Background

Familial hypercholesterolemia (FH) is an autosomal dominant disorder characterized by very elevated levels of low-density lipoprotein cholesterol (LDL-C), which lead to increased risks of premature cardiovascular diseases (CVDs) such as coronary artery disease (CAD) (Nordestgaard BG et al. 2013). The prevalence of FH is estimated to be 1:311 worldwide and 1:250 in the United States (Akioyamen et al. 2017; Hu et al. 2020). Early diagnosis and treatment of FH has been shown to reduce an individual’s risk of CVD through a combination of lifestyle changes and medications such as statins (Wiegman et al. 2004; Luirink et al. 2019; Fahed et al. 2022). Due to the potential to significantly reduce morbidity and mortality with accurate and early detection and treatment, FH has been recognized by the Center for Disease Control and Prevention (CDC) as a tier 1 genetic disorder (Sturm et al. 2018).

Despite the high prevalence and treatability of the condition, FH remains underdiagnosed and undertreated. Nordestgaard et al. point to clinicians’ lack of awareness of the condition worldwide and individuals with FH remaining clinically asymptomatic until onset of CVD in adulthood (2013). Different detection strategies have been proposed to identify cases of undiagnosed FH in the population (Martin et al. 2017). Cascade screening for FH through systematic, stepwise lipid screening in family members of individuals with FH is recommended, but this strategy first requires the identification of independent index cases of FH (Morris et al. 2012).

Universal lipid screening (ULS) for children during visits with pediatric providers has been proposed as the primary solution to increase early diagnosis of FH and to identify index cases of FH (Klančar et al. 2015; Wald et al. 2017). Therefore, the American Academy of Pediatrics (AAP), the National Heart, Lung, and Blood Institute (NHLBI), and National Lipid Association (NLA) and recently in 2019 the American Heart Association and American College of Cardiology recommended ULS for children ages 9–11 years old and repeat screenings between 17 and 21 years old (Daniels et al. 2008; Daniels et al. 2011; Goldberg et al. 2011; Grundy SM et al. 2018).

ULS in children involves cholesterol screening and potential referral for FH evaluation including clinical and genetic evaluations with pediatric lipid specialists (Daniels et al. 2011). ULS in combination with reverse cascade lipid screening - testing parents and relatives of children with elevated LDL-C level - has been shown to diagnose missed cases of FH (Wald et al. 2017). Despite the publication of the NHLBI/AAP recommendation, Allen-Tice et al. recently found that only 4% of eligible pediatric patients received ULS services in a regional primary care setting (2020). Furthermore, current data on parents’ awareness of the ULS recommendation and experiences with their children’s FH diagnosis and care is lacking (Martin et al. 2017; Siegel et al. 2019).

Since parents and guardians are the gatekeepers of their children’s healthcare decisions and management, parent perspectives on screening and treatment of FH in children are important to explore. The current body of work exploring parent and child views about FH has largely been conducted in Australia and Europe, where the population and healthcare systems differ from the United States (Tonstad 1996; Keenan et al. 2019; Bowman et al. 2019; de Jongh et al. 2003). Therefore, the generalizability of current studies is limited to specific geographic populations and respective healthcare systems. It is critical to address the gaps in knowledge pertaining to the parents’ perspectives on FH in children and ULS in the United States.

The goals of the study were twofold: (1) provide insight into the facilitators and barriers to FH diagnosis and care in children as well as the impact of early intervention, (2) explore parent perspectives on ULS in the United States. Understanding the challenges, motivators, and resources involved in diagnosis and care for pediatric FH may guide future public health recommendations.

Methods

This was a qualitative research study that utilized semi-structured interviews to explore parent experience with their children’s FH diagnosis and care. This study was approved by the Northwestern Institutional Review Board (IRB: STU00215729).

Inclusion criteria

Participants were eligible to participate if they met the following criteria: parents or legal guardians (e.g. stepparents, foster parents) of a child or children diagnosed with FH who are 18 years old or younger, English speaking, reside in the United States, and willing to participate in a phone interview.

