Risk Of Fetal Loss Research Articles

Epidemiologic Approaches for Measuring and Understanding Abortion in Dairy Cows

This paper offers methods for measuring abortion risk and undertaking abortion diagnostic investigations. In addition, some of the associations found between demographic and reproductive features of the dam and subsequent abortion are described. The cohort life table method is used to compute risk of fetal loss (abortion) for pre-defined time intervals (eg. days or weeks) during the gestation period, as well as overall proportion of cows that abort. In contrast, the abortion density method calculates abortion risk for a defined calendar time (eg. per month) as the number of abortions per cowdays- at risk. Both methods are standardized to account for the changing number of cows at risk of abortion, as a result of culling, death, abortion, and calving. Thus, both methods will produce higher and more realistic estimates for abortion risk than are typically calculated. These measures and statistical modeling have been used to estimate the expected magnitude of abortion for dairies (ranging from 8% to 19%) and to identify associations between demographic or reproductive features of the dam and subsequent risk of abortion. Some factors discussed are effects of a previous abortion, dam gravidity and age, days open at time of conception, and season. Analytic methods also are presented for herd-based diagnosis of abortion related to infectious agents or other exposures. These methods permit estimates of the risk, or proportion, of abortions attributable to exposure to an infectious agent or to other putative abortifacient agents.

P10.30: Low risk of fetal loss and complications following genetic amniocentesis: experience on 942 cases

P10.30: Low risk of fetal loss and complications following genetic amniocentesis: experience on 942 cases

Outcomes of pregnancy in women with tetralogy of fallot

ObjectivesWe sought to determine pregnancy outcomes in patients with tetralogy of Fallot (TOF). BackgroundPregnancy outcomes in patients with TOF are incompletely defined. MethodsClinical, hemodynamic, and obstetric data were reviewed for women with TOF and prior pregnancy. ResultsOf 72 respondents, 43 (mean age, 26 years) had 112 pregnancies (range, 1 to 5); 82 pregnancies were successful. Eight women had unrepaired TOF at the time of their 20 successful pregnancies. At first assessment (age ≥18 years), six patients had pulmonary hypertension, three had moderate or severe right ventricular (RV) systolic dysfunction, and 13 had severe RV dilation due to pulmonic regurgitation. Sixteen patients had 30 miscarriages (27%) and one term stillbirth. Mean overall birth weight was 3.2 kg (range, 2.1 to 4.2 kg). Unrepaired TOF (p = 0.05) and morphologic pulmonary artery abnormality (p = 0.03) were independently predictive of infant birth weight. Six patients had cardiovascular complications during pregnancy: supraventricular tachycardia in two, heart failure in two, pulmonary embolism in a patient with pulmonary hypertension, and progressive RV dilation in a patient with severe pulmonic regurgitation. Five infants (6%) had congenital anomalies. ConclusionsPatients with TOF have an increased risk of fetal loss, and their offspring are more likely to have congenital anomalies than offspring in the general population. Adverse maternal events, although rare, may be associated with left ventricular dysfunction, severe pulmonary hypertension, and severe pulmonic regurgitation with RV dysfunction.

Analyse génétique du fœtus à partir du sang maternel

Circulating fetal DNA in maternal plasma and serum was first demonstrated by Lo et al. in 1997 and has become a useful tool for prenatal diagnosis less than five years later. There is more and more evidence that the trophoblastic cells act as the major source of this circulating fetal DNA. Contrary to fetal cells analysis in maternal blood which requires isolation and enrichment procedures, fetal DNA analysis is relatively easy to perform with the use of real-time PCR. Non-invasive fetal sex and fetal RHD genotype determination are, to date, the two main clinical indications. Those newly offered possibilities have changed the management of pregnant women who are carriers for X-linked genetic disorders; prenatal diagnosis by choriovillous sampling could only be performed for male fetuses avoiding an unnecessary risk of fetal loss for female fetuses. Moreover, fetal RHD genotyping by maternal blood analysis could be useful in RhD-negative women at risk of immunization in order to adapt prophylactic anti-D injection.

