Long-term neurological outcomes of offspring misdiagnosed with fetal growth restriction.

OBJECTIVE: Fetal growth restriction (FGR) is a major determinant of adverse short- and long-term perinatal outcomes. The current definition of FGR (estimated fetal weight measurement < 10th percentile) may lead, at times, to a false diagnosis of fetuses that are eventually born appropriate for gestational age (AGA). Our objective was to investigate the potential association between a misdiagnosis of antepartum fetal growth restriction and long-term neurological outcomes in offspring. STUDY DESIGN: A population-based cohort analysis was performed including deliveries between the years 1991-2020 in a tertiary medical center. We compared neurological hospitalization during childhood among AGA infants falsely diagnosed as FGR versus AGA infants without a false FGR diagnosis. A Kaplan-Meier survival curve was used to assess cumulative morbidity and a Cox proportional hazards model was employed to control for confounders. RESULTS: During the study period, 324,620 AGA infants met the inclusion criteria; 3249 of them were falsely classified as FGR. These offspring had higher rates of hospitalizations due to various neurological conditions, as compared to those without an FGR diagnosis (OR 1.431, 95% CI 1.278-1.608; P < 0.001). In addition, cumulative hospitalization incidence was elevated in the FGR group (log-rank P-value < 0.001). When controlling for confounders, a false FGR diagnosis remained independently associated with long-term neurological morbidities (adjusted HR 1.086, 95% CI 1.003-1.177, P = 0.043). CONCLUSION: Misdiagnosis of FGR in the antepartum period is associated with an increased risk for offspring long-term neurological morbidities.

Term and Preterm Birth Initiation Is Associated with the Macrophages Shifting to M1 Polarization in Gestational Tissues in Mice.

Inflammation in gestational tissues plays critical role in parturition initiation. We sought to investigate the leukocyte infiltration and cytokine profile in uterine tissues to understand the inflammation during term and preterm labor in the mouse model. Preterm birth was induced by the administration of lipopolysaccharide (LPS) or RU38486. The populations of leukocytes were determined by flow cytometry. Macrophages were the largest population in the myometrium and decidua in late gestation. The macrophage population was significantly changed in the myometrium and decidua from late pregnancy to term labor and significantly changed at LPS- and RU386-induced preterm labor. Neutrophils, T cells, and NKT cells were increased in LPS- and RU38486-induced preterm labor. The above changes were accompanied by the increased expression of cytokines and chemokines. In late gestation, M2 macrophages were the predominant phenotype in gestational tissues. M1 macrophages significantly increased in these tissues at term and preterm labor. IL-6 and NLRP3 expression was significantly increased in macrophages at labor, supporting that macrophages exhibit proinflammatory phenotypes. NLRP3 inflammasome inhibitor MCC950 mainly suppressed macrophage infiltration in the myometrium at term labor and preterm labor. Our data suggest that the M1 polarization of macrophages contributes to inflammation linked to term and preterm labor initiation in gestational tissues.

Immune Deviation in the Decidua During Term and Preterm Labor.

The maternal-fetal immune disorder is considered to be an important factor of preterm birth (PTB); however, the underlying mechanism is still not fully understood. This study was designed to explore the innate and adaptive immune features in the decidua during term and preterm labor. Women delivered at term or preterm were classified into four groups: term not in labor (TNL, N=19), term in labor (TL, N=17), preterm not in labor (PNL, N=10), and preterm in labor (PIL, N=10). Decidua basalis and parietalis were collected and analyzed for macrophage subtypes (M1 and M2) as well as T helper 1 (Th1), Th2, Th17 and regulatory T (Treg) cells by flow cytometry and immunohistochemistry. Our results demonstrated significantly decreased frequencies of M2 cells and elevated M1/M2 ratio in the PIL group compared to that in the PNL group in both decidua basalis and parietalis, whereas no significant differences were found between the above two groups in both sites in terms of the polarization status of Th cells. On the contrary, macrophage subsets were comparable in the TL and TNL groups, whereas elevated Th1 percentages and Th1/Th2 ratio were observed in TL women compared to that in TNL women in the decidua. Interestingly, although the frequencies and ratios of Th17 and Treg were comparable among the four groups, the Th17/Treg ratios of these groups were significantly increased in decidua basalis than that in decidua parietalis. Collectively, the M1/M2 imbalance is associated with the breakdown of maternal-fetal immune tolerance during PTB, whereas the aberrant Th1/Th2 profile plays an important role in immune disorder during term labor. Moreover, Th17/Treg deviation is more remarkable in decidua basalis than in decidua parietalis.

