Impact of Caesarean section on subsequent fertility: a systematic review and meta-analysis.

STUDY QUESTION: Is there an association between a Caesarean section and subsequent fertility? SUMMARY ANSWER: Most studies report that fertility is reduced after Caesarean section compared with vaginal delivery. However, studies with a more robust design show smaller effects and it is uncertain whether the association is causal. WHAT IS KNOWN ALREADY: A previous systematic review published in 1996 summarizing six studies including 85 728 women suggested that Caesarean section reduces subsequent fertility. The included studies suffer from severe methodological limitations. STUDY DESIGN, SIZE, DURATION: Systematic review and meta-analysis of cohort studies comparing subsequent reproductive outcomes of women who had a Caesarean section with those who delivered vaginally. PARTICIPANTS/MATERIALS, SETTING, METHODS: Searches of Cochrane Library, Medline, Embase, CINAHL Plus and Maternity and Infant Care databases were conducted in December 2011 to identify randomized and non-randomized studies that compared the subsequent fertility outcomes after a Caesarean section and after a vaginal delivery. Eighteen cohort studies including 591 850 women matched the inclusion criteria. Risk of bias was assessed by the Newcastle-Ottawa scale (NOS). Data extraction was done independently by two reviewers. The meta-analysis was based on a random-effects model. Subgroup analyses were performed to assess whether the estimated effect was influenced by parity, risk adjustment, maternal choice, cohort period, and study quality and size. MAIN RESULTS AND THE ROLE OF CHANCE: The impact of Caesarean section on subsequent pregnancies could be analysed in 10 studies and on subsequent births in 16 studies. A meta-analysis suggests that patients who had undergone a Caesarean section had a 9% lower subsequent pregnancy rate [risk ratio (RR) 0.91, 95% confidence interval (CI) (0.87, 0.95)] and 11% lower birth rate [RR 0.89, 95% CI (0.87, 0.92)], compared with patients who had delivered vaginally. Studies that controlled for maternal age or specifically analysed primary elective Caesarean section for breech delivery, and those that were least prone to bias according to the NOS reported smaller effects. LIMITATIONS, REASONS FOR CAUTION: There is significant variation in the design and methods of included studies. Residual bias in the adjusted results is likely as no study was able to control for a number of important maternal characteristics, such as a history of infertility or maternal obesity. WIDER IMPLICATIONS OF THE FINDINGS: Further research is needed to reduce the impact of selection bias by indication through creating more comparable patient groups and applying risk adjustment

A population-based cohort study of the effect of Caesarean section on subsequent fertility

STUDY QUESTION Is there an association between Caesarean section and subsequent fertility? SUMMARY ANSWER There is no or only a slight effect of Caesarean section on future fertility. WHAT IS KNOWN ALREADY Previous studies have reported that delivery by a Caesarean section is associated with fewer subsequent pregnancies and longer inter-pregnancy intervals. The interpretation of these findings is difficult because of significant weaknesses in study designs and analytical methods, notably the potential effect of the indication for Caesarean section on subsequent delivery. STUDY DESIGN, SIZE, DURATION Retrospective cohort study of 1 047 644 first births to low-risk women using routinely collected, national administrative data of deliveries in English maternity units between 1 April 2000 and 31 March 2012. PARTICIPANTS/MATERIALS, SETTING, METHODS Primiparous women aged 15–40 years who had a singleton, term, live birth in the English National Health Service were included. Women with high-risk pregnancies involving placenta praevia, pre-eclampsia, eclampsia (gestational or pre-existing), hypertension or diabetes were excluded from the main analysis. Kaplan–Meier analyses and Cox proportional hazard models were used to assess the effect of mode of delivery on time to subsequent birth, adjusted for age, ethnicity, socio-economic deprivation and year of index delivery. MAIN RESULTS AND THE ROLE OF CHANCE Among low-risk primiparous women, 224 024 (21.4%) were delivered by Caesarean section. The Kaplan–Meier estimate of the subsequent birth rate at 10 years for the cohort was 74.7%. Compared with vaginal delivery, subsequent birth rates were marginally lower after elective Caesarean for breech (adjusted hazard ratio, HR 0.96, 95% CI 0.94–0.98). Larger effects were observed after elective Caesarean for other indications (adjusted HR 0.81, 95% CI 0.78–0.83), and emergency Caesarean (adjusted HR 0.91, 95% CI 0.90–0.93). The effect was smallest for elective Caesarean for breech, and this was not statistically significant in women younger than 30 years of age (adjusted HR 0.98, 95% CI 0.96–1.01). LIMITATIONS, REASONS FOR CAUTION We used birth cohorts from maternity units with good quality parity information. The data are likely to be nationally representative because the characteristics of the deliveries in included and omitted units were similar. There may be residual bias in our adjusted results due to unmeasured maternal factors such as obesity and voluntary absence of conception. Any residual bias would lead to an overestimate of the effect of Caesarean section on fertility, and the true effect is therefore likely to be smaller than the effect reported in our study. WIDER IMPLICATIONS OF THE FINDINGS Our results provide strong evidence that there is no or only a slight effect of Caesarean section on future fertility. The clinical and social circumstances leading to the Caesarean section have a greater effect on future fertility than the Caesarean section itself. This finding is important in light of rising Caesarean section rates. STUDY FUNDING/COMPETING INTEREST(S) IG-U is supported by the Lindsay Stewart R&D Centre, Royal College of Obstetricians and Gynaecologists, UK. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER n/a

