Higher Rate Of Fetal Loss Research Articles

High Rate of Severe Fetal Outcomes Associated with Maternal Parvovirus B19 Infection in Pregnancy

Objective. To augment the understanding of parvovirus B19 infection in pregnancy with respect to maternal characteristics and their corresponding fetal outcomes. Study Design. Retrospective case-series of all women referred to Magee-Women_s Hospital with serologically-documented parvovirus B19 infection during pregnancy from 1998–2001. Results. All 25 cases that are available for analysis occurred from January through June. The frequency of cases varied substantially from year to year, with 14 cases in 1998, 0 cases in 1999 and 2000, and 11 cases in 2001. In contrast to previous reports, the minority of women [4/25(16%)] experienced symptoms attributable to parvovirus B-19 infection although 3 of 25 (12%) fetuses developed hydrops fetalis and 4/25 (16%) suffered an intrauterine of fetal death. Conclusions. These findings suggest that parvovirus B19 infection in pregnancy follows seasonal and annual trend variation, may produce a lower frequency of maternal symptoms and a higher fetal loss rate than previously reported. Synopsis. Maternal parvovirus B19 infection follows seasonal and annual variation is often asymptomatic and may have higher fetal loss rates than previously reported. Continued surveillance is warranted.

A pivotal role for galectin-1 in fetomaternal tolerance

A successful pregnancy requires synchronized adaptation of maternal immune-endocrine mechanisms to the fetus. Here we show that galectin-1 (Gal-1), an immunoregulatory glycan-binding protein, has a pivotal role in conferring fetomaternal tolerance. Consistently with a marked decrease in Gal-1 expression during failing pregnancies, Gal-1-deficient (Lgals1-/-) mice showed higher rates of fetal loss compared to wild-type mice in allogeneic matings, whereas fetal survival was unaffected in syngeneic matings. Treatment with recombinant Gal-1 prevented fetal loss and restored tolerance through multiple mechanisms, including the induction of tolerogenic dendritic cells, which in turn promoted the expansion of interleukin-10 (IL-10)-secreting regulatory T cells in vivo. Accordingly, Gal-1's protective effects were abrogated in mice depleted of regulatory T cells or deficient in IL-10. In addition, we provide evidence for synergy between Gal-1 and progesterone in the maintenance of pregnancy. Thus, Gal-1 is a pivotal regulator of fetomaternal tolerance that has potential therapeutic implications in threatened pregnancies.

Negative Appendectomy in Pregnant Women Is Associated with a Substantial Risk of Fetal Loss

The preoperative diagnosis of acute appendicitis is often inaccurate in pregnant women, and complicated appendicitis is associated with a high rate of fetal loss. The study objective was to evaluate rates of fetal loss and early delivery in pregnant patients undergoing appendectomy, using a large population-based database. Using the California Inpatient File, we retrospectively analyzed all women undergoing appendectomy between 1995 and 2002 for pregnancy, diagnosis, operative technique, fetal loss, and early delivery during the same hospitalization as appendectomy. Of 94,789 women who underwent appendectomy, 3,133 were pregnant. Complicated appendicitis was found in 30% of pregnant women and 29% of nonpregnant women (p=NS). The rate of negative appendectomy was considerably higher in pregnant compared with nonpregnant women (23% versus 18%, p < 0.05). Rates of fetal loss and early delivery were considerably higher in women with complex appendicitis (6% and 11% respectively; p < 0.05) in comparison with negative (4% and 10%) and simple (2% and 4%) appendicitis. Using multivariate logistic regression, complicated and negative appendicitis (odds ratio [OR] 2.69 and 1.88 respectively, compared with simple) remained major positive predictors of fetal loss. Also, laparoscopy was associated with a higher rate of fetal loss compared with open appendectomy (odds ratio=2.31). The current approach to possible acute appendicitis in pregnant women puts 23% at risk for fetal loss, even though they have a normal appendix. These data indicate that reducing fetal loss in pregnant women suspected of having acute appendicitis will require more accurate diagnosis to avoid unnecessary operation.

