Pre-delivery fibrinogen level is a predictor for severity of placental abruption.

Objective: To determine pre-delivery fibrinogen levels in predicting adverse maternal or neonatal outcomes in patients with placental abruption. Materials and method: We conducted a retrospective study of all women admitted for placental abruption between January 2012 and May 2018. Postpartum hemorrhage (PPH), disseminated intravascular coagulation (DIC), massive blood transfusion and hospitalization in intensive care unit parameters were evaluated for maternal outcomes. For the neonatal outcomes, the 5th minute APGAR score, umbilical artery pH and stillbirth were evaluated. Results: The mean predelivery fibrinogen levels were 221.3 ± 111.6 mg/dL. In multivariate logistic regression analysis, fibrinogen level was determined as an independent indicator for PPH, red cell concentrate (RCC) and fresh frozen plasma (FFP) transfusion. When fibrinogen levels decreased below 130 mg/dL, the risk of PPH increased and when fibrinogen levels decreased below 100 mg/dL, the risk of overt DIC and also the risk of red cell concentrate and fresh frozen plasma transfusion increased. In terms of the fetal results, there may be adverse neonatal outcomes when fibrinogen levels are below 250 mg/dL. Conclusion: Predelivery fibrinogen levels are good indicators for predicting adverse maternal outcomes in placental abruption cases. In addition, fibrinogen levels might be a guide for management of placental abruption cases.

Evaluation of right side foetal myocardial performance index in pregestational and gestational diabetes mellitus.

The aim of our study is to investigate the myocardial performance index (MPI) of the right side of the foetal heart in pregestational and gestational diabetes mellitus and to compare it with non-diabetic pregnancies. This prospective cross-sectional study was conducted between August 2018 and March 2019 at Kanuni Sultan Suleyman Research and Training Hospital. Women with pregestational or gestational diabetes mellitus at 24-34 weeks of gestation were included in the study and non-diabetic pregnant women were included as the control group. MPI of the right side of the foetal heart were evaluated and compared between the groups. A total of 65 pregestational or gestational diabetic patients and 65 non-diabetic patients were included in the study. Isovolumetric contraction time and isovolumetric relaxation time values were significantly longer in the diabetic group (p < .001). Ejection time values were significantly shorter in the diabetic group (p < .001). MPI values were significantly higher in the diabetic group than the non-diabetic group (p < .001). In conclusion, MPI of the right side of the foetal heart is significantly higher in pregestational and gestational diabetes than in the non-diabetic group.IMPACT STATEMENTWhat is already known on this subject? Gestational diabetes mellitus causes foetal cardiomyopathy and foetal diastolic dysfunction. Myocardial performance index (MPI) is a non-invasive, Doppler-derived myocardial performance assessment that is independent of both heart rate and ventricular anatomy.What do the results of this study add? MPI of the right side of the foetal heart was significantly higher in pregestational and gestational diabetes than in the non-diabetic group. There was no difference in right ventricular MPI between pregestational and gestational groups in diabetic pregnancies, and between insulin using and not insulin using groups.What are the implications of these findings for clinical practice and/or further research? Our study results are promising. MPI of the right side of the foetal heart is significantly higher in pregestational and gestational diabetes than in the non-diabetic group. Prospective cohort studies evaluating serial MPI and evaluating by postpartum foetal echocardiography are needed to evaluate possible adverse effects of diabetes on foetal cardiac functions.

Assessment of fetal right ventricular myocardial performance index changes following intrauterine transfusion.

