European consensus statement on essential colposcopy.

This European consensus statement on essential colposcopy provides standards for the general colposcopist seeing women referred for colposcopy with an abnormal cervical screening test (including cytology and HPV tests) or with a clinically suspicious cervix. The article gives guidance regarding the aims and conduct of colposcopy. Recommendations are provided on colposcopy technique, the management of common colposcopy issues, treatment and follow-up of after treatment of CIN or early stage cervical. Colposcopists should make an informed decision on the management of each individual that is referred and organize appropriate follow-up. Cervical cancer is still a major health issue and the quality of care can only improve if there is a structured guidance for women with an abnormal smear or suspicious cervix.

Lymphocyte characterization of decidua basalis spiral arteries with acute atherosis in preeclamptic and normotensive pregnancies.

Uteroplacental acute atherosis (AA) is a common spiral arterial lesion in preeclampsia, characterized by intramural foam cells, fibrinoid necrosis, and a perivascular immune cell infiltrate. A clear definition of this infiltrate is lacking. Therefore, our aim was to characterize lymphocytes in pre-defined zones regarding spiral arteries with or without AA, from preeclamptic and normotensive pregnancies. Lymphocytes were characterized in decidua basalis samples (n = 91), previously evaluated for AA, around spiral arteries in three pre-defined zones; 1) intramural, 2) perivascular and 3) interstitial. Adjacent serial sections were immunostained to identify different T-cell populations (CD3+, CD8+, FOXP3+), and NK-cells (CD56+). CD3+CD8- T-cells were also identified. These were presumed to be largely CD4+ T-cells. AA was associated with significantly higher intramural CD3+ cell concentrations in Zone 1, in both normotensives and preeclamptics. In preeclamptics only, this difference extended into Zone 2. Similar results were observed for CD3+CD8- cells. AA was also associated with increased intramural CD8+ concentration; however, the number of cells was low. Regulatory T-cells (FOXP3+) were generally scarce or absent in all pre-defined zones. Although intramural NK-cells (CD56+) were scarce, the intramural concentration was significantly lower in spiral arteries with AA compared to without AA in preeclamptics. Our main finding was that CD3+CD8-FoxP3- T-cells were associated with AA. We therefore suggest that T-cells, of a non-regulatory CD4+ subtype, could be involved in the formation of spiral artery AA in the decidua basalis. Whether AA gives rise to, or is partly mediated by increased T-cell concentration around the lesions, remains to be determined.

HLA-DR is aberrantly expressed at feto-maternal interface in pre-eclampsia.

In normal pregnancy, villous cytotrophoblast and syncytiotrophoblast do not express HLA Class I and Class II molecules, while invasive extravillous trophoblast only express class I HLA-C and the atypical class Ib antigens, HLA-G, -E and -F. Inadequate maternal tolerance of invasive trophoblast has been proposed as a possible immunologic trigger of poor trophoblast invasion and subsequent occurrence of pre-eclampsia. This study aimed to investigate possible aberrant expression of class II HLA-DR on placentae and syncytiotrophoblast-derived extracellular vesicles (STEVs), obtained by dual placental perfusion, from pre-eclampsia (n = 23) and normal pregnant (n = 14) women. Here we demonstrate that HLA-DR can be detected in syncytiotrophoblast from a significant proportion of pre-eclampsia but not control placentae. HLA-DR was also observed, by flow cytometry, on STEVs and associated with placental alkaline phosphatase to validate their placental origin. HLA-DR positive syncytiotrophoblast was detected in placental biopsies from pre-eclampsia but not normal control cases, using immunohistochemistry. The HLA may be fetal or maternal origin. In the latter case a possible mechanism of acquisition is trogocytosis.

Trophoblast Glycoprotein (TPGB/5T4) in Human Placenta: Expression, Regulation, and Presence in Extracellular Microvesicles and Exosomes.

