PlGF Ratio Research Articles

Mid-Trimester Uterine Artery Doppler for Aspirin Discontinuation in Pregnancies at High Risk for Preterm Preeclampsia: Post Hoc Analysis of StopPRE Trial

(BJOG. 2024;131(3):334–342. doi: 10.1111/1471-0528.17631) Preeclampsia (PEC) is characterized by hypertension and proteinuria or organ dysfunction after 20 weeks of gestation. The cause of the condition has not been fully elucidated; however, PEC is associated with a defect in the development of the placenta in early-onset patients. In unaffected individuals, uterine artery flow impedance (UtA) decreases during early gestation through week 24. However, if pulsatility index (PI) in UtA remains high, it is a sign of maladaptation and is commonly found in patients with preterm PEC. An additional consequence of impaired placentation is uteroplacental ischemia, during which the levels of placental growth factor (PIGF) are decreased and soluble fms-like tyrosine kinase-1 (sFlt-1) increases. In screening first trimester patients for risk of PEC, UtAPI and PIGF may be used. Clinicians prescribe aspirin daily as a preventative measure in patients who screen at risk for PEC. Although the incidence of PEC greatly decreases with this treatment, it is also noteworthy that screening for risk of PEC during the first trimester results in a high false positive rate. Thus, most women pre-emptively receiving aspirin for PEC are false positives. The authors previously performed a study where aspirin was discontinued in patients between 24 and 28 weeks of gestation with a normal sFlt-1/PlGF ratio of ≤38, identifying false positives cases. Although this study showed promising results, the ratio may not be available for use in every clinic. Thus, in this study, the authors examine whether UtAPI can be a correlate for these angiogenic factors and act as an alternative screening measure at 24 to 28 weeks of gestation with the same purpose to discontinue aspirin and assess incidence of preterm PEC.

Oxidative Stress and Placental Pathogenesis: A Contemporary Overview of Potential Biomarkers and Emerging Therapeutics.

Oxidative stress (OS) plays a crucial role in placental pathogenesis and pregnancy-related complications. This review explores OS's impact on placental development and function, focusing on novel biomarkers for the early detection of at-risk pregnancies and emerging therapeutic strategies. We analyzed recent research on OS in placental pathophysiology, examining its sources, mechanisms, and effects. While trophoblast invasion under low-oxygen conditions and hypoxia-induced OS regulate physiological placental development, excessive OS can lead to complications like miscarriage, preeclampsia, and intrauterine growth restriction. Promising OS biomarkers, including malondialdehyde, 8-isoprostane, and the sFlt-1/PlGF ratio, show potential for the early detection of pregnancy complications. Therapeutic strategies targeting OS, such as mitochondria-targeted antioxidants, Nrf2 activators, and gasotransmitter therapies, demonstrate encouraging preclinical results. However, clinical translation remains challenging. Future research should focus on validating these biomarkers in large-scale studies and developing personalized therapies to modulate placental OS. Emerging approaches like extracellular vesicle-based therapies and nanomedicine warrant further investigation for both diagnostic and therapeutic applications in pregnancy-related complications. Integrating OS biomarkers with other molecular and cellular markers offers improved potential for the early identification of at-risk pregnancies.

Very low sFlt-1/PlGF ratio in foetal growth restriction: clinical insights from a case study

Very low sFlt-1/PlGF ratio in foetal growth restriction: clinical insights from a case study

A-308 Placental Growth Factor Kryptor Immunoassay Reveals Quality Control Imprecision and Drift

