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A few studies reported association between placenta praevia (PP) and placental abruption (PA) with maternal iron deficiency anaemia (IDA), which is not an established risk factor for these conditions. This retrospective case-control study was performed to determine the relationship between IDA with PP and PA.Maternal characteristics, risk factors for and incidence of antepartum haemorrhage overall, and PP and PA, were compared between women with IDA only and controls without IDA or haemoglobinopathies matched for exact age and parity (four controls to each index case), who carried singleton pregnancy to ≥22 weeks and managed under our care from 1997 to 2019.There were 1,176 women (0.8% of eligible women in the database) with IDA only, who exhibited slightly but significantly different maternal characteristics, and increased antepartum haemorrhage overall (3.4% versus 2.2%, p = 0.031, OR 1.522, 95% CI 1.037-2.234) and PP (1.8% versus 0.9%, p = 0.010, OR 1.953, 95% CI 1.164-3.279), but not PA (1.2% versus 1.1%, p = 0.804, OR 1.077, 95% CI 0.599-1.936). When stratified by parity status, increased PP was found in nulliparous women only. On multivariate analysis adjusting for parity, previous abortion history, overweight and obesity, short stature, other antenatal complications as a composite factor, preterm (37) delivery, previous caesarean delivery, and infant gender, IDA was associated with PP (aOR 3.485, 95% CI 1.959-6.200) and PA (aOR 2.181, 95% CI 1.145-4.155).Both PP and PA are increased in women with IDA, the prevention of which could be a means to reduce the occurrence of both PP and PA.

The study aimed to investigate whether serum sFlt-1 (soluble fms-like tyrosine kinase-1) at 11-13 weeks’ gestation in pregnancies that subsequently developed preeclampsia was different from those without preeclampsia and compare screening performance of the International Prediction of Pregnancy Complications (IPPIC) reported models, which include various combinations of maternal factors, systolic blood pressure, diastolic blood pressure, PlGF (placental growth factor) and sFlt-1 and the competing risk (CR) models, which include various combinations of maternal factors, mean arterial pressure (MAP) and PlGF for predicting any-onset, early-onset, and late-onset preeclampsia. This was a prospective multicenter study in 7877 singleton pregnancies. The differences of the predictive performance between the IPPIC and CR models were compared. There were 141 women (1.79%) who developed preeclampsia, including 13 cases (0.17%) of early-onset preeclampsia and 128 cases (1.62%) of late-onset preeclampsia. In pregnancies that developed preeclampsia compared to unaffected pregnancies, median serum sFlt-1 levels and its MoMs were not significantly different ( p >0.05). There was no significant association between gestational age at delivery and log 10 sFlt-1 and log 10 sFlt-1 MoM ( p >0.05). The areas under the curve of CR models were significantly higher than the IPPIC models for the prediction of any-onset and late-onset preeclampsia but not for early-onset preeclampsia. In conclusion, there are no significant differences in the maternal serum sFlt-1 levels at 11-13 weeks’ gestation between women who subsequently develop preeclampsia and those who do not. Moreover, the CR models for the prediction of any-onset and late-onset preeclampsia perform better than the IPPIC reported model.

Research Question To investigate the effect of adding an anti-spasmodic to an existing ultrasound-guided manual vacuum aspiration (USG-MVA) protocol to alleviate immediate post-procedure abdominal cramping pain in women treated for early pregnancy loss. Design : Double-blind, placebo-controlled, randomised control trial conducted between February 2018 and January 2020 in a university-affiliated tertiary hospital. 111 women were assigned to receive a 1ml intravenous injection containing either a 20mg hyoscine butylbromide (HBB) (n = 55) or saline (n =56) as a control immediately before the USG-MVA procedure. The primary outcome was whether adding a 20mg dose HBB to the current pain control regimen reduced abdominal pain. Secondary outcomes were vaginal pain, complications and side effects, women's pre- and post-procedure's psychological state, physiological stress (saliva alpha-amylase (sAA) and procedure pain control satisfaction. Two-way mixed ANOVA was used to evaluate for main effects and interactions. Results VAS abdominal pain scores in the HBB group were 16% lower immediately and 21% lower two hours postoperatively, though not statistically significant. Two-way ANOVA indicated that time (F (1,108) =83.41,p Conclusions Anti-spasmodics can be helpful in the reduction of USG-MVA associated abdominal cramping pain, though our results showed HBB produced an insignificant decrease in abdominal pain score. Further studies with longer-acting or larger doses of anti-spasmodics are warranted.

Recent evidence from a meta-analysis indicates that maternal prenatal exposure, single or repeated, to non-steroidal anti-inflammatory drugs (NSAIDs) or non-opioid painkillers, is associated with increased risk of cerebral palsy and cognitive-behavioral disorders in offspring. One potential route of action is interference with the neurulation process and hence early brain development.To examine the effect of prenatal exposure to common NSAIDs and non-opioid drugs on neurulation using anMouse embryos from in-bred Institute of Cancer Research albino strain mice were exteriorized on embryonic day 7.5 and cultured for 48 h in either 1 mL heat-inactivated rat serum + 0.1% dimethyl sulfoxide ("Control") or 1 mL of rat serum supplemented with six increasing concentrations of laboratory-grade aspirin, paracetamol, and ibuprofen ("Experimental"). After culture, embryo morphological and developmental parameters were documented using standardized scoring systems at each dosage concentration. The assessed concentration in rat serum culture ranged from 1.23 to 13.57 mg/mL for aspirin and 0.06-4.93 mg/mL for paracetamol and ibuprofen. The equivalent respective human dosages were 600-6600 mg and 30-2400 mg.Between-group comparisons ("Control" vs "Experimental") and post-hoc pair-wise tests, adjusted for multiple comparisons, indicating no statistically significant effect on crown-rump length (This study has demonstrated that there are no safety concerns regarding high-dose aspirin, ibuprofen, and paracetamol on mice's embryonic development.

