Chorioamniotic Membranes Research Articles

Neutrophil extracellular traps in acute chorioamnionitis: Amechanism of host defense.

Neutrophil extracellular traps (NETs) were recently described as a mechanism for microbial killing in the amniotic cavity of women with intra-amniotic infection. Such a clinical condition can result in acute chorioamnionitis, a placental lesion characterized by the infiltration of maternal neutrophils in the chorioamniotic membranes. Herein, we investigated whether these infiltrating neutrophils form NETs in the chorioamniotic membranes from women who underwent spontaneous term or preterm labor with acute chorioamnionitis. Chorioamniotic membrane samples were collected from women who underwent spontaneous term or preterm labor with acute chorioamnionitis (n=10 each). Controls included chorioamniotic membrane samples from women who delivered at term or preterm with or without labor in the absence of acute chorioamnionitis (n=10 each). NETs were visualized and semiquantified in the chorioamniotic membranes by using antibodies against neutrophil elastase and histone H3 in combination with DAPI staining. Neutrophil extracellular traps were abundant in the chorioamniotic membranes from women who underwent spontaneous term or preterm labor with acute chorioamnionitis. NETs were rarely found, or not visualized at all, in the chorioamniotic membranes from women who delivered at term or preterm with or without labor in the absence of acute chorioamnionitis. Neutrophil extracellular traps are abundant in the chorioamniotic membranes from women who underwent spontaneous term or preterm labor with acute chorioamnionitis. These findings suggest that chorioamniotic neutrophils can form NETs as a mechanism of host defense against infection or danger signals.

A Case of Complete Chorioamniotic Membrane Separation after Amniocentesis Resulted with a Healthy Term Delivery

Separation between amniotic and chorionic membranes is a normal sonographic finding before 14th weeks of gestation. As pregnancy progresses, these membranes fuse and chorionic cavity becomes obliterated. Chorioamniotic membrane separation may occur spontaneously or as a complication of invasive intrauterine procedures. Following invasive fetal intervention, resulting in a condition referred to as chorioamniotic membrane separation (CMS) and it is reported to be associated with adverse perinatal fetal outcomes. Here we present a case of CMS that had occurred after a second trimester amniocentesis and resulted with the delivery of a term healthy baby. Complete post-interventional CMS may complicate pregnancy progression. Although there are no established guidelines to follow, close follow-up may CMS can be managed to be a morbid, rather than mortal condition.

Expression patterns of the chromosome 21 MicroRNA cluster (miR-99a, miR-125b and let-7c) in chorioamniotic membranes

Trisomy 21 (T21) is the most common chromosome abnormality in humans and is associated with a spectrum of phenotypes, including cognitive impairment, congenital heart defects and immune system defects. In addition, T21 is also associated with abnormalities of fetal membranes including chorioamniotic separation, delayed fusion of the chorioamniotic membranes, defects in syncytiotrophoblast formation, as well as amniocyte senescence. There is evidence indicating miRNAs encoded by sequences on chromosome 21 (Chr-21) are involved in several of the cognitive and neurological phenotypes of T21, but the role of Chr-21 derived miRNAs in fetal membrane abnormalities associated with T21 has not been investigated. In the current study, we determined the expression patterns of three miRNAs derived from a cluster on Chr-21 – hsa-miR-99a, hsa-miR-125b and hsa-let-7c in chorioamniotic membranes obtained from term pregnancies with spontaneous rupture (n = 20). Tissue and location specific expression patterns within the chorioamniotic membranes were identified. The rupture zone in the choriodecidua had distinct expression patterns compared to other fetal membrane locations. Despite the increased gene dosage associated with T21, the expression of all three miRNAs was reduced in cultured T21 amniocytes as compared to cultured euploid amniocytes. In silico analysis of experimentally validated targets of the three miRNAs suggest these Chr-21 derived miRNAs play a potential role in fetal membrane rupture and the fetal membrane defects associated with T21.

HMGB1 Induces an Inflammatory Response in the Chorioamniotic Membranes That Is Partially Mediated by the Inflammasome.

