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The association between intrauterine growth restriction and cardiovascular disease (CVD) later in life might be confounded by familial factors. We conducted a binational register-based cohort study to assess associations of birth weight for gestational age (GA), a proxy for intrauterine growth restriction, and GA with CVD risk in early adulthood, before and after addressing familial factors via sibling comparison. We included 3,410,334 live nonmalformed singleton births from Sweden (1973–1996) and Denmark (1978–1998). During a median follow-up period of 10 years from age 18 years onwards, 29,742 individuals developed incident CVD (hypertension, ischemic heart disease, or cerebrovascular disease). Compared with individuals born with appropriate birth weight for GA (AGA; 10th–90th percentiles) or full term (39–40 gestational weeks), individuals born severely small for GA (SGA; ≤3rd percentile) or preterm (22–36 weeks) were at increased risk of CVD (hazard ratio (HR) = 1.38 (95% confidence interval (CI): 1.32, 1.45) and HR = 1.31 (95% CI: 1.25, 1.38), respectively). The association was attenuated when comparing individuals born SGA with their AGA siblings (HR = 1.11, 95% CI: 0.99, 1.25) but remained robust when comparing individuals born preterm with their term siblings (HR = 1.21, 95% CI: 1.07, 1.37). Our findings suggest that both SGA and preterm birth are associated with CVD risk in early adulthood, with greater familial confounding noted for SGA birth. [ABSTRACT FROM AUTHOR]

Objectives: The study aimed to investigate the association between maternal body mass index (BMI) in early pregnancy and children's intellectual disability (ID) risk in the absence of chromosomal disorders, neurofibromatosis and tuberous sclerosis, taking adverse birth outcomes, maternal hypertension/diabetes and maternal socioeconomic status into consideration.Methods: We conducted a cohort study of singletons without common genetic defects born in Sweden during 1992-2006, and followed them from birth until 31 December 2014 (n=1 186 836). Cox proportional hazards models were used to analyse the association between maternal BMI in early pregnancy and the risk of offspring's ID.Results: The risk of ID was higher in children born to mothers who were underweight (HR=1.21, 95% CI=1.07 to 1.36), overweight (HR=1.28, 95% CI=1.21 to 1.34) or had obesity class I (HR=1.63, 95% CI=1.53 to 1.74), obesity class II (HR=2.08, 95% CI=1.88 to 2.30) and obesity class III (HR=2.31, 95% CI=1.46 to 3.65) than in children born to normal weight mothers. Results remained consistent after excluding children with adverse birth outcome or born to mothers with gestational hypertension/diabetes. Analysis stratified by maternal education and annual household income showed that the association between maternal underweight and children's ID risk was attenuated among children of mothers with tertiary education or with high income.Conclusions: Our findings suggest that maternal underweight or overweight/obesity in early pregnancy was associated with the development of ID in their offspring. This association was independent of the effect of adverse birth outcomes and maternal hypertension/diabetes. High socioeconomic status may attenuate the risk of ID among children of underweight mothers. This study highlights the importance of improving health education before conception to reduce children's ID risk. [ABSTRACT FROM AUTHOR]

Maternal hypertensive disorders during pregnancy (HDP) have been associated with neuropsychiatric problems in offspring. We aim to investigate the associations between specific types of maternal HDP and offspring neurodevelopmental disorders and further examine whether the timing of onset and severity of HDP would affect these associations. The study population consisted of 4,489,044 live-born singletons in Denmark during 1978–2012 and Sweden during 1987–2010. Maternal HDP was categorized into chronic hypertension, gestational hypertension, and pre-eclampsia; pre-eclampsia was further stratified according to timing (early-onset, late-onset), or severity (moderate, severe) of the disease. Neurodevelopmental disorders, including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and intellectual disability (ID), were defined by ICD-coded register diagnosis. Cox regression was used to calculate hazard ratios (HR) while adjusting for potential confounders, and sibling analyses assessed the influence of unmeasured shared familial factors. Maternal HDP was associated with increased risks of ADHD (HR, 1.24; 95% confidence interval [CI], 1.20–1.28), ASD (1.29 [1.24–1.34]), and ID (1.58 [1.50–1.66]) in offspring, respectively, which was mostly driven by pre-eclampsia. The strongest associations were observed for early-onset and severe pre-eclampsia, and the corresponding HRs for ADHD, ASD and ID were 1.93 [1.73–2.16], 1.86 [1.61–2.15], and 3.99 [3.42–4.65], respectively. The results were similar in the sibling analyses. The associations between maternal HDP and offspring neurodevelopmental disorders were consistent across the subgroups of sex, preterm status, parity, maternal age and psychiatric disorders. Maternal HDP, especially early-onset pre-eclampsia, are associated with increased risks of ADHD, ASD, and ID in particular, independent of shared familial factors. [ABSTRACT FROM AUTHOR]