Abstract Background The utility and value of determining the soluble fms-like tyrosine kinase-1 to placental growth factor (sFlt-1/PlGF) ratio for predicting the likelihood of progression to pre-eclampsia in pregnant women admitted with hypertension are increasingly becoming widely recognized. A key finding of the multi-center PRAECIS trial (NEJM Evid 2022;1(12)) is the observation that sFlt-1/PlGF ratios ≥ 40 correlate with higher risk for adverse maternal outcomes. The sFlt-1 and PlGF immunoassays performed on the ThermoFisher Scientific B·R·A·H·M·S Kryptor autoanalyzer became the first FDA-approved tests in 2023 for determining sFlt-1/PlGF ratio. In this study, an evaluation of the analytical performance of the sFlt-1 and PlGF KRYPTOR immunoassays was performed, which included analyte measuring range (AMR), accuracy, precision, and stability studies. Methods Calibration and QC materials (consisting of lyophilized recombinant human proteins), test reagents and solutions, and consumables were purchased and provided by ThermoFisher Scientific. Analytical runs were performed according to vendor’s instructions by trained medical laboratory scientists. Between-day precision of our two instruments for both immunoassays was assessed by assaying all three levels of sFlt-1 and PlGF QC materials, as well as patient serum pools with low PlGF concentration, once to twice daily for multiple consecutive days. Results While the analytical performance of the sFlt-1 immunoassay was robust and performed according to expectation (within-day CV <1% and between-day CV <3%), the PlGF immunoassay was surprisingly less reliable. Imprecision and inaccuracy of the PlGF immunoassay at the low end of its analytical measurement range was reflected by both sporadically out-of-control between-day measurements of all three QC levels (with target ranges of 24 - 36 pg/mL, 80 - 120 pg/mL, and 320 - 480 pg/mL), as well as slow downward drifts of particularly the low level QC material. In one instance, a downtrend was observed from 28 pg/mL to 14 pg/mL over 6 days, even with fresh reagents, solutions, and calibration. Such shortened stability of the PlGF assay does not meet the vendor’s claims of calibration stability of 15 days and onboard kit stability of 29 days. Using vendor’s provided material, the AMR of both sFlt-1 and PlGF were adequately verified and showed excellent linearity (r2> 0.99). Conclusions Despite low level QC imprecision and drift, the sFlt-1/PlGF ratios determined using the B·R·A·H·M·S Kryptor analyzers are acceptable for clinical use but with the caveat that we will perform batch testing with bracketing QCs and conduct stringent QC monitoring, frequent calibrations, and reduce the onboard kit stability as defined by ThermoFisher Scientific. Our findings serve as a reminder that FDA approval does not preclude thorough verification studies of any assay prior to implementation for clinical use.

Intermanufacturer assessment of diagnostic performance of angiogenic ratio vs glycosylated fibronectin in women with suspected pre-eclampsia.

To compare the diagnostic performance of different manufacturers' immunoassays for the soluble fms-like tyrosine kinase-1 (sFlt-1)-to-placental growth factor (PlGF) ratio with that of a point-of-care (PoC) test for glycosylated fibronectin (GlyFn) in women with suspected pre-eclampsia (PE). This was a prospective, single-center, double-blinded, non-interventional study of East Asian women with a singleton pregnancy who presented with hypertension with or without clinical features of PE after 20 weeks' gestation between January 2020 and March 2022. Maternal serum samples were collected at the time of presentation, and subsequent management followed the departmental protocol, based on gestational age, severity of hypertension, fetal condition and presence of severe PE features. Women diagnosed with PE at presentation were excluded. PE was diagnosed according to the 2018 International Society for the Study of Hypertension in Pregnancy classification. Levels of sFlt-1 and PlGF were measured using the Cobas e411 (Roche Diagnostics), BRAHMS KRYPTOR (ThermoFisher Scientific) and iMAGIN 1800 (Ningbo Aucheer) platforms. GlyFn levels were measured using the Lumella™ GlyFn PoC test (DiabetOmics Inc.). The predictive performance of each test to rule out PE within 7 days and rule in PE within 28 days from the date of presentation was assessed. Based on the PROGNOSIS study, a sFlt-1/PlGF ratio of ≤ 38 on the Roche platform was used to predict the absence of PE within 7 days. The sFlt-1/PlGF ratio was classified as high or low using platform-specific thresholds equivalent to a Roche sFlt-1/PlGF ratio of 38, which were derived using Passing-Bablok regression. GlyFn was categorized as high or low using two reported clinical management thresholds (263 μg/mL and 510 μg/mL). Overall, 236 women with suspected PE were included, of whom 70 (29.7%) were diagnosed with PE; 36 (51.4%) and 70 (100%) developed PE within 7 days and 28 days, respectively. Eighty-eight (37.3%) women had a sFlt-1/PlGF ratio of > 38 on the Roche platform, 79 (33.5%) women had a sFlt-1/PlGF ratio of > 55 on the KRYPTOR platform and 96 (40.7%) women had a sFlt-1/PlGF ratio of > 40 on the iMAGIN 1800 platform. Furthermore, 62 (26.3%) and four (1.7%) women had a GlyFn level of > 263 μg/mL and > 510 μg/mL, respectively. The negative predictive value (NPV) of the sFlt-1/PlGF ratio measured on the Roche, KRYPTOR and iMAGIN 1800 platforms to rule out PE within 7 days after presentation was 83.3%, 82.0% and 82.9%, respectively, while that for GlyFn > 263 μg/mL and > 510 μg/mL was 82.6% and 70.4%, respectively. The corresponding positive predictive values (PPV) to rule in PE within 28 days after presentation were 50.5%, 52.3% and 46.7%, respectively, for the sFlt-1/PlGF ratio, and 35.4% and 50.0%, respectively, for GlyFn > 263 μg/mL and > 510 μg/mL. The predictive performance of different manufacturers' assays for the sFlt-1/PlGF ratio to rule in and rule out PE were similar once standardized to a common threshold. Our findings suggest that the sFlt-1/PlGF ratio and GlyFn using a cut-off of 263 μg/mL can both be utilized to rule out PE within 7 days after assessment, with a moderate NPV. The PPV for ruling in PE within 28 days remains poor. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Economic analysis of the use of the Flt-1/PlGF preeclampsia ratio compared to the standard of care in Uruguay

