Perinatal and 2-year neurodevelopmental outcome in late preterm fetal compromise: the TRUFFLE 2 randomised trial protocol

Introduction: Following the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years. Methods and analysis: Women with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the estimated fetal weight or abdominal circumference is <10th percentile or has decreased by 50 percentiles since 18-32 weeks will be included for observational data collection. Participants will be randomised if cerebral blood flow redistribution is identified, based on umbilical to middle cerebral artery pulsatility index ratio values. Computerised cardiotocography (cCTG) must show normal fetal heart rate short term variation (≥4.5 msec) and absence of decelerations at randomisation. Randomisation will be 1:1 to immediate delivery or delayed delivery (based on cCTG abnormalities or other worsening fetal condition). The primary outcome is poor condition at birth and/or fetal or neonatal death and/or major neonatal morbidity, the secondary non-inferiority outcome is 2-year infant general health and neurodevelopmental outcome based on the Parent Report of Children's Abilities-Revised questionnaire. Ethics and dissemination: The Study Coordination Centre has obtained approval from London-Riverside Research Ethics Committee (REC) and Health Regulatory Authority (HRA). Publication will be in line with NIHR Open Access policy. Trial registration number: Main sponsor: Imperial College London, Reference: 19QC5491. Funders: NIHR HTA, Reference: 127 976. Study coordination centre: Imperial College Healthcare NHS Trust, Du Cane Road, London, W12 0HS with Centre for Trials Research, College of Biomedical & Life Sciences, Cardiff University. IRAS Project ID: 266 400. REC reference: 20/LO/0031. ISRCTN registry: 76 016 200

The role of apoptosis in preterm premature rupture of the human fetal membranes

The present study was designed to examine apoptotic cell death via the caspase-dependent pathway in human fetal membranes

Association of placental T2 relaxation times and uterine artery Doppler ultrasound measures of placental blood flow

Purpose: To investigate whether, in the second trimester of pregnancy, placental T-2 relaxation time (determined using magnetic resonance imaging (MRI)) is related to impedance to flow in the uterine arteries. Methods: In 40 singleton pregnancies at 24-29 weeks' gestation, uterine artery pulsatility index (PI) was measured by Doppler ultrasound and T-2 relaxation time was measured by echo planar MRI at 1.5 T. The significance of the associations between T-2 relaxation time, uterine artery PI and birth weight were examined. Results: In 25 pregnancies that delivered small for gestational age (SGA) neonates with birth weight below the 10th percentile, compared to those with appropriate for gestational age (AGA) birth weight, the T-2 relaxation time was significantly decreased (88 ms vs. 149 ms, p &lt;0.0001) and uterine artery PI was increased (1.96 vs. 1.00, p &lt;0.0001). There were significant associations between placental T-2 relaxation time and log(10) uterine artery PI (r = -0.749, p &lt;0.0001), and between T-2 relaxation and birth weight percentile (r = 0.693, p &lt;0.0001). Conclusion: The T-2 relaxation time during the second trimester is shorter in pregnancies that subsequently deliver SGA neonates and the measurement is strongly correlated with impedance to flow in the uterine arteries.</p

The incidence of biliary sludge in first trimester pregnancies with hyperemesis gravidarum and its effect on the course of hyperemesis gravidarum

Pregnancy is one of the risk factors for biliary sludge (BS) formation. In this cross-sectional study, a total of 959 pregnant women were included. Serum aspartate aminotransferase, alanine aminotransferase, sodium, potassium, triglycerides, cholesterol levels and the presence of ketones in urine were determined. The presence of BS was investigated using maternal abdominal ultrasound. The incidence of BS in pregnancies complicated by hyperemesis gravidarum (HG) was 14%. The degree of ketonuria and low birth weight were statistically higher in pregnancies with maternal BS than women without sludge. Total weight gain during pregnancies with BS was statistically lower than controls. The incidence of BS in pregnancies with HG does not appear to increase due to HG-related complications, such as dehydration, starvation and weight loss. However, the severity of HG may be worse when HG is associated with sludge.Impact Statement What is already known on this subject? The incidence of biliary sludge (BS) in pregnant women ranges between 10.9% and 36%. Some clinical conditions, such as pregnancy, prolonged fasting, total parenteral nutrition, rapid weight loss and ceftriaxone treatment can play a role in the formation of gallbladder sludge. What do the results of this study add? This is the first study to investigate the incidence of BS in hyperemesis gravidarum (HG) pregnancies. Results show that HG may transiently be associated with BS. HG is more likely to cause a transient increase in new sludge formation. The symptoms and complications related to HG may be more severe when HG is associated with BS. What are the implications of these findings for clinical practice and/or further research? Our study showed that BS can be found in HG patients, and HG can be a predisposing factor for new sludge formation, although this association is generally driven by advanced maternal age and increased baseline serum lipid and alanine aminotransferase levels. BS may also be independently associated with an increased risk of subsequent preterm delivery in women with HG

