Pre-eclampsia and gestational hypertension are less common in HIV infected women

ObjectiveTo determine whether pre-eclampsia and gestational hypertension are less common in HIV infected women.MethodsThis prospective cohort study was performed in the Western Cape province of South Africa. HIV negative and positive pregnant women without chronic renal or chronic hypertensive disease were continuously recruited. During the study period HIV positive patients received either mono- or triple (HAART) antiretroviral therapy for prevention of vertical transmission or maternal care. Only routine clinical management was performed. The development of hypertensive disease during pregnancy was recorded.Results1093 HIV positive and 1173 HIV negative cases were identified during pregnancy and evaluated again after delivery. Significantly fewer cases of pre-eclampsia n = 35 (3.2%) were recorded in the HIV positive group than in the HIV negative group, n = 57 (4.9%) (p = 0.045; OR 0.65 95% CI 0.42–0.99). There were also significantly fewer cases of gestational hypertension recorded in the HIV positive group compared to the HIV negative group (p = 0.026; OR 0.53 95% CI 0.30–0.94). Multiple logistic regression analysis confirmed the reductive effect of HIV on pre-eclampsia and gestational hypertension.ConclusionPre-eclampsia and gestational hypertension are less common in HIV infected women being managed with mono- or triple anti-retroviral therapy.     

Body mass index and hypertensive disorders of pregnancy

ObjectivesWe compared the incidence of the hypertensive disorders of pregnancy in obese women with women of a normal body mass index (BMI).Study designProspective observational study in which BMI was calculated accurately early in pregnancy. Women were enrolled after a sonographic confirmation of an ongoing pregnancy. To reduce confounding variables the study was confined to white European women with a singleton pregnancy.Main outcome measuresIncidence of pre-eclampsia and gestational hypertension.ResultsIn 2230 women, 16.8% were obese. Pre-eclampsia was diagnosed in 3.3% (n = 74) and gestational hypertension in 3.0% (n = 67). Both pre-eclampsia (p = 0.01) and gestational hypertension (p < 0.01) were common in obese women compared with normal weight women. Overall 13.1% of obese women developed a hypertensive disorder during pregnancy. When analysed by parity pre-eclampsia occurred in 2.1% of primigravidas and 0.3% of multigravidas. Pre-eclampsia was increased in obese multigravidas (p = 0.001), but not obese primigravidas, suggesting that parity is more influential than obesity in the development of pre-eclampsia.ConclusionsObese multigravidas are more likely to develop hypertensive disorders in pregnancy and obese primigravidas are more likely to develop gestational hypertension. This is important in clinical practice because maternal weight, unlike parity, is potentially modifiable before or during pregnancy.     

Lipid concentration in small for gestational age (SGA)pregnancies and hypertensive disorders

ObjectiveLow maternal serum lipid and high maternal serum lipid have both been associated with some complications in pregnancy. The lipid profiles in pregnancies complicated by small for gestational age (SGA) or hypertension disorders have been compared with those of normal pregnancies.MethodIn a prospective study, 900 pregnant women between 13 and 23 weeks of pregnancy were studied. Primarily, serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, were measured. Ultimately, the serum lipid levels at 13–23 weeks of pregnancies were compared between the women who later suffered from hypertension disorders or SGA and the matched women with normal pregnancies.ResultsAt 13–23 weeks of pregnancy, the mean triglyceride levels were significantly higher in the women who later experienced preeclampsia when compared with normal, matched pregnancies with an appropriate weight for gestational age and women who had gestational hypertension (p = 0.001 and p = 0.014, respectively). Also, triglyceride levels were significantly higher in women with neonates with large for gestational age (LGA) in comparison with those who gave birth to neonates with SGA (p = 0.012) and with uncomplicated matched pregnant women who gave birth to neonates with weight >10th and <90th percentile for their gestational age (p = 0.007).ConclusionOnly the levels of TG and not any other lipids evaluated were found to be different in pregnancies complicated by preeclampsia when compared to pregnancies complicated by SGA.     

