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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.

Objective-To evaluate the length of the second stage of labor in relation to increasing maternal prepregnancy BMI among nulliparous parturients, and to determine whether route of delivery differs among obese, overweight, and normal weight women reaching the second stage.Methods-We performed a secondary analysis of a multicenter trial of fetal pulse oximetry, conducted among 5,341 nulliparas who were induced or labored spontaneously at 36 weeks or more of gestation. Normal weight was defined as BMI of 18.5-24.9 kg/m 2 , overweight was a BMI of 25.0-29.9 kg/m 2 , and obese was a BMI of 30 kg/m 2 or higher.Results-Of the 5,341 women, 97% had prepregnancy BMI recorded. Of these, 3,739 had a BMI 18.5 kg/m 2 or higher and reached the second stage of labor. Increasing maternal BMI was not associated with second stage duration: normal weight 1.1 hr, overweight 1.1 hr, and obese 1.0 hr (p=0.13) . Among women who reached the second stage, as BMI increased, so did the likelihood that the woman had undergone induction of labor. Even so, the lack of association between Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access

Objective-The underlying pathophysiology of preeclampsia is thought to be abnormal trophoblast invasion of the spiral arteries, leading to maldevelopment of uteroplacental perfusion. We estimated whether uterine artery Doppler measurements made in the early second trimester would predict the subsequent development of preeclampsia.Methods-Uterine artery Doppler measurements prior to 21 weeks of gestation (median 16.6 weeks) were correlated with subsequent development of preeclampsia in a cohort of 2,188 lowrisk nulliparous women in a randomized control trial of antioxidant supplementation for prevention of preeclampsia. Preeclampsia developed in 165 (7.5%) women.Results-Development of preeclampsia overall was associated with increased resistance index (RI), pulsatility index (PI), a PI or RI multiples of the median (MoM) at or above the 75 th %ile, but not the presence of a notch or a bilateral notch prior to 21 weeks. The sensitivity was 43% (95% CI 35-51) and specificity 67% (95% CI 65-69) for prediction of preeclampsia overall. The presence of a notch or bilateral notch, RI and PI MoM were significantly associated with early onset (before 34 weeks of gestation) vs late onset or no preeclampsia (OR = 6.9 (95% CI 2.3-20.9), sensitivity 78% (95% CI 52-94), specificity 66% (95% CI 64-68)). The presence of a notch Conclusion-Our data show poor sensitivity of second-trimester Doppler ultrasound measurements for prediction of preeclampsia overall in a well-characterized, low-risk, nulliparous population. The technique has utility in identifying poor trophoblast invasion of spiral arteries of a magnitude that severely compromises uteroplacental blood flow and gives early-onset disease.

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