Preeclampsia In Singleton Pregnancies Research Articles

A comparative study of performance of first trimester FMF algorithm for prediction of preeclampsia in singleton and twin pregnancies in coastal Karnataka

Preeclampsia is one of the most common disorders of pregnancy known to complicate 5-10% of all the pregnancies, and it is a component of the deadly triad (along with haemorrhage and infection), that contributes greatly to maternal morbidity and mortality rates. The prevalence of preeclampsia in twin pregnancy is 3-4 fold compared to singleton pregnancy. Timely diagnosis and prevention of this condition is therefore critical. Multiple maternal factors and placental biomarkers have shown to predict preeclampsia in singleton pregnancies. Previous Studies have shown that the proposed algorithms for preeclampsia screening in singletons can also be applied in twins, but with slight modifications and lower accuracy. To study the various parameters included in FMF screening algorithm in first trimester for preeclampsia in singleton and twin pregnancies. To find diagnostic accuracy of screening parameters to predict preeclampsia later in second and third trimester. To study sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) in singleton and twin pregnancy. This prospective observational cohort study conducted in department of Obstetrics and Gynecology, Kasturba Medial College, Hospital, Manipal. Patients were recruited from August 2021 to November 2022. A total of 295 pregnant women were included of which 255 were singleton gestation and 40 were twin gestation. All parameters mentioned in FMF algorithm were obtained between 11week to 13+6 weeks. Patients were followed until delivery for occurrence of pre-eclampsia. Individual parameters of first trimester FMF algorithm of pre-eclampsia screening were analyzed in terms of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) in both singleton and twin study subjects and results were then compared among the groups. In this study a total of 295 pregnant women were recruited. 255 were single gestation of which 47 had preeclampsia and 40 were twin gestation of which 4 had preeclampsia. In the cohort of singleton pregnant women with pre-eclampsia, mean age was noted to be higher (32.77±4.27). They had higher BMI (mean 27.61±3.74) and first trimester MAP was also higher. Similarly, cohort of twin pregnancy with preeclampsia had higher mean of maternal age, BMI and MAP (30.33 ±4.46, 22.83 ± 2.93 and 90.40 ± 1.45 respectively). The Preeclampsia group in both singleton and twin subjects had lower serum concentration and lower MoM values of PAPP-A and PlGF while higher values of free beta HCG and uterine artery PI. Therefore the FMF algorithm for first trimester screening of preeclampsia was found to be a good predictor in both singleton and twin pregnancy. The first trimester FMF algorithm for preeclampsia screening had similar utility in the prediction of preeclampsia in both singleton and twin pregnancy with its individual parameters and combined risk model. However, its accuracy was slightly lesser among twins. Therefore, same screening model can be applicable in singleton and twin gestation.

Predictive Value of Sflt-1/Plgf Ratio for Occurrence of Preeclampsia in Singleton Pregnancies: A Retrospective Study

Introduction: Preeclampsia is multisystem disorder of pregnancy, characterized by endothelial and placental dysfunction. It is classified as an early onset (which occurs < 34 weeks) and late onset (which occurs ≥ 34 weeks). There is an increase of level of antiangiogenic factor of soluble form similar to tyrosine kinase 1 (sFlt-1) and decrease of level of proangiogenic placental growth factor (PlGF) at preeclampsia. High ratio sFlt-1/PlGF is connected to occurrence of preeclampsia. Materials and Methods: There was a retrospective study of the Clinic for Gynecology and Obstetrics of the University Clinical Center of Republic of Srpska (KGA UKC RS), which was implemented in period January 1st, 2020 – December 31st, 2021 and which included 224 patients hospitalized at the Department of Perinatology for suspected preeclampsia development, from 26+0 weeks of gestation until birth. One of the key criteria for the inclusion of patients in the study is the use of the sFlt-1/PlGF ratio as a marker for the onset of preeclampsia, and the determination of protein values in 24-hour urine (biuret). The antenatal state of the fetus was also monitored by ultrasound measurement of the flow resistance ratio (Ri) through the middle cerebral artery and the umbilical artery (C/U), as well as the values of the newborn’s Apgar score in the first and fifth minute of life (AS 1 and 5). The patients included in the study were divided into two groups according to gestational age: group 1 (<33+6 NG) and group 2 (≥34NG). For the purposes of the research, data from patient protocol books for the specified period, as well as corresponding data from the Clinical Information System (KIS), were used. Results: Calculated values for cut off 38 for group 1 are: NPV= 76.9%, PPV=72.0%, sensitivity=85.7%, specificity=58.8%, and for group 2 are: NPV= 89 ,1%, PPV=40.8%, sensitivity=72.1%, specificity=68.5%. For cut off 85, the calculated values for group 1 are: NPV= 82.4%, PPV=85.7%, sensitivity=85.7%, specificity=82.4%, and for group 2 they are: NPV= 84.9 %, PPV=70.4%, sensitivity=44.2%, specificity=94.4%. For cutt off 110, the calculated values for group 1 are: NPV= 77.8%, PPV=85%, sensitivity=81%, specificity=82.4%, and for group 2 they are: NPV= 83.5 %, PPV=72.7%, sensitivity=37.2%, specificity=95.8%. The measured value of protein in 24h urine (biuret) in comparison with the measured values of the sFlt-1/PlGF ratio have statistical significance for predicting the onset of preeclampsia. Statistical data processing obtained by examining the measured values of the sFlt-1/PlGF ratio and the antenatal and natal condition of the fetus (C/U and AS 1 and 5) showed statistical significance, except for C/U for group 2, where p=0.32. Conclusion: Determination of the sFlt-1/PlGF ratio as well as biuret and monitoring of the antenatal and postnatal state of the fetus significantly contributes to the timely diagnostic of preeclampsia, which impacts reducing the incidence of undesirable outcomes for the mother and the fetus.

