Prediction of labour outcomes using prelabour computerised cardiotocogram and maternal and fetal Doppler indices: A prospective cohort study.

OBJECTIVES: To investigate the association and the potential value of prelabour fetal heart rate short-term variability (STV) determined by computerised cardiotocography (cCTG) and maternal and fetal Doppler in predicting labour outcomes. DESIGN: Prospective cohort study. SETTING: The Prince of Wales Hospital, a tertiary maternity unit, in Hong Kong SAR. POPULATION: Women with a term singleton pregnancy in latent phase of labour or before labour induction were recruited during May 2019-November 2021. METHODS: Prelabour ultrasonographic assessment of fetal growth, Doppler velocimetry and prelabour cCTG monitoring including Dawes-Redman CTG analysis were registered shortly before induction of labour or during the latent phase of spontaneous labour. MAIN OUTCOME MEASURES: Umbilical cord arterial pH, emergency delivery due to pathological CTG during labour and neonatal intensive care unit (NICU)/special care baby unit (SCBU) admission. RESULTS: Of the 470 pregnant women invited to participate in the study, 440 women provided informed consent and a total of 400 participants were included for further analysis. Thirty-four (8.5%) participants underwent emergency delivery for pathological CTG during labour. A total of 6 (1.50%) and 148 (37.00%) newborns required NICU and SCBU admission, respectively. Middle cerebral artery pulsatility index (MCA-PI) and MCA-PI z-score were significantly lower in pregnancies that required emergency delivery for pathological CTG during labour compared with those that did not (1.23 [1.07-1.40] versus 1.40 [1.22-1.64], p = 0.002; and 0.55 ± 1.07 vs. 0.12 ± 1.06), p = 0.049]. This study demonstrated a weakly positive correlation between umbilical cord arterial pH and prelabour log10 STV (r = 0.107, p = 0.035) and the regression analyses revealed that the contributing factors for umbilical cord arterial pH were smoking (p = 0.006) and prelabour log10 STV (p = 0.025). CONCLUSIONS: In pregnant women admitted in latent phase of labour or for induction of labour at term, prelabour cCTG STV had a weakly positive association with umbilical cord arterial pH but was not predictive of emergency delivery due to pathological CTG during labour.

Incidence of intrauterine adhesion after ultrasound-guided manual vacuum aspiration (USG-MVA) for first-trimester miscarriages: a prospective cohort study.

PURPOSE: Ultrasound-guided manual vacuum aspiration (USG-MVA) is a feasible and effective outpatient treatment to treat early pregnancy loss. METHODS: This was a prospective observational study at a university-affiliated hospital. All women undergoing either a USG-MVA or electric vacuum aspiration (EVA) were invited to return 3-6 months later for follow-up at which women completed a questionnaire to document their post-evacuation menstrual and reproductive history, and underwent a hysteroscopy if they were not pregnant. The severity of intrauterine adhesion (IUA), if present, was graded (Stage I-III) according to the American fertility society classification. RESULTS: A total of 292 women had a hysteroscopy after their initial surgical evacuation, USG-MVA 169(57.9%) versus EVA 123(42.1%). Women undergoing EVA as opposed to a USG-MVA had a 12.9% higher incidence of IUA (24.1% vs. 37.0%, p = 0.042) equivalent to 1.84 times higher risk (95% CI 1.01-3.34; p = 0.048). Women having EVA continued to show an increased but not statistically significant trend towards an increased risk of IUA after adjusting for the type of miscarriage (aOR = 1.3; 95% CI 0.66-2.50; p = 0.46). CONCLUSION: There were no significant differences in their reproductive outcomes and fewer women post-USG-MVA complained of hypomenorrhea. IUA may still occur in women undergoing USG-MVA but it is lower than the rate in women undergoing EVA. Clinical trials registry The trial was registered with the Centre for Clinical Research and Biostatistics - Clinical Trials Registry (CCRBCTR), a partner registry of the WHO Primary Registry-Chinese Clinical Trials Registry (ChiCTR) with a Unique Trial Number: CUHK_CCRB00541 on 22 Dec 2016.

Ultrasound-guided manual vacuum aspiration (USG-MVA) with cervical preparation for early pregnancy loss: A cost-effectiveness analysis.