Doppler Ultrasonography in Assessment of Fetal Well-being

After completing this article, readers should be able to: 1. Describe the calculations used to measure fetal systemic and placental vascular impedance in the umbilical artery via Doppler ultrasonography. 2. Delineate the two primary uses of measurement of middle cerebral artery flow velocity. 3. List the fetal conditions in which Doppler flow velocity has been studied. The Doppler principle, discovered by Johann Christian Andreas Doppler in 1842, (1) was used initially in astronomy and later in the military, in various branches of industry, and more recently in medicine. Doppler shift is based on the perceived change in frequency of an energy waveform as the source and the receiver move toward or away from each other. The Doppler shift principle applies to light waves as well as sound waves. In biology, Doppler ultrasonography is used noninvasively, primarily to measure flow velocity in blood vessels. Flow velocity depends on the volume and speed of effluent relative to the diameter of the vessel. Estimating fetal vascular resistance through study of Doppler flow velocity provides a means to assess, albeit indirectly, fetal physiology and pathology. Johnson and colleagues (2) in 1965, made the earliest mention of the use of Doppler effect in obstetrics. The use of Doppler ultrasonography to investigate the pattern of waveforms in the umbilical artery during pregnancy initially was reported in 1977 by Fitzgerald and Drumm. (3) Subsequently, Wladimiroff and associates (4) reported on Doppler assessment of cerebral blood flow in the human fetus. The addition of color mapping has enhanced the utility of the Doppler effect in sonographic assessment of the fetus. The fetal umbilical artery (UA) and middle cerebral artery (MCA) have evolved as the primary targets of fetal Doppler studies (Figs. 1 and 2). Figure 1. Color Doppler view of circle of Willis. Arrows show anterior (ACA), middle (MCA), and posterior cerebral …

Pregnancy and pre-existing diabetes: key concerns.

Women with pre-existing diabetes in pregnancy are at increased risk of fetal loss, fetal congenital anomaly and abnormal fetal growth. Obstetric complications are more likely and good peripartum care is essential. This article also considers preconceptual counselling which may minimize these risks.

Hereditary thrombophilia and fetal loss: a prospective follow-up study

As the placental vessels are dependent on the normal balance of procoagulant and anticoagulant mechanisms, inherited thrombophilia may be associated with fetal loss. We performed a prospective study to investigate the relation between inherited thrombophilia and fetal loss, and the influence of thromboprophylaxis on pregnancy outcome. Women were enrolled in the European Prospective Cohort on Thrombophilia (EPCOT). These included women with factor (F)V Leiden or a deficiency of antithrombin, protein C or protein S. Controls were partners or acquaintances of thrombophilic individuals. A total of 191 women (131 with thrombophilia, 60 controls) had a pregnancy outcome during prospective follow-up. Risk of fetal loss and effect of thromboprophylaxis were estimated by frequency calculation and Cox regression modelling. The risk of fetal loss appeared slightly increased in women with thrombophilia without a previous history of fetal loss who did not use any anticoagulants during pregnancy (7/39 vs. 7/51; relative risk 1.4; 95% confidence interval 0.4, 4.7). Per type of defect the relative risk varied only minimally from 1.4 for FV Leiden to 1.6 for antithrombin deficiency compared with control women. Prophylactic anticoagulant treatment during pregnancy in 83 women with thrombophilia differed greatly in type, dose and duration, precluding solid conclusions on the effect of thromboprophylaxis on fetal loss. No clear benefit of anticoagulant prophylaxis was apparent. Women with thrombophilia appear to have an increased risk of fetal loss, although the likelihood of a positive outcome is high in both women with thrombophilia and in controls.

Analysis of fetal blood cells in the maternal circulation: challenges, ongoing efforts, and potential solutions.

The invasive procedures amniocentesis and chorionic villus sampling (CVS) are routinely applied in pregnancies at risk for fetal abnormalities and the results obtained are the gold standard for prenatal diagnosis. Because these methods of fetal cell procurement involve a 0.5-2% risk for fetal loss, they are recommended mainly in cases at high risk for fetal genetic or cytogenetic abnormalities. The development of a reproducible, reliable, noninvasive method based on retrieval of rare fetal cells from the maternal circulation will render testing feasible for the general population. Despite intensive investigation, a satisfactory, clinically acceptable method has not yet emerged. Several cell types have been targeted to this end, mostly nucleated red blood cells (NRBC), CD34+ hematopoietic progenitors, and trophoblasts. Although these cell types have been unequivocally proven to be present in the maternal circulation, each bears a significant disadvantage, rendering their application in clinical testing currently impossible: NRBC cannot be expanded in culture, thereby ruling out metaphase chromosome analysis, an essential component of prenatal diagnosis. CD34+ cells do posses the potential for in vitro proliferation, however, they have been found to persist in the maternal circulation after delivery, thereby complicating diagnosis in consecutive pregnancies. Trophoblasts are not consistently detected in the maternal circulation. Moreover, due to the lack of a definitive fetal cell marker and a reliable sorting method, foolproof fetal cell identification of any of these cell types is not possible. This report outlines the obstacles that impede development of a method for noninvasive fetal cell sampling for prenatal genetic diagnosis, along with a description of our efforts to analyze simultaneously two fetal blood cell types, NRBC and CD34+ cells in maternal blood during pregnancy, and the problems encountered. This work and that of others lead us to suggest potential future directions to help develop this important technique.

