The sFlt1/PlGF ratio predicts faster fetal deterioration in early fetal growth restriction: A historical cohort study.

INTRODUCTION: The velocity of fetal deterioration in fetal growth restriction is extremely variable, which makes monitoring and counseling very challenging. The soluble fms-like tyrosine kinase to placental growth factor (sFlt1/PlGF) ratio provides a readout of the vasoactive environment that correlates with preeclampsia and fetal growth restriction and that could be useful to predict fetal deterioration. Previous studies showed a correlation between higher sFlt1/PlGF ratios and lower gestational ages at birth, although it is unclear whether this is due to the increased incidence of preeclampsia. Our goal was to evaluate whether the sFlt1/PlGF ratio predicts faster fetal deterioration in early fetal growth restriction. MATERIAL AND METHODS: This was a historical cohort study in a tertiary maternity hospital. Data from singleton pregnancies with early fetal growth restriction (diagnosed before 32 gestational weeks) confirmed after birth monitored between January 2016 and December 2020 were retrieved from clinical files. Cases of chromosomal/fetal abnormalities, infection and medical terminations of pregnancy were excluded. The sFlt1/PlGF ratio was acquired at diagnosis of early fetal growth restriction in our unit. The correlation of log10 sFlt1/PlGF with latency to delivery/fetal demise was assessed with linear, logistic (positive sFlt1/PlGF if >85) and Cox regression excluding deliveries for maternal conditions and controlling for preeclampsia, gestational age at time of ratio test, maternal age and smoking during pregnancy. Receiver-operating characteristic (ROC) analysis tested the performance of sFlt1/PlGF ratio in predicting delivery for fetal reasons in the following week. RESULTS: 125 patients were included. Mean sFlt1/PlGF ratio was 91.2 (SD 148.7) and 28% of patients had a positive ratio. A higher log10 sFlt1/PlGF ratio predicted shorter latency for delivery/fetal demise in linear regression after controlling for confounders, ß = -3.001, (-3.713 to -2.288). Logistic regression with ratio positivity confirmed these findings (latency for delivery 5.7 ± 3.32 weeks for ratios ≤85 vs 1.9 ± 1.52 weeks for ratios >85); ß = -0.698 (-1.064 to -0.332). Adjusted Cox regression showed that a positive ratio confers a significantly positive hazard ratio (HR) for earlier delivery/fetal demise, HR 9.869 (5.061-19.243). ROC analysis showed an area under the curve of 0.847 (SE ± 0.06). CONCLUSIONS: sFlt1/PlGF ratio is correlated with faster fetal deterioration in early fetal growth restriction, independently of preeclampsia.

The effects of spinal anaesthesia for elective caesarean section on uterine and umbilical arterial pulsatility indexes in normotensive and chronic hypertensive pregnant women: a prospective, longitudinal study.

BACKGROUND: Despite the known effects of neuraxial blockade on major vessel function and the rapid decrease in uterine vascular impedance, it is unclear how the blockade affects the utero-placental circulation in the near-term. We hypothesize that among women with chronic hypertension, a loss of sympathetic tonus consequent to spinal block may cause significant changes in the utero-placental haemodynamics than the changes typical in normal pregnant women. Therefore, the main study objective was to analyse the effect of spinal anaesthesia for caesarean section on uterine and umbilical arterial impedance in pregnant women at term diagnosed with stage-1 chronic hypertension. METHODS: A prospective, longitudinal study was performed in singleton pregnant women (203 low-risk and 33 with hypertension) scheduled to undergo elective caesarean section. The mean arterial blood pressure and pulsatility indexes for the uterine and umbilical arteries were recorded before and after spinal anaesthesia was performed using 8-9 mg hyperbaric bupivacaine (5 mg/mL) and 2-2.5 µg sufentanil (5 µg/mL). Multiple linear regression models with errors capable of correlation or with unequal variances were fitted using the generalized least squares. RESULTS: In normotensive women, the mean arterial blood pressure decreased after administering spinal anaesthesia (p < 0.05). The pulsatility index of the uterine and umbilical arteries did not change after spinal anaesthesia. In the hypertensive women, the mean arterial blood pressure (p < 0.05) and uterine artery pulsatility index (p < 0.05) decreased. In both groups, the umbilical artery pulsatility index did not change after spinal anaesthesia. CONCLUSIONS: In stage-1 chronic hypertensive pregnant women at term, spinal anaesthesia for caesarean section reduces uterine artery impedance but not umbilical artery impedance.

