Gestational age at birth and risk of intellectual disability without a common genetic cause.

Preterm birth is linked to intellectual disability and there is evidence to suggest post-term birth may also incur risk. However, these associations have not yet been investigated in the absence of common genetic causes of intellectual disability, where risk associated with late delivery may be preventable. We therefore aimed to examine risk of intellectual disability without a common genetic cause across the entire range of gestation, using a matched-sibling design to account for unmeasured confounding by shared familial factors. We conducted a population-based retrospective study using data from the Stockholm Youth Cohort (n = 499,621) and examined associations in a nested cohort of matched outcome-discordant siblings (n = 8034). Risk of intellectual disability was greatest among those born extremely early (adjusted OR24 weeks = 14.54 [95% CI 11.46-18.44]), lessening with advancing gestational age toward term (aOR32 weeks = 3.59 [3.22-4.01]; aOR37weeks = 1.50 [1.38-1.63]); aOR38 weeks = 1.26 [1.16-1.37]; aOR39 weeks = 1.10 [1.04-1.17]) and increasing with advancing gestational age post-term (aOR42 weeks = 1.16 [1.08-1.25]; aOR43 weeks = 1.41 [1.21-1.64]; aOR44 weeks = 1.71 [1.34-2.18]; aOR45 weeks = 2.07 [1.47-2.92]). Associations persisted in a cohort of matched siblings suggesting they were robust against confounding by shared familial traits. Risk of intellectual disability was greatest among children showing evidence of fetal growth restriction, especially when birth occurred before or after term. Birth at non-optimal gestational duration may be linked causally with greater risk of intellectual disability. The mechanisms underlying these associations need to be elucidated as they are relevant to clinical practice concerning elective delivery around term and mitigation of risk in post-term children.

Parental Mental Illness and the Likelihood of Child Out-of-Home Care: A Cohort Study.

OBJECTIVES: To detail the relationship between parental mental illness and the likelihood of out-of-home care (OHC) among their children, and to identify factors which modify this relationship. METHODS: Using Swedish national registers, children born in 2000 to 2011 (n = 1 249 463) were linked to their parents. Time-dependent parental mental illness (nonaffective and affective psychosis, substance misuse, depression, anxiety and stress, eating disorders, personality disorders, attention deficit hyperactivity disorder, autism, and intellectual disability), was identified through International Classification of Diseases codes. RESULTS: After adjustment for socioeconomic factors, children living with mentally ill parents were 4 times as likely to be placed in OHC than children without (95% confidence interval [CI] 4.24-4.61). The highest hazard ratio (HR) was in the youngest children aged 0 to 1 year (5.77, 95% CI 5.42-6.14), exposed to maternal illness (HR 4.56, 95% CI 4.37-4.76), and parental intellectual disability (HR 4.73, 95% CI 4.09-5.46). Children with parental mental illness with multiple risk factors were at particularly high risk. Compared with children without parental mental illness, and those with university-educated parents, children whose parents had mental illness and only had education to age 16 had a 15 times higher risk of OHC (95% CI 13.75-16.54). CONCLUSIONS: Children with parental mental illness are considerably more likely to be removed from home into care during childhood, particularly during the first year of life and if they are from socially disadvantaged families. Greater knowledge of these risks should lead to increased support for vulnerable new families.

Prevention of Childhood Adversities and Children's Common Mental Disorders and School Grades.