Prediction of spontaneous preterm birth and preterm prelabor rupture of membranes using maternal factors, obstetric history and biomarkers of placental function at 11-13 weeks.

To determine whether first-trimester biomarkers of placental function can be used to screen for spontaneous preterm birth (sPTB), and to develop prediction models using maternal factors, obstetric history and biomarkers of placental function at 11-13 weeks for the calculation of patient-specific risk for sPTB. This was a retrospective secondary analysis of data derived from a prospective cohort study on first-trimester screening for pre-eclampsia in singleton pregnancies attending for routine Down syndrome screening at 11 + 0 to 13 + 6 weeks' gestation at a tertiary obstetric unit between December 2016 and September 2019. A split-sample internal validation method was used to explore and develop prediction models for all sPTB at < 37 weeks and for PTB at < 37 weeks after preterm prelabor rupture of membranes (PPROM) using maternal risk factors, uterine artery Doppler indices, serum placental growth factor (PlGF), pregnancy-associated plasma protein-A (PAPP-A) and β-human chorionic gonadotropin (β-hCG). Screening performance was assessed using receiver-operating-characteristics (ROC)-curve analysis, with calculation of the areas under the ROC curves (AUCs). A total of 9298 singleton pregnancies were included in this study. sPTB at < 37 weeks occurred in 362 (3.89%) cases, including 231 (2.48%) cases of PPROM. sPTB at < 34 weeks occurred in 87 (0.94%) cases, including 39 (0.42%) cases of PPROM. Identified maternal risk factors for sPTB at < 37 weeks included chronic hypertension, conception using in-vitro fertilization and history of PTB. Maternal risk factors for PPROM at < 37 weeks included conception using in-vitro fertilization and history of PTB. Median PlGF multiples of the median (MoM) and PAPP-A MoM were significantly reduced in women with sPTB at < 37 weeks, as well as in those who had PPROM, compared to those who delivered at term. Screening by a combination of maternal risk factors, PAPP-A and PlGF achieved better performance in predicting sPTB at < 37 weeks (AUC, 0.630 vs 0.555; detection rate (DR), 24.8% vs 16.6% at a false-positive rate (FPR) of 10%; P ≤ 0.0001) and PPROM at < 37 weeks (AUC, 0.643 vs 0.558; DR, 28.1% vs 17.0% at a FPR of 10%; P ≤ 0.0001) than using maternal risk factors alone. Both models were successfully applied to the internal validation dataset, with AUCs of 0.628 and 0.650, respectively. We demonstrated that low levels of maternal serum PAPP-A and PlGF in the first trimester are associated with increased risks of sPTB and PPROM at < 37 weeks. However, further research is needed to identify additional biomarkers to improve the screening performance of the combined model that includes maternal risk factors, PAPP-A and PlGF before clinical application. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

STATIN trial: predictive performance of competing-risks model in screening for pre-eclampsia at 35-37 weeks' gestation.

To examine the predictive performance of a previously reported competing-risks model of screening for pre-eclampsia (PE) at 35-37 weeks' gestation by combinations of maternal risk factors, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and serum soluble fms-like tyrosine kinase-1 (sFlt-1) in a validation dataset derived from the screened population of the STATIN study. This was a prospective third-trimester multicenter study of screening for PE in singleton pregnancies by means of a previously reported algorithm that combines maternal risk factors and biomarkers. Women in the high-risk group were invited to participate in a trial of pravastatin vs placebo, but the trial showed no evidence of an effect of pravastatin in the prevention of PE. Patient-specific risks of delivery with PE were calculated using the competing-risks model, and the performance of screening for PE by maternal risk factors alone and by various combinations of risk factors with MAP, UtA-PI, PlGF and sFlt-1 was assessed. The predictive performance of the model was examined by, first, the ability of the model to discriminate between the PE and no-PE groups using the area under the receiver-operating-characteristics curve (AUC) and the detection rate at a fixed false-positive rate of 10%, and, second, calibration by measurements of calibration slope and calibration-in-the-large. The study population of 29 677 pregnancies contained 653 that developed PE. In screening for PE by a combination of maternal risk factors, MAP, PlGF and sFlt-1 (triple test), the detection rate at a 10% false-positive rate was 79% (95% CI, 76-82%) and the results were consistent with the data used for developing the algorithm. Addition of UtA-PI did not improve the prediction provided by the triple test. The AUC for the triple test was 0.923 (95% CI, 0.913-0.932), demonstrating very high discrimination between affected and unaffected pregnancies. Similarly, the calibration slope was 0.875 (95% CI, 0.831-0.919), demonstrating good agreement between the predicted risk and observed incidence of PE. The competing-risks model provides an effective and reproducible method for third-trimester prediction of term PE. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Pre-eclampsia in pregnancies resulting from oocyte donation, natural conception or IVF: a systematic review and meta-analysis.

