8.1 VASCULAR ENDOTHELIAL GROWTH FACTOR165B AND PRE-ECLAMPSIA

V. L. Bills, D. O. Bates¹, P. W. Soothill². ¹University of Bristol, Bristol, UK, ²St Michael’s Hospital, Bristol, UK

Introduction: The vascular endothelial growth factor (VEGF) family of glycoproteins plays a key role in the regulation of angiogenesis, vascular permeability and vasodilatation, with high levels occurring in pre-eclamptic plasma. Novel VEGF₁₆₅b isoforms, formed by alternatively splicing exon 8 of the VEGF gene, are not described in pregnancy. VEGF₁₆₅b inhibits conventional VEGF₁₆₅-mediated vasodilatation and angiogenesis and increases vessel permeability.

Materials and Methods: We developed an ELISA to measure plasma VEGF₁₆₅b concentrations using a VEGF₁₆₅b-specific capture antibody (R&D MAB3045) and a biotinylated pan-VEGF detection antibody. The ELISA is sensitive to 30 pg/ml. We quantified soluble fms-like tyrosine kinase (sFlt1) and soluble endoglin (sEng) concentrations in the same plasma by ELISA.

Results: Pre-eclampsia is associated with an eightfold increase in plasma VEGF₁₆₅b from first trimester to pre-delivery, compared with a twofold increase in normotensive plasma (p<0.0012). At 12 weeks, VEGF₁₆₅b was lower in patients who later developed pre-eclampsia compared with normotensive patients. Low first trimester VEGF₁₆₅b predicts the elevated pre-delivery sFlt1 of pre-eclampsia. sFlt1 and sEng are not useful predictors of pre-eclampsia at 12 weeks’ gestation, because there were no concentration differences in either molecule between the two groups (see table).

Conclusions: Pregnant women who later develop pre-eclampsia have low first trimester VEGF₁₆₅b. VEGF₁₆₅b (but not sFlt1 or sEng) may be a clinically useful first trimester serum marker for increased pre-eclampsia risk. The role of VEGF₁₆₅b in disease pathogenesis remains unknown.

8.2 HAEMODYNAMIC AND PLACENTAL MARKERS TO PREDICT PRE-ECLAMPSIA

A. Khalil¹, S. Muttukrishna², K. Harrington¹, E. Jauniaux². ¹Queen Mary, University of London, London, UK, ²University College London, London, UK

Early identification of women at risk of pre-eclampsia facilitates targeted surveillance and intervention. Changes in some haemodynamic and vascular markers precede the onset of clinical pre-eclampsia.

In a longitudinal study, we prospectively measured uterine artery Doppler pulsatility index (UAD PI), augmentation index (AIx-75—a measure of arterial stiffness) using pulse wave analysis, blood pressure (BP), placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), soluble endoglin (sEng), inhibin A and activin A at 22⁺⁰–24⁺⁰ weeks’ gestation. We evaluated the ability of these markers, alone and in combination, to predict pre-eclampsia. We measured serum markers using specific ELISA.

Of 205 women recruited, 14 developed pre-eclampsia. Pre-eclampsia cases were matched 1 : 2 to controls.

The data were normally distributed after logarithmic transformation. PlGF was significantly lower and all other markers were higher in women who subsequently developed pre-eclampsia. Data are presented as receiver operator characteristic areas for those variables that best predicted pre-eclampsia: UAD mean PI 0.91 (CI 0.85 to 0.96); AIx-75 0.92 (CI 0.87 to 0.96); PlGF 0.84 (CI 0.72 to 0.97); sFlt-1 0.71 (CI 0.59 to 0.80); sEng 0.79 (CI 0.66 to 0.92); mean BP 0.78 (CI 0.65 to 0.91); sFlt-1/PlGF 0.86 (CI 0.74 to 0.98); sFlt-1+sEng/PlGF 0.85 (CI 0.72 to 0.97); inhibin A 0.72 (CI 0.59 to 0.87); activin A 0.87 (CI 0.8 to 0.94). Multiple logistic regression of different combinations of parameters found that the combination of mean PI, log PlGF and AIx-75 was the best predictor of pre-eclampsia (receiver operator characteristic area 0.98 (CI 0.96 to 1)). For a false positive rate of 5%, this combination has a detection rate of 93%.