Preeclampsia (PE) is a pregnancyrelated hypertensive disorder that can lead to severe complications and adverse maternal and fetal outcomes. This study aimed to estimate the economic impact of integrating the sFlt-1/PlGF ratio into Uruguay's healthcare system as part of routine clinical practice for diagnosing. A decision tree model was used to estimate the annual economic impact on the Uruguayan healthcare system for a hypothetical cohort of women with suspected PE. This included relevant costs associated with diagnosis, monitoring, and treatment from the initial presentation of suspected PE until childbirth. The study analyzed the annual costs under two scenarios: the standard of care and a scenario incorporating the sFlt-1/PlGF ratio for PE, using 2022 as the reference year. Various deterministic and probabilistic sensitivity analyses were performed. The economic model estimated that the implementation of the sFlt-1/PlGF ratio could save the Uruguayan healthcare system $95,432,678 Uruguayan pesos (2,320,269 United States Dollars [USD]) annually, representing a 5 % reduction in costs compared with the standard of care. These savings were primarily due to a reduction in hospitalizations of women with suspected PE. The estimated economic impact equated to an annual net saving of approximately $10,602 Uruguayan pesos (258 USD) per patient. The introduction of the sFlt-1/PlGF ratio into the Uruguayan healthcare system is likely to generate savings due to the optimization of the management of hospitalizations for women with suspected preeclampsia (PE). However, the potential for savings will primarily depend on the current hospitalization rate of these women (the efficiency of managing high-risk PE pregnancies) and the length of stay for hospitalized women.

A loss of tuning of both pro-coagulant and inflammatory responses in monocytes in patients with preeclampsia

An imbalance between pro- and anti-angiogenesis is one of the leading causes of preeclampsia (PE). Monocytes, known as regulators of angiogenesis during immune responses, cooperate with platelets, but the specifics of these responses during pregnancy remain unclear. In this study, we investigated the relationship between pro-coagulant responses on monocytes [platelet activation marker CD61 as a monocyte-platelet aggregate (MPA), tissue factor (CD142), etc.], inflammatory responses [soluble CD40 ligand (sCD40L), soluble suppression of tumorigenesis-2 (sST2), etc.], and the balance of angiogenesis [soluble Fms-related receptor tyrosine kinase 1/placental growth factor (sFlt-1/PLGF) ratio]. In PE, markers of pro-coagulant and inflammatory responses were higher than those in normal pregnancy (NP). Interestingly, in NP, these markers harmonized with the sFlt-1/PLGF ratio, but not in PE. Furthermore, ex vivo examinations showed that upregulation of CD142 induced by additional platelet activation with adenosine diphosphate was diminished in PE. Conversely, low-dose aspirin, which is used as a preventive treatment for PE, could inhibit the increase of CD61 and sST2 under inflammatory stimuli and platelet activation in NP but not in PE. These results indicate that monocytes in PE upregulate basal activity and lose responsiveness to stimulation. The elevation of pro-coagulant and inflammatory responses may be mitigated by prophylaxis with low-dose aspirin. Therefore, the findings suggesting a loss of tuning of both pro-coagulant and inflammatory responses on monocytes help in understanding the pathology of PE. The harmonization between pro-coagulant responses, inflammatory responses, and angiogenesis may serve as useful indicators for the prediction and preventive treatment of PE.