INTRODUCTION: Severe fetal anemia may cause cardiac ischemia, reduced contractility, and dysfunction. The purpose of our study is to evaluate right ventricular myocardial performance index (MPI) before and after intrauterine transfusion (IUT) in patients who underwent this procedure because of fetal anemia due to Rh-D alloimmunization. MATERIALS AND METHODS: This prospective cohort study was conducted between January 2018 and June 2019 at Kanuni Sultan Suleyman Research and Training Hospital, Istanbul, Turkey. The pregnant women who were applied IUT because of fetal anemia due to Rh-D alloimmunization in our perinatology clinic were included in the study. Fetal right ventricular MPI before and 24 h after IUT were evaluated. RESULTS: A total of 28 IUTs were performed in 17 pregnant women during the study period. The isovolumetric contraction time (ICT) and isovolumetric relaxation time (IRT) values measured before IUT, were found to be significantly longer compared to the ICT and IRT values measured after IUT. The MPI values measured after transfusion was found to be higher than before transfusion. CONCLUSIONS: The fetal right ventricular MPI increases 24 h after IUT. This increase in the right ventricular MPI might be used as a marker for predicting adverse fetal outcomes following IUT.

Maternal serum mitofusin-2 levels in patients with preeclampsia: the possible role of mitochondrial dysfunction in preeclampsia.

Purpose: Hypoxia alters mitochondria function and our aim was to measure mitochondrial fusion protein mitofusin-2 (Mfn2) in patients with preeclampsia.Materials and methods: This cross-sectional study was conducted including 82 pregnant women, 27 with normal pregnancy and 55 with preeclampsia (27 with early-onset preeclampsia and 28 with late-onset preeclampsia). Maternal serum levels of Mfn2 were measured by using enzyme-linked immunosorbent assay kits.Results: The mean serum mitofusin-2 levels were higher in women with preeclampsia than in the control group (68.02 ± 8.7 pg/mL vs. 99.72 ± 37.27 pg/mL, p < .0001). The mean serum mitofusin-2 level was found to be the highest in the early-onset preeclampsia (EOPE) group (EOPE: 101.6 ± 38.5 pg/mL). Maternal serum mitofusin-2 levels correlated with both systolic and diastolic blood pressures as well as uterine artery pulsatility index. The optimal cutoff value of Mfn2 for determining preeclampsia was 75.3 pg/mL.Conclusion: Mfn2 has regulatory roles in stress response. Maternal serum Mfn2 is higher in patients with preeclampsia suggesting that Mfn2 increases in the maternal system as a stress response against hypoxia and endothelial dysfunction.What do the results of this study add? Hypoxia causes mitochondrial dysfunction that has been linked to the etiology of many diseases including preeclampsia. Mitofusin-2 is a mitochondrial fusion protein, and the levels can be altered in preeclampsia. For the first time, we showed that maternal levels of mitofusin-2 are higher in patients with preeclampsia. Further, we reported the correlation of mitofusin-2 with blood pressures and uterine artery pulsatility index. These findings will open up other avenues for researchers to investigate other mitochondrial molecules while under stress.

The assessment of cardiac function with tissue Doppler imaging in fetuses with congenital diaphragmatic hernia.

Introduction: This study aimed to evaluate the cardiac function of fetuses with congenital diaphragmatic hernia by conventional echocardiography and spectral tissue Doppler imaging (s-TDI) and to evaluate the relationship between cardiac function and the severity of pulmonary hypoplasia. We also aimed to investigate the effect of diaphragmatic hernia side on fetal cardiac function.Methods: Fetal cardiac function were evaluated in 28 fetuses (20 with left-sided and 8 with right-sided) complicated with isolated congenital diaphragmatic hernia (CDH) and 56 gestational age matched control in this single center prospective study. s-TDI measurements were obtained at the right atrioventricular valve annulus. The annular peak velocities and their ratios, the time periods of cardiac cycle and myocardial performance index were calculated.Results: In comparison to controls, significantly prolonged isovolumetric contraction time (ICT') and isovolumetric relaxation time (IRT') and, significantly shortened ejection time (ET') were observed in fetuses with CDH by s-TDI. Fetuses with CDH also had higher myocardial performance index (MPI') z-scores compared to controls. There were no significant differences in terms of s-TDI cardiac function parameters between fetuses with right- and left-sided CDH. In correlation analysis, a significant positive correlation was found between ET' value and o/e LHR.Conclusion: The signs of both systolic and diastolic altered function were observed in fetuses with CDH with s-TDI independent of the side of the hernia, and a significant positive correlation was observed between fetal cardiac systolic function and the severity of pulmonary hypoplasia.

