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Doppler velocimetry of the umbilical and uteroplacental circulation: a critical review.
During the past 8 years, there have been more than 300 articles published describing Doppler studies in the field of obstetrics. This review will analyze the data dealing with the umbilical and uteroplacental circulation. This is being done with the goal of formulating an opinion of the role of Doppler in the practice of clinical obstetrics. We have concluded from prospective studies that there is no clear definition of abnormal umbilical flow velocity before 30 weeks, except for absent end-diastolic velocity after the 20th week. Most of the prospective studies on the uteroplacental circulation have suffered from a lack of knowledge of the umbilical circulation, or only one uterine artery was studied. Most investigations until now have focused on demonstrating the pathophysiological correlations with Doppler studies. With the exception of a few dissenting voices, most have demonstrated strong correlations at probability levels of less than 0.01. A few studies have emerged that have attempted to evaluate Doppler as a screening or surveillance tool. The results have not been encouraging. In populations with a low perinatal mortality, it will be difficult to prove that Doppler will reduce perinatal mortality. Studies of Doppler efficacy will have to be designed to show improved usage and efficacy of fetal surveillance. Since Doppler uniquely identifies the fetus at risk for hypoxia before term, it could replace our current risking system for the detection of fetal disease.(ABSTRACT TRUNCATED AT 250 WORDS)
In utero haematopoietic stem cell transplantation. Experiences in mice, sheep and humans.
Early prenatal diagnosis and in utero therapy of certain fetal diseases have the potential to reduce fetal morbidity and mortality. The intrauterine transplantation of stem cells provides in some instances a therapeutic option before definitive organ failure occurs. Clinical experiences show that certain diseases, such as immune deficiencies or inborn errors of metabolism, can be successfully treated using stem cells derived from bone marrow. However, a remaining problem is the low level of engraftment that can be achieved. Efforts are made in animal models to optimise the graft and study the recipient's microenvironment to increase long-term engraftment levels. Our experiments in mice show similar early homing of allogeneic and xenogeneic stem cells and reasonable early engraftment of allogeneic murine fetal liver cells (17.1% donor cells in peripheral blood 4 weeks after transplantation), whereas xenogeneic HSC are rapidly diminished due to missing self-renewal and low differentiation capacities in the host's microenvironment. Allogeneic murine fetal liver cells have very good longterm engraftment (49.9% donor cells in peripheral blood 16 weeks after transplantation). Compared to the rodents, the sheep model has the advantage of body size and gestation comparable to the human fetus. Here, ultrasound-guided injection techniques significantly decreased fetal loss rates. In contrast to the murine in utero model, the repopulation capacities of allogeneic ovine fetal liver cells are lower (0.112% donor cells in peripheral blood 3 weeks after transplantation). The effect of MHC on engraftment levels seems to be marginal, since no differences could be observed between autologous and allogeneic transplantation (0.117% donor cells vs 0.112% donor cells in peripheral blood 1 to 2 weeks after transplantation). Further research is needed to study optimal timing and graft composition as well as immunological aspects of in utero transplantation.
Fetal growth restriction due to placental disease.
Normal fetal growth depends on the genetically predetermined growth potential and its modulation by the health of the fetus, placenta and the mother. Fetuses that are small because of intrauterine growth restriction (IUGR) are at higher risk for poor perinatal and long-term outcome than those who are appropriately grown. Of the many potential underlying processes that may result in IUGR, placental disease is clinically the most relevant. Fetal cardiovascular and behavioral responses to placental insufficiency and the metabolic status are interrelated. The concurrent evaluation of fetal biometry, amniotic fluid volume, heart rate patterns, arterial and venous Doppler, and biophysical variables therefore allow the most comprehensive fetal evaluation in IUGR. In the absence of successful intrauterine therapy, the timing of delivery is perhaps the most critical aspect of the antenatal management. A discussion of the fetal responses to placental insufficiency and a management protocol that accounts for multiple Doppler and biophysical parameters as well as gestational age is provided in this review.