Foetal cardiac function in third trimester pregnancies with reduced fetal movements

*Gül, Murat ( Aksaray, Yazar )The objective of our study was to investigate the possible relationship between poor perinatal outcome and foetal cardiac functions in pregnant women with reduced foetal movements (RFM). This cross-sectional study included 126 pregnant women with normal foetal movements (Group 1, Controls) and 42 pregnant women over 32 weeks gestation with RFM (Group 2). Group 2 was further divided into two subgroups according to their perinatal outcome: normal perinatal outcome (Group 2a) and poor perinatal outcome (Group 2b). Cardiotocography, the E/A ratio in both atrioventricular valves, myocardial performance index (MPI) and foetal tricuspid annular plane systolic excursion (f-TAPSE) were evaluated. Foetuses with poor perinatal outcome had a higher MPI (p =.003), higher tricuspid and mitral E/A (p <.001), and lower f-TAPSE values (p <.001). In regression analysis, f-TAPSE was the only parameter (p =.04) independently associated with poor perinatal outcome. İn conclusion, examining f-TAPSE may predict adverse perinatal outcome in pregnancies with RFM.IMPACT STATEMENTWhat is already known on this subject? Reduced foetal movement (RFM) is associated with adverse pregnancy outcome. Cardiotocography, amniotic fluid assessment, estimated birthweight, foetal Doppler and formal foetal movement count (kick chart) are generally used in the clinical assessment of pregnancies with reduced foetal movements. These tests, we currently use to assess foetal wellbeing in women with reduced foetal movements, have limited sensitivity in predicting foetal compromise. What do the results of this study add? Foetal cardiac Doppler may potentially be used as an important adjunct to the conventional management of women with a perception of reduced foetal movements. What are the implications of these findings for clinical practice and/or further research? Foetal echocardiographic evaluation, such as f-TAPSE, may influence clinical practice by enabling improved risk stratification for poor perinatal outcome, thus allowing more timely definitive intervention. This could help to decrease the rate of stillbirth related to reduced foetal movements. The few established echocardiographically derived parameters, which can asses global right ventricle function, are not always easy to obtain, however, f-TAPSE is easily obtainable using ultrasound and it appears to be a clinically useful echocardiographic measurement of right ventricular function

Factors preventing materno-fetal transmission of SARS-CoV-2

Saǧlam, Aylin ( Aksaray, Yazar )Although many pregnant women have been infected by coronavirus, the presence of intrauterine vertical transmission has not been conclusively reported yet. What prevents this highly contagious virus from reaching the fetus? Is it only the presence of a strong placental barrier, or is it the natural absence of the some receptor that the viruses use for transmission? We, therefore, need to comprehensively understand the mechanism of action of the mammalian epithelial barriers located in two different organs with functional similarity. The barriers selected as potential targets by SARS-CoV-2 are the alveolo-capillary barrier (ACB), and the syncytio-capillary barrier (SCB). Caveolae are omega-shaped structures located on the cell membrane. They consist of caveolin-1 protein (Cav-1) and are involved in the internalisation of some viruses. By activating leukocytes and nuclear factor-κB, Cav-1 initiates inflammatory reactions. The presence of more than one Cav-1 binding sites on coronavirus is an important finding supporting the possible relationship between SARS-CoV-2-mediated lung injury. While the ACB cells express Cav-1 there is no caveolin expression in syncytiotrophoblasts. In this short review, we will try to explain our hypothesis that the lack of caveolin expression in the SCB is one of the most important physiological mechanisms that prevents vertical transmission of SARS-CoV-2. Since the physiological Cav-1 deficiency appears to prevent acute cell damage treatment algorithms could potentially be developed to block this pathway in the non-pregnant population affected by SARS-CoV-2