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Postmortem chorionic villus sampling: correlation of cytogenetic and ultrasound findings.

We performed chorionic villus samplings (CVS) in 795 cases in the first trimester during a 13-month period. Of these 35 were found to have a blighted ovum or missed abortion prior to the procedure. Nineteen women consented to have CVS. Ultrasonographic and cytogenetic findings in these 19 pregnancies were correlated. Expected gestational age was determined by last menstrual period. Observed gestational age was determined by crown rump length (CRL) (12 pregnancies) or gestational sac (GS) (7 pregnancies without fetal pole). The differences in days between the estimated and observed gestational ages was determined for each pregnancy. In all 19 CVS samples cytogenetic diagnosis documented aneuploidy. Ten cases had chromosome abnormalities virtually always lethal in the embryonic period (group I). Nine pregnancies had defects with moderate potential for fetal viability (group II). Gestations with low viability potential (group I) had estimated minus observed gestational age discrepancies (23.4 +/- 8.3 days) significantly greater than gestations with moderate viability potential (group II) (8.9 +/- 4.3 days) (P less than .001). The absence of a fetal pole was more common in group I. CVS in pregnancies with missed abortion or blighted ovum is feasible and has a high likelihood of documenting aneuploidy. Furthermore, the more severe the anomaly the more likely there will be very early fetal demise or intrauterine growth retardation.

Abortion, Missed↗

Ultrasound detection of placental insufficiency in women with 'unexplained' abnormal maternal serum screening results.

Serious placental insufficiency results in perinatal death or preterm birth from ischemic-thrombotic pathology, a process which has its origins in placental maldevelopment in the first trimester. A proportion of at-risk pregnancies may be identified from abnormalities in first or second trimester serum screening data, uterine artery Doppler waveforms or placental shape and texture at the time of the 18-20-week anatomical examination. In combination, these tests may be capable of recognizing a subset of at-risk pregnancies with 50% positive predictive values. Early recognition before fetal viability affords opportunities to direct women to regional perinatal care centres for enhanced maternal-fetal surveillance, corticosteroids to enhance fetal lung maturation, prophylactic measures to prevent pre-eclampsia and optimal decision making around the time of delivery. The creation of regional screening programs to use screening data with a placental focus is likely to be cost-effective, because existing patterns of care are utilized. More importantly, this strategy can direct women to participate in clinical research programs designed to reduce morbidity and mortality from this common group of conditions.

Biomarkers↗

Late-term abortion.

Recent proposed federal legislation banning certain abortion procedures, particularly intact dilatation and extraction, would modify the US Criminal Code such that physicians performing these procedures would be liable for monetary and statutory damages. Clarification of medical procedures is important because some of the procedures used to induce abortion prior to viability are identical or similar to postviability procedures. This article reviews the scientific and medical information on late-term abortion and late-term abortion techniques and includes data on the prevalence of late-term abortion, abortion-related mortality and morbidity rates, and legal issues regarding fetal viability and the balance of maternal and fetal interests. According to enacted American Medical Association (AMA) policy, the use of appropriate medical terminology is critical in defining late-term abortion procedures, particularly intact dilatation and extraction, which is a variant of but distinct from dilatation and evacuation. The AMA recommends that the intact dilatation and extraction procedure not be used unless alternative procedures pose materially greater risk to the woman and that abortions not be performed in the third trimester except in cases of serious fetal anomalies incompatible with life. Major medical societies are urged to collaborate on clinical guidelines on late-term abortion techniques and circumstances that conform to standards of good medical practice. More research on the advantages and disadvantages of specific abortion procedures would help physicians make informed choices about specific abortion procedures. Expanded ongoing data surveillance systems estimating the prevalence of abortion are also needed.

Abortion, Legal↗

Very low alpha-fetoprotein in Down syndrome maternal serum screening.

