Mental and Emotional Health of Caregivers of Youth with Sickle Cell Disease: A Systematic Review

Abstract

People of African descent and those identifying as Black and/or Latino experience a disproportionate burden of sickle cell disease (SCD), a chronic, serious blood condition. Caregivers of children with chronic medical conditions report worse mental health than others. Disease associated stressors can affect caregivers of children with SCD. We conducted a systematic review to summarize the prevalence of mental health symptoms in caregivers of children with SCD and if symptoms were associated with the child’s SCD. This review is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We searched PubMed, PsycINFO and Embase identifying 1,322 records of which 40 met criteria for inclusion in this review. Findings suggest caregivers experience mental health problems and poorer mental health was associated with worse child SCD-related outcomes and treatment adherence. Efforts should be made to routinely screen SCD caregiver mental health and to refer accordingly.

Sickle cell disease (SCD) is a chronic, inherited blood condition characterized by physical symptoms of fatigue, severe pain episodes, and susceptibility to infection starting in early childhood with consequent risk of hospitalization and reduced lifespan. ¹ People of African descent have the highest frequency of SCD and sickle cell trait among racial/ethnic groups. In the United States (U.S.) and elsewhere, most people with SCD self-identify as Black and/or Latino. ^2,3 Those communities are disproportionately subject to under-resourced conditions⁴ and higher social vulnerability. ^5–8 Individuals with SCD and their families may be subject to stressors related to the condition and/or socioeconomic challenges, including health-related stigma and discriminatory practices^9,10 in social or medical contexts.

For children and adolescents living with SCD, chronic and acute health threats and adverse social factors increase their risks of adverse mental health, especially depression and anxiety. ¹¹ Adolescents with chronic health conditions, including SCD, commonly report depressive symptoms and anxiety. ^12–19 Being the parent of a child with a serious chronic medical condition can be taxing due to challenges from logistical, financial, and psychological stressors. ^20,21 A recent systematic review and meta-analysis examining behavioral and mental health outcomes of parents of children with a variety of chronic medical conditions reported worse parental mental health and more frequent and severe symptoms of anxiety and depression compared with parents of healthy children. ²² In that review, only one report assessed mothers of children with SCD and it focused exclusively on depressive mood. ²³

To our knowledge, no systematic review has focused on mental health symptoms among caregivers of children with SCD. Here we asked about mental health symptoms of caregivers of children with SCD. Specifically we set out to synthesize the literature regarding: (1) the symptoms caregivers report and how they were assessed; (2) the prevalence of the symptoms among caregivers of children with SCD was; (3) how those symptoms compared with those of caregivers of healthy children or children with a different chronic condition; (4) the associations of caregiver mental health symptoms with severity of clinical symptoms of the children with SCD in their care; and (5) the gaps exist in the literature.

Methods

The reporting of this systematic review adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. ²⁴ A review protocol was developed in advance and registered in the PROSPERO (CRD42020178326), to which the study team adhered.

Search strategy and selection criteria.

A comprehensive literature search was conducted on April 1, 2020 and updated on August 24, 2022 in the PubMed (pubmed.gov), PsycINFO (EBSCO) and Embase (ELSEVIER) databases. The search compromised the following components: mental health, caregivers, and SCD. The full search strategies are available from the authors upon request. Search results were imported into an EndNote Citation Manager library, which was used to remove duplicate records. Unique records were imported into Covidence, (https://www.covidence.org), which was used to facilitate screening and data extraction.

Studies were included in this review if they met the following criteria: original research; caregiver (i.e., parent or primary caregiver) of a youth with SCD were study participants; caregiver mental health symptoms (e.g., anxiety, depressive symptoms) and emotional health (e.g., parenting stress) were assessed; a cross-sectional study design was used; and written in the English language. Studies that used data from larger longitudinal studies were included in this review if the secondary data analyses were performed at study baseline and were cross-sectional. All authors participated in the selection of studies with two reviewers independently assessing each study’s title and abstract with discrepancies discussed by the full team until agreement was reached regarding study inclusion or exclusion. Next, two authors independently reviewed the full text of remaining studies with discrepancies regarding inclusion rectified by the team until consensus was reached.

Data extraction.

Using an iterative process, the researchers developed a comprehensive data extraction form. The tool included the following fields: (1) study characteristics—first and last authors’ names, publication year, location, funding source; (2) sample characteristics—number and demographics of youth with SCD (i.e., sex, age, percent of the sample with hemoglobin SS [HbSS]), as well as any other control samples, number and demographics of caregivers (i.e., sex, age, marital status, highest education level, socioeconomic status [SES]); (3) mental and emotional health symptoms/constructs assessed and the measures used; (4) descriptive statistics for caregiver mental health; and (5) results of analyses testing associations between caregiver mental health and youth SCD-related outcomes. Two authors independently extracted the data for each study; the team resolved differences in the data extracted by consensus.

Quality appraisal.

Two authors independently appraised each study using the Newcastle-Ottawa Quality Assessment scale, a validated tool, ²⁵ adapted for cross-sectional studies. ²⁶ The scale contains eight items within three domains: selection (four criteria addressing sample representativeness, sample size, recruitment, and ascertainment of the exposure); comparability (one criterion addressing steps undertaken to statistically control for confounding variables); and outcome (three criteria addressing assessment of the outcome and appropriateness of the statistical test). The study team met weekly to review appraisals; discrepancies in ratings were discussed until consensus was achieved. Following consensus, the study team categorized overall study quality as good, fair, or poor consistent with recommendations of the Agency for Healthcare Research and Quality. ²⁷ Details on scoring criteria within each domain and categorization of overall study quality are available from the authors upon request.

Data synthesis.

The broad study question addressed in this review as well as the heterogeneity in the included studies preclude a meta-analysis. Therefore, summary tables of evidence were created and examined. When creating the table summarizing participant characteristics (Table 1), caregiver demographic variables were collapsed for ease of interpretation as follows: (1) marital status = married or had a domestic partner; (2) highest education level = high school graduate or less, and at least some college or trade school; and (3) SES = lower income (U.S. settings: less than or equal to $30,000 [U.S. dollars not adjusted for inflation] or caregiver receives public assistance/insurance; non-U.S. settings in low/middle-income countries: proportion in lower half of the range of SES variable presented). Participant characteristics, when reported, were summarized across studies.

Table 1.

