Disease exposure in infancy affects women's reproductive outcomes and offspring health in southern Sweden 1905-2000.

Ample evidence demonstrates that early-life adversity negatively affects morbidity and survival in late life. We show that disease exposure in infancy also has a continuous impact on reproduction and health across the female life course and even affects early-life health of the next generation. Using Swedish administrative data, obstetric records, and local infant mortality rates as a measure of disease exposure, we follow women's reproductive careers and offspring health 1905-2000, examining a comprehensive set of outcomes. Women exposed to disease in infancy give birth to a lower proportion of boys, consistent with notions that male fetuses are more vulnerable to adverse conditions and are more often miscarried. Sons of exposed mothers are also more likely to be born preterm and have higher birthweight suggesting in utero out-selection. Exposed women have a greater risk of miscarriage and of male stillbirth, but their overall likelihood of giving birth is not affected.

Very Early-Life Risk Factors for Developing Dementia: Evidence From Full Population Registers.

OBJECTIVES: Very early-life conditions are recognized as critical for healthy brain development. This study assesses early-life risk factors for developing dementia. In the absence of historical medical birth records, we leverage an alternative full population approach using demographic characteristics obtained from administrative data to derive proxy indicators for birth complications and unfavorable birth outcomes. We use proxy variables to investigate the impact of early-life risk factors on dementia risk. METHODS: We use administrative individual-level data for full cohorts born 1932-1950 in Sweden with multigenerational linkages. Records on hospitalization and mortality are used to identify dementia cases. We derive 3 birth risk factors based on demographic characteristics: advanced maternal age, narrow sibling spacing, and twin births, and apply survival analysis to evaluate long-term effects on dementia risk. We control for confounding using multiple indicators for socio-economic status (SES), including parental surnames, and by implementing a sibling design. As comparison exposure, we add low education from the 1970 Census. RESULTS: The presence of at least 1 birth risk factor increases dementia risk (HR = 1.059; 95% CI: 1.034, 1.085). The occurrence of twin births poses a particularly heightened risk (HR = 1.166; 95% CI: 1.084, 1.255). DISCUSSION: Improvements to the very early-life environment hold significant potential to mitigate dementia risk. A comparison to the influence of low education on dementia (the largest known modifiable risk factor) suggests that demographic birth characteristics are of relevant effect sizes. Our findings underscore the relevance of providing assistance for births experiencing complications and adverse health outcomes to reduce dementia cases.

Macroeconomic fluctuations and individual use of psychotropic medications: evidence from Swedish administrative data.

BACKGROUND: A growing literature finds that adult mental health worsens during economic downturns. Current insights on the relationship between macroeconomic fluctuations and psychotropic medication are based on self-reported information or aggregate measures on prescriptions. This study assesses the relationship between local macroeconomic conditions and individual use of psychotropic medication as reported in administrative registers. METHODS: We use local information on unemployment linked to individual-level longitudinal data on detailed psychotropic drug consumption from administrative registers, for individuals in working age (20-65) in Sweden 2006-13. Any psychotropic medication uptake and the related number of redeemed prescriptions are the primary outcomes. Mortality is considered a secondary outcome. RESULTS: Among young men (aged 20-44) and older women (aged 45-65), we find reduced use of psychotropic medication (2-4% compared to the mean) when the local labor market conditions deteriorate. The relationship is driven by reduced use of antidepressants. The same age-gender groups experience a significantly higher risk of mortality in bad times. CONCLUSIONS: This study shows that economic downturns may not only put strain on individuals' mental health but also on their access to psychopharmaceutic treatments.

Disease and fertility: Evidence from the 1918-19 influenza pandemic in Sweden.

What are the consequences of a severe health shock like an influenza pandemic on fertility? Using rich administrative data and a difference-in-differences approach, we evaluate fertility responses to the 1918-19 influenza pandemic in Sweden. We find evidence of a small baby boom following the end of the pandemic, but we show that this effect is second-order compared to a strong long-term negative fertility effect. Within this net fertility decline there are compositional effects: we observe a relative increase in births to married women and to better-off families. Several factors - including disruptions to the marriage market and income effects - contribute to the long-term fertility reduction. The results are consistent with studies that find a positive fertility response following natural disasters, but we show that this effect is short-lived.

Does Prolonged Education Causally Affect Dementia Risk When Adult Socioeconomic Status Is Not Altered? A Swedish Natural Experiment in 1.3 Million Individuals.

