Abnormal Placental Morphology Research Articles

Maternal Perception of Reduced Fetal Movements Is Associated with Altered Placental Structure and Function

BackgroundMaternal perception of reduced fetal movement (RFM) is associated with increased risk of stillbirth and fetal growth restriction (FGR). DFM is thought to represent fetal compensation to conserve energy due to insufficient oxygen and nutrient transfer resulting from placental insufficiency. To date there have been no studies of placental structure in cases of DFM.ObjectiveTo determine whether maternal perception of reduced fetal movements (RFM) is associated with abnormalities in placental structure and function.DesignPlacentas were collected from women with RFM after 28 weeks gestation if delivery occurred within 1 week. Women with normal movements served as a control group. Placentas were weighed and photographs taken. Microscopic structure was evaluated by immunohistochemical staining and image analysis. System A amino acid transporter activity was measured as a marker of placental function.Placentas from all pregnancies with RFM (irrespective of outcome) had greater area with signs of infarction (3.5% vs. 0.6%; p<0.01), a higher density of syncytial knots (p<0.001) and greater proliferation index (p<0.01). Villous vascularity (p<0.001), trophoblast area (p<0.01) and system A activity (p<0.01) were decreased in placentas from RFM compared to controls irrespective of outcome of pregnancy.ConclusionsThis study provides evidence of abnormal placental morphology and function in women with RFM and supports the proposition of a causal association between placental insufficiency and RFM. This suggests that women presenting with RFM require further investigation to identify those with placental insufficiency.

A case of confined placental mosaicism with double trisomy associated with stillbirth

We present a case of stillbirth in which the fetus was well grown and karyotypically normal, but the placenta was morphologically abnormal and had confined placental mosaicism (CPM) for a double trisomy of chromosomes 12 and 15. A compilation of published cases of CPM reveals that whilst approximately 80% of pregnancies progress normally, there is an association with abnormal placental morphology, intrauterine growth restriction, fetal abnormalities and stillbirth. This case highlights the potential adverse effects of CPM and the benefit of placental examination in determining the cause of stillbirth.

Transient reduction of placental angiogenesis in PAI-1-deficient mice

Murine placentation is associated with the invasion of maternal endometrium by trophoblasts and an extensive maternal and fetal angiogenesis. Plasminogen activator inhibitor-1 (PAI-1) is transiently produced by spongiotrophoblasts and trophoblast giant cells at 10.5-11.5 days postcoitum (dpc). Knowing the key contribution of PAI-1 in the regulation of angiogenesis, we have now analyzed the consequence of PAI-1 deficiency on murine placentation. Morphological and quantitative computer-assisted image analysis revealed abnormal placental morphology in PAI-1-/- mice at 10.5 and 12.5 dpc. At 10.5 dpc, the genetic ablation of PAI-1 resulted in a transient reduction of both maternal and fetal vascularizations in the placenta and increased trophoblast cell density. This was associated with a poorer development of the labyrinth and an extension of the decidua. A larger spongiotrophoblast layer appeared at 12.5 dpc in PAI-1-deficient mice. Placental morphology was normalized at 14.5 dpc. Microarray analyses performed on laser capture microdissected labyrinths revealed that 46 genes were differentially expressed between the two genotypes at 10.5 dpc. However, only 11 genes were still differently modulated at 14.5 dpc, when normalization of placental morphology had taken place. This transcriptomic profiling highlighted a dysregulation in the expression of placenta-related cathepsin family members. Altogether our data provide evidence for a transient impaired placental morphology in PAI-1-deficient mice that is then normalized, leading to normal embryonic development.

Congenital Toxoplasmosis: A Review of its Pathology, Immune Response and Current Treatment Options.

