Delineating morbidity patterns in preterm infants at near-term age using a data-driven approach
BMC Pediatrics, vol. 24, pp. 249
Abstract
BACKGROUND: Long-term survival after premature birth is significantly determined by development of morbidities, primarily affecting the cardio-respiratory or central nervous system. Existing studies are limited to pairwise morbidity associations, thereby lacking a holistic understanding of morbidity co-occurrence and respective risk profiles. METHODS: Our study, for the first time, aimed at delineating and characterizing morbidity profiles at near-term age and investigated the most prevalent morbidities in preterm infants: bronchopulmonary dysplasia (BPD), pulmonary hypertension (PH), mild cardiac defects, perinatal brain pathology and retinopathy of prematurity (ROP). For analysis, we employed two independent, prospective cohorts, comprising a total of 530 very preterm infants: AIRR ("Attention to Infants at Respiratory Risks") and NEuroSIS ("Neonatal European Study of Inhaled Steroids"). Using a data-driven strategy, we successfully characterized morbidity profiles of preterm infants in a stepwise approach and (1) quantified pairwise morbidity correlations, (2) assessed the discriminatory power of BPD (complemented by imaging-based structural and functional lung phenotyping) in relation to these morbidities, (3) investigated collective co-occurrence patterns, and (4) identified infant subgroups who share similar morbidity profiles using machine learning techniques. RESULTS: First, we showed that, in line with pathophysiologic understanding, BPD and ROP have the highest pairwise correlation, followed by BPD and PH as well as BPD and mild cardiac defects. Second, we revealed that BPD exhibits only limited capacity in discriminating morbidity occurrence, despite its prevalence and clinical indication as a driver of comorbidities. Further, we demonstrated that structural and functional lung phenotyping did not exhibit higher association with morbidity severity than BPD. Lastly, we identified patient clusters that share similar morbidity patterns using machine learning in AIRR (n=6 clusters) and NEuroSIS (n=8 clusters). CONCLUSIONS: By capturing correlations as well as more complex morbidity relations, we provided a comprehensive characterization of morbidity profiles at discharge, linked to shared disease pathophysiology. Future studies could benefit from identifying risk profiles to thereby develop personalized monitoring strategies. TRIAL REGISTRATION: AIRR: DRKS.de, DRKS00004600, 28/01/2013. NEuroSIS: ClinicalTrials.gov, NCT01035190, 18/12/2009.
Authors 12
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Octavia-Andreea Ciora corresponding
Fraunhofer Institute for Cognitive Systems
Affiliation as printed
Fraunhofer Institute for Cognitive Systems IKS, Munich, Germany. octavia.ciora@iks.fraunhofer.de
Fraunhofer Institute for Cognitive Systems IKS, Munich, Germany
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Tanja Seegmüller corresponding
LMU Klinikum · Ludwig-Maximilians-Universität München
Affiliation as printed
Center for Comprehensive Developmental Care (CDeC(LMU)) at the Social Pediatric Center (iSPZ Hauner), LMU University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany. tanja.seegmueller@campus.lmu.de
Center for Comprehensive Developmental Care (CDeC(LMU)) at the Social Pediatric Center (iSPZ Hauner), LMU University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany
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Fraunhofer Institute for Cognitive Systems
Affiliation as printed
Fraunhofer Institute for Cognitive Systems IKS, Munich, Germany
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Helmholtz Munich · LMU Klinikum · German Center for Lung Research · Ludwig-Maximilians-Universität München
Affiliation as printed
Center for Comprehensive Developmental Care (CDeC(LMU)) at the Social Pediatric Center (iSPZ Hauner), LMU University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany
Institute for Lung Health and Immunity and Comprehensive Pneumology Center, Helmholtz Zentrum München, Member of the German Lung Research Center (DZL), Munich, Germany
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LMU Klinikum · Ludwig-Maximilians-Universität München
Affiliation as printed
Department of Radiology, LMU University Hospital, Ludwig-Maximilians-Universität München, Member of the German Lung Research Center (DZL), Munich, Germany
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LMU Klinikum · Ludwig-Maximilians-Universität München
Affiliation as printed
Division of Neonatology, Department of Pediatrics, Dr. von Hauner Children's Hospital, LMU University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany
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Helmholtz Munich · LMU Klinikum · German Center for Lung Research · Ludwig-Maximilians-Universität München
Affiliation as printed
Center for Comprehensive Developmental Care (CDeC(LMU)) at the Social Pediatric Center (iSPZ Hauner), LMU University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany
Division of Neonatology, Department of Pediatrics, Dr. von Hauner Children's Hospital, LMU University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany
Institute for Lung Health and Immunity and Comprehensive Pneumology Center, Helmholtz Zentrum München, Member of the German Lung Research Center (DZL), Munich, Germany
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Affiliation as printed
Metabolomics and Analytics Centre, LACDR, Leiden University, Leiden, Netherlands
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University of Zurich · University Hospital Zurich
Affiliation as printed
Department of Neonatology, University Hospital Zurich and University of Zurich, Zurich, Switzerland
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University Children's Hospital Tübingen · University of Tübingen
Affiliation as printed
Department of Neonatology, University Children's Hospital Tübingen, Tübingen, Germany
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Fraunhofer Institute for Cognitive Systems
Affiliation as printed
Fraunhofer Institute for Cognitive Systems IKS, Munich, Germany
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Helmholtz Munich · LMU Klinikum · German Center for Lung Research · Ludwig-Maximilians-Universität München
Affiliation as printed
Center for Comprehensive Developmental Care (CDeC(LMU)) at the Social Pediatric Center (iSPZ Hauner), LMU University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany
Institute for Lung Health and Immunity and Comprehensive Pneumology Center, Helmholtz Zentrum München, Member of the German Lung Research Center (DZL), Munich, Germany
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