What is the prevalence of pre-eclampsia (PE) in pregnancies after oocyte donation (OD) compared to natural conception (NC) and to IVF with autologous oocytes (AO)? Overall the prevalence of PE after OD was 4-5 times higher than after NC and 2-3 times higher than after IVF with AO. The indication for OD is expanding to lesbian women requesting shared lesbian motherhood. Previous reviews have shown that the risk of PE is higher in pregnancies after OD than after NC and after IVF with AO. Classification on the severity of PE is lacking as is the relationship with known risk factors such as maternal age and multiple gestations. Furthermore the actual prevalence of PE in pregnancies resulting from OD is not known. A systematic review and meta-analysis was conducted. A literature search was performed using the following databases: PubMed, EMBASE and CINAHL, OpenGrey and Greynet from January 1980 through July 2020. We included retrospective and prospective cohort studies. The study population consisted of pregnancies after OD and NC or IVF and data had to be available about prevalence of PE. We compared the risk of (severe) PE in OD versus NC and IVF pregnancies, subgrouped by plurality and maternal age. We calculated individual and pooled odds ratios (OR) and prevalence estimates with 95% CI using a random effect model, while heterogeneity was assessed by the I2. In total, 27 studies comprising of 7089 OD pregnancies, 1 139 540 NC pregnancies and 72 742 IVF pregnancies were available for analysis. The risks of PE and severe PE was increased in OD pregnancies compared to NC pregnancies (pooled OR of all subgroups: 5.09, 95% CI: 4.29-6.04; I2 = 19% and OR: 7.42, 95% CI: 4.64-11.88; I2 = 49%, respectively). This suggests that compared to a PE risk of 2.9% with NC, the risk with OD was between 11.5% and 15.4%. Compared to a severe PE risk of 0.5% with NC, the risk with OD was between 2.3% and 5.6%. The pooled adjusted OR for PE was 3.24 (95% 2.74-3.83) for OD versus NC pregnancies. The risks of PE and severe PE were also increased in OD pregnancies compared to IVF pregnancies (pooled OR of all subgroups: 2.97, 95% CI: 2.49-3.53; I2 = 51% and OR: 2.97, 95% CI: 2.15-4.11; I2 = 0%, respectively). This suggests that compared to a PE risk of 5.9% with IVF, the risk with OD was between 13.5% and 18.0%. Compared to a severe PE risk of 3.3% with IVF, the risk with OD was between 6.8% and 12.2%. The pooled adjusted OR for PE was 2.67 (95% 2.28-3.13) for OD versus IVF. The pooled prevalence of PE in singleton pregnancies after OD was 10.7% (95% CI 6.6-15.5) compared to 2.0% (95% CI 1.0-3.1) after NC and 4.1% (95% CI 2.7-5.6) after IVF. The prevalence in multiple pregnancies was 27.8% (95% CI 23.6-32.2) after OD, 7.5% (95% CI 7.2-7.8) after NC and 9.7% (95% CI 6.2-13.9) after IVF. The precise definition of PE is still a matter of debate. The different criteria could have affected the prevalence estimate. Nearly one in six women will suffer PE after OD. Although it is uncertain whether these risks are consistent for lesbian couples undergoing shared motherhood, we feel that women who can conceive naturally could be advised to reconsider. In women with primary ovarian insufficiency, we feel that factors that may increase risk of PE ever further, such as double embryo transfer, should be avoided whenever possible. No funding or competing interests. CRD42020166899.

P–762 Preeclampsia in pregnancies resulting from oocyte donation, IVF or natural conception. A systematic review and meta-analysis

Abstract Study question What is the prevalence of preeclampsia (PE) in pregnancies after oocyte donation (OD) compared to natural conception (NC) and to IVF with autologous oocytes? Summary answer PE prevalence in singleton pregnancies after OD was five times higher than in NC and almost three times higher than after IVF with autologous oocytes. What is known already: The indication for OD is expanding to lesbian women requesting shared lesbian motherhood. Previous reviews showed that the risk of PE is higher in pregnancies after OD than after IVF with autologous oocytes and natural conception. Classification on severity of PE is lacking as is the relationship with known risk factors such as maternal age and multiple gestations. Furthermore the actual prevalence of PE following in pregnancies resulting from OD is not known. Study design, size, duration Systematic review and meta-analysis. A literature search was performed using the following databases: PubMed, EMBASE and CINAHL, OpenGrey and Greynet from January 1980 through July 2020. Participants/materials, setting, methods We included retrospective and prospective cohort studies. The study population consisted of pregnancies after OD and NC or IVF and data had to be available about prevalence of PE. We compared the risk of (severe) PE in OD versus NC and IVF pregnancies, subgrouped by parity and maternal age. We calculated individual and pooled odds ratios (OR) and prevalence estimates with 95% CI using a random effect model, while heterogeneity was assessed by the I2. Main results and the role of chance We included 28 studies comprising of 7131 OD pregnancies, 1.139.540 NC pregnancies and 72.763 IVF pregnancies were available for analysis. The risk of PE and severe PE was increased in OD pregnancies compared to NC pregnancies (pooled OR of all subgroups: 5.09, 95% CI: 4.29 – 6.04; I2 = 19% and OR: 7.42 (95% CI: 4.64–11.88; I2 = 49%). The pooled adjusted OR for PE was 3.24 (95% 2.74 – 3.83) for OD versus natural pregnancies.The risk of PE and severe PE was increased in OD pregnancies compared to IVF pregnancies (pooled OR of all subgroups: 2.96, 95% CI: 2.49 – 3.51; I2 = 51% and OR: 2.97, 95% CI: 2.15 – 4.11; I2 = 0%). The pooled adjusted OR for PE was 2.67 (95% 2.28 – 3.13) for OD versus IVF.The pooled prevalence of PE in singleton pregnancies after OD was 10.7% (95% CI 6.6 – 15.5) compared to 4.1% (95% CI 2.7 – 5.6) after IVF and 2% (95% CI 1.0 – 3.1) after NC. The prevalence in multiple pregnancies was 27.8% (95% CI 23.6 –32.2) after OD, 9.7% (95% CI 6.2 – 13.9) after IVF and 7.5% (95% CI 7.2 – 7.8) after NC. Limitations, reasons for caution The precise definition of PE is still a matter of debate. The different criteria could have affected the prevalence estimate. Wider implications of the findings: Nearly one in six women will suffer PE after OD. Women who can conceive naturally i.e. shared lesbian motherhood, should be discouraged to turn to OD. In women with premature ovarian failure factors that increase risk of PE should be avoided. We suggest therefore single embryo transfer. Trial registration number Not applicable

