital health intervention designed to support the physical and mental well-being of caregivers managing children undergoing GHt. This study aims to evaluate the clinical feasibility of ACDP and its impact on treatment adherence, contributing to the growing body of evidence supporting the integration of DH solutions in chronic disease management.

Family caregivers (ie, parents) of children with suboptimal adherence to GHt were recruited to the study at the Pediatric Endocrinology Unit at the Miguel Servet Children’s University Hospital and were provided with access to the ACDP for 3 months. The protocol was prospectively registered in ClinicalTrials.gov (NCT04812665).

Participants were assessed twice (at recruitment and at 3 months’ follow-up). The data collected were (1) demographic data (only at recruitment); (2) positive mood assessed with the Positive and Negative Affect Schedule (PANAS) [26]; (3) distress assessed using the Depression Anxiety and Stress Scale-21 (DASS-21) [27], general well-being assessed using the Mental Health Continuum Short Form (MHC-SF) [28], and self-efficacy assessed using the Generalized Self-Efficacy Scale (GSES) [29]; (4) HrQoL assessed using the KIDSCREEN-10 [30] and the Quality of Life in Short Stature Youth (QoLISSY) [31]; and (5) GHt adherence (%) by Easypod-Connect.

The inclusion criteria were as follows:

Only one legal guardian per child can participate in the study.

The ACDP is a noninvasive, digitally delivered intervention designed to support family caregivers of children with chronic conditions. Specifically tailored for the context of GHt, the ACDP offers condition-specific educational content, evidence-based caregiving strategies, and self-management tools to help caregivers monitor progress and remain engaged with their child’s treatment. To promote emotional well-being and adherence, the program delivers personalized motivational messages generated by an artificial intelligence–driven health recommender system. This system tailors its recommendations using both objective and patient-reported data: objective adherence data are collected via Easypod-Connect, an electronic auto-injector device that monitors and transmits GH administration data, while patient-reported outcomes are assessed at baseline and at 3-month follow-up using validated psychometric instruments (see Table 1). The ACDP is part of the Adhera Health Precision Digital Companion Platform [32], which has been developed using the best practices regarding data protection and quality management in accordance with the ISO (International Organization for Standardization) 27001 and ISO 13465 guidelines.

Participants’ questionnaire answers were digitally recorded through a Microsoft Forms form and extracted to a Microsoft Excel database. Descriptive analysis (means, SDs, and percentages) was used for demographic data. After checking the normality of each variable, pre-post P values of the psychometrics’ parameters were checked using the Student t and Wilcoxon tests.

This study protocol was reviewed and approved by the Spanish Ethics Committee C.P.-C.I. PI20/494. Written informed consent was obtained from participants (or their parent/legal guardian/next of kin) to participate in the study.

The privacy and confidentiality of all research participants were strictly maintained; all data were de-identified before analysis, and no personally identifiable information was collected or reported. Participants were not compensated for their participation in this study.

A total of 65 parents provided informed consent. Of these, 14 were excluded from the analysis, as they did not access the digital intervention. The final sample’s (n=51) characteristics are described in Table 2. Participants were 42.14 (SD 5.78) years old on average, and the sample mostly comprised women (n=35, 68.6%). The average age of the child taken care of was 7.9 (SD 2.9) years, receiving GHt for 36.51 (SD 28.43) months. Regarding the education level, 15 (29.4%) caregivers hold a university degree, 20 (39.2%) have professional training, 12 (23.5%) finished high school, and 4 (7.8%) finished primary school.

The management of children undergoing GHt has been reported to be burdensome [14]; specifically, it can be a time-consuming and exhausting process as family caregivers need to (1) ensure that their children receive the injections at the right time and at the correct dosage while providing emotional support and (2) address any mental health issues that may arise. Family caregivers’ fatigue and stress can negatively influence treatment adherence and the child’s health [14,15]. This research contributes to the emerging work in supporting family caregivers of children undergoing GHt using digital tools [28] by showing that the ACDP can effectively empower family caregivers of children with GHD, including improvements in the well-being of both parents and children while promoting self-management of the condition.

