Environmental conditions during blood spot drying, particularly ambient temperature, can interfere with neonatal plasma C0 measurements and are major causes of false-positive results in primary carnitine deficiency screening.
The false-positive rate for primary carnitine deficiency in newborn screening was 94.0%.
Plasma C0 (free carnitine) levels at both initial screening and reanalysis were significantly lower in the recall-positive group compared to the false-positive group.
Ambient temperature was the most predictive independent risk factor for false-positive PCD diagnosis among all environmental and procedural variables examined.
Environmental conditions during blood spot drying were identified as major causes of false-positive results in PCD newborn screening.
The study design involved categorizing initially screen-positive neonates into false-positive and recall-positive groups based on a three-step process of initial screening, reanalysis, and genetic testing.
This research suggests that a large proportion of babies who initially test positive for a metabolic condition called primary carnitine deficiency (PCD) during routine newborn screening are actually false alarms — not truly affected. In this study of over 104,000 newborns screened across multiple centers over six years, 94% of initially positive results turned out to be false positives. The study found that environmental conditions — especially the temperature and humidity present while the newborn blood spots were drying on filter paper — played a major role in causing these misleading results. Ambient temperature was identified as the single strongest predictor of whether a positive result was false or real. This matters because PCD screening relies on measuring a substance called free carnitine (C0) from a tiny dried blood spot collected shortly after birth. If the blood spot is dried under unfavorable environmental conditions, the C0 measurement can be artificially altered, triggering a false alarm. Babies and families who receive false-positive results may experience unnecessary anxiety, follow-up testing, and medical interventions. The study also found that babies who truly had PCD tended to have much lower C0 levels at both their initial test and at retesting, which could potentially help distinguish real cases from false positives more efficiently. This research suggests that controlling the environmental conditions — particularly temperature — during the blood spot collection and drying process could substantially reduce the number of false-positive PCD results in newborn screening programs. Screening laboratories and healthcare providers may benefit from implementing stricter environmental controls or quality standards for dried blood spot preparation to improve the accuracy of PCD screening and reduce unnecessary parental concern and medical follow-up.
Shang Z, Liu J, Leng Q, Pan K, Tang L, Hu Y, et al.. (2026). Environmental risk factors for false-positive results in newborn screening for primary carnitine deficiency: a multicenter large-scale retrospective cohort study.. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. https://doi.org/10.1080/14767058.2026.2712087