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Fetal viability and fetal growth after prolonged uterine contractions induced by progesterone withdrawal in late pregnancy in rats.

The hypothesis that sustained uterine contractile activity is the direct cause of fetal death after progesterone withdrawal in late pregnancy in rats was investigated. Pregnant rats were subjected to progesterone withdrawal on day 15 of pregnancy by injecting 2 mg mifepristone (RU 486) kg-1 or by ovariectomy with oestradiol replacement (200 ng day-1). Uterine contractile activity (force and frequency) at 4 h, but not at 2 h, in rats injected with mifepristone was significantly higher than in rats injected with vehicle. The contractile activity in mifepristone-treated rats remained higher than in control rats, at 12, 24 and 48 h. Fetal viability 36 h after mifepristone injection, when uterine contractions had lasted for 32 h, was not significantly different from fetal viability in rats injected with vehicle, but at 42 h after mifepristone injection, fetal viability was significantly reduced. In ovariectomized rats, uterine contractile activity at 12, 24, 36 and 48 h, but not at 8 h, was significantly greater than in ovariectomized rats with progesterone replacement (4 mg day-1). Fetal viability at 42 h after the operation, when uterine contractions had lasted for 30 h, was not significantly reduced, but it was significantly reduced at 48 h. When ovariectomized rats had been left to develop uterine contractions for a period before progesterone was injected, deprivation of progesterone and prolonged uterine contractions for about 30 h did not reduce fetal viability or fetal growth determined on day 18, but it did so 3 days later, on day 21. Administration of 5 mg isoxuprine kg-1 twice a day, which suppressed uterine contractions, improved fetal viability in ovariectomized rats at the earlier stage, but not at the later stage. Nevertheless, isoxuprine did improve fetal growth at the later stage in these ovariectomized rats. It is concluded that increased uterine contractile activity sustained for 32 h or less does not reduce fetal viability, but longer periods of contraction may be the cause of fetal death.

Animals↗

Accuracy of real-time sonography in the determination of fetal viability.

After 8 weeks of fetal age, real-time ultrasonography is a simple, rapid, and highly reliable technic for differentiating a viable from a dead fetus. Fetal movements are invariably detected after 8 weeks of fetal life, and a discrete, fluid-filled, intrathoracic pulsating heart can be seen after 11-12 weeks of fetal life. Absence of these findings, as observed by two independent examiners each viewing the fetus for 3 minutes with real-time sonography, provides reliable evidence of fetal demise. A prospective evaluation of 390 consecutive fetuses yielded only one false positive diagnosis of fetal viability. No living fetus was diagnosed as being dead.

Female↗

Limits of fetal viability and its enhancement.

According to Websters Encyclopedic Unabridged Dictionary of the English Language, viable of a fetus it means having reached such a stage of development as to be capable of living, under normal conditions, outside the uterus. Viability exists as a function of biomedical and technological capacities, which are different in different parts of the world. As a consequence, there is, at the present time, no worldwide, uniform gestational age that defines viability. Viability is not an intrinsic property of the fetus because viability should be understood in terms of both biological and technological factors. It is only in virtue of both factors that a viable fetus can exist ex utero and thus later achieve independent moral status. Moreover, these two factors do not exist as a function of the autonomy of the pregnant woman. When a fetus is viable, that is, when it is of sufficient maturity so that it can survive into the neonatal period and later achieve independent moral status given the availability of the requisite technological support, and when it is presented to the physician, the fetus is a patient. In the United States viability presently occurs at approximately 24 weeks of gestational age (Chervenak, L.B. McCullough; Textbook of Perinatal Medicine, 1998). In Portugal, the mortality increase significantly with GA<25 weeks. At 25 weeks mortality was 44.4% and at 26 weeks was 24.4% (I. Macedo et al. Matemidade Dr. Alfredo da Costa, Lisbon, 2000). In Poland during last years we observe also a very significant decrease of perinatal mortality. There are several aspects of fetal viability: ethical, social, psychological and medical. Ethical aspects There is a compelling conceptual and clinical reason to reject Primum non nocere as the primary principle of perinatal ethics; virtually all medical interventions involve unavoidable risks of harm, for example, amniocentesis. If Primum non nocere were to be made the primary principle of perinatal ethics, virtually all of perinatal medicine would be unethical. Social aspects Greatly increased advances in perinatal medicine lead on one hand to a high quality of care expected and demanded by both the health care professionals and patients, but on the other hand the resources available for responding to the expectations and demands are becoming increasingly stretched. Even in the high-income countries, the available resources are scarce in relation to these demands a high quality of care expected and demanded by both the health care professionals and patients, but on the other hand the resources available for responding to the expectations and demands are becoming increasingly stretched. Medical aspects During the preconceptional period the most important actions are: family planning, education, analysis of previous obstetrical miscarriages and prevention of congenital malformations (folic acid). Pregnancy presents several problems, which can significantly influence fetal viability. Proper management of these problems can improve perinatal outcome. Among others prevention of prematurity is the most important goal of contemporary perinatal medicine. Enhancement of fetal viability There are several possibilities to enhance fetal viability. The most important are: organization of perinatal care, introduction of new technologies to perinatal medicine, intensive fetal therapy and early detection of fetal distress. Three levels system of perinatal care, transport in utero, introduction and promotion of new methods, continues education of staff are characteristic for the modern organization of perinatal medicine. Echocardiography, Color Doppler Energy, 3D sonography, prenatal diagnosis (cordocentesis, analysis of fetal cells in maternal blood,.), fetal pulse oximetry, mathematical analysis of the signal are the methods which should be used at the highest level of perinatal care. Today, the prospect of survival is only about 1 in 10 at 23 weeks, and if the child lives it is more likely to be handicapped that not. At 24 weeks the chance of a normal survivor is about 50%, and after this the odds are in favor of a normal survivor. Considering this data, intensive care should be an optional choice for fetuses at 23 and 24 weeks of gestation and should be offered to every fetus at 25 weeks or more.

