Disrupted redox balance in utero-placenteal junction may be the main culprit in the occurrence of abruptio placenta.

OBJECTIVE: To determine the oxidant/antioxidant balance and proinflammatory status in amniotic fluids collected during cesarean section of patients diagnosed with abruptio placenta. PATIENTS AND METHODS: Twenty-five patients diagnosed with ablatio placenta with intact membranes who went to emergency cesarean section were included in the study. A diagnosis of AP was made in those who had at least one of the following criteria or, in suspicious cases, two findings. (i) Antepartum hemorrhage starting after 20 weeks of gestation, (ii) presence of retroplacental hematoma on ultrasonography, (iii) severe fetal distress or death, (iv) localized or diffuse uterine tenderness or pain. The control group consisted of 25 patients who presented for delivery, who were not diagnosed with AP, and whose membranes were intact. NF-κB, total oxidant capacity (TOC), total antioxidant capacity (TAC), and oxidative stress index (TOC/TAC=OSI) levels were measured in amniotic fluids collected during cesarean section from both groups. RESULTS: Amniotic fluid TAS values of the AP group were significantly lower than the healthy controls (1.14±0.33 vs. 9.05.±3.40, p<0.01). Amniotic fluid TOS values were significantly increased in the AP group (36.1±8.10 vs. 11.4±2.77, p<0.02). OSI values were significantly higher in the AP group (31.6±9.03 vs. 1.26±0.02, p<0.01). Amniotic fluid NF-κB expression of the AP group was approximately 5 times higher than the control group (10.4±2.56 ng/mL vs. 1.86±0.30 ng/mL, p<0.01). High blood pressure and smoking history were significantly higher in the AP group. Gestational age and fetal birth weight of the AP group were lower than the control group. CONCLUSIONS: Since the increase in amniotic fluid oxidant capacity and proinflammatory cytokine synthesis cannot be neutralized by the antioxidant system, hypoxic cell damage may lead to premature separation of the placenta.

Molecular Changes on Maternal-Fetal Interface in Placental Abruption-A Systematic Review.

Placental abruption is the separation of the placenta from the lining of the uterus before childbirth. It is an infrequent perinatal complication with serious after-effects and a marked risk of maternal and fetal mortality. Despite the fact that numerous placental abruption risk factors are known, the pathophysiology of this issue is multifactorial and not entirely clear. The aim of this review was to examine the current state of knowledge concerning the molecular changes on the maternal-fetal interface occurring in placental abruption. Only original research articles describing studies published in English until the 15 March 2021 were considered eligible. Reviews, book chapters, case studies, conference papers and opinions were excluded. The systematic literature search of PubMed/MEDLINE and Scopus databases identified 708 articles, 22 of which were analyzed. The available evidence indicates that the disruption of the immunological processes on the maternal-fetal interface plays a crucial role in the pathophysiology of placental abruption. The features of chronic non-infectious inflammation and augmented immunological cytotoxic response were found to be present in placental abruption samples in the reviewed studies. Various molecules participate in this process, with only a few being examined. More advanced research is needed to fully explain this complicated process.

Histological distribution pattern of hemosiderin deposition on the chorionic plate and fetal membrane of diffuse chorioamniotic hemosiderosis related to chronic abruption oligohydramnios sequence.

INTRODUCTION: Chronic abruption oligohydramnios sequence (CAOS) is histologically characterized by diffuse chorioamniotic hemosiderosis (DCH). However, the criteria for the histological evaluation of the extent of CAOS-related hemosiderin deposition (HD) of the membranes and the difference in HD between the chorionic plate (CP) and fetal membrane (FM) are not well studied. This case control study compared the degree and distribution pattern of HD on CP and FM to present the histological features of DCH and the criteria for histological evaluation. METHODS: From the medical records of Kyoto University Hospital (2010-2019), we selected 20 CAOS cases that were clinically diagnosed by Elliot's criteria. Twenty non-CAOS cases matched to the CAOS group by gestational age were selected as controls. We compared the clinical data and pathological features in the two groups. We performed iron staining in all the cases and analyzed HD in CP and FM according to the histological score (H-Score: 0-12), which was determined as the density (0-3) multiplied by the extent of staining (0-4). RESULTS: HD was found in 100% (20/20) of CAOS and 15% (3/20) of control cases. In both the FM and CP, CAOS cases showed a significantly higher HS than control cases (CAOS, HS = 4-12; Control, HS = 0-1, p < 0.0001). Three CAOS patients presented HD alone in the CP. The HS of the CP was significantly higher than that of the FM (p = 0.0003). DISCUSSION: CAOS presented DCH with HS ≥ 4. This study showed that the CP might be more suitable for evaluating DCH than the FM.