Maternal serum CA-125 level is elevated in severe preeclampsia

AimThe aim of this study was to determine the relationship between serum concentrations of cancer antigen-125 (CA-125) and pre-eclampsia severity.MethodsWe evaluated 91 females with a singleton pregnancy. Serum CA-125 levels were measured in subjects with severe pre-eclampsia (n = 34) and those with mild pre-eclampsia (n = 24). Females with healthy pregnancies (n = 31) served as the control group. The three study groups were statistically similar in terms of maternal age, gestational age, and body mass index.ResultsThe CA-125 level was significantly higher in the severe pre-eclampsia group than that in the mild pre-eclampsia and control groups (p < 0.05). No significant difference in CA-125 levels between the mild pre-eclampsia and control groups was observed. CA-125 level was positively correlated with proteinuria (r = 0.489, p = 0.000), systolic blood pressure (r = 0.503, p = 0.018), and diastolic blood pressure (r = 0.532, p = 0.000). In contrast, CA-125 was negatively correlated with birth weight (r = 0.266, p = 0.012) and gestational age at birth (r = 0.250, p = 0.018).ConclusionsCA-125 level increased in severe pre-eclampsia, which reflected abnormal trophoblastic invasion and chronic inflammation. Elevated levels of CA-125 in pre-eclamptic patients may be a marker of the disease severity.     

Serum S100B in pregnancy complicated by preeclampsia: A case-control study

BackgroundSerum S100B is a protein produced and released primarily by astrocytes of the Central Nervous System (CNS). Elevated levels of serum S100B are associated with several types of pathological conditions of the brain, including the eclampsia in pregnant women. The aim of this study was to compare serum S100B concentrations in pregnant women with severe and mild preeclampsia (PE) with S100B serum levels in normotensive pregnant women.Material and methodsSerum S100B protein was measured in normotensive pregnant women (n = 15) and in women with mild PE (n = 12) or severe PE (n = 34). The serum S100B level (μg/L) was determined by an luminometric assay.ResultsSixty-one expectant mothers were studied, aged 26.6 ± 8.7 (mean ± SD) years and with a gestational age of 33.3 ± 4.2 weeks. The severe PE group demonstrated higher S100B levels (0.20 ± 0.19), as compared with mild PE (0.07 ± 0.05) or normotensive groups (0.04 ± 0.05).ConclusionElevated serum S100B levels in pregnant women with severe PE suggest that some kind of neural damage and subsequent astrocytic release of S100B is not dependent on the progression from severe preeclampsia to eclampsia.     

Does a patient information sheet lead to better understanding of pre-eclampsia? A randomised controlled trial

ObjectiveTo investigate whether a structured patient information sheet would improve women’s satisfaction and understanding of pre-eclampsia, its management and risks.Study designA randomised, controlled trial conducted in a referral centre in South Africa. Seventy-four women with early pre-eclampsia, who qualified for expectant management, were enroled. They all completed an anonymous, structured, and self-administered questionnaire before randomisation.Cases (n = 37) received a patient information sheet addressing key features of pre-eclampsia; controls (n = 37) received a welcome note. Within 5–7 days, but still before delivery, they completed the same questionnaire again.Main outcome measuresPrimarily assessing their general understanding and knowledge of pre-eclampsia, secondarily to assess their satisfaction and the impact of the information received.ResultsThe patient information sheet improved their understanding of the immediate and long-term risks (p < 0.01) and the chance of recurrence (p < 0.01). Controls had good levels of understanding and appreciation. Most women in both groups felt well informed but levels of concern remained high.ConclusionsThe structured information sheet improved patients’ understanding and knowledge in a limited way but did not alleviate their anxiety. Although women appear to be generally well counselled in the study unit, measures to alleviate associated anxiety should be investigated.     

Macular thickness measured by optical coherence tomography correlates with proteinuria in pre-eclampsia

ObjectivesPre-eclampsia is associated with ocular changes. The aim of this study was to examine the macular changes of patients with early-onset severe pre-eclampsia using optical coherence tomography (OCT).MethodsThis prospective study was performed at Tygerberg Academic Hospital, a secondary and tertiary referral centre in Cape Town, South Africa. Twenty women with early onset pre-eclampsia and 20 women without hypertensive or vascular complications, matched for gestational age, were examined before and after delivery.ResultsThere was a trend showing a positive correlation between increased central retinal thickness and increasing proteinuria in patients with pre-eclampsia antepartum (left eye r = 0.52, p = 0.04) and postpartum (left eye r = 0.60, p = 0.01). A positive correlation between average central 1 mm and proteinuria was noted antepartum (left eye r = 0.63, p = 0.01) and postpartum (right eye r = 0.52, p = 0.03). There were no significant correlations between blood pressure and any of the retinal parameters. Two of the 23 patients with pre-eclampsia developed serous retinal detachments, both of which resolved completely postpartum.ConclusionsMacular thickness parameters measured using OCT correlated with the degree of proteinuria in pre-eclampsia. These changes reversed soon after delivery.     