Alvarez waves in pregnancy: a comprehensive review.

Alvarez waves are local rhythmic contractions of the myometrium with high frequency and low intensity. They can be detected using internal or external tocography and electrohysterography. Some researchers correlate these small contractions with the initiation of labor, since they have been described as a pattern representing the uterine response to prostaglandin production. Other authors either do not validate a causality relation between Alvarez waves and labor or suggest that they have low predictive value for preterm labor. Alvarez waves' research has become a multidisciplinary subject with inputs ranging from medical science, biomedical engineering, and related areas. A comprehensive review is herein conducted to summarize the state of the art regarding Alvarez waves and their role in the initiation of labor, namely in preterm birth. The results show that a large number of studies have analyzed and characterized Alvarez waves without necessarily digging into their relationship with labor. Publications were categorized in three groups: (A) reports about morphology and characterization of Alvarez waves; (B) publications reporting a positive causality relation between Alvarez waves and labor; and (C) publications reporting an absence of causality regarding the previous hypothesis. Studies in group B outnumbered those in group C. A critical analysis is presented.

Metabolomics in Prenatal Medicine: A Review.

Pregnancy is a complicated and insidious state with various aspects to consider, including the well-being of the mother and child. Developing better non-invasive tests that cover a broader range of disorders with lower false-positive rates is a fundamental necessity in the prenatal medicine field, and, in this sense, the application of metabolomics could be extremely useful. Metabolomics measures and analyses the products of cellular biochemistry. As a biomarker discovery tool, the integrated holistic approach of metabolomics can yield new diagnostic or therapeutic approaches. In this review, we identify and summarize prenatal metabolomics studies and identify themes and controversies. We conducted a comprehensive search of PubMed and Google Scholar for all publications through January 2020 using combinations of the following keywords: nuclear magnetic resonance, mass spectrometry, metabolic profiling, prenatal diagnosis, pregnancy, chromosomal or aneuploidy, pre-eclampsia, fetal growth restriction, pre-term labor, and congenital defect. Metabolite detection with high throughput systems aided by advanced bioinformatics and network analysis allowed for the identification of new potential prenatal biomarkers and therapeutic targets. We took into consideration the scientific papers issued between the years 2000-2020, thus observing that the larger number of them were mainly published in the last 10 years. Initial small metabolomics studies in perinatology suggest that previously unidentified biochemical pathways and predictive biomarkers may be clinically useful. Although the scientific community is considering metabolomics with increasing attention for the study of prenatal medicine as well, more in-depth studies would be useful in order to advance toward the clinic world as the obtained results appear to be still preliminary. Employing metabolomics approaches to understand fetal and perinatal pathophysiology requires further research with larger sample sizes and rigorous testing of pilot studies using various omics and traditional hypothesis-driven experimental approaches.

Characterizing the immune cell population in the human fetal membrane.

