Prenatal serum screening is a crucial step during pregnancy to estimate the risk of fetal genetic conditions. However, using race in these assessments can increase false positive results and unnecessary testing. The College of American Pathologists (CAP) recently obtained a grant to address the use of race in clinical algorithms, aiming to advance health equity for those receiving biochemical prenatal serum screening.
We speak with Ricky D. Grisson, Assistant Professor of Clinical Pathology at Brown University, about the importance of re-evaluating prenatal serum screening guidelines.
Why is it important to re-evaluate the use of race in biochemical prenatal serum screening algorithms from a diagnostic perspective?
Race is a social construct, not a biological one. In biochemical prenatal serum screening, several factors influence risk estimates for trisomies 13, 18, and 21, as well as open neural tube defects. If evidence shows that differences once attributed to race are actually the result of other biological or social-behavioral factors, then race should be removed from the equations used for estimating those risks.
Diagnostic calculations must be grounded in sound scientific evidence. Failing to do so risks perpetuating the false belief that racial health differences and disparities are rooted in genetics.
What are the potential diagnostic consequences of continuing to use race-adjusted algorithms?
Adjusting fetal anomaly risk calculations based on maternal race may increase false-positive results, leading to heightened stress and anxiety, as well as unnecessary diagnostic testing.
What will be the scope of the evidence-based guideline CAP is developing, and how will it be used by diagnostic laboratories?
The guideline, informed by a systematic review of the literature, will assess whether excluding race-based adjustments in the calculation of certain key biomarkers yields diagnostic test characteristics and patient-centered outcomes equivalent to those obtained with race-based adjustments. It will address risk assessments for open neural tube defects, as well as trisomies 18 and 21. The final key questions will be posted on the CAP website once approved by the expert panel.
How will the race-neutral algorithms be validated?
We will conduct a prospective case-control clinical trial involving three well-defined racial groups, with participants matched on key demographic variables before receiving maternal serum screening as part of routine prenatal care. For each participant, we will also collect standardized data on social-behavioral determinants of health (SBDOH).
By combining demographic, biochemical, SBDOH, and outcome data, we will assess whether biochemical differences persist between the equally sized racial groups. We will then create a modern multivariable regression model to predict biochemical results and fetal anomaly risk, and compare its performance to conventional race-based risk assessment models. Once complete outcome data are available, we will evaluate the sensitivity and specificity of the modern model against the conventional model.
Improving test performance typically involves enhancing the screening technology itself. However, prior retrospective studies suggest that advanced biostatistical methods can remove race from the model while maintaining – or even improving – performance. While we cannot guarantee that a prospectively developed, race-agnostic model will match or outperform current race-based models, our goal is to rigorously test this possibility while controlling for historically important demographic variables. If differences persist, we will explore remaining confounders, whether biological or social-behavioral.
In summary, this study will use modern analytical techniques to uncover the biological and social-behavioral factors that may underlie fetal anomaly risk – factors that have previously been attributed to race.
How might this guideline and accompanying research reshape laboratory protocols and risk reporting in prenatal biochemical screening?
Based on the findings of the guideline committee and the clinical research team, we will propose whether the use of race should continue in prenatal maternal serum screening. We anticipate that this recommendation could have a domino effect, prompting risk prediction software vendors to update their programs and equations – similar to the removal of race from eGFR calculations following the release of the CKD-EPI 2021 equation. In that case, progressive education and guidance from the National Kidney Foundation and the American Society of Nephrology led laboratories and clinicians to adopt a race-free method for estimating kidney function.
How do you foresee this work influencing test interpretation and communication between the lab and clinical teams?
Based on previous retrospective studies of race in prenatal maternal serum screening, we anticipate that this work will demonstrate race to be unimportant for fetal anomaly risk assessment using maternal biochemistry. A complete participant outcomes analysis should help clarify the risks and benefits of a race-free algorithm.
We also expect that collaboration between laboratory and clinical teams will be strengthened, as the guideline committee includes both clinical and laboratory stakeholders. Early involvement of clinical stakeholders is critical to ensuring clear communication of results, outcomes, and any resulting practice changes.
How does this project align with broader efforts to reduce diagnostic bias and promote equitable care in prenatal testing?
During the COVID-19 pandemic, the American Medical Association explicitly recognized racism as a public health threat, providing an opportunity for medical specialty societies to critically reassess systemic racial practices embedded in clinical guidelines and recommendations. Today, medical education and clinical practice – particularly through specialty societies – continue to respond to this call by reexamining and eliminating race-based teachings and recommendations.
In parallel, several state commissions and departments of health have developed programs and strategic plans to promote prenatal and maternal–infant health equity. The initiative by CAP, NyLa Laboratories, and our specialty society partners aligns with these broader medical and societal efforts to advance health equity.
In what ways might these changes improve patient outcomes, particularly in historically underrepresented populations?
The changes we are pursuing may improve patient outcomes by reinforcing the need to challenge long-standing misconceptions that treat race as a biological construct. By demonstrating how to critically reassess the literature and generate new clinical evidence, our efforts could provide a model for looking beyond race as a simple explanatory variable. Identifying causal biological and social–behavioral factors underlying prenatal and maternal–infant health disparities may help shift the focus of medical and public health systems toward these true risk factors and away from race as a proxy for disease. Such a change in orientation could have far-reaching implications for both historically advantaged and disadvantaged populations.
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