OBJECTIVE Asymptomatic carriage of COVID-19 in pregnant women has been reported. We sought to ascertain the impact of high quality rapid PCR testing for COVID-19 in an unselected cohort of pregnant women attending our maternity unit. DESIGN Retrospective cohort analysis SETTING Cambridge, East of England POPULATION All pregnant women who were admitted to Rosie maternity unit over a 4-week period (May to June 2020) METHODS Pregnant women were screened for COVID-19 using nasopharyngeal and oropharyngeal swabs on admission. Samples were analysed using the SAMBA-II RT-PCR machine. Symptoms were defined as cough and/or fever that could not be attributed to an obstetric cause. RESULTS NP and OP swabs were obtained from 457/465 women during the study period (98%). The median turnaround time for results was 5.3 hours (IQR 2.6-8.9). 92% of results were returned within 24 hours. In our cohort, only one woman tested positive, giving a screen positive rate of 0.2% (1/457). One woman who tested negative developed a fever postnatally following discharge but was lost to follow-up. There was no correlation between asymptomatic carriage and regional prevalence of COVID-19. CONCLUSIONS Testing using the SAMBA-II machine was acceptable to the vast majority of pregnant women requiring admission and had a low turnaround time. Asymptomatic carriage is low, but not correlated to community prevalence rates. Screening pregnant women on admission will remain an important component in order to minimise nosocomial infection and spread within healthcare workers as COVID-19 rates increase in the UK.

Abstract Objective To examine the occurrence and independent risk factors for surgical site infection (SSI) after caesarean section (CS). Design A hospital-based case-control study. Setting University Hospital. Population Women who were readmitted with SSI after CS during the years 2014-2016 (n=75). Controls were selected at a ratio of 2:1 (n=148). Methods Cases (women with SSI following CS) and controls (women without SSI following CS) were compared with respect to maternal and pregnancy characteristics using multivariable logistic regression analysis. Main Outcome Measures Anticipated risk factors for SSI. Results The occurrence of SSI requiring rehospitalisation was 0.38% and 5.5% after elective and emergency CS, respectively. Obesity was four times more common in women with SSI than in women without SSI (OR 4.1, 95% CI 1.5-11.3). Signs of infection during labour was almost five times more common (OR 4.7, 95% CI 1.7-13.0). Attempted vaginal delivery by pushing before CS was more than five times more common (OR 5.6, 95% CI 1.3-24.3). Pre-existing psychiatric disease was a significant predictor for SSI. Conclusions Emergency CS was a significant characteristic for SSI. Obesity, signs of infection prior to delivery, attempt of vaginal delivery by pushing before CS and pre-existing psychiatric disease, were independent risk factors for SSI. Women with either of these risk factors should be carefully monitored and evaluated for signs of infection in the postpartum period.

Objective: To identify the characteristics of and measures taken by Japanese medical facilities providing maternity services that have recorded cases of nosocomial infection with SARS-CoV-2, which causes coronavirus disease 2019 (COVID-19). Design: A nationwide questionnaire survey: case-control study. Setting: Medical facilities providing maternity service in Japan. Population: 1,418 medical facilities providing maternity service (65% of all delivery facilities in Japan). Methods: A nationwide questionnaire survey about nosocomial COVID-19 was conducted in July 2020. A case-control study was conducted by including medical facilities providing maternity service with (Cases) and without (Control) nosocomial COVID-19. Main outcome measures: Contributed characteristics and variables associated with nosocomial COVID-19. The number of treated pregnant women with COVID-19 until June 2020 and cases of nosocomial COVID-19 in Japan. Results: Seventy-five COVID-19-positive pregnant women were treated in 48 facilities. Responses from Nosocomial infection was reported in 4.1% of the facilities. Nine reports developed a nosocomial infection in the maternity ward or obstetric department. Variables that contributed to nosocomial COVID-19 were chest CT on admission (adjusted odds ratio [95% confidence interval], 4.76 [2.44–9.27]), PCR test for SARS-CoV-2 before delivery (2.27 [1.21–4.25]), transfer of pregnant women with fever to another hospital (0.21 [0.06–0.71]), and private clinics (0.17 [0.05–0.60]). Conclusion: Nosocomial infection is likely to occur in large hospitals that treat a higher number of patients than private clinics do. Nosocomial infection can occur even in medical facilities performing COVID-19 screening tests, such as chest CT and PCR test.

Objective: To explore whether CNV-seq can be used as a first-tier diagnostic method or even replace karyotyping for prenatal diagnosis alone. Method: A retrospective study was conducted to 4230 amniocentesis samples with CNV-seq detection and G-banding karyotyping simultaneously. The indications for prenatal diagnosis included abnormal result on Down’s Syndrome Screening, abnormal fetal ultrasound, abnormal result on noninvasive prenatal screening, and so on. The results that lead to birth defects definitely were defined as abnormalities, which included aneuploidy, mosaic aneuploidy, large deletion/duplication and pathogenic copy number variations (pCNVs). Results: 278 cases of abnormalities was identified by karyotyping with an abnormal detection rate of 6.69%(283/4230). In addition, for all the abnormalities identified by karyotyping, CNV-seq also identified another 58 cases of abnormalities. A total of 341 cases of abnormalities were identified by CNV-seq with an abnormal detection rate of 8.06%(341/4230), higher than that of karyotyping. Abnormal detection rate of CNV-seq for the groups with abnormal result on noninvasive prenatal screening, abnormal fetal ultrasound, abnormal parental chromosome, adverse pregnancy history, abnormal result on Down’s Syndrome Screening, volunory testing and advanced maternal age were increased by 2.53%, 1.91%, 1.44%, 1.24%, 1.01%, 0.99% and 0.62% over the karyotyping respectively. Conclusion: CNV-seq and karyotyping had the same effectiveness in identifying aneuploidies, but CNV-seq had absolute superiority in the detection of low proportion of mosaics, imbalanced structural abnormalities. This prevents the birth of fetuses with these chromosome abnormalities that cannot be identified by karyotyping. CNV-seq can replace karyotyping in prenatal diagnosis for chromosome test alone.

