Richard Hiscock

Gestational Diabetes Mellitus: Clinical Predictors and Long-Term Risk of Developing Type 2 Diabetes A retrospective cohort study using survival analysis

OBJECTIVE—We sought to determine the long-term risk of type 2 diabetes following a pregnancy complicated by gestational diabetes mellitus (GDM) and assess what maternal antepartum, postpartum, and neonatal factors are predictive of later development of type 2 diabetes. RESEARCH DESIGN AND METHODS—This was a retrospective cohort study using survival analysis on 5,470 GDM patients and 783 control subjects who presented for postnatal follow-up at the Mercy Hospital for Women between 1971 and 2003. RESULTS—Risk of developing diabetes increased with time of follow-up for both groups and was 9.6 times greater for patients with GDM. The cumulative risk of developing type 2 diabetes for the GDM patients was 25.8% at 15 years postdiagnosis. Predictive factors for the development of type 2 diabetes were use of insulin (hazard ratio 3.5), Asian origin compared with Caucasian (2.1), and 1-h blood glucose (1.3 for every 1 mmol increase above 10.1 mmol). BMI was associated with an increased risk of developing type 2 diabetes but did not meet the assumption of proportional hazards required for valid inference when using Cox proportional hazards. CONCLUSIONS—While specific predictive factors for the later development of type 2 diabetes can be identified in the index pregnancy, women with a history of GDM, as a group, are worthy of long-term follow-up to ameliorate their excess cardiovascular risk.

Effectiveness of tension-free vaginal tape compared with transobturator tape in women with stress urinary incontinence and intrinsic sphincter deficiency: a randomized controlled trial.

OBJECTIVE: To compare efficacy of transobturator tape with tension-free vaginal tape (TVT) in the treatment of stress urinary incontinence in women with intrinsic sphincter deficiency. METHODS: One hundred sixty-four women diagnosed with urodynamic stress incontinence and intrinsic sphincter deficiency with or without concomitant pelvic organ prolapse repair were randomized to receive TVT or transobturator tape. The primary outcome was the presence or absence of urodynamic stress incontinence at 6 months postoperatively. Secondary outcomes were the rate of operative complications, symptomatic stress incontinence requiring further surgery, and quality-of-life questionnaires. RESULTS: Of 180 women eligible to participate, 164 were enrolled and underwent surgery. Of the 138 patients assessed at 6 months with urodynamic studies, 14 of 67 (21%) had urodynamic stress incontinence in the TVT group compared with 32 of 71 (45%) in the transobturator tape group (P=.004), with nine women in the transobturator tape group having repeat sling surgery compared with none in the TVT group. In the intention-to-treat analysis, the incident rate difference for request of repeat surgery was 9.7% (95% confidence interval [CI] 0–19.9); repeat surgery would be requested in one of every six transobturator tape procedures compared with 1 of every 16 TVT procedures. The risk ratio of repeat surgery was 2.6 (95% CI 0.9–9.3) times higher in the transobturator tape group. CONCLUSION: Retropubic TVT is a more effective operation than the transobturator tape sling in women with urodynamic stress incontinence and intrinsic sphincter deficiency. CLINICAL TRIAL REGISTRATION: www.actr.org.au, Australian New Zealand Clinical Trials Registry, ACTRN12608000093381 LEVEL OF EVIDENCE: I

Risk factors for mesh erosion after transvaginal surgery using polypropylene (Atrium) or composite polypropylene/polyglactin 910 (Vypro II) mesh

The objective of this study was to identify the risk factors associated with the occurrence of mesh erosion (ME) during the first 6 post-operative months in patients having undergone transvaginal repair of pelvic organ prolapse (POP) with Atrium or Vypro II mesh. We retrospectively reviewed the records of 198 consecutive patients who underwent vaginal reconstructive surgery reinforced either by Atrium or Vypro II mesh between February 1999 and July 2003. Univariable and multivariable logistic regression was performed to assess associations between measured covariates and ME. Fourteen patients [7.1%, 95% confidence interval (CI): 3.9–11.6] developed vaginal ME. We found that, in the Vypro II mesh patients, the surgeon experienced in the technique had less erosions than less experienced surgeons (2.9 vs 15.6%, p=0.02). There was no statistically significant difference between the monofilament polypropylene (Atrium) and the composite polypropylene/polyglactin 910 (Vypro II) mesh (7.2 vs 6.9%, p=0.41) when adjusted for surgeon experience and patient age. There was no association between mesh type (Atrium or Vypro II) and vaginal ME following transvaginal repair of POP. Surgeon experience and patient age were associated with ME.

Three-year follow-up of tension-free vaginal tape compared with transobturator tape in women with stress urinary incontinence and intrinsic sphincter deficiency.