Recruitment and sampling

We utilized purposeful sampling to recruit participants fitting the inclusion criteria. The participants were recruited through the Family Heart Foundation using an online screening questionnaire that gathered respondents’ demographics including race and ethnicity of the participants and their children and participant’s interest in a follow-up interview study. The questionnaire was open from October 2021 to February 2022. A total of 29 participants began the questionnaire. Twelve participants completed the demographics section only, did not meet the eligibility criteria and were not required to complete the rest of the survey. An interview invitation was sent to the 17 eligible respondents via their preferred contact method (i.e., phone or email). Three of the 17 individuals did not respond to invitations to schedule an interview. All individuals who completed the survey had the option to enter a raffle to win two randomly selected $50 gift cards.

Data collection and analysis

Prior to the interviews, we emailed participants an electronic consent form and a list of main questions to consider. All participants also provided verbal consent to participate at the start of the interview. Upon completion of the interviews, all interview participants were mailed a $50 Visa gift card as compensation for their time.

The study team developed an interview guide that included both closed and open-ended questions on the topics of (1) participant’s experiences with their children’s FH diagnosis including clinical screening, and genetic testing of FH; (2) potential barriers and facilitators to diagnosis and treatment of FH; (3) participant’s perspectives on ULS. The interview guide was piloted twice after IRB approval. One pilot interview participant met the eligibility criteria and was consented to be included in the study.

All interviews were conducted over the telephone by HT in a closed room. Interviews lasted approximately 30–70 min and were audio recorded and transcribed verbatim for analysis by HT. Two members of the research team (HT and JY) conducted open and axial coding on four transcripts to develop a codebook. The initial coding process was done through an inductive approach by creating structural codes based on the study’s aims, followed by open coding using an iterative memoing process (documenting reflections and interpretations) on the transcripts. Once the finalized codebook was applied to one new transcript, two new codes were added. No new codes were added afterwards. The finalized coding structure was applied to all transcripts by HT using Dedoose software (version 9.0.46). Themes regarding parental experience with children’s FH diagnosis and care were developed through categorization of the identified codes.

Results

The participants

A total of fourteen respondents participated in a phone interview. Nine interview participants reported a diagnosis of FH and five participants were the partners of a patient with FH. While we did not ask the participants about their educational or professional backgrounds, six participants independently reported having an educational and/or professional background in health-related fields (i.e. nurse, science teacher, health major). One participant reported their child was diagnosed with homozygous FH while the remaining participants reported their children were diagnosed with heterozygous FH. The median age of the first child to be diagnosed with FH among the families was six years old (ranging from two-nine years old). Five participants reported their children underwent genetic testing. All participants reported a family history of FH or FH related symptoms. The majority of the participants identified as “White”, while the racial and ethnic backgrounds of their children were more diverse than the participants (Table 1).

Table 1 Participant characteristics
Full size table

Themes

Three main themes were identified: (1) role of family history in facilitating child’s FH diagnosis, (2) barriers and challenges in post-diagnosis care, (3) attitudes towards universal lipid screening in children.

Theme 1: role of family history in facilitating child’s FH diagnosis

Family history played a multifaceted role in facilitating lipid screening in children. A majority of the parents (12/14) shared that having a family history of FH or FH-related symptoms prompted them to request screening for their children from their pediatric providers. Participants also highlighted that their family history provided them with the knowledge to navigate the healthcare system to obtain the appropriate screening for their children, especially in situations where providers were not readily aware of the screening guidelines or FH as a condition.

Family history as a driver for screening

All participants reported a family history of high cholesterol, premature CVDs and/or a FH diagnosis. One participant was motivated to inquire about screening due to their partner’s premature heart attacks. Eleven participants acknowledged their decision to have their children screened for FH was driven by their awareness and knowledge of FH as a condition and the perceived importance of early treatment for FH. Further, some participants described wanting to disrupt the generational pattern of CVDs as a key motivator to seeking out a diagnosis in their children. For example:

P12 (mother, White, Master’s degree)It’s good to know just because it affects his future. I know that I can get him on medication the earliest possible and make sure that he doesn’t follow the same course that my father followed, that I might potentially follow. You know what I mean? Every generation seems to be a little bit healthier as they get older.

