Preterm Preeclampsia Research Articles

On the pathogenesis of preeclampsia: a new pre-pregnancy risk factor for preterm and term preeclampsia and evidence from recurrences supporting their common origin

On the pathogenesis of preeclampsia: a new pre-pregnancy risk factor for preterm and term preeclampsia and evidence from recurrences supporting their common origin

Repeat placental growth factor-based testing in women with suspected preterm pre-eclampsia: A multi-centre randomised controlled trial

Repeat placental growth factor-based testing in women with suspected preterm pre-eclampsia: A multi-centre randomised controlled trial

First trimester screening program for preterm preeclampsia prediction in an Italian obstetric population and aspirin prophylaxis: our preliminary results

First trimester screening program for preterm preeclampsia prediction in an Italian obstetric population and aspirin prophylaxis: our preliminary results

Adverse foetal outcomes in patients with increased risk of preterm preeclampsia in the first trimester of pregnancy: a prospective study

Adverse foetal outcomes in patients with increased risk of preterm preeclampsia in the first trimester of pregnancy: a prospective study

Association of pregnancy complications and postpartum maternal leukocyte telomeres in two diverse cohorts: a nested case-control study

BackgroundBiologic strain such as oxidative stress has been associated with short leukocyte telomere length (LTL), as well as with preeclampsia and spontaneous preterm birth, yet little is known about their relationships with each other. We investigated associations of postpartum maternal LTL with preeclampsia and spontaneous preterm birth.MethodsThis pilot nested case control study included independent cohorts of pregnant people with singleton gestations from two academic institutions: Cohort 1 (hereafter referred to as Suburban) were enrolled prior to 20 weeks’ gestation between 2012 and 2018; and Cohort 2 (hereafter referred to as Urban) were enrolled at delivery between 2000 and 2012. Spontaneous preterm birth or preeclampsia were the selected pregnancy complications and served as cases. Cases were compared with controls from each study cohort of uncomplicated term births. Blood was collected between postpartum day 1 and up to 6 months postpartum and samples were frozen, then simultaneously thawed for analysis. Postpartum LTL was the primary outcome, measured using quantitative polymerase chain reaction (PCR) and compared using linear multivariable regression models adjusting for maternal age. Secondary analyses were done stratified by mode of delivery and self-reported level of stress during pregnancy.Results156 people were included; 66 from the Suburban Cohort and 90 from the Urban Cohort. The Suburban Cohort was predominantly White, Hispanic, higher income and the Urban Cohort was predominantly Black, Haitian, and lower income. We found a trend towards shorter LTLs among people with preeclampsia in the Urban Cohort (6517 versus 6913 bp, p = 0.07), but not in the Suburban Cohort. There were no significant differences in LTLs among people with spontaneous preterm birth compared to term controls in the Suburban Cohort (6044 versus 6144 bp, p = 0.64) or in the Urban Cohort (6717 versus 6913, p = 0.37). No differences were noted by mode of delivery. When stratifying by stress levels in the Urban Cohort, preeclampsia was associated with shorter postpartum LTLs in people with moderate stress levels (p = 0.02).ConclusionOur exploratory results compare postpartum maternal LTLs between cases with preeclampsia or spontaneous preterm birth and controls in two distinct cohorts. These pilot data contribute to emerging literature on LTLs in pregnancy.

P-782 Are pregnancy complications associated with the method of conception in female same-sex couples? Results of a retrospective, matched cohort study comparing ROPA and IUI

