Additional information Data on the prevalence of pre-eclampsia in Australia are limited. In 2012, hypertension or pre-eclampsia were the reasons for 9.0–13.2% of labour inductions in New South Wales, Queensland, South Australia, Tasmania and the Northern Territory and 1.3–2.4% of caesarean sections in Queensland, South Australia, Tasmania and the Northern Territory. Data collection methods varied and, for other states and territories, were unavailable or unpublished (). There were nine maternal deaths related to hypertensive disorders of pregnancy between 2008 and 2012 (). These deaths were all due to pre-eclampsia and its complications, and all deaths were classified as direct. The maternal mortality rate during 2008–2012 for hypertensive disorders of pregnancy was 0.6 per 100,000 women who gave birth compared with 0.4 per 100,000 women who gave birth in 2006–2010, and 0.8 per 100,000 women who gave birth in 2003–2005. Advice to EWG The identified evidence and additional information will inform the narrative.
Q1 What is the prevalence and incidence of pre-eclampsia, including population-specific groups Estimated prevalence and incidence of pre-eclampsia in cohort studies Study ref LoE N Aim/ methods Findings Comments () III-2 5,784 Aim: To examine the effect of a combination of screening and treatment with low-dose aspirin on the prevalence of early-onset (PE). Methods: Retrospective analysis of two consecutive cohorts of women screened for early PE. The first was observed to determine whether algorithms developed to screen for PE at 11 to 13+6 weeks gestation could be applied to our population. High-risk women in the second cohort were offered aspirin (150mg at night), with treatment starting immediately after screening. The prevalence of early PE and the proportion of women with PE delivering at 34-37 weeks' gestation were compared. There were 12 (0.4%) cases of early PE in the observational cohort and one (0.04%) in the interventional cohort (P<0.01). Among all women with PE delivering before 37 weeks, 25 (0.83%) were in the observational cohort and 10 (0.37%) in the interventional cohort (P=0.03). () III-2 3,014 Aim: to validate the Fetal Medicine Foundation (FMF) multiple logistic regression algorithm for prediction of risk of in an Australian population. Methods: All women who attended first trimester screening were assessed. After delivery, risks of early-onset (delivery prior to 34 weeks) pre-eclampsia, late pre-eclampsia and gestational hypertension were calculated using the FMF risk algorithm. Of women who had a live birth, 12 were delivered before 34 weeks due to early pre-eclampsia (0.4%) and 71 (2.4%) due to late pre-eclampsia (after 34 weeks).
() III-2 691,738 Aim: To determine the incidence of preeclampsia and eclampsia and associated mortality in Australia between 2000 and 2008. Methods: Analysis of statutorily collected datasets of singleton births in New South Wales using International Classification of Disease coding. Analyzed using cross tabulation, logistic regression, and means testing, where appropriate. The overall incidence of preeclampsia was 3.3% with a decrease from 4.6% to 2.3%. The overall rate of eclampsia was 8.6/10,000 births or 2.6% of preeclampsia cases, with an increase from 2.3% to 4.2%. The relative risk of eclampsia in pre-eclamptic women in 2008 was 1.9 (95%CI 1.28 to 2.92) when compared with the year 2000. The relative risk of a woman with preeclampsia/eclampsia dying in the first 12 months following birth compared with normotensive women is 5.1 (95%CI 3.07 to 8.60). () III-2 37,424 Aim: To examine trends in maternal and newborn health characteristics for all mothers who were recorded as Aboriginal in the Western Australian Midwives' Notification System from 1986 to 2009. Methods: Births were categorised into time intervals (1986-1989, 1990-1993, 1994-1997, 1998-2001, 2002-2005, 2006-2009). Trends in maternal demographic characteristics, pre-existing medical conditions, pregnancy complications and neonatal characteristics were examined. The prevalence of pre-eclampsia decreased (6.8-4.0%, P < 0.001).