BACKGROUND: Many parallels exist between growth and development of the placenta and that of cancer. One parallel is shared expression of antigens that may have functional importance and may be recognized by the immune system. Here, we characterize expression and regulation of one such antigen, Trophoblast glycoprotein (TPGB; also called 5T4), in the placenta across gestation, in placentas of preeclamptic (PE) pregnancies, and in purified microvesicles and exosomes. METHODS: Trophoblast glycoprotein expression was analyzed by real-time reverse transcription-polymerase chain reaction (RT-PCR), Western blot, and immunohistochemistry. Regulation of 5T4 in cytotrophoblast cells was examined under either differentiating conditions of epidermal growth factor or under varying oxygen conditions. Microvesicles and exosomes were purified from supernatant of cultured and perfused placentas. RESULTS: Trophoblast glycoprotein expression was prominent at the microvillus surface of syncytiotrophoblast and on the extravillous trophoblast cells, with minimal expression in undifferentiated cytotrophoblasts and normal tissues. Trophoblast glycoprotein expression was elevated in malignant tumors. In cytotrophoblasts, 5T4 was induced by in vitro differentiation, and its messenger RNA (mRNA) was increased under conditions of low oxygen. PE placentas expressed higher 5T4 mRNA than matched control placentas. Trophoblast glycoprotein was prominent within shed placental microvesicles and exosomes. CONCLUSION: Given the potential functional and known immunological importance of 5T4 in cancer, these studies reveal a class of proteins that may influence placental development and/or sensitize the maternal immune system. In extravillous trophoblasts, 5T4 may function in epithelial-to-mesenchymal transition during placentation. The role of syncytiotrophoblast 5T4 is unknown, but its abundance in shed syncytial vesicles may signify route of sensitization of the maternal immune system.

Angiogenic factors: potential to change clinical practice in pre-eclampsia?

Pre-eclampsia is a complex disease with significant maternal and fetal morbidity and mortality. Its syndromic nature makes diagnosis and management difficult. The field is rapidly evolving with the definition of pre-eclampsia being challenged by some organisations, with proteinuria no longer being essential in the presence of other features. In the last decade, angiogenic factors, in particular soluble fms-like tyrosine kinase 1 (sFlt-1), have emerged as important molecules in the pathogenesis of pre-eclampsia. Here we review the most recent evidence regarding the potential of these factors as biomarkers and therapeutic targets for pre-eclampsia. TWEETABLE ABSTRACT: A review of angiogenic factors, sFlt-1 and PlGF, in the diagnosis, prediction and management of pre-eclampsia.

Predicting delivery of a small-for-gestational-age infant and adverse perinatal outcome in women with suspected pre-eclampsia.

OBJECTIVE: To evaluate the test performance of 47 biomarkers and ultrasound parameters for the prediction of delivery of a small-for-gestational-age (SGA) infant and adverse perinatal outcome in women presenting with suspected pre-eclampsia. METHODS: This was a prospective, multicenter observational study in which 47 biomarkers and ultrasound parameters were measured in 397 women with a singleton pregnancy presenting with suspected preterm pre-eclampsia between 20 + 0 and 36 + 6 weeks' gestation, with the objective of evaluating them as predictors of subsequent delivery of a SGA infant and adverse perinatal outcome. Women with confirmed pre-eclampsia at enrollment were excluded. Factor analysis and stepwise logistic regression were performed in two prespecified groups stratified according to gestational age at enrollment. The primary outcome was delivery of a SGA infant with a birth weight < 3rd customized centile (SGA-3), and secondary outcomes were a SGA infant with a birth weight < 10th customized centile and adverse perinatal outcome. RESULTS: In 274 women presenting at 20 + 0 to 34 + 6 weeks' gestation, 96 (35%) delivered a SGA-3 infant. For prediction of SGA-3, low maternal placental growth factor (PlGF) concentration had a sensitivity of 93% (95% CI, 84-98%) and negative predictive value (NPV) of 90% (95% CI, 76-97%) compared with a sensitivity of 71% (95% CI, 58-82%) and a NPV of 79% (95% CI, 68-87%) for ultrasound parameters (estimated fetal weight or abdominal circumference < 10th centile). No individual biomarker evaluated had a better performance than did PlGF, and marker combinations made only small improvements to the test performance. Similar results were found in 123 women presenting between 35 + 0 and 36 + 6 weeks' gestation. CONCLUSION: In women presenting with suspected preterm pre-eclampsia, measurement of PlGF offers a useful adjunct for identifying those at high risk of delivering a SGA infant, allowing appropriate surveillance and timely intervention. © 2017 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Disclosing the results of the invasive cervical cancer review to patients: a survey of lead colposcopists across England.

