Fetal Wastage Research Articles

Traitement du syndrome des antiphospholipides par les échanges plasmatiques et les immunoglobulines intraveineuses (IVIg)

Four patients followed for clinical symptoms due to antiphospholipid antibodies have been treated by plasmatic exchanges and intravenous immunoglobulins. Lupus anticoagulant decreased in three patients, although this treatment was less effective on anticardiolipin antibodies. Clinical benefit was clear in one case of Soulier-Boffa syndrome (birth of one normal child after three fetal wastages).

National chimpanzee breeding program: Primate research institute.

The Primate Research Institute (PRI) dedicated a colony of 81 proven breeders (60 females, 21 males) to the National Chimpanzee Breeding and Research Program (NCBRP). When possible, infants were left with their mothers for a minimum of 18 months. Programs to define and reduce fetal wastage and neonatal mortality were implemented. Pregnancies were diagnosed both by RIA for serum chorionic gonadotropin and by ultrasound prior to day 30 of pregnancy. Of 65 pregnancies detected by ultrasound and RIA, 15 (23%) resulted in fetal loss. Without the use of ultrasound and RIA, only 8 of these losses would have been detected. Infant mortality (7 of 53 live births; 13%) was primarily due to maternal abuse or problems related to premature delivery. The incidence of losses due to maternal abuse has been reduced by placing females in single cages 2 weeks prior to their estimated delivery date so endangered infants can be recognized and removed. The new system provided the first opportunity for most of the mothers to care for their infants; 25 succeeded (in 2 instances in the second pregnancy only) and 12 did not (infants from 2 mothers were removed due to delivery of twins). During this 26-month period the colony grew by 46 infants (58%), half of which will be retained as future breeders. Thus, the NCBRP goal of achieving a self-sustaining population appears viable.

Effects of heavy metals on alpha-fetoprotein in maternal sera and amniotic fluid of pregnant mice

This report describes the effects of low levels of copper, nickel and lead salts on the concentrations of α-fetoprotein (AFP) in the sera and amniotic fluid of pregnant Nylar mice. During the early and mid-gestation (9–17 days), pregnant mice were injected intraperitoneally twice with heavy-metal salt solutions and were autopsied two days following the second injection. Maternal sera and amniotic fluid (AF) were collected and AFP levels were quantified by radial immunodiffusion. Metal levels determined by X-ray fluorescence spectroscopy in individual samples confirmed the presence of trace metals in the fetus. Low doses of nickel and copper were associated with elevated AFP levels in amniotic fluid in 15–17 day pregnant animals, while maternal serum AFP levels mostly remained unchanged. Decreased concentrations of maternal serum AFP occurred with increased doses of copper and lead in contrast to elevated concentrations of AFP in amniotic fluid. Futhermore, there was an increase in fetal wastage when higher doses of copper and lead were administered. A reduction of secondary litter size (F 1 generation) with low dosage levels of lead was also observed. These results imply that the fetal-maternal transfer of AFP may either be impaired or reflect increased leakage or decreased placental permeability in the presence of sublethal doses of copper and lead. These findings suggest that the parallel measurements of AFP concentrations in sera and amniotic fluid might be employed for assessment of embryo- and fetotoxicity when heavy metal intake is suspected during pregnancy.

Gonadal status and reproductive function following treatment for Hodgkin's disease in childhood: The Stanford experience

