Objective
To determine if change in maternal angiogenic biomarkers between the first and second trimesters predicts pre-eclampsia in low-risk nulliparous women.
Design
A nested case–control study of change in maternal plasma soluble Flt-1 (sFlt-1), soluble endoglin (sEng) and placenta growth factor (PlGF). We studied 158 pregnancies complicated by pre-eclampsia and 468 normotensive nonproteinuric controls.
Setting
A multicentre study in 16 academic medical centres in the USA.
Population
Low-risk nulliparous women.
Methods
Luminex assays for PlGF, sFlt-1 and sEng performed on maternal EDTA plasma collected at 9–12, 15–18 and 23–26 weeks of gestation. Rate of change of analyte between first and either early or late second trimester was calculated with and without adjustment for baseline clinical characteristics.
Main outcome measures
Change in PlGF, sFlt-1 and sEng.
Results
Rates of change of PlGF, sEng and sFlt-1 between first and either early or late second trimesters were significantly different in women who developed pre-eclampsia, severe pre-eclampsia or early-onset pre-eclampsia compared with women who remained normotensive. Inclusion of clinical characteristics (race, body mass index and blood pressure at entry) increased sensitivity for detecting severe and particularly early-onset pre-eclampsia but not pre-eclampsia overall. Receiver operating characteristics curves for change from first to early second trimester in sEng, PlGF and sFlt-1 with clinical characteristics had areas under the curve of 0.88, 0.84 and 0.86, respectively, and for early-onset pre-eclampsia with sensitivities of 88% (95% CI 64–99%), 77% (95% CI 50–93%) and 77% (95%CI 50–93%) for 80% specificity, respectively. Similar results were seen in the change from first to late second trimester.
Conclusion
Change in angiogenic biomarkers between first and early second trimester combined with clinical characteristics has strong utility for predicting early-onset pre-eclampsia.
Intramyomatous arteries were smaller and more often showed arteriosclerotic changes in leiomyomas removed from women treated with GnRH-a compared with those given placebo. The estrogen deprivation induced by GnRH-a may cause a relative vasoconstriction of myomatous vessels. Whether this decreased vessel size is the principal contributor to decreased myoma size will require further study.
BackgroundPreterm birth is the principal factor contributing to adverse outcomes in multiple pregnancies. Randomized controlled trials of progestogens to prevent preterm birth in twin pregnancies have shown no clear benefits. However, individual studies have not had sufficient power to evaluate potential benefits in women at particular high risk of early delivery (for example, women with a previous preterm birth or short cervix) or to determine adverse effects for rare outcomes such as intrauterine death.Methods/designWe propose an individual participant data meta-analysis of high quality randomized, double-blind, placebo-controlled trials of progestogen treatment in women with a twin pregnancy. The primary outcome will be adverse perinatal outcome (a composite measure of perinatal mortality and significant neonatal morbidity). Missing data will be imputed within each original study, before data of the individual studies are pooled. The effects of 17-hydroxyprogesterone caproate or vaginal progesterone treatment in women with twin pregnancies will be estimated by means of a random effects log-binomial model. Analyses will be adjusted for variables used in stratified randomization as appropriate. Pre-specified subgroup analysis will be performed to explore the effect of progestogen treatment in high-risk groups.DiscussionCombining individual patient data from different randomized trials has potential to provide valuable, clinically useful information regarding the benefits and potential harms of progestogens in women with twin pregnancy overall and in relevant subgroups.
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