OBJECTIVE: To establish the frequency of very low maternal serum AFP and to differentiate congenital AFP deficiency from those diseases known to be associated with low AFP. METHODS: AFP values below 2 microg/L and borderline values up to 3 microg/L were retrospectively analysed in 839 773 singleton pregnancies included in a programme for routine screening of trisomy 21 maternal serum markers. RESULTS: Serum AFP was undetectable (< or =2 microg/L) in 8 cases, giving a frequency of 1/105 000. The calculated risk of Down syndrome was > or =1/250 in 5 cases. Fetal karyotype was normal. Seven of these pregnancies went to term (39-41 weeks) uneventfully, and birth weight was normal (3050-4110 g). In the 8th case, fetal death occurred at 35 weeks due to severe maternal diabetes. AFP levels between 2.1 and 3.0 microg/L were noted in 7 other cases. The calculated risk of Down syndrome was > or =1/250 in 5 cases, and fetal karyotype was normal. Pregnancies went to term in 4 cases (33-41 weeks), and birth weight was normal (3000-3380 g). In 3 cases, low hCG (<0.6 MoM) was associated with low AFP, and fetal death occurred at 15 to 16 weeks. CONCLUSION: Once technical errors have been excluded (repeat assay in a second run, calcium assayed to exclude the interference of EDTA for fluorimetric methods, dilution to exclude interfering antibodies, running on an alternative analyser, checking a second sample), very low second-trimester maternal serum AFP should prompt ultrasound examination in order to check fetal viability. Congenital AFP deficiency, an extremely rare disorder (1/100 000), should be suspected. It has no consequences for fetal and infant development, and parents should be reassured.

Adult↗

Alloimmunization against well defined polymorphic major histocompatibility or class I MHC transfected L cells antigens can prevent poly IC induced fetal death in mice.

METHOD: It is possible to induce increased fetal resorption in a number of inbred murine matings by injecting Poly (I) Poly (C12U) 3.5 days postconception, a maneuver associated with natural killer-mediated damage to the feto placental unit such as occurs in spontaneous fetal resorptions. RESULTS: We show here that alloimmunization can block this effect. In addition, maternal immune responses induced by alloimmunization against isolated mutant class I or class II, as well as by immunization with class I MHC alloantigens (Kd) transfected L cells are sufficient to restore normal fetal viability. It is not necessary that the maternal immune response be specifically directed against paternal alloantigens fr the fetal protection to ensue, since the effect occurs in inbred matings when the mother is immunized against unrelated class I or class II alloantigens. As in previous studies conducted in the murine species, not all MHC alloimmunizations are protective. In addition, as control, immunization with a monomorphic class I MHC molecular (37), transfected L cells, sheep red blood cells or hen egg lysozyme is without effect. CONCLUSION: These results indicate that defined MHC antigens can mediate fetal protection from induced fetal resorption, and suggest that one driving force in promoting MHC antigen polymorphism in mammals is their capacity to confer protection from NK mediated fetal demise.

Animals↗

Fluoresein diacetate uptake to determine the viability of human fetal cerebral cortical cells.

We investigated the accuracy of fluorescein diacetate uptake as an indicator of the viability of human fetal cerebral cortical cells. Cortical cells from 16-26-week-old normal fetuses were studied. The cortices were dissociated mechanically with normal saline to make a suspension. Fluorescein diacetate uptake and trypan blue exclusion were compared as methods for examining cell viability. Our results show that fluorescein diacetate uptake is a simple and sensitive method for examining human fetal cortical cell viability.

Cell Survival↗

Fetal and maternal considerations in the management of stage I-B cervical cancer during pregnancy.

The timing of treatment for stage I-B cervical carcinoma diagnosed during pregnancy is complicated by conflicting concerns for fetal survival and control of malignancy. There were 11 pregnant women with stage I-B cervical carcinoma diagnosed prior to fetal viability since 1969. Six patients were managed with termination of pregnancy and radical hysterectomy with pelvic lymphadenectomy. In 5 patients, treatment was delayed for 6 to 17 weeks and then delivery was accomplished by cesarean section followed directly by radical hysterectomy and pelvic lymphadenectomy. Two of the infants experienced complicated neonatal courses and would have benefited from additional delay. Benefits that could be achieved by delaying delivery for the fetus were calculated from a review of 600 inborn infants without congenital anomalies admitted to the neonatal intensive care (NICU) during 1984 and 1985. Neonatal mortality decreased from 32.8% at 26-27 weeks to 2.7% at 34-35 weeks gestation. Similar improvements in neonatal morbidity were demonstrated. Although adverse maternal outcomes were not associated with delay, an evaluation of risk cannot be derived from this series. Significant fetal benefit can accrue from relatively short delays in planned delivery dates. When stage I-B cervical carcinoma is diagnosed during pregnancy and when fetal survival is desired, delivery should be delayed to achieve fetal maturity, rather than only potential viability.

