Implementation of First-trimester Screening and Prevention of Preeclampsia: a Stepped Wedge Cluster-randomized Trial in Asia.

BACKGROUND: This trial aimed to assess the efficacy, acceptability and safety of a first-trimester screen-and-prevent strategy for preterm preeclampsia (PE) in Asia. METHODS: Between 1st August 2019 and 28th February 2022, this multicenter stepped wedge cluster randomized trial included maternity/diagnostic units from ten regions in Asia. The trial started with a period where all recruiting centers provided routine antenatal care without study-related intervention. At regular six-week intervals, one cluster was randomized to transit from non-intervention phase to intervention phase. In the intervention phase, women underwent first-trimester screening for preterm PE using a Bayes theorem-based triple-test. High-risk women, with adjusted risk for preterm PE ≥ 1 in 100, received low-dose aspirin from <16 weeks until 36 weeks. RESULTS: Overall, 88.04% (42,897/48,725) of women agreed to undergo first-trimester screening for preterm PE. Among those identified as high-risk in the intervention phase, 82.39% (2,919/3,543) received aspirin prophylaxis. There was no significant difference in the incidence of preterm PE between the intervention and non-intervention phases (adjusted odds ratio [aOR] 1.59; 95% confidence interval [CI] 0.91 to 2.77). However, among high-risk women in the intervention phase, aspirin prophylaxis was significantly associated with a 41% reduction in the incidence of preterm PE (aOR 0.59; 95%CI 0.37 to 0.92). Additionally, it correlated with 54%, 55% and 64% reduction in the incidence of PE with delivery at <34 weeks (aOR 0.46; 95%CI 0.23 to 0.93), spontaneous preterm birth <34 weeks (aOR 0.45; 95%CI 0.22 to 0.92) and perinatal death (aOR 0.34; 95%CI 0.12 to 0.91), respectively. There was no significant between-group difference in the incidence of aspirin-related severe adverse events. CONCLUSIONS: The implementation of the screen-and-prevent strategy for preterm PE is not associated with a significant reduction in the incidence of preterm PE. However, low-dose aspirin effectively reduces the incidence of preterm PE by 41% among high-risk women. The screen-and-prevent strategy for preterm PE is highly accepted by a diverse group of women from various ethnic backgrounds beyond the original population where the strategy was developed. These findings underpin the importance of the widespread implementation of the screen-and-prevent strategy for preterm PE on a global scale.

Biomarkers at 6 weeks' gestation in the prediction of early miscarriage in pregnancy following assisted reproductive technology.

INTRODUCTION: Miscarriage is a major concern in early pregnancy among women having conceived with assisted reproductive treatments. This study aimed to examine potential miscarriage-related biophysical and biochemical markers at 6 weeks' gestation among women with confirmed clinical pregnancy following in vitro fertilization (IVF)/embryo transfer (ET) and evaluate the performance of a model combining maternal factors, biophysical and biochemical markers at 6 weeks' gestation in the prediction of first trimester miscarriage among singleton pregnancies following IVF/ET. MATERIAL AND METHODS: A prospective cohort study was conducted in a teaching hospital between December 2017 and January 2020 including women who conceived through IVF/ET. Maternal mean arterial pressure, ultrasound markers including mean gestational sac diameter, fetal heart activity, crown rump length and mean uterine artery pulsatility index (mUTPI) and biochemical biomarkers including maternal serum soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), kisspeptin and glycodelin-A were measured at 6 weeks' gestation. Logistic regression analysis was carried out to determine significant predictors of miscarriage prior to 13 weeks' gestation and performance of screening was estimated by receiver-operating characteristics curve analysis. RESULTS: Among 169 included pregnancies, 145 (85.8%) pregnancies progressed to beyond 13 weeks' gestation and had live births whereas 24 (14.2%) pregnancies resulted in a miscarriage during the first trimester. In the miscarriage group, compared to the live birth group, maternal age, body mass index, and mean arterial pressure were significantly increased; mean gestational sac diameter, crown rump length, mUTPI, serum sFlt-1, glycodelin-A, and the rate of positive fetal heart activity were significantly decreased, while no significant differences were detected in PlGF and kisspeptin. Significant prediction for miscarriage before 13 weeks' gestation was provided by maternal age, fetal heart activity, mUTPI, and serum glycodelin-A. The combination of maternal age, ultrasound (fetal heart activity and mUTPI), and biochemical (glycodelin-A) markers achieved the highest area under the curve (AUC: 0.918, 95% CI 0.866-0.955), with estimated detection rates of 54.2% and 70.8% for miscarriage before 13 weeks' gestation, at fixed false positive rates of 5% and 10%, respectively. CONCLUSIONS: A combination of maternal age, fetal heart activity, mUTPI, and serum glycodelin-A at 6 weeks' gestation could effectively identify IVF/ET pregnancies at risk of first trimester miscarriage.