However, a significant family history of premature CVDs or a FH diagnosis did not always result in a seamless process for lipid screening in children. Four participants recalled feeling brushed off or not believed by their pediatric providers when requesting screening for their children due to the provider’s lack of knowledge of FH. For example:

P3 (Mother, Filipino, Doctorate degree)Even when he was an infant, I would ask the pediatrician, “oh my husband… he had these heart attacks, is there anything we should be concerned about with the kids?” Because I’m just worried, I think we should address these issues. And everybody kind of just pooh-poohed me.

Lack of provider awareness and knowledge

The lack of provider awareness and knowledge of FH was a common theme that emerged from the participants’ accounts of obtaining lipid screening for their children. Only two participants reported that routine lipid screening for children was offered by their pediatric providers.

Half of the participants described their pediatric providers being amenable to screening after learning about their family histories. A majority of the participants also communicated that family history was a critical tool in prompting their pediatric providers to order screening. For example, three participants reported their personal diagnosis of FH facilitated screening in their children by having the knowledge to educate their pediatric providers.-

P5 (Mother, White, Bachelor’s degree)I asked his pediatrician and I said “can you order me a lipid panel.” And they were like “why,” so I explained it to him…I just said I have a genetic condition and I really want it done and so we did.… I always constantly feel like I’m educating medical people on the condition.

Theme 2: barriers and challenges in post-diagnosis are

Several barriers and challenges emerged from the parental accounts regarding navigating and obtaining post-diagnosis treatment for pediatric FH. Participants reported a lack of direction after diagnosis and concerns regarding medication in children. Similar to their pre-diagnosis experience, participants continued to describe being proactive in seeking out specialized care for their children.

Barriers to specialists

One barrier was the lack of a clear path to specialized care after diagnosis. Some participants recalled having to independently research and obtain specialized care for their children due to: (1) perceived limitation of non-lipid specialists’ ability to treat pediatric FH, and/or (2) a lack of referral from their pediatric provider after diagnosis. For example:

P9 (Mother, White, Bachelor’s degree)so I didn’t really get a recommendation as far as like a specialist that I need to take him to…there wasn’t really an action plan after we got a diagnosis … so I just had to kind of figure it out on my own.

Another barrier was the lack of specialists in their area or under their insurance plan:

P7 (Father, White, high school degree or equivalent)But the specialist, the FH specialists are few and far between in my area… that’s very concerning as a parent of a child with FH. I don’t want to have to be her specialist. I’m her biggest supporter, her biggest advocate but I can’t write the prescriptions.

P2 (Mother, Pakistani, Master’s degree)knowing that their cholesterol is so high and not doing anything about it doesn’t make me feel great. So we are switching some insurances around and going to try to go to a lipid specialist clinic and ask them to just get a second opinion rather than just wait. I don’t just want to risk it because one doctor said it’s just a number.

These participants perceived the access to a specialist or a second opinion to be a pivotal part in the treatment and management of FH in their children.

Uncertainty about medications for children

Participants raised varying concerns about medication in children including: (1) side effects of medication in children, (2) timing of starting medication, (3) a perceived lack of clear management guidelines or a lack of research on the effect of different medications in children. These concerns led some participants to seek out additional medical advice for earlier treatment or question the current recommendation: For example:

P6 (Mother, White, some college, no degree)I mean he probably could stand to have a lower cholesterol and the ability to try some of the other drugs that are out there that are not approved yet. There’s not a lot of research studies for his age group (age 12) on those medications because those kids seem like they’re not sick enough, they’re healthy, why would you want to give him this medication? They don’t have any plaque, it’s like it’s a weird gray area for treating them.