Adult↗

Effect of ethanol and nicotine in the pregnant rat.

Treatment of pregnant Sprague-Dawley rats on day 9 of gestation with both ethanol (0.02 ml/gm of a 12.5% or 25% solution, i.p.) and nicotine (5 mg/kg, s.c.) resulted in no significant adverse effects on embryonic development and fetal viability.

Abnormalities, Drug-Induced↗

Developmental toxicity of mangafodipir trisodium and manganese chloride in Sprague-Dawley rats.

Mangafodipir trisodium (MnDPDP) is a manganese chelate being developed as a contrast agent for magnetic resonance imaging of the hepatobiliary system. The intended clinical dose is 5 mumol/kg. The potential for MnDPDP to induce embryotoxicity and/or teratogenicity in Sprague-Dawley rats was investigated. Twenty five inseminated rats/group were intravenously administered 0, 2, 5, or 20 mumol/kg MnDPDP from days 6-17 of gestation. Maternal toxicity was not observed at any dose of MnDPDP. There were no treatment-related effects on the numbers of fetuses, fetal viability, numbers of resorptions, implantations and corpora lutea, or the percent of pre- and post-implantation losses. However, at 20 mumol/kg, fetal body weights were significantly decreased (3.3 g vs. 3.9 g for control) and increased skeletal malformations were observed (141/270 vs. 0/285 in control). The malformations were of a specific type, which included angulated or irregularly shaped clavicle, femur, fibula, humerus, ilium, radius, scapula, tibia, and/or ulna. To better define the developmental stage that is most susceptible to the effects of MnDPDP, a segmented developmental study was conducted. Twelve inseminated rats were administered 0, 20, 40, or 80 mumol/kg MnDPDP on days 6-8, 9-11, 12-14, or 15-17 of gestation. Skeletal malformations, identical to those seen in the previous study, were increased in a dose-dependent manner with the highest incidence occurring in fetuses from females dosed from days 15-17 of gestation. A third study, in which 15 rats/group were dosed intravenously with 0, 5, 20, or 40 mumol/kg MnCl2 on days 6-17 of gestation, produced identical skeletal malformations to those seen with MnDPDP, indicating that manganese is the active moiety responsible for these specific malformations.

Abnormalities, Drug-Induced↗

The influence of the experience of the investigator on the rate of sonographic diagnosis of fetal malformations in Vienna.

The quality of prenatal ultrasound may be influenced by different factors. In this study, the influence of the experience of the investigator on the quality of routine ultrasound screening during pregnancy was evaluated. We related the detection rate of fetal malformations in routine ultrasound screening in the region of Vienna to the experience level of the examiner. All 323 cases of fetal malformations registered by the obstetrical departments of Vienna or registered by the Vienna perinatal mortality statistics of 1990 and 1991 were evaluated. For analysis we used the medical charts or the patient-held antenatal records ("Mutter-Kind-Pass'). Obstetricians in private offices (level I) detected 22 per cent, the examiner in the hospital (level I-II) 40 per cent, and the examiner in the centre for prenatal diagnosis and therapy (level III) 90 per cent of all fetal malformations. The detection rate before the 24th week of gestation was significantly different (25 per cent vs. 34 per cent vs. 58 per cent). Our results suggest that an important factor for the quality of prenatal ultrasound investigation is the education of the sonographers. Furthermore, each pregnant woman should undergo ultrasound screening once in a level II or III centre before 24 weeks or before fetal viability.

Austria↗

First trimester ultrasonography of multiple gestations: a review.

The objective was to review current literature pertaining to first trimester ultrasonography of multiple gestations. To this goal, all manuscripts published in the English language regarding this topic were selected and reviewed in a MEDLINE search from 1966 through May 1998. Additional sources were identified through cross-referencing. Current widespread application of first trimester ultrasonography and especially transvaginal sonography has introduced a new dimension in both diagnostic and management aspects of multiple gestations. Application of first trimester ultrasonography in multiple gestations enables an earlier and more precise depiction of important anatomical details regarding fetal viability, chorionicity, pregnancy outcome, structural abnormalities, pathophysiology of developmental disorders (such as twin reverse arterial perfusion [TRAP] sequence), early sonographic signs associated with fetal aneuploidy (nuchal translucency and abnormal crown-rump length), and potential fetal growth discordancy. First trimester ultrasonography also assists in guiding operative procedures including: amniocentesis, chorionic villus sampling, and selective fetal reduction. Enhanced information obtained with high-resolution, first trimester transvaginal ultrasonography is rapidly becoming a standard for establishing critical information that will assist clinicians to stratify management of multiple gestations. Given the increasing incidence of multiple gestations because of various assisted reproductive technology modalities, it is important that obstetricians become aware of the potential advantages of first trimester ultrasonography in clinical management of multiple gestations.

