Eva Visca

Induction of fetal hemoglobin synthesis with recombinant human erythropoietin in anemic patients with heterozygous beta‐thalassemia during pregnancy

OBJECTIVE Recombinant human erythropoietin (rhEPO) increases fetal hemoglobin synthesis in nonpregnant thalassaemic patients. We used rhEPO in 4 pregnant patients with heterozygous beta-thalassemia and anemia to study its effect on erythropoiesis, F cell production, and HbF synthesis. METHODS Patients were treated with a combination therapy of rhEPO and iron. The effect on HbF synthesis was assessed by the percentage of F reticulocytes, F cells, and total HbF, erythropietis by reticulocyte count, and hemoglobin measurements and iron status by ferritin levels, transferrin saturation, and percentage of hypochromic red cells. RESULTS RhEPO caused an increase of F reticulocytes (1.5 to 10.5 fold), F cells (5.0 to 7.7 fold), and HbF (1.4 to 2.2 fold). All patients showed an increase of young, immature reticulocytes and had elevated reticulocytes at the end of therapy. Hemoglobin increased with a range from 0.3 to 1.5 g/dL. Transferrin saturation and ferritin levels were normal at the end of the study. There was an increase of the percentage of hypochromic red cells, indicating functional iron deficiency after rhEPO administration despite supplemental iron. CONCLUSIONS RhEPO stimulates both HbF synthesis and erythropoiesis in pregnant patients with heterozygous beta-thalassemia and anemia. Since it is known that high HbF levels ameliorate thalassemia symptoms in nonpregnant patients, use of rhEPO for the treatment of severe anemia in thalassaemic patients during pregnancy might be further evaluated.

Influence of volume preloading on uteroplacental and fetal circulation during spinal anaesthesia for caesarean section in uncomplicated singleton pregnancies.

Objective: Effects of volume preloading during spinal anaesthesia for elective caesarean section on maternal blood pressure, feto-maternal circulation and fetal outcome. Patients and Methods: In a pilot study a randomised trial was performed in 22 healthy women with uncomplicated, singleton pregnancies at 36–40 weeks of gestation undergoing elective caesarean section under spinal anaesthesia. In the low volume group (group A) patients received 150 ml of crystalloid solution for preloading, in the high volume group (group B) they were given 15 ml/kg of crystalloid solution for preloading before the initiation of spinal anaesthesia. Maternal blood pressure was monitored intermittently. Hypotension was defined as a decrease in systolic pressure to less than 80% of the baseline value. The Doppler flow evaluation consisted of measurements from the uterine artery at the placental site, fetal umbilical artery and fetal middle cerebral artery. Pulsatility indices were derived before and after fluid preloading, and when spinal anaesthesia was established. The neonatal outcome was assessed by Apgar scores, arterial acid base status and neurologic and adaptive capacity scores (NACS). Results: The incidence of maternal hypotension in both groups was 45.5% (n = 10); 3 cases occurred in group A compared to 7 cases in group B (n.s.). There was no evidence that the high dose volume is useful in preventing maternal hypotension. The pulsatility indices of uterine arteries, umbilical arteries and middle cerebral arteries were not altered. Statistical analysis showed no changes in neonatal outcome concerning umbilical arterial pH, Apgar score and NACS (n.s.) between groups A and B. Conclusions: Our preliminary results suggest that high dose crystalloid volume preloading has no preventive function in the avoidance of maternal hypotension in healthy parturients undergoing elective caesarean section under spinal anaesthesia, and shows no harmful effects on neonatal outcome as long as maternal hypotension is corrected immediately. However, the statistical significance may reflect the small sample size, and larger series are needed before changing the current management.

Sonographic diagnosis of gestational trophoblastic disease in early pregnancy

Gestational trophoblastic disease (GTD) is classified as a metastatic or non-metastatic lesion, furthermore, villous GTD is distinguished from non-villous GTD. Because of their higher incidence and their risk of persistent gestational trophoblastic neoplasia (pGTN), early diagnosis of molar pregnancies is of clinical importance. Advances in ultrasound (US) technology and frequent application of transvaginal sonography in early pregnancy have changed the clinical and pathological presentation of molar pregnancies. Based on US imaging and histopathological examination of products of conception, the majority of cases are diagnosed in early pregnancy, either as incidental findings or in women presenting with symptoms of miscarriage. Molar pregnancies have characteristic sonographic features which are more pronounced as pregnancy advances. In early pregnancy, overall US detection rates for molar pregnancies range between 34-56% depending on gestational age, sonographic features, histologic morphology, apparative equipment, and operator expertise. There also seems to be an intrinsic limit to US detection rates based on histomorphometric features of the hydropic villi. Thus, in early pregnancy, lack of typical sonographic features does not exclude molar pregnancy. If a condition predisposing for pGTN is not recognized at the time of evacuation, prognosis is worse. With increasing demand for medical management of miscarriages and abortions, when products of conception are usually not submitted for histological examination, sonographic assessment of the chorion is mandatory. In the case of suspicious findings, surgical management and histological examination are indicated.

