Improving clinical interpretation of serum alpha-fetoprotein in children: using continuous and discrete reference
Dien Minh Tran1, Phuc Huu Phan1, Tung Viet Cao1
1Vietnam National Children's Hospital, Hanoi, Vietnam.
Insights
Continuous age-specific reference intervals for serum alpha-fetoprotein (AFP) offer better interpretation in early childhood. Discrete intervals are suitable for older children with stable AFP levels.
Area of Science:
- Biochemistry
- Pediatrics
- Clinical Chemistry
Background:
- Serum alpha-fetoprotein (AFP) levels are critical in pediatric diagnostics.
- Establishing accurate reference intervals is essential for interpreting AFP concentrations in children.
- Rapid changes in AFP during early infancy pose challenges for traditional discrete reference intervals.
Purpose of the Study:
- To establish discrete and continuous age-specific reference intervals for serum AFP in children.
- To evaluate the utility of continuous modeling for AFP interpretation in early infancy.
- To compare the performance of continuous versus discrete reference intervals.
Main Methods:
- Prospective, cross-sectional study of 3,680 healthy Vietnamese children (birth to <19 years).
- Serum AFP measured using Roche Cobas Pro platform.
- Continuous age-specific reference intervals modeled using GAMLSS for ages 0-3 years.
- Discrete intervals derived nonparametrically.
Main Results:
- AFP concentrations highest neonatally, declining rapidly in infancy, then stabilizing.
- Minimal sex differences observed, not supporting sex-specific intervals.
- Continuous intervals provided higher temporal resolution in early infancy compared to discrete partitions.
- Clinical case demonstrated limitations of discrete intervals versus continuous ones.
Conclusions:
- Continuous age-specific reference intervals enhance clinically meaningful interpretation in early childhood.
- Discrete reference intervals remain appropriate for older children with stable AFP concentrations.
- Continuous modeling improves diagnostic accuracy during rapid AFP decline in infancy.
Objectives:
To establish discrete and continuous age-specific reference intervals for serum alpha-fetoprotein in children and to evaluate whether continuous modeling improves interpretation during early infancy, when concentrations decline rapidly.
Methods:
In this prospective, cross-sectional study, serum alpha-fetoprotein was measured in 3,680 apparently healthy Vietnamese children from birth to <19 years using the Roche Cobas Pro platform. Discrete age-specific reference intervals were derived nonparametrically. For ages 0-3 years, continuous age-specific reference intervals were modeled using GAMLSS (generalized additive model for location, scale, and shape), and age-specific percentile tables were generated from fitted curves. Sex- and weight-related effects were assessed, and clinical utility was illustrated with a representative case.
Results:
Alpha-fetoprotein concentrations were highest in the neonatal period and declined steeply during the first months of life, then stabilized at low levels in later childhood. Sex differences were minimal and did not support sex-specific reference intervals. Continuous reference intervals for ages 0-<3 years represented the central 95 % of AFP concentrations and provided higher temporal resolution than discrete partitions in early infancy. A high-resolution percentile table (daily from 0 to 90 days; monthly from 4 to 12 months) enabled age-resolved interpretation. After age adjustment, body weight was not independently associated with alpha-fetoprotein. In the clinical case, serial values intermittently exceeded discrete upper limits yet remained within continuous age-specific percentiles, highlighting limitations of discrete partitions.
Conclusions:
Continuous age-specific reference intervals improve clinically meaningful interpretation during early childhood, whereas discrete reference intervals remain appropriate for older children with stable alpha-fetoprotein concentrations.
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