Study and Participant Characteristics, and Mental Health Symptoms and Emotional Health Measured

First Author, Year N (Caregiver) Country Funding Source (“†” study includes control group(s))	Youth Characteristics	Caregiver Characteristics	Mental Health / Emotional Health Construct
Asnani, 202144 • N=64 • Jamaica • Foundation/Other	• N=64 • Female: NR • Age: 0.5 – 1 year • HbSS: NR	• Female: 100% • Age: 28.8±5.9 years • Married/Domestic Partner: 68.7% • Education: ≤ HS=74.6% • Low Income:* 55.4	• Depressive symptoms • Parenting stress
Bakare, 200836, † • N=45 • Nigeria • NR	• N=45 • Female: 42.2% • Age: 13.8±2.7 years • HbSS: 100%	• Female: 100% • Age: 40.6±3.6 years • Married/Domestic Partner: 91.9% • Education: < College=55.6% • Low Income:* NR	• Distress
Baker, 201733, † • N=48 • USA • NR	• N=48 • Female: 50.0% • Age: 10.8±4.6 years • HbSS: 66.7%	• Female: NR • Age: 36.9±8.1 years • Married/Domestic Partner: 14.6% • Education: NR • Low Income:* NR	• Anxiety and depressive symptoms combined
Barakat, 200747 • N=27 (Preschool sample) • N=41 (Adolescent sample) • USA • Government	Preschool • N=27 • Female: 33.3% • Age: 4.3±0.1 years • HbSS: 55.6% • Adolescent • N=41 • Female: 48.8% • Age: 15.1±1.9 years • HbSS: 73.2%	Preschool • Female: 92.6% • Age: 31.3±7.3 years • Married/Domestic Partner: 44.4% • Education: ≤ HS=63% • Low Income:* 74% Adolescent • Female: 80.5% • Age: 44.0±10.2 years • Married/Domestic Partner 56.1% • Education: ≤ HS=36.6% • Low Income:* 58.5%	• Parenting stress
Barbarin, 199957, † • N=327 • USA • Government & Foundation/Other	• N=327 • Female: 44.0% • Age: 8.9 years • HbSS: NR	• Female: 96.0% • Age: NR • Married/Domestic Partner: 40% • Education: Mean=12.0 years • Low Income:* 59%	• Distress • Anxiety • Depressive symptoms • Parenting stress • Reaction to illness
Bioku, 202139 • N=121 • Nigeria • NR	• N=121 • Female: NR • Age: 10–19 years; mean NR • HbSS: NR	• Female: 76.0% • Age: 43.59±6.39 years • Married/Domestic Partner: 86.8% • Education: ≤ HS=77.6% • Low Income:* NR	• Distress
Brown, 199358, † • N=61 • USA • Government & Foundation/Other	• N=61 • Female: 54% • Age: 8.75±4.0 years • HbSS: 74.5%	• Female: 100.0% • Age: NR • Married/Domestic Partner: 42.0% • Education: NR • Low Income:* NR	• Distress
Brown, 200052 • N=55 • USA • Government	• N=55 • Female: 31.0% • Age: 9.2±2.6 years • HbSS: 78%	• Female: 100.0% • Age: 33.3±7.6 years • Married/Domestic Partner: 29.0% • Education: ≤ HS=66% • Low Income:* 86%	• Distress
Caprini, 202141 • N=100 • Brazil • Government	• N=100 • Female: 47.0% • Age: 8.9±5.4 years • HbSS: NR	• Female: 80.0% • Age: NR • Married/Domestic Partner: NR • Education: NR • Low Income:* 91%	• Anxiety • Depressive symptoms • Parenting stress
Cone-Dekle 198837, † • N=25 • USA • NR	• N=25 • Female: NR • Age: 6.7±2.49 years • HbSS: NR	• Female: NR • Age: NR • Married/Domestic Partner: 60.0% • Education: NR • Low Income:* NR	• Depressive symptoms (2 partner families only) • Parenting stress
Connelly, 200566 • N=58 • USA • NR	• N=58 • Female: 43.0% • Age: 11.8±2.8 years • HbSS: 77.0%	• Female: 88.0% • Age: NR • Married/Domestic Partner: NR • Education: Average=HS Graduate • Low Income:* NR	• Distress
Devine, 199848 • N=74 • USA • Government	• N=74 • Female: 36.0% • Age: 9.75±2.9 years • HbSS: 71.6%	• Female: NR • Age: 33.9±7.22 years • Married/Domestic Partner: 25.7% • Education ≤ HS=100% • Low Income:* 96%	• Distress
Green 202254 • N=38 • USA • Government	• N=36 • Female: 41.7% • Age: 14.2±1.9 • HbSS: NR	• Female: 81.6% • Age:43.9±9.1 • Married/Domestic Partner: NR • Education: ≤ HS=50% • Low Income:* NR	• Depressive symptoms
Hofmann, 200742 • N=11 • France • NR	• N=11 • Female: 18.2% • Age: 11.8±2.2 years • HbSS: 81.9%	• Female: NR • Age: NR • Married/Domestic Partner: NR • Education: NR • Low Income:* NR	• Post-traumatic stress disorder symptoms
Ievers, 199849 • N=67 • USA • Government	• N=67 • Female: 39.0% • Age: 9.93±3.06 • HbSS: 70.1%	• Female: 92.0% • Age: 33.67±6.64 years • Married/Domestic Partner: 24.90% • Education: ≤HS=22%, 12.6 mean years of school • Low Income:* 95 %	• Distress • Anxiety • Depressive symptoms
Ingerski, 201034, † • N=28 • USA • Government & Foundation/Other	• N=28 • Female: 58.3% • Age: 11.2±4.8 years • HbSS: NR	• Female: 78.3% • Age: 40.2±11.7 • Married/Domestic Partner: 33.3% • Education: NR • Low Income:* 68%	• Post-traumatic stress disorder symptoms
Johnson, 202255 • N=74 • USA • Government	• N=74 • Female: 55.4% • Age: 14.20±2.47 • HbSS: 75.7%	• Female: 93.2% • Age: 41.39±7.78 • Married/Domestic Partner: 39.2% • Education: ≤ HS=13.5% • Low Income:* 43.25%	• Parenting stress
Kuerten, 202045 • N=103 • Kenya • Government & Foundation/Other	• N=103 • Female: 37.9% • Age: 5.39±2.61 years • HbSS: 100%	• Female: 83.6% • Age: NR • Married/Domestic Partner: NR • Education: ≤ HS=80.6% • Low Income:* NR	• Depressive symptoms • Reaction to illness
Ladd, 201664 • N=30 • USA • NR	• N=30 • Female: 56.7% • Age: 5.34±4.9 years • HbSS: 53.3%	• Female: 100.0% • Age: 30.83±4.89 years • Married/Domestic Partner: NR • Education: NR • Low Income:* NR	• Anxiety