BACKGROUND AND AIM: Approximately one in four women will experience a miscarriage in their lifetime. Ultrasound-guided manual vacuum aspiration (USG-MVA) is an ideal outpatient surgical treatment alternative to traditional surgical evacuation. We aimed to examine the cost-effectiveness of US-MVA with cervical preparation for treatment of early pregnancy loss from the perspective of public healthcare provider of Hong Kong. METHODS: A decision-analytic model was designed to simulate outcomes in a hypothetical cohort of patients with early pregnancy loss on four interventions: (1) US-MVA, (2) misoprostol, (3) surgical evacuation of uterus by dilation and curettage (surgical evacuation), and (4) expectant care. Model inputs were retrieved from published literature and public data. Model outcome measures were total direct medical cost and disutility-adjusted life-year (DALY). Base-case model results were examined by sensitivity analysis. RESULTS: The expected DALYs (0.00141) and total direct medical cost (USD736) of US-MVA were the lowest of all interventions in base-case analysis, and US-MVA was the preferred cost-effective option. One-way sensitivity analysis showed that the misoprostol group became less costly than the US-MVA group if the evacuation rate of misoprostol (base-case value 0.832) exceeded 0.920. In probabilistic sensitivity analysis, At the willingness-to-pay (WTP) threshold of 49630 USD/DALY averted (1x gross domestic product per capita of Hong Kong), the US-MVA was cost-effective in 72.9% of the time. CONCLUSIONS: US-MVA appeared to be cost-saving and effective for treatment of early pregnancy loss from the perspective of public healthcare provider of Hong Kong.

Effectiveness of Interactive Digital Decision Aids in Prenatal Screening Decision-making: Systematic Review and Meta-analysis.

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.

Iron deficiency anaemia associated with increased placenta praevia and placental abruption: a retrospective case-control study.

BACKGROUND/OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

First trimester preeclampsia screening and prediction.

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.

Assessment of embryo morphology following perinatal exposure to aspirin, ibuprofen and paracetamol using whole embryo culture system.

BACKGROUND: 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. OBJECTIVE: To examine the effect of prenatal exposure to common NSAIDs and non-opioid drugs on neurulation using an in vitro whole embryo culture system. METHODS: Mouse 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. RESULTS: 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 (p > .21), head length (p > .28), somite number (p > .25), incidence of absent hindlimb buds (p > .18), yolk sac circulation score (p > .07) and posterior neuropore closure (p > .35) in the aspirin, paracetamol and ibuprofen experiments. All embryos had forelimb buds, closed anterior neuropores and none had neural tube defects. CONCLUSION: This study has demonstrated that there are no safety concerns regarding high-dose aspirin, ibuprofen, and paracetamol on mice's embryonic development.

Hyoscine butylbromide in pain reduction associated with ultrasound-guided manual vacuum aspiration: a randomized placebo-controlled trial.

RESEARCH QUESTION: What is the effect of adding an anti-spasmodic drug 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, randomized controlled trial conducted between February 2018 and January 2020. Participants were assigned to receive a 1-ml intravenous injection containing 20-mg hyoscine butylbromide (HBB) (n=55) or saline (n =56) as a control immediately before USG-MVA. Primary outcome was reduced abdominal pain after adding a 20-mg dose of HBB to the current pain control regimen. Secondary outcomes were vaginal pain, complications and side-effects, women's pre- and post-procedure psychological state, physiological stress (saliva alpha-amylase) and procedure pain control satisfaction. Two-way mixed ANOVA was used to evaluate the main effects and interactions. RESULTS: VAS abdominal pain scores in the HBB group were 16% lower immediately after and 21% lower 2 h after surgery (not statistically significant). Two-way ANOVA indicated that time (F[1108] = 83.41, P < 0.001) was the only significant main effect for reduced abdominal pain after the procedure and vaginal pain score (F[1108] = 180.1, P < 0.0001) but not drug received. No adverse events were reported. No significant difference was found for psychological state, physiological stress and procedure pain control satisfaction between the two groups. CONCLUSIONS: Anti-spasmodic drugs can help to reduce abdominal cramping pain associated with USG-MVA; HBB produced an insignificant decrease in abdominal pain score. Further studies with longer acting or larger doses of anti-spasmodic drugs are warranted.

