Variation in immunoreactive trypsinogen concentrations among Michigan newborns and implications for cystic fibrosis newborn screening.

OBJECTIVE To investigate variation in immunoreactive trypsinogen (IRT) concentrations by race, sex, birth weight, and gestational age and their implications for the use of percentile-based cutoffs for cystic fibrosis (CF) newborn screening (NBS) programs. PATIENTS AND METHODS This cross-sectional population-based study of resident infants screened in Michigan investigates associations between demographic and perinatal variables and IRT concentrations after controlling for covariates. This study also analyzed how 96th and 99.8th IRT concentration percentiles values calculated by Michigan NBS vary by demographic and perinatal factors. Characteristics of infants having high (≥99.8th percentile) IRT concentrations and negative DNA tests are also explored. RESULTS IRT mean concentrations and percentiles vary significantly by race, birth weight, gestational age, and to a lesser degree by sex. The greatest variation in mean IRT concentrations was observed among racial categories; black infants had an adjusted mean concentration of 36 ng/ml and Asian/Pacific Islander infants had a mean concentration of 25 ng/ml compared to an average concentration of 28 ng/ml in white infants and infants of other races. CONCLUSIONS Variation in IRT concentrations resulted in the over-representation of certain groups referred for secondary testing, particularly referrals for sweat testing based on very high (≥99.8th percentile) concentrations alone, which is no longer recommended in Michigan. Further research may be warranted to evaluate initial IRT cutoffs used for CF NBS.