Variation Among Immunoreactive Trypsinogen Concentrations, Michigan Newborn Screening, 10/2007-4/2008. Steven J. Korzeniewski, MA, MSc, Maternal & Child Health Epidemiology Section Manager Grigorescu, V., Young, W., Hawkins, H., Cavanaugh, K., Nasr, S.Z., Langbo, C. Outline. Background
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Variation Among Immunoreactive Trypsinogen Concentrations, Michigan Newborn Screening, 10/2007-4/2008
Steven J. Korzeniewski, MA, MSc,
Maternal & Child Health Epidemiology Section Manager
Grigorescu, V., Young, W., Hawkins, H., Cavanaugh, K., Nasr, S.Z., Langbo, C.
Public Health Implications
CF Screening in MI commenced Oct. 2007
IRT is used to identify infants at increased risk of CF for DNA testing.
Mutation analysis, using a panel of 40 CF mutations among > 96th percentile.
In the absence of a mutation sweat testing is recommended only among infants having IRT concentrations > 99.8th percentile.
Anecdotal evidence suggested a high rate of false positives among NICU infants
This study explores variations in IRT concentrations in hopes of developing a strategy to reduce false positives.
R1: Do IRT concentrations vary among the general population by sex, race, birth weight, gestational age, and fetal growth ratio?
Data: Newborn screening IRT concentrations and infant demographic data collected from Oct 2007-April 2008 were used for this study.
Analysis: Crude and adjusted generalized linear models (GLM) of the association between demographic variables and IRT concentrations
Least squares means and p-values are reported
LS-means are within-group adjusted means, they estimate the marginal means for a balanced population (as opposed to the unbalanced design). Also called estimated population marginal means by Searle, Speed, and Milliken (1980).
We also calculated means and percentiles (96th, 99.8th) by race and gestational age strata
At one year (Oct 2007-Oct 2008)
Effect modification of race by gestational age absolved
Racial variation remained significant in both crude & adjusted models
Failure to account for racial variation results in:
Over sampling of black infants
those at lower risk of CF
Under sampling of white infants
those at the greater risk of CF
False positive and false negative rates could be inflated
However, no false negatives have been detected thus far
Calculation of IRT % cutoffs stratified by race would:
Reduce the FPR & Improve PPV
Require further research to discern appropriate cutoffs, particularly for racial minorities or those with missing data
Require significant change in laboratory operating procedures
Sorting of cards
Verification of Race information
Development of strategy to calculate cutoffs over time
Co-Investigators: Grigorescu, V., Young, W., Hawkins, H., Cavanaugh, K., Nasr, S.Z., Langbo, C.
NBS Follow-up Staff
CF Advisory Committee