A point-of-care urine test to predict adverse maternal and neonatal outcomes in Asian women with suspected preeclampsia.

OBJECTIVES: To assess clinical utility of the urine Congo red dot test (CRDT) in predicting composite adverse maternal and neonatal outcomes in women with suspected preeclampsia (PE). METHODS: CRDT result and pregnancy outcomes were prospectively documented in women with new onset or pre-existing hypertension, new or pre-existing proteinuria, PE symptoms and suspected PE-related fetal growth restriction or abnormal Doppler presenting from 20 weeks' gestation between January 2020 and December 2022. Participants and clinicians were blinded to the CRDT result and managed according to internally agreed protocols. Composite maternal outcome was defined as PE, postpartum hemorrhage, intensive care unit admission, and maternal death. Composite neonatal outcome was defined as small for gestational age, preterm birth, 5-min Apgar score < 7, neonatal intensive care unit admission, and neonatal death. RESULTS: Two hundred and forty-four women out of two hundred and fifty-one (97.2%) had a negative CRDT. All seven women with positive CRDT had both adverse maternal and neonatal outcomes, giving positive predictive values (PPV) of 100%. Rates of composite adverse maternal and neonatal outcomes in CDRT negative women were 103/244 [42.2%, 95% confidence interval (CI) 36.2%-48.5%] and 170/244 (69.7%, 95% CI 63.6%-75.1%), respectively. CRDT negative predictive values (NPV) for adverse maternal and neonatal outcomes were, respectively, 141/244 (57.8%, 95% CI 48.6%-68.2%) and 74/244 (30.3%, 95% CI 23.8%-38.1%). CONCLUSION: CRDT had low NPV but high PPV for adverse maternal and neonatal outcomes in women with suspected PE. Its role in clinical management and triage of women with suspected PE is limited as it cannot identify those at low risk of developing adverse outcomes.

First Trimester Screening for Gestational Diabetes Mellitus with Maternal Factors and Biomarkers.

INTRODUCTION: This study aimed to identify risk factors among maternal characteristics, obstetric history, and first trimester preeclampsia-specific biomarkers that were associated with subsequent development of gestational diabetes mellitus (GDM) and evaluate the performance of the prediction models. METHODS: This study was a secondary analysis of a prospective cohort study. The performance of the prediction models was assessed by area under the receiver operating characteristic curve (AUROC). RESULTS: A total of 837 (8.9%) cases of GDM and 8,535 (91.1%) unaffected cases were included. The AUROC of the prediction model combining maternal characteristics and obstetric history (0.735) was better than that of the model utilizing maternal characteristics (AUROC 0.708) and preeclampsia-specific biomarkers (AUROC 0.566). Among the preeclampsia-specific biomarkers, the mean arterial pressure (MAP) contributed to the increasing risk of GDM; however, its addition did not improve the AUROC of the model combining maternal characteristics and obstetric history (0.738). CONCLUSION: The first trimester prediction model for GDM with maternal characteristics and obstetric history achieves moderate predictability. The inclusion of MAP in the model combining maternal characteristics and obstetric history does not improve the screening performance for GDM. Future studies are needed to explore the effect of blood pressure control from early pregnancy on preventing GDM.

Bradycardia-to-delivery interval and fetal outcomes in umbilical cord prolapse.

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 < 7) was 80% when bradycardia-to-delivery interval was >20 minutes, and 17.2% when the interval was <20 minutes. CONCLUSIONS: There is significant correlation between bradycardia-to-delivery interval and cord arterial pH in umbilical cord prolapse with fetal bradycardia but not in cases with decelerations or normal heart rate. The drop of cord arterial pH is rapid and urgent delivery is essential in such situations.

