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.

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.

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.

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 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.

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.

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.

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.

Maternal height and risk of hypertensive disorders in pregnancy.

PURPOSE: The relationship between maternal height and gestational hypertensive disorders was examined in a cohort of Chinese gravidae managed in 1997-2013 to clarify the association between short stature with preeclampsia (PE) and gestational hypertension (GH). MATERIALS AND METHODS: Retrospective study of 87 290 gravidae categorized by their height into four quartile groups. The impact of short stature, defined as height in the lowest quartile, on incidence of PE and GH was studied in relation to the presence of risk factors. The independent role of short stature was determined by regression analysis. RESULTS: The 25th, 50th, and 75th percentile values of height were 154 cm, 158 cm, and 161 cm respectively. The incidence of PE, but not GH, was inversely correlated with height (p = .025). Short stature altered the impact of parity status, advanced age, high body mass index, infant gender, and medical history, on incidence of PE but not GH. On regression analysis, short stature increased risk of PE (adjusted RR 1.134, 95%CI 1.005-1.279) but reduced GH (adjusted RR 0.836, 95%CI 0.718-0.974). CONCLUSIONS: Maternal short stature should be defined according to distribution in a specific ethnic group, and it exerts a significant but opposite effect on the incidence of PE versus GH.

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.

Prior abortion history and pregnancy hypertensive disorders in primiparous gravidae.

OBJECTIVES: To explore the relationship between prior abortion history with incidence of pregnancy hypertensive disorders (PHD), including gestational hypertension (GH) and pre-eclampsia (PE), to determine whether the secular increases in GH and PE in developed countries could be related in part to the decreased incidence of abortion. STUDY DESIGN: A single center retrospective cohort study on primiparous Chinese gravidae managed in 1997-2015 in our hospital. MAIN OUTCOME MEASURES: The occurrence of PHD, GH and PE with respect to the presence or otherwise of prior abortions, with the analysis stratified for risk factors that include advanced age, high body mass index (BMI), history of medical disorders, birth before 34 weeks, and maternal hepatitis B virus (HBV) infection and rubella non-immunity which have been shown to influence the occurrence of PHD in our population. RESULTS: The 23,698 (39.3%) of the 60,335 gravidae in the cohort with ≥ one prior abortion had higher incidence of advanced age, HBV infection, rubella non-immunity, and high BMI, but lower incidence of PHD, GH, PE and birth before 34 weeks gestation. The difference in the incidence of GH and PE between gravidae having one versus those with two or more abortions was minimal, and the effect of abortion on PHD was influenced by the other risk factors. On regression analysis, prior abortion reduced PHD (aRR 0.761, 95% CI 0.684-0.846), GH (aRR 0.660, 95% CI 0.563-0.773), and PE (aRR 0.857, 95% CI 0.745-0.987). CONCLUSIONS: Prior abortion reduces the subsequent development of GH and PE in primiparous women.

Impact of Maternal BMI on Rubella Nonimmunity at Antenatal Screening.

OBJECTIVE: The aim of this study was to examine the relationship between BMI and the incidence of rubella nonimmunity among pregnant women with regard to the World Health Organization categories. METHODS: This was a retrospective cohort study of 117,063 eligible gravidas, managed between 1998 and 2015 in a university hospital of Hong Kong, China. BMI at antenatal booking was banded using the following World Health Organization definitions: < 18.5 kg/m2 , 18.5 to 24.9 kg/m2 , 25.0 to 29.9 kg/m2 , and ≥30.0 kg/m2 . Maternal rubella nonimmunity status by BMI was assessed. Incidence rates were also assessed after adjusting for maternal advanced age, short stature < 151 cm, mothers' birthplace, and postobstetric history covariates. RESULTS: Rubella nonimmunity incidence increased as the BMI increased (P < 0.001). Gravidas with high BMI were more likely to be nonimmune if born in Hong Kong (odds ratio [OR], 1.234; 95% CI: 1.159-1.315; P < 0.001) compared with those born outside of Hong Kong (OR, 1.066; 95% CI: 0.997-1.141; P = 0.063). After adjusting for covariates, women with BMI ≥ 25 kg/m2 had 1.127 (P < 0.001; 95% CI: 1.074-1.182) greater odds of being nonimmune. CONCLUSIONS: High maternal BMI (≥ 25.0 kg/m2 ) is associated with reduced rubella immunity, an effect confined to gravidas with almost complete vaccine coverage in childhood.

