Experience of an NIHR Clinical Lectureship (medical/dental) and the determining factors for a clinical academic career post lectureship: a mixed-method evaluation.

OBJECTIVES: The objective of this study is to investigate early-to-late postdoctoral clinical academic progression and the experiences of NIHR Clinical Lectureship (CL) fellows, considering enablers and barriers to success, and identifying the factors associated with immediate progression to a clinical academic role following completion of the award. SETTING: Datasets of CL awardees across the UK. PARTICIPANTS: For semistructured interviews, n=40 CL awardees that had finished their award within the previous 5 years. For quantitative analysis, n=1226 completed or currently active CL awardees. OUTCOME MEASURES: The responses from the semistructured interviews to the defined questions on experiences during the award, postaward progression, and enablers and barriers to academic progression. Other primary outcome measures were quantitative data on first destinations postaward, demographic data, and whether an awardee had previously held an NIHR Academic Clinical Fellowship (ACF) or was a recipient of the Academy of Medical Sciences (AMS) Starter Grant. RESULTS: CL awardees identified numerous benefits to the award, with the majority achieving their aims. Most awardees progressed to a clinical academic role; however, some returned to a clinical only position, citing concerns around the time pressure associated with balancing clinical and academic responsibilities, and the competition to attain further postdoctoral awards. The region of the award partnership, year of award end and success in applying for an AMS Starter Grant were associated with progression to a clinical academic role. Gender, holding an ACF and having a craft or non-craft specialty had no independent statistical association with clinical academic progression. CONCLUSIONS: The CL is a valued element of the Integrated Academic Pathway. By addressing issues around later postdoctoral progression opportunities, responding to challenges experienced by CLs, and by understanding the factors identified in this study associated with clinical academic progression, it should be possible to increase the proportion of CLs that become fully independent clinical academic research leaders. PARTICIPANTS: 1226 NIHR CLs active or completed on the award between 2006 and 2020.

Antidepressants in pregnancy: applying causal epidemiological methods to understand service-use outcomes in women and long-term neurodevelopmental outcomes in exposed children.

Background: Antidepressants are commonly prescribed during pregnancy, despite a lack of evidence from randomised trials on the benefits or risks. Some studies have reported associations of antidepressants during pregnancy with adverse offspring neurodevelopment, but whether or not such associations are causal is unclear. Objectives: To study the associations of antidepressants for depression in pregnancy with outcomes using multiple methods to strengthen causal inference. Design: This was an observational cohort design using multiple methods to strengthen causal inference, including multivariable regression, propensity score matching, instrumental variable analysis, negative control exposures, comparison across indications and exposure discordant pregnancies analysis. Setting: This took place in UK general practice. Participants: Participants were pregnant women with depression. Interventions: The interventions were initiation of antidepressants in pregnancy compared with no initiation, and continuation of antidepressants in pregnancy compared with discontinuation. Main outcome measures: The maternal outcome measures were the use of primary care and secondary mental health services during pregnancy, and during four 6-month follow-up periods up to 24 months after pregnancy, and antidepressant prescription status 24 months following pregnancy. The child outcome measures were diagnosis of autism, diagnosis of attention deficit hyperactivity disorder and intellectual disability. Data sources: UK Clinical Practice Research Datalink. Results: Data on 80,103 pregnancies were used to study maternal primary care outcomes and were linked to 34,274 children with at least 4-year follow-up for neurodevelopmental outcomes. Women who initiated or continued antidepressants during pregnancy were more likely to have contact with primary and secondary health-care services during and after pregnancy and more likely to be prescribed an antidepressant 2 years following the end of pregnancy than women who did not initiate or continue antidepressants during pregnancy (odds ratioinitiation 2.16, 95% confidence interval 1.95 to 2.39; odds ratiocontinuation 2.40, 95% confidence interval 2.27 to 2.53). There was little evidence for any substantial association with autism (odds ratiomultivariableregression 1.10, 95% confidence interval 0.90 to 1.35; odds ratiopropensityscore 1.06, 95% confidence interval 0.84 to 1.32), attention deficit hyperactivity disorder (odds ratiomultivariableregression 1.02, 95% confidence interval 0.80 to 1.29; odds ratiopropensityscore 0.97, 95% confidence interval 0.75 to 1.25) or intellectual disability (odds ratiomultivariableregression 0.81, 95% confidence interval 0.55 to 1.19; odds ratiopropensityscore 0.89, 95% confidence interval 0.61 to 1.31) in children of women who continued antidepressants compared with those who discontinued antidepressants. There was inconsistent evidence of an association between initiation of antidepressants in pregnancy and diagnosis of autism in offspring (odds ratiomultivariableregression 1.23, 95% confidence interval 0.85 to 1.78; odds ratiopropensityscore 1.64, 95% confidence interval 1.01 to 2.66) but not attention deficit hyperactivity disorder or intellectual disability; however, but results were imprecise owing to smaller numbers. Limitations: Several causal-inference analyses lacked precision owing to limited numbers. In addition, adherence to the prescribed treatment was not measured. Conclusions: Women prescribed antidepressants during pregnancy had greater service use during and after pregnancy than those not prescribed antidepressants. The evidence against any substantial association with autism, attention deficit hyperactivity disorder or intellectual disability in the children of women who continued compared with those who discontinued antidepressants in pregnancy is reassuring. Potential association of initiation of antidepressants during pregnancy with offspring autism needs further investigation. Future work: Further research on larger samples could increase the robustness and precision of these findings. These methods applied could be a template for future pharmaco-epidemiological investigation of other pregnancy-related prescribing safety concerns. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (15/80/19) and will be published in full in Health Technology Assessment; Vol. 27, No. 15. See the NIHR Journals Library website for further project information.