PROBLEM: This study localized CD45+ immune cells and compared changes in their numbers between term, not in labor (TNIL) and term, labor (TL) human fetal membranes. METHOD OF STUDY: Fetal membranes (amniochorion) from normal TNIL and TL subjects were analyzed by immunohistochemistry (IHC), immunofluorescence (IF), and flow cytometry for evidence of total (CD45+ ) immune cells as well as innate immune cells (neutrophils, macrophages and NK cells) using specific markers. Fetal origin of immune cells was determined using polymerase chain reaction (PCR) for SRY gene in Y chromosome. RESULTS: CD45+ cells were localized in human fetal membranes for both TNIL and TL. A threefold increase in CD45+ cells was seen in TL fetal membranes of (7.73% ± 2.35) compared to TNIL (2.36% ± 0.78). This increase is primarily contributed by neutrophils. Macrophages and NK cells did not change in the membranes between TNIL and TL. Leukocytes of fetal origin are present in the fetal membranes. CONCLUSION: The fetal membranes without decidua contain a small proportion of immune cells. Some of these immune cells in the fetal membrane are fetal in origin. There is a moderate increase of immune cells in the fetal membranes at term labor; however, it is unclear whether this is a cause or consequence of labor. Further functional studies are needed to determine their contribution to membrane inflammation associated with parturition.

Reprint of: Myometrial activation: Novel concepts underlying labor.

Term labour is a state of physiological inflammation orchestrated by multiple uterine tissues (both fetal and maternal). This physiological inflammation preceding and accompanying labour onset is characterized by an increase in cytokine and chemokine secretion by the fetal membranes, as well as uterine tissues (i.e., decidua and myometrium). Pro-inflammatory cytokines and chemokines activate circulating maternal peripheral leukocytes as well as the uterine vascular endothelium to permit leukocyte infiltration into the uterus. This inflammatory milieu, in the absence of infection, is required for the initiation of labour as the uterine-infiltrated leukocytes secrete matrix metalloproteinases to induce fetal membrane rupture and cervical ripening as well as various labour mediators, which promote contractions of the myometrium. Myometrial activation at term and the onset of labour contractions are directly related to the changes in the ovarian/placental hormone progesterone and its downstream mediators (i.e., the progesterone receptors, PRA/B), which are also critical for maintenance of pregnancy. Our recent data provides direct evidence in support of local and functional P4 withdrawal in the uterine muscle (myometrium) via the activator protein-1 (AP-1) mediated pathway. This review outlines known mechanisms regulating activation of human labour, including progesterone and cytokine signaling. Understanding of the molecular mechanism of myometrial activation and labour onset could facilitate the development of new therapeutics for high-risk pregnant women to prevent premature uterine activation and preterm birth.

Myometrial activation: Novel concepts underlying labor.

Term labour is a state of physiological inflammation orchestrated by multiple uterine tissues (both fetal and maternal). This physiological inflammation preceding and accompanying labour onset is characterized by an increase in cytokine and chemokine secretion by the fetal membranes, as well as uterine tissues (i.e., decidua and myometrium). Pro-inflammatory cytokines and chemokines activate circulating maternal peripheral leukocytes as well as the uterine vascular endothelium to permit leukocyte infiltration into the uterus. This inflammatory milieu, in the absence of infection, is required for the initiation of labour as the uterine-infiltrated leukocytes secrete matrix metalloproteinases to induce fetal membrane rupture and cervical ripening as well as various labour mediators, which promote contractions of the myometrium. Myometrial activation at term and the onset of labour contractions are directly related to the changes in the ovarian/placental hormone progesterone and its downstream mediators (i.e., the progesterone receptors, PRA/B), which are also critical for maintenance of pregnancy. Our recent data provides direct evidence in support of local and functional P4 withdrawal in the uterine muscle (myometrium) via the activator protein-1 (AP-1) mediated pathway. This review outlines known mechanisms regulating activation of human labour, including progesterone and cytokine signaling. Understanding of the molecular mechanism of myometrial activation and labour onset could facilitate the development of new therapeutics for high-risk pregnant women to prevent premature uterine activation and preterm birth.

Isolation and characterization of human amniotic fluid-derived exosomes.