Logan, 200265 • N=70 • USA • NR	• N=70 • Female: 45.7% • Age: 14.5±1.4 years • HbSS: NR	• Female: 72.9% • Age: NR • Married/Domestic Partner: 43.5% • Education: Median=Some College or Vocational School • Low Income:* Median income: $25,000-$49,999	• Distress • Parenting stress
Menezes, 201329, † • N=100 • Brazil • NR	• N=100 • Female: 64.0% • Age: Range 5–18 years Mean NR • HbSS: NR	• Female: NR • Age: NR • Married/Domestic Partner: NR • Education: NR • Low Income:* NR	• Distress
Moody, 202167 • N=150 • USA • Unfunded	• N=150 • Female: 52% • Age: 12.5 years • HbSS: 65%	• Female: NR • Age: NR • Married/Domestic Partner: 46.0% • Education ≤ HS: 37.3% • Low Income:* 53%	• Parenting stress
Noll, 199430, † • N=32 • USA • NR	• N=32 • Female: NR • Age: 11.3±1.34 years • HbSS: 50%	• Female: NR • Age: 36.9±6.6 years • Married/Domestic Partner: NR • Education: Mean years: 12.4 ± 1.5 • Low Income:* NR	• Distress • Depressive symptoms
Olley, 199740 • N=200 • Nigeria • NR	• N=200 • Female: 48.5% • Age: 8.9 years • HbSS: NR	• Female: 100.0% • Age: 34.5 years • Married/Domestic Partner: 89.5% • Education: At least primary education: 59.5% • Low Income:* NR	• Parenting stress
Panepinto, 201050 • N=66 • USA • Government	• N=66 • Female: 51.5% • Age: 5–18 Mean NR • HbSS: 66.7%	• Female: 84.8% • Age: NR • Married/Domestic Partner: NR • Education: ≤ HS=47 % • Low Income:* 43.9%	• Distress
Pantaleao, 201962 • N=30 • USA • NR	• N=30 • Female: 36.7% • Age: 11.2±2.9 years • HbSS: 70%	• Female: 80.0% • Age: 46.7±14.0 years • Married/Domestic Partner: 53.3% • Education: NR • Low Income:* 23.3%	• Parenting stress • Reaction to illness
Psihogios, 201759 • N=83 • USA • Government & Foundation/Other	• N=83 • Female: 49.4% • Age: 8.47±2.1 years • HbSS: 60.2%	• Female: 90.0% • Age: NR • Married/Domestic Partner: NR • Education: ≤ HS=26.5% • Low Income:* 31.3% below the poverty line	• Parenting stress
Raphael, 201351 • N=150 • USA • Government	• N=150 • Female: 47.3% • Age: Range: 1–17 years Mean NR • HbSS: NR	• Female: 91.7% • Age: NR • Married/Domestic Partner: 41.1% • Education: ≤ HS: 24% • Low Income:* NR	• Parenting stress
Reader, 202060 • N=136 • USA • Government & Foundation/Other	• N=136 • Female: 52.2% • Age: 8.8±5.57 years • HbSS: 58.8%	• Female: 89.7% • Age: >21 years: 97.1% • Married/Domestic Partner: 39.7% • Education: ≤ HS=32.3% • Low Income:* 65%	• Distress • Post-traumatic stress disorder symptoms
Sharpe, 199461 • N=55 • USA • Government & Foundation/Other	• N=55 • Female: 47.3% • Age: 8.67±4.0 • HbSS: 74%	• Female: 100% • Age: 33.17±6.1 years • Married/Domestic Partner: 29.6% • Education: ≤ HS= 85% • Low Income:* NR	• Distress
Sil, 201656 • N=100 • USA • Foundation/Other	• N=100 • Female: 61.0% • Age: 13.54±2.74 years • HbSS: 77.0%	• Female: 87% • Age: 41.82±6.54 years • Married/Domestic Partner: 42.0% • Education: ≤ HS=28 % • Low Income:* 46%	• Reaction to illness
Sil, 202112 • N=73 • USA • Government	• N=73 • Female: 57.3% • Age: 14.24±2.48 years • HbSS: 72.7%	• Female: 88.3% • Age: 41.1±7.7 years • Married/Domestic Partner: 41.7% • Education: ≤ HS=15.6% • Low Income:* 40.3%	• Anxiety • Depressive symptoms • Parenting stress
Smith, 201663 • N=30 • USA • NR	• N=30 • Female: 53.3% • Age: 14.4±2.02 years • HbSS: NR	• Female: 85.2% • Age: 39.32±7.52 years • Married/Domestic Partner: 18.5% • Education: ≤ HS=mothers – 30.7%; fathers – 63.6% • Low Income:* NR	• Parenting stress
Tarazi, 200753 • N=26 • USA • Government	• N=26 • Female: 35.0% • Age: 4.3±0.83 years • HbSS: 58%	• Female: 92.3% • Age: 31.4±7.4 years (mothers) • Married/Domestic Partner: 46.2% • Education: ≤ HS=19.2% • Low Income:* 55.9%	• Parenting stress
Tunde-Ayinmode, 201132, † • N=100 • Nigeria • NR	• N=100 • Female: 48% • Age: Range: 7–14 years Mean NR • HbSS: NR	• Female: 100.0% • Age: 31–40 years Mean NR • Married/Domestic Partner: 93% • Education: ≤ HS=47.0% • Low Income:* NR	• Distress
Unal, 201143 • N=40 • Turkey • NR	• N=40 • Female: 27.5% • Age: 9.3±3.6 years • HbSS: 67.0% (Divided into 3 groups by no. of pain crises)	• Female: 100% • Age: 3 Groups: 33.9±6.5, 35.5±6.6, 33.6±5.6 years (NS) • Married/Domestic Partner: 100% • Education: ≤ HS=100% • Low Income:* NR	• Anxiety • Depressive symptoms
van den Tweel, 200831, † • N=54 • Netherlands • Government & Foundation/Other	• N=60 • Female: NR • Age: 9.2±4.2 years • HbSS: 81.7%	• Female: 100.0% • Age: 37.4±7.2 years • Married/Domestic Partner: 39% • Education: ≤ HS=91% • Low Income:* NR	• Depressive symptoms
Varughese, 202038 • N=42 • USA • Government	• N=43 • Female: NR • Age: 0.708 ± 0.625 • HbSS: 48.8%	• Female: 88.0% • Age: 26.3±6.9 years • Married/Domestic Partner: NR • Education: ≤ HS=59.5% • Low Income:* NR	• Distress • Parenting stress
Wonkam, 201446 • N=130 • Cameroon • Foundation/Other	• N=130 • Female: NR • Age: Median:10.0 years • HbSS: 100%	• Female: 80.0% • Age: Median: 38 years • Married/Domestic Partner: 77.1% • Education: ≤ HS=78.9% • Low Income:* 89%	• Parenting stress
Yousif, 202235 • N=170 • Sudan • Unfunded	• N=170 • Female: NR • Age: NR • HbSS: NR	• Female: NR • Age: NR • Married/Domestic Partner: NR • Education: NR • Low Income:* NR	• Distress • Anxiety • Depressive symptoms

