Maternal and neonatal risk factors for childhood type 1 diabetes: a matched case-control study

Peer reviewedPublisher PD

Association of early life factors and acute lymphoblastic leukaemia in childhood: historical cohort study

In a historical cohort study of all singleton live births in Northern Ireland from 1971–86 (n=434 933) associations between early life factors and childhood acute lymphoblastic leukaemia were investigated. Multivariable analyses showed a positive association between high paternal age (⩾35 years) and acute lymphoblastic leukaemia (relative risk=1.49; 95% confidence interval (CI)=0.96–2.31) but no association with maternal age. High birth weight (⩾3500 g) was positively associated with acute lymphoblastic leukaemia (relative risk=1.66; 95% CI=1.18–2.33). Children of mothers with a previous miscarriage or increased gestation (⩾40 weeks) had reduced risks of ALL (respective relative risks=0.49; 95% CI=0.29–0.80, and 0.67; 95% CI=0.48–0.94). Children born into more crowded households (⩾1 person per room) had substantially lower risks than children born into less crowded homes with also some evidence of a lower risk for children born into homes with three adults (relative risks=0.56; 95% CI=0.35–0.91 and 0.58; 95% CI=0.21–1.61 respectively). These findings indicate that several early life factors, including living conditions in childhood and maternal miscarriage history, influence risk of acute lymphoblastic leukaemia in childhood

Survival trends of cancer amongst the south Asian and non-south Asian population under 30 years of age in Yorkshire, UK.

Introduction: Several studies have shown differences in survival trends between ethnic groups across adults with cancer in the UK. It is unclear whether these differences exist exclusively in the older adult population or whether they begin to emerge in children and young adults. Methods: Subjects (n = 3534) diagnosed with cancer under 30 years of age in Yorkshire between 1990 and 2005 were analysed. Differences in survival rates for diagnostic subgroups were estimated by ethnic group (south Asian or not) using Kaplan–Meier estimation and Cox regression. Results: When compared to non-south Asians (all other ethnic groups excluding south Asians) a significant increased risk of death was seen for south Asians with leukaemia (hazard ratio (HR) = 1.75; 95% confidence interval (CI) = 1.11–2.76) and lymphoma (HR = 2.05; 95% CI = 1.09–3.87), whereas south Asians with solid tumours other than central nervous system tumours had a significantly reduced risk of death(HR = 0.50; 95% CI = 0.28–0.89). This was independent of socioeconomic deprivation. Conclusion: We found evidence of poorer survival outcomes for south Asians compared to non-south Asian children and young adults with leukaemia and lymphoma, but better outcomes for south Asian children and young adults with other solid tumours. This needs to be explained, and carefully addressed in the on-going development of cancer services

Deep learning to detect optical coherence tomography-derived diabetic macular edema from retinal photographs: a multicenter validation study

PURPOSE: To validate the generalizability of a deep learning system (DLS) that detects diabetic macular edema (DME) from two-dimensional color fundus photography (CFP), where the reference standard for retinal thickness and fluid presence is derived from three-dimensional optical coherence tomography (OCT). DESIGN: Retrospective validation of a DLS across international datasets. PARTICIPANTS: Paired CFP and OCT of patients from diabetic retinopathy (DR) screening programs or retina clinics. The DLS was developed using datasets from Thailand, the United Kingdom (UK) and the United States and validated using 3,060 unique eyes from 1,582 patients across screening populations in Australia, India and Thailand. The DLS was separately validated in 698 eyes from 537 screened patients in the UK with mild DR and suspicion of DME based on CFP. METHODS: The DLS was trained using DME labels from OCT. Presence of DME was based on retinal thickening or intraretinal fluid. The DLS's performance was compared to expert grades of maculopathy and to a previous proof-of-concept version of the DLS. We further simulated integration of the current DLS into an algorithm trained to detect DR from CFPs. MAIN OUTCOME MEASURES: Superiority of specificity and non-inferiority of sensitivity of the DLS for the detection of center-involving DME, using device specific thresholds, compared to experts. RESULTS: Primary analysis in a combined dataset spanning Australia, India, and Thailand showed the DLS had 80% specificity and 81% sensitivity compared to expert graders who had 59% specificity and 70% sensitivity. Relative to human experts, the DLS had significantly higher specificity (p=0.008) and non-inferior sensitivity (p 50%) and a sensitivity of 100% (p=0.02 for sensitivity > 90%). CONCLUSIONS: The DLS can generalize to multiple international populations with an accuracy exceeding experts. The clinical value of this DLS to reduce false positive referrals, thus decreasing the burden on specialist eye care, warrants prospective evaluation