Objectives: Mask-wearing can induce relative hypoxia, affecting hematologic parameters. We aimed to evaluate the effect of the COVID-19 mask-wearing on hematological laboratory components and obstetrical outcome among women delivering during this period. Design: Retrospective cohort study Setting: Tertiary medical center. Population: Pregnant women delivering a singleton gestation. Methods: Obstetrical outcome and laboratory results of women admitted for delivery throughout the mask-wearing period were compared to those delivering during the parallel period in 2019, and to a larger cohort derived from nine pre-pandemic years Main outcome measure: Hematological, delivery and neonatal outcomes characteristics. Results: Overall, 1,939 women delivered during the COVID-19 pandemic. Compared with the pre-pandemic period, the mean hemoglobin and fibrinogen levels were significantly higher during the mask-wearing period [12.15±1.1 vs. 11.96±1.2, p<0.001 and 472±103.6 vs. 448±85.1 (mg/dL), p<0.001, respectively]. Platelets levels were lower [200±56.0 vs. 206±57.5 (K/microL), p<0.001]. The rate of delivery<34 weeks of gestation was lower during the mask-wearing period [1.1% vs. 2%, OR-0.57 (95% CI, 0.37-0.88), p=0.01], while cesarean delivery and postpartum hemorrhage rates were higher [[26.7% vs. 24.4%, OR- 1.13 (95% CI, 1.02-1.25), p=0.022 and 4.1% vs. 2.8%, OR- 1.5 (95% CI 1.2-1.8), p=0.001, respectively], Conclusion: A hard-to-ventilate space created by wearing a mask may be the underlying cause of the observed higher hemoglobin level among pregnant women. This change might have a biological relation to changes in the rate of obstetrical outcome. Funding: no external funding. Keywords: COVID-19, preterm birth, cesarean delivery, composite neonatal outcomes, hemoglobin, fibrinogen, platelets, mask-wearing.

Objective: To investigate the outcomes of fetuses or neonates of pregnant women with premature ventricular contractions (PVCs). Design: Prospective cohort study. Setting: University-affiliated tertiary hospital. Population: 6, 148 pregnant women with normal cardiac structure and function and 103 with a PVC burden >0.5% among them. Methods: 103 pregnant women with PVCs were divided into two groups based on the presence or absence of adverse fetal or neonatal events. The adverse outcomes were compared between the groups. Main outcome measures: Adverse fetal and neonatal events: premature birth (<37 weeks gestation), small-for-gestational-age birth weight (<10th percentile for gestational age or <2500 g), respiratory distress syndrome, intraventricular hemorrhage and fetal death (after 20 weeks gestation and before birth). Results: A total of 17 adverse events (12 cases) occurred among 103 pregnant women with PVCs, which was significantly higher than that among women without PVCs (11.65% vs. 2.93%, p<0.01). Compared with that of the women without adverse events, the median PVC burden of women with adverse fetal or neonatal outcomes was significantly higher (9.02% vs. 2.30%, p<0.01). Multivariate logistic regression analysis demonstrated that PVC burden was associated with adverse fetal or neonatal outcomes among pregnant women with PVCs (OR: 1.34, 95% CI (1.11-1.61), p<0.01). Conclusions: Frequent PVCs have adverse effects on pregnancy, and the PVC burden might be an important factor associated with adverse fetal and neonatal outcomes among pregnant women with PVCs. Our cohort study indicated that the higher the PVC burden is, the higher the likelihood of adverse events would be.

We describe a novel surgical technique of 31 patients with histopathologically–confirmed placenta accreta spectrum (PAS) disorders managed by a multidisciplinary team using prophylactic infrarenal abdominal aortic cross-clamping technique during cesarean hysterectomy. We conclude that this new surgical procedure is a safe and effective technique to reduce operative blood loss. Hopefully, our pioneer work will stimulate others to develop protocols assessing this innovative technique to improve surgical outcome of PAS disorders.