[CHANGES IN THE FETAL PHONOCARDIOGRAM DURING THE TREATMENT OF LATE TOXICOSIS IN PREGNANCY WITH PHENOTHIAZINE AND MAGNESIUM SULFATE].
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Parvovirus B19 infection in pregnancy.
Transplacental transmission of human parvovirus B19 (B19 virus) to the fetus is an important cause of intrauterine death, abortion, stillbirth, and nonimmune hydrops fetalis. Adverse outcome of pregnancy can occur after symptomatic and asymptomatic maternal infection. Only rare cases of congenital malformations and fetal disease in live-born infants have been associated with intrauterine B19 virus infection. Laboratory results obtained from paired maternal and fetal cord blood samples indicate that a reliable diagnosis of fetal B19 virus infection should be based on detection of parvovirus B19 DNA.
Management strategies for infectious diseases in pregnancy.
This review presented the clinical manifestations, diagnostic and therapeutic options, and preventive strategies for several congenital infections. The infections discussed show the spectrum of modes of vertical transmission and severity of fetal disease encountered, in addition to the successes and limitations of the current medical interventions. Further improvements in diagnostic techniques and therapies for managing the infected fetus are likely to occur during the next decade. Similarly, the widespread adaptation of new and sensitive diagnostic assays, such as the polymerase chain reaction, is likely to further improve our ability to identify infectious agents as the primary cause of certain abnormal fetal conditions. Where specific diagnostic tests and therapies have proven successful in preventing or treating fetal infections, universal screening programs should be given serious consideration. Of paramount importance, however, is the active research on the development of preventive interventions designed to prevent maternal infections and vertical transmission. Although specific immunotherapies, vaccines, and drug therapies hold great promise for controlling the spread of some infections, it cannot be overemphasized that some serious infectious complications of pregnancy may be avoided by simple preconception or early antenatal maternal counseling.
[CONGENITAL HEART BLOCK. ITS INTRAUTERINE DIAGNOSTIC POSSIBILITIES].
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Treatment of the fetus in utero: evolving concepts.
The rapidly evolving ability to detect the presence of major anomalies in the developing fetus and the emerging prospect of intrauterine treatment of some of these disorders are coupled to create an exciting new frontier in care of the high-risk pregnancy. Preliminary reports suggest that in some highly selected instances perinatal death and morbidity may be prevented by intrauterine surgical procedures. The technical ability to treat the disorder as described is at hand and is unlikely to be the limiting factor in the advance of this area of fetal treatment. However, the very fact that treatment is possible cannot be considered as proof of efficacy. The physician faced with the knowledge that a potentially treatable condition is present in a given fetus may feel the necessity of instituting treatment, but the validity of such an approach is far from established. It is our opinion that efforts should be made to set at the earliest point proper controlled scientific studies from which the benefit, if any, of this surgical approach to fetal disease may be established. Such clinical studies should be conducted in concert with studies in appropriate animal models. It should be noted that fetal surgical treatment is not without potentially lethal fetal and maternal complications. Before such risks, however small, are taken, it seems reasonable to determine the long-term benefits of the surgical procedure. To this end, participation in the International Fetal Surgery Registry is encouraged.
Neuroimaging and pediatrics.
The emphasis in understanding significant categories of pediatric brain and spinal cord lesions, such as brain neoplasms, white matter diseases, fetal abnormalities and lesions of the pituitary gland, is changing towards a clinical perspective with respect to modern imaging techniques. The initial experience with magnetic resonance imaging (MRI), Doppler sonography, computerized tomography (CT), and high-resolution ultrasound (US) is now being consolidated, compared and contrasted with each other and with the increasing clinical experience, particularly in diseases that are peculiar to childhood.
[A case of intrauterine tuberculosis infection].
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Medical fetal therapy.