Maternal and neonatal outcome in pre-eclamptic mothers with elevated liver enzymes: A prospective analytical study

Introduction: Hypertensive disorders during pregnancy may cause damage to liver which may manifest biochemically as a deranged liver function test and subsequent maternal morbidity and mortality any elevation in liver enzymes in a pre-eclamptic patient is significant and influences fetomaternal outcome this study evaluates the liver enzymes as a diagnostic and therapeutic tool in the management of preeclampsia and establishes a correlation between severity of liver function test derangement and severity of fetomaternal complications and use it as a predictive tool of severity of preeclampsia and for termination of pregnancy. Aim was to evaluate maternal and neonatal outcome in pre-eclamptic mothers with and without transaminitis. Primary objective of the study was to compare the maternal and neonatal outcome in pregnant women with preeclampsia in singleton pregnancies with gestational age >24 weeks with and without transaminitis. Secondary objective was to correlate the severity of liver enzyme derangement in preeclamptic mothers with adverse maternal and / or fetal outcome and use it as a predictive tool of severity of preeclampsia and for termination of pregnancy Materials and Methods: This prospective cohort study was conducted on 281 patients after approval by the institute ethics committee informed consents were taken from patients inclusion and exclusion criteria were met all enrolled patients were classified into mild, moderate and severe hypertension and managed as per standard guidelines. Specific investigations were performed if during any visit ast >25 iu/l and/or alt >32iu/l and/or alp > 418 iu/l, patients were called again after a week and blood pressure and fetomaternal well-being was assessed termination of pregnancy was done as per standard guideline statistical analysis done and hypothesis established. Results: From the present study it can be derived that at ast >66 iu/l and alt > 64 iu/l poor maternal outcome is expected with ast >60 iu/l and alt>

Intrahepatic cholestasis of pregnancy is associated with an increased risk of gestational diabetes and preeclampsia.

BackgroundPrevious studies have shown that intrahepatic cholestasis of pregnancy (ICP) is associated with an increased incidence of adverse perinatal outcomes, and this supports the contention that ICP is associated with increased risk for both gestational diabetes mellitus (GDM) and preeclampsia. The purpose of this study was to review adverse maternal and perinatal outcomes of ICP in the Chinese population, and to investigate the association between ICP and GDM, as well as between ICP and preeclampsia.MethodsWe conducted a retrospective cohort study in which we compared pregnancies affected by ICP with all other deliveries during the study period. Data from women with singleton pregnancies who delivered in 14 representative hospitals in China between October 1, 2016 and September 30, 2017 were collected from our database system. We then performed logistic regression analysis to determine the odds ratios (OR) and 95%CIs of the adverse pregnancy outcomes among women with or without ICP.ResultsA total of 95,728 singleton births were included in the study, and among these, 911 pregnancies were diagnosed as having ICP, resulting in an incidence of 0.95%. Women with ICP were more likely to have GDM [adjusted odds ratio (aOR), 1.406; 95% CI, 1.179–1.677; P<0.001] and preeclampsia (aOR, 2.241; 95% CI, 1.678–2.992; P<0.001) compared with those who did not have ICP. Women in the ICP group exhibited higher rates of scheduled cesarean deliveries (aOR, 3.527; 95% CI, 2.981–4.173; P<0.001) and cesarean deliveries during labor (aOR, 4.388; 95% CI, 1.815–10.612; P=0.027). Women with ICP were also more likely to have iatrogenic preterm delivery (aOR, 2.449; 95% CI, 1.92–3.122; P<0.001) and admission to the neonatal intensive care unit (aOR, 1.572; 95% CI, 1.318–1.874; P<0.001). There was no increased risk of stillbirth in the cohort of ICP cases (aOR, 0.430; 95% CI, 0.049–3.767; P=0.259).ConclusionsICP was associated with an increased risk of GDM and preeclampsia in singleton pregnancies. Pregnancies with ICP therefore have significantly increased risks of adverse perinatal outcomes.

ROLE OF MIDDLE CEREBRALARTERY DOPPLER INDICES IN CASES OF PREECLAMPSIAAND IN FETAL OUTCOME

INTRODUCTION Hypertensive disorders of pregnancy contribute greatly to maternal and perinatal morbidity and mortality globally, particularly in developing countries. Pre-eclampsia is characterized by hypertension and significant proteinuria during pregnancy. Doppler ultrasonography is an important noninvasive and quick technique that can detect Intrauterine growth restriction (IUGR) at an early stage and reliably predict any adverse perinatal outcome in hypertensive pregnancies. Doppler velocimetry of the umbilical artery and middle cerebral artery strongly correlate with pregnancy outcome. In this study we have done Doppler indices of middle cerebral artery at the time of presentation of pre- eclampsia. AIM AND OBJECTIVE To evaluate the role of Doppler velocimetry in predicting fetal outcome in patients with pre-eclampsia in singleton pregnancies using doppler indices of Middle cerebral artery at the time of presentation. MATERIALS AND METHODS A single centric observational descriptive study was conducted for a period of 18 month from June 2017 to November 2018 using Siemens ACUSON S2000 color Doppler diagnostic system with curvilinear probe array with frequency 3.5MHz. 50 pre-eclampsia patients were enrolled into the study. Prior institutional ethics committee clearance was obtained for study. Informed consent was obtained from subjects for inclusion of their test result in study. Reference studies were used.