Reduction of high fetal loss rate by anticoagulant treatment during pregnancy in antithrombin, protein C or protein S deficient women

Hereditary thrombophilia is associated with an increased risk of fetal loss. Assuming that fetal loss is due to placental thrombosis, anticoagulant treatment might improve pregnancy outcome. In an observational family cohort study, we prospectively assessed the effects of anticoagulant drugs on fetal loss rates in women with hereditary deficiencies of antithrombin, protein C or protein S. The cohort contained 376 women (50 probands and 326 deficient or non-deficient relatives). Probands were consecutive deficient patients with venous tromboembolism. Thromboprophylaxis during pregnancy was recommended in deficient women, irrespective of prior venous thromboembolism, and in non-deficient women with prior venous thromboembolism. Outcome of first pregnancy was analysed in 55 eligible women. Of 37 deficient women, 26 (70%) received thromboprophylaxis during pregnancy, compared with three of 18 (17%) non-deficient women. Fetal loss rates were 0% in deficient women with thromboprophylaxis versus 45% in deficient women without (P = 0.001) and 7% in non-deficient women without thromboprophylaxis (P = 0.37). The adjusted relative risk of fetal loss in women who received thromboprophylaxis versus women who did not was 0.07 (95% confidence interval 0.001-0.7; P = 0.02). Our data suggest that anticoagulant treatment during pregnancy reduces the high fetal loss rate in women with hereditary deficiencies of antithrombin, protein C or protein S.

ASSOCIATION BETWEEN MATERNAL-FETAL GENETIC HISTOCOMPATIBILITY AND MATERNAL UNDERNUTRITION IN MICE: INFLUENCE ON INTRAUTERINE GROWTH

The purpose of this study was to evaluate the effects of maternal-fetal genetic histocompatibility and the association of that condition with maternal undernutrition regarding fetal growth and litter size. Fetuses that were either syngeneic or allogeneic with the mothers were bred, using mice of well-defined syngeneic strains (A/J and Balb/c). Pregnant mice were fed using either unrestricted normal diet with 22% protein, consumed ad libitum, or a diet containing 14% protein, with intake restricted to 70% of that consumed by the unrestricted group. At the end of gestation, the number of fetoplacental units and fetal losses, the fetal and placental weight, and the weights of fetal brain and liver were recorded. Fetuses from undernourished mothers showed a reduction in body, placental, and brain weight (P < 0.01); the association of undernourishment with maternal-fetal genetic compatibility resulted in a greater impairment of fetal growth (P < 0.01). A reduction in the number of viable fetuses per female in the dietary-restricted groups was observed. (P < 0.01). Although the concurrence of maternal-fetal genetic compatibility resulted in a trend towards a greater reduction in the number of viable fetuses as well as in a higher rate of fetal loss, these differences did not reach statistical significance. In mice, the occurrence of maternal-fetal genetic histocompatibility alone did not change fetal growth; maternal undernutrition during pregnancy resulted in growth stunting of progenies with reduction of litter size; and the association of these 2 factors produced greater reduction of fetal weight.

Effect of the Nuclear-Donor Cell Lineage, Type, and Cell Donor on Development of Somatic Cell Nuclear Transfer Embryos in Cattle

Potential applications of somatic cell nuclear transfer to agriculture and medicine are currently constrained by low efficiency and high rates of embryonic, fetal, and neonatal loss. Nuclear transfer efficiency in cattle was compared between three donor-cell treatments from a single animal, between four donor-cell treatments in sequential stages of differentiation from a single cell lineage and genotype, and between the same cell type in two donors. Cumulus and granulosa donor cells resulted in a greater proportion of viable day-7 embryos than ear-skin cells; pregnancy rate and losses were not different among treatments. The least differentiated cell type in the follicular cell lineage, preantral follicle cells, resulted in fewer cloned blastocysts (11%) than cumulus (30%), granulosa (23%), and luteal (25%) donor cells. Cloned blastocysts that did develop from preantral follicle cells (75%) were more likely to progress through implantation into later stages of pregnancy than cloned blastocysts from cumulus (10%), granulosa (9%), and luteal (11%) donor cells (p < 0.05). Day-7 embryo development from granulosa cells was similar between two donors (19 vs. 24%) and proved to be a poor indicator of further development as day-30 pregnancy rates varied threefold between donors (48 vs. 15%, p < 0.05). Results reported here emphasize the crucial role of the nuclear donor cell in the outcome of the nuclear-transfer process.