Toxoplasmosis, caused by the protozoan parasite Toxoplasma gondii, is one of the most common parasites of man and other warm-blooded animals. Humans are infected through contaminated food, water, and blood transfusion, organ transplantation or from mother to foetus through the placenta. Severe congenital infections occur as a result of primary T. gondii infection in early pregnancy. Transmission of T.gondii to the foetus can result in serious health problems, including mental retardation, seizures, blindness and death. Frequency of foetal infection is higher when maternal infection occurs later in pregnancy and sequelae are more severe when maternal infections occur early in the first trimester of pregnancy. The ability of the parasite to survive intracellularly largely depends on the blocking of different proapoptotic signaling cascades of the host cells. During pregnancy, however, alterations in the incidence of apoptosis are associated with abnormal placental morphology and function. Both cellular and humoral immune responses control T.gondii infection. Toxoplasma is asymptomatic, infected women can only be detected by serological testing. In many instances, congenital toxoplasmosis can be prevented by educating pregnant women and women of childbearing age about the route of transmission. The need for screening suspected cases of T. gondii will help reduce transmission to the foetus. Keywords: Toxoplasmosis, Congenital toxoplasmosis, Toxoplasmosis and immunosuppression. Toxoplasma gondii.

Apoptosis and S Phase of the Cell Cycle in BeWo Trophoblastic and HeLa Cells are Differentially Modulated by Toxoplasma gondii Strain Types

Transplacental transmission of Toxoplasma gondii causes congenital toxoplasmosis, one of the most severe forms of infection. The ability of the parasite to survive intracellularly largely depends on the blocking of different proapoptotic signaling cascades of the host cells. During pregnancy, however, alterations in the incidence of apoptosis are associated with abnormal placental morphology and function. The aim of this study was to evaluate the incidence of apoptosis and cell proliferation in trophoblastic (BeWo cell line) and uterine cervical (HeLa cell line) cells infected with a highly virulent RH strain or a moderately virulent ME49 strain of T. gondii. BeWo and HeLa cells were infected with RH or ME49 tachyzoites (2:1 and 5:1; parasite:cell) or medium alone (control). After 2 h, 6 h and 12 h of incubation, cells were fixed in 10% formalin and analyzed by immunohistochemistry to determine the apoptosis (expression of cytokeratin 18 neo-epitope – clone M30) and cell in S phase (expression of proliferating cell nuclear antigen – PCNA) indices. RH strain-infected BeWo and HeLa cells showed a lower apoptosis index than non-infected controls, whereas a higher apoptosis index was found in ME49 strain-infected cells compared to controls. In addition, RH-infected cells displayed lower apoptosis index than ME49-infected cells, even though active caspase-3 was detected in both cell types infected with either RH or ME49 strains as well in non-infected cells in all analyzed times of infection. Also, the cell S phase indices were higher in ME49 strain-infected BeWo and HeLa cells as compared to non-infected controls and RH strain-infected cells. These results indicate that RH and ME49 strains of T. gondii possess opposing mechanism of interference in apoptosis and cell cycle S phase of both BeWo and HeLa cells and these differences can be associated to evasion strategies of the parasite to survive inside the host cells.

22 VASCULAR ENDOTHELIAL GROWTH FACTOR mRNA EXPRESSION IN FETAL MEMBRANES DURING EARLY PREGNANCY AS A BIOMARKER FOR DEVELOPMENT OF HYDROPS PLACENTA LATER IN PREGNANCY IN BOVINE EMBRYOS CREATED THROUGH SOMATIC CELL NUCLEAR TRANSFER (SCNT)

