Valvuloplasty of fetal pulmonary atresia with intact ventricular septum and hypoplastic right heart: Mid-term follow-up results

ObjectiveThis study aimed to analyze and evaluate the results of mid-term follow-up after fetal pulmonary valvuloplasty (FPV) in fetuses with pulmonary atresia with intact ventricular septum (PA/IVS).MethodsFrom August 31, 2018, to May 31, 2019, seven fetuses with PA/IVS and hypoplastic right heart were included in this study. All underwent echocardiography by the same specialist and were operated on by the same team. Intervention and echocardiography data were collected, and changes in the associated indices noted during follow-up were analyzed.ResultsAll seven fetuses successfully underwent FPV. The median gestational age at FPV was 27.54 weeks. The average FPV procedural time was 6 ?min. Persistent bradycardia requiring treatment occurred in 4/7 procedures. Finally, five pregnancies were successfully delivered, and the other two were aborted. Compared to data before fetal cardiac interventions (FCI), tricuspid valve annulus diameter/mitral valve annulus diameter (TV/MV) and right ventricle diameter/left ventricle diameter (RV/LV) of all fetuses had progressively improved. The maximum tricuspid regurgitation velocity decreased from 4.60 ?m/s to 3.64 ?m/s. The average follow-up time was 30.40 ?± ?2.05 months. During the follow-up period, the diameter of the tricuspid valve ring in five children continued to improve, and the development rate of the tricuspid valve was relatively obvious from 6 months to 1 year after birth. However, the development of the right ventricle after birth was relatively slow. It was discovered that there were individual variations in the development of the right ventricle during follow-up.ConclusionThe findings support the potential for the development of the right ventricle and tricuspid valve in fetuses with PA/IVS who underwent FCI. Development of the right ventricle and tricuspid valve does not occur synchronously during pregnancy. The right ventricle develops rapidly in utero, but the development of tricuspid valve is more apparent after birth than in utero.     

Association Between Abnormal Fetal Head Growth and Autism Spectrum Disorder

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Prenatal diagnosis of fetal right ventricular diverticulum with massive pericardial effusion in one of monochorionic diamniotic twins: a case report with a favorable outcome following in utero pericardiocentesis

BackgroundCongenital ventricular diverticulum is a rare abnormality that may occur as an isolated malformation. Most cases are accompanied by pericardial effusion. Prenatal counseling can be difficult because the prognosis is uncertain and there is no consensus approach to prenatal management.Case presentation: We describe a case of congenital cardiac diverticulum complicated by large pericardial effusion in one of monochorionic diamniotic twins. The case was diagnosed by ultrasonography at 21 weeks of gestation. Therapeutic pericardiocentesis at 22 weeks resulted in complete resolution of the effusion and led to a favorable fetal outcome. We summarize the interventions and pregnancy outcomes in cases of cardiac diverticula reported in the literature.ConclusionsBetter awareness of clinical features, in utero therapies, and pregnancy outcomes could help define and improve prenatal management of congenital ventricular diverticula.     

Intrauterine fetal resuscitation

The delivery of oxygen to the fetus is dependent on adequate maternal blood oxygen concentration, uterine blood supply, placental transfer and fetal gas transport. Any disturbance in these factors, singly or in combination, can result in progressive fetal hypoxia and acidosis. The term fetal distress is non-specific but is usually applied to certain characteristic features on electronic fetal monitoring, confirmed if possible by fetal blood sampling. The aim of intrauterine fetal resuscitation (IUFR) measures is to increase oxygen delivery to the placenta and umbilical blood flow in an attempt to reverse fetal hypoxia and acidosis, so that labour may continue safely or to improve the fetal condition while arranging urgent delivery. IUFR measures include maternal re-positioning into left lateral or alternatives (i.e. right lateral or knee–elbow if necessary), rapid infusion of 1000 ml crystalloid (except in fluid-restricted or pre-eclamptic patients), decreasing uterine contractions by stopping oxytocics and administering acute tocolytics (terbutaline 250 μg SC or IV, glyceryl trinitrate 60–180 μg IV or sublingual spray, two puffs). A vasopressor (i.e. ephedrine) may be required in cases of maternal hypotension.     

Stabilization and formulation of a recombinant Human Cytomegalovirus vector for use as a candidate HIV-1 vaccine

Live attenuated viral vaccine/vector candidates are inherently unstable and infectivity titer losses can readily occur without defining appropriate formulations, storage conditions and clinical handling practices. During initial process development of a candidate vaccine against HIV-1 using a recombinant Human Cytomegalovirus vector (rHCMV-1), large vector titer losses were observed after storage at 4 °C and after undergoing freeze-thaw. Thus, the goal of this work was to develop candidate frozen liquid formulations of rHCMV-1 with improved freeze-thaw and short-term liquid stability for potential use in early clinical trials. To this end, a virus stability screening protocol was developed including use of a rapid, in vitro cell-based immunofluorescence focus assay to quantitate viral titers. A library of ∼50 pharmaceutical excipients (from various known classes of additives) were evaluated for their effect on vector stability after freeze-thaw cycling or incubation at 4 °C for several days. Certain additives including sugars and polymers (e.g., trehalose, sucrose, sorbitol, hydrolyzed gelatin, dextran 40) as well as removal of NaCl (lower ionic strength) protected rHCMV-1 against freeze-thaw mediated losses in viral titers. Optimized solution conditions (e.g., solution pH, buffers and sugar type) slowed the rate of rHCMV-1 titer losses in the liquid state at 4 °C. After evaluating various excipient combinations, three new candidate formulations were designed and rHCMV-1 stability was benchmarked against both the currently-used and a previously reported formulation. The new candidate formulations were significantly more stable in terms of reducing rHCMV-1 titer losses after 5 freeze-thaw cycles or incubation at 4 °C for 30 days. This case study highlights the utility of semi-empirical design of frozen liquid formulations of a live viral vaccine candidate, where protection against infectivity titer losses due to freeze-thaw and short-term liquid storage are sufficient to enable more rapid initiation of early clinical trials.