One participant further highlighted the need for a multidisciplinary team of specialists who are keeping up with the evolving treatment guidelines to provide updated care for children:

P11 (Father, White, Doctorate degree)I think the model’s got to change. There’s got to be more comprehensive kind of lipidologist, cardiologist knowing when to start the statins, when to change them, when to use the newer agents, this is all rapidly progressing.

Theme 3: attitudes towards universal lipid screening (ULS) in children

Parental attitudes towards ULS in children was another key theme in the participants’ accounts. All participants were in favor of ULS in children and agreed that a childhood diagnosis of FH can lead to early treatment and prevention of premature CVD. Many participants voiced the importance of early lipid screening and having the knowledge to make decisions for their children’s care. Other parents referred to their negative experiences in seeking out an FH evaluation or prolonged undiagnosed FH in the family as reasons in wanting increased public awareness of FH.

There was unanimous support for ULS in children from the participants. One perceived benefit of screening was having the knowledge and awareness to manage FH:

P10 (Father, White, Master’s degree)I’m very in favor of lipid screening being a part of the normal doctor’s visits. You can’t, you can’t adequately manage something you don’t know about so hoping it is not a very good management strategy… testing doesn’t mean you have to do anything but the testing gives you the knowledge so you can do something.

Other participants reported their perceived value of ULS stemmed from their own negative experience in seeking out lipid screening for their children or with undiagnosed FH in the family. For example:

P3 (Mother, Filipino, Doctorate degree)the only reason we got a diagnosis is because I went all crazy and hounded all the doctors and that, I feel like if I hadn’t done that then we wouldn’t have been diagnosed, probably not even yet… so what I think is that it should really be more something that they screen for in pediatrics because through pediatrics you will find adult cases of it, like my husband. I think it’s just important, I don’t think people should die young.

Many participants described the importance of increasing knowledge and awareness of FH in the general public to help parents make decisions regarding their child’s care. Two participants further described the value of ULS in offering equal opportunity to screening for children with or without a known family history of FH related symptoms:

P7 (Father, White, High school degree or equivalent) … Early detection is really the only way to get on top of it and keep or prevent the children from being a cardiac patient…like my father, like me, and so many others, everybody shares the same story of losing a family member…It’s heartbreaking the amount of people that don’t know [their family history], it’s just wrong to me. It’s an injustice to the kids that grow up and people like me that you’re having to do the research on your own.

A case of reverse cascade screening was described by one participant. For P4, her son’s elevated LDL level triggered an evaluation for her husband, who was found to have FH. This was the only account where routine lipid screening in children identified an undiagnosed FH in the family:

P4 (Mother, Pakistani and White, Doctorate degree)But my son is the person who got an official FH diagnosis ‘cause my husband didn’t know his high cholesterol until he was in his 30s…[the pediatrician] just routinely screened for cholesterol at his annual appointment.

At the time of the interview, ten participants expressed awareness of the recommended lipid screening in children. Of these ten, eight participants became aware of the recommendation from independent research or their backgrounds in healthcare. Two participants were informed by their pediatric providers regarding pediatric lipid screening recommendation.

Discussion

The findings of this article add to parental experiences with FH diagnosis and care in children in the United States. The three main themes identified through this qualitative study were: (1) the important role of family history in facilitating child’s FH diagnosis, (2) barriers & challenges in post-diagnosis care for FH in children, (3) favorable attitudes towards universal lipid screening in children.