Effect of homocysteine on pregnancy: A systematic review.

Research purpose was to put together the available pieces of present scientific data and to close the gap in the knowledge of Hcy levels in pregnancy and its association with some pregnancy complications. Scientific data were taken from research papers published between January 1990 and December 2017, and found on the Internet (PubMed, ClinicalKey and Embase databases) by the following tags entered in English, Russian, French and German languages: pregnancy, homocysteine, pregnancy complications, pregnancy loss, preeclampsia, intrauterine growth restriction, and placental abruption. The review showed that Hcy levels range in uncomplicated pregnancy. Upon that, Hcy level tends to decrease during the second and third trimesters. Some studies have revealed a link between polymorphism and abortion. Sufficient data were obtained indicating the relationship between HHcy and PE. Placental abruption was also associated with high Hcy levels increasing the risk 5.3-fold, but still there are data not supporting the hypothesis that Hcy levels correlate with placental abruption.

Maternal Early Pregnancy Serum Metabolomics Profile and Abnormal Vaginal Bleeding as Predictors of Placental Abruption: A Prospective Study.

BACKGROUND & OBJECTIVE: Placental abruption, an ischemic placental disorder, complicates about 1 in 100 pregnancies, and is an important cause of maternal and perinatal morbidity and mortality worldwide. Metabolomics holds promise for improving the phenotyping, prediction and understanding of pathophysiologic mechanisms of complex clinical disorders including abruption. We sought to evaluate maternal early pregnancy pre-diagnostic serum metabolic profiles and abnormal vaginal bleeding as predictors of abruption later in pregnancy. METHODS: Maternal serum was collected in early pregnancy (mean 16 weeks, range 15 to 22 weeks) from 51 abruption cases and 51 controls. Quantitative targeted metabolic profiles of serum were acquired using electrospray ionization liquid chromatography-mass spectrometry (ESI-LC-MS/MS) and the Absolute IDQ® p180 kit. Maternal sociodemographic characteristics and reproductive history were abstracted from medical records. Stepwise logistic regression models were developed to evaluate the extent to which metabolites aid in the prediction of abruption. We evaluated the predictive performance of the set of selected metabolites using a receiver operating characteristics (ROC) curve analysis and area under the curve (AUC). RESULTS: Early pregnancy vaginal bleeding, dodecanoylcarnitine/dodecenoylcarnitine (C12 / C12:1), and phosphatidylcholine acyl-alkyl C 38:1 (PC ae C38:1) strongly predict abruption risk. The AUC for these metabolites alone was 0.68, for early pregnancy vaginal bleeding alone was 0.65, and combined the AUC improved to 0.75 with the addition of quantitative metabolite data (P = 0.003). CONCLUSION: Metabolomic profiles of early pregnancy maternal serum samples in addition to the clinical symptom, vaginal bleeding, may serve as important markers for the prediction of abruption. Larger studies are necessary to corroborate and validate these findings in other cohorts.

An imbalance of COX level is not related to placental abruption.

AIMS: Muscularised basal plate arteries (MA) or chorioamnionitis (CA) are often present in placental abruption. The aim of this study was to evaluate the placental expression of COX 1 and COX 2 in cases of placental abruption with MA or CA hypothesising that an imbalance in COX placental expression might be implicated in its pathogenesis. METHODS: COX 1 and COX 2 placental immunostaining was analysed in 16 placentas with abruption (nine with MA, seven with CA), in 26 normal placentas and in 10 gestational age-matched MA or CA cases without abruption. RESULTS: COX 1 and COX 2 protein expression was observed in all cases, both in placental abruption and in normal placentas. No differences in distribution of immunoreactivity were observed either between cases and controls or between MA and CA. The mean COX 1 ratio between COX-positive cells and all stromal cells was significantly lower in placental abruption with MA (0.14±0.05) when compared with cases with CA (0.35±0.06) and normal placenta (0.23±0.02; p<0.001). The mean COX 2 ratio was lower in placental abruption with MA than in normal placenta (0.09±0.06 vs 0.18±0.05: p<0.001). In contrast, no difference in COX 1 and COX 2 ratio was observed between MA cases with or without abruption and between CA cases with or without abruption. CONCLUSIONS: It is hypothesised that an imbalance of normal COX level may be present in cases with MA and CA but it is not related to placental abruption.

