Factors influencing illness uncertainty in parents of children with congenital adrenal hyperplasia in a developing country: A cross-sectional study

Background

Congenital adrenal hyperplasia (CAH) is the most common cause of ambiguous genitalia in 46,XX disorders (differences) of sex development (DSD) in a newborn characterized by enzyme deficiency involved in steroidogenesis in the adrenal gland, in which 90% of cases are caused by 21-hydroxylase deficiency (Idris et al., 2014; Juniarto et al., 2018; Pezzuti et al., 2014; Tsuji et al., 2015; Zainuddin et al., 2019). This will result in cortisol and aldosterone deficiency and excessive androgen hormone production (Speiser et al., 2018; Szulczewski et al., 2017), with the incidence ranging from ~1:14,000 to 1:18,000 (Speiser et al., 2018). Data from the Indonesian Pediatrics Society registry in 2009 showed there were 69 children with CAH [56 (81%) girls and 13 (19%) boys]. However, this number surged to 439 children (303 (69%) girls and 136 (31%) boys) in 2020 (Armstrong et al., 2020). In addition, the Center for Biomedical Research (CEBIOR) recorded 84 patients with CAH were evaluated from 2004 to 2016 jointly by a multidisciplinary team from the Dr. Kariadi Hospital and Faculty of Medicine Diponegoro University, Semarang (Juniarto et al., 2018).

Unlike many Western countries, a newborn screening program to detect CAH is unavailable in Indonesia (Gidlöf et al., 2014; Held et al., 2015; Odenwald et al., 2015; Speiser et al., 2018; Tsuji et al., 2015). This causes many late-diagnosed CAH cases (Ediati et al., 2015), which leads to delayed treatment (Juniarto et al., 2018), virilization, masculinization (Bizic et al., 2018), psychological problems like gender dysphoria (Juniarto et al., 2018), stigmatization (Ediati et al., 2017), emotional and behavior problem (Ediati et al., 2015), cross-gender role behavior (Ediati et al., 2017; Idris et al., 2014), and fertility issues (Witchel, 2017). Because of these, parents may develop illness uncertainty, leading to developing psychological problems, such as stress (Hullmann et al., 2011; Wisniewski & Sandberg, 2015), depression (De Silva et al., 2014; Perez et al., 2019), and anxiety (McConkie-Rosell et al., 2018; Perez et al., 2019; Wisniewski & Sandberg, 2015). Furthermore, parents of children with CAH in Vietnam reported that the scarcity of CAH medicines and low incomes, particularly from remote and rural families, caused many parents to be unable to afford the drugs their children need (Armstrong et al., 2020). In addition, the diagnosis and treatment delay due to ambiguous genitalia uncovered cost of laboratory workup by National Health Assurance (or called JKN – Jaminan Kesehatan Nasional), and inaccessible fludrocortisone brings complexities in the management of CAH in a developing country like Indonesia (Armstrong et al., 2020).

Illness uncertainty, described as the inability to determine the meaning of illness-related events, has several factors that may contribute to its development: symptom pattern, event familiarity, event congruence, cognitive capacity, education, social support, and credible authority (Mishel, 1988). Understanding what causes uncertainty may help nurses and other healthcare professionals with patients’ experiences regarding their illnesses. In addition, a patient should develop a coping mechanism to cope with the uncertainty, and nurses play a critical role in helping patients to comprehend illness uncertainty and cope. This could help patients and their families increase their quality of life (Smith & Liehr, 2018).

A previous study reported that mothers and fathers of DSD children scored higher uncertainty but lower than parents of children with chronic illness (Perez et al., 2019). Unfortunately, the study was conducted not only on parents of children with CAH but also on parents of children with 46, XX DSD, 46,XY DSD, and sex chromosomal DSD. To our knowledge, this is the first study of illness uncertainty in parents of children with CAH in a developing country. This study aimed to identify factors contributing to illness uncertainty in parents to promote early detection, prevention, and better management of children with CAH.

