Preeclampsia In Nulliparous Women Research Articles

Prospective Validation of First-Trimester Screening for Preterm Preeclampsia in Nulliparous Women (PREDICTION Study).

Fetal Medicine Foundation (FMF) studies suggest that preterm preeclampsia can be predicted in the first trimester by combining biophysical, biochemical, and ultrasound markers and prevented using aspirin. We aimed to evaluate the FMF preterm preeclampsia screening test in nulliparous women. We conducted a prospective multicenter cohort study of nulliparous women recruited at 11 to 14 weeks. Maternal characteristics, mean arterial blood pressure, PAPP-A (pregnancy-associated plasma protein A), PlGF (placental growth factor) in maternal blood, and uterine artery pulsatility index were collected at recruitment. The risk of preterm preeclampsia was calculated by a third party blinded to pregnancy outcomes. Receiver operating characteristic curves were used to estimate the detection rate (sensitivity) and the false-positive rate (1-specificity) for preterm (<37 weeks) and for early-onset (<34 weeks) preeclampsia according to the FMF screening test and according to the American College of Obstetricians and Gynecologists criteria. We recruited 7554 participants including 7325 (97%) who remained eligible after 20 weeks of which 65 (0.9%) developed preterm preeclampsia, and 22 (0.3%) developed early-onset preeclampsia. Using the FMF algorithm (cutoff of ≥1 in 110 for preterm preeclampsia), the detection rate was 63.1% for preterm preeclampsia and 77.3% for early-onset preeclampsia at a false-positive rate of 15.8%. Using the American College of Obstetricians and Gynecologists criteria, the equivalent detection rates would have been 61.5% and 59.1%, respectively, for a false-positive rate of 34.3%. The first-trimester FMF preeclampsia screening test predicts two-thirds of preterm preeclampsia and three-quarters of early-onset preeclampsia in nulliparous women, with a false-positive rate of ≈16%. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02189148.

Early cost-effectiveness analysis of screening for preeclampsia in nulliparous women: A modelling approach in European high-income settings.

BackgroundPreeclampsia causes substantial maternal and perinatal morbidity and mortality and significant societal economic impact. Effective screening would facilitate timely and appropriate prevention and management of preeclampsia.ObjectivesTo develop an early cost-effectiveness analysis to assess both costs and health outcomes of a new screening test for preeclampsia from a healthcare payer perspective, in the United Kingdom (UK), Ireland, the Netherlands and Sweden.MethodsA decision tree over a 9-month time horizon was developed to explore the cost-effectiveness of the new screening test for preeclampsia compared to the current screening strategy. The new test strategy is being developed so that it can stratify healthy low risk nulliparous women early in pregnancy to either a high-risk group with a risk of 1 in 6 or more of developing preeclampsia, or a low-risk group with a risk of 1 in 100 or less. The model simulated 25 plausible scenarios in a hypothetical cohort of 100,000 pregnant women, in which the sensitivity and specificity of the new test were varied to set a benchmark for the minimum test performance that is needed for the test to become cost-effective. The input parameters and costs were mainly derived from published literature. The main outcome was incremental costs per preeclampsia case averted, expressed as an incremental cost-effectiveness ratio (ICER). Deterministic and probabilistic sensitivity analyses were conducted to assess uncertainty.ResultsBase case results showed that the new test strategy would be more effective and less costly compared to the current situation in the UK. In the Netherlands, the majority of scenarios would be cost-effective from a threshold of €50,000 per preeclampsia case averted, while in Ireland and Sweden, the vast majority of scenarios would be considered cost-effective only when a threshold of €100,000 was used. In the best case analyses, ICERs were more favourable in all four participating countries. Aspirin effectiveness, prevalence of preeclampsia, accuracy of the new screening test and cost of regular antenatal care were identified as driving factors for the cost-effectiveness of screening for preeclampsia.ConclusionThe results indicate that the new screening test for preeclampsia has potential to be cost-effective. Further studies based on proven accuracy of the test will confirm whether the new screening test is a cost-effective additional option to the current situation.

