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1.  Fetal Growth and Schizophrenia: A Nested Case-Control and Case-Sibling Study 
Schizophrenia Bulletin  2012;39(6):1337-1342.
The association between low birth weight and schizophrenia has been suggested by many studies. Small for gestational age (SGA) is a measure used as a proxy for intrauterine growth restriction. We aim to examine if children who are born SGA are at increased risk of developing schizophrenia and whether an association may be explained by factors shared among siblings. We linked 3 population-based registers: the Danish National Medical Birth Register, the Danish Psychiatric Central Register, and the Danish Civil Registration register to identify all persons born between 1978 and 2000. A nested case-control study and a case-sibling study design were used. There were 4650 cases of schizophrenia. Incidence rate ratios (IRRs) were estimated using conditional logistic regression. SGA was defined as the lowest 10th birth weight percentile for a given sex and gestational age. SGA was associated with an IRR of 1.23 (95% CI: 1.11–1.37) for schizophrenia in the case-control study. An IRR of 1.28 (95% CI: 0.97–1.68) was found in the case-sibling study. There is a modest association between SGA and schizophrenia. Our results indicate that this association is due to an independent effect of factors associated with low birth weight for gestational age per se, rather than other factors shared by siblings.
PMCID: PMC3796081  PMID: 23236080
register; Denmark; cohort study; epidemiology
2.  Where GWAS and Epidemiology Meet: Opportunities for the Simultaneous Study of Genetic and Environmental Risk Factors in Schizophrenia 
Schizophrenia Bulletin  2013;39(5):955-959.
PMCID: PMC3756798  PMID: 23907349
genome-wide association study;  epidemiology; Mendelian randomization; interaction; polygene score
3.  Cesarean Section and Rate of Subsequent Stillbirth, Miscarriage, and Ectopic Pregnancy: A Danish Register-Based Cohort Study 
PLoS Medicine  2014;11(7):e1001670.
Louise Kenny and colleagues conduct a population-based cohort study in Denmark to assess the likelihood of stillbirth, miscarriage, and ectopic pregnancy following cesarean section compared to women who gave birth by vaginal delivery.
Please see later in the article for the Editors' Summary
With cesarean section rates increasing worldwide, clarity regarding negative effects is essential. This study aimed to investigate the rate of subsequent stillbirth, miscarriage, and ectopic pregnancy following primary cesarean section, controlling for confounding by indication.
Methods and Findings
We performed a population-based cohort study using Danish national registry data linking various registers. The cohort included primiparous women with a live birth between January 1, 1982, and December 31, 2010 (n = 832,996), with follow-up until the next event (stillbirth, miscarriage, or ectopic pregnancy) or censoring by live birth, death, emigration, or study end. Cox regression models for all types of cesarean sections, sub-group analyses by type of cesarean, and competing risks analyses for the causes of stillbirth were performed. An increased rate of stillbirth (hazard ratio [HR] 1.14, 95% CI 1.01, 1.28) was found in women with primary cesarean section compared to spontaneous vaginal delivery, giving a theoretical absolute risk increase (ARI) of 0.03% for stillbirth, and a number needed to harm (NNH) of 3,333 women. Analyses by type of cesarean section showed similarly increased rates for emergency (HR 1.15, 95% CI 1.01, 1.31) and elective cesarean (HR 1.11, 95% CI 0.91, 1.35), although not statistically significant in the latter case. An increased rate of ectopic pregnancy was found among women with primary cesarean overall (HR 1.09, 95% CI 1.04, 1.15) and by type (emergency cesarean, HR 1.09, 95% CI 1.03, 1.15, and elective cesarean, HR 1.12, 95% CI 1.03, 1.21), yielding an ARI of 0.1% and a NNH of 1,000 women for ectopic pregnancy. No increased rate of miscarriage was found among women with primary cesarean, with maternally requested cesarean section associated with a decreased rate of miscarriage (HR 0.72, 95% CI 0.60, 0.85). Limitations include incomplete data on maternal body mass index, maternal smoking, fertility treatment, causes of stillbirth, and maternally requested cesarean section, as well as lack of data on antepartum/intrapartum stillbirth and gestational age for stillbirth and miscarriage.