Pregnancies obtained via somatic cell nuclear transfer (SCNT) show an increased incidence of pregnancy complications, including poor placental vascularization, hydrops placenta, and abnormal placental morphology. In a preliminary study of hydrops placentas from SCNT clones v. control cow placentas close to term, we observed a thickening of the endometrial epithelium, which appeared pseudostratified; in addition, the subepithelial endometrial vascular bed consisted of large, rare arterioles with thick basement membranes compared with the normal capillary bed observed in control animals. The fetal membranes of hydrops placenta from bovine SCNT clones also exhibited macroscopic morphological differences, which included edema, increased membrane thickness, and a gelatinous appearance. All of these morphological differences were similar to those we have reported for sheep SCNT clones (Palmieri et al. 2007 Placenta 28, 577–584). In the search for biomarkers that may indicate abnormal placental development early in pregnancy, placental tissues were collected on day 40 from pregnancies established after transfer of embryos created through SCNT (n = 17) or IVF (n = 6). Nuclear donor cells used to obtain SCNT embryos were those we have previously found to be highly susceptible to hydrops (from 5 to 19%), whereas the incidence of hydrops in IVF and controls in our laboratories did not exceed 0.5%. A sample of fetal membranes was fixed in 10% buffered formalin for histological analysis; another sample was snap-frozen in liquid nitrogen for analysis of mRNA levels for vascular endothelial growth factor (VEGF) and its receptors (KDR and FLT) by quantitative, real-time RT-PCR. Histological analysis of cell proliferation rate was performed using immunohistochemical localization of proliferating cell nuclear antigen and image analysis software (Image-Pro Plus). There were no differences (P = 0.39) in the rate of cell proliferation of the trophoblast in SCNT v. IVF (29.4 ± 4.9% v. 22.1 ± 3%). However, VEGF mRNA expression was less (P &lt; 0.04) in the fetal membranes of SCNT than IVF on day 40 of pregnancy (0.30 ± 0.04 v. 0.53 ± 0.12, normalized to α-actin mRNA levels). The mRNA expression for KDR and FLT were similar in SCNT and IVF. These data suggest that the lower expression of VEGF, a major placental angiogenic factor, in fetal membranes of early pregnant SCNT fetuses may be an early biomarker for the development of hydrops placenta later in pregnancy. NDAES Proj. ND01727.

ABSTRACTS: 2 Mouse PAI‐1 promotes placentation by increasing foetal and maternal angiogenesis

Introduction: Murine placentation is associated with trophoblast cells invasion of the maternal endometrium and extensive maternal and foetal angiogenesis. Both processes involve proteases‐dependent extracellular matrix remodelling. Among the protease inhibitors, plasminogen activator inhibitor‐1 (PAI‐1) is transiently produced by spongiotrophoblasts and trophoblast giant cells at days 10.5‐11.5 day post‐coitum (dpc). Although accumulating evidence demonstrates the key role of PA‐1 in pathological angiogenesis, its function during placental vascularisation remains to be elucidated. PAI‐1 knockout mice are fertile and the litter sizes are normal. We have therefore analysed the consequence of PAI‐1 deficiency on murine placentation.Material and Methods: We have studied the possible role of PAI‐1 by quantitating the placental vessel density, the relative thickness of the labyrinth, decidua and spongiotrophoblast at day 10.5, 12.5 and 14.5 dpc in mice deficient for PAI‐1 or in control mice. An original method of computer‐assisted image analysis allowed us to quantify alterations of several placental compartments identified with specific monoclonal antibodies (keratin, desmin, fibrinogen and MECA‐32). To investigate the differentially expressed genes, we performed laser capture microdissection (LCM), followed by genome‐wide expression profiling using high‐density oligonucleotides microarray analysis (GeneChip Mouse Genome 430 2.0 Array, Affymetrix). Data were analysed using Ingenuity Pathways Analysis (Ingenuity Systems®, http://www.ingenuity.com).Results: At 10.5 and 12.5 dpc, an abnormal placental morphology was observed in both labyrinth and spongiotrophoblast layers in PAI‐1‐/‐ mice. Lack of PAI‐1 resulted in a transient decreased maternal and fetal vascularisation of the placenta that caused (1) an enhancement in the decidua/labyrinth and labyrinth/spongiotrophoblast thickness ratios, (2) a significant increase of trophoblast density. Normalization of placental morphology occurred by day 14.5 dpc in PAI‐1 deficient mice. Statistical analysis of microarrays revealed 706 genes differentially expressed between PAI‐1 deficient and normal mice in the labyrinth zone at 10.5 dpc. At 14.5 dpc, only 205 genes are differentially expressed. Using Ingenuity Pathways Analysis, most of those genes were found to be associated to lipid metabolism, cellular growth and proliferation.Conclusion: Despite a transient PAI‐1 requirement for optimal placental angiogenesis, this gene does not appear to be essential for trophoblast invasion and placentation.

