Antiseizure medication use during pregnancy and children's neurodevelopmental outcomes.

The teratogenic potential of valproate in pregnancy is well established; however, evidence regarding the long-term safety of other antiseizure medications (ASMs) during pregnancy remains limited. Using routinely collected primary care data from the UK and nationwide Swedish registries to create a cohort of 3,182,773 children, of which 17,495 were exposed to ASMs in pregnancy, we show that those exposed to valproate were more likely to receive a diagnosis of autism, intellectual disability, and ADHD, when compared to children not exposed to ASMs. Additionally, children exposed to topiramate were 2.

Psychiatric comorbidities in epilepsy: population co-occurrence, genetic correlations and causal effects.

Background: Psychiatric comorbidities are common in patients with epilepsy. Reasons for the co-occurrence of psychiatric conditions and epilepsy remain poorly understood.

Aim: We aimed to triangulate the relationship between epilepsy and psychiatric conditions to determine the extent and possible origins of these conditions.

Analyses Using Multiple Imputation Need to Consider Missing Data in Auxiliary Variables.

Auxiliary variables are used in multiple imputation (MI) to reduce bias and increase efficiency. These variables may often themselves be incomplete. We explored how missing data in auxiliary variables influenced estimates obtained from MI.

Childhood trauma as a mediator between autistic traits and depression: evidence from the ALSPAC birth cohort.

Background: Autism and autistic traits have been associated with greater risk of childhood trauma and adulthood psychopathology. However, the role that childhood trauma plays in the association between autism, autistic traits and depression in adulthood is poorly understood.

Methods: We used a UK-based birth cohort with phenotype and genotype data on autism, autistic traits, childhood trauma and depression in up to 9,659 individuals prospectively followed up from birth until age 28 years.

Maternal smoking during pregnancy and offspring risk of intellectual disability: a UK-based cohort study.

Background: Observational studies have described associations of maternal smoking during pregnancy with intellectual disability (ID) in the exposed offspring. Whether these results reflect a causal effect or unmeasured confounding is still unclear.

Methods: Using a UK-based prospectively collected birth cohort (the Avon Longitudinal Study of Parents and Children) of 13,479 children born between 1991 and 1992, we assessed the relationship between maternal smoking at 18 weeks' gestation and offspring risk of ID, ascertained through multiple sources of linked information including primary care diagnoses and education records.

First-trimester use of antiseizure medications and the risk of miscarriage: a population-based cohort study.

Background: Antiseizure medications (ASMs) during the first trimester of pregnancy have been associated with an increased risk of miscarriage.

Methods: We carried out a population-based cohort study using routinely collected healthcare data from the UK, 1995-2018. Pregnancies were identified in the Clinical Practice Research Datalink and we estimated the HR of miscarriage associated with prescriptions of ASMs during the first trimester of pregnancy, using Cox regression, adjusting for potential confounders, including ASM indications.

Childhood Adversity and Incident Psychotic Experiences in Early Adulthood: Cognitive and Psychopathological Mediators.

Background And Hypothesis: Childhood adversity is often described as a potential cause of incident psychotic experiences, but the underlying mechanisms are not well understood. We aimed to examine the mediating role of cognitive and psychopathological factors in the relation between childhood adversity and incident psychotic experiences in early adulthood.

Study Design: We analyzed data from the Avon Longitudinal Study of Parents and Children, a large population-based cohort study.

Trends and patterns of antiseizure medication prescribing during pregnancy between 1995 and 2018 in the United Kingdom: A cohort study.

Objective: To examine antiseizure medication (ASM) prescription during pregnancy.

Design: Population-based drug utilisation study.

Setting: UK primary and secondary care data, 1995-2018, from the Clinical Practice Research Datalink GOLD version.

Intellectual disability in the children of the Avon Longitudinal Study of Parents and Children (ALSPAC).

Intellectual disability (ID) describes a neurodevelopmental condition involving impaired cognitive and functional ability. Here, we describe a multisource variable of ID using data from the Avon Longitudinal Study of Parents and Children (ALSPAC).  The multisource indicator variable for ID was derived from i) IQ scores less than 70 measured at age 8 and at age 15, ii) free text fields from parent reported questionnaires, iii) school reported provision of educational services for individuals with a statement of special educational needs for cognitive impairments, iv) from relevant READ codes contained in GP records, iv) international classification of disease diagnoses contained in electronic hospital records and hospital episode statistics and v) recorded interactions with mental health services for ID contained within the mental health services data set.

Bias amplification of unobserved confounding in pharmacoepidemiological studies using indication-based sampling.

Purpose: Estimating causal effects in observational pharmacoepidemiology is a challenging task, as it is often plagued by confounding by indication. Restricting the sample to those with an indication for drug use is a commonly performed procedure; indication-based sampling ensures that the exposed and unexposed are exchangeable on the indication-limiting the potential for confounding by indication. However, indication-based sampling has received little scrutiny, despite the hazards of exposure-related covariate control.