To ascertain the impact of therapy on gonadal function and reproductive outcome among children treated for Hodgkin's disease, we reviewed the experience at Stanford University Medical Center during the years 1965–1986. There were 240 children 15 years of age or younger, 92 girls and 148 boys; with median follow-up of 9 years, maximum follow-up was 26 years. Of this cohort, data on gonadal function were available on 20 boys, 5 of whom were considered prepubescent; they had no clinical evidence of sexual maturation and were less than 13 years of age. Evaluation of the boys included testicular biopsy, semen analyses, and the ability to procreate. Serum gonadotropin hormone levels (FSH, LH) were studied in 11 boys who also had semen analyses. Sexual maturation was attained in all boys without the need for androgen replacement. Among the eight boys treated with radiation alone, four were able to father a child (3 following 40–45 Gy pelvic radiation dose, 1 without pelvic radiation) from 3–19 years following treatment. Three others who received 30–44 Gy pelvic radiation were oligospermic when tested at 10 to 15 years post-treatment. Semen analyses in 10 of 12 (83%) boys who had been treated with six cycles of MOPP with or without pelvic radiation revealed absolute azoospermia with no evidence of recovery as along as 11 years of follow-up. Following prolonged azoospermia, 2 of the 12 boys (17%) had recovery of fertility, with normalization of sperm count and/or ability to procreate at 12 and 15 years following treatment. There was no correlation with serum gonadotropin levels and sterility. Data on menstrual history, pregnancy and offspring were available in 86 (92%) of the girls. Seventy-five of the 86 girls (87%) have normal menstrual function. However, none of the females who underwent pelvic radiation without prior oophoropexy has maintained ovarian function. Both the prepubescent and postpubescent boys were affected by 6 cycles of MOPP whether or not pelvic radiation was administered. On the other hand, in girls similarly treated, ovarian injury was directly related to both the number of cycles of chemotherapy and the ovarian radiation dose. The chances of maintaining gonadal function following combined modality treatment are significantly greater among girls than boys. The progeny of patients treated for Hodgkin's disease appear normal and no excess fetal wastage has been noted.

Autoimmunity and pregnancy loss

Certain autoimmune conditions, such as systemic lupus erythematosus (SLE), are associated with pregnancy loss. Almost 30 years ago, investigators published data that focused on fetal wastage in women with antiphospholipid antibodies (aPLs) and that included fetal loss as one clinical criterion for the diagnosis of antiphospholipid syndrome (APS) [1,2]. After these initial publications, interest in other autoimmune disorders as possible causes of pregnancy loss has increased. This interest prompted an ongoing effort to link the presence of a specific autoantibody or patterns of autoantibodies to recurrent pregnancy loss. A multitude of candidate autoantibodies have been evaluated, and some clinicians routinely perform assays for multiple autoantibodies in the evaluation of women with recurrent pregnancy loss; however, there is only modest evidence to support the concept that most autoantibodies cause pregnancy loss. This article discusses the potential association between several specific autoimmune conditions and recurrent pregnancy loss. Recurrent pregnancy loss may be caused by a myriad of factors, including anatomic, hormonal, thrombotic, autoimmune, genetic, infectious, or unknown causes. Most women with two or three unexplained, consecutive embryonic losses are otherwise healthy and have no other signs or symptoms that might be considered part of an autoimmune condition.

HIV-1 and pregnant women

The major goals of this study were to measure the current prevalence and estimate the annual incidence of HIV-1 infection in young pregnant women from urban Malawi, to identify factors that were associated with HIV-1 infection, and to examine adverse pregnancy outcomes. Four hundred and sixty-one consecutive pregnant women were studied when they presented for prenatal care. The overall seroprevalence for HIV-1 infection in these urban populations was 17.6% (81 out of 461) during early 1989. Based on previous seroprevalence in similar unselected pregnant women, the estimated annual incidence of HIV-1 seroconversion in urban pregnant women ranged from 3 to 4% per annum between 1985 and 1987 and from 7 to 13% between 1987 and 1989. HIV-1 infection was significantly associated with reactive syphilis serology. Reported history of sexually transmitted disease was also correlated with HIV-1 infection but was not statistically significant. Other variables, such as history of transfusion, history of tuberculosis, parity or occupation were not associated with HIV-1 infection. History of spontaneous abortion was significantly associated with reactive syphilis serology, HIV-1 infection and history of sexually transmitted disease. In logistic regression analysis, HIV-1 infection remained the only significant variable that was correlated with spontaneous abortion. This study suggests that HIV-1 infection may play a role in fetal wastage.