Foetal aortic flow velocity waveforms in healthy and hypertensive pregnant women.

BACKGROUND: The foetal aortic Doppler frequency spectrum is influenced by cardiac output and contractility of the foetal heart as well as vascular compliance, blood viscosity and impedance of the arterial vascular system. The present study aimed at comparing Doppler flow pulsatility (PI) and resistance (RI) indexes of foetal proximal descending aorta (AoF) in the first, second and third trimesters of pregnancy, in low risk women and in those with chronic arterial hypertension, who had normal pregnancy outcomes. METHODS: A longitudinal and prospective study was carried out in 101 singleton pregnancies (71 low-risk pregnancies and 30 with essential hypertension). Multivariate regression had to be considered due to the experiment's nature: two different indexes were read on the same set of individuals, once at each trimester of the pregnancy [1st (11-14 weeks), 2nd (19-22 weeks) and 3rd (28-32 weeks) trimesters]. The response variable was denoted as index d, in a subject with hypertensive status h (hypertensive or normotensive), at continuous time t. RESULTS: In both groups, AoF-PI and AoF-RI showed a small, but significant increase from the first to the second (1.850 ± 0.339 vs 2.110 ± 0.242 for PI, and 0.829 ± 0.068 vs 0.857 ± 0.038 for RI; p < 0.001) and the first to the third (1.850 ± 0.339 vs 2.163 ± 0.282 for PI, and 0.829 ± 0.068 vs 0.864 ± 0.037 for RI; p < 0.001) trimesters of pregnancy. The global model showed that while AoF-RI trends were converging as time progressed, the AoF-PI values exhibited a divergent trend (p < 0.05). CONCLUSIONS: Chronic stable hypertension in pregnancies with normal outcome, evidences an upward regular trend of foetal descending aorta pulsatility index that is similar to the normotensive condition.

Regulatory T cells in preeclampsia: some answers, more questions?

This Commentary highlights the article by Hsu et al (in this issue) reporting an enrichment in induced regulatory T cells (iTregs) in normal pregnancy but not in preeclampsia, implicating iTreg defect as central to the pathogenesis of preeclampsia.

Lipid levels including oxidized LDL in women with history of preeclampsia.

Preeclampsia (PE), a leading cause of maternal and perinatal morbidity and mortality worldwide, is a hypertensive disorder of unknown aetiology characterized by proteinuria, coagulation abnormalities and different systemic manifestations. Since there are no studies regarding the evaluation of oxidized LDL (oxLDL) in women with a history of PE, we focused on the evaluation of lipid profile and oxLDL plasma concentration several years after pregnancy to see if these women have any modifications in these parameters that may be linked to the risk of cardiovascular disease (CVD) in the future. Ninety women with a history of PE and 60 controls in a median interval of 6 years after pregnancy were recruited. Plasma oxLDL levels were measured using a two-site enzyme immunoassay. Concentration of cholesterol, triglycerides (TG), HDL-cholesterol (HDLc) and LDL-cholesterol (LDLc) were measured by automated enzymatic assays. To evaluate apoA and apoB levels automated immunoturbidimetric assays were used. In the group of women with a history of PE, gestational age at delivery was significantly earlier in comparison with the control group, whereas birth weight was significantly lower and there were more caesarean sections. Systolic and diastolic blood pressures were significantly higher in women with a history of PE than in the control group. Significantly higher obesity anthropometric markers (BMI and waist-to-hip ratio) were found in women with a history of PE. As consistent with other authors' findings, blood pressure was higher in these women, but lipid profile did not seem to play a role in the increased risk of cardiovascular disease.