Abstract Study question Are pregnancies in female same-sex couples at a higher risk when using reception of oocytes from partner (ROPA) compared to those following intrauterine insemination (IUI)? Summary answer In female same-sex couples, pregnancies following ROPA demonstrated a higher incidence of preterm birth and first-trimester bleeding. What is known already Reception of Oocytes from PArtner (ROPA) enables both partners to contribute biologically to the desired pregnancy. However, oocyte donation, often performed in case of (premature) ovarian failure, is associated with an increased risk of hypertensive disorders of pregnancy/preeclampsia. Female same-sex couples typically comprising healthy, young women without underlying subfertility problems, are a priori at low absolute risk for pregnancy complications. Few studies have investigated the incidence of pregnancy complications and/or obstetrical outcomes in this specific group of women. Further insights and formal data could guide clinicians and patients in making informed decisions regarding the preferred method of conception. Study design, size, duration A retrospective, single-center, matched cohort study was performed including 577 unique female same-sex couples using donor semen who became pregnant after reproductive treatment (88 pregnancies following ROPA and 489 following IUI). None of the patients who opted for ROPA had (failed) IUI before. The study covered the period from January 2015 to January 2023. Participants/materials, setting, methods Pregnancies following ROPA were matched with pregnancies following IUI for age (+/-4 years), BMI (+/-4 kg/m2), parity (nulliparous vs multiparous) and date of embryo transfer/IUI (+/-1year) in a 1:1 ratio. Statistical Package for Social Sciences (SPSS) v26.0 was used for statistical analysis. Kolmogorov-Smirnov test was used to evaluate the normal distribution of continuous variables. Normally distributed data were analyzed with the student t-test and categorical variables were analyzed with the chi-square test. Main results and the role of chance After matching, 154 pregnancies (77 ROPA versus 77 IUI) were eligible for the study. Age (mean age 31.4±4.0 for ROPA versus 31.2±4.3 years for IUI, p = 0.48) and BMI (24.5±3.9 kg/m2 versus 25.2±4.4 kg/m2, for respectively ROPA versus IUI, p = 0.32) were comparable between groups after matching. Two ROPA pregnancies were excluded from further analysis due to elective termination of pregnancy (radiusaplasia and trisomy 21). Both groups experienced two stillbirths (two unexplained mors in utero, one chorioamnionitis and one intrapartum death). No significant difference in hypertensive disorders of pregnancy (HDP) (10.7% (8/75) versus 13.7% (10/73) for ROPA and IUI respectively, p = 0.53) or preeclampsia rates (11.0% (8/73) and 6.7% (5/75) for ROPA and IUI respectively, p = 0.33) was observed. ROPA-associated preeclampsia cases were often preterm (<37weeks’ gestation) compared to IUI (5/8 versus 1/5). ROPA pregnancies had a higher incidence of preterm birth (15.1% vs 1.3%,p<0.002) and first trimester bleeding was significantly more frequent (12.3% vs 0%,p<0.001). No statistically significant differences were observed between groups in neonatal weight, fetal structural malformations and cesarean section delivery rates. Limitations, reasons for caution The study is limited by its retrospective design and inherent bias. Despite reducing the sample size, matching enhanced study robustness. Recognized risk factors for hypertensive disorder of pregnancy, like the use of donor sperm, may mitigate differences associated with conception methods in this population. Wider implications of the findings The study points out potentially increased obstetrical risks following ROPA. These data are crucial to counsel and guide female same-sex couples in their decision regarding the method of conception. The risk of hypertensive disorders of pregnancy, specifically preterm preeclampsia, associated with ROPA warrants further attention, urging larger prospective studies. Trial registration number not applicable

First trimester screening program for preterm preeclampsia prediction in an Italian obstetric population and aspirin prophylaxis: our preliminary results

First trimester screening program for preterm preeclampsia prediction in an Italian obstetric population and aspirin prophylaxis: our preliminary results

Adverse foetal outcomes in patients with increased risk of preterm preeclampsia in the first trimester of pregnancy: a prospective study

Adverse foetal outcomes in patients with increased risk of preterm preeclampsia in the first trimester of pregnancy: a prospective study

Implementation of First-Trimester Screening and Prevention of Preeclampsia: A Stepped Wedge Cluster-Randomized Trial in Asia.