Routinely collected antenatal data for longitudinal prediction of preeclampsia in nulliparous women: a population-based study

The objective was to evaluate the sequentially updated predictive capacity for preeclampsia during pregnancy, using multivariable longitudinal models including data from antenatal care. This population-based cohort study in the Stockholm-Gotland Counties, Sweden, included 58,899 pregnancies of nulliparous women 2008–2013. Prospectively collected data from each antenatal care visit was used, including maternal characteristics, reproductive and medical history, and repeated measurements of blood pressure, weight, symphysis-fundal height, proteinuria, hemoglobin and blood glucose levels. We used a shared-effects joint longitudinal model including all available information up until a given gestational length (week 24, 28, 32, 34 and 36), to update preeclampsia prediction sequentially. Outcome measures were prediction of preeclampsia, preeclampsia with delivery < 37, and preeclampsia with delivery ≥ 37 weeks’ gestation. The area under the curve (AUC) increased with gestational length. AUC for preeclampsia with delivery < 37 weeks’ gestation was 0.73 (95% CI 0.68–0.79) at week 24, and increased to 0.87 (95% CI 0.84–0.90) in week 34. For preeclampsia with delivery ≥ 37 weeks’ gestation, the AUC in week 24 was 0.65 (95% CI 0.63–0.68), but increased to 0.79 (95% CI 0.78–0.80) in week 36. The addition of routinely collected clinical measurements throughout pregnancy improve preeclampsia prediction and may be useful to individualize antenatal care.

1134 Low dose aspirin administration in all nulliparous women with singleton pregnancy: a cost-effectiveness analysis

Preterm birth is a major risk factor for neonatal mortality. Studies show that aspirin decreases the development of preeclampsia in nulliparous women. Additionally, the ASPIRIN trial showed that aspirin initiation between 6 and 13 weeks gestation reduces preterm birth incidence. This study investigates the cost-effectiveness of aspirin initiation in the 1st trimester for prevention of preterm birth in nulliparous women. A cost-effectiveness model using TreeAge 2020 software was designed to compare maternal and neonatal outcomes of aspirin administration versus no aspirin administration in nulliparous women with singleton pregnancies. We used a theoretical cohort of 100,000 women. Outcomes included preterm delivery < 34 weeks, preterm delivery < 37 weeks, maternal death, hypertensive disorders, spontaneous abortion, intrauterine fetal demise, neonatal neurodevelopmental delay, and infant death. All values were derived from the literature. The willingness-to-pay threshold was $100,000/quality adjusted life year (QALY) and QALYs were discounted at a rate of 3%. Sensitivity analyses evaluated the power of our model. In our theoretical cohort, we found that aspirin prophylaxis in the 1st trimester would result in 523 fewer cases of preterm delivery < 37 weeks and 539 fewer cases of preterm delivery < 34 weeks. Additionally, there would be 3,873 decreased cases of hypertensive disorders. Aspirin therapy was the dominant strategy, resulting in increased QALYs and decreased costs, saving $194 million. Sensitivity analyses showed that the results were consistent over a wide range of assumptions. Even if there was less of a reduction in hypertensive disorders (baseline probability 0.057) than predicted with aspirin administration, there was still an impact in reduction of preterm deliveries. Our model found that aspirin initiation during the 1st trimester in all nulliparous women results in decreased rates of preterm delivery. These results are significant as it is cost effective to administer aspirin to all nulliparous singleton women regardless of hypertensive status.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

First-Trimester Preterm Preeclampsia Screening in Nulliparous Women: The Great Obstetrical Syndrome (GOS) Study

ObjectivesTo estimate the ability of a combination of first-trimester markers to predict preterm preeclampsia in nulliparous women. MethodsWe conducted a prospective cohort study of nulliparous women with singleton gestations, recruited between 110 and 136 weeks gestation. Data on the following were collected: maternal age; ethnicity; chronic diseases; use of fertility treatment; body mass index; mean arterial blood pressure (MAP); serum levels of pregnancy-associated plasma protein A (PAPP-A), placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), alpha fetoprotein (AFP), free beta human chorionic gonadotropin (ß-hCG); and mean uterine artery pulsatility index (UtA-PI). We constructed a proportional hazard model for the prediction of preterm preeclampsia selected based on the Akaike information criterion. A receiver operating characteristic curve was created with the predicted risk from the final model. Our primary outcome was preterm preeclampsia and our secondary outcome was a composite of preeclampsia, small for gestational age, intrauterine death, and preterm birth. ResultsAmong 4659 nulliparous women with singleton gestations, our final model included 4 variables: MAP MoM, log10PlGF MoM, log10AFP MoM and log10UtA-PI MoM. We obtained an area under the curve of 0.84 (95% CI 0.75–0.93) with a detection rate of preterm preeclampsia of 55% (95% CI 37%–73%) and a false-positive rate of 10%. Using a risk cut-off with a false-positive rate of 10%, the positive predictive value for our composite outcome was 33% (95% CI 29%–37%). ConclusionsThe combination of MAP, maternal serum PlGF and AFP, and UtA-PI are useful to identify nulliparous women at high risk of preterm preeclampsia but also at high risk of other great obstetrical syndromes.