Spontaneous preterm labor occurs in two subsets of patients with sterile intra-amniotic inflammation, a process induced by alarmins such as high-mobility group box-1 (HMGB1). Inflammasomes are implicated in the process of spontaneous preterm labor. Therefore, we investigated whether HMGB1 initiates an inflammasome-associated inflammatory response in the chorioamniotic membranes. Incubation of the chorioamniotic membranes with HMGB1 1) induced the release of mature IL-1beta and IL-6; 2) upregulated the mRNA expression of the pro-inflammatory mediators NFKB1, IL6, TNF, IL1A, IFNG, and HMGB1 receptors RAGE and TLR2; 3) upregulated the mRNA expression of the inflammasome components NLRP3 and AIM2 as well as NOD proteins (NOD1 and NOD2); 4) increased the protein concentrations of NLRP3 and NOD2; 5) increased the concentration of caspase-1 and the quantity of its active form (p20); and 6) upregulated the mRNA expression and active form of MMP-9. In addition, HMGB1 concentrations in chorioamniotic membrane extracts from women who underwent spontaneous preterm labor were greater than in those from women who had undergone spontaneous labor at term. Collectively, these results show that HMGB1 can induce an inflammatory response in the chorioamniotic membranes, which is partially mediated by the inflammasome. These results provide insight into the mechanisms whereby HMGB1 induces preterm labor and birth in mice and explain why the concentration of this alarmin is increased in women who undergo spontaneous preterm labor.

A case report of chorioamniotic membrane separation with chorionic hematoma

A shallow olfactory sulcus has been reported in schizophrenia, possibly reflecting abnormal forebrain development during early gestation. However, it remains unclear whether this anomaly exists prior to the onset of psychosis and/or differs according to illness stage. In the current study, magnetic resonance imaging was used to investigate the length and depth of the olfactory sulcus in 135 ultra high-risk (UHR) individuals [of whom 52 later developed psychosis (UHR-P) and 83 did not (UHR-NP)], 162 patients with first-episode psychosis (FEP), 89 patients with chronic schizophrenia, and 87 healthy controls. While there was no group difference in the length of the sulcus, UHR-P subjects had significantly shallower olfactory sulcus at baseline as compared with UHR-NP and control subjects. The depth of this sulcus became increasingly more superficial as one moved from UHR-P subjects to FEP patients to chronic schizophrenia patients. Finally, the depth of the olfactory sulcus in the UHR-P subjects was negatively correlated with the severity of negative symptoms. These findings suggest that the altered depth of the olfactory sulcus, which exists before psychosis onset, could be predictive of transition to psychosis, but also suggest ongoing changes of the sulcus morphology during the course of the illness.

Maternal Chorioamnionitis and Postnatal Outcomes of Infants Born below 26 weeks of Gestational Age

Introduction: Acute chorioamnionitis (ACAM) is the most common lesion reported in the placenta, both in cases with preterm prelabor rupture of membranes and preterm labor with intact membranes. The histopathologic features of ACAM include amniotropic infiltration by both maternal and fetal neutrophils in the chorioamniotic membranes and the umbilical cord. ACAM is most likely associated with adverse outcomes in the neonates, but the clinicopathologic significance of ACAM is unclear in extreme premature infants. The aim of this study was to investigate the effect of the severity of ACAM on the short- and long-term outcomes of preterm infants below 26 weeks’ gestation.

OP17.06: Incidence and outcome of chorioamniotic membrane separation after fetoscopic laser surgery in monochorionic twin pregnancy

OP17.06: Incidence and outcome of chorioamniotic membrane separation after fetoscopic laser surgery in monochorionic twin pregnancy

The Management of Myelomeningocele Study: obstetrical outcomes and risk factors for obstetrical complications following prenatal surgery

