Reduced uterine perfusion pressure as a model for preeclampsia and fetal growth restriction in murine: a systematic review and meta-analysis

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 327; no. 1; pp. H89 - H107
• Main Authors: van Kammen, Caren M, Taal, Seija E L, Wever, Kimberley E, Granger, Joey P, Lely, A Titia, Terstappen, Fieke
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.07.2024
• Series: Cardiovascular Complications of Pregnancy
• Subjects: Animals; Bias; Blood Pressure; Design standards; Disease Models, Animal; Female; Fetal Growth Retardation - physiopathology; Fetal Weight; Fetuses; Heterogeneity; Kinases; Meta-analysis; Mice; Perfusion; Phenotypes; Pre-eclampsia; Pre-Eclampsia - diagnosis; Pre-Eclampsia - physiopathology; Preeclampsia; Pregnancy; Proteinuria; Regression analysis; Reproducibility; Review; Systematic review; Tyrosine; Uterus; Uterus - blood supply; Uterus - physiopathology; Vascular Endothelial Growth Factor Receptor-1 - blood; Vascular Endothelial Growth Factor Receptor-1 - metabolism; Weight; reduced uterine perfusion pressure; preeclampsia; fetal growth restriction; placental insufficiency; pregnancy
• ISSN: 0363-6135; 1522-1539; 1522-1539
• DOI: 10.1152/ajpheart.00056.2024

The reduced uterine perfusion pressure (RUPP) model is frequently used to study preeclampsia and fetal growth restriction. An improved understanding of influential factors might improve reproducibility and reduce animal use considering the variability in RUPP phenotype. We performed a systematic review and meta-analysis by searching Medline and Embase (until 28 March, 2023) for RUPP studies in murine. Primary outcomes included maternal blood pressure (BP) or proteinuria, fetal weight or crown-rump length, fetal reabsorptions, or antiangiogenic factors. We aimed to identify influential factors by meta-regression analysis. We included 155 studies. Our meta-analysis showed that the RUPP procedure results in significantly higher BP (MD = 24.1 mmHg; [22.6; 25.7]; = 148), proteinuria (SMD = 2.3; [0.9; 3.8]; = 28), fetal reabsorptions (MD = 50.4%; [45.5; 55.2]; = 42), circulating soluble FMS-like tyrosine kinase-1 (sFlt-1) (SMD = 2.6; [1.7; 3.4]; = 34), and lower fetal weight (MD = -0.4 g; [-0.47; -0.34]; = 113. The heterogeneity (variability between studies) in primary outcomes appeared ≥90%. Our meta-regression identified influential factors in the method and time point of BP measurement, randomization in fetal weight, and type of control group in sFlt-1. The RUPP is a robust model considering the evident differences in maternal and fetal outcomes. The high heterogeneity reflects the observed variability in phenotype. Because of underreporting, we observed reporting bias and a high risk of bias. We recommend standardizing study design by optimal time point and method chosen for readout measures to limit the variability. This contributes to improved reproducibility and thereby eventually improves the translational value of the RUPP model.