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

Probabilistic linkage without personal information successfully linked national clinical datasets: Linkage of national clinical datasets without patient identifiers using probabilistic methods.

BACKGROUND: Probabilistic linkage can link patients from different clinical databases without the need for personal information. If accurate linkage can be achieved, it would accelerate the use of linked datasets to address important clinical and public health questions. OBJECTIVE: We developed a step-by-step process for probabilistic linkage of national clinical and administrative datasets without personal information, and validated it against deterministic linkage using patient identifiers. STUDY DESIGN AND SETTING: We used electronic health records from the National Bowel Cancer Audit (NBOCA) and Hospital Episode Statistics (HES) databases for 10,566 bowel cancer patients undergoing emergency surgery in the English National Health Service. RESULTS: Probabilistic linkage linked 81.4% of NBOCA records to HES, versus 82.8% using deterministic linkage. No systematic differences were seen between patients that were and were not linked, and regression models for mortality and length of hospital stay according to patient and tumour characteristics were not sensitive to the linkage approach. CONCLUSION: Probabilistic linkage was successful in linking national clinical and administrative datasets for patients undergoing a major surgical procedure. It allows analysts outside highly secure data environments to undertake linkage while minimising costs and delays, protecting data security, and maintaining linkage quality

Model for risk adjustment of postoperative mortality in patients with colorectal cancer.

BACKGROUND: A model was developed for risk adjustment of postoperative mortality in patients with colorectal cancer in order to make fair comparisons between healthcare providers. Previous models were derived in relatively small studies with the use of suboptimal modelling techniques. METHODS: Data from adults included in a national study of major surgery for colorectal cancer were used to develop and validate a logistic regression model for 90-day mortality. The main risk factors were identified from a review of the literature. The association with age was modelled as a curved continuous relationship. Bootstrap resampling was used to select interactions between risk factors. RESULTS: A model based on data from 62 314 adults was developed that was well calibrated (absolute differences between observed and predicted mortality always smaller than 0·75 per cent in deciles of predicted risk). It discriminated well between low- and high-risk patients (C-index 0·800, 95 per cent c.i. 0·793 to 0·807). An interaction between age and metastatic disease was included as metastatic disease was found to increase postoperative risk in young patients aged 50 years (odds ratio 3·53, 95 per cent c.i. 2·66 to 4·67) far more than in elderly patients aged 80 years (odds ratio 1·48, 1·32 to 1·66). CONCLUSION: Use of this model, estimated in the largest number of patients with colorectal cancer to date, is recommended when comparing postoperative mortality of major colorectal cancer surgery between hospitals, clinical teams or individual surgeons

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

Early academic achievement in children with isolated clefts: a population-based study in England

OBJECTIVES: We used national data to study differences in academic achievement between 5-year-old children with an isolated oral cleft and the general population. We also assessed differences by cleft type. METHODS: Children born in England with an oral cleft were identified in a national cleft registry. Their records were linked to databases of hospital admissions (to identify additional anomalies) and educational outcomes. Z-scores (signed number of SD actual score is above national average) were calculated to make outcome scores comparable across school years and across six assessed areas (personal development, communication and language, maths, knowledge of world, physical development andcreative development). RESULTS: 2802 children without additional anomalies, 5 years old between 2006 and 2012, were included. Academic achievement was significantly below national average for all six assessed areas with z-scores ranging from -0.24 (95% CI -0.32 to -0.16) for knowledge of world to -0.31 (-0.38 to -0.23) for personal development. Differences were small with only a cleft lip but considerably larger with clefts involving the palate. 29.4% of children were documented as having special education needs (national rate 9.7%), which varied according to cleft type from 13.2% with cleft lip to 47.6% with bilateral cleft lip and palate. CONCLUSIONS: Compared with national average, 5-year-old children with an isolated oral cleft, especially those involving the palate, have significantly poorer academic achievement across all areas of learning. These outcomes reflect results of modern surgical techniques and multidisciplinary approach. Children with a cleft may benefit from extra academic support when starting school

Establishing a composite neonatal adverse outcome indicator using English hospital administrative data