Extracellular vesicles (EVs), specifically exosomes of 50-150nm, have emerged as important communication channels between cells and tissues and can be isolated from multiple biofluids including blood, urine and amniotic fluid. No standardized approach for exosome isolation from these biofluids has been established. This chapter outlines an optimized approach for isolating exosomes from human amniotic fluid samples. Like plasma, amniotic fluid contains many protein and cellular contaminants that requires multiple steps for cleanup. Therefore, to ensure samples contain minimal contaminants, including larger EVs, we also outline multiple methods for characterization of isolated exosomes for size, morphology and protein markers.

Brucellosis in pregnancy: case reports with different outcomes in an endemic region.

Different outcomes of brucellosis in pregnancy regarding the fetus/neonate and the mother are described. Medical records of five pregnant women with brucellosis were retrospectively analyzed. Patients were treated in several departments of infectious diseases in the Republic of Macedonia between 1995 and 2009. The diagnosis of brucellosis was based on clinical findings compatible with the disease supported by detection of specific antibodies. Pregnancy outcomes in patients were as follows: spontaneous abortion, intrauterine fetal death, premature delivery in two cases (one with twin pregnancy) and term delivery. One of the women experienced relapse. Follow-up results of neonates showed no infection and their normal growth and development. Brucellosis, especially if acquired in early pregnancy, can have an impact on pregnancy outcome. In endemic regions, in pregnant women with persisting fever and unspecific manifestations one should always have in mind brucellosis. In these areas, cases with unexplained spontaneous abortion, intrauterine fetal death and premature delivery should also be investigated for brucellosis.

Changes in mediators of pro-cell growth, senescence, and inflammation during murine gestation.

PROBLEM: Senescence of the fetal membranes and senescence-associated inflammation have been associated with parturition at term and pre-term in both mice and humans. Using a pregnant mouse model, we determined changes in multiple molecular signalers contributing to senescence and inflammation associated with parturition. METHOD OF STUDY: Fetal membranes were collected from timed-pregnant CD-1 mice on gestation days (E) 13, 15, 17, 18, and 19. Immunohistochemistry (IHC) localized pro-cell growth factors glycogen synthase kinase 3ß (GSK3ß) and ß-catenin. Gestational age-associated changes in pro-cell growth vs senescence mediators (p38 mitogen-activated protein kinase [p38MAPK]), prooxidants (heme oxygenase-1 [HO-1], peroxisome proliferator-activated receptor γ [PPARγ]), and pro- and anti-inflammatory cytokines (IL-6, IL-8, IL-10, and IL-1ß) were determined by Western blots and Luminex assays. RESULTS: Fetal membrane expressions of phosphorylated forms of GSK3ß (inactivation) and p38MAPK (activation) increased, while ß-catenin expression decreased, as gestation progressed. Antioxidant HO-1 expression decreased while PPARγ increased toward term gestation. IL-6 and IL-8 concentrations were highest on E19 (day of delivery), while IL-10 and IL-1ß concentrations were highest on E15. CONCLUSION: Mouse fetal membranes showed a progressive senescence marker increase coincided with downregulation of cell growth factors. Development of senescence is associated with inflammation. Senescence-associated changes are natural and physiologic and indicative of fetal membranes' readiness for parturition.

The origin of amniotic fluid monocytes/macrophages in women with intra-amniotic inflammation or infection.