Perinatal outcomes of intrauterine transfusion for foetal anaemia due to red blood cell alloimmunisation.

The aim of this study was to evaluate the maternal and neonatal outcomes of patients who underwent intrauterine transfusion (IUT) for foetal anaemia due to red blood cell alloimmunisation and to determine the factors that affected the outcomes. All pregnancies that were treated with IUT due to Rh immunisation between January 2015 and June 2018 in the Kanuni Sultan Süleyman Training and Research Hospital, Department of Obstetrics and Gynaecology, were evaluated retrospectively. IUT due to non-Rh alloimmunisation, parvovirus B19 infection, chronic fetomaternal haemorrhage and foetal anaemia due to homozygous alpha-thalassemia were not included in the study. The perinatal and neonatal outcomes of the patients were retrospectively analysed. The gestational age, ultrasonography findings before and after IUT, laboratory results, complications related to IUT, and data on the newborns were recorded. The cases were divided into two groups, those with complication and those without complications, and their perinatal outcomes were compared. A total of 110 IUTs were performed in 42 foetuses. The survival rate after transfusion was 80.95%. Procedure-related complications were found in 12.7% of cases. There were no significant differences between the demographic and clinical characteristics of the patients with and without complications. The survival rate was lower and perinatal mortality was higher in foetuses with hydrops fetalis. IUT is a safe and effective procedure that can be used in the treatment of foetal anaemia in experienced centres. Survival rates can be increased by referring patients to experienced perinatology centres, by improving the IUT technique, and by reducing technique-related complications.Impact statementWhat is already known on this subject? The predominant use of IUT is to treat foetal anaemia due to red blood cell alloimmunisation. Despite the decrease after anti-D immune globulin prophylaxis, Rh immunisation is still a major cause of foetal anaemia. However, foetal survival rates have increased with the use of IUT.What do the results of this study add? The survival rates were increased after the development of a high-resolution ultrasound. Because foetal monitoring can be performed by ultrasonography, cord accidents and overload findings can be detected during transfusion, which allows for early interventions and increases survival rates.What are the implications of these findings for clinical practice and/or further research? The IUT procedure can be used in the treatment of foetal anaemia in experienced centres. After the technique was improved, the complication rates related to the procedure were decreased and foetal survival rates were increased. Further studies on the use of different IUT techniques will extend our findings.

Maternal serum galectin-1 and galectin-3 levels in pregnancies complicated with preterm prelabor rupture of membranes.

Objective: To investigate maternal serum galectin-1 and galectin-3 levels in pregnancies complicated with preterm prelabor rupture of membranes (PPROM) and to compare with pregnancies delivered at term.Materials and methods: In this cross-sectional study, 40 women with singleton pregnancies complicated with PPROM between 24 and 34 weeks of gestation were compared with gestational age-matched 40 pregnant women with no obstetrics complications, who delivered at term. The maternal serum galectin-1 and galectin-3 levels were measured.Results: Patients complicated with PPROM had significantly higher levels of galectin-1 (p = .001) and galectin-3 (p = .003) than the control group. Maternal serum galectin-3 levels were found significantly negatively correlated with the gestational age at delivery and birth weight.Conclusion: Maternal serum galectin-1 and galectin-3 levels were significantly higher in pregnancies complicated with PPROM. Galectin-1 and galectin-3, with their regulatory effects in key biological processes, may be both an initiating factor in the pathophysiology of PPROM, a marker in the prediction, and a target of preventing strategies of PPROM.

Increased maternal C1q/TNF-related protein-1 (CTRP-1) serum levels in pregnancies with preeclampsia.

