Environmental risk factors for false-positive results in newborn screening for primary carnitine deficiency: a multicenter large-scale retrospective cohort study.

OBJECTIVE

To identify environmental risk factors contributing to false-positive results in newborn screening for primary carnitine deficiency (PCD) and to evaluate their predictive performance.

METHODS

A multicenter retrospective cohort study was conducted, including 104,451 neonates who underwent newborn screening for inherited metabolic disorders between February 2019 and June 2025. Based on initial screening, reanalysis, and genetic testing, neonates were categorized into a false-positive group (n = 735) and a recall-positive group (n = 47). Baseline data and environment-related testing information were collected, including season of blood collection, ambient temperature and humidity during the drying process, as well as the quality of the dried blood spots. Univariate and multivariate logistic regression analyses were performed to identify independent influencing factors, and receiver operating characteristic (ROC) curves were used to evaluate predictive performance.

RESULTS

Among 782 initially screen-positive cases, the false-positive rate was 94.0% (735/782). However, plasma C0 levels at both initial screening and reanalysis were significantly lower in the recall-positive group. Ambient temperature was the most predictive independent risk factor for PCD diagnosis among multiple environmental and procedural variables identified by multivariate analysis.

CONCLUSION

Environmental conditions during blood spot drying can interfere with neonatal plasma C0 measurements and are major causes of false-positive results in PCD screening.