Methods

Results

Participants consisted of 37 (46%) fathers and 43 (54%) mothers of children with CAH. The mean age of the participants was 35 ± 7.7 years, with most of them [44 (55%)] aged ≥ 35 years. The majority of parents (74%) had an upper-secondary education. Overall, 84% of parents had children with SW-CAH. Data from two parents were excluded from bivariate analysis by genitoplasty and the child’s current gender because they were parents of two children with CAH raised as a boy and a girl. Therefore, their response on PPUS-Indonesia might be biased as it is difficult to specify whether their response on uncertainty was referring to the son or daughter conditions or might not have represented both genders equally. Among 56 parents of girls with CAH, only 14% of their children had undergone genitoplasty (Table 1).

The majority of parents in the study showed a low level of uncertainty, as indicated by an average score of PPUS at 42.3 ± 12.91. Although none reported a high level of uncertainty, 39% of parents reported a moderate level of uncertainty (Table 2).

Table 3 displays the comparison analysis results between parent-related and child-related factors and the PPUS score. Parents of children with SW-CAH showed a higher score of uncertainty (44.2 ± 12.77) than parents of children with SV-CAH (32.6 ± 8.86). In addition, the type of CAH significantly affected the uncertainty perceived by parents (p = 0.003).

Table 4 demonstrates the results of the comparison analysis of parent-child-related factors between low and moderate levels of uncertainty. Significant differences in illness uncertainty were found between groups of parents with SW-CAH and SV-CAH, as well as parents with and without experience of child mortality due to CAH. All parents of children with SV-CAH reported low uncertainty, whereas parents of SW-CAH reported lower to moderate uncertainty (p = 0.001). Parents who had lost their children due to CAH were more likely to have a moderate level of illness uncertainty, whereas parents who never experienced child mortality due to CAH were more likely to report a low level of illness uncertainty (χ²(1, 80) = 4.893; p = 0.027). No significant differences were found across different groups based on parent-related and child-related factors between low and moderate levels of uncertainty. In our data, two factors are associated with illness uncertainty in parents of children with CAH. First, parents with a history of child death due to CAH. They were more likely to report moderate uncertainty than parents without experience of child death due to CAH. Second, CAH type. None of the parents from the simple virilizing CAH group reported a moderate level of uncertainty. In contrast, almost half of the parents from the salt-wasting group reported a moderate level of uncertainty.

Sensitivity analysis using Fisher’s exact test was performed for two variables found to be significant in the chi-square test, i.e., type of CAH and child death due to CAH. Each variable was split based on the parent’s gender, and a comparison was made between these two variables and PPUS score hypothetical category. Illness uncertainty was significantly different between fathers of SW-CAH and SV-CAH. All fathers of SV-CAH reported a low level of uncertainty (p = 0.009) (Table 5).

Logistic regression, which was conducted for parents’ gender, the number of children with CAH, child death due to CAH, and type of CAH, found no significant impact on the PPUS score hypothetical category.

Discussion

The study aimed to investigate factors influencing illness uncertainty experienced by parents of children with CAH in a developing country. Our study findings showed that there were two factors affecting illness uncertainty in parents of children with CAH: the type of CAH and the presence of child mortality due to CAH. The chi-square test was performed to analyze the presence of child mortality, which was in line with the chi-square assumptions. Parents of children with the salt-wasting type of CAH and parents who experienced the loss of their children due to CAH are more likely to report higher illness uncertainty than other parents who have not. The study findings are important as higher uncertainty among parents of children with CAH reflects the need to seek appropriate information related to CAH and its treatment to reduce the uncertainty level of parents.

Parents of children with CAH in the present study reported somewhat low to moderate levels of uncertainty, and none reported a high level of uncertainty. A previous study about psychological distress experienced by parents of children with DSD showed a comparable level of uncertainty (Suorsa et al., 2015). This might indicate that their children with CAH have received medical treatment and regularly visit the pediatric endocrinology clinic to maintain their health. The role of healthcare professionals in delivering appropriate information regarding CAH to parents and the availability of guidelines about CAH that parents can refer to (Speiser et al., 2018) may play an essential role in reducing illness uncertainty in these parents of children with CAH.