Pre-Induction Transperineal Ultrasound Assessment for the Prediction of Labor Outcome.

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.

Age-specific prevalence of hepatitis B virus infection in young pregnant women, Hong Kong Special Administrative Region of China.

OBJECTIVE: To investigate the age-specific prevalence of hepatitis B virus (HBV) infection in young pregnant women in Hong Kong Special Administrative Region (SAR), China, and to determine whether an increase in prevalence occurs during adolescence. METHODS: HBV prevalence was quantified using data from routine antenatal screening for hepatitis B surface antigen (HBsAg) in 10 808 women aged 25 years or younger born in Hong Kong SAR and managed at a single hospital between 1998 and 2011. The effect on prevalence of maternal age, parity and birth before or after HBV vaccine availability in 1984 was assessed, using Spearman's correlation and multiple logistic regression analysis. FINDINGS: Overall, 7.5% of women were HBsAg-positive. The prevalence ranged from 2.3% to 8.4% in those aged ≤ 16 and 23 years, respectively. Women born in or after 1984 and those younger than 18 years of age were less likely to be HBsAg-positive (odds ratio, OR: 0.679; 95% confidence interval, CI: 0.578-0.797) and (OR: 0.311; 95% CI: 0.160-0.604), respectively. For women born before 1984, there was no association between HBsAg carriage and being younger than 18 years of age (OR: 0.60; 95% CI: 0.262-1.370) Logistic regression analysis showed that the prevalence of HBsAg carriage was influenced more by the woman being 18 years old or older (adjusted OR, aOR: 2.80; 95% CI: 1.46-5.47) than being born before 1984 (aOR: 1.42; 95% CI: 1.21-1.67). CONCLUSION: Immunity to HBV in young pregnant women who had been vaccinated as neonates decreased in late adolescence.

Biomarkers in the prediction of complications in pregnancy after assisted reproductive technology.

OBJECTIVES: To compare the temporal changes in mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), placental growth factor (PlGF), and soluble fms-like tyrosine kinase-1 (sFlt-1) across gestation between assisted reproductive technology (ART) pregnancies complicated with great obstetrical syndromes (GOS) or gestational diabetes (GDM) ± large-for-gestational-age (LGA) fetus, and uncomplicated ART pregnancies. METHODS: This was a prospective longitudinal study of 143 women with singleton pregnancies who conceived through ART at the Department of Obstetrics and Gynecology, Prince of Wales Hospital, the Chinese University of Hong Kong, Hong Kong SAR between December 2017 and January 2020. The participants were followed up at 6-6+3, 11-13+6, 20-24+6, 30-34+6, and 35-37+6 weeks for the measurement of MAP, UtA-PI, PlGF, and sFlt-1. A linear mixed-effects analysis was performed to compare the biomarkers in the GOS, GDM ± LGA, and uncomplicated groups across gestation. RESULTS: Thirty-three (23.1%) and fifty-five (31.5%) women were diagnosed with GOS and GDM ± LGA, respectively. The GOS group had higher estimated marginal mean log10 MAP mulitples of the median (MoM) across gestation, compared with the uncomplicated group (0.00771 vs -0.02022; P < 0.001), when adjusting for clinical visits and days of embryo transfer. The absolute mean log10 MAP MoM in the GOS group was found to be significantly higher than that of the uncomplicated group at all clinical visits from 6 weeks onwards. Furthermore, the estimated marginal mean log10 PlGF MoM was significantly lower in the GOS group across gestation, compared with the uncomplicated group (-0.04226 vs 0.05566; P = 0.010). The significant difference in log10 PlGF MoM was observed from 11-13+6 to 30-34+6 week of gestation (P < 0.05). However, no significant differences in the estimated marginal means of log10 UtA-PI MoM and log10 sFlt-1 MoM between GOS and uncomplicated groups were observed. GDM ± LGA group had a lower estimated marginal mean log10 PlGF MoM throughout pregnancy compared with the uncomplicated group (-0.01536 vs 0.05572; P = 0.032). In the individual visit analysis, the significant difference was observed at the 20-24+6 and 35-37+6 weeks visits (P < 0.05). There were no significant differences in estimated marginal mean log10 MoM of MAP, UtA-PI, and sFlt-1 between GDM ± LGA and uncomplicated groups during pregnancy. CONCLUSION: Our study has revealed that among pregnancies conceived through ART, GOS is associated with higher MAP and lower PlGF from early gestation until late third trimester, while GDM ± LGA is associated with lower PlGF during the second half of pregnancy. The same degree of differences in MAP and PlGF persists from early until late gestation in the GOS group and these findings highlight the importance of early screening during the first trimester to identify women who are at risk for developing GOS following ART procedures. Lastly, the potential of PlGF in predicting the development of GDM from the second trimester of pregnancy requires further investigation.

