Risk Of Preterm Preeclampsia Research Articles

744: Aspirin strategies for preeclampsia prevention: a cost-effectiveness analysis

To evaluate the cost-effectiveness of aspirin (ASA) prophylaxis guided by biomarker values and ultrasound indices for preeclampsia prevention compared to approaches based on clinical risk assessment. We designed a decision analysis model to compare the costs and effectiveness of four strategies to guide ASA use in pregnancy: (1) biomarkers and ultrasound risk assessment (2) the United States Preventive Services Task Force (USPSTF) risk factor based approach, (3) universal ASA, and (4) no ASA. In the base case model, we assumed that ASA reduced the risk of preterm preeclampsia by 61% but did not reduce the risk of term preeclampsia. Sensitivity analyses that varied these and other assumptions were performed to assess the model’s robustness. Threshold analyses were performed to identify the costs and risks of ASA-related complications (e.g., gastrointestinal bleeding and respiratory sensitivity) at which the preferred strategy shifted. The primary outcome was the incremental cost effectiveness ratio (ICER) defined as the cost needed to avert one case of preeclampsia. An ICER less than 100,000 USD was considered cost-effective based on literature describing maternal and neonatal costs associated with preeclampsia. Under baseline estimates, universal ASA use is the dominant strategy (i.e., costs the least and provides the greatest health benefit). For every 100,000 women, universal ASA use would save $19,216,551 and result in 308 fewer cases of preeclampsia compared to ASA use guided by biomarker and ultrasound risk assessment (Table 1). In univariate and multivariate analyses, the model was sensitive only to the probability of ASA administration. When ASA use in the universal strategy was below 55%, following USPSTF guidelines became more cost effective. Threshold analysis revealed that only when the rate of GI bleeding with ASA exceeded 0.94% or the rate of respiratory complications exceeded 38% was universal ASA no longer the dominant strategy. In a Monte Carlo analysis, universal ASA was the most cost-effective strategy in 89% of simulations. Universal aspirin administration, as compared to several other strategies for preeclampsia risk assessment and selected ASA use is a dominant strategy across a broad range of relevant probabilities.

Risk assessment for preterm preeclampsia in first trimester: Comparison of three calculation algorithms

ObjectiveTo better adjust the risk for preeclampsia, multifactorial models in first trimester of pregnancy have found the way in clinical practice. This study compares the available test algorithms. Study designIn a cross-sectional study between November 2013 and April 2016 we compared the tests results of three first trimester testing algorithms for preeclampsia in 413 women. Risk for preterm preeclampsia was calculated with three different algorithms: Preeclampsia Predictor™ Software by PerkinElmer (PERK), ViewPoint® Software by GE Healthcare (VP) and the online calculator of the Fetal Medicine Foundation (FMF).We analyzed the data descriptively and determined Cohen's Kappa to assess the agreement among the algorithms. ResultsVP classified 89(21.5%) women, PERK 43(10.4%) women and FMF 90 (21.8%) women as having high risk for preterm preeclampsia (<34 weeks of gestation for VP and PERK and <37 weeks of gestation for FMF). Agreement between tests ranged from moderate to substantial (PERK/VP: κ = 0.56, PERK/ FMF: κ = 0.50, and VP/ FMF: κ = 0.72). ConclusionThe three algorithms are similar but not equal. This may depend on chosen cut off, but also on test properties. This study cannot decide which algorithm is the best, but differences in results and cut offs should be taken into account.

Aspirin versus placebo in pregnancies at high risk for preterm pre-eclampsia.

A recent multicentre placebo-controlled trial by Rolnick etal. has indicated that taking 150 mg aspirin daily in women at high risk of pre-eclampsia reduced the incidence of the disease from 4.3% to 1.5% in comparison with placebo. Although the findings of this study are important, a high proportion of women withdrew their consent and not all safety outcomes have been reported. This journal watch article discusses the paper in more detail.