Mosaic normal/unbalanced karyotype and recurrent fetal wastage

Mosaic normal/unbalanced karyotype and recurrent fetal wastage

Maternotoxicity and fetotoxicity of an angiotensin-converting enzyme inhibitor, enalapril, in rabbits

When enalapril, an angiotensin-converting enzyme (ACE) inhibitor, was orally administered to inseminated rabbits at dosages of 0.1 to 30 mg/kg/day for 13 days in a range-finding study, nephrotoxicity, as measured by elevated serum urea nitrogen concentrations, occurred at 1 mg/kg/day and higher dosages and significant ( p ≤ 0.05) increases in fetal wastage were observed at dosages as low as 3 mg/kg/day. Saline supplementation during treatment prevented this rise in urea nitrogen. Fetal wastage was significantly ( p ≤ 0.05) increased in the absence of maternotoxicity when saline-supplemented females were treated with enalapril at 30 mg/kg/day. A developmental toxicity study of enalapril in saline-supplemented rabbits produced no evidence of teratogenicity at 3, 10, and 30 mg/kg/day. The period of sensitivity of fetuses to the toxic effects of enalapril was found to be limited to middle-to-late gestation (Gestational Days 14–27). A single oral dose of enalapril (30 mg/kg) on Day 26 of gestation resulted in 100% fetal deaths. On the basis of the work done by Broughton Pipkin et al. [1982, J. Physiol. (London) 323, 415–422] and Broughton Pipkin and Wallace (1986, Brit. J. Pharmacol. 87, 533–542), which demonstrated that the sheep fetus becomes markedly hypotensive when the dam is treated with captopril or enalapril during late pregnancy, we believe that the observed fetotoxicity of enalapril in rabbits is also due to fetal hypotension. On the basis of published evidence indicating that the renin-angiotensin system in rabbits and in humans is not developed until middle-to-late gestation, we believe our results support the premise that incidental exposure to enalapril early in human pregnancy is unlikely to be associated with an increased risk of fetotoxicity. However, our results and those cited above demonstrate that ACE inhibitors are fetotoxic in late gestation in rabbits and sheep, and should be given in pregnancy only if the potential benefit justifies the potential risk to the fetus.

Translocation Down’s syndrome

Among the 500 Down syndrome children karyotyped, 15 (3%) were due to translocation; 10 were 21;21 translocation and five 14;21. There were 9 cases of de novo translocations, while 6 were inherited from father or mother. Family history was characteristic in all the translocation cases, with younger parental age, fetal wastage in the family, recurrence and with the affected child often being either the first or the only liveborn in the family. The pattern of translocation in Madras and the significance of family history in genetic counselling are discussed.

Fetal Wastage and Nonrecognition in Human Pregnancy

Fetal Wastage and Nonrecognition in Human Pregnancy

Cushingʼs Syndrome in Pregnancy

Fertility and childbearing rarely occur in Cushing's syndrome because amenorrhea, oligomenorrhea, infertility, and abortions characterize the disease. Currently, a total of 53 cases of Cushing's syndrome and pregnancy have been reported. When Cushing's syndrome occurs during pregnancy, approximately 56 per cent of the cases are associated with adrenal cortical adenoma or carcinoma. Excluding Cushing's disease, nearly 21 percent of the cases are caused by adrenal carcinoma. The maternal catabolic state of glucocorticoid excess contributes to poor fetal outcome with many of the cases complicated by either fetal wastage or prematurity. However, congenital malformations are not seen more frequently than in normal pregnancy. Pregnancy may or may not influence Cushing's syndrome, but Cushing's syndrome definitely complicates pregnancy.

Maternotoxicity and Fetotoxicity of an Angiotensin-Converting Enzyme Inhibitor, Enalapril, in Rabbits