Objective: Metabolic changes and inflammation are involved in the pathogenesis of preeclampsia. Complement C1q tumor necrosis factor-related protein-1 (CTRP-1) is a pleiotropic molecule that possesses insulin-sensitizing effects and is also involved in lipid metabolism and inflammatory responses. The aim of the study was to investigate CTRP-1 levels in pregnancies with preeclampsia.Material and methods: Serum concentrations of CTRP-1 were measured in 29 pregnant women with early-onset preeclampsia (EOPE), 24 pregnant women with late-onset preeclampsia (LOPE), and 26 women with uncomplicated pregnancies using an enzyme-linked immunosorbent assay method.Results: Patients with both EOPE and LOPE had significantly higher serum concentrations of CTRP-1 compared to the healthy controls (p < .001). However, no significant difference was found between the EOPE and LOPE groups regarding CTRP-1 levels (p = 1.000). Correlation analysis showed that CTRP-1 levels were positively correlated with systolic blood pressure (p < .001), diastolic blood pressure (p < .001), and mean UtA PI (p < .001) but negatively correlated with gestational age at delivery (p = .001) and birth weight (p < .001).Conclusions: Serum CTRP-1 levels were significantly higher in patients with both EOPE and LOPE than in healthy pregnant women.

Comparison of fetal cardiac functions between small-for-gestational age fetuses and late-onset growth-restricted fetuses.

Background This study aimed to investigate fetal cardiac functions by spectral tissue Doppler imaging (s-TDI) in pregnancies complicated with late-onset fetal growth restriction (LO-FGR) and small-for-gestational age (SGA). Methods Forty pregnancies complicated with late-onset FGR and 40 pregnancies complicated with SGA between the 34th and 37th weeks of gestation were enrolled in this study. Forty gestational age-matched pregnant women with no obstetrics complication were randomly selected as a control group. Small fetuses were classified as fetal growth restriction or SGA according to estimated fetal weight (EFW), umbilical artery pulsatility index (PI), cerebroplacental ratio (CPR) and uterine artery PI. s-TDI measurements were obtained at the right atrioventricular valve annulus. Results SGA and LO-FGR fetuses had significantly lower A' and S' values, and higher E'/A' ratio than the control group (P < 0.001). In comparison to controls, significantly prolonged isovolumetric contraction time (ICT') and isovolumetric relaxation time (IRT') and, significantly shortened ejection time (ET') were observed in fetuses with SGA and LO-FGR. Increased myocardial performance index (MPI') values were also found in fetuses with SGA and LO-FGR compared to controls. Conclusion The signs of cardiac dysfunction were observed both in fetuses with SGA and LO-FGR. The fetal cardiac function assessment with s-TDI could be a valuable method in the diagnosis of true growth restricted fetuses and in the management of these fetuses.

Wnt signaling pathway in early- and late-onset preeclampsia: evaluation with Dickkopf-1 and R-Spondin-3 glycoproteins.

OBJECTIVE: Wnt signaling has been identified as an essential pathway that can direct cell proliferation, migration, and tissue homeostasis. This study aimed to evaluate the role of Wnt signaling pathway in early-onset and late-onset preeclampsia (PE) using serum Dickkopf-1 and R-Spondin-3 glycoproteins. STUDY DESIGN: A total of 80 pregnant women were included in this study. The patients were divided into three groups: (1) control (2) early-onset PE, and (3) late-onset PE. The serum levels of Dickkopf-1 and R-Spondin-3 were measured using an enzyme-linked immunosorbent assay. RESULTS: Of the 80 pregnant women enrolled in the study, 27 were control, 27 had early-onset PE, and 26 had late-onset PE. No differences were found in the maternal age, gravida, parity, and body mass index among the groups (P = 0.536, 0.230, 0.202, and 0.642, respectively). The serum level of Dickkopf-1 was significantly higher in the early-onset PE group compared with the control group (P = 0.006). The serum level of Dickkopf-1 was statistically similar in control group compared to late-onset PE group (P = 0.064). However, no significant difference was found in the serum levels of Dickkopf-1 and R-Spondin-3 between the early- and late-onset PE groups (P > 0.05). Additionally, the Spearman's correlation analysis revealed a significant negative correlation between maternal serum level of Dickkopf-1 and maternal age (r = - 0.522, P = 0.005). CONCLUSION: The increased serum level of Dickkopf-1 might be associated with the process of pathogenesis of early-onset PE. Further studies would elucidate their exact roles in the pathogenesis of PE.