This trial aimed to assess the efficacy, acceptability, and safety of a first-trimester screen-and-prevent strategy for preterm preeclampsia in Asia. Between August 1, 2019, and February 28, 2022, this multicenter stepped wedge cluster randomized trial included maternity/diagnostic units from 10 regions in Asia. The trial started with a period where all recruiting centers provided routine antenatal care without study-related intervention. At regular 6-week intervals, one cluster was randomized to transit from nonintervention phase to intervention phase. In the intervention phase, women underwent first-trimester screening for preterm preeclampsia using a Bayes theorem-based triple-test. High-risk women, with adjusted risk for preterm preeclampsia ≥1 in 100, received low-dose aspirin from <16 weeks until 36 weeks. Overall, 88.04% (42 897 of 48 725) of women agreed to undergo first-trimester screening for preterm preeclampsia. Among those identified as high-risk in the intervention phase, 82.39% (2919 of 3543) received aspirin prophylaxis. There was no significant difference in the incidence of preterm preeclampsia between the intervention and non-intervention phases (adjusted odds ratio [aOR], 1.59 [95% CI, 0.91-2.77]). However, among high-risk women in the intervention phase, aspirin prophylaxis was significantly associated with a 41% reduction in the incidence of preterm preeclampsia (aOR, 0.59 [95% CI, 0.37-0.92]). In addition, it correlated with 54%, 55%, and 64% reduction in the incidence of preeclampsia with delivery at <34 weeks (aOR, 0.46 [95% CI, 0.23-0.93]), spontaneous preterm birth <34 weeks (aOR, 0.45 [95% CI, 0.22-0.92]), and perinatal death (aOR, 0.34 [95% CI, 0.12-0.91]), respectively. There was no significant between-group difference in the incidence of aspirin-related severe adverse events. The implementation of the screen-and-prevent strategy for preterm preeclampsia is not associated with a significant reduction in the incidence of preterm preeclampsia. However, low-dose aspirin effectively reduces the incidence of preterm preeclampsia by 41% among high-risk women. The screen-and-prevent strategy for preterm preeclampsia is highly accepted by a diverse group of women from various ethnic backgrounds beyond the original population where the strategy was developed. These findings underpin the importance of the widespread implementation of the screen-and-prevent strategy for preterm preeclampsia on a global scale. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03941886.

Prediction model of preeclampsia using machine learning based methods: a population based cohort study in China.

Preeclampsia is a disease with an unknown pathogenesis and is one of the leading causes of maternal and perinatal morbidity. At present, early identification of high-risk groups for preeclampsia and timely intervention with aspirin is an effective preventive method against preeclampsia. This study aims to develop a robust and effective preeclampsia prediction model with good performance by machine learning algorithms based on maternal characteristics, biophysical and biochemical markers at 11-13+6 weeks' gestation, providing an effective tool for early screening and prediction of preeclampsia. This study included 5116 singleton pregnant women who underwent PE screening and fetal aneuploidy from a prospective cohort longitudinal study in China. Maternal characteristics (such as maternal age, height, pre-pregnancy weight), past medical history, mean arterial pressure, uterine artery pulsatility index, pregnancy-associated plasma protein A, and placental growth factor were collected as the covariates for the preeclampsia prediction model. Five classification algorithms including Logistic Regression, Extra Trees Classifier, Voting Classifier, Gaussian Process Classifier and Stacking Classifier were applied for the prediction model development. Five-fold cross-validation with an 8:2 train-test split was applied for model validation. We ultimately included 49 cases of preterm preeclampsia and 161 cases of term preeclampsia from the 4644 pregnant women data in the final analysis. Compared with other prediction algorithms, the AUC and detection rate at 10% FPR of the Voting Classifier algorithm showed better performance in the prediction of preterm preeclampsia (AUC=0.884, DR at 10%FPR=0.625) under all covariates included. However, its performance was similar to that of other model algorithms in all PE and term PE prediction. In the prediction of all preeclampsia, the contribution of PLGF was higher than PAPP-A (11.9% VS 8.7%), while the situation was opposite in the prediction of preterm preeclampsia (7.2% VS 16.5%). The performance for preeclampsia or preterm preeclampsia using machine learning algorithms was similar to that achieved by the fetal medicine foundation competing risk model under the same predictive factors (AUCs of 0.797 and 0.856 for PE and preterm PE, respectively). Our models provide an accessible tool for large-scale population screening and prediction of preeclampsia, which helps reduce the disease burden and improve maternal and fetal outcomes.

Comparison of different methods of first-trimester screening for preterm pre-eclampsia: cohort study.

