Are obstetric outcomes affected by female genital mutilation?

INTRODUCTION AND HYPOTHESIS: Female genital mutilation (FGM) has been associated with adverse obstetric and neonatal outcomes, such as postpartum haemorrhage (PPH), perineal trauma, genital fistulae, obstructed labour and stillbirth. The prevalence of FGM has increased in the UK over the last decade. There are currently no studies available that have explored the obstetric impact of FGM in the UK. The aim of our study was to investigate the obstetric and neonatal outcomes of women with FGM when compared with the general population. METHODS: We conducted a retrospective case-control study of consecutive pregnant women with FGM over a 5-year period between 1 January 2009 and 31 December 2013. Each woman with FGM was matched for age, ethnicity, parity and gestation with subsequent patients without FGM (control cohort) over the same 5-year period. Outcomes assessed were mode of delivery, duration of labour, estimated blood loss, analgaesia, perineal trauma and foetal outcomes. RESULTS: A total of 242 eligible women (121 FGM, 121 control) were identified for the study. There was a significant increase in the use of episiotomy in the FGM group (p = 0.009) and a significant increase in minor PPH in the control group during caesarean sections (p = 0.0001). There were no differences in all other obstetric and neonatal parameters. CONCLUSIONS: In our unit, FGM was not associated with an increased incidence of adverse obstetric and foetal morbidity or mortality.

Altered urothelial ATP signaling in a major subset of human overactive bladder patients with pyuria.

Overactive Bladder (OAB) is an idiopathic condition, characterized by urgency, urinary frequency, and urgency incontinence, in the absence of routinely traceable urinary infection. We have described microscopic pyuria (≥10 wbc/µl) in patients suffering from the worst symptoms. It is established that inflammation is associated with increased ATP release from epithelial cells, and extracellular ATP originating from the urothelium following increased hydrostatic pressure is a mediator of bladder sensation. Here, using bladder biopsy samples, we have investigated urothelial ATP signaling in OAB patients with microscopic pyuria. Basal, but not stretch-evoked, release of ATP was significantly greater from the urothelium of OAB patients with pyuria than from non-OAB patients or OAB patients without pyuria (<10 wbc/µl). Basal ATP release from the urothelium of OAB patients with pyuria was inhibited by the P2 receptor antagonist suramin and abolished by the hemichannel blocker carbenoxolone, which differed from stretch-activated ATP release. Altered P2 receptor expression was evident in the urothelium from pyuric OAB patients. Furthermore, intracellular bacteria were visualized in shed urothelial cells from ∼80% of OAB patients with pyuria. These data suggest that increased ATP release from the urothelium, involving bacterial colonization, may play a role in the heightened symptoms associated with pyuric OAB patients.

Is chronic urinary infection a cause of overactive bladder?

Overactive bladder (OAB) is a diagnosis resulting from a combination of multiple underlying factors. Current traditional treatments are based on anticholinergic blockade which have marginal benefits and are associated with poor tolerability and continuation rates. There is mounting evidence that chronic low grade bacterial bladder colonisation may exacerbate OAB symptoms and may explain why the current treatment strategies are not always successful. However, standard diagnostic laboratory tests to identify the presence of such bacterial infection are unreliable. Newer technologies such as RNA sequencing and extended culture techniques, show that urine is not sterile and organisms that are found in urine may be responsible for OAB symptoms. This article aims to review the current evidence suggesting that micro-organisms in urine may be important in the aetiology of OAB or may exacerbate OAB symptoms.

The risk and severity of developing symptomatic palpitations when prescribed mirabegron for overactive bladder.

