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NMR identifies potential biomarkers for predicting pre-eclampsia risk

“Urinary metabolic profiling in early pregnancy revealed specific, significant changes in the metabolism of women who later developed pre-eclampsia or gestational hypertension”

Pre-eclampsia is a serious hypertensive disorder of pregnancy that can give rise to life-threatening complications in childbirth. It develops in around 8% of pregnancies worldwide and accounts for 14% of peripartum maternal deaths. Furthermore, it increases the risk of developing chronic cardiovascular disorders.

Pre-eclampsia typically occurs at 20 weeks gestation but may have a later onset. It is thus important that pregnant women are monitored for hypertensive disorders throughout their pregnancy so treatment can be initiated to minimize the risks.

Since the most common signs and symptoms of pre-eclampsia are similar to those of a range of other conditions and may arise during a healthy pregnancy, the condition can develop unnoticed. Additionally, the presence of pre-eclampsia cannot be confirmed using a single biomarker test. A diagnosis of pre-eclampsia is generally given if blood pressure increases during pregnancy to ≥140 mmHg systolic or ≥90 mmHg diastolic concomitantly with proteinuria, renal insufficiency, thrombocytopaenia, liver damage, or pulmonary and/or cerebral oedema. Eclampsia is a severe form of pre-eclampsia that results in convulsive seizures and/or coma during childbirth.

With the successful identification of biomarkers for a range of conditions being achieved through metabolomic studies, metabolic profiling has now been applied to the early prediction of pre-eclampsia. Predictive models using a combination of maternal characteristics, biochemical, and biophysical markers at 11‑13 weeks gestation have predicted the later onset of pre-eclampsia with 30%–60% sensitivity.

The latest metabolomic study analyzed urine and serum samples collected from 599 women between 11+0- and 13+6-weeks gestation. 1H NMR analyses were performed using a Bruker Avance IVDr system i.e. Bruker Avance III Ultrashielded Plus 600 MHz spectrometer equipped with a 5 mm QCI cryoprobe.

Around 4% of the women developed pre-eclampsia during their pregnancy and slightly fewer experienced gestational hypertension. Such hypertensive disorders were more common among women with higher body mass index and higher mean arterial pressure at study enrolment.

Urinary spectral profiles were found to differ between women who went on to have healthy pregnancies and those who later developed a hypertensive disorder. Indeed, there was a characteristic clustering of urine samples from women who later developed pre-eclampsia or gestational hypertension. This was not apparent for the serum samples.

The later occurrence of pre-eclampsia was correctly predicted from urinary metabolic profiles with 51.3% sensitivity. The metabolite hippurate appeared to be an especially powerful predictor of pre-eclampsia with false positives recorded in 10% of cases.

Predictions of pre-eclampsia from serum metabolomic profiles were less accurate, with a sensitivity of only 15%. The most important predictive markers were lipid levels.

The specific, significant changes in metabolism observed during early pregnancy in this study could inform the development of much needed new and improved predictive biomarkers of pre-eclampsia.

These latest findings confirm the potential for metabolomic analyses in the prediction of pre-eclampsia during the early stages of pregnancy.

Austdal M, et al. Int. J. Mol. Sci. 2015;16:21520-21538. doi:10.3390/ijms160921520