Notes:

All studies utilized a cross-sectional study design; Noll 1994 and Reader 2020 analyzed data part of prospective cohort studies; Psihogios 2017 analyzed baseline data from a randomized clinical trial

^*=% Lower Income, US settings: ≤ $30,000 of US Studies only and not adjusted for current USD, or caregiver receives public assistance; non-US settings in low/middle income countries: proportion in lower half of the range of SES variable presented

^†=Study includes control group

Abbreviations: NR=not reported; HbSS=homozygous hemoglobin S disease; HS=high school; USA=United States of America

To organize the caregiver mental and emotional health symptoms when synthesizing study findings, mental and emotional health symptoms were grouped into four broad categories: (1) psychological adjustment; (2) anxiety and depressive symptoms; (3) parenting stress; and (4) other mental health symptoms. Within each category, we summarize across studies the proportion of caregivers who meet or exceed clinical cut-point scores when reported.

Results

Study selection.

Figure 1 details the identification of studies. Of 1,322 records identified 186 records met criteria for full text review and 40 met criteria for inclusion in this review. Reasons for exclusion at the full text review stage are available from the authors upon request.

Figure 1.

PRISMA flow diagram

Characteristics of included studies and samples.

As detailed in Table 1, studies were published between 1993 and 2022 with sample sizes ranging from 11 to 327 participants and represent data from 3,234 caregivers of 3,239 youth with SCD. All 40 studies reported one or more characteristics of both the caregivers and children allowing synthesis of data. Among caregivers, most (90.3%) were females who ranged in age between 18 and 55 years.

Approximately half of the caregivers (52.7%) were married or had a domestic partner. Similarly, half (50.3%) were high school graduates or less; the majority (63.2%) reported low income. Youth age ranged widely from as young as 1.2 months to as old as 18 years; approximately half (49.7%) were female and most (75.7%) has been diagnosed with hemoglobin SS (HbSS), a genotype that reflects the most serious form of the disease. ²⁸

While most studies lacked a comparison group, three studies included community-based control group samples of caregivers of youth without a chronic condition, ^29–31 three included control groups of caregivers of youth with a chronic condition other than SCD, ^32–35 and two included both types of control samples. ^36,37 Two studies, while lacking a control group, made comparisons of caregiver mental health with normative samples from their respective countries. ^31,38 Studies took place primarily in the United States (n=27), as well as in Nigeria (n=4), ^32,36,39,40 Brazil (n=2), ^29,41 and France, ⁴² Netherlands, ³¹ Turkey, ⁴³ Jamaica, ⁴⁴ Sudan, ³⁵ Kenya, ⁴⁵ and Cameroon⁴⁶ (n=1 each). Twenty-two studies reported an external funding source, which included government funding (n=11), ^{38,41,47–55} foundations or other sources (n=3), ^44,46,56 and both government and foundations (n=8). ^{31,34,45,57–61}

Quality appraisal.

Table 2 summarizes quality appraisal by domain and overall quality. Of 40 included studies, 19 were assessed as either good (n=15) or fair (n=4) with the remaining studies (n=21) assessed as poor quality. Regarding sample selection, most (n=28) authors described their sample as representative of youth with SCD followed at their clinic. However, few authors justified their sample size using a power analysis (n=6) ^{40,45,56,59,62,63} or reported a recruitment response rate and/or comparability of responders versus non-responders (n=4). ^31,44,51,59 Caregiver mental health was measured using at least one established validated instrument in all but two studies. ^40,57 Regarding comparability, in half of the studies (n=21) data analysis failed to control for any confounding factor. Within the outcome domain, maternal mental health symptoms were assessed using self-report instruments with only six studies^{42,51,53,62,64,65} using either blinded assessors or record linkage for more objective symptom measurement. All but three authors^35,40,42 clearly described their statistical analysis plan and reported study findings using p-values and confidence intervals. Overall, the body of research was assessed as poor due to risk of bias and sample selection, and lack of statistical control of confounders.

Table 2.

Risk of Bias of Included Studies

Author	Year	Risk of Bias Ratings			Composite Rating
		Selection (of *****)	Comparability (of **)	Outcome (of ***)
Ansai et al.	2021	****		**	Poor
Bakare et. al.	2008	***		**	Poor
Baker et al.	2017	***	**	**	Good
Barakat et al.	2007	***	**	**	Good
Barbarin et al.	1999	**		**	Poor
Bioku	2021	**	**	**	Fair
Brown et al.	1993	***		**	Poor
Brown et al.	2000	**	**	**	Fair
Caprini et al.	2021	**		**	Poor
Cone-Dekle	1988	**		**	Poor
Connelly et al.	2005	**	**	*	Poor
Devine et al.	1998	**	**	**	Fair
Green et al.	2022	**		**	Poor
Hofmann et al.	2007	**		**	Poor
Ievers et al.	1998	**		**	Poor
Ingersky et al.	2010	***	**	**	Good
Johnson et al.	2022	***	**	**	Good
Kuerten et al.	2020	***		**	Poor
Ladd	2016	***	**	***	Good
Logan et al.	2002	***	**	***	Good
Menezes et al.	2013	**	**	**	Fair
Moody	2021	***	**	**	Good
Noll et al.	1994	***		**	Poor
Olley et al.	1997	***		*	Poor
Panepinto et al.	2010	***	**	**	Good
Pantaleao et al.	2019	****	**	***	Good
Psihogios et al.	2017	*****	**	**	Good
Raphael et al.	2013	****	**	***	Good
Reader et al.	2020	***		**	Poor
Sharpe et al.	1994	***	**	**	Good
Sil et al.	2016	***	**	**	Good
Sil et al.	2021	***	**	**	Good
Smith	2016	****		**	Poor
Tarazi et al.	2007	***	**	***	Good
Tunde-Ayinmode	2011	***		**	Poor
Unal et al.	2011	**		**	Poor
van den Tweel et al.	2008	****		**	Poor
Varughese et al.	2020	***		**	Poor
Wonkam et al.	2014	***		**	Poor
Yousiff et al.	2022	**		*	Poor

