Newborn screening for neurodevelopmental diseases: Are we there yet?

In the US, newborn screening (NBS) is a unique health program that supports health equity and screens virtually every baby after birth, and has brought timely treatments to babies since the 1960's. With the decreasing cost of sequencing and the improving methods to interpret genetic data, there is an opportunity to add DNA sequencing as a screening method to facilitate the identification of babies with treatable conditions that cannot be identified in any other scalable way, including highly penetrant genetic neurodevelopmental disorders (NDD). However, the lack of effective dietary or drug-based treatments has made it nearly impossible to consider NDDs in the current NBS framework, yet it is anticipated that any treatment will be maximally effective if started early. Hence there is a critical need for large scale pilot studies to assess if and how NDDs can be effectively screened at birth, if parents desire that information, and what impact early diagnosis may have. Here we attempt to provide an overview of the recent advances in NDD treatments, explore the possible framework of setting up a pilot study to genetically screen for NDDs, highlight key technical, practical, and ethical considerations and challenges, and examine the policy and health system implications.

A comparison of retesting rates using alternative testing algorithms in the pilot implementation of critical congenital heart disease screening in Minnesota.

Prior to state-wide implementation of newborn screening for critical congenital heart disease (CCHD) in Minnesota, a pilot program was completed using the protocol recommended by the Secretary's Advisory Committee on Heritable Disorders in Newborns and Children (SACHDNC). This report compares the retesting rates for newborn screening for CCHDs using the SACHDNC protocol and four alternative algorithms used in large published CCHD screening studies. Data from the original Minnesota study were reanalyzed using the passing values from these four alternative protocols. The retesting rate for the first pulse oximeter measurement ranged from 1.1 % in the SACHDNC protocol to 9.6 % in the Ewer protocol. The SACHDNC protocol generated the lowest rate of retesting among all tested algorithms. Our data suggest that even minor modifications of CCHD screening protocol would significantly impact screening retesting rate. In addition, we provide support for including lower extremity oxygen saturations in the screening algorithm.

Inadequacies of hospital-level critical congenital heart disease screening data reports: implications for research and quality efforts.

OBJECTIVE: Assess the quality of critical congenital heart disease (CCHD) screening data reports in California, where CCHD screening is not mandatory but reporting is. STUDY DESIGN: Retrospective review of California hospital-level CCHD screening data to evaluate data reliability and adherence to state screening and reporting recommendations. Data were evaluated for internal consistency and compared to two databases. RESULTS: Over one-third of hospitals did not submit data. Only 70.7% of the Vital Records live births were reported in CCHD screening data. Only 46% of reporting hospitals submitted data with matching numbers of completed screens and results, and 22% matched their respective live births in a second database. CONCLUSION: CCHD data reporting in California is incomplete, which may miss 359 CCHD cases/year from non-reporting. Data inconsistencies may miss additional cases. Mandatory screening, reporting, and improvements in data reliability are urgently needed to inform screening modifications and enhance timely detection and disease surveillance.

Considerations for Newborn Screening for Critical Congenital Heart Disease in Low- and Middle-Income Countries.

We propose several considerations for implementation of critical congenital heart disease (CCHD) screening for low- and middle-income countries to assess health system readiness for countries that may not have all the downstream capacity needed for treatment of CCHD. The recommendations include: (1) assessment of secondary and tertiary level CHD health services, (2) assessment of birth delivery center processes and staff training needs, (3) data collection on implementation and quality surgical outcomes, (4) budgetary consideration, and (5) consideration of the CCHD screening service as part of the overall patient care continuum.

Updated Strategies for Pulse Oximetry Screening for Critical Congenital Heart Disease.

Seven years after its addition to the US Recommended Uniform Screening Panel, newborn screening for critical congenital heart disease (CCHD) using pulse oximetry became mandatory in the United States. Although CCHD newborn screening reduces morbidity and mortality, there remain important opportunities to improve. An expert panel convened for a 1-day meeting in September 2018, including subject matter experts and representatives from stakeholder organizations. Presentations on CCHD outcomes, variations in approach to screening, and data and quality improvement helped identify improvement opportunities. The expert panel concluded that sufficient evidence exists to recommend modifying the current American Academy of Pediatrics algorithm by (1) requiring an oxygen saturation of at least 95% in both (formerly either) the upper and lower extremities to pass and (2) requiring only 1 repeat screen instead of 2 for cases that neither pass nor fail initially. The panel underscored the importance of improving public health reporting by further specifying the targets of screening and criteria for reporting outcomes (false-negative and false-positive cases). The panel also highlighted the need to ensure sufficient public health funding for CCHD newborn screening and opportunities for education and global implementation. Newborn screening for CCHD using pulse oximetry has led to significant improvements in child health outcomes. However, further important work is required to understand and improve the effectiveness and efficiency of screening.

Lessons Learned From Newborn Screening for Critical Congenital Heart Defects.

Newborn screening for critical congenital heart defects (CCHD) was added to the US Recommended Uniform Screening Panel in 2011. Within 4 years, 46 states and the District of Columbia had adopted it into their newborn screening program, leading to CCHD screening being nearly universal in the United States. This rapid adoption occurred while there were still questions about the effectiveness of the recommended screening protocol and barriers to follow-up for infants with a positive screen. In response, the Centers for Disease Control and Prevention partnered with the American Academy of Pediatrics to convene an expert panel between January and September 2015 representing a broad array of primary care, neonatology, pediatric cardiology, nursing, midwifery, public health, and advocacy communities. The panel's goal was to review current practices in newborn screening for CCHD and to identify opportunities for improvement. In this article, we describe the experience of CCHD screening in the United States with regard to: (1) identifying the target lesions for CCHD screening; (2) optimizing the algorithm for screening; (3) determining state-level challenges to implementation and surveillance of CCHD; (4) educating all stakeholders; (5) performing screening using the proper equipment and in a cost-effective manner; and (6) implementing screening in special settings such as the NICU, out-of-hospital settings, and areas of high altitude.

Implementation of critical congenital heart disease screening in Minnesota.

OBJECTIVE: To assess the level of preparedness and resources needed in Minnesota for the implementation of newborn screening for critical congenital heart diseases (CCHDs). METHODS: A cross sectional survey of all birth centers in Minnesota was performed to assess the capacity to deliver care essential for the CCHD screening program. Compliance with the screening algorithm, nursing workload, and cost were assessed by using a pilot program implemented in 6 normal newborn nurseries. RESULTS: Ninety-one of 99 eligible centers participated in the survey and 90 reported the ability to screen newborns in accordance with recommendations. Only 22 centers, with 63% of births, had access to echocardiography and routinely stocked prostaglandins for neonatal use. Our pilot study screened 7549 newborns with 6 failed screens and 1 CCHD diagnosis. Two of the failed screens were due to misinterpretation of the algorithm, 1 failed screen was not reported, and 4 failed screens were not recognized. Repeated screens were required for 115 newborns, with 29% of retesting due to misinterpretation of the algorithm. The mean nursing time required was 5.5 minutes, and the cost was $5.10 per screen. CONCLUSIONS: In Minnesota, two-thirds of newborns are born in centers with resources for initial diagnosis and management of CCHD. Implementation of a pilot screening program demonstrated minimal increase in nursing workload, but identified problems with interpretation of the algorithm and data reporting. This pilot project suggests the need for simplification of the algorithm, additional training of health care providers, and development of a centralized reporting mechanism.