Intervening on modifiable risk factors to prevent dementia is of key importance, since progress-modifying treatments are not currently available. Education is inversely associated with dementia risk, but causality and mechanistic pathways remain unclear. We aimed to examine the causality of this relationship in Sweden using, as a natural experiment, data on a compulsory schooling reform that extended primary education by 1 year for 70% of the population between 1936 and 1949. The reform introduced substantial exogenous variation in education that was unrelated to pupils' characteristics. We followed 18 birth cohorts (n = 1,341,842) from 1985 to 2016 (up to ages 79-96 years) for a dementia diagnosis in the National Inpatient and Cause of Death registers and fitted Cox survival models with stratified baseline hazards at the school-district level, chronological age as the time scale, and cohort indicators. Analyses indicated very small or negligible causal effects of education on dementia risk (main hazard ratio = 1.01, 95% confidence interval: 0.98, 1.04). Multiple sensitivity checks considering only compliers, the pre-/post- design, differences in health-care-seeking behavior, and the impact of exposure misclassification left the results essentially unaltered. The reform had limited effects on further adult socioeconomic outcomes, such as income. Our findings suggest that without mediation through adult socioeconomic position, education cannot be uncritically considered a modifiable risk factor for dementia.

Debt and mental health: new insights about the relationship and the importance of the measure of mental health.

BACKGROUND: Empirical research suggests that household debt and payment difficulties are detrimental to mental health. Despite well-known measurement problems that may contaminate analyses using subjective self-reported health measures, our knowledge is very limited concerning the effect of payment difficulties on 'objective' measures of mental health. Moreover, few studies use longitudinal data to examine the relationship. This study combines rich survey data and longitudinal data from administrative registers on a representative sample of the Swedish population to examine the relationship between payment difficulties and subjective and objective measures of mental health. METHODS: We use data from a large survey of Swedish inhabitants (The Swedish Living Conditions Surveys) combined with data from administrative registers. We investigate both directions of the relationship between mental ill health and payment difficulties, controlling for previous mental health status and previous experiences of payment difficulties. We compare the association between payment difficulties and a self-reported measure of anxiety with the associations between payment difficulties and objective measures of mental ill health from a register of psychopharmaceutical drug consumption. RESULTS: Payment difficulties associate with subjectively reported mental ill health, but less to psychopharmaca use. For objective measures, we find stronger evidence of a link running from mental ill health to later payment difficulties. CONCLUSIONS: Self-reported and objective measures of mental problems may convey different messages regarding the impact of payment difficulties on mental health. Policy measures depend on whether the primary target group is individuals with severe mental problems or individuals with mild anxiety.

Globalization, democracy, and child health in developing countries.

Good health is crucial for human and economic development. In particular poor health in childhood is of utmost concern since it causes irreversible damage and has implications later in life. Recent research suggests globalization is a strong force affecting adult and child health outcomes. Yet, there is much unexplained variation with respect to the globalization effect on child health, in particular in low- and middle-income countries. One factor that could explain such variation across countries is the quality of democracy. Using panel data for 70 developing countries between 1970 and 2009 this paper disentangles the relationship between globalization, democracy, and child health. Specifically the paper examines how globalization and a country's democratic status and historical experience with democracy, respectively, affect infant mortality. In line with previous research, results suggest that globalization reduces infant mortality and that the level of democracy in a country generally improves child health outcomes. Additionally, democracy matters for the size of the globalization effect on child health. If for example Côte d'Ivoire had been a democracy in the 2000-2009 period, this effect would translate into 1200 fewer infant deaths in an average year compared to the situation without democracy. We also find that nutrition is the most important mediator in the relationship. To conclude, globalization and democracy together associate with better child health in developing countries.

The impact of the 1918 Spanish flu epidemic on economic performance in Sweden: an investigation into the consequences of an extraordinary mortality shock.

We study the impact of the 1918 influenza pandemic on short- and medium-term economic performance in Sweden. The pandemic was one of the severest and deadliest pandemics in human history, but it has hitherto received only scant attention in the economic literature--despite representing an unparalleled labour supply shock. In this paper, we exploit seemingly exogenous variation in incidence rates between Swedish regions to estimate the impact of the pandemic. The pandemic led to a significant increase in poorhouse rates. There is also evidence that capital returns were negatively affected by the pandemic. However, contrary to predictions, we find no discernible effect on earnings.

Effects of compulsory schooling on mortality: evidence from Sweden.