Three decades of neonatal vaccination has greatly reduced antenatal prevalence of hepatitis B virus infection among gravidae covered by the program.

OBJECTIVES: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Heart Failure and Frailty in the Community-Living Elderly Population: What the UFO Study Will Tell Us.

Heart failure and frailty are clinical syndromes that present with overlapping phenotypic characteristics. Importantly, their co-presence is associated with increased mortality and morbidity. While mechanical and electrical device therapies for heart failure are vital for select patients with advanced stage disease, the majority of patients and especially those with undiagnosed heart failure would benefit from early disease detection and prompt initiation of guideline-directed medical therapies. In this article, we review the problematic interactions between heart failure and frailty, introduce a focused cardiac screening program for community-living elderly initiated by a mobile communication device app leading to the Undiagnosed heart Failure in frail Older individuals (UFO) study, and discuss how the knowledge of pre-frailty and frailty status could be exploited for the detection of previously undiagnosed heart failure or advanced cardiac disease. The widespread use of mobile devices coupled with increasing availability of novel, effective medical and minimally invasive therapies have incentivized new approaches to heart failure case finding and disease management.

Protocol for measurement of mean arterial pressure at 10-40weeks' gestation.

The study aimed to identify the simplest protocol for the measurement of mean arterial pressure (MAP) across 10-40weeks' gestation. 2726 women with uncomplicated singleton pregnancy attending for their routine hospital visit between 10 and 40weeks' 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 10-40weeks' gestation, BP recordings can be obtained by a simpler protocol using the average of two measurements in both arms.

Impact of the two-dose rubella vaccination regimen on incidence of rubella seronegativity in gravidae aged 25 years and younger.

OBJECTIVE: This study compared the incidence of rubella seronegativity among gravidae of 25 year-old and younger, between those born in Hong Kong after 1983 when the two-dose rubella vaccination was implemented, versus gravidae born before, to examine the impact of the two-dose regimen. METHODS: In this retrospective cohort study, the incidence of antenatal rubella seronegativity in our parturients managed in1997-2015 was analysed by their age from ≤16 to 25 years, and the effect of year of birth was determined adjusting for confounding factors including teenage status, obstetric history, anthropometric factors, and health parameters including anaemia, thalassaemia trait and hepatitis B carrier status. RESULTS: Among the 12743 gravidae, the 6103 gravidae born after 1983 had overall higher rubella seronegativity (9.1% versus 4.4%, OR 2.061, 95% CI 1.797-2.364), with significant difference (p = 0.006) and inverse correlation (p<0.001) with age, in contrast to the 6640 gravidae born in/before 1983 whom there was significant difference (p = 0.027) but a positive correlation (p = 0.008) with age. For each year of age, the former had significantly higher incidence of rubella seronegativity except for those of ≤16 years. Regression analysis confirmed that birth after 1983 was independently associated with rubella seronegativity (aOR 2.207, 95% CI 1.902-2.562). CONCLUSION: There was a significant trend between rubella seronegativity with age in young gravidae, but the pattern was opposite between gravidae born after versus in/before 1983, with the former having a higher incidence of seronegativity at all ages. Young women covered by the two-dose rubella immunisation programme have a paradoxically higher incidence of rubella seronegativity.

Prior pregnancy and antenatal rubella sero-negativity-evidence of persistent maternal immunologic alteration?

PROBLEM: It is unclear if the immunologic alterations induced by pregnancy could persist. METHOD OF STUDY: Antenatal rubella sero-negativity was correlated with gravidity, abortions and parity in 112 083 gravidae managed during 1997-2015, with further analysis stratified for factors known to influence rubella serology. RESULTS: The 10.2% sero-negative gravidae had different characteristics, and the incidence showed significant difference and positive trend (P<.001 for both) with gravidity, abortions and parity. The pattern remained consistent when analysis was stratified for advanced age, high body mass index and medical history, but was negated by hepatitis B virus infection except for abortions, and by high body mass index for parity. For gravidity 2-4, no difference in rubella sero-negativity was found between gravidae with all previous pregnancies ended in abortion vs delivery. CONCLUSION: Prior pregnancies diminished rubella immunity in a dose-dependent manner, which may be a reflection of the cumulative effect of pregnancy-associated maternal immunologic alteration.