Note: Overall composite rating: good = 3–5 stars in selection domain, 1–2 stars in comparability domain and 2–3 stars in outcome domain; fair = 2 stars in selection domain, 1–2 stars in comparability domain and 2–3 stars in outcome domain; poor = 0–1 in selection domain or 0 stars in comparability domain or 0–1 in outcome domain.

Caregiver mental health.

Table 3 provides detail regarding measurement used, prevalence of the mental health issue, and study findings and reported associations for caregiver psychological adjustment, anxiety/depressive symptoms, parenting stress/strain, and other mental health symptoms.

Table 3.

Mental and Emotional Health Findings by Construct and Instrument

Construct (# Studies)	Instrument (# Studies, type of control groups) Score range/Cutoff	Mean±SD, % Above Cutoff	Caregiver Mental Health Comparisons or Associations (comparisons with control groups listed first where reported)
Psychological Adjustment
Distress (18 studies)	SCL-90-R Global Severity Index (7 studies, 30,48,49,52,58,61,66 1 with a control group30) Cutoff: T score>63 (90th percentile=high distress)	• 51.0±11.766 to 56.6±14.152 • Above cutoff: 30%49 to 47%30	• Distress of caregivers of youth with SCD did not differ from that of caregivers of children without a chronic condition. 30 • Association between caregiver distress and child SCD coping strategies mixed: significantly correlated; 48,58 not correlated. 61 • Association between caregiver distress and perception of child symptom severity mixed: significantly correlated; 66 not correlated. 52
	BSI-GSI (2 studies, 38,50 1 with normative sample comparisons38) Cutoff: T score >63 (90th percentile)	• 52.8±11.050 • Above cutoff: 19.7%50	• SCD caregiver distress did not differ from the BSI normative sample. 38 • Distress negatively associated with caregiver child concordance regarding child’s health-related quality of life. 50
	GHQ-12 (2 studies, 36,391 study with control group36) Cutoff: ≥2, 36 ≥339	• Mean NR • Above cutoff: 43.8%39 to 62.2%36	• Caregivers of children with SCD hospitalized more frequently reported emotional distress. 39  Compared to caregivers of children without a chronic condition, more mothers of children with SCD reported distress (62.2% versus 35.6%) but distress similar compared to mothers of children with T1DM (53.3%).36
	Distress Thermometer (1 study) 60 Range: 0–10; higher score=greater distress	• 3.6±3.1 • Cutoff NR	• Not tested
	SF-36 (1 study with a control group) 29 Range: 0–100; lower scores = worse health	• 74.9±36.6 • Cutoff NR	• Caregivers of children with SCD had greater distress compared to caregivers of children without a chronic condition (74.9±36.6 versus 100.0±0).
	Stressful Life Events Questionnaire (1 study) 65 Range: 0–9; higher score=greater distress	• 2.9±2.0 • Cutoff NR	• Not tested
	SRQ (1 study with 2 control groups) 32 Cutoff: ≥5=psychiatric morbidity	• Mean NR • 28%	• Psychiatric morbidity of SCD caregivers (28%) did not differ from caregivers of children with either asthma (20%) or acute medical illness (25%).  No association between SCD caregiver psychiatric morbidity and child clinic visits in past 6 months or previous hospitalizations.
	Investigator developed scale (2 studies) 40,46 Range: 0–340, higher scores=greater distress	• 2.3±0.5040 to 2.4 (Median) 46 • Cutoff NR	• Greater distress reported by caregivers of children with >3 painful crises. 46
	Depression, Anxiety, Stress Scale-21 (1 study with a control group) 35 Range: 0–21; higher scores-greater distress	• Moderate and higher: 32.4%	• Proportion with at least moderate levels of distress not significantly different that caregivers of children with diabetes.
Anxiety/Depressive Symptoms
Anxiety (7 studies)	BAI (1 study) 41 Range: 0–63 Cutoff: 0–7=minimal; 8–15=mild; 16–25=moderate; 26–63=severe anxiety	• Mean NR • Above cutoff: 13% moderate and 8% severe anxiety	• Not tested
	GAD-7 (2 studies) 12,55 Range: 0–21 Cutoffs: 8–15=mild; 16–25= moderate; 26–63= severe anxiety	• Mean Range: 4.7±0.312 to 4.7±4.955 • Cutoff NR in either study	• Caregiver anxiety symptoms related to increased child pain intensity and functional disability; child chronic pain did not moderate this relationship. 12  Not tested55
	SCL-90-R Anxiety subscale (1 study) 49 Cutoff: T score>63 (90th percentile)	• Mean NR • Cutoff NR	• Caregiver55 anxiety not associated with child’s disease severity.
	STAI (1 study) 64 Range 20–80 Cutoff: >39–40=clinically significant anxiety	• 30.6±9.6 • Cutoff NR	• Caregiver anxiety not associated with child’s pain.
	Investigator developed scale (1 study) 57 Range: 3–12; higher scores=greater anxiety	• 4.9 • Cutoff NR	• Caregiver anxiety greater for those of children with severe disease severity compared to children with mild and moderate disease severity.
	Depression, Anxiety, Stress Scale-21 (1 study) 35 Range: 0–21; higher scores=greater anxiety	• Moderate and higher: 26.5%	• Proportion with at least moderate anxiety symptoms not significantly different that caregivers of children with diabetes.
Depressive symptoms (12 studies)	BDI (2 studies) 41,43 Range 0–63 Cutoff: 21–30=moderate; 31–40= severe; >40=extreme depression	• 7.9±4.4 to 17.0±1.443 • Above cutoff: 13% moderate; 8% severe41	• No differences in caregiver depression by number of painful crises. 43
	CES-D (1 study) 44 Range 0–60 Cutoff: ≥16=depression	• 16.6±12.0 • Cutoff NR	• Not tested
	CESD-R-10 (2 studies) 12,55 Range: 0–30 Cutoff: ≥10=depression	• Mean range: 8.4±0.312 to 8.4±6.3. 55 • Cutoff NR	• Caregiver depressive symptoms associated with increased child pain intensity and functional disability; child chronic pain did not moderate relationship. 12 • Not tested. 55
	SCL-90-R Depression subscale (2 studies, 30,49 1 with a control group30) Cutoff: T score>63 (90th percentile)	• 53.5±14.049 • Above cutoff: 22%30	• Caregiver depression not associated with child’s disease severity. 49 • No differences in depression between caregivers of children with SCD and a comparison group of community caregivers of children matched on sex and race as the child with SCD. 30