() III-2 2,261 Aim: to investigate whether multivitamin use during pregnancy is associated with a reduced risk of pre-eclampsia. Methods: The effect of multivitamin use on incidence of pre-eclampsia in lean and overweight/obese women was analysed using data collected between 2006 and 2011 as part of the Environments for Healthy Living Project, Griffith University, Australia. Body mass index (BMI)>25 was associated with increased in risk (OR 1.97; 95%CI 0.93 to 4.16). First trimester multivitamin use was associated with a 67% reduction in risk (95%CI: 0.14 to 0.75). Stratification by BMI demonstrated a 55% reduction in pre-eclampsia risk (95%CI: 0.30 to 0.86) in overweight (BMI: 25-29.9) and 62% risk reduction (95%CI: 0.16, 0.92) in obese (BMI:>30) cohorts that supplemented with multivitamins in the first trimester of pregnancy. First trimester folate supplementation demonstrated significance upon stratification by overweight status for women with BMI >25 (AOR 0.55 95%CI: 0.31 to 0.96). Women aged 45 years or older Study ref LoE N Aim/ methods Findings Comments () III-2 49,126 Aim: to determine maternal and perinatal outcomes of pregnancies in women aged 45 years or older compared to women aged years. Methods: Data on births at 20 or more weeks' gestation were obtained from the Victorian Perinatal Data Collection for the years 2005 and 2006 and selected maternal and perinatal outcomes for women of very advanced maternal age (VAMA) aged 45 years or older (n=217) compared to women aged 30-34 years (n=48,909). There was weak evidence for an increased risk of pre-eclampsia (OR 1.86; 95% 0.9 to 3.6; p=0.052).
Women by planned place of birth Study ref LoE N Aim/ methods Findings Comments () III-2 258,161 Aim: to determine whether a retrospective linked data study using routinely collected data was a viable means to compare perinatal and maternal outcomes and interventions in labour by planned place of birth at the onset of labour in one Australian state. Methods: A population-based cohort study was undertaken using routinely collected linked data from the NSW Perinatal Data Collection, Admitted Patient Data Collection, Register of Congenital Conditions, Registry of Birth Deaths and Marriages and the Australian Bureau of Statistics over 8 years. Pre-eclampsia was reported in 1.1% of women who planned to give birth in the hospital, 0.6% of women who planned to give birth in a birth centre and 0.1% of women who planned to give birth at home (p<0.001).
Women who experience vaginal bleeding in pregnancy Study ref LoE N Aim/ methods Findings Comments () III-2 3,431 Aim: To describe patterns of vaginal bleeding in the first 20 weeks of pregnancy and evaluate the association between patterns of bleeding and risk of subsequent in nulliparous women. Methods: Participating centres of the Screening for Pregnancy Endpoints (SCOPE) study in Auckland (New Zealand), Adelaide (Australia), Manchester and London (UK) and Cork (Ireland). Population. Healthy nulliparous women (n= 3431). Logistic regression was used to assess the association between bleeding characteristics and pre-eclampsia while controlling for known determinants of pre-eclampsia. Vaginal bleeding during the first 20 weeks was experienced by 780 (23%) women. Risk of pre-eclampsia was not associated with the presence or absence of bleeding (aOR 0.96; 95% CI 0.67 to 1.38). Analyses confined to women with vaginal bleeding showed that any bleeding episode of five or more consecutive days, compared with shorter episodes, increased risk of approximately twofold (aOR 2.15, 95% CI 1.01 to 4.57), as did multiple compared with single episodes of bleeding (aOR 2.33, 95%CI 1.16 to 4.67).
Q2 What are the risk factors for developing pre-eclampsia? Study ref LoE N Aim/ methods Findings Comments () I 92 studies 25,356,688 pregnancies Aim: To develop a practical evidence based list of clinical risk factors that can be assessed by a clinician at < 16 weeks' gestation to estimate a woman's risk of pre-eclampsia. Methods: Systematic review and of cohort studies from PubMed and Embase databases, 2000-15. Cohort studies with >1,000 participants that evaluated the risk of pre-eclampsia in relation to a common and generally accepted clinical risk factor assessed at <16 weeks' gestation. Two independent reviewers extracted data from included studies. A pooled event rate and pooled relative risk for pre-eclampsia were calculated for each of 14 risk factors. The pooled relative risk for each risk factor significantly exceeded 1.0, except for prior intrauterine growth restriction. Women with antiphospholipid antibody syndrome had the highest pooled rate of (17.3%, 95% confidence interval 6.8% to 31.4%). Those with prior pre-eclampsia had the greatest pooled relative risk (8.4, 7.1 to 9.9). Chronic hypertension ranked second, both in terms of its pooled rate (16.0%, 12.6% to 19.7%) and pooled relative risk (5.1, 4.0 to 6.5) of pre-eclampsia. Pregestational diabetes (pooled rate 11.0%, 8.4% to 13.8%; pooled relative risk 3.7, 3.1 to 4.3), prepregnancy body mass index (BMI) >30 (7.1%, 6.1% to 8.2%; 2.8, 2.6 to 3.1), and use of assisted reproductive technology (6.2%, 4.7% to 7.9%; 1.8, 1.6 to 2.1) were other prominent risk factors.
