Potential predictors in neonaticide: the impact of the circumstances of pregnancy

This study aims to evaluate the psychosocial factors of neonaticide, especially the circumstances before delivery, the relationships of the pregnant women, and their social environment awareness of women's pregnancy. This nationwide study was register-based, comprising all known neonaticides in Austria and Finland between 1995 and 2005. Cases (n = 28) were obtained by screening the death certificates from coroner's departments and by analyzing them along with all further available reports. Few women (17.9 %, 5/28) admitted their pregnancy to others. Although most (16/28) offenders were in a relationship, the partner had knowledge of the pregnancy in only three cases. The main motive for negation of the pregnancy (named in 60.8 % of cases) was fear of abandonment/negative response from others. The fertility rate among the women was high, but half of those with children had lost the custody of them. In neonaticide, the lack of awareness surrounding offenders' pregnancy, as well as the awareness of social environment, is more relevant than any other social variable.     

Down's syndrome and maternal cancer. A preliminary study

The possible association between maternal cancer and Down's syndrome was studied in a register-based case-control study of 962 women who had an infant with Down's syndrome born during 1973-1981, and to each two controls, matched for maternal age, parity, and year of delivery. A total of 952 complete triplets was obtained. Among them, 63 Down's syndrome mothers and 79 control mothers were found in a cancer registry for the period 1958-1982 (odds ratio 1.6;95% conf. interval 1.3-2.0). Of these, 14 Down's syndrome mothers and 20 controls had malignant lesions (odds ratio 1.4, 0.9-2.2), and 49 Down's syndrome mothers and 55 controls had cervical cancer in situ (odds ratio 1.8, 1.4-2.3). This risk increase was present both before and after the delivery of the Down's syndrome infant. Various explanations of these findings are discussed and the need for further data is stressed.     

The birth rate of hypospadias in the Turku area in Finland

Reports based on national registers of congenital malformations have suggested that the birth rate of hypospadias has increased during the last few decades. Register-based information may, however, have pitfalls because of changes in diagnostics, reporting accuracy and registration system. The aim of this study was to determine the current birth rate of hypospadias in Turku University Central Hospital (TUCH) in Finland. This was a prospective study on live-born boys born in TUCH from 1997 to 1999. In the total birth cohort (n=5,798) as well as in a special subcohort group (n=1,505) 0.3% of boys had hypospadias. Only one scrotal hypospadias was found in a boy who had a chromosomal anomaly. Other hypospadias were glandular or coronal. No increase was found in the birth rate of hypospadias when comparing our result with register-based data of boys born in Finland during the years 1970 to 1986 and surgically treated for hypospadias by the age of 8 years. No difference was found either from malformation register-based data concerning the nationwide birth rate of hypospadias during the years 1993 to 1998. Due to differences in national registration systems between countries, prospective studies with equal assessment criteria are needed in order to make reliable international comparisons.     

Neonaticides may be more preventable and heterogeneous than previously thought – neonaticides in Finland 1980–2000

Summary Neonaticide is a sad and infrequent crime with possibly a high level of underreporting. The aim of this study was to examine the circumstances of neonaticide, and whether there are subtypes of offenders, or suggestions for prevention. The study was retrospective and register-based using comprehensive nation-wide material of all cases of suspected neonaticide during 1980–2000 in Finland. Out of the 50 suspected cases, 32 women were included in the final analyses as neonaticide offenders. Most women (91%) had concealed their pregnancy, which was not the first for 66%. Most (66%) were not quite sure why they had offended, and the most frequent (63%) method of operation was neglect. Four women were diagnosed psychotic and formed a specific group. We concluded that there might be specific subgroups of offenders – even though our small population limited conclusions. Furthermore, prevention might be heightened. We call for international joint projects for enlarged material to enable grouping, as well as education and discussion among the public and the professionals to prevent neonaticide, unify its jurisprudence and improve the treatment of the offenders.     

