Abstract
OBJECTIVE
Wide-spread endothelial dysfunction is thought to underlie the maternal symptoms of preeclampsia. Endothelial dysfunction is strongly associated with abnormal circulating lipoprotein cholesterol levels. This systematic review aimed to assess whether maternal circulating high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and very-low-density lipoprotein cholesterol levels were altered before or at the time of preeclampsia diagnosis. This may provide an understanding of the pathogenesis of preeclampsia and the predictive and diagnostic utility of lipoprotein cholesterol levels in distinguishing pregnancies complicated by preeclampsia from normal pregnancies.
DATA SOURCES
Literature searches were conducted in Ovid MEDLINE, Embase, Cumulative Index of Nursing and Allied Health Literature, and Google Scholar from inception to April 2024 for studies reporting high-density lipoprotein, low-density lipoprotein, and very-low-density lipoprotein levels in normal pregnancies and pregnancies complicated by preeclampsia.
STUDY ELIGIBILITY CRITERIA
The selected studies included the following: population of pregnant women, exposure to preeclampsia, blood samples collected during a specific trimester of pregnancy, and at least 1 primary outcome (high-density lipoprotein, low-density lipoprotein, or very-low-density lipoprotein). Of note, 2 reviewers were involved in the study selection. The excluded studies included pregnancies complicated by other risk factors for preeclampsia (eg, preexisting hypertension, diabetes mellitus, and obesity) and other pregnancy-related hypertensive disorders (pregnancy-induced hypertension, eclampsia, and hemolysis, elevated liver enzymes, and low platelet count).
METHODS
The quality of the included studies was evaluated using the Newcastle-Ottawa Scale for case-control, cohort, and cross-sectional studies.
RESULTS
A total of 41 studies were included. The quality of the studies was generally good. However, 59% of the studies did not control for the gestational age at which the blood samples were collected. No consistent change in high-density lipoprotein or low-density lipoprotein levels was found before preeclampsia diagnosis in the first, second, or third trimesters of pregnancy. Very-low-density lipoprotein was significantly elevated in 2 of 2 studies that reported levels before preeclampsia diagnosis in the late second (>23 weeks of gestation) or third trimester of pregnancy. After preeclampsia diagnosis in the third trimester of pregnancy, very-low-density lipoprotein levels were significantly elevated in 9 of 11 studies, and high-density lipoprotein levels were significantly decreased in 15 of 19 studies.
CONCLUSION
Very-low-density lipoprotein is highly atherogenic, and its elevation before and at the time of preeclampsia diagnosis suggests a role in the pathogenesis of the endothelial dysfunction associated with preeclampsia. Both very-low-density lipoprotein and high-density lipoprotein show promise as prospective (very-low-density lipoprotein–only) diagnostic biomarkers for preeclampsia.