Importance: Adversity during childhood can limit children's chances of achieving their optimal developmental and psychological outcomes. Well-designed observational studies might help identify adversities that are most implicated in this, thereby helping to identify potential targets for developing interventions. Objective: To compare the association between preventing childhood poverty, parental mental illness and parental separation, and the population rate of offspring common mental disorders (ages 16-21 years) or average school grades (age 16 years). Design, Setting, and Participants: A population-based, longitudinal cohort study using Swedish registries was conducted. A total of 163 529 children born in Sweden between January 1, 1996, and December 31, 1997, were followed up until their 21st birthday. They were linked to registries using Sweden's national personal identification number. Children were linked to birth parents, hospital records, and school data. Parents were linked to registries containing health, income, sociodemographic, and obstetric data. Analyses were conducted between January 10, 2021, and August 26, 2022. Exposures: Childhood adversities of relative poverty (household disposable income <50% of the median), parental inpatient admission for a mental illness, or parental separation. Adversities were categorized into developmental periods: ages 0 to 3, 4 to 7, 8 to 11, and 12 to 16 years. Main Outcomes and Measures: The main outcomes were children's hospital records with a diagnosis of anxiety or depression between ages 16 and 21 years and school grades at the end of compulsory education (age 16 years). The parametric g-formula modeled population changes in outcomes associated with the counterfactual, hypothetical preventing adversity exposures, accounting for fixed and time-varying confounders. Adjustments were made for parental demographic characteristics, obstetric variables, and socioeconomic data at birth. Results: A total of 163 529 children were included in the cohort (51.2% boys, 51.4% born in 1996). Preventing all adversities was associated with an estimated change in the prevalence of offspring common mental disorders from 10.2% to 7.6% and an improvement in school grades with an SD of 0.149 (95% CI, 0.147-0.149). Preventing parental separation provided for the greatest improvement, with an estimated 2.34% (95% CI, 2.23%-2.42%) fewer children with a common mental disorder and an improvement in school grades by 0.127 SDs (0.125-0.129). Greater improvements were shown by hypothetically targeting adolescents (age 12-16 years) and those whose parents had a mental illness when the child was born. Conclusions and Relevance: The results of this cohort modeling study suggest that preventing childhood adversity could provide notable improvements in the rates of common mental disorders and school grades. Many children might achieve better life outcomes if resources are properly allocated to the right adversities (parental separation), the right groups (children with parental mental illness), and at the right time (adolescence).

Prenatal stress and risk of asthma hospitalization in the offspring: a Swedish population-based study.

OBJECTIVE: Recent research suggested that maternal stress and anxiety increase the risk of asthma and eczema in the offspring. In this study, we aimed to study whether maternal exposure to death of a spouse or a child is associated with risk of asthma hospitalization in the offspring using a very large population-based cohort. METHODS: In a cohort of 3.2 million births in Sweden between January 1, 1973, and December 31, 2004, mothers were considered exposed if their spouse or child died up to 6 months before or during pregnancy. Offspring were followed up from birth to their death, migration, first hospitalization with asthma, or December 31, 2006, whichever came first; hospital admissions were identified by linkage of several national Swedish registers. Log-linear Poisson regression was used for data analysis. RESULTS: Overall, the risk of offspring asthma was increased with any prenatal exposure to bereavement in any exposure period (adjusted relative risk [RR] = 1.20 [95% confidence interval {CI} = 1.03-1.39]). The risk was higher when the exposure period was restricted to pregnancy only (adjusted RR = 1.43 [95% CI = 1.06-1.92]). Furthermore, the risk of asthma was increased in relation to death of a spouse during pregnancy (adjusted RR = 1.59 [95% CI = 1.10-2.30]). CONCLUSIONS: These findings suggest that prenatal exposure to severe life events increases the risk of hospitalization for asthma in the offspring. Fetal programming may be a plausible explanation for the association.

Association between parental mental illness and autoimmune diseases in the offspring - A nationwide register-based cohort study in Sweden.