The Management of Myelomeningocele Study was a multicenter randomized trial to compare prenatal and standard postnatal closure of myelomeningocele. The trial was stopped early at recommendation of the data and safety monitoring committee and outcome data for 158 of the 183 randomized women published. In this report, pregnancy outcomes for the complete trial cohort are presented. We also sought to analyze risk factors for adverse pregnancy outcome among those women who underwent prenatal myelomeningocele repair. Pregnancy outcomes were compared between the 2 surgery groups. For women who underwent prenatal surgery, antecedent demographic, surgical, and pregnancy complication risk factors were evaluated for the following outcomes: premature spontaneous membrane rupture ≤34 weeks 0 days (preterm premature rupture of membranes), spontaneous membrane rupture at any gestational age, preterm delivery at ≤34 weeks 0 days, nonintact hysterotomy (minimal uterine wall tissue between fetal membranes and uterine serosa, or partial or complete dehiscence at delivery), and chorioamniotic membrane separation. Risk factors were evaluated using χ2 and Wilcoxon tests and multivariable logistic regression. A total of 183 women were randomized: 91 to prenatal and 92 to postnatal surgery groups. Analysis of the complete cohort confirmed initial findings: that prenatal surgery was associated with an increased risk for membrane separation, oligohydramnios, spontaneous membrane rupture, spontaneous onset of labor, and earlier gestational age at birth. In multivariable logistic regression of the prenatal surgery group adjusting for clinical center, earlier gestational age at surgery and chorioamniotic membrane separation were associated with increased risk of spontaneous membrane rupture (odds ratio, 1.49; 95% confidence interval, 1.01-2.22; and odds ratio, 2.96, 95% confidence interval, 1.05-8.35, respectively). Oligohydramnios was associated with an increased risk of subsequent preterm delivery (odds ratio, 9.21; 95% confidence interval, 2.19-38.78). Nulliparity was a risk factor for nonintact hysterotomy (odds ratio, 3.68; 95% confidence interval, 1.35-10.05). Despite the confirmed benefits of prenatal surgery, considerable maternal and fetal risk exists compared with postnatal repair. Early gestational age at surgery and development of chorioamniotic membrane separation are risk factors for ruptured membranes. Oligohydramnios is a risk factor for preterm delivery and nulliparity is a risk factor for nonintact hysterotomy at delivery.

Prediction of early neonatal infection in pregnancies with prelabour rupture of membranes

Background: The uncertainty of predicting which pregnancies will have early onset neonatal infection (EONI) with prelabour rupture of membranes (PROM) is a challenge to obstetricians because presence of this condition impacts the decision to do expectant or active management of the case. The most common maternal markers of infection used in our practice are C-reactive protein, white blood cell count, and amniotic fluid glucose concentration. Objective: The primary objective of the study is to evaluate the accuracy of measuring C-reactive protein and leukocytes in maternal serum and amniotic fluid glucose concentration to predict early onset neonatal infection. The secondary objective of the study is to determine maternal fetal outcome in pregnancies with prelabour rupture of membranes. Material and methods: This prospective cross-sectional study enrolled 170 pregnant patients who experienced prelabour rupture of chorioamniotic membranes.. The maternal serum and amniotic fluid samples were taken at admission and later used to analyze whether/how the test results were a predictor of early onset neonatal infection. Results: Â C-reactive protein concentrations were significantly associated with early onset neonatal infection. Maternal CRP had 92.0% sensitivity and specificity of 62.8 % for predicting early onset neonatal infection. Maternal serum white blood cell count and amniotic fluid glucose concentrations estimation after pre-labour rupture of membranes showed poor predictive value in neonatal early onset infection. Conclusion: C-reactive protein was more sensitive in predicting Early Onset Neonatal Infection than either white blood cell count or amniotic fluid glucose concentration.

Differential immunophenotype of macrophages in acute and chronic chorioamnionitis.

The aim of this study was to investigate the involvement and immunophenotype of macrophages in acute chorioamnionitis (ACA) and chronic chorioamnionitis (CCA), marking amniotic fluid infection and anti-fetal rejection, respectively. Chorioamniotic membranes from (1) gestational age-matched cases without chorioamnionitis, (2) cases with ACA, and (3) cases with CCA were studied after immunohistochemical staining using antibodies against CD14, CD68, CD163, and DC-SIGN. Macrophages increased prominently in the chorionic trophoblastic layer of both ACA and CCA cases in contrast to non-inflammatory cases. Macrophages in the decidua and the chorioamniotic membranes of ACA cases expressed CD14. Macrophages in the chorionic trophoblastic layer of CCA cases were characterized by CD68 positivity. DC-SIGN-positive cells were increased in the chorioamniotic mesodermal layer of CCA cases. Macrophages participate in the inflammatory response in ACA and CCA. The differential immunophenotypes of macrophages in the decidua and chorioamniotic membranes of ACA and CCA cases suggest their disease-specific and region-specific roles at the feto-maternal interface.

A Role for the Inflammasome in Spontaneous Labor at Term.