Utility of placental biomarkers and fetoplacental Dopplers in predicting likely placental pathology in early and late fetal growth restriction – A prospective study

IntroductionThe aim of this study was to evaluate the association between placental abnormalities, placental biomarkers, and fetoplacental Dopplers in a cohort of pregnancies complicated by fetal growth restriction (FGR). We also ascertained the risk of perinatal mortality, severe neurological morbidity, and severe non-neurological morbidity by type of placental abnormality. MethodsThis was a prospective cohort study. Multivariable logistic regression was used to evaluate the effect of early vs. late FGR, placental biomarkers and fetoplacental Dopplers on Maternal Vascular Malperfusion (MVM) which was the commonest placental abnormality identified. ResultsThere were 161 (53.5 %) early FGR and 140 (46.5 %) late FGR cases. MVM abnormalities were present in 154 (51.2 %), VUE in 45 (14.6 %), FVM in 16 (5.3 %), DVM in 14 (4.7 %) and CHI in 4 (1.3 %) cases. The odds of MVM were higher in early compared to late FGR cohort (OR 1.89, 95%CI 1.14, 3.14, p = 0.01). Low maternal PlGF levels <100 ng/L (OR 2.34, 95%CI 1.27,4.31, p = 0.01), high sFlt-1 level (OR 2.13, 95%CI 1.35, 3.36, p = 0.001) or elevated sFlt-1/PlGF ratio (OR 3.48, 95%CI 1.36, 8.91, p = 0.01) were all associated with MVM. Increased UA PI > 95th centile (OR 2.91, 95%CI 1.71, 4.95, p=<0.001) and mean UtA PI z-score (OR 1.74, 95%CI 1.15, 2.64, p = 0.01) were associated with higher odds of MVM. Rates of severe non-neurological morbidity were highest in the MVM, FVM, and CHI cohorts (44.8 %, 50 %, and 50 % respectively). ConclusionMVM was the commonest placental abnormality in FGR, particularly in early-onset disease. Low maternal PlGF levels, high sFlt-1 levels, elevated sFlt-1/PlGF ratio, and abnormal fetoplacental Dopplers were also significantly associated with MVM. MVM, FVM, and CHI abnormalities were associated with lower median birthweight, higher rates of preterm birth, operative birth for non-reassuring fetal status, and severe neonatal non-neurological morbidity.

The sFLT-1/PlGF ratio versus biochemical parameters in prediction of adverse outcomes in preeclamptic women

The sFLT-1/PlGF ratio versus biochemical parameters in prediction of adverse outcomes in preeclamptic women

Predictive Value of the sFlt-1/PlGF Ratio and Interleukin-6 for the Presence of Placental Lesions in Spontaneous Preterm Labor with Intact Membranes with Delivery within 7 Days.

The aim of the study was to identify predictive values of the soluble fms-like tyrosine kinase/placental growth factor (sFlt-1/PlGF) ratio and interleukin (IL)-6, assessed with a clinically available method in a large-volume biochemistry laboratory, in maternal blood, amniotic fluid, and umbilical cord blood for the presence of the placental lesions consistent with maternal vascular malperfusion (MVM) and acute histological chorioamnionitis (HCA), respectively. This retrospective study included 92 women with preterm labor with intact membranes (PTL) delivered within 7 days of admission with gestational ages between 22+0 and 34+6 weeks. The sFlt-1/PlGF ratio and IL-6 were assessed in stored samples of maternal serum, amniotic fluid, and umbilical cord serum using Elecsys® sFlt-1, PlGF, and IL-6 immunoassays. Women with MVM had a higher sFlt-1/PlGF ratio in the maternal serum, compared to those without MVM (19.9 vs. 4.6; p &lt; 0.0001), but not in the amniotic fluid or umbilical cord blood. A cut-off value of 8 for the sFlt-1/PlGF ratio in maternal serum was identified as optimal for predicting MVM in patients with PTL. Women with HCA had higher concentrations of IL-6 in maternal serum, compared to those without HCA (11.1 pg/mL vs. 8.4 pg/mL; p = 0.03), amniotic fluid (9,216 pg/mL vs. 1,423 pg/mL; p &lt; 0.0001), and umbilical cord blood (20.7 pg/mL vs. 10.7 pg/mL, p = 0.002). Amniotic-fluid IL-6 showed the highest predictive value. A cut-off value of IL-6 concentration in the amniotic fluid of 5,000 pg/mL was found to be optimal for predicting HCA in PTL. Maternal serum sFlt-1/PlGF and amniotic fluid IL-6 concentrations can be used for liquid biopsy to predict placental lesions in women with PTL who deliver within 7 days.