Ethics, Medical↗

Low iron diet and parenteral cadmium exposure in pregnant rats: the effects on trace elements and fetal viability.

The effects of latent iron deficiency combined with parenteral subchronic or acute cadmium exposure during pregnancy on maternal and fetal tissue distribution of cadmium, iron and zinc, and on fetal viability were evaluated. Timed-pregnant Sprague-Dawley rats were fed on semisynthetic test diets with either high iron (240 mg kg) or low iron (10 mg kg), and concomitantly exposed to 0, 3 or 5 mg cadmium (as anhydrous CdCl2) per kilogram body weight. Animals were exposed to cadmium from gestation day 1 through 19 by subcutaneously implanted mini pumps (Subchronic exposure) or on gestation day 15 by a single subcutaneous injection (Acute exposure). All rats were killed on gestation day 19. Blood samples, selected organs and fetuses were removed and prepared for element analyses by atomic absorption spectrometry. Low iron diet caused decreases in maternal body weight, maternal and fetal liver weights, placental weights and tissue iron concentrations. By cadmium exposure, both subchronic and acute, tissue cadmium concentrations were increased and the increase was dose-related, maternal liver and kidney zinc concentrations were increased, and fetal zinc concentration was decreased. Cadmium concentration in maternal liver was additionally increased by low iron diet. Acute cadmium exposure caused lower maternal body and organ weights, high fetal mortality, and decreased fetal weights of survivors. In conclusion, parenteral cadmium exposure during pregnancy causes perturbations in essential elements in maternal and fetal compartments. Acute cadmium exposure in the last trimester of gestation poses a risk for fetal viability especially when combined with low iron in maternal diet.

Animal Feed↗

Cadmium exposure on day 12 of gestation in the Wistar rat: distribution, uteroplacental blood flow, and fetal viability.

The effects of cadmium exposure (40 mumole CdCl2/kg, s.c.) on day 12 of gestation were evaluated in the Wistar rat. At 16-18 hours following such cadmium exposure, blood flow (as determined by radiolabeled microspheres) to the chorioallantoic placenta (CAP) was significantly reduced by 35%; at 24-26 hours, blood flow to the CAP had returned to control levels and was still unaffected at 38-43 hours. Uterine blood flow was not significantly altered at any of these timepoints. Between 16-18 and 24-26 hours after cadmium exposure, the concentration of cadmium in the placenta decreased significantly, while total cadmium content did not change. By 38-43 hours after cadmium exposure, total cadmium content of the placenta had increased significantly, although cadmium concentration was unchanged. There were no adverse effects on fetal viability or growth, as determined on day 20 of gestation. In sharp contrast, near-term (day 18) exposure to 40 or 50 mumole CdCl2/kg (s.c.) resulted in 53% and 82% mean incidences of fetolethality, respectively, within 24 hours. Administration of 50 mumole CdCl2/kg (sc) on day 12 also had no effect on fetal growth but resulted in increased fetolethality (12%). Thus midgestational cadmium exposure and its accompanying alterations in placental blood flow do not compromise fetal viability or growth. The differential response to cadmium at mid- and late gestation, in terms of fetolethality, is not due to maternal cadmium dose.

