Jason Waugh

Diagnostic Accuracy of Placental Growth Factor in Women With Suspected Preeclampsia A Prospective Multicenter Study

Background— Hypertensive disorders of pregnancy are a major contributor to death and disability for pregnant women and their infants. The diagnosis of preeclampsia by using blood pressure and proteinuria is of limited use because they are tertiary, downstream features of the disease. Placental growth factor (PlGF) is an angiogenic factor, a secondary marker of associated placental dysfunction in preeclampsia, with known low plasma concentrations in the disease. Methods and Results— In a prospective multicenter study, we studied the diagnostic accuracy of low plasma PlGF concentration (<5th centile for gestation, Alere Triage assay) in women presenting with suspected preeclampsia between 20 and 35 weeks’ gestation (and up to 41 weeks’ gestation as a secondary analysis). The outcome was delivery for confirmed preeclampsia within 14 days. Of 625 women, 346 (55%) developed confirmed preeclampsia. In 287 women enrolled before 35 weeks’ gestation, PlGF <5th centile had high sensitivity (0.96; 95% confidence interval, 0.89–0.99) and negative predictive value (0.98; 0.93–0.995) for preeclampsia within 14 days; specificity was lower (0.55; 0.48–0.61). Area under the receiver operating characteristic curve for low PlGF (0.87, standard error 0.03) for predicting preeclampsia within 14 days was greater than all other commonly used tests, singly or in combination (range, 0.58–0.76), in women presenting with suspected preeclampsia (P<0.001 for all comparisons). Conclusions— In women presenting before 35 weeks’ gestation with suspected preeclampsia, low PlGF has high sensitivity and negative predictive value for preeclampsia within 14 days, is better than other currently used tests, and presents an innovative adjunct to management of such women.

Optimal bedside urinalysis for the detection of proteinuria in hypertensive pregnancy: a study of diagnostic accuracy

Objective  To compare semi‐quantitative visual and automated methods of urine testing with fully quantitative point of care urinalysis for the detection of significant proteinuria (0.3 g/24 hours) in pregnancy complicated by hypertension.

Hidden errors of aneroid sphygmomanometers.

BackgroundMeasurement of blood pressure remains the most commonly performed screening test in medical practice. With the likely removal of mercury sphygmomanometers from the workplace alternative devices are required. Of these the aneroid sphygmomanometer is popular both in the community and hospital setting. We investigated the accuracy of all the aneroid and mercury sphygmomanometers during dynamic calibration within a tertiary referral maternity hospital. MethodsWe compared the accuracy of 39 aneroid and 36 mercury sphygmomanometers to a recently calibrated and serviced mercury sphygmomanometer (the accepted gold standard). All devices were in current clinical use. Using three blinded, trained observers, 30 different pressures were checked throughout the pressure range following British Hypertension Society protocol guidelines. ResultsOnly 31 (86%) of the mercury devices and 36 (92%) of the aneroid devices were in adequate working condition and suitable for analysis. Significantly more aneroid devices had systematic errors of > 5 mmHg (19 versus 3%, P < 0.05). Fifty percent of aneroid devices had at least one reading > 10 mmHg out compared to only 10% of mercury devices (chi square programme). ConclusionsAneroid sphygmomanometers in apparent good working order are inaccurate compared to mercury devices. Some of these faults can only be detected during dynamic testing. To minimize the risk of erroneous blood pressure recording, aneroid devices should be regularly checked for accuracy using dynamic calibration methods as recommended in validation protocols.

Factors influencing repeat caesarean section: qualitative exploratory study of obstetricians' and midwives' accounts

Objective  To explore the views of health professionals on the factors influencing repeat caesarean section.

Assessing the onset of pre-eclampsia in the hospital day unit: summary of the pre-eclampsia guideline (PRECOG II).

Pre-eclampsia remains a leading cause of maternal death, with 72% of pre-eclampsia cases associated with substandard care.1 One in 10 pregnant women develop partial signs or symptoms (73 000 a year in the United Kingdom); about 20% of these progress to pre-eclampsia.2 3 This article summarises recommendations from the Pre-Eclampsia Community Guideline (PRECOG) Group4 under the auspices of the charity Action on Pre-eclampsia. The recommendations cover the assessment of women with suspected pre-eclampsia by hospital midwives in day assessment units and complements our previous community based advice.5 6 PRECOG recommendations (see table 1⇓ for definitions used) are based on systematic review of evidence and expert consensus, graded A, B, C, or D; a “good practice point”(GPP) is based on the guideline development group’s experience (box 1). The grading is shown in parentheses after each recommendation. View this table: Table 1  Definitions used in the PRECOG recommendations #### Box 1 Levels of evidence on which recommendations are based*† ##### Grading of recommendations ##### Grading (level) of evidence

Urine protein estimation in hypertensive pregnancy: which thresholds and laboratory assay best predict clinical outcome?