Performance of Fetal Medicine Foundation algorithm for first trimester preeclampsia screening in an indigenous south Asian population.

BACKGROUND: To evaluate the performance of the Fetal Medicine Foundation (FMF) preterm preeclampsia (PE) screening algorithm in an indigenous South Asian population. METHODS: This was a prospective observational cohort study conducted in a tertiary maternal fetal unit in Delhi, India over 2 years. The study population comprised of 1863 women carrying a singleton pregnancy and of South Asian ethnicity who were screened for preterm pre-eclampsia (PE) between 11 and 14 weeks of gestation using Mean Arterial Pressure (MAP), transvaginal Mean Uterine Artery Pulsatility Index (UtAPI) and biochemical markers - Pregnancy Associated Plasma Protein-A (PAPP-A) and Placental Growth Factor.. Absolutemeasurements of noted biomarkers were converted to multiples of the expected gestational median (MoMS) which were then used to estimate risk for preterm PE < 37 weeks using Astraia software. Women with preterm PE risk of ≥1:100 was classified as as high risk. Detection rates (DR) at 10% false positive rate were calculated after adjusting for prophylactic aspirin use (either 75 or 150 mg). RESULTS: The incidence of PE and preterm PE were 3.17% (59/1863) and 1.34% (25/1863) respectively. PAPP-A and PlGF MoM distribution medians were 0.86 and 0.87 MoM and significantly deviated from 1 MoM. 431 (23.1%) women had a risk of ≥1:100, 75 (17.8%) of who received aspirin. Unadjusted DR using ≥1:100 threshold was 76%.Estimated DRs for a fixed 10% FPR ranged from 52.5 to 80% depending on biomarker combination after recentering MoMs and adjusting for aspirin use. CONCLUSION: The FMF algorithm whilst performing satisfactorily could still be further improved to ensure that biophysical and biochemical markers are correctly adjusted for indigenous South Asian women.

Adaptive risk prediction system with incremental and transfer learning.

Currently, popular methods for prenatal risk assessment of fetal aneuploidies are based on multivariate probabilistic modelling, that are built on decades of scientific research and large-scale multi-center clinical studies. These static models that are deployed to screening labs are rarely updated or adapted to local population characteristics. In this article, we propose an adaptive risk prediction system or ARPS, which considers these changing characteristics and automatically deploys updated risk models. 8 years of real-life Down syndrome screening data was used to firstly develop a distribution shift detection method that captures significant changes in the patient population and secondly a probabilistic risk modelling system that adapts to new data when these changes are detected. Various candidate systems that utilize transfer -and incremental learning that implement different levels of plasticity were tested. Distribution shift detection using a windowed approach provides a computationally less expensive alternative to fitting models at every data block step while not sacrificing performance. This was possible when utilizing transfer learning. Deploying an ARPS to a lab requires careful consideration of the parameters regarding the distribution shift detection and model updating, as they are affected by lab throughput and the incidence of the screened rare disorder. When this is done, ARPS could be also utilized for other population screening problems. We demonstrate with a large real-life dataset that our best performing novel Incremental-Learning-Population-to-Population-Transfer-Learning design can achieve on par prediction performance without human intervention, when compared to a deployed risk screening algorithm that has been manually updated over several years.

Ovarian reserve and recurrence 1 year post-operatively after using haemostatic sealant and bipolar diathermy for haemostasis during laparoscopic ovarian cystectomy.

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-Müllerian 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.

A technical and clinical evaluation of the new ThermoFisher BRAHMS unconjugated estriol and inhibin-A assays and their use in second trimester Down syndrome screening.

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.

Impact of replacing or adding placental growth factor on Down syndrome screening: A prospective cohort study.

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. METHODS: A total of 11,518 women with a singleton pregnancy who underwent the first trimester combined test between December 2016 and December 2019 were included. PlGF was measured and estimated term risk for trisomy 21 was calculated by (1) adding PlGF to the combined test and (2) replacing PAPP-A with PlGF. RESULTS: Twenty-nine pregnancies had trisomy 21. The combined tests detection rate (DR), false positive rate (FPR) and screen positive rate (SPR) were 89.7%, 5.7% and 6% respectively. DR when adding PlGF to the combined test or replacing PAPP-A 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. Change in FPR and SPR was not significant (p > 0.1 for all). CONCLUSION: Adding PlGF to the combined test or replacing PAPP-A with PlGF did not improve trisomy 21 DR and resulted in a non-significant marginal change in FPR and SPR.