To compare the predictive performance of three different mathematical models for first-trimester screening of pre-eclampsia (PE), which combine maternal risk factors with mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and serum placental growth factor (PlGF), and two risk-scoring systems. This was a prospective cohort study performed in eight fetal medicine units in five different regions of Spain between September 2017 and December 2019. All pregnant women with singleton pregnancy and a non-malformed live fetus attending their routine ultrasound examination at 11 + 0 to 13 + 6 weeks' gestation were invited to participate in the study. Maternal characteristics and medical history were recorded and measurements of MAP, UtA-PI, serum PlGF and pregnancy-associated plasma protein-A (PAPP-A) were converted into multiples of the median (MoM). Risks for term PE, preterm PE (< 37 weeks' gestation) and early PE (< 34 weeks' gestation) were calculated according to the FMF competing-risks model, the Crovetto et al. logistic regression model and the Serra et al. Gaussian model. PE classification was also performed based on the recommendations of the National Institute for Health and Care Excellence (NICE) and the American College of Obstetricians and Gynecologists (ACOG). We estimated detection rates (DR) with their 95% CIs at a fixed 10% screen-positive rate (SPR), as well as the area under the receiver-operating-characteristics curve (AUC) for preterm PE, early PE and all PE for the three mathematical models. For the scoring systems, we calculated DR and SPR. Risk calibration was also assessed. The study population comprised 10 110 singleton pregnancies, including 32 (0.3%) that developed early PE, 72 (0.7%) that developed preterm PE and 230 (2.3%) with any PE. At a fixed 10% SPR, the FMF, Crovetto et al. and Serra et al. models detected 82.7% (95% CI, 69.6-95.8%), 73.8% (95% CI, 58.7-88.9%) and 79.8% (95% CI, 66.1-93.5%) of early PE; 72.7% (95% CI, 62.9-82.6%), 69.2% (95% CI, 58.8-79.6%) and 74.1% (95% CI, 64.2-83.9%) of preterm PE; and 55.1% (95% CI, 48.8-61.4%), 47.1% (95% CI, 40.6-53.5%) and 53.9% (95% CI, 47.4-60.4%) of all PE, respectively. The best correlation between predicted and observed cases was achieved by the FMF model, with an AUC of 0.911 (95% CI, 0.879-0.943), a slope of 0.983 (95% CI, 0.846-1.120) and an intercept of 0.154 (95% CI, -0.091 to 0.397). The NICE criteria identified 46.7% (95% CI, 35.3-58.0%) of preterm PE at 11% SPR and ACOG criteria identified 65.9% (95% CI, 55.4-76.4%) of preterm PE at 33.8% SPR. The best performance of screening for preterm PE is achieved by mathematical models that combine maternal factors with MAP, UtA-PI and PlGF, as compared to risk-scoring systems such as those of NICE and ACOG. While all three algorithms show similar results in terms of overall prediction, the FMF model showed the best performance at an individual level. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Does metformin prolong pregnancy in preterm pre-eclampsia? A study protocol for a South African, hospital-based double-blind, randomised, placebo-controlled trial

IntroductionPreterm pre-eclampsia is a leading cause of maternal morbidity and mortality. The Pre-eclampsia Intervention 2 (PI 2) trial suggested that metformin sustained release (XR) may prolong gestation by a week...

High Transferability of Neutralizing Antibodies against SARS-CoV-2 to Umbilical Cord Blood in Pregnant Women Vaccinated with BNT162b2 XBB.1.5: A Retrospective Cohort Study.

