Maureen Macleod

Changes in Endothelial Function Precede the Clinical Disease in Women in Whom Preeclampsia Develops

Endothelial dysfunction is important in the pathophysiology of preeclampsia. No study has examined endothelial function sequentially at different gestations before development of the clinical syndrome and after delivery (to compare maternal from placental influences). We sought to determine whether endothelial function changes before the clinical development of preeclampsia. We measured skin microvascular function using iontophoresis of acetylcholine and sodium nitroprusside, and laser Doppler imaging at 22, 26, 34 weeks’ gestation and 6 weeks postpartum in women identified as being at increased risk of preeclampsia, based on uterine artery Doppler waveforms at 18 to 20 weeks, and controls with normal Doppler waveforms. Fifty-four women remained normotensive and preeclampsia developed in 15. In normotensive and preeclamptic women, acetylcholine responses were augmented during pregnancy compared with postpartum responses (P<0.001). Sodium nitroprusside responses were augmented during pregnancy compared with those postpartum (P<0.005) in preeclamptic women only. Microvascular responses were augmented in women in whom preeclampsia developed, compared with those in normotensive women, at 26 and 34 weeks for acetylcholine (P<0.05 and P<0.001, respectively) and at 22 and 26 weeks for sodium nitroprusside (P<0.05 and P<0.02, respectively). Postpartum acetylcholine and sodium nitroprusside responses were not significantly different between preeclamptic and normal women. Microvascular responses are enhanced during pregnancy in women in whom preeclampsia develops to a level above that seen in normotensive women. These changes precede the onset of clinical disease and might be related to a compensatory increased sensitivity of the microcirculation to nitric oxide.

A randomised controlled trial of routine versus restrictive use of episiotomy at operative vaginal delivery: a multicentre pilot study.

Objective  To compare the maternal and neonatal outcomes of operative vaginal delivery in relation to the use of episiotomy.

MMP-2 Levels are Elevated in the Plasma of Women Who Subsequently Develop Preeclampsia

Objective. To determine levels of matrix metalloproteinase (MMP)-2 and MMP-9, and the tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-2 in the plasma of women destined to develop preeclampsia prior to the onset of clinical disease. Study Design. Plasma samples were taken from women whose pregnancies were subsequently complicated by preeclampsia and from normal pregnant women at 22 and 26 weeks and at delivery or diagnosis. Following equal protein loading, MMP-2 and 9 and TIMP–1 and 2 were quantified using zymography and Western blot analysis, respectively. Results. Plasma MMP-2 levels were significantly elevated at 22 weeks (p = 0.02) and at diagnosis (p = 0.003) in the preeclampsia group, but there was no difference at 26 weeks. TIMP-1 levels were significantly reduced in the preeclampsia group at 26 weeks (p = 0.0002), but TIMP-2 levels were not quantifiable. Conclusion. At all three gestational time points an imbalance in the MMP-2:TIMP-1 ratio was found in patients who subsequently developed preeclampsia. We speculate that increased net MMP-2 activity may contribute to the endothelial dysfunction that is central to the pathophysiology of preeclampsia.

A prospective cohort study of maternal and neonatal morbidity in relation to use of episiotomy at operative vaginal delivery

Objective  To evaluate the maternal and neonatal morbidity of operative vaginal delivery in relation to the use of episiotomy.

In Preeclampsia, the Circulating Factors Capable of Altering In Vitro Endothelial Function Precede Clinical Disease

The pathophysiology of preeclampsia involves the release of a circulating factor(s) from a hypoperfused placenta that activates the maternal endothelium. This study investigated the effect on in vitro endothelial function of plasma taken from women in whom preeclampsia subsequently developed. Women at increased risk for an adverse pregnancy outcome were identified using Doppler waveform analysis. Plasma samples (22 and 26 weeks) were incubated with myometrial vessels taken from women with uncomplicated pregnancies. Wire myography was used to study the effect of plasma on the endothelium-dependent vessel behavior. Incubation of vessels from normal pregnant women with plasma from women in whom preeclampsia subsequently developed (n=19) significantly reduced endothelium-dependent relaxation, compared with vessels incubated with plasma from normal pregnant women (n=48). This effect was demonstrable for plasma taken at 22 weeks (residual constriction 47.1±6.6% versus 32.0±4.4%, P=0.004 at 1-hour incubation; and 59.1±8.4% versus 42.3±5.9%, P=0.001 at 18-hour incubation) and 26 weeks (59.2±5.2% versus 29.1±5.6%, P<0.001 at 1 hour; and 63.3±7.6% versus 31.9 +/-7.2%, P<0.0001 at 18 hours). Endothelial-dependent relaxation was unaltered after incubation with plasma taken from women in whom normotensive intrauterine growth restriction subsequently developed (n=19). This study supports the hypothesis that plasma, from women in whom preeclampsia develops, collected weeks before diagnosis is capable of altering endothelial function.

Cohort study of maternal and neonatal morbidity in relation to use of episiotomy at instrumental vaginal delivery.

Objective  The aim of this study was to investigate the maternal and neonatal morbidity related to use of episiotomy for vacuum and forceps deliveries.