Family history is a facilitator for pediatric FH diagnosis

We found that family history played multiple parts in facilitating FH diagnosis in children. First, a majority of our study participants reported their awareness of FH was a result of a FH diagnosis in the family. Second, there was a generational impact on both the parents’ decision to seek out screening for their children as well as their beliefs regarding the critical role of early intervention in breaking the generational pattern of premature CVD in the family. Previous studies on parental attitudes towards treatment of FH in children found similar parental motivation in wanting their children to benefit from early intervention that other family members did not receive (Keenan et al. 2019; Tobik et al. 2023). A family history of FH or FH related symptoms triggered our study participants to seek out early screening in children. However, it is important to recognize that relying on parents to have the knowledge to proactively seek out screening in children may lead to missed diagnosis of FH. Especially when family history can sometimes be incomplete or unavailable and not all individuals have the same degree of awareness or knowledge of FH to pursue screening in children. Additionally, with early adequate treatment, CVD risk will be lessened in families, thus changing risk models and evaluation strategies (Wiegman 2018).

Parents experience barriers to diagnosis and care for their children with FH

Our study demonstrates a lack of readiness or willingness of the providers to order screening. This finding draws attention to the lack of routine screening or knowledge of FH in pediatric care previously described in the literature (Dixon et al. 2014; Allen-Tice et al. 2020; Zhang et al. 2022). As a consequence, some of our study participants described provider resistance to order screening in their children despite a family history of FH. Many participants further assumed a more active role in educating providers on the condition to procure screening for their children. While parents taking on the role of an expert in the clinic is the first to be described in the context of FH, our results resonate with other studies on families of children with rare diseases (Brady et al. 2020). It is important to note that our participants were strong advocates of their children receiving lipid screening; with many parents citing their ability to get the providers to order the appropriate screening was due to their training in health-related fields and/or their knowledge of the type of test to request. For a few of our study participants, having to educate their pediatric providers about FH led them to question the ability of these providers in treating and managing FH in their children. Our results underscore a need for increased provider awareness of FH and readiness to screen for FH in children as well as the importance of parent-provider collaboration in diagnosing pediatric FH in the United States.

Several factors impacted our study participants’ access to various specialists including pediatric providers’ referral practice, parental preference for certain specialists, family’s geographical location, and/or child’s insurance plan. For some study participants, they described having to research and establish post-diagnosis care for their children independently due to a lack of referral to specialists or a perceived limitation of non-lipid specialists’ ability in treating pediatric FH. This reflects previous studies that have reported inconsistent referral practice among pediatricians and found that pediatricians expressed uneasiness in treating dyslipidemia in children (Dixon et al. 2014; de Ferranti et al. 2017; Soukup et al. 2021; Peterson et al. 2021). Despite these barriers, our parents indicated they were motivated and able to obtain follow-up care for their children as a result of their familiarity with the healthcare system through having FH themselves and/or their ability to find online resources such as the Family Heart Foundation. We hypothesize that other parents without a similar background, motivation, or access to the same resources are less likely to get the same care for their children. Opportunities exist to reduce barriers to post-diagnosis care for children with FH through increasing training in primary providers and providing additional resources for families after diagnosis. Future studies are needed to identify other key barriers and resources for providers as well as parents who are caring for children with FH, especially when disparities in treatment have been shown to exist among pediatric and adult patients with FH (Amrock et al. 2017; de Ferranti et al. 2021; Kalra 2021; Langslet et al. 2021).

Similar to other studies, our parents also had varying views on the risks and benefits as well as the timing of medication in children with FH (Keenan et al. 2019). Some study participants expressed wanting to delay medication in children, while other participants wanted to seek out additional advice from other specialists (i.e. lipid specialist) regarding starting medication earlier than the recommended age. Previous regional and national studies on provider practices found only a small fraction of pediatricians expressed willingness to start treatment at the recommended ages (de Ferranti et al. 2017; Peterson et al. 2021). We hypothesize parental views on medication in children may be influenced by multiple factors including the advice from their pediatric provider and the parent’s ability to seek out updated treatment and management guidelines (Keenan et al. 2019). Given that medication is an essential part of treating and managing patients with FH, it is recommended that pediatric providers counsel parents on the safety, as well as the potential side-effects, of medication in children to allow for their children to receive the maximum benefits of early diagnosis and intervention.