OBJECTIVE: To compare the efficacy of tension-free vaginal tape (TVT) to transobturator tape in the treatment of women with stress urinary incontinence (SUI) and intrinsic sphincter deficiency at 3-year follow-up. METHODS: One hundred sixty-four women were randomized to either TVT or transobturator tape after diagnosis of urodynamic stress incontinence and intrinsic sphincter deficiency. Concomitant pelvic organ prolapse surgery was not an exclusion criterion. The primary outcome assessed at 3-year follow-up was symptomatic stress incontinence requiring repeat surgery. Secondary outcomes were quality-of-life parameters assessed by validated questionnaires and numerical success score. RESULTS: One hundred sixty-four women were enrolled in the study. At 3 years, 15 of the 75 (20%) women in the transobturator tape group underwent repeat surgery to correct SUI compared with one of the 72 (1.4%) in the TVT group. In other words, if TVT had been used exclusively, repeat surgery would have been avoided in one in six patients. The risk ratio of repeat surgery was 15 (95% confidence interval 2–113; P<.001) times greater in the transobturator tape group. In the transobturator tape group, the median time to repeat surgery was 15.6 months compared with 43.7 months for TVT (P<.001). The quality-of-life outcomes did show an improvement in both groups before and after surgery but no difference between the two slings in the Urogenital Distress Inventory short form, the Incontinence Impact Questionnaire short form, and a patient-rated numerical success score. CONCLUSION: The long-term cure rates for retropubic TVT are significantly greater than for transobturator tape in women with urodynamic stress incontinence and intrinsic sphincter deficiency. Urethral functions tests such as urethral closure pressure and Valsalva leak point pressures are of value in determining what surgery to perform. CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, www.anzctr.org.au, ACTRN12608000093381. LEVEL OF EVIDENCE: I

Assessment of neonatal resuscitation performance using video recording in a perinatal centre

Aim:  To assess the quality of neonatal resuscitation using video recordings in a perinatal centre.

Double blind, randomised, placebo-controlled trial to evaluate the efficacy of esomeprazole to treat early onset pre-eclampsia (PIE Trial): a study protocol

Introduction Pre-eclampsia is a major complication of pregnancy, globally responsible for 60 000 maternal deaths per year, and far greater numbers of fetal losses. There is no definitive treatment other than delivery. A drug that can quench the disease process could be useful to treat early onset pre-eclampsia, as it could allow pregnancies to safely continue to a gestation where fetal outcomes are significantly improved. We have generated preclinical data to show esomeprazole, a proton pump inhibitor used for gastric reflux, has potent biological effects that makes it a worthwhile therapeutic candidate. Esomeprazole potently decreases soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin secretion from placenta and endothelial cells, and has biological actions to mitigate endothelial dysfunction and oxidative stress. Methods and analysis We propose undertaking a phase II, double blind, randomised controlled clinical trial to examine whether administering 40 mg esomeprazole daily may prolong gestation in women with early onset pre-eclampsia. We will recruit 120 women (gestational age of 26+0 to 31+6 weeks) who will be randomised to receive either esomeprazole or an identical placebo. The primary outcome will be the number of days from randomisation to delivery. Secondary outcomes include maternal, fetal and neonatal composite and individual outcomes. Maternal outcomes include maternal death, eclampsia, pulmonary oedema, severe renal impairment, cerebral vascular events and liver haematoma or rupture. Neonatal outcomes include neonatal death within 6 weeks after the due date, intraventricular haemorrhage, necrotising enterocolitis and bronchopulmonary dysplasia. We will examine whether esomeprazole can decrease serum sFlt-1 and soluble endoglin levels and we will record the safety of esomeprazole in these pregnancies. Ethics and dissemination This study has ethical approval (Protocol V.2.4, M14/09/038, Federal Wide assurance Number 00001372, IRB0005239), and is registered with NHREC (ID 3649) and the Pan African Clinical Trial Registry (PACTR201504000771349). Data will be presented at international conferences and published in peer-reviewed journals.

Stability of absolute copy number of housekeeping genes in preeclamptic and normal placentas, as measured by digital PCR

Measuring mRNA expression is fundamental to placental research. Ideally, mRNA transcript numbers are directly quantified. However, PCR analysis using the ΔΔCT method relies on the stability of housekeeping genes and only reports relative expression. Digital PCR (dPCR) directly quantifies mRNA copy number and is more accurate than quantitative PCR. We quantified absolute mRNA copy number of housekeeping genes in normotensive pre-term (n = 20), severe preeclamptic (n = 11) and term (n = 12) placenta using dPCR. Whilst there was some variation, we confirm absolute mRNA copy number of GAPDH, TOP1, CYC1 and YWHAZ in placenta does not significantly alter between these cohorts, or across gestation.

