Gary Mires

Poor glycated haemoglobin control and adverse pregnancy outcomes in type 1 and type 2 diabetes mellitus: systematic review of observational studies.

BackgroundGlycaemic control in women with diabetes is critical to satisfactory pregnancy outcome. A systematic review of two randomised trials concluded that there was no clear evidence of benefit from very tight versus tight glycaemic control for pregnant women with diabetes.MethodsA systematic review of observational studies addressing miscarriage, congenital malformations and perinatal mortality among pregnant women with type 1 and type 2 diabetes was carried out. Literature searches were performed in MEDLINE, EMBASE, CINAHL and Cochrane Library. Observational studies with data on glycated haemoglobin (HbA1c) levels categorised into poor and optimal control (as defined by the study investigators) were selected. Relative risks and odds ratios were calculated for HbA1c and pregnancy outcomes. Adjusted relative risk estimates per 1-percent decrease in HbA1c were calculated for studies which contained information on mean and standard deviations of HbA1c.ResultsThe review identified thirteen studies which compared poor versus optimal glycaemic control in relation to maternal, fetal and neonatal outcomes. Twelve of these studies reported the outcome of congenital malformations and showed an increased risk with poor glycaemic control, pooled odds ratio 3.44 (95%CI, 2.30 to 5.15). For four of the twelve studies, it was also possible to calculate a relative risk reduction of congenital malformation for each 1-percent decrease in HbA1c, these varied from 0.39 to 0.59. The risk of miscarriage was reported in four studies and was associated with poor glycaemic control, pooled odds ratio 3.23 (95%CI, 1.64 to 6.36). Increased perinatal mortality was also associated with poor glycaemic control, pooled odds ratio 3.03 (95%CI, 1.87 to 4.92) from four studies.ConclusionThis analysis quantifies the increase in adverse pregnancy outcomes in women with diabetes who have poor glycaemic control. Relating percentage risk reduction in HbA1c to relative risk of adverse pregnancy events may be useful in motivating women to achieve optimal control prior to conception.

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, Double-Blinded, Placebo-Controlled Study of the Phosphodiesterase Type 5 Inhibitor Sildenafil for the Treatment of Preeclampsia

Objective: To determine if the phosphodiesterase type 5 inhibitor sildenafil prolongs pregnancy in women with preeclampsia. Methods: Women with preeclampsia at gestational ages 24–34 weeks were recruited from nine hospitals in the UK, and randomly assigned to sildenafil citrate or placebo. Medication was increased every 3 days from 20 mg three times daily (tid), to 40 mg, and 80 mg tid. The primary endpoint was prolongation of pregnancy from randomisation to delivery (days). Secondary endpoints were markers of maternal disease and cord pH at delivery and infant weight. Details of all adverse events were also collected. Plasma samples were taken to establish pharmacokinetic information. Data analysed on a modified intention to treat analysis. The study had a power of >95% to detect a difference of 5 days. Results: Of 35 women, 17 were allocated to sildenafil and 18 to placebo. There was no difference in time from randomisation to delivery in the two treatment groups, with a median time of 4 days (range 1–15) in the sildenafil group and 4.5 days (range 1–30) in the placebo group. Sildenafil achieved maximum drug concentrations of 48 ng/ml, 88 ng/ml, and 271 ng/ml after 3 days of 20 mg, 40 mg and 80 mg tid, respectively. Conclusion: We have safely conducted a clinical trial of a drug not routinely used during pregnancy. Sildenafil in the escalating dose regimen 20–80 mg tid was well tolerated, with no increase in maternal or fetal morbidity or mortality but did not prolong pregnancy duration in women with preeclampsia. (ClinicalTrials.gov number, NCT 00141310).

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.

The effect of fetal heart rate on umbilical artery flow velocity waveforms

Umbilical artery flow velocity waveforms were obtained using continuous wave Doppler ultrasound in 85 normal pregnancies (25 antepartum, 60 intrapartum) to examine the relation between fetal heart rate, end systolic/end diastolic ratio (A/B ratio) and resistance index (RI). Our results demonstrated a significant negative correlation between fetal heart rate, A/B ratio and RI (in the antepartum group r= ‐0·49, and in the labouring group r= ‐0·65). It is therefore important when performing mathematical analysis of umbilical artery flow velocity profiles to make a statistical allowance for fetal heart rate.

Characteristics of doctors and nurses as perceived by students entering medical school: implications for shared teaching.

Introduction  Debate continues with respect to when to introduce interprofessional education for maximal potential benefit. One perspective is that interprofessional education should be introduced early in the undergraduate curriculum before students develop stereotyped impressions of other professional groups. However, it may be that students at entry to medical school have already developed these stereotypical impressions. This study examines perceived professional characteristics of doctors and nurses by students entering medical school.

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.

Randomised controlled trial of cardiotocography versus Doppler auscultation of fetal heart at admission in labour in low risk obstetric population

Abstract Objective: To compare the effect of admission cardiotocography and Doppler auscultation of the fetal heart on neonatal outcome and levels of obstetric intervention in a low risk obstetric population. Design: Randomised controlled trial. Setting: Obstetric unit of teaching hospital Participants: Pregnant women who had no obstetric complications that warranted continuous monitoring of fetal heart rate in labour. Intervention: Women were randomised to receive either cardiotocography or Doppler auscultation of the fetal heart when they were admitted in spontaneous uncomplicated labour. Main outcome measures: The primary outcome measure was umbilical arterial metabolic acidosis. Secondary outcome measures included other measures of condition at birth and obstetric intervention. Results: There were no significant differences in the incidence of metabolic acidosis or any other measure of neonatal outcome among women who remained at low risk when they were admitted in labour. However, compared with women who received Doppler auscultation, women who had admission cardiotocography were significantly more likely to have continuous fetal heart rate monitoring in labour (odds ratio 1.49, 95% confidence interval 1.26 to 1.76), augmentation of labour (1.26, 1.02 to 1.56), epidural analgesia (1.33, 1.10 to 1.61), and operative delivery (1.36, 1.12 to 1.65). Conclusions: Compared with Doppler auscultation of the fetal heart, admission cardiotocography does not benefit neonatal outcome in low risk women. Its use results in increased obstetric intervention, including operative delivery. What is already known on this topic The admission cardiotocogram is a short recording of the fetal heart rate immediately after admission to the labour ward Opinion varies about its value in identifying a potentially compromised fetus In low risk women, the incidence of intrapartum fetal compromise is low What this study adds Compared with Doppler auscultation of the fetal heart, admission cardiotocography has no benefit on neonatal outcome in low risk women Admission cardiotocography results in increased obstetric intervention, including operative delivery

Obstetric outcome of natural and assisted conception twin pregnancies is similar

Background. The risk of obstetric intervention and adverse fetal or neonatal outcome is considerably higher in multiple gestation than in singleton pregnancy. How assisted conception influences obstetric management and outcome in twin pregnancies has not been evaluated.

Multiprofessional education in undergraduate curricula can work

A multiprofessional educational programme about labour was introduced into the undergraduate curriculum for medical students and the diploma course for midwifery students. The students gained knowledge about labour and a better understanding of each others role in the care of the labouring women. The change in awareness of professional responsibility was greatest for medical students; it was evident in medical students taught in medical-student-only groups and also in those taught alongside midwives. Differences in professional attitudes between the medical and midwifery students at the start of the course were less marked following completion of the course. The programme was well received by both students and tutors; both groups advocated the use of mixed medical/midwifery teaching in other areas of the curricula.We conclude that multiprofessional learning has a role in medical and nursing education when the intended educational objectives are clearly defined and the educational strategy and learning op...