Evaluation of the value of the first and third trimester maternal mean platelet volume (MPV) for prediction of pre-eclampsia

IntroductionPre-eclampsia is one of the most serious complications of pregnancy and one of the major causes of maternal mortality. Thus its prediction is a matter for serious concern.ObjectiveThe purpose of the present study is to determine the value of mean platelet volume (MPV) measurement in the first and third trimesters of pregnancy for the prediction of pre-eclampsia.MethodA prospective nested case–control study was performed on pregnant women who were at 9–12 weeks of pregnancy. In the first trimester and again in 26–28 weeks, MPV was calculated. All eligible women were then monitored to delivery and the MPV of women who were pre-eclamptic was compared with the MPV of normotensive women.ResultsPre-eclamptic women were compared with 269 normotensive women. MPV at the first trimester of pre-eclamptic women was significantly higher than normotensive women (10.2 ± 1.06 fl VS 9.68 ± 1.09 fl, P = 0.008). Also, MPV at the third trimester of pregnancy of pre-eclamptic women was more than normotensives (10.16 ± 1.23 fl VS 9.62 ± 1.12 fl, P = 0.009).Area under the curve in receiver operating characteristics (ROC) curve was calculated as 0.64 for the predictive value of MPV at the first and third trimesters of pregnancy, which showed a low value of this test for predicting of pre-eclampsia.ConclusionMPV at the first and third trimesters of pregnancy are higher in women who eventually would be pre-eclamptic, but has low predictive value and is not a good predictor of pre-eclampsia.     

The effect of calcium supplementation on blood pressure in non-pregnant women with previous pre-eclampsia: An exploratory,randomized placebo controlled study

BackgroundEpidemiological findings suggest that the link between poverty and pre-eclampsia might be dietary calcium deficiency. Calcium supplementation has been associated with a modest reduction in pre-eclampsia, and also in blood pressure (BP).MethodsThis exploratory sub-study of the WHO Calcium and Pre-eclampsia (CAP) trial aims to determine the effect of 500 mg/day elemental calcium on the blood pressure of non-pregnant women with previous pre-eclampsia. Non-pregnant women with at least one subsequent follow-up trial visit at approximately 12 or 24 weeks after randomization were included.ResultsOf 836 women randomized by 9 September 2014, 1st visit data were available in 367 women of whom 217 had previously had severe pre-eclampsia, 2nd visit data were available in 201 women. There was an overall trend to reduced BP in the calcium supplementation group (1–2.5 mmHg) although differences were small and not statistically significant. In the subgroup with previous severe pre-eclampsia, the mean diastolic BP change in the calcium group (−2.6 mmHg) was statistically larger than in the placebo group (+0.8 mmHg), (mean difference −3.4, 95% CI −0.4 to −6.4; p = 0.025). The effect of calcium on diastolic BP at 12 weeks was greater than in those with non-severe pre-eclampsia (p = 0.020, ANOVA analysis).ConclusionsThere is an overall trend to reduced BP but only statistically significant in the diastolic BP of women with previous severe pre-eclampsia. This is consistent with our hypothesis that this group is more sensitive to calcium supplementation, however results need to be interpreted with caution.     

Characteristics of hypertensive disorders in twin versus singleton pregnancies

ObjectiveTo determine the characteristics of hypertensive disorders of pregnancy in twin compared with singleton pregnancies.Study designAnalysis of a prospectively recorded database of 4976 hypertensive pregnancies.Main outcome measuresComparison of progression to pre-eclampsia and maternal and neonatal outcomes.ResultsThere were 3942 singleton and 214 twin pregnancies. De novo hypertension in twin pregnancy was diagnosed earlier (p < 0.001). In singleton pregnancies with de novo hypertension (n = 3161), 60% had an initial diagnosis of gestational hypertension (GH) and 40% had pre-eclampsia (PE). In twin pregnancies with de novo hypertension (n = 199), 35% of women were initially diagnosed with GH and 65% with PE (p < 0.001). At delivery, 46% of the singletons had GH and 54% had PE, compared with twin pregnancies where 23% had GH and 77 % had PE (p < 0.001). The progression from GH to PE for twins was twice that of singleton pregnancies (p < 0.001).There were 781 singleton and 15 twin pregnancies with chronic hypertension (CH). Twin pregnancies complicated by CH were more likely to progress to PE than singletons (p < 0.01). The gestation at delivery was earlier for twin pregnancies (p < 0.001) and there were more twins that were smaller for gestational age (p < 0.001). There were no differences in maternal outcomes.ConclusionWomen carrying twins with de novo hypertension are more likely to present earlier, have initial PE and to subsequently progress from GH to PE. Neonatal outcomes are worse in such pregnancies.     

