Thursday, June 12, 2014

SpectroscopyNOW-Predicting pre-eclampsia: NMR metabolomics


Predicting pre-eclampsia: NMR metabolomics

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  • Published: May 7, 2014
  • Categories: NMR Knowledge Base
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Under pressure

Marie Austdal - Researchers in Norway have found a useful set of biomarkers in urine and serum samples using NMR spectroscopy that are different between women who are not pregnant, those with normal pregnancies, and those with the debilitating and potentially life-threatening condition of pre-eclampsia.
Researchers in Norway have found a useful set of biomarkers in urine and serum samples using NMR spectroscopy that are different between women who are not pregnant, those with normal pregnancies, and those with the debilitating and potentially life-threatening condition of pre-eclampsia.
Marie Austdal, Ragnhild Bergene Skråstad, Astrid Solberg Gundersen, Rigmor Austgulen, Ann-Charlotte Iversen, Tone Frost Bathen of the Norwegian University of Science and Technology (NTNU), in Trondheim, Norway, have explored how NMR metabolomics might be used to study pre-eclampsia, for improved phenotyping and elucidating potential clues to the condition's aetiology and pathogenesis.
Pre-eclampsia is characterized by high blood pressure, hypertension, and a high concentration of protein in the urine of some pregnant women, there is often associated damage to the liver, kidneys and maternal endothelium. It can give rise to intrauterine growth restriction and if left untreated may develop into eclampsia, which are life-threatening seizures during pregnancy. It is one of the more common complications of pregnancy although the cause is yet to be elucidated definitively and there is no cure. That said, early delivery of the baby and placenta usually dispels the symptoms, but that brings with it the associated problems of premature birth.

Gestation problem

By definition, the condition arises after the 20th week of pregnancy, most often close to full term but in some cases the syndrome appears very early, and these are the most life-threatening to both mother and baby. It has been linked to inadequate development of the placenta during the first trimester of pregnancy thought to be caused by an inappropriate immune response. However, some cases develop after the delivery of the baby. Antihypertensive medication is usually prescribed to bring the blood pressure into a healthy range and preclude the development of seizures. However, intravenous magnesium sulfate is sometimes used and steroids are administered to promote the development of the foetal lung. New insights into the cause and effects of the disease revealed by the NMR studies offer new hope for the future control of this condition.
The team explains that identifying biomarkers for pre-eclampsia could allow much more timely detection and so lead to healthier mothers and children. The collaboration is based at the Centre of Molecular Inflammation Research (CEMIR) and the MR Cancer Group at the Norwegian University of Science and Technology (NTNU) and details are reported in the journal Plos One.

Maternal metabolism

"We have found that the metabolism in women who experience pre-eclampsia is clearly different from women with normal pregnancies," explains team member and NTNU graduate student Marie Austdal. "The differences suggest that pre-eclampsia has a similar profile to cardiovascular disease, and the inflammatory processes are reflected in the blood and urine of affected women. This abnormal metabolism may be present earlier, so that the disease may be predicted before onset." The biomarkers identified by the team correlate with metabolic issues in women as the condition develops during pregnancy. They were able to show a clear and significant difference in metabolomic profile between women from all three groups. Specifically, these differences could be linked to an increase in very low density lipoprotein (VLDL) fats and cholesterol for the pre-eclamptic women, and also reflect an increased stress response and inflammation in pre-eclampsia.
It is presumed that metabolic changes occur earlier than the manifestation of hypertension and proteinuria, which are the standard diagnostic symptoms. If it were possible to detect the onset of pre-eclampsia before it does any damage or its progress becomes entrenched, then it might be possible to intervene medically and prevent some women from developing the disease in the first place. The next step will simply be to use NMR to analyse samples taken from women in the earliest stages of pregnancy.
"The next step in this research is to analyse samples taken much earlier in pregnancy, around gestational week 12," Austdal told SpectroscopyNow. "Metabolomic profiling with NMR at this early stage may help identify women at risk of developing pre-eclampsia, so that they may be followed up more closely by their doctor during pregnancy. This research may also give clues to how and why the disease develops, an area in which many questions still remain."

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