Practices of sickle cell disease genetic screening and testing in the prenatal population

Abstract

BACKGROUND:

Genetic screening and testing are technologies historically underutilized in Black populations despite predicting diseases like sickle cell disease (SCD), which is predominantly found in Blacks. We surveyed prenatal patients to understand choices, beliefs and experiences surrounding genetic screening and testing, specifically for SCD.

METHODS:

In this cross-sectional study, we surveyed 322 women during prenatal visits. Responses were analyzed to identify barriers to care and education about testing and screening for SCD. Patients rated whether they agreed or disagreed with statements regarding sickle cell health behaviors. We used χ² tests to compare categorical variables by self-reported race. Binary logistic regression was used to determine the odds ratios and confidence intervals for each outcome.

RESULTS:

Women were a mean (SD) age of 33.3 (6.1). 42.9% of patients self-identified as White while 41.3% of patients self- identified as Black. Screening questions were adjusted for differences in race, insurance, and education levels to show significant differences in responses between Blacks and Whites for screening for SCD (p = 0.047, OR 95% CI = 0.455 [0.210–0.989]) and plans to meet with genetic counselors (p = 0.049, OR 95% CI = 0.299 [0.090–0.993]). The statements “if sickle cell is not in their family, then it is likely not in themselves or their children,” was significantly different between Black and White populations (p = 0.011, OR 95% CI = 0.207 [0.081–0.526]).

CONCLUSION:

Our findings suggest gaps in screening, testing, education, and pregnancy management choices between Black and White patients. Research should focus on decreasing these healthcare gaps and improving education that address concerns about SCD for relevant populations.

Keywords

Genetic screening provider practices sickle cell

Abbreviations

Cystic Fibrosis

Confidence Interval

CVS

Chorionic Villus Sampling

GW MFA

GW Medical Faculty Associates

Ob/Gyn

Obstetrics and Gynecology

Odds ratio

SCD

Sickle Cell Disease

SCT

Sickle Cell Trait

Standard Deviation

1 Background

According to the CDC (2020), sickle cell disease (SCD) occurs in 1 in every 365 Black births, and sickle cell trait (SCT) occurs in 1 in every 13 Black births [1]. Complications of SCD include acute chest syndrome, stroke, infection, and organ failure, and has an estimated annual cost per patient ranging from $18,859 to $43,586 [2] SCD is also a historically underfunded orphan disease [3] 1 per 365 black individuals are born with SCD compared to 1 per 2500 white individuals born with cystic fibrosis (CF). Despite this, in a study comparing 90,000 SCD patients and 30,000 CF patients, NIH funding per person with CF was $2,807 with a SD of $175, compared to SCD with a mean funding of $812 per person and a standard deviation of 147 (P < 0.001). There are also disparities in philanthropic expenditures: $7690 with a standard deviation of $3974 for CF, compared to $102 with a standard deviation of $13.7 for SCD (P < 0.001).

Compared to other orphan and chronic diseases, SCD has fewer comprehensive health care centers and specialized providers, decreased counseling and prophylactic treatments compared to other chronic diseases [4]. Inequalities in treatment are also linked to 60% of SCD patients using Medicare and Medicaid for insurance. This limits access to specialized care, decreases use of primary care providers and increases emergency department visits. Until now, modern genetic screening and testing, as well as education, has not been as extensively researched and offered to minority populations, including Black patients at risk for SCD [5]. Additionally, the perceived burden of SCD may affect prenatal genetic testing and screening choices. In a United States study that conducted focus groups for adults living with SCD or SCT, it was found that reproductive decisions were largely based on previous experiences of suffering and the severity associated with the disease [6].

Disparities in genetic testing are further compounded since it has been shown Black patients have differences in knowledge about genetic testing and types of health insurance compared to their White counterparts. Additionally there are significant concerns about the misuse of genetic material and mistrust in physicians and the medical system [7]. The National Sickle Cell Anemia Control Act of 1972 was an attempt to increase healthcare for those with SCD or SCT. Instead, it resulted in job and insurance discrimination for these patients [8].

The goal of this research is to investigate current education, genetic testing, and genetic screening practices for SCD in prenatal populations. This research will help clarify potential healthcare barriers to improve counseling patients about SCD and to decrease inequalities in care for SCD patients.

2 Methods

2.1 Patients and procedures

Participants included 500 women attending prenatal appointments at the George Washington Medical Faculty Associates (GW MFA) offices in Washington, DC. Participants were approached by a recruiter and asked if they qualified to fill out either a prenatal or gynecological survey and were then given privacy to fill out the survey. Data was collected between July 2019 and May 2021. If gynecological patients incorrectly offered to fill out the prenatal survey, their data was excluded. Participants were at least 18 years of age and were competent enough in English to read information sheets about the survey and respond to the survey questions. The study was approved by the George Washington University Committee on Human Research, Institutional Review Board. All survey questions were voluntary and patient information was non-identifiable to a specific patient.