External validation of a simple risk score based on the ASPRE trial algorithm for preterm pre-eclampsia considering maternal characteristics in nulliparous pregnant women: a multicentre retrospective cohort study.

To validate the performance of a first-trimester simple risk score based on the ASPRE trial algorithm for pre-eclampsia. Multicentre retrospective cohort analysis. Four Italian hospitals. Unselected nulliparous women at 11-13weeks of gestation from January 2014 through to January 2018. Model performance was evaluated based on discrimination and calibration. Delivery before 37weeks of gestation with a diagnosis of pre-eclampsia. Based on 73 preterm pre-eclampsia cases and 7546 controls (including 101 cases of late pre-eclampsia), the area under the receiver operating characteristics curve was 0.659 (95% CI 0.579-0.726). The sensitivity was 32.9% (95% CI 22.1-43.7) at a false-positive rate of 8.8%. The positive likelihood ratio was 3.74 (95% CI 2.67-5.23), the positive predictive value was 3.49% (95% CI 2.12-4.86%) and the negative predictive value was 99.3% (95% CI 99.1-99.5%). The sensitivity and positive likelihood ratio were approximately 40% lower than in the original study. The calibration analysis showed a good agreement between observed and expected risks (P=0.037). Comparison with the Fetal Medicine Foundation (FMF) algorithm yielded a difference in the area under the curve of 0.084 (P=0.007). In our Italian population, the simple risk score had a lower performance than expected for the prediction of preterm pre-eclampsia in nulliparous women. The FMF algorithm applied to the same data set resulted in a better prediction. Simple risk score predicts preterm pre-eclampsia in Italy.

Prediction of pre-eclampsia in nulliparous women using routinely collected maternal characteristics: a model development and validation study

BackgroundGuidelines recommend identifying in early pregnancy women at elevated risk of pre-eclampsia. The aim of this study was to develop and validate a pre-eclampsia risk prediction model for nulliparous women attending routine antenatal care “the Western Sydney (WS) model”; and to compare its performance with the National Institute of Health and Care Excellence (NICE) risk factor-list approach for classifying women as high-risk.MethodsThis retrospective cohort study included all nulliparous women who gave birth in three public hospitals in the Western-Sydney-Local-Health-District, Australia 2011–2014. Using births from 2011 to 2012, multivariable logistic regression incorporated established maternal risk factors to develop and internally validate the WS model. The WS model was then externally validated using births from 2013 to 2014, assessing its discrimination and calibration. We fitted the final WS model for all births from 2011 to 2014, and compared its accuracy in predicting pre-eclampsia with the NICE approach.ResultsAmong 12,395 births to nulliparous women in 2011–2014, there were 293 (2.4%) pre-eclampsia events. The WS model included: maternal age, body mass index, ethnicity, multiple pregnancy, family history of pre-eclampsia, autoimmune disease, chronic hypertension and chronic renal disease. In the validation sample (6201 births), the model c-statistic was 0.70 (95% confidence interval 0.65–0.75). The observed:expected ratio for pre-eclampsia was 0.91, with a Hosmer-Lemeshow goodness-of-fit test p-value of 0.20. In the entire study sample of 12,395 births, 374 (3.0%) women had a WS model-estimated pre-eclampsia risk ≥8%, the pre-specified risk-threshold for considering aspirin prophylaxis. Of these, 54 (14.4%) developed pre-eclampsia (sensitivity 18% (14–23), specificity 97% (97–98)). Using the NICE approach, 1173 (9.5%) women were classified as high-risk, of which 107 (9.1%) developed pre-eclampsia (sensitivity 37% (31–42), specificity 91% (91–92)). The final model showed similar accuracy to the NICE approach when using lower risk-threshold of ≥4% to classify women as high-risk for pre-eclampsia.ConclusionThe WS risk model that combines readily-available maternal characteristics achieved modest performance for prediction of pre-eclampsia in nulliparous women. The model did not outperform the NICE approach, but has the advantage of providing individualised absolute risk estimates, to assist with counselling, inform decisions for further testing, and consideration of aspirin prophylaxis.