Maternotoxicity and Fetotoxicity of an Angiotensin-Converting Enzyme Inhibitor, Enalapril, in Rabbits. MINSKER, D. H., BAGDON, W. J., MACDONALD, J. S., ROBERTSON, R. T., AND BOKELMAN, D. L. (1990). Fundam. Appl. Toxicol14, 461–470. When enalapril, an angiotensin-converting enzyme (ACE) inhibitor, was orally administered to inseminated rabbits at dosages of 0.1 to 30 mg/kg/day for 13 days in a range-finding study, nephrotoxicity, as measured by elevated serum urea nitrogen concentrations, occurred at 1 mg/kg/day and higher dosages and significant (p ≤ 0.05) increases in fetal wastage were observed at dosages as low as 3 mg/kg/day. Saline supplementation during treatment prevented this rise in urea nitrogen. Fetal wastage was significantly (p ≤ 0.05) increased in the absence of maternotoxicity when saline-supplemented females were treated with enalapril at 30 mg/kg/day. A developmental toxicity study of enalapril in saline-supplemented rabbits produced no evidence of teratogenicity at 3, 10, and 30 mg/kg/ day. The period of sensitivity of fetuses to the toxic effects of enalapril was found to be limited to middle-to-late gestation (Gestational Days 14-27). A single oral dose of enalapril (30 mg/kg) on Day 26 of gestation resulted in 100% fetal deaths. On the basis of the work done by Broughton Pipkin el al. [1982, J. Physiol. (London) 323, 415–422] and Broughton Pipkin and Wallace (1986, Brit. J. Pharmacol87, 533–542), which demonstrated that the sheep fetus becomes markedly hypotensive when the dam is treated with captopril or enalapril during late pregnancy, we believe that the observed fetotoxicity of enalapril in rabbits is also due to fetal hypotension. On the basis of published evidence indicating that the renin-angiotensin system in rabbits and in humans is not developed until middle-to-late gestation, we believe our results support the premise that incidental exposure to enalapril early in human pregnancy is unlikely to be associated with an increased risk of fetotoxicity. However, our results and those cited above demonstrate that ACE inhibitors are fetotoxic in late gestation in rabbits and sheep, and should be given in pregnancy only if the potential benefit justifies the potential risk to the fetus.

The elusive listeriosis in pregnancy: The Carlisle experience

SummaryWe present eight cases of proved listeriosis in pregnancy at the City Maternity Hospital, Carlisle. In 1981, the infection was uniformly lethal to the fetus, contributing about 15 per cent to our perinatal deaths that year. A high index of suspicion and prompt treatment resulted in a two-thirds fetal salvage in 1982. Unfortunately, this clinical watchfulness ‘slipped' in 1987–1988 with the two cases eluding us resulting in fetal wastage. The diagnosis, successful treatment, and hence fetal survival are related to a keen index of suspicion exercised by both general practitioners and physicians.

Impairment of the protein C anticoagulant pathway in a patient with systemic lupus erythematosus, anticardiolipin antibodies and thrombosis

We have identified an inhibitor of the protein C anticoagulant pathway in the plasma of a patient with systemic lupus erythematosus and a history of recurrent deep vein thrombosis, fetal wastage, and seizures. The patient's plasma contained anticardiolipin antibodies as well as a weak lupus anticoagulant. Examination of this patient's plasma revealed normal levels of protein C and protein S antigen, normal levels of functional protein C, as well as essentially normal levels of every blood coagulation factor. In a modified prothrombin time assay, the activated protein C-mediated prolongation of the clotting time observed in normal plasma was not observed in this patient's plasma. Gel permeation chromatography of the patient's plasma revealed that the inhibitory material was a high molecular weight protein that coeluted with the IgM peak. The inhibitor did not appear to circulate as a complex with protein C, since the inhibitor could easily be separated from protein C during fractionation procedures, and did not interfere with the activation of protein C in plasma as assessed by a functional amidolytic assay. Our findings suggest that the recurrent thrombotic episodes observed in this patient may have occurred as a result of the patient's antiphospholipid antibody neutralizing specific phospholipids essential for the full expression of the anticoagulant activity of activated protein C.

The performance of Brahman-Shorthorn and Sahiwal-Shorthorn beef cattle in the dry tropics of northern Queensland. 1. Reproductive rates and liveweights of F1 and backcross females

A breeding program was established at Swan's Lagoon Beef Cattle Research Station in the dry tropics of northern Queensland to evaluate the productivity of cattle which were genotypically at least one-half Bos indicus. Brahman or Sahiwal bulls were initially mated to B. taurus cows (predominantly Shorthorn) to produce the first filial generation (F1 1/2 Brahman and F1 1/2 Sahiwal). First backcross 314 Brahman and first backcross 314 Sahiwal were derived from crossing F1 1/2 Brahman or F1 1/2 Sahiwal cows to their respective sire breeds. This paper reports on the female reproductive rates and liveweight performance in 2 data sets: 1972-79, F1 1/2 Brahman v. F1 1/2 Sahiwal; 1975-83, first backcross 3/4 Brahman v. first backcross 3/4 Sahiwal. In both data sets, significant differences in fertility (pregnancy rate and calving date) between F1 or first backcross groups were infrequent, and where differences did occur, they were often inconsistent due to cross x year interactions. The difference between weaning rates and pregnancy rates (representing foetal and calf wastage) was 5 percentage units higher in Sahiwal crosses than Brahman crosses for lactating cows Year effects significantly (P<0.05) influencd both fertility and liveweight, demonstrating the extent of seasonal influences on cattle production in the dry tropics. Generally Brahman-cross cows were heavier throughout than their Sahiwal counterparts. Among lactating cows, F1 1/2 Brahman were 21 kg heavier at start of mating than F1 1/2 Sahiwal, while first backcross 3/4 Brahman were 29 kg heavier than first backcross 3/4 Sahiwal.

