Relationship between the sFlt-1/PlGF ratio and the optical coherence tomographic features of chorioretina in patients with preeclampsia

This study aimed to evaluate the correlation between ophthalmologic factors and the serologic indicator soluble fms-like tyrosine kinase 1 (sFlt-1): placental growth factor (PlGF) ratio in patients with preeclampsia using optical coherence tomography (OCT) and OCT angiography (OCT-A). A total of 52 pregnant patients (104 eyes) diagnosed with preeclampsia were recruited during their hospital stay. The associations between the sFlt-1/PlGF ratio and chorioretinal measurements, including the choroidal thickness (CT), foveal avascular zone, vascular density, and ganglion cell layer+ were evaluated. Central and nasal subfield CT of the left eye (p = 0.039; p = 0.010) and nasal subfield CT of the right eye (p = 0.042) were lower in the high sFlt-1/PlGF ratio group (≥38). Pearson’s correlation test showed a negative correlation between the sFlt-1/PlGF ratio and central subfield CT; however, this was not statistically significant (p = 0.648). Linear regression analysis revealed a significant association between the sFlt-1/PlGF ratio and central subfield CT (β coefficient, -6.66; p = 0.01) and between sFlt-1 and central subfield CT (β coefficient, -5.65; p = 0.00). Thus, an increase in the sFlt-1/PlGF ratio resulted in a decrease in central subfield CT.

Early-pregnancy prediction of risk for pre-eclampsia using maternal blood leptin/ceramide ratio: discovery and confirmation

ObjectiveThis study aimed to develop a blood test for the prediction of pre-eclampsia (PE) early in gestation. We hypothesised that the longitudinal measurements of circulating adipokines and sphingolipids in maternal serum over the course of pregnancy could identify novel prognostic biomarkers that are predictive of impending event of PE early in gestation.Study designRetrospective discovery and longitudinal confirmation.SettingMaternity units from two US hospitals.ParticipantsSix previously published studies of placental tissue (78 PE and 95 non-PE) were compiled for genomic discovery, maternal sera from 15 women (7 non-PE and 8 PE) enrolled at ProMedDx were used for sphingolipidomic discovery, and maternal sera from 40 women (20 non-PE and 20 PE) enrolled at Stanford University were used for longitudinal observation.Outcome measuresBiomarker candidates from discovery were longitudinally confirmed and compared in parallel to the ratio of placental growth factor (PlGF) and soluble fms-like tyrosine kinase (sFlt-1) using the same cohort. The datasets were generated by enzyme-linked immunosorbent and liquid chromatography-tandem mass spectrometric assays.ResultsOur discovery integrating genomic and sphingolipidomic analysis identified leptin (Lep) and ceramide (Cer) (d18:1/25:0) as novel biomarkers for early gestational assessment of PE. Our longitudinal observation revealed a marked elevation of Lep/Cer (d18:1/25:0) ratio in maternal serum at a median of 23 weeks’ gestation among women with impending PE as compared with women with uncomplicated pregnancy. The Lep/Cer (d18:1/25:0) ratio significantly outperformed the established sFlt-1/PlGF ratio in predicting impending event of PE with superior sensitivity (85% vs 20%) and area under curve (0.92 vs 0.52) from 5 to 25 weeks of gestation.ConclusionsOur study demonstrated the longitudinal measurement of maternal Lep/Cer (d18:1/25:0) ratio allows the non-invasive assessment of PE to identify pregnancy at high risk in early gestation, outperforming the established sFlt-1/PlGF ratio test.

INOVASIA Study: A Randomized Open Controlled Trial to Evaluate Pravastatin to Prevent Preeclampsia and its Effects on sFlt1/PLGF Levels

Objectives To evaluate the effect of pravastatin to prevent preeclampsia (PE) in pregnant women at a high risk of developing preeclampsia and the maternal and perinatal outcomes and the sFlt1/PLGF ratio. Study Design This is an open labelled RCT part of INOVASIA trial. Pregnant women at a high risk of developing PE were recruited and randomized into an intervention group (40) and a control group (40). The inclusion criteria consisted of pregnant women with positive clinical risk factor and abnormal uterine artery doppler examination at 10-20 weeks gestational age. The control group received low dose aspirin (80 mg/day) and calcium (1 g/day), while the intervention group received additional pravastatin (20 mg twice daily) starting from 14-20 weeks gestation until delivery. Research blood samples were collected before the first dose of pravastatin and before delivery. The main outcome was the rate of maternal preeclampsia, maternal-perinatal outcomes, and sFlt-1, PLGF, sFlt-1/PlGF ratio and sEng levels. Results The rate of preeclampsia was (non-significantly) lower in the pravastatin group compared with the control group (17.5% vs 35%). The pravastatin group also had a (non-significant) lower rate of severe preeclampsia, HELLP syndrome, acute kidney injury and severe hypertension. The rate of (iatrogenic) preterm delivery was significantly (p=0.048) lower in the pravastatin group (n=4) compared with the controls (n=12). Neonates in the pravastatin group had significantly higher birthweights (2931 + 537 vs 2625 + 872 g; p=0.006), lower Apgar scores < 7 (2.5 vs 27.5%, p=0.002), composite neonatal morbidity (0 vs 20%, p=0.005) and NICU admission rates (0 vs 15%, p=0.026). All biomarkers show a significant deterioration in the control group compared with non significant changes in the pravastatin group. Conclusions Pravastatin holds promise in the secondary prevention of preeclampsia and placenta-mediated adverse perinatal outcomes by improving the angiogenic imbalance.