The American obstetrician, Joseph DeLee, ‘father of modern obstetrics’, founded the Chicago Lying-in Hospital in 1931 with his vision for womens’ health captured in a set of five stone plaques at the top of the cloister of the hospital’s building. Four of the five stone plaques are engraved with the names of pioneering clinicians whose contributions to the field of obstetrics and gynaecology have been seminal: Jan Palfyn (1650-1730), for introducing the obstetric forceps in the 1720s, Hendrik Van Deventer (1651-1724), for discovering obstetric anatomical disorders, William Smellie (1697-1763), for improving the design of the forceps, and Eduardo Porro (1842 –1902), for introducing hysterectomy to stop postpartum haemorrhage. The fifth stone plaque, in the centre, which is still blank today, is reserved for the physician/scientist who discovers the cause and cure of preeclampsia according to legend.That clusters of preeclamsia occur in family units prompted the question whether preecclampsia is an inherited disorder, and if so, what is the mode of inheritance? Familial clustering opened the possibility of deploying genome wide association studies (GWAS) for the identification of candidate genes and susceptibility loci for the development of preeclampsia and researchers have focused on this question since the discovery of DNA. However, till date, there has been no clearly defined causal relationship between a preeclampsia genotype and phenotype except for heterozygous women who are pregnant with long-chain hydroxyacyl-CoA dehydrogenase deficient fetus who have nearly 80% chance of developing HELLP syndrome or acute fatty liver of pregnancy. Defining the genetics and mode of inheritance of preeclampsia is challenged in part by the involvement of two genomes (maternal and fetal), and a wide spectrum of women who meet the diagnostic criteria according to the International Society for the Study of Hypertension in Pregnancy.There is persuasive literature that coexisting maternal medical disorders such as diabetes, chronic hypertension, renal disease, autoimmune disease, antiphospholipid antibody syndrome and other maternal-fetal risk factors including obesity, dyslipidemia, nulliparity, previous/family history of preeclampsia, and multifetal gestation, increase the risk of preeclampsia. In this issue of the Journal, Gray and colleagues (BJOG 2020 xxxx) used single nucleotide polymorphisms (SNPs) for 21 distinct clinical traits for increased risk of preeclampsia within 7 categories (cardiovascular, inflammatory/ autoimmune, insulin resistance, liver, obesity, renal, and thrombophilia) from the European GWAS to test the hypothesis that women with genetic predisposition to these disorders would have increased risk of preeclampsia in a case/control sample of data from the largest known US preeclampsia GWAS. The authors’ findings that; a) risk alleles for raised diastolic blood pressure and increased BMI were strongly associated with preeclampsia risk (more so for the early-onset disease variant), b) risk alleles for raised alkaline phosphatase levels, increased HDL, GFR, and venous thromboembolism were protective, and c) no significant associations for the other traits examined, are consistent with the current status of preeclampsia and HELLP as highly complex disorders with variable clinical presentations depending on pre-pregnancy maternal conditions, fetal/placental genotypes, and maternal adaptation to the challenge of pregnancy.So, preeclampsia is far from a Mendelian inherited type of genetic disease and the search for its cause and cure continues 90 years after DeLee’s vision!Conflict of interest: None. A completed disclosure of interest form is available to view online as supporting information.

Tweetable abstract: Identical twin pregnancies have more preterm births and other complications than fraternal twin pregnancies.Mini-CommentaryA decade ago, Professor Kypros Nicolaides of Kings’ College opined, “There is NO diagnosis of twins. There are only monochorionic or dichorionic twins. This diagnosis should be written in capital red letters across the top of the patient’s chart.” (Quoted by Moise and Johnson, Am J Obstet Gynecol 2010; 203:1-2.) To make this diagnosis, it is essential to establish chorionicity as early as possible in every twin pregnancy.Monochorionic twin pregnancies have long been known to have higher rates of miscarriage, congenital anomalies, stillbirth, and neonatal death than dichorionic twin pregnancies. Intertwin vascular anastomoses are present in most monochorionic twin placentas, leading to complications such as twin-twin transfusion syndrome (TTTS), twin anemia-polycythemia sequence (TAPS), twin reversed arterial perfusion (TRAP) sequence, and unequal placental sharing (UPS).Monochorionic twins require intensive antenatal surveillance. Because of the increased risk of congenital anomalies, fetal echocardiogram is recommended in addition to routine ultrasound fetal anatomy survey. Because of the risk of TTTS, TAPS, TRAP and UPS, sonographic surveillance is recommended every 2 weeks starting at 16 weeks of gestation. Because of the risk of stillbirth, serial antenatal cardiotocography is recommended. Scheduled delivery is recommended earlier for monochorionic twins than for dichorionic twins (NICE Guideline 137, 2019; ACOG, Obstet Gynecol 2019;133:e151-5; Cheong-See et al, BMJ 2016;354:i4353).Regardless of chorionicity, 60% of twins are born preterm, resulting in substantial perinatal morbidity and mortality. Prevention of preterm birth (PTB) is a major priority for management of twin pregnancy.The systematic review by Marleen and colleagues is the first of several studies planned by the authors to evaluate risk factors for PTB in twin pregnancy. Prior reports have suggested that monochorionic twins have higher rates of PTB than dichorionic twins but, as the authors note, there has been no prior systematic review of this association. It is not surprising that the review shows an increased overall rate of PTB among monochorionic twins in all gestational age ranges, given that complications such as stillbirth, TTTS, TAPS, TRAP, and UPS often result in iatrogenic PTB. Indeed, iatrogenic PTB before 37 weeks of gestation should be routine for monochorionic twins because of the increasing risk of stillbirth past 36+6 weeks cited in the current NICE Guidelines (2019, op. cit .). However, Marleen and colleagues also report that spontaneous PTB at <37 weeks and ≤34 weeks is increased in monochorionic twin pregnancy, which cannot be directly explained by monochorionic placental complications.The overarching goal of Marleen and colleagues is to develop tools to predict which twin pregnancies are at risk of PTB so that preventive measures can be taken. Unfortunately, it is not currently known what preventive measures will reduce the high risk of early spontaneous PTB among monochorionic twin pregnancies. Prophylactic bedrest, hospitalization, uterine activity monitoring, tocolysis, cerclage, cervical pessary, and progestogens have not proven effective for unselected twin pregnancies. Future research will be needed to determine the value of such interventions for women with twin pregnancy plus additional risk factors such as a short cervix, prior PTB, or monochorionicity.Acknowledgements: NoneDisclosure of Interests: C Andrew Combs declares “No relevant or competing interests”Contribution to Authorship: CAC did 100% of the planning, writing, and submission.Details of Ethics Approval : Not applicableFunding: NoneReferences: Cited in-line per instructions for Mini-CommentaryTables/Figures: None