Significance of the sFlt-1/PlGF Ratio in Certain Cohorts - What Needs to be Considered?

The sFlt-1/PlGF ratio is an established tool in clinical practice, where it is part of a diagnostic algorithm and informs the prognosis of preeclampsia (PE). Maternal and gestational comorbidities can affect the performance of the sFlt-1/PlGF ratio and its constituent elements, and a good understanding of the potential pitfalls is required. The objective of this paper was to provide a current narrative review of the literature on the diagnostic and predictive performance of the sFlt-1/PlGF ratio in specific patient cohorts. Potential factors which can negatively affect the clinical interpretability and applicability of the sFlt-1/PlGF ratio include chronic kidney disease, twin pregnancy, and maternal obesity. Pathophysiological mechanisms related to these factors and disorders can result in different concentrations of sFlt-1 and/or PlGF in maternal blood, meaning that the use of standard cut-off values in specific cohorts can lead to errors. To what extent the cut-off values should be adapted in certain patient cohorts can only be clarified in large prospective cohort studies. This applies to the use of the ratio both for diagnosis and prognosis.

The ability of sFlt-1/PlGF ratio for preeclampsia characterization

The ability of sFlt-1/PlGF ratio for preeclampsia characterization

Plasma soluble fms-like tyrosine kinase 1 to placental growth factor ratio of 11.5 multiples of median predicts preeclampsia with severe features within 2 weeks of testing

BackgroundAngiogenic imbalances, characterized by an excess of antiangiogenic factors (soluble fms-like tyrosine kinase 1 [sFlt-1]) and reduced angiogenic factors (VEGF and placental growth factor [PlGF]), contribute to the mechanisms of disease in preeclampsia. The ratio of sFlt-1 to PlGF has been used as a biomarker for preeclampsia, but cut-off values may vary with gestational age and assay platform. ObjectivesTo compare multiples of the median (MoM) of maternal plasma sFlt-1/PlGF ratio, sFlt-1, PlGF, and conventional clinical and laboratory values to predict preeclampsia with severe features. Study DesignWe conducted a cohort study across 18 U.S. centers involving hospitalized hypertensive individuals between 23-35 weeks' gestation. Receiver operating characteristic curve (ROC) analyses of maternal plasma biomarkers, highest systolic or diastolic blood pressures, and laboratory values at enrollment were performed for the prediction of preeclampsia with severe features. Their areas under the curve (AUC) were compared, and quasi-Poisson regression models were fitted to estimate relative risks. The primary outcome was preeclampsia with severe features within two weeks of enrollment. Secondary outcomes were a composite of severe adverse maternal outcomes (elevated liver enzymes, low platelets count, placental abruption, eclampsia, disseminated intravascular coagulation, and pulmonary edema) and a composite of severe adverse perinatal outcomes (birthweight <3rd percentile, very preterm birth [<32 weeks] and fetal/neonatal death). ResultsOut of 543 individuals included in the study, preeclampsia with severe features within two weeks was observed in 33.1% (n=180) of them. A ROC-derived cut-off of 11.5 MoM for sFlt-1/PlGF plasma ratio provided sensitivity (90.6%), specificity (76.9%), positive predictive value (66.0%), negative predictive value (94.3%), positive likelihood ratio (3.91), negative likelihood ratio (0.12), and accuracy (81.4%) for preeclampsia with severe features within two weeks. This cut-off was used to compare test positive cases (≥ cut-off) and test negative cases (< cut-off). Preeclampsia with severe features (66.0% vs. 5.7%; <0.001), and composites of severe adverse maternal (8.11% vs. 2.7%; p=0.006) or perinatal outcomes (41.3% vs. 10.14%; p=0.001) within two weeks were more frequent in test positive cases than test negative cases. sFlt-1/PlGF plasma ratio ≥11.5 MoM was independently associated with preeclampsia with severe features (adjusted incidence rate ratio [aIRR]: 9.08, 95% CI: 6.11 to 14.06; p<0.001) and a composite of severe adverse perinatal outcomes (aIRR: 9.42, 95% CI: 6.36 to 14.53; p<0.001), but not with a composite of severe adverse maternal outcomes (aIRR: 2.20, 95% CI: 0.95 to 5.54; p=0.08).The AUC of sFlt-1/PlGF plasma ratio in MoM (0.91; 95% CI: 0.89-0.94) for preeclampsia with severe features within two weeks was significantly higher (p<0.001 for all comparisons) than either plasma biomarker alone or any other parameter, with the exception of absolute sFlt-1/PlGF plasma ratio values. ConclusionsSFlt-1/PlGF plasma ratio ≥11.5 MoM among hospitalized, hypertensive patients between 23- and 35-week’s gestation predicts progression to preeclampsia with severe features and severe adverse perinatal outcomes within two weeks.