The Prognostic Value of Angiogenic Markers in Twin Pregnancies to Predict Delivery Due to Maternal Complications of Preeclampsia.

The sFlt-1 (soluble fms-like tyrosine kinase-1), PlGF (placental growth factor), and their ratio are useful for predicting delivery because of preeclampsia in singleton pregnancies. Evidence on the utility of sFlt-1/PlGF ratio in twin pregnancies is lacking. We aimed to evaluate the predictive value of sFlt-1/PlGF ratio for delivery because of preeclampsia in twins. A retrospective data analysis of 164 twin pregnancies with suspected preeclampsia was performed. The sFlt-1/PlGF ratio, which was known to clinicians, was significantly higher in women who delivered within 1 and 2 weeks compared with those who did not (median: 98.9 and 84.2 versus 23.5 pg/mL, respectively; P<0.001). The area under the curve values sFlt-1/PlGF ratio levels were 0.88 (95% CI, 0.83-0.84) and 0.88 (95% CI, 0.83-0.93) for predicting delivery because of preeclampsia within 1 and 2 weeks of blood sampling, respectively. The predictive accuracy of sFlt-1/PlGF was independent of gestational age at sampling and chorionicity (P>0.100 for interaction). The area under the curve values of sFlt-1/PlGF were significantly higher than for PlGF alone (mean 0.88 and 0.88 versus 0.81 and 0.80) for predicting delivery because of preeclampsia within 1 and 2 weeks of blood sampling (P=0.055 and 0.001, respectively). sFlt-1/PlGF ratio lower than 38 was able to rule-out delivery within 1 and 2 weeks with a negative predictive value of 98.8% and 96.4% for delivery because of preeclampsia within 1 and 2 weeks, respectively. A cutoff of 38 is applicable for ruling out delivery because of preeclampsia in twin pregnancies.

Recurrent or first preeclampsia in multiparae: A case-control study of singleton pregnancies in Reunion Island

Recurrent or first preeclampsia in multiparae : a case-control study of singleton pregnancies in Reunion IslandPhuong Lien Tran, Pierre-Yves Robillard, Coralie Dumont, Chloé Schweizer, Asma Omarjee, Glorianne Lazaro, Silvia Iacobelli, Malik Boukerrou ObjectiveTo compare multiparous women with a first occurrence of preeclampsia and those with recurrent preeclampsia in singleton pregnancies. Study designa 17.5-year (2001–2018) case-control study conducted in the University’s maternity of South Reunion (Indian Ocean), comparing 125 patients with recurrent preeclampsia and 742 patients with a first episode of the disease (controls). Statistical analyses were performed with use of the Student t-test for comparison of continuous data and the Chi-square or Fisher exact test for comparison of categorical variables. ResultsThere was no difference between the two groups concerning socio-demographic characteristics, post-partum haemorrhage, perinatal mortality rates. Nevertheless, recurrent preeclamptic women had a higher risk to present with prior chronic hypertension (OR 2.05 [1.30–3.23], p = 0.002), and to experience an early onset preeclampsia (< 34 weeks) compared to controls (OR 1.69 [1.15–2.48], p = 0.007). Women with recurrent preeclampsia were more prone to have C-sections (OR 1.63 [1.06–2.51], p = 0.024) mainly because of maternal indications (89.2% vs 76.4%, p = 0.008). Newborns from recurrent preeclampsia were more likely to have very low birthweight < 1500 g (OR 1.79 [1.16–2.77], p = 0.001), while there was no significant difference for gestational ages (34.1 vs 34.7 weeks). ConclusionRecurrent multiparous preeclamptic women presented more severe maternal disease (with a higher rate of early onset preeclampsia). Persistent hypertension in women with a history of preeclampsia is a risk factor for developing recurrent preeclampsia, and these patients should be monitored more closely.

Predictive performance of the competing risk model in screening for preeclampsia

The established method of screening for preeclampsia is to identify risk factors from maternal demographic characteristics and medical history; in the presence of such factors the patient is classified as high risk and in their absence as low risk. However, the performance of such an approach is poor. We developed a competing risks model, which allows combination of maternal factors (age, weight, height, race, parity, personal and family history of preeclampsia, chronic hypertension, diabetes mellitus, systemic lupus erythematosus or antiphospholipid syndrome, method of conception and interpregnancy interval), with biomarkers to estimate the individual patient-specific risks of preeclampsia requiring delivery before any specified gestation. The performance of this approach is by far superior to that of the risk scoring systems. The objective of the study was to examine the predictive performance of the competing risks model in screening for preeclampsia by a combination of maternal factors, mean arterial pressure, uterine artery pulsatility index, and serum placental growth factor, referred to as the triple test, in a training data set for the development of the model and 2 validation studies. The data for this study were derived from 3 previously reported prospective, nonintervention, multicenter screening studies for preeclampsia in singleton pregnancies at 11+0 to 13+6 weeks' gestation. In all 3 studies, there was recording of maternal factors and biomarkers and ascertainment of outcome by appropriately trained personnel. The first study of 35,948 women, which was carried out between February 2010 and July 2014, was used to develop the competing risks model for prediction of preeclampsia and is therefore considered to be the training set. The 2 validation studies were comprised of 8775 and 16,451 women, respectively, and they were carried out between February and September 2015 and between April and December 2016, respectively. Patient-specific risks of delivery with preeclampsia at <34, <37, and <41+3 weeks' gestation were calculated using the competing risks model and the performance of screening for preeclampsia by maternal factors alone and the triple test in each of the 3 data sets was assessed. We examined the predictive performance of the model by first, the ability of the model to discriminate between the preeclampsia and no-preeclampsia groups using the area under the receiver operating characteristic curve and the detection rate at fixed screen-positive rate of 10%, and second, calibration by measurements of calibration slope and calibration in the large. The detection rate at the screen-positive rate of 10% of early-preeclampsia, preterm-preeclampsia, and all-preeclampsia was about 90%, 75%, and 50%, respectively, and the results were consistent between the training and 2 validation data sets. The area under the receiver operating characteristic curve was >0.95, >0.90, and >0.80, respectively, demonstrating a very high discrimination between affected and unaffected pregnancies. Similarly, the calibration slopes were very close to 1.0, demonstrating a good agreement between the predicted risks and observed incidence of preeclampsia. In the prediction of early-preeclampsia and preterm-preeclampsia, the observed incidence in the training set and 1 of the validation data sets was consistent with the predicted one. In the other validation data set, which was specifically designed for evaluation of the model, the incidence was higher than predicted, presumably because of better ascertainment of outcome. The incidence of all-preeclampsia was lower than predicted in all 3 data sets because at term many pregnancies deliver for reasons other than preeclampsia, and therefore, pregnancies considered to be at high risk for preeclampsia that deliver for other reasons before they develop preeclampsia can be wrongly considered to be false positives. The competing risks model provides an effective and reproducible method for first-trimester prediction of early preeclampsia and preterm preeclampsia as long as the various components of screening are carried out by appropriately trained and audited practitioners. Early prediction of preterm preeclampsia is beneficial because treatment of the high-risk group with aspirin is highly effective in the prevention of the disease.

