9.1 MYOMETRIAL CONTRACTILITY STUDIES IN DIABETIC PREGNANT WOMEN

S. Alqahtani¹, F. Dawood², S. Quenby¹, S. Wray¹. ¹University of Liverpool, Liverpool, UK, ²Liverpool Women’s NHS Foundation Trust, Liverpool, UK

Several studies worldwide have shown a higher Caesarean section rate in diabetic compared with non-diabetic women. Local audit conducted at our hospital revealed an emergency Caesarean section rate of 37.4% compared with 13.2% for non-diabetic women. We have investigated whether there is an intrinsic contractility problem in the myometria of pregnant diabetic women.

Methods: Myometrial biopsies were obtained during term elective Caesarean section from 20 diabetic and 68 non-diabetic women and were subjected to in-vitro laboratory testing. All the diabetic women had good antenatal glycaemic control. Contractility was measured simultaneously with intracellular calcium signalling using fluorescent Indo-1. Contractility was also measured in 0-glucose solutions and with the addition of 700 pM insulin. Myometrial glycogen content was measured in millimoles.

Results: The entire set of diabetic samples contracted worse than the non-diabetic samples. The amplitude and the duration of contractions were significantly reduced (to 76.6 ± 6% and 44 ± 10%, respectively, relative to control 100%). Similar changes were observed in intracellular calcium transients. A significant reduction in the glycogen stores (11.3 ± 1.3 mmol) occurred in diabetic samples compared with 16.6 ± 2.0 mmol in non-diabetic samples. In 0-glucose solution, a more rapid reduction in force amplitude and cessation of contractility was observed in the diabetic compared with paired control samples. Myometrial contractility was reduced in both control and diabetic samples exposed to insulin.

Conclusions: Even under standardised conditions, myometrial contractility is worse in term diabetic uteri and may underlie the increased risk of emergency Caesarean section. This may be exacerbated by decreased metabolic reserves.

9.2 A PHYSIOLOGICAL APPROACH TO STIMULATING LABOUR: PULSE, A RANDOMISED CONTROLLED TRIAL OF PULSATILE VERSUS CONTINUOUS OXYTOCIN ADMINISTRATION

S. E. Crawshaw¹, P. N. Baker², C. Stanley², F. Safari³, P. Seed³, A. H. Shennan³, R. M. Tribe³. ¹University of York, York, UK, ²University of Manchester, Manchester, UK, ³King’s College, London, UK

Introduction: Induction and augmentation of labour are associated with high rates of medical intervention. Continuous oxytocin infusion protocols are routinely used to stimulate uterine contractions, but can cause uterine hyperstimulation and fetal distress. As continuous exposure to oxytocin is associated with oxytocin receptor downregulation, pulsatile oxytocin infusion protocols may provide an effective and more physiological approach to stimulation of uterine contractions.

Aim: To improve the current method of oxytocin induction and augmentation of labour. We hypothesised that low-dose pulsatile infusion of oxytocin is associated with lower Caesarean section and intervention rates compared with a continuous oxytocin infusion protocol.

Methods: A randomised controlled trial (n  =  1031 women) was conducted in two large UK maternity units with local ethics committee approval. Pregnant women requiring oxytocin for induction or augmentation were recruited, with written informed consent, and were randomly assigned to either a continuous or pulsatile (discrete 10 s boluses every 6 minutes) oxytocin infusion protocols. The infusion dose was increased every 30 minutes according to NICE guidelines. Primary outcome measures were Caesarean section rate (induction group) and intervention rate (Caesarean section/instrumental delivery rate for the augmentation group).

Results and Conclusions: In the induction group, Caesarean section rates (38% versus 38%, n  =  NS) and spontaneous vaginal delivery rates are similar in the pulsatile and continuous infusion groups. As the low-dose pulsatile infusion is as effective as the standard continuous infusion, our results suggest that current clinical protocols for induction should be reassessed.

Funding: GlaxoSmithKline Giving Committee/Tommy’s the baby charity).