Medical fetal therapy describes any therapy in which a pharmacological agent is administered to a woman or her fetus in order to avoid or alleviate fetal disease. Treatment of the fetus with blood products or injection of other agents can also be considered to be medical fetal therapy. This chapter reviewed the application of medical fetal therapy to the prevention of NTDs, treatment of endocrinological and metabolic disorders, such as CAH, thyroid disease and others, and the medical management of cardiac arrhythmias. Several haematological disorders and reviews of recent advances in genetic manipulation involving the use of stem-cell implantation were discussed. The field of medical fetal therapy has been extremely exciting and continues to evolve at a rapid pace. No doubt, future advances involving genetic manipulation or the use of molecular genetic techniques for diagnosis will continue to keep this field at the forefront of treatment and prevention of fetal disorders.
Fetal blood sampling.
Fetal blood sampling is accepted and widely practiced by experienced perinatologists. Its facile and safe access to the fetal circulation has broadened the spectrum of congenital disorders diagnosed prenatally. Some fetal disease states can now be identified and treated earlier, directly, more quickly, and more effectively than before, resulting in improved patient care. The volume of fetal blood to be retrieved and collection media for blood (Table 7) will be dictated by the indication for the procedure and thus the desired laboratory tests. These items and the preferred sampling site should be planned in advance by the operator. However, a flexible approach to fetal blood sampling should be maintained, anticipating the variability of fetal positions, cord insertions, and ultimate specimen volume. Teamwork among the perinatologist, sonographer, laboratory, and patient will continue to expand the role of fetal blood sampling in obstetrics.
Maternal Listeria monocytogenes septicemia with sparing of the fetus.
A case of maternal Listeria monocytogenes septicemia at 19 week's gestation is presented. Successful treatment of the mother with ampicillin resulted in remission of maternal symptoms and subsequent term delivery of an unaffected infant, indicating fetal disease is not an inevitable consequence of maternal Listeria sepsis.
Fetal origins of adult disease.
The term 'fetal origins of adult disease' was coined on the basis of the inverse association between low birth weight and blood pressure, adult-onset diabetes, coronary heart disease, and stroke seen in numerous epidemiological studies. However, it seems unlikely that birth weight is involved in causal pathways underlying these observations, and if it were then the significance to public health of these findings is very limited because of our inability to modify birth weight to a relevant extent in humans. There has been a major focus on maternal nutrition. Despite evidence that experimental manipulation of maternal nutrition in animals influences offspring birth weight and programme measures related to cardiovascular disease, human studies in general provide limited and unconvincing evidence that differences in maternal macronutrient intake are important. Nevertheless there is a need to understand the underlying causal pathways, and the utility of studies of twins and possible mechanisms are discussed.
Novel fetal imaging techniques.
Fetal imaging technology is evolving rapidly, and new techniques are being evaluated to establish their role in the assessment of the fetus. It is essential that these methods of fetal imaging are carefully assessed to ascertain if they provide additional information to assist in the clarification or understanding of fetal disease states that is not already provided by current conventional imaging techniques.
Pathogenesis and prenatal diagnosis of human cytomegalovirus infection.
Congenital human cytomegalovirus (HCMV) infection is the leading infectious cause of mental retardation and sensorineural deafness. Intrauterine transmission and adverse outcome are mainly related to primary maternal infection. Mechanisms of intrauterine transmission are slowly being unraveled and compelling evidence of the importance of using HCMV clinical strains rather than laboratory-adapted strains for in vitro studies is growing. In the absence of a vaccine or a specific antiviral therapy which could be safely administered to pregnant women with primary HCMV infection, the option of prenatal diagnosis has a crucial role in the management of pregnancy complicated by primary HCMV infection. Reliability of prenatal results, however, is still a major concern presenting the risk of either false-negative or false-positive results. However, as more light is shed on the natural history of HCMV infection during pregnancy and fetal life, the predictive value of negative prenatal diagnosis results is becoming more defined, thus improving the quality of counseling. In addition, the availability of different assays for detection of HCMV in both fetal blood and amniotic fluid samples will eventually reduce the risk of false-positive results. Finally, the identification of reliable prognostic markers of fetal disease remains the ultimate goal and a major challenge.