Objective. To determine what threshold for proteinuria could best predict clinical outcome and whether this threshold could be applied universally to any biochemical assay. Design. A prospective observational study of hypertensive pregnancies referred for further assessment after in a UK University hospital (n = 197). Twenty-four hour urine protein was measured by two different assays [benzethonium chloride assay (BCA) and Bradford assay]. The differences between the two assays were calculated from Receiver Operating Characteristic (ROC) curves. Commonly used thresholds for defining preeclampsia (0.3 and 0.5 g/24 hours) were explored for both assays for the prediction of adverse clinical outcomes (severe hypertension, Birthweight < 10th percentile, preterm delivery, and a composite biochemical/haematological derangement). Results. The two assays are not equivalent. The prevalence of > 300 mg/24 hour proteinuria and, hence, the prevalence of preeclampsia differed between the two assays. ROC curve analysis demonstrates that the two assays are similar in terms of overall performance as predictive tests. However the threshold of 300 mg/24 hours performs poorly as a predictor of clinical risk. Likelihood ratios (LR) for the BCA at the 300 mg/L threshold for each clinical outcome do not achieve statistical significance. At the 500 mg/L threshold, the LR + for the BCA assay does achieve statistical significance for severe hypertension (LR + : 1.51 95% CI 0.99–2.28) and for birthweight < 10th percentile (LR + : 1.72 95% CI 1.11–2.66). For the Bradford assay at the 300 mg/24 hour threshold, the LR + does achieve statistical significance for birthweight < 10th percentile (LR + : 1.71 95% CI 1.41–4.31). However, at the 500 mg/24 hour threshold, the LR + is significant for severe hypertension (LR + : 2.15 95% CI 1.07–4.34), birthweight < 10th percentile (LR + : 2.79 95% CI 1.4–5.54) and biochemical disease (LR + : 2.47 95% CI 1.22–5.01). Conclusions. This study suggests that thresholds for proteinuria need to be higher (possibly ≥ 0.5 g/24 hours) and there is the need for a “gold standard” proteinuria assay against which all other measures of quantification can be assessed.

Practices and views on fetal heart monitoring:A structured observation and interview study

Objective  To assess and explain deviations from recommended practice in National Institute for Clinical Excellence (NICE) guidelines in relation to fetal heart monitoring.

Patient Initiated Home Blood Pressure Recordings Are Accurate in Hypertensive Pregnant Women

Objective. We undertook this study to determine the accuracy and reliability of patient initiated blood pressure measurement and recording. Methods. We recruited 72 women from the antenatal hypertension clinic in a university teaching hospital. All were at high risk for preeclampsia and were asked to measure and record their blood pressure three times per day at home using a validated blood pressure device with an internal memory. Results. From 979 measurements taken only 28 (2.9% were inaccurate). The inaccurate readings were restricted to three women. On further questioning two women admitted that the device had been used by other family members thus making comparison with the memory impossible. Thus the true nonconcordance rate amongst participants was 1/72 (1.4%). Conclusions. We conclude that blood pressure recordings taken and documented by high‐risk women at home are accurate. This allows more frequent measurements to be taken without the inconvenience of additional visits to hospital and may therefore lead to the earlier detection of preeclampsia.

Urinary microalbumin/creatinine ratios: reference range in uncomplicated pregnancy

During uncomplicated pregnancy, the development of proteinuria is accepted as a poor prognostic sign and is associated with increasing maternal and perinatal mortality and morbidity. Physiological proteinuria increases with increasing gestation and one of its largest constituents is albumin. The reference range for the (micro)albumin/creatinine ratio (ACR) has not been described for normal pregnancy. This prospective cross-sectional study describes the gestation-specific 95% reference ranges for urinary microalbumin concentration, creatinine concentration and ACR in uncomplicated pregnancy. There is a significant increase ( P =0.016) in the ACR in the third trimester. The mean difference is 0.091 mg of albumin/mmol of creatinine (95% confidence interval, 0.014-0.168). Our results describe the first well-defined gestation-specific 95% reference range for a point-of-care measurement of the ACR. These data are essential if such testing is to be employed in antenatal care.

EFFECT OF CONCENTRATION AND BIOCHEMICAL ASSAY ON THE ACCURACY OF URINE DIPSTICKS IN HYPERTENSIVE PREGNANCIES

Objective: To assess how urine concentration and biochemical assay influence the assessment of proteinuria. Methods: This was a prospective study to assess the accuracy of detection and quantification of proteinuria within the day assessment unit and antenatal ward of a teaching hospital in Leicester, United Kingdom. We studied hypertensive pregnancies (of mixed parity) referred to day care assessment or attending the antenatal hypertension clinic after 20 completed weeks of gestation (n = 197). Aliquots of a well-mixed 24-h urine collection were tested by routine dipstick urinalysis and then assayed for protein using the Benzethonium Chloride and the Bradford assays (n = 197). Main Outcome Measures: Total protein excretion in 24 h and protein concentration per liter of urine for both biochemical assays were compared to semiquantitative dipstick protein measurement. Results: The prevalence of proteinuria in the study group varied according to the method used for testing. Dipstick urinalysis recorded the lowest prevalence (16.2%) and the Benzethonium Chloride assay measuring total protein excretion in 24 h recorded the highest (70.1%). When the positive and negative predictive values for dipstick urinalysis were calculated, performance was found to be dependent on both the units of measurement compared and the type of assay used as the “gold standard.” Positive predictive values ranged from 87.5% to 96.9% and negative predictive values ranged from 35.2% to 92.1%. Conclusions: The prevalence of proteinuria in hypertensive pregnancies is dependent on the method used to detect it. The amount of protein assessed quantitatively is further dependent on the biochemical assay employed. However, regardless of the quantitative assessment, dipstick urinalysis has a significant false-negative rate. This first reporting of a variation in performance between dipstick urinalysis and two different biochemical assays in pregnancy may be explained in relation to protein assay specificity and the observed protein compositions of the samples on electrophoretic analysis. The significance of proteinuria should be considered in light of the method used to detect it, but, ultimately, it must be related to clinical outcome.