Normal and abnormal vaginal flora
Louis Pasteur was inspired to change his field of study from chemistry to the study of disease when three of his five children died of typhoid. His personal loss became humanity’s gain. His ability to develop new ways of thinking about things (paradigm shifts) was extraordinary, for example he was the first to appreciate that molecules could be produced in mirror image structures (isomerism) and that biological systems usually produce only one of the two options. But it was his realisation that the world is full of microorganisms that changed our approach to medicine most fundamentally. Although he was not the first to propose the germ theory of disease, it was his researches on such diverse topics as fermentation, diseases of silkworms, production of vaccines and the development of ‘pasteurisation’, that established the ubiquity of invisible living particles, notably bacteria. Many bacteria are incredibly hardy, living in rocks kilometres deep in the earth’s crust, or miles down in the superheated water of deep-sea volcanic vents, and some have even been found living permanently in the high atmosphere (Lighthart and Shaffer Appl Environ Microbiol 1995;61:1492–6). Of particular interest to gynaecologists is the bacterial microcosm of the vagina. In men, the pathway from the germinal tissue of the testes to the outside world is closed off from the rest of the body. But in women, the shedding of eggs into the peritoneal cavity requires there to be a pathway to the outside world through which the baby can eventually emerge. The inside of the body (the space between the epithelium of the skin and the endothelium of the intestine) is normally bacteria free but the reproductive tract of the female provides a potential avenue for the invasion of the peritoneal cavity by bacteria. The body marshals many defences against invasion, including the activities of leucocytes, the plugging of the cervix with thick mucus, which is only easily passable at ovulation, and the secretion of defensins that attack the microbial cell membrane. But as on the skin, a major protective element is the normal flora that exists within the vagina. The conditions there are harsh, with no light and little oxygen. However, there is an abundant source of nutrition. The glycogen secreted by the endometrial cells primarily to support the developing embryo is a plentiful energy source. The microbes that flourish as a result are described in detail by Lamont et al. from the USA National Institute of Child Health and Human Development on page 533. They put forward the intriguing view that the vaginal microflora should be considered as part of the human super-organism (produced not only by human genes but also by those of the microorganisms in or on us, and without which we could not digest our food or defend ourselves against pathogens). Of the many bacteria that have been identified within the vagina, the lactobacilli are numerically dominant, and by producing lactic acid they maintain an acid environment that is protective against invasion by many species of pathogenic bacteria. In the 1990s there was a brief fashion among the lay public to treat disturbances of the vaginal flora by inoculation with natural yoghurt, which is produced by the action of lactobacilli—unfortunately, however, not the strains useful in humans (of which there are at least 20, just 15% of the total species so far identified). The sheer complexity of the normal flora, and the equally complex abnormal flora that are just beginning to be understood, is mind-boggling. Read Lamont et al.’s review and prepare to be amazed.
Caesarean section for twins
In 2007, I pointed out in an editorial in the BMJ (Steer BMJ 2007;334:545–6) that the majority of twin pregnancies are now being delivered by elective caesarean section because of particular concerns about the safety of vaginal delivery for the second twin (twin B). At the time, the only evidence I could find about this latter aspect was a single randomised study performed at the end of the 1980s and a few small retrospective studies. We are therefore pleased to publish on page 523 in this month’s BJOG a systematic review and meta-analysis of this topic by Rossi and her colleagues. They managed to identify 18 relevant papers, 12 of which reported neonatal outcomes for both twins. All but four reported better outcomes for twin A than twin B, but importantly, meta-analysis of the four papers that compared attempted vaginal delivery and planned caesarean section, showed no difference in morbidity or mortality in twin B by mode of delivery. Equally important is their finding that when the first twin (A) is in cephalic presentation, vaginal delivery is safer than caesarean section. This may be associated with delivery at an earlier gestation when caesarean section is chosen, i.e. iatrogenic prematurity. They conclude that women should be counselled that a trial of labour is a safe option in the absence of risk factors likely to increase the risk that the second twin will need a caesarean delivery. Certainly, if women with twin pregnancies and no obvious additional risk factors are keen to attempt a vaginal birth, there seems no evidence-based reason to discourage them.
Early external cephalic version—a turn for the worse?