OBJECTIVE: To survey lead colposcopists to explore the extent to which patients are currently being invited to discuss the results of their invasive cervical cancer review, the reasons why this might not be happening and the clinician experience. METHODS: An online survey was sent to lead colposcopists across England. They were asked whether they offered the review to patients, if they did how they did so and what their experience was and if they did not, why not. RESULTS: There was a 68.5% (N = 122) response rate, with 53% of respondents currently offering the review meetings. Patients were predominantly invited to the review meeting face to face and clinicians' experiences were mixed with a variety of positive and negative aspects of the meetings given. For those clinicians not currently offering a review meeting, there were a variety of reasons: 25% cited a lack of awareness of the guidelines, 19% time constraints, 12% a fear of causing additional distress and 2% a fear of litigation. Open-ended responses demonstrated a considerable amount of misunderstanding about the process. CONCLUSION: Despite National Health Service Cervical Screening Programme guidelines, not all clinicians offer review meetings to patients and those who do offer them do not always offer them to all women. Patient research needs to be conducted to explore the value of the meetings further, and there is a need to do more to engage clinicians in the process.

Awareness and knowledge of HPV and cervical cancer in female students: A survey (with a cautionary note).

We conducted a survey to explore levels of awareness and knowledge of human papillomavirus (HPV) and cervical cancer in 170 female students and whether mode of data collection (online vs. paper) affected the results. 27% of women named HPV as a cause of cervical cancer with online respondents more likely to do so. 75% of women had heard of HPV. More online respondents had heard of HPV than paper respondents. 127 women reported having heard of HPV, with a mean knowledge score of 2.989 (standard deviation [SD] 1.599). Online respondents scored higher (3.57, SD 1.316) than paper respondents (2.688, SD 1.591). Knowledge and awareness of HPV and its link to cervical cancer appear to have increased which may be related to the HPV vaccination programme. However, there is still a considerable number of women with little to no knowledge of HPV. Online surveys may result in an inflated estimation of awareness and knowledge.

Isolation of syncytiotrophoblast microvesicles and exosomes and their characterisation by multicolour flow cytometry and fluorescence Nanoparticle Tracking Analysis.

The human placenta releases multiple types and sizes of syncytiotrophoblast (STB) extracellular vesicles (EV) into the maternal circulation that exhibit diverse biological activities. The placental perfusion technique enables isolation of these STBEV, but conventional flow cytometry can only be used to phenotype EV down to ∼300 nm in size. Fluorescence Nanoparticle Tracking Analysis (fl-NTA) has the potential to phenotype EV down to ∼50 nm, thereby improving current characterisation techniques. The aims of this study were to prepare microvesicle and exosome enriched fractions from human placental perfusate (n=8) and improve fl-NTA STBEV detection. Differential centrifugation and filtration effectively removed contaminating red blood cells from fresh placental perfusates and pelleted a STB microvesicle (STBMV) fraction (10,000×g pellet - 10KP; NTA modal size 395±12 nm), enriched for the STB marker placental alkaline phosphatase (PLAP) and a STB exosome (STBEX) fraction (150,000×g pellet - 150KP; NTA modal size 147±6 nm), enriched for PLAP and exosome markers Alix and CD63. The PLAP positivity of 'standard' 10KP and 150KP pools (four samples/pool), determined by immunobead depletion, was used to optimise fl-NTA camera settings. Individual 10KP and 150KP samples (n=8) were 54.5±5.7% (range 17.8-66.9%) and 30.6±5.6% (range 3.3-51.7%) PLAP positive, respectively. We have developed a reliable method for enriching STBMV and STBEX from placental perfusate. We also standardised fl-NTA settings and improved measurement of PLAP positive EV in STBMV. However, fl-NTA is not as sensitive as anti-PLAP Dynabead capture for STBEX detection, possibly due to STBEX having lower surface expression of PLAP. These important developments will facilitate more detailed studies of the role of STBMV and STBEX in normal and pathological pregnancies.

