Abstract
STUDY QUESTION
What is the impact of cancer in females aged ≤39 years on subsequent chance of pregnancy?
SUMMARY ANSWER
Cancer survivors achieved fewer pregnancies across all cancer types, ...and the chance of achieving a first pregnancy was also lower.
WHAT IS KNOWN ALREADY
The diagnosis and treatment of cancer in young females may be associated with reduced fertility but the true pregnancy deficit in a population is unknown.
STUDY DESIGN, SIZE, DURATION
We performed a retrospective cohort study relating first incident cancer diagnosed between 1981 and 2012 to subsequent pregnancy in all female patients in Scotland aged 39 years or less at cancer diagnosis (n = 23 201). Pregnancies were included up to end of 2014. Females from the exposed group not pregnant before cancer diagnosis (n = 10 271) were compared with general population controls matched for age, deprivation quintile and year of diagnosis.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Scottish Cancer Registry records were linked to hospital discharge records to calculate standardized incidence ratios (SIR) for pregnancy, standardized for age and year of diagnosis. Linkage to death records was also performed. We also selected women from the exposed group who had not been pregnant prior to their cancer diagnosis who were compared with a matched control group from the general population. Additional analyses were performed for breast cancer, Hodgkin lymphoma, leukaemia, cervical cancer and brain/CNS cancers.
MAIN RESULTS AND THE ROLE OF CHANCE
Cancer survivors achieved fewer pregnancies: SIR 0.62 (95% CI: 0.60, 0.63). Reduced SIR was observed for all cancer types. The chance of achieving a first pregnancy was also lower, adjusted hazard ratio = 0.57 (95% CI: 0.53, 0.61) for women >5 years after diagnosis, with marked reductions in women with breast, cervical and brain/CNS tumours, and leukaemia. The effect was reduced with more recent treatment period overall and in cervical cancer, breast cancer and Hodgkin lymphoma, but was unchanged for leukaemia or brain/CNS cancers. The proportion of pregnancies that ended in termination was lower after a cancer diagnosis, and the proportion ending in live birth was higher (78.7 vs 75.6%, CI of difference: 1.1, 5.0).
LIMITATIONS, REASONS FOR CAUTION
Details of treatments received were not available, so the impact of specific treatment regimens on fertility could not be assessed. Limited duration of follow-up was available for women diagnosed in the most recent time period.
WIDER IMPLICATIONS OF THE FINDINGS
This analysis provides population-based quantification by cancer type of the effect of cancer and its treatment on subsequent pregnancy across the reproductive age range, and how this has changed in recent decades. The demonstration of a reduced chance of pregnancy across all cancer types and the changing impact in some but not other common cancers highlights the need for appropriate fertility counselling of all females of reproductive age at diagnosis.
STUDY FUNDING/COMPETING INTEREST(S)
This study was funded by NHS Lothian Cancer and Leukaemia Endowments Fund. Part of this work was undertaken in the MRC Centre for Reproductive Health which is funded by the MRC Centre grant MR/N022556/1. RAA has participated in Advisory Boards and/or received speaker's fees from Beckman Coulter, IBSA, Merck and Roche Diagnostics. He has received research support from Roche Diagnostics, Ansh labs and Ferring. The other authors have no conflicts to declare.
The proportion of births via cesarean section (CS) varies worldwide and in many countries exceeds WHO-recommended rates. Long-term health outcomes for children born by CS are poorly understood, but ...limited data suggest that CS is associated with increased infection-related hospitalisation. We investigated the relationship between mode of birth and childhood infection-related hospitalisation in high-income countries with varying CS rates.