2.2 Prenatal survey

The surveys given to obstetrical patients included 23 questions, composed of multiple choice, Likert scales, and short answer questions. The survey took approximately ten minutes to complete. Question subject matter included demographics such as age, ethnicity, education, and insurance coverage. The survey also asked about pregnancy status and personal or family history with SCD and SCT, as well as with genetic screening and testing. Finally, the survey asked patients to rank their level of agreement with statements about SCD and genetic screening and testing.

2.3 Data analysis

All prenatal data was analyzed using SPSS software for statistical computing and descriptive statistics. We used χ² tests to compare categorical variables by race self-reporting. Binary logistic regression was used to determine the odds ratios and 95% confidence intervals for each of the outcome variables. P value significance was set at ≤0.05. The data was adjusted solely for race (Model 1), and race, insurance, and education (Model 2). P values and odds ratios were generated for each of the adjusted data categories. Data analysis of the Likert scale was adjusted to either Agree (Strongly Agree and Agree) or Not Agree (Neutral, Disagree, Strongly Disagree). Similarly, education level grouped college graduates and graduate/professional degree as one category of “college degree or more.”

3 Results

A total of 322/500 patient surveys were analyzed (Table 1). Surveys were not analyzed if most of the survey was incomplete or patients completed a gynecological survey. Patient surveys were also excluded from analysis if the patient did not identify as White or Black since there was not a large enough sample size from Asian, American Indian or Alaska Native, Native Hawaiian/ Other Pacific Islander or the Hispanic/Latino populations to generate significant data. The age range for patients was between 20 years and 57 years, with the average patient age of 33.3 years. The highest percentage of patients had a graduate/professional degree and the majority had previous pregnancies and health insurance. Patients ranged from 4 to 41 weeks pregnant with the average patient 24.6 weeks pregnant.

Table 1
Prenatal maternal characteristics and exposures by race

Overall N = 322 Black N = 132 White N = 137

Participant Characteristics N (%)

Average Age (Standard Deviation) 33.3 (6.3)

Race/Ethnicity (%)

White 137 (42.9)

Black 132 (41.3)

American Indian or Alaska Native 7 (2.2)

Asian 18 (5.6)

Native Hawaiian or other Pacific Islander 1 (0.3)

Hispanic or Latino 15 (4.7)

Other 12 (3.7)

Education

Less than high school diploma 5 (1.5) 2 (1.5) 0 (0)

High school diploma, GED, or equivalent 99 (30.7) 89 (67.4) 3 (2.3)

College Graduate 71 (22.0) 20 (15.2) 38 (27.7)

Graduate/Professional Degree 146 (45.3) 20 (15.2) 96 (70.1)

Number of Pregnancy

First one 120 (37.3) 35 (26.5) 60 (43.8)

Previous Pregnancy 202 (62.7) 97 (73.5) 77 (56.2)

Health Insurance Status

Yes 310 (96.2) 127 (96.2) 134 (97.8)

No 12 (3.7) 5 (3.8) 3 (2.8)

	Overall N = 322	Black N = 132	White N = 137
Participant Characteristics N (%)
Average Age (Standard Deviation)	33.3 (6.3)
Race/Ethnicity (%)
White	137 (42.9)
Black	132 (41.3)
American Indian or Alaska Native	7 (2.2)
Asian	18 (5.6)
Native Hawaiian or other Pacific Islander	1 (0.3)
Hispanic or Latino	15 (4.7)
Other	12 (3.7)
Education
Less than high school diploma	5 (1.5)	2 (1.5)	0 (0)
High school diploma, GED, or equivalent	99 (30.7)	89 (67.4)	3 (2.3)
College Graduate	71 (22.0)	20 (15.2)	38 (27.7)
Graduate/Professional Degree	146 (45.3)	20 (15.2)	96 (70.1)
Number of Pregnancy
First one	120 (37.3)	35 (26.5)	60 (43.8)
Previous Pregnancy	202 (62.7)	97 (73.5)	77 (56.2)
Health Insurance Status
Yes	310 (96.2)	127 (96.2)	134 (97.8)
No	12 (3.7)	5 (3.8)	3 (2.8)

Most patients reported in question 1 that they had not been screened for SCD in their current pregnancy (Table 2). There was a significant difference (p = 0.003) between Black and White populations for question 1, with Black patients being less likely to report being screened for SCD than White patients (OR 95% CI = 0.425 [0.240–0.751]). The majority of screened and/or tested patients did not think their provider had explained the difference between genetic testing and screening (question 2). Black patients were less likely to report having the difference in genetic testing/screening explained than White patients (p = 0.005, OR 95% CI = 0.373 [0.188–0.740]). Within the small percentage of patients planning to meet with genetic counselors, Blacks were significantly (p = 0.001) less likely to plan to meet with a genetic counselor than White patients according to question 3 responses (OR 95% CI = 0.207 [0.081–0.526]).