Mental illness has been previously linked with autoimmune diseases, yet the associations between parental mental illness and offspring's risk of autoimmune diseases is largely unknown. We conducted a population-based cohort study of 2,192,490 Swedish children born between 1991 and 2011 and their parents to determine the associations between parental mental illness and risk of autoimmune diseases among the offspring. Time-dependent diagnoses of parental mental illness (psychosis, alcohol/drug misuse, depression, anxiety, eating disorders, personality disorders, attention deficit hyperactivity disorder, autism spectrum disorder) and offspring autoimmune diseases (type 1 diabetes (T1D), juvenile idiopathic arthritis (JIA), systemic lupus erythematosus, psoriasis, multiple sclerosis, inflammatory bowel disease (IBD), coeliac disease) were identified from inpatient/outpatient healthcare visits. Associations were measured by hazard ratios (HRs) adjusted for potential confounders. Overall, parental mental illness was associated with a small increase in risk of offspring's autoimmune diseases (HR 1.05, 95% CI 1.02-1.08). However, parental common mental disorder (anxiety/depression) was associated with higher risk of JIA, psoriasis, and T1D (HR T1D 1.11, 95% CI 1.01-1.22), while maternal psychosis with reduced risk of coeliac disease (HR 0.68, 95% CI 0.49-0.95) and paternal alcohol/drug misuse with reduced risk of IBD (HR 0.80, 95% CI 0.64-0.99). Maternal eating disorders were associated with a markedly increased risk for T1D (HR 1.41, 95% CI 1.05-1.89). Further studies are needed to confirm these findings and to understand underlying mechanisms. There is a need for greater clinical awareness about potential risk of JIA, psoriasis, and T1D among children of parents with common psychiatric morbidity.

Labour market position of young people and premature mortality in adult life: A 26-year follow-up of 569 528 Swedish 18 year-olds.

BACKGROUND: Throughout the industrialized world, demand for low skilled labour is falling. The length of schooling is increasing in response, but so is the proportion of individuals not finishing upper secondary school. The objective of this study was to evaluate the associations between labour market positions at age 18 and all-cause and suicide- and accident-specific mortality in later adulthood. METHODS: Labour market positions at age 18 were categorized for all Swedes born 1972-77 (n=630 959) into four main groups: employed, successful students, students not about to qualify (SNAQs), and individuals not in employment, education or training (NEETs). Cox proportional hazard models were fitted to assess all-cause, suicide and accident mortality up to 2016 (ages 39-44), adjusting for high school grades, parental and own prior psychiatric diagnoses, and childhood socioeconomic status. FINDINGS: SNAQs had substantially increased all-cause (men: HR=2.10; 95% CI 1.92-2.28, women: HR=1.64; 95% CI: 1.44-1.86), suicide (men: HR=2.16; CI: 1.86-2.51, women: HR=2.10; 95% CI 1.64-2.69), and accident specific (men: HR=2.08; 95% CI 1.77-2.44, women: 1.87; 95% CI 1.33;2.62) mortality risks compared to successful students. The risks were similar for NEETs. There was no increased risk among full-time employed compared to successful students. INTERPRETATION: Expanding the educational system may be a natural response to falling demand for low skilled labour but not by far one that corrects the major societal challenge of it. Unless educational systems adequately respond to this challenge, only more inequality is to be expected ahead. FUNDING: This work was supported by a grant to FR and AL from the Swedish Research Council for Health, Working Life, and Welfare with contract number (2014-2009).

Prevalence of parental mental illness and association with socioeconomic adversity among children in Sweden between 2006 and 2016: a population-based cohort study.

BACKGROUND: Children of parents with mental illness are a vulnerable group, but their numbers and their exposure to adversity have rarely been examined. We examined the prevalence of children with parents with mental illness in Sweden, trends in prevalence from 2006 to 2016, and these children's exposure to socioeconomic adversity. METHODS: We did a population-based cohort study among all children (aged <18 years) born in Sweden between Jan 1, 1991, and Dec 31, 2011, and their parents, followed up between Jan 1, 2006, and Dec 31, 2016. We included children who were identified in the Total Population Register and linked to their birth parents, excluding adopted children and those with missing information on both birth parents. We used a comprehensive register linkage, Psychiatry Sweden, to follow up for indicators of parental mental illness and socioeconomic adversity. Marginal predictions from a standard logistic regression model were used to estimate age-specific, 3-year period prevalence of parental mental illness and trends in prevalence for 2006-16. Using cross-sectional data on each child, indicators of socioeconomic adversity were compared between children with and without concurrent parental mental illness using logistic regression. FINDINGS: Of 2 198 289 children born in Sweden between Jan 1, 1991, and Dec 31, 2011, we analysed 2 110 988 children (96·03% of the total population). The overall prevalence of children with diagnosed parental mental illness between 2006 and 2016 was 9·53% (95% CI 9·50-9·57). This prevalence increased with age of the child, from 6·72% (6·65-6·78) of the youngest children (0 to <3 years) to 10·80% (10·73-10·89) in the oldest (15 to <18 years). The prevalence of diagnosed parental mental illness increased from 8·62% (8·54-8·69) in 2006-09 up to 10·95% (10·86-11·03) in 2013-16. Children with any type of parental mental illness had markedly higher risk of socioeconomic adversity, such as living in poorer households or living separately from their parents. INTERPRETATION: Currently, 11% of all Swedish children have a parent with a mental illness treated within secondary care. These children have markedly higher risk of broad socioeconomic adversity than do other children. There is a need to understand how socioeconomic adversity and parental mental illness influence vulnerability to poor life outcomes in these children. FUNDING: European Research Council, National Institute for Health Research, Region Stockholm, and the Swedish Research Council.

