Estimating a population cumulative incidence under calendar time trends

Abstract Background The risk of a disease or psychiatric disorder is frequently measured by the age-specific cumulative incidence. Cumulative incidence estimates are often derived in cohort studies with individuals recruited over calendar time and with the end of follow-up governed by a specific date. It is common practice to apply the Kaplan\u2013Meier or Aalen\u2013Johansen estimator to the total sample and report either the estimated cumulative incidence curve or just a single point on the curve as a description of the disease risk. Methods We argue that, whenever the disease or disorder of interest is influenced by calendar time trends, the total sample Kaplan\u2013Meier and Aalen\u2013Johansen estimators do not provide useful estimates of the general risk in the target population. We present some alternatives to this type of analysis. Results We show how a proportional hazards model may be used to extrapolate disease risk estimates if proportionality is a reasonable assumption. If not reasonable, we instead advocate that a more useful description of the disease risk lies in the age-specific cumulative incidence curves across strata given by time of entry or perhaps just the end of follow-up estimates across all strata. Finally, we argue that a weighted average of these end of follow-up estimates may be a useful summary measure of the disease risk within the study period. Conclusions Time trends in a disease risk will render total sample estimators less useful in observational studies with staggered entry and administrative censoring. An analysis based on proportional hazards or a stratified analysis may be better alternatives

Having children with multiple partners is associated with reduced risk of malignant melanoma: an observation seeking a plausible explanation

Anne V Olesen1,2,3, Erik T Parner4, Preben B Mortensen5, Cecilia H Ramlau-Hansen6, Jørn Olsen71Institute of Public Health, Department of Epidemiology, University of Aarhus; 2Unit for Psychiatric Research, Aalborg Psychiatric Hospital; 3Department of Clinical Epidemiology, Aarhus University Hospital; 4Institute of Public Health, Department of Biostatistics; 5National Centre for Register-based Research; 6Department of Occupational Medicine, Aarhus University Hospital, Denmark; 7Department of Epidemiology, School of Public Health, University of California, Los Angeles, USAObjective: We examined the association between the number of partners that mothers and fathers have children with and occurrence of cutaneous malignant melanoma (CMM).Methods: We conducted a complete registry-based follow-up of all Danish mothers born after 1935 from the birth of their second child until CMM, death, emigration, or end of study in 2002. We conducted a similar follow-up of the corresponding fathers. Incidence rate ratios (IRR) and confidence intervals (CI) were estimated by Poisson regression.Results: This study corroborates that women having children with three or more men are half as likely to have CMM as women who have children with one man: incidence rate ratio (IRR) = 0.51, 95% CI: 0.29, 0.91; having children by two fathers reduces risk among women by 20%: IRR = 0.80, 95% CI: 0.70, 0.91. Fathers with multiple partners tend to face a similar risk reduction.Conclusion: The similar patterns of mothers and fathers challenge us to consider and propose likely mechanisms common to both sexes. The patterns of reduced risk have now been reported in two large independent complete population-based studies in Sweden and Denmark.Keywords: malignant melanoma, epidemiology, children with multiple partner

Apgar score and risk of autism

Low Apgar score has been associated with higher risk for several neurological and psychiatric disorders, including cerebral palsy and intellectual disability. Studies of the association between Apgar score and autism spectrum disorder (ASD) have been inconsistent. We aimed to investigate (1) the association between low Apgar score at 5 min and risk for ASD, and (2) the modifying effects of gestational age and sex on this association in the largest multinational database of ASD. We included prospective data from 5.5 million individuals and over 33,000 cases of ASD from Norway, Sweden, Denmark and Western Australia who were born between 1984 and 2007. We calculated crude and adjusted risk ratios (RR) with 95% confidence intervals (95% CIs) for the associations between low Apgar score and ASD. All analyses for ASD were repeated for autistic disorder (AD). We used interaction terms and stratified analysis to investigate the effects of sex, gestational age, and birth weight on the association. In fully adjusted models, low Apgar scores (1–3) (RR, 1.42; 95% CI, 1.16–1.74), and intermediate Apgar scores (4–6) (RR, 1.50; 95% CI, 1.36–1.65) were associated with a higher RR of ASD than optimal Apgar score (7–10). The point estimates for low (RR, 1.88; 95% CI, 1.41–2.51) and intermediate Apgar score (RR, 1.54; 95% CI, 1.32–1.81) were larger for AD than for ASD. This study suggests that low Apgar score is associated with higher risk of ASD, and in particular AD. We did not observe any major modifying effects of gestational age and sex, although there seems to be substantial confounding by gestational age and birth weight on the observed association.</p

Birth seasonality and risk of autism spectrum disorder

Season of birth has been hypothesized to be a risk factor for autism spectrum disorder (ASD). However, the evidence has been mixed and limited due to methodological challenges. We examine ASD birth trends for 5,464,628 births across 5 countries. ASD birth prevalence data were obtained from the International Collaboration for Autism Registry Epidemiology database, including children born in Denmark, Finland, Norway, Sweden, and Western Australia. Empirical mode decomposition and cosinor modeling were used to assess seasonality. We show seasonal variation in ASD births for the countries of Finland and Sweden. There was a modest increase in risk for children born in the fall and a modest decrease in risk for children born in the spring. Solar radiation levels around conception and the postnatal period were inversely correlated with seasonal trends in ASD risk. In the first multinational study of birth seasonality of ASD, there was evidence supporting the presence of seasonal trends in Finland and Sweden. The observations that risk was highest for fall births (i.e., conceived in the winter) and lowest for spring births (i.e., conceived in the summer), and sunlight levels during critical neurodevelopmental periods explained much of the seasonal trends, are consistent with the hypothesis that a seasonally fluctuating risk factor may influence risk of ASD.</p

Recurrence Risk of Autism in Siblings and Cousins: A Multinational, Population-Based Study

Objective:Familial recurrence risk is an important population-level measure of the combined genetic and shared familial liability of autism spectrumdisorder (ASD). Objectives were to estimate ASD recurrence risk among siblings and cousins by varying degree of relatedness and by sex.Method:This is a population-based cohort study of livebirths from 1998 to 2007 in California, Denmark, Finland, Israel, Sweden and WesternAustralia followed through 2011 to 2015. Subjects were monitored for an ASD diagnosis in their older siblings or cousins (exposure) and for their ASDdiagnosis (outcome). The relative recurrence risk was estimated for different sibling and cousin pairs, for each site separately and combined, and by sex.Results:During follow-up, 29,998 cases of ASD were observed among the 2,551,918 births used to estimate recurrence in ASD and 33,769 cases ofchildhood autism (CA) were observed among the 6,110,942 births used to estimate CA recurrence. Compared with the risk in unaffected families, therewas an 8.4-fold increase in the risk of ASD following an older sibling with ASD and a 17.4-fold increase in the risk of CA following an older sibling withCA. A 2-fold increase in the risk for cousin recurrence was observed for the 2 disorders. There also was a significant difference in sibling ASD recurrencerisk by sex.Conclusion:The present estimates of relative recurrence risks for ASD and CA will assist clinicians and families in understanding autism risk in thecontext of other families in their population. The observed variation by sex underlines the need to deepen the understanding of factors influencing ASD familial risk.</p

Regression analysis of censored data using pseudo-observations

We draw upon a series of articles in which a method based on pseudovalues is proposed for direct regression modeling of the survival function, the restricted mean, and the cumulative incidence function in competing risks with right-censored data. The models, once the pseudovalues have been computed, can be fit using standard generalized estimating equation software. Here we present Stata procedures for computing these pseudo-observations. An example from a bone marrow transplantation study is used to illustrate the method