Prevalence and Clinical Significance of Commonly Diagnosed Genetic Disorders in Preterm Infants
Authors: Everett Selin S. , Bomback Miles , Sahni Rakesh , Wapner Ronald J. , Tolia Veeral N. , Clark Reese H. , Lyford Alex , Hays Thomas 
Published: July 2023

AbstractBackground and ObjectivesPreterm infants (<34 weeks’ gestation) experience high rates of morbidity and mortality before hospital discharge. Genetic disorders substantially contribute to morbidity and mortality in related populations. The prevalence and clinical impact of genetic disorders is unknown in this population. We sought to determine the prevalence of commonly diagnosed genetic disorders in preterm infants, and to determine the association of disorders with morbidity and mortality.MethodsThis was a retrospective multicenter cohort study of infants born from 23 to 33 weeks’ gestation between 2000 and 2020. Genetic disorders were abstracted from diagnoses present in electronic health records. We excluded infants transferred from or to other health care facilities prior to discharge or death when analyzing clinical outcomes. We determined the adjusted odds of pre-discharge morbidity or mortality after adjusting for known risk factors.ResultsOf 320,582 infants, 4196 (1.3%) had genetic disorders. Infants with trisomy 13, 18, 21, or cystic fibrosis had greater adjusted odds of severe morbidity or mortality. Of the 17,427 infants who died, 566 (3.2%) had genetic disorders. Of the 65,968 infants with a severe morbidity, 1319 (2.0%) had genetic disorders.ConclusionsGenetic disorders are prevalent in preterm infants, especially those with life-threatening morbidities. Clinicians should consider genetic testing for preterm infants with severe morbidity and maintain a higher index of suspicion for life-threatening morbidities in preterm infants with genetic disorders. Prospective genomic research is needed to clarify the prevalence of genetic disorders in this population, and the contribution of genetic disorders to preterm birth and subsequent morbidity and mortality.Article SummaryGenetic disorders were found in 1.3% of preterm infants and at a higher rate (2.0%) in infants who died or developed severe morbidity.What’s Known on This SubjectPrevious research described the prevalence and associated short-term morbidity and mortality of trisomy 13, 18, and 21 in preterm infants. The prevalence of other commonly diagnosed genetic disorders and associated short-term morbidity and mortality in preterm infants is unknown.What This Study AddsIn a multicenter, retrospective cohort of 320,582 preterm (<34 weeks’ gestation) infants, we found that 1.3% had genetic disorders diagnosed through standard care. Multiple disorders were associated with increased adjusted odds of morbidities or mortality prior to hospital discharge.Contributors Statement PageSelin S. Everett conceptualized and designed the study, conducted analyses, drafted the initial manuscript, and critically reviewed and revised the manuscript.Dr. Thomas Hays conceptualized and designed the study, drafted the initial manuscript, and critically reviewed and revised the manuscript.Miles Bomback conceptualized and designed the study and critically reviewed and revised the manuscript.Drs. Veeral N. Tolia and Reese H. Clark coordinated and supervised data collection and critically reviewed and revised the manuscript.Dr. Rakesh Sahni conceptualized and designed the study and critically reviewed and revised the manuscript.Dr. Alex Lyford conducted analyses and critically reviewed and revised the manuscript. Dr. Ronald J. Wapner reviewed and critically revised the manuscript.All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.