Association between maternal and paternal mental illness and risk of injuries in children and adolescents: nationwide register based cohort study in Sweden.

OBJECTIVE: To determine the association between parental mental illness and the risk of injuries among offspring. DESIGN: Retrospective cohort study. SETTING: Swedish population based registers. PARTICIPANTS: 1 542 000 children born in 1996-2011 linked to 893 334 mothers and 873 935 fathers. EXPOSURES: Maternal or paternal mental illness (non-affective psychosis, affective psychosis, alcohol or drug misuse, mood disorders, anxiety and stress related disorders, eating disorders, personality disorders) identified through linkage to inpatient or outpatient healthcare registers. MAIN OUTCOME MEASURES: Risk of injuries (transport injury, fall, burn, drowning and suffocation, poisoning, violence) at ages 0-1, 2-5, 6-9, 10-12, and 13-17 years, comparing children of parents with mental illness and children of parents without mental illness, calculated as the rate difference and rate ratio adjusted for confounders. RESULTS: Children with parental mental illness contributed to 201 670.5 person years of follow-up, while children without parental mental illness contributed to 2 434 161.5 person years. Children of parents with mental illness had higher rates of injuries than children of parents without mental illness (for any injury at age 0-1, these children had an additional 2088 injuries per 100 000 person years; number of injuries for children with and without parental mental illness was 10 235 and 72 723, respectively). At age 0-1, the rate differences ranged from 18 additional transport injuries to 1716 additional fall injuries per 100 000 person years among children with parental mental illness compared with children without parental mental illness. A higher adjusted rate ratio for injuries was observed from birth through adolescence and the risk was highest during the first year of life (adjusted rate ratio at age 0-1 for the overall association between any parental mental illness that has been recorded in the registers and injuries 1.30, 95% confidence interval 1.26 to 1.33). Adjusted rate ratios at age 0-1 ranged from 1.28 (1.24 to 1.32) for fall injuries to 3.54 (2.28 to 5.48) for violence related injuries. Common and serious maternal and paternal mental illness was associated with increased risk of injuries in children, and estimates were slightly higher for common mental disorders. CONCLUSIONS: Parental mental illness is associated with increased risk of injuries among offspring, particularly during the first years of the child's life. Efforts to increase access to parental support for parents with mental illness, and to recognise and treat perinatal mental morbidity in parents in secondary care might prevent child injury.

Association of Hydroxylmethyl Glutaryl Coenzyme A Reductase Inhibitors, L-Type Calcium Channel Antagonists, and Biguanides With Rates of Psychiatric Hospitalization and Self-Harm in Individuals With Serious Mental Illness.