Is the risk of bipolar disorder in twins equal to the risk in singletons? A nationwide register-based study

BACKGROUND: A previous study demonstrated a higher rate of schizophrenia in dizygotic twins than in the general population, and a higher rate of schizophrenia in siblings of dizygotic twins than in siblings of monozygotic twins and singletons, pointing to a common genetic predisposition for dizygotic twinning and schizophrenia. The aim of the present study was to investigate whether these findings also apply to bipolar disorder. METHODS: Through record linkage between The Danish Twin Register, The Danish Psychiatric Central Register and The Danish Civil Registration System, the rate of bipolar disorder (diagnosed for the first time during admission to hospital) in dizygotic and monozygotic twins was compared with the rate in singletons, and the rate in siblings and parents of twins was compared with the rate in siblings and parents of singletons. RESULTS: The rate of bipolar disorder was the same in dizygotic twins, monozygotic twins and singletons as well as for parents and siblings of dizygotic twins, monozygotic twins and singletons. LIMITATIONS: The study is a register-based study, only including hospitalized patients. CONCLUSION: This study shows that there is an equal rate of bipolar disorder in twins and in singletons. Assuming that DZ twinning is under some genetic influence, a differential relationship between schizophrenia and DZ twinning on one hand and bipolar disorder and DZ twinning on the other hand may suggest differences in the genetic basis of the two diseases. The finding that the rate of bipolar disorder in monozygotic twins is the same as the rate of bipolar disorder in singletons supports studies finding no association between bipolar disorder and obstetric complications.     

Immediate adverse events after second trimester medical termination of pregnancy: results of a nationwide registry study

BACKGROUND Increasing gestational age is associated with an increased risk of complications in studies assessing surgical termination of pregnancy (TOP). Medical TOP is widely used during the second trimester and little is known about the frequency of complications. This epidemiological study was undertaken to assess the frequency of adverse events following the second trimester medical TOP and to compare it with that after first trimester medical TOP. METHODS This register-based cohort study covered 18 248 women who underwent medical TOP in Finland between 1 January 2003 and 31 December 2006. The women were identified from the Abortion Registry. Adverse events related to medical TOP within 6 weeks were obtained from the Hospital Discharge Registry. RESULTS When compared with first trimester medical TOP, second trimester medical TOP increased the risk of surgical evacuation [Adj. odds ratio (OR) 7.8; 95% confidence interval (CI) 6.8-8.9], especially immediately after fetal expulsion (Adj. OR 15.2; 95% CI 12.8-18.0). The risk of infection was also elevated (Adj. OR 2.1; 95% CI 1.5-2.9). Within the second trimester, increased length of gestation did not influence the risk of surgical evacuation or infection after medical TOP. CONCLUSIONS Medical TOP during the second trimester is generally safe. Surgical evacuation of the uterus is avoided in about two-thirds of cases, though it is much more common than after first trimester medical TOP. The risks of surgical evacuation and infection do not increase with gestational weeks in the second trimester TOP.     

Rheumatic heart disease: A review of the current status of global research activity

Rheumatic heart disease (RHD) is a serious and long-term consequence of acute rheumatic fever (ARF), an autoimmune sequela of a mucosal infection by Streptococcus pyogenes (Group A Streptococcus, Strep A). The pathogenesis of ARF and RHD is complex and not fully understood but involves host and bacterial factors, molecular mimicry, and aberrant host innate and adaptive immune responses that result in loss of self-tolerance and subsequent cross-reactivity with host tissues. RHD is entirely preventable yet claims an estimated 320 000 lives annually. The major burden of disease is carried by developing nations and Indigenous populations within developed nations, including Australia. This review will focus on the epidemiology, pathogenesis and treatment of ARF and RHD in Australia, where: streptococcal pyoderma, rather than streptococcal pharyngitis, and Group C and Group G Streptococcus, have been implicated as antecedents to ARF; the rates of RHD in remote Indigenous communities are persistently among the highest in the world; government register-based programs coordinate disease screening and delivery of prophylaxis with variable success; and researchers are making significant progress in the development of a broad-spectrum vaccine against Strep A.     

The provision of information and informed decision-making on prenatal screening for Down syndrome: a questionnaire- and register-based survey in a non-selected population

Objective

Evaluating the information provision procedure about prenatal screening for Down syndrome, using informed decision-making as a quality-indicator.

Methods

Questionnaire- and register-based surveys. Midwives associated with 59 midwifery practices completed process data for 6435 pregnancies. Pregnant women (n = 510) completed questionnaires on informed decision-making.