Fetal sex () I 22 studies 3,163,735 women Aim: to conduct a systematic review and meta-analysis to objectively evaluate the relationship between fetal sex and maternal risk of pre-eclampsia/eclampsia. Methods: Studies from January 1950 to April 2015 were identified from PUBMED and EMBASE. Selection criteria: This systematic review and meta-analysis evaluated 22 articles reporting data on fetal sex and prevalence of pre-eclampsia/eclampsia. Data collection and analysis: Data were extracted by two independent reviewers. Pooled estimates of the relative risk (RR) were calculated by random-effects model. Pooled analyses of these studies showed no association between male fetal sex and maternal risk of (RR 1.01; 95%CI 0.97 to 1.05); however, a subgroup analysis including only studies that evaluated the non-Asian population (n=2,931,771) demonstrated that male fetal sex was associated with increased maternal risk of pre-eclampsia/ eclampsia (RR 1.05; 95%CI 1.03 to 1.06; P=0.33).
Assisted reproductive technology Study ref LoE N Aim/ methods Findings Comments Oocyte donation () I 19 studies 86,515 pregnancies Aim: to determine whether pregnancies that were achieved via oocyte donation, compared with pregnancies achieved via other assisted reproductive technology methods or natural conception, demonstrate increased risk of preeclampsia or gestational hypertension. Methods: Comparative studies of pregnancies that were achieved with oocyte donation vs other methods of assisted reproductive technology or natural conception with preeclampsia or gestational hypertension were included as 1 of the measured outcomes. Two reviewers independently selected studies, which were assessed for quality with the use of methodological index for non-randomized studies, and extracted the data. Statistical analysis was conducted. Our pooled data demonstrated that the risk of preeclampsia is higher in oocyte-donation pregnancies compared with other methods of assisted reproductive technology (OR 2.54; 95%CI 1.98 to 3.24; P<0.0001) or natural conception (OR 4.34; 95%CI 3.10 to 6.06; P <.0001). Subgroup analysis conducted for singleton and multiple gestations demonstrated a similar risk for preeclampsia and gestational hypertension in both singleton and multiple gestations.
() I 11 studies Aim: to determine whether there is a higher incidence of preeclampsia (PE) in pregnancies achieved by oocyte donation (OD) compared with pregnancies achieved by in vitro fertilization with autologous oocytes (IVF). Methods: A systematic review was performed to identify relevant studies published from January 1994 until April 2015 with at least an abstract in English using PubMed, ISI Web of Knowledge, and clinicaltrials.gov. The studies included in this systematic review were retrospective and prospective cohort studies of women reporting results on the association between oocyte donation vs. in vitro fertilization (exposure) and preeclampsia (outcome). Oocyte donation is a risk factor for the development of PE compared to IVF cycles, with a weighted OR of 3.12 under a fixed effects method (FEM: no heterogeneity between the studies). The weighted OR under a random effects model was 2.9 (95%CI 2.19 to 3.85). The meta-regression analysis showed that neither multiple pregnancies (estimate = 0.08; p = 0.19) nor patient age (estimate = -2.29; p = 0.13) significantly explained the variability of the effect of oocyte donation on PE. Q statistic was 12.78 (p = 0.237), suggesting absence of heterogeneity between the studies. Donor insemination () I 7 studies 10,898 women Aim: to evaluate whether women who conceive with donor sperm have an increased risk of preeclampsia compared with those who use their partner's sperm. Methods: Studies that compared women who were impregnated by donor (n=2,342) and partner (n=8,556) sperm were included. The main outcomes assessed were preeclampsia and gestational hypertension rates. Conception using donor sperm was associated with an increased risk of preeclampsia (OR 1.63, 95%CI 1.36 to 1.95) compared with using a partner's sperm. No difference was observed in the risk of gestational hypertension (OR 0.94, 95% CI 0.43-2.03). Included studies were observational