OBJECTIVES: Mirabegron is a new selective ß3-adrenoreceptor agonist licensed for the treatment of overactive bladder (OAB). In clinical trials, mirabegron is well-tolerated with a low side-effect profile. There is little data available on the risks in a non-selected population. The presence of ß-adrenoreceptors in cardiac and vascular tissue leads to the possibility of the development of adverse cardiovascular events. We conducted a consecutive cohort study to assess the risk of developing palpitations, the severity of the condition and to investigate any underlying risk factors that predispose patients with OAB to develop palpitations whilst taking mirabegron. STUDY DESIGN: A consecutive cohort of patients with OAB was studied between February 2013 and June 2014. Patients were prescribed mirabegron 50mg daily and outcomes assessed at 6 weeks. Patients with known cardiac arrhythmias were excluded. In patients who developed palpitations, a detailed account of their symptoms and medical history were documented and a 12-lead electrocardiogram (ECG) was performed to assess heart rate, QT interval and the presence of any persisting arrhythmia was conducted. RESULTS: A total of 279 patients were started on mirabegron. Eight patients (2.9%) reported palpitations whilst taking the drug. Two patients with a history of palpitations with no history of prolonged QT interval or arrhythmia on ECG developed worsening palpitations. The QTc was prolonged in two patients at 0.458 and 0.441s (QTc <420). Three patients developed chest pain or tightness. The palpitations resolved once therapy was stopped and did not result in serious adverse events such as hospitalisation. CONCLUSIONS: Palpitations in an unselected population have a similar incidence to that demonstrated in previous drug trials. Palpitations may be associated with a worsening of cardiovascular dysfunction.

Programmed aortic dysfunction and reduced Na+,K+-ATPase activity present in first generation offspring of lard-fed rats does not persist to the second generation.

We have previously reported that male and female offspring of Sprague-Dawley rats fed a diet rich (approximately 50% of caloric intake from fat) in animal fat (lard) during pregnancy and suckling (OHF) demonstrate cardiovascular dysfunction, including blunted endothelium-dependent vasodilatation in the aorta as well as reduced renal Na(+),K(+)-ATPase activity. Cardiovascular dysfunction has been reported in other models of developmental programming and some researchers describe transmission from F(1) to F(2) generations. Here we report a study of vascular function, as assessed in isolated rings of aorta mounted in an organ bath, and renal Na(+),K(+)-ATPase activity in 6-month-old male and female F(2) offspring of lard-fed and control-fed (OC) dams (n = 13 per diet group). An increase in brain (OC 0.61 +/- 0.01% versus OHF 0.66 +/- 0.02% of bodyweight) and kidney weights (OC 0.32 +/- 0.01% versus OHF 0.37 +/- 0.01% of bodyweight) was observed in female F(2) offspring of lard-fed dams compared with F(2) controls (P < 0.03). Constrictor responses to phenylephrine in the aorta were not different from F(2) controls (repeated measures ANOVA, P = 0.85). Also, endothelium-dependent dilator function, as assessed by responses to acetylcholine (repeated measures ANOVA, P = 0.96) and passive distensibility in the absence of extracellular calcium (repeated measures ANOVA, P = 0.68), was similar. Additionally, renal Na(+),K(+)-ATPase activity was not statistically different from that observed in control animals (ANOVA, P = 0.89). Although a maternal diet rich in animal fat has deleterious effects on parameters of cardiovascular risk in F(1) animals, it does not appear that disorders previously reported in the F(1) generation are transmitted to the F(2) generation.

Developmental programming of aortic and renal structure in offspring of rats fed fat-rich diets in pregnancy.

Evidence from human and animal studies suggests that maternal nutrition can induce developmental programming of adult hypertension in offspring. We have previously described a model of maternal dietary imbalance in Sprague-Dawley rats whereby administration of a maternal diet rich in animal lard programmes the development of increased blood pressure, insulin resistance, dyslipidaemia, obesity and mesenteric artery endothelial dysfunction in adult offspring. To further characterize the mechanism of hypertension in this model we have examined vascular and renal structure in adult offspring of Sprague-Dawley rats fed a control diet (OC) or lard-rich diet (OHF) during pregnancy and suckling followed by a control diet post-weaning. To gain further insight, we assessed aortic reactivity and elasticity in an organ bath preparation and renal renin and Na+,K+-ATPase activity. Plasma aldosterone concentration was also measured. Stereological examination of the aorta in OHF demonstrated reduced endothelial cell volume and smooth muscle cell number compared with OC. Adult OHF animals showed increased aortic stiffness and reduced endothelium-dependent relaxation. Renal stereology showed no differences in kidney weight, glomerular number or volume in OHF compared with OC, but renin and Na+,K+-ATPase activity were significantly reduced in OHF compared with controls. Programmed alterations to aortic structure and function are consistent with previous observations that exposure to maternal high fat diets produces systemic vascular changes in the offspring. Despite normal renal stereology, altered renal Na+,K+-ATPase and renin activity offers further insight into the mechanism underlying the increased blood pressure characteristic of this model.