Cardiac and extra-cardiac flow velocity waveforms in the growth-retarded human fetus

The central theme in this thesis is the documentation of Doppler flow velocity waveforms in a number of cardiac and extra-cardiac arterial vessels with emphasis on changes in the flow velocity waveforms relative to intrauterine growth retardation and fetal and neonatal condition. The following questions were addressed: 1) What is the reproducibility of flow velocity waveform recording in the fetal cardiac outflow tract (ascending aorta, pulmonary artery, ductus arteriosus); (Chapter 3); 2) Do flow velocity waveforms from the fetal cardiac outflow tract depict changes in the presence of intrauterine growth retardation. If so, how do these changes relate to changes in flow velocity waveforms from the umbilical artery; (Chapter 4); 3) How do fetal cardiac and extra-cardiac flow velocity waveforms relate to (i) fetal heart rate patterns in predicting fetal distress and (ii) neonatal outcome in intrauterine growth retardation; (Chapter 5)

Doppler flow velocity waveforms in the fetal cardiac outflow tract: Reproducibility of waveform recording and analysis

__Abstract__ Reproducibility of flow velocity waveform recording and analysis was studied at fetal cardiac level (ductus arteriosus, pulmonary artery and ascending aorta) in 42 normal pregnancies. The flow velocity parameters studied were the peak systolic velocity (PSV), acceleration time (ACT), acceleration velocity (ACV), average velocity (AV) and flow velocity integral (FVI). In each patient, two consecutive measurements were performed (time delay 15 min) and of each measurement two hardcopies were analysed. A high reproducibility was achieved for the PSV, AV and FVI in all vessels studied; the coefficients of variation between readings of hardcopies were ≤3%, and the coefficients of variation between tests within patients were ≤7%. A moderate reproducibility was achieved for the ACT in the ascending aorta and pulmonary artery; the variation between tests was large for the ductus arteriosus. The reproducibility of the ACV was poor

Periconception maternal folate status and human embryonic cerebellum growth trajectories: The Rotterdam predict study

We aimed to investigate whether periconceptional maternal folate status affects human embryonic cerebellar size and growth trajectories. In a prospective periconceptional cohort participants filled out questionnaires and received weekly transvaginal 3D-ultrasounds between 7+0 and 12+6 weeks gestational age (GA). Viable non-malformed singleton pregnancies were selected for cerebellar measurements; transcerebellar diameter, (TCD), left and right cerebellar diameters (LCD, RCD). Linear mixed models were performed to estimate associations between questionnaire data on the timing of maternal folic acid supplement initiation and longitudinal cerebellar measurements as a function of crown-rump length (CRL) and GA. Maternal red blood cell folate concentrations were analysed before 8 weeks GA to validate the associations. A total of 263 serial high quality three-dimensional ultrasound scans of 135 pregnancies were studied. Preconceptional compared to postconceptional initiation of folic acid use was associated with slightly larger cerebellar diameters per millimetre increase of CRL (TCD: β = 0.260mm, 95%CI = 0.023-0.491, p<0.05; LCD: β = 0.171mm, 95%CI = 0.038-0.305, p<0.05; RCD: β = 0.156mm, 95%CI = 0.032-0.280, p<0.05) and with proportional cerebellar growth (TCD/CRL:β = 0.015mm/mm, 95%CI = 0.005-0.024, p<0.01; LCD/CRL:β = 0.012mm/mm, 95%CI = 0.005-0.018, p<0.01; RCD/ CRL:β = 0.011mm/mm, 95%CI = 0.005-0.017, p

ZZ-boson polarization as a model-discrimination analyzer

Determining the spin of any new particle is critical in identifying the true theory among various extensions of the Standard Model (SM). The degree of $Z$-boson polarization in any two-body decay process $A\to B Z$ is sensitive to the spin assignments of two new particles $A$ and $B$. Considering all possible spin-0, 1/2 and 1 combinations in a renormalizable field theory, we demonstrate that $Z$-boson polarization can indeed play a role of a decisive and universal analyzer in distinguishing the different spin assignments.Comment: 10 pages, 3 figures, 1 tabl

Growth trajectories of the human fetal brain in healthy and complicated pregnancies and associations with neurodevelopmental outcome in the early life course

Background There is a need for non-invasive prenatal markers of the brain to assess fetuses at risk for poor postnatal neurodevelopmental outcome. Periconceptional maternal conditions and pregnancy complications impact prenatal brain development. Aims To investigate associations between growth trajectories of fetal brain structures and neurodevelopmental outcome in children in the early life course. Study design Periconceptional prospective observational cohort. Subjects Singleton pregnancies were included in the Rotterdam periconception cohort. Two- and three-dimensional ultrasound scans at 22, 26 and 32 weeks gestational age were analysed. Outcome measures Head circumference (HC), cerebellum, corpus callosum (CC), Sylvian fissure, insula and parieto-occipital fissure (POF) were measured. Neurodevelopment was evaluated using the Age-and-Stages-questionnaire-3 (ASQ-3) and the Child-Behaviour-Checklist (CBCL) at 2 years of age. Linear mixed models, used to estimate the prenatal brain growth trajectories, and linear regression models, used to evaluate the associations between prenatal brain structures and neurodevelopmental outcomes, were applied in the total study population, and in subgroups: fetal growth restriction (FGR), preterm birth (PTB), fetal congenital heart

Under-reported aspects of diagnosis and treatment addressed in the Dutch-Flemish guideline for comprehensive diagnostics in disorders/differences of sex development

We present key points from the updated Dutch-Flemish guideline on comprehensive diagnostics in disorders/differences of sex development (DSD) that have not been widely addressed in the current (inter)national literature. These points are of interest to physicians working in DSD (expert) centres and to professionals who come across persons with a DSD but have no (or limited) experience in this area. The Dutch-Flemish guideline is based on internationally accepted principles. Recent initiatives striving for uniform high-quality care across Europe, and beyond, such as the completed COST action 1303 and the European Reference Network for rare endocrine conditions (EndoERN), have generated several excellent papers covering nearly all aspects of DSD. The Dutch-Flemish guideline follows these international consensus papers and covers a number of other topics relevant to daily practice. For instance, although next-generation sequencing (NGS)-based molecular diagnostics are becoming the gold standard for genetic evaluation, it can be difficult to prove variant causality or relate the genotype to the clinical presentation. Network formation and centralisation are essential to promote functional studies that assess the effects of genetic variants and to the correct histological assessment of gonadal material from DSD patients, as well as allowing for maximisation of expertise and possible cost reductions. The Dutch-Flemish guidelines uniquely address three aspects of DSD. First, we propose an algorithm for counselling and diagnostic evaluation when a DSD is suspected prenatally, a clinical situation that is becoming more common. Referral to ultrasound sonographers and obstetricians who are part of a DSD team is increasingly important here. Second, we pay special attention to healthcare professionals not working within a DSD centre as they are often the first to diagnose or suspect a DSD, but are not regularly exposed to DSDs and may have limited experience. Their thoughtful communication to patients, carers and colleagues, and the accessibility of protocols for first-line management and efficient referral are essential. Careful communication in the prenatal to neonatal period and the adolescent to adult transition are equally important and relatively under-reported in the literature. Third, we discuss the timing of (NGS-based) molecular diagnostics in the initial workup of new patients and in people with a diagnosis made solely on clinical grounds or those who had earlier genetic testing that is not compatible with current state-of-the-art diagnostics