This study found that cesarean section is associated with a small increased rate of subsequent stillbirth and ectopic pregnancy. Underlying medical conditions, however, and confounding by indication for the primary cesarean delivery account for at least part of this increased rate. These findings will assist women and health-care providers to reach more informed decisions regarding mode of delivery.
Please see later in the article for the Editors' Summary
Editors' Summary
Globally, increasing numbers of babies are being delivered by cesarean section (a surgical operation in which the baby is delivered through a cut made in the mother's abdomen and womb) instead of naturally through their mother's vagina. In England in 2010, for example, nearly 25% of all babies were delivered by cesarean section (also called C-section) compared to only 2% in the 1950s; in China and some parts of South America cesarean rates are now between 40% and 50%. A cesarean section is usually performed when a vaginal birth would endanger the life of the mother or her unborn child because, for example, the baby is in the wrong position. Some cesareans are performed as emergency procedures, but others are planned in advance when the need for the operation becomes clear during pregnancy (an elective cesarean). Some planned cesarean sections are also undertaken because the mother has requested a cesarean delivery in the absence of any medical reasons for such a delivery.
Why Was This Study Done?
Cesarean sections save lives but do they have any negative impacts on the outcome of subsequent pregnancies? With so many cesarean sections being undertaken, it is important to be sure that the procedure does not increase the rates of subsequent miscarriage, stillbirth, or ectopic pregnancy. Miscarriage—the loss of a fetus (developing baby) that is unable to survive independently—is the commonest complication of early pregnancy, affecting about one in five women who know they are pregnant. Stillbirth is fetal death after about 20–24 weeks of pregnancy; the exact definition of stillbirth varies between countries. About four million stillbirths occur each year worldwide. Ectopic pregnancy—development of the fetus outside the womb—occurs in 1%–2% of all pregnancies. In this population-based cohort study, the researchers investigate the rates of subsequent stillbirth, miscarriage, and ectopic pregnancy following a cesarean section among women living in Denmark. A population-based cohort study determines the baseline characteristics of the individuals in a population, and then follows the population over time to see whether specific characteristics are associated with specific outcomes.
What Did the Researchers Do and Find?
The researchers obtained data for 832,996 women from Danish national registers about their first live birth (including whether they had a cesarean) then followed the women (again using the registers) until they had a stillbirth, miscarriage, or ectopic pregnancy, or a second live birth. The researchers used these data and statistical models to estimate the risk of stillbirth, miscarriage, and ectopic pregnancy following a cesarean compared to a spontaneous vaginal delivery after controlling for the possibility that the cesarean was performed because of an indication that might increase the risk of a subsequent event (confounding). Women who had had a cesarean had a 14% increased risk of a stillbirth in their next pregnancy compared to women who had had a vaginal delivery, corresponding to an absolute risk increase of 0.03%. In other words, 3,333 women would need to have a cesarean to result in one extra stillbirth in subsequent pregnancy (a “number needed to harm” of 3,333). Compared to vaginal delivery, having a cesarean increased the risk of a subsequent ectopic pregnancy by 9% (an absolute risk increase of 0.1% and a number needed to harm of 1,000) but did not increase the rate of subsequent miscarriages.
What Do These Findings Mean?
These findings show that, among women living in Denmark, cesarean section is associated with a slightly increased rate of subsequent stillbirth and ectopic pregnancy. Part of this increase can be accounted for by underlying medical conditions and by confounding by the indication for the primary cesarean section. The accuracy of these findings may be affected by limitations in the study such as incomplete data on some factors (for example, the smoking history of the mother) that might have affected the risk of stillbirth, miscarriage, and ectopic pregnancy, and by misclassification or underreporting of the study outcomes. Given the global increase in cesarean rates, these findings suggest that cesarean delivery is not associated with an increased rate of subsequent stillbirth, miscarriage, or ectopic pregnancy, an important finding for both expectant mothers and health-care professionals that nonetheless needs to be confirmed in further large-scale studies. Finally, these findings highlight the need for women to consider all their options thoroughly before requesting a cesarean section on non-medical grounds.