A combination of UAD PI, pulse wave analysis AIx-75 and serum PlGF in the second trimester can achieve a clinically useful prediction of pre-eclampsia.

8.3 MINIMALLY INVASIVE HAEMODYNAMIC MONITORING ACCURATELY DEMONSTRATES THE PROFOUND CARDIOVASCULAR EFFECTS OF A 5-UNIT SYNTOCINON BOLUS AT CAESAREAN SECTION

A. Carlin¹, N. Daniel¹, L. Bricker¹, S. Walkinshaw¹, P. Barclay¹, Z. Alfirevic². ¹Liverpool Women’s Hospital, Liverpool, UK, ²University of Liverpool, School of Reproductive and Developmental Biology, Liverpool, UK

Introduction: The cardiovascular effects of standard doses of oxytocin were first displayed in a study over 30 year’s ago.1 The potentially dangerous consequences of these effects in pregnant women with either cardiac disease or hypovolaemia secondary to blood loss was highlighted by two related mortalities in the Confidential Enquires into Maternal Deaths 1997–1999.2 Non-invasive tests do not show the true extent of the haemodynamic effects of syntocinon, therefore we used the LidCO Plus system to provide continuous cardiovascular data during Caesarean delivery.

Methods: The trial was approved by the local research ethics committee and 35 uncomplicated healthy women gave written consent to participate. All the women had Caesarean section at 39 weeks under standard spinal anaesthetic and an intravenous bolus of 5 units of syntocinon after delivery of the fetus. Arterial lines were needed for calibration and pulse contour analysis used to obtain continuous data from the LidCO Plus system.

Results: Baseline was defined as the mean value during the last 20 s before the injection of syntocinon. Mean baseline values were: cardiac output (CO) 6.6 l/min, systemic vascular resistance 1155 dynes × s/cm⁵/m², heart rate (HR) 91 bpm and mean arterial pressure (MAP) 94 mm Hg. At 10 s post-injection profound changes were noted: CO +20%, systemic vascular resistance (SVR) −44%, HR +6% and MAP −20%. Maximal effect was seen at 30 s (CO +28%, SVR −83%, HR +10%, MAP−34%) with values returning to baseline within 130 s.

Conclusions: Small doses of intravenous oxytocin produce profound and rapid changes in maternal haemodynamics at Caesarean section.

8.4 HYPEREMESIS IN PREGNANCY STUDY: A RANDOMISED CONTROLLED TRIAL OF MIDWIFE-LED “OUTPATIENT” CARE

C. McParlin¹, D. Carrick-Sen¹, I. N. Steen², P. Taylor¹, S. C. Robson². ¹Newcastle upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, UK, ²Newcastle University, Newcastle upon Tyne, UK

Background: Nausea and vomiting (NVP) in pregnancy is a frequent debilitating condition resulting in increased healthcare use and reduced quality of life (QoL). The aim of this pilot randomised controlled trial was to investigate the effect of a complex intervention, rapid rehydration combined with ongoing midwifery support, as compared with routine inpatient care.

Methods: 53 women attending the Maternity Assessment Unit with severe NVP were randomly allocated to intervention (rapid intravenous hydration (3 litres over 6 h), intravenous cyclizine, discharge home with advice leaflet, oral cyclizine and ongoing support involving two telephone calls from a specialist midwife; n  =  27) or control (admission and routine care; n  =  26) groups. Physical symptoms were measured using the pregnancy unique quantification of emesis and vomiting score (PUQE) on admission and for 7 days. QoL was measured on days 1 and 7 via SF36.v2 score and satisfaction with care on day 7.

Results: Groups were comparable at baseline in terms of demographics, blood and urine results, severity of symptoms and reported QoL. Protocol adherence was greater in the intervention group (93% versus 69%, p = 0.04). There were no differences between the groups on day 7 in terms of mean PUQE score, QoL and satisfaction with care. Re-admission rates were similar, whereas total admission time with NVP was higher in the control group (94 h versus 27 h, p = 0.001). Obstetric outcomes were comparable in the two groups.

Conclusions: This study suggests that a policy of rapid rehydration plus ongoing midwifery support is an effective alternative management option for treating women with severe NVP. A larger randomised controlled trial with economic analysis appears justified.