Objective: To evaluate whether early-onset severe preeclampsia prior to 34 weeks’ gestation is clinically different when associated with antiphospholipid antibodies. Design: A retrospective case-control study. Setting: Single university-affiliated tertiary referral center Population: 55 women with singleton pregnancies who delivered prior to 34 weeks’ gestation due to preeclampsia with severe features. Methods: Out of the 101 women with preeclampsia with severe features, the antiphospholipid antibodies status of 55 was available for analysis. The study group comprised 20 women with positive antiphospholipid antibodies (positive-aPL group), while the control group comprised 35 women without antiphospholipid antibodies (negative-aPL group). Main outcome measures: Obstetric and neonatal outcomes, laboratory results and pregnancy complications. Results: Positive-aPL women were hospitalized earlier (29, IQR 26.3–32, vs. 32, IQR 28-33 weeks gestation, p=0.05), gave birth at a significantly earlier gestational age (30, IQR 28.3-32.8 vs. 33, IQR 30-34, p=0.02) with a lower mean birth weight (1266.7±579.6 vs. 1567.3±539.7 grams, p=0.058) compared with negative-aPL women. Furthermore, platelet nadir was significantly lower for positive-aPL compared with negative-aPL women (97.2±49.7103/µL vs 141.3±61.13/µL, p<0.001) and maximal serum creatinine was higher (1.02±0.32 mg/dL vs. 0.92±0.13 mg/dL, p=0.03). Rates of neonatal complications were low and comparable between groups, although there was a trend for higher perinatal mortality among study group infants. Conclusions: The presence of antiphospholipid antibodies in women with early-onset preeclampsia with severe features is associated with earlier, more severe multi-organ involvement. Expedited screening for antiphospholipid antibodies in cases of early-onset severe preeclampsia may be considered.

Objective Acute fatty liver of pregnancy (AFLP) substantially contributes to maternal and neonatal morbidity and mortality. The aim of this study was to investigate angiogenic profiles by measuring soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PLGF) in pregnancies compromised by AFLP and to compare them to those complicated by HELLP (haemolysis, elevated liver enzyme, low platelet) syndrome. Methods In pregnant patients affected by AFLP or HELLP syndrome sFlt-1 and PLGF serum levels were measured. To assess the diagnostic potential of these angiogenic markers in AFLP as well as discriminating it from HELLP syndrome, non-parametric tests were used and receiver-operating-curves (ROC) were calculated. Results Six cases with AFLP and 48 women with HELLP syndrome were included into the study. Patients with AFLP showed significantly higher sFlt-1 levels (median: 57570pg/ml [range: 31609-147170pg/ml]) than patients with HELLP syndrome (9713pg/ml [1348-30781pg/ml ; p<0.001). PLGF serum levels were increased in patients with AFLP compared to those with HELLP syndrome (197 pg/ml [127-487pg/ml] versus 40 pg/ml [9-644pg/ml], respectively, p<0.01,). sFlt-1/PLGF-ratios were not significantly different between AFLP and HELLP syndrome patients (192 [157-1159] versus 232 [3-948], respectively, NS). A sFlt-1 cut-off value of 31100pg/ml allowed differentiating between these two diseases with a sensitivity and specificity of 100%. Conclusions AFLP is associated with very high serum levels of sFlt-1. Besides the suggested Swansea criteria to diagnose AFLP a sFlt-1 value above 31100 pg/ml may be also an additional biochemical feature improving discrimination between AFLP and HELLP syndrome. Funding:NA Keywords:AFLP, HELLP syndrome, preeclampsia, sFLT-1, PLGF

Objectives To evaluate the severe outcomes in pregnancies with pernicious placenta previa and prior cesarean delivery, and to analyze the predictive examinations and prevention strategies regarding severe complications in these women. Design Multicentre retrospective cohort study. Setting Thirteen hospitals in China. Population Selected 747 women with pernicious placenta previa and prior cesarean history. Methods The basic data relating to pregnancy, the examinations during gestation and the outcomes were collected and analyzed. Main outcome measures Outcomes including massive bleeding, placenta implantation and hysterectomy were monitored. Results Our results showed that placental implantation occurred in 47.5% of patients and the hysterectomy rate was 10.4%. The incidence of massive bleeding and blood transfusion was 55.8% and 64%, respectively. The women with placenta implantation predicted by both ultrasound and MRI had higher blood loss than those diagnosed only by either one of the examinations. Surprisingly, vascular occlusion had no effect on the occurrence of severe hemorrhage and hysterectomy. The latter was even higher in the vascular blocking group compared to that in the non-blocking group (34.2% and 8.6%, respectively). Conclusions: The pregnancies with pernicious placenta previa and prior cesarean delivery, had a dramatically higher risk of placenta implantation, hysterectomy and massive hemorrhage. MRI combined with ultrasound examination presented high accuracy in predicting severe outcomes in these patients. Vascular occlusion does not appear to be an effective approach to prevent severe outcomes. Surgical hemostasis should be the key goal in blocking massive bleeding, preserving the uterus and improving the prognosis of the patients.