OBJECTIVE: We adapted a composite neonatal adverse outcome indicator (NAOI), originally derived in Australia, and assessed its feasibility and validity as an outcome indicator in English administrative hospital data. DESIGN: We used Hospital Episode Statistics (HES) data containing information infants born in the English National Health Service (NHS) between 1 April 2014 and 31 March 2015. The Australian NAOI was mapped to diagnoses and procedure codes used within HES and modified to reflect data quality and neonatal health concerns in England. To investigate the concurrent validity of the English NAOI (E-NAOI), rates of NAOI components were compared with population-based studies. To investigate the predictive validity of the E-NAOI, rates of readmission and death in the first year of life were calculated for infants with and without E-NAOI components. RESULTS: The analysis included 484 007 (81%) of the 600 963 eligible babies born during the timeframe. 114/148 NHS trusts passed data quality checks and were included in the analysis. The modified E-NAOI included 23 components (16 diagnoses and 7 procedures). Among liveborn infants, 5.4% had at least one E-NAOI component recorded before discharge. Among newborns discharged alive, the E-NAOI was associated with a significantly higher risk of death (0.81% vs 0.05%; p<0.001) and overnight hospital readmission (15.7% vs 7.1%; p<0.001) in the first year of life. CONCLUSIONS: A composite NAOI can be derived from English hospital administrative data. This E-NAOI demonstrates good concurrent and predictive validity in the first year of life. It is a cost-effective way to monitor neonatal outcomes

A step-wise approach to developing indicators to compare the performance of maternity units using hospital administrative data.

Hospital administrative data are attractive for comparing performance of maternity units because of their often large sample sizes, lack of selection bias and the relatively low costs of accessing these data compared with conducting primary data collection. However, using administrative data to develop indicators can also present challenges including varying data quality, the limited detail on clinical risk factors and a lack of structural and user experience measures. This review illustrates how to develop performance indicators for maternity units using hospital administrative data, including methods to address the challenges that administrative data pose. TWEETABLE ABSTRACT: How to develop maternity indicators from administrative data

UK experience of liver transplantation for erythropoietic protoporphyria

Erythropoietic protoporphyria (EPP) is characterised by excess production of free protoporphyrin from the bone marrow, most commonly due to deficiency of the enzyme ferrochelatase. Excess protoporphyrin gives rise to the cutaneous photosensitivity characteristic of the disease, and in a minority of patients leads to end-stage liver disease necessitating liver transplantation (LT). There is limited information regarding the timing, impact and long-term outcome of LT in such patients, thus we aimed to identify the indications and outcomes of all transplants performed for EPP in the UK using data from the UK Transplant Registry. Between 1987 and 2009, five patients underwent LT for EPP liver disease. Median follow-up was 60 months, and there were two deaths at 44 and 95 months from causes unrelated to liver disease. The remaining recipients are alive at 22.4 years, 61 months and 55 months after transplant. A high rate of postoperative biliary stricturing requiring multiple biliary interventions was observed. Recurrent EPP-liver disease occurred in 4/5 (80%) of patients but graft failure has not been observed. Given the role of biliary obstruction in inducing EPP-mediated liver damage, we suggest that consideration should be given for construction of a Roux loop at the time of transplant. Thus we demonstrate that although EPP liver transplant recipients have a good long-term survival, comparable to patients undergoing LT for other indications, biliary complications and disease recurrence are almost universal, and bone marrow transplantation should be considered where possible

Multishot versus Single-Shot Pulse Sequences in Very High Field fMRI: A Comparison Using Retinotopic Mapping

High-resolution functional MRI is a leading application for very high field (7 Tesla) human MR imaging. Though higher field strengths promise improvements in signal-to-noise ratios (SNR) and BOLD contrast relative to fMRI at 3 Tesla, these benefits may be partially offset by accompanying increases in geometric distortion and other off-resonance effects. Such effects may be especially pronounced with the single-shot EPI pulse sequences typically used for fMRI at standard field strengths. As an alternative, one might consider multishot pulse sequences, which may lead to somewhat lower temporal SNR than standard EPI, but which are also often substantially less susceptible to off-resonance effects. Here we consider retinotopic mapping of human visual cortex as a practical test case by which to compare examples of these sequence types for high-resolution fMRI at 7 Tesla. We performed polar angle retinotopic mapping at each of 3 isotropic resolutions (2.0, 1.7, and 1.1 mm) using both accelerated single-shot 2D EPI and accelerated multishot 3D gradient-echo pulse sequences. We found that single-shot EPI indeed led to greater temporal SNR and contrast-to-noise ratios (CNR) than the multishot sequences. However, additional distortion correction in postprocessing was required in order to fully realize these advantages, particularly at higher resolutions. The retinotopic maps produced by both sequence types were qualitatively comparable, and showed equivalent test/retest reliability. Thus, when surface-based analyses are planned, or in other circumstances where geometric distortion is of particular concern, multishot pulse sequences could provide a viable alternative to single-shot EPI