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Objective: To compare the pain relief and side effects of intramuscular pethidine with intramuscular diamorphine in labour., Design: Double-blind randomised controlled trial., Setting: The labour ward in a UK teaching hospital., Participants: Sixty-nine nulliparous women and 64 multiparous women in labour who requested narcotic analgesia and remained undelivered one hour after trial entry., Methods: Nulliparous women were randomised to receive either 150 mg intramuscular pethidine or 7.5 mg intramuscular diamorphine. Multiparous women were randomised to receive either 100 mg intramuscular pethidine or 5 mg intramuscular diamorphine. All participants received the anti-emetic prochloroperazine at the same time as the trial drugs., Main Outcome Measures: Maternal analgesia assessed by a visual analogue score and verbal scales of pain intensity and pain relief, maternal sedation and vomiting, neonatal outcome assessed by Apgar scores and the need for resuscitation., Results: More women allocated to receiving pethidine than to diamorphine reported slight or no pain relief at 60 minutes after administration of these drugs (P = 0.03). This trend was repeated in most of the other measures for maternal analgesia. There was no difference in maternal sedation, but the incidence of vomiting within 60 minutes was lower for women who received diamorphine (P = 0.02). Pethidine was associated with lower Apgar scores at 1 minute (P < 0.05)., Conclusion: Intramuscular diamorphine in labour appears to have some benefits, compared with intramuscular pethidine, but the trial was small and further research, particularly into alternative opioids and long term effects on the infants is still needed.

Objective: To investigate the reasons for the rise in caesarean section rate and note any change in indications., Design: A retrospective, descriptive study comparing the years 1962 and 1992., Setting: A large city centre teaching hospital., Results: There was an overall increase in the caesarean section rate from 6-8% in 1962 to 18.1% in 1992. No single cause contributed more than 30% towards this increase. The main indications in both years were similar: failure to progress (42.2% vs 36.7%) and fetal indications (18.1% vs 18.9%). The largest relative increases were in the malpresentation group (10.8% vs 16%) and previous caesarean section (4.5% vs 15.2%)., Conclusions: These results suggest that there has been a lowering in the overall threshold concerning the decision to carry out a caesarean section rather than changes in obstetric management. Obstetricians and the women in their care have to decide whether the current balance between risk and benefit is acceptable or whether they wish to alter the underlying philosophy if any significant reduction is to be sustained.

Objective: To compare the efficacy and acceptability of the levonorgestrel intrauterine system and norethisterone for the treatment of idiopathic menorrhagia., Design: A randomised comparative parallel group study., Setting: Gynaecology outpatient clinic in a teaching hospital., Participants: Forty-four women with heavy regular periods and a measured menstrual blood loss exceeding 80 ml., Methods: Twenty-two women had a levonorgestrel intrauterine system inserted within the first seven days of menses, and 22 women received norethisterone (5 mg three times daily) from day 5 to day 26 of the cycle for three cycles., Main Outcome Measures: The main outcome measure was the change in objectively assessed menstrual blood loss after three months of treatment., Results: When menstrual blood loss at three months was expressed as a percentage of the control, the levonorgestrel intrauterine system reduced menstrual blood loss by 94% (median reduction 103 ml; range 70 to 733 ml), and oral norethisterone by 87% (median reduction 95 ml; range 56 to 212 ml). After three cycles of treatment 76% of the women in the levonorgestrel intrauterine system group wished to continue with the treatment, compared with only 22% of the norethisterone group., Conclusions: Both the levonorgestrel intrauterine system and oral norethisterone in this regimen provided an effective treatment for menorrhagia in terms of reducing menstrual blood loss to within normal limits. The levonorgestrel intrauterine system was associated with higher rates of satisfaction and continuation with treatment, and thus offers an effective alternative to currently available medical and surgical treatments for menorrhagia.

Objective: To determine changes in the incidence and pattern of eclampsia within the same geographical area over a 60-year period., Design: A retrospective, descriptive study of 1259 consecutive women classified, at the time, as having had an eclamptic convulsion between the years 1931 and 1990., Setting: A large city centre teaching hospital and the surrounding catchment area., Main Outcome Measures: The changes in the incidence and timing of the convulsion and the outcomes for the mother and baby., Results: Over the study period, the incidence of eclampsia fell by more than 90%, from 74.1/10,000 in the 1930s to 7.2/10,000 in the 1980s. Most of the reduction occurred over the first four decades, with little change in the last 20 years. Overall, 44% of the cases of eclampsia occurred in the antenatal period, 33% intrapartum and 23% postpartum. Since the biggest decreases were seen in the incidence of antenatal and particularly intrapartum eclampsia, there has been a relative increase in the proportion of eclampsia occurring postpartum. Maternal death from eclampsia occurred in 15.1% of cases between 1931 and 1940, 13.4% between 1941 and 1950, but fell dramatically to < or = 3.9% after 1950. There has been no maternal death since 1964. Apart from the first decade, postpartum eclampsia was associated with significantly less risk of death to the mother throughout the study period. Perinatal death rate has fallen steadily from 432.6/1000 cases of eclampsia between 1931 and 1940 over the first three decades, to 168.7/1000 between 1961 and 1970. There has been little change since, although a lower proportion of neonatal deaths occurred as stillbirths., Conclusions: We found a significant reduction in both the incidence of eclampsia and associated morbidity in this population over the last 60 years. This has occurred in association with the introduction of the National Health Service, widespread antenatal care for all and a general improvement in health and welfare. Any further reduction in the incidence in the UK may be difficult to achieve. Since the incidence of eclampsia is now low, efforts should perhaps be directed at minimising the morbidity associated with severe pre-eclampsia rather than prevention of convulsions.