Arterial stiffness () I 23 studies Aim: to investigate the association between preeclampsia and arterial stiffness. Method: A systematic review and was conducted using MEDLINE, EMBASE, and the Cochrane Library. A significant increase in all arterial stiffness indices combined was observed in women with preeclampsia vs women with normotensive pregnancies [SMD 1.62, 95%CI 0.73 to 2.50]; carotid-femoral pulse wave velocity (cfPWV) and augmentation index (AIx) were also significantly increased (WMD cfPWV 1.04, 95%CI 0.34 to 1.74; WMD AIx 15.10, 95%CI 5.08 to 25.11), whereas carotid-radial PWV (crPWV) increase did not reach significance (WMD crPWV 0.99, 95%CI to 2.05). Periodontal disease Study ref LoE N Aim/ methods Findings Comments () I 15 studies (13 case-control; 2 cohort) 1,089 women with Aim: to ascertain the relationship between PD and preeclampsia. Methods: The PubMed database was searched up to January 12, 2013, for relevant observational studies on an association between PD and the risk of preeclampsia. Data were extracted and analyzed independently by two authors. The was performed using comprehensive meta-analysis software. Based on a random-effects a significant association between PD and preeclampsia was identified (OR 2.79, 95% CI 2.01 to 3.01, P<0.0001). Although the causality remains unclear, the association between PD and preeclampsia may reflect the induction of PD by the preeclamptic state, or it may be part of an overall exaggerated inflammatory response to pregnancy. 0.07
Yang, W., et al. (2014). "Evaluation of association of maternal IL-10 polymorphisms with risk of preeclampsia by A Journal of cellular and molecular medicine 18(12): 2466-2477. Relevant to research not practice Zhang, G., et al. (2016). "Association between gene polymorphisms on chromosome 1 and susceptibility to pre-Eclampsia: An updated meta-analysis." Medical Science Monitor 22: 2202-2214. Relevant to research not practice Zhu Q, Zhang L, Chen X et al (2016) Association between zinc level and the risk of preeclampsia: a meta-analysis. Arch Gynecol Obstet 293(2): 377-82. Overlap with higher quality systematic review
() III-2 120 Aim: to evaluate placental protein-13 (PP-13) and pregnancy-associated plasma protein-A (PAPP-A) in first trimester maternal serum, for predicting pre-eclampsia. Methods: A prospective case-control study included women with (n=30) and pregnant controls (n=90). Women with were divided into two subgroups: early (n=9) and late-onset (n=21), and PP-13 and PAPP-A levels were compared between the groups and the comparison of risks for were calculated. There was a significant inverse correlation between PAPP-A and late pre-eclampsia (p=0.003), with a value of 0.805 (ROC analysis area under curve 0.751). There was a significant reverse correlation between PAPP-A and early (p=0.02). There was no significant relationship between PP13 and early pre-eclampsia, nor with late pre-eclampsia (p=0.7, p=0.6, respectively). It was concluded that neither of these markers can serve as a sufficient and reliable screening test of pre-eclampsia because of inadequate sensitivity in the Turkish pregnant population. () Cohort III-2 500 Aim: to find indicators with sufficient positive predictive value. Methods: Serum TNF-alpha and uterine artery Doppler were measured at 11-13 weeks in low-risk pregnant women. TNF-alpha cut-off value >14. pg/mL had a sensitivity of 67.8% and a specificity of 98% in predicting PE with PPV of 79.4% and NPV of 96.4%. Mean uterine artery PI >1.7 had a 100% sensitivity and 84.4% specificity in predicting PE, with a PPV of 41.7% and NPV of 100%. off
() Validation study — 871–2,962 Aim: To evaluate the performance of published first-trimester prediction algorithms for pre-eclampsia (PE) in a prospectively enrolled cohort of women. Methods: A MEDLINE search identified first-trimester screening-prediction algorithms for early-onset (requiring delivery < 34 weeks) and late-onset (requiring delivery > 34 weeks) PE. Maternal variables, ultrasound parameters and biomarkers were determined prospectively in singleton pregnancies enrolled between 9 and 14 weeks. Prediction algorithms were applied to this population to calculate predicted probabilities for PE. The performance of the prediction algorithms was compared with that in the original publication and evaluated for factors explaining differences in prediction. One early PE prediction algorithm performed better than in the original publication (80% detection rate (DR) of early PE for 10% false-positive rate (FPR)); the remaining five prediction algorithms underperformed (29-53% DR). Prediction algorithms for late PE also underperformed (18-31% DR, 10% FPR). Applying the screening cut-offs based on the highest Youden index probability scores correctly detected 40-80% of women developing early PE and 71-82% who developed late PE. Exclusion of patients on first-trimester aspirin resulted in DRs of 40-83% and 65-82% for early and late PE, respectively. Two of the studies included in this review (; ) were included in this validation study and found to underperform.
