Andrew Shennan

Blood pressure measurement in severe pre-eclampsia

Hypertensive disease in pregnancy remains a leading cause of maternal mortality. Death is often associated with cerebral haemorrhage with severe hypertension being the most important aetiological factor. Accurate measurement of blood pressure (BP) is essential to prevent maternal morbidity and mortality, and most units rely on indirect BP measurements. Some automated BP monitors under-record in pregnancy and particularly in pre-eclampsia when compared with mercury sphygmomanometry. There are no published data comparing intra-arterial measurements in severe pre-eclampsia with mercury sphygmomanometry and automated devices. The objective of this study was to determine the best non-invasive method for measuring BP in women with severe hypertension. We recruited nine women who required invasive monitoring for complications of severe preeclampsia/eclampsia (eg, pulmonary oedema) and four controls with other medical conditions requiring invasive monitoring. All women were studied within 12 hours of delivery. Women gave verbal consent and the study was approved by the University of Cape Town research ethics committee. Comparison was made between intra-arterial BP and three methods of non-invasive BP measurement: conventional sphygmomanometry and two automated BP devices, the Dinamap XL 9301 (Johnson and Johnson Medical, Tampa, USA) and the SpaceLabs Scout (SpaceLabs, Redmond, USA). The signal from the radial arterial line was recorded digitally on to an IBM PC for subsequent analysis. A static calibration was performed at 0 and 100 mm Hg and optimum dynamic calibration verified with a fast-flush test. All patients were semi-recumbant and the radial catheter, transducer, BP cuff, and sphygmomanometer were at heart level. All sphygmomanometry readings were obtained by a single trained observer who was blinded to intra-arterial BP. Diastolic BP was recorded at the disappearance of sounds. Intra-arterial BP was recorded for 15 s followed by an indirect BP on the same arm. This cycle repeated ten times for each automated BP device and for mercury sphygmomanometry as recommended by the Association for the Advancement of Medical Instrumentation. The ten comparisons on each individual were reduced to a summary measure. For each indirect BP measuring device the mean and standard deviation of the differences from intra-arterial measurements were calculated. The 95% confidence intervals of the mean of the differences were calculated and if they were significantly different from zero the non-invasive measurements were considered significantly different from the intra-arterial measurements. In pre-eclamptic women both automated monitors significantly underestimated systolic and mean BP by 11–18 mm Hg (see table). Diastolic BP was also underestimated by the Dinamap (11 mm Hg). Individual measurements were underestimated by up to 40 mm Hg. Conventional sphygmomanometry underestimated systolic by 7 mm Hg, overestimated diastolic by 6 mm Hg, and therefore a calculated mean arterial pressure (MAP) was only 2 mm Hg less than intra-arterial pressure. At present the use of automated monitors for the management of women with pre-eclampsia must be regarded with caution. We do not know if the difficulty is specific to the two monitors that we have studied, or is more general since no other monitor has been evaluated in this way. Despite the disadvantages of mercury sphygmomanometry, it is the technique that should be used to confirm severe hypertension. If an automated BP monitor is to be used in a woman with pre-eclampsia, its accuracy must be verified by comparison with conventional sphygmomanometry in each individual.

Ambulatory or conventional blood pressure measurement in pregnancy — Which is the better predictor of severe hypertension?