Theoretically, there are several reasons to expect education to have a positive effect on health. Empirical research suggests that education can be an important health determinant. However, it has not yet been established whether education and health are indeed causally related, and the effects found in previous studies may be partially attributable to methodological weaknesses. Moreover, existing evidence on the education-health relationship generally uses information of fairly recent schooling reforms, implying that health outcomes are observed only over a limited time period. This paper examines the effect of education on mortality using information on a national roll-out of a reform leading to one extra year of compulsory schooling in Sweden. In 1936, the national government made a seventh school year compulsory; however, the implementation was decided at the school district level, and the reform was implemented over 12 years. Taking advantage of the variation in the timing of the implementation across school districts, by using county-level proportions of reformed districts, census data and administrative mortality data, we find that the extra compulsory school year reduced mortality. In fact, the mortality reduction is discernible already before the age of 30 and then grows in magnitude until the age of 55-60.

Health. Happiness. Inequality.

At the beginning of June 2010, the conference 'Health. Happiness. Inequality. Modelling the Pathways between Income Inequality and Health' was held in Darmstadt, Germany. Invited speakers and presenters traveled from all over the world; and researchers from several different subdisciplines were represented at the conference. The common denominator of participants was an interest in how societal income inequality affects individual health and life satisfaction. New and fascinating research results were presented and participants engaged in many interesting discussions.

Income inequality and health: importance of a cross-country perspective.

This paper uses a unique dataset-containing information collected in 2006 on individuals aged 40-79 in 21 countries throughout the world to examine whether individual income, relative income in a reference group, and income inequality are related to health status across middle/low and high-income countries. The dependent variable is self-assessed health (SAH), and as a robustness check, activities of daily living (ADL) are considered. The focus is particularly on assumptions regarding an individual's reference group and on how the estimated relationships depend on the level of economic development. Correcting for national differences in health reporting behavior, individual absolute income is found to be positively related to individual health. Furthermore, in the high-income sample, there is strong evidence that average income within a peer-age group is negatively related to health, thus supporting the relative income hypothesis. In middle/low-income countries, it is instead average regional income that is negatively associated with health. Finally, there is evidence of a negative relationship between income inequality and individual health in high-income countries. Overall, the results suggest that there might be important differences in these relationships between high-income and middle/low-income countries.

A case of Cornelia de Lange syndrome from Sudan.

BACKGROUND: Brachmann de Lange syndrome (BDLS) is a multiple congenital anomaly syndrome characterized by a distinctive facial appearance, prenatal and postnatal growth deficiency, psychomotor delay, behavioral problems, and malformations of the upper extremities. CASE PRESENTATION: Here we present for the first time a case of BDLS from Sudan, a 7-month-old female infant, who was referred as a case of malnutrition. The patient was from a Sudanese western tribe. Clinical investigation showed that the child was a classical case of BDLS, but with some additional clinical findings not previously reported including crowded ribs and tied tongue. CONCLUSION: Reporting BDLS cases of different ethnic backgrounds could add nuances to the phenotypic description of the syndrome and be helpful in diagnosis.

Fusion of the SEC31L1 and ALK genes in an inflammatory myofibroblastic tumor.

Inflammatory myofibroblastic tumor (IMT) is a neoplasm composed of myofibroblastic spindle cells and infiltrating inflammatory cells. Cytogenetic analyses have revealed that a subgroup of IMT, in particular among children and young adults, harbors clonal chromosomal rearrangements involving chromosome band 2p23. Further, molecular genetic studies have shown that these rearrangements target the ALK gene, serving as the 3'-partner in fusion genes with various translocation partners. In the present study, we describe the finding of a novel SEC31L1/ALK fusion gene in an intraabdominal IMT of a young man. G-band analysis revealed a translocation t(2;4)(p23;q21) and subsequent fluorescence in situ hybridization with locus-specific probes strongly indicated disruption of the ALK locus on chromosome 2. Immunostaining with monoclonal mouse anti-human CD246 ALK Protein showed diffuse cytoplasmic positivity. Using reverse primers for the ALK-gene, we could, by 5'-RACE methodology, amplify a single 1.2 kb fragment. Sequence analysis showed that the fragment was a hybrid cDNA product in which nt 3012 of SEC31L1 (NM_016211), located in band 4q21, was fused in-frame to nt 4080 of ALK (NM_004304). RT-PCR with two sets of primer pairs specific for SEC31L1 and ALK amplified two transcripts, which at sequencing corresponded to two types of chimeric SEC31L1/ALK transcripts. In the long, type I, transcript nt 3012 of SEC31L1 (NM_016211) was fused in-frame to nt 4080 of ALK. In the short, type II, transcript nt 2670 of SEC31L1 was fused in-frame to nt 4080 of ALK. Genomic PCR and subsequent sequencing showed that the breakpoints were located in intron 23 of SEC31L1 and intron 20 of ALK.