Validation of the first-trimester machine learning model for predicting pre-eclampsia in an Asian population.

OBJECTIVES: To evaluate the performance of an artificial intelligence (AI) and machine learning (ML) model for first-trimester screening for pre-eclampsia in a large Asian population. METHODS: This was a secondary analysis of a multicenter prospective cohort study in 10 935 participants with singleton pregnancies attending for routine pregnancy care at 11-13+6 weeks of gestation in seven regions in Asia between December 2016 and June 2018. We applied the AI+ML model for the first-trimester prediction of preterm pre-eclampsia (<37 weeks), term pre-eclampsia (≥37 weeks), and any pre-eclampsia, which was derived and tested in a cohort of pregnant participants in the UK (Model 1). This model comprises maternal factors with measurements of mean arterial pressure, uterine artery pulsatility index, and serum placental growth factor (PlGF). The model was further retrained with adjustments for analyzers used for biochemical testing (Model 2). Discrimination was assessed by area under the receiver operating characteristic curve (AUC). The Delong test was used to compare the AUC of Model 1, Model 2, and the Fetal Medicine Foundation (FMF) competing risk model. RESULTS: The predictive performance of Model 1 was significantly lower than that of the FMF competing risk model in the prediction of preterm pre-eclampsia (0.82, 95% confidence interval [CI] 0.77-0.87 vs. 0.86, 95% CI 0.811-0.91, P = 0.019), term pre-eclampsia (0.75, 95% CI 0.71-0.80 vs. 0.79, 95% CI 0.75-0.83, P = 0.006), and any pre-eclampsia (0.78, 95% CI 0.74-0.81 vs. 0.82, 95% CI 0.79-0.84, P < 0.001). Following the retraining of the data with adjustments for the PlGF analyzers, the performance of Model 2 for predicting preterm pre-eclampsia, term pre-eclampsia, and any pre-eclampsia was improved with the AUC values increased to 0.84 (95% CI 0.80-0.89), 0.77 (95% CI 0.73-0.81), and 0.80 (95% CI 0.76-0.83), respectively. There were no differences in AUCs between Model 2 and the FMF competing risk model in the prediction of preterm pre-eclampsia (P = 0.135) and term pre-eclampsia (P = 0.084). However, Model 2 was inferior to the FMF competing risk model in predicting any pre-eclampsia (P = 0.024). CONCLUSION: This study has demonstrated that following adjustment for the biochemical marker analyzers, the predictive performance of the AI+ML prediction model for pre-eclampsia in the first trimester was comparable to that of the FMF competing risk model in an Asian population.

Nonremoval of an abnormally invasive placenta at cesarean section with postoperative uterine artery embolization.

OBJECTIVE: To evaluate the outcome of three different modes of management of abnormally invasive placenta over a 6-year period. DESIGN: Retrospective cohort study. SETTING: Tertiary hospital in Hong Kong. POPULATION: In 39 757 deliveries, 25 cases of abnormally invasive placenta were identified at cesarean section. METHODS: Identification of cases by hospital database and review of medical records. MAIN OUTCOME MEASURES: Blood loss, blood transfusion requirement, operative time, duration of hospital stay, secondary postpartum hemorrhage and endometritis. RESULTS: Six women were managed by leaving the placenta in situ and by postoperative uterine artery embolization. Ten women were managed by an extirpative approach and nine women with direct cesarean hysterectomy. The success rate of nonremoval of the placenta with uterine artery embolization was 4/6 (67%). The intraoperative blood loss, blood transfusion requirements and operation times were lowest in the group with nonremoval of the placenta, although a higher secondary complication rate and a longer hospital stay followed. CONCLUSION: Nonremoval of an abnormally invasive placenta at cesarean section and prophylactic postoperative uterine artery embolization are an alternative to elective cesarean hysterectomy.

