Prematurity Clinical Trial
Official title:
Expression Profiling of Bacterial Lipopolysaccharide Activated Neutrophil in Pre-Term, Term Infants and Adults
This study will examine the response of white blood cells to bacterial infection in blood
taken from the umbilical cords of newly delivered infants. The blood samples will be taken
from both male infants who were carried to term and male infants who were born prematurely,
and genetic studies will compare these blood samples to samples drawn from healthy adult male
volunteers. The study is designed to look at the ways in which the immune systems of newborn
infants respond to bacterial infection.
Participants in this study will be pregnant Chinese women admitted to the labor ward of the
Prince of Wales Hospital (Sha Tin district of New Territories, Hong Kong SAR) for normal
spontaneous delivery. Those with known blood-borne infectious diseases such as HIV and
hepatitis B will be excluded from this study.
Cord blood and placenta samples will be collected after the completion of delivery. The
samples collected for this study will be restricted to male newborns. A comparison group of
blood samples will be drawn from healthy male adults between 25 and 35 years of age....
Bacterial infection in preterm neonates is a significant clinical problem. Neutrophils play a
critical role in the bactericidal process, which is immature in newborns though their
peripheral blood neutrophil counts are similar to or higher than that of older children and
adults. The use of steroids to enhance lung maturation in premature infants complicates this
problem. Many studies have shown different biological activities between lipopolysaccharide
(LPS) activated neonatal cord blood neutrophils and adult peripheral blood neutrophils. In
spite of a number of previous studies, the genetic basis of this differential response to
LPS-activation remains unknown. In this study, we will identify the differential gene
expression profiles of LPS-activated adult peripheral blood versus cord blood neutrophils
from both term and preterm infants by whole genome ligonucleotide microarray. We will
investigate the priming effect of histologic chorioamnionitis (HCA), a severe
infection/inflammation implicated in many neonatal diseases, on the immune response in
neutrophils in terms of gene expression. The effect of prenatal administration of steroids on
the immune response in preterm neutrophils is another question we will address in the
proposed study. This study will provide insight into the molecular basis for genetic
regulation of neutrophil development. We expect to identify novel genes with differential
expressions in LPS-activated cord blood neutrophils when compared to those of LPS-activated
adult cells. Aberrant transcripts due to the priming effect of HCA to the immune response in
term neutrophils will also provide insight on the defense mechanism of subsequent exposures
to bacterial infection.
This is a collaborative study. All samples will be collected by our Collaborators at the
Chinese University of Hong Kong, Hong Kong. We will perform expression profiling in the
Laboratory of Clinical Genomics at NICHD. This protocol has been approved by the Joint
Clinical Research Ethics Committee of the Chinese University of Hong Kong and Hospital
Authority of Hong Kong.
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