The effect of interaction between parity, gestational diabetes, and pregravid obesity on the incidence of preeclampsia

Objective: To examine the effect of parity, prepregnancy obesity and gestational diabetes on the incidence of preeclampsia in singleton pregnancies using a population-based dataset.Methods: We used the national perinatal information system (NPIS) to identify singleton pregnancies complicated by preeclampsia and analyzed dichotomous-independent variables: being obese or normal weight before pregnancy, being primiparous or multiparous, and being without gestational diabetes mellitus (GDM), with GDMA1, or GDMA2.Results: We found a significantly higher incidence of pregravid obesity among primiparas with preeclampsia (OR 1.6, 95% CI 1.55, 1.66). The data indicate that multiparas had always a significantly lower incidence of preeclampsia, regardless if the women had GDMA1, GDMA2 or had no GDM, and regardless of being of normal weight or obese before pregnancy. The data indicate that the incidence of preeclampsia was not influenced by GDM status, irrespective of parity pregravid BMI category.Conclusions: Our data indicate that GDM is not significantly associated with the development of preeclampsia.

Hypertensive disorders in pregnancy and stillbirth rates: a facility-based study in China.

ObjectiveTo assess the association between hypertensive disorders in pregnancy and the stillbirth rate.MethodsWe obtained all data from China’s National Maternal Near Miss Surveillance System for 2012 to 2016. Associations between hypertensive disorders in pregnancy and stillbirths, stratified by fetus number and gestational age, were assessed using Poisson regression analysis with a robust variance estimator.FindingsFor the period, 6 970 032 births, including 66 494 stillbirths, were reported to the surveillance system. The weighted stillbirth rate in women with a hypertensive disorder in pregnancy was 21.9 per 1000 births. The risk was higher in those who had received few antenatal care visits or who were poorly educated. For singleton pregnancies, the adjusted risk ratio (aRR) for a stillbirth among women with hypertensive disorders in pregnancy compared with normotensive women was 3.1 (95% confidence interval, CI: 2.85–3.37). The aRR for hypertensive disorder subtypes was: 6.66 (95% CI: 5.57–7.96) for superimposed preeclampsia; 4.15 (95% CI: 3.81–4.52) for preeclampsia or eclampsia; 2.32 (95% CI: 1.87–2.88) for chronic hypertension; and 1.21 (95% CI: 1.08–1.36) for gestational hypertension. For multiple pregnancies, the association between stillbirths and hypertensive disorders in pregnancy was not significant, except for superimposed preeclampsia (aRR: 1.95; 95% CI: 1.28–2.97).ConclusionTo minimize the incidence of stillbirths, more attention should be paid to chronic hypertension and superimposed preeclampsia in singleton pregnancies and to superimposed preeclampsia in multiple pregnancies. Better quality antenatal care and improved guidelines are needed in China.

Is the risk of preeclampsia higher in donor oocyte pregnancies? A systematic review and meta-analysis.

ObjectivePreeclampsia (PE) occurs in 4.6% of pregnancies worldwide. The social phenomenon of increasing maternal age has raised the demand for donor oocytes. Egg donation has allowed women with poor ovarian reserve, premature ovarian failure, genetic disorders or surgical menopause to get pregnant. Recipients provide a unique model of immune response because of the differences in the genetic makeup of mothers and fetuses. In PE, immune tolerance may be impaired as a result of having non-autologous eggs implanted. Egg donation is a highly successful assisted reproductive technology, despite the significant number of issues arising from the implantation of non-autologous eggs. This study aimed to determine whether there is an association between egg donation and preeclampsia.MethodsA systematic review of the literature available in PubMed and Google Scholar was carried out from January of 1995 to August of 2016 using the terms 'oocyte donation, preeclampsia', 'oocyte donation, in vitro fertilization, preeclampsia', 'oocyte donation, preeclampsia, outcomes pregnancies', 'oocyte donation, obstetric outcome.' Only six retrospective cohort studies met the selection criteria.ResultThe meta-analysis revealed a statistically significant association between egg donation and onset of preeclampsia (OR 4.50; 95% CI: 3.28-6.19; p<0.0001).ConclusionOocyte donation is associated with increased risk of preeclampsia in singleton pregnancies. Therefore, it is crucial to properly record and assess this finding when egg donation is the chosen assisted reproductive technology to attain pregnancy.