Prospective assessment of the Hong Kong Hospital Authority universal Down syndrome screening programme.

OBJECTIVE: To evaluate the performance of the locally developed universal Down syndrome screening programme. DESIGN: Population-based cohort study in the period July 2010 to June 2011 inclusive. SETTING: Four Hong Kong Hospital Authority Departments of Obstetrics and Gynaecology and a central university-based laboratory for maternal serum processing and risk determination. PARTICIPANTS: Women were offered either a first-trimester combined test (nuchal translucency, free beta human chorionic gonadotropin, and pregnancy-associated plasma protein-A) or nuchal-translucency-only test, or a second-trimester double test (alpha-fetoprotein and total human chorionic gonadotropin) for detection of Down syndrome according to their gestational age. Those with a trisomy 21 term risk of 1:250 or higher were offered a diagnostic test. RESULTS: A total of 16 205 pregnancies were screened of which 13 331 (82.3%) had a first-trimester combined test, 125 (0.8%) had a nuchal-translucency test only, and 2749 (17.0%) had a second-trimester double test. There were 38 pregnancies affected by Down syndrome. The first-trimester screening tests had a 91.2% (31/34) detection rate with a screen-positive rate of 5.1% (690/13 456). The second-trimester test had a 100% (4/4) detection rate with a screen-positive rate of 6.3% (172/2749). There were seven (0.9%) pregnancies that miscarried following an invasive diagnostic test. There were two Down syndrome-affected live births, both with an estimated first-trimester trisomy 21 term risk lower than 1:250. CONCLUSION: The universal screening programme offered at the four units was effective and achieved the expected detection rates and low false-positive rates, and to maintain these, the current emphasis on training, quality control, and regular auditing must continue.

[Perinatal outcome of monochorionic twin pregnancies].

OBJECTIVE: To study the perinatal outcome of monochorionic (MC) twin pregnancies. METHODS: The 197 cases of MC twin pregnancies delivered in obstetric unit of Prince of Wales Hospital from Jan. 2005 to Dec. 2010 were enrolled in this retrospective study,which were divided into 3 groups:uncomplicated MC pregnancy (136 cases), twin to twin transfusion syndrome (TTTS, 32 cases), selective intrauterine growth restriction (sIUGR, 29 cases). RESULTS: (1) The gestational age at delivery in TTTS (30 weeks vs.37 weeks, P<0.01) or sIUGR (34 weeks vs.37 weeks, P<0.01) group were significantly lower than those in uncomplicated MC pregnancy. The number of live-born in TTTS (36 cases) or sIUGR (47 cases) group were significantly lower than those in uncomplicated MC pregnancy (261 cases, P<0.01). (2) The incidence of fetal death (IUFD) in TTTS [34% (11/32) vs. 4% (6/136), P<0.01] or sIUGR group [28% (8/29) vs. 4% (6/136), P<0.01] were significantly higher than those in uncomplicated MC pregnancy group. (3) The incidence of birth weight (BW) discordance>25% in TTTS [5/15 vs.7.7% (10/130), P<0.05] or sIUGR [33% (7/21) vs. 7.7% (10/130), P<0.05] group were significantly higher than those in uncomplicated MC pregnancy group. (4) The incidence of preterm delivery before 37 weeks was 49% (66/136) and 69% (20/29) respectively in uncomplicated MC pregnancy and sIUGR. The incidence of preterm delivery in sIUGR group were significantly higher than that in uncomplicated MC pregnancy group (P<0.05). (5) The incidence of perinatal mortality in TTTS[12%(5/41) vs.0.4% (1/262), P<0.01] or sIUGR [10%(5/52) vs. 0.4% (1/262), P<0.01] group were significantly higher than those in uncomplicated MC pregnancy group. (6) The incidence of estimated fetal weight (EFW) discordance>25% was 17% (23/136) in uncomplicated MC pregnancy, 52% (15/29) in sIUGR, 63% (20/32) in TTTS. In uncomplicated MC pregnancy or sIUGR, pregnancies with EFW discordance>25% was associated with lower gestational age at delivery, higher incidence of preterm delivery and admission to NICU than those with EFW discordance≤25% (P<0.05). In uncomplicated MC pregnancy, pregnancies with EFW discordance>25% was associated with higher incidence of neonatal asphyxia (Apgar score 1 minute≤7) than those with EFW discordance≤25% (P<0.05). (7) Compared to uncomplicated MC pregnancy, the incidence of umbilical artery (UmA) flow abnormality was higher in TTTS[38% (12/32) vs. 9.6% (13/136), P<0.01] or sIUGR [41% (12/29) vs. 9.6% (13/136), P<0.01]. The incidence of IUFD in pregnacies with UmA flow abnormality was 2/13, 6/12 and 5/12 respectively in uncomplicated MC pregnancy, TTTS and sIUGR. CONCLUSIONS: MC pregnancies complicated by either TTTS or sIUGR have poorer perinatal outcome as compared with uncomplicated MC pregnancies. MC pregnancies with EFW discordance>25% and UmA flow abnormality are associated with even worse perinatal outcome. Close fetal monitoring is needed in MC pregnancies in order to reduce perinatal mortality.