Diagnostic accuracy of placental growth factor and ultrasound parameters to predict the small-for-gestational-age infant in women presenting with reduced symphysis-fundus height.

OBJECTIVES: To assess the diagnostic accuracy of placental growth factor (PlGF) and ultrasound parameters to predict delivery of a small-for-gestational-age (SGA) infant in women presenting with reduced symphysis-fundus height (SFH). METHODS: This was a multicenter prospective observational study recruiting 601 women with a singleton pregnancy and reduced SFH between 24 and 37 weeks' gestation across 11 sites in the UK and Canada. Plasma PlGF concentration < 5(th) centile, estimated fetal weight (EFW) < 10(th) centile, umbilical artery Doppler pulsatility index > 95(th) centile and oligohydramnios (amniotic fluid index < 5 cm) were compared as predictors for a SGA infant < 3(rd) customized birth-weight centile and adverse perinatal outcome. Test performance statistics were calculated for all parameters in isolation and in combination. RESULTS: Of the 601 women recruited, 592 were analyzed. For predicting delivery of SGA < 3(rd) centile (n = 78), EFW < 10(th) centile had 58% sensitivity (95% CI, 46-69%) and 93% negative predictive value (NPV) (95% CI, 90-95%), PlGF had 37% sensitivity (95% CI, 27-49%) and 90% NPV (95% CI, 87-93%); in combination, PlGF and EFW < 10(th) centile had 69% sensitivity (95% CI, 55-81%) and 93% NPV (95% CI, 89-96%). The equivalent receiver-operating characteristics (ROC) curve areas were 0.79 (95% CI, 0.74-0.84) for EFW < 10(th) centile, 0.70 (95% CI, 0.63-0.77) for low PlGF and 0.82 (95% CI, 0.77-0.86) in combination. CONCLUSIONS: For women presenting with reduced SFH, ultrasound parameters had modest test performance for predicting delivery of SGA < 3(rd) centile. PlGF performed no better than EFW < 10(th) centile in determining delivery of a SGA infant.

Colposcopy training and assessment across the member countries of the European Federation for Colposcopy.

OBJECTIVES: Colposcopy training and assessment is not uniform across Europe with individual countries determining their own required standards and regulations. In light of the significant changes in colposcopic practice that have occurred over the past decade and the expansion of the European Federation for Colposcopy (EFC) membership, a study was conducted firstly, to assess the current requirements for training in each of the member countries and secondly, to review an EFC-approved core training curriculum for colposcopy. STUDY DESIGN: A questionnaire survey of the EFC representatives from all member countries investigating their country's current practices/requirements with regard to training, assessment and accreditation for colposcopy. A two-round Delphi consultation with representation from the full, associate and three potential member countries was conducted using a 5-point Likert scale for scoring opinions. The results were analysed with respect to each country's population size and World Bank economic classification. RESULTS: For the questionnaire survey, responses were received from 31/34 countries invited to participate. Training programmes were reported to be in place in 21 of the 31 countries but only 17 of the 21 countries had a committee overseeing the training programme. An assessment was part of the training programme in 20 countries with multiple choice questions and portfolios the most common assessment tools. Countries with a population size less than 2 million have a statistically significant lower probability of having a structured training/assessment programme, 1/5 compared to 20/26 for a populations greater than 2 million, p=0.013. For the Delphi study, responses were received from 34/39 countries invited to participate. Of the 51 competencies previously identified only 2 did not receive full support: 'perform bacterial swabs' and 'provide data to national body'. There was no significant difference in the responses given by member, associate member or potential member countries. CONCLUSIONS: There is considerable variation in colposcopy training and assessment across Europe. This study has enabled consensus opinion with the EFC on the contents of an EFC core curriculum. The revised curriculum has a mandate from the EFC member countries to be implemented across Europe as the standard for colposcopic training.

