Identification of risk factors, pathological changes and protein biomarkers of spontaneous preterm labour with intact membranes of Malay patients
Each year, there are about 15 million babies born prematurely and one million babies die from the syndrome. In Malaysia, 12.3% of the babies are born prematurely yearly and the Malay has the highest incidence rate (74.7%). Spontaneous preterm labour with intact membranes (sPTL-IM) is one of th...
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| Format: | Thesis |
| Language: | English |
| Published: |
2018
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| Subjects: | |
| Online Access: | http://psasir.upm.edu.my/id/eprint/85533/1/FPSK%28p%29%202019%2013%20ir.pdf |
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| Summary: | Each year, there are about 15 million babies born prematurely and one million babies die
from the syndrome. In Malaysia, 12.3% of the babies are born prematurely yearly and
the Malay has the highest incidence rate (74.7%). Spontaneous preterm labour with
intact membranes (sPTL-IM) is one of the most common types of preterm birth (PTB).
To date, the reliability of all available prediction tools to predict pregnant women at risk
of sPTL-IM is low. Therefore, the search for a more reliable screening tool is urgently
needed. This study applies risk factor assessments as well as placental pathological and
comparative proteome studies among Malay pregnant women in Malaysia to understand
the pathophysiology of sPTL-IM syndrome for the improvement or development of a
novel screening tool. To prove the former, a case-control study using secondary data
(medical records) was conducted on 537 cases and 1022 controls to identify the risk
factors associated with sPTL-IM-birth in Malay patients. Among the cases,
preeclampsia, placenta previa, history of PTB, and teenage pregnancy are significantly
more prevalent. Remarkably, 54.9% of sPTL-IM-births were due to spontaneous
unexplained preterm labour with intact membranes (suPTL-IM). Among these Malay
pregnant women, 16.6% were in potentially high-risk pregnancy. The resulting analyses
have drawn attention to investigate the placental pathological changes and molecular
impairment of suPTL-IM-high-risk-birth, since less attention has been paid by other
researchers in this context. Pathological evaluation of the haematoxylin and eosinstained
suPTL-IM-placenta sections revealed a higher degree of inflammation in the
membranes compared to control. Prior to the study of molecular impairment of suPTLIM-
delivered placentae, a total of 12 mechanical and chemical protein extraction
protocols were carried out to determine the best protein extraction condition to extract
proteins from placental cotyledon. The results demonstrated that DNase/lithium
chloride-dense sucrose homogenisation coupled dichloromethane-methanol
precipitation method exhibited the best extraction efficacy with excellent reproducibility.
The extraction method was then applied to extract proteins from both foetal and maternal
originated placental cotyledons and the differential protein expression profiles of suPTLIM-
delivered placentae were studied using a gel-based proteomics approach. Two proteins were overexpressed, and nine proteins were underexpressed by at least 2-folds
in the foetal side of suPTL-IM-placenta. Whereas in the maternal side of suPTL-IMplacenta,
two proteins were underexpressed by at least 2-folds. These proteins are
involved in four distinct functional classes namely inflammation, oxidative stress,
anticoagulation, and extracellular matrix remodelling. These results had contributed to
the selection of a panel biomarkers which consisted of vimentin, cytokeratin 8, S 100A9,
peroxiredoxin 3, and protein PP4-X. These proteins are known to be related to
maintenance of placental cytoplasm architecture, oxidative stress and anticoagulation
and were successfully validated using Western blotting technique. The findings suggest
a ‘defined’ set of risk factors associated with sPTL-IM but lack of predictive value.
Furthermore, proteins involved in inflammation, oxidative stress, anticoagulation, and
extracellular matrix remodelling functions could be used as potential biomarkers for
screening of suPTL-IM-birth in high risk pregnancies. This study suggests that the
differentially expressed proteins found in the suPTL-IM placenta provide an important
first step towards developing a multiplex biomarker-based screening tool for early
prediction of suPTL-IM-birth. |
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