Results

Midwives offered information to 98.5% of women; 62.6% of them wished to receive information, of these, 81.9% actually received information. Decision-relevant knowledge was adequate in 89.0% of responding women. Knowledge about Down syndrome was less adequate than knowledge about the screening program. Participants in the screening program had higher knowledge scores on Down syndrome and on the screening program than non-participants. Of the women who intended to participate (35.8%), 3.1% had inadequate knowledge. A total of 75.5% of women made an informed decision; 94.3% of women participating in the screening program, and 64.9% of women not participating.

Conclusion

This quality assurance study showed high levels of informed decision-making and a relatively low participation rate in the national screening program for Down syndrome in the Netherlands. Knowledge of the Down syndrome condition needs to be improved.

Practice implications

This evaluation may serve as a pilot study for quality monitoring studies at a national level.     

Neuromotor, cognitive, language and behavioural outcome in children born following IVF or ICSI-a systematic review

BACKGROUND: The effect of in vitro fertilization (IVF) or intracytoplasmicsperm injection (ICSI) on the developing human brain is unclear.The objective of this study is to evaluate neurodevelopmental(ND) outcome of children born following these techniques. METHODS: This systematic review includes studies which compare a groupof children born following IVF/ICSI to children born after naturalconception by assessing outcome in terms of neuromotor development,cognition, speech/language and behaviour. Specific attentionis paid to the studies’ methodological quality based onstudy design, attrition, blinding of the assessor, validityof ND tests used, confounders included and group size or poweranalysis. RESULTS: Twenty-three out of 59 studies had a good methodological qualityincluding 9 register-based (RB) and 14 controlled studies. RBstudies suggested that IVF/ICSI per se does not increase therisk for severe cognitive impairment (i.e. mental retardation)or neuromotor handicaps such as cerebral palsy (CP), the associationof IVF/ICSI and CP being brought about by the association ofassisted conception with risk factors, like preterm birth. Ingeneral, controlled studies of good quality did not report anexcess of ND disorders in IVF/ICSI-children. However, the majorityof studies followed the children during infancy only, therebyprecluding pertinent conclusions on the risk of ND disordersthat come to the expression at older ages, such as fine manipulativedisability or dyslexia. CONCLUSIONS: A negative effect of assisted conception on the developing humanbrain is not identified; however, further research of high methodologicalquality in children beyond pre-school age is needed.     

A three generations nation-wide population study of family load estimates in bipolar disorder with different age at onset

Objectives

This nation-wide register-based study investigates how often bipolar disorder (BD) occurs in affected families compared to control families by estimating the family load as a random effect; this effect measures the degree of dependence among family members in relation to BD. Furthermore, the study addresses the impact of certain risk factors, namely, sex, age at onset of BD, degree of urbanization, year of birth, month of birth, and maternal and paternal age at birth.

Method

A total of N=1204 children and adolescent psychiatric cases born between 1950 and 1997 and registered in the Danish Central Psychiatric Register (DPCR) developed BD before the age of 58 years. N=3553 controls without any psychiatric diagnosis were matched for age, gender, and region of residence. Psychiatric diagnoses were also obtained on the relatives, e.g. parents, siblings, and offspring as a part of the Danish Three Generation Study (3GS). A family component was obtained by using different regression models.

Results

Familial factors accounted for 20% of the variation in disease outcome when controlling for year and month of birth, sex, and degree of urbanization. Only female sex was associated with an increased hazard ratio of BD. Also having a mother, father or a sibling with the disorder was proven to be a significant risk factor. Furthermore, case relatives did not develop BD earlier than control relatives.

Conclusion

These findings based on a very large and representative dataset provide further and very solid evidence for the high family aggregation of BD.     

