Tiny Babies, Big Data: ICD Billing Code Patterns in Neonates Diagnosed with Genetic Disease in the Neonatal Intensive Care Unit

Abstract Purpose Genetic diseases often present and are first diagnosed in the neonatal intensive care unit (NICU). Accurate identification of neonates with genetic diagnoses (GDs) in electronic health records (EHR) would enable a more complete understanding of their phenotypic spectrum, advancing care and personalized medicine. Prior research has used International Classification of Diseases (ICD) billing codes as proxies for GDs, though their accuracy for detecting confirmed GDs is uncertain. We evaluate the ICD codes for neonates with confirmed GDs and compare ICD billing code patterns between neonates with and without GD in two independent NICU cohorts. Methods Retrospective analysis of patients admitted to the Boston Children’s Hospital (BCH) level IV NICU (1,344 neonates) and Nationwide Children’s Hospital (NCH)’s neonatal network (33,315 neonates, mixed Level III/IV). For both cohorts, GDs captured by phecodes, aggregates of ICD codes, were compared with confirmed GDs. Two separate phenome-wide association studies (PheWAS) compared phecode patterns between neonates with GDs and those without, adjusting for sex, age at admission, gestational age, and NICU length of stay. Results Genetic phecodes were able to correctly identify 43.5% of neonates that received a GD in the BCH or NCH NICUs. Among 719 individuals with two or more genetic phecodes at BCH or NCH, 566 (78.72%) had a true GD. The BCH PheWAS analysis revealed a statistically significant positive association with atrioventricular septal defects and a negative association with bronchopulmonary dysplasia. The NCH pheWAS revealed 179 significantly associated phecodes, including many congenital anomalies. Conclusion The use of ICD codes to identify NICU infants with GDs is neither sensitive nor accurate, though phecode analysis demonstrated stronger accuracy than sensitivity. Our data highlight clinical features of NICU infants more commonly seen in those that receive a GD (congenital heart defects) and those that are not (BPD). Our results can help to better predict and identify NICU neonates that receive a GD.