406: Association between the new ACC/AHA stage 1 hypertension and insulin resistance in nulliparous women

The recent American College of Cardiology/American Heart Association (ACC/AHA) guidelines introduced stage 1 hypertension (HTN), defined as blood pressure (BP) of 130-139 mmHg systolic or 80-89 mmHg diastolic. The significance of this lower threshold in pregnancy is understudied. Given the association between maternal insulin resistance and adverse pregnancy outcomes, including preeclampsia, we aimed to determine whether stage 1 HTN before 20 weeks is associated with mid-trimester insulin resistance. Secondary analysis of a multicenter randomized trial of vitamin C/E vs placebo to prevent preeclampsia in nulliparous women. Women with two BPs≥135/85 or with a history or current use of anti-hypertensives were excluded from the trial. Women were randomized < 17 weeks and a subset had fasting plasma glucose and insulin tested at 22-26 weeks. Insulin resistance was calculated using indirect indices of homeostasis model assessment of insulin resistance (HOMA-IR) and the quantitative insulin sensitivity check (QUICKI). Women with stage 1 HTN before 20 weeks were compared with women without HTN using univariate and multivariate analyses controlling for BMI, race, treatment group, and gestational age at testing. Of the 1,178 women who had testing,142 (12%) hadstage 1 HTN before 20 weeks. Women with stage 1 HTN were older, more likely to be obese (BMI ≥30 kg/m2) and less likely to be Hispanic. Fasting maternal glucose, insulin, HOMA-IR, and QUICKI results did not differ between women with and without stage 1 hypertension (all p > 0.05). Results remained consistent in multivariate analyses. Compared with women without HTN, women with stage 1 HTN were not more likely to have HOMA-IR results ≥ 75thpercentile (adjusted odds ratio, 0.95; 95% confidence interval, 0.61-1.5) or QUICKI results ≤ 25thpercentile (adjusted odds ratio 0.98; 95% confidence interval 0.63 – 1.5). Stage 1 HTN before 20 weeks of gestation as defined by the new ACC/AHA guidelines is not significantly associated with mid-trimester insulin resistance.

Clinical risk assessment in early pregnancy for preeclampsia in nulliparous women: A population based cohort study.

ObjectiveTo evaluate the capacity of multivariable prediction of preeclampsia during pregnancy, based on detailed routinely collected early pregnancy data in nulliparous women.Design and settingA population-based cohort study of 62 562 pregnancies of nulliparous women with deliveries 2008–13 in the Stockholm-Gotland Counties in Sweden.MethodsMaternal social, reproductive and medical history and medical examinations (including mean arterial pressure, proteinuria, hemoglobin and capillary glucose levels) routinely collected at the first visit in antenatal care, constitute the predictive variables. Predictive models for preeclampsia were created by three methods; logistic regression models using 1) pre-specified variables (similar to the Fetal Medicine Foundation model including maternal factors and mean arterial pressure), 2) backward selection starting from the full suite of variables, and 3) a Random forest model using the same candidate variables. The performance of the British National Institute for Health and Care Excellence (NICE) binary risk classification guidelines for preeclampsia was also evaluated. The outcome measures were diagnosis of preeclampsia with delivery <34, <37, and ≥37 weeks’ gestation.ResultsA total of 2 773 (4.4%) nulliparous women subsequently developed preeclampsia. The pre-specified variables model was superior the other two models, regarding prediction of preeclampsia with delivery <34 and <37 weeks, both with areas under the curve of 0.68, and sensitivity of 30.6% (95% CI 24.5–37.2) and 29.2% (95% CI 25.2–33.4) at a 10% false positive rate, respectively. The performance of these customizable multivariable models at the chosen false positive rate, was significantly better than the binary NICE-guidelines for preeclampsia with delivery <37 and ≥37 weeks’ gestation.ConclusionMultivariable models in early pregnancy had a modest performance, although providing advantages over the NICE-guidelines, in predicting preeclampsia in nulliparous women. Use of a machine learning algorithm (Random forest) did not result in superior prediction.

Prediction of Preeclampsia in Nulliparous Women according to First Trimester Maternal Factors and Serum Markers