Transient gestational hypertension: Not always a benign event

ObjectivePregnancy outcome in women with transient gestational hypertension (TGH);defined as de novo blood pressure elevation after 20 weeks gestation that normalizes by subsequent evaluation in a Day Assessment Unit.Study designRetrospective cohort analysis of hypertensive pregnancies between 2003 and 2008.Main outcome measuresFinal hypertensive delivery diagnosis and composites of adverse maternal and fetal outcome.ResultsOverall 1417 women were referred; 890 met criteria; 41% (65% of study population) had TGH. Twenty percent with TGH developed gestational hypertension and 19% preeclampsia. Women with TGH who developed preeclampsia had similar composite adverse maternal outcomes to other preeclamptic women (51% vs. 63%; p = 0.24) but fewer adverse fetal outcomes (50% vs. 71%; p < 0.01) due to less prematurity (30% vs. 45%; p = 0.02) and small for gestational age babies (33% vs. 51%; p = 0.02). Within the TGH population;developing gestational hypertension or preeclampsia was associated with referral at gestation <33 weeks (RRR 2.8; p < 0.01);initial average systolic blood pressure 130–139 mmHg (RRR 2.1; p < 0.01) and initial average diastolic blood pressure 80–89 mmHg (RRR 3.2; p < 0.01).ConclusionTGH after 20 weeks is common in pregnancy. Although initial assessment implies low risk;the risk of progression to gestational hypertension or preeclampsia is substantial and warrants appropriate clinical surveillance.     

OS001. Pregnancy outcome in subsequent pregnancies after eclampsia

IntroductionEclampsia in the previous pregnancy may have impact on future reproductive performance of the women. Few studies have been conducted in recent years to review the subsequent pregnancy outcome. In this study women with previous eclampsia were followed up in subsequent pregnancy and outcome was compared with normotensive control group.ObjectivesTo study the risk of recurrence of hypertension and associated complications in subsequent pregnancies following eclampsia.MethodsFifty-three pregnant women with previous history of eclampsia were supervised and delivered in PGIMER, Chandigarh, India (2001 April–2011 March) were studied prospectively. The pregnancy outcome was compared with 106 age and gravida matched controls who had remained normotensive in previous pregnancies. The data analysis was done by Chi-square test and Student ‘t’ test.ResultsAmongst women with previous eclampsia eight women (15%) were found to have underlying chronic hypertension. The incidence of gestational hypertension and pre-eclampsia was 37.7% amongst these women, compared to 7.5% in control group (p = 0.0001). Preterm deliveries mainly due to preterm inductions were higher (32%) amongst women with previous eclampsia compared to 12% amongst controls (p = 0.0004). Incidence of intra uterine growth restriction was significantly higher amongst cases (15% vs 1.5%, p = 0.0003).ConclusionWomen with previous eclampsia have higher incidence of chronic hypertension. These women are at significant risk to develop hypertensive disorders of pregnancy and its related complications. The recurrence of eclampsia is low with aggressive and vigilant antenatal care.     

Plasma antithrombin levels correlate with albumin and total protein in gestational hypertension and preeclampsia

ObjectiveTo analyze the antithrombin-III (AT-III) activity in the plasma in relation to the serum albumin and total protein in preeclampsia and gestational hypertension.Study designThe medical records of 139 patients who were diagnosed with gestational hypertension (n = 33) and preeclampsia (n = 106) were reviewed, and the relationships between the activity of AT-III and serum albumin or total protein were evaluated.Main outcome measuresThe plasma AT-III activity in gestational hypertension and preeclampsia was correlated with the serum albumin and TP levels.ResultsThere were significant correlations between AT-III activity and albumin in gestational hypertension (r = 0.504, p = 0.003) and preeclampsia (r = 0.343, p = 0.003). There were also significant correlations between AT-III activity and TP in gestational hypertension (r = 0.619, p = 0.001) and preeclampsia (r = 0.366, p = 0.001). Regression coefficients between AT-III and albumin and between AT-III and TP in gestational hypertension (23.7 and 14.0, respectively) were significantly steeper than those in preeclampsia (14.6 and 9.6, respectively).ConclusionsThe plasma AT-III activity in gestational hypertension and preeclampsia was correlated with the serum albumin and TP levels. This suggests that AT-III activity is more likely to decrease in gestational hypertension than in preeclampsia.     

