| Popis: |
Prediction of preeclampsia risk is key to informing effective maternal care. Current screening for preeclampsia at 11 -13 weeks' gestation using maternal demographic characteristics and medical history with measurements of mean arterial pressure, uterine artery pulsatility index and serum placental growth factor can identify about 75% of women who develop preterm preeclampsia with delivery at37 weeks' gestation. Further improvements to preeclampsia screening tests will likely require integrating additional biomarkers. Recent research suggests the existence of distinct maternal risk profiles. Biomarker evaluation should therefore account for the possibility that a biomarker only predicts preeclampsia in a specific maternal phenotype.Verification of metabolite biomarkers as preterm preeclampsia predictors early in pregnancy in all women and across body mass index (BMI) groups.Observational case-control study drawn from a large prospective study on the early prediction of pregnancy complications in women attending their routine first hospital visit at King's College Hospital, London, UK, in 2010-2015. Pregnant women underwent a complete first-trimester assessment, including the collection of blood samples for biobanking. In 11-13 weeks' plasma samples of 2501 singleton pregnancies levels of pre-selected metabolites implicated in the prediction of pregnancy complications were determined using a targeted liquid chromatography-mass spectrometry method, yielding high-quality quantification data on 50 metabolites. Ratios of amino acid levels involved in arginine biosynthesis and nitric oxide synthase pathways were added to the list of biomarkers. Placental growth factor and pregnancy-associated plasma protein-A were also available for all study subjects, serving as comparator risk predictors. Data on 1635 control and 106 preterm preeclampsia pregnancies were considered for this analysis, normalized using multiples of medians. Prediction analyses were performed across the following patient strata: all subjects, and the BMI classes25 kg/mLevels of 13 metabolites were associated with preterm preeclampsia in the entire study population (p0.05) with particularly significant associations found for five of them, namely 2-hydroxy-(2/3)-methylbutyric acid, 25-hydroxyvitamin D3, 2-hydroxybutyric acid, alanine, dodecanoylcarnitine and 1-(1Z-octadecenyl)-2-oleoyl-sn-glycero-3-phosphocholine (p0.01). Fold changes in seven amino acid ratios, all involving glutamine or ornithine, were also significantly different between cases and controls (p0.01). The predictive performance of some metabolites and ratios differed according to BMI classification; for example, ornithine (p0.001) and several ornithine-related ratios (p0.0001 - p0.01) were only strongly associated with preterm preeclampsia in the BMI25 kg/mSingle metabolites and ratios of amino acids related to arginine bioavailability and nitric oxide synthase pathways were associated with preterm preeclampsia risk at 11 -13 weeks' gestation. Differential prediction was observed across BMI classes, supporting the existence of distinct maternal risk profiles. Future studies in preeclampsia prediction should account for the possibility of different maternal risk profiles to improve etiological and prognostic understanding and, ultimately, clinical utility of screening tests. |
Full Text from ScienceDirect