Parental expectations of raising a child with disability in decision-making for prenatal testing and termination of pregnancy: A mixed methods study.

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.

Placental microRNA dataset of monochorionic twin pregnancies with and without selective fetal growth restriction.

To compare the whole genomic microRNA (miRNA) between the selective fetal growth restriction (sFGR) twin and the normally growing (control) co-twin in monochorionic (MC) twin pregnancies. MC twin pregnancies with or without sFGR were recruited, and their placental miRNAs were profiled by microarray. The ratio of the placental miRNA of the sFGR twin to that of the normally larger co-twin were calculated and compared to that of the control twin pairs. The miRNA microarray intensity amongst normal and sFGR large and small twins are shown. The expression data presented here will facilitate other researchers who are working on placental regulation and mechanism in pregnancy complicated by fetal growth restriction. The dataset supports the research article entitle "Whole genome miRNA profiling revealed miR-199a as potential placental pathogenesis of selective fetal growth restriction in monochorionic twin pregnancies" [1].

Whole genome miRNA profiling revealed miR-199a as potential placental pathogenesis of selective fetal growth restriction in monochorionic twin pregnancies.

INTRODUCTION: 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. METHODS: 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). RESULTS: 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. DISCUSSION: 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.

Perioperative prophylactic internal iliac artery balloon occlusion in the prevention of postpartum hemorrhage in placenta previa: a randomized controlled trial.

BACKGROUND: Placenta previa remains one of the major causes of massive postpartum hemorrhage and maternal mortality worldwide. OBJECTIVE: To determine whether internal iliac artery balloon occlusion during cesarean delivery for placenta previa could reduce postpartum hemorrhage and other maternal complications. STUDY DESIGN: This was a prospective randomized controlled trial conducted at a tertiary university obstetric unit in Hong Kong. Pregnant women who were diagnosed to have placenta previa at 34 weeks (defined as lower placenta edge within 2 cm from the internal os) and required cesarean delivery were invited to participate. Eligible pregnant women were randomized into internal iliac artery balloon occlusion (Occlusion) group or standard management (Control) group. Those randomized to the Occlusion group had internal iliac artery balloon catheter placement performed before cesarean delivery and then balloon inflation after delivery of the baby. The primary outcome was the reduction of postpartum hemorrhage in those with internal iliac artery balloon occlusion. Secondary outcome measures included hemoglobin drop after delivery; amount of blood product transfusion; incidence of hysterectomy; maternal complications including renal failure, ischemic liver, disseminated intravascular coagulation, and adult respiratory distress syndrome; length of stay in hospital; admission to intensive care unit; and maternal death. RESULTS: Between May 2016 and September 2018, 40 women were randomized (20 in each group). Demographic and obstetric characteristics were similar between the 2 groups. In the Occlusion group, 3 women did not receive the scheduled procedure, as it was preceded by antepartum hemorrhage that required emergency cesarean delivery, and 1 woman had repeated scan at 36 weeks showing the placental edge was slightly more than 2 cm from the internal os. Intention-to-treat analysis found no significant differences between the Occlusion and the Control groups regarding to the median intraoperative blood loss (1451 [1024-2388] mL vs 1454 [888-2300] mL; P = .945), the median length of surgery (49 [30-62] min vs 37 [30-51] min; P = .204), or the need for blood transfusion during operation (57.9% vs 50.0%; P = .621). None of the patients had rebleeding after operation, complication related to internal iliac artery procedure, or any other maternal complications. Reanalyzing the data using on-treatment approach showed the same results. CONCLUSION: The use of prophylactic internal iliac artery balloon occlusion in placenta previa patients undergoing cesarean delivery did not reduce postpartum hemorrhage or have any effect on maternal or neonatal morbidity.

Development of Gestational Age-Specific Thyroid Function Test Reference Intervals in Four Analytic Platforms Through Multilevel Modeling.

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.

The predictive value of cervical shear wave elastography in the outcome of labor induction.

