Plasma lipids are dysregulated preceding diagnosis of preeclampsia or delivery of a growth restricted infant

Background Lipids serve as multifunctional metabolites that have important implications for the pregnant mother and developing fetus. Abnormalities in lipids have emerged as potential risk factors for pregnancy diseases, such as preeclampsia and fetal growth restriction. The aim of this study was to assess the potential of lipid metabolites for detection of late-onset preeclampsia and fetal growth restriction. Methods We used a case-cohort of 144 maternal plasma samples at 36 weeks' gestation from patients before the diagnosis of late-onset preeclampsia (n = 22), delivery of a fetal growth restricted infant (n = 55, defined as <5th birthweight centile), gestation-matched controls (n = 72). We performed liquid chromatography-tandem mass spectrometry (LC-QQQ)-based targeted lipidomics to identify 421 lipids, and fitted logistic regression models for each lipid, correcting for maternal age, BMI, smoking, and gestational diabetes. Findings Phosphatidylinositol 32:1 (AUC = 0.81) and cholesterol ester 17:1 (AUC = 0.71) best predicted the risk of developing preeclampsia or delivering a fetal growth restricted infant, respectively. Five times repeated five-fold cross validation demonstrated the lipids alone did not out-perform existing protein biomarkers, soluble tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) for the prediction of preeclampsia or fetal growth restriction. However, lipids combined with sFlt-1 and PlGF measurements improved disease prediction. Interpretation This study successfully identified 421 lipids in maternal plasma collected at 36 weeks' gestation from participants who later developed preeclampsia or delivered a fetal growth restricted infant. Our results suggest the predictive capacity of lipid measurements for gestational disorders holds the potential to improve non-invasive assessment of maternal and fetal health. Funding This study was funded by a grant from National Health and Medical Research Council. Copyright & COPY; 2023 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

This study aimed to assess the potential of lipid metabolites for detection of late-onset preeclampsia and fetal growth restriction. The study identified phosphatidylinositol 32:1 and cholesterol ester 17:1 as the lipids with the best predictive capacity for the risk of developing preeclampsia or delivering a fetal growth restricted infant. The results suggest that lipid measurements have the potential to improve non-invasive assessment of maternal and fetal health.