Age-specific risk of fetal loss observed in a second trimester serum screening population

The purpose of this study was to investigate age-specific spontaneous fetal loss rates of pregnancies without known chromosomal or structural abnormalities from mid-second trimester onward. The study consisted of 264,653 women screened between October 1995 and September 2000 with available pregnancy outcomes. Pregnancies associated with fetal chromosomal or structural abnormalities, insulin dependent diabetes mellitus, and multiple pregnancies were excluded. Spontaneous fetal losses at or after 15 weeks of gestation were identified. Women were grouped according to maternal age at expected date of delivery. Spontaneous fetal loss rates in each group were evaluated after adjusting fetal losses associated with amniocentesis and identifiable ethnic groups. Fetal loss rates increased in both younger and older women. The lowest rate was seen in women at mid-20s. Compared with Caucasian and Asian women, black women had higher fetal loss rate at nearly every age group. The results of the study provided a baseline age-specific spontaneous fetal loss rate of pregnancies at a specified gestational window.

Major histocompatibility antigen expression on the bovine placenta: its relationship to abnormal pregnancies and retained placenta

In viviparous animals, regulation of expression of major histocompatibility complex (MHC) class I antigens by the trophoblast cells, which constitute the outermost layer of the placenta, seems to be critical for maternal immunological acceptance of an allogeneic fetus. Cattle are unusual in this regard, since the bovine trophoblast cells, in specific regions of the uterine/placental interface, normally express MHC class I antigens during the third trimester of gestation. This expression appears to be biologically relevant as MHC class I compatibility between a cow and her fetus has been associated with an increased incidence of placental retention. We have found significant differences in lymphocyte populations, cytokine production, and trophoblast cell apoptosis in the placentomes of MHC-compatible and -incompatible pregnancies at parturition. This suggests that maternal immunological recognition of fetal MHC class I proteins triggers an immune/inflammatory response that contributes to placental separation at parturition in cattle. Early in pregnancy, a complete shutdown of MHC class I expression by trophoblast cells appears to be critical for normal placental development and fetal survival. In bovine somatic cell nuclear transfer (SCNT) pregnancies, there is an extremely high rate of fetal loss between days 30 and 90 of pregnancy. We have shown that in bovine SCNT pregnancies, between days 34 and 63 of gestation, there is both abnormal expression of MHC class I antigens by trophoblast cells and an abnormal accumulation of lymphocytes within the uterine stroma. Consequently, it is likely that activation of the maternal mucosal immune system, within the uterus at the same time when placentomes are being established, interferes with the process of placentome development and leads to immune-mediated abortion. Our data suggest that bovine MHC-compatible pregnancies provide a unique model for studying regulation of the uterine immune system, as well as immune-mediated placental rejection.

Pediatric paradox: heterogeneity in the birth cohort.

Comparisons of birth-weight-specific infant mortality indicate that low-birth-weight African American infants have lower mortality than low-birth-weight European American infants despite higher infant mortality overall-the "pediatric paradox." One explanation is heterogeneity in birth weight. Analyses of African American and European American births suggest that birth cohorts consist of two heterogeneous subpopulations. One appears to account for normal births, whereas the other may consist of compromised births. Estimates of infant mortality indicate that the compromised subpopulation has higher overall mortality but lower birth-weight-specific mortality. We attribute lower birth-weight-specific infant mortality in the compromised subpopulation to higher rates of fetal loss. Compared to European American birth cohorts, African American birth cohorts have (1) higher birth-weight-specific mortality in the normal subpopulation, (2) larger compromised subpopulations, and (3) lower birth-weight-specific mortality in the compromised subpopulation. Consequently, the pediatric paradox is attributable to greater rates of compromised pregnancies and higher fetal losses among African Americans.