About one in seven women experience depression during pregnancy. Left untreated, this may harm them and their unborn babies. However, the decision to take antidepressants during pregnancy is difficult because women often worry about the risks to their unborn baby. Research findings have been inconsistent, so women often do not have clear information to enable them to make informed decisions. We studied women's and children's outcomes after starting (compared with not starting) or continuing (compared with stopping) antidepressants in pregnancy. We used a large UK primary care database and several novel methods of analysis. We tracked 80,103 pregnancies of women with depression for up to 2 years after pregnancy. We also tracked 34,274 children from these pregnancies for at least 4 years to check for developmental outcomes. Women prescribed antidepressants were more likely than women not prescribed antidepressants to use general practice and mental health services during and after pregnancy, and to be prescribed antidepressants 2 years after pregnancy. This suggests that antidepressants were being prescribed to women with greater clinical need. Women who continued antidepressants in pregnancy had no higher likelihood than those who discontinued antidepressants of autism, attention deficit hyperactivity disorder or intellectual disability in their children. This should reassure women making the decision to continue taking their medications in pregnancy. Women who started antidepressants in pregnancy may possibly have had a slightly higher likelihood of autism in their children than those who did not start them. These findings were not seen in all analyses and were based on smaller numbers; therefore, they should be viewed with caution. Importantly, over 98 in every 100 children of women who initiated or continued antidepressants in pregnancy did not receive an autism diagnosis. The findings may help women and clinicians make informed decisions on treatment with antidepressants in pregnancy.

Assessment of non-directed computer-use behaviours in the home can indicate early cognitive impairment: A proof of principle longitudinal study.

OBJECTIVES: Computer-use behaviours can provide useful information about an individual's cognitive and functional abilities. However, little research has evaluated unaided and non-directed home computer-use. In this proof of principle study, we explored whether computer-use behaviours recorded during routine home computer-use i) could discriminate between individuals with subjective cognitive decline (SCD) and individuals with mild cognitive impairment (MCI); ii) were associated with cognitive and functional scores; and iii) changed over time. METHODS: Thirty-two participants with SCD (n = 18) or MCI (n = 14) (mean age = 72.53 years; female n = 19) participated in a longitudinal study in which their in-home computer-use behaviour was passively recorded over 7-9 months. Cognitive and functional assessments were completed at three time points: baseline; mid-point (4.5 months); and end point (month 7 to 9). RESULTS: Individuals with MCI had significantly slower keystroke speed and spent less time on the computer than individuals with SCD. More time spent on the computer was associated with better task switching abilities. Faster keystroke speed was associated with better visual attention, recall, recognition, task inhibition, and task switching. No significant change in computer-use behaviour was detected over the study period. CONCLUSION: Passive monitoring of computer-use behaviour shows potential as an indicator of cognitive abilities, and can differentiate between people with SCD and MCI. Future studies should attempt to monitor computer-use behaviours over a longer time period to capture the onset of cognitive decline, and thus could inform timely therapeutic interventions.Supplemental data for this article can be accessed online at http://dx.doi.org/10.1080/13607863.2022.2036946.