The Biology and Diagnostic Applications of Fetal DNA and RNA in Maternal Plasma

Abstract As conventional methods for prenatal diagnosis, such as amniocentesis and chorionic villus sampling, are associated with a risk of fetal loss, the pursuit of safe noninvasive alternatives has been a long-sought goal in medicine. The discovery of the presence of extracellular fetal nucleic acids in the maternal circulation has offered new avenues for the realization of this goal. The number of potential applications of fetal nucleic acids analysis from maternal plasma has grown substantially in recent years. Noninvasive prenatal rhesus D genotyping has been introduced into routine use by some centers. Although certain limitations are preventing the wider adoption of circulating fetal nucleic acids analysis for clinical use, promising developments with the potential to overcome the present limitations have emerged recently. Albeit the rapid growth in the number of potential applications, much work is required to elucidate the little-known physiological mechanisms of circulating fetal nucleic acid release and clearance. Furthermore, in recent years, there is a greater appreciation of the impact of certain technical factors on the interpretation of research data on circulating fetal nucleic acids. Further rapid development in this emerging area is expected over the next few years.

Maternal thrombophilias are not associated with early pregnancy loss.

We investigated the association between inherited and acquired maternal thrombophilias and adverse pregnancy events. A cohort of 491 patients with a history of adverse pregnancy outcomes was evaluated for activated protein C resistance, factor V Leiden and prothrombin G20210A mutations, hyperhomocysteinemia, deficiencies of antithrombin, protein C and S and both anticardiolipin antibodies and lupus anticoagulants. The study had an 80% power to detect a 15% difference in the prevalence of thrombophilia for 1(st) trimester loss. In our high-risk cohort the presence of 1 maternal thrombophilia or more than one thrombophilia were found to be protective of recurrent losses at < 10 weeks (1 thrombophilia: OR: 0.55, 95% CI: 0.33-0.92; > 1 thrombophilia: OR: 0.48, 95%CI:0.29-0.78). In contrast, the presence of maternal thrombophilia(s) was modestly associated with an increased risk of losses > 10 weeks (1 thrombophilia: OR:1.76, 95%CI: 1.05-2.94, >1 thrombophilia: OR:1.66, 95%CI:1.03-2.68). Women who experienced only euploid losses were not more likely to have an identified thrombophilia than women who experienced only aneuploid losses (OR 1.03; 0.38-2.75). The presence of maternal thrombophilia was associated with an increased risk of fetal loss after 14 weeks, fetal growth restriction, abruption and preeclampsia. There was a significant "dose-dependent" increase in the risk of abruption (OR:3.60, 95%CI: 1.43-9.09) and preeclampsia (OR:3.21, 95%CI:1.20-8.58). In conclusion, these data indicate maternal thrombophilias are not associated with pregnancy wastage prior to 10 weeks of gestation.

Should prenatal diagnostic testing be offered to all pregnant women on economic grounds?

In many industrialised nations, women who are identified as at risk for fetal Down's syndrome or other chromo-somal abnormalities, by a combination of epidemiological risk factors (eg, age or family history) and test results (eg, serum screening), are counselled and offered fetal karyo-typing. Fetal karyotyping is an invasive diagnostic test based on culture and examination of fetal cells obtained by amniocentesis or chorionic villus sampling. The technique helps parents to make informed choices about the course of the pregnancy, but does carry an increased risk of fetal loss.