Interleukin-1 family cytokines and their regulatory proteins in normal pregnancy and pre-eclampsia.

Maternal systemic inflammation is a feature of pre-eclampsia, a condition in pregnancy characterized by hypertension and proteinuria. Pre-eclampsia is caused by the placenta; many placental factors contribute to the syndrome's progression, and proinflammatory cytokines have been identified previously as one such mediator. The interleukin (IL)-1 family of cytokines are key regulators of the inflammatory network, and two naturally occurring regulatory molecules for IL-1 family cytokines, IL-1RA and sST2, have been found previously to be elevated in maternal blood from women with pre-eclampsia. Here we investigate more recently identified IL-1 family cytokines and regulatory molecules, IL-1RAcP, IL-37, IL-18BP, IL-36α/ß/γ/Ra and IL-38 in pre-eclampsia. Pregnant women have more circulating IL-18BP and IL-36Ra than non-pregnant women, and sIL-1RAcP is elevated from women with pre-eclampsia compared to normal pregnancies. The placenta expresses all the molecules, and IL-37 and IL-18BP are up-regulated significantly in pre-eclampsia placentas compared to those from normal pregnancies. Together, these changes contribute to the required inhibition of maternal systemic cytotoxic immunity in normal pregnancy; however, in pre-eclampsia the same profile is not seen. Interestingly, the increased circulating levels of sIL-1RAcP and increased placental IL-18BP and IL-37, the latter of which we show to be induced by hypoxic damage to the placenta, are all factors which are anti-inflammatory. While the placenta is often held responsible for the damage and clinical symptoms of pre-eclampsia by the research community, here we show that the pre-eclampsia placenta is also trying to prevent inflammatory damage to the mother.

Cytological follow-up after hysterectomy: is vaginal vault cytology sampling a clinical governance problem? The University Hospital of North Staffordshire approach.

OBJECTIVES: Vaginal vault cytology sampling following hysterectomy is recommended for specific indications in national guidelines. However, clinical governance issues surround compliance with guidance. Our first study objective was to quantify how many patients undergoing hysterectomy at the University Hospital of North Staffordshire (UHNS) had vault cytology advice in their histology report and, if indicated, whether it was arranged. The second was to devise a vault cytology protocol based on local experience and national guidance. METHODS: The local cancer registry was searched. Clinical, clerical and histological data for all patients undergoing hysterectomy were collected. RESULTS: In total, 271 patients were identified from both the gynae-oncology and benign gynaecology teams. Of these, 24% (65/271) were gynae-oncology patients with a mean age of 69 years. The benign gynaecology team had 76% (206/271) of patients with a mean age of 55 years. Subsequently, 94% (256/271) had cytology follow-up advice in their histopathology report. Ultimately, from both cohorts, 39% (18/46) had follow-up cytology performed when indicated. CONCLUSION: A high proportion of cases complied with national guidance. However, a disappointingly high number did not have vault cytology sampling when this was indicated. This is probably a result of the complex guidance that is misunderstood in both primary and secondary care. Vault follow-up of patients after hysterectomy rests with the team performing the surgery. Vault cytology, if indicated, should be performed in secondary care and follow-up should be planned. The protocol set out in this article should be followed to avoid unnecessary clinical governance failings.

Antenatal cardiotocogram quality and interpretation using computers.

OBJECTIVE: To test the application in practice of computerized fetal heart rate (FHR) analysis in pregnancy. DESIGN: Randomized distribution of subjects with computerized analysis automatically revealed or concealed. SETTING: A district general hospital and a teaching hospital outside London. SUBJECTS: 2869 pregnant women studied within a year. OUTCOME MEASURES: Quality and duration of the cardiotocogram; quantitative measurement of FHR variation; number of stillbirths. RESULTS: With interactive advice to the operator, records were of improved quality (up to 28% without signal loss) with potentially much reduced recording time. The short-term FHR variation measured in the last records before intervention is reported for the first time. CONCLUSION: The benefits of using the computers include improvement in record quality and saving of time. In addition, where interpretation depended on estimation of FHR variation there was prima facie evidence of observer misinterpretation; visual analysis was unreliable. A larger trial is now required with more rigorous constraints on intervention.