Gendered play behaviours in autistic and non-autistic children: A population-based cohort study.

LAY ABSTRACT: Non-autistic children tend to show gendered patterns of play behaviours - boys are more likely to play with 'masculine' toys, and girls are more likely to play with 'feminine' toys. However, little is known about whether autistic children follow these patterns as well. We looked at the masculinity and femininity of autistic and non-autistic children's play behaviours at multiple time points. Parents reported their children's play behaviours at ages 30, 42 and 57 months, and children reported their own play behaviours at 8 years old. We found no difference between autistic and non-autistic girls, who both showed more feminine play behaviours as they got older. Autistic boys' play behaviours were reported as less masculine than non-autistic boys at 42 and 57 months, and at 8 years old. We also found that non-autistic boys' play tended to become more masculine as they got older, but this was not the case for autistic boys. Our findings suggest that differences in autistic and non-autistic boys' play behaviours may develop at around 42 months old.

Father absence and trajectories of offspring mental health across adolescence and young adulthood: Findings from a UK-birth cohort.

BACKGROUND: High prevalence of parental separation and resulting biological father absence raises important questions regarding its impact on offspring mental health across the life course. We specifically examined whether these relationships vary by sex and the timing of exposure to father absence (early or middle childhood). METHODS: This study is based on up to 8409 children from the Avon Longitudinal Study of Parents and Children (ALSPAC). Participants provided self-reports of depression (Clinical Interview Schedule-Revised) at age 24 years and depressive symptoms (Short Mood and Feelings Questionnaire) between the ages of 10 and 24 years. Biological father absence in childhood was assessed through maternal questionnaires at regular intervals from birth to 10 years. We estimated the association between biological father absence and trajectories of depressive symptoms using multilevel growth-curve modelling. RESULTS: Early but not middle childhood father absence was strongly associated with increased odds of offspring depression and greater depressive symptoms at age 24 years. Early childhood father absence was associated with higher trajectories of depressive symptoms during adolescence and early adulthood compared with father presence. Differences in the level of depressive symptoms between middle childhood father absent and father present groups narrowed into adulthood. LIMITATIONS: This study could be biased by attrition and residual confounding. CONCLUSIONS: We found evidence that father absence in childhood is persistently associated with offspring depression in adolescence and early adulthood. This relationship varies by sex and timing of father's departure, with early childhood father absence emerging as the strongest risk factor for adverse offspring mental health trajectories Further research is needed to identify mechanisms that could inform preventative interventions to reduce the risk of depression in children who experience father absence.

Maternal smoking during pregnancy and offspring intellectual disability: sibling analysis in an intergenerational Danish cohort.