Background: Overweight and obese pregnant women face higher risk of several critical birth outcomes, including an overall increased risk of congenital abnormalities. Only few studies have focused on associations between maternal overweight and the genital anomalies in boys, cryptorchidism and hypospadias, and results are inconclusive.Methods: We performed a population-based cohort study and assessed the associations between maternal body mass index (BMI) in early pregnancy and occurrence of cryptorchidism and hypospadias. All live-born singleton boys born in Sweden from 1992 to 2012 were included. From the Swedish Patient Register, information on cryptorchidism and hypospadias was available. Data were analysed using Cox proportional hazards regression adjusted for potential confounders. Mediation analyses were performed to estimate how much of the association between BMI and genital anomalies were mediated through obesity-related diseases.Results: Of the 1 055 705 live-born singleton boys born from 1992 to 2012, 6807 (6.4 per 1000) were diagnosed with hypospadias and 16 469 (15.6 per 1000) were diagnosed with cryptorchidism, of which 9768 (9.3 per 1000) underwent corrective surgery for cryptorchidism. We observed dose-response associations between maternal BMI and hypospadias and cryptorchidism. Boys of mothers with BMI ≥40.0 kg/m2 had the highest adjusted hazard ratios for hypospadias (HR 1.35, 95% confidence interval [CI] 1.04, 1.76) and cryptorchidism (HR 1.25, 95% CI 1.00, 1.58). A substantial proportion of the associations between BMI and the genital anomalies were mediated through preeclampsia.Conclusion: This large register-based study adds to the current literature and indicates that the occurrence of hypospadias and cryptorchidism increase with maternal overweight and obesity severity. [ABSTRACT FROM AUTHOR]

Objectives: The study aimed to investigate the association between maternal body mass index (BMI) in early pregnancy and children's intellectual disability (ID) risk in the absence of chromosomal disorders, neurofibromatosis and tuberous sclerosis, taking adverse birth outcomes, maternal hypertension/diabetes and maternal socioeconomic status into consideration., Methods: We conducted a cohort study of singletons without common genetic defects born in Sweden during 1992-2006, and followed them from birth until 31 December 2014 (n=1 186 836). Cox proportional hazards models were used to analyse the association between maternal BMI in early pregnancy and the risk of offspring's ID., Results: The risk of ID was higher in children born to mothers who were underweight (HR=1.21, 95% CI=1.07 to 1.36), overweight (HR=1.28, 95% CI=1.21 to 1.34) or had obesity class I (HR=1.63, 95% CI=1.53 to 1.74), obesity class II (HR=2.08, 95% CI=1.88 to 2.30) and obesity class III (HR=2.31, 95% CI=1.46 to 3.65) than in children born to normal weight mothers. Results remained consistent after excluding children with adverse birth outcome or born to mothers with gestational hypertension/diabetes. Analysis stratified by maternal education and annual household income showed that the association between maternal underweight and children's ID risk was attenuated among children of mothers with tertiary education or with high income., Conclusions: Our findings suggest that maternal underweight or overweight/obesity in early pregnancy was associated with the development of ID in their offspring. This association was independent of the effect of adverse birth outcomes and maternal hypertension/diabetes. High socioeconomic status may attenuate the risk of ID among children of underweight mothers. This study highlights the importance of improving health education before conception to reduce children's ID risk., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: The role of psychological stress in the aetiology of atrial fibrillation (AF) is unclear. The death of a child is one of the most severe sources of stress. We aimed to investigate whether the death of a child is associated with an increased risk of AF., Methods and Results: We studied parents with children born during 1973-2014 included the Swedish Medical Birth Register (n = 3 924 237). Information on death of a child, AF and socioeconomic, lifestyle and health-related covariates was obtained through linkage to nationwide population and health registers. We examined the link between death of a child and AF risk using Poisson regression. Parents who lost a child had a 15% higher risk of AF than unexposed parents [incidence rate ratio (IRR) and 95% confidence intervals (CI): 1.15 (1.10-1.20)]. An increased risk of AF was observed not only if the child died due to cardiovascular causes [IRR (95% CI): 1.35 (1.17-1.56)], but also in case of deaths due to other natural [IRR (95% CI): 1.15 (1.09-1.21)] or unnatural [IRR (95% CI): 1.10 (1.02-1.19)] causes. The risk of AF was highest in the 1st week after the loss [IRR (95% CI): 