I can remember clearly the first external cephalic version (ECV) I performed, which was in 1978. In those days, the orthodoxy was that turning breech babies before 36 weeks of gestation was potentially dangerous because it might precipitate preterm labour, resulting in the birth of a baby that would have severe respiratory distress syndrome, while attempting to turn babies after 36 weeks of gestation was inadvisable because it was difficult and potentially traumatic because of the decrease in amniotic fluid volume towards the due date. I was doing a ward round with two students when we came to a lady with a previously undiagnosed breech presentation at 41 weeks gestational age who had been admitted for induction of labour. I smiled when she asked the obvious question ‘if the baby is the wrong way round, why don’t you just turn it the right way round?’ I explained to her (and for the benefit of the students) that the amniotic fluid would have decreased so that that the baby’s position would be fixed, and just to make the point, I gently attempted to turn the baby round. To everyone’s amazement (including mine) the baby turned round extremely easily. Subsequently, whenever I diagnosed a breech presentation in the antenatal clinic, I attempted a gentle ECV, and found that about a third were easy to turn. Eventually, general policy caught up with me and now ECV at 36/37 to 38 weeks of gestation is the evidence-based norm, although it has been complicated by detailed protocols involving restriction of the procedure to the labour ward, overnight fasts (in case of the need for emergency caesarean section, although I have never seen such a case in 32 years), subcutaneous tocolytics, scans and cardiotocography. Although tocolytics increase the version rate to about 60% (being especially useful in nullipara), over the last 30 years, neonatal care has advanced to such an extent that the risk associated with early delivery has been substantially reduced, and Hutton and her colleagues in 68 centres in 21 countries agreed that it was worth reassessing the value of earlier version. The result of their prospective randomised controlled trial involving 1543 women is reported on page 564. Although there was a significantly higher success rate in the early (34–356/7 weeks) ECV group compared with the late group (37 weeks or more)—58.9% versus 50.9%—the associated 4% reduction in caesarean section rate (52% versus 56%) was not significant (P = 0.12). The rate of preterm birth (<37 weeks of gestation) was slightly higher in the early group (6.5%) than in the late group (4.4%) but again the difference was not statistically significant, and there was no significant difference in neonatal morbidity or mortality. However, these conclusions are based on a ‘frequentist’ approach, and from the Bayesian perspective the data strengthen a prior belief that early ECV increases the success rate of ECV at the expense of a higher preterm birth rate. Given that the trial did not produce a decisive result one way or the other, the authors concluded that the study findings should be discussed with women ‘so that they can make an informed choice as to what is best for them and their infants’, which I would argue should always apply except in the direst emergencies.
Other uses of Viagra
Sildenafil citrate (trade name Viagra) has become famous for its efficacy in correcting erectile dysfunction. But its ability to dilate particular vascular beds has also been beneficial in other areas of medicine, for example it has substantially improved the outlook for people suffering from pulmonary hypertension. Because it crosses the placenta, there has been interest in its potential efficacy in improving fetal growth. On page 615 Pellicer et al. report their study of this hypothesis in rats and found that sildenafil significantly increased fetal and neonatal weight, with the liver being most markedly affected. No obviously harmful effects were observed. On page 624, von Dadelszen et al. report a pilot study of sildenafil given to ten women with severe early-onset intrauterine growth restriction, compared with 17 nonrandomised controls. Treatment resulted in significantly increased fetal abdominal circumference growth velocity. Small numbers limit the conclusions that can be drawn, but the findings are encouraging enough to suggest that an adequately sized prospective trial is justified. Use of sildenafil as a prophylactic against early onset pre-eclampsia remains controversial (Downing J Hypertens Pregnancy 2010;29:248–50).
The purpose of a journal is not just to publish papers, but to evaluate, select and improve them. Beyond this, we aim to provide helpful material to develop readers’ understanding of both methodology and content. This month, Journal Club Editor Dimitrios Siassakos has produced a template to structure discussion about meta-analysis, using the Rossi et al. twins paper as an example. Also, to accompany the paper by Smith et al. on page 557, he has produced a video podcast available via http://www.bjog.org/view/0/index.html, in which you can see Professor Gordon Smith answering questions about his research. He and his team have found an intriguing relationship between recurrent miscarriage and a family history of ischaemic heart disease. In the paper and podcast, Professor Smith speculates about a possible vascular pathology underlying both processes. And on page 596, Dr Siassakos is the first author of a paper examining the added value of specific behaviours (such as directive leadership style and situational awareness) on the efficiency of team performance in an obstetric emergency. On page 550, Lier et al. suggest that the introduction of the transobturator tape has added value (in terms of cost effectiveness) over the original tension-free tape for the management of stress urinary incontinence. Is three-dimensional ultrasound of added value (by the assessment of fetal lung volumes) when predicting infant respiratory outcome in association with congenital diaphragmatic hernia? The paper by Prendergast et al. on page 608 suggests that it is.
Apologies to Nick Reed of the Royal Shrewsbury Hospital, who in January I wrongly described as a guest editor for our forthcoming special issue on gynaecological oncology. It should have been Nicholas Reed of the Beatson Oncology Centre in Glasgow! Which gives me a chance to remind you that this issue will be an outstanding opportunity to showcase your best oncology research to a wide general audience—the deadline for submissions of 31 May fast approaches, so please get writing.