Background Monocytes, after neutrophils, are the most abundant white blood cells found in the amniotic cavity of women with intra-amniotic inflammation/infection. However, the origin of such cells has not been fully investigated. Herein, we determined (1) the origin of amniotic fluid monocytes/macrophages from women with intra-amniotic inflammation/infection, (2) the relationship between the origin of amniotic fluid monocytes/macrophages and preterm or term delivery and (3) the localization of monocytes/macrophages in the placental tissues. Methods Amniotic fluid samples (n = 16) were collected from women with suspected intra-amniotic inflammation or infection. Amniotic fluid monocytes/macrophages were purified by fluorescence-activated cell sorting, and DNA fingerprinting was performed. Blinded placental histopathological evaluations were conducted. Immunohistochemistry was performed to detect CD14+ monocytes/macrophages in the placental tissues. Results DNA fingerprinting revealed that (1) 56.25% (9/16) of amniotic fluid samples had mostly fetal monocytes/macrophages, (2) 37.5% (6/16) had predominantly maternal monocytes/macrophages and (3) one sample (6.25% [1/16]) had a mixture of fetal and maternal monocytes/macrophages. (4) Most samples with predominantly fetal monocytes/macrophages were from women who delivered early preterm neonates (77.8% [7/9]), whereas all samples with mostly maternal monocytes/macrophages or a mixture of both were from women who delivered term or late preterm neonates (100% [7/7]). (5) Most of the women included in this study presented acute maternal and fetal inflammatory responses in the placenta (85.7% [12/14]). (6) Women who had mostly fetal monocytes/macrophages in amniotic fluid had abundant CD14+ cells in the umbilical cord and chorionic plate, whereas women with mostly maternal amniotic fluid monocytes/macrophages had abundant CD14+ cells in the chorioamniotic membranes. Conclusion Amniotic fluid monocytes/macrophages can be of either fetal or maternal origin, or a mixture of both, in women with intra-amniotic inflammation or infection. These immune cells could be derived from the fetal and maternal vasculature of the placenta.

Fetal adrenal gland size and the ability to predict spontaneous term labor.

OBJECTIVE: The objective of this study was to evaluate whether ultrasound measured fetal adrenal gland size can be a predictor of spontaneous term labor. STUDY DESIGN: This study was a diagnostic test accuracy study using a prospective cohort design evaluating the ability of 2-dimensional ultrasound measurement of fetal adrenal gland total length, total width, fetal zone length and fetal zone width in women in the third trimester to predict the primary outcome of spontaneous term labor. Secondary outcomes were vaginal delivery, length of labor, and maternal and neonatal morbidities. RESULTS: Of 43 patients recruited, 3 were excluded. 11 (25.6%) presented in spontaneous labor and 29 (67.4%) underwent induction of labor. Patient demographics were similar for all included except for admission cervical exam and oxytocin use. A receiver operative curve was created to assess test predictability. Weighted width of fetal adrenal gland was the best predictor of spontaneous labor amongst variables measured with an area under the curve of 0.674, p = 0.93. w/W ≥ 0.41 had a sensitivity of 91.0%, specificity of 44.8%, positive predictive value of 38.5% and a negative predictive value of 92.3%. Maternal and neonatal morbidities were not different between the spontaneous labor group and the induction of labor group. CONCLUSION: Ultrasound measured fetal w/W was moderately predictive of spontaneous labor.

Building a predictive model for successful vaginal delivery in nulliparas with term cephalic singleton pregnancies using decision tree analysis.

AIM: To establish a model predicting successful vaginal delivery (VD) in nulliparas with term cephalic singleton pregnancies. METHODS: We retrospectively identified 6799 term nulliparas with cephalic singletons (6416 VD and 383 cesarean section [CS] due to dystocia) who entered labor (cervical dilation ≥2 cm) between September 2014 and August 2015. Using VD as the dependent variable and age, maternal body height, educational attainment, gravidity, gestational age, pre-pregnancy body mass index (BMI), BMI upon admission for delivery, gestational weight gain, gestational hypertension and gestational diabetes as the independent variables, predictors of VD success were identified using a multivariate binary logistic regression and then ranked with decision-tree analysis. RESULTS: While multiple factors are associated with improved VD success, we found body height, gestational age, and intrapartum BMI to be the best predictors of successful VD. Our predictive model has a classification accuracy, sensitivity and specificity of 76.6%, 96.7% and 16.4%, respectively, and it was subsequently confirmed by both internal and external validation. CONCLUSION: Our predictive model indicates body height, gestational age and intrapartum BMI as the major predictors of successful VD in low-risk patients.