Fetal death: a condition with a dissociation in the concentrations of soluble vascular endothelial growth factor receptor-2 between the maternal and fetal compartments.

OBJECTIVE: An anti-angiogenic state has been implicated in the pathophysiology of preeclampsia, fetal growth restriction and fetal death. Vascular endothelial growth factor (VEGF), an indispensible angiogenic factor for embryonic and placental development exerts its angiogenic properties through the VEGF receptor (VEGFR)-2. A soluble form of this protein (sVEGFR-2) has been recently detected in maternal blood. The aim of this study was to determine if fetal death was associated with changes in the concentrations of sVEGFR-2 in maternal plasma and amniotic fluid. STUDY DESIGN: Maternal plasma was obtained from patients with fetal death (n = 59) and normal pregnant women (n = 134). Amniotic fluid was collected from 36 patients with fetal death and the control group consisting of patients who had an amniocentesis and delivered at term (n = 160). Patients with fetal death were classified according to the clinical circumstances into the following groups: (1) unexplained; (2) preeclampsia and/or placental abruption; (3) chromosomal and/or congenital anomalies. Plasma and amniotic fluid concentrations of sVEGFR-2 were determined by ELISA. Non-parametric statistics and logistic regression analysis were applied. RESULTS: (1) Patients with a fetal death had a significantly lower median plasma concentration of sVEGFR-2 than normal pregnant women (p < 0.001). The median plasma concentration of sVEGFR-2 in patients with unexplained fetal death and in those with preeclampsia/abruption, but not that of those with congenital anomalies, was lower than that of normal pregnant women (p = 0.006, p < 0.001 and p = 0.2, respectively); (2) the association between plasma sVEGFR-2 concentrations and preterm unexplained fetal death remained significant after adjusting for potential confounders (OR: 3.2; 95% CI: 1.4-7.3 per each quartile decrease in plasma sVEGFR-2 concentrations); (3) each subgroup of fetal death had a higher median amniotic fluid concentration of sVEGFR-2 than the control group (p < 0.001 for each); (4) the association between amniotic fluid sVEGFR-2 concentrations and preterm unexplained fetal death remained significant after adjusting for potential confounders (OR: 15.6; 95% CI: 1.5-164.2 per each quartile increase in amniotic fluid sVEGFR-2 concentrations); (5) among women with fetal death, there was no relationship between maternal plasma and amniotic fluid concentrations of sVEGFR-2 (Spearman Rho: 0.02; p = 0.9). CONCLUSION: Pregnancies with a fetal death, at the time of diagnosis, are characterized by a decrease in the maternal plasma concentration of sVEGFR-2, but an increase in the amniotic fluid concentration of this protein. Although a decrease in sVEGFR-2 concentration in maternal circulation depends upon the clinical circumstances of fetal death, an increase in sVEGFR-2 concentration in amniotic fluid seems to be a common feature of fetal death. It remains to be determined if the perturbation in sVEGFR-2 concentrations in maternal and fetal compartments observed herein preceded the death of a fetus.

Involvement of human decidual cell-expressed tissue factor in uterine hemostasis and abruption.