Risk of pre-eclampsia after fresh or frozen embryo transfer in patients undergoing oocyte donation

ObjectivesDifferent perinatal and neonatal adverse outcomes have been reported to be increased in frozen embryo transfer pregnancies compared with fresh embryo transfer with patient’s own oocytes. Concerning preeclampsia, it has also been reported to be increased after frozen embryo transfer.The objective of this study is to asses if there is an increased risk of preeclampsia and gestational hypertension in pregnancies achieved with oocyte donation after frozen embryo transfer compared to fresh embryo transfer. Study designRetrospective cohort study of 433 patients who underwent a cycle with donated oocytes either after fresh (n = 353) or frozen embryo transfer (n = 80) between March 2013 and April 2016 at a large fertility clinic. Participants are pregnant patients who reached the 20th week of gestation. The risk of preterm preeclampsia (presenting before 37 weeks of gestation), term preeclampsia (presenting at or after 37 weeks of gestation) and gestational hypertension are presented as unadjusted and adjusted odds ratio (OR). ResultsFrozen embryo transfer have similar risk for developing preterm preeclampsia compared to fresh embryo transfer, with an OR of 1.95 (CI 95% 0.72, 5.26, p = 0.18), as well as term preeclampsia (OR 0.3, 95%CI 0.04, 2.35, p = 0.25), and gestational hypertension (OR 1.45, 95% CI 0.75, 2.81, P = 0.27). ConclusionsDespite a high prevalence of preeclampsia in pregnancies achieved by oocyte donation, the freezing-thawing process does not confer more risk than the fresh embryo transfers in preterm preeclampsia, term preeclampsia or gestational hypertension.

Low-dose aspirin at ≤16 weeks of gestation for preventing preeclampsia and its maternal and neonatal adverse outcomes: A systematic review and meta-analysis.

The aim of the present meta-analysis study was to evaluate the efficacy of low-dose aspirin, commenced at ≤16 weeks of gestation, in preventing preterm and term preeclampsia, as well as associated maternal and neonatal adverse events in women at risk of preeclampsia. The Embase, PubMed, Cochrane Central Register of Controlled Trials and the Web of Science databases were searched for relevant random controlled trials (RCTs) published between January 1979 and October 2017. After quality assessment and data extraction, a meta-analysis was performed using RevMan 5.3 software. Outcomes of interest were preeclampsia with subgroups of preterm preeclampsia (delivery at <37 weeks) and term preeclampsia, as well as maternal adverse outcomes, including gestational hypertension, postpartum hemorrhage and preterm birth, and neonatal adverse outcomes, including intrauterine growth retardation (IUGR) or small for gestation age infant (SGA), stillbirth or death, and newborn weight. A total of 10 RCTs involving 3,168 participants were included. The meta-analysis demonstrated that, compared with placebo or no treatment, low-dose aspirin was associated with a significant reduction in the overall risk ratio (RR) of preeclampsia regardless of the time to delivery [RR=0.67; 95% confidence interval (CI)=0.57–0.80]. This was apparent for preterm preeclampsia (RR=0.35; 95% CI=0.13–0.94) but not for term preeclampsia (RR=1.01; 95% CI=0.60–1.70). Except for postpartum hemorrhage, low-dose aspirin also significantly reduced the risk of maternal and neonatal adverse outcomes. In conclusion, low-dose aspirin in women at risk of preeclampsia, commenced at ≤16 weeks of gestation, was associated with a reduced risk of preterm preeclampsia, and of adverse maternal and neonatal outcomes.

Aspirin Versus Placebo in Pregnancies at High Risk for Preterm Preeclampsia

(N Engl J Med. 2017;377(7):613–622) Professional associations recommend the prophylactic use of low-dose aspirin (60 to 80 mg d) in pregnant women who are considered to be at high risk for preeclampsia. However, some studies suggest that aspirin started after 16 weeks of gestation does not have a significant benefit, and there remain major challenges in identifying women at high risk for this condition.

Aspirin for pregnancies at high risk for preterm pre-eclampsia.

Aspirin for pregnancies at high risk for preterm pre-eclampsia.

Aspirin Versus Placebo in Pregnancies at High Risk for Preterm Preeclampsia

(Abstracted from N Engl J Med 2017;377:613–622) Since 1979, multiple studies have shown that low-dose aspirin in pregnancy can lower the occurrence of preeclampsia. Subsequent studies have shown that doses greater than 100 mg/d started before 16 weeks of gestation are most effective.