Infections in early life and childhood leukaemia risk: a UK case–control study of general practitioner records

We investigated infections in early life (diagnosed in general practice) and subsequent risk of childhood leukaemia in the UK General Practice Research Database (GPRD). All children born at GPRD practices and subsequently diagnosed with leukaemia were identified as cases and were individually matched (on year of birth, sex and practice) to up to 20 controls. The final analysis included 162 leukaemia cases and 2215 matched controls. Conditional logistic regression demonstrated no evidence that children with one or more recorded infection in the first year of life had a reduced risk of leukaemia (OR=1.05, 95%CI 0.69, 1.59; P=0.83) or acute lymphoblastic leukaemia (ALL; OR=1.05, 95%CI 0.64–1.74; P=0.84). Our study provides no support for the Greaves hypothesis, which proposes that reduced or delayed exposure to infections in early life increases the risk of childhood ALL

Day-care, early common infections and childhood acute leukaemia: a multicentre French case–control study

We conducted a case–control study to investigate the role of early infections in the aetiology of childhood acute leukaemias. The study included 280 incident cases (240 acute lymphoblastic leukaemia and 40 acute non-lymphoblastic leukaemia) and 288 hospital controls, frequency matched by age, gender, hospital, catchment area of the hospital and ethnic origin. Data were obtained from standardised face-to-face interviews of the mothers. The interviews included questions on early common infections, day-care attendance, breast-feeding, birth order and infantile diseases. Odds ratios were estimated using an unconditional regression model including the stratification variables, parental socio-economic status and perinatal characteristics. Birth order was not associated with childhood leukaemia (acute lymphoblastic or acute non-lymphoblastic). A statistically-significant inverse association was observed between childhood leukaemia and day-care attendance (odds ratio=0.6, 95% Confidence Interval=(0.4–1.0)), repeated early common infections (⩾4 per year before age two, odds ratio=0.6 (0.4–1.0)), surgical procedures for ear–nose–throat infections before age two (odds ratio=0.5 (0.2–1.0)) and prolonged breast-feeding (⩾6 months, odds ratio=0.5 (0.2–1.0)). In the multivariate model including day-care attendance, early common infections and breast-feeding, results concerning breast-feeding remained unchanged. A statistically significant interaction between day-care attendance and repeated early common infections was observed. When the interaction was taken into account, the simple effects of day-care and early common infections disappeared (odds ratio=1.1 (0.5–2.3) and odds ratio=0.8 (0.5–1.3), respectively) while the joint effect of day-care attendance and early common infections was negatively associated with childhood leukaemia (odds ratio=0.3 (0.1–0.8)). All the above associations were observed both for acute lymphoblastic leukaemia and acute non-lymphoblastic leukaemia. Our results support Greaves' hypothesis, even though they are not specific of common leukaemia

Cancer incidence among the south Asian and non-south Asian population under 30 years of age in Yorkshire, UK.

Few studies have examined epidemiological differences between ethnic groups for children and young adults with cancer

Childhood solid tumours in relation to population mixing around the time of birth

In a retrospective cohort study of 673 787 live births in the Northern Region of England, 1975 - 1994, we investigated whether a higher level of population mixing around birth was a risk factor for solid tumours, by diagnostic group (Hodgkin's disease, brain and spinal tumours, neuroblastoma, other solid tumours), diagnosed during 1975-2001 under age 15 years. Logistic regression was used to relate risk to population mixing, based on (i) all movers and (ii) incomers from outside the region. Both ward and county district level analyses were performed. There was a decreased risk of brain and spinal tumours with increasing population mixing based on incomers from outside the region (OR for trend across three categories = 0.79, 95% CI: 0.66-0.95, P = 0.01 in the ward level analysis). Although this may be because of chance, it is consistent with a role of exposure to infection and immunological response in the aetiology of these tumours. For other tumour groups, there was no consistent evidence of an association between risk and population mixing