Cell-free fetal nucleic acids as prenatal biomarkers

INTRODUCTION Cell-free fetal nucleic acids in maternal plasma or serum have become important tools in the pursuance of new methods for non-invasive prenatal diagnosis, such as the determination of fetal blood groups and fetal gender. During these pioneering explorations, elevations in the concentration of these new-found biological analytes were noted in several pregnancy-related disorders, including preterm labor, pre-eclampsia and malimplantation. As these elevations appeared to occur before onset of clinical symptoms, it was proposed that such analyses might assist in screening for at-risk pregnancies. A major problem with these early studies is that they relied on the quantitation of Y-chromosome-specific gene sequences, and as such could be applied only in those cases where the fetus was male. Recent developments that might permit gender-independent analysis include epigenetic markers, as well as the analysis of cell-free placentally derived mRNA species. AREAS COVERED This article focuses specifically on prognostic markers, which enable at-risk pregnancies to be identified, allowing the modification of pregnancy management and in turn improvement of pregnancy outcome. The authors also provide their opinion on the progress and future challenges that lie ahead. EXPERT OPINION Accurate quantification of fetal nucleic acids and the specificity of these elevations for particular disorders remain controversial issues. Regarding the multifactorial etiology of some pregnancy disorders, the use of fetal nucleic acids as prenatal markers is restricted to well-defined high-risk groups.

Prenatal diagnosis of a case of ectrodactyly in 2D and 3D ultrasound.

Die Entdeckungsrate von Extremitätenfehlbildungen pränatal ist abhänig von der Art und dem Ausmass der Anomalie und dem Vorhandensein von begleitenden Malformationen (Stoll and EUROSCAN study group. Prenat Diagn 2000; 20:811-8). Die apparative Ausstattung, die technischen Untersuchungsbedingungen, das Gestationsalter, die Lage des Fetus und die Erfahrung des Untersuchers spielen ebenso eine Rolle. Zur Verbesserung der Sensitivität des zweidimensionalen Ultraschalls (2D US) ist im Screening die systematische Untersuchung der fetalen Extremitäten notwendig, um die Darstellung von Defekten, die Eingrenzung des Spektrums der Differentialdiagnosen, die Verbesserung der elterlichen Beratung, wie auch das Management der perinatalen, fachübergreifenden Untersuchungen und der Therapie zu ermöglichen. Die dreidimensionale Ultraschalldiagnostik (3D US) erlaubt eine schnelle und umfassende Darstellung von komple-

Sonographische Befunde bei materno-fetalen Infektionen

Mindestens 5% aller Frauen erkranken an einer symptomatischen, viralen Infektion wahrend der Schwangerschaft. Weit mehr Schwangere durchleben eine akute Infektion, welche subklinisch oder ganzlich asymptomatisch verlauft und somit in der Regel unentdeckt bleibt [1]. Eine transplazentare Transmission mit konsekutiver fetaler Infektion ist kein seltenes Ereignis und kann schwerwiegende Folgen fur die Schwangerschaft und die Gesundheit des Kindes haben. Die bedeutendsten diesbezuglichen materno-fetalen Infektionen werden unter dem Akronym TORCH (Toxoplasmose, Others, Roteln, Cytomegalie, Herpes) subsummiert. Bei begrundetem Verdacht auf eine potentiell embryopathische oder fetopathische Infektion kann mittels eines positiven Polymerase Chain Reaction (PCR)-Befundes im Fruchtwasser die fetale Infektion bewiesen werden, jedoch nicht die Frage oder das Ausmas einer intrauterinen Schadigung beantwortet werden. Denn Infektion heist nicht zwangslaufig Erkrankung. Die meisten betroffenen Feten erscheinen sonographi...

Experiences with In Utero Transplantation of Mesenchymal Stem Cells

In utero stem cell transplantation (IUT) has become a valuable therapeutic option in fetuses with congenital immunologic disorders, such as severe combined immunodeficiency (SCID) or bare lymphocyte syndrome [1, 2]. However, other diseases such as thalassemias, storage defects, or osteogenesis imperfecta have either resulted in no detectable engraftment or microchimerism with uncertain effect on the phenotype. Although IUT was performed as early as the end of first trimester, neither bone marrow nor fetal liver cells resulted in relevant engraftment. It can be postulated that the fetal immune system deletes the allogeneic stem cells since several studies suggest that the fetal thymus is colonized in the first third of gestation [3]. A fetal T-cell-mediated alloresponse is evident as early as the second trimester and has cleared most allogeneic cells by term [4, 5]. In principle, IUT could result in long-term chimerism when performed early enough in pregnancy since, for instance, persistent blood group chimerism has been demonstrated for dizygotic twins [6]. But obviously, also the “transmaternal” traffic of cells from a first born to the next infant in a later pregnancy leads to tolerance induction within the T-cell population [7]. The early presentation of allogeneic cells to the developing fetal thymus results in specific tolerance, whereas later appearance (for instance, due to IUT of allogeneic hematopoietic stem cells at embryonic day 14 post conception/E14) leads to clearance of allogeneic cells from the circulation within months by the recipient’s immune system [8].