#1728 New onset proteinuria in two pregnancies: glomerulopathy or preeclampsia?

Abstract Background and Aims Distinguishing between preeclampsia in pregnant women and a new onset glomerulonephritis could be challenging. Method Here, we present two cases on new onset proteinuria during pregnancy which were diagnosed with primary membranous nephropathy and their treatment. Results Case 1. A 27-year-old patient, G6P5A1, was referred to our attention at the 14th week of gestation (wg) for new onset proteinuria of about 5 g/day. She had a personal history of preeclampsia and was already under low-dose Aspirin since the beginning of this pregnancy. She was normotensive, her serum albumin was about 1.8 g/dl (Fig. 1A) and showed no edema. Due to the timing of pregnancy, a glomerular disease was suspected, and she was started on oral prednisolone 20 mg/day. Complementary explorations found a normal SFlT-1 to PlGF ratio as well as normal renal function and positive anti-PLA2R antibodies. A diagnosis of membranous nephropathy diagnosis was, therefore, made. Cyclosporine (CsA) 300 mg twice daily was started, prednisolone was rapidly tapered, and partial remission was rapidly attained. The rest of her pregnancy was uneventful until the 36 wg when hypertension, increase in proteinuria and findings of IUGR developed; on the account of the diagnosis of superimposed preeclampsia, delivery was decided (caesarian section) giving birth to a healthy female baby weighting 1.9 kg (1st Intergrowth centile). After the delivery the patient underwent two injection of Rituximab (Rtx) (1 g 2 weeks apart) and CsA was discontinued. The patient achieved partial remission, and her antibody titer decreased but remained positive. A renal biopsy is scheduled to guide future treatment options. Case 2. A 44-year-old patient, G3P2A1, without history of previous preeclampsia, was referred to our attention at 32 wg for new onset proteinuria around 5 g/day first discovered at 10 wg. Her blood pressure was normal. She was already under Aspirin treatment, based on a suspicion of preeclampsia, which was however ruled out by the timing of proteinuria onset. At referral additional investigations revealed an increase in proteinuria up to 19 g/l, normal renal function, gestational diabetes, normal SFlT-1 to PlGF ratio and a serum albumin around 1.4 g/dl (Fig. 1B). Anti-PLA2R antibodies were positive, and a membranous nephropathy was diagnosed at 34 wg. Immunosuppression treatment was waived considering the timing of pregnancy and supportive treatment by LMW heparin was started. The patient delivered at 37 wg by urgent cesarian section on the account of onset of hypertension, giving birth to a male baby weighting 2760 g (37th Intergrowth centile). CsA treatment was started 5 days after delivery and Rtx infusion followed 2 weeks after delivery, on the account of her decision to breastfeed. CsA was discontinued 2 months after Rtx first injection with complete sustained remission and undetectable PLA2R antibodies. Conclusion Preeclampsia is the most frequent complication of pregnancy. In particular before the 20 wg the distinction between an hypertensive disorder of pregnancy (HDP) and primary glomerular disease is fundamental but may be difficult. In our cases, the early onset of proteinuria was in favor of a primitive disease of the kidney. Complementary explorations allowed diagnosing membranous nephropathy. The treatment of glomerulonephritides, either of new onset or chronic, during pregnancy is challenging. Renal biopsy has a higher risk of complications, especially in mid-pregnancy, and finding positive anti PLA2R antibodies may allow avoiding the histological examination. It is worth noting that preeclampsia developed in both cases towards the end of gestation, stressing the role of chronic kidney disease as a major risk factor for HDP. The SFlT-1 to PlGF ratio could come in handy both for differential diagnosis and for diagnosis of superimposed preeclampsia.

