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Cut-off values in newborn screening for inborn errors of metabolism in Saudi Arabia
Adbul Rafiq Khan1, Ali Alothaim1, Ahmed Alfares2
1From the Department of Pathology and Laboratory Medicine, King Abdulaziz Medical City, Riyadh, Saudi Arabia.
Insights
Newborn screening in Saudi Arabia now has established population-based cut-off values and analyte ratios, improving early detection of disorders. This study provides crucial data for refining screening protocols and minimizing harmful effects in newborns.
Area of Science:
- Biochemistry
- Genetics
- Public Health
Background:
- Newborn screening is vital for early detection of disorders in asymptomatic infants, enabling timely interventions.
- Saudi Arabia lacked population-specific data on screening cut-offs and performance metrics.
- Establishing local benchmarks is crucial for optimizing screening effectiveness.
Purpose of the Study:
- To establish population-based cut-off values and analyte ratios for newborn screening assays in Saudi Arabia.
- To clinically validate these established cut-off values and ratios.
- To provide data for improving the accuracy and efficiency of newborn screening programs.
Main Methods:
- A population-based screening approach was employed across tertiary care hospitals and laboratories.
- Analyzed 74,000 dry blood spot (DBS) samples from 2013-2020 using tandem mass spectrometry (TMS) and genetic screening processors.
- Confirmed positive results using gas chromatography-mass spectrometry, high-performance liquid chromatography, and TMS.
Main Results:
- Population-based cut-off values were calculated and compared with true positive and proficiency samples.
- False positive rates were below 0.04 for most analytes, with biotinidase (BTD) showing the highest at 0.14, often due to pre-analytical errors.
- Analytical positive predictive values consistently exceeded 80% over the eight-year study period.
Conclusions:
- Clinical disease ranges and specific analyte ratios have been successfully established for newborn screening in the local population.
- The established values demonstrate excellent screening specificity and sensitivity for early disease detection.
- Further wider, population-based studies are recommended to continually refine screening protocols.
Background:
Newborn screening identifies individuals affected by a specific disorder within an apparently healthy population prior to the appearance of symptoms so that appropriate interventions can be initiated in time to minimize the harmful effects. Data on population based cut-off values, disease ranges for true positive cases, false positive rates, true positive rates, cut-off verification and comparisons with international cut-off ranges have not been done for Saudi Arabia.
Objective:
Establish population-based cut-off values and analyte ratios for newborn screening assays and clinically validate the values.
Design:
Population-based screening.
Setting:
Tertiary care hospitals and laboratories.
Methods:
After method verification, initial cut-off values were established by analyzing 400-500 dry blood spot (DBS) samples which were further evaluated after one year. About 74 000 patient results were reviewed to establish cut-off ranges from DBS samples received from five different hospitals during 2013-2020. Analysis was performed by tandem mass spectrometry (TMS) and a genetic screening processor. Confirmation of initial positive newborn screening results for different analytes were carried out using gas chromatography-mass spectrometry, high performance liquid chromatography and TMS.
Main Outcome Measures:
Cut-off values, ratios, positive predictive values, false positive rate, true positive rate and disease range.
Sample Size:
74 000 samples.
Results:
Population based cut-off values were calculated at different percentiles. These values were compared with 156 true positive samples and 80 proficiency samples. The false positive rate was less than 0.04 for all the analytes, except for valine, leucine, isovalerylcarnitine (C5), biotinidase (BTD), 17-hydroxyprogesterone and thyroid stimulating hormone. The highest false positive rate was 0.14 for BTD which was due to pre-analytical errors. The analytical positive predictive values were greater than 80% throughout the eight years.
Conclusion:
We have established clinical disease ranges for most of the analytes tested in our lab and several ratios which gives excellent screening specificity and sensitivity for early detection. The samples were representative of the local populations.
Limitations:
Need for wider, population-based studies.
Conflict Of Interest:
None.