Additional Information
Please access these websites via the online version of this summary at
The American Congress of Obstetricians and Gynecologists provides patient fact sheets on cesarean birth, miscarriage, and ectopic pregnancy
The US-based non-profit Nemours Foundation provides information about cesarean sections, miscarriage and stillbirth, and ectopic pregnancy (in English and Spanish)
The UK National Health Service Choices website provides information for patients about cesarean section, miscarriage, stillbirth, and ectopic pregnancy
MedlinePlus provides links to additional resources about cesarean section, miscarriage, stillbirth, and ectopic pregnancy (in English and Spanish)
The UK non-profit organization Healthtalkonline provides personal stories about cesarean delivery, miscarriage, and stillbirth
PMCID: PMC4077571  PMID: 24983970
5.  Correction: Genetic and Familial Environmental Effects on Suicide – An Adoption Study of Siblings 
PLoS ONE  2014;9(1):10.1371/annotation/41113674-7ca2-42a5-a364-f646ff85c2e7.
PMCID: PMC3883185
6.  The Risk of Schizophrenia and Child Psychiatric Disorders in Offspring of Mothers with Lung Cancer and Other Types of Cancer: A Danish Nationwide Register Study 
PLoS ONE  2013;8(11):e79031.
Maternal immune responses and brain-reactive antibodies have been proposed as possible causal mechanisms for schizophrenia and some child psychiatric disorders. According to this hypothesis maternal antibodies may cross the placenta and interact with the developing CNS of the fetus causing future neurodevelopmental disorders. Therefore, we investigated if children of mothers with cancer might be at higher risk of developing psychiatric disorders, with particular focus on small-cell lung cancer, which is known to induce production of antibodies binding to CNS elements.
Nationwide population-based registers were linked, including the Danish Psychiatric Central Register and The Danish Cancer Registry. Data were analyzed as a cohort study using survival analysis techniques. Incidence rate ratios (IRRs) and accompanying 95% confidence intervals (CIs) were used as measures of relative risk.
In general, parental cancer was not associated with schizophrenia in the offspring (IRR, 0.98; 95% CI, 0.95-1.01). Furthermore, we found no temporal associations with maternal cancer in general; neither around the pregnancy period. However, maternal small-cell lung cancer increased the risk of early-onset schizophrenia and maternal small-cell lung cancer diagnosed within 20 years after childbirth increased the risk of schizophrenia. Parental cancer was not associated with child psychiatric disorders (IRR, 1.01; 95% CI, 0.98-1.05) except for the smoking related cancers. There was a significantly increased risk of child psychiatric disorders in offspring of both mothers (IRR, 1.35; 95% CI, 1.16-1.58) and fathers (IRR, 1.47; 95% CI, 1.30-1.66) with lung cancer of all types.
In general, parental cancer did not increase the risk of schizophrenia nor of child psychiatric disorders. However, maternal small-cell lung cancer increased the risk of schizophrenia in subgroups; and lung cancer in general increased the risk of child psychiatric disorders, which could be due to risk factors associated with parental smoking.
PMCID: PMC3815227  PMID: 24223877
7.  Genetic and Familial Environmental Effects on Suicide – An Adoption Study of Siblings 
PLoS ONE  2013;8(10):e77973.
While there is clear evidence of familial influences on suicide, the origin of these is less certain. We have investigated genetic and familial environmental factors by studying the occurrence of suicide in biological and adoptive siblings of adoptees who died by suicide compared to siblings of surviving adoptees.
We used the Danish Adoption Register and Danish population registers to compare 221 siblings of adoptees who died by suicide with the siblings of 1,903 adoptees who did not die by suicide. All adoptions in the Danish Adoption Register are non-familial, i.e. the adoptive parents are biologically unrelated to the adoptee. Analyses were conducted on incidence rates of suicide in biological and adoptive siblings given occurrence of suicide in the adoptees while also taking into account psychiatric disorders.