Evaluation of FGF-19 and ß-klotho as biomarkers in patients with intrahepatic cholestasis of pregnancy.

INTRODUCTION: Fibroblast growth factor-19 (FGF-19) and its co-receptor, beta-klotho, regulate bile acid synthesis in the liver as an enterohepatic feedback mechanism. In this study, our aim was to investigate the circulating FGF-19 and ß-klotho levels in intrahepatic cholestasis of pregnancy (ICP) cases. MATERIAL AND METHODS: A cross-sectional study including 40 women whose pregnancies were complicated with ICP were recruited for the study group. Forty randomly selected healthy pregnant women comprised the control group. The patient characteristics, including maternal age, gravidity, parity, gestational age at the time of diagnosis, body mass index (BMI), and obstetric history, were recorded. The serum FGF-19 and ß-klotho concentrations were measured using an enzyme-linked immunosorbent assay. RESULTS: Maternal age, gravidity, parity, body mass index at assessment, and gestational age at blood sampling were similar between the two groups (p > 0.05). Moreover, there were no significant differences in the FGF-19 and ß-klotho concentrations between the two groups (p = 0.341 and p = 0.086, respectively). A positive correlation was detected between the ß-klotho and FGF-19 levels, as well as between the FGF-19 level and BMI (r = 0.368, p = 0.020 and r = 0.389, p = 0.013, respectively). CONCLUSIONS: The serum FGF-19 and ß-klotho concentrations did not differ between the pregnancies with ICP and the healthy controls. However, in some cases, abnormalities in the FGF-19, ß-klotho, and FGFR4 signaling system may play roles in the pathogenesis of ICP.

Maternal cytoglobin (CYGB) serum levels in normal and preeclamptic pregnancies.

OBJECTIVE: To investigate cytoglobin levels in women with preeclampsia and women with uncomplicated pregnancies. MATERIALS AND METHODS: A cross-sectional study including 26 pregnant women complicated with early-onset preeclampsia (EO-PE) and 26 pregnant women complicated with late-onset preeclampsia (LO-PE) were recruited for the study group. Twenty-seven healthy pregnant women selected randomly were included in the control group. The serum CYGB concentrations were measured using an enzyme-linked immunosorbent assay. RESULTS: Gestational age at delivery and mean birth weight were significantly lower in the preeclampsia groups than in the control group and were found to be the lowest in the EO-PE group (p < .001). Serum CYGB levels were significantly higher in the EO-PE and LO-PE groups as compared with the control group (9.99 (6.08) ng/ml (EOPE), 10.04 (7.04) ng/ml (LOPE) versus 2.84 (0.82) ng/ml), (p < .001). However, a significant difference was not found between the EO-PE and LO-PE groups regarding CYGB levels (p = 1.000). CONCLUSIONS: Serum CYGB levels were significantly higher in patients with EO-PE and LO-PE as compared to healthy pregnant women.

Increased levels of the novel hepatokine fetuin B in patients with intrahepatic cholestasis of pregnancy.