Aspirin for Evidence-Based Preeclampsia Prevention trial: influence of compliance on beneficial effect of aspirin in prevention of preterm preeclampsia

The Aspirin for Evidence-Based Preeclampsia Prevention trial was a multicenter study in women with singleton pregnancies. Screening was carried out at 11-13 weeks' gestation with an algorithm that combines maternal factors and biomarkers (mean arterial pressure, uterine artery pulsatility index, and maternal serum pregnancy-associated plasma protein A and placental growth factor). Those with an estimated risk for preterm preeclampsia of >1 in 100 were invited to participate in a double-blind trial of aspirin (150 mg/d) vs placebo from 11-14 until 36 weeks' gestation. Preterm preeclampsia with delivery at <37 weeks' gestation, which was the primary outcome, occurred in 1.6% (13/798) participants in the aspirin group, as compared with 4.3% (35/822) in the placebo group (odds ratio in the aspirin group, 0.38; 95% confidence interval, 0.20 to 0.74). We sought to examine the influence of compliance on the beneficial effect of aspirin in prevention of preterm preeclampsia in the Aspirin for Evidence-Based Preeclampsia Prevention trial. This was a secondary analysis of data from the trial. The proportion of prescribed tablets taken was used as an overall measure of compliance. Logistic regression analysis was used to estimate the effect of aspirin on the incidence of preterm preeclampsia according to compliance of <90% and ≥90%, after adjustment for the estimated risk of preterm preeclampsia at screening and the participating center. The choice of cut-off of 90% was based on an exploratory analysis of the treatment effect. Logistic regression analysis was used to investigate predictors of compliance ≥90% among maternal characteristics and medical history. Preterm preeclampsia occurred in 5/555 (0.9%) participants in the aspirin group with compliance ≥90%, in 8/243 (3.3%) of participants in the aspirin group with compliance <90%, in 22/588 (3.7%) of participants in the placebo group with compliance ≥90%, and in 13/234 (5.6%) of participants in the placebo group with compliance <90%. The odds ratio in the aspirin group for preterm preeclampsia was 0.24 (95% confidence interval, 0.09-0.65) for compliance ≥90% and 0.59 (95% confidence interval, 0.23-1.53) for compliance <90%. Compliance was positively associated with family history of preeclampsia and negatively associated with smoking, maternal age <25 years, Afro-Caribbean and South Asian racial origin, and history of preeclampsia in a previous pregnancy. The beneficial effect of aspirin in the prevention of preterm preeclampsia appears to depend on compliance.

Aspirin versus Placebo in Pregnancies at High Risk for Preterm Preeclampsia

BackgroundPreterm preeclampsia is an important cause of maternal and perinatal death and complications. It is uncertain whether the intake of low-dose aspirin during pregnancy reduces the risk of preterm preeclampsia.MethodsIn this multicenter, double-blind, placebo-controlled trial, we randomly assigned 1776 women with singleton pregnancies who were at high risk for preterm preeclampsia to receive aspirin, at a dose of 150 mg per day, or placebo from 11 to 14 weeks of gestation until 36 weeks of gestation. The primary outcome was delivery with preeclampsia before 37 weeks of gestation. The analysis was performed according to the intention-to-treat principle.ResultsA total of 152 women withdrew consent during the trial, and 4 were lost to follow up, which left 798 participants in the aspirin group and 822 in the placebo group. Preterm preeclampsia occurred in 13 participants (1.6%) in the aspirin group, as compared with 35 (4.3%) in the placebo group (odds ratio in the aspirin group, 0.38; 95% confidence interval, 0.20 to 0.74; P=0.004). Results were materially unchanged in a sensitivity analysis that took into account participants who had withdrawn or were lost to follow-up. Adherence was good, with a reported intake of 85% or more of the required number of tablets in 79.9% of the participants. There were no significant between-group differences in the incidence of neonatal adverse outcomes or other adverse events.ConclusionsTreatment with low-dose aspirin in women at high risk for preterm preeclampsia resulted in a lower incidence of this diagnosis than placebo. (Funded by the European Union Seventh Framework Program and the Fetal Medicine Foundation; EudraCT number, 2013-003778-29; Current Controlled Trials number, ISRCTN13633058.)