Objective: To evaluate the performance of maternal risk factors (BMI and mean arterial pressure [MAP]) and first-trimester maternal serum markers in the early prediction of preeclampsia (PE) in nulliparous women. Material and Methods: This was a case-cohort study based on a cohort of 14,207 nulliparous women. A total of 213 cases with term PE (from 37 weeks + 0 days) and 55 cases with preterm PE (before 37 weeks + 0 days) were identified and validated. Randomly, 449 controls were selected. Serum samples previously collected for the double test (pregnancy-associated plasma protein A [PAPP-A] and free β human chorionic gonadotrophin [hCGβ]) as part of the first-trimester screening program were retrieved and analyzed for placental growth factor (PlGF), soluble fms-like tyrosine kinase 1 (sFlt-1), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and neutrophil gelatinase-associated lipocalin (NGAL). Concentrations were transformed to multiples of the median (MoM). Multivariate regression analysis was used for prediction models. Receiver-operating characteristics (ROC) curves were used for evaluation of the screening performance. Results: In preterm PE, the PlGF (0.79 MoM), sFlt-1 (0.86 MoM), NGAL (1.15 MoM), and PAPP-A (0.89 MoM) medians were significantly altered. In term PE, PlGF (0.90 MoM) and NT-proBNP (0.86 MoM) medians were significantly reduced. The combination of MAP and PlGF yielded a 39% detection rate of preterm PE for a 10% false-positive rate. The combination of MAP, BMI, and PlGF yielded a 33% detection rate of term PE with a 10% false-positive rate. Conclusion: First-trimester MAP, maternal serum PlGF, and NGAL are markers of preterm PE. Maternal serum sFlt-1 is a significant marker of preterm PE, but only early in the first trimester. First-trimester maternal serum NT-proBNP is not a predictor of PE. Screening performance for PE with these markers individually or in combination is modest.

First-Trimester Uterine Artery Doppler for the Prediction of Preeclampsia in Nulliparous Women: The Great Obstetrical Syndrome Study.

This study aimed to estimate the performance of first-trimester uterine artery (UtA) pulsatility index (PI) for the prediction of preeclampsia (PE). We conducted a prospective cohort study of nulliparous women with singleton gestation at 11 to 13 6/7 weeks. UtA-Doppler's was performed on both UtAs and the mean UtA-PI was reported in multiple of median (MoM) adjusted for gestational age. Using receiver operating characteristic curves and their area under the curves (AUC); we calculated the performance of UtA-PI for the prediction of PE. Proportional hazard models were used to develop prediction models combining UtA-PI and maternal characteristics. Out of 4,676 participants with completed follow-up, 232 (4.9%) developed PE, including 202 (4.3%) term and 30 (0.6%) preterm PE. Mean UtA-PI decreased with gestational age between 11 and 13 6/7 weeks (p < 0.001). First-trimester UtA-PI was associated with preterm (AUC: 0.69; 95% CI [confidence interval]: 0.57-0.80) but not with term (AUC: 0.52; 95% CI: 0.48-0.56) PE. UtA-PI combined with maternal characteristics could predict 45% of preterm PE at a false positive rate of 10%. First-trimester UtA-PI decreases with gestational age between 11 and 13 6/7 weeks and is associated with the risk of preterm but not term PE.

First-Trimester Placental Growth Factor for the Prediction of Preeclampsia in Nulliparous Women: The Great Obstetrical Syndromes Cohort Study

Background: First-trimester maternal serum markers have been associated with preeclampsia (PE). We aimed to evaluate the performance of first-trimester placental growth factor (PlGF) for the prediction of PE in nulliparous women. Subjects and Methods: We conducted a prospective cohort study of nulliparous women with singleton pregnancy at 11–13 weeks. Maternal serum PlGF concentration was measured using B·R·A·H·M·S PlGFplus KRYPTOR automated assays and reported in multiple of the median adjusted for gestational age. We used proportional hazard models, along with receiver operating characteristic curves and areas under the curve (AUC). Results: Out of 4,652 participants, we observed 232 (4.9%) cases of PE including 202 (4.3%) term and 30 (0.6%) preterm PE. PlGF was associated with the risk of term (AUC = 0.61, 95% confidence interval [CI] 0.57–0.65) and preterm PE (AUC = 0.73, 95% CI 0.64–0.83). The models were improved with the addition of maternal characteristics (AUC for term PE 0.66, 95% CI 0.62–0.71; AUC for preterm PE 0.81, 95% CI 0.72–0.91; p < 0.01). At a false-positive rate of 10%, PlGF combined with maternal characteristics could have predicted 26% of term and 55% of preterm PE. The addition of pregnancy-associated plasma protein A did not significantly improve the prediction models. Conclusion: First-trimester PlGF combined with maternal characteristics is useful to predict preterm PE in nulliparous women.

Pregnancy Weight Gain Before Diagnosis and Risk of Preeclampsia: A Population-Based Cohort Study in Nulliparous Women.