Inflammasomes are signaling platforms that, upon sensing pathogens and sterile stressors, mediate the release of mature forms of interleukin (IL)-1β and IL-18. The aims of this study were to determine (i) the expression of major inflammasome components in the chorioamniotic membranes in spontaneous labor at term, (ii) whether there are changes in the inflammasome components associated with the activation of caspase-1 and caspase-4, and (iii) whether these events are associated with the release of the mature forms of IL-1β and IL-18. Chorioamniotic membranes were collected from women at term with and without spontaneous labor. mRNA abundance and protein concentrations of inflammasome components, nucleotide-binding oligomerization domain-containing (NOD)1 and NOD2 proteins, caspase-1, caspase-4, IL-1β, and IL-18 were quantified by qRT-PCR (n=28-29 each), ELISA (n=10 each) or immunoblotting (n=8 each), and immunohistochemistry (n=10 each). Active caspase-1 and caspase-4, as well as mature IL-18, were determined by immunoblotting (n=4 each), and pro- and mature forms of IL-1β were determined by ELISA (n=4-7 each). Inflammasome components and NOD proteins were expressed in the chorioamniotic membranes obtained from women at term. The chorioamniotic membranes from women who underwent labor had (i) higher concentrations of NLRP3 (NOD-like receptor family, pyrin domain-containing protein 3) and NOD1 protein, (ii) greater immunoreactivity for caspase-1 and caspase-4, (iii) a greater quantity of the active form of caspase-1 (p20), and (iv) higher mRNA abundance and protein concentrations of pro- and mature IL-1β. However, mRNA abundance and protein concentrations of the mature form of IL-18 were not increased in tissues from women who underwent labor at term. Spontaneous labor at term is characterized by the expression of inflammasome components, which may participate in the activation of caspase-1 and lead to the cleavage and release of mature IL-1β by the chorioamniotic membranes. These results support the participation of the inflammasome in the mechanisms responsible for spontaneous parturition at term.

Re: Chorioamniotic membrane separation after fetoscopy in monochorionic twin pregnancy: incidence and impact on perinatal outcome. J. U. Ortiz, E. Eixarch, A. Peguero, S. M. Lobmaier, M. Bennasar, J. M. Martinez and E. Gratacós. Ultrasound Obstet Gynecol 2016; 47: 345-349.

Linked Comment: Ultrasound Obstet Gynecol 2016; 47: 345–349

Chorioamniotic membrane separation after fetoscopy in monochorionic twin pregnancy: incidence and impact on perinatal outcome.

To evaluate the incidence of chorioamniotic membrane separation (CMS) after fetoscopy in monochorionic diamniotic (MCDA) twins and its impact on pregnancy outcome. The study group comprised a consecutive series of 338 women with an MCDA pregnancy complicated by twin-twin transfusion syndrome (TTTS) or selective intrauterine growth restriction (sIUGR) treated with selective laser photocoagulation of communicating vessels (SLPCV) or cord occlusion (CO). Data obtained included cervical length, gestational age at procedure, type and duration of surgery and placental location. The incidence of CMS, the rates of miscarriage and preterm prelabor rupture of membranes (PPROM), gestational age at delivery and neonatal survival were recorded. Of the study population of MCDA pregnancies, 270 (79.9%) had TTTS and 68 (20.1%) had sIUGR. SLPCV was performed in 252 (74.6%) cases and CO in 86 (25.4%). Postoperative CMS was observed in 70 (20.7%) cases. Patients with CMS had higher rates of miscarriage (14.3% vs 7.1%; P = 0.049), PPROM before 32 weeks (43.3% vs 13.7%; P < 0.001) and preterm delivery before 32 weeks (53.3% vs 26.1%; P < 0.001) and a lower rate of neonatal survival of at least one twin (81.7% vs 93.6%; P = 0.003). Multivariate analysis showed that gestational age at surgery was the only independent predictor, with the highest proportion of CMS occurring in cases that underwent surgery before 18 weeks' gestation (odds ratio, 2.941 (95% CI, 1.640-5.275); P < 0.001). There was no influence of cervical length, placental location, duration of surgery or type of surgery on the risk of CMS. CMS complicated one-fifth of all MCDA pregnancies that underwent fetoscopy. It appeared to be more common in those who underwent surgery before 18 weeks' gestation and was associated with poorer outcomes. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Study Of The Effect Of Chorioamniotic Membrane Sealing Drug (Amnioseal) In Premature Rupture Of Membranes: A Randomised Control Trial