The risk of suicide in full siblings of adoptees who died by suicide before age 60 years was significantly higher than in full siblings of adoptees who had not died by suicide (incidence rate ratios (IRR) = 5.01; 95% confidence interval [CI] = 1.28 - 19.6). This increase persisted after adjustment for history of psychiatric admission of siblings (IRR = 4.19; 95% CI = 1.00 - 17.5).
Genetic factors influence risk of suicide, probably independently of psychiatric disorder. This is relevant in provision of advice to families, including possible prevention of suicide.
PMCID: PMC3798411  PMID: 24147105
8.  Paternal Age and General Cognitive Ability—A Cross Sectional Study of Danish Male Conscripts 
PLoS ONE  2013;8(10):e77444.
Offspring of older men have impaired cognitive ability as children, but it is unclear if this impairment persists into adulthood. The main objective of this study was to explore the association between paternal age at offspring birth and general cognitive ability as young adults.
Population-based cross-sectional study with prospectively collected data on obstetric factors and parental education.
Nationwide Danish sample.
Male conscripts (n = 169,009).
Primary and secondary outcome measures
General cognitive ability as assessed by the Børge Priens test score, an intelligence test with components related to logical, verbal, numerical and spatial reasoning.
We observed an inverse U-shaped association between paternal age and general cognitive ability (slightly lower test scores in the offspring of fathers aged less than 25 years and older than 40 years, compared with fathers aged 25 to 29 years). However, after adjustment for maternal age, parental education and birth order the shape of the association changed. Offspring of fathers younger than 20 still showed slightly lower cognitive ability (-1.11 (95% CI -1.68 to -0.54)), but no significant impairments were identified in the men whose fathers were older than 29 years at the time of their birth (e.g. the mean difference in test score in the offspring of fathers aged 40 to 44 years were -0.03 [95% CI (-0.27 to 0.20)] compared with fathers aged 25 to 29 years).
We did not find that the offspring of older fathers had impaired cognitive ability as young adults. Whereas, we found a tendency that the offspring of teen fathers have lower cognitive ability. Thus, our results suggest that any potentially deleterious effects of older fathers on general cognitive ability as young adults may be counter-balanced by other potentially beneficial factors.
PMCID: PMC3792927  PMID: 24116230
9.  Schizophrenia – a predictor of suicide during the second half of life? 
Schizophrenia Research  2011;134(2-3):111-117.
Little is known about the suicide risk of older adults diagnosed with schizophrenia. The purpose of the study is to examine whether older adults diagnosed with schizophrenia have an elevated risk of dying by suicide, examine trends by age, and identify predictors of death by suicide.
Individual-level register data on all older adults aged 50+ living in Denmark during 1990–2006 (N=2 899 411) were assessed using survival analysis. The impact of predictors was adjusted for a series of socio-demographic and health-related covariates.
In all, 248 suicides were identified among older adults diagnosed with schizophrenia. The suicide rate ratios of men and women aged 50–69 years with a diagnosis of schizophrenia was 7.0 [95%CI: 5.8 – 8.4] and 13.7 [95%CI: 11.3 – 16.6], respectively, when compared to those with no diagnosis. With increasing age a lower rate ratio was found; for men and women aged 70+ it was 2.1 [95%CI: 1.1 – 3.9] and 3.4 [95%CI: 2.0 – 5.8], respectively. Adjusted analyses revealed an elevated risk of suicide for diagnoses of schizophrenia, greater number of hospitalizations, recent admission (for men), recent discharge, previous suicide attempt, recent suicide attempt, comorbidity of mood disorders, personality disorders, and substance abuse (for women).
We found an elevated mortality risk of suicide for both men and women aged 50 years and over diagnosed with schizophrenia. Health care staff should be aware of elevated risk, particularly in older women diagnosed with schizophrenia, in relation to chronic disease courses, recent discharge, and suicide attempt.