Schizophrenia in the genetic isolate of Finland

We compared the features of schizophrenia in the homogeneous population of Finland (population about 5,000,000) and in an internal isolate in northeastern Finland inhabited in the 1680s by a small group of founders (current population about 18,000) in a register-based epidemiological study. We identified all cases with a diagnosis of schizophrenia in Finland born between 1940–1969 using three national computerized registers and found a total of 267 schizophrenia patients in the internal isolate and 29,124 in Finland. The lifetime prevalence was 2.21% in the internal isolate and 1.21% in Finland, respectively. The age-corrected lifetime risk was 3.2% in the internal isolate and 1.1% in the whole country. The risk of schizophrenia to siblings in the internal isolate was 6.4% (95% confidence interval 0.052, 0.078), 9.1% (95% CI 0.062, 0.130), and 6.8% (95% CI 0.028, 0.135) given 1, 2, or 3 affected siblings, and for all Finland 4.2% (95% CI 0.036, 0.043), 6.4% (95% CI 0.058, 0.071), and 8.7% (95% CI 0.068, 0.107) given 1, 2, or 3, affected siblings, respectively. The mean number of children in schizophrenia families and thus the number of families having at least two affected individuals were clearly higher in the isolate (24.9% vs 9.2%). We did not find any other epidemiological features differing between these two regions. It seems that the family material collected from the internal isolate is a representative subsample from the entire country and hopefully it enables easier identification of at least some predisposing genes for schizophrenia due to its unique population structure. Am. J. Med. Genet. 74:353–360, 1997. © 1997 Wiley-Liss, Inc.     

Risk of infectious diseases among first-degree relatives of transplant recipients who develop CMV infection: is the infectious phenotype inheritable?

Transplant recipients are at high risk of cytomegalovirus (CMV) infection. Mechanisms explaining the variation in risk of infections are far from fully elucidated. We hypothesised that host genetics explains part of the variation in risk of infection and examined if relatives of recipients with CMV infection have higher rates of severe infections compared to relatives of recipients without this infectious phenotype. In a register-based study, we included first-degree relatives of transplant recipients and examined the risk of hospitalisation due to overall infection or viral infection and risk of death among relatives of recipients who developed CMV infection within the first year of transplantation compared to relatives of recipients without CMV. Analyses were adjusted for sex, age and calendar year. We included 4470 relatives who were followed for 103,786 person-years, median follow-up 24 years [interquartile range (IQR) 12–36]. There were a total of 1360 infection-related hospitalisations in the follow-up period, incidence rate (IR) 13.1/1000 person-years [95% confidence interval (CI), 12.4; 13.8]. 206 relatives were hospitalised with viral infection, IR 1.8/1000 person-years (95% CI, 1.6; 2.0). There was no increased risk of hospitalisation due to infections, IR ratio (IRR) 0.99 (95% CI, 0.88; 1.12), nor specifically viral infections, IRR 0.87 (95% CI, 0.63; 1.19), in relatives of recipients with CMV compared to relatives of recipients without CMV. Also, no difference was seen in analyses stratified by transplant type, family relation and CMV serostatus. The risk of hospitalisation due to infection is not increased among first-degree relatives of transplant recipients with CMV infection compared to relatives of recipients without CMV.     