Ultrasound Detection of Placental Insufficiency in Women With Elevated Second Trimester Serum Alpha-Fetoprotein or Human Chorionic Gonadotropin

ObjectiveWe evaluated the role of placental morphology ultrasound and uterine artery Doppler in predicting adverse perinatal outcomes in women with unexplained elevated serum alpha-fetoprotein (AFP) or human chorionic gonadotropin (hCG) levels in the second trimester of pregnancy. MethodsWomen with a serum AFP > 2.0 MoM (n = 83) or serum hCG > 2.5 MoM (n = 68) had placental imaging at 19–23 weeks’ gestation. Abnormal placental morphology (i.e., a maximum thickness of > 4 cm or > 50%of length) and abnormal uterine artery Doppler [UTAD] (mean pulsatility index > 1.45) were related to placental complications of pregnancy. Relative risks were derived for all women. Likelihood ratios were derived for the subset (55/83) in the group with elevated AFP who had no medical and/or obstetrical risk factors. ResultsCompared with elevated serum hCG, an elevated serum AFP was associated with higher rates of perinatal mortality (15.6% vs. 4.3%), preterm birth at < 32 weeks’ gestation (26.5% vs. 7.3%), small-for-gestational age (SGA) birth weight < 10th centile (24.1% vs. 10.3%) and severe intrauterine growth restriction (IUGR) (8.4% vs. 2.8%). Thirty-seven (44.5%) women with elevated serum AFP had an adverse perinatal outcome, and 23 of these women (67%) had no prior medical and/or obstetric risk factors. Abnormal tests of placental function were more common in the elevated serum AFP group than in the hCG group (UTAD 30.1% vs. 11.6%; placental morphology 30.2% vs. 16.2%). Abnormal UTAD and abnormal placental morphology had similar positive likelihood ratios for a range of adverse perinatal events in the elevated AFP group (1.3–4.4) and were increased when both tests were abnormal (likelihood ratio 5.0 for preeclampsia, 4.5 for preterm delivery < 32 weeks, 4.9 for intrauterine fetal demise). In the elevated hCG group abnormal UTAD and abnormal placental morphology predicted SGA (likelihood ratios 5.2 and 4.9) and IUGR (likelihood ratios 4.7 and 7.3) but did not predict preeclampsia or preterm birth. ConclusionAssessment of placental function using either morphology or UTAD at 19–23 weeks’ gestation identifies a subset of women at increased risk of adverse perinatal events with an elevated serum AFP. These tests have more limited value in women with an elevated serum hCG because of the lower prevalence of adverse perinatal events.

Maternal diabetes affects specific extracellular matrix components during placentation

During embryo implantation, invasive trophoblast cells mediate embryo invasion into the decidualized stroma, forming a rich network of lacunae that connect the embryonic tissues to the maternal blood vessels. Placentation is probably guided by the composition and organization of the endometrial extracellular matrix. Certain pathological conditions that occur during pregnancy, including diabetes, have been linked to abnormal placental morphology and consequent fetal morbidity. We used immunoperoxidase techniques to identify members of the collagen, proteoglycan and glycoprotein families in the various compartments of the rat placenta and to determine whether experimentally induced diabetes affects placental morphology and alters the distribution of these molecules during pregnancy. Single injections of alloxan (40 mg kg(-1) i.v.) were used to induce diabetes on day 2 of pregnancy in Wistar rats. Placentas were collected on days 14, 17, and 20. Type I and III collagen, as well as the proteoglycans decorin and biglycan, were found to be distributed throughout the placentas of control and diabetic rats. In both groups, laminin expression decreased at the end of pregnancy. In contrast, fibronectin was detected in the labyrinth region of diabetic rats at all gestational stages studied, whereas it was detected only at term pregnancy in the placentas of control rats. These results show for the first time that some extracellular matrix molecules are modulated during placental development. However, as diabetic rats presented increased fibronectin deposition exclusively in the labyrinth region, we speculate that diabetes alters the microenvironment at the maternal-fetal interface, leading to developmental abnormalities in the offspring.

