Background Newborn screening (NBS) occupies a unique space at the intersection of translational science and public health. As the only truly population-based public health program in the United States, NBS offers the promise of making the successes of translational medicine available to every infant with a rare disorder that is difficult to diagnose clinically, but for which strong evidence indicates that presymptomatic treatment will substantially improve outcomes. Realistic NBS policy requires data, but rare disorders face a special challenge: Screening cannot be done without supportive data, but adequate data cannot be collected in the absence of large-scale screening. The magnitude and scale of research to provide this expanse of data require working with public health programs, but most do not have the resources or mandate to conduct research. Methods To address this gap, we have established Early Check, a research program in partnership with a state NBS program. Early Check provides the infrastructure needed to identify conditions for which there have been significant advances in treatment potential, but require a large-scale, population-based study to test benefits and risks, demonstrate feasibility, and inform NBS policy. Discussion Our goal is to prove the benefits of a program that can, when compared with current models, accelerate understanding of diseases and treatments, reduce the time needed to consider inclusion of appropriate conditions in the standard NBS panel, and accelerate future research on new NBS conditions, including clinical trials for investigational interventions. Trial registration Clinicaltrials.gov registration # NCT03655223 . Registered on August 31, 2018.

Prior to statewide newborn screening (NBS) for spinal muscular atrophy (SMA) in North Carolina, U.S.A., we offered voluntary screening through the Early Check (EC) research study. Here, we describe the EC experience from October 2018 through December 2020. We enrolled a total of 12,065 newborns and identified one newborn with 0 copies of SMN1 and two copies of SMN2, consistent with severe early onset of SMA. We also detected one false positive result, likely stemming from an unrelated blood disorder associated with a low white blood cell count. We evaluated the timing of NBS for babies enrolled prenatally (n = 932) and postnatally (n = 11,133) and reasons for delays in screening and reporting. Although prenatal enrollment led to faster return of results (median = 13 days after birth), results for babies enrolled postnatally were still available within a timeframe (median = 21 days after birth) that allowed the opportunity to receive essential treatment early in life. We evaluated an SMA q-PCR screening method at two separate time points, confirming the robustness of the assay. The pilot project provided important information about SMA screening in anticipation of forthcoming statewide expansion as part of regular NBS.

Background Many research studies fail to enroll enough research participants. Patient-facing electronic health record applications, known as patient portals, may be used to send research invitations to eligible patients. Objective The first aim was to determine if receipt of a patient portal research recruitment invitation was associated with enrollment in a large ongoing study of newborns (Early Check). The second aim was to determine if there were differences in opening the patient portal research recruitment invitation and study enrollment by race and ethnicity, age, or rural/urban home address. Methods We used a computable phenotype and queried the health care system’s clinical data warehouse to identify women whose newborns would likely be eligible. Research recruitment invitations were sent through the women’s patient portals. We conducted logistic regressions to test whether women enrolled their newborns after receipt of a patient portal invitation and whether there were differences by race and ethnicity, age, and rural/urban home address. Results Research recruitment invitations were sent to 4510 women not yet enrolled through their patient portals between November 22, 2019, through March 5, 2020. Among women who received a patient portal invitation, 3.6% (161/4510) enrolled their newborns within 27 days. The odds of enrolling among women who opened the invitation was nearly 9 times the odds of enrolling among women who did not open their invitation (SE 3.24, OR 8.86, 95% CI 4.33-18.13; P<.001). On average, it took 3.92 days for women to enroll their newborn in the study, with 64% (97/161) enrolling their newborn within 1 day of opening the invitation. There were disparities by race and urbanicity in enrollment in the study after receipt of a patient portal research invitation but not by age. Black women were less likely to enroll their newborns than White women (SE 0.09, OR 0.29, 95% CI 0.16-0.55; P<.001), and women in urban zip codes were more likely to enroll their newborns than women in rural zip codes (SE 0.97, OR 3.03, 95% CI 1.62-5.67; P=.001). Black women (SE 0.05, OR 0.67, 95% CI 0.57-0.78; P<.001) and Hispanic women (SE 0.07, OR 0.73, 95% CI 0.60-0.89; P=.002) were less likely to open the research invitation compared to White women. Conclusions Patient portals are an effective way to recruit participants for research studies, but there are substantial racial and ethnic disparities and disparities by urban/rural status in the use of patient portals, the opening of a patient portal invitation, and enrollment in the study. Trial Registration ClinicalTrials.gov NCT03655223; https://clinicaltrials.gov/ct2/show/NCT03655223