BACKGROUND: Maternal smoking has known adverse effects on fetal development. However, research on the association between maternal smoking during pregnancy and offspring intellectual disability (ID) is limited, and whether any associations are due to a causal effect or residual confounding is unknown. METHOD: Cohort study of all Danish births between 1995 and 2012 (1 066 989 persons from 658 335 families after exclusions), with prospectively recorded data for cohort members, parents and siblings. We assessed the association between maternal smoking during pregnancy (18.6% exposed, collected during prenatal visits) and offspring ID (8051 cases, measured using ICD-10 diagnosis codes F70-F79) using logistic generalised estimating equation regression models. Models were adjusted for confounders including measures of socio-economic status and parental psychiatric diagnoses and were adjusted for family averaged exposure between full siblings. Adjustment for a family averaged exposure allows calculation of the within-family effect of smoking on child outcomes which is robust against confounders that are shared between siblings. RESULTS: We found increased odds of ID among those exposed to maternal smoking in pregnancy after confounder adjustment (OR 1.35, 95% CI 1.28-1.42) which attenuated to a null effect following adjustment for family averaged exposure (OR 0.91, 95% CI 0.78-1.06). CONCLUSIONS: Our findings are inconsistent with a causal effect of maternal smoking during pregnancy on offspring ID risk. By estimating a within-family effect, our results suggest that prior associations were the result of unmeasured genetic or environmental characteristics of families in which the mother smokes during pregnancy.

Migration and risk of intellectual disability with and without autism: A population-based cohort study.

OBJECTIVE: To investigate whether parental migration, parental region of origin, timing of child's birth in relation to maternal migration and parental reason for migration are associated with intellectual disability (ID) with and without autism. METHODS: We used a register-based cohort of all individuals aged 0-17 years in Stockholm County during 2001-2011. General estimating equation logistic model and additionally sibling comparison were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). The models were adjusted for child's sex and birth year and parental age at child's birth, and additionally for migrant-specific variables in the analyses including only children with migrant parent(s). RESULTS: Within the eligible sample of 670,098 individuals, 3781 (0.6%) had ID with autism, and 5076 (0.8%) had ID without autism. Compared with children with Swedish-born parents, children with both parents born abroad had an increased risk of ID with autism (OR = 1.6, CI 1.5-1.8) and ID without autism (OR = 1.9, CI 1.7-2.0). Among these children with both parents born abroad, it was protective of ID with autism when the child's birth occurred before and later than four years after maternal migration, which was replicated in the sibling comparison. The associations with both conditions were more pronounced with parental origin in regions comprising low- and middle-income countries and with reasons other than work or study. CONCLUSIONS: Parental migration is associated with ID regardless of co-occurrence of autism. Our results indicate an association between environmental factors during pregnancy related to migration and offspring ID with autism, although further confirmative studies are needed.

Anxiety Disorders in Adults with Autism Spectrum Disorder: A Population-Based Study.

Anxiety is common in children with ASD; however, the burden of specific anxiety disorders for adults with ASD is under-researched. Using the Stockholm Youth Cohort, we compared anxiety disorder diagnoses among autistic adults (n = 4049), with or without intellectual disability, and population controls (n = 217,645). We conducted additional sibling analyses. Anxiety disorders were diagnosed in 20.1% of adults with ASD compared with 8.7% of controls (RR = 2.62 [95% CI 2.47-2.79]), with greatest risk for autistic people without intellectual disability. Rates of almost all individual anxiety disorders were raised, notably obsessive-compulsive disorder and phobic anxiety disorders. Anxiety disorders were more common in full siblings and half-siblings of people with ASD. The implications of this are explored.

Intelligence in offspring born to women exposed to intimate partner violence: a population-based cohort study.

Background: Intimate partner violence (IPV) is a risk factor for developmental problems in offspring. Despite a high prevalence of IPV in the UK and elsewhere, the longer-term outcomes of offspring born to exposed mothers remain under-researched. Methods: Population-based cohort study. We assessed IPV prevalence by type and timing for 3,153 mother-child pairs with complete data within our study population and examined associations between IPV and offspring IQ. We used multiple-imputation to evaluate bias due to our exclusion of observations with missing covariate data. Results: Nearly one in five mothers reported IPV during the study period, with 17.6% reporting emotional violence and 6.8% reporting physical violence. Taking into account potential confounders, the IQ scores of children born to mothers exposed to physical violence remained lower than those of maternally unexposed children (full-scale IQ = -2.8 points [95%CI -4.9 to -0.7], verbal IQ = -2.2 [95%CI -4.4 to -0.1], performance IQ = -2.7 [95%CI  -5.0 to -0.5]) and odds of below-average intelligence (IQ<90) remained increased for full-scale (OR 1.48 [95%CI 1.03 to 2.14] and performance IQ (OR 1.48 [95%CI 1.08 to 2.04]) but not verbal IQ (OR 1.06 [95%CI 0.69 to 1.64]). Most physical violence occurred postnatally, and relative odds were most substantial when mothers were exposed to violence across pre-/perinatal and postnatal study periods (OR performance IQ<90 = 2.97 [95%CI 1.30 to 6.82]). Conclusions: Maternal exposure to physical IPV is associated with lower offspring IQ at age 8. Associations persisted after adjusting for potential confounders and were driven by violence occurring postnatally.