Evaluation of first trimester maternal serum inhibin-A for preeclampsia screening.

BACKGROUND: International professional organizations recommend aspirin prophylaxis to women screened high risk for preterm preeclampsia (PE) in the first trimester. The UK Fetal Medicine Foundation (FMF) screening test for preterm PE using mean arterial pressure (MAP), uterine artery pulsatility index (UTPI) and placental growth factor (PlGF) was demonstrated to have lower detection rate (DR) in Asian population studies. Additional biomarkers are therefore needed in Asian women to improve screening DRs as a significant proportion of women with preterm and term PE are currently not identified. OBJECTIVES: To evaluate maternal serum inhibin-A at 11-13 weeks as an alternative to PlGF or as an additional biomarker within the FMF screening test for preterm PE. STUDY DESIGN: This is a nested case-control study using pregnancies initially screened at 11-13 weeks for preterm PE using the FMF triple test in a non-intervention study conducted between December 2016 and June 2018. Inhibin-A levels were retrospectively measured in 1,792 singleton pregnancies, 112 (1.7%) with PE matched for time of initial screening with 1,680 unaffected pregnancies. Inhibin-A levels were transformed to multiple of the expected median (MoM). The distribution of log10 inhibin-A MoM in PE and unaffected pregnancies and the association between log10 inhibin-A MoM and gestational age (GA) at delivery in PE were assessed. The screening performance determined by area under receiver operating characteristic curves (AUC) and detection rates (DRs) at a 10% fixed false positive rate (FPR), for preterm and term PE was determined. All risks for preterm and term PE were based on the FMF competing risk model and Bayes theorem. Differences in AUC (ΔAUC) between different biomarker combinations were compared using the Delong test. McNemar's test was used to assess the off-diagonal change in screening performance at a fixed 10% FPR after adding inhibin-A or replacing PlGF in the preterm PE adjusted risk estimation model. RESULTS: Inhibin-A levels in unaffected pregnancies were significantly dependent on GA, maternal age and weight and were lower in parous women with no previous history of PE. Mean log10 inhibin-A MoM in any-onset PE (p<0.001), preterm (p<0.001) and term PE (p = 0.015) pregnancies were all significantly higher than that of unaffected pregnancies. Log10 inhibin-A MoM was inversely but not significantly correlated (p = 0.165) with GA at delivery in PE pregnancies. Replacing PlGF with inhibin-A in the FMF triple test reduced AUC and DR from 0.859 and 64.86% to 0.837 and 54.05%, the ΔAUC was not statistically significant. AUC and DR when adding inhibin-A to the FMF triple test were 0.814, 54.05% and the -0.045 reduction in AUC was statistically significant (p = 0.001). At a fixed 10% FPR, replacing PlGF with inhibin-A identified 1 (2.7%) additional pregnancy but missed 5 (13.5%) pregnancies which subsequently developed preterm PE identified by the FMF triple test. Adding inhibin-A missed 4 (10.8%) pregnancies and did not identify any additional pregnancies with preterm PE. CONCLUSION: Replacing PlGF by inhibin-A or adding inhibin-A as an additional biomarker in and to the FMF triple screening test for preterm PE does not improve screening performance and will fail to identify pregnancies that are currently identified by the FMF triple test.