Table 2

Prenatal responses to screening/testing experience

	Overall N = 322	Black N = 132	White N = 137
Measured Outcomes N (%)
Question 1: Patient was screened for Sickle Cell Anemia
No	235 (72.9)	88 (66.7)	113 (82.5)
Question 2: Provider explained the difference between testing/screening
Yes	58 (18.0)	31 (23.5)	14 (10.2)
No	255 (79.2)	98 (74.2)	120 (87.6)
Question 3: Patient plans to meet with genetic counselor
Yes	33 (10.2)	24 (18.2)	6 (4.4)
No	267 (82.9)	101 (76.5)	122 (89.1)

When the responses to the three questions were adjusted for differences in race and insurance, there were still significant differences for all three questions (Question 1: p = 0.004, OR 95% CI 0.426 [0.240–0.757], Question 2: p = 0.006, OR 95% CI =0.380 [0.191–0.756], Question 3: p = 0.002, OR 95% CI 0. 220 [0.086–0.561]). Adjusting for race, insurance and education levels, significant differences remained between Blacks and Whites for question 1(p = 0.047, OR 95% CI = 0.455 [0.210–0.989]) and question 3 (p = 0.049, OR 95% CI = 0.299 [0.090–0.993]).

Patients were asked to rate whether they agree or disagree with statement 1, that “if sickle cell is not in their family, then it is likely not in themselves or their children.” The majority of patients agreed with this statement (Table 3). There was a significant difference in response to statement 1 between Blacks and White populations, with Blacks more likely to agree with this statement (p < 0.0001, OR 95% CI = 5.668 [3.263–9.846]). The majority of patients disagreed with statement 2, that they would not use information from SCD screens or tests to manage their pregnancies. There were no significant differences for statement 2 between Black and White populations.

Table 3

Level of agreement with statements about sickle cell, pregnancy and partner wishes

	Overall N = 322	Black N = 132	White N = 137
Survey Statements N (%)
Statement 1: “If sickle cell is not in my family, then I do not think it likely in me or my children.”
Agree	163 (50.6)	42 (31.8)	90 (65.7)
Not Agree	129 (40.1)	82 (62.1)	31 (22.6)
Statement 2: “I would not use information from genetic screening/testing in managing my pregnancy.”
Agree	44 (13.7)	17 (12.9)	23 (16.8)
Not Agree	247 (76.7)	104 (78.8)	99 (72.3)
Statement 3: “I would not terminate a pregnancy for sickle cell anemia.”
Agree	206 (64.0)	97 (7.3)	79 (57.7)
Not Agree	78 (24.2)	23 (17.4)	40 (29.2)
Statement 4: “My partner does not want to get sickle cell screening.”
Agree	15 (4.7)	11 (8.3)	2 (1.5)
Not Agree	271 (84.2)	110 (83.3)	118 (86.1)
Statement 5: “I am already too late in pregnancy to have testing.”
Agree	38 (11.8)	12 (9.1)	19 (13.9)
Not Agree	239 (74.2)	107 (81.1)	97 (70.8)

The majority of patients agreed with statement 3, that they would not terminate their pregnancy for a SCD diagnosis. There was a significant (p = 0.009) differences in Black and White responses to this question. Black patients were more likely to disagree with this statement and consider termination (OR 95% CI = 0.448 [0.246–0.815]). Most patients disagreed with statement 4, that their partner did not want them to get sickle cell screening, also with significant (p = 0.023) differences between Black and White populations (OR 95% CI = 0.169 [0.037–0.782]). Black patients were more likely to have partners that wanted them to be screened. Finally, the majority of patients disagreed with statement 5, that they were too far along in their pregnancy to have genetic testing, with no significant differences between Black and White populations.

After adjusting for race and insurance, there were still significant differences for all these statements between White and Black populations. While adjusting for race and education levels, only responses to statement 1 remained significant (p = 0.011, OR 95% CI = 2.579 [1.245–5.342]).