Association of Autistic Traits With Depression From Childhood to Age 18 Years.

Importance: Population-based studies following trajectories of depression in autism spectrum disorders (ASD) from childhood into early adulthood are rare. The role of genetic confounding and of potential environmental intermediaries, such as bullying, in any associations is unclear. Objectives: To compare trajectories of depressive symptoms from ages 10 to 18 years for children with or without ASD and autistic traits, to assess associations between ASD and autistic traits and an International Statistical Classification of Diseases, 10th Revision (ICD-10) depression diagnosis at age 18 years, and to explore the importance of genetic confounding and bullying. Design, Setting, and Participants: Longitudinal study of participants in the Avon Longitudinal Study of Parents and Children birth cohort in Bristol, United Kingdom, followed up through age 18 years. Data analysis was conducted from January to November 2017. Main Outcomes and Measures: Depressive symptoms were assessed using the Short Mood and Feelings Questionnaire (SMFQ) at 6 time points between ages 10 and 18 years. An ICD-10 depression diagnosis at age 18 years was established using the Clinical Interview Schedule-Revised. Exposures were ASD diagnosis and 4 dichotomized autistic traits (social communication, coherence, repetitive behavior, and sociability). An autism polygenic risk score was derived using the Psychiatric Genomics Consortium autism discovery genome-wide association study summary data. Bullying was assessed at ages 8, 10, and 13 years. Results: The maximum sample with complete data was 6091 for the trajectory analysis (48.8% male) and 3168 for analysis of depression diagnosis at age 18 years (44.4% male). Children with ASD and autistic traits had higher average SMFQ depressive symptom scores than the general population at age 10 years (eg, for social communication 5.55 [95% CI, 5.16-5.95] vs 3.73 [95% CI, 3.61-3.85], for ASD 7.31 [95% CI, 6.22-8.40] vs 3.94 [95% CI, 3.83-4.05], remaining elevated in an upward trajectory until age 18 years (eg, for social communication 7.65 [95% CI, 6.92-8.37] vs 6.50 [95% CI, 6.29-6.71], for ASD 7.66 [95% CI, 5.96-9.35] vs 6.62 [95% CI, 6.43-6.81]). Social communication impairments were associated with depression at age 18 years (adjusted relative risk, 1.68; 95% CI, 1.05-2.70), and bullying explained a substantial proportion of this risk. There was no evidence of confounding by the autism polygenic risk score. Analysis in larger samples using multiple imputation led to similar but more precise results. Conclusions and Relevance: Children with ASD and ASD traits have higher depressive symptom scores than the general population by age 10 years, which persist to age 18 years, particularly in the context of bullying. Social communication impairments are an important autistic trait in relation to depression. Bullying, as an environmental intermediary, could be a target for interventions.

Investigating ethnic variations in reporting of psychotic symptoms: a multiple-group confirmatory factor analysis of the Psychosis Screening Questionnaire.