Objective(s) : To study and compare the effectiveness of chorioamniotic Membrane sealing drug (Amnioseal) in premature rupture of membrane (PROM) with conventional treatment in terms of prolongation in gestational age and perinatal outcome. Method(s): This randomized control trial conducted in dept. of obs and gynae, SMS Medical College, Jaipur. 210 antenatal patients (pts) with prelabour PROM recruited for the study. They divided into 2 groups of gestational age 24-30 weeks (Group A) and 31-36 weeks (Group B). These groups further subdivided into A1, A2 and B1, B2 respectively. Out of them A1, B1 were cases and A2, B2 were controls. All the patients put on rest, antibiotics, prophylactic corticosteroids and tocolytics (conventional treatment). Amnioseal added to conventional treatment in cases of A1, B1. Results observed. Result(s) : In 24-30 weeks i.e. group A ,Mean prolongation of gestational age was 6.00 ± 3.87 wks (cases A1) versus 5.56 ± 3.46 wks (controls A2) while in 31-36 weeks i.e. group B, prolongation was 4.00 ± 2.42 weeks (cases B1) versus 3.50 ± 2.84 weeks (controls B2)(significant). In-group A mean birth weight was 1.80 ± 0.76 kg (in A1) versus 1.66 ± 0.72 kg (in A2), while 2.43 ± 0.44 kg (in B1) versus 2.20 ± 0.52 kg (in B2) (significant). Perinatal outcome was better in cases (A1 & B1). Conclusion(s): Membrane sealing drug (Amnioseal) has a definite role in PROM as it helps in prolongation of gestational age and improves fetal outcome

Diagnosis of Premature Rupture of Membranes by the Detection of Thyroid Hormones in Vaginal Secretions

Background:: Premature rupture of membranes (PROM) and preterm PROM (PPROM) are the rupture of the fetal chorioamniotic membranes before the onset of labor contractions. Objectives:: To evaluate whether detection of thyroid hormones in vaginal washouts can be used to diagnose premature rupture of membranes (PROM). Patients and Methods:: Total T4 (thyroxin), total T3 (triiodothyronine), and free T4 concentrations in vaginal washouts were analyzed in 45 women with the diagnosis of PROM and compared with 45 normal pregnancies (controls). A Student's t-test was used for comparison of thyroid hormone values and a ROC curve was used for analyzing the diagnostic accuracy. Results:: There were no differences between the patients with PROM and the control women regarding maternal age, gestational age, and parity. The mean concentration of total T4 in the PROM group and the control subjects were 2.1 ± 1.3 µg/mL and 1.55 ± 0.58 µg/, respectively (P = 0.01). Total T3 concentration in the PROM group was significantly higher compared to the controls (1.28 ± 0.42 ng/ vs. 0.8 ± 0.26 ng/, P < 0.0001). Also, free T4 concentration was significantly higher in the PROM group as compared with the controls (0.026 ± 0.034 ng/ vs.0.007 ± 0.004 ng/, P < 0.0001). The ROC curve analysis showed that total T4 = 1.685 µg/ had a sensitivity of 62%, specificity of 76%, positive predictive value (PPV) of 71.8%, and negative predictive value (NPV) of 66.7%. Total T3 = 0.82 ng/ gave a sensitivity of 91%, specificity of 64%, PPV of 72%, and NPV of 87.8%. Free T4 = 0.01 ng/ gave a sensitivity of 51%, specificity of 82%, PPV of 74.2%, and NPV of 62.7%. The best cutoff values were total T4 = 1.685 ng/, total T3 = 0.82 ng/, and free T4 = 0.01 ng/. Conclusions:: Detecting total T4, total T3, and free T4 in vaginal washouts of patients suspected of PROM suspected is a simple, available, rapid, and inexpensive method for the diagnosis of PROM. However, a combination of three tests is recommended.

