Environmental risk factors for false-positive results in newborn screening for primary carnitine deficiency: a multicenter large-scale retrospective cohort study.
Environmental conditions, especially temperature, can significantly impact newborn screening results for primary carnitine deficiency, leading to high false-positive rates.
Where it sits
this study against the rest of the l-carnitine (levocarnitine) corpusSummary and findings
This study aimed to identify environmental risk factors leading to false-positive results in newborn screening for primary carnitine deficiency (PCD) among 104,451 neonates. The false-positive rate was found to be 94.0%. Ambient temperature was identified as the most predictive independent risk factor for PCD diagnosis.
Abstract
<h4>Objective</h4>To identify environmental risk factors contributing to false-positive results in newborn screening for primary carnitine deficiency (PCD) and to evaluate their predictive performance.<h4>Methods</h4>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 (<i>n</i> = 735) and a recall-positive group (<i>n</i> = 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.<h4>Results</h4>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.<h4>Conclusion</h4>Environmental conditions during blood spot drying can interfere with neonatal plasma C0 measurements and are major causes of false-positive results in PCD screening.
Background
This paper addresses the issue of false-positive results in newborn screening for primary carnitine deficiency (PCD), a condition that can lead to serious health issues if not diagnosed correctly. Prior knowledge indicated that environmental factors could influence screening outcomes, but specific risk factors had not been thoroughly evaluated. Understanding these factors is crucial for improving screening accuracy and reducing unnecessary follow-ups.
Methods
A multicenter retrospective cohort study was conducted involving 104,451 neonates screened for inherited metabolic disorders from February 2019 to June 2025. Neonates were categorized into a false-positive group (n=735) and a recall-positive group (n=47) based on screening results, reanalysis, and genetic testing. Environmental data, including season of blood collection, ambient temperature, and humidity, were collected, and logistic regression analyses were performed to identify influencing factors.
Results
The primary finding was a false-positive rate of 94.0% (735/782) among initially screen-positive cases. Additionally, plasma C0 levels were significantly lower in the recall-positive group, although specific numeric values were not reported in the abstract. Ambient temperature emerged as the most predictive independent risk factor for PCD diagnosis.
Interpretation
The findings suggest that environmental conditions, particularly ambient temperature during blood spot drying, significantly affect the accuracy of PCD screening results. While the statistical significance of the findings is clear, the clinical implications depend on the extent to which these environmental factors can be controlled in practice. The study's retrospective nature and reliance on a large cohort may limit the generalizability of the results.
Key findings
- False-positive rate was 94.0% (735/782) among initially screen-positive cases.
- Plasma C0 levels were significantly lower in the recall-positive group.
- Ambient temperature was identified as the most predictive independent risk factor.
Limitations
- Retrospective cohort design may introduce bias.
- Data collected from multiple centers could vary in quality.
- Specific numeric values for plasma C0 levels not reported.
- No long-term follow-up data provided.