On the etiology of anal squamous carcinoma

The thesis is based on 13 publications in English and a review of the literature. The underlying work was done with the overall aim to describe incidence patterns for anal squamous carcinoma (anal SC) and to contribute new insight into the causes of this neoplasm. The work, supported by the Danish Cancer Society, was carried out in the period 1991-2000 while I was employed at 1) the Danish Cancer Registry, 2) Statens Serum Institute, Department of Epidemiology Research, and 3) the National Cancer Institute, Viral Epidemiology Branch, Maryland. Study designs employed include a ) population-based incidence studies in Denmark and the United States, b) register-based case-control studies and cohort studies for the scrutiny of multiple cancer patterns among patients with anal SC and for the study of anal SC risk among individuals with certain non-malignant diseases of the anal region as well as among persons with the acquired immuno-deficiency syndrome (AIDS), c) a nationwide interview-based case-control study of risk factors for anal SC and in Denmark and Sweden, and d) a combined molecular biological and histological analysis examining the association of human papillomavirus (HPV) status with histopathological and anatomical characteristics in anal SC tissues. The epidemiology of anal SC has changed remarkably during the second half of the 20th century. In Denmark, age-adjusted incidence rates per 100,000 person-years increased during the period 1943-1997 from around 0.2 among both men an women to 0.5 among men and 1.0 among women. Where systematically studied, incidence rates of anal SC have also been found to increase in a few other countries (Sweden and the United States). Register-based multiple cancer studies have shown an excess of previous and subsequent genital cancers of squamous histology among women with anal SC. This is likely to reflect common susceptibility toward infection with cancer-associated HPV types shared by all anogenital organs covered by squamous epithelium. A study based on data from the United States supports the possible role of anogenital SC-associated HPV types in the development of some tonsillar cancers. Observations in other register-based investigations and in the Danish-Swedish case-control study challenge the long held belief that benign anal lesions (e.g. hemorrhoids) and anal inflammation (e.g. in association with Crohn's disease) are linked to an increased risk of anal SC. The work documents strong links between a variety of sexual behavior measures and the risk of anal SC. The previously observed excess of anal SC among homosexual men is confirmed. Unlike in previous studies, an increased risk of anal SC associated with promiscuous heterosexual activity is also documented among both men and women. Measures of sexual extroversion, rather than sexual preference, are linked to the risk of anal SC presumably by means of higher rates of anal HPV infection in people with such behaviors. A new hypothesis is proposed to explain how smoking, the only consistently observed non-sexual risk factor in previous studies, might be associated with anal SC risk. A study of the short-term cancer profile among 309.365 AIDS patients in the United States provided no evidence to support immunosuppression as a major risk factor for anal SC in the first two years after the AIDS diagnosis. With the introduction around 1996 of highly active anti-retroviral therapy regimens, however, the future may hold a para-doxical increase in the incidence of anal SC along with the increased life expectancy in this population. Examination of tumor tissues from patients in Denmark and Sweden by the polymerase chain reaction techique showed a high proportion of anal SCs to be positive for types of HPV that are associated with high risk of cervical cancer (90%, 100%, and 58% among women, homosexual men, and heterosexual men, respectively). Tumor tissues from control subjects with adenocarcinoma of the rectum were consistently HPV-negative. A combined molecular biological and histological analysis showed that anal SCs with likely origin in the anal canal are 7.5 times more likely to be HPV-positive than anal SCs with likely origin in the perianal skin. Additionally, cancer of the anal canal are more likely than those of the perianal skin to be characterized histologically by small or medium-sized tumor cells, basaloid features, and little or no keratinization. Epidemiological studies from the past two decades have contributed imprtantly to our current understanding of anal SC and its causes. Most cases of this neoplasm can now be considered as a consequence of sexually or otherwise acquired infection in the anal mucosa with types of HPV already known to be involved in cancers of the uterine cervix. Expectedly, the upward trend in the incidence of anal SC seen over the past half century will continue in many years to come. However, there is currently widespread, yet cautious, optimism regarding the prospects for a prophylactic HPV vaccine. It this optimism is justified, the future may bring drastic reductions in the incidence of HPV-associated morbidities, including SC.     

The effect of migration on the incidence and mortality of bloodstream infection: a Danish register-based cohort study

ObjectivesTo investigate bloodstream infection (BSI) related to migrant status by comparing the incidence and mortality in migrants with that in non-migrants.MethodsIn this register-based cohort study we linked a cohort of migrants and non-migrants with a bacteraemia database covering two regions in Denmark. We included first-time BSI between January 2000 and December 2015 in individuals ≥18 years. Migrants were categorized according to status: refugees or family-reunified migrants. Incidence rate ratio and mortality rate ratio were analysed using Poisson regression.ResultsWe identified 493 080 non-migrants, of which 3405 had BSI, and 80 740 migrants with 576 cases; of the latter, 40 222 were family-reunified migrants with 226 cases and 40 518 were refugees with 350 cases. Refugees had a higher risk of BSI than non-migrants (adjusted IRR 1.19, 95%CI 1.01–1.40). Family-reunified migrants and refugees had a higher risk of Gram-negative BSIs (adjusted IRR 1.23, 95%CI 1.00–1.51 and 1.57, 95%CI 1.32–1.86), respectively, and a lower risk of Gram-positive BSIs (adjusted IRR 0.65, 95%CI 0.51–0.83 and 0.77, 95%CI 0.63–0.95), respectively, compared to non-migrants. Originating from Southeast Asia and the Pacific was associated with an increased risk of BSI compared to non-migrants (adjusted IRR 1.26, 95%CI 1.07–1.49). We found no differences in the adjusted 30-day or 90-day mortality according to migrant status.ConclusionsVulnerability towards BSI differs according to migrant status. Refugees had a higher risk of BSI overall. Both refugees and family-reunified migrants had a higher incidence of Gram-negative BSI than non-migrants. Similarly, migrants from Southeast Asia and the Pacific had a higher risk of BSI than non-migrants.     