Aspirin for Evidence-Based Preeclampsia Prevention trial: effect of aspirin in prevention of preterm preeclampsia in subgroups of women according to their characteristics and medical and obstetrical history

The Combined Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence-Based Preeclampsia Prevention trial demonstrated that in women who were at high risk for preterm preeclampsia with delivery at <37 weeks' gestation identified by screening by means of an algorithm that combines maternal factors and biomarkers at 11-13 weeks' gestation, aspirin administration from 11 to 14 until 36 weeks' gestation was associated with a significant reduction in the incidence of preterm preeclampsia (odds ratio 0.38; 95% confidence interval, 0.20 to 0.74; P=0.004). We sought to examine whether there are differences in the effect of aspirin on the incidence of preterm preeclampsia in the Aspirin for Evidence-Based Preeclampsia Prevention trial in subgroups defined according to maternal characteristics and medical and obstetrical history. This was a secondary analysis of data from the Aspirin for Evidence-Based Preeclampsia Prevention trial. Subgroup analysis was performed to assess evidence of differences in the effect of aspirin on incidence of preterm preeclampsia in subgroups defined by maternal age (<30 and ≥30 years), body mass index (<25 and ≥25 kg/m2), racial origin (Afro-Caribbean, Caucasian and other), method of conception (natural and assisted), cigarette smoking (smoker and non-smoker), family history of preterm preeclampsia (present and absent), obstetrical history (nulliparous, multiparous with previous preterm preeclampsia and multiparous without previous preterm preeclampsia), history of chronic hypertension (present and absent). Interaction tests were performed on the full data set of patients in the intention to treat population and on the data set of patients who took ≥ 90% of the prescribed medication. Results are presented as forest plot with P values for the interaction effects, group sizes, event counts and estimated odds ratios. We examined whether the test of interaction was significant at the 5% level with a Bonferroni adjustment for multiple comparisons. There was no evidence of heterogeneity in the aspirin effect in subgroups defined according to maternal characteristics and obstetrical history. In participants with chronic hypertension preterm preeclampsia occurred in 10.2% (5/49) in the aspirin group and 8.2% (5/61) in the placebo group (adjusted odds ratio, 1.29; 95% confidence interval, 0.33-5.12). The respective values in those without chronic hypertension were 1.1% (8/749) in the aspirin group and 3.9% (30/761) in the placebo group (adjusted odds ratio, 0.27; 95% confidence interval, 0.12-0.60). In all participants with adherence of ≥90% the adjusted odds ratio in the aspirin group was 0.24 (95% confidence interval, 0.09-0.65); in the subgroup with chronic hypertension it was 2.06 (95% confidence interval, 0.40-10.71); and in those without chronic hypertension it was 0.05 (95% confidence interval, 0.01-0.41). For the complete data set the test of interaction was not significant at the 5% level (P= .055), but in those with adherence ≥90%, after adjustment for multiple comparisons, the interaction was significant at the 5% level (P= .0019). The beneficial effect of aspirin in the prevention of preterm preeclampsia may not apply in pregnancies with chronic hypertension. There was no evidence of heterogeneity in the aspirin effect in subgroups defined according to maternal characteristics and obstetrical history.

Predicting preeclampsia from a history of preterm birth.