Placental miR-1301 is dysregulated in early-onset preeclampsia and inversely correlated with maternal circulating leptin.

INTRODUCTION: miRNAs are small non-coding RNAs important for the regulation of mRNA in many organs including placenta. Adipokines and specifically leptin are known to be dysregulated in preeclampsia, but little is known regarding their regulation by miRNAs during pregnancy. METHODS: We performed high-throughput sequencing of small RNAs in placenta from 72 well-defined patients: 23 early-onset preeclampsia (PE), 26 late-onset PE and 23 controls. The regulation of some miRNAs was confirmed on qRT-PCR. Maternal circulating levels and placental mRNA of leptin, resistin and adiponectin were measured using Bio-Plex and qRT-PCR. RESULTS: We found that miR-1301, miR-223 and miR-224 expression was downregulated in early-onset PE, but not in late-onset PE, compared to controls. In silico analysis predicted the leptin gene (LEP) to be a target for all three miRNAs. Indeed, we found significant correlation between maternal circulating levels of leptin and placental LEP expression. In addition, we found a significant inverse correlation between maternal circulating leptin/placental LEP expression and placental miR-1301 expression levels. Interestingly, placental expression of miR-1301 was also correlated with newborn weight percentile and inversely correlated with both maternal systolic and diastolic blood pressure prior to delivery. DISCUSSION: Our results confirm that placenta is a major site of LEP expression during pregnancy. It further suggests that miR-1301 could be involved in the regulation of leptin during pregnancy and may play a role in early-onset PE. CONCLUSIONS: miR-1301 is dysregulated in early-onset preeclampsia and could possibly play a role in the regulation of leptin during pregnancy.

Phase-rectified signal averaging for intrapartum electronic fetal heart rate monitoring is related to acidaemia at birth.

OBJECTIVE: Recent studies suggest that phase-rectified signal averaging (PRSA), measured in antepartum fetal heart rate (FHR) traces, may sensitively indicate fetal status; however, its value has not been assessed during labour. We determined whether PRSA relates to acidaemia in labour, and compare its performance to short-term variation (STV), a related computerised FHR feature. DESIGN: Historical cohort. SETTING: Large UK teaching hospital. POPULATION: All 7568 Oxford deliveries that met the study criteria from April 1993 to February 2008. METHODS: We analysed the last 30 minutes of the FHR and associated outcomes of infants. We used computerised analysis to calculate PRSA decelerative capacity (DC(PRSA)), and its ability to predict umbilical arterial blood pH ≤ 7.05 using receiver operator characteristic (ROC) curves and event rate estimates (EveREst). We compared DC(PRSA) with STV calculated on the same traces. MAIN OUTCOME MEASURE: Umbilical arterial blood pH ≤ 7.05. RESULTS: We found that PRSA could be measured in all cases. DC(PRSA) predicted acidaemia significantly better than STV: the area under the ROC curve was 0.665 (95% CI 0.632-0.699) for DC(PRSA), and 0.606 (0.573-0.639) for STV (P = 0.007). EveREst plots showed that in the worst fifth centile of cases, the incidence of low pH was 17.75% for DC(PRSA) but 11.00% for STV (P < 0.001). DC(PRSA) was not highly correlated with STV. CONCLUSIONS: DC(PRSA) of the FHR can be measured in labour, and appears to predict acidaemia more accurately than STV. Further prospective evaluation is warranted to assess whether this could be clinically useful. The weak correlation between DC(PRSA) and STV suggests that they could be combined in multivariate FHR analyses.

The effect of augmentation of labour with syntocinon on the fetal CTG using objective computerised analysis: a nested case-control study.