() Cohort III-2 176 Aim: To evaluate the NICE and PRECOG guidelines risk factors for to identify mothers at risk before 20 weeks' gestation. Cases (n=64) and controls (n=112) were classified retrospectively as screen positive or negative as recommended by the two guidelines The NICE guideline had a higher sensitivity rate of 77% (95%CI 65 to 87%) vs 59% (95% CI 46 to 71%) but a lower specificity of 54% (95% CI 44 to 64%) vs 81% (95% CI 73 to 88%) with the PRECOG guideline. Based on an incidence of pre-eclampsia of 4% the PPVs of PRECOG and NICE guidelines were estimated at only 11% and 7%, respectively. The most discriminatory risk factor was history of pre-eclampsia in a previous pregnancy. () Cohort III-2 615 Aim: To determine the diagnostic accuracy of preeclampsia (PE) screening test offered in early pregnancy for the prediction of the risks for early-onset (requiring delivery <32 weeks gestation) and late onset (requiring delivery ≥32 weeks gestation) disease. Methods: In women with singleton pregnancy, the risk for PE was calculated by the combined effect of multiple variables: serum PlGF, PAPP-A, maternal age, parity, ethnicity, MAP, BMI, UtA PI, and previous history of PE or hypertension (HT). The results of the screening test in three different groups of women were validated by pregnancy outcome: control group; history of PE without HT; and (iii) history of HT without PE. The multivariate screening effectively identified cases of PE with >97% specificity. The detection rate (DR) was 93.8% for late-onset PE at a false positive rate (FPR) of 2.3% and 44.4% for early-onset PE at an FPR of 0.0%. The incidence of PE was 7% overall, with 1.52% and 5.43% for early- and late-onset PE, respectively. The study demonstrated 96.6% diagnostic accuracy of the multi-variable screening test to predict the risk of PE in the first trimester. The negative predictive value (>98%) reinforces the utility of cost-effective noninvasive screening test for the early detection of PE.