Objective: Evaluate the clinical usefulness of cell-free DNA screening (cfDNA screening) in pregnancies with nuchal translucency (NT) between 95th and 99th percentile. Design: Subgroup analysis of a multicenter prospective cohort study Setting: 12 different secondary and tertiary health care institutions in Korea Sample: 7,547 singleton pregnant women with NT between 95th and 99th percentile Methods: All participants were provided with information about aneuploidy screening or diagnostic testing and selected the first tier test after NT assessment. The first tier test included maternal serum screening tests (MSS), cfDNA screening and invasive test (IT). Main outcome measures: First-tier test preference and chromosomal abnormalities in pregnancies with NT between 95th and 99th percentile Results: A total of 7,547 singleton pregnant women were enrolled and 6,717 cases with known pregnancy outcomes were analyzed. Among these, 89 (1.3%) cases showed NT between 95th and 99th percentile. As the first-tier test, 47 (52.8%) cases chose cfDNA screening, 33 (37.1%) cases selected IT, and nine (10.1%) cases underwent MSS. Chromosomal abnormalities were found in five cases (5.6%), including four cases with trisomy 21 (T21) and one with a balanced translocation. No significant chromosomal abnormalities undetected by cfDNA screening were noted in pregnancies with NT between 95th and 99th percentile. Conclusion: cfDNA screening in pregnancies with NT between 95th and 99th percentile may be considered as an acceptable alternative to invasive test for women intending to avoid the risk of miscarriage.

Background The global increase in caesarean section (CS) rates is concerning and a better understanding of this phenomenon can allow us to identify strategies to reduce it. Aims To determine the CS rate in two hospitals in Victoria-Australia, and analyse the contribution of specific obstetric population to changes in CS rates over time using the Robson classification. Materials and Methods Retrospective observational study of all women delivering at two hospitals in Victoria between July 2014 and June 2019. The overall CS rate, the size of each Robson group, the CS rate per group, and the absolute and relative contribution of each group to the overall CS rate were calculated. Additionally, trends over time and comparison between the two hospitals were also analysed. Results There were 7894 CS during the study period, giving an overall CS rate of 32.7%. The greatest contributor was Robson group 5 with 35.2%, followed by group 2 with 26.6% and lastly group 1 with 10.3%. Over the five-year period, CS rates at both hospitals increased 1.5% per year (95% CI: 0.1-2.9, p-value: 0.04) from 30.7% in 2015 to 36.0% in 2019. There were not major differences in the CS between the two hospitals. Conclusion The major groups contributing to our CS rate are groups 5, 2 and 1 and efforts aiming to reduce our CS rate should therefore target these groups. Strategies to reduce CS rates should include increasing the availability of VBAC, reviewing our protocols for IOL, and improving management and surveillance of labour.

At a time when political protesting regarding racial injustice is commonly seen, medical professionals ought to recognize when racial and ethnic insensitivity may exist in our collective medical practice. A case in point relates to the use of prediction models for successful vaginal trials of labor after Cesarean (VTOL). 1-3Such algorithms can include verifiable correlates to vaginal births after Cesarean (VBAC), such as prior vaginal births, estimated fetal weight (EFW), persistent cesarean indications, body mass index (BMI), and even type of labor onset. The accuracy of these algorithms used to predict successful VBAC in a patient contemplating a VTOL has been recently questioned. 4-6 The inclusion of a racial component may be of questionable value here, since the anthropomorphic indicators of pelvic dimensions are less clear cut, 7especially when soft tissue description may offer a different correlation to the capacity for vaginal delivery. 8Although this last reference examined the obligate contribution of the soft tissues to the birth canal dimensions beyond its bony limitations, it related this to the prediction of soft tissue injuries. It nonetheless describes the consequential role of the pelvic soft tissues as part of the birth canal, unrelated to the possibly genetically determined bony pelvis dimensions. Pertinent to this discussion is the notion that Race, and ethnicity, have a role in determining vaginal delivery capability (e.g. in VBAC), when a sociodemographic basis may be confused with a biologically defined one.Measurement of the bony pelvic dimensions with magnetic resonance imaging (MRI), relating to an individual’s Race, has revealed the usual range as would be expected in any population, somewhat correlated with Race. Whether these described dimensions (e.g. inter-tuberous or ischial spinous diameter or pelvic inlet size) meaningfully correlates with the capacity to vaginally deliver, is open to some question, since there may be an essential role of the pelvic soft tissues (e.g. the levator muscles of the pelvic floor) with regard to vaginal delivery capability. X-Ray pelvimetry, and pelvimetry through other imaging modalities, has long been abandoned as a predictor of the capacity to vaginally deliver, due to its repeated documented failure.9 So, the inclusion of Race or ethnicity in an algorithm used to predict VBAC success, may inappropriately be using this demographic indicator. When the use of this specific factor (i.e. race/ethnicity) in a prediction model was shown to not be successful, the interpretation was simply articulated as “not predictive of VBAC success” and “unexpected”.10 In fact though, the underestimation of the probability of a successful VBAC because of a patient’s assignment of ethnicity or race, should be highlighted, as the ramifications of such counseling of a low probability of success, is significant when it can be shown to be inaccurate.This is of considerable importance since these prediction models can influence shared decision-making. The tendency to desire having a vaginal birth has been shown to correlate with certain racial/ethnic groups, and this influence is indeed relevant.11 The relationship of VBAC success prediction in the Latina community is particularly worthy of note, given some reported disparate findings.11 Interestingly, whatever the complex interactions of the pelvic bony dimensions and soft tissue dynamics are, the vaginal birth statistics do not appear to show significant differences between women in different racial/ethnic groups, in the United States. 12 The use of racial identity may not therefore be statistically relevant to any of the algorithms used for successful VTOL prediction. If encouragement of vaginal births is desirable when appropriate, then perhaps this racial categorization should be avoided. At least, we may need to properly establish and validate these algorithms within appropriately selected populations and follow described prediction model development.13