Animals↗

The role of a single progesterone measurement in the diagnosis of early pregnancy failure and the prognosis of fetal viability.

OBJECTIVE: To assess the role of a single maternal serum progesterone measurement in the immediate diagnosis of early pregnancy failure and in the long term prognosis of fetal viability. DESIGN: A prospective comparative study of women presenting with vaginal bleeding and abdominal pain in early pregnancy. The comparison group was defined retrospectively as women who presented with abdominal pain without history of, or the subsequent occurrence of, vaginal bleeding and whose pregnancies continued to viability. The study groups were defined retrospectively as threatened-continuing, non-continuing (including blighted ovum, missed abortion, incomplete and complete abortion) and tubal pregnancy groups, according to the outcome of the pregnancies. SETTING: The emergency room at the gynaecology department of a teaching hospital. SUBJECTS: Four hundred and eighty-nine women presenting with singleton pregnancy, vaginal bleeding and/or abdominal pain in the first 18 weeks of pregnancy. The comparison group comprised 131 women without vaginal bleeding whose pregnancies continued to viability. The study group comprised 358 women with 148 threatened-continuing pregnancies, 175 non-continuing and 35 tubal pregnancies. INTERVENTIONS: A 10 ml blood sample was taken and pelvic ultrasonography was performed at presentation. Otherwise, conventional management was used. MAIN OUTCOME MEASURES: Progesterone levels were interpreted in accordance with the outcome of the pregnancy: comparison, threatened-continuing, non-continuing or tubal. Viability was defined as 28 weeks or more weeks of gestation. RESULTS: Progesterone levels were significantly lower in the non-continuing and tubal pregnancy groups than in the comparison and threatened-continuing groups (P < 0.001 in all cases). A cut-off level at 45 nmol/1 was found to differentiate between the viable (comparison and threatened-continuing) pregnancies and the abnormal (non-continuing and tubal) pregnancies with 87.6% sensitivity and 87.5% specificity. CONCLUSIONS: A single serum progesterone measurement taken in early pregnancy is valuable in the immediate diagnosis of early pregnancy failure and the long term prognosis of viability.

Abdominal Pain↗

Premature rupture of membranes before fetal viability.

The outcome of 53 cases expectantly managed with premature rupture of membranes (PROM) before fetal viability (16 to 25 weeks) was retrospectively reviewed. Forty-one percent of patients developed amnionitis, four had prolonged hospital stays (longer than seven days), and one each had sepsis and pelvic thrombophlebitis. Twenty-two mothers (41%) had no complications. No serious long-term maternal sequelae were noted. Eighteen patients were delivered after 26 weeks, and there were 13 surviving neonates with birth weights ranging from 740 to 2170 g.

Abortion, Spontaneous↗

Use of an ultrasonic blood flow monitor for determining fetal viability in the rhesus monkey (Macaca mulatta). A preliminary study.

Ultrasonic stethoscopy proved to be a reliable and convenient technique for determing fetal viability in Macaca mulatta. Examinations, begun at day 150 of gestation in 33 monkeys and between days 32 and 58 in four other animals, were repeated at intervals of one to seven days. The earliest time of detecting blood flow in the fetal placenta was 42 days of gestation, fetal heart sounds geing discerned later. Three types of fetal cardiac rhythms were recognized: (1) a constant rate during most of pregnancy, (2) fluctuations associated with uterine contractions during labor, and (3) sudden transient bradycardia during violent rotations of the cephalically presented fetus.

Animals↗

Diagnosis of ventriculomegaly before fetal viability.

Thirteen cases of documented ventriculomegaly were diagnosed between 19 and 24 weeks of gestation. In 11 cases, the lateral ventricle/hemispheric width ratio was abnormally increased at the time of the first ultrasound examination, and in two, the lateral ventricle/hemispheric width ratios were initially in the high normal range. Severe ventriculomegaly was observed in both of the latter cases when repeat examinations were performed two weeks later. In 12 cases (92%), the biparietal diameter (BPD) was appropriate for gestational age, whereas the BPD was increased in only one. Two of the affected fetuses were found in conjunction with normal twins. This series suggests that fetal ventriculomegaly can be accurately diagnosed before fetal viability using the lateral ventricle/hemispheric width ratio.

Brain↗