Intérêt du génotypage du sexe fœtal dans le sang maternel dans les indications de diagnostic génétique préimplantatoire de sexe

Objective. – Couples with a risk of transmitting X-linked diseases included in a preimplantation genetic diagnosis (PGD) center need early and rapid fetal sex determination during pregnancy in two situations. The first situation corresponds to control of embryo sexing after PGD, the second one being that of couples in PGD program having a spontaneous pregnancy. Determination of fetal sex can be achieved by karyotyping using invasive procedures such as chorionic villus sampling (CVS), amniocentesis or cordocentesis and by non-invasive procedures such as ultrasound (US) examination. CVS is the earliest invasive procedure for fetal sex determination and molecular analysis of X-linked genetic disorders during the first trimester but it is associated with a risk of fetal loss. US allows reliable fetal sex determination only during the second trimester. Recently, reliable non-invasive fetal sex determination was realized by using SRY gene amplification in maternal serum. Patients and methods. – We report the prospective use of fetal sex determination in maternal serum in our PGD center. Management of pregnancies was performed using this non-invasive procedure in four cases of embryo sexing control and nine cases of spontaneous pregnancies in couples included in PGD program for X-linked diseases. Results. – Fetal sex results using SRY gene amplification on maternal serum were in complete concordance with fetal sex observed by cytogenetic analysis or US examination, as well as at birth. Discussion and conclusion. – This new strategy allowed rapid sex determination during the first trimester and permitted to avoid performing invasive procedures in nine pregnancies.

Traumatisme de la rate au cours de la grossesse (à propos d’un cas)

Splenic injury during pregnancy after blunt abdominal trauma is rare. The physiological and anatomical changes during pregnancy modify the clinical, biological and radiological signs. The authors report a case of a 30-year-old-woman in the 32nd week of pregnancy, with an isolate splenic injury after a motor vehicle accident. Splenectomy was realised 4 days after an initial decision of abstaining from surgery. In pregnancy, the frequency of recurrent bleeding, the possibility of concomitant uterine injuries and the risk of foetal loss should modify the surgeon’s attitude to splenic rupture after abdominal blunt trauma.

Probing the fetal genome: progress in non-invasive prenatal diagnosis

Progress in our understanding of the molecular basis of heritable diseases, through identification of specific mutations, has provided a foundation for the development of DNA-based prenatal diagnosis. Genetic analysis of fetal DNA is now routinely performed from chorionic villus samples obtained as early as the tenth week of gestation or by amniocentesis from week 15 onwards. However, both of these approaches involve invasive procedures with increased risk of fetal loss. To avoid such complications, attempts have been made to develop non-invasive tests through the identification, characterization and isolation of fetal cells or free fetal DNA from the maternal circulation. Recently, progress has been made towards the development of novel strategies that are expected to provide non-invasive means for early prenatal diagnosis in pregnancy.

Pituitary tumors and pregnancy.

Tumors vary in how they affect pregnancy depending upon the hormone secreted. Some hormone oversecretion syndromes must be controlled to allow pregnancy to proceed without undue maternal and fetal morbidity (Cushing's disease and hyperthyroidism) whereas treatment during pregnancy for other tumors is not necessary. Surveillance for tumor growth during pregnancy is necessary primarily for prolactinomas. A literature search was conducted to identify the effects of pregnancy on pre-existing pituitary tumors and the effects on the outcome of pregnancy due to hormone oversecretion by pituitary tumors. Results show that hyperprolactinemia and Cushing's disease may interfere with fertility and usually need to be controlled to allow for conception. Cushing's syndrome, acromegaly and hyperthyroidism secondary to hypersecretion of thyroid-stimulating hormone (TSH) may increase maternal morbidity (gestational diabetes, hypertension) and fetal morbidity and mortality. Intervention is warranted to remove a tumor that secretes adrenocorticotropic hormone (ACTH) during pregnancy to reduce the risk of fetal loss and to control hyperthyroidism. In contrast, surgery or medical therapy for adenomas that secrete growth hormone (GH) and for clinically nonfunctioning adenomas is not indicated during pregnancy. Pregnancy may cause an increase in the size of tumors that secrete prolactin (PRL), especially macroadenomas, so close surveillance is indicated and re-institution of bromocriptine therapy may be necessary to treat such an increase in tumor size. An increase in the size of other types of tumors during pregnancy is very rare.

Techniques de prélèvements fœtaux

This article describes the current techniques of foetal sampling. All of them are actually ultrasound guided, and therefore generally very safe. Nevertheless, an elaborate learning process remains indispensable, in addition to a particular attention to the quality of the physician–patient dialogue. The choice of a technique depends on the indication and on the term of the pregnancy. The most frequently used technique is amniocentesis which presents a low risk of foetal loss, estimated between 0.2 and 0.5 percent. The interest of chorionic villus sampling is the possibility to obtain results at an earlier stage of pregnancy, with a lower risk taking when compared to early amniocentesis. We prefer the transabdominal chorionic villus sampling to the transvaginal. Foetal blood sampling is still required in some cases, but the risk of complications is higher – around 1 percent.

Fetal expressed gene analysis in maternal blood: a new tool for noninvasive study of the fetus.