Vascular injury increases access and binding of plasma-derived factor VII to perivascular cell membrane-bound tissue factor (TF). The resulting TF/VIIa complex promotes hemostasis by cleaving pro-thrombin to thrombin leading to the fibrin clot. In human pregnancy, decidual cell-expressed TF prevents decidual hemorrhage (abruption). During placentation, trophoblasts remodel decidual spiral arteries into high conductance vessels. Shallow trophoblast invasion impedes decidual vascular conversion, producing an inadequate uteroplacental blood flow that elicits abruption-related placental ischemia. Thrombin induces several biological effects via cell surface protease activated receptors. In first trimester human DCs thrombin increases synthesis of sFlt-1, which elicits placental ischemia by impeding angiogenesis-related decidual vascular remodeling. During pregnacy, the fibrillar collagen-rich amnion and choriodecidua extracellular matrix (ECM) provides greater than additive tensile strength and structural integrity. Thrombin acts as an autocrine/paracrine mediator that degrades these ECMs by augmenting decidual cell expression of: 1) matrix metalloproteinases and 2) interleukin-8, a key mediator of abruption-associated decidual infiltration of neutrophils, which express several ECM degrading proteases. Among the cell types at the maternal fetal interface at term, TF expression is highest in decidual cells indicating that this TF meets the hemostatic demands of labor and delivery. TF expression in cultured term decidual cells is enhanced by progestin and thrombin suggesting that the maintenance of elevated circulating progesterone provides hemostatic protection and that abruption-generated thrombin acts in an autocrine/paracrine fashion on decidual cells to promote hemostasis via enhanced TF expression.

The increase in metallothionein and ectopic decidual immunoreactivity with respect to the progression of labor at term and the lack of analogical changes in placental abruption.

PROBLEM: The coexistence of immune and decidual cells is related to the development of a resistance to immune-mediated apoptosis in both ectopic and eutopic decidua. This unique feature of endometrial cells seems to be linked with the expression of metallothionein (MT), an inhibitor of apoptosis. METHOD OF STUDY: The MT immunoreactivity level was assessed in 82 eutopic (CC) and ectopic (cesarean scar deciduosis - CSD) decidual tissue samples obtained from patients during cesarean sections at term and from patients on whom cesarean sections were performed on account of placental abruption (PA). RESULT: Statistically, significantly higher levels of MT immunoreactivity were found in eutopic and ectopic decidua sampled during cesarean sections performed on patients with advanced labor when compared to the levels found in tissues sampled during cesarean sections on patients without labor. No differences were observed in the MT immunoreactivity levels in decidual tissue samples derived from patients who had undergone cesarean sections on account of PA with respect to the progression of labor at the time of the surgical procedure. Statistically, the decidual MT immunoreactivity levels were significantly higher in the PA than the CC subgroups and in the PA than the CSD subgroups correlating with the stage of labor. CONCLUSION: MT in decidual cells seems to be responsible for the proper coexistence between decidual cells and activated immune cells that infiltrate both eutopic and ectopic decidua during cesarean section and PA.

Predictors of umbilical artery acidosis in preterm delivery.

OBJECTIVE: The purpose of this study was to investigate the significance of preterm acidosis and its risk factors. STUDY DESIGN: From a cohort of 786 consecutive singleton neonates who were born after spontaneous or iatrogenic preterm delivery at 24.0-33.6 weeks of gestation from January 1993 to December 2005 with an evaluation of umbilical artery pH at delivery, we extracted demographic, obstetric, neonatal, and placental histologic variables and related them to umbilical artery evidence of fetal acidemia, which was defined as pH <7.10. Excluded were stillbirths and neonates with major congenital anomalies. Fetal distress was defined as nonreassuring fetal hearth rate tracing or biophysical profile or appearance of thick meconium at delivery. Statistical analysis included 1-way analysis of variance and logistic regression with a probability value of <.05 considered significant. RESULTS: Neonates with umbilical cord evidence of acidosis (n = 34) were born more frequently after abruption (P < .001), fetal distress (P < .001), and by cesarean delivery (P < .04) and were born less frequently after a complete course of corticosteroids (P = .03) and labor (P = .05) than nonacidotic babies (n = 752). Acute inflammatory lesions at placental histologic evaluation were less frequent (P = .049), and placental vascular lesions were more common in acidotic than in nonacidotic preterm neonates (P = .039). Logistic regression analysis demonstrated that cord acidosis was associated independently with the occurrence of abruptio placentae (odds ratio, 7.3; 95% CI, 2.9, 18.8), fetal distress (odds ratio, 12.0; 95% CI, 4.9, 18.3), and vascular placental lesions (odds ratio, 2.8; 95% CI, 1.2, 6.8) CONCLUSION: In preterm infants, umbilical artery acidosis is significantly more common in the presence of placental abruption, fetal distress, and histologic evidence of placental vascular disease.

Tocolysis and delayed delivery versus emergency delivery in cases of non-reassuring fetal status during labor.

