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

Diurnal and position-induced variability of impedance cardiography measurements in healthy subjects

Cardiovascular (CV) parameters and their measurements are subject to variation. In this study, we evaluated the reproducibility of impedance cardiography (ICG) measurements following orthostatic and diurnal challenges for a set of 22 CV parameters in ten randomly selected healthy nonpregnant women. A standard protocol was used to record a consecutive series of measurements for each parameter before and after three position changes. This series of measurements was performed twice (AM and PM sessions). For each parameter, measurement-shift following position change was evaluated at 5% cutoff and compared between sessions. Intra- and intersession intraclass correlation (ICC) was calculated for individual measurements per position using repeated-measures analysis of variance. Intra- and intersession Pearson's correlation coefficient (PCC) was calculated for mean values per position. Intersession correlation for measurement-shift following position change was 0·42 (5/12) for pressure parameters, whereas this was 0·96 (52/54) for other parameters. Inter- and intrasession ICC for individual measurements varied between 0·02 and 1 for all parameters, however inter- and intrasession PCC for mean values was consistently >0·80 for stroke volume (SV), stroke index (SI), cardiac output (CO), acceleration and velocity index (ACI and VI), thoracic fluid content (TFC), TFC index (TFCI) and heart period duration (HPD). We conclude that in healthy subjects under standardised conditions, reproducibility of means of multiple ICG measurements is high for SV, SI, CO, ACI, VI, TFC, TFCI and HPD. From our data, we cannot draw conclusions on trends in diseased subjects.status: publishe

Hepatic hemodynamics and fetal growth: a relationship of interest for further research.

It is well known that hepatic hemodynamics is an important physiologic mechanism in the regulation of cardiac output (CO). It has been reported that maternal cardiac output relates to neonatal weight at birth.In this study, we assessed the correlation between maternal hepatic vein Doppler flow parameters, cardiac output and neonatal birth weight.Healthy women with uncomplicated second or third trimester pregnancy attending the outpatient antenatal clinic of Ziekenhuis Oost-Limburg in Genk (Belgium), had a standardized combined electrocardiogram-Doppler ultrasound with Impedance Cardiography, for measurement of Hepatic Vein Impedance Index (HVI  =  [maximum velocity - minimum velocity]/maximum velocity), venous pulse transit time (VPTT  =  time interval between corresponding ECG and Doppler wave characteristics) and cardiac output (heart rate x stroke volume). After delivery, a population-specific birth weight chart, established from a cohort of 27000 neonates born in the index hospital, was used to define customized birth weight percentiles (BW%). Correlations between HVI, VPTT, CO and BW% were calculated using Spearman's ρ, linear regression analysis and R2 goodness of fit in SPSS 22.0.A total of 73 women were included. There was a negative correlation between HVI and VPTT (ρ = -0.719, p < 0.001). Both HVI and VPTT correlated with CO (ρ = -0.403, p < 0.001 and ρ = 0.332, p < 0.004 resp.) and with BW% (ρ =  -0.341, p < 0.003 and ρ = 0.296, p < 0.011 resp.).Our data illustrate that the known contribution of hepatic hemodynamics in the regulation of cardiac output is also true for women with uncomplicated pregnancies. Our study is the first to illustrate a potential link between maternal hepatic hemodynamics and neonatal birth weight. Whether this link is purely associative or whether hepatic vascular physiology has a direct impact on fetal growth is to be evaluated in more extensive clinical and experimental research

Congenital High Airway Obstruction Syndrome (CHAOS) as part of Fraser syndrome: ultrasound and autopsy findings

Congenital High Airway Obstruction Syndrome (CHAOS) is a potential lethal condition. We describe a case report of CHAOS, with additional malformations diagnosed at 20 weeks. Autopsy findings are suggestive for Fraser syndrome (cryptophthalmos-syndactyly syndrome; OMIM 219000). The diagnosis was confirmed by mutation analysis of FRAS1.status: publishe

Maternal venous hemodynamics in gestational hypertension and preeclampsia

BACKGROUND: To evaluate characteristics of venous hemodynamics, together with cardiac and arterial function, in uncomplicated pregnancies (UP), non-proteinuric gestational hypertension (GH) and preeclampsia (PE). METHODS: In this observational cross-sectional study, venous hemodynamics was assessed using a standardised protocol for combined electrocardiogram (ECG)-Doppler ultrasonography, together with a non-invasive standardised cardiovascular assessment using impedance cardiography (ICG) in 13 women with UP, 21 with GH, 34 with late onset PE ≥ 34 w (LPE) and 22 with early onset PE 15% higher (P ≤ .010) in LPE and EPE, as compared to GH and UP. Next to this, >30% lower values for VI and ACI (P ≤ .029), and > 15% lower values for APTT (P ≤ .012) were found in GH, LPE and EPE, as compared to GH. CONCLUSION: In comparison to UP, similar abnormalities of central arterial function and APTT were found in GH, EPE and LPE. Proteinuria of LPE and EPE was associated with increased RIVI, this was not observed in GH.status: publishe

Maternal venous Doppler characteristics are abnormal in pre-eclampsia but not in gestational hypertension

To compare functional characteristics of maternal thoraco-abdominal arteries and veins in proteinuric and non-proteinuric hypertension in pregnancy.status: publishe

Demographic data, neonatal outcome and maternal cardiovascular characteristics in healthy pregnant women.

<p>Data are presented as median ± interquartile range.</p><p>HVI: hepatic vein index, CO: cardiac output, VPTT: venous pulse transit time.</p><p>Demographic data, neonatal outcome and maternal cardiovascular characteristics in healthy pregnant women.</p