Coronavirus disease 2019 (COVID-19) can lead to severe respiratory illness, rapid disease progression, and higher rates of intensive care unit admission in pregnant women. Infection during pregnancy is associated with an increased risk of preterm delivery, cesarean section, fetal dysfunction, preeclampsia, and perinatal death. Vertical transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from pregnant women to their fetuses has also been observed. Although severe infections in neonates and infants are rare, newborns can experience serious consequences from COVID-19 due to their suboptimal humoral immune system protection. The amino acids in the structural proteins of SARS-CoV-2 are constantly mutating. Since around January 2023, COVID-19, caused by omicron-type SARS-CoV-2 variants, has been prevalent globally. These variants can evade the immune response triggered by traditional mRNA-based COVID-19 vaccines, such as BNT162b2. Therefore, vaccination with BNT162b2 XBB.1.5, which provides protection against omicron-type SARS-CoV-2 variants, is recommended. This retrospective cohort study included 148 pregnant women who received the BNT162b2 XBB.1.5 vaccine at 30 partner medical institutions from September 2023 to January 2024. We examined the titers of anti-spike glycoprotein SARS-CoV-2 immunoglobin G (IgG) and IgA in the blood and umbilical cord blood obtained from the participants using ELISA. Anti-spike glycoprotein SARS-CoV-2 IgG and IgA titers were highest in the blood and cord blood at late gestational age (28-34 weeks). No serious side effects or adverse events were observed in either the pregnant women or their newborns. Pregnant women who received the BNT162b2 XBB.1.5 vaccine during gestational weeks 28 to 34 had the highest titers of anti-omicron SARS-CoV-2 variant antibodies in their blood. Moreover, these antibodies were transferred to their umbilical cord blood. To validate our findings, large cohort clinical studies involving numerous pregnant women are warranted. This study was funded by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS) and Grants-in-Aid for Medical Research from the Japan Agency for Medical Research and Development (AMED).

Planned Delivery or Expectant Management for Late Preterm Pre-Eclampsia in Low-Income and Middle-Income Countries (CRADLE-4): A Multicenter, Open-Label, Randomized Controlled Trial

(Lancet. 2023;402:386–396) Pre-eclampsia is a relatively common condition and poses a disproportionately high risk to women in low-income and middle-income countries where it is a leading cause of maternal morbidity and mortality, estimated to have caused more than 42,000 deaths. The only known treatment is delivery, but there are also risks associated with preterm delivery that can contribute to both maternal and neonatal outcomes. Evidence suggests delivery at 37 weeks optimizes outcomes for both mother and infant, but there is little evidence about delivery in the late preterm gestational period leading up to that, between 34 and 36 and 6/7 weeks. Research in higher income settings has shown that fetal death in these cases is rare, but there are factors in such settings that are unavailable or unrealistic in low-income and middle-income settings. This study aimed to address the gap in knowledge by assessing outcomes related to planned delivery between 34 and 37 weeks in women with pre-eclampsia compared with expectant management during the same gestational period in India and Zambia.

Left Atrial Mechanics Following Preeclamptic Pregnancy.

Preterm preeclampsia is a pregnancy complication associated with myocardial dysfunction and premature cardiovascular disease morbidity and mortality. Left atrial (LA) strain is a noninvasive index of left ventricular end diastolic pressure and an early marker of heart failure risk. This study aimed to evaluate LA strain during the postpartum period in participants with and without preterm preeclampsia and to assess whether this varied in the presence of hypertension, cardiac dysfunction or both. In this longitudinal cohort study, 321 women from 28 hospitals with preterm preeclampsia (cases) underwent cardiovascular assessment 6 months postpartum. This is a secondary analysis of the PHOEBE study (ISRCTN01879376). An uncomplicated pregnancy control group (n=30) was recruited from a single center for comparison. A full cross-sectional transthoracic echocardiogram was performed, and from these images, the myocardial strain of the left atrium, including reservoir, conduit, and contractile strain, as well as LA stiffness, were calculated. At 6 months postpartum, compared with controls, prior preeclampsia was associated with a significantly attenuated LA reservoir, conduit, and contractile strain, as well as increased LA stiffness (all P<0.001). LA strain was further reduced in preeclamptic women who had and had not developed hypertension, systolic, or diastolic dysfunction at 6 months postpartum (all P<0.05). LA mechanics were significantly attenuated at 6 months postpartum in participants with preterm preeclampsia, whether or not they remained hypertensive or had evidence of ventricular dysfunction. Further studies are needed to determine whether postnatal LA strain may identify women at greater risk for future cardiovascular disease.