AIM: To determine whether fetal intrauterine resuscitation using tocolysis and delayed delivery is better for the fetus than emergency delivery when fetal hypoxia is suspected because of a non-reassuring fetal heart-rate (FHR) pattern using conventional heart rate monitoring. METHODS: This was a prospective and randomized study, conducted between 2001 and 2004 at Pereira Rossell Hospital, Montevideo, Uruguay. The population consisted of 390 fetuses, in which intrauterine distress was diagnosed using electronic FHR monitoring. Of these, 197 were randomly assigned to the emergency delivery group and 193 to the fetal intrauterine resuscitation group. The inclusion criteria were: term singleton pregnancy, in labor, cephalic presentation, and no placental accidents. RESULTS: The time between randomization and birth was 16.9 +/- 7.6 min (mean +/- SD) for the emergency delivery group, and 34.5 +/- 11.7 min (mean +/- SD) for the resuscitation group. The relative risk (RR) of acidosis in the umbilical artery (pH < 7.1) in the emergency delivery group was 1.47 (0.95-2.27). The RR of base deficit < or =12 mEq/L in the emergency delivery group was higher than in the resuscitation group (RR = 1.48 [1.0-2.2], P = 0.04). When considering the need for admission to the neonatal care unit, the relative risk was higher in the emergency delivery group than in the resuscitation group (RR = 2.14 [1.23.3.74], P = 0.005). No maternal adverse effects were reported. CONCLUSION: Tocolysis and delayed delivery renders better immediate neonatal results than emergency delivery when fetal distress is suspected because of a non-reassuring fetal heart pattern. In addition, it may decrease the need for emergency delivery without increasing maternal and fetal adverse side-effects.

RCAS1 decidual immunoreactivity during placental abruption: immune cell presence and activity.

PROBLEM: RCAS1 is a protein responsible for the suppression of cytotoxic immune response during gestation. The present study evaluates the immunoreactivity level of RCAS1 with respect to immune cell status during placental abruption (PA) and retained placental tissue (RPT). METHOD OF STUDY: RCAS1, CD3, CD56, CD69 and CD25 immunoreactivity was assessed by immunohistochemistry in 66 decidual samples derived from PA and from RPT. RESULTS: RCAS1 immunoreactivity was statistically significantly higher in decidual tissue samples derived from patients with RPT than in those derived from patients with PA. A statistically significantly lower number of CD56(+) and CD3(+) cells and immunoreactivity level of CD69 were found in patients with RPT, compared to those with PA. CONCLUSION: Placental abruption seems to be associated with excessive accumulation and activity of CD3(+) and CD56(+) cells in decidua, which processes might, in turn, result from an insufficient RCAS1 decidual level.

Polymorphisms in methionine synthase reductase and betaine-homocysteine S-methyltransferase genes: risk of placental abruption.

OBJECTIVES: Methionine synthase reductase (MTRR) and betaine-homocysteine S-methyltransferase (BHMT) are two enzymes that regulate homocysteine metabolism. Elevated homocysteine (hyperhomocysteinemia) is associated with adverse pregnancy outcomes and vascular disease. We assessed whether polymorphisms in MTRR (66A-->G; I22M) and BHMT (742G-->A; R239Q) were associated with abruption. We further evaluated whether homocysteine levels differed between cases and controls for MTRR and BHMT genotypes. METHODS: Data were derived from the New Jersey Placental Abruption Study (NJ-PAS)-an ongoing, multicenter, case-control study since August 2002. Women with a clinical diagnosis of abruption were recruited as incident cases (n=196), and controls (n=191) were matched to cases based on maternal race/ethnicity and parity. Total plasma homocysteine concentrations were evaluated in a subset of 136 cases and 136 controls. DNA was genotyped for the MTRR and BHMT polymorphisms. RESULTS: Frequencies of the minor allele of MTRR were 40.8% and 42.2% in cases and controls, respectively (adjusted OR 0.79, 95% CI 0.45, 1.40). The corresponding rates for BHMT were 33.9% and 31.7%, respectively (adjusted OR 1.93, 95% CI 0.99, 4.09). Distributions for the homozygous mutant form of MTRR were similar between cases and controls (OR 1.18, 95% CI 0.62, 2.24). The rate of homozygous mutant BHMT genotype was 2.8-fold (OR 2.82, 95% CI 1.84, 4.97) higher in cases than controls. Stratification of analyses based on maternal race did not reveal any patterns in association. CONCLUSIONS: In this population, there was an association between the homozygous mutant form of BHMT (742G-->A) polymorphism and increased risk for placental abruption.