Pathophysiology of the Clinical Manifestations of Preeclampsia

Five to 7% of all pregnancies are complicated by preeclampsia. Proteinuria and hypertension dominate the clinical picture, because the chief target organ is the kidney (glomerular endotheliosis). The pathogenesis of preeclampsia is complex; numerous genetic, immunologic, and environmental factors interact. It has been suggested that preeclampsia is a two-stage disease (1). The first stage is asymptomatic, characterized by abnormal placental development during the first trimester resulting in placental insufficiency and the release of excessive amounts of placental materials into the maternal circulation. This in turn leads to the second, symptomatic stage, wherein the pregnant woman develops characteristic hypertension, renal impairment, and proteinuria and is at risk for the HELLP syndrome (hemolysis, elevated liver function enzymes and low platelets), eclampsia, and other end-organ damage. This review focuses on the pathophysiology of stages 1 and 2 and then considers the potential that changes in soluble angiogenic factors may underlie much of the disease process. On the basis of the observation that the only definitive cure for preeclampsia is delivery of the placenta and that women who experience a molar pregnancy, in which a placenta develops without a fetus, frequently develop severe preeclampsia, it is reasonable to assume that the placenta plays a central role in the pathogenesis of the disease. Pathologic examination of placentas from preeclamptic pregnancies generally reveals placental infarcts and sclerotic narrowing of arteries and arterioles, with characteristic diminished endovascular invasion by cytotrophoblasts and inadequate remodeling of the uterine spiral arterioles (2). Although gross pathologic changes are not always seen in the placentas of women with preeclampsia, placental profiles including abnormal uterine artery Doppler and placental morphology have been used to identify a subset from a cohort of high-risk women who go on to develop the syndrome (3). Uterine artery Doppler studies that assess the pulsatility index (PI) reveal increased …

Perinatal Physiology in Cloned And Normal Calves: Hematologic And Biochemical Profiles

Although a majority of clones are born normal and apparently healthy, mortality rates of nearly 30% are described in many reports. Such losses are a major limitation of cloning technology and represent substantial economic investment as well as justifiable animal health and welfare concerns. Prospective, controlled studies are needed to understand fully the causes of neonatal mortality in clones and to develop preventive and therapeutic strategies to minimize losses. We report here the findings of studies on the hematologic and biochemical profiles of cloned and control calves in the immediate 48-h postpartum period. Cloned calves were similar to control calves for a majority of parameters studied including blood gases, concentrations of plasma proteins, minerals and electrolytes, and white blood cell, neutrophil, lymphocyte, and platelet counts. The most notable differences between clones and controls in this study were reduced red- and white-blood cell counts in clones at birth and 1 h of age. As a group, plasma electrolyte concentrations were more variable in clones, and the variability tended to be shifted either higher (sodium, chloride) or lower (potassium, bicarbonate) than in controls. Previously, we noted differences in carbohydrate parameters, the length of time required for clones to make the neonatal adaptation to life ex utero, and morphology of the cloned placenta. Taken together, our findings suggest that cloned calves experience greater difficulty adjusting to life ex utero and that further research is warranted to determine the nature of the relationship between the physiological differences noted here in clones at birth and concomitant abnormal placental morphology.