MDS/AML-associated cytogenetic abnormalities in multiple myeloma and monoclonal gammopathy of undetermined significance: evidence for frequent de novo occurrence and multipotent stem cell involvement of del(20q).

Multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) are characterized cytogenetically by 14q32 rearrangements, -13/13q-, and various trisomies. Occasionally, karyotypic patterns characteristic of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) occur in MM, often signifying therapy-related (t)-MDS/t-AML. Comparison of cytogenetic features in all published MMs (n = 993) and t-MDS/t-AML post-MM (n = 117) revealed significant differences in complexity and ploidy levels and in most genomic changes. Thus, these features often can be used to distinguish between MM and t-MDS/t-AML. Rarely, myeloid-associated aberrations are detected in MM without any signs of MDS/AML. To characterize such abnormalities in MM/MGUS, we ascertained all 122 MM and 26 MGUS/smoldering MM (SMM) cases analyzed in our department. Sixty-six (54%) MMs and 8 (31%) MGUS/SMMs were karyotypically abnormal, of which 6 (9%) MMs and 3 (38%) MGUS/SMMs displayed myeloid abnormalities, that is, +8 (1 case) and 20q- (8 cases) as the sole anomalies, without any evidence of MDS/AML. One patient developed AML, whereas no MDS/AML occurred in the remaining 8 patients. In one MGUS with del(20q), fluorescence in situ hybridization analyses revealed its presence in CD34+CD38- (hematopoietic stem cells), CD34+CD38+ (progenitors), CD19+ (B cells), and CD15+ (myeloid cells). The present data indicate that 20q- occurs in 10% of karyotypically abnormal MM/MGUS cases and that it might arise at a multipotent progenitor/stem cell level.

High frequencies of chromosomal aberrations in multiple myeloma and monoclonal gammopathy of undetermined significance in direct chromosome preparation.

Although many cases of multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) are cytogenetically normal, interphase fluorescence in situ hybridization (FISH) analyses reveal aberrations in the majority of the cases. Most likely, non-neoplastic cells are more prone to divide in culture than neoplastic cells. Direct chromosome preparations (DCP) would be one way to circumvent this methodological problem. We have investigated 47 bone marrow samples from 39 patients by DCP. A median of 58 metaphases (range 9-158) was analysed per sample. Interphase FISH analyses using probes to detect IGH rearrangements, -13/13q-, +3, +7, and +11 were also performed. Abnormal karyotypes were detected in 15 (63%) of 24 MM and in 4 (50%) of eight MGUS/smouldering MM (SMM) cases that could be successfully cytogenetically analysed. Age, sex, or degree of bone marrow plasma cell (PC) infiltration did not influence the karyotypic patterns (P > 0.05). However, the frequencies of aberrant karyotypes varied in relation to the Colcemide concentrations used - 7% (30 ng/ml) versus 69% and 67% (100 and 200 ng/ml, respectively) (P = 0.01). Combining the G-banding and FISH results, abnormalities were detected in 29 of 31 (94%) MM and in six of eight (75%) MGUS/SMM patients. Thus, cytogenetic and FISH analyses after DCP using 100-200 ng Colcemide/ml identified aberrations in most MM/MGUS/SMM, irrespective of PC percentages.

A pooled analysis of karyotypic patterns, breakpoints and imbalances in 783 cytogenetically abnormal multiple myelomas reveals frequently involved chromosome segments as well as significant age- and sex-related differences.

The cytogenetic features (ploidy, complexity, breakpoints, imbalances) were ascertained in 783 abnormal multiple myeloma (MM) cases to identify frequently involved chromosomal regions as well as a possible impact of age/sex. The series included MM patients from the Mitelman Database of Chromosome Aberrations in Cancer and from our own laboratory. Hyperdiploidy was most common, followed by hypodiploidy, pseudodiploidy and tri-/tetraploidy. Most cases were complex, with a median of eight changes per patient. The distribution of modal numbers differed between younger and older patients, but was not related to sex. No sex- or age-related differences regarding the number of anomalies were found. The most frequent genomic breakpoints were 14q32, 11q13, 1q10, 8q24, 1p11, 1q21, 22q11, 1p13, 1q11, 19q13, 1p22, 6q21 and 17p11. Breaks in 1p13, 6q21 and 11q13 were more common in the younger age group. The most frequent imbalances were + 9, - 13, + 15, + 19, + 11 and - Y. Trisomy 11 and monosomy 16 were more common among men, while -X was more frequent among women. Loss of Y as the sole change and + 5 were more common in elderly patients, and - 14 was more frequent in the younger age group. The present findings strongly suggest that some karyotypic features of MM are influenced by endogenous and/or exogenous factors.