The sFlt-1/PlGF Ratio at 12, 24, and 32 Weeks Gestation in Twin Pregnancies as a Predictor of Late Preterm Birth and Perinatal Event Secondary to Prematurity.

Background: Preterm birth impacts 60% of twin pregnancies, with the subsequent risk of complications in both newborns secondary to the immaturity of organs. This study aims to assess the utility of the sFlt-1/PlGF ratio throughout pregnancy in predicting late preterm birth and adverse perinatal outcomes related to prematurity in twin pregnancies. Methods: This is a prospective cohort study developed at a tertiary hospital. All pregnant women with a twin pregnancy who signed the informed consent were included. The sFlt-1/PlGF ratio was measured at 12, 24, and 32 weeks' gestation. Results: Seventy patients were included, from which 54.3% suffered late preterm birth. Results revealed a significant difference in sFlt-1/PlGF ratio at week 32 between term and preterm groups, with a one-unit increase associated with a 1.11-fold increase in the probability of preterm birth. The sFlt-1/PlGF ratio at week 32 alone presented considerable predictive capacities (sensitivity of 71%, specificity of 72%, a PPV of 75%, and an NPV of 68%. Similarly, at week 24, a one-unit increase in sFlt-1/PlGF ratio was associated with a 1.24-fold increase in the probability of adverse perinatal events due to prematurity. Combining parity, maternal age, conception method, BMI, and chorionicity, the model yielded better predictive capacities (sensitivity of 82%, specificity of 80%, PPV of 58%, NPV of 93%). Conclusions: The potential of the sFlt-1/PlGF ratio as a predictive tool for preterm birth and adverse perinatal outcomes secondary to prematurity in twin pregnancies is underscored.

KPs improve renal function and blood vessels function by balance the sFlt-1:PlGF ratio in L-NAME-induced SHRSP preeclampsia rats

Preeclampsia (PE) is one of the major problems for global healthy burden. It affects 2 to 8% of all pregnancies and causes both maternal and infant morbidity and mortality. Kefir peptides are products from many kinds of prebiotic fermentation in whole milk by kefir grain. In this study, we used the N(ω)-nitro-L-arginine methyl ester (L-NAME) in drinking water to mimic the preeclampsia in spontaneous hypertension rat stroke-prone (SHRSP) pregnant rats, the rats were assigned to five treatment groups: the normal group, untreated group, L-NAME group, L-NAME+KPs (LD and HD dose diets) for 20-day experiment. Data showed that rats only gave the L-NAME group induced severe high blood pressure, urine protein, placenta damage, and embryo reabsorption. After KPs pre-administration significantly reduced urine protein production and generalized vessel endothelial dysfunction, anti-oxidative, and anti-inflammation levels in SHRSP rats placenta. In conclusion, kefir peptides is a multipurpose peptide that can suppress oxidative stress, HIF-1a, anti-TNF-α and IL-6 inflammation levels, reducing urine protein production and generalized vessel endothelial dysfunction and balance the sFlt-1:PlGF ratio through blocking eNOS/NO. KPs might be a promising protective nutraceutical agent for early pregnancies. The Higher Education Sprout Project by the Ministry of Education (MOE-112-S-0023) in Taiwan. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