Childhood Trauma As a Mediator of the Association Between Autistic Traits and Psychotic Experiences: Evidence From the Avon Longitudinal Study of Parents and Children Cohort.

Background: Little is known on whether associations between childhood autistic traits and psychotic experiences persist into adulthood and whether genetic confounding and childhood trauma influence them. Here we investigate the associations between childhood autistic traits and psychotic experiences until young adulthood and assess the influence of schizophrenia polygenic risk and childhood traumatic experiences, using the Avon Longitudinal Study of Parents and Children (ALSPAC) population-based birth cohort.

Study Design: We used a measure of broad autistic traits (autism factor mean score), and four dichotomised measures of autistic traits capturing social communication difficulties (age 7), repetitive behaviours (age 5), sociability (age 3), and pragmatic language (age 9).

Maternal vitamin D during pregnancy and offspring autism and autism-associated traits: a prospective cohort study.

Background: There has been a growing interest in the association between maternal levels of vitamin D during pregnancy and offspring autism. However, whether any associations reflect causal effects is still inconclusive.

Methods: We used data from a UK-based pregnancy cohort study (Avon Longitudinal Study of Parents and Children) comprising 7689 births between 1991 and 1992 with maternal blood vitamin D levels recorded during pregnancy and at least one recorded outcome measure, including autism diagnosis and autism-associated traits.

Mode of delivery and maternal sexual wellbeing: A longitudinal study.

Objectives: To investigate the association between mode of delivery and subsequent maternal sexual wellbeing.

Design: Prospective birth cohort study.

Setting: Avon (in Bristol area), UK.

Maternal smoking and smokeless tobacco use during pregnancy and offspring development: sibling analysis in an intergenerational Swedish cohort.

Background: The association between maternal smoking in pregnancy and offspring intellectual disability (ID) is less well understood than that of smoking and fetal growth restriction. As fetal growth and cognitive development may share similar confounding structures, comparison of the two associations may improve understanding of the causal nature of the association with ID. Furthermore, comparisons of smoking with smokeless tobacco use may aid identification of mechanisms of action.

Association of maternal pre-pregnancy BMI and breastfeeding with NAFLD in young adults: a parental negative control study.

Background: The importance of the maternal-infant dyad in the genesis of nonalcoholic fatty liver disease (NAFLD) is of increasing interest. The Avon Longitudinal Study of Parents and Children (ALSPAC) showed that at age 24, 1 in 5 had NAFLD measured by transient elastography and controlled attenuation parameter (CAP). Our aim was to investigate the association between breastfeeding duration and maternal pre-pregnancy BMI on offspring NAFLD in young adulthood.

Caesarean section and its relationship to offspring general cognitive ability: a registry-based cohort study of half a million young male adults.

Background: A relationship between caesarean section and offspring cognitive ability has been described, but data are limited, and a large-scale study is needed.

Objective: To determine the relationship between mode of delivery and general cognitive ability.

Methods: A cohort of 579 244 singleton males, born between 1973 and 1987 who conscripted before 2006, were identified using the Swedish population-based registries.

Childhood trauma and cognitive biases associated with psychosis: A systematic review and meta-analysis.

Childhood trauma is associated with an increased risk of psychosis, but the mechanisms that mediate this relationship are unknown. Exposure to trauma has been hypothesised to lead to cognitive biases that might have causal effects on psychotic symptoms. The literature on whether childhood trauma is associated with psychosis-related cognitive biases has not been comprehensively reviewed.

Simulations and directed acyclic graphs explained why assortative mating biases the prenatal negative control design.

Objective: The negative control design can be used to provide evidence for whether a prenatal exposure-outcome association occurs by in utero mechanisms. Assortative mating has been suggested to influence results from negative control designs, although how and why has not yet been adequately explained. We aimed to explain why mutual adjustment of maternal and paternal exposure in regression models can account for assortative mating.

Familial confounding of the association between maternal smoking in pregnancy and autism spectrum disorder in offspring.

Evidence supports no link between maternal smoking in pregnancy and autism spectrum disorder (autism) overall. To address remaining questions about the unexplained heterogeneity between study results and the possibility of risk for specific autism sub-phenotypes, we conducted a whole-population cohort study in Denmark. We followed births 1991-2011 (1,294,906 persons, including 993,301 siblings in 728,271 families), from 1 year of age until an autism diagnosis (13,547), death, emigration, or December 31, 2012.

The proportion of missing data should not be used to guide decisions on multiple imputation.

Objectives: Researchers are concerned whether multiple imputation (MI) or complete case analysis should be used when a large proportion of data are missing. We aimed to provide guidance for drawing conclusions from data with a large proportion of missingness.

Study Design And Setting: Via simulations, we investigated how the proportion of missing data, the fraction of missing information (FMI), and availability of auxiliary variables affected MI performance.