Objective: To determine whether circulating levels of cell adhesion molecules, markers of endothelial damage and leucocyte activation, were increased in pre-eclampsia., Design: Serum was prepared from peripheral venous blood and stored at -70 degrees C. The cell adhesion molecules, VCAM-1, E-Selectin and ICAM-1, were measured by ELISA., Setting: Department of Obstetrics and Gynaecology, Royal Infirmary, Glasgow., Subjects: Sixteen primigravid women with pre-eclampsia were recruited for the study. The preeclampsia group were compared with 18 healthy primigravid women with uncomplicated pregnancies., Results: The pre-eclamptic group had significantly higher serum levels of the cell adhesion molecule VCAM-1 (t = 3.673; P < 0.001). There were no significant differences in the adhesion molecules ICAM-1 or E-Selectin., Conclusions: Endothelial damage and dysfunction are common to all the pathological features of pre-eclampsia. This study shows that concentrations of cell adhesion molecules, which indicate leucocyte-endothelial attachment and activation, are elevated in the serum of patients with pre-eclampsia. Such increases in soluble circulating cell adhesion molecules may reflect increased expression of these molecules on the endothelium and thereby explain the mechanism for leucocyte activation in pre-eclampsia.

Objective: To determine the prevalence of lupus anticoagulant and raised anticardiolipin antibodies in women with a history of two or more miscarriages in the first trimester of pregnancy., Design: A prospective study of lupus anticoagulant and anticardiolipin antibody levels in unselected women with a history of two or more first trimester miscarriages., Setting: The prepregnancy clinic and miscarriage antenatal clinic in a tertiary referral centre., Subjects: Two hundred and forty-three women, of whom 113 (47%) had a past history of two miscarriages, and 130 (53%) had three or more miscarriages., Main Outcome Measures: Quantitative detection of lupus anticoagulant and anticardiolipin antibodies; number of miscarriages in women in the normal and the abnormal groups., Results: Of the 243 women tested, 41 (16.8%) had an abnormality of lupus anticoagulant or anticardiolipin antibodies. This was significantly different from the normal population as previously reported. Sixteen women (6.6%) were positive for lupus anticoagulant, 20 (8.2%) had elevated anticardiolipin antibodies, and five (2%) had both abnormalities. The most frequently positive test for lupus anticoagulant was the dilute Russel viper venom time, and IgG was the most frequently elevated anticardiolipin antibody. Of the women with a history of only two miscarriages, 15% had an abnormality of lupus anticoagulant or anticardiolipin antibodies, compared with 18.5% of those with a history of three or more miscarriages. This did not reach statistical significance. There were 117 (48%) primary miscarriers and 126 (52%) secondary miscarriers. Of the primary miscarriers, 17% had an abnormality, compared to 18% of the secondary miscarriers., Conclusions: These findings provide further evidence of an association between lupus anticoagulant and anticardiolipin antibodies and early pregnancy loss. It is not known if these are the cause of miscarriage, markers for miscarriage, or if antiphospholipid antibodies develop as a result of a noncontinuing pregnancy. Further studies comparing various treatments are required before women with these antibodies can be optimally managed.

Objective: To review the obstetric and gynaecological problems in women with congenital coagulopathies., Design: Retrospective review., Setting: Regional Adult Haemophilia Unit, Glasgow Royal Infirmary., Subjects: All women in contact with the Unit over a period of 30 years, comprising eight with von Willebrand's disease, 18 obligate carriers of haemophilia A and five obligate carriers of Christmas disease. Each woman was interviewed and details of their obstetric and gynaecological histories were obtained and their case records were reviewed., Main Outcome Measures: Haemostatic changes associated with pregnancy and gynaecological problems., Results: In 14 pregnancies in seven patients with von Willebrand's disease, there were four primary and four secondary post-partum haemorrhages and a large perineal haematoma complicating an episiotomy. These problems arose despite the endogenous rise in factor VIIIc seen with pregnancy. All women seen with von Willebrand's disease complained of menorrhagia and had been referred to gynaecologists. Treatment included danazol, tranexamic acid and the contraceptive pill. Diagnostic curettage resulted in severe haemorrhage in one woman and two women with pelvic pain and dyspareunia were found to have spontaneous broad ligament haematomas, one requiring surgery. In 43 pregnancies in obligate carriers of haemophilia A and Christmas disease there were five post-partum haemorrhages and a large perineal haematoma., Conclusion: In von Willebrand's disease it should be noted that adequate laboratory correction of factor VIIIc levels does not ensure clinical haemostasis; hence platelet function should also be measured. Patients with congenital coagulopathies pose particular problems for the obstetrician and gynaecologist and should be managed in close association with the local haemophilia centre.