The impact of a bodyweight and physical activity intervention (BeWEL) initiated through a national colorectal cancer screening programme: randomised controlled trial

Objective To evaluate the impact of a diet and physical activity intervention (BeWEL) on weight change in people with a body mass index >25 weight (kg)/height (m)2 at increased risk of colorectal cancer and other obesity related comorbidities. Design Multicentre, parallel group, randomised controlled trial. Setting Four Scottish National Health Service health boards. Participants 329 overweight or obese adults (aged 50 to 74 years) who had undergone colonoscopy after a positive faecal occult blood test result, as part of the national bowel screening programme, and had a diagnosis of adenoma confirmed by histopathology. 163 were randomised to intervention and 166 to control. Intervention Participants were randomised to a control group (weight loss booklet only) or 12 month intervention group (three face to face visits with a lifestyle counsellor plus monthly 15 minute telephone calls). A goal of 7% reduction in body weight was set and participants received a personalised energy prescription (2508 kJ (600 kcal) below that required for weight maintenance) and bodyweight scales. Motivational interviewing techniques explored self assessed confidence, ambivalence, and personal values concerning weight. Behavioural strategies included goal setting, identifying intentions of implementation, self monitoring of body weight, and counsellor feedback about reported diet, physical activity, and weight change. Main outcome measures The primary outcome was weight change over 12 months. Secondary outcomes included changes in waist circumference, blood pressure, fasting cardiovascular biomarkers, and glucose metabolism variables, physical activity, diet, and alcohol consumption. Results At 12 months, data on the primary outcome were available for 148 (91%) participants in the intervention group and 157 (95%) in the control group. Mean weight loss was 3.50 kg (SD 4.91) (95% confidence interval 2.70 to 4.30) in the intervention group compared with 0.78 kg (SD 3.77) (0.19 to 1.38) in the control group. The group difference was 2.69 kg (95% confidence interval 1.70 to 3.67). Differences between groups were significant for waist circumference, body mass index, blood pressure, blood glucose level, diet, and physical activity. No reported adverse events were considered to be related to trial participation. Conclusions Significant weight loss can be achieved by a diet and physical activity intervention initiated within a national colorectal cancer screening programme, offering considerable potential for risk reduction of disease in older adults. Trial registration Current Controlled Trials ISRCTN53033856.

A cohort study of maternal and neonatal morbidity in relation to use of sequential instruments at operative vaginal delivery

OBJECTIVE To evaluate the risk factors and maternal and neonatal morbidity associated with sequential use of instruments (vacuum and forceps) at operative vaginal delivery. STUDY DESIGN A cohort study of 1360 nulliparous women delivered by a single instrument (vacuum or forceps) or by both instruments, within two university teaching hospitals in Scotland and England. Outcomes were compared for use of sequential instruments versus use of any single instrument. A sub-group analysis compared sequential instruments versus forceps alone. Outcomes of interest included anal sphincter tears, postpartum haemorrhage, urinary retention, urinary incontinence, prolonged hospital admission, neonatal trauma, low Apgar scores, abnormal cord bloods and admission to the neonatal intensive care unit (NICU). RESULTS Use of sequential instruments at operative vaginal delivery was associated with fetal malpositions, Odds Ratio (OR) 1.8 (95% Confidence Interval (CI) 1.3-2.6), and large neonatal head circumference (>37 cm) (OR 5.0, 95% CI 2.6-9.7) but not with maternal obesity or grade of operator. Sequential use of instruments was associated with greater maternal and neonatal morbidity than single instrument use (anal sphincter tear 17.4% versus 8.4%, adjusted OR 2.1, 95% CI 1.2-3.3; umbilical artery pH <7.10, 13.8% versus 5.0%, adjusted OR 3.3, 95% CI 1.7-6.2). Sequential instrument use had greater morbidity than single instrument use with forceps alone (anal sphincter tear OR 1.8, 95% CI 1.1-2.9; umbilical artery pH <7.10 OR 3.0, 95% CI 1.7-5.5). CONCLUSIONS The use of sequential instruments significantly increases maternal and neonatal morbidity. Obstetricians need training in the appropriate selection and use of instruments with the aim of completing delivery safely with one instrument.

Supporting postpartum weight loss in women living in deprived communities: design implications for a randomised control trial

Background/Objectives:Pregnancy is a life stage where excess weight gain may occur and the postpartum period is often characterised by weight retention. The aim of the current study was to evaluate the feasibility of undertaking a randomised controlled trial of a weight loss intervention (WeighWell) in postpartum women living in areas of social disadvantage.Subjects/Methods:The study aimed to recruit 60 women who were not pregnant, 6–18 months postpartum with a body mass index >25 kg/m2 living in areas of deprivation within Tayside, UK. Recruitment strategies focused on visits to community groups; writing directly to postpartum women living in areas of deprivation and primary care teams who covered the most deprived 15% of the population and advertising in community settings. The 12-week intervention used motivational interviewing techniques to promote an energy deficit diet and increased physical activity, delivered by three face-to-face consultations plus three structured telephone calls.Results:Of 142 women screened, 63 were eligible and 52 (83%) were recruited and randomised to an intervention (n=29) or comparison group (n=23). Over the 12-week intervention, body weight changed significantly by −1.6±2.0 kg in the intervention group compared with +0.2±2.2 kg in the comparison group, indicating the potential efficacy of the intervention. Loss to follow-up was 24% in the intervention group and 39% for the comparison group.Conclusions:The findings support the development of a definitive trial that embraces personalised recruitment strategies and the development of approaches to improve retention over a clinically relevant intervention period.

Maternal and neonatal morbidity in relation to the instrument used for mid-cavity rotational operative vaginal delivery: a prospective cohort study.

To compare the maternal and neonatal morbidity associated with alternative instruments used to perform a mid‐cavity rotational delivery.