OBJECTIVESnOur purpose was to investigate the benefit, if any, of automated blood pressure monitoring over obstetric day unit conventional blood pressure measurement in the assessment of hypertensive pregnancies.nnnSTUDY DESIGNnA prospective, observational study was carried out in two large teaching hospitals. Three hundred and forty-eight women with a confirmed clinic blood pressure of at least 140/90 mm Hg were recruited. Conventional blood pressure measurements (< or =5) were obtained on the day unit and simultaneously an ambulatory blood pressure monitor was applied for 24 hours. The predictive ability of day unit assessment (blood pressure > 140/90 mm Hg) and automated blood pressure monitoring (blood pressure > 130/85 mm Hg) was compared. Principal outcome measures included the occurrence of severe hypertension (> 160/110 mm Hg) and proteinuria (> 500 mg or 2+) within (a) 2 weeks and (b) the remainder of the pregnancy. Thompsons method was used to compare sensitivity and specificity of the day unit blood pressure and automated blood pressure monitoring.nnnRESULTSnThree hundred and forty-eight women were recruited to the study. The comparison between automated blood pressure monitoring and conventional blood pressure measurement for both sensitivity and specificity for systolic and diastolic blood pressure revealed increased sensitivity and decreased specificity with automated blood pressure monitoring for all principal outcomes except development of proteinuria for systolic blood pressure. Sensitivity for the outcomes was increased with automated blood pressure monitoring by between 14% and 27% for systolic blood pressure and between 7% and 39% for diastolic blood pressure, with the greatest improvement seen for the development of severe hypertension within 2 weeks of assessment.nnnCONCLUSIONSnIn the assessment of hypertensive pregnancies, automated blood pressure measurement was a significantly better predictor (compared with conventional day unit assessment) for the development of severe hypertension within 2 weeks of assessment for both systolic and diastolic blood pressure.

The QUiPP App: a safe alternative to a treat-all strategy for threatened preterm labor

To evaluate the impact of triaging women at risk of spontaneous preterm birth (sPTB) using the QUiPP App, which incorporates a predictive model combining history of sPTB, gestational age and quantitative measurements of fetal fibronectin, compared with a treat‐all policy (advocated by the UK National Institute for Health and Care Excellence) among women with threatened preterm labor before 30 weeks gestation.

Effect of antioxidant supplementation on pre-labour rupture of the membranes

Background Previous research exists to suggest vitamin C and E supplementation reduces the incidence of PROM (pre-labour rupture of the membranes) and preterm PROM (PPROM), conditions that precede up to a third of premature births.1 Antioxidants have a theoretical membrane protective effect against reactive oxygen species and collagen degradation.2 Aim To assess whether supplementation with vitamin C and E influences occurrence of PROM and PPROM in high risk pregnancy. Methods Data were analysed from the VIP trial (1000 mg vitamin C and 400 IU E vs Placebo in women at risk for pre-eclampsia) involving high risk women between 14+0 and 21+6 weeks gestation, across 25 UK centres. Demographics and pregnancy outcome were recorded,3 including time of rupture of membranes prior to labour and gestational age at delivery. Results Of 2411 participants, 154 (6.4%) women experienced PROM (n=113) or PPROM (n=41). The risk ratio for antioxidant supplementation in these pregnancies was 0.95 (95% CI 0.66 to 1.3) for PROM and 0.87 (0.47 to 1.60) for PPROM. There was no significant effect of antioxidants on PROM or PPROM when analysed by singleton/multiple pregnancy sub-groups. Conclusion These results suggest that there is no proven benefit of antioxidant supplementation in the reduction of PROM and PPROM, in singleton or multiple pregnancies. Further research is required to determine the pathophysiology and prevention of this life-threatening condition.

PFM.07 Quantitative fetal fibronectin testing as a predictor of spontaneous preterm delivery after cervical surgery

Introduction Quantitative fetal fibronectin (qfFN) testing has demonstrated accuracy at predicting sPTB in high-risk asymptomatic women (previous preterm birth or late miscarriage). It is not known whether qfFN has predictive accuracy in pregnancy after cervical surgery (a potentially different risk mechanism). This study compares the predictive value of qfFN in these two high-risk groups. Methods A prospective blinded secondary analysis of a larger observational study of cervicovaginal fluid fFN concentration (ng/ml) in asymptomatic women using rapid bedside 10q qfFN testing (Hologic™). Prediction of sPTB using qfFN concentrations in primiparous women who had undergone at least one surgical cervical procedure (n = 319) were compared with prediction in women who had one previous spontaneous preterm birth or late miscarriage (n = 236). Iatrogenic deliveries before the gestation of interest were excluded. Results The rate of sPTB <37 weeks in cervical surgery group was 4.1% compared with 19.4% in previous sPTB group. ROC curves for prediction of sPTB <34 and <37 weeks’ were comparable in both groups (34 weeks: 0.98 vs. 0.74, p = 0.05; 37 weeks: 0.604 vs 0.659, p = 0.62). An fFN concentration of >200 ng/ml had comparable positive prediction for sPTB <37 weeks’ in the cervical surgery group vs. previous sPTB group (42.9%; 95% CI 9.9–81.6 vs 54.5%; 95% CI 32.2–75.6) whilst negative prediction remained high for both groups (96.8% 95% CI 94.1–98.4 vs. 84.3% 95% CI 78.6–88.9). Conclusions Prediction of sPTB using qfFN in women with cervical surgery is useful, and has comparative accuracy to that in women with a history of sPTB.