57: Histological evidence of reparative activity of chorioamniotic membrane after open fetal surgery for myelomeningocele

57: Histological evidence of reparative activity of chorioamniotic membrane after open fetal surgery for myelomeningocele

Chorioamniotic membrane separation and preterm premature rupture of membranes complicating in utero myelomeningocele repair

Since the results of the Management of Myelomeningocele Study were published, maternal-fetal surgery for the in utero treatment of spina bifida has become accepted as a standard of care alternative. Despite promise with fetal management of myelomeningocele repair, there are significant complications to consider. Chorioamniotic membrane separation and preterm premature rupture of membranes are known complications of invasive fetal procedures. Despite their relative frequency associated with fetal procedures, few data exist regarding risk factors that may be attributed to their occurrence or the natural history of pregnancies that are affected with chorionic membrane separation or preterm premature rupture of membranes related to the procedure. The objective of this study was to review chorioamniotic membrane separation and preterm premature rupture of membranes in a cohort of patients undergoing fetal management of myelomeningocele repair including identification of risk factors and outcomes. This was a retrospective review of patients undergoing fetal management of myelomeningocele repair and subsequent delivery from January 2011 through December 2013 at 1 institution. Patients were identified through the institutional fetal management of myelomeningocele repair database and chart review was performed. Perioperative factors and outcomes among patients with chorioamniotic membrane separation and preterm premature rupture of membranes were compared to those without. Risk factors associated with the development of chorioamniotic membrane separation and preterm premature rupture of membranes were determined. A total of 88 patients underwent fetal management of myelomeningocele repair and subsequently delivered during the study period. In all, 21 patients (23.9%) were diagnosed with chorioamniotic membrane separation by ultrasound and preterm premature rupture of membranes occurred in 27 (30.7%). Among the chorioamniotic membrane separation patients, 10 (47.6%) were diagnosed with global chorioamniotic membrane separation and 11 (52.4%) with local chorioamniotic membrane separation. Earlier gestational age at the time of fetal surgery was a significant risk factor for the development of chorioamniotic membrane separation (P= .01) and preterm premature rupture of membranes (P < 0.0001). Chorioamniotic membrane separation was significantly associated with preterm premature rupture of membranes (59.1% vs 21.2%, P= .008) and earlier gestational age at delivery (32.1 ± 4.2 vs 34.4 ± 3.5 weeks, P= .01). The average number of days from chorioamniotic membrane separation to preterm premature rupture of membranes was 11.0 ± 10.1 and from chorioamniotic membrane separation to delivery was 31.0 ± 22.5. The mean time interval between fetal management of myelomeningocele repair and preterm premature rupture of membranes was 47.9 days. Mean latency period from preterm premature rupture of membranes to delivery was 25 days. Gestational age at delivery was significantly lower in patients with preterm premature rupture of membranes (31.6 ± 3.4 vs 34.9 ± 3.5 weeks, P= .0001). Using logistic regression analysis, nulliparity, gestational age at fetal management of myelomeningocele repair, and membrane separation remained significant risk factors for preterm premature rupture of membranes. Chorioamniotic membrane separation after fetal management of myelomeningocele repair is a significant risk factor forsubsequent development of preterm premature rupture of membranes and preterm delivery. Fetal management of myelomeningocele repair <23 weeks is associated with higher rates of preterm premature rupture of membranes and chorioamniotic membrane separation. Therefore fetal management of myelomeningocele repair should be deferred until ≥23 weeks to mitigate these complications. Nulliparity also appears to increase the risk for preterm premature rupture of membranes.

Chronic Placental Inflammation in Twin Pregnancies.

Background:Chronic placental inflammation, such as villitis of unknown etiology (VUE) and chronic chorioamnionitis (CCA), is considered a placental manifestation of maternal anti-fetal rejection. The aim of this study is to investigate its frequency in twin pregnancies compared to singleton pregnancies.Methods:Three hundred twin placentas and 1,270 singleton placentas were consecutively collected at a tertiary medical center in Seoul, Republic of Korea from 2009 to 2012. Hematoxylin and eosin sections of tissue samples (full-thickness placental disc and chorioamniotic membranes) were reviewed.Results:Non-basal VUE was more frequent in twin placentas than in singleton placentas (6.0% vs 3.2%, p < .05). In preterm birth, CCA was found less frequently in twin placentas than in singleton placentas (9.6% vs 14.8%, p < .05), reaching its peak at an earlier gestational age in twin placentas (29–32 weeks) than in singleton placentas (33–36 weeks). CCA was more frequent in twin pregnancies with babies of a different sex than with those with the same sex (13.8% vs 6.9%, p=.052). Separate dichorionic diamniotic twin placentas were affected by chronic deciduitis more frequently than singleton placentas (16.9% vs 9.7%, p<.05).Conclusions:The higher frequency of non-basal VUE in twin placentas and of CCA in twin placentas with different fetal sex supports the hypothesis that the underlying pathophysiological mechanism is maternal anti-fetal rejection related to increased fetal antigens in twin pregnancies. The peak of CCA at an earlier gestational age in twin placentas than in singleton placentas suggests that CCA is influenced by placental maturation.