() Cohort III-2 120,492 Aim: to develop a model for preeclampsia based on maternal demographic characteristics and medical history. Methods: Singleton pregnancies at weeks' gestation (2704 [2.2%] with preeclampsia. A survival-time model for the gestational age at delivery with preeclampsia was developed from variables of maternal characteristics and history. This approach assumes that, if the pregnancy was to continue indefinitely, all women would experience preeclampsia and that whether they do so or not before a specified gestational age depends on competition between delivery before or after development of preeclampsia. A 5-fold cross validation study was conducted to compare the performance of the new model with the National Institute for Health and Clinical Excellence (NICE) guidelines. In the new model, increased risk for preeclampsia, with a consequent shift in the Gaussian distribution of the gestational age at delivery with preeclampsia to the left, is provided by advancing maternal age, increasing weight, Afro-Caribbean and South Asian racial origin, medical history of chronic hypertension, diabetes mellitus and systemic lupus erythematosus or antiphospholipid syndrome, family history and personal history of preeclampsia, and conception by IVF. The risk for preeclampsia decreases with increasing maternal height and in parous women with no previous preeclampsia. At a screen-positive rate of 11%, as defined by NICE, the new model predicted 40%, 48%, and 54% of cases of total preeclampsia and preeclampsia requiring delivery at <37 and <34 weeks' gestation, respectively, which were significantly higher than the respective values of 35%, 40%, and 44% achieved by application of NICE guidelines. 13
() Cohort III-2 150 Aim: to analyze whether estimation of serum PlGF levels in late second trimester can act as a predictor of preeclampsia. Methods Nulliparous women were divided into three groups: normotensive (n=30), mild (n=60) and severe (n=60) preeclampsia. Serum samples collected from the study groups were subjected to ELISA, and serum PlGF level was calculated. Mean serum PlGF levels were found to be significantly low in mild and severe pre-eclampsia as compared to normal pregnancy. Serum PlGF levels were highest at 26–28 weeks and were lowered at 28–30 and 30–32 weeks of gestation within each of the three study groups. Cut-off value of serum PlGF levels for predicting and severe pre-eclampsia were <20 and <107 pg/mL, respectively. () Cohort III-2 722 Aim: To determine whether maternal serum PlGF estimation in early second trimester (20-22 weeks) can predict the occurrence of early onset preeclampsia and/or early onset (<32 wks) IUGR. Methods: Singleton pregnancies were screened and serum PlGF levels were estimated at 20-22 weeks of gestation. A cut-off value of <155 pg/mL for serum PlGF was determined by ROC analysis. Univariate logistic regression analysis was used to analyze the association between serum PlGF level <155 pg/mL and the two outcome measures OR was computed. Maternal serum PlGF level <155 pg/mL at 20-22 weeks of gestation had a strong association with early onset preeclampsia (OR 8.35; 95%CI 1.79 to 18.94; P=0.007). The sensitivity of serum PlGF <155 pg/mL for predicting early onset preeclampsia was 82.
() Cohort III-2 1,011 Aim: To explore major risk factors and early prediction methods in the pathogenesis of early onset preeclampsia. Methods: Prenatal screening was performed in second trimester using enzyme-linked immunosorbent assay and epidemiological correlation factors were obtained by telephone. Predictive model of early onset preeclampsia was established and evaluated by single and multiple factor logistic analysis. Women with early onset had significantly elevated hCG (P<0.001). Major risk factors were pregestational BMI >24 (OR 3.649, 95%CI 1.600 to 8.321, P=0.002), history of hypertension, diabetes and nephritis (OR 55.724, 95%CI 8.223 to 377.614, P<0.001), family history of hypertension (OR 6.777, 95%CI 2.917 to 15.742, P<0.001) and risk coefficient for trisomy 21 (OR 3.688, 95%CI 1.013 to 13.429, P=0.048). 0.792 (95 % CI 0.701–0.882). () 243 Aim: To develop a model for prediction of late preeclampsia based on maternal history and characteristics, MAP, and circulating levels of mRNA for the placenta- specific 1 (PLAC1) gene in maternal plasma at 14–18 weeks. Method: A Gaussian model was fitted to the log distribution of the multiple of the median (log MoM) PLAC1 mRNA in the PE group and in the unaffected group. Likelihood ratios for log MoM of circulating levels of mRNA for the PLAC1 gene were used to combine the a priori risk from maternal characteristics with MAP to produce patient-specific risks for each case. Screening by maternal characteristics (including BMI, woman's mother's history of PE, previous PE, and parity) (a priori risk) and MAP detected 46.8% of all cases of late PE at a fixed FPR of 10%. The addition of PLAC1 yielded a DR of 62.8% at the same level of FPR. PLAC1 alone yielded a DR of 30.2%.