BACKGROUND: Epidemiological evidence suggests risk for psychosis varies with ethnicity in Western countries. However, there is little evidence to date on the cross-cultural validity of screening instruments used for such comparisons. METHODS: Combining two existing UK population-based cohorts, we examined risk for reporting psychotic symptoms across White British (n = 3467), White Irish (n = 851), Caribbean (n = 1899), Indian (n = 2590), Pakistani (n = 1956) and Bangladeshi groups (n = 1248). We assessed the psychometric properties of the Psychosis Screening Questionnaire (PSQ) with a multiple-group confirmatory factor analysis, assessing the equivalence of factor loadings, response thresholds and residual variances in an analysis of measurement non-invariance. RESULTS: Compared with prevalence among British Whites (5.4%), the prevalence of self-reported psychotic symptoms was greater in the Caribbean group (12.7%, adjusted OR = 2.38 [95% CI 1.84-3.07]). Prevalence was also increased among Pakistani individuals (8.3%, adjusted OR = 1.36 [1.01-1.84]) although this difference was driven by a greater likelihood of reporting paranoid symptoms. PSQ items for thought interference, strange experience and hallucination were measured in equivalent ways across ethnic groups. However, our measurement models suggested that paranoid symptoms were measured less reliably among ethnic minorities than among British Whites and appeared to exaggerate latent differences between Pakistani and White British groups when measurement non-invariance was not accounted for. CONCLUSIONS: Notwithstanding evidence for measurement non-invariance, the greater risk for reporting psychotic symptoms among Caribbean individuals is unlikely to be an artefact of measurement. Greater residual variance in the recording of paranoid symptoms among ethnic minority respondents warrants caution in using this item to investigate ethnic variation in psychosis risk.

Association Between Autism Spectrum Disorders With or Without Intellectual Disability and Depression in Young Adulthood.

Importance: Depression is a frequently occurring mental disorder and may be common in adults with autism spectrum disorders (ASD), but there is a lack of longitudinal population-based studies examining this association. Whether any increased risk of depression in ASD has a shared familial basis and whether it differs by co-occurring intellectual disability is not well known. Objectives: To examine whether individuals with ASD are more likely to be diagnosed as having depression in adulthood than the general population and their nonautistic siblings and to investigate whether these risks differ by the presence or absence of intellectual disability. Design, Setting, and Participants: Population-based cohort study with a nested sibling comparison. The Stockholm Youth Cohort is a total population record linkage study that includes all children and young people (age range, 0-17 years) who were ever resident in Stockholm County, Sweden, between January 2001 and December 2011 (n = 735 096). Data analysis was conducted between January 5 and November 30, 2017, in Stockholm County, Sweden. Main Outcomes and Measures: Clinical diagnosis of depressive disorders was identified using the Stockholm County Adult Psychiatric Outpatient Register and the Swedish National Patient Register. Results: Participants were 223 842 individuals followed up to age 27 years by 2011, of whom 4073 had diagnosed ASD (mean [SD] age, 21.5 [2.7] years; 65.9% male; 2927 without intellectual disability and 1146 with intellectual disability) and 219 769 had no ASD (mean [SD] age, 22.1 [2.8] years; 50.9% male). By age 27 years, 19.8% (n = 808) of individuals diagnosed having ASD had a diagnosis of depression compared with 6.0% (n = 13 114) of the general population (adjusted relative risk [RR], 3.64; 95% CI, 3.41-3.88). The risk of a depression diagnosis was higher in ASD without intellectual disability (adjusted RR, 4.28; 95% CI, 4.00-4.58) than in ASD with intellectual disability (adjusted RR, 1.81; 95% CI, 1.51-2.17). Nonautistic full-siblings (adjusted RR, 1.37; 95% CI, 1.23-1.53) and half-siblings (adjusted RR, 1.42; 95% CI, 1.23-1.64) of individuals with ASD also had a higher risk of depression than the general population. Compared with their nonautistic full-siblings, individuals with ASD had more than a 2-fold risk of a depression diagnosis (adjusted odds ratio, 2.50; 95% CI, 1.91-3.27) in young adulthood. Conclusions and Relevance: According to this study's results, ASD, particularly ASD without intellectual disability, is associated with depression by young adulthood compared with the general population. It appears that this association is unlikely to be explained by shared familial liability. Future research to identify modifiable pathways between ASD and depression may assist in the development of preventive interventions.

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.

Prevalence of Autism Spectrum Disorders with and without Intellectual Disability by Gestational Age at Birth in the Stockholm Youth Cohort: a Register Linkage Study.