OBJECTIVE: To investigate the effect of syntocinon augmentation on the fetal cardiotocogram (CTG) using computerised analysis. We hypothesised that syntocinon will have no direct effects on the fetal heart rate if used correctly. STUDY DESIGN: A retrospective, nested case-control study. SETTING: Intrapartum CTG records from the digital archive at the John Radcliffe Hospital, Oxford, UK. SUBJECTS: 110 women with singleton pregnancies of >36 weeks gestation, no known congenital abnormality, spontaneous onset of labour and syntocinon augmentation for failure to progress, with start time of syntocinon recorded, from between August 1998 and December 1999, extensively matched to 110 controls who had normally progressing labours. METHODS: Eight different CTG features were measured during four time points with OxSys, a computerised numerical analysis system. STATISTICAL ANALYSIS: Differences in the CTG features over time in cases and controls using ANOVA and Friedman's ANOVA and at each time point between case-control pairs using Student's t-test and the Wilcoxon signed rank test. RESULTS: After administration, syntocinon increased the frequency, decreased the duration and decreased the resting time between contractions (p<0.001), resulting in no significant difference between normally progressing labours and those requiring augmentation. The case group had a significantly higher signal stability index (SSI) and fewer decelerations compared to the control group - differences which disappeared after augmentation was commenced (p=0.025 and 0.033 respectively). Syntocinon did not affect the baseline heart rate, short term variability (STV) or phase rectified signal averaging (PRSA) (p=0.518, 0.215 and 0.138) in comparison with controls. There was a significant increase in the PRSA in babies born with acidaemia (arterial pH≤7.05) 60-120min after syntocinon was commenced that was not seen with in babies with a normal pH (p=0.002). CONCLUSION: Syntocinon "normalises" ineffective uterine activity without any direct effect on the fetal heart rate. Therefore its administration does not confound objective computerised analysis. There may be a specific response in PRSA shortly after commencing syntocinon augmentation in the fetus which is subsequently born acidaemic which requires further investigation.

IFPA Senior Award Lecture: making sense of pre-eclampsia - two placental causes of preeclampsia?

Incomplete spiral artery remodelling is the first of two stages of pre-eclampsia, typically of early onset. The second stage comprises dysregulated uteroplacental perfusion and placental oxidative stress. Oxidatively stressed syncytiotrophoblast (STB) over-secretes proteins that perturb maternal angiogenic balance and are considered to be pre-eclampsia biomarkers. We propose that, in addition and more fundamentally, these STB-derived proteins are biomarkers of a cellular (STB) stress response, which typically involves up-regulation of some proteins and down-regulation of others (positive and negative stress proteins respectively). Soluble vascular growth factor receptor-1 (sVEGFR-1) and reduced growth factor (PlGF) then exemplify positive and negative STB stress response proteins in the maternal circulation. Uncomplicated term pregnancy is associated with increasing sVEGFR-1 and decreasing PlGF, which can be interpreted as evidence of increasing STB stress. STB pathology, at or after term (for example focal STB necrosis) demonstrates this stress, with or without pre-eclampsia. We review the evidence that when placental growth reaches its limits at term, terminal villi become over-crowded with diminished intervillous pore size impeding intervillous perfusion with increasing intervillous hypoxia and STB stress. This type of STB stress has no antecedent pathology, so the fetuses are well-grown, as typifies late onset pre-eclampsia, and prediction is less effective than for the early onset syndrome because STB stress is a late event. In summary, abnormal placental perfusion and STB stress contribute to the pathogenesis of early and late onset pre-eclampsia. But the former has an extrinsic cause - poor placentation, whereas the latter has an intrinsic cause, 'microvillous overcrowding', as placental growth reaches its functional limits. This model explains important features of late pre-eclampsia and raises questions of how antecedent medical risk factors such as chronic hypertension affect early and late sub-types of the syndrome. It also implies that all pregnant women may be destined to get pre-eclampsia but spontaneous or induced delivery averts this outcome in most instances.