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Zero-filled values enhanced the performance of CRP vs RBP: TTR index in ELBW infants

Journal of Perinatology volume 26, pages 319–320 (2006)Cite this article

Recently, Ambalavanan et al.1 reported on the usefulness of the retinol-binding protein to transthyretin (RBP:TTR) index in assessing vitamin A status of extremely low birth weight (ELBW) infants 28 days after being dosed with vitamin A supplements. The authors demonstrated that the index was more accurate than retinol alone or RBP alone1, 2 in determining vitamin A status during inflammation. Moreover, they used the RBP:TTR index to predict the likelihood of death/bronchopulmonary dysplasia (BPD) in this population.1 However, the index was developed as a biomarker of vitamin A status and not as a marker of morbidity or sepsis.3, 4 Although the authors did not provide an explanation for this analysis, they compared the index to C-reactive protein (CRP). They showed using receiver operating characteristics curve (ROC) analysis that the area-under-the-curve (AUC) for CRP (0.85, confidence interval (CI) 0.76–0.92) was higher than for the RBP:TTR index (0.68, CI 0.57–0.78) albeit a non-significant difference.1 This is no surprise; CRP is an acute phase protein and a well-documented marker of infections and sepsis.5 However, the higher performance of CRP in predicting death/BPD at 36 weeks might result from a narrowing of the distribution of CRP concentrations in this population of low birth weight infants.

In Figures 1 and 3,1 15–20% of CRP concentrations were zero-filled values, whereas for the other analytes, including RBP and TTR, the spectrum of values was wide including low and high concentrations. This caused a spectrum bias by narrowing the CRP test preferentially to detectable high concentrations, undoubtedly, from infants with morbidity and sepsis and thus, infants with higher risk of dying. The test's performance, that is, higher AUC, for CRP was higher because of this spectrum bias; however, this was not the case for the RBP:TTR index, whose distribution of values included equally non-disease and disease infants. Although spectrum bias results from how characteristics of patient are used in selecting the study population,6 in the present case, it appears to have originated from how CRP concentrations were determined. Thus, this bias cannot be considered a spectrum effect for which reporting the characteristics of the population would suffice in correcting it.6

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References

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  1. Discovery, Mead Johnson Nutritionals, Evansville, IN, USA

    Francisco J Rosales

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Rosales, F. Zero-filled values enhanced the performance of CRP vs RBP: TTR index in ELBW infants. J Perinatol 26, 319–320 (2006). https://doi.org/10.1038/sj.jp.7211485

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