Interpreting Neonatal hyperCKemia Identified Through Duchenne Muscular Dystrophy Newborn Screening: A Predictive...

With implementation of newborn screening (NBS) for Duchenne muscular dystrophy (DMD), creatine kinase-muscle (CK) values will be reported on newborns. Maternal, labor, delivery, and newborn factors may elevate CK levels, raising concern for DMD. Predictive modeling could aid hyperCKemia interpretation while awaiting diagnostic confirmation.

In this single-center, prospective cohort study, parents of 8365 newborns were offered DMD-NBS. Electronic health records provided data on candidate predictors of hyperCKemia defined by values > 97th or 99th percentiles, or 2000 ng/mL in babies with normal DMD sequences. Exposures included maternal, newborn and perinatal factors. Associations between predictors and hyperCKemia were evaluated using univariate logistic regression. A multivariable prediction model for the 97th percentile was derived using backward stepwise logistic regression and externally validated in a cohort of 2672 newborns.

HyperCKemia > 97th percentile was the main outcome. Univariate analyses revealed associations between hyperCKemia and maternal ethnicity, primiparity, labor and delivery complications, oxytocin induction or augmentation, duration of ruptured membranes, forceps or vacuum-assisted delivery, neonatal resuscitation, sex, gestational age, birth weight, and Apgar scores. Lower odds of hyperCKemia were associated with later hour-of-life at sample collection and birth by cesarean section. The final model included parity, shoulder dystocia, forceps or vacuum-assisted delivery, gestational age, neonatal resuscitation, Apgar score (1 min), and time of sample collection.

Elevated CK levels may be used for DMD-NBS. Multiple perinatal factors are associated with transient non-DMD hyperCKemia. Our model considers the potential combined impact of such factors and generates a non-disease likelihood for preliminary hyperCKemia interpretation.