9.3 RESIDENT OBSTETRIC CONSULTANT COVER: DOES IT MAKE A DIFFERENCE TO VAGINAL DELIVERY RATES OR PERINATAL MORBIDITY?

F. Siddiqui, A. Green, J. Moore, L. Kean. Nottingham University NHS Trust (City Campus), Nottingham, UK

NICE and the RCOG recommend 24 h resident consultant cover on the labour ward. At Nottingham City Hospital there was resident on-call consultant cover for 2 days of the week. This study reviews the vaginal and operative delivery rates and perinatal morbidity on the nights with resident consultant cover compared with senior specialist registrar cover.

Methods: Between January 2004 and November 2006 consultants covered 2 nights a week. Nights covered by a consultant were compared with nights covered in the same week by a specialist registrar. We calculated the number of Caesarean sections, operative vaginal deliveries, fetal blood sampling, unexpected admissions to the neonatal unit, arterial cord pH<7.1 and major post-partum haemorrhage (>1000 ml). Non-parametric tests were used to compare the two groups.

Results: There was a significant increase in the vaginal delivery rate with consultant cover (65% versus 50.9%; p<0.05). There was no difference in the operative vaginal delivery rates, although there were significantly more forceps deliveries with consultant cover. There were more category 2 Caesarean sections with consultant cover, although a reduction in the category 1 Caesarean section rate. There were significantly less fetal blood sampling. There was a lower incidence of low Apgar (7 versus 11; p>0.05), neonatal unit admissions (3 versus 6; p>0.05) and cord pH <7.1 (4 versus 6; p>0.05) associated with consultant cover, although these changes were not significant. There was a significant reduction in the incidence of post-partum haemorrhage (10 versus 14; p<0.05).

Discussion: Resident consultant labour ward cover is associated with an increase in the normal vaginal delivery rate. This is associated with lower neonatal and maternal morbidity. There is, however, an overall increase in Caesarean sections.

9.4 THE EFFECT OF BARUSIBAN ON PLASMA CONCENTRATIONS AND UTERINE CONTRACTILITY IN THREATENED PRETERM LABOUR: A RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL

S. Thornton¹, T. M. Goodwin², G. Greisen³, M. Hedegaard³, J. C. Arce⁴. ¹Warwick Medical School, Coventry, UK, ²University of Southern California, Los Angeles, California, USA, ³Rigshospitalet, Copenhagen, Denmark, ⁴Ferring Pharmaceuticals, Copenhagen, Denmark

Objective: Atosiban is a mixed oxytocin/vasopressin antagonist with marked tocolytic activity. Preclinical studies suggest that barusiban, a specific oxytocin antagonist, also markedly reduces uterine contractility. The object was to determine plasma concentrations, contractions and side effects following barusiban or placebo in threatened preterm labour (PTL).

Methods: 163 women in threatened PTL (34 + 0−35 + 6 weeks) with cervix ⩽15 mm were randomly assigned to a single intravenous dose of barusiban (0.3, 1, 3, 10 mg) or placebo. Rescue tocolytics were prohibited. The primary endpoint was women who did not deliver within 48 h. Plasma concentrations were determined by mass spectrometry. Uterine contractions and maternal/neonatal outcomes were determined.

Results: The mean plasma concentrations at 2 h were 11, 39, 139 and 537 ng/ml in women who received 0.3, 1, 3 and 10 mg barusiban, respectively. The concentration was not related to contraction frequency (mean frequency at 2–2.5 h: 4.4, 5.0, 6.6, 5.9 and 6.1 for placebo and barusiban, respectively). There was no significant difference in the percentage of women who did not deliver within 48 h (72% for placebo and 65%–88% for barusiban groups). Barusiban was well tolerated, although side effects were increased at higher concentrations. Postpartum blood loss and time to lactation were not significantly increased. There were no major safety concerns.

Conclusions: A single dose of selective oxytocin antagonist barusiban (0.3–10 mg) increased plasma concentrations to those calculated to be effective but did not delay delivery or reduce uterine contractions in women with threatened PTL and short cervical length. The results contrast with those of the mixed oxytocin/vasopressin antagonist, atosiban.