Accuracy of Gestational Age Estimated by Menstrual Dating in Women Seeking Abortion Beyond Nine Weeks

ObjectiveWe sought to quantify the accuracy of estimating gestational age by reported last menstrual period among women seeking surgical abortion. We observed that women seeking surgical abortion underestimated their gestational age when making the appointment, leading to poor allocation of resources. This tendency to underestimate has not previously been reported and differs from the accurate dating reported among women choosing either medical abortion or continuation of the pregnancy.MethodsWe performed a retrospective review of randomly selected medical records for women with abortions scheduled at 9 to 20 weeks’ gestation (n = 415) at two clinics in Vancouver between 2002 and 2008.ResultsThe mean gestational age calculated by menstrual dates (14.3, SD 3.9) was 1.2 (95% CI 0.9 to 1.4) weeks less than that calculated by ultrasound (15.5, SD 3.4) (P < 0.001). Greater gestational age was associated with a larger discrepancy (r = 0.192, P < 0.001). Variables other than gestational age (maternal age, parity, previous abortions, illicit drug use, and contraceptive method at conception) were not significant predictors of inaccurate menstrual dating.ConclusionWomen seeking surgical abortion for pregnancies of 9 to 20 weeks underreport gestational age by an average of 1.2 weeks using menstrual dating. We found that women who intended to continue with their pregnancy overestimated their gestational age, those seeking very early abortion estimated most accurately, and those seeking surgical abortion at more than nine weeks had a clinically significant underestimation of their gestational age. Clinicians referring and counselling women who are considering surgical abortion must facilitate timely access to clinical or ultrasound dating of their pregnancy.     

Maternal hemodynamics influence fetal hemodynamics in normal and hypertensive pregnancy

ObjectivesThis observational case-control study aims to test whether there is a relationship between maternal systemic hemodynamics, maternal renin-angiotensin system and fetal hemodynamics in normal and hypertensive pregnancy.Study designFour groups of non-pregnant women (n = 18), pregnant controls (n = 25), women with gestational hypertension (n = 21) and preeclampsia (n = 10) were included.Main outcome measuresMaternal echocardiography parameters, plasma renin and aldosterone were correlated with fetal Doppler parameters in third trimester pregnancy.ResultsHigher maternal mean arterial pressure and total peripheral vascular resistance were associated with lower fetal middle cerebral artery pulsatility index (PI) (r = ?.51, p < 0.01 and r = ?.49, p < 0.01, respectively); mean arterial pressure correlated negatively with ductus venosus PI (r = ?.35, p = 0.01); higher maternal plasma aldosterone levels were associated with lower maternal uterine artery resistance (r = ?0.33, p = 0.03).ConclusionsIt seems that maternal hemodynamics influence fetal hemodynamics with protective adaptation in fetal cerebral and ductus venosus blood flow observed as maternal blood pressure and vascular resistance increase.     

Correlations of selected vaginal cytokine levels with pregnancy-related traits in women with bacterial vaginosis and mycoplasmas

The aim of this study was to examine correlations between vaginal inflammatory cytokines (IL-1α, IL-1β, IL-6 and IL-8) and pregnancy-related traits (gestational age, birth-weight, BMI, weight gain during pregnancy and vaginal pH). Differences in correlation coefficients were examined among bacterial vaginosis (BV) status and the presence or absence of mycoplasmas. A total of 105 women between the 22nd and 34th week of pregnancy were enrolled in this study. There was a strong negative correlation between IL-1α and weight gain during pregnancy (r = −0.877, p < 0.001) and a strong positive correlation between IL-6 and BMI (r = 0.670, p = 0.024) in women with normal vaginal flora and mycoplasmas. These correlations were not present in women who had normal flora and no mycoplasmas. In women with BV and no mycoplasmas, there were significant correlations of gestational age with IL-6 (r = 0.727, p = 0.027) and IL-8 (r = 0.689, p = 0.040); however, these correlations were not significant in women with mycoplasmas. Our findings support the conclusion that correlations between inflammatory cytokines and pregnancy-related traits are dependent on context, suggesting that expression is labile. In particular, BMI and gestational age correlation differs depending on BV status and the presence or absence of BV-related mycoplasmas such as Mycoplasma hominis and Ureaplasma urealyticum.     