Participants have reported a better quality of life and general health, as well as improvements in key points such as cognitive symptoms, mood, and emotional and social well-being. Most families involved in the study achieved optimal levels of adherence after the study. We found a statistically significant increase in positive affect (from 30.78, SD 7.27 at baseline to 36.53, SD 8.65 at the 3-month follow-up) with a statistically significant decrease in negative affect (from 18.98, SD 6.02 to 14.57, SD 4.18), which was measured using the PANAS. Also, the MHC-SF revealed a statistically significant increase in general well-being (from 0.62, SD 0.17 to 0.69, SD 0.21), social well-being (from 0.52, SD 0.19 to 0.65, SD 0.22) and general self-efficacy (from 31.31, SD 5.51 to 33.43, SD 5.31), with an increase in emotional (from 0.67, SD 0.20 to 0.71, SD 0.20), and psychological well-being (from 0.67, SD 0.18 to 0.72, SD 0.23). KIDSCREEN-10 revealed a statistically significant increase in HrQoL (from 49.19, SD 10.82 at baseline to 60.89, SD 16.86 at the 3-month follow-up) and a statistically significant increase in general health (3.43, SD 0.81 to 4.22, SD 0.81). Regarding the quality of life of youths with short stature, we found a statistically significant increase in scores on the physical scale (from 75.57, SD 19.51 to 81.94, SD 18.38), social scale (from 69.83, SD 20.35 to 77.72, SD 18.15), coping scale (from 40.98, SD 17.25 to 48.48, SD 21.32), height-related beliefs scale (from 8.31, SD 25.96 to 66.30, SD 28.20), treatment scale (from 53.54, SD 17.77 to 67.37, SD 21.93), and child’s future scale (from 73.63, SD 25.57 to 82.65, SD 17.98), as well as an increase in HrQoL (from 74.94, SD 15.93 to 80.67, SD 14.46), and emotional scale (from 79.41, SD 15.07 to 82.35, SD 13.53). Lastly, we found statistically significant increases in growth rate on the child’s short stature on the family’s section of the QoLISSY (from 68.45, SD 18.94 to 77.72, SD 18.20) and treatment adherence (from 80.27, SD 4.77 to 88.98, SD 9.84).

Our findings show that at baseline, 21.56% (n=11) of caregivers reported depression symptoms, categorized as mild (11.76%, n=6), moderate (7.84%, n=4), and extremely severe (1.96%, n=1). Post intervention, depression was reduced to only severe (1.96%, n=1). Anxiety levels at baseline were mild (7.84%, n=4), moderate (13.73%, n=7), and severe (1.96%, n=1) for 23.53% (n=12) of caregivers. After the intervention, 11.76% (n=6) of caregivers reported mild (5.88%, n=3) or moderate (5.88%, n=3) anxiety levels. Stress symptoms also improved; initially, 23.5% (n=12) reported mild (7.84%, n=4), moderate (13.72%, n=7), and severe (1.96%, n=1) stress. Following the intervention, stress symptoms reduced to 7.84% (n=4), with only mild (5.88%, n=3) and severe (1.96%, n=1) symptoms remaining.

This is a local study conducted in Zaragoza (Spain) with a small sample and no comparison arm. Because of inclusion/exclusion criteria, people with low digital literacy were not able to participate. Although the general prevalence of GHD is higher in boys, most caregivers participating in this study had daughters who have GHD; thus, parents of boys with GHD might have been underrepresented.

The findings from this study align with and extend previous research on digital interventions aimed at supporting family caregivers of children undergoing GHt. Prior studies have highlighted the significant burden on family caregivers managing GHt, including the physical, emotional, and psychological stress that can negatively impact treatment adherence and the overall health of the child [13]. The ACDP demonstrates notable advancements in this area by providing a comprehensive digital health intervention that effectively supports both the physical and mental well-being of caregivers [33].

Previous research by Arriba et al [34] suggested that mobile solutions could potentially improve GHt adherence by addressing the emotional states of parents and caregivers. Our study, albeit observational, provides further evidence that digital tools appear to significantly enhance adherence rates by improving caregivers’ psychological states. In particular, our study revealed a statistically significant increase in treatment adherence from baseline (below 85%) to postintervention levels, with 75% of families reaching optimal adherence.

Furthermore, the mental well-being of caregivers showed substantial improvement, a finding consistent with earlier work by de Arriba et al [34], which highlighted the positive impact of the ACDP on caregivers’ mental health. Our findings show that at baseline, 21.56% (n=11) of caregivers reported depression symptoms, categorized as mild (11.76%, n=6), moderate (7.84%, n=4), and extremely severe (1.96%, n=1). Anxiety and stress levels also showed marked reductions, aligning with the findings from the study by Cervera-Torres et al [22], which emphasized the importance of digital health support for emotional and self-management needs.

Moreover, our study’s comprehensive assessment of quality of life and well-being metrics—using tools such as the PANAS, MHC-SF, and KIDSCREEN-10—demonstrated significant improvements in cognitive symptoms, mood, emotional and social well-being, and general health. These results further extend the insights from the study by Savage et al [13], which discussed the transformative potential of patient-generated data in integrated care models for GHt. The significant increases in positive affect, general well-being, social well-being, and self-efficacy among participants underscore the holistic benefits of digital health interventions.

In conclusion, the ACDP showed favorable acceptance for family caregivers of children undergoing GHt. It is a promising tool and has been demonstrated to add value to the patient and caregiver journey by improving GHD management while supporting the overall well-being of family caregivers. It has helped parents improve their mental well-being as well as treatment adherence. This study provides insights into how digital interventions can better support families of children undergoing GHt.