Expanded Newborn Screening: Outcome in Screened and Unscreened Patients at Age 6 Years

TLDR

Tandem mass spectrometry is widely used for newborn screening, yet long‑term outcome data are lacking. The study aimed to assess six‑year clinical outcomes in Australian infants identified by screening versus clinical diagnosis. A cohort analysis of over two million infants born 1994‑2002 recorded intellectual, physical, educational, and health outcomes, comparing 461,500 screened and 1,017,800 unscreened children. Screening reduced mortality and severe disability at age six, with only 2 of 461,500 screened infants versus 21 of 1,551,200 unscreened experiencing significant morbidity or death, and fewer diagnosed inborn errors among the screened group.

Abstract

Tandem mass spectrometry is widely applied to routine newborn screening but there are no long-term studies of outcome. We studied the clinical outcome at six years of age in Australia.In a cohort study, we analyzed the outcome at 6 years for patients detected by screening or by clinical diagnosis among >2 million infants born from 1994 to 1998 (1,017,800, all unscreened) and 1998 to 2002 (461,500 screened, 533,400 unscreened) recording intellectual and physical condition, school placement, other medical problems, growth, treatment, diet, and hospital admissions. Results were analyzed separately for medium-chain acyl-CoA dehydrogenase deficiency (MCADD) and other disorders, and grouped patients as those who presented clinically or died in the first 5 days of life; patients presented later or diagnosed by screening, and those with substantially benign disorders.Inborn errors, excluding phenylketonuria, were diagnosed in 116 of 1,551,200 unscreened infants (7.5/100,000 births) and 70 of 461,500 screened infants (15.2/100,000 births). Excluding MCADD, 21 unscreened patients with metabolic disorders diagnosed after 5 days of life died or had a significant intellectual or physical handicap (1.35/100,000 population) compared with 2 of the screened cohort (0.43/100,000; odds ratio: 3.1 [95% CI: 0.73-13.32]). Considering the likely morbidity or mortality among the expected number of never-diagnosed unscreened patients, there would be a significant difference. Growth distribution was normal in all cohorts.Screening by tandem mass spectrometry provides a better outcome for patients at 6 years of age, with fewer deaths and fewer clinically significant disabilities.