Background Biomarkers have been proposed for identification of women at increased risk of developing pre-eclampsia.Objectives To investigate the capacity of circulating placental growth factor (PlGF), vascular endothelial growth factor (VEGF), soluble fms-like tyrosine kinase-1 (sFLT1) and soluble endoglin (sENG) to predict pre-eclampsia.Search strategy Medline and Embase through October 2010 and reference lists of reviews, without constraints.Selection criteria We included original publications on testing of PlGF, VEGF, sFLT1 and sENG in serum or plasma of pregnant women at <30 weeks of gestation and before clinical onset of pre-eclampsia.Data collection and analysis Two reviewers independently identified eligible studies, extracted descriptive and test accuracy data and assessed methodological quality. Summary estimates of discriminatory performance were obtained. Main resultsWe included 34 studies. Concentrations of PlGF (27 studies) and VEGF (three studies) were lower in women who developed pre-eclampsia: standardised mean differences (SMD) )0.56 (95% CI )0.77 to )0.35) and )1.25 (95% CI )2.73 to 0.23). Concentrations of sFLT1 (19 studies) and sENG (ten studies) were higher: SMD 0.48 (95% CI 0.21-0.75) and SMD 0.54 (95% CI 0.24-0.84). The summary diagnostic odds ratios were: PlGF 9.0 (95% CI 5.6-14.5), sFLT1 6.6 (95% CI 3.1-13.7), sENG 4.2 (95% CI 2.4-7.2), which correspond to sensitivities of 32%, 26% and 18%, respectively, for a 5% falsepositive rate.Author's conclusions PlGF, sFLT1 and sENG showed modest but significantly different concentrations before 30 weeks of gestation in women who developed pre-eclampsia. Test accuracies of all four markers, however, are too poor for accurate prediction of pre-eclampsia in clinical practice.Keywords Biomarkers, placental growth factor, pre-eclampsia, soluble endoglin, soluble fms-like tyrosine kinase-1, vascular endothelial growth factor.Please cite this paper as: Kleinrouweler C, Wiegerinck M, Ris-Stalpers C, Bossuyt P, van der Post J, von Dadelszen P, Mol B, Pajkrt E, for the EBM CON-NECT Collaboration. Accuracy of circulating placental growth factor, vascular endothelial growth factor, soluble fms-like tyrosine kinase 1 and soluble endoglin in the prediction of pre-eclampsia: a systematic review and meta-analysis. BJOG 2012;119:778-787.

Health care provision is increasingly focused on the prediction of patients' individual risk for developing a particular health outcome in planning further tests and treatments. There has been a steady increase in the development and publication of prognostic models for various maternal and fetal outcomes in obstetrics. We undertook a systematic review to give an overview of the current status of available prognostic models in obstetrics in the context of their potential advantages and the process of developing and validating models. Important aspects to consider when assessing a prognostic model are discussed and recommendations on how to proceed on this within the obstetric domain are given. We searched MEDLINE (up to July 2012) for articles developing prognostic models in obstetrics. We identified 177 papers that reported the development of 263 prognostic models for 40 different outcomes. The most frequently predicted outcomes were preeclampsia (n = 69), preterm delivery (n = 63), mode of delivery (n = 22), gestational hypertension (n = 11), and small-for-gestational-age infants (n = 10). The performance of newer models was generally not better than that of older models predicting the same outcome. The most important measures of predictive accuracy (ie, a model's discrimination and calibration) were often (82.9%, 218/263) not both assessed. Very few developed models were validated in data other than the development data (8.7%, 23/263). Only two-thirds of the papers (62.4%, 164/263) presented the model such that validation in other populations was possible, and the clinical applicability was discussed in only 11.0% (29/263). The impact of developed models on clinical practice was unknown. We identified a large number of prognostic models in obstetrics, but there is relatively little evidence about their performance, impact, and usefulness in clinical practice so that at this point, clinical implementation cannot be recommended. New efforts should be directed toward evaluating the performance and impact of the existing models.

ObjectiveTo systematically review the literature on human gene expression data of placental tissue in pre-eclampsia and to characterize a meta-signature of differentially expressed genes in order to identify novel putative diagnostic markers.Data SourcesMedline through 11 February 2011 using MeSH terms and keywords related to placenta, gene expression and gene expression arrays; GEO database using the term “placent*”; and reference lists of eligible primary studies, without constraints.MethodsFrom 1068 studies retrieved from the search, we included original publications that had performed gene expression array analyses of placental tissue in the third trimester and that reported on differentially expressed genes in pre-eclampsia versus normotensive controls. Two reviewers independently identified eligible studies, extracted descriptive and gene expression data and assessed study quality. Using a vote-counting method based on a comparative meta-profiling algorithm, we determined a meta-signature that characterizes the significant intersection of differentially expressed genes from the collection of independent gene signatures.ResultsWe identified 33 eligible gene expression array studies of placental tissue in the 3rd trimester comprising 30 datasets on mRNA expression and 4 datasets on microRNA expression. The pre-eclamptic placental meta-signature consisted of 40 annotated gene transcripts and 17 microRNAs. At least half of the mRNA transcripts encode a protein that is secreted from the cell and could potentially serve as a biomarker.ConclusionsIn addition to well-known and validated genes, we identified 14 transcripts not reported previously in relation to pre-eclampsia of which the majority is also expressed in the 1st trimester placenta, and three encode a secreted protein.

Objective: To evaluate the outcome of fetuses with prenatally diagnosed omphalocele and to investigate the predictive value of the omphalocele circumference/abdominal circumference (OC/AC) ratio – a measure for the relative size of the omphalocele. Materials and Methods: This study includes all fetuses prenatally diagnosed with omphalocele at our centre between 1995 and 2007. Medical records and footage of ultrasound examinations were reviewed. Omphalocele was classified in four groups: isolated, chromosomal, syndromic, and multiple anomalies. Results: Eighty-eight cases were identified: 21 (24%) were isolated and 67 had additional structural anomalies. Of the 44 fetuses (50%) with chromosomal anomalies, 2 had omphalocele as a solitary finding. Fifty-three pregnancies (60%) were terminated because of the size of the lesion or associated structural or chromosomal anomalies. Twenty-one cases resulted in a live birth, of which 17 were vaginal deliveries (81%, all uncomplicated) including 3 cases of giant omphalocele (≧5 cm). The OC/AC ratio was found predictive for herniation of the liver, respiratory insufficiency and type of surgical reconstruction. Currently, 12/88 fetuses (14%) are alive and well, including 2 infants with multiple anomalies. Conclusion: Identification of omphalocele should arouse suspicion of genetic abnormalities, even in cases that appear isolated. The OC/AC ratio may influence counselling regarding the postnatal course.

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