85 Comparison of maternal characteristics and perinatal outcomes of early and late onset preeclampsia in a tertiary care hospital of Pakistan

Introduction Preeclampsia has two clinical entities: Early onset preeclampsia (EOP) and late onset preeclampsia (LOP). The two clinical entities could be distinct with respect to maternal characteristics and perinatal outcomes. Objectives To compare the maternal characteristics of women delivered as EOP and LOP and their perinatal outcomes. Methods We retrospectively analyzed 456 cases of preeclampsia in singleton pregnancies delivered at Aga Khan University Hospital, Karachi, Pakistan (1990–2016). Preeclampsia was defined as blood pressure of ⩾ 140/90 mmHg (taken twice, 6 h apart) combined with 2+ on dipstick protein analysis in the absence of urinary tract infection. Subjects were classified as EOP if the disease manifested before 34 weeks of gestation and LOP when manifestation was at ⩾ 34 weeks of gestation. Maternal characteristics and perinatal outcomes were compared between the two groups using students t test, Mann Whitney U test and Pearson χ 2 test, where appropriate. Results Mothers with EOP were found to be older as compared to mothers with LOP and this association was weakly significant (p value = 0.049). Significantly greater proportions of mothers with EOP had past history of preeclampsia as compared to those with LOP (p value 0.004). Proportions of primigravida were four times less common amongst EOP than LOP. However, the difference was not statistically significant (p value 0.41). There was no significant difference noted in body mass index between the two groups [EOP mean = 29.87 (SD 5.70 ± 5.24) LOP mean = 28.84 (SD 10 ± 5.71)]. EOP were four folds less likely to have cardio-metabolic disorders such as obesity and diabetes mellitus compared to LOP [Obesity 50% vs 12%; p value 0.10; Diabetes mellitus 12.8% vs 3.3%; p value 0.84). These results however, remained non-significant. The mean gestational age at delivery for EOP was significantly more remote from term as compared to LOP (31 vs 37 weeks; p value 0.001). Mothers with EOP were 1.6 times likely to be delivered by emergency section as compared to LOP (85% vs 52%; p value 0.001). Neonates born to EOP mothers demonstrated significantly less Apgar score ( 7) (p-value 0.001), were twice more likely to be admitted to neonatal intensive care unit (NICU), and to be born with intra-uterine growth restriction (IUGR) as compared to LOP (p value 0.001). EOP group were 3 times more likely to deliver low birth weight (LBW) neonates (mean birth weight = 1.33 vs 2.72 p value 0.001) and 9 times more likely to have stillbirth (1.2% vs 0.2%; p value 0.001) in comparison to LOP group. Conclusion Within the preeclamptic cohorts, mothers with EOP were older and were more likely to deliver preterm babies through emergency caesarean section. Neonates born to EOP experienced more adverse outcomes in terms of poor Apgar score 7, stillbirth, admission to NICU, LBW and IUGR as compared to those born to LOP.

O23. STEPS (Study of Early Preeclampsia in Spain): sFlt-1/PlGF for the prediction of early-onset preeclampsia in singleton pregnancies

Introduction The soluble fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio is CE-mark approved for short-term prediction of preeclampsia in women with clinical suspicion of the syndrome (gestational age 24weeks+0d–36weeks+6d). Objectives We evaluated sFlt-1/PlGF as a predictive marker for early-onset preeclampsia in women at high risk of preeclampsia. Methods STEPS (prospective/multicenter) included pregnant women with preeclampsia risk factors (including history of IUGR/preeclampsia/eclampsia/HELLP syndrome, pre-gestational diabetes, antiphospholipid antibodies, and abnormal uterine artery Doppler). Primary objective: to show that sFlt-1/PlGF was predictive of early-onset preeclampsia ( ® sFlt-1 and PlGF assays, cobas electrochemiluminescence platform, Roche Diagnostics, Germany); bilateral uterine artery Doppler; blood pressure/proteinuria/preeclampsia status assessment. Results were compared by ANOVA/Dunnet and Wilcoxon signed-rank test. For prediction of early-onset preeclampsia, the area under the curve (AUC) of receiver operating characteristic curves (ROC) was calculated. Singleton pregnancies are reported. Results 819 subjects were enrolled. Of 442 women with singleton pregnancies 42 (9.5%) developed preeclampsia (14 early-onset/28 late-onset). The mean (SD) sFlt-1/PlGF ratio at 20, 24, and 28 weeks was: 7.86 (8.61), 5.9 (12.38) and 4.59 (5.65) for subjects who did not develop preeclampsia (control); 53.15 (61.79), 69.25 (105.53) and 180.37 (241.83) for early-onset preeclampsia; and 7.81 (4.45), 5.09 (3.34) and 13.39 (34.52) for late-onset preeclampsia. Compared with early-onset preeclampsia the sFlt-1/PlGF ratio was significantly lower for control, chronic hypertension, transient hypertension, and late-onset preeclampsia (Figure). Prediction of early-onset preeclampsia (ROC AUC [95% CI]) was best for sFlt-1/PlGF plus clinical data (0.94 [0.90–0.98], 0.94 [0.89–1.0], 0.94 [0.86–1.0], at 20, 24 and 28 weeks) vs sFlt-1/PlGF alone (0.78 [0.62–0.95], 0.82 [0.65–0.98], 0.86 [0.72–1.0]) or Doppler alone (0.71 [0.56–0.86], 0.73 [0.54–0.91], 0.87 [0.74–1.0]). Conclusion The sFlt-1/PlGF ratio can improve prediction of early-onset preeclampsia for women at high risk of preeclampsia.