Objective To examine attitudes toward prenatal testing and termination of pregnancy (TOP) among parents and obstetric providers in relation to their views on raising a child with disability. Methods An explanatory sequential mixed methods study. A survey among 274 parents and 141 providers was followed by interviews with 26 parents and 10 providers. Using multivariate analysis, the relationships between attitudes were examined. Thematic analysis was used to identify the reasons behind the attitudes. Results In comparison with providers, parents reported more positive attitudes toward raising a child with disability and more moral views about TOP. Providers reported more variations in attitudes toward offering prenatal testing and TOP. Significant associations were found between attitudes toward prenatal testing, raising a child with disability, reproductive autonomy, and TOP. Three major themes were identified: (1) meanings of parenthood from genetic tests; (2) views toward TOP and parental responsibility; and (3) implications of advanced extended prenatal genetic testing. Conclusions Perceived social–cultural norms of disabilities and parental expectations of raising a child with disability influence decision-making regarding TOP. Practice Implications As more conditions of the fetus are able to be detected, the social–cultural implications of the technology and disabilities need to be addressed in antenatal care.

Objectives: To investigate (i) the association between pre-labor maternal-fetal Dopplers and fetal heart rate short-term variability (FHR STV) with arterial cord blood pH and (ii) the potential value of pre-labor maternal-fetal Dopplers, FHR STV and Dawes-Redman criteria in predicting composite neonatal morbidity at term in a cohort of unselected women.Method: A prospective study in 218 women with term singleton pregnancy in latent phase of labor or due to undergo induction of labor. Data on maternal characteristics, maternal-fetal Dopplers indices and computerized cardiotocography (CTG) findings of FHR STV and Dawes-Redman criteria were collected. Pearson correlation analysis was used to determine the relationship between maternal-fetal Dopplers and FHR STV and arterial cord blood pH. Logistic regression analysis was used to determine which factors amongst maternal characteristics, labor onset, indication of labor induction, estimated fetal weight (EFW), maternal-fetal Dopplers, FHR STV and Dawes-Redman criteria were significant predictors of composite neonatal morbidity and arterial cord blood pH less than 7.2.Result: Of the 218 cases, 12 (5.5%) women were delivered by emergency operative delivery for pathological CTG, and 42 babies (19.3%) had composite neonatal morbidities. Arterial cord blood pH was not associated with maternal-fetal Doppler indices and FHR STV, but rather it was associated with maternal age and body mass index. The composite neonatal morbidity and arterial cord blood pH less than 7.2 were not significantly associated with maternal characteristics, labor onset, indication of labor induction, pre-labor assessment of EFW, maternal-fetal Doppler indices, FHR STV and Dawes-Redman criteria by computerized CTG.Conclusion: In unselected women in latent phase of labor or undergoing induction of labor at term, admission maternal-fetal Doppler indices, FHR STV and Dawes-Redman criteria are not predictive of composite neonatal morbidity.

Background: A population-based reference interval (RI) of thyroid hormones in pregnancy using a standardized methodology is crucial for clinicians to make accurate diagnoses and important for the comparison of test results obtained from different analytic platforms. Methods: We enrolled 600 healthy Chinese women to obtain longitudinal serum samples across gestation, after exclusion of subjects with antibodies to thyroid peroxidase, thyroglobulin or thyrotropin receptor. Gestational age-specific RIs were constructed by using polynomial regression equations with MLwiN. Results: Free thyroxine (fT4) levels rose to a peak at the 7th-8th gestational weeks and then declined gradually till 28th week, while thyrotropin (TSH) level decreased from early pregnancy to a nadir at the 9th week. The data support the recent notion by the American Thyroid Association to raise the TSH upper RI to 4.0 mIU/L. We also demonstrate that thyroid hormone reference ranges are not affected in a mildly iodine-deficient population and by including women with the presence of antibodies against thyroid peroxidase and thyroglobulin who are otherwise healthy. Conclusions: The study highlights a methodology in constructing gestational age-specific thyroid function test RIs on different analytic platforms to provide a better interpretation and comparison of results obtained across different platforms.

BACKGROUND Increasing prenatal screening options and limited consultation time have made it difficult for pregnant women to participate in shared decision-making. Interactive digital decision aids (IDDAs) could integrate interactive technology into health care to a facilitate higher-quality decision-making process. OBJECTIVE The objective of this study was to assess the effectiveness of IDDAs on pregnant women’s decision-making regarding prenatal screening. METHODS We searched Cochrane Central Register of Controlled Trials, MEDLINE, Embase, PsycINFO, World Health Organization International Clinical Trials Registry Platform, Google Scholar, and reference lists of included studies until August 2021. We included the randomized controlled trials (RCTs) that compared the use of IDDAs (fulfilling basic criteria of International Patient Decision Aid Standards Collaboration and these were interactive and digital) as an adjunct to standard care with standard care alone and involved pregnant women themselves in prenatal screening decision-making. Data on primary outcomes, that is, knowledge and decisional conflict, and secondary outcomes were extracted, and meta-analyses were conducted based on standardized mean differences (SMDs). Subgroup analysis based on knowledge was performed. The Cochrane risk-of-bias tool was used for risk-of-bias assessment. RESULTS Eight RCTs were identified from 10,283 references, of which 7 were included in quantitative synthesis. Analyses showed that IDDAs increased knowledge (SMD 0.58, 95% CI 0.26-0.90) and decreased decisional conflict (SMD –0.15, 95% CI –0.25 to –0.05). Substantial heterogeneity in knowledge was identified, which could not be completely resolved through subgroup analysis. CONCLUSIONS IDDAs can improve certain aspects of decision-making in prenatal screening among pregnant women, but the results require cautious interpretation. CLINICALTRIAL

