Addressing the Burdens That Newborn Screening Imposes on Underserved Communities

Column Author: Meghan Strenk, MS, CGC, MS, CGC | Genetic Counselor

Courtney Berrios, MS | Genetic Counselor, Research Assistant Professor of Pediatrics, University of Missouri-Kansas City School of Medicine

Jeremy Garrett, PhD | Director, Pediatric Bioethics Fellowship; Research Associate, Bioethics, Associate Professor of Pediatrics, University of Missouri-Kansas City School of Medicine

Column Editor: Brian Carter, MD | Neonatal/Perinatal Medicine, Bioethics; Neonatologist; Pediatric Bioethicist; Interim Director, Pediatric Bioethics | Professor of Pediatrics, University of Missouri-Kansas City School of Medicine

Newborn screening (NBS) began in the 1960s with testing for phenylketonuria (PKU), which, when identified and treated early, significantly reduces morbidity. While NBS is rightly viewed as a public health success resulting in overall positive impacts on the health and well-being of newborns, its benefits and burdens are not always distributed equitably. Here, we present real-world data from the Children’s Mercy NBS referral center that demonstrates some of these disparities.

Over the past six decades, NBS has been expanded with the creation of a Recommended Uniform Screening Panel (RUSP) developed through the Department of Health and Human Services. The RUSP recommends the conditions that should be added to state newborn screening panels, and currently includes 37 core conditions and 26 secondary conditions. Several conditions on the current RUSP are lysosomal storage disorders (LSDs). Missouri was the first U.S. state to start screening for LSDs, with four LSDs, including Pompe disease and mucopolysaccharidosis type 1 (MPS1), added to its screening panel in 2013.

The Children’s Mercy NBS referral center serves counties in the western half of Missouri, coordinating evaluation and confirmatory testing following an abnormal newborn screen. Data from our first six years of LSD referrals (Strenk 2019) showed patterns inconsistent with population distributions in our region, particularly for the Black population (3.2% of referral area population but 19.9% of LSD referrals) and the Asian/Pacific Islander population (0.2% of referral area population but 7.4% of LSD referrals).

When focusing on these populations specifically, we found even more striking disparities, particularly with pseudodeficiency alleles, which yield low enough enzyme results to give positive NBS results but do not cause disease. Pseudodeficiency explained 24% of NBS referrals for Pompe disease. Of these, 75% reported Pacific Islander or Asian ethnicity. Many of these families speak a rare language for which it is difficult to find an interpreter. Similarly, pseudodeficiency explained 29% of positive NBS results for MPS1, with 85% of those pseudodeficiencies in Black infants.

Our data from 2013 to 2019 also showed that when carrier status and pseudodeficiency are included, the NBS false positive rate was 73% for Pompe disease and 88% for MPS1. This finding indicates that a substantial number of families had babies who were burdened by the diagnostic process but did not ultimately require long-term follow-up. While the outcome is different for babies who are diagnosed, the diagnostic process is burdensome and can elicit the same stress and concern regardless of the outcome.

Since the data above were collected, the Missouri NBS lab instituted secondary screening for both MPS1 and Pompe disease (i.e., additional testing performed on the NBS bloodspot to separate infants who are carriers or have a pseudodeficiency from infants who truly have one of these conditions). While the data have not been collated or reviewed as they were in 2019,  clinicians anecdotally report a significant reduction in referrals of infants for additional testing for these conditions since this additional process was instituted. However, while secondary screening may reduce the logistical burdens of attending appointments (travel, expense, communication, etc.), it does not alleviate—and may actually extend—emotional burdens for families if they are made aware of the initial screening result before an extended secondary screening process is completed.

As we reflect on our experience with NBS for LSDs, we recognize several lessons we have learned. First, NBS has allowed population screening that can diagnose all individuals with a disease. That is, the spectrum of disease can be broader than expected (e.g., more people have late-onset Pompe disease than infantile onset Pompe disease, which was unanticipated prior to NBS) and the presence of other factors can impact the screening result (e.g., pseudodeficiencies). In addition, the distribution of disease or pseudodeficiencies may be different than anticipated (e.g., pseudodeficiencies in minority ethnicities). Finally, more information from NBS labs (secondary screening) can promote greater equity in the process by preventing disproportionate numbers of referrals of already underserved populations. However, it is important to recognize that more information may reduce logistical burdens without alleviating the emotional burdens of additional testing for families.

Inarguably, when considering the benefits versus burdens of NBS, the balance certainly tilts toward overall benefit to the health and well-being of newborns and children. However, these benefits are not always distributed equitably, and they are accompanied by significant—and similarly disparate—burdens. Underserved communities disproportionately burdened by NBS false positives have no advocacy group. Health care providers who are aware of inequitable benefits and burdens of NBS should advocate for changes to the system. Recognizing only the aggregate successes of NBS prevents us from seeing its inequities. Only by addressing these inequities can we realize the full potential of NBS for improving public health.

References:

1. Strenk ME, Berrios C, Garrett JR. Addressing the burdens that newborn screening imposes on underserved communities. Am J Bioeth. 2023;23(7):79-82.
2. Strenk M, Gadea RN, Heese BA, Gannon JL. Newborn screening for four lysosomal storage disorders: one center’s experience over six years. Poster presented at: the National Society of Genetic Counselors 38th Annual Education Conference; November 5-8, 2019; Salt Lake City, UT.
3. Recommended uniform screening panel. HRSA. Health Resources and Services Administration. March 30, 2023. https://www.hrsa.gov/advisory-committees/heritable-disorders/rusp