Anti-idiotype immunomodulation of experimental anti-phospholipid syndrome via effect on Th1/Th2 expression.

Mice with experimental anti-phospholipid syndrome (APS), induced by active immunization with a human anti-cardiolipin MoAb (H-3), were treated with mouse anti-idiotypic MoAb (anti-H3, named S2.9) and with an irrelevant anti-idiotype. The immunized mice produced high titres of mouse anti-cardiolipin antibodies along with clinical manifestations of experimental APS: prolonged activated partial thromboplastin time (aPTT), thrombocytopenia and high rate of fetal loss. Treatment with the specific anti-Id (S2.9) as a whole molecule or F(ab)2 fraction, resulted in a decrease in serum levels of the anti-cardiolipin antibodies, rise in platelet count, shortened aPTT and reduced rate of fetal loss. The anti-Id effect was associated with a rise in the number of IL-2 and interferon-gamma (IFN-gamma)-secreting cells (Th1) and reduction in IL-4- and IL-6-secreting cells (Th2). The beneficial effect of the anti-Id treatment in mice with experimental APS induced by active immunization with an idiotype further supports the idiotypic aetiology of experimental APS and points to the role of Th1 cytokines in suppression of its manifestations.

In utero therapy for lower urinary tract obstruction.

Lower urinary tract obstruction has a significant impact on neonatal and child health. Pulmonary hyperplasia and renal impairment could be direct or indirect consequences of this condition leading to significant morbidity and mortality. Evaluation of fetuses with suspected lower urinary tract obstruction is performed not only to confirm the diagnosis but also to assess renal prognosis. Ultrasound examination and urinary analysis aid in the evaluation of these fetuses. The decision to perform fetal intervention in these cases is a difficult one. Vesico-amniotic fetal shunting, open fetal surgery and more recently endoscopic fetal surgery for this condition are available as possible modalities of fetal intervention. Case selection for fetal intervention is extremely important in order to both avoid unnecessary intervention in those unlikely to survive, and also to avoid procedure related complications in fetuses likely to do well without intervention. Vesico-amniotic shunting has the advantage of bypassing the obstruction, however it is often associated with complications. Open fetal surgery is not usually recommended because of the complications and high fetal loss rate. Endoscopic surgery to visualise and treat the cause of lower urinary tract obstruction has been tried. Fetal endoscopic surgery is in its infancy and endoscopic procedures are limited to a few groups. This current review addresses evaluation, case selection and therapeutic options for lower urinary tract obstruction in utero. It also discusses the limited data against which the efficacy of the various options can be assessed. The current state of fetal intervention is detailed in the present review.

Twin-to-twin transfusion syndrome: treatment by amniodrainage and septostomy

Objective: Severe previable twin-to-twin transfusion syndrome (TTTS) is associated with a high fetal loss rate and is therefore usually treated. In this paper, serial amniodrainage and inter-twin septostomy are reviewed in terms of technical aspects and fetal outcome. Study design: A review of the literature using a MEDLINE DATA search between 1990 and 2000 was done in order to describe the mechanisms and technical aspects of both procedures with their physiopathological consequences. In addition, data from our experience with septostomy are given. Results: Amniodrainage increases survival rate, with outcome ranging from 40 to 87% (mean: 56%). Inter-twin septostomy is associated with a mean fetal survival rate ranging from 57 to 83% (mean: 70%). Conclusion: In severe TTTS, amniodrainage and septostomy are simple therapeutic alternatives with a survival rate similar to what is currently reported for laser coagulation of placental vessels.

Outcomes of 17,137 pregnancies in 2 urban areas of Ukraine.