Introduction Bishop score, the traditional method to assess cervical condition, is not a promising predictive tool of the outcome of labor induction. As an objective assessment tool, many cervical ultrasound measurements have been proposed to represent the individual components of the Bishop score, but none of them can measure the cervical stiffness. Cervical shear wave elastography is a novel tool to assess the cervical stiffness quantitatively. Material and methods A total of 475 women who required labor induction were studied prospectively. Prior to routine digital assessment of the Bishop score, transvaginal sonographic measurement of cervical length, posterior cervical angle, angle of progression and shear wave elastography was performed. Shear wave elastography measurement was made at the inner, middle and outer regions of the cervix to assess homogeneity. Association of labor induction outcomes including the overall cesarean section and subgroups of cesarean section for failure to enter active phase, with cervical sonographic parameters and the Bishop score, were assessed using multivariate regression analyses. The predictive accuracy of the outcomes using models based on ultrasound measurement and the Bishop score was compared using the area under the receiver‐operating characteristics curves. Results Among 475 women, 82 (17.3%) required cesarean section. Shear wave elasticity was significantly higher in the inner cervical region than in other regions, indicating a greater stiffness (P

Background Preterm birth is the leading cause of death in children under the age of five years. Transvaginal cervical length (TVCL) assessment can be used to predict preterm delivery risk at the mid-trimester scan. To optimise the screening tool, developing and maintaining quality standards is important. Aims To develop an Australian reference range for TVCL at 18.0-21.0 weeks' gestation, quality standards for measurement and audit mechanisms for ultrasound operators. Materials and methods A retrospective audit was performed of consecutive patients scanned at 18.0-21.0 weeks' gestation. Each TVCL measurement ultrasound image was reviewed, and exclusions were made based on a defined set of quality criteria. Fractional polynomial Bayesian methodology was used to establish a reference range. Central tendency, dispersion plots and cumulative sum charts for operators in the original reference range cohort were created. These plots were then applied to a second validation cohort of operators to establish the efficacy of this quality assurance audit tool. Results Median TVCL from 1031 participants was 36.0 mm (interquartile range 32.7-40.0 mm), which was independent of gestational age. The quality audit tool was applied to 15 operators from the reference cohort with a mean cervix length multiple of the median of 1.01 and a mean SD log10 cervix length multiple of the median of 0.06. Of the 22 operators in the validation cohort, 20 (90.9%) demonstrated ideal or acceptable central tendency results, and 19 (86.4%) remained in the appropriate cumulative sum zone. Conclusion An Australian cervix length measurement reference range at 18.0-21.0 weeks' gestation has been developed along with a validated quality assurance audit tool for ultrasound operators.

Study question Does Buscopan® reduce abdominal pain experienced by women undergoing ultrasound-guided manual vacuum aspiration (USG-MVA)? Summary answer The addition of 20mg Buscopan® intravenous injection was not associated with a statistical reduction in pain score but leads to a higher patient satisfaction score. What is known already Ultrasound-guided Manual Vacuum aspiration is a feasible and effective out-patient treatment option for treating early pregnancy loss. However, it is associated with a moderate amount of pain due to uterine contraction. Study design, size, duration This randomised, double-blinded, placebo-controlled trial was conducted in a university-affiliated tertiary hospital. The study assessed whether 1 ml of 20mg Buscopan® intravenous injection 5 minutes before the USG-MVA will reduce the abdominal pain experienced by the women immediately and 2 hours after the procedure. Participants were randomised between June 2018 to January 2020 using a computer-generated number series in a 1:1 ratio. Participants/materials, setting, methods Women aged 18 years or older with first-trimester miscarriage undergoing the USG-MVA procedure were eligible. In total, 122 participants out of 128 eligible were included. Of whom, 111 underwent the USG-MVA procedure, 60 randomised to the Buscopan® group, and 62 to the placebo group. Main results and the role of chance The median abdominal pain scores in the Buscopan® group were 16.0% and 21.2% lower than the placebo group immediately post-procedure and 2 hours after the procedure in the Buscopan® group. Repeated measures ANOVA indicated that the both vaginal and abdominal pain scores improved significantly with the time (Vaginal F(1,108)= 180.1,p Abdominal F(1,108)=83.41,p Limitations, reasons for caution This study was a single-centre study, thus one should be cautious in the overall generalisability of the results. Wider implications of the findings Few studies have evaluated the use of anti-spasmodic agents to minimise uterine contraction pain in women undergoing outpatient uterine evacuation. We consider Buscopan® a useful adjunct in the pain control of USG-MVA to specifically reduce uterine cramps. Further larger studies are required to evaluate its efficacy Trial registration number ChiCTR1800014590

To evaluate second-trimester Down syndrome screening performance of the new ThermoFisher BRAHMS GOLD unconjugated estriol (uE3) and inhibin-A assays. Serum samples were analyzed for levels of uE3 and inhibin-A using the ThermoFisher BRAHMS GOLD immunoanalyzer and compared to other platforms. Levels were transformed to multiples of the median (MoM) in unaffected pregnancies. Log10 MoM distributions in unaffected and Down syndrome pregnancies were assessed for central tendency (mean) and dispersion (SD). Empirical and estimated screening performances were determined. Correlation between BRAHMS and AutoDELFIA® uE3 and inhibin-A were 0.63 and 0.97, respectively, the respective mean difference was 31.3% [95%CI 50.2% to -112.8%] and -23.3% [95%CI -41.9% to -4.7%]. Passing-Bablok indicated significant systematic (-2.78 [95%CI -3.57 to -2.04]) and proportional bias (1.30 [95%CI 1.15 to -1.47]) between uE3 assays and significant proportional bias (0.71[95%CI 0.65-0.78]) between inhibin-A assays. The uE3 and inhibin-A log10 MoM distribution mean [SD] in unaffected and Down syndrome pregnancies were 0.0024 [SD = 0.2341] and -0.0001 [SD = 0.2078], and -0.2028 [SD = 0.2495] and 0.3645 [SD = 0.2576], respectively. The new BRAHMS uE3 and inhibin-A assays had an 81-83% detection rate for Trisomy21 for a 5% false-positive rate. The new BRAHMS assays achieved the expected screening performance provided the risk estimation model is adjusted to account for the higher BRAHMS uE3 MoM measurement distribution variance.