Maternal medicine: Morphometric placental villous and vascular abnormalities in early‐ and late‐onset pre‐eclampsia with and without fetal growth restriction

To evaluate placental morphology in pregnancies complicated by early- and late-onset pre-eclampsia (PET) with and without fetal growth restriction (FGR) using stereological techniques. A total of 69 pregnant women were studied. Twenty women had pregnancies complicated by PET, 17 by FGR and 16 by both PET and FUR; the remaining 16 were from gestational-age-matched controls. Each group was further classified into early onset (<34 weeks) and late onsets (>34 weeks) based on gestational ages. NPIMR at Northwick Park and St Marks Hospital. placentae from pregnant women. Formalin-fixed, wax-embedded sections stained with anti-CD34 antibodies and counterstained with haematoxylin. Volumes, surface areas, lengths, diameters and shape factors of the villous tissues and fetal vasculature in the intermediate and terminal villi of all the groups studied. Terminal villi volume and surface area were compromised in early-onset PET cases, late-onset PET had no impact on peripheral villi or vasculature features. The morphology of the vascular and villous subcomponents in the intermediate and terminal villi was significantly influenced by late-onset FGR, whereas early-onset FGR caused a reduction in placental weight. Length estimates were not influenced by PET, FGR or age of onset. Intermediate arteriole shape factor was significantly reduced in late-onset FGR. Isolated early-onset PET was associated with abnormal placental morphology, but placentas from late-onset PET were morphologically similar to placentas from gestational-age-matched controls, confirming the existence of two subsets of this condition and supporting the hypothesis that late-onset PET is a maternal disorder and not a placental disease.

Measures of Maternal-Fetal Interaction in Day-30 Bovine Pregnancies Derived from Nuclear Transfer

Embryonic mortality and abnormal placental morphology have been reported by most researchers studying nuclear transfer (NT), and it now is accepted that placental anomalies and poor development of cloned embryos are related. As early as day 50 of gestation, cloned bovine concepti exhibit poor structural organization of the developing placentomes. These experiments were designed to identify alterations in maternal-fetal interactions during establishment of the placentas of NT-derived embryos at day 30 of gestation. Bovine NT embryos were produced using cultured fibroblast cells from a single Hereford donor cow, and control embryos were derived from in vitro fertilization (IVF). Following in vivo culture in ligated sheep oviducts, day-8 blastocysts were transferred to synchronized recipient heifers. Tissues recovered from viable day-30 pregnancies were analyzed by real-time RT-PCR, immunohistochemistry, and quantitative histological techniques. Immunoperoxidase staining of caruncular tissue from NT- and IVF-derived pregnancies revealed no significant differences in expression of the extracellular matrix proteins, collagen type IV and laminin, or the receptor subunits, integrins alpha1 and alpha3, suggesting that altered expression of these proteins at day 30 of gestation is not a primary cause of abnormal placentome structure in cloned concepti. Percentage of binucleate cells (BNC) within the trophoblast also was similar in NT- and IVF-derived pregnancies; however, expression of the BNC-specific placental lactogen (PL) transcript was elevated in NT-derived concepti (p < 0.05). These results indicate that regulation of PL transcription was altered in cloned day-30 placental tissues, suggesting the presence of irregular fetal-maternal signaling patterns that might undermine continued development of NT-derived concepti.

Prognostic value of placental ultrasound in pregnancies complicated by absent end-diastolic flow velocity in the umbilical arteries