Circulating angiogenic factors and placental abruption.

OBJECTIVE: Abnormalities in circulating angiogenic factors have been reported in diseases of abnormal placentation, such as preeclampsia and intrauterine growth restriction. Our objective was to determine whether circulating angiogenic factors are altered in another placental vascular disease, abruptio placentae. METHODS: In a nested case-control study of nulliparous pregnancies, we examined levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt-1) in serum collected prospectively from 31 women who later developed placental abruption and from 31 normal control subjects. All serum specimens were collected before the onset of hypertension or abruption and before labor or delivery. Serum angiogenic factors were compared within 3 gestational age windows: early (20 weeks or less), middle (21-32 weeks), and late (33 weeks or more) pregnancy. RESULTS: During early pregnancy women who developed placental abruption had lower PlGF and higher sFlt-1 concentrations and higher sFlt-1/PlGF ratios than women with normal pregnancies. In mid-pregnancy these differences became greater, reaching statistical significance for PlGF concentration (431 versus 654 pg/mL, P<.01) and the sFlt-1/PlGF ratio (25.3 versus 2.5, P<.01). When the women with placental abruption were subdivided into those who did (n=10) and those who did not (n=21) develop preeclampsia or gestational hypertension, significant alterations in angiogenic factors were noted only in women who later developed hypertension in pregnancy. Among these women, PlGF concentrations were decreased in mid-pregnancy (160 versus 723 pg/mL, P<.001), and the mid-pregnancy sFlt-1/PlGF ratio was increased (70.1 versus 2.3, P=.001). CONCLUSION: Serum levels of the proangiogenic factor PlGF were decreased, and those of the antiangiogenic ratio sFlt-1/PlGF were increased in nulliparous women who subsequently developed hypertension and placental abruption.

The molecular changes during placental detachment.

OBJECTIVES: RCAS1 is a membrane protein that plays a role in the maintenance of maternal immune tolerance during pregnancy. The work presented here demonstrates the results of RCAS1 expression in placenta in cases of placental abruption and patients with retained placental tissue during the third stage of labor. STUDY DESIGN: The placenta tissue samples were obtained during vaginal and cesarean delivery (derived from 117 pregnancies). Pregnant women were divided into four groups according to the onset of labor and the time of placental detachment in term labors. The samples were analyzed by the Western blot method. Statistical analysis was performed using the Shapiro-Wilk procedure. The Mann-Whitney test and Student's t-test were applied to compare the differences between parametric data. RESULTS: The average relative amount of RCAS1 observed in those patients with retained placental tissue was statistically significantly higher than in the patients with placental abruption. CONCLUSION: The differences observed in placental RCAS1 levels confirm the participation of this protein in the inhibition of maternal immune response during gestation. The present results also indicate that RCAS1 participates in the changes in the maternal immune system that take place during parturition and reinforce its potential involvement in the mechanism of placental abruption.

Intervilosite crónica masiva da placenta / Intervilositis crónica masiva de placenta / Massive chronic intervillositis of placeta

A intervilosite crónica massiva é uma patologia raras vezes diagnosticada na placenta, com uma incidência inferior a 0.5%. O exame histológico da placenta mostra uma infiltração massiva do espaço intervilositário por células inflamatórias, sem lesões de vilite crónica associadas. Estas alterações vão comprometer a função placentar originando um compromisso fetal que se manifesta sob a forma de atraso de crescimento fetal intra-uterino, parto pré-termo ou morte fetal. Descreve-se um caso clínico, ilustrativo deste tipo de patologia, referente a uma mulher de 31 anos, II gesta, O para, com antecedentes de morte fetal intra-uterina às 13 semanas de gestação em gravidez anterior, tendo registado na actual gravidez um valor elevado de alfa-feto-proteína às 16 semanas de gestação e morte fetal intra-uterina inesperada às 18 semanas. O exame histológico da placenta demonstrou a presença de uma intervilosite crónica massiva. Este caso realça, ainda, o valor do exame anátomo-patológico da placenta em todos os casos de morte fetal in-trauterina, e a sua importância para o diagnóstico da etiopatogenia e prognóstico de futuras gestações (AU)