We conducted a multicountry population-based cohort study of all recorded singleton live births from January 1, 1996 to December 31, 2015 using record-linked birth and hospitalisation data from Denmark, Scotland, England, and Australia (New South Wales and Western Australia). Birth years within the date range varied by site, but data were available from at least 2001 to 2010 for each site. Mode of birth was categorised as vaginal or CS (emergency/elective). Infection-related hospitalisations (overall and by clinical type) occurring after the birth-related discharge date were identified in children until 5 years of age by primary/secondary International Classification of Diseases, 10th Revision (ICD-10) diagnosis codes. Analysis used Cox regression models, adjusting for maternal factors, birth parameters, and socioeconomic status, with results pooled using meta-analysis. In total, 7,174,787 live recorded births were included. Of these, 1,681,966 (23%, range by jurisdiction 17%-29%) were by CS, of which 727,755 (43%, range 38%-57%) were elective. A total of 1,502,537 offspring (21%) had at least 1 infection-related hospitalisation. Compared to vaginally born children, risk of infection was greater among CS-born children (hazard ratio (HR) from random effects model, HR 1.10, 95% confidence interval (CI) 1.09-1.12, p < 0.001). The risk was higher following both elective (HR 1.13, 95% CI 1.12-1.13, p < 0.001) and emergency CS (HR 1.09, 95% CI 1.06-1.12, p < 0.001). Increased risks persisted to 5 years and were highest for respiratory, gastrointestinal, and viral infections. Findings were comparable in prespecified subanalyses of children born to mothers at low obstetric risk and unchanged in sensitivity analyses. Limitations include site-specific and longitudinal variations in clinical practice and in the definition and availability of some data. Data on postnatal factors were not available.
In this study, we observed a consistent association between birth by CS and infection-related hospitalisation in early childhood. Notwithstanding the limitations of observational data, the associations may reflect differences in early microbial exposure by mode of birth, which should be investigated by mechanistic studies. If our findings are confirmed, they could inform efforts to reduce elective CS rates that are not clinically indicated.
Highlights • There are case reports of oesophageal cancer in patients with eating disorders. • We followed up a cohort of patients hospitalised previously with eating disorders. • These patients were ...at significantly increased risk of oesophageal cancer. • All cancers were squamous cell carcinomas in females with prior anorexia nervosa. • Indirect evidence suggests confounding by established risk factors.
Advances in cancer management have resulted in improved survival rates, particularly in children and young adults. However, treatment may adversely affect reproductive outcomes among female cancer ...survivors. The objective of this study was to investigate their risk of adverse perinatal outcomes compared to the general population.
We performed a population-based analysis, including all female cancer survivors diagnosed before the age of 40 years between 1981 and 2012. Pregnancy and perinatal complications were identified through linkage of the Scottish Cancer Registry with hospital discharge records based on the Community Health Index (CHI) database. We compared 1,629 female cancer survivors with a first ever singleton pregnancy after diagnosis, with controls matched on age, deprivation quintile, and year of cancer diagnosis selected from the general population (n = 8,899). Relative risks and 95%-confidence intervals of perinatal risks were calculated using log-binomial regression.
Survivors were more likely to give birth before 37 weeks of gestation (relative risk (RR) 1.32, 95%-CI 1.10-1.59), but did not show an increased risk of low birth weight (<2.5kg: RR 1.15, 95%-CI 0.94-1.39), and were less likely to give birth to offspring small for gestational age (RR 0.81, 95%-CI 0.68-0.98). Operative delivery and postpartum haemorrhage were more common but approached rates in controls with more recent diagnosis. The risk of congenital abnormalities was not increased (RR 1.01, 95%-CI 0.85-1.20).
Cancer survivors have an increased risk of premature delivery and postpartum haemorrhage, but their offspring are not at increased risk for low birth weight or congenital abnormalities. In recent decades there has been a normalisation of delivery method in cancer survivors, nevertheless careful management remains appropriate particularly for those diagnosed in childhood.
Primary hyperparathyroidism (PHPT) is functionally characterized by an inappropriately raised secretion of parathyroid hormone, leading to raised serum calcium levels. Some patients are referred for ...parathyroidectomy, and some are managed conservatively. The aim of the audit was to compare the mortality outcomes between the two groups.
We retrospectively identified a cohort of inpatients with a main or secondary diagnosis of PHPT between 1986 and 2010 and followed them up to the end of 2011. The risk of mortality in PHPT patients compared to the background general population was estimated by calculating standardized mortality ratios (SMRs), adjusting for age, sex, and person-years at risk. Mortality in surgically treated patients was compared to conservatively treated patients using Cox regression, taking account of the Charlson Comorbidity Index.