2.87 (1.44-5.75)] and remained 10-40% elevated on the long term., Conclusions: Death of a child was associated with a modestly increased risk of AF. Our finding that an increased risk was observed also after loss of a child due to unnatural deaths suggests that stress-related mechanisms may also be implicated in the development of AF., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aim: To compare the prevalence and trends of antipsychotic drug use during pregnancy between countries across four continents., Methods: Individually linked health data in Denmark (2000-2012), Finland (2005-2014), Iceland (2004-2017), Norway (2005-2015), Sweden (2006-2015), Germany (2006-2015), Australia (New South Wales, 2004-2012), Hong Kong (2001-2015), UK (2006-2016), and the US (Medicaid, 2000-2013, and IBM MarketScan, 2012-2015) were used. Using a uniformed approach, we estimated the prevalence of antipsychotic use as the proportion of pregnancies where a woman filled at least one antipsychotic prescription within three months before pregnancy until birth. For the Nordic countries, data were meta-analyzed to investigate maternal characteristics associated with the use of antipsychotics., Results: We included 8,394,343 pregnancies. Typical antipsychotic use was highest in the UK (4.4%) whereas atypical antipsychotic use was highest in the US Medicaid (1.5%). Atypical antipsychotic use increased over time in most populations, reaching 2% in Australia (2012) and US Medicaid (2013). In most countries, prochlorperazine was the most commonly used typical antipsychotic and quetiapine the most commonly used atypical antipsychotic. Use of antipsychotics decreased across the trimesters of pregnancy in all populations except Finland. Antipsychotic use was elevated among smokers and those with parity ≥4 in the Nordic countries., Conclusion: Antipsychotic use during pregnancy varied considerably between populations, partly explained by varying use of the typical antipsychotic prochlorperazine, which is often used for nausea and vomiting in early pregnancy. Increasing usage of atypical antipsychotics among pregnant women reflects the pattern that was previously reported for the general population., Competing Interests: Declaration of competing interest JR, CC, LP, and GB, are employees of the Centre for Pharmacopidemiology which receives funding from pharmaceutical companies and regulatory authorities for drug safety/utilization studies, unrelated to the submitted work. BTB has participated as an investigator on grants to the Brigham and Women's Hospital from Pfizer, GSK, Lilly, Baxalta, and Pacira, not related to the topic of the submitted work. SH-D has participated as investigator in projects funded by Pfizer, GSK, and Lilly; and consulted for Boehringer-Ingelheim, Roche and UCB as a methods advisor for pregnancy studies. KFH has participated as an investigator on grants to the Brigham and Women's Hospital from Boehringer Ingelheim, Pfizer, Lilly and GSK, not related to the topic of the submitted work. The other authors declare no personal conflict of interest., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Mortality in children under five years has been widely studied, whereas mortality at 5-9 years has received little attention. Using unique data from national registers in three Nordic countries, we aimed to characterize mortality directionality in children aged 0 to 9 years., Methods and Findings: The cohort study included all children born in Denmark from 1973 to 2008 (n = 2,433,758), Sweden from 1973 to 2006 (n = 3,400,212), and a random sample of 89.3% of children born in Finland from 1987 to 2007 (n = 1,272,083). Children were followed from 0 to 9 years, and cumulative mortality and mortality rates were compared by age, gender, cause of death, and calendar periods. Among the 7,105,962 children, there were 48,299 deaths during study period. From 1981-1985 to 2001-2005, all-cause mortality rates were reduced by between 34% and 62% at different ages. Overall mortality rate ratio between boys and girls decreased from 1.25 to 1.21 with the most prominent reduction in children aged 5-9 years (from 1.59 to 1.19). Neoplasms, diseases of the nervous system and transport accidents were the most frequent cause of death after the first year of life. These three leading causes of death declined by 42% (from 6.2 to 3.6 per 100,000 person years), 43% (from 3.7 to 2.1) and 62% (from 3.9 to 1.5) in boys, and 25% (from 4.1 to 3.1 per 100000 person years), 42% (from 3.4 to 1.9) and 63% (from 3.0 to 1.1) in girls, respectively. Mortality from neoplasms was the highest in each age except infants when comparing cause-specific mortality, and half of deaths from diseases of the nervous system occurred in infancy. Mortality rate due to transport accidents increased with age and was highest in boys aged 5-9 years., Conclusions: Mortality rate in children aged 0-9 years has been decreasing with diminished difference between genders over the past decades. Our results suggest the importance of further research on mortality by causes of neoplasms, and causes of transport accidents-especially in children aged 5-9 years.