Newborn screening for metabolic conditions has long-term benefits

State-mandated screening at birth for rare, serious medical conditions occurs in 4 to 5 million newborns and detects 5,000 to 6,000 affected infants each year. A 2017 American Family Physician article reviewed various conditions that are targeted by newborn screening: amino acid disorders, fatty acid oxidation disorders, organic acid disorders, hemoglobinopathies, endocrine disorders, and miscellaneous diseases (including congenital hearing loss and critical congenital heart defects). With a combined incidence of 1 out of every 1,500 births, inborn errors of metabolism are the most common conditions detected by newborn screening.

After tandem mass spectrometry made it possible to test for many conditions using a single blood sample, the federal Health Resources and Services Administration's Maternal and Child Health Bureau commissioned the American College of Medical Genetics (ACMG) to create a uniform list of conditions for newborn screening panels in 2005. However, the ACMG's recommended core panel of 29 conditions was criticized by the U.S. Preventive Services Task Force (USPSTF) for not taking an evidence-based approach. In a position paper, the USPSTF noted that the ability to detect a condition with high diagnostic accuracy was insufficient to include it in the panel:

A newborn screening program is not just a panel of screening tests. ... It is also parental education, follow-up, diagnosis, treatment and management, and program evaluation, and all of the various parts of the system must be in place and working well to realize the benefits of screening. ... Moreover, a newborn screening panel should be expanded only if the newborn screening program is fully prepared to make all the components of the complex system available for the new disorders. Expansion would be costly and might not be the best use of scarce health care resources, given the many other unmet child health needs.

Reinforcing the USPSTF's concerns, an analysis by the Centers for Disease Control and Prevention projected that if all 50 states expanded their newborn screening panels to align fully with the ACMG recommendations, "although such an expansion would have increased the number of children identified by 32% (from 4,370 to 6,439), these children would have had many rare disorders that require local or regional capacity to deliver expertise in screening, diagnosis, and management." A cross-sectional survey of Ontario primary care clinicians found that family physicians had limited knowledge of conditions identified by newborn screening tests, and many were not comfortable leading detailed discussions of abnormal results with parents or guardians.

The U.S. Secretary of Health and Human Services' Advisory Committee on Heritable Disorders in Newborns and Children (SACHDNC) subsequently developed a more rigorous framework to evaluate conditions nominated as additions to the uniform screening panel, requiring an independent systematic evidence review of key questions based on an analytic framework similar to those used for USPSTF reviews. In a separate document, the SACHDNC outlined questions for newborn screening long-term follow-up data systems to answer to make sure that programs achieve their goals of improved outcomes for children and families.

An observational study published last month in Pediatrics reported the clinical outcomes of 306 individuals with inherited metabolic diseases identified by a university hospital laboratory performing Germany's newborn screening panel from 1999 to 2016. The German national panel is less extensive than the ACMG's, consisting of 2 endocrine and 12 inherited metabolic diseases, and the nearly 2 million newborns screened during the study period represented 15 percent of Germany's live births. 28 individuals presented with metabolic symptoms prior to newborn screening results being available; the rest were successfully enrolled in specialized metabolic/nutritional therapy while still asymptomatic. Although nearly 1 in 4 individuals eventually developed irreversible disease-specific clinical signs, 88% had normal cognitive outcomes, and more than 95% showed normal development and attended regular kindergarten and primary schools.