PMCID: PMC3266451  PMID: 22018943
Aged; Elderly; Aged; 80 and over; Self-Injurious Behavior; Geriatric Psychiatry; Mental Disorders
10.  Toxoplasma gondii Seropositivity and Suicide rates in Women 
Toxoplasma gondii (T. gondii) is an intracellular protozoan parasite that infects roughly a third of the world population. In an immunocompetent host, infection is generally chronic and asymptomatic, as the immune system keeps T. gondii confined to cysts and the intracellular space within muscle and brain. Seropositivity has been linked to schizophrenia, car accidents, changes in personality, and more recently, suicidal attempts. Very recently, seroprevalence for 20 European countries was found to be associated with increased suicide rates. Although suicide rates were age-standardized, given that T. gondii seroprevalence increases with age, and blood samples were drawn in women, we now retested in women only the association between suicide and T. gondii seropositivity, stratified by age. Simple correlations between ranked T. gondii seropositivity and suicide rate identified statistically significant relationships in women 60 and older (p<0.05); adjusting for GDP, the statistical significance expanded to include women 45 and older. The strongest association was in the 60-74 group where, after adjustment for GDP, the relationship (p=0.007) resisted Bonferroni adjustment for multiple comparisons. In conclusion, the results suggest that a positive relationship between rates of infection with T. gondii and suicide is apparent in women of postmenopausal age. Prospective studies are necessary to further confirm this association predictively and explore mechanisms mediating this relationship.
PMCID: PMC3128543  PMID: 21716055
Toxoplasmosis; Toxoplasma gondii; suicide; Europe
11.  Autoimmune diseases, bipolar disorder, and non-affective psychosis 
Bipolar disorders  2010;12(6):638-646.
Clinic-based studies of immune function, as well as comorbidity of autoimmune diseases, bipolar disorder, and schizophrenia, suggest a possible autoimmune etiology. Studies of non-affective psychosis and schizophrenia suggest common etiologies. The objective was to determine the degree to which 30 different autoimmune diseases are antecedent risk factors for bipolar disorder, schizophrenia, and non-affective psychosis.
A cohort of 3.57 million births in Denmark was linked to the Psychiatric Case Register and the National Hospital Register. There were 20,317 cases of schizophrenia, 39,076 cases of non-affective psychosis, and 9,920 cases of bipolar disorder.
As in prior studies, there were a range of autoimmune diseases which predicted raised risk of schizophrenia in individuals who had a history of autoimmune diseases, and also raised risk in persons whose first-degree relatives had an onset of autoimmune disease prior to onset of schizophrenia in the case. These relationships also existed for the broader category of non-affective psychosis. Only pernicious anemia in the family was associated with raised risk for bipolar disorder (relative risk: 1.7), suggesting a small role for genetic linkage. A history of Guillain-Barré syndrome, Crohn’s disease, and autoimmune hepatitis in the individual was associated with raised risk of bipolar disorder.
The familial relationship of schizophrenia to a range of autoimmune diseases extends to non-affective psychosis, but not to bipolar disorder. The data suggest that autoimmune processes precede onset of schizophrenia, but also non-affective psychosis and bipolar disorder.
PMCID: PMC2950824  PMID: 20868462
autoimmune disease; bipolar disorder; epidemiology; non-affective psychosis; register; schizophrenia
12.  The prevalence of 30 ICD-10 autoimmune diseases in Denmark 
Immunologic research  2010;47(1-3):228-231.
Epidemiologic studies of autoimmune diseases have not considered them in the aggregate. The objective was to estimate the prevalence of 30 autoimmune diseases separately and in aggregate according to ICD-10 classification. The lifetime prevalence of the entire population of 5,506,574 persons alive in Denmark on October 31, 2006, was estimated by linking records of all visitors to hospitals and specialty clinics via National Patient Registers from January 1, 1977 through October 31, 2006. The prevalences vary from 0.06/1,000 for Pemphigus to 8.94/1,000 for Type 1 diabetes. Nearly 4% of the population had one or more autoimmune disease. The general conclusion is that autoimmune diseases as an aggregate are common.
PMCID: PMC2892249  PMID: 20066507
Prevalence; Autoimmune diseases; Registers; Denmark
13.  Psychiatric illness, socioeconomic status, and marital status in people committing suicide: a matched case‐sibling‐control study 
Study objective
Suicides cluster in both families and persons with psychiatric disorders and socioeconomic disadvantages. This study compares these factors between suicide cases, their siblings, and population based controls in an attempt to evaluate both the familial and the individual element of these factors.