4 Discussion

Overall, we found that the most significant differences between races are between approaches to education, testing/screening, and beliefs and practices surrounding a gestational diagnosis of SCD. Despite SCD predominantly affecting the Black population, Blacks reported that they were less likely to be screened than Whites for SCD. Black patients were also less likely to meet with genetic counselors. Furthermore, Black patients reported less frequency of providers explaining the differences between genetic screening and testing. While it is unlikely that providers specifically screen less for SCD in Black patients than White patients, this gap in screening may reflect overall decreased use of genetic testing and screening in Black patients than White patients. Regardless, considering the severity of SCD, Black patients should be screened, educated, and meet with genetic counselors at least equally, compared to their White counterparts. It is important to note, that these significant differences remained, even when adjusted by education and insurance, showing that it is not a difference in insurance coverage or education level that is causing differences in screening, knowledge, and usage of genetic counselors. However, the quality and coverage of the insurance is not listed, which may affect these answers and the data was heavily skewed to a patient population with both relatively high insurance coverage and education level.

Similarly, we saw differences across races regarding patient knowledge of family history, and usage of genetic testing/screening to manage their pregnancies. Regarding the Black patients being more likely to agree with the statement “If sickle cell is not in my family, then I do not think it likely in me or my children,” this difference may be contributed to personal family history with SCD or reflect patient knowledge about a disease particularly relevant to their own race/ethnicity. Personal experience of the pain and suffering associated with SCD might also influence Black patients’ greater likelihood of considering terminating a fetus with a SCD diagnosis compared to White patients. Interestingly, in contrast to previous studies, we found that Black patients’ partners overall supported SCD screening, in contrast to previous studies which contradicted this [9]. This increase in support may be associated with increased educational efforts by Ob/Gyn practices about the importance of genetic screening.

Healthcare disparities in prenatal care have been previously examined, but no specific study have addressed SCD and compared rates of genetic testing in Black and White populations. A similar study compared disparities in screening and awareness of high cholesterol in the prenatal population [10]. This study also used a convenience sample, and similarly found that non-Hispanic black women had both lower odds of having a previous lipid screening and awareness that high cholesterol is related to high risk of cardiovascular disease. While this study also highlights the need for better prenatal care for Black patients, out study focuses on a disease specific to the Black population. In another study discussing disparities in prenatal care, the authors reported that while Black women were less likely to receive prenatal care, they were also less likely to report perceived barriers to care [11]. While this study reflects a broader scope of disparities between Black and White prenatal care, it reflects the need for the healthcare system to focus on eliminating these disparities between Black and White patients.

Limitations to this study include that patient surveys were voluntary, based on convenience sampling, and based on patient self- identification of race. As there is no standardized patient sample to compare the study population and clinic population, this study may not be generalizable to all patients, especially patients in other populations that have different demographics. Additionally, while education and insurance status may reflect income, we did not directly assess socio-economic status and that effect on screening or knowledge. However, a strength of the study is that patients were randomly sampled between 8:00 am–5:00 pm regardless of reason for their prenatal visit which increases the likelihood of generalizability. Additionally, patients were required to answer on a binary agree or disagree without room for explanations and data is self-reported so any recall bias may skew results.

5 Conclusions

The study findings suggest that Black patients experience disparities in education and genetic screening and testing practices compared with White patients. Additionally, Black patients have distinctive opinions about family history and pregnancy management based on a SCD diagnosis. This suggests that providers need to increase their educational and testing/screening efforts in the Black populations, particularly about SCD. In addition, SCD educational practices should be updated to reflect concerns or opinions for relevant populations, in this case, Black populations. Future research should focus on studies assessing the effectiveness of educational tools that address concerns about SCD specific to the Black populations as well as a standardized protocol for screening and testing patients at risk for SCD.

Disclosure statements

Ethics approval and human research statement

Research involving human subjects submitted to the Journal of Neonatal-Perinatal Medicine was conducted in accordance with the ethical standards of all applicable national and institutional committees and the World Medical Association’s Helsinki Declaration. A fact sheet and information about the study was provided to women at their prenatal visit and informed consent was obtained from the participants, before they completed the survey. The study protocol was approved by The George Washington University’s institutional review board.

Consent for publication

Not applicable.

Availability of data and materials

The datasets used during the current study are available from the corresponding author on reasonable request.

Competing interests

The authors declare that they have no competing interests.

Funding

No funding to be declared for this study.

Authors’ contributions

AP, ACB, NG, and JW conceptualized and designed the study, analyzed, and interpreted the data, and drafted the initial manuscript. CM, VCC, JS, and JW interpreted the data and critically reviewed the manuscript for important intellectual content.

All authors read and approved the final manuscript.

Footnotes

Acknowledgments

JS is supported by a grant from the Health Resources and Services Administration UA6MC31609 which supports the Pregnancy-Related Care Research Network.

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