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 < 0.001). Both inner cervical shear wave elasticity and cervical length were independent predictors of overall cesarean section (respective adjusted odds ratio [95% CI] 1.338 [1.001-1.598] and 1.717 [1.077-1.663]) and cesarean section for failure to enter active phase (respective adjusted odds ratio [95% CI] 1.689 [1.234-2.311] and 2.556 [1.462-4.467]), after adjusting for other covariates. Outcome prediction models using inner cervical shear wave elasticity and cervical length, had increased area under curve compared with models using the Bishop score (0.888 vs 0.819, P = 0.009). CONCLUSIONS: The cervix is not a homogenous structure, with the inner cervix having the highest stiffness, which is an independent predictor of overall cesarean section, and specifically for those indicated because of failure to enter active phase. Models based on shear wave elastography and cervical length had higher predictive accuracy than models based on the Bishop score.

Progression of glucose intolerance and cardiometabolic risk factors over a decade in Chinese women with polycystic ovary syndrome: A case-control study.

BACKGROUND: Polycystic ovary syndrome (PCOS) is associated with increased metabolic risk, though data on long-term follow-up of cardiometabolic traits are limited. We postulated that Chinese women with PCOS would have higher risk of incident diabetes and cardiometabolic abnormalities than those without PCOS during long-term follow-up. METHODS AND FINDINGS: One hundred ninety-nine Chinese women with PCOS diagnosed by the Rotterdam criteria and with a mean age of 41.2 years (SD = 6.4) completed a follow-up evaluation after an average of 10.6 ± 1.3 years. Two hundred twenty-five women without PCOS (mean age: 54.1 ± 6.7 years) who underwent baseline and follow-up evaluation over the same period were used for comparison. Progression of glycaemic status of women both with and without PCOS was assessed by using 75-g oral glucose tolerance test (OGTT) screening with the adoption of 2009 American Diabetes Association diagnostic criteria. The frequency of impaired glucose regulation, hypertension, and hyperlipidaemia of women with PCOS at follow-up has increased from 31.7% (95% CI 25.2%-38.1%) to 47.2% (95% CI 40.3%-54.2%), 16.1% (95% CI 11.0%-21.2%) to 34.7% (95% CI 28.1%-41.3%), and 52.3% (95% CI 45.3%-59.2%) to 64.3% (95% CI 57.7%-71.0%), respectively. The cumulative incidence of diabetes mellitus (DM) in follow-up women with PCOS is 26.1% (95% CI 20.0%-32.2%), almost double that in the cohort of women without PCOS (p < 0.001). Age-standardised incidence of diabetes among women with PCOS was 22.12 per 1,000 person-years (95% CI 10.86-33.37) compared with the local female population incidence rate of 8.76 per 1,000 person-years (95% CI 8.72-8.80) and 10.09 per 1,000 person-years (95% CI 4.92-15.26, p < 0.001) for women without PCOS in our study. Incidence rate for women with PCOS aged 30-39 years was 20.56 per 1,000 person-years (95% CI 12.57-31.87), which is approximately 10-fold higher than that of the age-matched general female population in Hong Kong (1.88 per 1,000 person-years, [95% CI 1.85-1.92]). The incidence rate of type 2 DM (T2DM) of both normal-weight and overweight women with PCOS was around double that of corresponding control groups (normal weight: 8.96 [95% CI 3.92-17.72] versus 4.86 per 1,000 person-years [95% CI 2.13-9.62], p > 0.05; overweight/obese: 28.64 [95% CI 19.55-40.60] versus 14.1 per 1,000 person-years [95% CI 8.20-22.76], p < 0.05). Logistic regression analysis identified that baseline waist-to-hip ratio (odds ratio [OR] = 1.71 [95% CI 1.08-2.69], p < 0.05) and elevated triglyceride (OR = 6.63 [95% CI 1.23-35.69], p < 0.05) are associated with the progression to T2DM in PCOS. Limitations of this study include moderate sample size with limited number of incident diabetes during follow-up period and potential selection bias. CONCLUSIONS: High risk of diabetes and increased cardiovascular disease risk factors among Chinese women with PCOS are highlighted in this long-term follow-up study. Diabetes onset was, on average, 10 years earlier among women with PCOS than in women without PCOS.