OBJECTIVES: To investigate liver-derived plasma protein fetuin B levels in healthy pregnant women and pregnant women with intrahepatic cholestasis of pregnancy (ICP). MATERIALS AND METHODS: Forty women with ICP and 40 healthy pregnant women were included in this cross-sectional study. The serum fetuin B levels of these patients were analyzed. The patients were followed up to delivery. RESULTS: Maternal age, gravida, parity, BMI at assessment, and gestational age at blood sampling were similar between the ICP and control groups (p > .05). However, the gestational age at delivery and the birth weight were significantly lower in the ICP group (p < .05). Total bile acid (TBA) levels and liver function tests were significantly higher in the ICP group than in the control group (p < .0001 and < .0001, respectively). In addition, serum fetuin B concentrations were significantly higher in the ICP group than in the control group (p < .0001). The best cutoff for fetuin B serum concentration was 5540.2 pg/mL. Serum values greater than this threshold had 80% sensitivity and 65% specificity for the diagnosis of ICP. CONCLUSIONS: Serum fetuin B was higher in patients with ICP compared to healthy pregnant women and might be a new biomarker.

Maternal serum sestrin 2 levels in preeclampsia and their relationship with the severity of the disease.

OBJECTIVE: To investigate sestrin 2 (SESN2) levels in preeclampsia (PE) cases and uncomplicated pregnancies. METHODS: Cross-sectional study including 26 pregnant women with PE, 24 with severe-PE, and 30 randomly selected healthy pregnant women. RESULTS: The mean arterial pressure, severe proteinuria, number of HELLP syndrome cases, and serum SESN2 levels in the severe PE group were significantly higher than those in the other groups (p < 0.001, p < 0.001, p = 0.006, and p = 0.004, respectively). Negative correlation was found between the birth interval (r = -.262, p = 0.019) and the SESN2 level. CONCLUSION: SESN2 seems to play a role in the pathophysiology of PE, especially in severe PE cases.

Could first- and second-trimester biochemical markers for Down syndrome have a role in predicting intrahepatic cholestasis of pregnancy?

INTRODUCTION: The aim of this study is to compare first- and second-trimester Down syndrome biochemical screening markers in intrahepatic cholestasis of pregnancy (ICP) and normal pregnancies. MATERIAL AND METHODS: This observational case-control study was conducted at Health Sciences University Zeynep Kamil Maternity and Children's Health Training and Research Hospital and the Department of Obstetrics and Gynecology at Erciyes University Medical Faculty during 2016-2017. The study included 165 patients, and consisted of 62 women who had been diagnosed with ICP (the ICP-diagnosed group) and 103 healthy pregnant women (the control group). First-trimester free ß-human chorionic gonadotropin (ß-hCG), pregnancy-associated plasma protein-A (PAPP-A) and second-trimester total ß-hCG, estriol (E3), α-fetoprotein (AFP), and inhibin A levels were compared between the two groups. RESULTS: The mean patient age was 28.67 ±5.96 years, with no significant difference between the groups (p > 0.05). Average PAPP-A levels were significantly lower in the ICP-diagnosed group (p < 0.001). When the cut-off value for PAPP-A was taken as ≤ 0.93 multiple of median (MoM), the sensitivity and specificity values for ICP were 73.8% and 56.3%, respectively (95% CI, AUC ± SE: 0.663 ±0.042). CONCLUSIONS: The decrease in PAPP-A MoM value indicates an increase in the risk of developing ICP, while changes in other markers were not sufficient to predict ICP.

Maternal copeptin levels in intrahepatic cholestasis of pregnancy.

PURPOSE: To investigate the copeptin levels in women with intrahepatic cholestasis of pregnancy (ICP) compared to women with uncomplicated pregnancies. MATERIALS AND METHODS: This cross-sectional study was conducted in 40 pregnant women with ICP and 38 randomly selected healthy pregnant women, who formed the control group. Serum copeptin concentrations were measured using an enzyme-linked immunosorbent assay. RESULTS: Maternal age, body mass index at assessment, and gestational age at blood sampling were similar between the two groups. Duration of pregnancy was shorter and mean birth weight was significantly lower in the ICP group compared to the control group. Total bile acid, alanine aminotransferase, aspartate aminotransferase, and gamma glutamyl transferase levels were significantly higher in the ICP group than in the control group. There was no significant difference in copeptin concentrations (2.54 (2.05) versus 2.43 (1.98) ng/ml; p = .5). CONCLUSIONS: Serum copeptin concentrations did not vary between the pregnancies complicated by ICP and the healthy pregnancy control group.

