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Metabolomic Study Uncovers Potential Biomarkers in Women with Preeclampsia

NEW YORK (GenomeWeb News) – Pregnant women with preeclampsia have a metabolic profile that is distinct from those of healthy pregnant women and women who are not pregnant, researchers from the Norwegian University of Science and Technology reported in PLOS One yesterday.

By comparing the serum and urine metabolomes of pregnant women with and without preeclampsia and non-pregnant women, researchers led by Norway's Tone Frost Bathen found nine urine metabolites that could distinguish pregnant women with preeclampsia from other pregnant women. Additionally, women with preeclampsia had higher levels of low- and very-low density lipoproteins and lower levels of high-density lipoproteins in their serum than either healthy pregnant women or women who were not pregnant. This lipoprotein profile, the researchers noted, is similar to that from people at risk for cardiovascular disease.

"We have found that the metabolism in women who experience preeclampsia is clearly different from women with normal pregnancies," said Marie Austdal, a doctoral candidate at NTNU and first author of the study, in a statement. "The differences suggest that preeclampsia has a similar profile to cardiovascular disease, and the inflammatory processes are reflected in the blood and urine of affected women."

Preeclampsia affects some three percent of pregnancies, and it is a possibly life-threatening complication marked by high blood pressure and high urine protein levels. While preeclampsia develops late in pregnancy, typically toward the end of the second or during the third trimester, it is thought to stem from an immune response triggered at the beginning of pregnancy and from an insufficient development of the placenta. The only treatment for the condition is delivery of the baby. Both mother and child are at increased risk for cardiovascular disease later in life.

To search for biomarkers for preeclampsia, the researchers collected serum and urine samples from 10 pregnant women with preeclampsia, 10 healthy pregnant women, and 10 non-pregnant women. The women were matched by age, and the pregnant women were also matched by gestational age.

Using magnetic resonance spectroscopy and a combination of 1D NOESY and 2D approaches, Bathen and colleagues examined the protein content of the samples, which they then analyzed using both principal component analysis and partial least squares discriminant analysis tools. They identified the spectra by matching them to reference metabolite databases using the Bruker AMIX software and Chenomx software.

The urine samples from the different groups of women clustered together in the researchers' PCA analysis. Some 21 metabolites, they found, were different between the three groups: nine metabolites differed between women with preeclampsia and healthy pregnant women, and 15 differed between healthy pregnant and non-pregnant women.

The serum samples, by contrast, showed a continuous trend of increasing serum lipid levels from non-pregnant women to pregnant women to pregnant women with preeclampsia. Additionally, pregnant women with preeclampsia had lower levels of histidine than healthy pregnant women.

These metabolite levels could distinguish the different groups of women. Healthy pregnant women, for instance, had higher amino acids levels in their urine than non-pregnant women. This, the researchers noted, has been found in other studies — pregnant women also have higher levels of choline and lactate in urine and higher alanine and lactate levels in serum — and is thought to be due to decreased renal function in healthy pregnancies.

Women with preeclampsia, though, had higher serum lipid content, particularly increased amounts of VLDL and LDL, as well as increased histidine and glycerol levels.

This profile, the researchers noted, is similar to that of people who are at risk of developing cardiovascular disease.

Additionally, women with preeclampsia had higher urine levels of choline and decreased amounts of glycine, p-cresol sulfate, and hippurate, which the researchers said could be linked to increased oxidative stress and kidney dysfunction. Urinary choline levels have previously been associated with fetal stress during the second trimester, the researchers noted.

While Bathen and colleagues uncovered these differences in women who had already developed preeclampsia during their pregnancies, they said that these metabolic changes could occur earlier on in pregnancy.

"This abnormal metabolism may be present earlier, so that the disease may be predicted before onset," Austdal added.

The Norwegian group is next studying samples obtained from women at earlier stages of their pregnancies to see if these metabolite differences could predict disease.