ObjectiveTo assess whether women with a history of preterm birth, independent on the presence of prelabour rupture of the membranes (PROM) and growth deviation of the newborn, are more likely to develop preeclampsia with preterm or preterm birth in a subsequent pregnancy.MethodsWe conducted a population-based cohort study, based on Medical Birth Registry of Norway between 1967 and 2012, including 742,980 women with singleton pregnancies who were followed up from their 1st to 2nd pregnancy. In the analyses we included 712,511 women after excluding 30,469 women with preeclampsia in the first pregnancy.ResultsAfter preterm birth without preeclampsia in the first pregnancy, the risk of preterm preeclampsia in the second pregnancy was 4–7 fold higher than after term birth (odds ratios 3.5; 95% confidence interval (CI) 3.0–4.0 to 6.5; 95% CI 5.1–8.2). The risk of term preeclampsia in the pregnancy following a preterm birth was 2–3 times higher than after term birth (odds ratios 1.6; 95% CI 1.5–1.8 to 2.6; 95% CI 2.0–3.4). After spontaneous non-PROM preterm birth and preterm PROM, the risk of preterm preeclampsia was 3.3–3.6 fold higher than after spontaneous term birth. Corresponding risks of term preeclampsia was 1.6–1.8 fold higher. No significant time trends were found in the effect of spontaneous preterm birth in the first pregnancy on preterm or term preeclampsia in the second pregnancy.ConclusionsThe results suggest that preterm birth, regardless of the presence of PROM, and preeclampsia share pathophysiologic mechanisms. These mechanisms may cause preterm birth in one pregnancy and preeclampsia in a subsequent pregnancy in the same woman. The association was particularly evident with preterm preeclampsia.

Importance of Timing First-Trimester Placental Growth Factor and Use of Serial First-Trimester Placental Growth Factor Measurements in Screening for Preeclampsia

Objective: The aims of this study were to test whether the performance of first-trimester placental growth factor (PlGF) in screening for preterm preeclampsia (PE) is gestational age dependent and to assess the value of serial first-trimester PlGF measurements in discriminating women at risk for PE. Methods: PlGF was measured in women with singleton pregnancies at their first antenatal visit at 8+0 to 10+6 and additionally at 11+0 to 14+0 weeks of gestation. The difference in absolute values of serial PlGF measurements was expressed as Δ-PlGF. Values were compared between pregnancies with normal outcome and those complicated by PE. Results: A total of 814 pregnancies were included, 18 (2.19%) developed PE that required delivery before 37 weeks of gestation. PlGF increases significantly from 8 to 14 weeks of gestation (ρ = 0.63; p < 0.0001) in normal pregnancies, but not so in preterm PE (ρ = 0.034; p = 0.893). PlGF discriminates between PE and uneventful pregnancies only after 10 weeks of gestation. Δ-PlGF was significantly lower in PE 5.3 (-1.1 to 9.3) pg/mL compared to uneventful pregnancies 17.3 (9.8-26.0) pg/mL (p = 0.0011). Conclusion: The discriminatory accuracy of PlGF increases from 10 to 14 weeks of gestation, and serial PlGF measurements might be of particular interest in PE screening.

Retinol-Binding Protein 4 and Lipids Prospectively Measured During Early to Mid-Pregnancy in Relation to Preeclampsia and Preterm Birth Risk.

Maternal retinol-binding protein 4 (RBP4) and lipids may relate to preeclampsia and preterm birth risk but longitudinal data are lacking. This study examines these biomarkers longitudinally during pregnancy in relation to preeclampsia and preterm birth risk. Maternal serum samples from the Calcium for Preeclampsia Prevention (CPEP) trial were analyzed at baseline: average 15 gestational weeks; mid-pregnancy: average 27 weeks; and at >34 weeks. We measured RBP4, total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides and lipoprotein (a) (Lp(a)). Cross-sectional logistic regression analyses estimated the odds ratio (OR) and 95% confidence intervals (CI) for preterm preeclampsia (n = 63), term preeclampsia (n = 104), and preterm delivery (n = 160) associated with RBP4 and lipids at baseline and mid-pregnancy compared with controls (n = 136). Longitudinal trajectories across pregnancy were assessed using mixed linear models with fixed effects. Adjusted models included clinical and demographic factors. RBP4 concentrations at baseline and mid-pregnancy were associated with a 4- to 8-fold increase in preterm preeclampsia risk but were not associated with term preeclampsia. RBP4 measured mid-pregnancy was also associated with preterm birth (OR = 6.67, 95% CI: 1.65, 26.84). Higher triglyceride concentrations in mid-pregnancy were associated with a 2- to 4-fold increased risk for both preeclampsia and preterm birth. Longitudinal models demonstrate that both preterm preeclampsia and preterm birth cases had elevated RBP4 throughout gestation. Elevated RBP4 is detectable early in pregnancy and its strong relation with preterm preeclampsia merits further investigation and confirmation to evaluate its potential use as a predictor, particularly among high-risk women.