A point-of care urine test to predict preeclampsia development in Asian women with suspected preeclampsia.

OBJECTIVES: To evaluate the diagnostic performance and clinical utility of the urine Congo red dot test (CRDT) in predicting preeclampsia (PE) within 7 days, 14 days and 28 days of assessment. STUDY DESIGN: A prospective single center double blind non-intervention study conducted from January 2020 to March 2022. Urine congophilia has been proposed as a point-of-care test for the prediction and rapid identification of PE. In our study, urine CRDT and pregnancy outcomes were assessed in women presenting with clinical features of suspected PE after 20 weeks of gestation. RESULTS: Among the 216 women analyzed, 78 (36.1 %) women developed PE, in which only 7 (9.0 %) of them had a positive urine CRDT test. The median (IQR) interval between the initial test and the diagnosis of PE was significantly shorter for women with a positive urine CRDT compared with women with a negative urine CRDT (1 day (0-5 days) vs 8 days (1-19 days), P = 0.027). The negative predictive value of a negative urine CRDT test for PE within 7 days, 14 days and 28 days of assessment were 83.73 % (95 %CI 81.75 %- 85.54 %), 78.92 % (95 % confidence interval [CI] 77.07 %- 80.71 %) and 71.77 % (95 %CI 70.06 %- 73.42 %) respectively. The sensitivity of the urine CRDT in ruling in PE within 7 days, 14 days and 28 days of assessment were 17.07 % (95 %CI 7.15 %- 32.06 %), 13.73 % (95 %CI 5.70 %- 26.26 %) and 10.61 % (95 %CI 4.37 %- 20.64 %), respectively. CONCLUSIONS: Urine CRDT alone has high specificity yet low sensitivity in the short-term prediction of PE in women with suspected PE. Further studies are required to evaluate its clinical utility.

Parity status and the relationship between antenatal rubella serology with obstetric outcome.

Routine antenatal rubella serological testing is adopted in many countries. In a population covered by universal childhood rubella immunization for four decades, we have observed an association between pre-eclampsia with maternal rubella seronegativity among multiparous gravidae. This retrospective cohort study was further performed to elucidate the interaction between parity status and rubella seronegativity on obstetric outcome in singleton pregnancies carried to ≥ 24 weeks gestation managed from 1997 to 2019, with the data retrieved from a computerized database used for annual statistics and auditing. Of the 133,926 singleton pregnancies eligible for the study, the 13,320 (9.9%) rubella seronegative gravidae had higher mean booking weight and body mass index (BMI), but shorter height, and higher incidence of advanced age (≥ 35 years), high BMI, short stature, and lower incidence of nulliparas. Univariate analysis showed that adverse obstetric outcomes were more frequently found among the multiparas. On multivariate analysis, there was increased postdated (> 41 weeks) pregnancy irrespective of parity status, while nulliparas had reduced gestational hypertension (aRR 0.714, 95% CI 0.567-0.899) and gestational diabetes (aRR 0.850, 95% CI 0.762-0.950), and multiparas had increased pre-eclampsia (aRR 1.261, 95% CI 1.005-1.582), neonatal death (aRR 2.796, 95% CI 1.243-6.291), and perinatal death (aRR 2.123, 95% CI 1.257-3.587). In conclusion, in a population covered by universal childhood rubella immunization, antenatal rubella seronegativity is associated with increased pre-eclampsia and perinatal loss only in multiparas, suggesting that the rubella seronegativity in these women served as proxy for some form of altered immune response which increases adverse pregnancy outcome.

Iron Deficiency Anaemia and Atonic Postpartum Haemorrhage Following Labour.

