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Filter Results:

Year

  • 2016 (1)
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Author

  • Conneely, Karen (2)
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Article

An epigenetic clock for gestational age at birth based on blood methylation data

by Anna K. Knight; Jeffrey M. Craig; Christiane Theda; Marie Bækvad-Hansen; Jonas Bybjerg-Grauholm; Christine S. Hansen; Mads V. Hollegaard; David M. Hougaard; Preben B. Mortensen; Shantel M. Weinsheimer; Thomas M. Werge; Patricia Brennan; Joseph Cubells; D. Jeffrey Newport; Zachary N. Stowe; Jeanie L.Y. Cheong; Philippa Dalach; Lex W. Doyle; Yuk J. Loke; Andrea A. Baccarelli; Allan C. Just; Robert O. Wright; Mara M. Tellez-Rojo; Katherine Svensson; Letizia Trevisi; Elizabeth M. Kennedy; Elisabeth B. Binder; Stella Iurato; Darina Czamara; Katri Räikkönen; Jari M.T. Lahti; Anu-Katriina Pesonen; Eero Kajantie; Pia M. Villa; Hannele Laivuori; Esa Hämäläinen; Hea Jin Park; Lynn B. Bailey; Sasha E. Parets; Varun Kilaru; Ramkumar Menon; Steve Horvath; Nicole R. Bush; Kaja Z. LeWinn; Frances A. Tylavsky; Karen Conneely; Alicia K Smith

2016

Subjects
  • Biology, Genetics
  • Health Sciences, General
  • Health Sciences, Obstetrics and Gynecology
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Abstract:Close

Background: Gestational age is often used as a proxy for developmental maturity by clinicians and researchers alike. DNA methylation has previously been shown to be associated with age and has been used to accurately estimate chronological age in children and adults. In the current study, we examine whether DNA methylation in cord blood can be used to estimate gestational age at birth. Results: We find that gestational age can be accurately estimated from DNA methylation of neonatal cord blood and blood spot samples. We calculate a DNA methylation gestational age using 148 CpG sites selected through elastic net regression in six training datasets. We evaluate predictive accuracy in nine testing datasets and find that the accuracy of the DNA methylation gestational age is consistent with that of gestational age estimates based on established methods, such as ultrasound. We also find that an increased DNA methylation gestational age relative to clinical gestational age is associated with birthweight independent of gestational age, sex, and ancestry. Conclusions: DNA methylation can be used to accurately estimate gestational age at or near birth and may provide additional information relevant to developmental stage. Further studies of this predictor are warranted to determine its utility in clinical settings and for research purposes. When clinical estimates are available this measure may increase accuracy in the testing of hypotheses related to developmental age and other early life circumstances.

Article

Relationship between Epigenetic Maturity and Respiratory Morbidity in Preterm Infants

by Anna Knight; Alicia Smith; Karen Conneely; Philippa Dalach; Yuk J. Loke; Jeanie L. Cheong; Peter G. Davis; Jeffrey M. Craig; Lex W. Doyle; Christiane Theda

2018

Subjects
  • Health Sciences, General
  • File Download
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Abstract:Close

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.
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