Female↗

Jarcho-Levin syndrome: two consecutive pregnancies in a Puerto Rican couple.

This report describes two consecutive pregnancies in a Puerto Rican woman that were complicated by the autosomal recessive form of Jarcho-Levin syndrome (spondylothoracic dysplasia). This syndrome, with multiple vertebral and rib malformations, leads to respiratory insufficiency and early neonatal death. The prenatal sonographic appearance is characterized by the presence of fanned-out ribs from fused thoracic vertebral bodies. The features that distinguish spondylothoracic dysplasia and another subtype of Jarcho-Levin syndrome, spondylocostal dysplasia, are discussed. Prenatal diagnosis allows for parental counselling and the possibility of termination of pregnancy if the lethal type of spondylothoracic dysplasia is diagnosed prior to fetal viability.

Adult↗

Intrauterine growth retardation and fetal losses are caused by epidermal growth factor deficiency in mice.

The plasma concentration of epidermal growth factor (EGF) in female mice increases during pregnancy. Sialoadenectomy (surgical removal of the submandibular glands) on day 13 of gestation attenuates the rise in plasma EGF and significantly reduces the percent of live pups on day 19 of pregnancy to 80% compared with 95% for the control animals. EGF replacement therapy given to the sialoadenectomized mice successfully prevented this reduction in the percent of live pups on day 19. The average weight of the live fetuses from sialoadenectomized mothers was significantly lower than those from the control mothers, i.e., 1.00 +/- 0.14 (SD) g vs. 1.13 +/- 0.07 g. The administration of anti-EGF antiserum to the sialoadenectomized mice further affected fetal viability; only 70% of the pups were alive on day 19, with a mean weight of 0.93 +/- 0.15 g. The mean weight of the fetal body and that of the liver caused by sialoadenectomy were similarly reduced, but the brain was not affected, which shows that the growth retardation was asymmetrical. These findings suggest that EGF plays a physiological role in fetal growth and that EGF deficiency may be a cause of asymmetrical intrauterine growth retardation, which might be due to uteroplacental dysfunction.

Animals↗

Luteolytic influence of intrauterine dead embryos in the early pregnant rat.

The present investigation was an endeavour to study if annihilation of embryos in the uterus of the rat before the establishment of placental luteotropic functions has any influence on corpus luteal function, and, if there is any, whether it is local or systemic. The responsibility of pregnancy maintenance was imposed on a single ovary by performing unilateral ovariectomy after implantation (on Day 5 postcoitum). The implantation sites in one uterine horn, either ipsilateral or contralateral to the remaining ovary, were selectively destroyed by injecting 0.1 ml of sterile normal saline to that particular horn only, and the peripheral progesterone level and viability of the embryos in the untreated horn, which depended on the functions of the remaining ovary, were examined. Selective killing of embryos in the uterine horn of the ovariectomized side did not exert any influence on the fetal viability in the untreated horn ( nonovariectomized side) and the peripheral progesterone level also remained statistically unaffected. On the contrary, induction of fetal resorptions in the uterine horn of the intact side produced a significant fall in the peripheral level of progesterone and induced resorption of embryos of the ovariectomized side also. The latter could significantly be prevented by simultaneous administration of exogenous progesterone, indicating luteolysis as the major, if not sole, factor responsible for fetal resorption in the untreated horn. The luteolytic effect was attributed neither to saline itself, nor to the distension of the uterine horn caused by saline injection. Luteolytic factors from the dead embryo-bearing horn which act locally on the adjacent ovary only, are discussed.

Animals↗

Estimation of fetal age from dimensions of atlas and axis ossification centers.