Importance: Drug repurposing is potentially cost-effective, low risk, and necessary in psychiatric drug development. The availability of large, routine data sets provides the opportunity to evaluate the potential for currently used medication to benefit people with serious mental illness (SMI). Objective: To determine whether hydroxylmethyl glutaryl coenzyme A reductase inhibitors (HMG-CoA RIs), L-type calcium channel (LTCC) antagonists, and biguanides are associated with reduced psychiatric hospitalization and self-harm in individuals with SMI. Design, Setting, and Participants: These within-individual cohort studies of patients with SMI compared rates of psychiatric hospitalization and self-harm during periods of exposure and nonexposure to the study drugs, with adjusting for a number of time-varying covariates. Participants included 142 691 individuals from the entire population of Sweden with a diagnosis of bipolar disorder (BPD), schizophrenia, or nonaffective psychosis (NAP) who were 15 years or older and who were treated with psychiatric medication from October 1, 2005, through December 31, 2016. Data were analyzed from April 1 through August 31, 2018. Interventions: Treatment with HMG-CoA RIs, LTCC antagonists, or biguanides. Main Outcomes and Measures: Psychiatric hospitalizations and self-harm admissions. Results: Among the 142 691 eligible participants, the HMG-CoA RI exposure periods were associated with reduced rates of psychiatric hospitalization in BPD (adjusted hazard ratio [aHR], 0.86; 95% CI, 0.83-0.89; P < .001), schizophrenia (aHR, 0.75; 95% CI, 0.71-0.79; P < .001), and NAP (aHR, 0.80; 95% CI, 0.75-0.85; P < .001) and reduced self-harm rates in BPD (aHR, 0.76; 95% CI, 0.66-0.86; P < .001) and schizophrenia (aHR, 0.58; 95% CI, 0.45-0.74; P < .001). Exposure to LTCC antagonists was associated with reduced rates of psychiatric hospitalization and self-harm in subgroups with BPD (aHRs, 0.92 [95% CI, 0.88-0.96; P < .001] and 0.81 [95% CI, 0.68-0.95; P = .01], respectively), schizophrenia (aHRs, 0.80 [95% CI, 0.74-0.85; P < .001] and 0.30 [95% CI, 0.18-0.48; P < .001], respectively), and NAP (aHRs, 0.89 [95% CI, 0.83-0.96; P = .002] and 0.56 [95% CI, 0.42-0.74; P < .001], respectively). During biguanide exposure, psychiatric hospitalization rates were reduced in subgroups with BPD (aHR, 0.80; 95% CI, 0.77-0.84; P < .001), schizophrenia (aHR, 0.73; 95% CI, 0.69-0.77; P < .001), and NAP (aHR, 0.85; 95% CI, 0.79-0.92; P < .001), and self-harm was reduced in BPD (aHR, 0.73; 95% CI, 0.62-0.84; P < .001) and schizophrenia (aHR, 0.64; 95% CI, 0.48-0.85; P < .001). Conclusions and Relevance: This study provides additional evidence that exposure to HMG-CoA RIs, LTCC antagonists, and biguanides might lead to improved outcomes for individuals with SMI. Given the well-known adverse event profiles of these agents, they should be further investigated as repurposed agents for psychiatric symptoms.

Validation study of randomly selected cases of PTSD diagnoses identified in a Swedish regional database compared with medical records: is the validity sufficient for epidemiological research?

OBJECTIVES: In Sweden, the patients' diagnoses are recorded in administrative registers. The research value of these registers is determined by their diagnostic validity, that is, if the diagnosis recorded meets the relevant diagnostic criteria. The aim of the study was to assess the validity of post-traumatic stress disorder (PTSD)-diagnoses as compared with case notes in medical records (MRs) and to test if there was a difference in validity by gender, migration status and those with and without psychotic symptoms. We hypothesised that the validity would be sufficient, using both Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV and DSM-5 but higher according to DSM-IV than DSM-5, and that the validity would be the same for men and women, but different for Swedish-born and migrants, and for those with and without psychotic symptoms. DESIGN AND SETTING: A validation of the register-diagnoses using MRs from treatment centres within the Region of Stockholm to examine whether patients with a register-diagnosis of PTSD fulfilled DSM criteria of PTSD according to the case notes in their MRs. PARTICIPANTS: A random sample of 187 patients aged 18-64, who had been diagnosed with PTSD (F43.1 in the ICD-10) were drawn from the Region of Stockholm's MR database 2013-2015. PRIMARY OUTCOME MEASURE: Validity of the PTSD diagnoses according to DSM-IV and DSM-5 as proportions of true positives with 95% CI. RESULTS: The hypothesised sufficient validity of the PTSD diagnoses was confirmed. Although the point-estimates for DSM-IV were higher than for DSM-5, the hypothesis that there would be significant differences in validity between DSM-IV and DSM-5 was not confirmed. There were no significant validity differences by gender, migration status and for those with and without psychotic symptoms. CONCLUSIONS: This study has found that validity of the PTSD diagnoses in the register of the Region of Stockholm to be sufficient for epidemiological research.