A total of 2,589 patients (77.9% females) were diagnosed with PHPT in Scotland over this period. Of patients diagnosed with PHPT, 41.6% (1,077/2,589) had died by the end of 2011. The SMR was 1.58 (95% confidence interval CI, 1.48 to 1.67). A total of 54.8% of the patients underwent surgery (SMR, 1.30; 95% CI, 1.18 to 1.43), while the rest were treated "conservatively" (SMR, 1.88; 95% CI, 1.73 to 2.03) (
<.001). When other significant variables including the Charlson Comorbidity Index were taken into account in the final model, the hazard ratio for the "conservatively" managed group was reduced to 1.49 (95% CI, 1.30 to 1.70;
<.0001).
Our study confirmed that inpatients diagnosed with PHPT have increased mortality. The risk of mortality was lower in those treated surgically compared with patients treated conservatively.
= confidence interval;
= hazard ratio;
= primary hyperparathyroidism;
= parathyroidectomy;
= standard mortality ratio;
= Scottish Morbidity Records.
Objective: To measure the increasing incidence of primary hyperparathyroidism (PHPT) in Scotland, to determine the relationship between PHPT and deprivation, and to investigate the relationship ...between parathyroidectomy (PTX) and social deprivation. Methods: We retrospectively identified a cohort of patients diagnosed with PHPT between 1986 and 2013 from the Scottish Morbidity Records (SMR01) database. The diagnosis of PHPT was made in accordance with the International Classification of Diseases code. Results: Between the years 1986 and 2013, 4002 patients were diagnosed with PHPT. There was a significant increase in the incidence of PHPT in this period (p < 0.0001), an association between the incidence of PHPT and deprivation (p < 0.0001) plus an association between a lower rate of PTX and deprivation (p < 0.001). Conclusion: The increase in incidence of PHPT may be due to a combination of increased awareness of PHPT, easier diagnosis, and an ageing population. The lower rate of PTX in relation to deprivation may reflect comorbidities, age, and uncertainty about the long-term benefits of PTX in asymptomatic patients.
IntroductionSevere acute pancreatitis (AP) requiring critical care admission (ccAP) impacts negatively on long-term survival.ObjectiveTo document organ-specific new morbidity and identify risk ...factors associated with premature mortality after an episode of ccAP.DesignCohort study.SettingElectronic healthcare registries in Scotland.ParticipantsThe ccAP cohort included 1471 patients admitted to critical care with AP between 1 January 2008 and 31 December 2010 followed up until 31 December 2014. The population cohort included 3450 individuals from the general population of Scotland frequency-matched for age, sex and social deprivation.MethodsRecord linkage of routinely collected electronic health data with population matching.Primary and secondary outcome measuresPatient demographics, comorbidity (Charlson Comorbidity Index), acute physiology, organ support and other critical care data were linked to records of mortality (death certificate data) and new-onset morbidity. Kaplan-Meier and Cox regression analyses were used to identify risk factors associated with mortality.Results310 patients with AP died during the index admission. Outcomes were not ascertained for five patients, and the deprivation quintile was not known for six patients. 340 of 1150 patients in the resulting postdischarge ccAP cohort died during the follow-up period. Greater comorbidity measured by the Charlson score, prior to ccAP, negatively influenced survival in the hospital and after discharge. The odds of developing new-onset diabetes mellitus after ccAP compared with the general population were 10.70 (95% CI 5.74 to 19.94). A new diagnosis of myocardial infarction, stroke, heart failure, liver disease, peptic ulcer, renal failure, cancer, peripheral vascular disease and lung disease was more frequent in the ccAP cohort than in the general population.ConclusionsThe persistent deleterious impact of severe AP on long-term outcome and survival is multifactorial in origin, influenced by pre-existing patient characteristics and acute episode features. Further mechanistic and epidemiological investigation is warranted.