Association between cervicovaginal cytokines and fetal fibronectin in women at risk of spontaneous preterm labour

Background An improved understanding of inflammatory events leading to cervical shortening in women at risk of spontaneous preterm labour (SPTL) is necessary. We undertook a longitudinal observational study to determine the relationship between cytokine and fetal fibronectin (fFN) concentrations in women at risk of SPTL. Methods Women (n=112) with at least one previous preterm delivery were recruited (14–24 weeks gestation) from two prematurity clinics and assessed (transvaginal cervical scans and cervico-vaginal fluid (CVF) swabs) every 2 weeks until 28 weeks. If cervical length shortened (<25 mm), women were randomised to cervical cerclage or progesterone and samples taken weekly. Concentrations of 11 cytokines were measured in CVF samples (n=477 from 78 women) using multiplex immunoassay. Concentrations of fFN were measured using ELISA (n=735 from 112 women). Data were analysed using STATA; results expressed as ratios (95% CI). Results There was no difference in CVF fFN concentrations in women destined to develop a short cervix (n=36) compared to high-risk women without a short cervix (n=76). Women with a positive fFN exhibited higher CVF concentrations of interleukin-6 (IL) (1.53 (1.21–1.94), p<0.001) IL-7 (1.19 (1.02–1.39), p=0.03), Granulocyte colony-stimulating factor (G-CSF) (1.25 (1.00–1.57), p=0.05), interferon-γ (IFN-γ) (1.28 (1.01–1.61), p=0.04), monocyte chemoattractant protein 1 (MCP-1) (1.18 (1.00–1.38), p=0.05) and Macrophage inflammatory protein 1β (MIP-1) (1.43 (1.04–1.97), p=0.03) at the same gestational age. Doubling concentrations of IL-6 and TNF α were associated with a positive fFN test 2 weeks later (1.32 (1.00–1.73), p=0.05 and 1.50 (CI 1.01 to 2.24), p=0.05, respectively). Conclusions Elevated CVF IL-6, IL-7, G-CSF, IFN-γ, MCP-1 and MIP-1β concentrations are associated with a positive fFN test. fFN does not appear to be involved in the processes leading to cervical shortening.

Nocturnal ambulatory blood pressure measurement.

EDITOR, - We disagree that the findings of R J O Davies and colleagues should be taken into account as part of clinical and epidemiological interpretation.1nnThe authors assume that the “aroused” ambulatory blood pressure is less accurate than the true physiological pressure. This is self evident but has no clinical relevance, as physiological pressure can never …

Threatened and Actual Preterm Labor

Introduction Despite the long-term focus on its prevention, preterm birth remains the leading cause of neonatal death, and the second leading cause of under-5 mortality, after pneumonia, worldwide. Of those babies who survive, many have severe long-term physical and neurodevelopmental morbidity. Management options for pregnant women with threatened preterm birth focus on delaying delivery using tocolysis, and administering antenatal therapy such as corticosteroids and, more recently, magnesium sulfate (for fetal lung development and neuroprotection respectively) to improve outcome for the infant once born. Given that most women who present with preterm contractions do not go on to deliver preterm infants, the challenge is to identify the appropriate recipients of these therapies. Prevention of preterm birth relies on screening and identifying women at the highest risk of later preterm birth and using interventions such as cervical cerclage, progesterone therapy, or a cervical pessary while the woman is still asymptomatic. While traditionally based on prior obstetric history alone, both transvaginal cervical length and cervical fluid biomarkers, such as fetal fibronectin and phosphorylated insulin-like growth factor binding protein, are increasingly recognized as being useful for the prediction of preterm birth in both symptomatic and asymptomatic women. This chapter reviews the management of preterm labor and delivery, the screening tools available to identify women at high risk, and potential preventive interventions. Summary of Terms Preterm labor (PTL) is defined by the World Health Organization (WHO) as the onset of labor before 37 completed weeks or 259 days of gestation, and after the gestation of viability (22–28 weeks dependent on definition and setting). The onset of labor refers to regular uterine contractions (at least one every 10 minutes), associated with documented cervical change or rupture of fetal membranes. In the absence of cervical change or ruptured membranes, a diagnosis of threatened PTL (TPTL) can be made. Most women diagnosed with TPTL do not go on to deliver preterm. Preterm birth (PTB) is the birth of an infant before 37 completed weeks’ gestation. The gestational endpoint of 37 weeks was decided upon by the WHO from a statistical analysis of the distribution of gestation of birth based on the first day of the last menstrual period.