The Effect of Intraperitoneal Ropivacaine on Pain after Laparoscopic Excision of Endometriosis

STUDY OBJECTIVE To compare the effects of ropivacaine and saline on pain after laparoscopic excision of endometriosis. DESIGN Randomized, double-blind, controlled trial (Canadian Task Force classification I). SETTING Womens hospital. PATIENTS Ninety-three women undergoing excision of endometriosis. INTERVENTION Laparoscopic excision of endometriosis, after which saline 100 mg (46 women) or ropivacaine 200 mg dissolved in 100 ml saline (47) was instilled intraperitoneally for postoperative analgesia. MEASUREMENTS AND MAIN RESULTS No differences were seen between groups during the first 7 hours after surgery with respect to pain scores, analgesic requirements, postoperative nausea and vomiting, or time to discharge. CONCLUSION We found no difference between ropivacaine and saline, instilled intraperitoneally, in their effects on pain after extensive excision of endometriosis.

Peak plasma anti-Xa levels after first and third doses of enoxaparin in women receiving weight-based thromboprophylaxis following caesarean section: a prospective cohort study

BACKGROUND Women undergoing caesarean section are at higher risk for thromboembolic complications following delivery than other parturients. The aim of this study was to determine whether higher doses of enoxaparin based on body weight are safe and more likely to achieve plasma anti-Xa levels within the accepted thromboprophylactic range. METHODS We undertook a prospective cohort study of 80 women undergoing caesarean section in a tertiary obstetric hospital with >6000 deliveries per year. Enoxaparin was administered after caesarean section using the Royal College of Obstetricians and Gynaecologists weight-adjusted dosing guidelines. Plasma anti-Xa levels were measured at baseline and 3-4 h after enoxaparin administration on days one and three postoperatively. The main outcomes of interest were plasma anti-Xa levels and the proportion of patients with plasma anti-Xa levels in the range of 0.2-0.4 IU/mL. RESULTS The proportion of women with anti-Xa levels between 0.2 and 0.4 IU/mL was 72% (95% CI 60-81%). Unadjusted mean anti-Xa levels were 0.26 ± 0.09 IU/mL and 0.28 ± 0.08 IU/mL on day one and day three respectively. No woman had levels >0.48 IU/mL. CONCLUSION The majority of women receiving weight-based enoxaparin thromboprophylaxis following caesarean section achieved plasma anti-Xa levels within the putative thromboprophylactic range. No woman achieved levels associated with an increased risk of bleeding (>0.8 IU/mL). These findings provide a safety basis for a large prospective study using this regimen.

Plasma MIC-1 and PAPP-a levels are decreased among women presenting to an early pregnancy assessment unit, have fetal viability confirmed but later miscarry.

Background We have recently shown first trimester Macrophage inhibitory cytokine-1 (MIC-1) and Pregnancy Associated Plasma Protein-A (PAPP-A) serum concentrations are depressed among asymptomatic women destined to miscarry. Here we examined whether plasma levels of MIC-1 and PAPP-A are depressed among women presenting to an Early Pregnancy Assessment Unit (EPAU), noted to have a confirmed viable fetus, but subsequently miscarry. Methods We performed a prospective cohort study, recruiting 462 women in the first trimester presenting to EPAU and had fetal viability confirmed by ultrasound. We obtained plasma samples on the same day and measured MIC-1, PAPP-A and human chorionic gonadotrophin (hCG), grouping the cohort according to whether they later miscarried or not. To correct for changes in analyte levels across gestation, we expressed the data as Multiples of the normal Median (MoMs). Results We recruited 462 participants presenting to EPAU at 5-12 weeks gestation. Most (80%) presented with symptoms of threatened miscarriage (e.g. abdominal pain, vaginal bleeding). 34 (7.4%) subsequently miscarried. Median plasma MIC-1 levels among those who miscarried were 50% of those with ongoing pregnancies (Miscarriage cohort MoM 0.50 (25th-75th centiles: 0.29-1.33) vs ongoing pregnancies MoM 1.00 (0.65-1.38); p=0.0025). Median plasma PAPP-A MoMs among those who miscarried was 0.57 (0.00-1.12), significantly lower than those with ongoing pregnancies (MoMs 1.00 (0.59-1.59); p=0.036). Plasma hCG levels were also significantly depressed among those who miscarried compared to those with ongoing pregnancies. However, the performance of MIC-1 as a diagnostic marker to predict miscarriage in this cohort was modest, and not improved with the addition of hCG. Conclusion MIC-1 and PAPP-A levels are significantly depressed in women presenting to EPAU with ultrasound evidence of fetal viability, but later miscarry. While they are unlikely to be useful as predictive biomarkers in this clinical setting, they probably play important roles in the maintenance of early pregnancy.