Ehlers-Danlos syndrome (EDS) is a group of connective tissue disorders that can result in a range of complications during pregnancy. Pregnant EDS patients generally have a favourable outcome, but those with vascular EDS are more likely to suffer from severe maternal complications. Early diagnosis of EDS and subtype characterization can aid in pre-pregnancy counselling, planning of antenatal care, risk assessment of obstetric and neonatal complications, and influence both obstetric and anaesthetic management of these patients. This piece aims to outline the obstetric implications of classical, hypermobile, and vascular EDS, and review the current literature regarding their optimal obstetric management.

The paper by Mulder et al. addresses the effect of pregnancy prolongation on maternal and fetal outcomes in women with early-onset pre-eclampsia diagnosed after 24 weeks of gestation (Mulder et al., BJOG 2020 xxxx). They report that pregnancy prolongation - from the time of pre-eclampsia diagnosis to delivery - is associated with improved offspring outcome and survival, without adverse consequences on short-term maternal cardiovascular and metabolic function. The maternal findings are apparently at odds with another recent study from New York (Rosenbloom et al. Obstet Gynecol 2020;135:27-35) which observed an increased risk of maternal cardiovascular events after pregnancy, in case of an interval of more than 7 days between the diagnosis of any hypertensive disorders of pregnancy and delivery.Some issues should be pointed out in order to avoid misunderstandings about these findings. Being Mulder et al.’s an observational study, readers cannot infer causality because women were not randomized to the length of pregnancy prolongation. Data are spread over a significant time period (from 1996 to 2017), and this aspect could be another confounder. Pre-eclampsia is a multi-organ syndrome based on chronic inflammation, oxidative stress and endothelial dysfunction leading to a persistent subclinical cardiovascular impairment and an increased risk of adverse events later in life (Sciatti et al., Eur J Prev Cardiol 2020 doi: 10.1177/2047487320925646), similarly to what happens in cases with heart failure with preserved ejection fraction. Myocardial geometry and ejection fraction are not sensitive enough to be altered by just a few days of pregnancy prolongation, and to forecast cardiovascular consequences. Only innovative techniques such as speckle-tracking imaging may document an impairment in myocardial contractility and relaxation in former pre-eclamptics, even if ejection fraction is normal.Pre-eclampsia is currently defined as new-onset hypertension combined with de-novo proteinuria and/or “adverse conditions” or “severe maternal/fetal complications” (Magee et al., Pregnancy Hypertens 2014;4:105-145). International guidelines recommend that women with severe forms of pre-eclampsia should be delivered immediately regardless of gestational age, while an expectant management should be considered for women with non-severe pre-eclampsia before term (Magee et al., Pregnancy Hypertens 2014;4:105-145; NICE guideline no. 133, 2019). Delaying delivery is expected to benefit newborn’s health, which is well exemplified by Mulder et al.’s findings. However, the fetus is often the protagonist of adverse conditions, and severe complications such as fetal growth restriction, often co-exist with early-onset pre-eclampsia, requiring longitudinal monitoring with Doppler ultrasound and cardiotocography. The timing of delivery depends on both maternal and fetal conditions. The lack of data about fetal growth and Doppler and cardiotocography findings (in cases with growth restricted babies) limits the generalisability of the results by Mulder et al. One would expect that a longer delay before delivery can be attained only in fetuses and mothers with milder clinical manifestations of disease.Word count: 455

Objectives: Twin-to-twin transfusion syndrome (TTTS) is a severe condition causing preterm delivery, fetal death, and neurodevelopmental disorders. The aim of this study was to develop a simple procedure for amnioreduction that would be controlled by the amniotic pressure and volume removed. Design: Prospective study of cases diagnosed with TTTS. Setting: Lis Maternity and Women’s Hospital, Israel. Population: Eleven patients with severe TTTS at stages II and III of Quintero classification were enrolled in the study. Methods: The amniotic pressure was measured along with the removed volume of the amniotic pressure between 17-34 weeks of gestation. The umbilical artery systolic/diastolic ratio for each twin was measured at the beginning and after every 500cc of removed amniotic fluid. Long-term neurodevelopmental outcome of infants with TTTS was performed. Main Outcome Measures: The survival rate was 86.4% although 91% of all twins were Quintero stage III. Results: 18 procedures were performed in this study without any maternal complications. The pattern of amniotic pressure versus the volume removed demonstrated an exponential relationship with a plateau. No tendency in the systolic/diastolic ratio variations was observed during the procedure. Of the 19 surviving twins, 13(59.1%) were considered neurologically normal, 5 (22.73%) neurologically subnormal and 1 (4.55%) abnormal. Results were compared to classical amnioreduction and laser technique procedures. Conclusions: The procedure resulted in a high rate of twin survival. The amniotic pressure was reduced towards normal values. The new procedure seems to be more efficient in terms of twin survival and positive long-term outcomes. Clinical trial ID: NCT04148