Maternal hepatitis B surface antigen status and incidence of pre‐eclampsia

The relationship between chronic hepatitis B virus (HBV) infection with atherosclerosis and cardiovascular disorders remains unclear, and the impact of maternal HBV infection on the development of pregnancy-induced hypertension (PIH) and pre-eclampsia (PE) is also controversial. This retrospective cohort study was conducted to examine the relationship between maternal hepatitis B surface antigen (HBsAg) status with PIH and PE in singleton pregnancies that delivered at 24weeks of gestation and beyond. Among the 86537 cases in the cohort, 10% were HBsAg positive, and overall 2.0% had PIH, of whom 56.3% developed PE. HBsAg-positive women had higher weight and body mass index (BMI), but lower incidences of advanced age, nulliparity, PIH (1.6% vs 2.0%, P=0.007) and PE (0.8% vs 1.1%, P=0.005). On multiple logistic regression analysis adjusting for the effects of nulliparity, advanced age, high BMI, and underlying renal, cardiac and autoimmune diseases, HBsAg carriage was associated with significantly reduced incidence of PIH (aOR 0.79, 95% CI 0.66-0.95) and PE (aOR 0.71, 95% CI 0.56-0.91). Our results indicate that maternal HBsAg carriage is independently associated with reduced PE. As chronic HBV infection alters the immune response of the individual, our observation could be related to enhanced maternal immunotolerance of the foetus and hence a reduction in the incidence of PE. The implications of our findings on the long-term health outcome of the infected women, from cardiovascular morbidity to malignancies, warrant further studies.

Maternal hemodynamics at 11–13 weeks' gestation and risk of pre‐eclampsia

Women who develop pre-eclampsia are at increased risk of cardiovascular disease and stroke in the subsequent decades. Individuals with cardiovascular disorders have increased central aortic systolic blood pressure (SBP(Ao) ) and arterial stiffness, as assessed by pulse wave velocity (PWV) and augmentation index (AIx). The aim of this study was to examine the potential value of assessment of SBP(Ao) , PWV and AIx at 11-13 weeks' gestation in identifying women who subsequently develop pre-eclampsia. This was a screening study for pre-eclampsia in singleton pregnancies at 11 + 0 to 13 + 6 weeks' gestation. Maternal history and characteristics were recorded and PWV, AIx (adjusted to a heart rate of 75 beats per min (AIx-75)) and SBP(Ao) measured. We compared these parameters in women who developed pre-eclampsia (n = 181) with those in unaffected controls (n = 6766) and examined their performance in screening for pre-eclampsia. In the pre-eclampsia group, compared to unaffected controls, there was an increase in AIx-75 (1.13 vs. 1.00 multiples of the median (MoM); P < 0.0001), PWV (1.06 vs. 1.00 MoM; P < 0.0001) and SBP(Ao) (1.09 vs. 1.00 MoM; P < 0.0001). In screening for pre-eclampsia by a combination of maternal variables and log(10) AIx-75 MoM, log(10) PWV MoM and log(10) SBP(Ao) MoM, the estimated detection rate was 56.9% at a false-positive rate of 10%. Compared with women who remain normotensive, women who develop pre-eclampsia have higher SBP(Ao) and arterial stiffness, which is apparent from the first trimester of pregnancy.

Study on clinical risk of maternal underlying medical conditions and onset of preeclampsia

To investigate the effect of clinical risk factors including maternal underlying medical conditions on the development of preeclampsia (PE) in order to improve and strengthen the early assessment of high clinical risk population of PE. Clinical observational data of patients with PE in Peking University Third Hospital from November 2008 to January 2011 were analyzed. Comparative analysis was made among medical conditions with PE (M-PE) sub-group and isolated PE (I-PE) sub-group and non-PE pregnancy with or without medical conditions (control group). Totally 159 cases, 43.09% (159/369) of total cases of PE had high clinical risk factors (multiple pregnancy and medical conditions) and 32.3% (97/300) of singleton PE accompanied with medical conditions. The incidence of PE in singleton pregnancies with medical conditions was significantly higher than those without medical conditions [15.0% (97/646) versus 4.45% (210/4719), P < 0.05]. In M-PE sub-group, the average age [(31.7 ± 4.5) versus (29.3 ± 5.2) year-old] and body mass index (BMI) in first trimester [(26.0 ± 5.6) versus (23.3 ± 3.7) kg/m(2)], the proportion with previous preeclampsia [11% (11/97) versus 4.9% (10/203)] and pregnancy loss in third trimester [11% (11/97) versus 3.0% (6/203)], were higher than those of I-PE sub-group (all P < 0.05). The onset of preeclampsia in M-PE sub-group was earlier than I-PE (32.9 versus 34.4 gestation weeks, P < 0.05). The proportion serious cases of PE occurring before 32 gestational weeks were higher in M-PE than that of I-PE sub-group [45% (44/97) versus 34.0% (69/203), P < 0.05]. Multivariate regression analysis showed that previous history of late pregnancy loss and irregular prenatal care were clinical risk factors for early-onset PE whether early-onset was defined as < 34 or < 32 gestational weeks respectively (all P < 0.05); medical conditions were risk factors for PE if early-onset was defined as < 32 gestational weeks (OR = 1.718, 95%CI: 1.005 - 2.937, P = 0.048). Multiple pregnancies and pregnancies with medical conditions exceed one-third of total subjects of PE. The onset of PE in subjects with maternal underlying medical conditions was earlier which is the subgroup should not be ignored. The difference of early pregnancy BMI may show the maternal heterogeneity in early onset and late onset of preeclampsia. Assessment of clinical risk factors including the underlying medical disorders for preeclampsia in early trimester should be strengthened.