Frequent terminations of pregnancy and high rates of fetal loss have been reported, but not confirmed, in the former eastern bloc. A census of pregnancies in Ukraine, a former eastern bloc country, was conducted to determine the rates of these events. All pregnancies registered in 2 urban areas were enumerated. During a 19-month period between 1992 and 1994, 17,137 pregnancies and their outcomes were recorded. Sixty percent of the pregnancies were voluntarily terminated, generally before the 13th week. In pregnancies delivered at 20+ weeks, fetal mortality was 29 per 1000, nearly 5 times the rate among Whites in the United States. There was a greater proportion of very early deliveries (20-27 weeks) in Ukraine, as well as higher death rates at all gestational ages. Perinatal mortality was estimated to be 35 per 1000, about 3 times the US rate. This is believed to be the first study in the former eastern bloc to ascertain all of the clinically recognized pregnancies in a specified period and to determine their outcomes. The data document elevated reproductive risks in a former Soviet state.

The ecology of low natural fertility in Ladakh.

The existence of very low rates of fertility among non-contracepting human populations has intrigued researchers in demography and reproductive ecology. Long inter-birth intervals, driven primarily by the lactational amenorrhoea associated with breast-feeding, have been shown to be important determinants of low natural fertility in several populations. Other reports have suggested that sterility brought about by sexually transmitted diseases (STDs) might also explain low fertility in some populations, especially in Africa. This report presents an analysis of 1981 Indian census data that documents low natural fertility in Ladakh, a high-altitude region of the Himalaya in north India. In Ladakh, there is evidence for low rates of marriage among women that may be attributable to the practice of polyandry, but also high rates of primary and secondary sterility within marriage, resulting in low completed parities for post-reproductive age married women. Age-specific fertility rates derived from the number of current births are also unexpectedly low. Hypotheses to explain very low fertility in Ladakh are considered from among the likely proximate determinants and evaluated using two supplementary sources of information derived from fieldwork in Ladakh in the early 1990s. The most likely explanations for low marital fertility include sterility from STDs, high rates of fetal loss, and possibly nutritional contraints on ovarian hormone status.

First-Trimester Multifetal Pregnancy Reduction: Evaluation of Technical Aspects and Risks from 2,756 Cases in the Literature

Objective: To evaluate the technical aspects, efficacy and safety of first-trimester multifetal pregnancy reduction in the management of multifetal pregnancies, an analysis of the international literature on first-trimester multifetal pregnancy reduction was made. Materials: Thirty-three studies were selected from an international review of the literature. Total fetal loss rate, risk of fetal loss after the procedure with the different techniques and gestational age at delivery were the main parameters studied. The Kruskal-Wallis test and Mann-Whitney test were used for statistical analysis. Results: 2,756 multifetal pregnancy reductions were performed (2,145 transabdominal, 363 transcervical, and 248 transvaginal procedures). Total fetal loss rates were different: 16.7% for the transabdominal, 24.8% for the transcervical and 10.9% for the transvaginal procedure (p = 0.03). The risk of fetal loss was 12% for the transabdominal, 20% for the transcervical, and 10% for the transvaginal approach at less 24 weeks of gestation (p = 0.04). There was no difference for the gestational age at the time of the procedure, the initial and final number of embryos, and the gestational age at delivery. Conclusion: Because the transvaginal approach seems to be the safer procedure, surgeons may opt for it. The transcervical approach has a high fetal loss rate and should be excluded.

The hidden mortality of monochorionic twin pregnancies.

In an ultrasound screening study at 10 to 14 weeks of gestation for measurement of fetal nuchal translucency thickness there were 102 monochorionic and 365 dichorionic twin pregnancies. In the monochorionic compared with the dichorionic pregnancies there was a higher rate of fetal loss before 24 weeks of gestation (12.2% versus 1.8%), perinatal mortality (2.8% versus 1.6%), prevalence of delivery before 32 weeks (9.2% versus 5.5%), and prevalence of birthweight below the 5th centile in both twins (7.5% versus 1.7%). However, the proportion of pregnancies with a birthweight discordancy of more than 25% was similar in the two groups (11.3% versus 12.1%).