Nested case‐control study. Information on causes of death, psychiatric admission, marital status, children, and socioeconomic factors was obtained from routine registers.
985 suicide cases, 1104 sex‐age (±3 years) matched siblings, and 16 619 controls.
Main results
The suicide rate ratios obtained from the case‐sibling and the case‐control analysis, respectively, were of similar magnitude. For example, in the case‐sibling analysis the adjusted suicide rate ratios associated with discharge from a psychiatric hospital within the previous 365 days, being unemployed the previous year, having a postgraduate degree and being single were 42.13 (95% CI 17.75 to 100.02), 1.78 (1.35 to 2.36), 0.51 (0.21 to 1.26), and 2.69 (1.91 to 3.79), respectively. The corresponding rate ratios obtained from the case‐control analysis were 47.91 (35.41 to 64.83), 1.76 (1.49 to 2.08), 0.45 (0.26 to 0.76), and 2.39 (1.87 to 3.07). Moreover, the analogous ratios when comparing siblings and controls were 1.98 (1.08 to 3.63), 1.22 (1.06 to 1.41), 0.65 (0.44 to 0.95), and 0.89 (0.75 to 1.06).
People who commit suicide deviate similarly from siblings and controls in exposure to hospitalised psychiatric disorders and socioeconomic disadvantages, although these factors contribute to the familial aggregation of suicides.
PMCID: PMC2566026  PMID: 16905722
siblings; suicide
14.  Work related violence and threats and the risk of depression and stress disorders 
To examine the risk of depression and stress related disorders as a function of occupational exposure to violence and threats.
Population based nested case‐control study.
All gainfully employed Danes.
Cases and controls
14 166 hospital inpatients and outpatients, aged 18–65, treated for affective or stress related disorders during 1995–1998 selected from The Danish Psychiatric Central Research Register and 58 060 controls matched for age, sex, and time, drawn from Statistics Denmark's Integrated Database for Labour Market Research.
Main outcome measure
Clinical psychiatric diagnosis (WHO ICD‐10) of affective (F30–39) or stress related (F40–48) disorders compared with controls by the occupation held the year before treatment. The occupation held the year before treatment was used as exposure proxy.
Potential exposure to occupational violence is associated with significantly increased relative risks of both disorders in either sex (women: depression RR 1.45 CI 1.27 to 1.65, stress RR 1.32 CI 1.19 to 1.46; men: depression RR 1.48 CI 1.18 to 1.86, stress RR 1.55 CI 1.29 to 1.84). Work related threats are associated with increase in the risk of depression in women (RR 1.48 CI 1.23 to 1.79) and the risk of stress related disorders in men (RR 1.59 CI 1.32 to 1.91). Risks rose with increasing prevalence of violence and threats. The results remain significant and only slightly attenuated after controlling for extent of professional contact with people other than colleagues.
Employment in occupations involving exposure to work related threats and violence is a risk factor for depression and stress related disorders in both sexes. These findings have implications for health and safety at work policies.
PMCID: PMC2566025  PMID: 16905721
depression; stress; occupation; violence; threats
15.  Epidemiology of Autoimmune Diseases in Denmark 
Journal of autoimmunity  2007;29(1):1-9.
An epidemiologic study of the autoimmune diseases taken together has not been done heretofore. The National Patient Register of Denmark is used to estimate population prevalence of 31 possible or probable autoimmune diseases. Record linkage is used to estimate 465 pairwise comorbidities in individuals among the 31 diseases, and familial aggregation among sibs, parents and offspring. The prevalence of any of the 31 diseases in the population is more than 5%. Within individuals, there is extensive comorbidity across the 31 diseases. Within families, aggregation is strongest for individual diseases, and weak across diseases. These data confirm the importance of the autoimmune diseases as a group, and suggest that common etiopathologies exist among them.
PMCID: PMC2717015  PMID: 17582741
Prevalence; comorbidity; autoimmune diseases; population register; sex ratio; familial aggregation
16.  Early Infections of Toxoplasma gondii and the Later Development of Schizophrenia 
Schizophrenia Bulletin  2007;33(3):741-744.