Genetic polymorphisms associated with adverse pregnancy outcomes in nulliparas

Adverse pregnancy outcomes (APOs) affect a large proportion of pregnancies and represent an important cause of morbidity and mortality worldwide. Yet the pathophysiology of APOs is poorly understood, limiting our ability to prevent and treat these conditions. To search for genetic markers of maternal risk for four APOs, we performed multi-ancestry genome-wide association studies (GWAS) for pregnancy loss, gestational length, gestational diabetes, and preeclampsia. We clustered participants by their genetic ancestry and focused our analyses on three sub-cohorts with the largest sample sizes: European, African, and Admixed American. Association tests were carried out separately for each sub-cohort and then meta-analyzed together. Two novel loci were significantly associated with an increased risk of pregnancy loss: a cluster of SNPs located downstream of the TRMU gene (top SNP: rs142795512), and the SNP rs62021480 near RGMA. In the GWAS of gestational length we identified two new variants, rs2550487 and rs58548906 near WFDC1 and AC005052.1, respectively. Lastly, three new loci were significantly associated with gestational diabetes (top SNPs: rs72956265, rs10890563, rs79596863), located on or near ZBTB20, GUCY1A2, and RPL7P20, respectively. Fourteen loci previously correlated with preterm birth, gestational diabetes, and preeclampsia were found to be associated with these outcomes as well.

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.

Repeat Placental Growth Factor-Based Testing in Women With Suspected Preterm Preeclampsia: A Stratified Analysis of the PARROT-2 Trial.

PlGF (placental growth factor)-based testing reduces severe maternal adverse outcomes. Repeat PlGF-based testing is not associated with improved perinatal or maternal outcomes. This planned secondary analysis aimed to determine whether there is a subgroup of women who benefit from repeat testing. Pregnant individuals with suspected preterm preeclampsia were randomized to repeat revealed PlGF-based testing, compared with usual care where testing was concealed. Perinatal and maternal outcomes were stratified by trial group, by initial PlGF-based test result, and by PlGF-based test type (PlGF or sFlt-1 [soluble fms-like tyrosine kinase-1]/PlGF ratio). A total of 1252 pregnant individuals were included. Abnormal initial PlGF-based test identified a more severe phenotype of preeclampsia, at increased risk of adverse maternal and perinatal outcomes. Repeat testing was not significantly associated with clinical benefit in women with abnormal initial results. Of women with a normal initial result, 20% developed preeclampsia, with the majority at least 3 to 4 weeks after initial presentation. Repeat test results were more likely to change from normal to abnormal in symptomatic women (112/415; 27%) compared with asymptomatic women (163/890; 18%). A higher proportion of symptomatic women who changed from normal to abnormal were diagnosed with preeclampsia, compared with asymptomatic women. Our results do not demonstrate evidence of the clinical benefit of repeating PlGF-based testing if the initial result is abnormal. Judicious use of repeat PlGF-based testing to stratify risk may be considered at least 2 weeks after a normal initial test result, particularly in women who have symptoms or signs of preeclampsia. URL: https://www.isrctn.com/ISRCTN85912420; Unique identifier: ISRCTN85912420.

Preterm preeclampsia as an independent risk factor for thromboembolism in a large national cohort

