Relationship between Epigenetic Maturity and Respiratory Morbidity in Preterm Infants

• Type of Material: Article
• Authors: Anna Knight, Emory University; Alicia Smith, Emory University; Karen Conneely, Emory University; Philippa Dalach, Murdoch Childrens Research Institute; Yuk J. Loke, Murdoch Childrens Research Institute; Jeanie L. Cheong, Murdoch Childrens Research Institute; Peter G. Davis, Murdoch Childrens Research Institute; Jeffrey M. Craig, Murdoch Childrens Research Institute; Lex W. Doyle, Murdoch Childrens Research Institute; Christiane Theda, Murdoch Childrens Research Institute
• Language: English
• Date: 2018-07-01
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018 Elsevier Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.jpeds.2018.02.074
• Title of Journal or Parent Work: Journal of Pediatrics
• ISSN: 0022-3476
• Volume: 198
• Start Page: 168
• End Page: +
• Grant/Funding Information: Supported by the National Health and Medical Research Council (NHMRC) of Australia (APP1083779 [to J.M.C., C.T., and J.L.C.] and 491246 [to L.D. and J.L.C.); the Centre of Research Excellence (APP1060733 [to L.D., P.D., and J.L.C]); and further funded by the Children’s Foundation (2014–134 [to J.M.C., L.D., and C.T.]). The Murdoch Childrens Research Institute is supported by the Victorian Government’s Operational Infrastructure Support Program.
• Keywords: DNA METHYLATION MICROARRAY; ASSOCIATIONS; GESTATIONAL-AGE; Life Sciences & Biomedicine; BIRTH; BRONCHOPULMONARY DYSPLASIA; DEXAMETHASONE THERAPY; SEX; Pediatrics; Science & Technology; OUTCOMES
• Research Categories: Health Sciences, General

Abstract

Objective: To assess associations between epigenetic maturity of extremely preterm babies (born at less than 28 weeks of gestation), neonatal interventions, and respiratory outcomes, including the administration of surfactant and postnatal corticosteroids, duration of assisted ventilation, and development of bronchopulmonary dysplasia (BPD). Study design: DNA was extracted from neonatal blood spots collected after birth from 143 extremely preterm infants born 1991-1992 in Victoria, Australia and used to determined DNA methylation (DNAm). A DNAm based gestational age was determined using our previously published method. The residual of DNAm gestational age and clinically estimated gestational age (referred to as “gestational age acceleration”) was used as a measure to assess developmental maturity. Associations between gestational age acceleration and respiratory interventions and morbidities were determined. Results: Infants with higher gestational age acceleration were less likely to receive surfactant (P =.009) or postnatal corticosteroids (P =.008), had fewer days of assisted ventilation (P =.01), and had less BPD (P =.02). Respiratory measures are known to correlate with gestational age; however, models comparing each with clinically estimated gestational age were improved by the addition of the gestational age acceleration measure in the model. Conclusions: Gestational age acceleration correlates with respiratory interventions and outcomes of extremely preterm babies. Surfactant and postnatal corticosteroid use, assisted ventilation days, and BPD rates were all lower in babies who were epigenetically more mature than their obstetrically estimated gestational age. This suggests that gestational age acceleration is a clinically relevant metric of developmental maturity.