() Cohort III-2 4,294 145 PE 161 GH Aim: To investigate the potential value of measuring MAP, sBP and dBP at weeks' gestation in the prediction of preeclampsia (PE) developing at or after 34 weeks. Methods: The a priori risks for intermediate and late PE from maternal demographic characteristics and medical history were determined. The a posteriori risks were calculated by combining the a priori risks with the likelihood ratios for MAP, sBP and dBP, which were calculated from fitted bivariate gaussian distributions. The mean multiple of median MAP, sBP and dBP were significantly higher in the intermediate and late PE groups than in the normal group. In screening by a combination of maternal characteristics and MAP, the estimated detection rates of intermediate and late PE, at a rate of 10%, were 70.3 and 62.0%, respectively. The respective detection rates for sBP were 62.2 and 59.3% and for dBP were 62.2 and 57.4%. () Cohort III-2 145 PE 4,294 control Aim: To investigate the potential value of measuring UtA pulsatility index (PI) at 30-33 weeks' gestation in the prediction of preeclampsia (PE) developing at or after 34 weeks. Methods: The a priori risks for intermediate- and late-PE from maternal demographic characteristics and medical history were derived by logistic regression analysis. The a posteriori risks were calculated by combining the a priori risks with the likelihood ratios for uterine artery PI, which were calculated from fitted bivariate gaussian distributions. In screening for PE by a combination of maternal characteristics and uterine artery PI, the estimated detection rates of intermediate- and late-PE, at a false-positive rate of 10%, were 70.3 and 54.6%, respectively.
Sequential testing/screening Study ref Design LoE N Aim/methods Results Comments () Cohort III-2 2,433 Aim: To compare performance of multimarker algorithm, risk profiles and their sequential application in prediction of preeclampsia and determining potential intervention targets. Methods: Maternal characteristics, ultrasound variables and serum biomarkers were collected prospectively at first trimester. Univariate analysis identified preeclampsia associated variables followed by logistic regression analysis to determine the prediction rule. Combined characteristics of the cardiovascular, metabolic and the personal risk factors were compared to the multimarker algorithm and the sequential application of both methods. While the multimarker algorithm had the lowest false negative rate, sequential application of cardiovascular and metabolic risk profiles in screen positives reduced false positives by 26% and identified blood pressure and metabolic risk in 49/54 (91%) women with subsequent preeclampsia as treatable risk factors.
Costs associated with screening, diagnosis and treatment for pre-eclampsia Study ref Design LoE N Aim/methods Results Comments () Economic analysis — 6 studies Aim: to provide an overview of the existing evidence on the health economics of screening, diagnosis and treatment options in pre-eclampsia. Methods: We searched PubMed, EMBASE and the Cochrane Library for studies on screening, diagnosis, treatment or prevention of published between 1994 and 2014. Full papers in English containing complete economic assessments were included. Three studies were on the cost effectiveness of treatment (two evaluated magnesium sulphate for prevention of seizures and the third induction of labour vs expectant monitoring). The other three studies were aimed at screening and diagnosis, in combination with subsequent preventive measures. The screening studies were quite diverse in their objectives as well as in their conclusions. One study concluded that screening is probably not worthwhile, while two other studies stated that in certain scenarios it may be cost effective to screen all pregnant women and prophylactically treat those who are found to be at high risk of developing pre-eclampsia. Universal screening for pre-eclampsia, using a biomarker, will be feasible only when accuracy is significantly increased. The two studies on magnesium sulphate were equivocal on the cost effectiveness in non-severe cases, and the other study suggested that induction of labour in term was more cost effective than expectant monitoring. Q4 What are the harms of not screening for pre-eclampsia? No studies identified
Q6 When in pregnancy should screening be carried out? Study ref Design LoE N Aim/methods Results Comments () Nested III-2 98 PE each matched to 5 control Aim: to examine the association between preeclampsia and biochemical markers, in matched first and second trimester maternal serum samples. Method: Stored samples were available from 'integrated' Down syndrome screening. Population distribution parameters and within and between trimester correlations were derived for cases and controls for six markers, as well as in case subgroups. Second trimester associations were stronger than those in the first (e.g. PAPP-A 2.45, p < 0.01). No associations were found that would provide important improvements in prediction. Q7 What are the benefits and risks of the predictive tests (eg PAPP-A) to identify women at risk of pre-eclampsia? See Q3 Q8 Should every woman be tested for proteinuria at every antenatal visit if blood pressure remains normal? No studies identified 2.2 Excluded studies for screening Background papers Background papers will inform revision of the narrative.