Repeated lipopolysaccharide exposure leads to placental endotoxin tolerance.

PROBLEM: Placental infection induces increased levels of pro-inflammatory cytokines, which have been implicated in the pathogenesis of pre-term labor. Endotoxin tolerance is a phenomenon in which exposure to a dose of endotoxin makes tissue less responsive to subsequent exposures. The objective of our study was to determine whether repeated exposure to endotoxin will induce a tolerant phenotype in normal human second-trimester placental tissue. METHODS OF STUDY: Human second-trimester placental explants from elective termination of pregnancy were cultured and exposed to endotoxin (LPS). After 24 hours, the media was collected for analysis, and the explants were re-exposed to LPS after adding fresh media for another 24 hours. This process was repeated for a total of 4 LPS doses. The media was collected from each day and analyzed for cytokine levels. RESULTS: The first LPS treatment stimulated the secretion of the pro-inflammatory cytokines IL-1ß and TNF-α. However, their production was significantly diminished with repeated LPS doses. Production of the anti-inflammatory cytokines, IL-1ra and IL-10, was also stimulated by the first LPS treatment, but secretion was more gradually and moderately decreased with repeated LPS doses compared to the pro-inflammatory cytokines. The ratios of the anti-inflammatory/pro-inflammatory mediators (IL-1ra/IL-1ß and IL-10/TNF-α) indicate a progressively more anti-inflammatory milieu with repeated LPS doses. CONCLUSION: Repeated LPS exposure of human second-trimester placental tissues induced endotoxin tolerance. We speculate that endotoxin tolerance at the maternal-fetal interface will protect the fetus from exaggerated inflammatory responses after repeated infectious exposure.

Colonization of Acinetobacter baumannii, Streptococcus agalactiae (GBS) and Candida albicans in preterm premature rupture of membrane (PPROM) compared to normal labor at term

Aims@#Preterm premature rupture of membrane (PPROM) is usually associated with maternal vaginal colonization of Group B Streptococci (GBS). However, there are reports on isolation of Acinetobacter baumannii in PPROM cases. In order to ascertain A. baumannii’s role in PPROM, we determine the colonization of A. baumannii and other common vaginal tract flora, i.e. GBS and Candida albicans, in women with PPROM, and compared them to those with normal labor at term (NLT). The transmissibility of the organisms to their babies was also investigated. @*Methodology and results@#A total of 218 high vaginal swabs from 108 and 100 women with PPROM and NLT respectively were collected. The transmission of these organisms to their 215 babies was determined by swabbing the ears and axillae. These were cultured for isolation of A. baumannii, GBS and C. albicans. Results showed that mothers with PPROM were predominantly colonized with GBS (32.4%), followed by C. albicans (19.4%) and A. baumannii (7.4%), compared to 10.9%, 17.3% and 7.2% respectively, in women with NLT. Between 34 to 50% of the babies of mothers with PPROM acquired the organisms, with GBS being the most significantly (p=0.000) transferred compared to other organisms. Co-existence of A. baumannii with either GBS or C. albicans, or both, did not enhance the occurrence of PPROM. @*Conclusion, significance and impact of study@#Colonization of A. baumannii in vaginal tract of pregnant women does not increase the possibility of PPROM, as compared to GBS.

Expression and regulation of metallothioneins in myometrium and fetal membranes.