Meeting recruitment targets for clinical trials and health research studies is a notable challenge. Unsuccessful efforts to recruit participants from traditionally underserved populations can limit who benefits from scientific discovery, thus perpetuating inequities in health outcomes and access to care. In this study, we evaluated direct mail and email outreach campaigns designed to recruit women who gave birth in North Carolina for a statewide research study offering expanded newborn screening for a panel of rare health conditions. Of the 54,887 women who gave birth in North Carolina from September 28, 2018, through March 19, 2019, and were eligible to be included on the study’s contact lists, we had access to a mailing address for 97.9% and an email address for 6.3%. Rural women were less likely to have sufficient contact information available, but this amounted to less than a one percentage point difference by urbanicity. Native American women were less likely to have an email address on record; however, we did not find a similar disparity when recruitment using direct‐mail letters and postcards was concerned. Although we sent letters and emails in roughly equal proportion by urbanicity and race/ethnicity, we found significant differences in enrollment across demographic subgroups. Controlling for race/ethnicity and urbanicity, we found that direct‐mail letters and emails were effective recruitment methods. The enrollment rate among women who were sent a recruitment letter was 4.1%, and this rate increased to 5.0% among women who were also sent an email invitation. WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? Under‐representation by traditionally underserved populations in clinical trials and health research is a challenge that may in part reflect inequitable opportunities to participate. WHAT QUESTION DID THIS STUDY ADDRESS? Are direct‐mail and email outreach strategies effective for reaching and recruiting women from traditionally underserved and rural populations to participate in large‐scale, population‐based research? WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? Despite sending recruitment letters and email invitations in roughly equal proportion by urbanicity and race/ethnicity, women living in rural areas were less likely to enroll (2.8%) than women from urban areas (4.2%). Additionally, enrollment rates decreased as the probability that women were members of a racial or ethnic minority group increased. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? Results from this study might encourage researchers to take a holistic and participant‐centered view of barriers to study enrollment that may disproportionately affect underserved communities, including differences in willingness to participate, trust, and access to resources needed for uptake.

A challenge in implementing population-based DNA screening is providing sufficient information, that is, understandable and acceptable, and that supports informed decision making. Early Check is an expanded newborn screening study offered to mothers/guardians whose infants have standard newborn screening in North Carolina. We developed electronic education and consent to meet the objectives of feasibility, acceptability, trustworthiness, and supporting informed decisions. We used two methods to evaluate Early Check among mothers of participating infants who received normal results: an online survey and interviews conducted via telephone. Survey and interview domains included motivations for enrollment, acceptability of materials and processes, attitudes toward screening, knowledge recall, and trust. Quantitative analyses included descriptive statistics and assessment of factors associated with knowledge recall and trust. Qualitative data were coded, and an inductive approach was used to identify themes across interviews. Survey respondents (n = 1,823) rated the following as the most important reasons for enrolling their infants: finding out if the baby has the conditions screened (43.0%), and that no additional blood samples were required (20.1%). Interview respondents (n = 24) reported the value of early knowledge, early intervention, and ease of participation as motivators. Survey respondents rated the study information as having high utility for decision making (mean 4.7 to 4.8 out of 5) and 98.2% agreed that they had sufficient information. Knowledge recall was relatively high (71.8–92.5% correct), as was trust in Early Check information (96.2% strongly agree/agree). Attitudes about Early Check screening were positive (mean 0.1 to 0.6 on a scale of 0–4, with lower scores indicating more positive attitudes) and participants did not regret participation (e.g., 98.6% strongly agreed/agreed Early Check was the right decision). Interview respondents further reported positive attitudes about Early Check materials and processes. Early Check provides a model for education and consent in large-scale DNA screening. We found evidence of high acceptability, trustworthiness and knowledge recall, and positive attitudes among respondents. Population-targeted programs need to uphold practices that result in accessible information for those from diverse backgrounds. Additional research on those who do not select screening, although ethically and practically challenging, is important to inform population-based DNA screening practices.