BACKGROUND: Preterm birth has been linked to increased risk of autism spectrum disorders (ASD), but how this risk changes with gestational age at birth has not been well characterised, especially with regard to co-occurring intellectual disability (ID). METHODS: Register-based cohort study of singleton births in 1984-2007 in Stockholm County, Sweden (N total: 480 728; n ASD: 10 025). We assessed overall and sex-specific, gestational week-specific prevalence estimates and risk ratios of ASD with and without ID. RESULTS: Preterm and postterm births were associated with elevated risk of ASD, and the relationship between gestational age at birth and ASD with and without ID differed in males and females. Risk of ASD without ID was higher in preterm births among both sexes and decreased continuously with increasing length of gestation. Risk of ASD with ID was higher in both preterm and postterm births among both sexes, with postterm birth in females being more highly associated with ASD with ID than that in males. CONCLUSIONS: The relationship between gestational age at birth and ASD differs by the presence/absence of co-occurring ID and fetal sex. Both preterm and postterm birth are associated with increased risk of ASD. Risk of ASD is not constant within conventionally defined gestational age at birth periods. Further research on mechanism underlying these associations is needed.

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.

Sex bias in autism spectrum disorder in neurofibromatosis type 1.

BACKGROUND: Despite extensive literature, little is known about the mechanisms underlying sex bias in autism spectrum disorder (ASD). This study investigates the sex differences in ASD associated with neurofibromatosis type 1, a single-gene model of syndromic autism. METHODS: We analysed data from n = 194 children aged 4-16 years with neurofibromatosis type 1. Sex differences were evaluated across the Autism Diagnostic Interview-Revised (ADI-R), Autism Diagnostic Observation Schedule (ADOS), verbal IQ, Social Responsiveness Scale (SRS) and Conners questionnaires. RESULTS: There was 2.68:1 male:female ratio in children meeting ASD criteria on the deep phenotyping measures. On symptom profile, males with neurofibromatosis type 1 (NF1) + ASD were more impaired on reciprocal social interaction and communication domains of the ADI-R but we found no differences on the restricted, repetitive behaviours (RRBs) domain of the ADI-R and no differences on the social on the ADOS. NF1 ASD males and females were comparable on verbal IQ, and the inattention/hyperactivity domains of the Conners questionnaire. CONCLUSIONS: There is a significant male bias in the prevalence of ASD in NF1. The phenotypic profile of NF1 + ASD cases includes greater social communication impairment in males. We discuss the implications of our findings and the rationale for using NF1 as a model for investigating sex bias in idiopathic ASD.

Ethnic density effects on health and experienced racism among Caribbean people in the US and England: a cross-national comparison.

Studies indicate an ethnic density effect, whereby an increase in the proportion of racial/ethnic minority people in an area is associated with reduced morbidity among its residents, though evidence is varied. Discrepancies may arise due to differences in the reasons for and periods of migration, and socioeconomic profiles of the racial/ethnic groups and the places where they live. It is important to increase our understanding of how these factors might promote or mitigate ethnic density effects. Cross-national comparative analyses might help in this respect, as they provide greater heterogeneity in historical and contemporary characteristics in the populations of interest, and it is when we consider this heterogeneity in the contexts of peoples' lives that we can more fully understand how social conditions and neighbourhood environments influence the health of migrant and racial/ethnic minority populations. This study analysed two cross-sectional nationally representative surveys, in the US and in England, to explore and contrast the association between two ethnic density measures (black and Caribbean ethnic density) and health and experienced racism among Caribbean people. Results of multilevel logistic regressions show that nominally similar measures of ethnic density perform differently across health outcomes and measures of experienced racism in the two countries. In the US, increased Caribbean ethnic density was associated with improved health and decreased experienced racism, but the opposite was observed in England. On the other hand, increased black ethnic density was associated with improved health and decreased experienced racism of Caribbean English (results not statistically significant), but not of Caribbean Americans. By comparing mutually adjusted Caribbean and black ethnic density effects in the US and England, this study examined the social construction of race and ethnicity as it depends on the racialised and stigmatised meaning attributed to it, and the association that these different racialised identities have on health.