Delayed age at transfer of adoptees to adoptive parents is associated with increased mortality irrespective of social class of the adoptive parents:a cohort study

Abstract Background Adverse early life experience and development may have long-term health consequences, but later environmental conditions may perhaps protect against the effects of such early life adversities. The aim was to investigate whether cause-specific and overall mortality rates among adoptees are associated with the age at which they were transferred to the adoptive family and whether the social class of the adoptive family modifies this association. Methods A cohort of 10,592 non-familial adoptions (biologically unrelated adoptee and adoptive parents) of Danish-born children formally granted in 1924–47 and with follow-up of total and cause-specific mortality through ages up to 85 years. The rates of death after the age of 16 from all causes combined, all natural causes, all external causes, and suicide were compared according to the age at which adoptees were transferred to their adoptive family by estimating hazard ratios in Cox regression models. Results Death rates from all causes were significantly higher in adoptees transferred between age 1 month and 4 years compared to those transferred immediately after birth with the hazard ratio peaking at 1.19 (95% confidence limit: 1.08 to 1.32) for adoptees transferred between 6 and 11 months. This result was primarily driven by a similar pattern for natural causes of death. For death from external causes and for suicide the hazard ratios were increasing with increasing age at transfer, and tests for trend were statistically significant. The social class of the adoptive family did not significantly modify these associations. Conclusions Transfer to an adoptive family later than at the time of birth may have adverse long-term consequences affecting overall and cause-specific mortality. These effects were not modified by the environment provided by the adoptive family as indicated by the social class of these families

Stability of the associations between early life risk indicators and adolescent overweight over the evolving obesity epidemic.

BACKGROUND: Pre- and perinatal factors and preschool body size may help identify children developing overweight, but these factors might have changed during the development of the obesity epidemic. OBJECTIVE: We aimed to assess the associations between early life risk indicators and overweight at the age of 9 and 15 years at different stages of the obesity epidemic. METHODS: We used two population-based Northern Finland Birth Cohorts including 4111 children born in 1966 (NFBC1966) and 5414 children born in 1985-1986 (NFBC1986). In both cohorts, we used the same a priori defined prenatal factors, maternal body mass index (BMI), birth weight, infant weight (age 5 months and 1 year), and preschool BMI (age 2-5 years). We used internal references in early childhood to define percentiles of body size (90) and generalized linear models to study the association with overweight, according to the International Obesity Taskforce (IOTF) definitions, at the ages of 9 and 15 years. RESULTS: The prevalence of overweight at the age of 15 was 9% for children born in 1966 and 16% for children born in 1986. However, medians of infant weight and preschool BMI changed little between the cohorts, and we found similar associations between maternal BMI, infant weight, preschool BMI, and later overweight in the two cohorts. At 5 years, children above the 90th percentile had approximately a 12 times higher risk of being overweight at the age of 15 years compared to children below the 50th percentile in both cohorts. CONCLUSIONS: The associations between early body size and adolescent overweight showed remarkable stability, despite the increase in prevalence of overweight over the 20 years between the cohorts. Using consequently defined internal percentiles may be a valuable tool in clinical practice

Preschool weight and body mass index in relation to central obesity and metabolic syndrome in adulthood.

BACKGROUND: If preschool measures of body size routinely collected at preventive health examinations are associated with adult central obesity and metabolic syndrome, a focused use of these data for the identification of high risk children is possible. The aim of this study was to test the associations between preschool weight and body mass index (BMI) and adult BMI, central obesity and metabolic alterations. METHODS: The Northern Finland Birth Cohort 1966 (NFBC1966) (N = 4111) is a population-based cohort. Preschool weight (age 5 months and 1 year) and BMI (age 2-5 years) were studied in relation to metabolic syndrome as well as BMI, waist circumference, lipoproteins, blood pressure, and fasting glucose at the age of 31 years. Linear regression models and generalized linear regression models with log link were used. RESULTS: Throughout preschool ages, weight and BMI were significantly linearly associated with adult BMI and waist circumference. Preschool BMI was inversely associated with high-density lipoprotein levels from the age of 3 years. Compared with children in the lower half of the BMI range, the group of children with the 5% highest BMI at the age of 5 years had a relative risk of adult obesity of 6.2(95% CI:4.2-9.3), of adult central obesity of 2.4(95% CI:2.0-2.9), and of early onset adult metabolic syndrome of 2.5(95% CI:1.7-3.8). CONCLUSIONS: High preschool BMI is consistently associated with adult obesity, central obesity and early onset metabolic syndrome. Routinely collected measures of body size in preschool ages can help to identify children in need of focused prevention due to their increased risk of adverse metabolic alterations in adulthood