Objectives: To assess whether adding placental growth factor (PlGF) or replacing pregnancy-associated plasma protein-A (PAPP-A) improves the first trimester combined test performance for trisomy 21. Design: Prospective observation Cohort Setting: The Chinese University of Hong Kong, China Sample: 11,518 women having a singleton pregnancy screened for trisomy 21 between December 2016 and December 2019 using the first trimester combined test. Methods: PlGF was prospectively measured and estimated term risk for trisomy 21 was calculated by 1) replacing PAPP-A with PlGF and 2) adding PlGF to the combined test which includes nuchal translucency, PAPP-A and free β-human chorionic gonadotropin (hCG). Main Outcome Measure: Screening performance, area under curve (AUC), detection rate (DR), screen positive rate (SPR) and false positive rate (FPR) Results: 29 women had trisomy 21. The combined tests DR, FPR and SPR were 89.7%, 5.7% and 6% respectively. DR when replacing PAPP-A or adding PlGF to the combined test remained unchanged. Replacing PAPP-A by PlGF increased FPR and SPR to 6.2% and 6.4% respectively. Adding PlGF to the combined test gave FPR and SPR rates of 5.5% and 5.7% respectively. Adding or replacing PlGF did not give a significant increase in AUC (p>0.48) over that of the combined test. Conclusion: Adding PlGF to the combined test or replacing PAPP-A with PlGF in the combined test did not improve trisomy 21 detection rate. Replacing PAPP-A by PlGF increased SPR, whilst adding PlGF resulted in only a marginal reduction in SPR.

Research question Is there a difference in the ovarian reserve 1 year post-operatively in those who used a haemostatic sealant or bipolar diathermy for haemostasis during laparoscopic ovarian cystectomy for ovarian endometriomas? Design This was an extended follow-up observational study of a previous randomized controlled trial where women aged 18 to 40 years with 3–8 cm unilateral or bilateral endometriomas were randomized to receive haemostasis by a haemostatic sealant or bipolar diathermy following ovarian cystectomy. The primary outcome was the ovarian reserve as assessed by antral follicle count (AFC) 1 year post-operatively. Secondary outcomes included the recurrence rate of ovarian endometrioma, the change in anti-Mullerian hormone (AMH) and FSH concentrations, and reproductive outcomes. Results The significant increase in AFC at 3 months after initial surgery (P = 0.025) in the haemostatic sealant group compared with the diathermy group was sustained at 1 year (P = 0.024) but there was no difference in AMH or FSH concentrations between the groups throughout the follow-up period. The recurrence rate in the FloSeal group was 7.7% (n = 3/39) compared with 22.2% (n = 8/36) in the diathermy group (P = 0.060). The recurrence rate in women who had bilateral lesions was significantly higher than those with unilateral lesions (risk ratio 5.33, interquartile range 1.55–18.38). No difference in reproductive outcomes was found between the two groups. Conclusions Applying haemostatic sealant after laparoscopic cystectomy of ovarian endometriomas produces a significantly greater improvement in AFC, which was apparent at 3-month follow-up, and was sustained at 1-year follow-up without compromising the recurrence rate.

INTRODUCTION Umbilical cord prolapse is a major obstetric emergency associated with significant perinatal complications. However, there is no consensus on the optimal decision-to-delivery interval, as many previous studies have shown poor correlation between the interval and umbilical cord arterial blood gas or perinatal outcomes. We aim to investigate whether bradycardia-to-delivery or decision-to-delivery interval was related to poor cord arterial pH or adverse perinatal outcome in umbilical cord prolapse. MATERIAL AND METHODS This was a retrospective study conducted at a university tertiary obstetric unit in Hong Kong. All women with singleton pregnancy complicated by cord prolapse during labor between 1995 and 2018 were included. Women were categorized into three groups. Group 1: persistent bradycardia; Group 2: any type of decelerations without bradycardia; and Group 3: normal fetal heart rate. The main outcome was cord arterial blood gas results of the newborns in different groups. Maternal demographic data and perinatal outcomes were reviewed. Correlation analysis between cord arterial blood gas result and time intervals including bradycardia-to-delivery, deceleration-to-delivery, and decision-to-delivery were performed for the different groups with Spearman test. RESULTS There were 34, 30, and 50 women in Groups 1, 2, and 3, respectively. Cord arterial pH and base excess did not correlate with decision-to-delivery interval in any of the groups, but they were inversely correlated with bradycardia-to-delivery interval in Group 1 (Spearman's ρ = -.349; P = .043 and Spearman's ρ = -.558; P = .001, respectively). The cord arterial pH drops at 0.009 per minute with bradycardia-to-delivery interval in Group 1 (95% CI 0.0180-0.0003). The risk of significant acidosis (pH 20 minutes, and 17.2% when the interval was

Preeclampsia is a major cause of maternal and perinatal morbidity and mortality. Early-onset disease requiring preterm delivery is associated with a higher risk of complications in both mothers and babies. Evidence suggests that the administration of low-dose aspirin initiated before 16 weeks' gestation significantly reduces the rate of preterm preeclampsia. Therefore, it is important to identify pregnant women at risk of developing preeclampsia during the first trimester of pregnancy, thus allowing timely therapeutic intervention. Several professional organizations such as the American College of Obstetricians and Gynecologists (ACOG) and National Institute for Health and Care Excellence (NICE) have proposed screening for preeclampsia based on maternal risk factors. The approach recommended by ACOG and NICE essentially treats each risk factor as a separate screening test with additive detection rate and screen-positive rate. Evidence has shown that preeclampsia screening based on the NICE and ACOG approach has suboptimal performance, as the NICE recommendation only achieves detection rates of 41% and 34%, with a 10% false-positive rate, for preterm and term preeclampsia, respectively. Screening based on the 2013 ACOG recommendation can only achieve detection rates of 5% and 2% for preterm and term preeclampsia, respectively, with a 0.2% false-positive rate. Various first trimester prediction models have been developed. Most of them have not undergone or failed external validation. However, it is worthy of note that the Fetal Medicine Foundation (FMF) first trimester prediction model (namely the triple test), which consists of a combination of maternal factors and measurements of mean arterial pressure, uterine artery pulsatility index, and serum placental growth factor, has undergone successful internal and external validation. The FMF triple test has detection rates of 90% and 75% for the prediction of early and preterm preeclampsia, respectively, with a 10% false-positive rate. Such performance of screening is superior to that of the traditional method by maternal risk factors alone. The use of the FMF prediction model, followed by the administration of low-dose aspirin, has been shown to reduce the rate of preterm preeclampsia by 62%. The number needed to screen to prevent 1 case of preterm preeclampsia by the FMF triple test is 250. The key to maintaining optimal screening performance is to establish standardized protocols for biomarker measurements and regular biomarker quality assessment, as inaccurate measurement can affect screening performance. Tools frequently used to assess quality control include the cumulative sum and target plot. Cumulative sum is a sensitive method to detect small shifts over time, and point of shift can be easily identified. Target plot is a tool to evaluate deviation from the expected multiple of median and the expected median of standard deviation. Target plot is easy to interpret and visualize. However, it is insensitive to detecting small deviations. Adherence to well-defined protocols for the measurements of mean arterial pressure, uterine artery pulsatility index, and placental growth factor is required. This article summarizes the existing literature on the different methods, recommendations by professional organizations, quality assessment of different components of risk assessment, and clinical implementation of the first trimester screening for preeclampsia.