Surgery for placenta accreta spectrum overlying the cesarean scar is challenging for excessive blood loss. Elective cesarean hysterectomy without disrupting the placenta was the generally accepted approach, however, with high maternal morbidity, loss of fertility and psychological trauma. Innovative approaches are being investigated for uterine preservation. A step-by-step surgical technique was developed in our group and has been used to preserve the uterus in all severe cases with placenta increta/percreta overlying the cesarean scar. The procedure details and the surgical outcomes are provided.

Objectives To identify the novel pathogenic genetic variants associated with intrahepatic cholestasis of pregnancy (ICP) disease by whole-exome sequencing (WES) approach. Design WES the DNA, and conduct association between genetic variants and total bile acids. Setting Jiangxi. Samples 151 ICP patients. Methods DNA samples from 151 ICP patients were subjected to WES. Rare novel exonic variants (minor allele frequencies: MAF < 1%) were performed for subsequent analysis. Main outcome measures Association of genetic variants with ICP and other clinical disorders. Results We detected 42 were novel. We classified these loci as four panels according to the prediction results, of which, 7 novel possible pathogenic mutations were identified which located in the known functional genes including ABCB4, ABCB11 and ABCC2 for first reported in damaging group. Besides, compare to reference, ABCC2 Ser1342Tyr modified protein structure showed a slight change in the chemical bond lengths of ATP-ligand binding amino acid side chains. And in placental tissue, the expression level of ABCC2 gene in ICP patients was significantly higher than healthy pregnant women. Moreover, the patients with two mutations in ABC family genes have higher average value of TBA, AST, DBIL, CHOL, TG and HDL compared to the patients which have one mutation, no mutation in ICP and local controls. Conclusion Our results provide new insights into the genetic architecture of ICP disease. They may contribute to genetic diagnose of ICP disease, and provide new treatment for ICP patients. Keywords WES, TBA, ABC transporters’ genes, novel variants, ICP, ABCC2 gene, Ser1342Tyr mutation

Mini-commentary on BJOG-20-0320.R1: Cesarean section in the second delivery to prevent anal incontinence after asymptomatic obstetrical anal sphincter injury: the EPIC multicenter randomized trialAn obstetric anal sphincter injury poses an important clinical dilemma for subsequent vaginal deliveries, which may be complicated by recurrent obstetric anal sphincter injury and / or worsening or de novo anal incontinence.Recurrent obstetric anal sphincter injury has a similar incidence to primary obstetric anal sphincter injury (6.3% vs 5.7%), and similar associated risk factors including instrumental delivery with either forceps [OR 3.12, 95% confidence interval (CI) 2.42-4.01) or ventouse (OR 2.44, 95%CI 1.83-3.25), birth weight ≥4 kg (OR 2.29, 95%CI 2.06-2.54) and previous fourth-degree tear (OR 1.7, 95%CI 1.24-2.36) (Jha S, Parker V: Int Urogynecol J. 2016 Jun;27(6):849-57).The risk of long-term anal incontinence is also related to the degree of sphincter tear. Women with a fourth-degree sphincter injury in the first delivery are at higher risk for anal incontinence compared to women with a third-degree injury (58.8% vs. 41.0%). (Jangö H et al. 2018 Feb;218(2):232.e1-232.e10. Am J Obstet Gynecol). Although primary caesarean may be protective against anal incontinence, the previous observational evidence is consistent in finding that adjusted odds of long-term anal incontinence do not differ significantly by mode of second delivery after obstetric anal sphincter injury, and specifically that subsequent elective cesarean delivery is not protective (Jangö H et al, Am J Obstet Gynecol. 2016;214(6):733.e1-733.e13.) However, previous observational studies may suffer from confounding by indication, due to widespread adoption of planned caesarean for subsequent deliveries in women with incontinence symptoms or persistent sphincter defectsThere have been no previous randomised trials to test whether anal incontinence could be prevented by planned cesarean section for the second delivery. Abramowitz and colleagues’ (Abramowitz L et al. BJOG 2020) RCT provides us with a better understanding of the role of caesarean in women with asymptomatic third degree anal sphincter injury. There was limited cross-over between groups: of the 112 women randomized to the vaginal delivery group, 17 (15.6%) had a caesarean section for obstetric indications. For those randomized to the planned cesarean section, 18 (16.58%) delivered vaginally. One fifth of the randomized women did not complete the post-partum follow-up, but their characteristics did not differ between the two study groups. In this RCT, planned cesarean section in the second delivery was unequivocally not protective against anal incontinence at 8 months post-partum, with low rates of symptoms in both groups (Vaizey score 1/24 vs. 1/24 p=0.34). As rates of incontinence were lower than expected, the trial may have been underpowered for a clinically relevant difference between groups. In an unplanned analysis, there was however, an interaction between baseline Vaizey score, and worsening symptoms after vaginal delivery, with significantly worse symptoms after vaginal delivery for women with pre-existing mild symptoms.The authors rightly suggest that the findings are useful when counseling women about risks and benefits of caesarean at their second delivery. These results do not support advising systematic cesarean after asymptomatic third degree obstetric anal sphincter injury. The medicalization of pregnancy associated with planned caesarean is undesirable from both individual and societal perspectives, and cesarean delivery is associated with a number of health risks when compared to vaginal delivery (NICE Clinical Guideline CG132, https://www.nice.org.uk/guidance/cg132/). Important questions remain for future work whether subsequent cesarean section may be useful in the long term, among women with mildly symptomatic anal incontinence, or for women with asymptomatic fourth degree obstetric anal sphincter injury.Disclosure of interests: Tähtinen declares honoraria from Olympus. Cartwright declares no conflicts of interest. Completed disclosure of interest forms are available to view online as supporting information.