Infections in the CNS during childhood and the risk of subsequent psychotic illness: a cohort study of more than one million Swedish subjects.

OBJECTIVE: Infections during early life have been suggested to play a role in the etiology of schizophrenia. Most studies have focused on fetal life; few have explored risk associated with infection during childhood. The results of these have been inconsistent. The present study aims to investigate whether there is an increased risk of schizophrenia and other nonaffective psychoses associated with viral or bacterial CNS infections during childhood and, if so, which specific agents are involved. METHOD: A national cohort consisting of 1.2 million children born between 1973 and 1985 was followed up by using Swedish national registers to retrieve data on hospital admissions for CNS infections at 0-12 years of age (bacterial: N=2,435, viral: N=6,550) as well as admissions for nonaffective psychotic illnesses from the 14th birthday (N=2,269). RESULTS: There was a slightly increased risk of nonaffective psychotic illness associated with viral CNS infections, as well as schizophrenia. There was no evidence of increased risk in relation to bacterial infections. When divided into specific agents, exposures to mumps virus or cytomegalovirus were associated with subsequent psychoses. CONCLUSIONS: Serious viral CNS infections during childhood appear to be associated with the later development of schizophrenia and nonaffective psychoses. The association with specific viruses suggests that the risk is related to infectious agents with a propensity to invade the brain parenchyma.

Thirty-year trends in dementia: a nationwide population study of Swedish inpatient records.

BACKGROUND: The continuous growth of the current dementia epidemic is contingent on the stability of age- and sex-specific trends over time. However, recent evidence suggests declining or stable trends. The aim of this study was to evaluate the real-world changes in the burden of dementia in older adults in Sweden from 1987 to 2016 by estimating age- and sex-specific incidence of dementia diagnosis in hospital inpatient records (dementia incidence). Differences in trends by sex, age, and educational levels were also examined. METHODS: The entire Swedish population aged 65 years and older was followed up from 1987 to 2016. Age-, sex-, and education-stratified dementia incidence rates for every follow-up year were estimated using the National Patient Register. Hazard ratio of receiving a dementia diagnosis in the inpatient records per 1 calendar year increase was estimated with discrete time logistic models with a complementary log-log link. RESULTS: After increase, especially in those >85 years of age, dementia incidence started to decrease in the last 5 years of the study period. After 2011, 1 calendar year increase was associated with lower hazard ratio of receiving a hospital diagnosis of dementia. The decrease had the highest magnitude in 70-74-year-olds (-5.5%), followed by 75-79-year-olds (-4.5%) and 80-84-year-olds (-4.0%). The decrease was present in both sexes and at all educational levels up to 90 years of age. Age was associated with the level of dementia incidence, and the trends differed by age group. Educational gradient was observed. University-educated older adults had the lowest rates of dementia. However, the trend over time did not substantially differ by sex or educational level. CONCLUSION: Our results provide more evidence that dementia incidence may be declining. They also suggest that at least in hospitals, the number of new patients with dementia may decrease in the future.

Perinatal Exposure to Traffic-Related Air Pollution and Autism Spectrum Disorders.