Effect of simulated dawn on quality of sleep – a community-based trial

BACKGROUND: Morning light exposure administered as simulated dawn looks a promising method to treat Seasonal Affective Disorder, but it may moreover help with resetting the inaccurate organisation of body clock functions relative to sleep occurring in winter among people in general. Disturbances in sleep patterns are common and may compromise wellbeing even in the short term. Our hypothesis was that simulated dawn could improve the subjective quality of sleep during winter. METHODS: A community-based trial with 100 volunteer subjects provided with dawn simulators. Study period lasted for eight weeks, and subjects used the dawn simulators for two weeks at a time, each subject acting as his own control (ABAB-design). Main outcome measure was subjective quality of sleep recorded each morning with Groningen Sleep Quality Scale. RESULTS: 77 subjects completed the trial. Quality of sleep improved while subjects were using dawn simulator-devices (p = 0.001). The treatment became beneficial after six days' use of dawn simulator, but the effect did not last after the use was ceased. CONCLUSION: Dawn simulation may help to improve the subjective quality of sleep, but the benefits are modest. Further research is needed to verify these findings and to elucidate the mechanism by which dawn simulation acts on the sleep-wake pattern

Fish under exercise

Improved knowledge on the swimming physiology of fish and its application to fisheries science and aquaculture (i.e., farming a fitter fish) is currently needed in the face of global environmental changes, high fishing pressures, increased aquaculture production as well as increased concern on fish well-being. Here, we review existing data on teleost fish that indicate that sustained exercise at optimal speeds enhances muscle growth and has consequences for flesh quality. Potential added benefits of sustained exercise may be delay of ovarian development and stimulation of immune status. Exercise could represent a natural, noninvasive, and economical approach to improve growth, flesh quality as well as welfare of aquacultured fish: a FitFish for a healthy consumer. All these issues are important for setting directions for policy decisions and future studies in this area. For this purpose, the FitFish workshop on the Swimming Physiology of Fish (http://www.ub.edu/fitfish2010) was organized to bring together a multidisciplinary group of scientists using exercise models, industrial partners, and policy makers. Sixteen international experts from Europe, North America, and Japan were invited to present their work and view on migration of fishes in their natural environment, beneficial effects of exercise, and applications for sustainable aquaculture. Eighty-eight participants from 19 different countries contributed through a poster session and round table discussion. Eight papers from invited speakers at the workshop have been contributed to this special issue on The Swimming Physiology of Fish

Early transcriptional response in the jejunum of germ-free piglets after oral infection with virulent rotavirus

Germ-free piglets were orally infected with virulent rotavirus to collect jejunal mucosal scrapings at 12 and 18 hours post infection (two piglets per time point). IFN-gamma mRNA expression was stimulated in the mucosa of all four infected piglets, indicating that they all responded to the rotavirus infection. RNA pools prepared from two infected piglets were used to compare whole mucosal gene expression at 12 and 18 hpi to expression in uninfected germ-free piglets (n = 3) using a porcine intestinal cDNA microarray. Microarray analysis identified 13 down-regulated and 17 up-regulated genes. Northern blot analysis of a selected group of genes confirmed the data of the microarray. Genes were functionally clustered in interferon-regulated genes, proliferation/differentiation genes, apoptosis genes, cytoskeleton genes, signal transduction genes, and enterocyte digestive, absorptive, and transport genes. Down-regulation of the transport gene cluster reflected in part the loss of rotavirus-infected enterocytes from the villous tips. Data mining suggested that several genes were regulated in lower- or mid-villus immature enterocytes and goblet cells, probably to support repair of the damaged epithelial cell layer at the villous tips. Furthermore, up-regulation was observed for IFN-γ induced guanylate binding protein 2, a protein that effectively inhibited VSV and EMCV replication in vitro (Arch Virol 150:1213–1220, 2005). This protein may play a role in the small intestine’s innate defense against enteric viruses like rotavirus