Weight gain in early pregnancy may influence a woman's risk of developing preeclampsia. However, the consequences of weight gain throughout pregnancy up to the diagnosis of preeclampsia are unknown. The aim of this study was to determine whether pregnancy weight gain before the diagnosis of preeclampsia is associated with increased risks of preeclampsia (overall and by preeclampsia subtype). The study population included nulliparous pregnant women in the Swedish counties of Gotland and Stockholm, 2008 to 2013, stratified by early pregnancy body mass index category. Electronic medical records were linked with population inpatient and outpatient records to establish date of preeclampsia diagnosis (classified as any, early preterm <34 weeks, late preterm 34-36 weeks, or term ≥37 weeks). Antenatal weight gain measurements were standardized into gestational age-specific z scores. Among 62 705 nulliparous women, 2770 (4.4%) developed preeclampsia. Odds of preeclampsia increased by ≈60% with every 1 z score increase in pregnancy weight gain among normal weight and overweight women and by 20% among obese women. High pregnancy weight gain was more strongly associated with term preeclampsia than early preterm preeclampsia (eg, 64% versus 43% increased odds per 1 z score difference in weight gain in normal weight women, and 30% versus 0% in obese women, respectively). By 25 weeks, the weight gain of women who subsequently developed preeclampsia was significantly higher than women who did not (eg, 0.43 kg in normal weight women). In conclusion, high pregnancy weight gain before diagnosis increases the risk of preeclampsia in nulliparous women and is more strongly associated with later-onset preeclampsia than early-onset preeclampsia.

First-trimester mean arterial blood pressure and the risk of preeclampsia: The Great Obstetrical Syndromes (GOS) study.

To estimate the predictive value of first-trimester mean arterial pressure (MAP) for the hypertensive disorders of pregnancy (HDP). We performed a prospective cohort study of nulliparous women recruited at 110/7-136/7 weeks. MAP was calculated from blood pressure measured on both arms simultaneously using an automated device taking a series of recordings until blood pressure stability was reached. MAP was reported as multiples of the median adjusted for gestational age. Participants were followed for development of gestational hypertension (GH), preeclampsia (PE), preterm PE (<37 weeks) and early-onset (EO) PE (<34 weeks). Receiver operating characteristic curves and the area under the curve (AUC) were used to estimate the predictive values of MAP. Multivariate logistic regressions were used to develop predictive models combining MAP and maternal characteristics. We obtained complete follow-up in 4700 (99%) out of 4749 eligible participants. GH without PE was observed in 250 (5.3%) participants, and PE in 241 (5.1%), including 33 (0.7%) preterm PE and 10 (0.2%) EO-PE. First-trimester MAP was associated with GH (AUC: 0.77; 95%CI: 0.74-0.80); term PE (0.73; 95%CI: 0.70-0.76), preterm PE (0.80; 95%CI: 0.73-0.87) and EO-PE (0.79; 95%CI: 0.62-0.96). At a 10% false-positive rate, first-trimester MAP could have predicted 39% of GH, 34% of term PE, 48% of preterm PE and 60% of EO-PE. The addition of maternal characteristics improved the predictive values (to 40%, 37%, 55% and 70%, respectively). First-trimester MAP is a strong predictor of GH and PE in nulliparous women.

Maternal Characteristics for the Prediction of Preeclampsia in Nulliparous Women: The Great Obstetrical Syndromes (GOS) Study

ObjectiveLow-dose aspirin started in early pregnancy significantly reduces the risk of preeclampsia (PE) in high-risk women, especially preterm PE. This study aimed to evaluate the influence of maternal characteristics on the risk of PE in nulliparous women. MethodsThe Great Obstetrical Syndromes (GOS) study recruited nulliparous women with singleton pregnancies at 11 to 13 weeks. The following maternal characteristics were collected: age, BMI, ethnicity, chronic diseases, smoking, and assisted reproductive technologies. Relative weight analyses were conducted, and predictive multivariate proportional hazard models were constructed. Receiver operating characteristic curve analyses with their area under the curve (AUC) were used to evaluate the value of each factor for the prediction of PE and preterm PE. The study also evaluated the SOGC guidelines for identification of women at high risk of PE. ResultsOf 4739 participants, 232 (4.9%) developed PE, including 30 (0.6%) with preterm PE. In univariate analyses, only BMI was significantly associated with the risk of PE (AUC 0.60; 95% CI 0.55–0.65) and preterm PE (AUC 0.64; 95% CI 054–0.73). Adding other maternal characteristics to BMI had a non-significant and marginal impact on the discriminative ability to the models for PE (AUC 0.62; 95% CI 0.58–0.66) and preterm PE (AUC 0.65; 95% CI 0.56–0.74). At a false-positive rate of 10%, maternal characteristics could have predicted 23% of PE and 19% of preterm PE. The SOGC guidelines were not discriminant for PE (detecting 96% of PE and 93% of preterm PE with a 94% false-positive rate). ConclusionIn nulliparous women, BMI is the most discriminant maternal characteristic for the prediction of PE. Maternal characteristics should not be used alone to identify nulliparous women at high risk of PE.