BACKGROUND: Studies from the United States indicate that exposure to air pollution in early life is associated with autism spectrum disorders (ASD) in children, but the evidence is not consistent with European data. OBJECTIVE: We aimed to investigate the association between exposure to air pollution from road traffic and the risk of ASD in children, with careful adjustment for socioeconomic and other confounders. METHOD: Children born and residing in Stockholm, Sweden, during 1993-2007 with an ASD diagnosis were identified through multiple health registers and classified as cases (n = 5,136). A randomly selected sample of 18,237 children from the same study base constituted controls. Levels of nitrogen oxides (NOx) and particulate matter with diameter ≤ 10 µm (PM10) from road traffic were estimated at residential addresses during mother's pregnancy and the child's first year of life by dispersion models. Odds ratios (OR) and 95% confidence intervals (CI) for ASD with or without intellectual disability (ID) were estimated using logistic regression models after conditioning on municipality and calendar year of birth as well as adjustment for potential confounders. RESULT: Air pollution exposure during the prenatal period was not associated with ASD overall (OR = 1.00; 95% CI: 0.86, 1.15 per 10-µg/m3 increase in PM10 and OR = 1.02; 95% CI: 0.94, 1.10 per 20-µg/m3 increase in NOx during mother's pregnancy). Similar results were seen for exposure during the first year of life, and for ASD in combination with ID. An inverse association between air pollution exposure and ASD risk was observed among children of mothers who moved to a new residence during pregnancy. CONCLUSION: Early-life exposure to low levels of NOx and PM10 from road traffic does not appear to increase the risk of ASD. Citation: Gong T, Dalman C, Wicks S, Dal H, Magnusson C, Lundholm C, Almqvist C, Pershagen G. 2017. Perinatal exposure to traffic-related air pollution and autism spectrum disorders. Environ Health Perspect 125:119-126; http://dx.doi.org/10.1289/EHP118.

Gestational age at birth and academic performance: population-based cohort study.

Background: Numerous studies suggest pre-term birth is associated with cognitive deficit. However, less is known about cognitive outcomes following post-term birth, or the influence of weight variations within term or post-term populations. We examined associations between gestational age (GA) and school performance, by weight-for-GA, focusing on extremely pre- and post-term births. Method: Record linkage study of Swedish children born 1973-94 ( n = 2 008 102) with a nested sibling comparison ( n = 439 629). We used restricted cubic regression splines to examine associations between GA and the grade achieved on leaving secondary education, comparing siblings to allow stronger causal inference with regard to associations between GA and school performance. Results: Grade averages of both pre- and post-term children were below those of full-term counterparts and lower for those born small-for-GA. The adjusted grades of extremely pre-term children (at 24 completed weeks), while improving in later study periods, were lower by 0.43 standard deviations (95% confidence interval 0.38-0.49), corresponding with a 21-point reduction (19 to 24) on a 240-point scale. Reductions for extremely post-term children (at 45 completed weeks) were lesser [-0.15 standard deviation (-0.17 to -0.13) or -8 points (-9 to -7)]. Among matched siblings, we observed weaker residual effects of pre-term and post-term GA on school performance. Conclusions: There may be independent effects of fetal maturation and fetal growth on school performance. Associations among matched siblings, although attenuated, remained consistent with causal effects of pre- and post-term birth on school performance.

Schizophrenia-risk and urban birth are associated with proteomic changes in neonatal dried blood spots.

In the present study, we tested whether there were proteomic differences in blood between schizophrenia patients after the initial onset of the disorder and controls; and whether those differences were also present at birth among neonates who later developed schizophrenia compared to those without a psychiatric admission. We used multiple reaction monitoring mass spectrometry to quantify 77 proteins (147 peptides) in serum samples from 60 first-onset drug-naive schizophrenia patients and 77 controls, and 96 proteins (152 peptides) in 892 newborn blood-spot (NBS) samples collected between 1975 and 1985. Both serum and NBS studies showed significant alterations in protein levels. Serum results revealed that Haptoglobin and Plasma protease C1 inhibitor were significantly upregulated in first-onset schizophrenia patients (corrected P < 0.05). Alpha-2-antiplasmin, Complement C4-A and Antithrombin-III were increased in first-onset schizophrenia patients (uncorrected P-values 0.041, 0.036 and 0.013, respectively) and also increased in newborn babies who later develop schizophrenia (P-values 0.0058, 0.013 and 0.044, respectively). We also tested whether protein abundance at birth was associated with exposure to an urban environment during pregnancy and found highly significant proteomic differences at birth between urban and rural environments. The prediction model for urbanicity had excellent predictive performance in both discovery (area under the receiver operating characteristic curve (AUC) = 0.90) and validation (AUC = 0.89) sample sets. We hope that future biomarker studies based on stored NBS samples will identify prognostic disease indicators and targets for preventive measures for neurodevelopmental conditions, particularly those with onset during early childhood, such as autism spectrum disorder.