	IPAT Depression Inventory (1 study with 2 control groups) 37	• 6.0±1.9 • Cutoff NR	• No differences in depression between caregivers of children with SCD, caregivers of children with T1DM and without a chronic condition.
	PHQ-2 (1 study) 45 Cutoff: Score ≥3	• 3.7±2.0 • Cutoff NR	• Caregiver depressive symptoms not associated with number of child pain crises in past 12 months.
	PROMIS Depression Scale (2 studies) 54 Cutoff: T score 55–60=mild; 60–70= moderate; >70=severe depression	• Above cutoff: 15.8%	• Not tested
	TAAQoL – Depressive Mood subscale (1 study with a normative sample comparisons31) Range: 0–100; lower score=greater depression	• Median (IQR) 58 (33, 66)	• Compared to caregivers of children without a chronic condition (67 [50, 88]) and to Dutch normative sample (83 [75, 92]), SCD caregivers had more severe depressive symptoms (p=0.02).
	Depression, Anxiety, Stress Scale-21 (1 study) 35 Range: 0–21; higher scores-greater depression	• Moderate and higher: 34.7%	• Proportion with at least moderate depressive symptoms not significantly different that caregivers of children with diabetes.
	Investigator developed scale (1 study) 57 Range: 4–16; higher scores=greater depression	• 9.5 • Cutoff NR	• Caregiver depression not associated with child illness severity.
Combined (1 study)	Family Symptom Inventory (1 study with 2 control groups) 33 Caregiver internalizing symptoms subscale (i.e., anxiety and depressive symptoms combined) Range 0 (never/rare)-3 (most days)	• 0.6±0.5 • Cutoff NR	• Caregivers of children with SCD reported fewer internalizing symptoms (0.6±0.5) compared to caregivers of children with cancer (0.9±0.8) and other hematological conditions (1.1±0.7, p<0.05). • Caregiver internalizing symptoms did not moderate association between child sleep and pain.
Parenting Stress
Parenting Stress (15 studies)	PIP (11 studies) 12,41,44,47,51,53,55,59,62,63,65 Range: 40–210 for Total Frequency and Total Difficulty	• Mean Range: • Frequency = 67.4±12.0344 to 114.9±32.541 • Difficulty = 71.4±18.7 44to 100.5±32.247 • Cutoff NR	• Caregiver perception of child’s pain burden mediated relationship between PIP score and ED visits. 62 • Higher scores associated with higher routine and urgent service use. 65 • Total score associated with caregiver perception of child’s SCD pain and ED visits. 62 • Total frequency negatively associated with child health-related quality of life. 59 • Total frequency associated with higher health care utilization. 51 • Total frequency and difficulty not associated with reported adherence; stratified by child age group, total difficulty associated with adherence for older youth only. 63 • Total frequency and difficulty higher among caregivers of youth who reported chronic pain versus episodic pain; neither score associated with hospital admissions in the prior year. 55
	Parent Stress Index (2 studies, 37,38 1 with 2 control groups, 37 1 with normative sample comparisons38)	• Mean NR • Cutoff NR	• Caregivers of children with SCD in 2 parent families had less stress around social isolation and relationships with spouse compared to caregivers of children with T1DM and non-disease controls. 37 • In single parent families, there were no differences in stress of caregivers of SCD compared to caregivers of children with type 1 diabetes and caregivers of children without a chronic condition. 37 • Compared to a normative sample, caregivers of children with SCD reported higher levels of situational/demographic life stress and stress due to child distractibility/hyperactivity. 38 • Caregivers of children with more severe genotypes reported higher levels on PSI subdomain of depression and isolation compared to those of children with milder genotypes. 38
	Parental Stress Scale (1 study) 67 Range 18–90; higher scores=greater stress	• 39.6±9.9 • Cutoff NR	• Increased parenting stress associated with worse child health-related quality of life.
	Investigator developed scale (1 study) 57 Range: 1 (never)-4 (almost all the time)	• 2.08 • Cutoff NR	• Caregivers of children with severe illness severity had more stress because of the SCD than those of children with mild and moderate illness severity.
Other
PTSD (3 studies)	SCID IV PTSD module (1 study) 42	• Mean NR • Prevalence: 40%	• Not tested
	Impact of Events Scale-R (1 study with 2 control groups) 34 Cutoff: ≥30 suggestive of PTSD	• 14.5±18.3 • Above cutoff: 0%	• Compared to caregivers of pediatric transplant candidates, caregivers of children with SCD had less traumatic stress symptoms; similar traumatic stress to caregivers of children with HIV.
	PCL-C-6 (1 study) 60 Range: 6–30 Cutoff: ≥14=positive PTSD screen	• 10.0±5.2 • Cutoff NR	• Not tested
Reaction to illness (4 studies)	PECI – Guilt and worry; Unresolved sorrow and anger subscales (2 studies) 45,62 Range: 0–4; higher scores=worse mental health	• Guilt and worry:1.6±0.862 to 2.2±0.745 • Unresolved sorrow/anger: 1.0±0.662 to 2.0±0.945	• Caregiver reaction to child’s pain not associated with frequency of pain crises during past year. 45 • Caregiver reaction to illness associated with perception of child’s SCD pain burden but not associated with ED visits. 62
	Investigator developed scale - Anger (1 study) 57 Range: 0–3; higher scores=greater anger	• 1.4 • Cutoff NR	• Caregivers of SCD children with severe illness had more anger than caregivers of children with mild and moderate illness severity.
	Pain Catastrophizing Scale (1 study) 56 13 items, 5-point scale Range 0–52; higher scores=higher levels of catastrophizing Cutoff: >30=clinically relevant level of catastrophizing	• 26.8±11.1 • Cutoff NR	• Caregiver catastrophizing associated with child pain intensity and frequency and functional disability.