STATINS PREVENT THE DELETERIOUS CONSEQUENCES OF PLACENTAL CHEMERIN UPREGULATION IN PREECLAMPSIA

Objective: Chemerin, an inflammatory adipokine, is upregulated in preeclampsia, and its placental overexpression results in preeclampsia-like symptoms in mice. Statins may lower chemerin. Design and method: Chemerin levels were determined in a prospective cohort study in women suspected of preeclampsia evaluating the predictive value of the soluble Fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio. Chemerin release was studied in perfused placentas and placental explants with or without the statins pravastatin and fluvastatin. We also addressed statin placental passage, and the effects of chemerin in chorionic plate and coronary arteries. Results: Serum chemerin was elevated in women with preeclampsia, and its addition to a predictive model yielded significant effects on top of the sFlt-1/PlGF ratio to predict preeclampsia and its fetal complications. Perfused placentas and explants of preeclamptic women released more chemerin and sFlt-1 and less PlGF than those of healthy pregnant women. Statins reversed this. Both statins entered the fetal compartment, and pravastatin's fetal/maternal concentration ratio was twice that of fluvastatin. Chemerin constricted plate arteries, and this was blocked by a chemerin receptor antagonist and pravastatin. Chemerin did not potentiate endothelin-1 in chorionic plate or coronary arteries. In explants, statins upregulated low-density lipoprotein receptor (LDLR) expression, which relies on the same transcription factor as chemerin, and NO release. Conclusions: Chemerin is a biomarker for preeclampsia, and statins both prevent its placental upregulation and effects, in an NO- and LDLR-dependent manner. Combined with their capacity to improve the sFlt-1/PlGF ratio, this offer an attractive mechanism by which statins may prevent or treat preeclampsia.

The use of sFlt-1/PlGF ratio during the first trimester of pregnancy

The use of sFlt-1/PlGF ratio during the first trimester of pregnancy

The sFLT-1/PlGF Ratio for the Prediction of Preeclampsia-Related Adverse Fetal and Maternal Outcomes in Women with Preexisting Diabetes.

To evaluate the predictive value of the sFlt-1/PlGF ratio for the prediction of preeclampsia in women with preexisting diabetes mellitus. This is a monocentric retrospective observational study conducted between January 2018 and December 2020. All singleton pregnancies with preexisting diabetes mellitus, who had a dosage of the sFlt-1/PlGF ratio between 30 and 34 + 6 weeks of gestation were included. The principal outcome was preeclampsia. The secondary outcomes were preterm preeclampsia, gestational hypertension, placental abruption, intrauterine fetal death, IUGR, small for gestational age and a composite outcome named "hypertensive disorder of pregnancy" including gestational hypertension, preeclampsia and HELLP syndrome (hemolysis, elevated liver enzymes and low platelet count). Of 63 patients, 22% presented preeclampsia. The area under the curve of sFlt-1/PlGF ratio was 0.90 (95% CI: 0.79-0.96) for the prediction of preeclampsia. The receiver operator characteristic analysis suggested that the optimal sFlt-1/PlGF cutoff to predict preeclampsia was 29, with a sensitivity of 86% (95% CI: 60.1-96.0) and a specificity of 92% (95% CI: 80.8-96.8). A cut-off of 38 provided a sensitivity of 71% (95% CI: 45.4-88.3), a specificity of 92% (95% CI: 80.8-96.8). Further analysis using multivariable methods revealed nephropathy was significantly associated with PE (p = 0.014). The use of the sFlt-1/PlGF ratio during the third trimester of pregnancy seems to be of interest as a prognostic tool to improve multidisciplinary management of patients with preexisting diabetes mellitus.

The sFlt-1/PlGF Ratio at 12, 24, and 32 Weeks Gestation in Twin Pregnancies as a Predictor of Placental Dysfunction.

Background: This study aims to assess the utility of the sFlt-1/PlGF ratio throughout pregnancy in predicting placental dysfunction and neonatal outcomes in twin pregnancies. Methods: Prospective study at a tertiary hospital. All pregnant women with a twin pregnancy who signed the informed consent were included. The sFlt-1/PlGF ratio was measured at 12, 24, and 32 weeks' gestation. Results: Seventy patients were included, and 30% developed placental dysfunction. Differences were found in the mean sFlt-1/PlGF ratios at week 32 (13.6 vs. 31.8, p = 0.007). Optimal cutoffs at 12, 24, and 32 weeks to identify patients who develop placental dysfunction were 32.5, 8.5, and 30.5, respectively, with ORs of 4.25 (1.13-20.69 95% IC; p = 0.044), 13.5 (3.07-67.90 95% IC; p = 0.001), 14.29 (3.59-66.84 95% IC; p < 0.001). The sFlt-1/PlGF ratio at 32 weeks was associated with gestational age at birth. The sFlt-1/PlGF ratio in weeks 24 and 32 had a statistically significant negative correlation with the birth weight percentile in both twins. Conclusions: The potential of the sFlt-1/PlGF ratio as a predictive tool for placental dysfunction in twin pregnancies is underscored.