Upper limb hemimelia in a twin pregnancy which was obtained by an ICSI and PGD in a woman with mosaic Turner's syndrome and the prognosis.

Turner's syndrome (TS) is depicted as a total or partial absence of X chromosome, and occurs in approximately 1/2200 of live born females. Generally, mosaic patients are diagnosed following karyotype analysis due to recurrent pregnancy loss, repeated in vitro fertilization (IVF) failure, and a history of malformed babies. The purpose of this case report is to show that even a selection of normal karyotype embryos can result in abnormalities for those with mosaic TS. A 32-year old patient who underwent IVF after ICSI-PGD, and was diagnosed with 45X/46XX karyotype. At the 12-week scan, one of the fetuses had an upper limb hemimelia in one arm, and feticide was applied to that fetus. The patient delivered a healthy, 2980 g female baby at the thirty-eighth week. In mosaic TS pregnancies (even those obtained by ICSI-PGD), fetal anomaly risk is high. Therefore, careful prenatal scanning is needed for these pregnancies.

Competing risk model in screening for preeclampsia by mean arterial pressure and uterine artery pulsatility index at 30-33 weeks' gestation.

OBJECTIVE: To assess risk for preeclampsia (PE) based on maternal characteristics, mean arterial pressure (MAP) and uterine artery pulsatility index (Ut-PI) at 30-33 weeks' gestation. METHODS: Screening study in singleton pregnancies including 2,140 that subsequently developed PE and 83,615 that were unaffected by PE, gestational hypertension or delivery of small-for-gestational-age neonates (normal group). We developed a survival time model for the time of delivery for PE by combination of maternal characteristics and history with MAP and Ut-PI multiple of the median (MoM) values (biophysical test). Data on third-trimester MAP and Ut-PI were available in 350 cases of PE and 13,878 of the normal group. The detection rate of PE requiring delivery within 4, 6 and 8 weeks of the visit was estimated. RESULTS: In pregnancies with PE the log10 MoM values of MAP and Ut-PI were inversely related to gestational age at delivery. Biophysical testing detected 90, 65 and 53% of PE with delivery within 4, 6 and 8 weeks of the visit, at a fixed false-positive rate of 5%. INTERPRETATION: Testing by maternal characteristics, Ut-PI and MAP at 30-33 weeks could identify 90% of pregnancies developing PE and requiring delivery within the subsequent 4 weeks.

Competing risks model in screening for preeclampsia by biophysical and biochemical markers at 30-33 weeks' gestation.

OBJECTIVE: To assess the risk for preeclampsia (PE) by maternal characteristics, uterine artery pulsatility index (Ut-PI), mean arterial pressure (MAP), serum placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) at 30-33 weeks' gestation. METHODS: This was a screening study in singleton pregnancies including 2,140 that developed PE and 83,615 that were unaffected by PE. We developed a survival time model for the time of delivery for PE by combining maternal characteristics and history with Ut-PI, MAP, PlGF and sFlt-1 multiple of the median (MoM) values (combined test). Data on third-trimester MAP and Ut-PI were available in 350 cases of PE, and 13,878 unaffected pregnancies and data on PlGF and sFlt-1 were available in 118 cases of PE and 3,734 unaffected pregnancies. Modelled detection rate of all PE and PE requiring delivery within 4 and 6 weeks of the visit was estimated. RESULTS: Screening by the combined test would detect 66, 98 and 86% of all PE and PE requiring delivery within 4 and 6 weeks of the visit, respectively, at a false positive rate of 5%. INTERPRETATION: Screening by biophysical and biochemical testing at 30-33 weeks could identify most pregnancies developing PE and requiring delivery within the subsequent 4 weeks.