Prednisone and Aspirin Don't Prevent Fetal Loss in Women with Autoantibodies

It is well known that women with antiphospholipid antibodies have a higher rate of fetal loss, but there is no proven way to prevent it. This trial

Variable effects on murine pregnancy of immunoglobulin G fractions from women with antiphospholipid antibodies

OBJECTIVE: Initial studies showed that passive immunization with human immunoglobulin G fractions containing antiphospholipid antibodies can result in murine fetal loss. We intended to use the murine model to study mechanisms of fetal loss associated with antiphospholipid antibodies. However, we have since found variable effects of antiphospholipid antibodies on murine pregnancy. The objective of this study was to determine the consistency of murine pregnancy loss from antiphospholipid antibody containing immunoglobulin G fraction. STUDY DESIGN: Pregnant C3H/HeN (mated with C57B1/6 males) and BALB/c (mated with BALB/c males) mice were passively immunized with antiphospholipid antibody containing human immunoglobulin G fraction from 20 women with antiphospholipid syndrome. The mice received either a single dose of 10 to 30 mg on day 12 of pregnancy or 10 mg per day on days 12 to 14 of gestation. Some mice receiving each dose of immunoglobulin G fraction were bled to confirm serum levels of anticardiolipin antibodies. Mice were killed on day 15 and the fetal status was determined. RESULTS: Overall, passive immunization with individual antiphospholipid antibody containing immunoglobulin G fractions resulted in 801 live pups (75%), 232 fetal deaths (22%), and 38 resorptions (3%) in 131 mice. The effect of immunoglobulin G fractions from individual patients was highly variable. Immunoglobulin G fraction from eight women resulted in high rates of fetal loss. However, in spite of high levels of anticardiolipin antibodies, fetal outcome was normal in mice immunized with immunoglobulin G fraction from the majority of women. The rate of fetal death did not uniformly increase with increasing doses of immunoglobulin G fraction and was unrelated to the donor's medical history. Fetal outcome was similar for both C3H/HeN and BALB/c mice. CONCLUSIONS: Human antiphospholipid antibodies have variable effects on murine pregnancy outcome. Characterization of antiphospholipid antibodies that do and do not cause murine fetal loss may provide insight into epitopes relevant to fetal loss associated with antiphospholipid syndrome.(Am J Obstet Gynecol 1997;177:229-33)

Uterine rupture and scar dehiscence. A five-year survey.

A review of the medical records from two public hospitals in Sydney was undertaken to determine the incidence of this uncommon complication. Twenty-seven cases of uterine rupture were reported out of 31,115 deliveries with an incidence of 0.086% (versus 0.05% in the current literature). The incidence associated with previous caesarean section was 0.038% (versus 0.8% in the current literature). Predisposing and associated factors in this review were similar to those reported by others. There was no maternal mortality in our series but the fetal mortality rate was 5 out of 27 cases. Uterine ruptures in the midtrimester were associated with high rates of maternal morbidity and fetal loss. Forty-eight per cent of patients with uterine rupture received epidural analgesia. The associated factors and outcomes are discussed. The current literature is reviewed in relation to this high-risk group of patients.

High prospective fetal loss rate in untreated pregnancies of women with recurrent miscarriage and antiphospholipid antibodies

Antiphospholipid antibodies (APA), lupus anticoagulant (LA) and/or anticardiolipin antibodies (ACA), are associated with thrombosis and recurrent miscarriage. We studied the outcome of 20 pregnancies in women (median age 32 years; range 23-41) with APA (14 LA positive; three immunoglobulin (Ig) G ACA positive; two IgM ACA positive and one LA and IgG ACA positive) and history of recurrent miscarriage (median 4; range 3-11) who declined pharmacological treatment in their next pregnancy. Comparison was made with a cohort of 100 consecutive women (median age 33 years; range 23-44) with recurrent miscarriage (median 4; range 3-10), in whom no underlying cause to account for their pregnancy losses was found. Of the 20 women with APA, 18 (90%) miscarried compared to 34 of the 100 women (34%) with normal investigations (P < 0.001). The majority (94%) of miscarriages in women with APA occurred in the first trimester. Fetal heart activity was seen prior to fetal death in 86% of women with APA compared to 43% of women with normal investigations (P < 0.01). The first trimester loss of embryonic pregnancies is the most common type of miscarriage in women with APA. This may be a result of defective implantation and subsequent placentation.