Introduction A scoring system combining clinical history and simple ultrasound parameters was developed to predict early pregnancy viability beyond the first trimester. The scoring system has not yet been externally validated. This study aimed to externally validate this scoring system to predict ongoing pregnancy viability beyond the first trimester. Methods This prospective observational cohort study enrolled women with singleton intrauterine pregnancies before 12 weeks of gestation. Women underwent examination and ultrasound scan to assess gestational sac size, yolk sac size, and fetal pulsation status. A pregnancy-specific viability score was derived in accordance with the Bottomley score. Pregnancy outcomes at 13 to 16 weeks were documented. Receiver-operating characteristic curve analysis was used to assess the discriminatory performance of the scoring system. Results In total, 1508 women were enrolled; 1271 were eligible for analysis. After adjustment for covariates, miscarriage (13%) was significantly associated with age ≥35 years (odds ratio [OR]=1.99, 95% confidence interval [CI]: 1.19-3.34), higher bleeding score (OR=2.34, 95% CI: 1.25-4.38), gestational age (OR=1.17, 95% CI: 1.13-1.22), absence of yolk sac (OR=4.73, 95% CI: 2.11-10.62), absence of fetal heart pulsation (OR=3.57, 95% CI: 1.87-6.84), mean yolk sac size (OR=1.25, 95% CI: 1.06-1.47), and fetal size (OR=0.82, 95% CI: 0.77-0.88). The area under the receiver operating characteristic curve was 0.91 (95% CI: 0.89-0.93). Viability score of ≥1 corresponded to a >90% probability of viable pregnancy. Conclusions The scoring system was easy to use. A score of ≥1 could be used to counsel women who have a high likelihood of viable pregnancy beyond the first trimester.

OBJECTIVE To ascertain whether stress biomarkers and psychological indices of stress may predict both conception and miscarriage rates in women undergoing in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI). DESIGN Prospective observational study. SETTING A university-affiliated tertiary hospital. POPULATION Infertile women who were undergoing fresh or frozen IVF/ICSI cycles. METHODS Women were recruited to (1) complete validated psychological questionnaires (visual analogue scale of stress, state-trait anxiety inventory, perceived stress scale, fertility problem inventory, Beck depression inventory, and general health questionnaire), at the time of embryo transfer (ET) and pregnancy testing (PT), and (2) provide saliva samples for α-amylase (sAA) measurement before and after ET and at PT. MAIN OUTCOME MEASURES Women were grouped according to subsequent reproductive outcome; scores/levels of all tests were then compared between groups at each time-point. RESULTS In all, 197 women completed the study, of which 92 conceived and 28 miscarried. The level of psychological stress, as measured by questionnaires, was highest at the time of PT, whereas the level of biological stress as measured by sAA level (IU/l) post-ET (1.8 × 105 ± 1.5 × 105 ) was significantly (P

Objective: To examine (1) the concordance of manual and automated para-symphyseal angle of progression (psAOP) measurements, (2) the repeatability of psAOP, head-symphysis distance, head-perineum distance, and sonographic cervical dilatation, and (3) the value of transperineal ultrasound (TPU) in predicting induction of labor (IOL) outcome. Methods: We performed a prospective study in 308 women with singleton pregnancies undergoing IOL at term. Logistic regression analysis was used to determine which maternal factors, Bishop score, method of IOL, and TPU parameters were significant predictors of cesarean section (CS) and CS due to no progress (CS-NP). Results: There was vaginal delivery in 225 (83.0%) and CS in 46 (17.0%) cases. The intra-class correlation coefficient between manual and automated psAOP was 0.866, but automated psAOP was 4.6° wider than manual measurement. All TPU parameters had an inter-observer intra-class correlation coefficient > 0.800. Significant independent prediction of CS and CS-NP was provided by maternal factors, previous vaginal delivery, and psAOP. There was no improvement in area under the receiver-operating characteristic curve with the addition of psAOP to maternal factors. Conclusions: All TPU parameters are reproducible. Comparing the three TPU parameters for fetal head station, only psAOP is a significant independent predictor of CS; however, it is unlikely to be useful in predicting IOL outcome.

Objectives To assess the suitability of the new INTERGROWTH-21 and WHO estimated fetal weight (EFW) references. Methods This was a prospective cross-sectional cohort study. Viable singleton pregnancies at 11-13 weeks were randomized to undergo a standardized fetal biometric scan after 20 weeks. EFW were predicted using both the Hadlock and INTERGROWTH-21 weight estimation models formulaes. Population specific EFW gestation references were constructed. Z-scores were used to compare the population specific reference against the two international size references, INTERGROWTH-21 and WHO. Gestation Adjusted Projection (GAP) was used to assess the difference predicted EFW on day of delivery and birthweight for fetuses having biometry scans ≥ 34 weeks. Results Fetuses of 970 participants had biometry scans. The median (Interquartile range (IQR)) number of scans per gestational week was 48 (43-53). Z-score comparison indicated that WHO 10th, 50th and 90th centiles of the EFW reference were consistently higher than the corresponding local centiles whilst INTERGROWTH-21 10th centile was lower. Less than 2%, of fetuses scanned on or after 34 weeks would be considered as potentially large for gestational age irrespective of which model was used to predict weight. Adopting the WHO international reference would result in approximately 1 in 6 fetuses being regarded as potentially small for gestation, a 50 percent increase over that determined using a population specific reference. Systematic error of extrapolated EFW were similar, ranging from 5.5% to 7.4%. Conclusions Centers seeking to use new references such as the INTERGROWTH-21 and or WHO international references as a means of determining whether a fetus is small or large for gestation would be advised to assess the suitability of these references within their own population using standardized methodology.