54 Can we prevent recurrent pre-term preeclampsia?

Preterm preeclampsia (PTPE) (<34 weeks of gestation) is a life-threatening complication of pregnancy with a high recurrence rate (20–60%). Low dose aspirin (ASA) may prevent recurrence, and some trials suggest that low molecular weight heparin (LMWH) and ASA together is more effective but results are inconclusive. We report the recurrence rate of PE in women with prior PTPE and the impact of therapy on fetal birth weight (BW) and gestational age at delivery (GA). We prospectively followed 41 women with PTPE in a prior pregnancy throughout 53 subsequent pregnancies. Women were screened for genetic and acquired thrombophilias and treated with either ASA or LMWH and ASA as determined by treating physicians. Maternal and fetal outcomes in subsequent pregnancies were ascertained including preeclampsia (PE), GA, and BW. The mean (±SD) age of the women was 36 ± 5 years at the time of their subsequent pregnancy, and BMI was 25.6 ± 5.4kg/m2. 66% were white, 5% black and 15% Hispanic. Genetic thrombophilias were detected in 91% and acquired thrombophilias in 36%. Thirteen women (25%) were not treated with ASA or LMWH, 12 (23%) received ASA alone, and 27 (52%) received LMWH ± ASA. PE recurred in 6 pregnancies (11%) and PTPE in 5 (9%). In subsequent pregnancies BW was higher (1473 ± 743 g prior pregnancy vs. 2880 ± 778 g in the subsequent pregnancies, p < 0.001), and GA at delivery was later (29 ± 4 weeks vs. 36 ± 4 weeks, p < 0.001). PE recurrence was numerically higher in the untreated group compared to those treated with ASA alone, or LMWH ± ASA (3/13 vs. 1/12 or 2/27). BW and GA increased similarly in subsequent pregnancies in all groups although women treated with LMWH ± ASA had a greater increase in GA (8.8 vs. 4.4 weeks, p = 0.021). The risk of recurrent PE or PTPE in women with prior PTPE was lower than reported in prior studies. BW and GA at delivery were significantly better in subsequent pregnancies. We found a trend towards a decreased incidence of PE and greater prolongation of pregnancy in those treated with LMWH ± ASA compared to no treatment or ASA alone. We propose an appropriately designed clinical trial to determine the benefits/risks of LMWH in women at risk for PTPE.

Pre-pregnancy maternal obesity and the risk of preterm preeclampsia in the American primigravida.

To estimate the risk of preterm preeclampsia in primiparous women by pre-pregnancy obesity class. A retrospective cohort study of primiparous women with singleton gestations was performed for deliveries from January 2003 to April 2014. Cases were stratified by delivery occurring either at ≥ 37 weeks or < 37 weeks. Pre-pregnancy maternal obesity was defined as a body mass index (BMI) ≥ 30 kg/m(2) . World Health Organization criteria were used to define BMI class of obesity. Multinomial logistic regression modeling estimated the association between term and preterm preeclampsia and pre-pregnancy obesity. Of 28,361 women with complete pre-pregnancy BMI data, 2,588 women (9.1%) had a diagnosis of preeclampsia. Women who developed preeclampsia prior to 37 weeks (n = 784) were more likely to be women with obesity compared to women who developed preeclampsia after 37 weeks (33.1% vs. 25.3%, P = 0.0001). Compared to normal-weight women without preeclampsia, the risk of preterm preeclampsia increased proportionally with pre-pregnancy obesity class, with women with a BMI ≥ 40 kg/m(2) having the greatest risk (RR 5.23, 95% CI: 3.86-7.09, P <0.001). The risk of preterm preeclampsia increased significantly as the severity of maternal pre-pregnancy obesity increased. Reduction in maternal pre-pregnancy BMI may be protective in mitigating such risk.

693: Risk of pre-term preeclampsia in the american primigravida: does pre-pregnancy maternal obesity class matter?

693: Risk of pre-term preeclampsia in the american primigravida: does pre-pregnancy maternal obesity class matter?