Excess Mortality Rate During Adulthood Among Danish Adoptees

BACKGROUND AND OBJECTIVE: Adoption studies have been used to disentangle the influence of genes from shared familial environment on various traits and disease risks. However, both the factors leading to adoption and living as an adoptee may bias the studies with regard to the relative influence of genes and environment compared to the general population. The aim was to investigate whether the cohort of domestic adoptees used for these studies in Denmark is similar to the general population with respect to all-cause mortality and cause-specific mortality rates. METHODS: 13,111 adoptees born in Denmark in 1917, or later, and adopted in 1924 to 1947 were compared to all Danes from the same birth cohorts using standardized mortality ratios (SMR). The 12,729 adoptees alive in 1970 were similarly compared to all Danes using SMR as well as cause-specific SMR. RESULTS: The excess in all-cause mortality before age 65 years in adoptees was estimated to be 1.30 (95% CI 1.26-1.35). Significant excess mortality before age 65 years was also observed for infections, vascular deaths, cancer, alcohol-related deaths and suicide. Analyses including deaths after age 65 generally showed slightly less excess in mortality, but the excess was significant for all-cause mortality, cancer, alcohol-related deaths and suicides. CONCLUSION: Adoptees have an increased all-cause mortality compared to the general population. All major specific causes of death contributed, and the highest excess is seen for alcohol-related deaths

The incidence of eating disorders in a Danish register study: Associations with suicide risk and mortality

Our aim was to characterize the incidence rates and cumulative incidence of anorexia nervosa (AN), bulimia nervosa (BN), and eating disorder not otherwise specified (EDNOS), and examine associations among eating disorder diagnoses, suicide attempts, and mortality. Individuals born in Denmark between 1989 and 2006 were included (N=966,141, 51.3% male). Eating disorders diagnoses (AN, Broad AN, BN, EDNOS) were drawn from the Danish Psychiatric Central Research Register (PCRR) and Danish National Patient Register (NPR). Suicide attempts and deaths were captured in the NPR, the PCRR, and the Danish Civil Registration System (CRS). In females, AN had a peak hazard at approximately age 15 years, BN at 22 years, and EDNOS had an extended peak that spanned 18 years to 22 years. Eating disorder diagnoses predicted a significantly higher hazard for death and suicide attempt compared with the referent of individuals with no eating disorders. In males, peak hazard for diagnosis was earlier than in females. The present study represents one of the largest and longest studies of eating disorder incidence and suicide attempts and death in both females and males. Eating disorders are accompanied by increased hazard of suicide attempts and death even in young adults

Genetic liability to bipolar disorder and onset of postpartum mental disorders

Introduction Childbirth triggers a broad range of diagnoses jointly defined as postpartum mental disorders (PMDs),1 but immediate onset within the first 30 days after delivery has been linked to an increased probability of converting to bipolar disorder (BD) diagnoses later.2 Building on these specific observations, we hypothesised that PMDs occurring within the first month after delivery have a higher bipolar genetic liability, measured as polygenic score (PGS), compared with those diagnosed 31–365 days post partum, and further speculated this association is specific to the PGS for BD compared with genetic liability to other severe mental disorders, such as major depressive disorder (MDD) and schizophrenia (SCZ). Methods We conducted a cohort study linking Danish national registers to the Integrative Psychiatric Research (iPSYCH) study,3 which included 93 608 individuals diagnosed with a major mental illness and a random sample of 50 615 subjects from the entire Danish population born during 1981–2005 (the subcohort). DNA was extracted from the blood and genotyped. We identified 2974 women with genetic data who had PMD, defined as any hospital admission or outpatient contact for mental illness (International Classification of Diseases, 10th Revision (ICD-10) codes F00–F99, excluding F10–F19 and F70–F79) 0–12 months after delivery.4 We similarly defined previous psychiatric history as hospital contact for mental illness at any time before the delivery. DNA was extracted from the blood and genotyped. We derived LDpred2-auto5 PGS from the latest genome-wide association study (GWAS) by Psychiatric Genomics Consortium. We also calculated PGS using the iPSYCH individual data. We then combined the PGS obtained from summary statistics and individual-level data through a linear combination.6The sample size for the discovery GWAS without the iPSYCH sample can be found elsewhere.6 We converted PGSs into z-scores using PGS distributions in women from the subcohort born during 1981–1997. We used logistic regression to estimate the odds ratios (ORs) of PMD that occurred within 30 days vs 31–365 days after delivery by the BD PGSs in the form of both per SD increase (continuous variable) and tertiles and adjusted for all the covariates listed in table 1 and the first 10 principal components to account for population stratification.7 To show the degree of specificity for genetic liability to BD, we also calculated PGSs for MDD and SZ as negative controls, as we did not expect to find an association between these estimates and the specific early onset of PMD. Given PMD among women without a psychiatric history prior to childbirth may be a distinct psychiatric phenotype, we, for additional comparative purposes, examined the associations in women with and without previous psychiatric history separately. Since we specified the hypotheses a priori, no corrections for multiple comparisons are needed.