To evaluate the impact of three decades of hepatitis B vaccination in infancy on antenatal prevalence of hepatitis B surface antigen (HBsAg) carriage in 93,134 Hong-Kong born gravidae managed in 1997-2015.Annual prevalence of HBsAg carriage on routine antenatal screening was examined with respect to maternal year of birth in three periods i.e. pre-1983 (before availability of vaccination), 1983-1988 (vaccination of infants born to HBsAg-carriers), and after 1988 (universal vaccination).Overall HBsAg carriage was 8.3% (7737/93,134), decreasing from 10.5% in 1997 to 6.5% in 2015 (p 0.001), and from 8.8%, 7.0% to 3.1%, respectively, for the three period-of-birth cohorts (p 0.001). Annual prevalence decreased from 9.9% in 1997 to 7.5% in 2015 (p 0.001) in the pre-1983 cohort, but showed neither difference nor trend in the other two cohorts. However, the annual prevalence showed significantly falling trends from the pre-1983 to the post-1988 cohorts for the years 2007-2008 and 2010-2015.A progressive decline in overall annual prevalence of antenatal HBsAg carriage was found, with a consistently significant decline among the three cohorts for the years 2007-2008 and 2010-2015, providing evidence that universal hepatitis B vaccination in infancy has reduced significantly antenatal prevalence of HBsAg carriage in Hong Kong.

Objective: To assess the association between body mass index (BMI) and adverse pregnancy outcomes.Materials and methods: A multicentre retrospective cohort study was conducted in three hospitals in Hong Kong including 67,248 women with singleton pregnancy at 11–13 weeks between 2010 and 2016. The relationship between maternal BMI and (1) miscarriage or stillbirth, (2) development of preeclampsia (PE), (3) gestational hypertension (GH), (4) development of gestational diabetes mellitus (GDM), (5) spontaneous preterm delivery (sPTD)

Objective To examine preferences for follow-up testing in women screened with high or intermediate risk for Down syndrome in the first or second trimester. Design Prospective cohort study. Setting Three public hospitals in Hong Kong, China. Sample Women with pregnancies termed as high risk (≥1:250; HR) or intermediate risk (1:251–1200; IR) for Down syndrome. Methods Women with pregnancies screened as HR were offered the choices of: (1) an invasive test plus chromosomal microarray (CMA) to obtain more detailed fetal genetic information; (2) non-invasive cell-free prenatal DNA screening (NIPT) to detect trisomies 13, 18 and 21, and to avoid procedure-related miscarriage; and (3) to decline any further testing. Women received standardised counselling informing them that the reporting times were identical, the procedure miscarriage risk was 0.1–0.2% and that there was no charge for screening. Women with IR pregnancies (1:251–1200) were offered NIPT as a secondary screening test. Main outcome measures Uptake rate for NIPT. Results Three hundred and forty-seven women had pregnancies deemed as HR; 344 (99.1%) women opted for follow-up testing, 216 (62.2%) of whom chose NIPT. Five hundred and seven of 614 women (82.6%) with IR risk chose NIPT. Seven (21%) of 34 women with nuchal translucency ≥3.5 mm opted for NIPT. Conclusion In a setting where reporting times are similar and there is no cost difference between options, approximately 60% of women with pregnancies classed as HR would opt for NIPT, offering simple but limited aneuploidy assessment, over a diagnostic procedure with comprehensive and more detailed assessment. Tweetable abstract 60% of pregnant Chinese women prefer NIPT over CMA when screened as high risk for Down syndrome.

OBJECTIVE To assess the potential of screening for pre-eclampsia (PE) in a Chinese population. DESIGN Case-control study. SETTING Teaching hospital in Hong Kong. POPULATION A total of 3330 women having a viable singleton pregnancy attending first-trimester Down-syndrome screening. METHODS Mean arterial pressure (MAP), bilateral uterine artery pulsatility index (UtA-PI), and placental growth factor (PlGF) were measured. Screening markers were transformed to multiples of the gestational median (MoM) and adjusted for maternal and pregnancy characteristics. MoM distributions in PE and non-PE pregnancies were compared with published expected values. PE screening performance was assessed using area under receiver operating curves (AUROC). MAIN OUTCOME MEASURES PE detection rate. RESULTS A total of 30 (0.9%) women developed either early (

To assess the clinical utility of the sFlt-1:PlGF ratio rule-in/rule-out pre-eclampsia either directly or after correcting each marker for gestation and maternal weight.This was a prospective cohort study. sFlt-1, PlGF were measured in 965 women randomized to undergo a single blood withdraw between 20 and 39 weeks of gestation. sFlt-1, PlGF and the sFlt-1:PlGF ratio temporal relationship was determined. sFlt-1 and PlGF were converted to multiples of the expected gestational median (MoM) and adjusted for maternal weight. The 90th centile of the adjusted sFlt-1MoM:PlGFMoM ratio was determined. Clinical utility of the sFlt-1:PlGF ratio (≥38) to rule in/rule-out pre-eclampsia (PE) after 20 weeks of gestation versus that of the sFlt-1MoM:PlGFMoM 90th percentile was assessed in 81 women admitted for management of antenatal hypertension.The sFlt-1:PlGF ratio had quadratic relationship with gestation whereas the sFlt-1MoM:PlGFMoM ratio log distribution that was Gaussian with a mean of zero and a standard deviation of 0.85 with a 90th percentile equal to 1.08. Thirty-four (42%) of the 81 women admitted for management of their antenatal hypertension had PE, 26 (76.4%) had a sFlt-1:PlGF ratio ≥ 38. Four of the remaining 8 PE affected pregnancies with sFlt-1:PlGF ratio38 delivered within 7 days, 3 were preterm. Two of the 3 preterm PE pregnancies had sFlt-1MoM:PlGFMoM exceeding 90th percentile.The relative level of the sFlt-1 to PlGF carries prognostic value. A sFlt-1MoM:PlGFMoM ratio exceeding the 90th centile resulted in additional detection of pregnancies which developed PE compared to the conventional sFlt-1:PlGF ratio.