Chorioamniotic membrane senescence: a signal for parturition?

Senescence is an important biological phenomenon involved in both physiologic and pathologic processes. We propose that chorioamniotic membrane senescence is a mechanism associated with human parturition. The present study was conducted to explore the association between senescence and normal term parturition by examining the morphologic and biochemical evidences in chorioamniotic membranes. Chorioamniotic membranes were collected from normal term deliveries; group 1: term labor and group 2: term, not in labor. Senescence-related morphologic changes were determined by transmission electron microscopy and biochemical changes were studied by senescence-associated (SA) β-galactosidase staining. Amniotic fluid samples collected from both term labor and term not in labor were analyzed for 14 SA secretory phenotype (SASP) markers. Morphologic evidence of cellular senescence (enlarged cells and organelles) and a higher number of SA β-galactosidase-stained amnion and chorion cells were observed in chorioamniotic membranes obtained from women in labor at term, when compared to term not in labor. The concentration of proinflammatory SASP markers (granulocyte macrophage colony-stimulating factor, interleukin-6 and -8) was significantly higher in the amniotic fluid of women in labor at term than women not in labor. In contrast, SASP factors that protect against cell death (eotaxin-1, soluble Fas ligand, osteoprotegerin, and intercellular adhesion molecule-1) were significantly lower in the amniotic fluid samples from term labor. Morphologic and biochemical features of senescence were more frequent in chorioamniotic membranes from women who experienced term labor. Senescence of chorioamniotic membranes were also associated with amniotic fluid SASP markers.

Transcriptomics of maternal and fetal membranes can discriminate between gestational-age matched preterm neonates with and without cognitive impairment diagnosed at 18-24 months.

BackgroundNeurocognitive impairment among children born preterm may arise from complex interactions between genes and the intra-uterine environment.Objectives(1) To characterize the transcriptomic profiles of chorioamniotic membranes in preterm neonates with and without neurocognitive impairment via microarrays and (2) to determine if neonates with neurocognitive impairment can be identified at birth.Materials/MethodsA retrospective case-control study was conducted to examine the chorioamniotic transcriptome of gestational-age matched very preterm neonates with and without neurocognitive impairment at 18–24 months’ corrected-age defined by a Bayley-III Cognitive Composite Score <80 (n = 14 each). Pathway analysis with down-weighting of overlapping genes (PADOG) was performed to identify KEGG pathways relevant to the phenotype. Select differentially expressed genes were profiled using qRT-PCR and a multi-gene disease prediction model was developed using linear discriminant analysis. The model’s predictive performance was tested on a new set of cases and controls (n = 19 each).Results 1) 117 genes were differentially expressed among neonates with and without subsequent neurocognitive impairment (p<0.05 and fold change >1.5); 2) Gene ontology analysis indicated enrichment of 19 biological processes and 3 molecular functions; 3)PADOG identified 4 significantly perturbed KEGG pathways: oxidative phosphorylation, Parkinson’s disease, Alzheimer’s disease and Huntington’s disease (q-value <0.1); 4) 48 of 90 selected differentially expressed genes were confirmed by qRT-PCR, including genes implicated in energy metabolism, neuronal signaling, vascular permeability and response to injury (e.g., up-regulation of SEPP1, APOE, DAB2, CD163, CXCL12, VWF; down-regulation of HAND1, OSR1)(p<0.05); and 5) a multi-gene model predicted 18–24 month neurocognitive impairment (using the ratios of OSR1/VWF and HAND1/VWF at birth) in a larger, independent set (sensitivity = 74%, at specificity = 83%).ConclusionsGene expression patterns in the chorioamniotic membranes link neurocognitive impairment in preterm infants to neurodegenerative disease pathways and might be used to predict neurocognitive impairment. Further prospective studies are needed.