La intervilositis crónica masiva es una patología de la placenta, raras veces diagnosticada, con una incidencia inferior al 0,5 0/0. El examen histológico de la placenta muestra una inflamación masiva del espacio intervillositario, por células inflamatorias, sin lesiones de vellosidades crónicas asociadas. Estas alteraciones van a comprometer la función placentaria, originando un compromiso fetal que se manifiesta en una forma de retraso del crecimiento intrauterino, parto pretérmino o muerte fetal. Se describe un caso clínico ilustrativo de este tipo de patología, referente a una mujer de 31 años, secundigestante y primípara, con antecedentes de muerte fetal intrauterina a las 13 semanas de gestación en el embarazo anterior. En este embarazo se registra un valor elevado de la alfa-fetoproteína a las 16 semanas y muerte inesperada a las 18 semanas de embarazo. El examen histológico de la placenta demostró una intervillositis crónica masiva. Este caso realza el valor del examen histológico de la placenta en todos casos de muerte fetal intrauterina y su importancia en el diagnóstico de la etiopatogenia y pronóstico de futuras gestaciones (AU)

Massive chronic intervillositis (MCI) is an infrequently recognized placental lesion which is reported in less than 0.5 0/0 of cases. MCI is characterized by prominent inflammatory infiltrate in the intervillous space in the absence of significant chronic villitis. MCI has been associated with poor pregnancy outcome, including intrauterine growth restriction, preterm delivery and intrauterine fetal death. We report such a case of a 31-year-old woman, gravida 2, para 0, with a past history of one intrauterine fetal death at 13 weeks pregnancy, who became pregnant, and an elevated maternal serum alpha-fetoprotein was noted at 16 weeks gestation. The intrauterine fetal death was diagnosed at 18 weeks gestation. Histological examination of the placenta demonstrated the presence of MCI. This case also underlines the importance of the routine histopathological examination of the placenta in all cases of intrauterine fetal death, in view of its importance in aetiological diagnostic and prognostic information for future pregnancy (AU)

Hyperhomocysteinaemia and protein S deficiency in complicated pregnancies.

OBJECTIVE: The aim of our study was to investigate whether women with placental abruption, intrauterine fetal death or small for gestational age infants have metabolic and/or haemostatic abnormalities which are known to be risk factors for intravascular thrombosis. DESIGN: For two years blood tests were performed at > 10 weeks after delivery on all women without hypertensive disorders either before or during pregnancy, who had been consecutively admitted to our hospital with placental abruption, intrauterine fetal death and small for gestational age. SAMPLE: A total of 62 women who had placental abruption (n = 31), intrauterine fetal death (n = 18) and a small for gestational age infant (n = 13). SETTING: Obstetric outpatient clinic in a university hospital (Free University Hospital, Amsterdam). METHODS: Presence of hyperhomocysteinaemia, various coagulation abnormalities and anticardiolipins was investigated. RESULTS: Abnormalities were found in 20 women in the placental abruption group (20/31, 65%), in 10 women in the intrauterine fetal death group (10/18, 56%) and in 11 women in the small for gestational age group (11/13, 85%). Eight out of these 31 women had more than one abnormality. In the group of 62 women protein S deficiency was demonstrated in 26%, hyperhomocysteinaemia in 24%, Protein C deficiency in 6%, anticardiolipin IgG in 11%, anticardiolipin IgM in 5%, Lupus anticoagulant in 2%. An antithrombin III deficiency was not found. Thirty-three women were tested for activated protein C resistance (9% positive) and factor V Leiden mutation (6% positive). Hyperhomocysteinaemia was treated with a daily oral dose of 250 mg pyridoxine and 5 mg folic acid. After six weeks of vitamin supplementation homocysteine levels were tested again. At that time a mean reduction of fasting homocysteine value of 68% (95% CI 57-79) was found and of post-load value of 65% (95% CI 55-76). CONCLUSIONS: Based on the results of our study, it can be concluded that women whose pregnancies are complicated by either placental abruption, intrauterine fetal death or small for gestational age, even if there is no history of thrombo-embolic disorders or hypertension during pregnancy, should be advised to undergo an examination for metabolic and/or haemostatic abnormalities.