Abbreviations: SD=standard deviation; SCL-90-R=Symptom Checklist-90-Revised; SCD=sickle cell disease; BSI-GSI= Brief Symptom Inventory, Global Severity Index; GHQ-12=General Health Questionnaire; NR=not reported; SF-36=Medical Outcomes Study 36 - Item Short-Form Health Survey; SRQ Self-Reporting Questionnaire; BAI=Beck Anxiety Inventory; GAD-7=Generalized Anxiety Disorder Scale; STAI=State Trait Anxiety Inventory; BDI=Beck Depression Inventory; CES-D= Center for Epidemiologic Studies Depression Scale; CESD-R-10= Center for Epidemiologic Studies Depression Scale Revised; PHQ-2=Patient Health Questionnaire; PROMIS= Patient-Reported Outcomes Measurement Information System; TAAQoL=TNO-AZL Adult Quality of Life Questionnaire; PIP=Pediatric Inventory for Parents; SCID IV= SCID IV= Structured Clinical Interview for DSM-IV; PCL-C-6= Post-Traumatic Checklist – 6 Item Civilian Version; PECI=Parent Experience of Child Illness

Psychological adjustment.

Caregiver distress was measured in 17 studies using nine self-report measures. Of these measures, the SCL-90-R Global Severity Index was most frequently used. ^{30,48,49,52,58,61,66} Four of the nine instruments used, SCL-90-R Global Severity Index, ^{30,48,49,52,58,61,66} Brief Symptom Inventory-Global Severity Index, ^38,50 General Health Questionnaire^36,39 and SRQ, ³² have validated cutoff scores indicating elevated levels of distress. In these studies, the prevalence of caregivers with elevated levels of distress ranged between 19.7% and 62.2%.^{50, 36}

In five studies, associations were tested between caregiver distress and perception of child disease severity, as indicated by frequent hospitalization or painful crises and poorer health-related quality of life. Results were mixed: three studies reported significant associations^39,50,66 and two studies reported no association. ^32,52 Similarly, divergent findings were reported for associations between caregiver distress and child coping strategies: two studies found significant associations, ^48,58 whereas one did not. ⁶¹

Three of these studies compared caregivers of children with SCD with caregivers of youth without a chronic condition, ^30,38,57 one to caregivers of children with another chronic illness, ³² and one to caregivers of youth without a chronic condition or caregivers of children with another chronic condition. ³⁶ Of these, results were heterogeneous; compared with caregivers of healthy children, caregivers of youth with SCD reported greater distress, ^29,36 less distress,⁵⁷ or no differences in distress. ^30,38 Both studies that compared caregivers of youth with SCD to caregivers of youth with either type 1 diabetes, asthma, or acute medical illness found no significant differences in distress experienced by caregivers. ^32,36

Anxiety/depressive symptoms.

Five studies examined caregiver anxiety symptoms each using a different self-report measure; ^{12,41,49,57,64} all but one study⁵⁷ used validated instruments. Of the five, one study used validated cutoff scores, reporting that 21% of caregivers were above the cutoff indicating moderate or severe anxiety. ⁴¹ Of the four studies that examined associations of caregiver anxiety symptoms to severity of the child’s SCD, two found that caregiver anxiety was associated with increased child disease severity. ^12,57

Twelve studies examined caregiver depressive symptoms, using nine self-report measures. Of these, two studies used the Becks Depression Inventory^41,43 and two used the SCL-90. ^30,49 Among the three studies that reported validated cutoff scores, ^30,41,54 the range of caregivers with elevated depressive symptoms was 15.8%⁵⁴ to 22%.³⁰

Four of those studies examined associations of caregiver depressive symptoms and perception of child disease severity, of which three found no association. ^43,45,49 One study found caregiver depressive symptoms were associated with increased child SCD severity, and that relationship was not moderated by child chronic pain. ¹²

Three studies compared caregivers of children with SCD with caregivers of children without a chronic illness and/or with a chronic illness other than SCD. Two found no significant differences between these groups. ^30,37 One Dutch study found that caregivers of youth with SCD had more severe depressive symptoms than caregivers of children without a chronic illness or a normative national adult population. ³¹

In one of those studies, the Family Symptom Inventory was used to assess combined anxiety and depressive symptoms (i.e., internalizing symptoms). In that study, caregivers of children with SCD reported fewer internalizing symptoms than caregivers of children with cancer or other hematological conditions. ³³

Parenting stress.

Stress or strain associated with parenting a child with SCD was assessed in 14 studies using four self-reported measures. Of these, 10 used these the Pediatric Inventory for Parents (PIP) ^{12,41,44,47,51,59,62,63,65} and two used the Parent Stress Index. ^37,38

Seven studies found significant associations between parenting stress and severity of the child’s SCD^{38,51,57,62,65} or with worse child health-related quality of life. ^59,67 Smith et al. ⁶³ found that, across their sample of 12- to 18-year-olds, parenting stress was not related to treatment adherence. However, when stratified by age, increased parenting stress was associated with poorer treatment adherence among youth older than age 14. ⁶³

Two studies compared parenting stress with control samples, with mixed findings; one study³⁸ finding no association to normative samples (i.e., the representative sample the measures were developed on). In contrast, the other study³⁷ reported that caregivers of youth with SCD from two-parent households—but not of one-parent households—experienced less parenting stress than caregivers of children with type 1 diabetes or children without a chronic illness.

Other mental health symptoms.