The atlas and axis ossification centers of 106 human fetal and neonate skeletons were measured. The skeletons belong to the collection in the Department of Forensic Medicine of the Albert Szent-Györgyi Medical University, Szeged, Hungary. The age of the skeletons ranged from 4 to 10 lunar months. Nine linear measurements on the atlas, seven on the axis neural arches ossification centers and three on each one of the axis centra ossification centers were taken. We did simple and multiple linear regression analysis to estimate the age of fetuses. The results show that it is possible to use regression equations to estimate the fetal body length and age from atlas and axis ossification centers measurements during the whole period of development studied. The study of size and shape of the ossification centers using factorial analysis (principal component analysis) shows that the shape of the dens of the axis might be useful to estimate fetal viability.

Age Determination by Skeleton↗

Low copper and brain abnormalities in fetus from triethylene tetramine dihydrochloride-treated pregnant mouse.

The effects of prenatal triethylene tetramine dihydrochloride (Trien-2HCl) exposure on fetal mice have been investigated on gestational day 19. Trien-2HCl was given throughout pregnancy at levels of 0 (control), 3,000, 6,000, or 12,000 ppm as drinking water, ad libitum. At the level of 12,000 ppm, the frequency of total resorption tended to be high and that of fetal viability tended to be low, as compared to controls. Decreased maternal weight was observed in body, but not in liver, at the level of 12,000 ppm. Fetal body and cerebrum weights significantly decreased at the levels of 6,000 and 12,000 ppm; however, fetal liver weight remained unchanged. Maternal serum copper concentration was not affected by the Trien-2HCl. Fetal copper concentrations of liver and cerebrum were significantly lower in the Trien-2HCl-treated groups than in the controls, with levels decreasing in a dose-related manner. When the copper and zinc concentrations in the group treated at 12,000 ppm were compared with those in controls, significant decreases in both metals were observed in placenta but not in maternal liver. Changes in fetal zinc concentration varied by tissues: i.e., an increase in liver and no change in cerebrum. Fetal abnormalities were frequently observed in brain, and the frequency was increased with increasing levels of the Trien-2HCl. These results suggest that fetal brain abnormalities caused by Trien-2HCl may be due in part to induction of copper deficiency, which is almost equivalent to that in brindled mutant mouse.

Animals↗

Acute cadmium exposure and ovarian steroidogenesis in cycling and pregnant rats.

The purpose of this study was to evaluate the effect(s) of acute in vivo cadmium (Cd) exposure on steroidogenesis in rat ovaries during different reproductive states. Sprague-Dawley rats were injected subcutaneously on the day of diestrus, or on day 7 or 16 of gestation with a single dose of 0, 3, or 5 mg Cd/kg bw, and evaluated 24 h later. Serum progesterone and estradiol concentrations were determined. Whole-ovary culture was used to evaluate Cd effects on the production of progesterone, testosterone, and estradiol. Liver, kidney, spleen, ovary, placenta, and blood were analyzed for Cd and iron (Fe) concentrations. No general toxic effects, no disruption of estrous cyclicity, and no change in fetal viability were seen. Histologic evaluation revealed moderate Cd-related thecal congestion in ovaries of pregnant rats. The highest Cd concentrations, except for liver, were found in the fetal portion of the placenta. Interestingly, Cd-related decreases in Fe concentration were found in several tissues from rats in proestrus and on gestation day 8, and in fetal placenta from rats on gestation day 17. Cadmium appears to interfere with normal steroidogenesis at a number of sites in the biosynthetic pathway with serum estradiol concentration and ovarian estradiol production the most affected. Acute Cd effects on steroidogenesis are most severe in rats evaluated in proestrus or in early pregnancy, while in late pregnancy steroidogenesis is relatively unaffected.

Animals↗

Childbearing, reproductive control, aging women, and health care: the projected ethical debates.

Of the many social trends that will have an impact on the ethical debates surrounding women's health in the 21st century, three are discussed: the shifting demographics of age and race in the United States; the fundamental change in the health care system to a community-based, preventive model; and the equal voice of women in the government. Using these trends as a framework, this article hypothesizes the ethical debates that will occur in the 21st century concerning such issues as fetal viability, abortion, contraception, infertility, genetic engineering, aggressive versus nonaggressive treatment of aging women, scarce resources, menopause, organ transplants, sexism in biomedical research, fertility in postmenopausal women, birthing centers, fetal surgery, and fetal therapy.

Aborted Fetus↗