Early exposure to several infectious agents has been associated with the later development of schizophrenia. Two recent studies assessed in utero or early postnatal exposure to Toxoplasma gondii. In one study of 63 individuals, who developed schizophrenia spectrum disorders, maternal sera obtained during pregnancy showed an increased risk (OR 2.61) of having IgG antibodies to T. gondii. In the other study of 71 individuals who developed schizophrenia, sera obtained shortly after birth also showed an increased risk (OR 1.79) of having IgG antibodies to T. gondii. Causal linking mechanisms are at present speculative but include possible direct effects of maternal IgG on the developing central nervous system (CNS) of the offspring. Additional studies are underway.
PMCID: PMC2526131  PMID: 17329231
birth cohort; nested case-control study; biobank
17.  The impact of nonlinear exposure-risk relationships on seasonal time-series data: modelling Danish neonatal birth anthropometric data 
Birth weight and length have seasonal fluctuations. Previous analyses of birth weight by latitude effects identified seemingly contradictory results, showing both 6 and 12 monthly periodicities in weight. The aims of this paper are twofold: (a) to explore seasonal patterns in a large, Danish Medical Birth Register, and (b) to explore models based on seasonal exposures and a non-linear exposure-risk relationship.
Birth weight and birth lengths on over 1.5 million Danish singleton, live births were examined for seasonality. We modelled seasonal patterns based on linear, U- and J-shaped exposure-risk relationships. We then added an extra layer of complexity by modelling weighted population-based exposure patterns.
The Danish data showed clear seasonal fluctuations for both birth weight and birth length. A bimodal model best fits the data, however the amplitude of the 6 and 12 month peaks changed over time. In the modelling exercises, U- and J-shaped exposure-risk relationships generate time series with both 6 and 12 month periodicities. Changing the weightings of the population exposure risks result in unexpected properties. A J-shaped exposure-risk relationship with a diminishing population exposure over time fitted the observed seasonal pattern in the Danish birth weight data.
In keeping with many other studies, Danish birth anthropometric data show complex and shifting seasonal patterns. We speculate that annual periodicities with non-linear exposure-risk models may underlie these findings. Understanding the nature of seasonal fluctuations can help generate candidate exposures.
PMCID: PMC2151954  PMID: 17937794
18.  Urbanization and traffic related exposures as risk factors for Schizophrenia 
BMC Psychiatry  2006;6:2.
Urban birth or upbringing increase schizophrenia risk. Though unknown, the causes of these urban-rural differences have been hypothesized to include, e.g., infections, diet, toxic exposures, social class, or an artefact due to selective migration.
We investigated the hypothesis that traffic related exposures affect schizophrenia risk and that this potential effect is responsible for the urban-rural differences. The geographical distance from place of residence to nearest major road was used as a proxy variable for traffic related exposures. We used a large population-based sample of the Danish population (1.89 million people) including information on all permanent addresses linked with geographical information on all roads and house numbers in Denmark. Schizophrenia in cohort members (10,755 people) was identified by linkage with the Danish Psychiatric Central Register.
The geographical distance from place of residence to nearest major road had a significant effect. The highest risk was found in children living 500–1000 metres from nearest major road (RR = 1.30 (95% Confidence Interval: 1.17–1.44). However, when we accounted for the degree of urbanization, the geographical distance to nearest major road had no significant effect.
The cause(s) or exposure(s) responsible for the urban-rural differences in schizophrenia risk were closer related to the degree of urbanization than to the geographical distance to nearest major road. Traffic related exposures might thus be less likely explanations for the urban-rural differences in schizophrenia risk.
PMCID: PMC1386659  PMID: 16423297
19.  Risk for schizophrenia and schizophrenia-like psychosis among patients with epilepsy: population based cohort study 
BMJ : British Medical Journal  2005;331(7507):23.
Objectives To investigate whether age at onset of epilepsy, type of epilepsy, family history of psychosis, or family history of epilepsy affect the risk of schizophrenia or schizophrenia-like psychosis among patients with epilepsy.
