TY - JOUR
T1 - Reduced uterine perfusion pressure as a model for preeclampsia and fetal growth restriction in murine
T2 - a systematic review and meta-analysis
AU - van Kammen, Caren M
AU - Taal, Seija E L
AU - Wever, Kimberley E
AU - Granger, Joey P
AU - Lely, A Titia
AU - Terstappen, Fieke
N1 - Publisher Copyright:
Copyright © 2024 The Authors.
PY - 2024/5
Y1 - 2024/5
N2 - 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];
n = 148), proteinuria (SMD = 2.3; [0.9; 3.8];
n = 28), fetal reabsorptions (MD = 50.4%; [45.5; 55.2];
n = 42), circulating soluble FMS-like tyrosine kinase-1 (sFlt-1) (SMD = 2.6; [1.7; 3.4];
n = 34), and lower fetal weight (MD = -0.4 g; [-0.47; -0.34];
n = 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.
AB - 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];
n = 148), proteinuria (SMD = 2.3; [0.9; 3.8];
n = 28), fetal reabsorptions (MD = 50.4%; [45.5; 55.2];
n = 42), circulating soluble FMS-like tyrosine kinase-1 (sFlt-1) (SMD = 2.6; [1.7; 3.4];
n = 34), and lower fetal weight (MD = -0.4 g; [-0.47; -0.34];
n = 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.
KW - fetal growth restriction
KW - placental insufficiency
KW - preeclampsia
KW - pregnancy
KW - reduced uterine perfusion pressure
UR - http://www.scopus.com/inward/record.url?scp=85196581988&partnerID=8YFLogxK
U2 - 10.1152/ajpheart.00056.2024
DO - 10.1152/ajpheart.00056.2024
M3 - Article
C2 - 38758122
SN - 0363-6135
VL - 327
SP - H89-H107
JO - American journal of physiology. Heart and circulatory physiology
JF - American journal of physiology. Heart and circulatory physiology
IS - 1
ER -