Investigating Parity as a Risk Factor for Developing Preeclampsia in Gestational Diabetes Mellitus [36F

INTRODUCTION: It is well established that patients with Gestational Diabetes Mellitus (GDM) are at a greater risk of developing preeclampsia than those not diagnosed with GDM. It has also been shown that nulliparous women are at an increased risk of developing preeclampsia compared to multiparous women. This study investigates the role of parity as a risk factor for preeclampsia in patients already diagnosed with GDM. METHODS: A retrospective chart review was conducted at SUNY Downstate Medical Center. Exact Mantel-Haenszel tests of trend were conducted for the outcome of preeclampsia (yes vs. no) from the following predictors: number of full-term deliveries, number of pre-term deliveries, and number of spontaneous/elective abortions. Step-down Bonferroni corrections to p-values were applied to correct for multiple testing. RESULTS: 636 patients with GDM and no prior history of diabetes were included. The population was composed of 30.3% nulliparous patients with a median age of 31 y/o and 37 weeks 2 days at delivery. The multipara (69.7%) population was similar with a median age of 32 y/o and 37 weeks 2 days at delivery. The results revealed that the frequency of developing preeclampsia in nulliparous women with GDM was more than twice that of multiparous women (8.81 to 4.06, p=0.086). CONCLUSION: As this value was approaching statistical significance, it warrants the necessity of further investigation of nulliparity as a risk factor for preeclampsia in GDM patients. This research was created in the effort to help physicians understand which patients are more at risk for preeclampsia thus aiding in counseling and management.

INFLUENCE OF ANGIOTENSIN CONVERTING ENZYME GENE POLYMORPHISM ON PREGNANCY OUTCOME IN WOMEN WITH HISTORY OF PRE-ECLAMPSIA

Background: Women who have had pre-eclampsia (PE) are more prone to recurrent negative pregnancy outcomes and altered utero-placental and umbilical flows in their future pregnancy. In addition, to an increased risk of later cardiovascular diseases, which clearly suggest a shared aetiology. Yet, the mechanisms involved have not been identified. Although, the causes of PE are not well understood, there is a possibility that PE has, at least in part, a genetic basis. The physiological remodelling of spiral arteries throughout pregnancy is mediated by the rennin-angiotensin system (RAS). The ACE I/D polymorphism of the ACE gene accounted for 47% of total phenotypic variance of the serum Angiotensin converting enzyme (ACE), contributing much to the variability of the ACE level. Previous studies failed to reproduce a persistent link of ACE I/D genotype and PE in nulliparous women. Objective: In this prospective study, we analysed the association of the ACE genotype and the recurrence of PE and/or fetal growth restriction (FGR) in subsequent pregnancy in women at high risk for a previous PE as primipara, without other known risk conditions. Patients and Methods: Sixty women with history of PE as primipara, with no known risk factors apart from nulliparity, were recruited in their second pregnancy. Their ACE genotyping were detected. Uterine arteries resistance indices (RI) and umbilical artery pulsatility index (PI), were recorded at 16th, 20th, 24th weeks of gestation and clinical pregnancy outcome was analyzed, as well. Results: ACE I/D genotype distribution among our cases of 90 Egyptian pregnant women were compatible to other races in literature. DD genotype was detected in 41.1% of our cases, 34.4% were ID genotype and 24.4% were II genotype. Significant difference in ACE I/D genotype and D-allele frequency were observed in cases with recurrent PE and/or FGR. Mid trimester uterine arteries resistance indices (RI) at 16th, 20th, 24th weeks of gestation, and umbilical artery pulsatility index (PI) at 20th, 24th weeks were significantly higher in DD genotype group compared to ID and II genotype respectively. In addition, DD genotype group had significantly lower gestational age at time of delivery, lower birth weight and placental weight. Conclusion: ACE DD genotype and D- allele frequency adversely affected pregnancy outcome and utero-placental and umbilical flow velocimetry in women with history of preeclampsia as nulliparous without known risk factors apart from nulliparity.

Effect of vitamin D supplementation in the reduce risk of preeclampsia in nulliparous women.