Design Comparison of population based data.
Setting Danish longitudinal registers.
Subjects The cohort comprised 2.27 million people.
Main outcome measures Epilepsy, psychosis, personal birth data.
Results We found an increased risk of schizophrenia (relative risk 2.48, 95% confidence interval 2.20 to 2.80) and schizophrenia-like psychosis (2.93, 2.69 to 3.20) in people with a history of epilepsy. The effect of epilepsy was the same in men and in women and increased with age. Family history of psychosis and a family history of epilepsy were significant risk factors for schizophrenia and schizophrenia-like psychosis, and the effect of epilepsy, both in cases and families, was greater among people with no family history of psychosis. In addition, the increased risk for schizophrenia or schizophrenia-like psychosis did not differ by type of epilepsy but increased with increasing number of admissions to hospital and, particularly, was significantly greater for people first admitted for epilepsy at later ages.
Conclusions There is a strong association between epilepsy and schizophrenia or schizophrenia-like psychosis. The two conditions may share common genetic or environmental causes.
PMCID: PMC558534  PMID: 15964859
20.  Change in suicide rates for patients with schizophrenia in Denmark, 1981-97: nested case-control study 
BMJ : British Medical Journal  2004;329(7460):261.
Objective To study the change in risk of suicide among patients with schizophrenia and related disorders.
Design Nested case-control design with linked data.
Setting 4 longitudinal Danish registers.
Participants 18 744 people aged up to 75 years who committed suicide in 1981-97 individually matched with 20 controls.
Results Over the time studied the reduction in suicide rate among patients with schizophrenia and schizophrenia spectrum disorder was similar to that seen in the general population (incidence rate ratio 1.00, 95% confidence interval 0.98 to 1.03). The reduction among patients with other psychosis in the schizophrenia spectrum was faster than the reduction seen in the general population. Among people admitted to hospital with schizophrenia the risk of suicide was highest in the first year after first admission, and the excess risk was largest in the younger age groups—that is, the risk decreased per year for every additional year of age.
Conclusion The suicide rate among patients with a diagnosis of schizophrenia and related disorders has fallen. This may be due to better psychiatric treatment, reduced access to means of suicide, or improvements in treatment after suicide attempts.
PMCID: PMC498022  PMID: 15213108
23.  Familial, psychiatric, and socioeconomic risk factors for suicide in young people: nested case-control study 
BMJ : British Medical Journal  2002;325(7355):74.
To estimate the risk of suicide in young people related to family and individual psychiatric and socioeconomic factors.
Population based nested case-control study.
Data from longitudinal Danish registers.
Cases and controls
496 young people aged 10-21 years who had committed suicide during 1981-97 in Denmark and 24 800 controls matched for sex, age, and time.
Main outcome measures
All suicides in Denmark compared with controls; parents and siblings identified from population based registers; inpatient information from discharge registers of national hospitals; and socioeconomic data from administrative registers.
Parental factors associated with an increased risk of suicide in young people were suicide or early death, admission to hospital for a mental illness, unemployment, low income, poor schooling, and divorce, as well as mental illness in siblings and mental illness and short duration of schooling in the young people themselves. The strongest risk factor was mental illness in the young people. The effect of the parents' socioeconomic factors decreased after adjustment for a family history of mental illness and a family history of suicide.
Recognising mental illness in young people and dealing with it appropriately could help prevent suicides. The high relative risk associated with a low socioeconomic status of the parents may be confounded and overestimated if not adjusted for mental illness and suicide in the family.
What is already known on this topicYoung people who commit suicide have a history of mental illness or a family history of mental illness or suicidal behaviourDysfunctional family backgrounds and socioeconomic adversity also contribute to suicide in young peopleTargets for preventive strategies are controversial, as few population based studies have been conducted and none have included all the risk factorsWhat this study addsSuicide is more likely among young people if a parent commits suicide or there is a history of mental illness in the individual and their siblingsSocioeconomic risk factors seem to be less importantPreventive strategies should be aimed at the early recognition and optimal treatment of mental illnesses
PMCID: PMC117126  PMID: 12114236

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