Seven studies examined other caregiver mental health symptoms. Of these, three assessed post-traumatic stress disorder (PTSD). ^34,42,60 Using a semi-structured clinical interview, the Structured Clinical Interview, one study reported that 40% of caregivers of a child hospitalized at least once for a vaso-occlusive crisis had PTSD. ⁴² In contrast, one study using a self-report measure reported that no caregivers had scores suggestive of PTSD. Interestingly, SCD caregivers were found to have levels of traumatic stress like those of caregivers of HIV-infected children but less traumatic stress than caregivers of pediatric transplant candidates. ³⁴ Still another study found that most SCD caregivers reported symptoms below the cut point suggestive of PTSD. ⁶⁰

All four studies assessing caregivers’ reaction to the child’s illness used self-report measures. Using the Parent Experience of Child’s Illness Scale (PECI) to assess guilt, worry, sorrow and anger, ^45,62 both studies reported that caregiver’s reaction to the illness was not associated with the child’s disease severity. In contrast, increased SCD severity was associated with anger (assessed using an investigator developed scale) ⁵⁷ and catastrophic thinking. ⁵⁶

Discussion

Our systematic review synthesized the findings of studies that examined the mental health symptoms experienced by caregivers of youth with SCD. Forty eligible studies from 10 countries assessed differing mental health symptoms using a range of tools. Samples were generally modest in size and comprised primarily of female caregivers. The most studied caregiver symptoms were caregiver distress, stress associated with parenting a child with SCD, and depression. While most studies used validated measures for each mental health construct, the measures used varied widely across studies. Relatively few studies included comparisons to caregivers of youth without a chronic condition or to caregivers of youth with a chronic condition other than SCD – only eight studies included a comparison group—either caregivers of children without a chronic illness and/or caregivers of a child with a different chronic illness, ^29–37 while two additional papers compared caregiver distress with a normative adult sample. ^31,38

Our findings from this review demonstrate that caregivers of children with SCD commonly experience mental health problems. This finding was consistent with results from a prior systematic review of caregivers over a range of pediatric chronic health conditions, ⁶⁸ where 20%⁵⁰ to 62%³⁶ of the caregivers exceeded clinical thresholds across the mental health measures used. Comparing the severity of mental health problems with caregivers of children without a chronic condition yielded mixed results. When significant differences were found, caregivers of youth with SCD had worse mental health, which is consistent with other reviews across several childhood serious chronic conditions, ^22,69 including cystic fibrosis⁷⁰ cancer, ⁷¹ and asthma. ⁷² When compared with caregivers of children with other chronic conditions, caregivers of youth with SCD did not suffer worse mental health.

Increased mental health problems among caregivers of youth with SCD relative to those with children without a chronic illness may be due to several disease-related factors. ⁷³ Caregivers experience stress around managing a life-threatening disease punctuated by acute, often unpredictable episodes of severe pain, fevers, and respiratory vulnerability. Caregiver stress also may derive from concerns related to the negative consequences of the child’s SCD (e.g., shortened life expectancy), evolving caregiver-youth roles and responsibilities, balancing demands of caring for their child with other demands, and fearing a lack of control over the disease. ^21,68,74 Additional risks to caregivers due to societal burdens may contribute to adverse mental health. Historically, youth with SCD and their caregivers have contended with disease-associated stigmatization and racism both outside and within the health care system in the U.S. ^73,75,76 Caregivers may have perceived blame or rejection by family, friends, and health care providers. ⁷⁷ Additionally, caregivers of youth with SCD can be financially burdened by the cost of health care (including through disruptions in job attendance, especially for single-parent and/or lower-income households). ⁵

Of the studies that assessed associations to the child’s SCD severity or treatment adherence, most (65%) studies reported that poorer caregiver mental health was associated with worse child SCD-related outcomes or treatment adherence. This finding has important implications for the health of youth with SCD, as caregivers with increased mental health challenges may be ill-equipped to provide needed care to their child with SCD. For example, caregiver anxiety or depression may impede their implementation of the child’s treatment plan or ability to smoothly communicate with health care providers. ⁷⁸ Additionally, while not the focus of this review, it is worth noting that having a caregiver with mental health problems increases the risk that the child will also experience poor mental health. ^22,70,79,80

Our interpretations are limited by the quality of the studies included in this review. Studies lacked control for confounding factors and/or failed to justify sample sizes. Across all the mental health constructs, there was considerable variability in the measures used to assess a given construct. Therefore, absolute levels of symptoms could not be aggregated. Similarly, while most studies utilized validated measures, those measures that lacked clinical cutoff scores limited comparisons regarding the levels adverse mental health. With few exceptions, all caregiver mental health data were assessed by self-report, which limited our understanding regarding diagnosed mental health. Male caregivers were not well represented, precluding our ability to stratify results by caregiver sex. Study samples were drawn largely from SCD centers, which tend to treat patients with more severe disease. In addition to selection biases, participating in a study of mental health within the context of the center may have led to a tendency for social desirability (i.e., wanting to appear in good health). Assessing the impact of SES on caregiver mental health was limited by the fact that standardized instruments to assess SES were not used in U.S.-based or international studies. A uniform definition of SCD severity does not exist, ⁸¹ and measures used varied by study. The studies included in this review were performed over a period of 29 years and in different regions of the U.S. and countries in Europe and sub-Saharan Africa. Some aspects of care and stressors are reasonably expected to differ by local culture and to have changed over three decades. Stressors under evolving conditions may differentially affect care features and affect caregiver mental health. For example, only two studies included in this review collected data during the COVID-19 pandemic starting in 2020. ^54,55 None of the studies reviewed had assessed caregiver’s resilience, despite the range of risks to their mental health and well-being.

Despite these limitations, this systematic review has important implications for identifying research gaps and for provision of health care. Rigorously designed studies are needed that utilize standardized, validated measures which have been critically reviewed and recommended by experts^82,83 to better understand the mental health of caregivers of children with SCD, as well as the implications for the child’s health. Future studies should also include assessments of factors such as social determinants of health, the availability of secondary (back-up) caregivers, pre-existing mental health challenges for caregivers and children with SCD, and the access to and use of resources by caregivers and youth. Additionally, socioeconomic data should be collected to facilitate comparisons across geographic locations. Moreover, longitudinal studies are needed to allow for the aggregation and validation of findings across studies for understanding the trajectory of caregiver mental health across different stages of their child’s diagnosis, e.g., following the time of their child’s diagnosis and during periods of more or fewer disease symptoms. ⁸⁴ Understanding the longer-term impact of caregiver mental health on their children’s health and mental health over the course of the child’s life is also an important feature.

Clinical implications of the findings include recognition of caregiver mental health issues and determining appropriate, available interventions. Based on our findings, the screening of caregiver mental health may be worth incorporating into the routine care of the child’s SCD treatment, along with referrals to appropriate psychosocial services when warranted. This systematic review supports the need to develop and rigorously evaluate screening for and interventions to improve the mental health of caregivers of youth with SCD. Given the known overall association of caregiver and youth mental health, ^22,70,79,80 mental health screening of and referral for youth with SCD may also be warranted.