Background:The exact role of vitamin D in the development and severity of preeclampsia is still unclear. The aim of the present study was to investigate the association between vitamin D supplement and preeclampsia in pregnant women.Materials and Methods:In this randomized controlled trial, in 2012, 140 nulliparous pregnant women in two groups received supplementation with 600 IU/day of vitamin D or supplementation free of vitamin D at 16 week gestation until the delivery. The main outcomes included the frequency of preeclampsia and subtypes by clinical severity and infant birth weight.Results:Mean of maternal age and gestational age at the delivery in all studied subjects were 25 ± 4.1 years and 37.4 ± 3 weeks, respectively, which were not statistically significant between the groups. Preeclampsia was observed in two subjects in case group compared to seven subjects in control group, which was not significant (P-value = 0.09). In case group, subjects with preeclampsia diagnosed as mild preeclampsia and in control group four subjects were mild, and three were severe. No significant differences were noted between the case and control groups in the frequency of preeclampsia subtypes by clinical severity. Infant birth weight in case group who was significantly higher than control group, which was statistically significant between groups (P-value = 0.09).Conclusion:In summary, our results demonstrated that vitamin D supplementation during the third trimester of pregnancy; despite the non-significant association between vitamin D supplementation and preeclampsia, reduce the risk of preeclampsia. However, further studies needs to be done.

Risk assessment for preeclampsia in nulliparous women at 11-13 weeks gestational age: prospective evaluation of two algorithms.

To evaluate two algorithms for prediction of preeclampsia in a population of nulliparous women in Norway. Prospective screening study. National Centre for Fetal Medicine in Trondheim, Norway. Five hundred and forty-one nulliparous women. The women were examined between 11(+0) and 13(+6) weeks with interviews for maternal characteristics and measurements of mean arterial pressure, uterine artery pulsatility index, pregnancy-associated plasma protein A and placental growth factor. The First Trimester Screening Program version 2.8 by The Fetal Medicine Foundation (FMF) was compared with the Preeclampsia Predictor TM version 1 revision 2 by Perkin Elmer (PREDICTOR). Prediction of preeclampsia requiring delivery before 37 weeks, before 42 weeks and late preeclampsia (delivery after 34 weeks). The performance of the two algorithms was similar, but quite poor, for prediction of preeclampsia requiring delivery before 42 weeks with an area under the curve of 0.77 (0.67-0.87) and sensitivity 40% (95% CI 19.1-63.9) at a fixed 10% false positive rate for FMF and 0.74 (0.63-0.84) and sensitivity 30% (95% CI 11.9-54.3) at a fixed 10% false positive rate for PREDICTOR. The FMF algorithm for preeclampsia requiring delivery <37 weeks had an area under the curve of 0.94 (0.86-1.0) and sensitivity of 80% (95% CI 28.4-99.5) at a 10% fixed false positive rate. Fetal Medicine Foundation and PREDICTOR algorithms had similar and only modest performance in predicting preeclampsia. The results indicate that the FMF algorithm is suitable for prediction of preterm preeclampsia.

Early pregnancy prediction of preeclampsia in nulliparous women, combining clinical risk and biomarkers: the Screening for Pregnancy Endpoints (SCOPE) international cohort study.

More than half of all cases of preeclampsia occur in healthy first-time pregnant women. Our aim was to develop a method to predict those at risk by combining clinical factors and measurements of biomarkers in women recruited to the Screening for Pregnancy Endpoints (SCOPE) study of low-risk nulliparous women. Forty-seven biomarkers identified on the basis of (1) association with preeclampsia, (2) a biological role in placentation, or (3) a role in cellular mechanisms involved in the pathogenesis of preeclampsia were measured in plasma sampled at 14 to 16 weeks' gestation from 5623 women. The cohort was randomly divided into training (n=3747) and validation (n=1876) cohorts. Preeclampsia developed in 278 (4.9%) women, of whom 28 (0.5%) developed early-onset preeclampsia. The final model for the prediction of preeclampsia included placental growth factor, mean arterial pressure, and body mass index at 14 to 16 weeks' gestation, the consumption of ≥3 pieces of fruit per day, and mean uterine artery resistance index. The area under the receiver operator curve (95% confidence interval) for this model in training and validation cohorts was 0.73 (0.70-0.77) and 0.68 (0.63-0.74), respectively. A predictive model of early-onset preeclampsia included angiogenin/placental growth factor as a ratio, mean arterial pressure, any pregnancy loss <10 weeks, and mean uterine artery resistance index (area under the receiver operator curve [95% confidence interval] in training and validation cohorts, 0.89 [0.78-1.0] and 0.78 [0.58-0.99], respectively). Neither model included pregnancy-associated plasma protein A, previously reported to predict preeclampsia in populations of mixed parity and risk. In nulliparous women, combining multiple biomarkers and clinical data provided modest prediction of preeclampsia.