Noninvasive approaches to prenatal diagnosis can avoid the risk of fetal loss associated with invasive procedures such as chorionic villus sampling, amniocentesis, and cordocentesis. Isolation of fetal cells from maternal blood requires further improvements before it can be applied in a clinical setting (1), but the reliability of cell-free fetal DNA analysis in maternal plasma or serum is now well established (2)(3)(4). As a result, it is currently used in specialized centers for the determination of fetal sex and fetal RhD status for the management of pregnant women at risk for X-linked disorders (5) or RhD alloimmunization (6). Because fetal DNA in maternal serum is circulating in an excess background of maternal DNA, clinical applications are restricted mainly to the detection of fetal sequences distinct from the mother’s DNA sequences. Fetal RNA in maternal blood may be an alternative source of fetal nucleic acids. Al-Mufti et al. (7) detected specific RhD mRNA in mononuclear fetal cells isolated from blood of RhD-negative pregnant women, and Lo’s group demonstrated the presence of Y-chromosome-specific ( ZFY ) mRNA in maternal plasma of women carrying a male fetus (8). These two applications, however, again require fetal sequences that differ from the mother’s. We have investigated the presence in maternal blood of fetal transcripts that may have the same sequence as that of the mother. Human chorionic gonadotropin (hCG) mRNA is a good candidate because it is a pregnancy-specific polypeptide hormone produced by the placenta and is specifically expressed in the fetal syncytiotrophoblast. We studied 43 pregnant women and 20 nonpregnant women who had previously given birth to at least one neonate. After receiving informed consent, we collected blood (2.5 mL) into PAXgeneTM tubes to reduce RNA degradation (9). All pregnancy samples were obtained before …

Risk of Amniocentesis in Women Screened Positive for Down Syndrome With Second Trimester Maternal Serum Markers

Muller, Françoise; Thibaud, Didier; Poloce, Françoise; Gelineau, Marie-Christine; Bernard, Marguerite; Brochet, Christine; Millet, Christine; Réal, Jean-Yves; Dommergues, Marc

Non-invasive prenatal diagnosis: on the horizon?

The launch of the genomics and postgenomics era has greatly expanded our understanding of the genetic basis of many diseases. In conjunction with the sociocultural trend to delay childbirth and to maintain smaller family units, extra demand may be placed on the existing prenatal diagnostic services. The inherent risk of fetal loss associated with current prenatal diagnostic procedures, such as amniocentesis and chorionic villus sampling, has spurred research into non-invasive prenatal diagnosis. Much research has been conducted on the exploitation of fetal genetic material present in the maternal circulation. The initial focus was on the isolation of intact fetal cells and subsequently, the existence of extracellular fetal DNA in maternal plasma was realized. Exciting developments have been achieved in recent years. A large-scale trial to evaluate the clinical utility of fetal cell isolation from maternal blood for fetal aneuploidy diagnosis was launched and data were recently published. Much has taken place in the research of fetal DNA analysis in maternal plasma and in one example, namely prenatal RhD determination, this type of analysis has been used in the clinical setting. This paper reviews the technological developments in non-invasive prenatal diagnosis.

Prenatal genetic testing by amniocentesis appears to result in a lower risk of fetal loss than chorionic villus sampling in singleton pregnancies achieved by intracytoplasmic sperm injection

ObjectiveTo compare pregnancy outcome after prenatal genetic testing by chorionic villus sampling (CVS) or amniocentesis in singleton pregnancies achieved by intracytoplasmic sperm injection (ICSI). DesignRetrospective analysis. SettingTertiary referral center. Patient(s)Eight hundred twenty-eight patients with singleton gestations achieved by ICSI. Intervention(s)Midtrimester amniocentesis (685 patients) and first-trimester CVS (143 patients). Main outcome measure(s)Fetal loss rate, preterm delivery rate, and proportion of babies born with low or very low birth weight. Result(s)A significant difference was observed in fetal loss rate between CVS and amniocentesis (3.7% vs. 0.9%, respectively). On the other hand, a similar preterm delivery rate was present between the two methods (11.2% vs. 12.4%, respectively). No significant difference was observed between amniocentesis and CVS in the proportion of babies with birth weight of either <1,500 g (1.8% vs. 3.8%, respectively) or between 1,500 and 2,500 g (8.2% vs. 4.6%, respectively). Conclusion(s)Amniocentesis appears to result in a lower risk of fetal loss as compared with CVS in patients with a singleton pregnancy achieved by ICSI.