Social adversity in childhood and the risk of developing psychosis: a national cohort study.

OBJECTIVE: There is conflicting evidence concerning the association of social childhood factors and subsequent psychosis. Previous studies have had inadequate designs. The aim of the present study was to describe a broad range of social factors during childhood and the risk of developing psychosis later in life in a national cohort. METHOD: The study population consisted of all children born in Sweden in 1963-1983-2.1 million persons-in family households participating in the national census of 1970, 1980, 1985, or 1990. Hazard ratios were estimated for five different indicators of socioeconomic position (living in rented apartments, low socioeconomic status, single-parent households, unemployment, and households receiving social welfare benefits) from hospital admissions for schizophrenia and other psychoses during 1987-2002. RESULTS: Increased age- and sex-adjusted hazard ratios for schizophrenia and other psychoses were found for all childhood socioeconomic indicators, ranking from lowest to highest hazard ratio: rented apartments, low socioeconomic status, single-parent households, unemployment, and households receiving social welfare benefits. Hazard ratios increased with an increasing number of adverse social factors present. Those with four measures of adversity had a 2.7-fold higher risk of schizophrenia than those with none. CONCLUSIONS: The results indicate that social adversity in childhood and fetal life is independently associated with the risk of developing schizophrenia and other psychoses later in life. The risks increased with an increasing number of exposures, suggesting a dose-response relationship.

Sick Leave and Work Participation Among Parents of Children with Autism Spectrum Disorder in the Stockholm Youth Cohort: A Register Linkage Study in Stockholm, Sweden.

This population-based register study explored the association between having a child with/without autism spectrum disorder (ASD) and parental sick leave and work participation. Parents of children with ASD living in Stockholm, Sweden in 2006 were more likely to be on sick leave, not in the labor force, or earning low income when compared to parents who did not have a child with ASD and these results remained after adjusting for familial socioeconomic factors and parental psychiatric care. Sick leave among parents was associated with having a child with ASD without intellectual disability (ID) but not ASD with ID. Although Sweden has policies helping families with children with ASD this study suggests that there exist unmet needs among these parents.

Advancing paternal age and schizophrenia: the impact of delayed fatherhood.

OBJECTIVE: It is well known that advancing paternal age is associated with an increased risk of schizophrenia in offspring, but the mechanism behind this association remains unknown. This study investigates if delayed fatherhood rather than advancing paternal age per se might explain the increased risk of schizophrenia in offspring associated with advancing paternal age. METHODS: This is a register-based study of the Swedish population looking at people born 1955-1985 who have 1 or 2 siblings (n = 2 589 502). The main analysis investigated whether the association between advancing paternal age and schizophrenia was explained by delayed fatherhood. Possible confounding factors were taken into account. Cox regression was used throughout. RESULTS: In the main analysis the association between advancing paternal age and increased risk of schizophrenia in offspring disappeared after controlling for delayed fatherhood (hazard ratio [HR] = 0.93, 95% CI = 0.72-1.21 comparing 45+ years old fathers to those 25-29), whereas delayed fatherhood showed an association with increased risk of schizophrenia in offspring comparing 35-39 and 40-44 years old fathers to 25-29 year olds (HR = 1.37, 95% CI = 1.18-1.58; HR = 1.81, 95% CI = 1.44-2.28, respectively). The results remained when controlling for possible confounders. CONCLUSIONS: This study suggests that the association between paternal age and schizophrenia is not due to paternal age per se, but rather to an unknown factor associated with both delayed fatherhood and schizophrenia.