Trends in rates of natural conceptions among Danish women born during 1960-1984

STUDY QUESTION The aim of the study was to analyse trends in the rate of natural conceptions (RNC) among birth cohorts of women born during the period 1960-1984. SUMMARY ANSWER In this nationwide study of Danish-born female cohorts born during the period 1960-1984, we found a gradual decline in the RNC with successive birth cohorts. WHAT IS KNOWN ALREADY Our results confirm the findings from a previous study on trends in RNC among native Danish women. STUDY DESIGN, SIZE, DURATION This is a register-based cohort study. Our data set included 803 435 native Danish women born in 1960-1984, of whom 68.2% had conceived at least one child as of 1 January 2008, by which time the follow-up was terminated. PARTICIPANTS/MATERIALS, SETTING, METHODS Data from Danish national registers were linked at the individual level using unique personal numbers assigned at birth to each resident. We analysed the data for the cohorts of native Danish women born in 1960-1984 and resident in Denmark in 2008. For these cohorts, we estimated the RNC per woman, defined as the mean number of live births minus live births after assisted reproductive technology (ART) plus the mean number of induced abortions. Births, abortions and births after ART were partly projected for the younger cohorts who had not finished their reproductive years before 2008. In addition, we looked at trends in hormonal contraception use. MAIN RESULTS In the main projection scenario, the RNC gradually declined with successive cohorts from 2.39 among women born in 1960 to 2.15 among women born in 1984, with stable values of 2.15-2.16 projected in the youngest cohorts analysed, 1979-1984. The projected decline was a consequence of a decrease in induced abortion rates and an increase in the use of ART among the younger cohorts. Furthermore, we projected a cohort increase in the share of women without natural conceptions. LIMITATIONS, REASONS FOR CAUTION A considerable portion of the results was based on projections, which involve uncertainty, especially concerning the results for women born in 1980 and later. In addition, information on IUI could not be included, which led to underestimation of the frequency of births after ART treatment. WIDER IMPLICATIONS OF THE FINDINGS The results of our study contribute new insights to the research field of declining fertility rates in Europe and many other parts of the world. STUDY FUNDING/COMPETING INTERESTS This study was supported by grants from Kirsten and Freddy Johansens Foundation and the European Commission project 'Developmental effects of environment on reproductive health' (grant no. 212844). None of the funding sources had any involvement in the study.     

Societal costs of personality disorders: A cross-sectional multicenter study of treatment-seeking patients in mental health services in Norway

Objective

There is a relatively small body of research on the cost-of-illness of personality disorders (PDs). Most studies only include borderline PD. The aim of this study was to investigate mean societal costs, including its components, (direct) health service costs and (indirect) productivity loss, among treatment-seeking patients with the broad range of all PDs according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5).

Methods

Cross-sectional data from 911 patients diagnosed with at least 1 PD were retrieved from the quality register of the Norwegian Network for Personality Disorders—a collaboration of PD treatment units within specialist mental health services. The patients were referred in the time period 2017–2020. Estimation of costs was based on a bottom-up approach, using information from a structured interview covering the 6-month period before assessment, whereas unit costs were retrieved from public reports, public records, or public agencies. The human capital approach was used to calculate productivity loss. Diagnoses were determined by semi-structured diagnostic interviews (Structured Clinical Interview for DSM-5-PD [SCID-5-PD]).

Results

The mean societal costs were €20.260 during the 6-month period before specialized treatment. The largest cost component was productivity loss (65%), whereas health service costs constituted 35%. The main contributors to societal costs from the underlying health service cost components were inpatient treatment (20.5%) and individual outpatient treatment (10.5%).

Conclusion

Societal costs were substantial among treatment-seeking patients with the broad range of DSM-5 PDs, comparable to the societal costs of schizophrenia, and significantly higher than the societal costs of both depression and anxiety disorders. The cost estimates converged with recent, register-based cost-of-illness studies of different PDs but exceeded previous findings from other bottom-up studies. Furthermore, the results underscore the importance of implementing effective and specialized treatment for patients with a broad range of PDs, not only to alleviate individual suffering but also to reduce the level of societal costs. The emphasis on productivity loss as a main contributor to the overall societal costs is substantiated, hence underlining the relevance of interventions focusing on improving occupational functioning.