The purpose of this study was to investigate the influence of postnatal x-ray pelvimetry after caesarean section on the management of the subsequent pregnancy. The case records of 331 women delivered by casearean section in their first pregnancy were reviewed. By standard radiological criteria, the pelvis was considered to be inadequate in 248 (75%) of them and adequate in 83 (25%). Of the women with a radiologically inadequate pelvis, 172 underwent an elective caesarean section. Seventy-six were allowed vaginal delivery: 51 of these women delivered vaginally and 25 required an emergency caesarean section. Of the women with a radiologically adequate pelvis, 61 achieved a vaginal delivery and 22 were delivered by caesarean section. All of the three cases of uterine rupture occurred in women with a radiologically adequate pelvis. This study suggests that x-ray pelvimetry is not a good predictor of the outcome of a trial of vaginal delivery. We conclude that the practice of routine postnatal pelvimetry should be abandoned.

Familial predisposition and patterns of genetic inheritance of eclampsia and pre-eclampsia were investigated through three or four generations in 94 families from the homogenous island population of Iceland. The families descended from index women delivered in the years 1931-47 and who had either eclampsia (n = 38) or severe pre-eclampsia (n = 69). Inheritance was followed both through sons and daughters. The prevalence of pre-eclampsia and eclampsia in daughters was significantly higher (23%) than that in daughters-in-law (10%). No difference was noted in the prevalence of these diseases by whether the daughter was born of an eclamptic or pre-eclamptic mother or whether she was a first or later born daughter. There was a non-significantly higher occurrence of pre-eclampsia among grand-daughters than in grand-daughters-in-law. No difference was seen by whether grand-daughters descended through sons or daughters. With increasing numbers of affected daughters or grand-daughters the probability rose of finding more affected women in a family. Hypotheses of single recessive and dominant gene inheritance were compared and maximum likelihood estimates for gene frequency obtained. For a single recessive gene model this was 0.31 reflecting a population prevalence of 9.6%, whereas a dominant model with incomplete penetrance gave 0.14 at 48% gene penetrance, corresponding to a population prevalence of 0.9% homozygous expression of severe disease and 11% heterozygous expression of milder disease. Either genetic model could fit the data.

The platelet count does not appear to change during normal pregnancy but a rise in the mean platelet volume (MPV) and platelet distribution width was found in the third trimester in this study of 208 healthy pregnant women. Alteration of all three platelet parameters was seen following delivery in 40 women studied sequentially. Moderately severe pregnancy-induced hypertension (PIH) was associated with no alteration of platelet parameters when compared with gestation-matched controls. Platelet abnormalities in severe PIH appeared to be related to the time of presentation and may be a reflection of the rate of progression of the underlying condition.

Blood viscosity ( Contraves L S 30) and its determinants were measured in 23 patients with mild/moderate pre-eclampsia, 10 patients with intrauterine growth retardation and 22 control subjects, matched for age and gestation. Both abnormal groups had a significantly increased blood viscosity at high shear rate (94 s-1) associated with increased haematocrit. Fibrinogen levels were also increased, but there were no significant differences between groups in plasma viscosity, low shear viscosity (0.94 s-1) or red cell deformability, measured by a low-shear washed cell system of filtration through 5-micron pore diameter Nuclepore filters. In the pre-eclamptic group, measurements were repeated after 1-2 weeks in nine patients treated with labetalol (a combined alpha and beta adrenergic blocker) and in 10 patients treated with bed rest. Labetalol reduced blood pressure but no change in rheology was seen in either group. Control of blood pressure by labetalol does not adversely affect rheology, in contrast to diuretics which are known to cause haemoconcentration and increased blood viscosity.

Prostacyclin and thromboxane have been implicated in the pathophysiology of several disorders of pregnancy, but there is little information on concentrations of these prostaglandins in normal pregnancy. The aim of our study was to determine the range of values throughout normal pregnancy and the puerperium and to compare this with concentrations in normal non-pregnant women. Measurement was by radioimmunoassay of prostacyclin and thromboxane metabolites. We observed a significant difference in prostacyclin metabolites in the first trimester, (mean 19.9, SEM 0.96 pg/ml) compared with the normal non-pregnant group (mean 15.9, SEM 0.68 pg/ml). There were no significant differences between values in the normal non-pregnant group and those in the second and third trimester or postnatally. The increase in prostacyclin in the first trimester may be associated with placentation and physiological vasodilation, and insensitivity to angiotensin II seen in early pregnancy. We noted a significant reduction in thromboxane metabolites in the second (mean 133, SEM 14.9 pg/ml) and third (mean 123, SEM 10.7 pg/ml) trimesters and the puerperium (mean 119, SEM 6.3 pg/ml) compared with the values in the normal non-pregnant group (mean 142, SEM 4.9 pg/ml). This may be due to increased platelet stability or decreased thromboxane synthesis.