Perturbation of gene expression of the chromatin remodeling pathway in premature newborns at risk for bronchopulmonary dysplasia.
BACKGROUND
One-third to one-half of all infants born before the 28th week of gestation develop bronchopulmonary dysplasia (BPD). Inflammatory regulators appear to be involved in the pathogenesis of BPD, possibly beginning in fetal life. To evaluate the feasibility of using expression profiling in umbilical cord tissue to discover molecular signatures for developmental staging and for determining risk of BPD, we conducted a cross-sectional study of infants born at less than 28 weeks of gestation (n = 54). Sections of umbilical cord were obtained at birth from 20 infants who later developed BPD and from 34 of their peers who did not develop BPD.


RESULTS
Umbilical cord expression profiles at birth exhibited systematic differences in bioenergetic pathways with respect to gestational age. Infants who subsequently developed BPD had distinct signatures involving chromatin remodeling and histone acetylation pathways, which have previously been implicated in several adult onset lung diseases. These findings are consistent with prior work on inflammatory processes and bioenergetics in prematurity.


CONCLUSIONS
This study of gene expression of the newborn umbilical cord implicates the chromatin remodeling pathways in those premature infants who subsequently develop BPD. Larger sample sizes will be required to generate prognostic markers from umbilical cord profiles.
Cohen
Jennifer
J
Children's Hospital, Boston, Division of Newborn Medicine, Boston, Longwood Avenue, Boston, MA 02115, USA. Jennifer.Cohen@childrens.harvard.edu
Van Marter
Linda J
LJ
Sun
Yao
Y
Allred
Elizabeth
E
Leviton
Alan
A
Kohane
Isaac S
IS
D000367:Age Factors; D001997:Bronchopulmonary Dysplasia / Q000175:diagnosis* / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D016000:Cluster Analysis; D003430:Cross-Sectional Studies; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000378:metabolism*; D025341:Principal Component Analysis; D018570:Risk Assessment; D014470:Umbilical Cord / Q000378:metabolism