Acute pancreatitis (AP) is a frequent cause of hospitalization with long-term health consequences, including type 3c diabetes mellitus (DM). The incidence and risk factors for new-onset morbidities ...after AP need to be clarified to inform a personalized medicine approach.
Using a longitudinal electronic healthcare record-linkage analysis, all patients admitted to hospital in Scotland with a first episode of AP between 1 April 2009 and 31 March 2012 and followed for a minimum of 5 years after their index AP admission were identified. All new-onset morbidity with specific focus on type 3c DM were analysed and, using time-split multiple regression.
A total of 2047 patients were included. AP requiring critical care was followed by 2 years of heightened risk (HR 5.24) of developing type 3c DM, increased risk of new-onset cardiac disease (HR 1.61), and renal disease (HR 2.96). The additional risk conferred by critical care AP had a negative interaction with time, whereas additional risk associated with male sex and a non-gallstone aetiology was long lasting.
Based on these findings, a personalized approach to include type 3c DM screening for a minimum of 2 years for individuals who required critical care when hospitalized with AP is recommended.
Introduction Childhood infection is a leading cause of morbidity and mortality worldwide, however, the epidemiology of infection-related hospitalisations (IRH) across high-income countries is not ...well described. Population-level data are valuable resources for studying the epidemiology of severe infections. Objectives and Approach We used data from our multi-country total population-based cohort study to describe the patterns of IRH across six populations in five countries. Our cohort study contains birth and hospitalisation data on all singleton live births from 1996-2015 from Australia (New South Wales and Western Australia), Denmark, Norway, Scotland, and England. Children were classified as having an IRH if they had an inpatient hospital admission that incurred at least one primary or secondary infectious disease discharge ICD code, at least one day after the birth-related discharge date and if they were less than five years of age at discharge. IRH were classified as overall and by clinical group. Here we present interim analyses from Denmark and Scotland, n=1,593,008 (further results will be presented at the conference). Results More boys than girls had an IRH by 5 years of age (boys 26%, girls 21%). By 1 year, 12% of boys and 9% of girls experienced their first IRH, whereas between 1-5 years of age, 14% of boys and 12% of girls experienced their first IRH. Overall, 7% of children had >1 IRH. The majority of infections were lower and upper respiratory tract infections, followed by viral and gastrointestinal infections. Infection was commoner in the lowest socio-economic status groups. Conclusion / Implications IRH remains a leading cause of hospitalisation in preschool children. Understanding the epidemiology of IRH in high-income countries is important for targeting appropriate interventions and reducing disease burden.
Introduction Asthma is now one of the most common long-term conditions in the UK. It is therefore important to develop a comprehensive appreciation of the healthcare and societal costs in order to ...inform decisions on care provision and planning. We plan to build on our earlier estimates of national prevalence and costs from asthma by filling the data gaps previously identified in relation to healthcare and broadening the field of enquiry to include societal costs. This work will provide the first UK-wide estimates of the costs of asthma. In the context of asthma for the UK and its member countries (ie, England, Northern Ireland, Scotland and Wales), we seek to: (1) produce a detailed overview of estimates of incidence, prevalence and healthcare utilisation; (2) estimate health and societal costs; (3) identify any remaining information gaps and explore the feasibility of filling these and (4) provide insights into future research that has the potential to inform changes in policy leading to the provision of more cost-effective care. Methods and analysis Secondary analyses of data from national health surveys, primary care, prescribing, emergency care, hospital, mortality and administrative data sources will be undertaken to estimate prevalence, healthcare utilisation and outcomes from asthma. Data linkages and economic modelling will be undertaken in an attempt to populate data gaps and estimate costs. Separate prevalence and cost estimates will be calculated for each of the UK-member countries and these will then be aggregated to generate UK-wide estimates. Ethics and dissemination Approvals have been obtained from the NHS Scotland Information Services Division's Privacy Advisory Committee, the Secure Anonymised Information Linkage Collaboration Review System, the NHS South-East Scotland Research Ethics Service and The University of Edinburgh's Centre for Population Health Sciences Research Ethics Committee. We will produce a report for Asthma-UK, submit papers to peer-reviewed journals and construct an interactive map.
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