The study aimed to identify the simplest protocol for the measurement of mean arterial pressure (MAP) across 10-40 weeks’ gestation. 2,726 women with uncomplicated singleton pregnancy attending for their routine hospital visit between 10-40 weeks’ gestation were recruited prospectively. The blood pressure (BP) was measured according to the National Heart Foundation of Australia (NHFA) protocol using automated devices. Linearizing regression models were determined for MAP derived from single, repeat and average measurements taken in the left and right arms using the same polynomial power of the best fit model determined using the NHFA protocol. Z-scores were used to compare the differences between the smoothed 50th percentiles. The first measurements taken in the left and right arms were on average 0.15SD and 0.12SD, respectively, higher than those obtained from the NHFA protocol. The second measurements taken in the left and right arms were both 0.26SD lower than the first measurement taken in the same arm and these values were lower than those from the NHFA protocol. The median MAP determined by the protocol of the average of two measurements taken in both arms was similar to the median MAP determined using the NHFA protocol (Z-score 0.0194SD). MAP derived by the average of two measurements in both arms had a quadratic relationship with gestation, with the measurement being the lowest in the mid-trimester. In conclusion, our study has demonstrated that at 10-40 weeks’ gestation, BP recordings can be obtained by a simpler protocol using the average of two measurements in both arms.

Funding Acknowledgements CUHK Direct Grant, CUHK Lui Che Woo Institute of Innovative Medicine, Food and Health Bureau of HKSAR (EF); Hong Kong Jockey Club Charities Trust (JW) Background/Introduction 6-min walk distance (6MWD) can indicate frailty extent, cardiac dysfunction, and heart failure (HF) trajectory. Association of 6MWD with diastolic dysfunction (DD) or cardiac biomarker in community-living elderly without a history of HF remains underexplored. Purpose This study aims to determine the association between 6MWD, serum N-terminal prohormone of B-type natriuretic peptide (NT-proBNP), and DD in a community-living elderly population without known HF. Methods Between Nov 2017 and Aug 2018, 302 Hong Kong Chinese aged ≥60 y and without known HF were recruited into the Undiagnosed heart Failure in Older individuals (UFO) study consisting of robust, pre-frail and frail older adults stratified by FRAIL scale in a ratio of 1:1:1. 6MWD was divided into tertiles. Transthoracic echocardiography and serum NT-proBNP were used to assess cardiac dysfunction. Diastolic function was classified according to international guidelines and NT-proBNP >300 pg/ml was considered elevated. Results The ages of participants in the bottom, middle and top tertiles were 80.3 ± 7.4, 73.9 ± 6.3 and 70.0 ± 5.7 years (P Using multiple linear regression analysis, S’ velocity, E:E’ ratio and E’ velocity were associated with 6MWD independent of age and sex. Associations between 6MWD and S’, left atrial volume index, E’ and E:E’ remained statistically significant even after adjusting for HT, DM, IHD, AF, stroke, chronic pulmonary disease and arthritis. No correlation was observed between 6MWD and left ventricular ejection fraction. Compared with the top tertile of 6MWD, the bottom tertile was associated with increased risks for grade II–IV DD (odds ratio (OR) 3.47, 95% confidence interval (CI) 1.52–7.96, P 300pg/ml (OR 10.20, CI 3.74–27.85, P Conclusion(s) In this cohort of community-living Hong Kong Chinese elderly recruited equally by frailty status, performance of 6MWD in the bottom and top tertiles was inversely associated with NT-proBNP levels but not with DD.

Placental-related mechanism of fetal growth restriction (FGR) is still unknown. Here we aimed to profile whole-genome miRNA between selective FGR twin (sFGR-T) and normally larger co-twin (sL-T) in monochorionic (MC) twin pregnancies and to further investigate effect of the miRNA on placental pathogenesis, including angiogenesis and mitochondrial functions.MC twin pregnancies with or without sFGR were recruited, and their placental miRNAs were profiled (n = 3 vs 5). Ratio of placental miRNAs in the sFGR twin pairs (sFGR-T/sL-T) were calculated and compared to that in the control twin pairs (cS-T/cL-T). Differentially expressed miRNAs and associated markers were validated qRT-PCR, immunohistochemistry staining (n = 8 vs 13) and electron microscopy (n = 3 vs 3).Placental miR-199a-5p was significantly upregulated in sFGR-T (p = 0.004), which was validated by qRT-PCR (1.03 vs 0.56; p = 0.020). Compared to control twin pairs, ratio of CD31-positive vessels and volume density of vessels in sFGR twin pairs was lower (0.65 vs 0.92 and 18.7% vs 36.3%; both p 0.001), while that of cyclooxygenase 2 (COX2)-positive trophoblast cells was higher (3.50 vs 2.22; p = 0.001), indicating an impaired angiogenesis and oxidative stress in the sFGR placenta. In addition, ratio of mitochondrial DNA (mtDNA) mitochondrial encoded NADH dehydrogenase 1 (MTND1) copy numbers (2.10 vs 0.90; p = 0.013), H-score ratios of mitochondrial markers citrate synthase (CS) and cytochrome c oxidase subunit 4 isoform 1 (COX4, 0.53 vs 0.95, p 0.001; 0.29 vs 1.06, p 0.001) in trophoblast cells of sFGR twin pairs were also altered significantly and correlated with angiogenesis. Furthermore, ratio of mitochondrial numbers per trophoblasts (8.67 vs 18.67; p = 0.006) and percentage of swollen mitochondria (84.33 vs 11.33; p = 0.003) were converted significantly, indicating mitochondrial damage.Our results suggested miR-199a-5p may play a role in the placental angiogenesis, oxidative stress and mitochondrial damage and dysfunction as an underlying pathogenesis of sFGR.