In addition, social support is also available by using social media (WhatsApp group) of parents who have children with CAH (Mishel, 1988) may reduce uncertainty experienced by parents of children with CAH. But still, some parents experienced a moderate level of illness uncertainty. More efforts are needed to identify relevant information to reduce the illness uncertainty for these parents. Do they receive less or too much information regarding CAH, and what kind of CAH-related information do they need to reduce illness uncertainty on these parents should be investigated in the follow-up study because lack or too much information, as well as seeking or avoiding information, may influence uncertainty (Kerr & Haas, 2014).

Most participants were parents of children with salt-wasting type CAH (44.2 ±1 2.77), and they had a significantly higher mean score of PPUS than children with simple virilizing type CAH (32.6 ± 8.86). According to Utari et al. (2016), 10 out of 79 (13%) children registered with CAH in Central Java, Indonesia, had died because of adrenal crises since 2009. The lack of newborn screening for CAH leads to delayed diagnosis and treatment. In addition, the most severe form of CAH, the salt-wasting type, made the body unable to regulate salt (sodium) levels in the blood because of a lack of aldosterone, making it prone to salt-wasting crisis (Falhammar et al., 2014). This made salt-wasting CAH contribute to a higher level of uncertainty. Therefore, patients with CAH need hydrocortisone and fludrocortisone for cortisol and aldosterone replacement therapy, respectively. However, fludrocortisone is unavailable in Indonesia (Armstrong et al., 2020) and might further increase the illness uncertainty among parents.

A significant difference in illness uncertainty was discovered between fathers of SW-CAH and fathers of SV-CAH. A previous study on parents of children with DSD found contradictory results where mothers scored higher uncertainty despite being insignificant (Perez et al., 2019). Our result might be explained by the patriarchy that most Indonesians embraced. Most of the participants of this study came from rural areas. In addition, most mothers who participated in this study were housewives and unemployed; thus, the only source of income for the family came from the fathers. Therefore, even though mothers might be involved in the general decision-making process, as the head of the family, the final decision is for the fathers to decide (Ferdoos & Zahra, 2016; Sarwono, 2012).

Child mortality due to CAH significantly affected illness uncertainty in parents. Parents of children with CAH who had lost their children due to CAH were more likely to report a higher level of uncertainty than parents who had never had such a grief loss. The result was similar to psychological distress experienced by parents of children who died from cancer (Sirkiä et al., 2000; Stroebe et al., 2006). Child loss was one of the deepest griefs experienced by parents (Davies, 2004). If a child died, the parent’s hope about the future would die, too (Christ et al., 2003). Parents who have encountered child loss might have an intense fear of losing the other child or, in CAH cases. Facing conflicting information about caring for children with CAH, therefore, might need specific support during bereavement (Gijzen et al., 2016). Further investigation is needed to explore the experiences of 18 parents who lost their children due to CAH and whether they need specific support and knowledge related to CAH to reduce the illness uncertainty of these particular parents.

The findings reported two factors significantly affecting illness uncertainty in parents with CAH. However, illness uncertainty did not significantly differ in most factors investigated, i.e., parental gender, age, educational level, monthly household income, number of children with CAH, child’s gender change due to CAH, child’s age when first diagnosed with CAH, child’s current gender, history of genitoplasty, and therapy duration. This might be because, nowadays, parents can easily search for their children’s condition on the internet before a medical appointment (Molzon et al., 2014). On the contrary, a previous multicenter study on parents of children with DSD found that parents of boys reported a higher illness uncertainty compared to parents of girls, and parents who were unsure of the gender of their child also reported greater uncertainty (Suorsa et al., 2015).

Conclusion

Parents of children with CAH had a low level of uncertainty; however, some parents still experienced moderate uncertainty. Salt-wasting type CAH and a history of child death due to CAH significantly affected parental uncertainty because of the impendence of salt wasting crisis and limitation of drug availability for salt-wasting type CAH. Therefore, these groups of parents would particularly need more support and attention and thus benefit from getting social support from other parents of children with CAH and regularly going to the medical appointment to consult and receive appropriate information from health care professionals. Nurses’ roles in caring for the patient extend beyond the physical need and providing holistic care, including psychosocial, cultural, and spiritual needs. In addition, nurses also played a role in educating the patient and their family so they could better understand the patient’s health, illnesses, and treatments, thus reducing uncertainty.