[The study on mechanism of abruptio placentae caused by chorioamnionitis].

The cause of abruptio placentae has not been elucidated yet. Although preeclampsia is frequently associated with abruptio placentae, the rate of abruptio placentae caused by preeclampsia has decreased recently. Many current reports have indicated that chorioamnionitis is an important cause of abruptio placentae. To clarify the relationship between chorioamnionitis and abruptio placentae, we performed immunostaining for fibronectin, fibronectin receptor and granulocyte elastase of placenta with or without abruptio placentae. In cases of abruptio placentae caused by chorioamnionitis, granulocyte elastase was stained strongly and fibronectin receptor was stained weakly in decidual cells, especially in the parts of granulocyte elastase invased. In III stage chorioamnionitis without abruptio placentae, granulocyte elastase was stained moderately and the intensity of fibronectin receptor did not decrease. There was no difference between fibronectin staining in all cases. When purified granulocyte elastase was added to the cultured decidual cells, the staining intensity of fibronectin receptor became weak in those cells. These results suggest that marked imbalance between neutrophil invasion and an inhibitor, such as alpha 1 antitrypsin, initiates granulocyte elastase release and promotes the reduction of the fibronectin receptor in decidual cells resulting in weakening of the adherence of decidual cells. This may be one of the mechanisms of abruptio placentae caused by chorioamnionitis.

Plasma fibronectin receptor levels during pregnancy complicated by preeclampsia and abruptio placentae.

The level of human fibronectin receptor (FNR) in plasma was measured by enzyme-linked immunosorbent assay in samples from normal pregnant women in the 1st trimester (n = 5), 2nd trimester (n = 7), 3rd trimester (n = 23), normal postpartum women day 1 (n = 4), day 2 (n = 5), day 3 (n = 8), nonpregnant women (n = 18), 20 preeclamptic patients in the 3rd trimester, and 8 patients with abruptio placentae in the 3rd trimester. In normal pregnancy, the mean value of FNR was 1.4 +/- 0.4 micrograms/ml in the 1st, 1.4 +/- 0.2 micrograms/ml in the 2nd, and 1.9 +/- 0.3 micrograms/ml (p less than 0.05) in the 3rd trimester. FNR values increased with pregnancy. During the puerperium, its level decreased with time, being 1.4 +/- 0.5 micrograms/ml (p less than 0.01) on day 1, 1.0 +/- 0.3 micrograms/ml on day 2, and 0.8 +/- 0.2 micrograms/ml on day 3. The level in preeclamptic patients was 2.0 +/- 0.4 micrograms/ml, and that in abruptio placentae was 2.7 +/- 0.4 micrograms/ml. There were significant differences between the levels in abruptio placentae versus preeclampsia (p less than 0.05) and 3rd-trimester normal pregnant women (p less than 0.01). In the immunohistochemical study, the surface of normal decidual cells stained weakly for FNR, and the decidual cell membranes of the cases of preeclampsia stained moderately or strongly. Decidual cells and their extracellular matrix close to hematomas of abruptio placentae stained very strongly for FNR.(ABSTRACT TRUNCATED AT 250 WORDS)

CA 125 levels in abruptio placentae.

The diagnosis of abruptio placentae is frequently difficult despite ultrasonography; additional diagnostic parameters would be useful. Maternal serum CA 125, which is believed to derive from the decidua, is elevated in the first trimester and immediately after delivery when placental separation occurs, possibly because of decidual disruption. Serum CA 125 was measured in 27 patients beyond 20 weeks' gestation who were first seen with vaginal bleeding and in 17 control patients of similar gestational age and labor status. Mean (+/- SD) CA 125 levels were higher (p less than 0.01) among patients with abruptio placentae (105.9 +/- 115 U/ml) than among those with alternate sources of bleeding (13.7 +/- 10 U/ml) or control patients (18.2 +/- 11.7 U/ml). Mean (+/- SD) serum CA 125 levels in seven control patients within 6 hours post partum (194 +/- 80.5 U/ml) were higher than those among patients first seen with abruptio placentae (p less than 0.01). Sensitivity and specificity of CA 125 for abruptio placentae were 70% and 94%, respectively. Our data support a decidual source for CA 125 and may indicate utility of CA 125 as a marker for abruptio placentae.