Genetic Influences on Incidence and Case-Fatality of Infectious Disease

BACKGROUND: Family, twin and adoption studies suggest that genetic susceptibility contributes to familial aggregation of infectious diseases or to death from infections. We estimated genetic and shared environmental influences separately on the risk of acquiring an infection (incidence) and on dying from it (case fatality). METHODS: Genetic influences were estimated by the association between rates of hospitalization for infections and between case-fatality rates of adoptees and their biological full- and half- siblings. Familial environmental influences were investigated in adoptees and their adoptive siblings. Among 14,425 non-familial adoptions, granted in Denmark during the period 1924-47, we selected 1,603 adoptees, who had been hospitalized for infections and/or died with infection between 1977 and 1993. Their siblings were considered predisposed to infection, and compared with non-predisposed siblings of randomly selected 1,348 adoptees alive in 1993 and not hospitalized for infections in the observation period. The risk ratios presented were based on a Cox regression model. RESULTS: Among 9971 identified siblings, 2829 had been hospitalised for infections. The risk of infectious disease was increased among predisposed compared with non-predisposed in both biological (1.18; 95% confidence limits 1.03-1.36) and adoptive siblings (1.23; 0.98-1.53). The risk of a fatal outcome of the infections was strongly increased (9.36; 2.94-29.8) in biological full siblings, but such associations were not observed for the biological half siblings or for the adoptive siblings. CONCLUSION: Risk of getting infections appears to be weakly influenced by both genetically determined susceptibility to infection and by family environment, whereas there appears to be a strong non-additive genetic influence on risk of fatal outcome

Polygenic risk scores, school achievement, and risk for schizophrenia: a Danish population-based study

Background: Studies have suggested that poor school achievement is associated with increased risk of schizophrenia; however, the possible genetic contribution to this association is unknown. We investigated the possible effect of the polygenic risk score (PRS) for schizophrenia (PRS) and for educational attainment (PRS) on the association between school performance and later schizophrenia. Methods: We conducted a case-cohort study on a Danish population-based sample born from 1987 to 1995 comprising 1470 individuals with schizophrenia and 7318 subcohort noncases. Genome-wide data, school performance, and family psychiatric and socioeconomic background information were obtained from national registers and neonatal biobanks. PRS and PRS were calculated using discovery effect size estimates from a meta-analysis of 34,600 cases and 45,968 controls and 293,723 individuals. Results: Higher PRS increased the risk (incidence rate ratio [IRR]: 1.28; 95% confidence interval [CI], 1.19–1.36), whereas higher PRS decreased the risk of schizophrenia (IRR, 0.87; 95% CI, 0.82–0.92) per standard deviation. Not completing primary school and receiving low school marks were associated with increased risk of schizophrenia (IRR, 2.92; 95% CI, 2.37–3.60; and IRR, 1.58; 95% CI, 1.27–1.97, respectively), which was not confounded by PRS or PRS. Adjusting for social factors and parental psychiatric history, effects of not completing primary school and receiving low school marks were attenuated by up to 25% (IRR, 2.19; 95% CI, 1.75–2.73; and IRR, 1.39; 95% CI, 1.11–1.75, respectively). Increasing PRS correlated with better school performance (p < .01; R = 7.6%). PRS and PRS was significantly negatively correlated (r = −.31, p < .01). Conclusions: The current PRS did not account for the observed association between primary school performance and risk of schizophrenia