Our findings, along with previous literature, suggest a lack of preparedness within the US healthcare system to treat children diagnosed with FH (Eichberger et al. 2022). Primary pediatric providers are recognized as well-positioned to identify cases of FH, but there may be a greater need for these providers to take on the additional role in managing pediatric FH due to a shortage of available specialists (de Ferranti et al. 2017; Zimmerman et al. 2019). Consequently, when implementing strategies to increase diagnosis of FH in pediatric patients, there is a need for complementary training and referral guidelines for primary pediatric providers.

Parents support universal lipid screening

All of the study participants were in favor of ULS for children. Participants expressed several reasons for their support. First, all participants emphasized the importance of early screening and intervention in preventing premature CVD in children. A few participants further went on to describe the benefit of ULS in offering equal opportunity for children whose family history may not be available. These findings suggest our study participants are knowledgeable about the advantage of ULS in children in finding cases of missing FH in the population. Overall, our study participants’ support for ULS was motivated by their family history of FH, knowledge about FH, and their beliefs in the benefits of early screening. Conversely, a regional study in the United States on parental support for ULS did not find an association between parental support and their knowledge about family history of abnormal cholesterol or CVD. The same study did identify a lack of understanding about the utility of ULS in children as a potential barrier to parents supporting ULS (Kern et al. 2020). We hypothesize that an increased public awareness and education regarding FH as a condition and the benefits of ULS in children may influence parental attitudes toward screening in the United States. Indeed, a study in Australia has suggested that public health approaches such as education about FH and ULS may be an appropriate way to increase awareness and diagnosis of FH (Bowman et al. 2019).

Currently, there is a lack of unanimous support from medical experts regarding their recommendations on ULS in children in the United States. The CDC recognizes FH as a tier 1 genetic condition and the NHLBI/AAP have published recommendations for ULS in children (Daniels et al. 2008; Daniels et al. 2011; Sturm et al. 2018). However, the US Preventive Services Task Force has yet to support this recommendation citing parental and children anxiety as a potential harm to screening (Guirguis-Blake et al. 2023). While it is important to recognize the previously identified challenges associated with lipid screening in children such as fear of phlebotomy and mislabeling of children, our understanding of parental experience with lipid screening in children is incomplete. Investigation into parental experience from a more diverse population is needed. (Lannon CM et al. 1992). Our study found that access to screening for all children was advocated by families affected by FH. These families reported screening in their children allowed for the diagnosis that enabled them to be proactive about establishing early treatment and management for their children. We suggest that it is best to offer ULS in children to parents and communicate the advantage of ULS to allow for parents to make informed decisions about their children’s care. Future studies are needed to examine parental views before and after lipid screening to identify resources to support parents during the process.

Limitations

Our study has several limitations. First, this was a purposeful sampling of participants who resided in the United States through the Family Heart Foundation. The findings may be subject to recruitment bias as our participants may be more in favor of ULS in children and more likely to be motivated to seek out screening in children due to their knowledge and awareness of FH as a condition. Furthermore, since FH is a severely underdiagnosed condition, the pool of parents with children having been diagnosed may be limited. The data, therefore, may not be generalizable to other populations. The majority of our interview participants were non-Hispanic White and a future recruitment strategy to include participants from underrepresented populations is needed. Lastly, the majority of the participants were biological mothers. Future studies involving other community members within the family system including fathers, children and young adults are needed to understand their experience with FH.

Conclusion

This study contributes to the expanding body of literature concerning parental experience in obtaining the diagnosis and care for their children’s FH in the United States. Participants emphasized the significance of family history in facilitating a diagnosis for their children. A lack of access to post-diagnosis care was a concern raised by the participants. Participants’ support for ULS was influenced by their perceived advantages of ULS including prevention of delay diagnosis, increased awareness of FH management, and identification of FH in situations where the family history is incomplete or absent. This work represents an important step towards overcoming barriers to the diagnosis and facilitation of optimal care for pediatric FH patients. Future work could investigate potential educational initiatives targeting both families and pediatric providers on screening recommendations, the progression of FH, and available treatment and management options.