Objective To identify risk factors strongly associated with failed mid-cavity vacuum-assisted delivery (VAD) and construct a risk model that can be used to guide obstetricians in choosing between the standard delivery room or the operating theatre. Design Observational analytical predictive prospective monocentric study. Setting University Hospital of Besançon, France, 2010-2018. Population All successful (n=903) and failed (n=194) attempts at mid-cavity VAD among term singleton deliveries. Methods Bivariate and multivariate analyses with logistic regression were used to determine the effects of 15 potential factors on the risk of VAD failure. Main outcome measures Mode of delivery following an attempt at mid-cavity VAD. Results The score comprised seven variables significantly associated with failed mid-cavity VAD: head-perineum distance ≥51 mm (p<0.001), bulky caput succedaneum (p<0.001), maternal height ≤1.54 m (p<0.001), duration of expulsive efforts before vacuum <21 minutes or >30 minutes (p=0.0013), duration from five centimetres to complete cervical dilation ≥3 hours (p=0.0091), term ≥42 weeks of gestation (p=0.032), and occiput-posterior or occiput-transverse fetal head position (p=0.041). The model was reliable (Hosmer-Lemeshow test =8.5; p=0.39) and accurate (concordance index =0.74). The threshold for a transfer to the operating theatre was set at 16.3 %. Advanced preparation of caesarean section equipment and anticipated extension of epidural analgesia were significantly associated with a decrease in the delay between VAD failure and birth by caesarean section (p<0.001). Conclusions This model could help obstetricians to better assess the risk of failed mid-cavity VAD and to choose the appropriate place to perform it. Keywords Vacuum-assisted delivery; mid-cavity.

Objectives: To reach consensus on evidence-based recommendations to develop HDP management pathways for Indonesian primary care. Design: A three-round Delphi survey Setting: N/A Population: Maternal health practitioners and experts, including GPs, midwives, nurses and health policy researchers from Indonesia and international background. Methods: Participants were asked to rate their agreement on whether each of 125 statements about HDP and HDP managements extracted from international guidelines were feasible in Indonesian primary care settings in a mix of quantitative and qualitative questions in three-rounds Delphi survey. A minimum of 70% agreement among participants was needed for a statement to be included for the HDP pathways that the pathways drafts were presented at the third-round survey. The participants’ free text questions responses and suggestions were analysed thematically. Main Outcome Measures: Agreement scores of the statements. Results: A total of 52 participants participated, 48, 45, and 37 of them completed the first, second and third-round survey respectively. The consensus was reached for 115 of the 125 statements on HDP definition, screening, management and long-term follow-up. The agreement scores ranged from 70.8-100.0% and potential implementation barriers were also identified. Drafts of HDP management pathways were also agreed upon and received suggestions from the participants. Conclusions: Most evidence-based HDP management recommendations achieved consensus represented in the developed HDP management pathways can be implemented in Indonesian settings. Further investigations are needed to explore the acceptability and feasibility of the pathways in practice.

Objective Pelvic Floor Fascial Mobilization (PFFM) is an innovative intervention to improve pelvic floor dysfunction. Design Pregnant women at 24-30 weeks gestation, complaining of pelvic pain, and or stress urinary incontinence, were prospectively randomized to PFFM (study group) vs. pelvic floor muscle training (PFMT). Strength and function of the pelvic floor muscles was compared before and after interventions. Setting- Outpatient pregnancy clinic at a tertiary medical center Sample- 40 women randomly allocated to PFFM or PFMT Methods Each patient was treated twice, one week apart and was assessed immediately before and after each intervention, and one week after the second treatment. Main Outcome Measures PFDI 20 questionnaire , Oxford grading scale, perineometry to measure pelvic floor symptoms function and strength, transvaginal ultrasound cervical length Results PFFM group Oxford scale improved from 2.65±1.18 to 3.45±1.28 after the first session (p<0.001) with no difference in the PFMT group 3.40±1.05 vs 3.40±1.05 (p=1). Cervical Length elongated in the PFFM group after one treatment (39.8±6.5 vs 43.4±10.2 mm, p<0.05, but not in the PFMT group 40.9±6.7 vs 40.0±8.6 respectively (p=n.s). Among 26 participants who lasted the entire study – PFMT was associated with more than 40% improvement in both Oxford as well as PFDI-20 and Perineometry was improved by 23% (23.13±15.15 vs 28.58±16.07 cmH2O (p<0.05) while no such difference was found with PFMT; 30.03±12.73 vs 30.25±9.61 cmH2O respectively (p=n.s). Conclusions PFFM may improve pelvic floor function and strength, alleviate symptoms and elongate the cervix. Further bigger study is needed to better evaluate this method.