BackgroundPreterm preeclampsia, a product of vascular dysfunction, is associated with prolonged hospital admission and proteinuria, significant risk factors for thromboembolism in pregnancy. The risk of thromboembolism in preterm preeclampsia warrants further investigation. ObjectivesTo determine the relationship between preterm preeclampsia and thromboembolic risk. We hypothesize that preterm preeclampsia is an independent risk factor for thromboembolism in pregnancy. Study DesignThis is a retrospective cohort study using the National Inpatient Sample database via HCUP-AHRQ from 2017-2019. All subjects with an ICD-10 code for pregnancy or peripartum encounter were included. Subjects were excluded if gestational age at delivery was less than 20 weeks or if they had a history of thromboembolism, inherited thrombophilia, or antiphospholipid syndrome. Patients with preterm (delivered less than 37 weeks) preeclampsia and term (delivered 37 weeks or greater) preeclampsia were compared to those without preeclampsia. The primary outcome was a composite of any thromboembolic event, including pulmonary embolism, deep vein thrombosis, cerebral thrombosis/transient ischemic attack (TIA), or other thromboses. The secondary outcomes were rates of each individual type of thromboembolic event. The groups were compared via analysis of variance, chi-squared, and logistic regression analyses. The logistic regression included those variables that differed between groups with p<0.05. ResultsOf individuals in the database more than 2.2 million met inclusion criteria. A total of 56,446 (2.7%) had preterm preeclampsia and 86,152 (6.7%) had term preeclampsia. Those with preterm preeclampsia were more likely to be older, identify as non-Hispanic black, be obese, have chronic hypertension among other chronic diseases, and be in the lowest quartile of income (p<0.001). Among patients with preterm preeclampsia, 0.32% experienced thromboembolism while those with term preeclampsia and without preeclampsia experienced thromboembolism 0.10% and 0.09%, respectively. After controlling for confounders that differed between groups with p<0.05, preterm preeclampsia remained independently associated with any thromboembolic event (aOR 2.21 95%CI 1.84-2.65) as well as each individual type of thromboembolism. Term preeclampsia was not associated with an increased risk of thromboembolism (aOR 1.18, 95%CI 0.94-1.48). ConclusionPreterm preeclampsia is independently associated with an increased risk of thromboembolic events.

Prepregnancy physiology and subsequent preterm preeclampsia

BackgroundPreeclampsia is a common pregnancy complication with debated etiology. ObjectiveTo evaluate the contribution of prepregnancy physiology, biochemistry and anthropometrics to the subsequent development of preterm preeclampsia. Study DesignOne-hundred twenty-four participants were recruited through open recruitment and targeted mailings. Participants included 81 nulliparous women and 43 with a history of preterm preeclampsia. We characterized cardiovascular function, metabolic profile, and body composition in 100 non-pregnant women who went on to subsequent pregnancy. Measures included plasma volume, baseline cardiovascular function and cardiovascular response to volume challenge, body composition and circulating biochemical measures. Pregnancy outcome was obtained through chart review. Prepregnancy metrics for women who developed preterm preeclampsia were compared with measurements for those who did not, with adjustment for a history of prior preterm preeclampsia. Logistic regression modeling was used to identify the strongest prepregnancy factors associated with preterm preeclampsia. ResultsPregnancy outcomes included 11 women with preterm preeclampsia, 7 women with term preeclampsia, 20 women with other hypertension affecting their pregnancy, and 62 with uncomplicated pregnancies. We observed no difference in maternal age, study cycle day, lean body mass, uterine hemodynamics, or flow mediated dilation across groups. Women with preterm preeclampsia had greater android fat content 3215+1143 vs. 1918+1510 grams (p=0.002), faster supine pulse, 77+7 vs. 67+10 beats per minute (p=0.001), higher supine diastolic blood pressure 82+6 vs. 68+6 mmHg (p< 0.001), increased cardiac output 5.6+1.1 vs. 4.6+1 L/min (p=0.002), faster aortic-popliteal pulse wave velocity 4.5+0.7 vs. 3.8+0.5 m/sec (p<0.001), and exaggerated cardiac output response to volume challenge 20+9 vs. 9+12 L/min (p=0.002) compared to those with other pregnancy outcomes. Women who developed preterm preeclampsia also had reduced renal vascular resistance index 0.86+0.08 vs. 0.97+0.12 (p=0.005) compared with other pregnancy outcomes when assessed prior to pregnancy. Women with subsequent preterm preeclampsia had higher serum c-reactive protein 10.7+12.5 vs. 4.1+5.8mg/mL (p=0.003) and greater insulin resistance, as assessed by HOMA-IR calculation 2.2+1.1 vs. 1.2+0.9 (p<0.001). ConclusionPrepregnancy physiology is linked to subsequent preterm preeclampsia. The same factors associated with metabolic syndrome are more prominent in patients who develop preterm pre-eclampsia than those who do not, including increased vessel stiffness, low vascular compliance, high cardiac output, reduced renal vascular resistance index, insulin resistance and increased android fat, all consistent with subclinical features of the metabolic syndrome.