Resource-sharing in multiple component working memory

Working memory research often focuses on measuring the capacity of the system and how it relates to other cognitive abilities. However, research into the structure of working memory is less concerned with an overall capacity measure but rather with the intricacies of underlying components and their contribution to different tasks. A number of models of working memory structure have been proposed, each with different assumptions and predictions, but none of which adequately accounts for the full range of data in the working memory literature. We report 2 experiments that investigated the effects of load manipulations on dual-task verbal temporary memory and spatial processing. Crucially, we manipulated cognitive load around the measured memory span of each individual participant. We report a clear effect of increasing memory load on processing accuracy, but only when memory load is increased above each participant’s measured memory span. However, increasing processing load did not affect memory performance. We argue that immediate verbal memory may rely both on a temporary phonological store and on activated traces in long-term memory, with the latter deployed to support memory performance for supraspan lists and when a high memory load is coupled with a processing task. We propose that future research should tailor the load manipulations to the capacities of individual participants and suggest that contrasts between models of working memory may be more apparent than real

Robot-assisted radical prostatectomy vs laparoscopic and open retropubic radical prostatectomy: functional outcomes 18 months after diagnosis from a national cohort study in England.

BACKGROUND: Robot-assisted radical prostatectomy (RARP) has been rapidly adopted without robust evidence comparing its functional outcomes against laparoscopic radical prostatectomy (LRP) or open retropubic radical prostatectomy (ORP) approaches. This study compared patient-reported functional outcomes following RARP, LRP or ORP. METHODS: All men diagnosed with prostate cancer in England during April - October 2014 who underwent radical prostatectomy were identified from the National Prostate Cancer Audit and mailed a questionnaire 18 months after diagnosis. Group differences in patient-reported sexual, urinary, bowel and hormonal function (EPIC-26 domain scores) and generic health-related quality of life (HRQoL; EQ-5D-5L scores), with adjustment for patient and tumour characteristics, were estimated using linear regression. RESULTS: In all, 2219 men (77.0%) responded; 1310 (59.0%) had RARP, 487 (21.9%) LRP and 422 (19.0%) ORP. RARP was associated with slightly higher adjusted mean EPIC-26 sexual function scores compared with LRP (3·5 point difference; 95% CI: 1.1-5.9, P=0.004) or ORP (4.0 point difference; 95% CI: 1.5-6.5, P=0.002), which did not meet the threshold for a minimal clinically important difference (10-12 points). There were no significant differences in other EPIC-26 domain scores or HRQoL. CONCLUSIONS: It is unlikely that the rapid adoption of RARP in the English NHS has produced substantial improvements in functional outcomes for patients

Epithelial-immune cell interplay in primary Sjogren syndrome salivary gland pathogenesis

In primary Sjogren syndrome (pSS), the function of the salivary glands is often considerably reduced. Multiple innate immune pathways are likely dysregulated in the salivary gland epithelium in pSS, including the nuclear factor-kappa B pathway, the inflammasome and interferon signalling. The ductal cells of the salivary gland in pSS are characteristically surrounded by a CD4(+) T cell-rich and B cell-rich infiltrate, implying a degree of communication between epithelial cells and immune cells. B cell infiltrates within the ducts can initiate the development of lymphoepithelial lesions, including basal ductal cell hyperplasia. Vice versa, the epithelium provides chronic activation signals to the glandular B cell fraction. This continuous stimulation might ultimately drive the development of mucosa-associated lymphoid tissue lymphoma. This Review discusses changes in the cells of the salivary gland epithelium in pSS (including acinar, ductal and progenitor cells), and the proposed interplay of these cells with environmental stimuli and the immune system. Current therapeutic options are insufficient to address both lymphocytic infiltration and salivary gland dysfunction. Successful rescue of salivary gland function in pSS will probably demand a multimodal therapeutic approach and an appreciation of the complicity of the salivary gland epithelium in the development of pSS. Salivary gland dysfunction is an important characteristic of primary Sjogren syndrome (pSS). In this Review, the authors discuss various epithelial abnormalities in pSS and the mechanisms by which epithelial cell-immune cell interactions contribute to disease development and progression