PF.08 Quantitative Fibronectin Can Be Used For Earlier Prediction of Preterm Birth from 18 Weeks, But the Positive Threshold Needs Redefining

Introduction Fetal fibronectin (fFN) is an excellent predictor of spontaneous preterm birth (sPTB) and is used qualitatively (<50 ng/ml negative threshold) from 22 weeks gestation. Its value at earlier gestations using a quantitative test (qfFN) is unknown. Methods A prospective secondary analysis of 431 asymptomatic women at high risk of sPTB, who underwent qfFN testing at 18–21 + 6 weeks. 327 women underwent later testing at 22–26 + 6 weeks (acting as their own controls). The end-points were sPTB/preterm premature rupture of membranes and delivery before 30, 34 and 37 weeks gestation and within 8 weeks of testing. Results Early qfFN predicted delivery within 8 weeks of testing, <30, <34 and <37 weeks with receiver operating characteristics (ROC) areas of 0.66 (0.54–0.80, p < 0.05), 0.68 (0.56–0.79, p < 0.01), 0.68 (0.58–0.78 p < 0.001) and 0.64 (0.57–0.72, p < 0.001). 22-week test prediction was ROC areas of 0.77 (0.63–0.91 p < 0.001), 0.78 (0.61–0.95, p < 0.001) and 0.79 (0.70–0.89, p < 0.001) respectively. A qFFN result of <10 ng/ml at earlier gestations had only 1%, 2% and 4.3% of women delivered within 8 weeks, <30 and <34 weeks gestation, rising to 6.7%, 8.1% and 14.1% with values between 10–49.9 ng/ml (all differences statistically significant, p = 0.03, 0.02, 0.004 by Fishers-Exact). The 22-week test had 1.0%, 1.0% and 2% respectively, rising to 6.7%, 3.3% and 14% with values between 10–49.9 ng/ml (p = 0.02, 0.23, 0.004). Conclusion qfFN is valid for screening for sPTB at 18 weeks, but has inferior predictive value to 22 weeks. Early identification may enable earlier targeted management. A threshold of <10 ng/ml is more appropriate than current practise to define low risk at 18 weeks.

Diurnal blood pressure difference in the assessment of preeclampsia.

Objective To evaluate diurnal variation in blood pressure (BP) in normal gravidas and those with preeclampsia, using ambulatory BP monitoring. Methods A cross-sectional comparative observational study was performed in three teaching hospital maternity units. Twenty-four normotensive and 24 preeclamptic women who were similar in age, weight, and mean duration of gestation (35 weeks) were studied. Diurnal variation and BP measurement were assessed using ambulatory BP monitors validated for use in pregnancy and for which normal reference ranges for pregnancy have been derived. Results At night, the BP fall was less in preeclamptic women than in normotensive women. The day-night BP difference decreased as average BP rose (diastolic gradient = −0.54 [95% confidence interval (CI) −0.77 to −0.31], systolic gradient = −0.36 [95% CI −0.58 to −0.14], where gradient denotes a unit increase in BP leading to an increase or decrease in the day-night difference). Conclusion The decrease in day-night BP difference observed in preeclampsia is inversely related to average BP. This blunting of the day-night BP difference may be a useful adjunctive measure of disease severity in preeclampsia.