PROBLEM: Metallothioneins (MTs) play important roles in regulating oxidative stress, inflammation, and hormone signaling. These processes play a major role in labor at term and preterm. The aims of this study were to characterize (a) temporal- and labor-associated changes and (b) the effect of pro-inflammatory and pro-labor insults on the expression of MT1 isoforms, MT2A, MT3, and MT4 in fetal membranes and myometrium. METHOD OF STUDY: The expression of MTs was assessed in fetal membranes and myometrium from nonlaboring and laboring women at preterm and term by RT-qPCR. Tissue explants were used to assess the effect of pro-inflammatory cytokines and Toll-like receptor (TLR) ligands on the expression of MTs in fetal membranes and myometrium. RESULTS: In fetal membranes, the expression of MT1A, MT1E, MT1F, MT1X, and MT2A was higher at term compared with preterm. Preterm labor and preterm histological chorioamnionitis were associated with increased expression of MT1A, MT1G, MT1M, MT1X, MT2A, and MT3. Term labor was associated with increased expression of MT1A, MT1F, MT1X, MT2A, and MT3 in fetal membranes and expression of MT1A, MT1E, MT1F, MT1G, MT1M, MT1X, MT2A, and MT3 in myometrium. Pro-inflammatory cytokines and TLR ligands increased the expression of MT1A, MT1E, MT1F, MT1G, MT1H, MT1X, and MT2A in fetal membranes and myometrium. CONCLUSION: Temporal-, labor-, and infection-associated increases in MT1 isoforms, MT2A, and MT3 have been observed in fetal membranes and/or myometrium. Furthermore, pro-inflammatory cytokines and bacterial and viral products increased the expression of MT1 isoforms, MT2A, MT3, and MT4 mRNA expression in fetal membranes and myometrium.

Related factors of prognosis of patients with gestational trophoblastic neoplasia after chemotherapy / 第二军医大学学报

Objective To explore the clinical factors influencing the prognosis of patients with gestational trophoblastic neoplasia (GTN) after chemotherapy. Methods The clinical data of 55 patients with gestational trophoblastic diseases in our hospital from 2009 to 2016 were retrospectively analyzed, including 26 cases with hydatidiform mole and 29 cases with GTN (23 cases of invasive mole and 6 cases of choriocarcinoma). Among them, 23 GTN patients with the follow-up human chorionic gonadotropin (HCG)5 U/L for 3 times after chemotherapy were included in this study. The age, reproductive history, lung metastasis, International Federation of Gynecology and Obstetrics (FIGO) stage and other clinical factors which might affect the cure time of GTN patients were analyzed by Cox regression analysis. The relationship between age and reproductive history and cure time were analyzed by Kaplan-Meier survival analysis. Results Cox regression univariate analysis showed that term delivery and abortion were related to the cure time of GTN patients (both P0.05), and the age was close to statistical significance (P=0.051). Cox multivariate analysis showed that term delivery was an independent factor influencing the cure time of GTN patients (P=0.020). Kaplan-Meier survival analysis showed that age (P=0.043), term delivery (P=0.016) and abortion (P=0.026) were related to the cure time of GTN patients after chemotherapy. Conclusion Older women or women who have histories of term delivery or abortion should be alerted to the occurrence of GTN, which has long cure time and the dynamic changes of blood HCG need to be closely monitored.

Lower limbs venous compression reduces the incidence of maternal hypotension following epidural analgesia during term labor.

OBJECTIVE(S): Every year in France, 10% to 20% of the 600 000 women given epidural analgesia during labor experience hypotension, which in 15% of cases is associated with fetal heart rate abnormalities. The efficiency of lower limbs venous compression in preventing the occurrence of maternal hypotension after neuraxial anesthesia has already been demonstrated, but only in the context of scheduled cesarean section. We assessed the preventive effect of medical lower limbs venous compression on the incidence of maternal hypotension after epidural analgesia during spontaneous term labor. STUDY DESIGN: This before/after, single-center study in a university hospital included 93 women in spontaneous labor at term who between 1 January and 31 March 2015 with epidural analgesia plus lower limbs compression and 202 women in spontaneous labor at term who delivered between 1 and 31 December 2014 with epidural analgesia without lower limbs compression (control group). The main outcome was maternal hypotension (systolic blood pressure <90mmHg and/or delta >20%) in the 15min after epidural analgesia. RESULTS: In the lower limbs compression group the incidence of hypotension 15min after epidural analgesia was significantly lower than in the control group (3.23% versus 23.3%, adjusted odds ratio=0.1 [0.03; 0.35]). The incidence of fetal heart rate abnormalities was unsignificantly lower in the lower limbs compression group than in the control group (10.7% versus 16.34%, p=0.22). CONCLUSION: The results suggest that medical lower limbs compression (20-36mmHg) in women in spontaneous labor at term, could significantly reduce the incidence of maternal hypotension following epidural analgesia. A prospective, randomized, open trial would allow confirmation of these preliminary results.

