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Maternal plasma phospholipids are altered in trisomy 21 cases and prior to preeclampsia and preterm outcomes.

The metabolite composition of blood plasma/serum has, through metabolomics, been increasingly used to detect metabolic changes related to disease. Lipid changes, in particular, are known to accompany onset and evolution of many diseases. In pregnancy, maternal blood lipids naturally undergo extensive changes and their deregulation has been associated with some prenatal disorders. For preeclampsia, for instance, changes have been noted in the levels of triglycerides and specific phospholipids, both at diagnosis and at pre-diagnostic stages (10–20 gestational weeks or g. w.). Pregnant women affected by gestational diabetes were shown to have elevated plasma cholesterol and triglycerides, before (13–15 g.w.) and after (24–32 g.w.) diagnosis. Furthermore, increased risk of spontaneous preterm birth has been suggested for women with high total cholesterol, low-density lipoprotein cholesterol and triglycerides, whereas altered levels of glycerolipids, glycerophospholipids, sterol lipids and sphingolipids have been found in pregnancies with poor outcomes (stillbirth, preterm, small for gestational age). Preeclampsia and preterm usually pose significant risks in pregnancy and, hence, the discovery of predictive biomarkers at the prediagnostic stages could be of great usefulness in prenatal health management. Furthermore, chromosomal disorders such as trisomy 21 (typically diagnosed through amniocentesis (2 trimester) or chorionic villous sampling (1 trimester), usually preceded by maternal serum screening) can still benefit from improved maternal blood markers with high sensitivities. In this report, we present, for the first time, preliminary results on phospholipids profiling of 2 trimester maternal blood plasma of women carrying fetuses diagnosed with trisomy 21 (T21) and of women at the pre-diagnostic stages of preterm. In addition, a pre-diagnostic preeclampsia group is also considered in order to add to previous suggestions of alterations to phospholipids. Plasma phospholipid extracts obtained for control and disorder groups were analyzed by hydrophilic interaction liquid chromatography/ mass spectrometry (HILIC-LC/MS) and subsequent uniand multivariate analysis. Findings unveil potential specific biomarkers of T21 and of the pre-diagnostic stages of preterm and preeclampsia. Samples were collected at the Maternity Bissaya Barreto, Coimbra, Portugal, under ethical committee approval (Refs. 18/04 and 29/09) and informed consents were obtained from each participating subject. Plasma was collected for pregnant women at 16–19 g.w. and all pregnancies were followed until birth, enabling several groups to be defined: (a) controls (n = 14); (b) T21 (n = 5), diagnosed ca. 2 weeks after collection; (c) pre-diagnostic