Objectives To (i) evaluate the applicability of the European-derived biomarker multiples of the median (MoM) formulae for risk assessment of preterm pre-eclampsia (PE) in seven Asian populations, spanning the east, southeast and south regions of the continent, (ii) perform quality-assurance (QA) assessment of the biomarker measurements and (iii) establish criteria for prospective ongoing QA assessment of biomarker measurements. Methods This was a prospective, non-intervention, multicenter study in 4023 singleton pregnancies, at 11 to 13 + 6 weeks' gestation, in 11 recruiting centers in China, Hong Kong, India, Japan, Singapore, Taiwan and Thailand. Women were screened for preterm PE between December 2016 and June 2018 and gave written informed consent to participate in the study. Maternal and pregnancy characteristics were recorded and mean arterial pressure (MAP), mean uterine artery pulsatility index (UtA-PI) and maternal serum placental growth factor (PlGF) were measured in accordance with The Fetal Medicine Foundation (FMF) standardized measurement protocols. MAP, UtA-PI and PlGF were transformed into MoMs using the published FMF formulae, derived from a largely Caucasian population in Europe, which adjust for gestational age and covariates that affect directly the biomarker levels. Variations in biomarker MoM values and their dispersion (SD) and cumulative sum tests over time were evaluated in order to identify systematic deviations in biomarker measurements from the expected distributions. Results In the total screened population, the median (95% CI) MoM values of MAP, UtA-PI and PlGF were 0.961 (0.956-0.965), 1.018 (0.996-1.030) and 0.891 (0.861-0.909), respectively. Women in this largely Asian cohort had approximately 4% and 11% lower MAP and PlGF MoM levels, respectively, compared with those expected from normal median formulae, based on a largely Caucasian population, whilst UtA-PI MoM values were similar. UtA-PI and PlGF MoMs were beyond the 0.4 to 2.5 MoM range (truncation limits) in 16 (0.4%) and 256 (6.4%) pregnancies, respectively. QA assessment tools indicated that women in all centers had consistently lower MAP MoM values than expected, but were within 10% of the expected value. UtA-PI MoM values were within 10% of the expected value at all sites except one. Most PlGF MoM values were systematically 10% lower than the expected value, except for those derived from a South Asian population, which were 37% higher. Conclusions Owing to the anthropometric differences in Asian compared with Caucasian women, significant differences in biomarker MoM values for PE screening, particularly MAP and PlGF MoMs, were noted in Asian populations compared with the expected values based on European-derived formulae. If reliable and consistent patient-specific risks for preterm PE are to be reported, adjustment for additional factors or development of Asian-specific formulae for the calculation of biomarker MoMs is required. We have also demonstrated the importance and need for regular quality assessment of biomarker values. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

BACKGROUND Cellular mitochondrial DNA (mtDNA) is organized as circular, covalently closed and double-stranded DNA. Studies have demonstrated the presence of short mtDNA fragments in plasma. It is not known whether circular mtDNA might concurrently exist with linear mtDNA in plasma. METHODS We elucidated the topology of plasma mtDNA using restriction enzyme BfaI cleavage signatures on mtDNA fragment ends to differentiate linear and circular mtDNA. mtDNA fragments with both ends carrying BfaI cleavage signatures were defined as circular-derived mtDNA, whereas those with no cleavage signature or with 1 cleavage signature were defined as linear-derived mtDNA. An independent assay using exonuclease V to remove linear DNA followed by restriction enzyme MspI digestion was used for confirming the conclusions based on BfaI cleavage analysis. We analyzed the presence of BfaI cleavage signatures on plasma DNA ends in nonhematopoietically and hematopoietically derived DNA molecules by sequencing plasma DNA of patients with liver transplantation and bone marrow transplantation. RESULTS Both linear and circular mtDNA coexisted in plasma. In patients with liver transplantation, donor-derived (i.e., liver) mtDNA molecules were mainly linear (median fraction, 91%; range, 75%–97%), whereas recipient-derived (i.e., hematopoietic) mtDNA molecules were mainly circular (median fraction, 88%; range, 77%–93%). The proportion of linear mtDNA was well correlated with liver DNA contribution in the plasma DNA pool (r = 0.83; P value = 0.0008). Consistent data were obtained from a bone marrow transplantation recipient in whom the donor-derived (i.e., hematopoietic) mtDNA molecules were predominantly circular. CONCLUSIONS Linear and circular mtDNA molecules coexist in plasma and may have different tissue origins.

OBJECTIVE To evaluate the effect of haemostatic sealant compared with bipolar coagulation on ovarian reserve after laparoscopic cystectomy for ovarian endometriomas. DESIGN Patient-blinded, randomised controlled trial. SETTING University-affiliated tertiary hospital. POPULATION Women aged 18-40 years with 3-8 cm unilateral or bilateral endometriomas. METHODS Ninety-four patients were randomised to receive haemostasis by the application of haemostatic sealant (n = 47) or standard care (n = 47). MAIN OUTCOME MEASURES Primary outcome was the effect on the antral follicular count 3 months after the operation as it captures the effect on the ovary subjected to treatment. Secondary outcomes included the change in anti-Mullerian hormone, follicular-stimulating hormone and peri-operative outcomes including haemostasis, complications, pain, and satisfaction scores. RESULTS A total of 94 patients aged 32.36 ± 4.92 years underwent laparoscopic cystectomy for ovarian endometriomas. The average diameter of the endometrioma was 4.21 ± 1.38 cm. The increase in antral follicle count of the affected ovaries at 3 months in the intervention group (+2.36 ± 0.37) was significantly (P = 0.013) higher than that in the control group (+1.08 ± 0.36). Repeated measures analysis of variance revealed significant effect with time (P