The purpose of this retrospective cohort study is to determine if iron deficiency anaemia (IDA) is associated with increased atonic postpartum haemorrhage (PPH) following labour. Women with singleton pregnancy carried to 24 or more weeks gestation, who were delivered under our care from 1997 to 2019, constituted the study population. A diagnosis of IDA was based on the finding of haemoglobin <10 g/dL and serum ferritin <15 µg/L in the absence of haemoglobinopathies. Women with elective caesarean section were excluded. Maternal characteristics, use of oxytocin, labour outcome and occurrence of PPH were compared between women with and without a diagnosis of IDA. The 1032 women (0.86%) with IDA exhibited slightly but significantly different maternal characteristics and had significantly higher incidence of total (4.5% versus 3.2%, p = 0.024) and atonic PPH (3.1% versus 2.0%, p = 0.011) despite similar incidences of labour induction, augmentation, and instrumental and intrapartum caesarean delivery. Multivariate analysis with adjustment for the effects of age, body mass index, height, parity, abortion history, labour induction and augmentation, instrumental delivery and infant macrosomia demonstrated that IDA was independently associated with total PPH (adjusted relative risk, aRR: 1.455, 95% confidence ratio, CI: 1.040-2.034) and atonic PPH (aRR: 1.588, 95% CI: 1.067-2.364). Our results indicate that despite the low prevalence in our population, IDA was independently associated with atonic PPH, probably consequent to placental adaptive changes in the presence of IDA. The correction and prevention of IDA could be the most important measure in countering the rising global prevalence of atonic PPH.

Prelabor short-term variability in fetal heart rate by computerized cardiotocogram and maternal fetal doppler indices for the prediction of labor outcomes.

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.

Prospective Evaluation of International Prediction of Pregnancy Complications Collaborative Network Models for Prediction of Preeclampsia: Role of Serum sFlt-1 at 11-13 Weeks' Gestation.

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 log10 sFlt-1 and log10 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.

Preterm birth rates in Chinese women in China, Hong Kong and Australia - the price of Westernisation.

BACKGROUND: The rates of preterm birth in Chinese women and the potential effects of differing environments are poorly understood. AIM: To determine the rate of preterm birth in Chinese women in China, Hong Kong and Western Australia. METHODS: The rates of preterm birth were obtained from records of 26,611 pregnancies in Jiangsu Province in mainland China, 48,976 pregnancies in Hong Kong and 185,798 pregnancies in Western Australia. RESULTS: Preterm birth rates increased from 2.6 and 2.9% in urban and rural Jiangsu Province, respectively, and 2.5% in China-born women in Western Australia who required an interpreter; to 4.9% in China-born women in Western Australia who did not require an interpreter; to 5.6% in non-resident Chinese women in Hong Kong; and 7.6% for women resident in Hong Kong. Within Western Australia, the rate of preterm birth was significantly less in women who were born in China and declared themselves to be Chinese (4.4%) than Caucasians (7.8%), other women who declared themselves to be 'Asian' (8.7%) and women of Aboriginal heritage (14.5%). CONCLUSIONS: The rate of preterm birth in China is relatively low but appears to differ in Chinese women in other environments. Differences between traditional Chinese and contemporary Western lifestyles, possibly including smoking and sexual practices, may contribute to the different rates of preterm birth. Further research in this area may provide avenues for the prevention of preterm birth and also help to prevent a possible rise in this complication of pregnancy as Chinese society continues on the path of economic and social reform.

Nausea and vomiting in health-related quality of life among Chinese pregnant women.

BACKGROUND: Nausea and vomiting in pregnancy (NVP) is the most common pregnancy complication affecting women during the first trimester of pregnancy. The cause of NVP remains unknown and factors associated with the occurrence of NVP are contradictory. There is currently little information on its effects of NVP in general and specifically in the Chinese population. AIMS: To assess the prevalence of NVP with different degree of severity and identify their relationship with health-related quality of life (HRQoL) and to determine its association with the sociodemographic and obstetric factors. METHODS: In a prospective cross-sectional study, 396 women who attended the antenatal clinic between 10 and 14 weeks of gestation were invited to complete a structured questionnaire covering maternal characteristics, severity of NVP and their HRQoL. The status of NVP and HRQoL was measured by the frequency of symptoms and the Medical Outcomes Study Short-Form-36 (SF-36) respectively. Logistic regression analysis was performed to delineate the factors associated with NVP. RESULTS: The prevalence of NVP was 90.9%. Almost all domains and dimensions of SF-36 were affected by the presence of NVP and its severity. Factors associated with the presence and severity of NVP were non-smoking, younger age and history of NVP in previous pregnancy. CONCLUSIONS: The various degrees of severity of NVP significantly impair both physical and mental HRQoL in Hong Kong Chinese women. Awareness and care should be given to women with symptoms of nausea or retching alone, as well as vomiting.