Two survival cases of acute fatty liver of pregnancy without fetal wastage Case report

Two survival cases of acute fatty liver of pregnancy without fetal wastage Case report

Maternal reproductive histories in ataxic cerebral palsy

Maternal reproductive histories of fetal wastage in 36 cases of ataxic cerebral palsy and in a control group of 60 mothers were compared. There was no significant difference between the groups. A history of fetal loss did not accompany this cerebral palsy syndrome where prenatal factors play an important role.

Turner’s Syndrome – Review of the Literature with Reference to a Successful Pregnancy Outcome

A 30-year-old Japanese female with Turner's syndrome had become pregnant and delivered a normal male infant by cesarean section. Her menarche was at age 14, and secondary sex characteristics developed normally. She had some features of Turner's syndrome, and cytogenetic studies from peripheral blood lymphocytes and several tissues revealed only 45,XO karyotype without evidence of mosaicism. To our knowledge, she is only the thirteenth case of monosomy X to achieve pregnancy. A review of the literature indicates a high incidence of fetal wastage and increased chromosomal errors in the offspring of women with a 45,XO cell line with or without mosaicism.

Susceptible period of nitrous oxide teratogenicity in Sprague-Dawley rats.

The susceptible period of nitrous oxide (N2O) teratogenicity was studied in 170 Sprague-Dawley rats. Seven groups of 20 timed-pregnant rats were exposed to 60% N2O for 24 hours on each of days 6-12 of gestation; a control group of 30 timed-pregnant rats was exposed to air on day 9. On day 20 of gestation, dams were killed and reproductive indices were determined; their fetuses were subsequently examined for external, skeletal, and visceral abnormalities. There were no differences among the groups in the number of implantations and live fetuses, mean fetal weight, and sex ratio. The incidence of fetal wastage was higher than control in N2O-treated groups exposed on days 8 and 11 of gestation. Skeletal malformations of the ribs and vertebrae were increased following exposure on day 9 of gestation. However, the specific minor anomaly, cervical rib, was increased only following exposure on day 8 of gestation. The incidences of right-sided aortic arch and left-sided umbilical artery, abnormalities indicative of altered laterality, were increased following exposure on day 8 of gestation. Nitrous oxide administration during organogenesis causes several reproductive defects by mechanisms which remain to be determined.

Neonatal Animal Models: Experimental Anencephaly and Similarities to Spina Bifida

Anencephaly and spina bifida are the two most common neural tube defects (NTDs) that occur in humans. They cause considerable fetal wastage and neonatal morbidity and mortality. Numerous animal models have been discovered and have been used to study these malformations. We used the scanning electron microscope (SEM) to compare the development of embryonic stages of spina bifida and anencephaly. Pregnant 180 g Sprague-Dawley rats were given either a 1 ml subcutaneous injection of 1% trypan blue on gestational days 7-8 or an intragastric administration of 75,000 units of vitamin A on gestational days 8-10 to produce embryos with spina bifida or anencephaly. Controls were given vehicle only. The SEM examination of day 9 and 10 embryos revealed no morphologic differences between controls and subjects. Subsequent gestational days showed closure of neural tubes in controls but progressive opening of neural tubes (in the rostral and caudal regions) in experimental subjects. Growth of the dysmorphic neural tube region with subsequent sponteneous necrosis late in gestation resulted in the mature malformations of anencephaly and spina bifida. This study emphasizes the similarities in the developmental stages of spina bifida and anencephaly. We also surveyed a large series of human anencephalic autopsy specimens and noted striking similarities to the animal model.