Human chorionic gonadotropin, angiogenic factors, and preeclampsia risk: a nested case–control study

To study whether human chorionic gonadotropin concentrations during pregnancy or combinations of human chorionic gonadotropin and other angiogenic factors, soluble fms-like tyrosine kinase 1 and placental growth factor (PlGF), are associated with preeclampsia risk. Nested case-control study. Population cohort of pregnant women. A total of 121 cases of preterm (<37 weeks) and 158 cases of term preeclampsia (≥37 weeks of gestation) and 356 women without preeclampsia (controls). Women with preeclampsia were identified by linkage to the Medical Birth Registry of Norway. Concentrations of human chorionic gonadotropin, soluble fms-like tyrosine kinase 1 and PlGF were measured in maternal serum samples collected in each trimester of pregnancy. Odds ratios of preterm and term preeclampsia. High human chorionic gonadotropin concentrations (highest quartile) in the first trimester were associated with reduced risk for preterm preeclampsia (OR 0.3, 95% CI 0.1-0.9), compared with low human chorionic gonadotropin (lowest quartile), whereas high human chorionic gonadotropin concentrations in the second trimester were associated with increased risk for preterm preeclampsia (OR 4.0, 95% CI 1.8-8.9). High human chorionic gonadotropin concentrations in the third trimester were associated with increased risk for term preeclampsia (OR 4.8, 95% CI 1.8-13.3). Concentrations of human chorionic gonadotropin above the median value combined with PlGF below the median in the second trimester were associated with very high risk for preterm preeclampsia (OR 36.9, 95% CI 8.2-165.8). The results suggest an important role of human chorionic gonadotropin in the pathophysiological processes that lead to preeclampsia. The combined association of human chorionic gonadotropin and PlGF indicates a possible synergism between underlying biological pathways.

Early Administration of Low-Dose Aspirin for the Prevention of Severe and Mild Preeclampsia

Objective: To compare the effect of early administration of aspirin on the risk of preterm and term preeclampsia. Method: A systematic review and meta-analysis of randomized controlled trials were performed. Women who were randomized to low-dose aspirin or placebo/no treatment at or before 16 weeks of gestation were included. The outcomes of interest were preterm preeclampsia (delivery ! 37 weeks) and term preeclampsia. Pooled relative risks (RR) with their 95% confidence intervals (CI) were computed. Results: The search identified 7,941 citations but only five trials on a combined total of 556 women fulfilled the inclusion criteria. When compared to controls, aspirin initiated ^ 16 weeks of gestation was associated with a major reduction of the risk of preterm preeclampsia (RR 0.11, 95% CI 0.04–0.33) but had no significant effect on term preeclampsia (RR 0.98, 95% CI 0.42–2.33). Conclusion: Low-dose aspirin administrated at or before 16 weeks of gestation reduces the risk of preterm but

Angiogenic factors in maternal circulation and preeclampsia with or without fetal growth restriction

To study associations of placental growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt-1) in maternal circulation with the risk of preeclampsia with and without fetal growth restriction. Nested case-control study. A cohort of 29 948 pregnant women in Norway. Cases were identified through linkage to the Medical Birth Registry of Norway. We selected 69 preterm and 36 term preeclampsia cases with delivery of a small-for-gestational-age (SGA) infant, 83 preterm and 154 term preeclampsia cases without SGA delivery, and 384 normotensive controls. We measured PlGF and sFlt-1 in maternal serum samples from each trimester. Odds ratios of preeclampsia subtypes by tertile categories of PlGF and sFlt-1. Low (lowest third) PlGF and sFlt-1 levels in the first trimester, and low (lowest third) increase in PlGF and strong (highest third) increase in sFlt-1 from first to second trimester were associated with increased risk of preterm preeclampsia, both with and without SGA offspring. For term preeclampsia with SGA offspring, the associations were similar to the findings for preterm preeclampsia. For term preeclampsia without SGA offspring, low increase in PlGF from first to second trimester and high sFlt-1 in the third trimester were associated with increased risk. Low PlGF and high sFlt-1 levels in maternal circulation are associated with subsequent development of preeclampsia, regardless of whether fetal growth is affected or not. For term preeclampsia without fetal growth restriction, the imbalance in angiogenic factors seems to appear later in pregnancy than for preterm preeclampsia.