Development of the Serum α-Fetoprotein Reference Range in Patients with Beckwith-Wiedemann Spectrum

Abstract

Objective: To establish reference ranges for serum α-fetoprotein (AFP) at various ages in patients with Beckwith-Wiedemann spectrum (BWSp), to better predict the risk for hepatoblastoma in this population.

Study design: A retrospective analysis of AFP measurements collected from patients with BWSp was performed. Factors including sex, prematurity, molecular diagnosis of patients, and performing laboratory were evaluated for significant differences. In total, 1372 AFP values were collected from 147 patients and the predictive AFP values at various ages were calculated to establish reference ranges. Mixed-effects polynomial regression models were used to study various potential factors affecting log(AFP) values.

Results: Overall, predicted AFP values declined to normal range for age (<10 ng/mL) by 14 months old. Patient sex and performing laboratory were found not to influence values. A significant difference was demonstrated between premature and nonpremature patients, and separate reference values were established. Significant differences in the predicted AFP value were not broadly apparent between molecular subtypes; however, interpretation was limited due to the small sample size of some of these subtypes.

Conclusions: Predictive AFP values were created for premature and nonpremature patients with BWSp to aid with interpretation and monitoring of the risk for hepatoblastoma. Further analysis is needed to determine whether AFP values differ within the less common molecular subtypes of patients with BWSsp.

Keywords: hepatoblastoma; tumor screening.

FIGURE 1A

Predictive Log(AFP) of age with 95% confidence intervals (CIs) by prematurity. Age corrected in premature patients (<37 weeks gestation) to gestational age of 38 weeks.

FIGURE 1B

Predictive Log(AFP) of age with 95% confidence intervals (CIs) by molecular diagnosis. Abbreviations: IC1 GOM (imprinting center 1 gain of methylation); IC2 LOM (imprinting center 2 loss of methylation); pUPD11 (paternal uniparental disomy of chromosome 11).