Are amniotic fluid neutrophils in women with intraamniotic infection and/or inflammation of fetal or maternal origin?

BACKGROUND: Neutrophils are the most abundant white blood cells found in the amniotic cavity of women with intraamniotic infection and/or inflammation. The current belief is that these neutrophils are of fetal origin. However, abundant neutrophils have been found in the amniotic fluid of women with a severe acute maternal inflammatory response but without a severe fetal inflammatory response in the placenta, suggesting that these innate immune cells can also be of maternal origin or a mixture of both fetal and maternal neutrophils. OBJECTIVE: We sought to investigate the origin of amniotic fluid neutrophils from women with intraamniotic infection and/or inflammation and to correlate these findings with acute histologic maternal and fetal inflammatory responses in the placenta. STUDY DESIGN: Amniotic fluid was collected from 15 women with suspected intraamniotic infection and/or inflammation (positive microbiological cultures and/or interleukin-6 concentrations ≥2.6 ng/mL). Amniotic fluid neutrophils were purified by fluorescence-activated cell sorting, DNA was extracted, and DNA fingerprinting was performed. DNA fingerprinting was also performed in the umbilical cord and maternal blood DNA. Fluorescence in situ hybridization was assayed in women with male neonates. Blinded placental histopathological evaluations were conducted. RESULTS: First, DNA fingerprinting revealed that 43% (6/14) of women who underwent a single amniocentesis had mostly fetal neutrophils in the amniotic fluid. Second, DNA fingerprinting showed that 36% (5/14) of the women who underwent a single amniocentesis had predominantly maternal neutrophils in the amniotic fluid. Third, DNA fingerprinting indicated that 21% (3/14) of the women who underwent a single amniocentesis had an evident mixture of fetal and maternal neutrophils in the amniotic fluid. Fourth, DNA fingerprinting revealed that a woman who underwent 2 amniocenteses (patient 15) had fetal neutrophils first, and as infection progressed, abundant maternal neutrophils invaded the amniotic cavity. Fifth, fluorescence in situ hybridization confirmed DNA fingerprinting results by showing that both fetal and maternal neutrophils were present in the amniotic fluid. Sixth, most of the women who had predominantly amniotic fluid neutrophils of fetal origin at the time of collection delivered extremely preterm neonates (71% [5/7]). Seventh, all of the women who had predominantly amniotic fluid neutrophils of maternal origin at the time of collection delivered term or late preterm neonates (100% [6/6]). Eighth, 2 of the women who had an evident mixture of fetal and maternal neutrophils in the amniotic fluid at the time of collection delivered extremely preterm neonates (67% [2/3]), and the third woman delivered a term neonate (33% [1/3]). Finally, most of the women included in this study presented acute maternal and fetal inflammatory responses in the placenta (87% [13/15]). CONCLUSION: Amniotic fluid neutrophils can be either predominantly of fetal or maternal origin, or a mixture of both fetal and maternal origin, in women with intraamniotic infection and/or inflammation. The findings herein provide evidence that both fetal and maternal neutrophils can invade the amniotic cavity, suggesting that both the fetus and the mother participate in the host defense mechanisms against intraamniotic infection.