Our objective was to evaluate the utility of gray-scale placental ultrasound for the detection of pathological lesions in the placentas of preterm pregnancies with abnormal fetoplacental blood flow (defined by absent or reversed end-diastolic flow velocities [ARED] in the umbilical arteries) before 32 weeks of gestation. Sixty consecutive structurally and chromosomally normal singleton pregnancies were evaluated. Pre-defined criteria were used to describe placental appearances using gray-scale real-time ultrasound. Proximal uterine artery Doppler waveforms were recorded using pulsed and color Doppler ultrasound. Each patient had a thrombophilia profile. Following delivery, a single perinatal pathologist reviewed each placenta at a gross and microscopic level blinded to the placental ultrasound findings. Placental shape or texture was abnormal on gray-scale ultrasound in 43/59 (73%) and echogenic cystic lesions (ECL) were found in 16 (27%). Uterine artery Doppler was abnormal in 47/60 (78%) cases. Thirty-eight pregnancies were subsequently delivered by planned Caesarean section in the fetal and/or maternal interest (birthweights 540–2300 g, mean gestational age 30.6 weeks) and 21 pregnancies resulted in the vaginal delivery of a stillborn fetus where fetal weight and/or gestational age did not justify Caesarean section (birthweights 85–600 g, mean gestational age 24.9 weeks). ECL had a low positive predictive value for both villous infarcts (63%) and for focal/massive perivillous fibrin deposition (40%). Nevertheless, the combination of abnormal uterine artery Doppler and abnormal gray-scale findings (abnormal placental morphology or ECL) was strongly predictive of stillbirth (17/21; sensitivity 81%, PPV 52%, p=0.006 Fisher's exact test). Pregnancies with ARED in the umbilical arteries have a high perinatal mortality associated with pathology of the placental villi. Ultrasound examination of the placenta and its maternal blood supply may contribute to the perinatal management of these pregnancies.

Vasa previa: prenatal diagnosis, natural evolution, and clinical outcome

Objective: To describe the prenatal ultrasonographic diagnosis, natural evolution, and clinical outcomes of vasa previa in a large population at a single institution. Methods: We attempted to view the internal cervical os of 93,874 women with second- and third-trimester pregnancies during an 8–year period. Echogenic parallel or circular lines near the cervix, seen by gray-scale ultrasonography, raised the possibility of vasa previa. Diagnosis was confirmed by Doppler and endovaginal studies if aberrant vessels over the internal cervical os were suspected. Abnormal placental morphology and velamentous cord insertion were documented if they were identified during prenatal scans. Ultrasonographic findings were correlated with clinical courses, perinatal outcomes, and placental pathology examinations. Results: Eighteen cases of vasa previa were suspected at a mean (± standard deviation) gestational age of 26.0 ± 6.3 weeks; the earliest diagnosis was at 15.6 weeks’ gestation. Eight of those cases initially showed placental edge over the internal os and later developed vasa previa after the placenta “receded” from the cervix. Six women had mild vaginal bleeding at a mean gestational age of 31.3 weeks. Three women had normal late third-trimester scans and were allowed to have uncomplicated vaginal deliveries. The remaining subjects delivered by cesarean. There were two deaths (one fetal and one neonatal), and minor preterm complications slightly prolonged infant hospitalizations. One set of preterm twins needed neonatal transfusions. Pathology findings included ten cases of velamentous insertion and three cases each of bilobed placentas, succenturiate lobes, and marginal cord insertion. Conclusion: Vasa previa was detected in asymptomatic women as early as the second trimester. Perinatal outcome was generally favorable, although several infants had slightly extended newborn nursery admissions due to mild complications of prematurity.

Placental Pathology in Patients Using Cocaine: An Observational Study

Objective: Although retroplacental hemorrhage is a major cause of fetal death, its etiology often remains obscure. In some reports, cocaine use by pregnant women has been associated with retroplacental hemorrhage and clinical abruptio placentae. This study was designed to assess the occurrence of chorionic villus hemorrhage, an entity shown recently to be associated with retroplacental hemorrhage, in the placentas of cocaine users. Methods: Twenty-nine placentas from cocaine users and 15 placentas from drug-free controls, as determined by questionnaire and urine toxicology screen, were examined prospectively, and pathological findings documented. The prevalence of retroplacental hemorrhage, chorionic villus hemorrhage, edema, chorioamnionitis, funisitis, infarction, fetal vessel thrombosis, and intervillus hemorrhage was examined in the two groups. Results: Chorioamnionitis was the most frequent finding in both groups (58% of cocaine users, 66% of controls). Edema of moderate severity or greater was found only in the cocaine-using group (17%). The prevalence of chorionic villus hemorrhage among women using cocaine also was 17%. Conclusion: Cocaine use during pregnancy may be associated with chorionic villus hemorrhage and villus edema, even in the absence of clinical abruptio placentae. The relationship between abnormal placental morphology and adverse perinatal outcomes remains to be determined.