Trophoblast calcyclin is elevated in placental tissue from patients with early pre-eclampsia

The aetiology of pre-eclampsia is thought to originate from aberrant spiral artery remodelling and invasion evoking cellular oxidative stress. Previously, we discovered differentially expressed proteins in trophoblast cells of pre-eclamptic pregnancies. One of these proteins is calcyclin (S100A6); a Ca²⁺-binding protein associated with cellular stress response.By immunohistochemistry on formalin-fixed paraffin-embedded placental tissue, calcyclin expression was compared between women with early pre-eclampsia (n = 72) and non-hypertensive control patients (n = 66) (χ², p = 0.006) blindly by two observers.Significantly more intense staining was seen in trophoblast cells of pre-eclamptic pregnancies compared to control placentas suggesting that trophoblast calcyclin is elevated in early pregnancy.     

2-Methoxyestradiol deficiency is strongly related to hypertension in early onset severe pre-eclampsia

Objective2-Methoxyestradiol (2ME) deficiency leading to placental insufficiency has been related to pre-eclampsia (PE). Here we investigate whether 2ME is related to clinical profiles and vasoactive factors in early onset severe PE patients.Methods28 severe PE patients and 20 uncomplicated normal pregnant women, with gestational weeks between 24 and 32 weeks, were recruited. All cases and controls had singleton pregnancies and were matched for maternal age, parity, body mass index, and gestational weeks. Plasma levels of 2ME, estradiol (E2), soluble Fms-like tyrosine kinase-1 (sFLT-1), endothelin-1 (ET-1), nitric oxide (NO) were determined.ResultsPE patients had significant lower 2ME [906(422–1768) vs. 2032(1400–2910) pg/mL, P = 0.002], higher sFLT-1 [5.55(3.24–11.22) vs. 3.13(2.17–5.36) ng/mL, P = 0.015] and higher NO [122.40(72.92–168.23) vs. 45.83(25.52–61.46) μmol/L, P = 0.0008] levels in their plasma than the controls. In the PE group, plasma 2ME level correlated negatively with systolic pressure (r = −0.48, P = 0.012), diastolic pressure (r = −0.52, P = 0.007) and mean arterial pressure (r = −0.54, P = 0.005) even after controlling for maternal age; 2ME level did not correlate with proteinuria, plasma levels of E2, sFLT-1, ET-1 or NO. In the control group, plasma 2ME level did not correlate with any of the above clinical profiles or laboratory measurements.Conclusions2ME levels were markedly lower in early onset severe PE and they correlated inversely with blood pressure only in women with PE. Although we cannot tell whether lower 2ME level is the causation or the result of PE, our study provides clinical evidences that 2ME deficiency is strongly related to hypertension in early onset severe PE patients.     

Accuracy of angiogenic biomarkers at ⩽20 weeks’ gestation in predicting the risk of pre-eclampsia: A WHO multicentre study

ObjectiveTo assess the accuracy of angiogenic biomarkers to predict pre-eclampsia.DesignProspective multicentre study. From 2006 to 2009, 5121 pregnant women with risk factors for pre-eclampsia (nulliparity, diabetes, previous pre-eclampsia, chronic hypertension) from Argentina, Colombia, Peru, India, Italy, Kenya, Switzerland and Thailand had their serum tested for sFlt-1, PlGF and sEng levels and their urine for PlGF levels at ⩽20, 23–27 and 32–35 weeks’ gestation (index tests, results blinded from carers). Women were monitored for signs of pre-eclampsia, diagnosed by systolic blood pressure ⩾140 mmHg and/or diastolic blood pressure ⩾90 mmHg, and proteinuria (protein/creatinine ratio ⩾0.3, protein ⩾1 g/l, or one dipstick measurement ⩾2+) appearing after 20 weeks’ gestation. Early pre-eclampsia was defined when these signs appeared ⩽34 weeks’ gestation.Main outcome measurePre-eclampsia.ResultsPre-eclampsia was diagnosed in 198 of 5121 women tested (3.9%) of whom 47 (0.9%) developed it early. The median maternal serum concentrations of index tests were significantly altered in women who subsequently developed pre-eclampsia than in those who did not. However, the area under receiver operating characteristics curve at ⩽20 weeks’ gestation were closer to 0.5 than to 1.0 for all biomarkers both for predicting any pre-eclampsia or at ⩽34 weeks’ gestation. The corresponding sensitivity, specificity and likelihood ratios were poor. Multivariable models combining sEng with clinical features slightly improved the prediction capability.ConclusionsAngiogenic biomarkers in first half of pregnancy do not perform well enough in predicting the later development of pre-eclampsia.