Uzan et al Table 1 Major risk factors for pre-eclampsia49 Risk factor OR or RR (95% CI) Antiphospholipid antibody 9.7 (4.3–21.7) syndrome Renal disease 7.8 (2.2–28.2) Prior pre-eclampsia 7.2 (5.8–8.8) Systemic lupus erythematosus 5.7 (2.0–16.2) Nulliparity 5.4 (2.8–10.3) Chronic hypertension 3.8 (3.4–4.3) Diabetes mellitus 3.6 (2.5–5.0) High altitude 3.6 (1.1–11.9) Multiple gestations 3.5 (3.0–4.2) Strong family history of CV disease 3.2 (1.4–7.7) (heart disease or stroke in $2 first-degree relatives) Obesity 2.5 (1.7–3.7) Family history of pre-eclampsia 2.3–2.6 (1.8–3.6) in first-degree relative Advanced maternal age 1.68 (1.23–2.29) for nulliparas (.40 years) 1.96 (1.34–2.87) for multíparas Abbreviations: CI, confidence interval; OR, odds ratio; RR, relative risk; CV, cardiovascular. of a personal or family history of venous thromboembolic disease, early pre-eclampsia, or pre-eclampsia with any intrauterine growth retardation, abruptio placentae, or in utero death.22,38 Percutaneous needle biopsy of the kidney should be performed only if kidney failure persists at three months postpartum or if signs of a systemic underlying condition or proteinuria persist at 6 months.23 Patients who have had severe pre-eclampsia may share predispositions with nonpregnant patients who have cardiovascular risk factors.39 Accordingly, long-term monitoring of cardiovascular, renal, and metabolic risk factors is recommended after severe pre-eclampsia.22 Prevention Primary prevention of pre-eclampsia is based on the detection of modifiable risk factors. The literature is plentiful regard- ing the risk factors for pre-eclampsia, but should be inter- preted with caution.4–8 Women at high risk are those with a personal history of severe pre-eclampsia, while those at low risk are defined as those who have never had pre-eclampsia but have at least one risk factor.2 There are numerous risk factors,4–8 including genetic risk factors, family history of pre-eclampsia, immunologic factors, nulliparity, a new part- ner, and demographic factors such as a maternal age .35 years, the woman’s own gestational age and birth weight (with elevated risks for women born before 34 weeks or weighing less than 2500 g at birth), factors related to the pregnancy, such as multiple pregnancy, congenital or chromosomal anomalies, a hydatidiform mole, or urinary infection, risk 472 submit your manuscript | www.dovepress.com Dovepress Dovepress factors associated with maternal disease, including chronic hypertension, kidney disease, obesity, insulin resistance, and diabetes, as well as thrombophilia, and environmental factors such as living at a high altitude and stress. Although the search for these risk factors is important, they may not effectively predict this pre-eclampsia by themselves. However, accurate prediction of pre-eclampsia would enable early and optimal management of women at high risk. Several predictive tests are being assessed currently. These include clinical tests, such as blood pressure measurement during the second trimester or 24-hour ambulatory blood pres- sure monitoring, but these lack sensitivity and specificity.40 Laboratory tests for oxidative response have been assessed, including assays for uric acid, urinary kallikrein, and fibronectin, but no evidence of their relevance has so far been found.40 Among the markers used to screen for tri- somy 21 during the second trimester (beta human chorionic gonadotropin, alpha fetoprotein, and unconjugated estriol), elevated alpha fetoprotein is associated with a higher risk of pre-eclampsia (unless there are neural tube abnormalities, as when beta human chorionic gonadotropin is elevated). Frequent monitoring of women with elevated levels could be useful, but these tests may not be carried out for screening purposes due to their low negative predictive value.40 Serum markers for trisomy 21 in the first trimester (pregnancy- associated plasma protein A, inhibin A, corticotropin- releasing hormone, and activin) have been tested, but their likelihood ratios seem to be insufficient. Imaging tests have been evaluated, including uterine artery Doppler ultrasound.41,42 Uterine artery Doppler ultra- sound is not advised during the first or second trimester in low-risk populations due to the excessive variability of likelihood ratios in this population, which allows for the prediction of only one-third of pre-eclampsia cases.43 In a high-risk population, the definition of which is often imprecise, uterine artery Doppler can be performed during the second trimester morphologic ultrasound examination and checked 1 month later in case of abnormal results (resistance index .0.58 or 90–95th percentile, unilateral or bilateral notch). The combination of a uterine artery Doppler examination during the f irst trimester and a three-dimensional ultrasound assessing placental volume may predict the risk of pre-eclampsia as early as the first trimester.44 In clinical practice, because no single marker effectively predicts the risk of pre-eclampsia, the current trend is to test a combination of markers. The most commonly used combination of markers assesses sFlt-1, placental growth Vascular Health and Risk Management 2011:7