Maternal factors affecting the integrity of the late gestation placental barrier to murine enterovirus infection.

Maternal factors that might impair the integrity of the late gestation placental barrier to enteroviruses were evaluated. Mice were inoculated with Theiler's murine encephalomyelitis virus (TMEV) on day 10-13 of gestation and sacrificed on day 16-18. Placentas and fetuses from dams with advanced age, forced daily swimming, short-term clamping of uteroplacental blood vessels, restricted dietary intake, or bacterial peritonitis were compared with tissues from TMEV-infected control mice. Increased maternal age, exercise, and malnutrition were associated with reduced fetal weight, and disturbed uteroplacental blood flow and severe malnutrition were associated with abnormal placental and fetal morphology. TMEV infection was observed sporadically by culture or in situ hybridization (or both) in fetuses from dams with interrupted uteroplacental blood flow, bacterial peritonitis, and older age but not in fetuses from control infected mice. This suggests that maternal factors, such as compromised uteroplacental blood flow, concomitant infection, and advanced age, may increase the risk of transplacental fetal infection.

Attenuating effect of zinc on abnormal placental morphology in 6-mercaptopurine treated rats.

Pregnant Sprague-Dawley rats were fed diets containing 9 (marginal level), 100 (control level), or 1,000 (very high level) ppm zinc and were given a single intraperitoneal injection of 6-mercaptopurine (6-MP, 55 mg/kg) or an equivalent volume of carboxymethylcellulose on day 11 of gestation. Live young and their placentas were recovered at surgery on day 21 of gestation: they were weighed, measured, and placentas were examined histologically. Placentas from drug treated animals were smaller in diameter and lighter in weight than controls; however, the placentas of animals fed the 1,000 ppm zinc diet were significantly heavier than those of the other drug-treated groups. Histologically, the placentas of the 6-MP treated dams showed a highly disproportionate reduction in the labyrinthine layer with larger, less subdivided maternal sinuses than in controls, reduction of fetal vasculature, vesiculation of trophoblast nuclei, deposition of PAS positive material in the septal wall, and fibrinous degeneration of trophoblast cells. These morphological changes were reduced in placental tissues of drug treated rats given 1,000 ppm of zinc. In contrast, no placental abnormalities were observed in rats not treated with 6-MP.

Ultrasonic couplings: Joseph Lucas (Industries) Ltd British Patent 1, 213, 471 (1970) Filed 26 Jan 1968

Pregnant women with sickle cell disease (SCD) are at high risk for sickle cell-related complications, obstetrical complications, and perinatal morbidity. Chronic inflammation and the proangiogenic environment associated with SCD have been associated with endothelial damage.It is unknown whether SCD complications could be associated with placental dysfunction or abnormal placental morphology. Moreover, circulating angiogenic factors in pregnant women with SCD are unexplored.Clinical records, placental and blood samples were collected at term delivery for 21 pregnant patients with SCD and 19 HbAA pregnant controls with adapted to gestational age birth weight newborns. Histological and stereological analyses and scanning electron microscopy (SEM) of the placenta, and PlGF and sFlt1 measurements in blood were performed.In the SCD group, the parenchyma-forming villi of placentas were thinner than in controls, and increased fibrinoid necrosis and an overabundance of syncytial knots were seen. SEM revealed elongated intermediate villous endings with a reduction in the number of terminal villi compared to controls, indicating a significant branching defect in SCD placentas. Finally, SCD patients had an imbalance in the angiogenic ratio of sFlt1/PlGF (p = 0.008) with a drop of PlGF concentrations.We evidence for the first time both abnormal placenta morphology and altered sFlt1/PlGF ratio in SCD patients, uncorrelated with maintained placental efficiency and fetal growth.